Dalbavancin Sequential Therapy for Gram-Positive Bloodstream Infection: A Multicenter Observational Study.

INTRODUCTION: Long-acting lipoglycopeptides such as dalbavancin may have utility in patients with Gram-positive bloodstream infections (BSI), particularly in those with barriers to discharge or who require prolonged parenteral antibiotic courses. A retrospective cohort study was performed to provide further multicenter real-world evidence on dalbavancin use as a sequential therapy for Gram-positive BSI. METHODS: One hundred fifteen patients received dalbavancin with Gram-positive BSI, defined as any positive blood culture or diagnosed with infective endocarditis, from 13 centers geographically spread across the United States between July 2015 and July 2021. RESULTS: Patients had a mean (SD) age of 48.5 (17.5) years, the majority were male (54%), with many who injected drugs (40%). The most common infection sources (non-exclusive) were primary BSI (89%), skin and soft tissue infection (SSTI) (25%), infective endocarditis (19%), and bone and joint infection (17%). Staphylococcus aureus accounted for 72% of index cultures, coagulase-negative Staphylococcus accounted for 18%, and Streptococcus species in 16%. Dalbavancin started a median (Q1-Q3) of 10 (6-19) days after index culture collection. The most common regimen administered was dalbavancin 1500 mg as one dose for 50% of cases. The primary outcome of composite clinical failure occurred at 12.2%, with 90-day mortality at 7.0% and 90-day BSI recurrence at 3.5%. CONCLUSIONS: Dalbavancin may serve as a useful tool in facilitating hospital discharge in patients with Gram-positive BSI. Randomized controlled trials are anticipated to validate dalbavancin as a surrogate to current treatment standards.

The prevalence of gram-negative bacteria with difficult-to-treat resistance and utilization of novel ß-lactam antibiotics in the southeastern United States.

Objective: To evaluate temporal trends in the prevalence of gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) in the southeastern United States. Secondary objective was to examine the use of novel ß-lactams for GNB with DTR by both antimicrobial use (AU) and a novel metric of adjusted AU by microbiological burden (am-AU). Design: Retrospective, multicenter, cohort. Setting: Ten hospitals in the southeastern United States. Methods: GNB with DTR including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp. from 2015 to 2020 were tracked at each institution. Cumulative AU of novel ß-lactams including ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol in days of therapy (DOT) per 1,000 patient-days was calculated. Linear regression was utilized to examine temporal trends in the prevalence of GNB with DTR and cumulative AU of novel ß-lactams. Results: The overall prevalence of GNB with DTR was 0.85% (1,223/143,638) with numerical increase from 0.77% to 1.00% between 2015 and 2020 (P = .06). There was a statistically significant increase in DTR Enterobacterales (0.11% to 0.28%, P = .023) and DTR Acinetobacter spp. (4.2% to 18.8%, P = .002). Cumulative AU of novel ß-lactams was 1.91 ± 1.95 DOT per 1,000 patient-days. When comparing cumulative mean AU and am-AU, there was an increase from 1.91 to 2.36 DOT/1,000 patient-days, with more than half of the hospitals shifting in ranking after adjustment for microbiological burden. Conclusions: The overall prevalence of GNB with DTR and the use of novel ß-lactams remain low. However, the uptrend in the use of novel ß-lactams after adjusting for microbiological burden suggests a higher utilization relative to the prevalence of GNB with DTR.

Evaluation of Short Versus Long Courses of Antibiotics in Critically Ill Patients With Gram-Negative Bloodstream Infections.

BACKGROUND: Short courses of antibiotics (7-10 days) are effective for uncomplicated gram-negative bloodstream infections (GN-BSI). However, prior studies have been limited to small cohorts of critically ill patients. OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of short courses of therapy compared with longer courses in patients admitted to the intensive care unit (ICU) with GN-BSI. METHODS: Propensity-matched, retrospective cohort study of critically ill patients with GN-BSI. The primary outcome was a composite of 30-day mortality or 60-day relapse. Secondary endpoints were components of the composite, 30-day relapse, cure with or without adverse drug events (ADE), and ADEs. Regression analysis was performed to identify factors predictive of the composite outcome. RESULTS: 225 patients were included in the propensity analysis, 145 in the long cohort and 80 in the short cohort. The primary outcome occurred in 3.8% of patients in the short group and 9.0% of patients in the long group (P = 0.24). There was no difference in 30-day mortality (3.8% vs 5.5%, P = 0.79), 60-day relapse (0% vs 3.4%, P = 0.23), or 30-day readmission (20% vs 22.8%, P = 0.76). ADEs were more common in the long group (47.2% vs 34.1%, OR 1.7, 95% CI 1.04-2.9), primarily attributable to diarrhea. CONCLUSION AND RELEVANCE: In critically ill patients with GN-BSI, there were no efficacy outcome differences in patients treated with a short course of antibiotics compared with longer. However, patients in the short group were less likely to experience ADE. These findings suggest that short courses of antibiotics are effective for GN-BSI in critically ill patients.

Performance of Methicillin-Resistant Staphylococcus aureus Polymerase Chain Reaction Nasal Screening for Ruling Out MRSA Pneumonia in Hospitalized, Immunocompromised Patients.

Background: Recent literature demonstrates support for using methicillin-resistant Staphylococcus aureus (MRSA) nasal swab polymerase chain reaction (NaPCR) screening as an antimicrobial stewardship tool aiding early de-escalation of anti-MRSA antimicrobials. However, immunocompromised patients have been underrepresented in previous studies despite increased risk of morbidity and mortality from multidrug-resistant organisms (MDRO). Objective: The purpose of this study was to determine the negative predictive value (NPV) of the MRSA NaPCR in hospitalized, immunocompromised adult patients with suspected pneumonia. Methods: A single-center, retrospective, observational review was conducted of hospitalized, immunocompromised adult patients that had an MRSA NaPCR obtained between March 1, 2020 and January 10, 2021. For inclusion, bacterial cultures must have been collected within 2 weeks after MRSA NaPCR. The primary outcome was the NPV of MRSA NaPCR in hospitalized, immunocompromised patients with suspected pneumonia. Secondary outcomes include NPV in other infections. Results: Between March 1, 2020 and January 10, 2021, 59 patients with 78 unique cultures, including 28 respiratory cultures, were included in the study. The NPV of the MRSA NaPCR for pneumonia was 91.7%. The NPV for bloodstream infections was 100% and for urinary tract infections was 100%, but interpretation of these results should be cautioned due to the small sample sizes. Conclusion: The NPV of MRSA NaPCR in pneumonia remains high in this study. The MRSA NaPCR has utility as a de-escalation tool in hospitalized, immunocompromised adult patients, but larger studies are warranted to evaluate all immunocompromised patient populations.

Evaluation of Anti-Methicillin-Resistant Staphylococcus aureus (MRSA) Prescribing Habits in Patients with a Positive MRSA Nasal Swab in the Absence of Positive Cultures.

Methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) nasal swabs are guideline-recommended de-escalation tools in certain patients with pneumonia. Prior studies have demonstrated reduced anti-MRSA therapy with negative results, but the impact on durations of therapy has been poorly elucidated in patients with positive PCRs. The objective of this review was to evaluate anti-MRSA treatment durations in patients with a positive MRSA PCR in the absence of MRSA growth on culture. This was a single-center, retrospective observational study evaluating 52 hospitalized, adult patients receiving anti-MRSA therapy with positive MRSA PCRs. The overall median duration of anti-MRSA therapy was five days, including a median of four days after PCR results. This was consistent among intensive care unit (ICU) and non-ICU patient populations and in patients with suspected community-acquired pneumonia (CAP). Among patients with hospital-acquired pneumonia (HAP), the median duration of anti-MRSA therapy was seven days, with a median of six days after PCR results. Overall, patients received a median duration of anti-MRSA therapy that would constitute a full treatment course for many respiratory infections, which indicates that providers may equate a positive MRSA nasal PCR with positive culture growth and highlights the need for education on the interpretation of positive tests.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications for Hospitalized Patients in 2021.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related, peer-reviewed literature that detailed an "actionable" intervention among hospitalized populations during 2021. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight "actionable" interventions used by antimicrobial stewardship programs in hospitalized populations to capture potentially effective strategies for local implementation.

Efficacy of Noncarbapenem ß-Lactams Compared to Carbapenems for Extended-Spectrum ß-Lactamase-Producing Enterobacterales Urinary Tract Infections.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales are frequent causes of urinary tract infections (UTIs). Severe infections caused by ESBL Enterobacterales are often treated with carbapenems, but optimal treatment for less severe infections such as UTIs is unclear. METHODS: This retrospective cohort study included patients admitted to 4 hospitals in an academic healthcare system with an ESBL UTI treated with either a noncarbapenem ß-lactam (NCBL) or a carbapenem for at least 48 hours from 1 April 2014 to 30 April 2018. Those who received an NCBL were compared to those receiving a carbapenem, with a primary outcome of hospital length of stay (LOS) and secondary outcomes of clinical and microbiological response, days until transition to oral therapy, rate of relapsed infection, and rate of secondary infections with a multidrug-resistant organism. RESULTS: Characteristics were similar among patients who received carbapenems (n = 321) and NCBLs (n = 171). There was no difference in LOS for the NCBL group compared to the carbapenem group (13 days vs 15 days, P = .66). The NCBL group had higher rates of microbiologic eradication (98% vs 92%, P = .002), shorter time to transition to oral therapy (5 days vs 9 days, P < .001), shorter overall durations of therapy (7 days vs 10 days, P < .001), and lower rates of relapsed infections (5% vs 42%, P = .0003). CONCLUSIONS: Patients treated with NCBLs had similar LOS, higher rates of culture clearance, and shorter durations of antibiotic therapy compared to patients treated with carbapenems, suggesting that treatment for ESBL UTIs should not be selected solely based on phenotypic resistance.

Anatomy integration blueprint: A fourth-year musculoskeletal anatomy elective model.

Current undergraduate medical school curricular trends focus on both vertical integration of clinical knowledge into the traditionally basic science-dedicated curricula and increasing basic science education in the clinical years. This latter type of integration is more difficult and less reported on than the former. Here, we present an outline of a course wherein the primary learning and teaching objective is to integrate basic science anatomy knowledge with clinical education. The course was developed through collaboration by a multi-specialist course development team (composed of both basic scientists and physicians) and was founded in current adult learning theories. The course was designed to be widely applicable to multiple future specialties, using current published reports regarding the topics and clinical care areas relying heavily on anatomical knowledge regardless of specialist focus. To this end, the course focuses on the role of anatomy in the diagnosis and treatment of frequently encountered musculoskeletal conditions. Our iterative implementation and action research approach to this course development has yielded a curricular template for anatomy integration into clinical years. Key components for successful implementation of these types of courses, including content topic sequence, the faculty development team, learning approaches, and hidden curricula, were developed. We also report preliminary feedback from course stakeholders and lessons learned through the process. The purpose of this report is to enhance the current literature regarding basic science integration in the clinical years of medical school.

Determination of specific absorbance (A|) for Zaleplon (Sonata) by spectrophotometry.

Specific absorbance (A|) is the maximum absorbance of a 1% solution over a 1-cm path length as measured by a spectrophotometer. If a reliable A| determination is available for a drug, it provides an extremely useful tool for the quantitative verification of a stock drug solution. Zaleplon was introduced into the market in 1999, and although the drug has been available for 10 years, A| has not been published in the literature. Zaleplon's A| was experimentally determined by a spectrophotometer at 229 nm in aqueous acid and verified with three independent external sources to be 1186 (1042-1262; n = 18). The experimentally determined A| of zaleplon is beneficial to a toxicology laboratory to verify the quantitative accuracy of a drug solution prior to its use in casework.

Zaleplon (Sonata) analysis in postmortem specimens by gas chromatography-electron capture detection.

Zaleplon (Sonata) is a sedative hypnotic prescription medication used for the short-term treatment of insomnia. Although Zaleplon was approved by the FDA in 1999, there has been limited postmortem information about the drug cited in the toxicology literature. Zaleplon was separated from postmortem biological specimens utilizing liquid-liquid extraction coupled with a solid-phase extraction technique, and detection was accomplished by a gas chromatography-electron capture detector. The method was linear from 5.0 to 150 ng/mL with the limit of quantitation and detection determined to be 3.0 and 0.50 ng/mL, respectively. The postmortem tissue distribution of zaleplon in seven cases was as follows: 6.1-1490 ng/mL central blood (seven cases), < 3.0-503 ng/mL femoral blood (five cases), 108 ng/mL harvest blood (one case), 343-679 ng/g liver (four cases), 950 ng/g spleen (one case), < 3.0-85 ng/mL bile (three cases), 3.8-106 ng/mL urine (four cases), < 3.0-486 ng/mL vitreous humor (five cases), and 0.005-3.4 mg total gastric contents (four cases). A validated method for the analysis of zaleplon and postmortem concentrations of autopsy specimens are reported to aid the forensic toxicologist with interpretation of future casework.

Oxycontin: the concept of a "ghost pill" and the postmortem tissue distribution of oxycodone in 36 cases.

Oxycodone is a semi-synthetic opioid that is structurally similar to codeine and equipotent to morphine in producing analgesic effects. Oxycodone has been prescribed in many immediate-release formulations including Percodan, Percocet, Tylox, Roxicodone, and Toxicet. In 1995, the Food and Drug Administration approved Oxycontin, a controlled-release form of oxycodone. Although the immediate-release forms of oxycodone can be prescribed in doses of 10-30 mg every 4 h, it is recommended that Oxycontin be prescribed in doses of 10-160 mg every 12 h. In a six-year period, the Los Angeles County Department of Coroner's Toxicology Laboratory detected oxycodone in 67 cases, 36 of which were determined to be the controlled-release form. The objectives of this paper are to provide general information about Oxycontin, including postmortem tissue distributions of oxycodone in cases in which the controlled-release form was identified, and to introduce the concept of ghost pills. A ghost pill is a seemingly intact but drug-free tablet that resembles an undigested pill. The isolation and identification of oxycodone from postmortem specimens was achieved using a basic, liquid-liquid extraction with screening and quantitation by gas chromatography-nitrogen-phosphorus detection and gas chromatography-mass spectrometry, respectively. Oxycodone-d3 was used as an internal standard for quantitation. The assays were linear from 0.10 to 5.0 mg/L. The tissue distribution ranges of oxycodone in the 36 case examples were heart blood 0.12-46 mg/L (36), femoral blood + < 0.10-13 mg/L (35), liver 0.11-6.1 mg/kg (16), urine 2.5-122 mg/L (22), bile 0.19-49 mg/L (15), vitreous 0.24-0.82 mg/L (6), and gastric 0.06-119 mg total (21).