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Early antibiotic treatment failure
Abstract
There is no consensus on the definition of treatment failure. It is usually based on clinical signs, although microbiological and other biological markers may prove of value in the future. The major risk factors associated with treatment failure include an inadequate antimicrobial spectrum of the prescribed antibiotic and lack of, or insufficient, control of the source of the infection. In certain patient subpopulations additional specific factors may play a role. Reported treatment failure rates are unacceptably high, reaching up to 64%. Treatment failure is highly clinically relevant, as indicated by the associated constant finding of significantly increased length of hospital stay, higher mortality and greater healthcare costs. Proposed future initiatives include consensus statements on validated variables and definitions, both for general patient populations and specific subgroups. Investigation of the relative impact of modifiable risk factors may allow for the development of a treatment failure score for adequate stratification of individual cases. In patients in the high-risk group, initial broad-spectrum antimicrobial coverage, and modifications to doses and the dosing schedule should be considered.
... When the stress is too sudden and severe, adaptation through mutation or migration may not be possible; thus, a population's survival chances would rely on their genetic variation. This scenario is especially relevant in the context of antimicrobial and antitumoral chemotherapy, where a substantial number of treatments fail due to the existence of resistant cells at the time of the first drug administration (Komarova and Wodarz 2005;García 2009). ...
... ⁷ ± 4.2x10 6 for the small-population with fosfomycin regime (9.5 h of incubation) and Nfinal=1.1x10¹¹ this bacterium, and it is known to be cost-free under standard laboratory conditions (Castañeda- García et al. 2009). However, we determined that in the presence of 8 mg/L of fosfomycin (1/2 x MIC for the wild-type, estimated by the microdilution method) knocking out glpT confers a growth rate 2.7 ± 0.4 times greater than the wild-type's, which, in terms of our model, is equal to r=5.4 ± 0.8 offspring per generation (values represent mean ± s.d). ...
... Fosfomycin resistance in this organism is acquired exclusively through the inactivation of the glycerol-3-phosphate antiporter GlpT (Castañeda- García et al. 2009). Such inactivation can presumably arise from a high variety of mutations in the glpT gene; and so it is reasonable to assume that, within the same population, two mutants displaying the same mutation probably belong to the same clone. ...
Any pathogen population sufficiently large is expected to harbor spontaneous drug-resistant mutants, often responsible for disease relapse after antibiotic therapy. It is seldom appreciated, however, that while larger populations harbor more mutants, the abundance distribution of these mutants is expected to be markedly uneven. This is because a larger population size allows early mutants to expand for longer, exacerbating their predominance in the final mutant subpopulation. Here, we investigate the extent to which this reduction in evenness can constrain the genetic diversity of spontaneous drug-resistance in bacteria. Combining theory and experiments, we show that even small variations in growth rate between resistant mutants and the wild-type result in orders-of-magnitude differences in genetic diversity. Indeed, only a slight fitness advantage for the mutant is enough to keep diversity low and independent of population size. These results have important clinical implications. Genetic diversity at antibiotic resistance loci can determine a population's capacity to cope with future challenges (i.e. second-line therapy). We thus revealed an unanticipated way in which the fitness effects of antibiotic resistance can affect the evolvability of pathogens surviving a drug-induced bottleneck. This insight will assist in the fight against multi-drug resistant microbes, as well as contribute to theories aimed at predicting cancer evolution.
... 7 The implications of ATF on patients can range from minor health complications, such as the need for additional antibiotic prescriptions to major health complications, such as hospitalizations or even death due to sepsis. 17 Similarly, ATF is associated with significantly increased LOS, higher mortality rates and greater health care costs. 18 From an ecological perspective, ATF can also contribute to antibiotic resistance which further promotes the occurrence of treatment failurea vicious cycle that is a major public health concern. ...
... 18 From an ecological perspective, ATF can also contribute to antibiotic resistance which further promotes the occurrence of treatment failurea vicious cycle that is a major public health concern. 17 To date, no population-based study has addressed whether excess weight is directly associated with ATF, although there have been some indications in the literature that this may be the case. The primary objective of this study was to determine, among persons receiving antibiotic therapy, the extent to which being overweight or obese is independently associated with ATF as indicated by secondary antibiotic prescriptions or hospitalizations for infections within 30 days following initial therapy when compared to normal-weight persons. ...
... A 30-day time interval for assessing whether a secondary antibiotic had been dispensed to study participants was selected as this corresponds to the time required in clinical practice to evaluate if symptoms had resolved for a range of acute infections, referred to as "the test of cure" physician visit. 17 Therefore, T 1 was used to denote the cut-off time for outcome assessment, while the outcome assessment period was generally defined as T 0 + 3 days to T 1 . The 3-day grace period instated after T 0 has been used in other ATF studies, since treatment failure is typically assessed 3 days after the initial infection diagnosis and allows sufficient time for initial antibiotic therapy to target the suspected causal microorganism. ...
Obesity, a major health issue, is also an important risk factor for infections. Evidence demonstrates that excess weight affects the disposition of antibiotics but little work has been done to explore if this results in antibiotic treatment failure (ATF). ATF has serious adverse health outcomes and may increase treatment resistance. Given that obese patients often have other health issues, it is important to determine if excess weight independently increases the likelihood of ATF.
Consenting patients (N = 18 014), randomly sampled from Santé Québec Health surveys (1992, 1998), were linked with administrative health databases. Patients were within the normal, overweight, and obese weight categories aged 20–79 years old, receiving at least one course of antibiotic therapy from the survey date until December 2005. ATF was defined as any additional antibiotic prescriptions or hospitalizations for infections within the 30 days after initial therapy. Logistic regression was used to assess the impact of excess weight on ATF after adjusting for patient characteristics, comorbidities, history of antibiotic use, antibiotic resistance, and flu season.
Of the final sample size (N = 6 179), 39.0% were overweight and 21.4% were obese. The most frequently prescribed antibiotics were amoxicillin (16.0%), ciprofloxacin (9.2%), phenoxymethylpenicillin (8.8%), trimethroprim/sulfamethoxazole (8.6%), and clarithromycin (8.5%). ATF occurred in 828 (13.4%) of the 6 179 study patients. Obesity was a significant predictor of ATF (adjusted OR 1.26; 95% CI 1.03–1.52).
Obesity is a significant risk factor for ATF, and this association may be due to the current “one size fits all” dosing strategy, which warrants further investigation. Copyright
... Age of viability is at 24 weeks thus a maximum of 118 days of life was considered. 6 3. Nephrotoxicity (drug-induced) -0.5 mg/dL or 50% rise in serum creatinine over 24-72 h time frame and a minimum 24-48 h of drug exposure or any of the following: decreased urine output, increased BUN, proteinuria, hematuria or casts in the urine. 4,7 4. Neurotoxicity -severe neurotoxic effects include seizures, hypertonicity, spasms, change/decrease in sensorium reported during treatment with colistin not explained by any other co-morbidity (meningitis, hypoglycemia, hypoxia, etc.). ...
... 1 Admitted patients < 118 days of corrected age with MDR-GNB isolates on blood, endotracheal aspirate, urine, cerebrospinal fluid (CSF), abscess on initial or repeat cultures and given colistin for a minimum of 3 days in order to properly assess antibiotic treatment response or failure were included. 6 Exclusion criteria were as follows: ...
Background: The global burden of multi-drug resistant gram-negative bacterial (MDR-GNB) infections has been increasing. Neonates are at a particularly high-risk and there is limited treatment option. The use of colistin has been reintroduced for this population. However, data on its use in neonates is scarce. Objective: To determine the effectiveness and adverse effects of intravenous colistin in neonates with multidrug-resistant gram-negative infections. Design: This is a retrospective cohort study of the clinical profile and outcome of neonates with MDR-GNB infections given colistin for a minimum of 3 days conducted from April 2015 to April 2019. Results: A total of 175 pediatric patients had MDR-GNB infections. 75 (43%) neonates met the inclusion criteria and received intravenous colistin. Of the 75 patients with MDR-GNB infections-that included sepsis, pneumonia, urinary tract infection and abscess, 37 (49.3%) were alive and 38 (50.7%) patients died. Nephrotoxicity was seen in 4% if patients and 2.6% patients had hypersensitivity reaction. MDROs isolated were Acinetobacter baumanii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Conclusion: Intravenous colistin is 50% effective and is relatively safe to use in neonates.
... Cholesterol is converted into bile acids by oxidation in the liver (neutral pathway) and hydroxylation in the extrahepatic tissue (acidic pathway), resulting in the production of cholic acid and chenodeoxycholic acid, which are stored in the gallbladder and released in the form of glycoland tauro-conjugated bile salts into the duodenum, the jejunum, and ileum (6,35). The conjugated bile salts are detergent-like amphipathic molecules responsible for cholesterol homeostasis and emulsification, solubilization, and absorption of dietary fats and fat-soluble vitamins (2,15). ...
... Over the past few decades, the misuse and overuse of antibiotics have contributed to alterations in the intestinal biota balance and the rapid emergence of antibiotic-resistant foodborne pathogens (43). Infections caused by the increasing spread of antibiotic-resistant bacteria have become a serious public health problem worldwide; these infections are primarily caused by the consumption of contaminated foods (23,28,35,42). Therefore, antibioticresistant foodborne pathogens can encounter bile stress when passing through the GI tract (38). ...
This study was designed to evaluate the effects of bile acid deconjugation by probiotic strains on the antibiotic susceptibility of antibiotic-sensitive and multiple antibiotic-resistant Salmonella Typhimurium and Staphylococcus aureus. Eight probiotic strains, Bifidobacterium longum B6, Lactobacillus acidophilus ADH, Lactobacillus brevis KACC 10553, Lactobacillus casei KACC 12413, Lactobacillus paracasei ATCC 25598, Lactobacillus rhamnosus GG, Leuconostoc mesenteroides KACC 12312, and Pediococcus acidilactici KACC 12307, were used to examine bile acid tolerance. The ability to deconjugate bile acids was evaluated using both thin-layer chromatography and high-performance liquid chromatography. The antibiotic susceptibility testing was carried out to determine the synergistic inhibitory activity of deconjugated bile acids. L. acidophilus, L. brevis, and P. acidilactici showed the most tolerance to the conjugated bile acids. P. acidilactici deconjugated glycocholic acid and glycodeoxycholate from 3.18 and 3.09 mM to the detection limits, respectively. The antibiotic susceptibility of selected foodborne pathogens was increased by increasing the concentration of deconjugated bile acids. The study results are useful for understanding the relationship between bile acid deconjugation by probiotic strains and antibiotic susceptibility in the presence of deconjugated bile acids, and they may be useful for designing new probiotic-antibiotic combination therapy based on bile acid deconjugation.
... Multiple studies indicate that an antibiotic treatment appropriate to the pathogen, during the early hours of an infection, can significantly reduce the mortality 3,4 . In clinical settings, however, early antibiotic treatments are commonly empirical and imperfect, mainly due to the long turnaround time of routine microbial identification 5,6 , resulting in increased mortality risk 7 . ...
... Today around 11,900 antibiotics had been discovered by 1994 of which around 7,140 (60%) were produced by these bacteria (Procopio, 2012;Safey et al., 2013). From the problem of old antibiotics for infectious disease treatment is failure leads to infectious diseases are increase (Garcia, 2009;Oancea and Stoia, 2010). Therefore, novel antibiotics had been continuously invented and developed (Raja and Prabakarana, 2011). ...
... Multiple studies indicate that an antibiotic treatment appropriate to the pathogen, during the early hours of an infection, can significantly reduce the mortality 3,4 . In clinical settings, however, early antibiotic treatments are commonly empirical and imperfect, mainly due to the long turnaround time of routine microbial identification 5,6 , resulting in increased mortality risk 7 . ...
The healthcare industry is in dire need of rapid microbial identification techniques for treating microbial infections. Microbial infections are a major healthcare issue worldwide, as these widespread diseases often develop into deadly symptoms. While studies have shown that an early appropriate antibiotic treatment significantly reduces the mortality of an infection, this effective treatment is difficult to practice. The main obstacle to early appropriate antibiotic treatments is the long turnaround time of the routine microbial identification, which includes time-consuming sample growth. Here, we propose a microscopy-based framework that identifies the pathogen from single to few cells. Our framework obtains and exploits the morphology of the limited sample by incorporating three-dimensional quantitative phase imaging and an artificial neural network. We demonstrate the identification of 19 bacterial species that cause bloodstream infections, achieving an accuracy of 82.5% from an individual bacterial cell or cluster. This performance, comparable to that of the gold standard mass spectroscopy under a sufficient amount of sample, underpins the effectiveness of our framework in clinical applications. Furthermore, our accuracy increases with multiple measurements, reaching 99.9% with seven different measurements of cells or clusters. We believe that our framework can serve as a beneficial advisory tool for clinicians during the initial treatment of infections. Label-free rapid deep-learning-based identification of bacterial species that classifies 3D refractive index tomograms into the species.
... We found a lack of consensus definition within study designs and infection subtypes but found that components of treatment failure definitions could be split into prescription, escalation of care, and clinical condition components. These categories of components have been described previously [39] and partly align with proposed criteria to define treatment failure in hospitalised patients, using clinical, treatment, laboratory, and radiological parameters [40]. In the proposed criteria, clinical parameters refer to symptomatic changes and deterioration, and treatment parameters refer to additional antibiotics or other treatment, including admission to ITU (escalation of care). ...
Antibiotic treatment failure is used as an outcome in randomised trials and observational studies of antibiotic treatment strategies and may comprise different events that indicate failure to achieve a desired clinical response. However, the lack of a universally recognised definition has led to considerable variation in the types of events included. We undertook a systematic review of published studies investigating antibiotic treatment strategies for common uncomplicated infections, aiming to describe variation in terminology and components of the antibiotic treatment failure outcomes. We searched Medline, Embase, and the Cochrane Central Register of Clinical trials for English language studies published between January 2010 and January 2021. The population of interest was ambulatory patients seen in primary care or outpatient settings with respiratory tract (RTI), urinary tract (UTI), or skin and soft tissue infection (SSTI), where different antibiotic prescribing strategies were compared, and the outcome was antibiotic treatment failure. We narratively summarised key features from eligible studies and used frequencies and proportions to describe terminology, components, and time periods used to ascertain antibiotic treatment failure outcomes. Database searches identified 2967 unique records, from which 36 studies met our inclusion criteria. This included 10 randomised controlled trials and 26 observational studies, with 20 studies of RTI, 12 of UTI, 4 of SSTI, and 2 of both RTI and SSTI. We identified three key components of treatment failure definitions: prescription changes, escalation of care, and change in clinical condition. Prescription changes were most popular in studies of UTI, while changes in clinical condition were most common in RTI and SSTI studies. We found substantial variation in the definition of antibiotic treatment failure in included studies, even amongst studies of the same infection subtype and study design. Considerable further work is needed to develop a standardised definition of antibiotic treatment failure in partnership with patients, clinicians, and relevant stakeholders.
... Complicating the treatment of bacterial infectious diseases is clinical failure of antimicrobial therapy against strains shown to be susceptible in clinical laboratory testing (antibiotic treatment failure [ATF]). Observations in multiple clinical settings have shown that ATF leads to prolonged hospital lengths of stay, use of multiple antibiotics, and increased morbidity and mortality [2,3]. The chronic persistence of bacteria (colonization) that can become pathogenic in susceptible hosts is an additional cause of morbidity related to infectious diseases. ...
Background:
When grown in human serum, laboratory isolates of Pseudomonas aeruginosa exhibit tolerance to antibiotics at inhibitory concentrations. This phenomenon, known as serum-associated antibiotic tolerance (SAT), could lead to clinical treatment failure of pseudomonal infections. Our purpose in this study was to determine the prevalence and clinical impact of SAT in Pseudomonas isolates in hospitalized children.
Methods:
The SAT phenotype was assessed in patients aged <18 years admitted with respiratory or blood cultures positive for P. aeruginosa. The SAT phenotype was a priori defined as a ≥2-log increase in colony-forming units when grown in human serum compared with Luria-Bertani medium in the presence of minocycline or tobramycin.
Results:
SAT was detected in 29 (64%) patients. Fourteen patients each (34%) had cystic fibrosis (CF) and tracheostomies. Patient demographics and comorbidities did not differ by SAT status. Among CF patients, SAT was associated with longer duration of intravenous antibiotics (10 days vs 5 days; P < .01).
Conclusions:
This study establishes that SAT exists in P. aeruginosa from human serum and may be a novel factor that contributes to differences in clinical outcomes. Future research should investigate the mechanisms that contribute to SAT in order to identify novel targets for adjunctive antimicrobial therapies.
... Canada (Davidson et al., 2002) Italy (Endimiani et al., 2005) USA (Kays et al., 2002) Hong Kong (Ho et al., 2001) Therapeutic window is the range between the amount of the drug that gives the desired effect and the drug may be ineffective or toxic if the drug therapeutic index is below or above the range, respectively (Tamargo et al., 2015). Treatment failure may occur by various factors such as an inadequate antibiotic coverage and concentration, deficient diagnosis, or resistance (Sánchez García, 2009). Poor quality antibacterial may lead to drug resistance or severe side effects if the therapeutic window of levofloxacin is not achieved (Boyd et al., 2009;Tamargo et al., 2015). ...
Counterfeit and substandard medicines are recognized as one of serious threats to public health. The product quality of antibacterial medicine will compromise patients’ recovery and increase the chance of antibacterial resistance. The review aims to provide a summary of low quality levofloxacin issues and the risk factors as well as suggesting the aspects of product quality that need to be regulated strictly. Quality of the active ingredient, levofloxacin, has an important role to contribute to successful therapy. The poor quality of raw material, directly and indirectly, causes treatment failure as the presence of insufficient dose, mislabeled content, and poor dissolution characteristics can lead to lower bioavailability. Identifying and reporting these factors can potentially help in improving the quality of drug marketed in various developing countries and may also reduce the incidences of treatment failure. Dissolution test is used for testing the dissolution profiles and the rate of drug release from solid formulation such as oral formulations, thus providing information regarding the in vivo performance of a formulation and its bioequivalence. On the other hand, quality-testing procedures are used for comparing the quality of products.
... As in previous studies [15], we studied antibiotic re-prescription as a proxy measure of treatment effectiveness. We defined antibiotic re-prescription as the earliest prescription of a UTI-specific antibiotic for the same UTI episode between 4 and 28 days after the date of the initial antibiotic prescription ( Supplementary Fig. 1B). ...
Background:
Urinary tract infections (UTIs) are major drivers of antibiotic prescribing in primary care. Inappropriate antibiotic prescribing for UTIs likely drives antibiotic resistance. We aimed to describe current investigation and antibiotic treatment to examine opportunities for improved antimicrobial stewardship.
Methods:
We identified a cohort of all patients with lower UTI diagnosis between 2011 and 2015 in the 390 primary care practices contributing data to ResearchOne in England. We examined investigation, antibiotic treatment and antibiotic re-prescription within 28 days according to guideline-defined patient groups. We assessed risk factors for re-prescription using mixed-effect logistic regression.
Findings:
In total, 494,675 UTIs were diagnosed in 300,354 patients. Median age was 54 years, and 83.3% were women. Same-day antibiotic was prescribed for 85.7% of UTIs; 56.8% were treated with trimethoprim, and urine sampling was undertaken in 25.0%. The antibiotic re-prescription rate was low (17,430, 4.1%) and increased slightly over time in men (from 5.2% in 2011 to 6.2% in 2015). Overall, 21.1% of pre-prescription were for the same antibiotic. The percentage of adults with recurrent UTIs ranged from 1.0% in 18-64 year-old men to 2.6% in women ≥ 65 years. The risk of antibiotic re-prescription increased with age, calendar year, recent antibiotic prescribing and treatment with antibiotic other than trimethoprim or nitrofurantoin.
Interpretation:
Most patients diagnosed with lower UTI in primary care receive same-day empirical antibiotics with little diversity in choice of agent. The antibiotic re-prescription rate is low. Microbiological investigation and re-prescription of the same antibiotic given for the initial episode happened in one quarter of UTIs.
Funding:
UK National Health Service Improvement.
... These are divided into those that could have been raised with the AST results only and those that required the expert knowledge implemented. The grade varies from Irrelevant (1) to High clinical relevance(5). ...
Antimicrobial Susceptibility Tests (ASTs) are performed in hospitals to detect whether an infectious agent is resistant or susceptible to a set of antimicrobials. When AST results are available, the evaluation of the patient’s antimicrobial therapy is a critical task to ensure its effectiveness against the found microorganism. Since not all the available antimicrobials can be tested in ASTs, clinicians rely on their expert knowledge to complement AST results and prescribe the most appropriate antimicrobials for each infection.
Our goal is to help physicians in this task by improving the detection of antimicrobial therapies at risk of failure by Clinical Decision Support Systems (CDSSs). With this aim, we have incorporated the EUCAST expert rules in antimicrobial susceptibility testing into a CDSS to improve the results of ASTs. In order to achieve this, we have combined both ontologies and production rules. Furthermore, we have evaluated the impact of EUCAST expert rules on the detection of antimicrobial therapies at risk of failure.
We performed a retrospective study with one year of clinical data, obtaining a total of 148 alerts from which 62 (41.9%) were based on the additional expert knowledge. Furthermore, the evaluation of the clinical relevance of 27 alerts resulted in 8 of them (29.7%) being clinically relevant. Of these, 6 were based on expert knowledge. Finally, an alarm fatigue study suggests that waiting between 48 and 72 h from the reception of the AST results can significantly reduce the number of alerts that are unnecessary in our CDSS because they are already being addressed in the hospital’s daily workflow.
In conclusion, we demonstrate that the incorporation of expert knowledge improves the capabilities of CDSSs as regards detecting the risk of antimicrobial therapy failure, which may improve the institutional outcomes in antimicrobial stewardship.
... Multi-drug resistant HA infections, including UTIs, are being increasingly reported, especially in southern Europe [5,21,22]. A large retrospective study in patients with LC conducted by Reukenet al. found that women predominantly developed UTI and that the risk of infection was more strongly associated with age than with severity of liver disease measured using the MELD score [23]. ...
Background
Cirrhosis-associated immune dysfunction syndrome (CAIDS) has been identified in patients with liver cirrhosis (LC), predisposing them to a wide variety of infections. In patients with LC, healthcare-associated infections involving multi-drug resistant (MDR) bacteria have increased significantly over the last decades. Among them, hospital-acquired urinary tract infections (HA-UTI) are the most common. This study aimed to investigate the rates of antimicrobial resistance among patients with LC and HA-UTI and to determine risk factors associated with their development among patients hospitalized in tertiary care facility in Serbia.
Methods
This retrospective study included 65 hospitalized patients with LC who had developed HA-UTI. We examined the epidemiology of these infections concerning resistance to the most commonly used antimicrobials and patient-specific risk factors associated with HA-UTI development by MDR pathogens.
Results
The most frequently isolated organisms were Enterococcus spp. (n = 34, 52.3%), Klebsiella spp. (n = 10, 15.4%), and E.coli (n = 6, 9.2%). Thirty-five isolates (53.8%) were identified as MDR, and 30 (46.2%) were non-MDR.We found a statistically significant difference in the distribution of MDR and non-MDR strains, based on Gram staining, with the majority of Gram-negative pathogens being MDR (p = 0.005). We identified age ≥ 65 years (p = 0.007), previous use of cephalosporins as empiric therapy (p = 0.042), and the presence of hepatic encephalopathy (p = 0.011) as independent risk factors for the development of MDR UTIs.
Conclusion
This is the first study from Serbia and the Balkans concerning the changing epidemiology of MDR UTI in patients with LC. Our study showed that more than half of HA-UTI was caused by MDR and the most common pathogen was Enterococcus spp. The overall resistance to ceftriaxone was 92%. Our findings underscore the need for institutions to individualize protocols for treatment of hospital-acquired infections, particularly in immunocompromised populations.
... The main reason for the low incidence of treatment success was the high frequency of empir- ical therapy involving polymyxin B treatment. It is well understood that the most common cause of antimicrobial treatment failure (ATF) is empirical antimicrobial treatment, which is often related to insuf- ficient (narrow) antimicrobial coverage.10In our study, inadequate empirical treatment was observed in 65 patients (26.3%). ...
What is known and objective
Polymyxins, especially polymyxin B, has become the last line of therapy against Gram‐negative pathogens’ carbapenemase producers. However, given increasing use of polymyxin B in clinical settings its therapeutic value has been evaluated worldwide due to its toxic effects. The aim of this study was to assess the efficacy and safety of antimicrobial therapy with polymyxin B in patients with multidrug‐resistant bacteria in Brazil.
Methods
This was a prospective cohort study in a 403‐bed academic tertiary care centre, located in the countryside of Brazil. Patients receiving polymyxin B intravenous treatment for at least 72 hours were eligible for the study. Antimicrobial susceptibility, adverse reactions and clinical outcomes were submitted for descriptive analysis. Main outcomes measure the following: Patients' conditions following treatment (Treatment Success, Mortality, Treatment Failure, Inadequate Empiric Treatment or Indeterminate Response) and toxicities induced by polymyxin B (nephrotoxicity and skin hyperpigmentation).
Results and discussion
Among 247 patients, treatment success was achieved in 25.1%, while mortality was observed in 32.8%. Empirical therapy was prescribed for 26.3% of the patients. Nephrotoxicity was reported in 40.5%. The carbapenemase producer, Klebsiella pneumonia, was the bacterium most associated with mortality (22.2%).
Conclusions
Even though polymyxin B is currently the main therapy against carbapenemase producers, its use demands robust criteria to lead to positive clinical outcomes.
... Treatment failure was assessed by physical examination, organic dysfunction, comorbidities, broadening antimicrobial spectrum, laboratory tests, and examination of microscopic images. Successful treatment was defined by an improvement in the signs and symptoms of infection, while failure was defined by the persistence of infection, clinical deterioration, or death [22,23]. ...
Purpose
Adjusting the antibiotic dose based on an estimation of the glomerular filtration rate (eGFR) may result in subdosing, which may actually be significantly more problematic for intensive care unit (ICU) patients than not adjusting the dose. The aim of this study was to assess the outcomes of antibiotic dose adjustment in ICU patients with renal impairment.
Methods
A retrospective cohort study was conducted in adult patients admitted to an ICU of a Brazilian hospital from January 2014 to December 2015. The eGFR was determined using Cockcroft–Gault and Modified Diet in Renal Disease equations for each day of hospitalization. Treatment failure was defined based on the clinical, laboratory, and radiological criteria.
Results
A total of 126 patients were assessed to meet the inclusion criteria and subsequently enrolled in the study (19.9% of patients admitted to the ICU during the study period). Of the 168 opportunities for dose adjustment, 99 (58.9%) adjustments were made. The mean eGFR in the group with dose adjustment was lower than that in the group without dose adjustment (38.5 vs. 40.7 mL/min/1.73 m², respectively). The treatment failure rate among patients with dose adjustment and those treated with the usual dose was 59.3 and 38.9%, respectively (p = 0.023), and the mortality rates in the respective groups were 74.1 and 55.5% (p = 0.033). An association between dose adjustment and treatment failure/mortality rates was also observed in the multivariate analysis including the prognostic score.
Conclusions
In ICU patients with renal impairment, adjustments in antibiotic dose based on eGFR, significantly increased the risk of treatment failure and death.
... taste, size, shape, or strength/concentration) dispensed to the same child within 2 days. This period was chosen, as changes within the first 2 days were most likely caused by challenges related to the administration of antibiotics rather than lack of clinical effect (17). Prescription change served as the dependent variable and was categorized as either 'yes' or 'no'. ...
Background:
Children commonly refuse to take antibiotics, which may induce parents to request new antibiotic prescriptions with different pharmaceutical characteristics.
Objectives:
To investigate prescription changes for children 0-12 years receiving oral liquid or solid antibiotic formulations and to explore the relationships between prescription changes and characteristics related to the child, prescriber and antibiotic.
Methods:
A population-based registry study based on data from the Norwegian Prescription Database (NorPD) from 2004 to 2016. Antibiotic prescription changes were defined as the dispensing of subsequent antibiotics with different pharmaceutical characteristics to the same child within 2 days after initial prescriptions. Data were analysed using multivariable logistic regression and generalized estimating equations.
Results:
Requests for new prescriptions followed 3.0% of 2 691 483 initial antibiotic prescriptions for children. Young children who received solid formulations (10.9%) and certain poor-tasting antibiotics (8.6%) had the highest proportions of new prescriptions. Penicillin V was most commonly changed, while macrolides/lincosamides dominated subsequent prescriptions. In order of magnitude, the characteristics associated with requests for new prescriptions were the children's ages, poor taste and concentration of liquids, size and shape of solids, prescribers born in recent decades, and girl patients. Reimbursed prescriptions and scored solids were associated with fewer requests.
Conclusions:
While only 3% of the antibiotic prescriptions were changed, the preference of broad-spectrum over narrow-spectrum antibiotics for young children in this study mirrors international prescription patterns. Avoiding the costs of children's refusal and consequent changes may thus be a motivation for choosing more preferred antibiotics.
... No consensus statements on the definition of treatment failure have been published [2]. The detection of treatment failure is mostly based on objective clinical criteria ( Fig. 1), but also on the less well-defined subjective decisions of the treating physicians. ...
... There is, however, no consensus on a definition of ATF in primary care [12], probably due to inherent problems of defining the aetiology of infections and the fact that many bacterial infections are not serious but self-limiting so the benefit from antibiotics is difficult to assess. Currie et al., using a pragmatic definition of ATF cases (first line antibiotic treatment replaced by a new antibiotic within 30 days), found an antibiotic failure rate of 15.4% [13]. ...
Background: Prescribing antibiotics for acute respiratory tract infections (RTIs) is common in primary healthcare although most of these infections are of viral origin and antibiotics may not be helpful. Some of these prescriptions will not be associated with a quick recovery, and might be regarded as cases of antibiotic treatment failure (ATF).
Objectives: We studied antibiotic treatment failure in patients with acute RTIs from a general practitioner (GP) perspective, aiming to explore (i) GPs’ views of ATF in primary care; (ii) how ATF influences the doctor-patient relationship; and (iii) GPs’ understanding of patients’ views of ATF.
Methods: Qualitative study based on semi-structured, recorded interviews of 18 GPs between August and October 2012. The interviews started with discussion of a unique case of acute RTI involving ATF, followed by a more general reflection of the topic. Interviews were analysed using qualitative content analysis.
Results: In patients with acute RTIs, GPs proposed and agreed to a medical definition of antibiotic treatment failure but believed patients’ views to differ significantly from this medical definition. GPs thought ATF affected their daily work only marginally. GPs used many communicative tools to maintain trust with patients in cases of ATF, but they did not consider such incidents to affect the doctor-patient relationship adversely.
Conclusion: These findings suggest a possible communication gap between doctors and patients, partly due to a narrow medical definition of ATF. Studies describing patients’ views are still missing.
General practitioners’ experiences and views on antibiotic treatment failure in acute respiratory infections or its effects on the doctor–patient relationship have not been studied previously.
... Treatment failure is the persistence of symptoms or deterioration following antibiotic initiation [8]. Common causes of treatment failure include incorrect initial diagnosis, host comorbidities such as HIV infection and malnutrition, and viral or antibiotic-resistant causative organisms [9]. ...
Pneumonia is the leading cause of infectious death amongst children globally, with the highest burden in Africa. Early identification of children at risk of treatment failure in the community and prompt referral could lower mortality. A number of clinical markers have been independently associated with oral antibiotic failure in childhood pneumonia. This study aimed to develop a prognostic model for fast-breathing pneumonia treatment failure in sub-Saharan Africa.
We prospectively followed a cohort of children (2-59 months), diagnosed by community health workers with fast-breathing pneumonia using World Health Organisation (WHO) integrated community case management guidelines. Cases were followed at days 5 and 14 by study data collectors, who assessed a range of pre-determined clinical features for treatment outcome. We built the prognostic model using eight pre-defined parameters, using multivariable logistic regression, validated through bootstrapping.
We assessed 1,542 cases of which 769 were included (32% ineligible; 19% defaulted). The treatment failure rate was 15% at day 5 and relapse was 4% at day 14. Concurrent malaria diagnosis (OR: 1.62; 95% CI: 1.06, 2.47) and moderate malnutrition (OR: 1.88; 95% CI: 1.09, 3.26) were associated with treatment failure. The model demonstrated poor calibration and discrimination (c-statistic: 0.56).
This study suggests that it may be difficult to create a pragmatic community-level prognostic child pneumonia tool based solely on clinical markers and pulse oximetry in an HIV and malaria endemic setting. Further work is needed to identify more accurate and reliable referral algorithms that remain feasible for use by community health workers.
... There are a variety of definitions of clinical responses, clinical cure and clinical failure utilized in the literature (Kullar et al. 2011a;Hidayat et al. 2006;Stryjewski et al. 2007). However, there is no consensus on the definition of treatment failure in the literature (Sánchez 2009). For this study vancomycin treatment failure was defined as re-initiation of vancomycin therapy for any reason during the hospital stay after a full course of treatment or a switch to an alternate MRSA agent (daptomycin, linezolid, or tigecycline), but not including a true vancomycin allergy. ...
Outcomes data for the efficacy of interventions designed to decrease the time to initial target vancomycin troughs are sparse.
A vancomycin therapeutic drug monitoring (TDM) program was initiated to reduce the time to initial target troughs and to examine the impact on clinical outcomes.
Single-center, pre- and post-intervention observational study in a 250 bed teaching facility. Adult inpatients treated with physician-guided, vancomycin therapy (historical control, CTRL) were compared to high trough, pharmacist-guided vancomycin therapy (TDM). Nephrotoxicity analyses were conducted to the ensure safety of the TDM. Clinical outcome analysis was limited to patients with normal renal function and culture-confirmed gram positive infections and a pre-defined MRSA subset.
340 patients met initial inclusion criteria for the nephrotoxicity analysis (TDM, n = 173; CTRL, n = 167). Acute kidney injury occurrence was similar between the CTRL (n = 20) and TDM (n = 23) groups (p = 0.7). Further exclusions yielded 145 patients with gram positive infections for clinical outcomes evaluation (TDM, n = 66; CTRL, n = 75). The time to initial target trough was shorter in the TDM group (3 vs. 5 days, p < 0.001). Patients in the TDM group discharged from the hospital more rapidly, 7 vs. 14 days (Hazards Ratio (HR), 1.41; 95% Confidence Interval [CI] 1.08-1.83; p = 0.01), reached clinical stability faster, 4 vs. 8 days (HR, 1.51; 95% CI 1.08-2.11; p = 0.02), and had shorter courses of vancomycin, 4 vs. 7 days (HR, 1.5; 95% CI 1.15-1.95; p = 0.003). In the MRSA infection subset (TDM, n = 36; CTRL, n = 35), patients in the TDM group discharged from the hospital more rapidly, 7 vs. 16 days (HR, 1.89; 95% CI 1.08-3.3; p = 0.03), reached clinical stability faster, 4 vs. 6 days (HR, 2.69; 95% CI 1.27-5.7; p = 0.01), and had shorter courses of vancomycin, 5 vs. 8 days (HR, 2.52; 95% CI 1.38-4.6; p = 0.003). Attaining initial target troughs in <5 days versus ≥5 days was associated with improved clinical outcomes. All cause in-hospital mortality, and vancomycin treatment failure occurred at comparable rates between groups.
Interventions designed to decrease the time to reach initial target vancomycin troughs can improve clinical outcomes in gram positive infections, and in particular MRSA infections.
... As a proxy measure of effectiveness of treatment and, by implication, bacterial sensitivity, we evaluated the proportion of antibiotic courses resulting in treatment failure. While there is no consensus definition of such failure, 12 several studies have defined it as the prescription of a different antibiotic within 30 days of the index date. [13][14][15] Other data in the Clinical Practice Research Datalink, however, could also be indicative of unresolved infections. ...
Objective:
To characterise failure of antibiotic treatment in primary care in the United Kingdom in four common infection classes from 1991 to 2012.
Design:
Longitudinal analysis of failure rates for first line antibiotic monotherapies associated with diagnoses for upper and lower respiratory tract infections, skin and soft tissue infections, and acute otitis media.
Setting:
Routine primary care data from the UK Clinical Practice Research Datalink (CPRD).
Main outcome measures:
Adjusted rates of treatment failure defined by standardised criteria and indexed to year 1 (1991=100).
Results:
From 58 million antibiotic prescriptions in CPRD, we analysed 10,967,607 monotherapy episodes for the four indications: 4,236,574 (38.6%) for upper respiratory tract infections; 3,148,947 (28.7%) for lower respiratory tract infections; 2,568,230 (23.4%) for skin and soft tissue infections; and 1,013,856 (9.2%) for acute otitis media. In 1991, the overall failure rate was 13.9% (12.0% for upper respiratory tract infections; 16.9% for lower respiratory tract infections; 12.8% for skin and soft tissue infections; and 13.9% for acute otitis media). By 2012, the overall failure rate was 15.4%, representing an increase of 12% compared with 1991 (adjusted value indexed to first year (1991) 112, 95% confidence interval 112 to 113). The highest rate was seen in lower respiratory tract infections (135, 134 to 136). While failure rates were below 20% for most commonly prescribed antibiotics (amoxicillin, phenoxymethylpenicillin (penicillin-V), and flucloxacillin), notable increases were seen for trimethoprim in the treatment of upper respiratory tract infections (from 29.2% in 1991-95 to 70.1% in 2008-12) and for ciprofloxacin (from 22.3% in 1991-95 to 30.8% in 2008-12) and cefalexin (from 22.0% in 1991-95 to 30.8% in 2008-12) in the treatment of lower respiratory tract infections. Failure rates for broad spectrum penicillins, macrolides, and flucloxacillin remained largely stable.
Conclusions:
From 1991 to 2012, more than one in 10 first line antibiotic monotherapies for the selected infections were associated with treatment failure. Overall failure rates increased by 12% over this period, with most of the increase occurring in more recent years, when antibiotic prescribing in primary care plateaued and then increased.
... Consequences of suboptimal dosing in sepsis include treatment failure, higher mortality rates, increased costs and adverse effects, and emergence of antimicrobial-resistant organisms. [24][25][26] Suboptimal low initial dosing is primarily driven by pharmacokinetic changes associated with severe sepsis and septic shock and the fear of toxicity in the setting of organ dysfunction. 27,28 Both of these factors can be mitigated by considering the key pharmacologic characteristics of antimicrobial agents when determining dosing. ...
Severe sepsis and septic shock are common problems in the emergency department patient population and require expert clinical skill by members of the emergency department team to maximize optimal patient outcomes. Although various guidelines have been developed for the management of these patients, issues around antimicrobial-related considerations in critically ill patients require further evidence-based attention. In this review article, important factors related to patient illness, microorganism, timing of antimicrobial administration, and source control are discussed.
... Staphylococcus aureus causes severe hospital-and communityassociated infections and its resistance against multiple classes of antibiotics leads primarily to high therapeutic failure rates. 1 Several resistant strains are now endemic in hospitals around the world causing, for example, an estimated 1.5 million cases of pneumonia per year. 2,3 Therefore, various immunotherapeutic approaches have been mooted as potential solutions to inadequate treatment of invasive infections using antibiotics. ...
Multi-antigen immunotherapy approaches against Staphylococcus aureus are expected to have the best chance of clinical success when used in combinatorial therapy, potentially incorporating opsonic killing of bacteria and toxin neutralization. We recently reported the development of a murine monoclonal antibody specific for the immunodominant staphylococcal antigen A (IsaA), which showed highly efficient staphylococcal killing in experimental infection models of S. aureus. If IsaA-specific antibodies are to be used as a component of combination therapy in humans, the binding specificity and biological activity of the humanized variant must be preserved. Here, we describe the functional characterization of a humanized monoclonal IgG1 variant designated, hUK-66. The humanized antibody showed comparable binding kinetics to those of its murine parent, and recognized the target antigen IsaA on the surface of clinically relevant S. aureus lineages. Furthermore, hUK-66 enhances the killing of S. aureus in whole blood (a physiological environment) samples from healthy subjects and patients prone to staphylococcal infections such as diabetes and dialysis patients, and patients with generalized artery occlusive disease indicating no interference with already present natural antibodies. Taken together, these data indicate that hUK-66 mediates bacterial killing even in high risk patients and thus, could play a role for immunotherapy strategies to combat severe S. aureus infections.
... Therapeutic failure was defined as an impaired clinical response and the need for alternate antimicrobial therapy. An impaired clinical response consisted of one or more of the following criteria: persistent fever, purulent bronchial secretions, organ dysfunction such as acute respiratory failure, with concurrent changes in laboratory results such as white blood cell count, C-reactive protein, chest radiograph and/or resistance appearance [14]. Inappropriate empirical treatment was not considered as therapeutic failure. ...
Introduction:
We describe incidence and patient factors associated with augmented renal clearance (ARC) in adult intensive care unit (ICU) patients.
Materials and methods:
A prospective observational study in a mixed cohort of surgical and medical ICU patients receiving antimicrobial therapy at the Ghent University Hospital, Belgium. Kidney function was assessed by the 24-hour creatinine clearance (Ccr); ARC defined as at least one Ccr of >130 mL/min per 1.73 m2. Multivariate logistic regression analysis: to assess variables associated with ARC occurrence. Therapeutic failure (TF): an impaired clinical response and need for alternate antimicrobial therapy.
Results:
Of the 128 patients and 599 studied treatment days, ARC was present in 51.6% of the patients. Twelve percent permanently expressed ARC. ARC patients had a median Ccr of 144 mL/min per 1.73 m2 (IQR 98-196). Median serum creatinine concentration on the first day of ARC was 0.54 mg/dL (IQR 0.48-0.69). Patients with ARC were significantly younger (P<.001). Age and male gender were independently associated with ARC whereas the APACHE II score was not. ARC patients had more TF (18 (27.3%) vs. 8 (12.9%); P=.04).
Conclusion:
ARC was documented in approximately 52% of a mixed ICU patient population receiving antibiotic treatment with worse clinical outcome. Young age and male gender were independently associated with ARC presence.
... The clinical data were collected for the first documented clinical encounter (where available), but this encounter may have occurred at variable times during the course of illness, limiting interpatient comparability. The definition of treatment failure was based on literature and presumed timing of clinical decision points for changing therapy; however, consensus on validated variables for such determination is lacking [26]. The timeframe for records reviews may have resulted in missing later episodes of disease recurrence. ...
Background:
Clinical recognition of tularemia is essential for prompt initiation of appropriate antibiotic treatment. Although fluoroquinolones have desirable attributes as a treatment option, limited data on efficacy in the US setting exist.
Methods:
To define the epidemiology of tularemia in Missouri, and to evaluate practices and outcomes of tularemia management in general, we conducted a detailed retrospective review and analysis of clinical records for patients reported to the state from 2000 to 2007.
Results:
We reviewed records of 121 of 190 patients (64%) reported with tularemia; 79 (65%) were males; the median age was 37 years. Most patients presented with ulceroglandular (37%) and glandular (25%) forms of tularemia, followed by pneumonic (12%), typhoidal (10%), oculoglandular (3%), and oropharyngeal (2%) forms. Most cases (69%) were attributed to tick bites. Median incubation period was 3 days (range, 1-9 days), and patients sought care after a median of 3 days of illness (range, 0-44 days). Systemic disease occurred more commonly in older patients. Patients were prescribed tetracyclines (49%), aminoglycosides (47%), and fluoroquinolones (41%). Nine of 10 patients treated with ciprofloxacin for ≥10 days recovered uneventfully, without accompanying aminoglycosides or tetracyclines.
Conclusions:
Tularemia is frequently initially misdiagnosed. A thorough exposure history, particularly for tick bites, and awareness of clinical features may prompt clinicians to consider tularemia and facilitate appropriate testing. Promising success with oral fluoroquinolones could provide an acceptable alternative to intravenous aminoglycosides or long courses of tetracyclines where clinically appropriate.
... 30,32 Also, given that the mortality associated with SSTIs is low in the antibiotic era, 32 other measures of clinical failure of therapy must be defined and agreed for more informative comparison of antimicrobial agents in clinical trials. 30,33 In conclusion we have shown that patients with SSTIs and a systemic inflammatory response have significantly worse outcomes than other patients with SSTIs. The majority of these patients receive clinically inadequate antimicrobial therapy with the currently recommended treatment for class IV being broadspectrum and intravenous. ...
Skin and soft tissue infections (SSTIs) are caused by bacterial invasion of the skin and underlying soft tissues and can present with a wide spectrum of signs, symptoms and illness severity. They are a common indication for antimicrobial therapy. However, there are few data on treatment outcomes or the validity of clinical severity scores.
Two hundred and five adult patients admitted to Ninewells Hospital, Scotland in 2005, and treated with antibiotics for SSTI, were identified. They were stratified into four classes of severity (class IV = most severe) based on sepsis, co-morbidity and their standardized early warning score (SEWS). Empirical antimicrobial therapy by severity class was compared with the recommendations of a UK guideline.
Thirty-five different empirical antimicrobial regimens were prescribed. Overall, 43% of patients were over-treated, this being particularly common in the lowest severity class I (65% patients). Thirty-day mortality was 9% (18/205) and 17 patients (8%) died during their index admission. Mortality (30 day) and inadequate therapy increased with severity class: I, no sepsis or co-morbidity (45% patients, 1% mortality, 14% therapy inadequate); II, significant co-morbidity but no sepsis (32% patients, 11% mortality, 39% therapy inadequate); III, sepsis but SEWS <4 (17% of patients, 17% mortality, 39% therapy inadequate); and IV, sepsis plus SEWS ≥ 4 (6% of patients, 33% mortality, 92% therapy inadequate).
SSTI in hospital is associated with significant mortality. Choice of empirical therapy is not evidence based, with significant under-treatment of severely ill patients.
... An increasing number of studies suggest that specific antiviral therapy is effective in reducing the morbidity and mortality associated with influenza [7, 8], and current guidelines for both seasonal and pandemic influenza recommend the treatment of patients requiring hospitalization for influenza [19, 20]. In outpatients, early therapy with specific antivirals is more effective than later therapy [21], and there is good evidence for bacterial infection requiring hospitalization that early, effective antibacterial therapy improves outcomes222324. Our data may be particularly important for clinicians considering empiric antiviral therapy, where understanding the pre-test probability of acute infection is needed for rational use. As in other studies of influenza in adults, our data suggest that reverse transcriptase polymerase chain reaction (RT-PCR) is significantly more sensitive than viral culture or DFA for influenza diagnosis, and these tests are, in turn, more sensitive than commercial rapid influenza tests. ...
The purpose of this investigation was to identify when diagnostic testing and empirical antiviral therapy should be considered for adult patients requiring hospitalization during influenza seasons. During the 2007/8 influenza season, six acute care hospitals in the Greater Toronto Area participated in active surveillance for laboratory-confirmed influenza requiring hospitalization. Nasopharyngeal (NP) swabs were obtained from patients presenting with acute respiratory or cardiac illness, or with febrile illness without clear non-respiratory etiology. Predictors of influenza were analyzed by multivariable logistic regression analysis and likelihoods of influenza infection in various patient groups were calculated. Two hundred and eighty of 3,917 patients were found to have influenza. Thirty-five percent of patients with influenza presented with a triage temperature >or=38.0 degrees C, 80% had respiratory symptoms in the emergency department, and 76% were >or=65 years old. Multivariable analysis revealed a triage temperature >or=38.0 degrees C (odds ratio [OR] 3.1; 95% confidence interval [CI] 2.3-4.1), the presence of respiratory symptoms (OR 1.7; 95% CI 1.2-2.4), admission diagnosis of respiratory infection (OR 1.8; 95% CI 1.3-2.4), admission diagnosis of exacerbation of chronic obstructive pulmonary disease (COPD)/asthma or respiratory failure (OR 2.3; 95% CI 1.6-3.4), and admission in peak influenza weeks (OR 4.2; 95% CI 3.1-5.7) as independent predictors of influenza. The likelihood of influenza exceeded 15% in patients with respiratory infection or exacerbation of COPD/asthma if the triage temperature was >or=38.0 degrees C or if they were admitted in the peak weeks during the influenza season. During influenza season, diagnostic testing and empiric antiviral therapy should be considered in patients requiring hospitalization if respiratory infection or exacerbation of COPD/asthma are suspected and if either the triage temperature is >or=38.0 degrees C or admission is during the weeks of peak influenza activity.
The polymyxin and lipopeptide classes of antibiotics are membrane-targeting drugs of last resort used to treat infections caused by multi-drug-resistant pathogens. Despite similar structures, these two antibiotic classes have distinct modes of action and clinical uses. The polymyxins target lipopolysaccharide in the membranes of most Gram-negative species and are often used to treat infections caused by carbapenem-resistant species such as Escherichia coli, Acinetobacter baumannii and Pseudomonas aeruginosa. By contrast, the lipopeptide daptomycin requires membrane phosphatidylglycerol for activity and is only used to treat infections caused by drug-resistant Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. However, despite having distinct targets, both antibiotic classes cause membrane disruption, are potently bactericidal in vitro and share similarities in resistance mechanisms. Furthermore, there are concerns about the efficacy of these antibiotics, and there is increasing interest in using both polymyxins and daptomycin in combination therapies to improve patient outcomes. In this review article, we will explore what is known about these distinct but structurally similar classes of antibiotics, discuss recent advances in the field and highlight remaining gaps in our knowledge.
We retrospectively evaluated whether initial procalcitonin (PCT) levels can predict early antibiotic treatment failure (ATF) in patients with gram-negative bloodstream infections (GN-BSI) caused by urinary tract infections from January 2018 to November 2019. Early ATF was defined as the following: (1) hemodynamically unstable or febrile at Day 3; (2) the need for mechanical ventilation or continuous renal replacement therapy at Day 3; (3) patients who died within 3 days (date of blood culture: Day 0). The study included 189 patients; 42 showed early ATF. Independent risk factors for early ATF were initial admission to the intensive care unit (odds ratio: 7.735, 95% confidence interval: 2.567–23.311; P < 0.001) and PCT levels ≥30 ng/mL (odds ratio: 5.413, 95% confidence interval: 2.188–13.388; P < 0.001). Antibiotic factors were not associated with early ATF. Initial PCT levels may be helpful to predict early ATF in these patients.
Bovine respiratory disease (BRD) is one of the most common indications for antimicrobial therapy in beef cattle production and research trials demonstrate that antibiotic therapy greatly improves clinical outcome for BRD. These trials also show that BRD treatment success rates are less than 100% and that there are opportunities to optimize antimicrobial prescribing and improve clinical outcomes if the underlying cause(s) of BRD treatment failures can be identified and addressed. As the etiology of BRD in an individual animal is frequently multi-factorial in nature; it is likely that BRD treatment failures also result from complex interactions between the drug, drug administrator, animal host, pathogens, and the environment. This review will focus specifically on the pharmacological aspects, specifically the interactions between the host and the drug and the drug and the drug administrator, of BRD treatment failures and the actions that veterinary practitioners can take to investigate and mitigate therapeutic failures in future cases.
Objectives:
To assess real-world treatment patterns and clinical outcomes associated with initial antibiotic therapy (IAT, antibiotics received ≤48 h post-initiation of antibiotic therapy), including level of IAT failure, and potential risk factors for IAT failure in healthcare-associated infections.
Methods:
Data were obtained from medical records of adult patients hospitalized with healthcare-associated pneumonia (HCAP) and nosocomial pneumonia (NP), including ventilator-associated pneumonia, from 1 July 2013 - 30 June 2014 in Brazil, France, Italy, Russia and Spain during the retrospective, observational study, RECOMMEND (NCT02364284; D4280R00005). Potential risk factors for IAT failure were explored using logistic regression analyses.
Results:
Mean (standard deviation) age and Deyo-Charlson Comorbidity Score were 66.0 (16.2) years and 2.4 (2.4), respectively (N=451). Most patients (62.5%) received monotherapy. Mean (standard deviation) duration of IAT was 8.8 (7.2) days. Multidrug resistant (MDR) pathogens were identified in 52.4% of patients with ≥1 pathogen isolated (154/294). IAT failure was recorded in 72.5% of patients and was significantly associated with isolation of a MDR pathogen and country using multivariate analyses.
Conclusions:
Real-world data demonstrate the burden of HCAP/NP, with high rates of IAT failure. The association of IAT failure with MDR pathogens highlights the urgent need to understand and account for local prevalence of MDR pathogens when selecting IAT for the management of HCAP/NP.
Objectives: To compare antibiotic treatment failure evaluated as switch from one type of antibiotics to another in ambulatory care.
Methods: Data on all dispensed doxycycline, amoxicillin, phenoxymethylpenicillin and macrolides in Norway June 2013 – May 2015, was retrieved from the Norwegian Prescription Database. We computed switch rates for the selected antibiotics on day 1–28 after initial dispensing, and the corresponding odds-ratios, adjusted for patients´ age and gender, and prescribers´ specialty.
Results: Of 1.860.036 dispensed antibiotics, 103.076 (5.5%) were switched within 28 days. Within 10 days after the index date, the switch rate was highest for phenoxymethylpenicillin (4.1%), followed by amoxicillin (2.5%), macrolides and doxycycline (2.2%).
Conclusions: The switch rate after initial dispensing of phenoxymethylpenicillin is higher than that of more broad-spectrum antibiotics. However, it is still low, supporting the recommendation of phenoxymethylpenicillin as first line treatment when an antibiotic is indicated for a respiratory tract infection in primary care.
Background
Despite recent progress, pneumonia remains the largest infectious killer of children globally. This paper describes outcomes of not treating community-diagnosed fast-breathing pneumonia on patient recovery.
Methods
We conducted an exploratory subanalysis of an observational prospective cohort study in Malawi. We recruited children (2–59 months) diagnosed by community health workers with fast-breathing pneumonia using WHO integrated community case management (iCCM) guidelines. Children were followed at days 5 and 14 with a clinical assessment of recovery. We conducted bivariate and multivariable logistic regression for the association between treatment of fast-breathing pneumonia and recovery, adjusting for potential confounders.
Results
We followed up 847 children, of whom 78 (9%) had not been given antibiotics (non-treatment). Non-treatment cases had higher baseline rates of diarrhoea, non-severe hypoxaemia and fever. Non-recovery (persistence or worsening of symptoms) was 13% and 23% at day 5 in those who did receive and those who did not receive co-trimoxazole. Non-recovery, when defined as worsening of symptoms only, at day 5 was 7% in treatment and 10% in non-treatment cases. For both definitions, combined co-trimoxazole and lumefantrine-artemether (LA) treatment trended towards protection (adjusted OR (aOR) 0.28; 95% CI 0.12 to 0.68/aOR 0.29; 95% CI 0.08 to 1.01).
Conclusion
We found that children who did not receive co-trimoxazole treatment had worse clinical outcomes; malaria co-diagnosis and treatment also play a significant role in non-recovery. Further research into non-treatment of fast-breathing pneumonia, using a pragmatic approach with consideration for malaria co-diagnosis and HIV status is needed to guide refinement of community treatment algorithms in this region.
Objective:
To recognise and prevent ADRs (including DDIs) in the elderly through a 4-year post-marketing active pharmacovigilance programme. The programme was designed to enhance high quality spontaneous reporting of ADRs in elderly patients by sampling the Italian population and was termed 'Pharmacovigilance in Geriatry (ViGer)'.
Methods:
ADRs were collected for adults aged over 65 years of age treated in nursing homes, continuing care retirement communities and territorial health services in Lombardy. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analysed with respect to time, sex, category of ADR, seriousness, suspected medicines, notoriety. We analysed all the potential DDIs.
Results:
We detected 1073 cases reports corresponding to 2110 ADRs. Vaccines, antibacterials for systemic use and antineoplastic agents were the pharmacotherapeutic subgroups most frequently involved. 18% of ADRs reports were classified as serious. In 752 reports patients were described as in polytherapy; in 55 patients (7.3%) the reported ADR were probably preventable because of DDIs involvement.
Conclusion:
The ViGer project demonstrated that active pos-marketing pharmacovigilance programmes are a valid strategy to increase awareness on geriatrics pharmacology, reduce underreporting and provide important information on previous unknown ADRs and DDIs, resulting in a therapy optimisation in clinical practice in the geriatric setting.
The goal of the »German Antibiotic Resistance Strategy« program (DART) is the reduction of antibiotic resistance as well as promoting the rational use and application of antibiotics for the overall section of non-indicated treatments. Under this precondition, studies in a communal child care clinic were conducted, which were based on a model project that was initiated by the Federal Ministry of Health. Over a period of three years, all antibiotic prescriptions were recorded and the diagnosis, the antibiotics prescribed, as well as the indication, were evaluated. The following data were levied: Diagnosis, age, gender, time of stay, treatment month and year, type and antibiotic administration duration. Diagnostics: C-reactive protein (CRP), Leukocytes with count of neutrophiles; microbiological results, thorax x-ray images. Diagnosis groups were formed based on the systematic index ICD-10-GM 2010. In the period from January 2009 until December 2011, 4481 patients received in-house treatment. Four hundred eighty (480) patients received a therapeutical treatment, which equals 10.7%. Diseases of the lower and upper respiratory systems attributed to the largest segment of 28.1%, followed by urinary tract infections with 15.8%, tonsillopharyngitis with 11%, infections of the upper respiratory systems with 9.2% as well as otitides with 8.1%. The ratio of symptom related microbiological results was 83.1% In 67.7% of the diagnosis relevant pathogens (73% bacteria, 27% viruses) were found. Antibiotics of the Cephalosporin group take the first place with 71.5%, followed by Macrolides with 13.3%, Aminopenicillins with 10.4% and Penicillin with 3.5%. After evaluating the indications according to guidelines, 58.8% of the antibiotic prescriptions proved to be indicated, 30.4% as not indicated, and 10.8% as conditionally indicated. These aspects indicate that additional analyses, as well as further education in the field of infectiology are necessary.
In this study we assessed the use of acridine orange as an alternative to optical density to quantify the growth of Lactobacillus bulgaricus ATCC 7517. The growth of bacteria in Lactobacillus de Man Rogosa Sharpe (MRS) medium was measured by both acridine orange (AO) and optical density (OD) measurements for 24 h. The relationship between both methods was compared via correlation analysis. The doubling time of bacteria based on the values of OD and AO obtained during 24 h growth were also calculated. The result shows strong correlation of cell growth between OD and AO during the first 10 hours of growth, but the correlation was less strong when analyzing the data from 0 to 24 hours. Growth rates, generation time and lag time were also similar. This study indicates that AO could be used in place of OD to prepare growth curves of Lactobacillus bulgaricus during the exponential phase of growth, and to compare growth rates, generation times or lag times.
Inactivation kinetics of a nanosecond-pulsed plasma jet against a panel of common pathogenic microorganisms was studied to assist the design and development of nonthermal plasma-based treatment schemes for pathogenic infection control. We evaluated the effectiveness of our cold-plasma in vitro against microbes with varying cell wall and membrane characteristics: the Gram-positive organisms Staphylococcus aureus and Staphylococcus epidermidis, the Gram-negative organisms Pseudomonas aeruginosa and Escherichia coli, and the yeast Candida albicans. We found that all of the organisms tested in this paper were rendered nonculturable (>;99.99%) by the end of the short plasma treatment times ranging from 30 to 180 s. Our results indicate that the pathogenic bacteria and yeast tested in this paper can be effectively rendered noncultivable within seconds using the He/(1%)O2 cold plasma, and that susceptibility to plasma may vary depending on the cell wall and membrane characteristics of the organisms in addition to the other resistant mechanisms of individual strain.
This article reviews the most important aspects of antibiotic treatment failure in respiratory tract infection which may occur with empirical as well as under target antibiotic therapy. Potential risk factors leading or predisposing to treatment failure exist in hospital acquired infections which cover polymicrobial aetiology with high multidrug resistance bacteria, changed conditions of pharmacokinetic and pharmacodynamic (PK/PD) parameters of antibiotics, bioavailability, drug interactions and inactivation. Microbial determinants of treatment failure includes bacterial physiology in laboratory cultures and inside the host, inadequate drug choice, lack of knowledge of PK/PD parameters with insufficient antibiotic level in target tissue. Differences between microbial in vitro tests and clinical outcome can be caused by varied CFU concentration, growing phase, nutritional, pH and redox conditions. Many factors of treatment failure are focused on bacterial biofilm structure and phenomenon of small-colony variants (SCVs) which both display reduced susceptibility to antimicrobial agents protected by matrix feature, enhanced production of PIA and by slow multiplication of biofilm forming cells.
This paper presents the form and validation results of APACHE II, a severity of disease classification system. APACHE II uses a point score based upon initial values of 12 routine physiologic measurements, age, and previous health status to provide a general measure of severity of disease. An increasing score (range 0 to 71) was closely correlated with the subsequent risk of hospital death for 5815 intensive care admissions from 13 hospitals. This relationship was also found for many common diseases.When APACHE II scores are combined with an accurate description of disease, they can prognostically stratify acutely ill patients and assist investigators comparing the success of new or differing forms of therapy. This scoring index can be used to evaluate the use of hospital resources and compare the efficacy of intensive care in different hospitals or over time.
EXECUTIVE SUMMARY This document is an update of the original 1993 statement on community-acquired pneumonia, incorporating new information about bacteriology, patient stratification, diagnostic evaluation , antibiotic therapy, and prevention. The statement includes a summary of the available literature, as well as evidence-based recommendations for patient management, developed by a multidisciplinary group composed of pulmonary, critical care, general internal medicine, and infectious disease specialists. The sections of this document are as follows: an overview of the purpose of our efforts and the methodology used to collect and grade the available data; a review of the likely etiologic pathogens causing community-acquired pneumonia (CAP), including a discussion of drug-resistant Streptococcus pneumoniae (DRSP); a proposed approach to patient stratification for the purpose of predicting the likely etiologic pathogens of different patient populations with CAP; a summary of available and recommended diagnostic studies; suggestions on how to define the need for hospitalization and admission to the intensive care unit (ICU) for patients with CAP; guidelines for antibiotic therapy of CAP, including principles of therapy and specific recommendations for each patient category; an approach to the nonre-sponding patient, as well as a discussion of when to switch to oral therapy and when to discharge an admitted patient with CAP who is responding to initial therapy; and recommendations for the use of pneumococcal and influenza vaccines.
The time to first antibiotic dose (TFAD) has been mentioned as an important performance indicator in community-acquired pneumonia (CAP). However, the advice to minimise TFAD to 4 hours (4 h) is only based on database studies. We prospectively studied the effect of minimising the TFAD on the early clinical outcome of moderate-severe CAP. On admission, patients' medical data and TFAD were recorded. Early clinical failure was expressed as the proportion of patients with clinical instability, admission to the intensive care unit (ICU) or mortality on day three. Of 166 patients included in the study, 27 patients (29.7%) with TFAD <4 h had early clinical failure compared to 23 patients (37.7%) with TFAD >4 h (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.35-1.35). In multivariate analysis, the pneumonia severity index (OR 1.03; 95%CI 1.01-1.04), confusion (OR 2.63; 95%CI 1.14-6.06), Staphylococcus aureus infection (OR 7.26; 95%CI 1.33-39.69) and multilobar pneumonia (OR 2.40; 95%CI 1.11-5.22) but not TFAD were independently associated with early clinical failure. Clinical parameters on admission other than the TFAD predict early clinical outcome in moderate-severe CAP. In contrast to severe CAP necessitating treatment in the ICU directly, in the case of suspected moderate-severe CAP, there is time to establish a reliable diagnosis of CAP before antibiotics are administered. Therefore, the implementation of the TFAD as a performance indicator is not desirable.
This paper presents the form and validation results of APACHE II, a severity of disease classification system. APACHE II uses a point score based upon initial values of 12 routine physiologic measurements, age, and previous health status to provide a general measure of severity of disease. An increasing score (range 0 to 71) was closely correlated with the subsequent risk of hospital death for 5815 intensive care admissions from 13 hospitals. This relationship was also found for many common diseases. When APACHE II scores are combined with an accurate description of disease, they can prognostically stratify acutely ill patients and assist investigators comparing the success of new or differing forms of therapy. This scoring index can be used to evaluate the use of hospital resources and compare the efficacy of intensive care in different hospitals or over time.
The aim of the study was to determine the causes and prognostic implications of antimicrobial treatment failures in patients with nonresponding and progressive life-threatening, community-acquired pneumonia. Forty-nine patients hospitalized with a presumptive diagnosis of community-acquired pneumonia during a 16-mo period, failure to respond to antimicrobial treatment, and documented repeated microbial investigation >/= 72 h after initiation of in-hospital antimicrobial treatment were recorded. A definite etiology of treatment failure could be established in 32 of 49 (65%) patients, and nine additional patients (18%) had a probable etiology. Treatment failures were mainly infectious in origin and included primary, persistent, and nosocomial infections (n = 10 [19%], 13 [24%], and 11 [20%] of causes, respectively). Definite but not probable persistent infections were mostly due to microbial resistance to the administered initial empiric antimicrobial treatment. Nosocomial infections were particularly frequent in patients with progressive pneumonia. Definite persistent infections and nosocomial infections had the highest associated mortality rates (75 and 88%, respectively). Nosocomial pneumonia was the only cause of treatment failure independently associated with death in multivariate analysis (RR, 16.7; 95% CI, 1.4 to 194.9; p = 0.03). We conclude that the detection of microbial resistance and the diagnosis of nosocomial pneumonia are the two major challenges in hospitalized patients with community-acquired pneumonia who do not respond to initial antimicrobial treatment. In order to establish these potentially life-threatening etiologies, a regular microbial reinvestigation seems mandatory for all patients presenting with antimicrobial treatment failures.
To evaluate the impact of appropriate initial antibiotic therapy (AB) on the outcome of ventilator-associated pneumonia (VAP).
Retrospective study (1992-97).
Episodes of VAP diagnosed on both clinical and microbiological criteria after > or = 48 h of mechanical ventilation (MV). Initial AB was considered appropriate when all significant organisms were susceptible to at least one of the antibiotics started after distal bronchial sampling. Antibiotic treatment was modified within 48 h when susceptibility testing was available. Outcome was recorded at the ICU and hospital discharge.
One hundred and eleven patients were included (SAPS II = 48 +/- 18, age = 62 +/- 14 years, mean duration of MV before VAP = 12 +/- 9 days). Initial AB was appropriate in 55 patients (49.5%). No difference between appropriate initial AB and inappropriate initial AB was found concerning severity indices at the time of VAP diagnosis. ICU length of stay was shorter with appropriate initial AB than with inappropriate initial AB for survivors (12 +/- 11 days vs 20 +/- 24 days, P = 0.01). Crude hospital mortality tended to be lower with appropriate initial AB than with inappropriate initial AB (47.3% vs 60.7%, odds ratio = 1.72, 95% CI = 0.81-3.7). Relative crude mortality reduction with appropriate initial AB was 22%, 95% CI = -10% to 45%.
Inappropriate initial AB of VAP during the first 48 h increased ICU length of stay after VAP diagnosis and tended to increase crude hospital mortality despite equal severity of illness at the time of VAP diagnosis, when compared to appropriate initial AB in a population of 111 ICU patients.
A total of 1,404 bacterial isolates were recovered from skin and soft tissue infections (SSTIs) from hospitalized patients in 24 sites in the United States (US) and 5 Canadian medical centers as part of the SENTRY Antimicrobial Surveillance Program. Isolates were collected between October and December, 2000. The rank order of pathogens was: Staphylococcus aureus (45.9%), Pseudomonas aeruginosa (10.8%), Enterococcus spp. (8.2%), Escherichia coli (7.0%), Enterobacter spp. (5.8%) and Klebsiella spp. (5.1%). The same order was observed in the US and Canada. Of note, almost 30% of S. aureus were oxacillin-resistant. Vancomycin resistance among enterococci was low (7.8%) representing a marked decrease from earlier SENTRY Program reports. Several antimicrobial agents remained very active against P. aeruginosa and Enterobacteriaceae isolates. In particular amikacin, cefepime, and the carbapenems (imipenem and meropenem) showed an excellent spectrum of activity (>95% susceptible). Extended-spectrum beta-lactamase production was observed in both E. coli (7.1%) and Klebsiella spp. (11.3%). Cefepime remained highly active, even against ceftazidime-resistant isolates of Enterobacter spp. The results of this study have identified the most common causes of SSTIs in hospitalized patients in North America, and can be used to make informed decisions concerning standards of empiric treatment for SSTIs in this region.
To assess the effect of baseline variables, including treatment, on clinical cure and survival rates in patients with Gram-positive, ventilator-associated pneumonia (VAP).
Retrospective analysis of two randomized, double-blind studies.
Multinational study with 134 sites.
544 patients with suspected Gram-positive VAP, including 264 with documented Gram-positive VAP and 91 with methicillin-resistant S. aureus (MRSA) VAP.
Linezolid 600 mg or vancomycin 1 g every 12 h for 7-21 days, each with aztreonam.
Clinical cure rates assessed 12-28 days after the end of therapy and excluding indeterminate or missing outcomes significantly favored linezolid in the Gram-positive and MRSA subsets. Logistic regression showed that linezolid was an independent predictor of clinical cure with odds ratios of 1.8 for all patients, 2.4 for Gram-positive VAP, and 20.0 for MRSA VAP. Kaplan-Meier survival rates favored linezolid in the MRSA subset. Logistic regression showed that linezolid was an independent predictor of survival with odds ratios of 1.6 for all patients, 2.6 for Gram-positive VAP, and 4.6 for MRSA VAP.
Initial linezolid therapy was associated with significantly better clinical cure and survival rates than was initial vancomycin therapy in patients with MRSA VAP.
Early failure is a matter of great concern in the treatment of community-acquired pneumonia. However, information on its causes and risk factors is lacking.
Observational analysis of a prospective series of 1383 nonimmunosuppressed hospitalized adults with community-acquired pneumonia. Early failure was defined as lack of response or worsening of clinical or radiologic status at 48 to 72 hours requiring changes in antibiotic therapy or invasive procedures. Concordance of antimicrobial therapy was examined for cases with an etiologic diagnosis.
At 48 to 72 hours, 238 patients (18%) remained febrile, but most of them responded without further changes in antibiotic therapy. Eighty-one patients (6%) had early failure. The main causes of early failure were progressive pneumonia (n = 54), pleural empyema (n = 18), lack of response (n = 13), and uncontrolled sepsis (n = 9). Independent factors associated with early failure were older age (>65 years) (odds ratio [OR], 0.35), multilobar pneumonia (OR, 1.81), Pneumonia Severity Index score greater than 90 (OR, 2.75), Legionella pneumonia (OR, 2.71), gram-negative pneumonia (OR, 4.34), and discordant antimicrobial therapy (OR, 2.51). Compared with treatment responders, early failures had significantly higher rates of complications (58% vs 24%) and overall mortality (27% vs 4%) (P<.001 for both).
Early failure is infrequent but is associated with high morbidity and mortality rates. Its detection and management require careful clinical assessment. Most cases occur because of inadequate host-pathogen responses. Discordant therapy is a less frequent cause of failure, which may be preventable by rational application of the current antibiotic guidelines.
In patients with community-acquired pneumonia, guidelines recommend antibiotic treatment for 7 to 21 d. Procalcitonin is elevated in bacterial infections, and its dynamics have prognostic implications.
To assess procalcitonin guidance for the initiation and duration of antibiotic therapy in community-acquired pneumonia.
In a randomized intervention trial, 302 consecutive patients with suspected community-acquired pneumonia were included. Data were assessed at baseline, after 4, 6, and 8 d, and after 6 wk. The control group (n = 151) received antibiotics according to usual practice. In the procalcitonin group (n = 151), antibiotic treatment was based on serum procalcitonin concentrations as follows: strongly discouraged, less than 0.1 microg/L; discouraged, less than 0.25 microg/L; encouraged, greater than 0.25 microg/L; strongly encouraged, greater than 0.5 microg/L. The primary endpoint was antibiotic use; secondary endpoints were measures of clinical, laboratory, and radiographic outcome.
At baseline, both groups were similar regarding clinical, laboratory, and microbiology characteristics, and Pneumonia Severity Index. Procalcitonin guidance reduced total antibiotic exposure (relative risk, 0.52; 95% confidence interval, 0.48-0.55; p < 0.001), antibiotic prescriptions on admission (85 vs. 99%; p < 0.001), and antibiotic treatment duration (median, 5 vs. 12 d; p < 0.001) compared with patients treated according to guidelines. After adjustment for Pneumonia Severity Index, the hazard ratio of antibiotic discontinuation was higher in the procalcitonin group than in the control group (3.2; 95% confidence interval, 2.5 to 4.2). Outcome was similar in both groups, with an overall success rate of 83%.
Procalcitonin guidance substantially reduces antibiotic use in community-acquired pneumonia. These findings may have important clinical and public health implications.
Antibiotic de-escalation, which consists of the initial institution of empiric broad-spectrum antibiotics followed by antibiotic streamlining driven by microbiological documentation, is thought to provide maximum benefit for the individual patient, while reducing the selection pressure for resistance.
To assess a carbapenem-based de-escalating strategy in nosocomial pneumonia (NP), a prospective observational study was conducted in critically ill patients with NP treated empirically with imipenem +/- aminoglycoside/glycopeptide in 24 intensive care units of Spanish general hospitals. Overall, 244 patients were assessable (91% with late-onset NP). The primary outcome was therapeutic success 7-9 days post therapy.
Microbial identification--based on cultures of tracheal aspirates in 82% of patients, cultures of protected specimen brush in 33%, and cultures of bronchoalveolar lavage in 4%--was only available for 131 (54%) patients. Initial antibiotics were inadequate for 23 (9%) patients. Of the remaining patients, antibiotics were streamlined in 56 (23%) patients and remained unchanged in 14 (6%) patients based on microbiology data, in 38 (16%) patients despite microbiology data favouring de-escalation, and in 113 (46%) patients due to unknown aetiology. Overall, de-escalation was implemented in only 23% of patients with potentially multiresistant pathogens, compared with 68% of patients with the remaining pathogens (P < 0.001). Response rates were 53% for patients continuously treated with imipenem-based regimens and 50% for the de-escalated patients. Higher Acute Physiology, Age, and Chronic Health Evaluation II scores were associated with greater mortality, whereas adequate empiric antibiotic therapy protected against fatal outcomes. No increase of superinfection rates caused by emerging pathogens was observed. The costs associated with de-escalation were mainly dependent on the duration of hospitalization.
This study mainly highlights the current practice of a specific algorithm of de-escalation solely based on the available microbiological data, and highlights the barriers to using it more widely. In this setting, de-escalation was less likely to occur in the presence of potentially multiresistant pathogens. Prior antibiotic administration and the low use of bronchoscopic techniques may have influenced negatively the implementation of de-escalation. Optimization of de-escalation strategies for NP should rely on a correct choice of empiric antibiotics, on appropriate microbiological investigations, and on a balanced interpretation of microbiological and clinical data.
To estimate the consequences of failure of initial antibiotic therapy for patients with complicated skin and skin-structure infections.
Retrospective cohort study.
Large US multihospital database.
We identified a total of 47,219 patients (age 18 years or older) who were admitted to the hospital for complicated skin and skin-structure infections from April 1, 2003, through March 31, 2004, and who received intravenous antibiotics during the first 2 hospital-days (ie, initial antibiotic therapy). Failure of therapy was defined as drainage, debridement, or receipt of other intravenous antibiotics at any subsequent time (except for changes to narrower-spectrum agents or any therapy change immediately before discharge). Predictors of failure of antibiotic therapy and mortality were examined using multivariate logistic regression. Analysis of covariance was used to estimate the impact of treatment failure on duration of intravenous antibiotic therapy, length of stay, and total inpatient charges.
For 10,782 admitted patients (22.8%), there was evidence of failure of initial antibiotic therapy. In multivariate analyses, treatment failure was associated with receipt of vasoactive medications during the first 2 hospital-days (odds ratio [OR], 1.66 [95% confidence interval {CI}, 1.19-2.31]), initiation of antibiotic therapy in the intensive care unit (OR, 1.53 [95% CI, 1.28-1.84]), and the patient's Charlson comorbidity index (OR per 1-point increase, 1.06 [95% CI, 1.04-1.08]); treatment failure was also was associated with a 3-fold increase in mortality (OR, 2.91 [95% CI, 2.34-3.62]). Compared with patients for whom initial treatment was successful, patients who experienced treatment failure received intravenous antibiotic therapy for a mean of 5.7 additional days, were hospitalized for a mean of 5.4 additional days, and incurred a mean of $5,285 (in 2003 dollars) in additional inpatient charges (all P<.01).
Failure of initial antibiotic therapy in the treatment of complicated skin and skin-structure infections is associated with significantly worse clinical and economic outcomes.
Lack of response to treatment in community acquired pneumonia (CAP) worsens outcome. We evaluated the systemic cytokine profile (tumour necrosis factor alpha, interleukin (IL)1, IL6, IL8 and IL10), C reactive protein (CRP) and procalcitonin (PCT) in patients with CAP who had treatment failure.
A prospective study was performed in hospitalised patients with CAP. Cytokines, PCT and CRP measurements were obtained on day 1 and after 72 h of treatment. Treatment failure was the endpoint evaluated, with separation of those with early (< or = 72 h) or late failure.
453 patients were included: 84 (18%) had treatment failure, of whom 38 (8%) were early failures. Median levels of IL6, PCT and CRP on days 1 and 3 and median levels of IL8 on day 1 were significantly higher in patients with any treatment failure. Logistic regression analysis demonstrated that values above the cut-off points for IL6 (> or = 169 pg/ml), IL8 (> or = 14 pg/ml) and CRP (> or = 21.9 mg/dl) on day 1 had independent predictive value for any treatment failure after adjustment for initial severity; relative risks (OR) found were 1.9, 2.2 and 2.6, respectively. Increased levels for CRP and PCT on day 1 were also independent predictors for early failure. Increased levels for IL6 and CRP were the best predictors of late failure.
Serum levels of CRP, IL6 and PCT on days 1 and 3 were independently associated with a higher risk of any treatment failure. Low levels of PCT and CRP on day 1 had a high negative predictive value for early failure.
A method for comparing death rates of groups of injured persons was developed, using hospital and medical examiner data for more than two thousand persons. The first step was determination of the extent to which injury severity as rated by the Abbreviated Injury Scale correlates with patient survival. Substantial correlation was demonstrated. Controlling for severity of the primary injury made it possible to measure the effect on mortality of additional injuries. Injuries that in themselves would not normally be life-threatening were shown to have a marked effect on mortality when they occurred in combination with other injuries. An Injury Severity Score was developed that correlates well with survival and provides a numerical description of the overall severity of injury for patients with multiple trauma. Results of this investigation indicate that the Injury Severity Score represents an important step in solving the problem of summarizing injury severity, especially in patients with multiple trauma.
Study objective
To evaluate the relationship between inadequate antimicrobial treatment of infections (both community-acquired and nosocomial infections) and hospital mortality for patients requiring ICU admission.
Design
Prospective cohort study.
Setting
Barnes-Jewish Hospital, a university-affiliated urban teaching hospital.
Patients
Two thousand consecutive patients requiring admission to the medical or surgical ICU.
Interventions
Prospective patient surveillance and data collection.
Measurements and results
One hundred sixty-nine (8.5%) infected patients received inadequate antimicrobial treatment of their infections. This represented 25.8% of the 655 patients assessed to have either community-acquired or nosocomial infections. The occurrence of inadequate antimicrobial treatment of infection was most common among patients with nosocomial infections, which developed after treatment of a community-acquired infection (45.2%), followed by patients with nosocomial infections alone (34.3%) and patients with community-acquired infections alone (17.1%) (p < 0.001). Multiple logistic regression analysis, using only the cohort of infected patients (n = 655), demonstrated that the prior administration of antibiotics (adjusted odds ratio [OR], 3.39; 95% confidence interval [CI], 2.88 to 4.23; p < 0.001), presence of a bloodstream infection (adjusted OR, 1.88; 95% CI, 1.52 to 2.32; p = 0.003), increasing acute physiology and chronic health evaluation (APACHE) II scores (adjusted OR, 1.04; 95% CI, 1.03 to 1.05; p = 0.002), and decreasing patient age (adjusted OR, 1.01; 95% CI, 1.01 to 1.02; p = 0.012) were independently associated with the administration of inadequate antimicrobial treatment. The hospital mortality rate of infected patients receiving inadequate antimicrobial treatment (52.1%) was statistically greater than the hospital mortality rate of the remaining patients in the cohort (n = 1,831) without this risk factor (12.2%) (relative risk [RR], 4.26; 95% CI, 3.52 to 5.15; p < 0.001). Similarly, the infection-related mortality rate for infected patients receiving inadequate antimicrobial treatment (42.0%) was significantly greater than the infection-related mortality rate of infected patients receiving adequate antimicrobial treatment (17.7%) (RR, 2.37; 95% CI, 1.83 to 3.08; p < 0.001). Using a logistic regression model, inadequate antimicrobial treatment of infection was found to be the most important independent determinant of hospital mortality for the entire patient cohort (adjusted OR, 4.27; 95% CI, 3.35 to 5.44; p < 0.001). The other identified independent determinants of hospital mortality included the number of acquired organ system derangements, use of vasopressor agents, the presence of an underlying malignancy, increasing APACHE II scores, increasing age, and having a nonsurgical diagnosis at the time of ICU admission.
Conclusions
Inadequate treatment of infections among patients requiring ICU admission appears to be an important determinant of hospital mortality. These data suggest that clinical efforts aimed at reducing the occurrence of inadequate antimicrobial treatment could improve the outcomes of critically ill patients. Additionally, prior antimicrobial therapy should be recognized as an important risk factor for the administration of inadequate antimicrobial treatment among ICU patients with clinically suspected infections.
To discuss the altered pharmacokinetic properties of selected antibiotics in critically ill patients and to develop basic dose adjustment principles for this patient population.
PubMed, EMBASE, and the Cochrane-Controlled Trial Register.
Relevant papers that reported pharmacokinetics of selected antibiotic classes in critically ill patients and antibiotic pharmacodynamic properties were reviewed. Antibiotics and/or antibiotic classes reviewed included aminoglycosides, beta-lactams (including carbapenems), glycopeptides, fluoroquinolones, tigecycline, linezolid, lincosamides, and colistin.
Antibiotics can be broadly categorized according to their solubility characteristics which can, in turn, help describe possible altered pharmacokinetics that can be caused by the pathophysiological changes common to critical illness. Hydrophilic antibiotics (e.g., aminoglycosides, beta-lactams, glycopeptides, and colistin) are mostly affected with the pathphysiological changes observed in critically ill patients with increased volumes of distribution and altered drug clearance (related to changes in creatinine clearance). Lipophilic antibiotics (e.g., fluoroquinolones, macrolides, tigecycline, and lincosamides) have lesser volume of distribution alterations, but may develop altered drug clearances. Using antibiotic pharmacodynamic bacterial kill characteristics, altered dosing regimens can be devised that also account for such pharmacokinetic changes.
Knowledge of antibiotic pharmacodynamic properties and the potential altered antibiotic pharmacokinetics in critically ill patients can allow the intensivist to develop individualized dosing regimens. Specifically, for renally cleared drugs, measured creatinine clearance can be used to drive many dose adjustments. Maximizing clinical outcomes and minimizing antibiotic resistance using individualized doses may be best achieved with therapeutic drug monitoring.
The charts of 480 patients with secondary bacterial peritonitis were reviewed. The antibiotics used were compared with the culture and sensitivity data obtained at surgery, and the outcomes of patients were evaluated. Patients treated with a single broad-spectrum antibiotic had a better outcome than patients treated with multiple drug treatment. Inadequate empiric antibiotic treatment was associated with poorer outcome than any other type of treatment. The outcome of this inadequate treatment group could not be improved by any antibiotic response to culture and sensitivity information after operation. Those patients treated with antibiotic coverage for anticipated organisms and having no cultures taken did as well as patients having cultures taken. Surgeons typically ignore culture data after operation, and only 8.8% of patients in this study had an appropriate change in antibiotic treatment after operation. A benefit from obtaining operative cultures could not be identified.
A method for comparing death rates of groups of injured persons was developed, using hospital and medical examiner data for more than 2,000 persons. The first step was determination of the extent to which injury severity as rated by the Abbreviated Injury Scale correlates with patient survival. Substantial correlation was demonstrated. Controlling for severity of the primary injury made it possible to measure the effect on mortality of additional injuries. Injuries that in themselves would not normally be life threatening were shown to have a marked effect on mortality when they occurred in combination with other injuries. An Injury Severity Score was developed that correlates well with survival and provides a numerical description of the overall severity of injury for patients with multiple trauma. Results of this investigation indicate that the Injury Severity Score represents an important step in solving the problem of summarizing injury severity, especially in patients with multiple trauma. The score is easily derived, and is based on a widely used injury classification system, the Abbreviated Injury Scale. Use of the Injury Severity Score facilitates comparison of the mortality experience of varied groups of trauma patients, thereby improving ability to evaluate care of the injured.
Objective
To assess the frequency of and the reasons for changing empiric antibiotics during the treatment of pnnumonia acquired in the intensive care unit (ICU).
Design
A prospective multicenter study of 1 year's duration.
Setting
Medical and surgical ICUs in 30 hospitals all over Spain.
Patients
Of a total of 16872 patients initially enrolled into the study, 530 patients developed 565 episodes of pneumonia after admission to the ICU.
Results
Empiric antibiotics were administered in 490 (86.7%) of the 565 episodes of pneumonia. The antimicrobials most frequently used were amikacin in 120 case, tobramycin in 110, ceftazidime in 96, and cefotaxime in 96. Monotherapy was indicated in 135 (27.6%) of the 490 episodes, a combination of two antibiotics in 306 episodes (62.4%), and a combination of three antibiotics in 49 episodes (10%). The empiric antibiotic treatment was modified in 214 (43.7%) cases because of isolation of a microorganism not covered by treatment in 133 (62.1%) cases, lack of clinical response in 77 (36%), and development of resistance in 14 (6.6%). Individual factors associated with modification of empiric treatment identified in the multivariate analysis were microorganism not covered (relative risk (RR)) 22.02; 95% confidence interval (CI) 11.54 to 42.60;p
There is considerable variability in rates of hospitalization of patients with community-acquired pneumonia, in part because of physicians' uncertainty in assessing the severity of illness at presentation.
From our analysis of data on 14,199 adult inpatients with community-acquired pneumonia, we derived a prediction rule that stratifies patients into five classes with respect to the risk of death within 30 days. The rule was validated with 1991 data on 38,039 inpatients and with data on 2287 inpatients and outpatients in the Pneumonia Patient Outcomes Research Team (PORT) cohort study. The prediction rule assigns points based on age and the presence of coexisting disease, abnormal physical findings (such as a respiratory rate of > or = 30 or a temperature of > or = 40 degrees C), and abnormal laboratory findings (such as a pH <7.35, a blood urea nitrogen concentration > or = 30 mg per deciliter [11 mmol per liter] or a sodium concentration <130 mmol per liter) at presentation.
There were no significant differences in mortality in each of the five risk classes among the three cohorts. Mortality ranged from 0.1 to 0.4 percent for class I patients (P=0.22), from 0.6 to 0.7 percent for class II (P=0.67), and from 0.9 to 2.8 percent for class III (P=0.12). Among the 1575 patients in the three lowest risk classes in the Pneumonia PORT cohort, there were only seven deaths, of which only four were pneumonia-related. The risk class was significantly associated with the risk of subsequent hospitalization among those treated as outpatients and with the use of intensive care and the number of days in the hospital among inpatients.
The prediction rule we describe accurately identifies the patients with community-acquired pneumonia who are at low risk for death and other adverse outcomes. This prediction rule may help physicians make more rational decisions about hospitalization for patients with pneumonia.
Early classification of patients presenting with peritonitis and intra-abdominal sepsis by means of objective scoring systems is desirable to select patients for 'aggressive' surgery and to compare results of different treatment regimens. However, none of the existing scoring systems has fulfilled all expectations.
Evaluation of the value of various scoring systems (Acute Physiology And Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score, Sepsis Severity Score, Multiple Organ Failure, Mannheim Peritonitis Index (MPI), Ranson and Imrie) was performed in 50 patients. Additionally, scoring systems were combined to obtain a 'combined score' for the prediction of peritonitis-related in-hospital death. Hazard ratios were calculated in a univariate and multivariate analysis.
In the univariate analysis all scoring systems, except Ranson and Imrie, predicted the primary outcome. In the multivariate analysis, only the APACHE II score (hazard ratio 6.7) and the MPI (hazard ratio 9.8) contributed independently to the prediction of outcome. All patients with an APACHE II score of 20 or more and a MPI of 27 or more died in hospital.
Combination of the APACHE II and the MPI provides the best scoring system fitting clinical goals.
To evaluate the relationship between inadequate antimicrobial treatment of infections (both community-acquired and nosocomial infections) and hospital mortality for patients requiring ICU admission.
Prospective cohort study.
Barnes-Jewish Hospital, a university-affiliated urban teaching hospital.
Two thousand consecutive patients requiring admission to the medical or surgical ICU.
Prospective patient surveillance and data collection.
One hundred sixty-nine (8.5%) infected patients received inadequate antimicrobial treatment of their infections. This represented 25.8% of the 655 patients assessed to have either community-acquired or nosocomial infections. The occurrence of inadequate antimicrobial treatment of infection was most common among patients with nosocomial infections, which developed after treatment of a community-acquired infection (45.2%), followed by patients with nosocomial infections alone (34.3%) and patients with community-acquired infections alone (17.1%) (p < 0.001). Multiple logistic regression analysis, using only the cohort of infected patients (n = 655), demonstrated that the prior administration of antibiotics (adjusted odds ratio [OR], 3.39; 95% confidence interval [CI], 2.88 to 4.23; p < 0.001), presence of a bloodstream infection (adjusted OR, 1.88; 95% CI, 1.52 to 2.32; p = 0.003), increasing acute physiology and chronic health evaluation (APACHE) II scores (adjusted OR, 1.04; 95% CI, 1.03 to 1.05; p = 0.002), and decreasing patient age (adjusted OR, 1.01; 95% CI, 1.01 to 1.02; p = 0.012) were independently associated with the administration of inadequate antimicrobial treatment. The hospital mortality rate of infected patients receiving inadequate antimicrobial treatment (52.1%) was statistically greater than the hospital mortality rate of the remaining patients in the cohort (n = 1,831) without this risk factor (12.2%) (relative risk [RR], 4.26; 95% CI, 3.52 to 5.15; p < 0.001). Similarly, the infection-related mortality rate for infected patients receiving inadequate antimicrobial treatment (42.0%) was significantly greater than the infection-related mortality rate of infected patients receiving adequate antimicrobial treatment (17.7%) (RR, 2.37; 95% CI, 1.83 to 3.08; p < 0.001). Using a logistic regression model, inadequate antimicrobial treatment of infection was found to be the most important independent determinant of hospital mortality for the entire patient cohort (adjusted OR, 4.27; 95% CI, 3.35 to 5.44; p < 0.001). The other identified independent determinants of hospital mortality included the number of acquired organ system derangements, use of vasopressor agents, the presence of an underlying malignancy, increasing APACHE II scores, increasing age, and having a nonsurgical diagnosis at the time of ICU admission.
Inadequate treatment of infections among patients requiring ICU admission appears to be an important determinant of hospital mortality. These data suggest that clinical efforts aimed at reducing the occurrence of inadequate antimicrobial treatment could improve the outcomes of critically ill patients. Additionally, prior antimicrobial therapy should be recognized as an important risk factor for the administration of inadequate antimicrobial treatment among ICU patients with clinically suspected infections.
The initial approach to managing patients with community-acquired pneumonia involves a determination of the presence of relevant factors that influence the likely etiologic pathogens. These factors include place of therapy (inpatient versus outpatient), the presence of cardiopulmonary disease, the presence of risk factors for drug-resistant pneumococci, the presence of risk factors for enteric gram-negative bacteria (including P. aeruginosa), and the severity of illness at presentation (mild, moderate, or severe). Once these assessments have been made, initial antimicrobial therapy can be selected according to the recommendations in Tables 2-5, and the choices will cover the most common pathogens likely for a given clinical setting. It is important to evaluate the response to initial therapy so that patients who are not adequately improving can be identified and properly evaluated. The approach advocated in Tables 2-5 is different from several common clinical practices that have no firm basis in published studies. The practices include the use of sputum Gram's stain to define the likely etiologic pathogen and to guide initial therapy of community-acquired pneumonia; the use of extensive diagnostic testing in the initial evaluation of etiology; and the use of clinical syndromes to predict microbial etiology. In several important areas of management, data are limited, and recommendations are not based on a firm scientific foundation. Future studies should focus on some of these pressing, but unanswered, questions: (1) How long should therapy be continued? (2) Should duration of therapy be related to severity of initial illness? (3) What role does antibiotic resistance play in the outcome of patients with CAP and how should initial therapy be modified to account for possible resistance? (4) Will newer diagnostic methods improve our ability to define the etiologic pathogens of community-acquired pneumonia, and will this information lead to improved outcomes? (5) What are the best criteria for defining the need for hospitalization? (6) How will antibiotic choices and guidelines for empiric therapy impact future patterns of antibiotic resistance? (7) Is atypical pathogen coinfection common and if so, is it prevalent all the time, or are there temporal and geographic variables to consider? Often the distinction between pneumonia and bronchitis is uncertain, since even the chest radiograph may not be sensitive to early forms of pneumonia. This document is focused on the management of CAP, but the role of antibiotic therapy in patients with AECB needs further study, with a particular focus on whether specific types of antibiotic therapy should be targeted to specific patient populations. However, for CAP, the committee believes that guidelines can be useful for initial patient management, and the guidelines suggest therapies for illnesses that are based on the premise of using the "right drug for the right patient," recognizing that patient profiles dictate different therapies for different clinical settings.
Few studies have assessed the actual costs associated with failure of initial empiric antibiotic therapy administered to patients with community-acquired intra-abdominal infections. The goals of this study were (i) to determine the frequency of unsuccessful initial empiric therapy in a real-world setting and (ii) to determine the associated impact on medical costs. Thus, a retrospective chart review was performed at four acute-care university hospitals in France. A total of 292 patients hospitalized for community-acquired intra-abdominal infection were included. The mean age of the cohort was 51 years, and 42% of the patients were female. The most commonly administered empiric regimens were intravenous amoxicillin/clavulanate alone (69 patients) or in combination with other antibiotics ( n=87) and piperacillin/tazobactam alone ( n=24) or in combination ( n=48). Other regimens included broad-spectrum penicillin, cephalosporins, and fluoroquinolones administered alone or in combination ( n=64). Empiric therapy was successful in 189 (65%) patients and unsuccessful in 103 (35%). Among the 292 patients with community-acquired infection, 15 died of the infection, 8 required reoperation and 80 required second-line antibiotic therapy. Patients with unsuccessful initial empiric therapy had significantly more parenteral antibiotic days (10.3 vs. 7.6 days) and a longer length of stay (16.2 vs. 12.8 days) compared to those with successful initial empiric therapy. A better selection of initial empiric antibiotic therapy may significantly influence the medical costs associated with patients who are hospitalized with community-acquired intra-abdominal infections.
Severity scoring systems are useful for assessing patient risk and predicting prognosis.
We developed a scoring system using data from a phase III study comparing antibiotics in hospitalized patients with complicated skin and soft tissue infections (study A), and used logistic regression analysis to identify factors contributing to treatment failure. We tested this system using data from a similar study (study B).
In study A (n = 682), cure rates were lower in patients with at least 1 comorbid condition (P <0.05) and in the highest risk class (P = 0.05); elevated blood urea nitrogen, hyponatremia, anemia, lesion size, and surgical wound infection were independent predictors of failure (P <0.05). In study B (n = 166), findings were similar and significant for risk class (P <0.05). In the combined analysis (n = 848), cure rates were higher for linezolid than for the comparator in all patients (85% versus 77%; P <0.01) and in subanalyses by comorbid conditions, median score, and risk class (P <0.05).
We developed and validated a scoring system in which baseline variables predicted outcome. Patients with higher severity scores generally had poorer outcomes regardless of treatment group. Our finding that linezolid was an independent predictor of cure merits further evaluation.
To prospectively evaluate the predictive factors for the nonresponse to empirical antibiotic treatment and mortality in patients with intensive care unit-acquired pneumonia.
A 1-yr prospective cohort of patients with suspicion of intensive care unit-acquired pneumonia.
Five medical and surgical intensive care units of Hospital Clinic in Barcelona.
A total of 71 patients with intensive care unit-acquired pneumonia were studied. The definition of nonresponse included at least one of the following: failure to improve the Pao2/Fio2 ratio or need of intubation because of pneumonia, persistence of fever or hypothermia and purulent respiratory secretions, worsening of pulmonary infiltrates, or occurrence of septic shock or multiple organ dysfunction not present at onset of pneumonia.
Clinical assessment, including severity scores, blood and quantitative cultures of respiratory secretions, and cytokine measurements in serum and bronchoalveolar lavage at onset of pneumonia and 72 hrs after antimicrobial treatment.
A total of 44 patients (62%) fulfilled criteria of nonresponse, and at least one cause of nonresponse could be determined in 28 cases (64%): inappropriate treatment in ten (23%), superinfection in six (14%), concomitant foci of infection in 12 (27%), and noninfectious causes in seven cases (16%). The remaining 16 patients with no definite cause of nonresponse presented with septic shock, multiple organ dysfunction, or acute respiratory distress syndrome. Increased levels of interleukin-6 at onset of pneumonia (odds ratio, 9.7; p =.014) was an independent predictor of nonresponse to treatment. Likewise, increased level of interleukin-6 at follow-up (odds ratio, 27; p =.001) was the only independent predictor for hospital mortality.
Increased systemic inflammatory response was the main predictor of nonresponse to treatment and mortality.
For patients with community-acquired pneumonia (CAP), clinical response during the first days of treatment is predictive of clinical outcome. As risk assessments can improve the efficiency of pneumonia management, a prospective cohort study to assess clinical, biochemical and microbiological predictors of early clinical failure was conducted in patients with severe CAP (pneumonia severity index score of >90 or according to the American Thoracic Society definition). Failure was assessed at day 3 and was defined as death, a need for mechanical ventilation, respiratory rate >25/min, PaO2 <55 mm Hg, oxygen saturation <90%, haemodynamic instability, temperature >38 degrees C or confusion. Of 260 patients, 80 (31%) had early clinical failure, associated mainly with a respiratory rate >25/minute (n = 34), oxygen saturation <90% (n = 28) and confusion (n = 20). In multivariate logistic regression analysis, failure was associated independently with altered mental state (OR 3.19, 95% CI 1.75-5.80), arterial PaH <7.35 mm Hg (OR 4.29, 95% CI 1.53-12.05) and PaO2 <60 mm Hg (OR 1.75, 95% CI 0.97-3.15). A history of heart failure was associated inversely with clinical failure (OR 0.30, 95% CI 0.10-0.96). Patients who failed to respond had a higher 28-day mortality rate and a longer hospital stay. It was concluded that routine clinical and biochemical information can be used to predict early clinical failure in patients with severe CAP.
Controlled studies that address risk factors for, and clinical outcomes after, infection with extended-spectrum beta-lactamase (ESBL)-producing organisms are scant, particularly in the intensive care unit (ICU). Our objectives were to elucidate risk factors for the acquisition of ESBL-producing organisms in ICU; and to compare mortality in patients with ESBL- and non-ESBL bloodstream infections (BSIs) after controlling for disease severity and timeliness of appropriate antibiotic therapy. A retrospective cohort study was undertaken in the ICU from March 2004 to May 2006. Cases included all adult ICU patients with a BSI due to an ESBL-producing E. coli or Klebsiella spp. (N=16); controls (N=39) comprised ICU patients with a BSI caused by a non-ESBL-producing E. coli or Klebsiella spp. Disease severity was measured using APACHE (Acute Physiological Assessment and Chronic Health Evaluation) and SOFA (Sequential Organ Failure Assessment) scores. Outcomes were recorded as discharge or death due to all causes. Although no statistically significant associations were demonstrated between individual risk factors and the acquisition of an ESBL-producing organism, appropriate therapy was delayed in cases (OR: 9.17; 95% CI: 2.00-42.20; P=0.0005) and survival estimates demonstrated a significantly increased early (<25 days after infection) mortality (OR for death 3.93; 95% CI: 1.05-14.63; P=0.03). Mortality in ICU, when adjusted for disease severity and appropriate antimicrobial therapy, though significant needs to be treated with caution due to the small number of cases (N=16 in 2 years). We believe that a high index of suspicion, early appropriate therapy and strict adherence to infection control are indicated in all patients at risk in ICU.
Although procalcitonin (PCT) measurement has been performed in patients with infectious diseases, there are few reports on its usefulness in community-acquired pneumonia (CAP) associated with systemic inflammatory response syndrome (SIRS). We investigated 88 patients who visited the internal medicine departments of Nagasaki University Hospital, Nagasaki, Japan, and its 11 affiliated hospitals in Japan because of CAP with or without SIRS. Of the 88 patients, 15 (17.0%), 43 (48.9%), and 30 (34.1%) were judged to have severe, moderate, and mild CAP, respectively. Although 87 patients (98.9%) had C-reactive protein (CRP) levels exceeding 0.3 mg/dL, only 30 patients (34.1%) had PCT levels more than 0.5 ng/mL. In addition, 93.3% (28/30) of patients with mild CAP had negative PCT, and 48.3% (28/58) of patients positive for PCT had moderate or severe CAP. Our findings suggest that PCT level might be more useful for estimating CAP severity than CRP level at the 1st visit.
The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention
- O Sp Baker
- Neill
- W Jr
- Long
- Niederman Ms
- La Mandell
- A Anzueto
- Jb Bass
- Broughton
- Wa
- Campbell
- Gd
Baker SP, O'Neill B, Haddon Jr W, Long WB. The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma 1974;14:187 96. 15. Niederman MS, Mandell LA, Anzueto A, Bass JB, Broughton WA, Campbell GD, et al. Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med 2001;163:1730 54.
Prognostic scoring systems to predict outcome in peritonitis and intra-abdominal sepsis
- Bosscha
APACHE II: a severity of disease classification system
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