Bacteriological relevance of linezolid vs. vancomycin in postoperative empirical treatment of osteoarticular infections: a retrospective single-center study.

BACKGROUND: In 2015, our center replaced vancomycin with linezolid for the postoperative empirical treatment of osteoarticular infections (OAI). OBJECTIVES: To assess the bacteriological relevance of linezolid for orthopedic postoperative probabilistic antibiotic therapy. METHODS: Analysis of an observational cohort of patients empirically treated with a combination of linezolid and piperacillin/tazobactam during the immediate postoperative stage for an OAI between July 1st 2015 and July 1st 2016, in a French reference center. RESULTS: Seventy-seven of 126 patients who received a probabilistic postoperative combination of linezolid with piperacillin/tazobactam had microbiological proof of infection. Sixty-six of 77 OAI involved material, including an osteosynthesis in 45 cases (68%) and prosthesis in 21 cases (32%). Infection was due to Gram-positive bacteria in 62 cases (80.5%), mostly S. aureus (n=32, 41.6%), and S. epidermidis (n=14, 18.2%) accounting for 74.2% of Gram-positive bacteria. Among 14 OAI due to S. epidermidis, 11 (78.6%) were due to methicillin-resistant strains. All the S. aureus and S. epidermidis strains were susceptible to linezolid (MICs ≤ 4 mg/L), except in one patient previously treated with linezolid who was infected with a linezolid-resistant S. epidermidis strain (MIC > 256 mg/L). CONCLUSION: Linezolid can be used empirically in postoperative antibiotic therapy of OAI before obtaining definitive microbial results. Although linezolid resistance is rare in this population, previous oxazolidinone treatment should be documented before initiation of probabilistic postoperative treatment to highlight potential linezolid resistance.

Is there an association between prior anti-inflammatory drug exposure and occurrence of peritonsillar abscess (PTA)? A national multicenter prospective observational case-control study.

The aim of this study was to evaluate whether recent systemic anti-inflammatory agents (AIAs) exposure in patients with sore throat managed with or without antibiotic therapy influenced the risk of peritonsillar abscess (PTA). We conducted a multicenter case-control study in 13 French university hospitals in 2009-2012 comparing patients admitted with PTA to matched controls: patients with sore throat but without PTA who were followed up for 10 days after visiting their primary-care physician. In the multivariate stepwise logistic regression model comparing 120 cases with PTA to 143 controls, factors significantly associated with PTA were male gender (odds ratio [OR], 2.0; p = 0.03), smoking (OR, 2.0; p = 0.03), and prior self-medication with systemic AIAs (OR, 3.5; p = 0.01). Topical treatment was associated with significant protection against PTA (OR, 0.3; p < 0.001). In conclusion, self-medication with systemic AIAs appears to be an independent factor associated with the occurrence of PTA. This is an important message as non-steroidal AIAs access is favored by their over-counter availability in pharmacies. This finding must be interpreted with caution due to the study design and a prospective, randomized study is needed to substantiate these possible causal risk factors.

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 ß-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 ß-lactams, continued for 3 months, should be considered an effective alternative to fluoroquinolones.

Levofloxacin at the usual dosage to treat bone and joint infections: a cohort analysis.

Fluoroquinolones are recommended for the treatment of bone and joint infections (BJIs), and levofloxacin is commonly used in this setting. However, no pre-marketing clinical study has supported its use, especially its dosage, for treating BJIs. This study aimed to assess the benefit-risk ratio of levofloxacin administered orally at a standard dosage of 500 mg once daily (OD) in a cohort of patients with BJIs. The medical records of patients admitted to a large French teaching hospital for BJI over a 1-year period and managed by a multidisciplinary team were reviewed. Patient data were recorded on a standardised form and the outcome was assessed at the end of antibiotic treatment and after 1-year of follow-up. A total of 230 patients were included, of whom 79 were treated with an antibiotic regimen including levofloxacin (34%). Most BJIs (97%) were surgically treated by wound debridement and/or removal or replacement of the infected device. Adverse drug reactions to levofloxacin leading to treatment discontinuation occurred in three patients (4%). The antibiotic treatment duration was significantly longer in patients treated with levofloxacin compared with other antibiotic regimens (median, 13 weeks vs. 6 weeks). Post-treatment outcomes were considered favourable (total or partial recovery, including orthopaedics aftermath) in 89-93% of patients, with no significant difference between treatment groups. In conclusion, oral levofloxacin at 500 mg OD is a well-tolerated and efficacious antibiotic treatment for BJIs. Our approach of following-up all treated patients is a useful way to validate specific clinical practices.

Infections Revealing Complement Deficiency in Adults: A French Nationwide Study Enrolling 41 Patients.

Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies.A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis.Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ±â€Š14 (15-67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ±â€Š1.95 (0.1-10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35% (n = 14/34).This large study emphasizes that complement deficiencies can be revealed in adults by infectious episodes. Most of them were meningococcal infections revealing common final pathway deficiency. To avoid undiagnosis or late diagnosis, adult displaying first episode of N meningitidis infection should be tested for complement deficiency.

Peritonsillar abscess (PTA): clinical characteristics, microbiology, drug exposures and outcomes of a large multicenter cohort survey of 412 patients hospitalized in 13 French university hospitals.

The aim of this study was to describe the epidemiology of hospitalized patients with peritonsillar abscess (PTA). We conducted a multicenter survey in 13 French university hospitals in 2009-2012 describing 412 patients. Median age was 29 year (range, 2-84) and current smoking habit was reported by 177 (43 %) patients. Most of the patients (92 %) had consulted a physician for sore throat within 10 days before admission for PTA diagnosis. Additional symptoms such as visible tonsil abnormalities (83 %), tender cervical adenopathy (57 %) and fever ≥ 38.5 °C (53 %) were also reported. A total of 65 % patients (269/412) reported recent systemic anti-inflammatory agents (AIAs) exposure by medical prescription (70 %), self-medication (22 %), or both (8 %); 61 % and 27 % reported recent exposure to antibiotic and topical treatments for sore throat, respectively. Non-steroidal AIAs were used most often (45 %), particularly arylpropionic derivatives. A rapid diagnosis antigen test (RDT) for Streptococcus pyogenes was performed in 70 (17 %) patients and was positive in 17 (24 %), of whom 9 (53 %) were exposed to AIAs and 14 (82 %) to antibiotics. To treat PTA, antibiotic therapy was given to 392 (95 %) patients. Of 333 antibiotic prescriptions, amoxicillin-clavulanic acid and metronidazole were the most prescribed antibiotics (42 and 17 %, respectively). Surgical drainage of the abscess was performed in 119 (29 %) cases and tonsillectomy in 75 (18 %) cases. The clinical outcome was favorable during the hospital stay in 404 (98 %) patients. In conclusion, patients with sore throat are often exposed to AIAs before PTA diagnosis, and antibiotic prescription was not often based on the RDT positivity.

Risk factors and pathogens involved in early ventilator-acquired pneumonia in patients with severe subarachnoid hemorrhage.

Ventilator-acquired pneumonia (VAP) is a common burden in intensive care unit (ICU) patients, but, to date, specific data are not available in patients with severe aneurysmal subarachnoid hemorrhage (SAH). A single neuro-ICU retrospective analysis of 193 patients with SAH requiring mechanical ventilation (MV) ≥48 h admitted from January 2005 to May 2010 was undertaken. The diagnosis of early VAP was prospectively upheld during a multidisciplinary staff meeting, according to the American Thoracic Society (ATS) 2005 guidelines with a threshold of 7 days after the onset of MV. Patients had a median age of 53 (44-62) years and 70 (36 %) were male. The median Glasgow coma scale (GCS) score before MV was 9 (5-14). 142 (74 %) patients had a World Federation of Neurosurgeons (WFNS) score ≥III. Aneurysm was secured with an endovascular coiling procedure in 162 (84 %) patients. 81 (48.7 %) patients declared an early VAP. On multivariate analysis, male sex (odds ratio [OR] 2.26, 95 % confidence interval [CI] [1.14-4.46]), use of mannitol before day 7 (OR 3.03, 95 % CI [1.54-5.95]), and achieving enteral nutrition ≥20 kcal kg(-1) day(-1) after day 7 (OR 2.91, 95 % CI [1.27-6.67]) remained independent risk factors of VAP. The main pathogens involved were methicillin-susceptible Staphylococcus aureus (MSSA) (34.9 %), Haemophilus influenzae (28.1 %), Streptococcus pneumoniae (15.5 %), and Enterobacteriaceae (10.7 %). Early VAP was associated with a longer duration of MV and ICU stay, but not with an excess of mortality. Early VAP bears significant morbidity in patients with severe SAH. Pathogens involved in early VAP are susceptible to antibiotics. Among modifiable risk factors of VAP, early enteral nutrition could be an easy and effective target.

The optimal aminoglycoside and its dosage for the treatment of severe Enterococcus faecalis infection. An experimental study in the rabbit endocarditis model.

Aminoglycosides are recommended for the treatment of Enterococcus faecalis infections, especially in severe and bacteremic infection. However, the optimal aminoglycoside or the optimal dosage remains uncertain. This study aimed to compare the activity of four aminoglycosides against E. faecalis (gentamicin, netilmicin, tobramycin, and amikacin) and two dosages of gentamicin. One clinical strain of E. faecalis was used to induce aortic endocarditis in the study rabbits. Each aminoglycoside was infused daily over 3 days with a computer-regulated flow simulating human pharmacokinetics of 15 mg/kg/day for amikacin, 6 mg/kg/day for netilmicin, and 3 mg/kg/day for gentamicin and tobramycin. Additionally, two dosages of gentamicin (simulating 3 or 6 mg/kg/day) were compared over 1 or 3 days of treatment. The in vivo efficacy was assessed according to the bacterial count in vegetations, in comparison with a control group. Of the four aminoglycosides tested, only gentamicin and netilmicin showed significant antibacterial efficacy after 3 days of treatment. After only 1 day of treatment, the high dosage of gentamicin (6 mg/kg/day) was more effective than the standard dosage (3 mg/kg/day). Among the tested aminoglycosides, gentamicin showed the best efficacy, with the best results after 24 h of treatment for the highest dosage.

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.

Spondylodiscitis due to Propionibacterium acnes: report of twenty-nine cases and a review of the literature.

Propionibacterium acnes is the most frequent anaerobic pathogen found in spondylodiscitis. A documented case required microbiological proof of P. acnes with clinical and radiological confirmation of inflammation in a localized region of the spine. Microbiological samplings were obtained by surgery or aspiration under radiological control. Twelve males and 17 females (median age, 42 years) with spondylodiscitis due to P. acnes were diagnosed within the last 15 years. Three patients were immunosuppressed. All patients reported back pain as the main symptom, and most were afebrile. Three patients had a peripheral neurological deficit, one a motor deficit, and two a sensory deficit attributable to the infection; and six patients had an epidural abscess. The most frequent risk factor was surgery, which was present in the history 28 of 29 (97%) patients. The mean delay between spinal surgery and onset of disease was 34 months, with a wide range of 0-156 months. Osteosynthesis material was present in twenty-two cases (76%). In 24 (83%) patients, additional surgery, such as débridement or spondylodesis, was performed. Previous osteosynthesis material was removed in 17 of the 22 (77%) patients where it was present. Total cure was reported in all patients, except one, after a mean duration of antibiotic therapy of 10.5 weeks (range, 2-28 weeks). In conclusion, spondylodiscitis due to P. acnes is an acute infection closely related to previous surgery. The most prominent clinical feature is pain, whereas fever is rare, and the prognosis is very good.

[Prior use of anti-inflammatory and antibiotic drugs in patients hospitalized for peritonsillar abscess]. / Analyse de l'exposition préalable aux anti-inflammatoires et aux antibiotiques d'une cohorte de 34 patients hospitalisés au CHU de Nantes pour phlegmon périamygdalien.

OBJECTIVE: The purpose of this study was to describe the characteristics of patients hospitalized for a peritonsillar abscess over a 1-year period and to evaluate the proportion of patients exposed to anti-inflammatory and antibiotic drugs before hospitalization. DESIGN: Adult patients hospitalized in the ENT department at the Nantes University Hospital were included in the study during 2006. Data related to prior use of anti-inflammatory and antibiotic drugs, microbiology and treatment was analyzed. RESULTS: Thirty-four patients were included in the study, 20 (59%) and 21 (62%) patients had been previously exposed to anti-inflammatory and antibiotic drugs, respectively. Half of the patients had received antibiotics despite the negativity of the rapid screening test. All diagnoses were made on pus examination after aspiration. Tonsillectomy was performed only in two cases. A total of 21 bacterial isolates (13 anaerobic and 9 aerobic) were identified. Single bacterial isolates were recovered in 8 infections. The most frequent bacteria were Streptococcus, Fusobacterium, and Prevotella. CONCLUSIONS: Many patients were exposed to both anti-inflammatory and antibiotic drugs, which did not prevent the peritonsillar abscess.

Recurrent abscesses due to Finegoldia magna, Dermabacter hominis and Staphylococcus aureus in an immunocompetent patient.

A case of recurrent abscesses in an immunocompetent patient is reported, involving the opportunistic human pathogen Dermabacter hominis, the virulent anaerobic pathogen Finegoldia magna and Staphylococcus aureus.

[Use of antibiotics in emergency units: qualitative and quantitative assessment]. / L'antibiothérapie aux urgences, évaluation par une approche qualitative et quantitative.

INTRODUCTION: Most antibiotic therapies are initiated in the emergency unit (EU). To better understand the antibiotic consumption survey in this unit, we compared our results to two neighbor hospitals. This quantitative data was then compared to a quality assessment of antibiotic prescription (audit). METHODS: The quantitative measure of antibiotic consumption (three markers: ceftriaxone, amoxicillin-clavulanate, and fluoroquinolones) based on the ratio DDD:1000 patient admitted in the EU was compared between one teaching hospital and the two neighbor hospitals. Qualitative measure: a retrospective clinical targeted audit of antibiotic prescriptions was performed. The compliance to guidelines for infection diagnosis and antibiotic treatment were assessed. RESULTS: Antibiotic consumption: the survey showed a higher consumption of the three antibiotics in the teaching hospital, especially for amoxicillin-clavulanate (3.7-5.5 higher). Audit: 93 files of EU patients were reviewed; their mean age was 71 years (18-96). Diagnosis was conform to the expert opinion in 70% of cases. No antibiotic was really necessary in 20% of cases, and delay between hospitalization and antibiotic prescription was relevant only for 56% of patients. The most frequently prescribed antibiotics were betalactams (penicillins 43%, third generation cephalosporin 21%, and fluoroquinolones 22%). The choice was conform to local and national guidelines in 78% of justified prescribed antibiotherapy. CONCLUSION: The qualitative assessment cannot explain the higher antibiotic consumption trend. The number of unjustified antibiotic prescriptions does not explain the variable antibiotic consumption.

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.

[CRP in the management of bacterial infections in emergency]. / Utilité du dosage de la CRP pour la prise en charge des infections bactériennes aux urgences.

OBJECTIVES: To assess the interest of measuring CRP in emergency for diagnosing bacterial infections and making decisions about antibiotics and to compare its practical usefulness with clinicians' conclusions. METHODS: Systematic CRP measurements in 80 consecutive patients admitted to emergency ward with possible bacterial infection. RESULTS: were not transmitted to the physician in charge. Patients' files were analyzed retrospectively in two phases. In phase 1, two senior physicians assessed the diagnosis and need for antibiotics on the basis of the admission (emergency unit) files. In phase 2, a panel of experts examined the complete files (including discharge notes) to determine the likelihood of infection (obvious or probable, unlikely or excluded) and appropriateness of emergency antibiotics. Their recommendations were used as the standard, against which the usefulness of the laboratory indicators (including CRP) and decisions of the emergency physicians were assessed. ROC curves were used to determine threshold values for CRP and body temperature. We then calculated the sensitivity, positive predictive value and negative predictive value of these cutoffs and compared them with those for the phase 1 clinician recommendations. RESULTS: The study included 76 patients (mean age: 74 years): 28 presented obvious or possible infections and 21 required emergency antibiotic therapy. Mean leukocyte values did not differ between groups. For diagnosis, the threshold value of CRP was 85 mg/L and of body temperature 37.8 degrees C; for prescribing antibiotics, the values were 130 mg/L and 38 degrees C, respectively. The sensitivity, specificity, negative and positive predictive values of CRP were, respectively, 79, 81, 76, and 83% for diagnosis of bacterial infection and 71, 71, 48 and 87% for prescription of an emergency antibiotic. These values were lower than those of clinician's conclusions. CONCLUSION: Because of the variability in the thresholds used in its interpretation, the lack of specificity, and its poor predictive value for treatment decisions, CRP is of little interest in the diagnosis and treatment of patients with bacterial infections in intensive care. The cost generated by this examination is therefore not justified.

Different aminoglycoside-resistant phenotypes in a rabbit Staphylococcus aureus endocarditis infection model.

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.