Nontuberculous mycobacterial immune reconstitution syndrome has a wide range of clinical presentations and severity. The long-term prognosis is favorable for HAART-adherent patients. Intra-abdominal disease is associated with greater morbidity than is peripheral lymphadenitis. The role of antimycobacterial therapy is uncertain, given the self-limited course of most nonabdominal cases.
A randomized trial was conducted to compare the efficacy and safety of fluconazole versus that of amphotericin B in the treatment of candidemia in non-neutropenic adults. Enrollment was stratified by disease severity (APACHE II score). Patients were randomized (1:1) to receive amphotericin B 0.6 mg/kg/day (cumulative dose 8 mg/kg) or fluconazole 800 mg intravenous loading dose, then 400 mg daily for four weeks (intravenous for at least 10 days). Patients were monitored for six months. A total of 106 patients were enrolled. A protocol amendment implemented midway through the trial required patients to be removed from the study and treated with amphotericin B if species identification indicated candidemia due to Candida glabrata or Candida krusei. Baseline characteristics were similar for the two groups; 103 patients (fluconazole, 50; amphotericin B, 53) met the major enrollment criteria. The intention-to-treat analysis indicated successful therapy in 50% of fluconazole recipients compared to 58% of the amphotericin B group (p = 0.39; one-sided 95% CI, -8 to 24%). The efficacy analysis included 84 patients (fluconazole, 42; amphotericin B, 42); successful outcomes were observed in 57% and 62% of cases in the fluconazole and amphotericin B groups, respectively (p = 0.66: one-sided 95% CI, -12 to 22%). The mortality at day 14 for the fluconazole group was 26% and for the amphotericin B group 21% (p = 0.52; chi-square test) and remained similar throughout the course of follow-up, Drug-related adverse events were more frequent with amphotericin B than with fluconazole and prompted switching of therapy for two (4%) and zero cases, respectively. Fluconazole and amphotericin B were associated with similar clinical response rates and survival in the treatment of candidemia among non-neutropenic patients; however, drug-related adverse events were more frequent with amphotericin B.
In patients with AIDS and M. avium complex bacteremia, treatment with the three-drug regimen of rifabutin, ethambutol, and clarithromycin leads to resolution of the bacteremia more frequently and more rapidly than treatment with rifampin, ethambutol, clofazimine, and ciprofloxacin, and survival rates are better.
Candidemia and invasive candidiasis (C/IC) are life-threatening opportunistic infections that add excess morbidity, mortality and cost to the management of patients with a range of potentially curable underlying conditions. The Association of Medical Microbiology and Infectious Disease Canada developed evidence-based guidelines for the approach to the diagnosis and management of these infections in the ever-increasing population of at-risk adult patients in the health care system. Over the past few years, a new and broader understanding of the epidemiology and pathogenesis of C/IC has emerged and has been coupled with the availability of new antifungal agents and defined strategies for targeting groups at risk including, but not limited to, acute leukemia patients, hematopoietic stem cell transplants and solid organ transplants, and critical care unit patients. Accordingly, these guidelines have focused on patients at risk for C/IC, and on approaches of prevention, early therapy for suspected but unproven infection, and targeted therapy for probable and proven infection.
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