In a randomized double-blind study, nine mycobacteremic patients with AIDS-related disseminated Mycobacterium avium complex (MAC) infection received clarithromycin or placebo in addition to a basic regimen that included isoniazid, ethambutol and clofazimine. All four patients receiving clarithromycin showed blood culture conversion and clinical response. Of the five patients treated without clarithromycin, two showed resolution of mycobacteremia and clinical response, while another two died without having shown response. The remaining patient deteriorated until a switch from placebo to clarithromycin led to blood culture conversion and rapid clinical improvement. After finishing six weeks of intensive treatment, clarithromycin was given in an open maintenance phase to all patients, initially in combination with rifabutin for 24 weeks and then alone. One patient had a relapse of MAC infection while receiving clarithromycin alone. The relapse was associated with acquired resistance to the drug. Clarithromycin appears to be a promising component of multi-drug therapy for patients with MAC infection. Monotherapy can lead to drug resistance.
The aim of this double-blind, randomized, placebo-controlled, 12-week study was to assess the efficacy of rifabutin (450 or 600 mg/d) in the treatment of disseminated nontuberculous mycobacterial infection in patients with AIDS. Companion drugs in both arms of the study were ethambutol, clofazimine, and isoniazid. Because of low accrual, the study was prematurely terminated when a total of 382 patients had been enrolled, of which 200 were eligible (i.e., their specimens were culture-positive for Mycobacterium avium complex [MAC] or Mycobacterium xenopi at baseline) and 102 were evaluable (i.e., they were eligible, were treated for a minimum of 6 weeks, and had at least one culture assessment after baseline). The original protocol called for a total of 220 evaluable patients. At week 12, rifabutin treatment was associated with higher, although nonsignificant, rates of bacteriologic conversion than was the placebo arm, with regard to both the eligible patients (25% vs. 18%) and the evaluable patients (45% vs. 38%). Corresponding median times to culture conversion were 42 vs. 63 days (eligible patients) and 43 vs. 69 days (evaluable patients). No significant difference was observed in clinical improvement, mortality, or toxicity between the two treatment arms. The addition of rifabutin to a triple-drug regimen may contribute to the clearance of disseminated MAC infection in patients with AIDS, without causing additional toxicity.
Background: Multi-drug resistant (MDR) pathogens are of increasing concern in clinical medicine. Patients with prosthetic joints as well as those with fractures are at risk of contracting infections. Extent and frequency of infections with MDR bacteria in patients with osteoarticular infections in Germany are largely unknown. Methods & Materials: A large case series of patients admitted to a specialized septic surgery ward in a tertiary referral center was analyzed for the presence of MDR bacteria in joint fluids, tissue samples and swabs taken from purulent secretions during surgery. Results: Patients admitted in 2014-2016 with osteoarticular infections with and without prosthetic material and positive microbiological samples were included in the analysis. In 274 individuals 554 microbiological samples were obtained which disclosed 656 pathogens. MDR bacteria were isolated in 43/656 (6.6%). The distribution of MDR pathogens comprised MRSA in 22 (3.4%) cases, VRE in 12 (1.8%), ESBL-producing Gram-negative bacteria (E. coli and K. pneumoniae) in 6 (0.9%), and non-fermenter with peculiar resistance patterns (MDR-Stenotrophomonas maltophilia, Colistin-resistant P. aeruginosa) in 3 (0.5%). Carbapenemase-producing bacteria were not retrieved. The numbers of detected MDR pathogens increased over the years (5.8% in 2014, 6.8% in 2015, and 8.3% in 2016) albeit not reaching statistical significance. Conclusion: MDR pathogens were frequently found in our large case series. Gram-positive pathogens (MRSA, VRE) are predominating the spectrum. Difficult-to-treat Gram-negative bacteria were rarely seen.
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