Impact of a pharmacy-driven MRSA nares screening protocol on vancomycin discontinuation in a tele-antimicrobial stewardship model.

A pharmacist-driven protocol for methicillin-resistant Staphylococcus aureus nares screening and empiric vancomycin discontinuation was instituted in a community healthcare system utilizing a tele-antimicrobial stewardship program to reduce inappropriate use of vancomycin. The protocol and associated intervention resulted in a significant decrease in both vancomycin utilization and the rate of acute kidney injury.

Transition to Oral Antibiotic Therapy for Hospitalized Adults With Gram-Negative Bloodstream Infections.

Importance: Management of gram-negative bloodstream infections (GN-BSIs) with oral antibiotics is highly variable. Objective: To examine the transition from intravenous (IV) to oral antibiotics, including selection, timing, and associated clinical and microbial characteristics, among hospitalized patients with GN-BSIs. Design, Setting, and Participants: A retrospective cohort study was conducted of 4581 hospitalized adults with GN-BSIs at 24 US hospitals between January 1 and December 31, 2019. Patients were excluded if they died within 72 hours. Patients were excluded from the oral therapy group if transition occurred after day 7. Statistical analysis was conducted from July 2022 to October 2023. Exposures: Administration of antibiotics for GN-BSIs. Main Outcomes and Measures: Baseline characteristics and clinical parameters reflecting severity of illness were evaluated in groups receiving oral and IV therapy. The prevalence of transition from IV to oral antibiotics by day 7, median day of transition, sources of infection, and oral antibiotic selection were assessed. Results: Of a total of 4581 episodes with GN-BSIs (median age, 67 years [IQR, 55-77 years]; 2389 men [52.2%]), 1969 patients (43.0%) receiving IV antibiotics were transitioned to oral antibiotics by day 7. Patients maintained on IV therapy were more likely than those transitioned to oral therapy to be immunosuppressed (833 of 2612 [31.9%] vs 485 of 1969 [24.6%]; P < .001), require intensive care unit admission (1033 of 2612 [39.5%] vs 334 of 1969 [17.0%]; P < .001), have fever or hypotension as of day 5 (423 of 2612 [16.2%] vs 49 of 1969 [2.5%]; P < .001), require kidney replacement therapy (280 of 2612 [10.7%] vs 63 of 1969 [3.2%]; P < .001), and less likely to have source control within 7 days (1852 of 2612 [70.9%] vs 1577 of 1969 [80.1%]; P < .001). Transitioning patients from IV to oral therapy by day 7 was highly variable across hospitals, ranging from 25.8% (66 of 256) to 65.9% (27 of 41). A total of 4109 patients (89.7%) achieved clinical stability within 5 days. For the 3429 episodes (74.9%) with successful source control by day 7, the median day of source control was day 2 (IQR, 1-3 days) for the oral group and day 2 (IQR, 1-4 days) for the IV group (P < .001). Common infection sources among patients administered oral therapy were the urinary tract (1277 of 1969 [64.9%]), hepatobiliary (239 of 1969 [12.1%]), and intra-abdominal (194 of 1969 [9.9%]). The median day of oral transition was 5 (IQR, 4-6 days). Total duration of antibiotic treatment was significantly shorter among the oral group than the IV group (median, 11 days [IQR, 9-14 days] vs median, 13 days [IQR, 8-16 days]; P < .001]. Fluoroquinolones (62.2% [1224 of 1969]), followed by ß-lactams (28.3% [558 of 1969]) and trimethoprim-sulfamethoxazole (11.5% [227 of 1969]), were the most commonly prescribed oral antibiotics. Conclusions and Relevance: In this cohort study of 4581 episodes of GN-BSIs, transition to oral antibiotic therapy by day 7 occurred in fewer than half of episodes, principally with fluoroquinolones, although this practice varied significantly between hospitals. There may have been additional opportunities for earlier and more frequent oral antibiotic transitions because most patients demonstrated clinical stability by day 5.

Identifying Effective Durations of Antibiotic Therapy for the Treatment of Carbapenem-resistant Enterobacterales Bloodstream Infections: A Multicenter Observational Study.

In a propensity-score-weighted cohort of 183 adults with carbapenem-resistant Enterobacterales bacteremia at 24 US hospitals, patients receiving short courses of active therapy (7-10 days, median 9 days) experienced similar odds of recurrent bacteremia or death within 30 days as those receiving prolonged courses of active therapy (14-21 days, median 14 days).

Stewardship-Guided T2Candida Testing Shortens Time to Antifungal Treatment and Reduces Antifungal Usage Among Medical Intensive Care Unit Patients With Septic Shock.

Background: Diagnosis of invasive candidiasis (IC) is limited by insensitivity and slow turnaround of cultures. Our objectives were to define the performance of T2Candida, a nonculture test, under guidance of a diagnostic stewardship program, and evaluate impact on time to antifungal initiation and antifungal utilization. Methods: This was a retrospective study of adult medical intensive care unit (MICU) patients with septic shock for whom T2Candida testing was performed from March 2017 to March 2020. Patients with positive T2Candida results during this period were compared to MICU patients who did not undergo T2Candida testing but had septic shock and blood cultures positive for Candida from January 2016 through March 2020. Results: Overall, 155 T2Candida tests from 143 patients were included. Nine percent of T2Candida tests were positive compared to 4.5% of blood cultures. Sensitivity, specificity, positive predictive value, and negative predictive value of T2Candida for proven and probable IC were 78%, 95%, 50%, and 99%, respectively. Patients who tested positive for T2Candida (n = 14) were diagnosed earlier and initiated on antifungal therapy sooner than patients with IC (n = 14) diagnosed by blood culture alone (median, 5.6 vs 60 hours; P < .0001). Median antifungal days of therapy/1000 patient-days were 23.3/month preimplementation and 15/month postimplementation (P  = .007). Following a negative T2Candida result, empiric antifungals were either not administered in 58% or discontinued within 72 hours in 96% of patients. Conclusions: Diagnostic stewardship guided T2Candida testing resulted in reduced time to IC diagnosis, faster initiation of antifungal therapy, and lower antifungal usage among MICU patients with septic shock.

Weighted Lottery to Equitably Allocate Scarce Supply of COVID-19 Monoclonal Antibody.

Importance: Equitable allocation of scarce medications is an important health policy goal. There are few data about attempts to achieve equitable allocation in the community setting. Objective: To describe the development and use of a weighted lottery to allocate a scarce supply of tixagevimab with cilgavimab as preexposure prophylaxis to COVID-19 for immunocompromised individuals and examine whether this promoted equitable allocation to disadvantaged populations. Design, Setting, and Participants: This quality improvement study analyzed a weighted lottery process from December 8, 2021, to February 23, 2022, that assigned twice the odds of drug allocation of 450 tixagevimab with cilgavimab doses to individuals residing in highly disadvantaged neighborhoods according to the US Area Deprivation Index (ADI) in a 35-hospital system in Pennsylvania, New York, and Maryland. In all, 10 834 individuals were eligible for the lottery. Weighted lottery results were compared with 10 000 simulated unweighted lotteries in the same cohort performed after drug allocation occurred. Main Outcomes: Proportion of individuals from disadvantaged neighborhoods and Black individuals who were allocated and received tixagevimab with cilgavimab. Results: Of the 10 834 eligible individuals, 1800 (16.6%) were from disadvantaged neighborhoods and 767 (7.1%) were Black. Mean (SD) age was 62.9 (18.8) years, and 5471 (50.5%) were women. A higher proportion of individuals from disadvantaged neighborhoods was allocated the drug in the ADI-weighted lottery compared with the unweighted lottery (29.1% vs 16.6%; P < .001). The proportion of Black individuals allocated the drug was greater in the weighted lottery (9.1% vs 7.1%; P < .001). Among the 450 individuals allocated tixagevimab with cilgavimab in the ADI-weighted lottery, similar proportions of individuals from disadvantaged neighborhoods accepted the allocation and received the drug compared with those from other neighborhoods (27.5% vs 27.9%; P = .93). However, Black individuals allocated the drug were less likely to receive it compared with White individuals (3 of 41 [7.3%] vs 118 of 402 [29.4%]; P = .003). Conclusions and Relevance: The findings of this quality improvement study suggest an ADI-weighted lottery process to allocate scarce resources is feasible in a large health system and resulted in more drug allocation to and receipt of drug by individuals who reside in disadvantaged neighborhoods. Although the ADI-weighted lottery also resulted in more drug allocation to Black individuals compared with an unweighted process, they were less likely to accept allocation and receive it compared with White individuals. Further strategies are needed to ensure that Black individuals receive scarce medications allocated.

Utility of triazole antifungal therapeutic drug monitoring: Insights from the Society of Infectious Diseases Pharmacists: Endorsed by the Mycoses Study Group Education and Research Consortium.

Triazole antifungals (i.e., fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole) are commonly used in clinical practice to prevent or treat invasive fungal infections. Most triazole antifungals require therapeutic drug monitoring (TDM) due to highly variable pharmacokinetics, known drug interactions, and established relationships between exposure and response. On behalf of the Society of Infectious Diseases Pharmacists (SIDP), this insight describes the pharmacokinetic principles and pharmacodynamic targets of commonly used triazole antifungals and provides the rationale for utility of TDM within each agent.

Antibiotic Myths for the Infectious Diseases Clinician.

Antimicrobials are commonly prescribed and often misunderstood. With more than 50% of hospitalized patients receiving an antimicrobial agent at any point in time, judicious and optimal use of these drugs is paramount to advancing patient care. This narrative will focus on myths relevant to nuanced consultation from infectious diseases specialists, particularly surrounding specific considerations for a variety of antibiotics.

Rapid Emergence of Potentially Transmissible Severe Acute Respiratory Syndrome Coronavirus 2 With Resistance to Combination Monoclonal Antibody Therapy.

Prolonged coronavirus disease 2019 may generate new viral variants. We report an immunocompromised patient treated with monoclonal antibodies who experienced rebound of viral RNA and emergence of an antibody-resistant (>1000-fold) variant containing 5 mutations in the spike gene. The mutant virus was isolated from respiratory secretions, suggesting the potential for secondary transmission.

Clindamycin Plus Vancomycin Versus Linezolid for Treatment of Necrotizing Soft Tissue Infection.

Background: Necrotizing soft tissue infections (NSTIs) are life-threatening infections. The aim of this study is to evaluate the safety of clindamycin plus vancomycin versus linezolid as empiric treatment of NSTIs. Methods: This was a retrospective, single-center, quasi-experimental study of patients admitted from 1 June 2018 to 30 June 2019 (preintervention) and 1 May 2020 to 15 October 2021 (postintervention). Patients who received surgical management within 24 hours of NSTI diagnosis and at least 1 dose of linezolid or clindamycin were included. The primary endpoint was death at 30 days. The secondary outcomes included rates of acute kidney injury (AKI) and Clostridioides difficile infection (CDI). Results: A total of 274 patients were identified by admission diagnosis code for NSTI or Fournier gangrene; 164 patients met the inclusion criteria. Sixty-two matched pairs were evaluated. There was no difference in rates of 30-day mortality (8.06% vs 6.45%; hazard ratio [HR], 1.67 [95% confidence interval {CI}, .32-10.73]; P = .65). There was no difference in CDI (6.45% vs 1.61%; HR, Infinite [Inf], [95% CI, .66-Inf]; P = .07) but more AKI in the preintervention group (9.68% vs 1.61%; HR, 6 [95% CI, .73-276]; P = .05). Conclusions: In this small, retrospective, single-center, quasi-experimental study, there was no difference in 30-day mortality in patients receiving treatment with clindamycin plus vancomycin versus linezolid in combination with standard gram-negative and anaerobic therapy and surgical debridement for the treatment of NSTIs. A composite outcome of death, AKI, or CDI within 30 days was more common in the clindamycin plus vancomycin group.

Evolving Real-World Effectiveness of Monoclonal Antibodies for Treatment of COVID-19 : A Cohort Study.

BACKGROUND: Treatment guidelines and U.S. Food and Drug Administration emergency use authorizations (EUAs) of monoclonal antibodies (mAbs) for treatment of high-risk outpatients with mild to moderate COVID-19 changed frequently as different SARS-CoV-2 variants emerged. OBJECTIVE: To evaluate whether early outpatient treatment with mAbs, overall and by mAb product, presumed SARS-CoV-2 variant, and immunocompromised status, is associated with reduced risk for hospitalization or death at 28 days. DESIGN: Hypothetical pragmatic randomized trial from observational data comparing mAb-treated patients with a propensity score-matched, nontreated control group. SETTING: Large U.S. health care system. PARTICIPANTS: High-risk outpatients eligible for mAb treatment under any EUA with a positive SARS-CoV-2 test result from 8 December 2020 to 31 August 2022. INTERVENTION: Single-dose intravenous mAb treatment with bamlanivimab, bamlanivimab-etesevimab, sotrovimab, bebtelovimab, or intravenous or subcutaneous casirivimab-imdevimab administered within 2 days of a positive SARS-CoV-2 test result. MEASUREMENTS: The primary outcome was hospitalization or death at 28 days among treated patients versus a nontreated control group (no treatment or treatment ≥3 days after SARS-CoV-2 test date). RESULTS: The risk for hospitalization or death at 28 days was 4.6% in 2571 treated patients and 7.6% in 5135 nontreated control patients (risk ratio [RR], 0.61 [95% CI, 0.50 to 0.74]). In sensitivity analyses, the corresponding RRs for 1- and 3-day treatment grace periods were 0.59 and 0.49, respectively. In subgroup analyses, those receiving mAbs when the Alpha and Delta variants were presumed to be predominant had estimated RRs of 0.55 and 0.53, respectively, compared with 0.71 for the Omicron variant period. Relative risk estimates for individual mAb products all suggested lower risk for hospitalization or death. Among immunocompromised patients, the RR was 0.45 (CI, 0.28 to 0.71). LIMITATIONS: Observational study design, SARS-CoV-2 variant presumed by date rather than genotyping, no data on symptom severity, and partial data on vaccination status. CONCLUSION: Early mAb treatment among outpatients with COVID-19 is associated with lower risk for hospitalization or death for various mAb products and SARS-CoV-2 variants. PRIMARY FUNDING SOURCE: None.

Tixagevimab Plus Cilgavimab Does Not Affect the Interpretation of Electrophoretic and Free Light Chain Assays.

OBJECTIVES: There is concern that the anti-severe acute respiratory syndrome coronavirus 2 therapeutic monoclonal antibodies, used as preexposure prophylaxis in patients with multiple myeloma, may appear as a detectable monoclonal protein by electrophoretic methods, resulting in misinterpretation or inability to measure therapeutic responses in some patients. In this pilot study, we characterize the effect of tixagevimab plus cilgavimab (Evusheld; T + C) on interpretation of serum protein electrophoresis (SPE), immunofixation electrophoresis (IFE), and serum free light chain (sFLC) assays. METHODS: We performed spiking experiments with T + C at serum maximum concentration following a 300-mg dose (1× Cmax) and at 10 times the concentration of Cmax (10× Cmax) with pooled serum samples. SPE and IFE technical procedures were performed on the SPIFE 3000, and sFLC and immunoglobulin G1 (IgG1) subtype quantitation was performed on the Optilite. RESULTS: T + C-associated interference was not visible as an M-spike in normogammaglobulinemic pooled samples. Hypogammaglobulemic pooled samples at 10× Cmax demonstrated an M-spike in SPE and immunoglobulin Gκ pattern in IFE. No increases were noted in the results of sFLC or IgG1 levels. CONCLUSIONS: This study indicates that T + C at pharmacologic Cmax is unlikely to interfere with SPE, IFE, sFLC, or IgG1 analyses when spiked into patient serum samples, but further evaluation of recently injected patients may be warranted.

Less Is More? Antibiotic Treatment Duration in Pseudomonas aeruginosa Ventilator-Associated Pneumonia.

Recommended antimicrobial treatment durations for ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa have evolved over the past few decades. In this Viewpoint, we provide a narrative review of landmark trials investigating antimicrobial treatment durations for VAP caused by P. aeruginosa, and appraise iterations of expert consensus guidelines based on these data. We highlight strengths and weaknesses of existing data on this topic and provide recommendations for future avenues of study.

Evaluation of Bebtelovimab for Treatment of Covid-19 During the SARS-CoV-2 Omicron Variant Era.

Background: Monoclonal antibody (mAb) treatment is associated with decreased risk of hospitalization and death in high-risk outpatients with mild to moderate coronavirus disease 2019 (COVID-19) caused by early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Bebtelovimab exhibits in vitro activity against the Omicron variant and its sublineages; however, clinical data are lacking. Methods: A retrospective cohort study was conducted comparing bebtelovimab-treated patients with propensity score-adjusted and matched nontreated control groups. Participants included high-risk outpatients eligible for bebtelovimab treatment under Emergency Use Authorization with a positive SARS-CoV-2 test from March 30 to May 28, 2022. Treated patients received single-dose intravenous treatment with bebtelovimab. The primary outcome was hospitalization or death over 28 days. Results: Before matching/statistical adjustment, mAb-treated patients were, on average, 10 years older than nontreated patients (61.6 vs 51.3 years) and had higher prevalence of obstructive sleep apnea, hypertension, chronic kidney disease, cancer, organ or cell transplant, and immunocompromised status (standardized mean differences ≥0.20). The adjusted odds ratio (OR) of hospitalization or death comparing 1006 treated with 2023 nontreated patients was 0.50 (95% CI, 0.31-0.80). Among 930 treated and 930 propensity score-matched nontreated patients, the incidence of hospitalization or death was 3.1% vs 5.5%, respectively (conditional OR, 0.53; 95% CI, 0.32-0.86). The lower odds ratio of hospitalization or death associated with bebtelovimab treatment was most evident in older patients, those with immunocompromised status, and fully vaccinated patients. Conclusions: Monoclonal antibody treatment with bebtelovimab among COVID-19 outpatients is associated with lower odds of hospitalization or death, particularly among immunocompromised and older patients.

Monoclonal Antibodies for Treatment of SARS-CoV-2 Infection During Pregnancy : A Cohort Study.

BACKGROUND: Monoclonal antibody (mAb) treatment decreases hospitalization and death in high-risk outpatients with mild to moderate COVID-19. However, no studies have evaluated adverse events and effectiveness of mAbs in pregnant persons compared with no mAb treatment. OBJECTIVE: To determine the frequency of drug-related adverse events and obstetric-associated safety outcomes after treatment with mAb compared with no mAb treatment of pregnant persons, and the association between mAb treatment and a composite of 28-day COVID-19-related hospital admission or emergency department (ED) visit, COVID-19-associated delivery, or mortality. DESIGN: Retrospective, propensity score-matched, cohort study. SETTING: UPMC Health System from 30 April 2021 to 21 January 2022. PARTICIPANTS: Persons aged 12 years or older with a pregnancy episode and any documented positive SARS-CoV-2 test (polymerase chain reaction or antigen test). INTERVENTION: Bamlanivimab and etesevimab, casirivimab and imdevimab, or sotrovimab treatment compared with no mAb treatment. MEASUREMENTS: Drug-related adverse events, obstetric-associated safety outcomes among persons who delivered, and a risk-adjusted composite of 28-day COVID-19-related hospital admission or ED visit, COVID-19-associated delivery, or mortality. RESULTS: Among 944 pregnant persons (median age [interquartile range (IQR)], 30 years [26 to 33 years]; White (79.5%; n = 750); median Charlson Comorbidity Index score [IQR], 0 [0 to 0]), 552 received mAb treatment (58%). Median gestational age at COVID-19 diagnosis or treatment was 179 days (IQR, 123 to 227), and most persons received sotrovimab (69%; n = 382). Of those with known vaccination status, 392 (62%) were fully vaccinated. Drug-related adverse events were uncommon (n = 8; 1.4%), and there were no differences in any obstetric-associated outcome among 778 persons who delivered. In the total population, the risk ratio for mAb treatment of the composite 28-day COVID-19-associated outcome was 0.71 (95% CI, 0.37 to 1.4). The propensity score-matched risk ratio was 0.61 (95% CI, 0.34 to 1.1). There were no deaths among mAb-treated patients compared with 1 death in the nontreated control patients. There were more non-COVID-19-related hospital admissions in the mAb-treated persons in the unmatched cohort (14 [2.5%] vs. 2 [0.5%]; risk ratio, 5.0; 95% CI, 1.1 to 21.7); however, there was no difference in the propensity score-matched rates, which were 2.5% mAb-treated vs. 2% untreated (risk ratio, 1.3; 95% CI, 0.58% to 2.8%). LIMITATIONS: Drug-related adverse events were patient and provider reported and potentially underrepresented. Symptom severity at the time of SARS-CoV-2 testing was not available for nontreated patients. CONCLUSION: In pregnant persons with mild to moderate COVID-19, adverse events after mAb treatment were mild and rare. There was no difference in obstetric-associated safety outcomes between mAb treatment and no treatment among persons who delivered. There was no difference in 28-day COVID-19-associated outcomes and non-COVID-19-related hospital admissions for mAb treatment compared with no mAb treatment in a propensity score-matched cohort. PRIMARY FUNDING SOURCE: No funding was received for this study.