Trends in antibiotic use before and during the coronavirus disease 2019 (COVID-19) pandemic across an integrated health system with different antimicrobial stewardship program models trends in antibiotic use by ASP model.

Changes in antimicrobial use during the pandemic in relation to long-term trends in utilization among different antimicrobial stewardship program models have not been fully characterized. We analyzed data from an integrated health system using joinpoint regression and found temporal fluctuations in prescribing as well as continuation of existing trends.

Tacrolimus enhances the potency of posaconazole against Rhizopus oryzae in vitro and in an experimental model of mucormycosis.

BACKGROUND: We hypothesized that tacrolimus, an inhibitor of the calcineurin pathway, would enhance the in vivo activity of posaconazole against Rhizopus oryzae, the Mucorales species most commonly associated with mucormycosis. METHODS: We examined patterns of growth inhibition and fungicidal activity of posaconazole and tacrolimus, alone and in combination, against R. oryzae in vitro, using multiple methods (ie, hyphal metabolic and fluorescent vital dye reduction assays and measurement of chitin concentrations), and in vivo, using 2 mucormycosis models: an invertebrate model (Drosophila) and a nonlethal murine model of cutaneous mucormycosis. RESULTS: Combinations of posaconazole and tacrolimus were synergistic in checkerboard assays for 4 clinical isolates of R. oryzae (48-hour fractional inhibitory concentration index, 0.187-0.281). Pharmacodynamic analysis of the combination revealed that the 90% effective concentration threshold of posaconazole activity against R. oryzae could be achieved with 2-fold lower drug concentrations (0.5-1 mg/L) when administered with tacrolimus (0.007-2 mg/L). In vivo, combination therapy was associated with improved survival in the fly model of mucormycosis (65% vs 57% posaconazole alone) and with significant reductions in cutaneous lesions and R. oryzae fungal burden, compared with animals that received posaconazole monotherapy, in the cutaneous model of mucormycosis. CONCLUSIONS: Combination posaconazole-tacrolimus therapy displays synergism in vitro and improved antifungal efficacy in vivo in 2 phylogenetically distinct models of mucormycosis.

Palatal mucormycosis in patients with hematologic malignancy and stem cell transplantation.

We present two patients with acute myelogenous leukemia who developed palatal mucormycosis, as well as a review of 15 well described reported cases of the same condition in patients who had hematologic malignancy and had undergone hematopoietic stem cell transplantation. Early diagnosis of palatal mucormycosis requires high suspicion of the disease along with a thorough oral examination. Mucormycosis is a devastating disease with a high mortality rate, thereby stressing the importance for early appropriate antifungal therapy in immunocompromised patients with palatal lesions while awaiting the results of histopathology and cultures.

Prior antimicrobial exposure and the risk for bloodstream infection with fluconazole-non-susceptible Candida strains.

Candida species are a common cause of bloodstream infection among hospitalized patients. Increasingly these infections are caused by strains resistant to commonly used antifungal agents. The aim of this study was to assess the association between exposure to specific antimicrobial agents and subsequent bloodstream infection with fluconazole-non-susceptible and fluconazole-susceptible Candida strains. A retrospective case-case-control study was performed. From 2002 to 2006, 50 consecutive patients with hospital-acquired bloodstream infection caused by Candida strains not fully susceptible to fluconazole were identified (case group 1). For comparison, 54 patients with fluconazole-susceptible candidaemia (case group 2) and a control group of 104 patients without candidaemia were studied. Models were adjusted for demographic and clinical risk factors. The risk for candidaemia associated with exposure to specific antimicrobial agents was assessed. Piperacillin/tazobactam (odds ratio (OR) 6.8, 95% confidence interval (CI) 1.4-32.2) and ciprofloxacin (OR 8.0, 95% CI 1.5-42.5), but not fluconazole, were significant risk factors for bloodstream infection with fluconazole-non-susceptible Candida. Only ciprofloxacin (OR 7.8, 95% CI 1.2-50.7) was associated with bloodstream infection with fluconazole-susceptible Candida. Despite adjustment for prior exposure to fluconazole, exposure to specific antibacterial agents was associated with hospital-acquired bloodstream infection with fluconazole-non-susceptible Candida.