Pharmacological study of cefoxitin as an alternative antibiotic therapy to carbapenems in treatment of urinary tract infections due to extended-spectrum-ß-lactamase-producing Escherichia coli.

Cefoxitin could be an alternative to carbapenems in extended-spectrum-beta-lactamase-producing Escherichia coli (ESBL-EC) infections. However, pharmacological and clinical data regarding cefoxitin are limited. Using a recent pharmacological model and the MICs of ESBL-EC collected from pyelonephritis, we determined the probabilities to reach four pharmacological targets: free cefoxitin concentrations above the MIC during 50% and 100% of the administration interval (T>MIC = 50% and T>MIC = 100%, respectively) and free cefoxitin concentrations above 4× MIC during 50% and 100% of the administration interval (T>4MIC = 50% and T>4MIC = 100%, respectively). Cefoxitin could be used to treat ESBL-EC pyelonephritis, but administration modalities should be optimized according to MICs in order to reach pharmacological targets.

Impact of a program combining pre-authorization requirement and post-prescription review of carbapenems: an interrupted time-series analysis.

The objective of this study was to assess the impact on carbapenems use of a program combining pre-authorization requirement and systematic post-prescription review of carbapenems prescriptions. The program was implemented in a 1,230-bed teaching tertiary hospital. Monthly carbapenems consumption was analyzed using a controlled interrupted time-series method and compared to that of vancomycin before and after implementation of the intervention. Compared to the pre-intervention period (14 monthly points), a significant and sustained decrease of carbapenems consumption [1.66 defined daily doses (DDD)/1,000 patient-days; p = 0.048] was observed during the intervention period (12 monthly points), despite an increasing trend in incidence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) isolates (0.02/1,000 patient-days per month; p = 0.093). As expected, vancomycin consumption was unaffected by the intervention. A total of 337 prescriptions were reviewed in the intervention period; most were microbiologically documented (81.3%; ESBL-PE: 39.2%). Three of four (76.6%) carbapenems prescriptions were modified within a median [interquartile range] of 2 [1; 4] days, either after infectious disease physician (IDP) advice (48.4%) or by ward physicians (28.2%). Most changes included de-escalating (52.2%) or reducing the planned duration (22.2%), which resulted in a median duration of treatment of only 3 [2; 7] days. The median length of stay and mortality rate were not influenced by the intervention. This reasonably practicable antimicrobial stewardship program including controlled delivery and systematic reevaluation of carbapenems prescriptions was able to reduce their use in our hospital, despite a rising ESBL-PE incidence.

Outbreak of NDM-1-producing Acinetobacter baumannii in France, January to May 2013.

We report the first outbreak of carbapenem-resistant NDM-1-producing Acinetobacter baumannii in Europe, in a French intensive-care unit in January to May 2013. The index patient was transferred from Algeria and led to the infection/colonisation of five additional patients. Concurrently, another imported case from Algeria was identified. The seven isolates were genetically indistinguishable, belonging to ST85. The bla(NDM-1) carbapenemase gene was part of the chromosomally located composite transposon Tn125. This report underscores the growing concern about the spread of NDM-1-producing A. baumannii in Europe.

Differential time to positivity of central and peripheral blood cultures is inaccurate for the diagnosis of Staphylococcus aureus long-term catheter-related sepsis.

OBJECTIVES: Differential time to positivity of cultures of blood drawn simultaneously from central venous catheter and peripheral sites is widely used to diagnose catheter-related bloodstream infections without removing the catheter. However, the accuracy of this technique for some pathogens, such as Staphylococcus aureus, is debated in routine practice. METHODS: In a 320-bed reference cancer centre, the charts of patients with at least one blood culture positive for S. aureus among paired blood cultures drawn over a six-year period were studied retrospectively. Microbiological data were extracted from the prospectively compiled database of the microbiology unit. Data concerning the 149 patients included were reviewed retrospectively by independent physicians blinded to the absolute and differential times to positivity, in order to establish or refute the diagnosis of catheter-related sepsis. Due to missing data, 48 charts were excluded, so 101 cases were actually analysed. The diagnosis was established in 62 cases, refuted in 15 cases and inconclusive in the remaining 24 cases. RESULTS: For the 64 patients with both central and peripheral positive blood cultures, the differential positivity time was significantly greater for patients with catheter-related bloodstream infections due to S. aureus (P<0.02). However, because of the high number of false-negative cases, the classic cut-off limit of 120 min showed 100% specificity but only 42% sensitivity for the diagnosis of catheter-related bloodstream infection due to S. aureus. CONCLUSIONS: These results strongly suggest that despite its high specificity, the differential time to positivity may not be reliable to rule out catheter-related bloodstream infection due to S. aureus.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) infections: are carbapenem alternatives achievable in daily practice?

OBJECTIVES: To avoid the use of carbapenems, alternatives such as cephamycin, piperacillin-tazobactam, and others are suggested for the treatment of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) infections. The aim of this study was to evaluate the frequency and the feasibility of antimicrobial de-escalation for ESBL-PE-related infections. METHODS: A prospective observational, bi centric cohort study was conducted. All patients with ESBL-PE infections were included. De-escalation was systematically suggested if patients were clinically stable and the isolate was susceptible to possible alternatives. RESULTS: Seventy-nine patients were included: 36 (45.6%) were children, 27 (34.1%) were hospitalized in intensive care units, and 37 (47%) were immunocompromised. Urinary tract infections, pneumonia, and catheter-related bloodstream infections accounted for 45.6%, 19%, and 10%, respectively, of the cohort. Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae were the three most frequent causative organisms isolated. On day 5, 47 (59.2%) of the patients were still receiving carbapenems. Antimicrobial resistance (44.7%), infection relapse (26.9%), and clinical instability (19.2%) were the most important reasons for not prescribing alternatives. E. coli-related infections appeared to be a protective factor against maintaining the carbapenem prescription (odds ratio 0.11, 95% confidence interval 0.041-0.324; p=0.0013). CONCLUSIONS: In clinical practice, less than 50% of patients with ESBL-PE-related infections were de-escalated after empirical treatment with carbapenems.

Distribution and antimicrobial susceptibility of bacteria from adults with community-acquired pneumonia or complicated skin and soft tissue infections in France: the nationwide French PREMIUM study.

The empirical therapy of community-acquired pneumonia (CAP) and complicated skin and soft tissue infections (cSSTIs) must be based on updated bacterial distribution and susceptibility data. A nationwide study consecutively collected 1288 isolates from CAP (n=467) and cSSTIs (n=821) from 18 French hospitals between 2012 and 2013. The MIC values of commonly used antimicrobial agents, including ceftaroline, were determined. Bacterial distribution featured Pneumococcus, Haemophilus influenzae, and Staphylococcus aureus for CAPs and S. aureus, ß-hemolytic streptococci and Enterobacteriaceae for cSSTIs. Antimicrobial susceptibility testing indicated i) the sustained third-generation cephalosporins and levofloxacin activity against pneumococci and H. influenzae, ii) no methicillin-resistant Staphylococcus aureus emergence among respiratory pathogens, iii) the high in vitro activity of ceftaroline against staphylococci from cSSTIs (98.7% susceptibility), and iv) the worrisome decreasing fluoroquinolone and third-generation cephalosporin susceptibilities among Enterobacteriaceae. This laboratory-based survey depicts a contrasting situation and supports the scoring of patients for the resistant pathogen risk before empirical therapy.

Prevalence and pathogenicity of binary toxin-positive Clostridium difficile strains that do not produce toxins A and B.

Clostridium difficile causes antibiotic-associated diarrhoea and pseudomembranous colitis. The main virulence factors of C. difficile are the toxins A (TcdA) and B (TcdB). A third toxin, called binary toxin (CDT), can be detected in 17% to 23% of strains, but its role in human disease has not been clearly defined. We report six independent cases of patients with diarrhoea suspected of having C. difficile infection due to strains from toxinotype XI/PCR ribotype 033 or 033-like, an unusual toxinotype/PCR ribotype positive for CDT but negative for TcdA and TcdB. Four patients were considered truly infected by clinicians and were specifically treated with oral metronidazole. One of the cases was identified during a prevalence study of A(-)B(-)CDT(+) strains. In this study, we screened a French collection of 220 nontoxigenic strains and found only one (0.5%) toxinotype XI/PCR ribotype 033 or 033-like strain. The description of such strains raises the question of the role of binary toxin as a virulence factor and could have implications for laboratory diagnostics that currently rarely include testing for binary toxin.

Intravascular catheter-related bloodstream infection caused by Abiotrophia defectiva in a neutropenic child.

Bacteraemia and endocarditis are the most frequently reported clinical infections due to Abiotrophia defectiva species. This species has been rarely implicated in infections in neutropenic patients. We report a rare case of long-term venous catheter-related infection caused by A. defectiva that occurred in a febrile child who had neutropenia and Langerhans' cell histiocytosis.