ABSTRACT
Pseudomonas aeruginosa is a common pathogen implicated in nosocomial infections with increasing resistance to a limited arsenal of antibiotics. Monte Carlo simulation provides antimicrobial stewardship teams with an additional tool to guide empiric therapy. We modeled empiric therapies with antipseudomonal ß-lactam antibiotic regimens to determine which were most likely to achieve probability of target attainment (PTA) of ≥90%. Microbiological data for P. aeruginosa was reviewed for 2012. Antibiotics modeled for intermittent and prolonged infusion were aztreonam, cefepime, meropenem, and piperacillin/tazobactam. Using minimum inhibitory concentrations (MICs) from institution-specific isolates, and pharmacokinetic and pharmacodynamic parameters from previously published studies, a 10,000-subject Monte Carlo simulation was performed for each regimen to determine PTA. MICs from 272 isolates were included in this analysis. No intermittent infusion regimens achieved PTA ≥90%. Prolonged infusions of cefepime 2000 mg Q8 h, meropenem 1000 mg Q8 h, and meropenem 2000 mg Q8 h demonstrated PTA of 93%, 92%, and 100%, respectively. Prolonged infusions of piperacillin/tazobactam 4.5 g Q6 h and aztreonam 2 g Q8 h failed to achieved PTA ≥90% but demonstrated PTA of 81% and 73%, respectively. Standard doses of ß-lactam antibiotics as intermittent infusion did not achieve 90% PTA against P. aeruginosa isolated at our institution; however, some prolonged infusions were able to achieve these targets.
ABSTRACT
BACKGROUND: Once-daily (QD), combination antiretroviral therapy (ART) can impact the willingness and ability of patients to take medications as directed. The impact of antiretroviral (ARV) drug adherence influenced by single-tablet (STR) versus multi-tablet regimens (MTR) among patients enrolled in the AIDS Drug Assistance Program (ADAP) in a rural environment has not yet been assessed. MATERIAL AND METHODS: A retrospective chart review evaluated adherence and outcomes in adult HIV-infected patients enrolled in the ADAP at 2 ambulatory clinics in the Southeast, taking either a QD STR (efavirenz [EFV]/emtricitabine/tenofovir [TDF]) or a QD protease inhibitor (PI)-based, MTR (atazanavir [ATV], ritonavir [RTV], and emtricitabine/TDF) by evaluating pharmacy refill records, patient self-reported adherence, and virologic response. RESULTS: A total of 389 patient records were analyzed (STR, n = 165 versus MTR, n = 224). There were more males, a higher percentage of treatment-naive patients, and more patients with a baseline CD4 count of >200 cells/mm(3) in the MTR group. Based on refill records, more patients on MTR were >90% adherent (61.6% versus 51.5%, P = .047). In a multivariable analysis, being treatment experienced was a negative predictor (odds ratio [OR] = 0.48, 0.29-0.78) for adherence. Regimen choice was not associated with adherence. More patients taking MTR were virologically suppressed at the end of the observation period. Regardless of the regimen, being >90% adherent was a significant predictor of virologic suppression (OR = 3.51, 1.98-6.23). CONCLUSION: Treatment-experienced patients enrolled in ADAP are less likely to be adherent. A QD PI-based MTR may result in comparable adherence to an STR in a rural HIV-infected population.