[Show abstract][Hide abstract] ABSTRACT: The use of systemic antifungal agents has increased in most tertiary care centers. However, antifungal stewardship has deserved very little attention. Our objective was to assess the knowledge of European prescribing physicians as a first step of an international program of antifungal stewardship.
Staff physicians and residents of 4 European countries were invited to complete a 20-point questionnaire that was based on current guidelines of invasive candidiasis and invasive aspergillosis.
121 physicians (44.6% staff, 55.4% residents) from Spain 53.7%, Italy 17.4%, Denmark 16.5% and Germany 12.4% completed the survey. Hospital departments involved were: medical 51.2%, ICUs 43%, surgical 3.3% and pharmaceutical 2.5%. The mean score of adequate responses (± SD) was 5.8 ± 1.7 points, with statistically significant differences between study site and type of physicians. Regarding candidiasis, 69% of the physicians clearly distinguished colonization from infection and the local rate of fluconazole resistance was known by 24%. The accepted indications of antifungal prophylaxis were known by 38%. Regarding aspergillosis, 52% of responders could differentiate colonization from infection and 42% knew the diagnostic value of galactomannan. Radiological features of invasive aspergillosis were well recognized by 58% of physicians and 57% of them were aware of the antifungal considered as first line treatment. However, only 37% knew the recommended length of therapy.
This simple, easily completed questionnaire enabled us to identify some weakness in the knowledge of invasive fungal infection management among European physicians. This survey could serve as a guide to design a future tailored European training program.
[Show abstract][Hide abstract] ABSTRACT: Micafungin is more active against biofilms with high metabolic activity; however, it is unknown whether this observation applies to caspofungin and anidulafungin and whether it is also dependent on the biomass production. We compare the antifungal activity of anidulafungin, caspofungin, and micafungin against preformed Candida albicans biofilms with different degrees of metabolic activity and biomass production from 301 isolates causing fungemia in patients admitted to Gregorio Marañon Hospital (January 2007 to September 2014). Biofilms were classified as having low, moderate, or high metabolic activity according XTT reduction assay or having low, moderate, or high biomass according to crystal violet assay. Echinocandin MICs for planktonic and sessile cells were measured using the EUCAST E.Def 7.2 procedure and XTT reduction assay, respectively. Micafungin showed the highest activity against biofilms classified according to the metabolic activity and biomass production (P < .001). The activity of caspofungin and anidulafungin was not dependent on the metabolic activity of the biofilm or the biomass production. These observations were confirmed by scanning electron microscopy. None of the echinocandins produced major changes in the structure of biofilms with low metabolic activity and biomass production when compared with the untreated biofilms. However, biofilm with high metabolic activity or high biomass production was considerably more susceptible to micafungin; this effect was not shown by caspofungin or anidulafungin.
Medical mycology: official publication of the International Society for Human and Animal Mycology 11/2015; DOI:10.1093/mmy/myv094 · 2.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to describe the epidemiologic and clinical characteristics and identify the risk factors of short-term and 1-year mortality in a recent cohort of patients with infective endocarditis (IE).From January 2008, multidisciplinary teams have prospectively collected all consecutive cases of IE, diagnosed according to the Duke criteria, in 25 Spanish hospitals.Overall, 1804 patients were diagnosed. The median age was 69 years (interquartile range, 55-77), 68.0% were men, and 37.1% of the cases were nosocomial or health care-related IE. Gram-positive microorganisms accounted for 79.3% of the episodes, followed by Gram-negative (5.2%), fungi (2.4%), anaerobes (0.9%), polymicrobial infections (1.9%), and unknown etiology (9.1%). Heart surgery was performed in 44.2%, and in-hospital mortality was 28.8%. Risk factors for in-hospital mortality were age, previous heart surgery, cerebrovascular disease, atrial fibrillation, Staphylococcus or Candida etiology, intracardiac complications, heart failure, and septic shock. The 1-year independent risk factors for mortality were age (odds ratio [OR], 1.02), neoplasia (OR, 2.46), renal insufficiency (OR, 1.59), and heart failure (OR, 4.42). Surgery was an independent protective factor for 1-year mortality (OR, 0.44).IE remains a severe disease with a high rate of in-hospital (28.9%) and 1-year mortality (11.2%). Surgery was the only intervention that significantly reduced 1-year mortality.
Medicine 10/2015; 94(43):e1816. DOI:10.1097/MD.0000000000001816 · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We compared in an vitro model the yields of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and conventional culture (CC) for the detection of catheter colonization with superficial catheter samples (SS). We used blood culture bottles (BCB) with an inserted cannula and incubated at 37 °C. The BCB were manipulated with different contaminations and when a BCB turned positive, SS were obtained to perform both techniques. To compare both techniques we analyzed the mean time to colonization (MTC) and the mean time to a result (MTR). The MTC (SD, days) by CC and MALDI-TOF was as follows: hub, 0.59 (0.79) versus 1.07 (1.39), P=0.06; surface: 0.62 (0.67) versus 0.82 (0.81), P<0.001. The MTR (SD, days) of CC and MALDI-TOF was as follows: hub: 1.58 (0.79) versus 2.25 (1.48), P=0.04; surface: 1.62 (0.67) versus 1.95 (0.80), P<0.001. In general, the use of MALDI-TOF performed directly with SS was no better than CC and did not anticipate colonization results.
[Show abstract][Hide abstract] ABSTRACT: Background:
Clostridium difficile infection (CDI) is the leading cause of hospital-acquired diarrhoea in developed countries. Although an optimal diagnosis is crucial, laboratory diagnostics remain challenging. Currently, the reference methods are direct cytotoxicity assay and toxigenic culture; however there is controversy in the interpretation of discordant results of these tests.
The aim of our study was to determine the clinical significance of detecting C. difficile only by toxigenic culture with a negative direct cytotoxicity assay.
We conducted a prospective study in which patients aged >2 years with CDI were enrolled and monitored at least 2 months after their last episode. Samples were tested by both cytotoxicity assay and toxigenic culture.
During the 6-month study period, we identified 169 episodes meeting CDI criteria that had been tested by both assays, out of which 115 were positive for both cytotoxicity assay and toxigenic culture, and 54 CDI episodes (31.9%) were positive only by toxigenic culture. Overall, patients median age was 71.3, 50.9% were male and the most frequent underlying disease was malignancy. The comparison of CDI episodes positive for both assays and by toxigenic culture only revealed the following, respectively: mild CDI (77.4% vs 94.4%; p=0.008), severe CDI (21.7% vs 5.6%; p=0.008), severe complicated (0.9% vs 0.0%; p=1.000), pseudomembranous colitis (1.7% vs 1.9% p=1.000), recurrence (17.4% vs 14.8%; p=0.825), overall mortality (8.7% vs 7.4%; p=1.000) and CDI related mortality (2.6% vs 0%; p=0.552).
CDI episodes positive by cytotoxicity assay were more severe than those positive only by toxigenic culture, however there were a significant proportion of CDI cases (31.9%) that would have been missed if only cytotoxicity had been considered as clinically significant for CDI treatment, including severe CDI cases. Our data suggest that a positive test by toxigenic culture with a negative result for cytotoxicity should not be interpreted as colonization.
[Show abstract][Hide abstract] ABSTRACT: Early sepsis attention is a standard of care in many institutions and the role of different specialists is well recognized. However, the impact of a telephone call from a specialist in Clinical Microbiology upon blood cultures request has not been assessed to the best of our knowledge.We performed telephone calls followed by an interview with physicians and nurses in charge of adult patients (> 18 years old) whose blood cultures had just been received in the Microbiology Laboratory in a tertiary hospital. Patients were randomly classified in 2 different groups: group A (telephone call performed) and group B (no telephone call). At the end of the telephonic intervention, recommendations on the use of microbiology and biochemical tests as well as on the management and antibiotic therapy of sepsis were made if required.We included 300 patients. Of those fulfilling standard criteria of sepsis, 30.3% of the nurses and 50% of the physicians immediately recognized it. Advice to optimize the use of biochemical and microbiological tests was provided in 36% of the cases and to improve antimicrobial therapy in 57.6%. The median number of days of antibiotic use in groups A and B were, respectively, 6 days (IQR: 2-12) vs 9 days (IQR: 4-16) P = 0.008 and the median number of prescribed daily doses of antimicrobials (6 [IQR: 3-17] vs 10 [IQR: 5-22] P = 0.016) were lower in group A. We estimate a reduction, only in the use of antibiotic, of 1.8 million Euros per year.A telephone call with management advice, immediately after the arrival of blood cultures in the Microbiology Laboratory improves the recognition of sepsis and the use of diagnostic resources and reduces antimicrobial consumption and expenses.
Medicine 10/2015; 94(39):e1454. DOI:10.1097/MD.0000000000001454 · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Streptococcus pneumoniae is an infrequent cause of severe infectious endocarditis (IE). The aim of our study was to describe the epidemiology, clinical and microbiological characteristics, and outcome of a series of cases of S. pneumoniae IE diagnosed in Spain and in a series of cases published since 2000 in the medical literature.We prospectively collected all cases of IE diagnosed in a multicenter cohort of patients from 27 Spanish hospitals (n = 2539). We also performed a systematic review of the literature since 2000 and retrieved all cases with complete clinical data using a pre-established protocol. Predictors of mortality were identified using a logistic regression model.We collected 111 cases of pneumococcal IE: 24 patients from the Spanish cohort and 87 cases from the literature review. Median age was 51 years, and 23 patients (20.7%) were under 15 years. Men accounted for 64% of patients, and infection was community-acquired in 96.4% of cases. The most important underlying conditions were liver disease (27.9%) and immunosuppression (10.8%). A predisposing heart condition was present in only 18 patients (16.2%). Pneumococcal IE affected a native valve in 93.7% of patients. Left-sided endocarditis predominated (aortic valve 53.2% and mitral valve 40.5%). The microbiological diagnosis was obtained from blood cultures in 84.7% of cases. In the Spanish cohort, nonsusceptibility to penicillin was detected in 4.2%. The most common clinical manifestations included fever (71.2%), a new heart murmur (55%), pneumonia (45.9%), meningitis (40.5%), and Austrian syndrome (26.1%). Cardiac surgery was performed in 47.7% of patients. The in-hospital mortality rate was 20.7%. The multivariate analysis revealed the independent risk factors for mortality to be meningitis (OR, 4.3; 95% CI, 1.4-12.9; P < 0.01). Valve surgery was protective (OR, 0.1; 95% CI, 0.04-0.4; P < 0.01).Streptococcus pneumoniae IE is a community-acquired disease that mainly affects native aortic valves. Half of the cases in the present study had concomitant pneumonia, and a considerable number developed meningitis. Mortality was high, mainly in patients with central nervous system (CNS) involvement. Surgery was protective.
Medicine 10/2015; 94(39):e1562. DOI:10.1097/MD.0000000000001562 · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Initiation of empirical antifungal therapy for invasive candidiasis (IC) is usually based on clinical suspicion. Serological biomarkers have not yet been studied as a means of ruling out IC. We evaluated the potential role of two combined biomarkers in stopping unnecessary antifungals in patients at risk of IC in the ICU and in other wards.
This was a prospective observational study including adults starting empirical antifungal treatment for suspected IC, at Gregorio Marañón Hospital, Madrid (Spain). Patients were stratified according to admission department (ICU or other wards) and final diagnosis (no IC or proven or probable IC). Type of candidiasis (candidaemia or deep-seated candidiasis) was also considered. The Candida albicans germ tube antibody (CAGTA) test and the β-d-glucan (BDG) test were performed on serum samples collected by venepuncture on days 0, 3 and 5 after starting empirical antifungal therapy.
Sixty-three ICU patients and 37 non-ICU patients were included. High-risk gastrointestinal surgery and sepsis in non-surgical patients were the main indications for empirical treatment (30% each). Patients had no IC (58%), proven IC (30%) or probable IC (12%). Overall, sensitivity and negative predictive value of the combination of both the CAGTA test and the BDG test were 97% for the entire population. The best performance was observed in ICU patients (sensitivity and negative predictive value of 100%). Among patients without IC, all biomarkers were negative in 31 patients.
Serial determination of CAGTA/BDG during empirical antifungal therapy has a high sensitivity and negative predictive value. If properly confirmed, this strategy could be used to discontinue antifungal treatment in at least 31% of patients as a complementary tool in antifungal stewardship programmes.
Journal of Antimicrobial Chemotherapy 08/2015; DOI:10.1093/jac/dkv241 · 5.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The impact of training programs on the care and maintenance of venous lines (VL) has been assessed mainly in patients admitted to the intensive care unit (ICU). Data on the impact of such programs in a whole general hospital are scarce. The objective of this study was to assess compliance with VL care after an extensive training program aimed at nurses caring for adult ICU and non-ICU patients.
We performed 2 point prevalence studies in a general hospital. A specialized nurse visited all hospitalized adult patients, performed a bedside inspection, and reviewed the nursing records for patients with a VL before and after a 1-year training program. The program included an interactive on-line teaching component and distribution of pocket leaflets and posters with recommendations on VL care.
Data recorded for the first and second prevalence studies were as follows: number of patients visited, 753 vs. 682; total number of patients with ≥ 1 VL implanted on the visit day, 653 (86.7 %) vs 585 (85.8 %); catheters considered unnecessary on the study day, 183 (22.9 %) vs 48 (7.1 %) (p < 0.001); number of catheters with local clinical evidence of infection on the study day, 18 (2.2 %) vs 12 (1.8 %) (p = 0.52); registration of insertion day (42.3 % vs 50.1 %; p = 0.003); and registration of day of dressing change (41.2 % vs 49.1 %; p = 0.003). Maintenance parameters improved more in non-ICU than in ICU patients.
A multidisciplinary teaching program to improve VL care and compliance with recommendations is effective. Point prevalence studies are easy to carry out and effective at demonstrating increases in compliance, mainly in non-ICU patients.
[Show abstract][Hide abstract] ABSTRACT: Binary toxin (BT) has been associated with strains causing more severe Clostridium difficile infection (CDI), such as ribotype 027. Data on the outcome of patients having BT present in ribotypes other than 027 are scarce. Our objective was to investigate the association between BT isolates and outcome of CDI in a non-027 ribotype setting. We prospectively included CDI episodes (January-June 2013 and March-June 2014) from symptomatic patients aged >2 years. Epidemiological and clinical data were recorded. BT genes were detected using multiplex PCR. During the study period, we identified 326 episodes of CDI, of which 319 were available for molecular analysis. Of these, 54 (16·9%) were caused by C. difficile strains with BT. Most (90·7%) isolates with BT were ribotype 078/126. CDI patients with BT-positive strains did not differ from those with BT-negative strains in terms of recurrence (13·0% vs. 15·5%, P = 0·835), treatment failure (0·0% vs. 2·3%, P = 0·594), overall mortality (11·1% vs. 9·1%, P = 0·612), or CDI-related mortality (0·0% vs. 1·9%, P = 0·612). Multivariate regression revealed no association between BT and poor outcome. In conclusion, in a non-027 setting, we found that most BT isolates were 078/126 and were not associated with poor outcome.
Epidemiology and Infection 06/2015; -1:1-6. DOI:10.1017/S095026881500148X · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Reactivation of cytomegalovirus (CMV) has been reported occasionally in immnunocompetent patients in the intensive care unit (ICU). The epidemiology and association of CMV infection with adverse outcome is not well defined in this population. Patients undergoing major heart surgery (MHS) are at a particularly high risk of infection. CMV infection has not been systematically monitored in MSH-ICU patients.
We assessed CMV plasma viremia weekly using a quantitative polymerase chain reaction assay in a prospective cohort of immunocompetent adults admitted to the MHS-ICU for at least 72 hours between October 2012 and May 2013. Risk factors for CMV infection and its potential association with continued hospitalization or death by day 30 (composited endpoint) were assessed using univariate and multivariate logistic regression analyses.
CMV viremia at any level was recorded in 16.5% of patients at a median of 17 days (range, 3-54 days) after admission to the MHS-ICU. Diabetes (adjusted OR, 5.6; 95% CI, 1.8-17.4; p=0.003) and transfusion requirement (>10 units) (adjusted OR, 13.7; 95% CI, 3.9-47.8; p<0.001) were independent risk factors associated with CMV reactivation. Reactivation of CMV at any level was independently associated with the composite endpoint (adjusted OR, 12.1; 95% CI, 2.3-64; p=0.003).
Reactivation of CMV is relatively frequent in immunocompetent patients undergoing MHS and is associated with prolonged hospitalization or death.
PLoS ONE 06/2015; 10(6):e0129447. DOI:10.1371/journal.pone.0129447 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Incidence, prognosis and need of performing blood cultures for anaerobic bacteria are under debate, mainly due to the belief that the presence of anaerobes in blood can be easily suspected on clinical basis. We aimed to assess these three points in a retrospective analysis of a 10-year experience in our tertiary hospital. All episodes of significant anaerobic bacteremia diagnosed from 2003 to 2012 were included. Risk factors for mortality and clinical predictability of anaerobic bacteremia were evaluated in 113 randomly selected episodes. Overall incidence of anaerobic bacteremia was 1.2 episodes/1000 admissions, with no significant changes during the 10-year study period. B. fragilis group (38.1 %) and Clostridium spp. (13.7 %) were the most frequent isolated microorganisms. As for the clinical study, 43.4 % of the patients had a comorbidity classified as ultimately fatal or rapidly fatal according to the McCabe and Jackson scale. Clinical manifestations suggestive of anaerobic involvement were present in only 55 % of the patients. Twenty-eight patients (24.8 %) died during the hospitalization. Independent predictive factors of mortality were a high Charlson's comorbidity index and presentation with septic shock, whereas, an adequate source control of the infection was associated with a better outcome. In our centre, incidence of anaerobic bacteremia remained stable during the last decade. The routine use of anaerobic BCs seems to be adequate, since in about half of the cases anaerobes could not be suspected on clinical bases. Moreover, prompt source control of infection is essential in order to reduce mortality of patients with anaerobic bacteremia.
European Journal of Clinical Microbiology 05/2015; 34(8). DOI:10.1007/s10096-015-2397-7 · 2.67 Impact Factor