Descriptive management of suspected acute cystitis in adult patients by French general practitioners during remote consultation.

OBJECTIVES: The main objective of this study was to analyze French general practitioners' (GP) online prescriptions for suspected acute cystitis using a single nationwide teleconsultation platform. PATIENTS AND METHODS: First, a descriptive study of management for suspected cystitis was conducted from the 1st of January to the 31st of December 2020. After which, following pedagogical intervention, a pre/post descriptive analysis of the antibiotics prescribed was carried out. RESULTS: Some 496,041 teleconsultations (TCs) were carried out in 2020 on the Qare platform. Among them, 15,089 TCs for cystitis with ICD-10 encoding (N30) were analyzed. Fosfomycin trometamol was the most prescribed antibiotic (n = 10297, 69%), while fluoroquinolones (n = 1568, 10.6%) were the second. Urine test strip was prescribed in 3157 (20%) and urine culture in 7033 (47%) of the TCs. July-August 2020 and July-August 2021 were compared and while a significant drop in fluoroquinolone prescriptions and a major increase in Fosfomycin trometamol were observed, there was no change in the prescriptions of urine culture. An average antibiotic conformity rate of 61.5% was observed before the intervention, and 68.8% afterwards. CONCLUSIONS: Cystitis is a recurrent reason for remote consultation. The study demonstrated sizable over-prescription of urine culture, ultrasound, and fluoroquinolones. Intervention should be improved and strengthened to guarantee continuous training and awareness of GP's on appropriate cystitis prescriptions in telemedicine.

Treatment With a Three-Drug Regimen for Pulmonary Tuberculosis Based on Rapid Molecular Detection of Isoniazid Resistance: A Noninferiority Randomized Trial (FAST-TB).

Background: The rationale behind the use of ethambutol in the standard tuberculosis treatment is to prevent the emergence of resistance to rifampicin in case of primary resistance to isoniazid. We evaluated whether early detection of isoniazid resistance using molecular testing allows the use an ethambutol-free regimen. Methods: FAST-TB, a phase 4, French, multicenter, open-label, non-inferiority trial, compared 2 strategies: (1) polymerase chain reaction (PCR)-based detection of isoniazid and rifampicin resistance at baseline using Genotype MTBDRplus version 2.0 followed by ethambutol discontinuation if no resistance was detected (PCR arm) and (2) a standard 4-drug combination, pending phenotypic drug-susceptibility results (C arm). Adult patients with smear-positive pulmonary tuberculosis were enrolled. The primary endpoint was the proportion of patients with treatment success defined as bacteriological or clinical cure at the end of treatment. A non-inferiority margin of 10% was used. Results: Two hundred three patients were randomized, 104 in the PCR arm and 99 in the C arm: 26.6% were female, median age was 37 (interquartile range, 28-51) years, 72.4% were born in Africa, and 5.4% were infected with human immunodeficiency virus. Chest x-ray showed cavities in 64.5% of the cases. Overall, 169 patients met criteria of treatment success: 87 of 104 (83.7%) in the PCR arm and 82 of 99 (82.8%) in the C arm with a difference of +0.8% (90% confidence interval, -7.9 to 9.6), meeting the noninferiority criteria in the intention-to-treat population (P = .02). Conclusions: In a setting with low prevalence of primary isoniazid resistance, a 3-drug combination with isoniazid, rifampicin, and pyrazinamide, based on rapid detection of isoniazid resistance using molecular testing, was noninferior to starting the recommended 4-drug regimen.

Real-world evaluation of ceftolozane/tazobactam therapy and clinical outcomes in France.

OBJECTIVES: To describe the real-world clinical use of ceftolozane/tazobactam (C/T) and associated outcomes in France. PATIENTS AND METHODS: Multicenter, prospective cohort study conducted in 22 hospitals. All adult patients who received at least one dose of C/T were asked to participate (2018-2019). Patients were treated according to standard hospital practice and followed up until C/T stop. RESULTS: At the time of the analysis, 84 patients were evaluated. The median age was 64.8 years, and 67.9% (57/84) of patients were males. Fifty-seven patients (57/82, 69.5%) had one or more risk factors for multidrug-resistant (MDR) infections (missing MDR risk factor data for two patients). Most patients were critically ill and had several comorbidities. A majority (59/84, 70.2%) of patients had nosocomial infections. Half of all patients (n=42) had a diagnosis of pneumonia, of which 69% (29/42) were hospital acquired. Overall, 90.5% (76/84) of patients had MDR bacteria. Pseudomonas aeruginosa was the most frequently isolated bacterium (71/80, 88.8%), including 93% (80/86) of C/T-susceptible strains. C/T was prescribed as the first-line treatment to 29.8% (25/84) of patients. A concomitant antibiotic treatment was prescribed to 48.8% (41/84) of patients, of whom 65.9% (27/41) were prescribed concomitant antibiotics at the same time as C/T initiation. Empirical C/T prescription was microbiologically appropriate in 11/16 patients after susceptibility testing. Most patients (44/72, 61.1%) were cured and four (4/72, 5.6%) deaths were reported. CONCLUSIONS: The results showed that C/T was most frequently prescribed for documented cases of P. aeruginosa infections. Most outcomes were positive, including among pneumonia patients.

Ibrutinib, a Bruton's tyrosine kinase inhibitor, a new risk factor for cryptococcosis.

PURPOSE: Invasive fungal diseases and especially Cryptococcus neoformans infections are increasingly reported in patients with hematological malignancies receiving ibrutinib, a Bruton's tyrosine kinase inhibitor. PATIENTS AND METHOD: We reported three additional cases and reviewed 16 previous published cases together with cases from the international pharmacovigilance database. RESULTS: Patients were mainly treated for chronic lymphocytic leukemia. Cryptococcosis mostly occurred during the first six months (66%) and especially the first two months (44%) of treatment. Clinical presentation is often pulmonary (68%) and the outcome is usually favorable despite ibrutinib continuation. CONCLUSION: Clinicians must be aware of this infection in patients with hematological malignancies on ibrutinib.

Should we reconsider cefazolin for treating staphylococcal meningitis? A retrospective analysis of cefazolin and cloxacillin cerebrospinal fluid levels in patients treated for staphylococcal meningitis.

OBJECTIVES: To assess the meningeal penetration of cefazolin and cloxacillin in individuals treated for methicillin-susceptible staphylococcal meningitis. METHODS: We retrospectively identified individuals treated for Staphylococcus meningitis with measurements of cefazolin or cloxacillin concentrations in cerebrospinal fluid (CSF) using a validated assay of liquid chromatography coupled with mass spectrometry at the Nantes University Hospital between January 2009 and October 2019. Staphylococcus meningitis was defined by a compatible clinical presentation and a microbiological confirmation (positive CSF culture or positive specific PCR). Medical charts were retrospectively reviewed to collect microbiological and clinical data, and to assess therapeutic success. RESULTS: Among the 17 included individuals, eight (47%) were treated with cefazolin and nine (53%) with cloxacillin. Median daily dosages of cefazolin and cloxacillin were 8 g (range 6-12 g) and 12 g (range 10-13 g), respectively. Cefazolin and cloxacillin were mainly administered by continuous infusion. Eleven individuals (65%) were men, median (interquartile range (IQR)) age was 54 years (50; 70), 14 (82%) had postoperative meningitis and 3 (18%) had haematogenous meningitis. Median (IQR) antibiotic CSF concentrations were 2.8 mg/L (2.1; 5.2) and 0.66 mg/L (0.5; 0.9) for cefazolin and cloxacillin groups, respectively. Cloxacillin was discontinued in two individuals for therapeutic failure. CONCLUSIONS: Patients with staphylococcal meningitis treated with high-dose continuous intravenous infusion of cefazolin achieved therapeutic concentrations in CSF. Cefazolin appears to be a therapeutic candidate that should be properly evaluated in this indication.

Cryptosporidiosis and microsporidiosis as causes of diarrhea in kidney and/or pancreas transplant recipients.

INTRODUCTION: Gastrointestinal disorders in solid organ recipients may have various origins including cryptosporidiosis and microsporidiosis. The prevalence of these infections is poorly known in solid organ transplant (SOT) patients in industrialized countries. METHODS: We prospectively assessed the infectious causes of diarrhea in SOT patients. Secondary objectives were to gain further insight into the main characteristics of cryptosporidiosis, and to assess risk factors for this infection. All adult kidney and/or pancreas recipients presenting with diarrhea and admitted to our facility between May 1, 2014 and June 30, 2015 were enrolled. A stool sample was analyzed using a standardized protocol including bacteriological, virological, and parasitological investigations. Data related to clinical symptoms, immunosuppression, and environmental potential risk factors were collected through a self-administered questionnaire and computerized medical records. RESULTS: Out of 73 enrolled patients, 36 had infectious diarrhea (49.3%). Viruses ranked first (17/36), followed by parasites and fungi (11/17). Cryptosporidiosis was the most common parasitic disease (n=6 patients). We observed four microsporidiosis cases. The estimated prevalence of cryptosporidiosis and microsporidiosis in this cohort was 3.7 and 2.40/00, respectively. No significant risk factor for cryptosporidiosis or microsporidiosis, neither environmental nor immunological, could be evidenced. CONCLUSION: Both cryptosporidiosis and microsporidiosis represent a significant cause of diarrhea in kidney transplant recipients.

Antibiotic prophylaxis of infective endocarditis in patients with predisposing cardiac conditions: French cardiologists' implementation of current guidelines.

BACKGROUND: To prevent infective endocarditis (IE), with the exception of the United Kingdom, antibiotic prophylaxis (AP) is recommended in patients with predisposing cardiac conditions (PCCs) worldwide. To conclude on the relevance of this strategy, how the current guidelines are applied is a crucial point to investigate. The first aim of this study was to assess cardiologists' implementation of the current guidelines. The secondary objective was to identify specific areas where the training and knowledge of French cardiologists could be improved. METHODS: A national online survey was carried out among the 2228 cardiologist members of the French Society of Cardiology. RESULTS: The high risk PCCs for which IE AP is recommended were correctly identified by the vast majority of the respondents so that IE AP is mostly prescribed correctly in such patients. But only 12% identified all the right indications for IE AP according to 13 predefined PCCs (3 at high-risk, 6 at moderate-risk and 4 at low-risk of IE) so that some IE AP misuses are recorded, overprescription in particular. Only 47% prescribed the proper amoxicillin schedule and only 15% prescribed the appropriate clindamycin schedule in cases with penicillin allergy. CONCLUSION: This study evidenced relevant areas where the training of cardiologists could be improved such as knowledge of the risk of IE for certain PCCs and some common invasive dental procedures. Cardiologists' knowledge should be improved before any conclusion can be drawn on the relevance of this AP strategy and its influence on IE incidence.

Linezolid versus vancomycin cost in the treatment of staphylococcal pneumonia.

OBJECTIVE: Staphylococcusaureus is involved in around 20% of nosocomial pneumonia cases. Vancomycin used to be the reference antibiotic in this indication, but new molecules have been commercialized, such as linezolid. Previous studies comparing vancomycin and linezolid were based on models. Comparing their real costs from a hospital perspective was needed. METHODS: We performed a bicentric retrospective analysis with a cost-minimization analysis. The hospital antibiotic acquisition costs were used, as well as the laboratory test and administration costs from the health insurance cost scale. The cost of each hospital stay was evaluated using the national cost scale per diagnosis related group (DRG), and was then weighted by the stay duration. RESULTS: Fifty-eight patients were included. All bacteria identified in pulmonary samples were S. aureus. The cost of nursing care per stay with linezolid was €234.10 (SD=91.50) vs. €381.70 (SD=184.70) with vancomycin (P=0.0029). The cost of laboratory tests for linezolid was €172.30 (SD=128.90) per stay vs. €330.70 (SD=198.40) for vancomycin (P=0.0005). The acquisition cost of linezolid per stay was not different from vancomycin based on the price of the generic drug (€54.92 [SD=20.54] vs. €40.30 [SD=22.70]). After weighting by the duration of stay observed, the mean cost per hospital stay was €47,411.50 for linezolid and €57,694.0 for vancomycin (NSD). CONCLUSION: These results, in favor of linezolid, support other former pharmacoeconomic study based on models. The mean cost per hospitalization stay was not statistically different between the two study groups, but a trend in favor of linezolid is emerging.

Risk factors for Cutibacterium acnes spinal implant-associated infection: a case-case-control study.

OBJECTIVES: The aim was to determine the characteristics of patients who developed Cutibacterium acnes spinal implant-associated infection (SIAI) and the associated risk factors. METHODS: We conducted two parallel case-control studies comparing 59 patients with SIAI caused by C. acnes (cases 1) and 93 patients with SIAI caused by other microorganisms (cases 2) diagnosed during 2010-2015 with 302 controls who underwent spinal instrumentation without subsequent infection. RESULTS: Late-onset infections (median time to diagnosis, 843 days versus 23 days; p < 0.001) were more common in cases 1 than in cases 2. However, 20/59 (34%) of cases 1 occurred within the first 3 months after the index surgery. In addition, cases 1 were less likely to have fever (27%, 16/59 versus 58%, 54/93; p 0.001) or wound inflammation (39%, 23/59 versus 72%, 67/93; p < 0.001). Moreover, 24/59 (40%) of cases 1 presented with polymicrobial infections, and staphylococcal pathogens accounted for 22/24 (92%) of the co-infections. By comparing and contrasting the two multivariate risk models (cases 1 versus controls and cases 2 versus controls), the following factors associated with C. acnes SIAI development were identified: age <54 years (adjusted odds ratio (aOR) 2.43, 95% confidence interval (CI) 1.09-5.58, p 0.03), a body mass index <22 kg/m2 (aOR 2.47, 95% CI 1.17-5.29, p 0.02), and thoracic instrumentation (aOR 16.1, 95% CI 7.57-37.0, p < 0.001). CONCLUSIONS: Future therapeutic and prophylactic studies on C. acnes SIAI should focus on young, thin patients who undergo spinal instrumentation procedures involving the thoracic spine.

PK/PD targets of amikacin and gentamicin in ICU patients.

OBJECTIVES: We aimed to evaluate the probability to achieve PK-PD targets in patients with sepsis hospitalized in the intensive care unit (ICU) after a single dose of 30mg/kg of amikacin or 8mg/kg of gentamicin. PATIENTS AND METHODS: This single-center prospective study included 138 ICU patients with severe sepsis or septic shock with an indication for intravenous amikacin (N=89) or gentamicin (N=49). Maximum concentration (Cmax) was measured 30 minutes after infusion completion. PK/PD objectives were respectively Cmax≥60mg/L and ≥30mg/L for amikacin and gentamicin for empirical therapy, and a Cmax/MIC ratio≥8, as per French guidelines. RESULTS: The median Simplified Acute Physiology Score II was 43 and ICU case fatality rate was 34.8%. A causative bacterial agent was identified in 94 patients (68.1%). Three pathogens had acquired aminoglycoside resistance and 15 were naturally resistant. The targeted Cmax for the first dose was achieved in 53 patients (59.6%) receiving amikacin, and one (2.2%) patient receiving gentamicin. Cmax/MIC ratio≥8 was obtained in all patients infected with susceptible pathogens (N=72). Factors associated with Cmax≥60mg/L of amikacin in multivariate analysis were dose per kg of adapted body weight (OR=1.39, P<0.001) and renal clearance estimated with CKD-EPI formula (OR=0.98, P=0.003). CONCLUSIONS: Despite high doses, amikacin and gentamicin first Cmax remain dramatically low in ICU patients. However, an adequate Cmax/MIC ratio was reached in all patients.

Incidence, characteristics, and mortality of infective endocarditis in France in 2011.

OBJECTIVES: We assessed the determinants of mortality in infective endocarditis (IE), using the national hospital discharge databases (HDD) in 2011. METHODS: IE stays were extracted from the national HDD, with a definition based on IE-related diagnosis codes. This definition has been assessed according to Duke criteria by checking a sample of medical charts of IE giving a predictive positive value of 86.1% (95% confidence interval (CI): 82.7% - 89.5%). The impact of heart valve surgery on survival has been studied if performed during the initial stay, and over the year of follow-up. Risk factors of in-hospital mortality were identified using logistic regression model for the initial stay and Cox Time-dependent model for the 1-year mortality. RESULTS: The analysis included 6,235 patients. The annual incidence of definite IEs was 63 cases/million residents. Staphylococci and Streptococci were the most common bacteria (44% and 45%, respectively). A valvular surgery was performed in 20% of cases, but substantial variations existed between hospitals. The in-hospital mortality was 21% (ranging 12% to 27% according to the region of patients), associated with age>70, chronic liver disease, renal failure, S. aureus, P. aeruginosa or candida infection and strokes whereas valvular surgery, a native valve IE or intraveinous drug use (right heart IE) were significantly protective for an initial death. The same factors were associated with the one-year mortality, except for valvular surgery which was associated with a 1.4-fold higher risk of death during the year post IE. CONCLUSION: We reported a high IE incidence rate. Valvular surgery was considerably less frequent in this study than in the previous published data (near 50%) whereas mortality was similar. Surgery was associated with higher survival if undergone within the initial stay. There were significant regional differences in frequency of surgery but it did not impact mortality.

Intraoperative bacterial analysis in nasal polyposis: Clinical and functional impact.

BACKGROUND: The impact of Staphylococcus aureus on onset of nasal polyposis has been the focus of numerous studies, but there have been few studies of other germs found in the ethmoid of operated patients or of their impact on post-operative results. MATERIAL AND METHODS: All patients undergoing endoscopic radical ethmoidectomy for nasal polyposis in the teaching hospital of Nantes (France) between 2006 and 2016 had intraoperative ethmoid cavity bacterial sampling. Phenotypic characteristics, pre- and post-operative symptoms and endoscopic findings were analyzed. Mann-Whitney tests and Kruskal-Wallis correlation analysis were used to assess clinical/bacteriological correlations. OBJECTIVES: The main objective was to describe bacterial colonization of patients undergoing surgery for nasal polyposis, and to assess correlations with phenotypic features, functional results and postoperative clinical course. RESULTS: One hundred and seven patients were included. A total of 26% were not infected, 55% mono-infected and 19% multi-infected. In 27.3%, staphylococci were isolated; in 30.5%, isolates were gram-negative bacilli. There were no significant correlations between presence or type of pathogen and symptom profile. CONCLUSION: This study confirmed the high rate of pathogenic bacteria in nasal cavities in case of polyposis, with high frequencies of S. aureus but also of gram-negative bacilli, raising the question of their involvement in the inflammatory reactions underlying the nasal polyposis.

Management of infective endocarditis and multidisciplinary approach.

INTRODUCTION: The morbi-mortality related to infective endocarditis (IE) remains high as the epidemiology has changed over the last years: ageing of patients, comorbidity and healthcare-associated infections. To optimize IE management, a weekly endocarditis multidisciplinary meeting (EMM) was set up at our facility. We present the activity report of the EMM. PATIENTS AND METHODS: All patients hospitalized for IE who were presented at the weekly EMM between January 2013 and June 2017 were prospectively included. The main objective was to assess the impact of the EMM on the management of community-acquired IE and healthcare-associated IE by analyzing in-hospital case fatality. RESULTS: Of the 1139 cases reported during the EMM for suspicion of IE, 493 (86% were definite cases) were selected for the study: 262 patients had community-acquired IE and 231 had healthcare-associated IE; 43% of IEs involved a valvular prosthesis. Following the EMM, infections were documented in 92% of cases: staphylococci in 45% of healthcare-associated IEs and streptococci in 44% of community-acquired IE cases. A septic embolism was diagnosed in 57% of cases. Finally, 49% of patients underwent surgery. The in-hospital case fatality was 12% with no significant difference between community-acquired IEs and healthcare-associated IEs. Case fatality was also significantly higher in elderly patients, in the absence of surgical treatment, initial heart failure, or Staphylococcus aureus IE. CONCLUSION: The weekly EMM allows our facility to follow the European Society of Cardiology guidelines and to adapt the management of each patient to improve IE prognosis.

Characteristics and outcome of multidrug-resistant tuberculosis in a low-incidence area.

OBJECTIVES: To characterize multidrug-resistant tuberculosis (MDR-TB) patients treated in a low endemic area in France and to determine risk factors for resistance. We also analyzed the efficacy and tolerability of tuberculosis (TB) treatment. METHODS: Between 2002-2013, all MDR-TB patients diagnosed in western France (hospitals belonging to the GERICCO group) were retrospectively included, with a follow-up period running until 2016. A case-control study (1:2), matched according to age, sex, and year of diagnosis, was performed to assess socio-demographic and clinical data, treatment strategies, and outcomes for the MDR-TB patients and controls treated for drug-susceptible tuberculosis during the same period. RESULTS: Of 134 TB patients, 44 were MDR-TB and 90 were drug-susceptible TB. Of the 44 MDR-TB patients (35 MDR and nine extensively drug-resistant [XDR]), 33 (75%) were males; the median age was 33 years; and 27 (61%) were born in Eastern Europe. Prior treatment failure was more frequently reported for XDR-TB (8/9) in Georgian patients. In multivariate analysis, risk contacts and prior TB history were associated with MDR-TB. Treatment failure was associated with MDR/XDR-TB and miliary TB. CONCLUSION: In western France, MDR-TB more frequently occurred in recent migrants from high-risk countries with a previous history of at-risk contact with other MDR-TB patients or previous TB treatment failure.

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.

Interest of proviral HIV-1 DNA genotypic resistance testing in virologically suppressed patients candidate for maintenance therapy.

Switch of antiretroviral therapy in virologically suppressed HIV-infected patients is frequent, to prevent toxicities, for simplification or convenience reasons. Pretherapeutic genotypic resistance testing on RNA can be lacking in some patients, which could enhance the risk of virologic failure, if resistance-associated mutations of the new regimen are not taken into account. Proviral DNA resistance testing in 69 virologically suppressed patients on antiretroviral treatment with no history of virological failure were pair-wised compared with pre-ART plasma RNA resistance testing. The median time between plasma (RNA testing) and whole blood (proviral DNA testing) was 47 months (IQR 29-63). A stop codon was evidenced in 23% (16/69) of proviral DNA sequences; these strains were considered as defective, non-replicative, and not taken into consideration. Within the non defective strains, concordance rate between plasma RNA and non-defective proviral DNA was high both on protease (194/220 concordant resistance-associated mutations=88%) and reverse transcriptase (28/37 concordant resistance-associated mutations=76%) genes. This study supports that proviral DNA testing might be an informative tool before switching antiretrovirals in virologically suppressed patients with no history of virological failure, but the interpretation should be restricted to non-defective viruses.

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.