Isavuconazole for the prophylaxis and treatment of invasive fungal disease: A single-center experience.

BACKGROUND: Invasive fungal disease (IFD) is a serious complication among the immunocompromised population. Isavuconazole is a newer broad-spectrum antifungal agent with promising efficacy and safety. However, there remains limited data to favor its use over current first-line agents. OBJECTIVES: We aimed to evaluate isavuconazole use and describe rates of associated breakthrough invasive fungal disease (bIFD). METHODS: A single-center, retrospective study was conducted to evaluate patients receiving isavuconazole for prophylaxis or treatment of IFD between July 1, 2017 and December 31, 2018. Patient-related and outcomes data were extracted from electronic medical records. Descriptive statistics were used to analyze our findings. RESULTS: A total of 54 patients received 61 isavuconazole courses. Isavuconazole was most commonly prescribed for primary prophylaxis in the acute myeloid leukemia (AML) and allogeneic hematopoietic stem cell transplant (HSCT) population along with treatment for possible invasive fungal disease. The primary reasons for choosing isavuconazole included QTc shortening effects, decreased risk of acute kidney injury, broader spectrum of activity, and concern for breakthrough invasive fungal disease on a different prophylactic agent. We found a breakthrough rate of 8.5% for patients and 7.8% for courses. CONCLUSIONS: Isavuconazole appears to be a promising alternative for prophylaxis and treatment of invasive fungal disease. We observed similar bIFD rates and improved tolerability when compared to historical data for posaconazole and voriconazole.

Characteristics of Antibiotic Prophylaxis and Risk of Surgical Site Infections in Primary Total Hip and Knee Arthroplasty.

BACKGROUND: Despite numerous antibiotic prophylaxis options for total hip arthroplasty (THA) and total knee arthroplasty (TKA), an assessment of practice patterns and comparative effectiveness is lacking. We aimed to characterize antibiotic utilization patterns and associations with infection risk and hypothesized differences in infection risk based on regimen. METHODS: A retrospective cohort study was performed using data from 436,724 THA and 862,918 TKA (Premier Healthcare Database; 2006-2016). Main exposures were antibiotic type and duration: day of surgery only (day 0) or through postoperative day 1 (day 1). The primary outcome was surgical site infection (SSI) <30 days postoperation. Mixed-effect models measured associations between prophylaxis regimen and SSI as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: SSI prevalence was 0.21% (n = 914) for THA and 0.22% (n = 1914) for TKA. Among THA procedures, the most commonly used antibiotics were cefazolin (74.1%), vancomycin (8.4%), "other" antibiotic combinations (7.1%), vancomycin + cefazolin (5.1%), and clindamycin (3.3%). Here, 51.8% received prophylaxis on day 0 only, whereas 48.2% received prophylaxis through day 1. Similar patterns existed for TKA. Relative to cefazolin, higher SSI odds were seen with vancomycin (OR = 1.36; CI 1.09-1.71) in THA and with vancomycin (OR = 1.29; CI = 1.10-1.52), vancomycin + cefazolin (OR = 1.35; CI = 1.12-1.64), clindamycin (OR = 1.38; CI = 1.11-1.71), and "other" antibiotic combinations (OR = 1.28; CI = 1.07-1.53) in TKA. Prophylaxis duration did not alter SSI odds. Results were corroborated in sensitivity analyses. CONCLUSION: Antibiotic prophylaxis regimens other than cefazolin were associated with increased SSI risk among THA/TKA patients. These findings emphasize a modifiable intervention to mitigate infection risk.

Variable pharmacokinetics of extended interval tobramycin or gentamicin among critically ill patients undergoing continuous venovenous hemofiltration.

BACKGROUND/AIMS: Aminoglycosides are a major weapon against serious Gram-negative rod infections, yet aminoglycoside usage is limited by the risk of nephrotoxicity. The risk of toxicity is reduced by extended-interval dosing of aminoglycosides, defined as 5 - 7 mg/kg given intravenously in intervals of 24 hours or greater based on serum drug concentrations. In critically ill patients undergoing continuous venovenous hemofiltration, there are few published reports of the pharmacokinetics of extended-interval dosing of aminoglycosides. METHODS: We evaluated the pharmacokinetics of extended-interval dosing of gentamicin and tobramycin in 9 critically ill patients on continuous venovenous hemofiltration at Dartmouth-Hitchcock Medical Center between April 2007 and September 2011. RESULTS: Aminoglycoside elimination half-life values were highly variable (median 7 hours, range 3 - 26 hours) and did not correlate with total body weight or estimated creatinine clearance derived from the dose of continuous venovenous hemofiltration. Five of 9 patients cleared infection, but only 4 patients survived to hospital discharge, 2 of whom were dialysis-dependent. CONCLUSION: Extended interval aminoglycoside dosing during continuous venovenous hemofiltration yields unpredictable half-lives and drug levels among high-risk critically ill patients. Close monitoring of serum aminoglycoside levels is required.

The clinical impact of early detection of ESBL-producing Enterobacterales with PCR-based blood culture assays.

BACKGROUND: Starting January 4, 2021, our health system core microbiology laboratory changed blood culture identification (BCID) platforms to ePlex BCID from BioFire BCID1 with the additional capability to detect the blaCTX-M-Type gene of ESBL-producing organisms. Clinical outcomes of ESBL bloodstream infections (BSI) after implementing ePlex BCID were unknown. METHODS: Patients with ESBL BSI were compared pre and postimplementation of ePlex BCID in this 11-hospital retrospective analysis (BioFire BCID1 in 2019 vs ePlex BCID in 2021). The primary outcome was time from the Gram stain result to escalation to a carbapenem. Secondary outcomes included in-hospital mortality, 30-day readmission rate, length of stay (LOS), and the duration of antimicrobial therapy. RESULTS: A total of 275 patients were analyzed. The median time of Gram stain result to escalation to carbapenem was reduced from 44.5 hours with BioFire BCID1 to 7.9 hours with ePlex BCID (P < .001). There were no significant differences in mortality, 30-day readmission, or LOS. The duration of antimicrobial therapy for ESBL BSI was lower in the ePlex BCID group (from 14.4 days to 12.7 days, P = .014). CONCLUSIONS: Timely detection of the blaCTX-M-Type gene by BCID provides valuable information for the early initiation of appropriate and effective antimicrobial therapy. Although it was not associated with lower mortality, 30-day readmission, or LOS, it may have benefits such as decreasing antimicrobial exposure to patients.

Overcoming challenges to removing inappropriate penicillin allergy labels: A quality improvement report.

Over 3 months, we provided monthly education to internal medicine residents and distributed resources regarding penicillin-allergy history taking. Allergy information in the electronic record was updated more often during the intervention compared to the period before the intervention (16.1% vs 10.9%; P = .02). Education and interdepartmental collaboration have the potential to affect provider behavior.

Impact of an electronic sepsis initiative on antibiotic use and health care facility-onset Clostridium difficile infection rates.

BACKGROUND: Although integrated, electronic sepsis screening and treatment protocols are thought to improve patient outcomes, less is known about their unintended consequences. We aimed to determine if the introduction of a sepsis initiative coincided with increases in broad-spectrum antibiotic use and health care facility-onset (HCFO) Clostridium difficile infection (CDI) rates. METHODS: We used interrupted time series data from a large, tertiary, urban academic medical center including all adult inpatients on 4 medicine wards (June 2011-July 2014). The main exposure was implementation of the sepsis screening program; the main outcomes were the use of broad-spectrum antibiotics (including 3 that were part of an order set designed for the sepsis initiative) and HCFO CDI rates. Segmented regression analyses compared outcomes in 3 time segments: before (11 months), during (14 months), and after (12 months) implementation of a sepsis initiative. RESULTS: Antibiotic use and HFCO CDI rates increased during the period of implementation and the period after implementation compared with baseline; these increases were highest in the period after implementation (level change, 50.4 days of therapy per 1,000 patient days for overall antibiotic use and 10.8 HCFO CDIs per 10,000 patient days; P < .05). Remarkably, the main drivers of overall antibiotic use were not those included in the sepsis order set. CONCLUSIONS: The implementation of an electronic sepsis screening and treatment protocol coincided with increased broad-spectrum antibiotic use and HCFO CDIs. Because these protocols are increasingly used, further study of their unintended consequences is warranted.