Nathalie Asseray

Efficacy of daptomycin combined with rifampicin for the treatment of experimental meticillin-resistant Staphylococcus aureus (MRSA) acute osteomyelitis

Daptomycin exhibits rapid bactericidal activity against Gram-positive organisms, including meticillin-resistant Staphylococcus aureus (MRSA). Daptomycin in combination with rifampicin needs to be assessed in bone infection. An MRSA acute osteomyelitis model was used. Daptomycin and vancomycin were compared, alone or in combination with rifampicin, over 4 days. Surviving bacteria were counted in bone, bone marrow and joint fluid. Vancomycin and daptomycin as single therapies were ineffective, but both combinations were significantly more effective than the corresponding monotherapy. Combination of daptomycin and rifampicin could prevent S. aureus from developing resistance. This combination could be a useful alternative to treat MRSA osteomyelitis at an early stage.

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.

Activity of Glycopeptides against Staphylococcus aureus Infection in a Rabbit Endocarditis Model: MICs Do Not Predict In Vivo Efficacy

ABSTRACT The in vivo efficacy of vancomycin and teicoplanin against five Staphylococcus aureus strains with different susceptibilities to them and methicillin was studied. Rabbits were allocated at random to groups for endocarditis induction with one of these five strains and then treated for 2 days with vancomycin or teicoplanin. Each treated group was compared with a control group infected with the same strain. Vancomycin and teicoplanin showed similar activities. Low MICs did not predict better in vivo results.

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.

Different Aminoglycoside-Resistant Phenotypes in a Rabbit Staphylococcus aureus Endocarditis Infection Model

ABSTRACT The impact of different types of enzymatic resistance on the in vivo antibacterial activity of aminoglycosides (amikacin, gentamicin, and netilmicin) was studied in the rabbit endocarditis model with four strains of Staphylococcus aureus. Animals were treated in a manner simulating the administration of a single daily human dose. Amikacin had no effect on the three kanamycin-resistant strains despite apparent susceptibility in the disk diffusion test. Gentamicin appears to be the preferable aminoglycoside for treatment of staphylococcal infections.

A questionnaire to document self‐medication history in adult patients visiting emergency departments

To develop the first questionnaire to obtain a complete medication history by documenting self‐medication history in adult patients admitted to a medical emergency department (ED).

Assessment of adverse drug event recognition by emergency physicians in a French teaching hospital

Objectives The frequency and the severity of drug-related visits in emergency department (ED) make the improvement of adverse drug event (ADE) recognition a crucial issue. As part of a research project aiming to improve the diagnosis and the management of ADEs in ED, the authors conducted a pilot study whose primary objective was to assess ADE recognition by emergency physicians. Methods The patients presenting to the ED were included at randomised time periods between 1 October 2007 and 31 March 2008 in this prospective cross-sectional study. The primary outcome was the frequency of ADEs that were attributed to a medication-related problem by the emergency physician. Results A total of 423 patients met the inclusion criteria, of which 95 experienced an ADE (22.5%; 95% CI 18.6% to 26.7%). Emergency physicians correctly attributed 33 of these cases (34.7%; 95% CI 25.3% to 45.2%) to a medication-related problem. Of the 28 cases in which the ADE was considered as a ‘direct drug effect’ (29.5%; 95% CI 20.6% to 39.7%), 16 were correctly identified by emergency physicians (57.1%; 95% CI 37.2% to 75.5%). Of the 67 cases in which the ADE was considered as a ‘drug involvement in a multifactorial pathological condition’ (70.5%; 95% CI 60.3% to 79.4%), 17 were correctly attributed (25.4%; 95% CI 15.5% to 37.5%). Conclusions ADEs are frequent in EDs and are not well recognised by emergency physicians, especially when the drug is involved in a multifactorial pathological condition.

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.

Establishing a pharmacy presence in the emergency department: opportunities and challenges in the French setting

Overview of clinical pharmacy practice around the world shows that pharmaceutical services in emergency departments (EDs) are far less common in Europe than in North America. Reported experiences have shown the impact of a clinical pharmacy service on drug utilisation and safety issues. This commentary presents the implementation of a pharmacy presence in the ED of a French tertiary care hospital. Our experience helps to define the role of the clinical pharmacist in the ED, including patient interviewing, providing medication reconciliation, promoting drug safety, and supporting specific interventions to improve quality of care and patient safety. The role of ED pharmacists in the improvement of quality of care is not necessarily limited to drug therapy, e.g. by helping outpatients to access care and treatment facilities as best suits their needs. Challenges of implementing ED pharmacy services have been identified well, but still require developing strategies to be overcome.