David Boutoille

In Vivo Efficacy of Continuous Infusion versus Intermittent Dosing of Linezolid Compared to Vancomycin in a Methicillin-Resistant Staphylococcus aureus Rabbit Endocarditis Model

ABSTRACT Linezolid is the first drug issued from the oxazolidinones, a novel class of antimicrobial agents with potent activity against gram-positive pathogens. A rabbit endocarditis model was used to compare the in vivo activities of different linezolid regimens mimicking intermittent dosing of 10 mg/kg of body weight every 12 h for 5 days or continuous (constant-rate) infusion of a daily dose of 20 mg/kg (for 5 days) or 40 mg/kg (for 3 and 5 days) and the activities of intermittent dosing and continuous infusion of vancomycin (for 5 days). The in vivo activities of these regimens were tested against three strains of methicillin-resistant Staphylococcus aureus. A human-like pharmacokinetic simulation was used for linezolid in order to improve the extrapolation of the results to human therapy. All linezolid regimens significantly reduced the numbers of S. aureus cells in aortic valve vegetations compared to the numbers in the control groups. Linezolid intermittent dosing had an in vivo bacteriostatic effect. Switching from intermittent dosing to continuous infusion (at the same dose) led to in vivo bactericidal activity, with a decrease of at least 3 log10 CFU/g of vegetation compared to the counts for the controls. After 5 days of treatment, continuous infusion of linezolid (corresponding to a daily dose of 40 mg/kg in humans) seemed to be at least as effective as vancomycin against the three strains. No resistant variant was isolated from the vegetations during any of the treatments. These data suggest that continuous infusion of linezolid could be an appropriate alternative to the use of glycopeptides for the treatment of severe methicillin-resistant S. aureus infections.

Significance of Propionibacterium acnes-positive samples in spinal instrumentation.

Study Design. A retrospective study about Propionibacterium acnes infections after Cotrel–Dubousset (CD) instrumentation. Objectives. To analyze the significance of P. acnes-positive deep samples after CD. Summary of Background Data. The diagnosis of spinal infections to P. acnes after CD is difficult. Methods. Patients with revision surgery and at least 1 P. acnes-positive deep sample, between 2000 and 2006 were included. Group A had 1 revision surgery and group B had 2 successive revision surgeries, with P. acnes-positive deep samples. Group A was divided into 2 subgroups according to the peroperative macroscopic aspect, subgroup A1 with septic tissues, subgroup A2 without septic tissues. The biologic characteristics of the patients and the surgical and medical treatments were assessed. Results. Sixty-eight patients were included, 60 in group A (A1 = 33, A2 = 27) and 8 in group B. Group A: 26 patients had 1 or 2 P. acnes-positive samples and 34 had at least 3 P. acnes-positive samples. Histology showed chronic inflammatory changes. C-reactive protein value median rate was 42 (A1) and 5 mg/L (A2). Twenty-two patients had a complete implant removal (14 with antibiotics, A1 = 12, A2 = 2). Nine patients had a total implant replacement (7 with antibiotics). Twenty-two patients had a partial implant removal (17 with antibiotics, A1 = 5, A2 = 12). Seven A1 patients had an irrigation and debridement (6 with antibiotics). The evolution was favorable for 28 patients. Seven patients had a documented sepsis. Group B: during the first revision, 8 patients had a partial implant removal (2 with antibiotics); during the second revision, all patients received antibiotics 4 of whom had a total implant removal. The long-term evolution was favorable for 6 patients. Conclusion. P. acnes infection of spinal instrumentation is difficult to diagnose. Results of at least 4 deep sample cultures, histology, and C-reactive protein values must be compared to the peroperative macroscopic aspect.

First Report of a Hip Prosthetic and Joint Infection Caused by Lactococcus garvieae in a Woman Fishmonger

ABSTRACT We describe the first case of hip prosthetic infection due to Lactococcus garvieae. The patient, a 71-year-old woman fishmonger, developed a hip infection 7 years after total hip arthroplasty. The origin of infection was possibly due to the manipulation or intake of seafood or fish contaminated with Lactococcus garvieae.

Salvage treatment of methicillin-resistant staphylococcal endocarditis with ceftaroline: a multicentre observational study

There are scarce data on the dosing of antibiotics in patients undergoing renal replacement therapy. 7 Our data suggest that extended dialysis eliminates colistin effectively and to a larger extent than regular intermittent outpatient haemodialysis. This is in line with recent data on two critically ill patients undergoing a modern type of intermittent dialysis (1.6 m 2 polymethylacrylate membrane, blood/dialysate flow 300/500 mL/min, duration 4 h), in whom a CMS dialyser clearance of 90 mL/min was reported. 8 Li et al. 9 described a dialyser clearance of 11.9 mL/min for colistin and 11.2 mL/min for CMS in one critically ill patient undergoing continuous venovenous haemodiafiltration, which due to its continuous mode would remove approximately the same amount of the drug. Lastly, dialyser clearance in five patients receiving continuous venovenous haemodiafiltration was recently reported to be 72 mL/min for colistin and 32 mL/min for CMS. 10 Thus, dosing colistin as recommended during regular haemodi-alysis is inadequate and would result in a significant under-dosing, which could be associated with a substantial risk, especially in critically ill patients in the ICU. A dose of 3 million units every 8 h seems to be adequate for patients undergoing daily extended dialysis for 9 h a day with a high flux 1.3 m 2 dialyser. This dose of 9 million units per day did not lead to accumulation of the drug. 2 Couet W, Gregoire N, Gobin P et al. Pharmacokinetics of colistin and colistimethate sodium after a single 80-mg intravenous dose of CMS in young healthy volunteers. 4 Curitis JR, Eastwood JB. Colistin sulphomethate sodium administration in the presence of severe renal failure and during haemodialysis and peritoneal dialysis. 5 Gobin P, Lemaitre F, Marchand S et al. Assay of colistin and colistin methanesulfonate in plasma and urine by liquid chromatography-tandem mass spectrometry. 6 Bode-Boger SM, Schopp B, Troger U et al. Intravenous colistin in a patient with serious burns and borderline syndrome: the benefits of therapeutic drug monitoring. 7 Scoville BA, Mueller BA. Medication dosing in critically ill patients with acute kidney injury treated with renal replacement therapy. Nation RL et al. Pharmacokinetics of colistin methanesulfonate and colistin in a critically ill patient receiving continuous venovenous hemodiafiltration. 10 Karvanen M, Plachouras D, Friberg LE et al. Colistin methanesulfonate and colistin pharmacokinetics in critically ill patients receiving continuous venovenous hemodiafiltration. Sir, b-Lactam agents have been the main antibacterial agents used for the treatment of …

Efficacy of ceftolozane in a murine model of Pseudomonas aeruginosa acute pneumonia: in vivo antimicrobial activity and impact on host inflammatory response

OBJECTIVES To assess the activity of ceftolozane, a novel oxyimino-cephalosporin, in comparison with ceftazidime and piperacillin/tazobactam against a multidrug-resistant Pseudomonas aeruginosa strain using a murine model of pneumonia. METHODS Quantitative bacteriology, survival, histological examination, myeloperoxidase activity, proinflammatory cytokine levels in lungs and endothelial permeability were evaluated to determine the effects of ceftolozane and comparators on P. aeruginosa-induced pneumonia. RESULTS After 48 h of treatment, ceftolozane reduced the bacterial load by 3-4 log(10) cfu/g of lung. Systemic dissemination of the pulmonary infection and development of lung damage were inhibited in all β-lactam-treated animals. P. aeruginosa-induced pneumonia led to elevated concentrations of tumour necrosis factor-α, interleukin (IL)-1β and macrophage inflammatory protein (MIP)-2 in the lungs. While the levels of proinflammatory cytokines decreased following ceftazidime and piperacillin/tazobactam therapy, ceftolozane exhibited increased concentrations of IL-1β and MIP-2 after 24 h of infection, resulted in significantly increased levels of recruited neutrophils within the infected lung without increasing lung endothelial permeability. CONCLUSIONS These data strongly support ceftolozane as an effective option for the treatment of severe P. aeruginosa respiratory infections by improving the early pulmonary inflammatory response without impairing 48 h post-infection homeostasis.

Evaluation of the tuberculin skin test and the interferon-γ release assay for TB screening in French healthcare workers

IntroductionUsing French cut-offs for the Tuberculin Skin Test (TST), results of the TST were compared with the results of an Interferon-γ Release Assay (IGRA) in Healthcare Workers (HCW) after contact to AFB-positive TB patients.MethodsBetween May 2006 and May 2007, a total of 148 HCWs of the University Hospital in Nantes, France were tested simultaneously with IGRA und TST. A TST was considered to indicate recent latent TB infection (LTBI) if an increase of >10 mm or if TST ≥ 15 mm for those with no previous TST result was observed. For those with a positive TST, chest X-ray was performed and preventive chemotherapy was offered.ResultsAll HCWs were BCG-vaccinated. The IGRA was positive in 18.9% and TST ≥ 10 mm was observed in 65.5%. A recent LTBI was believed to be highly probable in 30.4% following TST. Agreement between IGRA and TST was low (kappa 0.041). In 10 (16.7%) out of 60 HCWs who needed chest X-ray following TST the IGRA was positive. In 9 (20%) out of 45 HCWs to whom preventive chemotherapy was offered following TST the IGRA was positive. Of those considered TST-negative following the French guidelines, 20.5% were IGRA-positive. In a two-step strategy - positive TST verified by IGRA - 18 out of 28 (64.3%) IGRA-positive HCWs would not have been detected using French guidelines for TST interpretation.ConclusionThe introduction of IGRA in contact tracings of BCG-vaccinated HCWs reduces X-rays and preventive chemotherapies. Increasing the cut-off for a positive TST does not seem to be helpful to overcome the effect of BCG vaccination on TST.

Relapse of Enterococcus hirae Prosthetic Valve Endocarditis

ABSTRACT Enterococcus hirae, a Gram-positive bacterium, is a rare isolate in clinical specimens. We report an unusual case of a relapse of prosthetic valve endocarditis due to E. hirae 6 months after the initial episode. Clonal relationship was proven by genomic analysis.

Combination of Quinupristin-Dalfopristin and Gentamicin against Methicillin-Resistant Staphylococcus aureus: Experimental Rabbit Endocarditis Study

ABSTRACT The combination of quinupristin-dalfopristin (Q-D) and gentamicin was tested against two strains of gentamicin- and dalfopristin-susceptible methicillin-resistant Staphylococcus aureus (MRSA). One strain was susceptible to macrolides, lincosamides, and streptogramin B type antibiotics (MLSB), and the other was constitutively resistant to these antibiotics by virtue of the ermA gene. The checkerboard method and time-kill curves showed that the combination of Q-D and gentamicin was indifferent. A rabbit endocarditis model simulated the pharmacokinetics achieved in humans receiving intravenous injections of Q-D (7.5 mg/kg of body weight three times a day) and gentamicin (3 mg/kg once daily). For the MLSB-susceptible strain, a 4-day regimen reduced mean bacterial titers (MBT) in vegetations from 8.5 ± 0.8 log CFU/g (control group) to 4.1 ± 2.6 (gentamicin), 3.0 ± 0.9 (Q-D), and 2.6 ± 0.5 log CFU/g (Q-D plus gentamicin). For the strain constitutively resistant to MLSB, a 4-day regimen reduced MBT in vegetations from 8.7 ± 0.9 log CFU/g (control group) to 5.0 ± 2.2 (gentamicin), 5.2 ± 2.2 (Q-D), and 5.1 ± 2.4 log CFU/g (Q-D plus gentamicin). The differences between control and treatment groups were significant for both strains (P < 0.0001), although there was no significant difference between treatment groups. No resistant variant was isolated from vegetations, and no significant difference in MBT in vegetations of treatment groups after 1-day regimens was observed. This experimental study found no additive benefit in combining Q-D and gentamicin against dalfopristin- and gentamicin-susceptible MRSA.

Improving diagnostic criteria for Propionibacterium acnes osteomyelitis: A retrospective analysis

Abstract The identification of Propionibacterium acnes in cultures of bone and joint samples is always difficult to interpret because of the ubiquity of this microorganism. The aim of this study was to propose a diagnostic strategy to distinguish infections from contaminations. This was a retrospective analysis of all patient charts of those patients with ≥1 deep samples culture-positive for P. acnes. Every criterion was tested for sensitivity, specificity, and positive likelihood ratio, and then the diagnostic probability of combinations of criteria was calculated. Among 65 patients, 52 (80%) were considered truly infected with P. acnes, a diagnosis based on a multidisciplinary process. The most valuable diagnostic criteria were: ≥2 positive deep samples, peri-operative findings (necrosis, hardware loosening, etc.), and ≥2 surgical procedures. However, no single criterion was sufficient to ascertain the diagnosis. The following combinations of criteria had a diagnostic probability of >90%: ≥2 positive cultures + 1 criterion among: peri-operative findings, local signs of infection, ≥2 previous operations, orthopaedic devices; 1 positive culture + 3 criteria among: peri-operative findings, local signs of infection, ≥2 previous surgical operations, orthopaedic devices, inflammatory syndrome. The diagnosis of P. acnes osteomyelitis was greatly improved by combining different criteria, allowing differentiation between infection and contamination.

The Microbiology of Community-acquired Peritonitis in Children.

Background: Microbiologic data are lacking regarding pediatric community-acquired peritonitis (CAP). Methods: We conducted a 2-year retrospective single center study. Consecutive children undergoing CAP surgery were included. Microbiology and antimicrobial susceptibility of peritoneal isolates were analyzed. Results: A total of 70 children from 3 months to 14 years of age were included. A total of 123 bacterial isolates were analyzed. Escherichia coli was the predominant aerobic organism (51% of isolates); 54.8% were susceptible to amoxicillin whereas 90.3% were susceptible to amoxicillin-clavulanate. Anaerobes accounted for 29% of isolates, and 94.3% of strains were susceptible to amoxicillin-clavulanate and 68.5% were susceptible to clindamycin. Pseudomonas aeruginosa was present in 6% of isolates and in 10% of children. The presence of E. coli resistant to amoxicillin or to amoxicillin-clavulanate was the only independent risk factor associated with postoperative peritonitis. Conclusion: Microbiology of pediatric CAP is similar to adult CAP with a predominancy of E. coli and anaerobes. P. aeruginosa in peritoneal samples had no apparent influence on the outcome.