[Show abstract][Hide abstract] ABSTRACT: Objective:
Our objective was to evaluate the impact of low versus borderline MIC of piperacillin/tazobactam on the clinical outcomes of patients with bacteraemia caused by Enterobacteriaceae who were treated with that antimicrobial.
Patients and methods:
A prospective observational multicentre cohort study was conducted in 13 Spanish university hospitals. Patients >17 years old with bacteraemia due to Enterobacteriaceae who received empirical piperacillin/tazobactam treatment for at least 48 h were included. Outcome variables were clinical response at day 21, clinical response at end of treatment with piperacillin/tazobactam and all-cause 30 day mortality. Univariate and multivariate logistic regression analyses were performed.
Overall, 275 patients were included in the analysis; 248 (90.2%) in the low MIC group (≤4 mg/L) and 27 (9.8%) in the borderline MIC group (8-16 mg/L). The biliary tract was the most common source of infection (48.4%) and Escherichia coli was the most frequent pathogen (63.3%). Crude 30 day mortality rates were 10.5% and 11.1% for the low MIC group and the borderline MIC group, respectively (relative risk = 1.06, 95% CI = 0.34-3.27, P = 1). Multivariate analysis of failure at day 21 and at end of treatment with piperacillin/tazobactam and 30 day mortality showed no trend towards increased clinical failure or mortality with borderline MICs (OR = 0.96, 95% CI = 0.18-4.88, P = 0.96; OR = 0.47, 95% CI = 0.10-2.26, P = 0.35; OR = 1.48, 95% CI = 0.33-6.68, P = 0.6).
We did not find that higher piperacillin/tazobactam MIC within the susceptible or intermediate susceptibility range had a significant influence on the outcome for patients with bacteraemia due to Enterobacteriaceae.
Journal of Antimicrobial Chemotherapy 11/2015; DOI:10.1093/jac/dkv362 · 5.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Most available information on carbapenemase-producing Enterobacteriaceae (CPE) is usually associated with specific types of infection or patient or with descriptions of outbreaks. The aim of this study was to comprehensively analyse the clinical epidemiology, clinical features and outcomes of colonisation and infections due to CPE in Spain.
A multicentre prospective cohort study was carried out in 34 Spanish hospitals from February to May 2013. All new patients testing positive for CPE in clinical samples were included. Logistic regression was used to identify predictors of mortality.
Overall, 245 cases were included. The most frequent organism was Klebsiella pneumoniae (74%) and the carbapenemases belonged to the OXA-48 (74%), metallo-β-lactamase (MBL) (24%) and KPC (2%) groups. Acquisition was nosocomial in 145 cases (60%) and health care-associated (HCA) in 91 (37%); 42% of the latter were nursing home residents, in whom OXA-48-producing K. pneumoniae ST405 predominated. MBLs and OXA-48 predominated in ICU and medical patients, respectively. Overall, 67% of patients had infections. The most frequent infections identified in this study were urinary tract (43%) and skin structure (21%) infections, and 10% of infections were bacteraemic. Crude mortality was 20%. Inappropriate antibiotic therapy was independently associated with an increased risk of death (OR=3.30; 95% CI: 1.34-8.11).
We found some differences in the epidemiology of CPE depending on the type of carbapenemase produced. Although a low proportion of CPE infections were bacteraemic, active antibiotic therapy was a protective factor for reducing mortality.
The Journal of infection 11/2015; DOI:10.1016/j.jinf.2015.10.008 · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives The objective of this study was to analyse whether there is an association between reduced susceptibility to biocides in Acinetobacter baumannii and (i) antimicrobial resistance (co-resistance), (ii) prevalent (epidemic) clones, (iii) changes in the fitness or (iv) expression of genes related to efflux pumps and porins.
Methods Susceptibility to biocides and antimicrobials was determined in 49 clonally unrelated isolates of A. baumannii. Biological cost, in terms of mean generation time, was determined by spectrophotometry. Quantitative real-time RT–PCR was used to determine the relative expression of genes encoding several efflux pumps and porins.
Results Reduced susceptibility to chlorhexidine digluconate, benzalkonium chloride and Irgasan® was associated with resistance to aminoglycosides, tetracycline and ciprofloxacin (P < 0.05). The MICs of carbapenems, aminoglycosides, doxycycline and ciprofloxacin for isolate Ab70 (epidemic clone) exposed to these biocides increased by ≥2 dilutions. Reduced susceptibility to Orsan® was more frequent among prevalent clones than non-prevalent clones (P < 0.05). Mean generation times for Ab70 before and after exposure to benzalkonium chloride were 57.8 and 78.1 min, respectively (P = 0.02). Relative expression of abeS and adeB was increased in Ab46 and Ab70 after exposure to chlorhexidine digluconate, but was decreased for ompA and carO after exposure to Irgasan®.
Conclusions Reduced susceptibility to biocides is associated with co-resistance to carbapenems, aminoglycosides, tetracycline and ciprofloxacin. Reduced susceptibility to Orsan® may be a marker of prevalent clones. Acquisition of reduced susceptibility to benzalkonium chloride has a biological cost. Exposure to biocides affects the relative expression of genes related to some efflux pump genes (increased expression) or porins (reduced expression).
Journal of Antimicrobial Chemotherapy 09/2015; · 5.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While infection control (IC) activities are facing new challenges, dedication of resources to IC are too frequently insufficient. Heterogeneity of resources among centres and countries are huge, a fact that at least partly explains the differences in the results obtained. In this article, we review and discuss the available recommendations on minimum requirements in IC related to organisational aspect, IC staffing and their training, ward staffing, structural issues, and microbiological support. A professional-based consensus about the minimum requirement for IC in European centres based on present challenges and society demands is needed.
Clinical Microbiology and Infection 08/2015; DOI:10.1016/j.cmi.2015.08.025 · 5.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Minimum inhibitory concentrations (MICs) have been used to denote susceptibility in vitro and to guide clinical practice. Our objective was to investigate whether the clinical outcomes of patients with invasive infections caused by Enterobacteriaceae treated with β-lactams were worse among those with a borderline susceptible MIC according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints than those with a lower MIC. Studies reporting MICs of β-lactams used for infection and clinical outcome were identified through a systematic literature search. Isolates were classified as "highly susceptible" (HS, those with MIC ≤1 dilution below the susceptibility breakpoint for the antibiotic used) and "borderline susceptible" (BS, isolates with MIC at the susceptibility breakpoint) using EUCAST criteria. Clinical outcomes were clinical cure and 30-day mortality. A meta-analysis was performed. Twenty-four studies were included. Taking all antimicrobials into consideration, the meta-analysis revealed no significant difference in mortality between HS and BS [odds ratio (OR) = 0.58; 95 % confidence interval (CI): 0.28-1.21; p = 0.148). However, HS was associated with higher cure rates than BS (OR = 3.73; 95 % CI: 1.76-7.92; p < 0.001). For specific antibiotics, no differences were found except for piperacillin-tazobactam, where higher clinical cure and lower mortality rates were seen with HS compared with BS isolates (OR = 3.17; 95 % CI: 1.09-9.20; p = 0.034 and OR = 0.12; 95 % CI: 0.02-0.92; p = 0.042; respectively). Our data suggest that HS isolates are associated with higher clinical cure rates than BS isolates according to EUCAST susceptibility breakpoints; this effect was evident only for piperacillin-tazobactam, probably because of limited numbers.
European Journal of Clinical Microbiology 06/2015; 34(9). DOI:10.1007/s10096-015-2408-8 · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introducción y objetivos: El objetivo del estudio es validar la capacidad
de predicción de mortalidad en distintos tiempos de las definiciones
de infección por Clostridium difficile (ICD) grave de la SHEA- IDSA
y de la ESCMID.
Material y métodos: Estudio observacional y retrospectivo de los
casos consecutivos de ICD ocurridos en un hospital universitario con
950 camas entre marzo de 2008 y julio de 2014. Se han considerado
como casos de ICD aquellos pacientes con un cuadro clínico compatible
y resultado microbiológico positivo en heces (detección de toxina
por EIA o detección de C. difficile toxigénico mediante PCR). Los
datos han sido extraídos revisando la historia clínica de todos los
casos. Se ha analizado si las definiciones de ICD grave de la SHEA- IDSA
(aumento ≥ 50% en creatinemia basal, leucocitosis > 15.000 cel/µL,
hipotensión o presencia de complicaciones: íleo paralitico, edema de
pared, dilatación colónica > 6 cm) y de la ESCMID (fiebre > 38,5 o
C, inestabilidad hemodinámica, necesidad de ventilación mecánica, aumento
≥ 50% en creatinemia basal, leucocitosis > 15.000 cel/µL o > 25%
de neutrófilos, albumina < 3,0 mg/dl, colitis pseudomenbranosa en la
colonoscopia, ácido láctico > 5 mM/L y complicaciones (ídem a SHEA
más peritonismo y rarefacción de la grasa colónica) eran predictores
de mortalidad en distintos tiempos de seguimiento. Se realizo el
análisis estadístico con el programa SPSS 15.0. Se incluyeron 150 casos,
de edad media 73 años, y 44% hombres; 65 casos (43%) presentaban
un índice de Charlson > 2 y 114 (66%) se clasificaron como de adquisición
nosocomial. La mortalidad fue del 8%, 20,7%, 28,7% y 34,7% a
los 7, 30, 90 días y un año, respectivamente. La asociación entre los
criterios de SHEA-IDSA y ESCMID y mortalidad se muestra en la tabla.
Controlando por edad y Charlson, la OR ajustada (IC95%) para la mortalidad
del criterio de gravedad de SHEA-IDSA fue de 1,88 (0,77-4,56),
1,66 (0,72-3,83) y 1,38 (0,60-3,16) para mortalidad en los días 30, 90
y 1 año; para el criterio de gravedad de ESCMID fueron fue de 1,96
(0,72-5,34), 2,34 (0,94-5,82) y 2,07 (0,89-4,81) para mortalidad en los
días 30, 90 y 1 año.
Conclusiones: La presencia de criterios de la SHEA-IDSA y ESCMID se
asociaron con un mayor riesgo de muerte a partir de los 90 días en el
análisis crudo; los criterios de la SHEA-IDSA además fueron predictores
de la mortalidad en el día 30. Sin embargo, ninguno de ellos fue
predictor de mortalidad controlando por variables clave.
XIX Congreso Sociedad Española de Enfermedades Infecciosas, Sevilla, España; 05/2015
[Show abstract][Hide abstract] ABSTRACT: The spread of multidrug-resistant Enterobacteriaceae related to the production of
extended-spectrum β-lactamases and carbapenemases is a serious public health
problem worldwide. Microbiological diagnosis and therapy of these infections are
challenging and controversial. Clinically relevant questions were selected and
the literature was reviewed for each of them. The information from the selected
articles was extracted and recommendations were provided and graded according to
the strength of the recommendations and quality of the evidence. The document was
opened to comments from the members from the Spanish Society of Infectious
Diseases and Clinical Microbiology, which were considered for inclusion in the
final version. Evidence-based recommendations are provided for the use of
microbiological techniques for the detection of extended-spectrum β-lactamases
and carbapenemases in Enterobacteriaceae, and for antibiotic therapy for
invasive/severe infections caused by these organisms. The absence of randomised
controlled trials is noteworthy; thus, recommendations are mainly based on
observational studies (that have important methodological limitations),
pharmacokinetic and pharmacodynamics models, and data from animal studies.
Additionally, areas for future research were identified.
[Show abstract][Hide abstract] ABSTRACT: Background and objectives: Among patients with bacteraemia due to S. aureus, persistence of positive blood cultures after 2-3 days of active therapy (persistent bacteraemia or PB) is considered a marker for complicated SAB. PB may be related bacterial determinants, hosts' features, or clinical management. The aim of this analysis is to investigate the hosts' and management variables associated to PB despite an adequate targeted therapy and early source control. Methods: Prospective cohort of SAB from 12 tertiary Spanish hospitals between 2008 and 2011. Two analyses were performed; (a) including only patients in whom follow-up blood cultures (FUBC) were performed 48-72 hours after start of active therapy; and (b) including all patients with SAB (those without FUBC were considered not to have PB). Those cases who died before 72 hours and those receiving palliative care for terminal conditions were excluded. Univariate analyses were performed by Chi-square test, and multivariate analyses by logistic regression. Results: 292 of the 496 (58.9%) included patients had FUBC; of them, 91 (31.2%) had PB. In the univariate analysis, PB was associated with high 14-day (RR 1.74; 95% CI 0.93-3.25, p= 0.08) and 30-day crude mortality (RR 1.77; 95% CI 1.03-3.01, p= 0.04). The variables associated with PB in multivariate analysis were a Pitt score >2 (OR 2.69; 95% CI: 1.13-6.37, p=0.03), skin and soft tissue infection as a source (OR 2.75; 95% CI: 0.87-8.65, p=0.08), and presence of septic metastasis (OR 3.45; 95% CI: 1.00-11.83, p=0.05). MRSA, early active therapy, and early source control were not associated. Among the whole series of patients with SAB (n=496), the variables associated with PB in multivariate analysis were a Pitt score >2 (OR 3.43; 95% CI: 1.62-7.27, p=0.001), skin and soft tissue infection as a source (OR 3.76; 95% CI: 1.35-10.46, p=0.01), presence of septic metastasis (OR 2.42; 95% CI: 0.90-6.46, p=0.08), and endocarditis diagnosis during the course of the SAB (OR 2.60; 95% CI: 0.99-6.84, p=0.05). Conclusion: The frequency of PB was high. The clinical variables associated with PB at the diagnosis were the severity of illness assessed by Pitt score and the skin and soft tissue source. The presence or development of septic metastasis during the bacteraemia and infectious endocarditis were also associated. It is crucial to performance FUBC because the presence of PB has clinical management and prognosis implications.
25th European Congress of Clinical Microbriology and Infectious Diseases, Copenhagen, Denmark; 04/2015
[Show abstract][Hide abstract] ABSTRACT: In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies, and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. The present article summarises the views of the B-debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the health-care setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance.