Detection of highly macrolide-resistant Legionella pneumophila strains from a hotel water network using systematic whole-genome sequencing.

OBJECTIVES: Implementation of an antibiotic resistance detection tool in Legionella daily surveillance at the French National Reference Centre for Legionella. METHODS: Systematic WGS of Legionella pneumophila isolates and bioinformatics detection of specific mutations linked to antibiotic resistance. Phenotypic validation of antibiotic resistance detected by WGS was performed by the broth microdilution method. RESULTS: More than 3000 L. pneumophila strains were screened for antibiotic resistance. A macrolide resistance-associated A2052G mutation in the 23S rRNA gene was identified in the genome of eight isolates from a hotel water network. High-level macrolide resistance (i.e. MICs of 1024-2048 mg/L for azithromycin and erythromycin) with no cross-resistance to other antimicrobials was phenotypically confirmed by antimicrobial susceptibility testing for the eight isolates. CONCLUSIONS: Systematic WGS of L. pneumophila is a powerful tool for first-line high-throughput screening of antibiotic resistance before phenotypic validation.

Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection.

BACKGROUND: The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear. METHODS: We performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points. RESULTS: A total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events. CONCLUSIONS: Among patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.).

Primary meningococcal arthritis in a COVID-19 18-year-old man: a case report and review of the literature.

BACKGROUND: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is associated with various complications. PMA (primary meningococcal arthritis) is a rare meningococcus-associated disease causing arthritis of the knee usually, without any signs of invasive meningococcal disease. No case of PMA in a COVID-19 (coronavirus disease, 2019) patient has yet been described. PMA mainly strikes young adults. PMA is not associated with any immunocompromising condition. It has a better outcome than usual septic arthritis CASE PRESENTATION: Herein, we report an 18-year-old man diagnosed with COVID-19, later admitted with persistent fever, right knee arthralgia and maculopapular rash. Due to family history, psoriasis and Henoch-Schönlein purpura were hypothesized and ruled out. Finally, synovial fluid culture confirmed Neisseria meningitidis serogroup B arthritis without any other symptoms of invasive meningococcal disease. Healing was achieved quickly with surgery and antibiotics. We concluded in a PMA. CONCLUSION: We describe here the first primary meningococcal arthritis in a COVID-19 patient and we hope to shine a light on this rare but serious complication.

Bacterial infection profiles in lung cancer patients with febrile neutropenia.

BACKGROUND: The chemotherapy used to treat lung cancer causes febrile neutropenia in 10 to 40% of patients. Although most episodes are of undetermined origin, an infectious etiology can be suspected in 30% of cases. In view of the scarcity of data on lung cancer patients with febrile neutropenia, we performed a retrospective study of the microbiological characteristics of cases recorded in three medical centers in the Picardy region of northern France. METHODS: We analyzed the medical records of lung cancer patients with neutropenia (neutrophil count < 500/mm(3)) and fever (temperature > 38.3°C). RESULTS: The study included 87 lung cancer patients with febrile neutropenia (mean age: 64.2). Two thirds of the patients had metastases and half had poor performance status. Thirty-three of the 87 cases were microbiologically documented. Gram-negative bacteria (mainly enterobacteriaceae from the urinary and digestive tracts) were identified in 59% of these cases. Staphylococcus species (mainly S. aureus) accounted for a high proportion of the identified Gram-positive bacteria. Bacteremia accounted for 60% of the microbiologically documented cases of fever. 23% of the blood cultures were positive. 14% of the infections were probably hospital-acquired and 14% were caused by multidrug-resistant strains. The overall mortality rate at day 30 was 33% and the infection-related mortality rate was 16.1%. Treatment with antibiotics was successful in 82.8% of cases. In a multivariate analysis, predictive factors for treatment failure were age >60 and thrombocytopenia < 20000/mm(3). CONCLUSION: Gram-negative species were the most frequently identified bacteria in lung cancer patients with febrile neutropenia. Despite the success of antibiotic treatment and a low-risk neutropenic patient group, mortality is high in this particular population.

Bronchial fistula associated with sunitinib in a patient previously treated with radiation therapy.

OBJECTIVE: To report a case of bronchial fistula associated with sunitinib in a patient previously treated with radiation therapy. CASE SUMMARY: A 40-year-old man with renal cell cancer diagnosed in 2005 and initially treated by radical nephrectomy presented in March 2007 with a recurrence with cerebral, mediastinal, and lung metastases. A thoracic computed tomography (CT) scan showed a subcarinal tumor obstructing the bronchus intermedius. The patient was initially treated with cerebral and thoracic radiotherapy and then with sunitinib 50 mg/day (4 weeks on, 2 weeks off). Two months after the beginning of treatment, a CT scan revealed a dramatic reduction in the size of the tumor, associated with a bronchial fistula. This was confirmed by flexible bronchoscopy, which showed complete necrosis of the tumor and a large perforation of the bronchus intermedius. Sunitinib was immediately withdrawn and antibiotic prophylaxis was instituted. It was not possible to place an endobronchial stent. Two weeks later, flexible bronchoscopy revealed the reappearance of a yellowish mass protruding into the bronchus intermedius (40% obstruction). A few months later, the obstruction of the bronchus intermedius progressed to 90% and was associated with a contralateral obstruction of the left mainstem bronchus (20%). A rigid bronchoscopy was then performed to clear the obstruction and an endobronchial stent was placed, with satisfactory initial results. In February 2008, the patient presented with new bronchial obstruction under the endobronchial stent but refused a rigid bronchoscopy and died in March 2008. DISCUSSION: Sunitinib, a multitarget tyrosine kinase inhibitor with antiangiogenic and antitumoral activities, has been approved for the treatment of advanced renal cell carcinoma. This treatment is generally well tolerated. Serious complications may occur, however. According to the Naranjo probability scale, the bronchial fistula was possibly related to sunitinib treatment. CONCLUSIONS: This is a rare case of a bronchial perforation leading to a fistula associated with sunitinib treatment after mediastinal radiation therapy. Clinicians may consider strict follow-up of patients with proximal lung metastases treated with sunitinib (CT scan and, if appropriate, placement of an endobronchial stent).