Impact of a pharmacy-driven transitions-of-care program on postdischarge healthcare utilization at a national comprehensive cancer center.

PURPOSE: Results of a study comparing readmission rates and medication adherence measures before and after implementation of a pharmacy-led transitions-of-care (TOC) program are reported. METHODS: A quasi-experimental case-control study was conducted to assess the impact of a TOC program including medication history-taking and reconciliation services, inpatient and discharge education, and 72-hour and 30-day postdischarge phone follow-up. Hospital and emergency room (ER) readmission rates were compared in cohorts of oncology patients admitted to a large teaching hospital during specified periods before TOC program implementation (the standard-of-care [SOC] group) or after program implementation (the TOC group). The primary outcome was unplanned hospital or ER readmission within 30 days after initial discharge. The secondary endpoint was first-fill medication adherence. Benefits associated with specific TOC interventions were assessed in subgroup analyses. RESULTS: After propensity score matching, both study groups consisted of 323 patients. The SOC group had 76 patients (23.5%) and the TOC group had 74 patients (22.9%) who were readmitted to the hospital or ER within 30 days, with a significant reduction in hospital readmissions in 1 subgroup of TOC patients versus SOC controls (absolute difference, -7.6%; p = 0.0159). CONCLUSION: While there were no significant overall differences in readmission rates between the TOC and SOC groups, hospital readmissions were reduced in the subgroup of TOC patients who received both medication history-taking and reconciliation services and phone follow-up as TOC interventions.

An institutional review of antimicrobial stewardship interventions.

In order to combat increasing rates of bacterial resistance, many institutions have implemented antimicrobial stewardship programmes (ASPs) to improve antibiotic use. To ascertain the potential impact of our stewardship programme at Baylor St Luke's Medical Center (Houston, TX), antimicrobial-related interventions were analysed over a 4-year period. ASP recommendations related to antimicrobial therapy from 2009 to 2012 were retrieved from the hospital electronic database and were retrospectively reviewed. The number of interventions for each time period was adjusted to the hospital census data. The interventions were randomly assessed and categorised for clinical significance based on established institutional guidelines. In total, 14654 non-duplicate antimicrobial therapy interventions were retrieved, of which 11874 (81.0%) were audited for accuracy. Approximately 13 interventions were made per 1000 patient-days, but there were no significant patterns observed regarding the number of interventions performed from month to month (range 8-21). The most frequent types of interventions were related to inappropriate dosing (39.0%), antimicrobial selection (20.5%) and drug allergy (13.0%). Serious adverse drug events (ADEs) were potentially avoided in 20.7% of all interventions. Cumulative potential cost avoidance was more than US$6.5 million. In our institution, proper drug and dose selection were the major components of the ASP. Without focusing solely on reduction of drug acquisition costs, implementation of an ASP could still be cost effective by improving the quality of patient care and avoiding ADEs with serious consequences.

Assessment of minocycline and polymyxin B combination against Acinetobacter baumannii.

Antimicrobial resistance among Acinetobacter baumannii is increasing worldwide, often necessitating combination therapy. The clinical utility of using minocycline with polymyxin B is not well established. In this study, we investigated the activity of minocycline and polymyxin B against 1 laboratory isolate and 3 clinical isolates of A. baumannii. Minocycline susceptibility testing was performed with and without an efflux pump inhibitor, phenylalanine-arginine ß-naphthylamide (PAßN). The intracellular minocycline concentration was determined with and without polymyxin B (0.5 µg/ml). Time-kill studies were performed over 24 h using approximately 10(6) CFU/ml of each strain with clinically relevant minocycline concentrations (2 µg/ml and 8 µg/ml), with and without polymyxin B (0.5 µg/ml). The in vivo efficacy of the combination was assessed in a neutropenic murine pneumonia model. Infected animals were administered minocycline (50 mg/kg), polymyxin B (10 mg/kg), or both to achieve clinically equivalent exposures in humans. A reduction in the minocycline MIC (≥ 4×) was observed in the presence of PAßN. The intracellular concentration and in vitro bactericidal effect of minocycline were both enhanced by polymyxin B. With 2 minocycline-susceptible strains, the bacterial burden in lung tissue at 24 h was considerably reduced by the combination compared to monotherapy with minocycline or polymyxin B. In addition, the combination prolonged survival of animals infected with a minocycline-susceptible strain. Polymyxin B increased the intracellular concentration of minocycline in bacterial cells and enhanced the bactericidal activity of minocycline, presumably due to efflux pump disruption. The clinical utility of this combination should be further investigated.

Assessment of antimicrobial combinations for Klebsiella pneumoniae carbapenemase-producing K. pneumoniae.

BACKGROUND: The prevalence of bla(KPC) among gram-negative bacteria continues to increase worldwide. Limited treatment options exist for this multidrug-resistant phenotype, often necessitating combination therapy. We investigated the in vitro and in vivo efficacy of multiple antimicrobial combinations. METHODS: Two clinical strains of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae were studied. The killing activities of six 2-agent combinations of amikacin, doripenem, levofloxacin, and rifampin were quantitatively assessed using a validated mathematical model. Combination time-kill studies were conducted using clinically relevant concentrations; observed bacterial burdens were modeled using 3-dimensional response surfaces. Selected combinations were further validated in a neutropenic murine pneumonia model, using human-like dosing exposures. RESULTS: The most enhanced killing effect in time-kill studies was seen with amikacin plus doripenem. Compared with placebo controls, this combination resulted in significant reduction of the bacterial burden in tissue at 24 hours, along with prolonged animal survival. In contrast, amikacin plus levofloxacin was found to be antagonistic in time-kill studies, showing inferior animal survival, as predicted. CONCLUSIONS: Our modeling approach appeared to be robust in assessing the effectiveness of various combinations for KPC-producing isolates. Amikacin plus doripenem was the most effective combination in both in vitro and in vivo infection models. Empirical selection of combinations against KPCs may result in antagonism and should be avoided.