Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms.

Ceftazidime-avibactam (CAZ-AVI) is a recently approved ß-lactam-ß-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.

Linezolid for the treatment of multidrug-resistant tuberculosis.

OBJECTIVES: In vitro studies have shown good activity of linezolid against Mycobacterium tuberculosis, including multidrug-resistant strains. However, clinical experience with linezolid in tuberculosis is scarce. METHODS: We report our clinical experience with five consecutive patients with multidrug-resistant tuberculosis infection treated with combination regimens that included linezolid. RESULTS: Two patients had multidrug-resistant Mycobacterium bovis infection, with resistance to 12 antituberculous agents (one of them with HIV co-infection and <50 CD4 cells/mm(3)). The other three patients were infected by multidrug-resistant M. tuberculosis strains, with resistance to all first-line drugs and other second-line drugs. All patients received linezolid in combination with thiacetazone, clofazimine or amoxicillin/clavulanate. Susceptibility tests showed linezolid MIC values < or =0.5 mg/L against all tuberculosis strains tested (standard proportion method, Middlebrook agar 7H10). In all cases, tuberculosis cultures from respiratory samples were sterile after 6 weeks of therapy. Three patients have clinical and microbiological cure of tuberculosis with a combination regimen with linezolid (range: 5-24 months). One patient was lost to follow-up at month 5. The remaining patient has completed 11 months of therapy and is still on treatment. Four patients developed anaemia and needed blood transfusions. In two of these patients, the linezolid daily-dose (600 mg twice a day) was successfully reduced to 50% (300 mg twice a day) to decrease toxicity while maintaining efficacy. Peripheral neuropathy (two patients) and pancreatitis (one patient) were other adverse events observed during linezolid treatment. CONCLUSIONS: In our experience, linezolid has been a valid alternative drug in the management of multidrug-resistant tuberculosis. The prolonged use of linezolid is frequently associated with toxicity, mainly anaemia and peripheral neuropathy, that requires special management.