Dominique Navas

Outbreak caused by Proteus mirabilis isolates producing weakly expressed TEM-derived extended-spectrum β-lactamase in spinal cord injury patients with recurrent bacteriuria.

Abstract We performed a retrospective extended-spectrum β-lactamase (ESBL) molecular characterization of Proteus mirabilis isolates recovered from urine of spinal cord injury patients. A incorrectly detected TEM-24-producing clone and a new weakly expressed TEM-derived ESBL were discovered. In such patients, ESBL detection in daily practice should be improved by systematic use of a synergy test in strains of P. mirabilis resistant to penicillins.

Good practice in antibiotic use: what about linezolid in a French university hospital?

Objective Linezolid represents an important advance in the treatment of methicillinresistant staphylococci. Its effectiveness should be preserved by appropriate uses. The aims of this survey were to describe the use of linezolid in clinical practice and to assess its overall safety. Methods This retrospective observational study included patients treated with linezolid in 2008 in all departments at the CHU Nantes. A data-collection card was completed using the patients’ medical files. Results A total of 179 patients from 23 different departments were included. Fifty-four per cent of indications were outside the Marketing Authorization criteria, and were mainly osteoarticular infections and septicaemia (22% and 8% of total prescriptions, respectively). Inefficacy of first-line antibiotic treatment (23%) and alterations in renal function (23%) were the main reasons for using linezolid, which was prescribed as a first-line therapy in 28% of patients. Fifty-three per cent of infections were documented microbiologically, of which 58% were due to a methicillin-resistant Staphylococcus. Conclusions Linezolid seems to be a possible therapeutic strategy in case of multiresistant bacteria and/or complex clinical situations. Because many prescriptions fall outside the Marketing Authorization criteria, this study highlights the need to have clinical data available for such situations.

Tigecycline option for the treatment of bone and joint infections caused by multidrug-resistant Staphylococcus epidermidis

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 3 aout 2011

Use of broad-spectrum antibiotics in French Eds: different trends for third-generation cephalosporins and fluoroquinolones.

Objectives Third-generation cephalosporins and fluoroquinolones are particularly prone to promoting bacterial resistance. Their use in Emergency Departments (EDs) is poorly known. Our objectives were to assess the use of antibacterial agents in French EDs. Methods This study is a retrospective study of antibiotics delivered to the adult units of 11 EDs of French academic centres in 2012, and to six of these EDs between 2009 and 2012. Results The total antibiotic use was 66.4 defined daily doses (DDD)/1000 ED visits in 2012, and it increased between 2009 and 2012 (yearly estimate, +1.8±0.9 DDD/1000 ED visits, P=0.048). The 3GC-FQ class, which grouped third-generation cephalosporins and fluoroquinolones, accounted for 39.2% of the total antibiotic use, and the use of this class of antibiotics was highly variable among EDs (range, 31.6–49.5% of total antibiotic use). The aminopenicillin and &bgr;-lactamase inhibitor/3GC-FQ ratio varied among EDs [median (range), 0.91 (0.52–1.25)]. Between 2009 and 2012, there was a significant decrease in the use of the 3GC-FQ class (yearly estimate, −0.8±0.4% of total antibiotic use), antipneumococcal fluoroquinolones (−0.8±0.3%) and other fluoroquinolones (−0.9%±0.3%), and there was a significant increase in the use of third-generation cephalosporins (+0.7±0.3%), aminoglycosides (+0.4±0.1%), imidazole derivatives (+0.4±0.1%) and lincosamides (+0.1±0.0%). Conclusion Fluoroquinolones and third-generation cephalosporins are widely used in the ED. Their use is highly variable among EDs. Third-generation cephalosporins were increasingly used between 2009 and 2012, whereas the use of fluoroquinolones decreased. Reduced use of cephalosporins in the ED, without increasing fluoroquinolone use, should be aimed at through antibiotic stewardship programs.

Stability and Compatibility of Antibiotics in Peritoneal Dialysis Solutions Applied to Automated Peritoneal Dialysis in The Pediatric Population

♦ Objectives: Assess the stability of several antibiotics in peritoneal dialysis (PD) solutions under common conditions of use in pediatrics, particularly in automated PD. ♦ Methods: Amoxicillin, cefazolin, cefepime, ceftazidime, imipenem, cotrimoxazole, tobramycin, vancomycin, and the association of ceftazidime + vancomycin and ceftazidime + tobramycin, were tested in 3 different PD solutions: bicarbonate/lactate solution with 2 glucose concentrations (Physioneal 1.36 and 3.86%; Baxter Healthcare Corporation, Deerfield, IL, USA) and an icodextrin-containing solution (Extraneal; Baxter Healthcare Corporation, Deerfield, IL, USA). Concentrations were those recommended in guidelines for the treatment of peritonitis in pediatrics. Physioneal bags were incubated at 37°C for 24 hours, whereas Extraneal bags were stored 12 hours at room temperature (22 ± 2°C) and then 12 hours at 37°C. Drug concentrations were determined using high performance liquid chromatography (HPLC). Each measure was taken in triplicate. Stability of antibiotics was defined as less than 10% degradation of the drug over time. ♦ Results: Cefazolin, cotrimoxazole, tobramycin, and vancomycin were stable under studied conditions. Ceftazidime was stable 24 hours in icodextrin, 12 hours in Physioneal 1.36% and 6 hours in Physioneal 3.86%. The association of tobramycin or vancomycin did not influence the stability of ceftazidime. Cefepime and amoxicillin were stable 6 h, 4 h, and 8 h in Physioneal 1.36%, 3.86% and Extraneal, respectively. The stability of imipenem was very low: 2 h in Physioneal and 6 h in Extraneal. Moreover, an increasingly yellow coloration was observed with the use of imipenem, whereas no color change or precipitation occurred in other bags. ♦ Conclusion: Cefazolin, tobramycin, cotrimoxazole, and vancomycin are stable in PD solutions up to 24 hours and can be administered in the PD bag for the treatment of peritonitis, even in automated PD under studied conditions. However, amoxicillin, cefepime, ceftazidime, and imipenem must be used with caution due to their lack of stability.

Gram-negative prosthetic joint infections managed according to a multidisciplinary standardized approach: risk factors for failure and outcome with and without fluoroquinolones

OBJECTIVES To describe the outcome and risk factors for treatment failure of 76 Gram-negative bacilli (GNB) prosthetic joint infections (PJIs) managed with a curative intent according to a standardized protocol derived from published guidelines. METHODS We analysed data from all the cases of GNB-PJI treated surgically over an 8 year period. Treatment failure was defined as persistence or recurrence of PJI signs during follow-up, resulting in additional surgery and/or antibiotic administration or death. RESULTS Treatment failure within the follow-up period (median = 2.6 years) was observed in 16 of 76 (21.1%) patients. The failure rate was similar whether the patients were treated with fluoroquinolones in the whole cohort (22.4% versus 16.7%, P = 0.75) and after stratification according to the surgical procedure. The low failure rate observed in patients not receiving fluoroquinolones might be explained by the standardized attitude of maintaining intravenous β-lactams throughout treatment duration (median = 90 days). In multivariate analysis, C-reactive protein level ≥175 mg/L was significantly associated with treatment failure (adjusted HR = 7.75, 95% CI = 2.66-22.59, P < 0.0001). CONCLUSIONS Management according to standardized procedures may improve the prognosis of GNB-PJI. Intravenous β-lactams, continued for 3 months, should be considered an effective alternative to fluoroquinolones.

Large discrepancies in linezolid use between French teaching hospitals: A comment on “Antimicrobial stewardship and linezolid”

We read with great interest in a recent issue of the International Journal of Clinical Pharmacy the article by Guillard et al. [1]. In this study, they stated that linezolid was used inappropriately in 40 % of cases in their hospital. We would like to discuss their results in light with a recent observational prospective study that we led in two large teaching hospitals: Nantes University Hospital (Hôtel-Dieu and Mother and Children’s sites) and Angers University Hospital, during a 6-month period in 2012. Each hospital included intensive care, dermatology, hematology, emergency, infectious disease (ID), pediatric, surgical and gynecology-obstetrics units, allowing comparison to Caen data. All prescriptions of linezolid were included. A datacollection card was created and completed using the patients’ medical files, prescriptions collected by the pharmacy and patients’ computerized files. Major results are shown in Table 1. Although linezolid use was mostly offlabel in each hospital, large discrepancies can be observed. In one hand, at Angers University Hospital, linezolid prescriptions concerned a majority of patients from intensive care unit (46 %). The treatment was mainly prescribed after microbiological documentation (78.6 %) and concerned staphylococci resistant to methicillin in 70 % of cases. On the other hand, at Nantes University Hospital, linezolid was prescribed in majority in medicine units (56 %), with no microbiological data in half of the cases. When these data were available, staphylococci resistant to methicillin was found in 33 % of biological samples. Concerning ventilator-associated pneumonia (VAP), Wunderink et al. [2] have shown that linezolid was non inferior and statistically superior to vancomycin in end-oftreatment clinical outcome as well as in microbiologic outcome at end of treatment and at end of study. Moreover, it is now well established that linezolid pulmonary diffusion is higher than vancomycin diffusion [3]. At Nantes University hospital, since Zephyr study publication, linezolid was prescribed in first line therapy for VAP. Compared to Nantes retrospective study performed in 2008 [4], this matter of fact could explain the increased prescription of linezolid in this indication (21.4 vs. 16.2 % in 2008). Moreover, de-escalation was systematically initiated after microbiological documentation. This finding underlines the necessity of rapid microbiological results (i.e. MRSA or not). We also observed an empiric use of linezolid at Nantes hematology unit especially for catheter-related infection. In this unit, the ecological environment reveals mostly coagulase-negative staphylococci resistant to methicillin. Therefore, oral route of linezolid presents a real advantage, especially after the removal of a central venous catheter. Linezolid pediatric use has been a special concern at Nantes University Hospital for many years to treat lung diseases or catheter-related infections [4]. Good pulmonary & G. G. Aubin aubin.guillaume@yahoo.com; guillaume.aubin@chunantes.fr