Development of an Electronic Definition for De-escalation of Antibiotics in Hospitalized Patients.

BACKGROUND: Antimicrobial stewardship programs (ASPs) promote the principle of de-escalation: moving from broad- to narrow-spectrum agents and stopping antibiotics when no longer indicated. A standard, objective definition of de-escalation applied to electronic data could be useful for ASP assessments. METHODS: We derived an electronic definition of antibiotic de-escalation and performed a retrospective study among 5 hospitals. Antibiotics were ranked into 4 categories: narrow-spectrum, broad-spectrum, extended-spectrum, and agents targeted for protection. Eligible adult patients were cared for on inpatient units, had antibiotic therapy for at least 2 days, and were hospitalized for at least 3 days after starting antibiotics. Number of antibiotics and rank were assessed at 2 time points: day of antibiotic initiation and either day of discharge or day 5. De-escalation was defined as reduction in either the number of antibiotics or rank. Escalation was an increase in either number or rank. Unchanged was either no change or discordant directions of change. We summarized outcomes among hospitals, units, and diagnoses. RESULTS: Among 39 226 eligible admissions, de-escalation occurred in 14 138 (36%), escalation in 5129 (13%), and antibiotics were unchanged in 19 959 (51%). De-escalation varied among hospitals (median, 37%; range, 31-39%, P < .001). Diagnoses with lower de-escalation rates included intra-abdominal (23%) and skin and soft tissue (28%) infections. Critical care had higher rates of both de-escalation and escalation compared with wards. CONCLUSIONS: Our electronic de-escalation metric demonstrated variation among hospitals, units, and diagnoses. This metric may be useful for assessing stewardship opportunities and impact.

Initial characterization of micafungin pulmonary delivery via two different nebulizers and multivariate data analysis of aerosol mass distribution profiles.

Pharmaceutical aerosols have been targeted to the lungs for the treatment of asthma and pulmonary infectious diseases successfully. Micafungin (Astellas Pharma US, Deerfield, IL, USA) has been shown to be an effective antifungal agent when administrated intravenously. Pulmonary delivery of micafungin has not previously been reported. In the present pilot study, we characterize the performance of two nebulizers and their potential for delivering micafungin to the lungs as well as the use of multivariate data analysis for mass distribution profile comparison. The concentration of micafungin sodium increased by 21% when delivered by the Acorn II nebulizer and by 20% when delivered by the LC Plus nebulizer, respectively, from the first to the second sampling period. The Acorn II nebulizer delivered a fine particle fraction FPF(5.8) (%<5.8 microm) of 92.5 +/- 0.8 and FPF(3.3) (%<3.3 microm) of 82.3 +/- 2.1 during the first sampling period. For the LC Plus nebulizer, FPF(5.8) was 92.3 +/- 0.1 and FPF(3.3) was 67.0 +/- 0.7 during the first sampling period. The mass median aerodynamic diameter (MMAD) increased from 1.67 +/- 0.05 to 1.77 +/- 0.04 mum (Acorn II nebulizer) and from 2.09 +/- 0.01 to 2.20 +/- 0.01 microm (Pari LC Plus nebulizer) from the first to the second sampling periods. These changes in MMAD were statistically significant by paired t test. Multivariate data analysis showed that this could be explained systematically by greater drug deposition on stages with larger cutoff sizes and reduced drug deposition on stages with smaller cutoff sizes rather than multimodal deposition or other anomalies in size distribution.

Feasibility and Value of Developing a Regional Antibiogram for Community Hospitals.

OBJECTIVETo determine the feasibility and value of developing a regional antibiogram for community hospitals.DESIGNMulticenter retrospective analysis of antibiograms.SETTING AND PARTICIPANTSA total of 20 community hospitals in central and eastern North Carolina and south central Virginia participated in this study.METHODSWe combined antibiogram data from participating hospitals for 13 clinically relevant gram-negative pathogen-antibiotic combinations. From this combined antibiogram, we developed a regional antibiogram based on the mean susceptibilities of the combined data.RESULTSWe combined a total of 69,778 bacterial isolates across 13 clinically relevant gram-negative pathogen-antibiotic combinations (median for each combination, 1100; range, 174-27,428). Across all pathogen-antibiotic combinations, 69% of local susceptibility rates fell within 1 SD of the regional mean susceptibility rate, and 97% of local susceptibilities fell within 2 SD of the regional mean susceptibility rate. No individual hospital had >1 pathogen-antibiotic combination with a local susceptibility rate >2 SD of the regional mean susceptibility rate. All hospitals' local susceptibility rates were within 2 SD of the regional mean susceptibility rate for low-prevalence pathogens (<500 isolates cumulative for the region).CONCLUSIONSSmall community hospitals frequently cannot develop an accurate antibiogram due to a paucity of local data. A regional antibiogram is likely to provide clinically useful information to community hospitals for low-prevalence pathogens.Infect Control Hosp Epidemiol 2018;39:718-722.

Recent advances in antifungal pharmacotherapy for invasive fungal infections.

Invasive fungal infections carry significant morbidity and mortality. Candida species have become one of the most frequent causes of bloodstream infections, and infections caused by molds such as Aspergillus are becoming more frequent in immunocompromised patients. As this population grows, more invasive fungal infections can be anticipated. In the past, treatment options have been limited for many of these infections due to toxicity and efficacy concerns with the available antifungals. Fortunately, the past few years have brought exciting developments in antifungal pharmacotherapy. Lipid-based formulations of amphotericin B were introduced in the 1990s to attenuate adverse effects caused by amphotericin B deoxycholate (Fungizone, Bristol-Myers Squibb). Most recently, the echinocandins have been added to our antifungal regimen with the introduction of caspofungin (Cancidas, Merck and Co.) and voriconazole (Vfend, Pfizer), a new triazole, has come to market. The introduction of the echinocandins has invigorated the discussion about combination antifungal therapy. Evidence-based studies using these new agents are accumulating, and they are assuming important roles in the pharmacotherapy of invasive fungal infections in seriously ill and complex patients.

Nebulizer delivery of micafungin aerosols.

STUDY OBJECTIVES: To determine the optimal nebulization system for aerosolizing micafungin and to further assess the physiochemical properties of aerosolized micafungin. DESIGN: In vitro experiment. SETTING: University research center. NEBULIZERS: Pari LC Star, Hudson Updraft, Small Volume Nebulizer, and Aeroclipse II. MEASUREMENTS AND MAIN RESULTS: Using a commercially available cascade impactor, the four nebulizers were tested for their ability to deliver micafungin to the lungs. Mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF) percent less than 3.3 µm (FPF(3.3)) and less than 5.8 µm (FPF(5.8)) were determined during two sampling periods for each of three trials of all nebulizers. The mean ± standard error of the mean MMAD for the nebulizers ranged from 1.93 ± 0.09 to 2.49 ± 0.25 µm; FPF(3.3) and FPF(5.8) were approximately 50% and 90%, respectively, for all nebulizers. CONCLUSION: Although all nebulizers appeared acceptable to deliver micafungin to the lungs, the Pari LC Star had the smallest MMAD and highest FPF(3.3) and FPF(5.8). These properties of the Pari LC Star should result in greater delivery of the aerosol to the lungs. Additional research on pulmonary delivery and clinical tolerability is warranted.