Real-World Dalbavancin Use for Serious Gram-Positive Infections: Comparing Outcomes Between People Who Use and Do Not Use Drugs.

Background: Dalbavancin has been used off-label to treat invasive bacterial infections in vulnerable populations like people who use drugs (PWUD) because of its broad gram-positive coverage and unique pharmacological properties. This retrospective, multisite study examined clinical outcomes at 90 days in PWUD versus non-PWUD after secondary treatment with dalbavancin for bacteremia, endocarditis, osteomyelitis, septic arthritis, and epidural abscesses. Methods: Patients at 3 teaching hospitals who received dalbavancin for an invasive infection between March 2016 and May 2022 were included. Characteristics of PWUD and non-PWUD, infection highlights, hospital stay and treatment, and outcomes were compared using χ2 for categorical variables, t test for continuous variables, and nonparametric tests where appropriate. Results: There were a total of 176 patients; 78 were PWUD and 98 were non-PWUD. PWUD were more likely to have a patient-directed discharge (26.9% vs 3.1%; P < .001) and be lost to follow-up (20.5% vs 7.14%; P < .01). Assuming loss to follow-up did not achieve clinical cure, 73.1% of PWUD and 74.5% of non-PWUD achieved clinical cure at 90 days (P = .08). Conclusions: Dalbavancin was an effective treatment option for invasive gram-positive infections in our patient population. Despite higher rates of patient-directed discharge and loss to follow-up, PWUD had similar rates of clinical cure at 90 days compared to non-PWUD.

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.

Evaluation of an Opt-Out Protocol for Antibiotic De-Escalation in Patients With Suspected Sepsis: A Multicenter, Randomized, Controlled Trial.

BACKGROUND: Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. This randomized, controlled trial evaluated an opt-out protocol to decrease unnecessary antibiotics in patients with suspected sepsis. METHODS: We evaluated non-intensive care adults on broad-spectrum antibiotics despite negative blood cultures at 10 US hospitals from September 2018 through May 2020. A 23-item safety check excluded patients with ongoing signs of systemic infection, concerning or inadequate microbiologic data, or high-risk conditions. Eligible patients were randomized to the opt-out protocol vs usual care. Primary outcome was post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted to encourage antibiotic discontinuation using opt-out language. If continued, clinicians discussed the rationale for continuing antibiotics and de-escalation plans. To evaluate those with zero post-enrollment DOT, hurdle models provided 2 measures: odds ratio of antibiotic continuation and ratio of mean DOT among those who continued antibiotics. RESULTS: Among 9606 patients screened, 767 (8%) were enrolled. Intervention patients had 32% lower odds of antibiotic continuation (79% vs 84%; odds ratio, 0.68; 95% confidence interval [CI], .47-.98). DOT among those who continued antibiotics were similar (ratio of means, 1.06; 95% CI, .88-1.26). Fewer intervention patients were exposed to extended-spectrum antibiotics (36% vs 44%). Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was unsafe (31%). Thirty-day safety events were similar. CONCLUSIONS: An antibiotic opt-out protocol that targeted patients with suspected sepsis resulted in more antibiotic discontinuations, similar DOT when antibiotics were continued, and no evidence of harm. CLINICAL TRIALS REGISTRATION: NCT03517007.

Evaluation of Vancomycin Accumulation in Patients With Obesity.

Background: Current vancomycin guidelines recommend early and frequent area-under-the-curve monitoring in patients with obesity. Vancomycin's volume of distribution is likely altered in patients with obesity, which may result in lower serum concentrations initially but lead to accumulation with continued use. The objective of this study was to evaluate the incidence of vancomycin accumulation in patients with obesity and identify potential factors associated with accumulation. Methods: This was a single-center, retrospective, observational study at a tertiary academic medical center. Adult patients with a body mass index (BMI) ≥ 30 kg/m2 and ≥ 2 vancomycin serum trough concentrations drawn in 2019 were screened for inclusion. The major endpoint was the incidence of vancomycin accumulation defined as ≥ 20% increase in trough concentration within the first 10 days of therapy. Key minor endpoints included incidence of acute kidney injury (AKI) and factors associated with accumulation. Results: Of the 443 patients screened, 162 were included. The median age was 56.5 years (interquartile range [IQR], 43-65.3), and 62.3% were male. The median weight was 112.7 kg (IQR, 99.8-122.6) and the median BMI was 36.8 kg/m2 (IQR, 33.1-41). The total daily dose median at initiation was 28.7 mg/kg per day (IQR, 25.4-31.2). Accumulation occurred in 99 of 162 patients (61.1%) and AKI occurred in 20 of 140 patients (14.3%). No specific factors were found to be associated with accumulation. Conclusions: Patients with obesity are likely to experience vancomycin accumulation within the first 10 days of therapy. Clinicians should use frequent monitoring of vancomycin and use caution when interpreting early concentrations in patients with obesity.

Which pharmacists are performing antimicrobial stewardship: A national survey and a call for collaborative efforts.

Objectives: To determine how pharmacists with formal antimicrobial stewardship program (ASP) responsibilities prioritize their time and pharmacists without formal antimicrobial stewardship program responsibilities contribute to ASP activities. Design: A nationwide survey. Respondents: Members of the American College of Clinical Pharmacy who subscribe to the following practice and research network e-mail listservs: infectious diseases, adult medicine, cardiology, critical care, hematology-oncology, immunology and transplantation, and pediatrics. Methods: A survey was distributed via listservs. Respondents were asked about their personal and institutional demographics and ASP activities. Results: In total, 245 pharmacists responded: 135 pharmacists with formal antimicrobial stewardship program responsibilities; 110 pharmacists without formal antimicrobial stewardship program responsibilities. Although most respondents had completed a general pharmacy residency (85%), only 20% had completed an infectious diseases (ID) specialty residency. Among pharmacists with formal antimicrobial stewardship program responsibilities, one-third had no formal training or certification in ID or ASP. Pharmacists without formal antimicrobial stewardship program responsibilities spent ∼12.5% of their time per week on ASP activities, whereas pharmacists with formal antimicrobial stewardship program responsibilities spent 28% of their time performing non-ASP activities. Pharmacists with formal antimicrobial stewardship program responsibilities were more likely than pharmacists without formal antimicrobial stewardship program responsibilities to perform antibiotic guideline development (P < .001), antibiotic-related education (P = .002), and direct notification of rapid diagnostic results (P = .018). Pharmacists with formal antimicrobial stewardship program responsibilities without formal ID training or certification spent less time on ASP activities and were more likely to perform lower-level interventions. Conclusions: Many ASP activities are being performed by pharmacists without formal ID training. To ensure the future success of ASPs, pharmacists with formal antimicrobial stewardship program responsibilities should have adequate training to meet more advanced metrics, and more pharmacists without formal antimicrobial stewardship program responsibilities should be included in basic interventions.

Vancomycin Area under the Concentration-Time Curve Estimation Using Bayesian Modeling versus First-Order Pharmacokinetic Equations: A Quasi-Experimental Study.

AIM: To evaluate the efficiency of Bayesian modeling software and first-order pharmacokinetic (PK) equations to calculate vancomycin area under the concentration-time curve (AUC) estimations. METHODS: Unblinded, crossover, quasi-experimental study at a tertiary care hospital for patients receiving intravenous vancomycin. Vancomycin AUC monitoring was compared using Bayesian modeling software or first-order PK equations. The primary endpoint was the time taken to estimate the AUC and determine regimen adjustments. Secondary endpoints included the percentage of vancomycin concentrations usable for AUC calculations and acute kidney injury (AKI). RESULTS: Of the 124 patients screened, 34 patients had usable vancomycin concentrations that led to 44 AUC estimations. Without electronic health record (EHR) integration, the time from assessment to intervention in the Bayesian modeling platform was a median of 9.3 min (quartiles Q1-Q3 7.8-12.4) compared to 6.8 min (Q1-Q3 4.8-8.0) in the PK equations group (p = 0.004). With simulated Bayesian software integration into the EHR, however, the median time was 3.8 min (Q1-Q3 2.3-6.9, p = 0.019). Vancomycin concentrations were usable in 88.2% in the Bayesian group compared to 48.3% in the PK equation group and there were no cases of AKI. CONCLUSION: Without EHR integration, Bayesian software was more time-consuming to assess vancomycin dosing than PK equations. With simulated integration, however, Bayesian software was more time efficient. In addition, vancomycin concentrations were more likely to be usable for calculations in the Bayesian group.

Omadacycline for the Treatment of Mycobacterium abscessus Disease: A Case Series.

BACKGROUND: Omadacycline is an aminomethylcycline antimicrobial approved by the US Food and Drug Administration in 2018 for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. It has in vitro activity against nontuberculous mycobacteria, including Mycobacterium abscessus complex, but clinical data for this indication are lacking. METHODS: Omadacycline use was reviewed at an 804-bed academic medical center. Patients were included if they received omadacycline for culture-proven M abscessus disease in 2019. RESULTS: Four patients received omadacycline for the treatment of culture-positive M abscessus disease in 2019. Two patients had cutaneous disease, 1 had pulmonary disease, and 1 had osteomyelitis and bacteremia. The patients received omadacycline for a median duration of 166 days (range, 104-227) along with a combination of other antimicrobial agents. Omadacycline-containing regimens were associated with a clinical cure in 3 of 4 patients, with 1 patient improving on ongoing treatment. Omadacycline's tolerability was acceptable for patients with M abscessus disease, with 1 patient discontinuing therapy in month 6 due to nausea. CONCLUSIONS: Omadacycline is a novel oral option for the treatment of M abscessus disease, for which safe and effective options are needed. Although this case series is promising, further data are required to determine omadacycline's definitive role in the treatment of M abscessus disease.

Interplay between Rapid Diagnostic Tests and Antimicrobial Stewardship Programs among Patients with Bloodstream and Other Severe Infections.

BACKGROUND: Antimicrobial stewardship programs (ASPs) aim to provide optimal antimicrobial therapy to patients quickly to improve the likelihood of overcoming infection while reducing the risk of adverse effects. Rapid diagnostic tests (RDTs) for infectious diseases have become an integral tool for ASPs to achieve these aims. CONTENT: This review explored the demonstrated clinical value of longer-standing technologies and implications of newer RDTs from an antimicrobial stewardship perspective. Based on available literature, the focus was on the use of RDTs in bloodstream infections (BSIs), particularly those that perform organism identification and genotypic resistance detection, phenotypic susceptibility testing, and direct specimen testing. Clinical implications of rapid testing among respiratory, central nervous system, and gastrointestinal infections are also reviewed. SUMMARY: Coupling RDTs with ASPs facilitates the appropriate and timely use of test results, translating into improved patient outcomes through optimization of antimicrobial use. These benefits are best demonstrated in the use of RDT in BSIs. Rapid phenotypic susceptibility testing offers the potential for early pharmacokinetic/pharmacodynamic optimization, and direct specimen testing on blood may allow ASPs to initiate appropriate therapy and/or tailor empiric therapy even sooner than other RDTs. RDTs for respiratory, central nervous system, and gastrointestinal illnesses have also shown significant promise, although more outcome studies are needed to evaluate their full impact.

Key Principles of Antiretroviral Pharmacology.

Antiretroviral therapy has advanced significantly since zidovudine was first approved. Although 31 antiretrovirals have been approved by the FDA, only about half of those are commonly used. Newer, more tolerable agents have made human immunodeficiency virus into a chronic condition, which can be managed with medication. The most common antiretroviral regimens consist of 2 nucleoside reverse transcriptase inhibitors plus a third agent, often an integrase inhibitor because of better tolerability and fewer drug interactions than other regimens. Understanding the dosage forms, adverse effects, and drug interactions of antiretrovirals allow clinicians to choose the most appropriate regimen for their patient. New developments, such as branded generic regimens and long-acting intramuscular injections, may play a larger role in the future.

The Asplenic Patient: Post-Insult Immunocompetence, Infection, and Vaccination.

BACKGROUND: Splenic injury can occur through multiple mechanisms and may result in various degrees of residual immunocompetence. Functionally or anatomically asplenic patients are at higher risk for infection, particularly with encapsulated bacteria. Vaccination is recommended to prevent infection with these organisms; however, the recommendations are routinely updated, and vaccine selection and timing are complex. METHODS: Review of the pertinent English-language literature, including the recommendations of the U.S. Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. RESULTS: Overwhelming post-splenectomy infection is associated with high morbidity and mortality rates. Patients requiring splenectomy for trauma-related injury appear to be at lower risk for infection than those undergoing splenectomy for a hematologic or oncologic indication. Initial vaccination is dependent on immunization history but generally should consist of the 13-valent pneumococcal conjugate, quadrivalent meningococcal conjugate, meningococcal serogroup B, and Haemophilus influenzae serotype b (Hib) vaccines. Antimicrobial prophylaxis for certain asplenic patients, such as children under the age of five y, may be indicated. CONCLUSION: Immunization remains a key measure to prevent overwhelming post-splenectomy infection. Consideration of new recommendations and indications, possible interactions, and timing remains important to including optimal response to the vaccines.

Potential Ceiling Effect of Healthcare Worker Influenza Vaccination on the Incidence of Nosocomial Influenza Infection.

OBJECTIVE To evaluate the effect of healthcare worker (HCW) influenza vaccination on the incidence of nosocomial influenza DESIGN Retrospective cross-sectional study SETTING A 550-bed tertiary-care academic medical center METHODS All admitted patients with a direct fluorescent antibody (DFA) or polymerase chain reaction (PCR) assay positive for influenza ordered between October 1 and May 31 from 2010 to 2015 were eligible for inclusion. Nosocomial influenza was defined as a positive influenza test collected ≥48 hours after admission in patients without influenza-like illness present within 24 hours of admission. Relative nosocomial influenza frequency was calculated by dividing the number of nosocomial cases by the total number of admitted patients with influenza for each season. A univariate logistic regression was used to determine the association between HCW influenza vaccination coverage and nosocomial influenza. RESULTS Over 5 seasons, 533 patients had positive influenza tests during their hospitalization; 29 of these patients (5.4%) acquired influenza during their hospitalization. HCW vaccination coverage increased over the 5 seasons from 47% to 90% (P<.001). Despite an initial decrease in relative nosocomial influenza frequency during the first year (9% to 4.9%), subsequent seasons failed to show an additional decrease in nosocomial infections (4.3%, 5.2%, and 4.8%, respectively); the overall decrease in nosocomial influenza from the first season to the final season was not significant (P=.282). No association was detected between HCW vaccination coverage and nosocomial influenza (odds ratio [OR], 0.990; 95% confidence interval [CI], 0.970-1.011). CONCLUSION HCW vaccination >50% may not have a significant effect on nosocomial influenza. Infect Control Hosp Epidemiol 2016;37:840-844.

Pulmonary Fungal Infection Caused by Neoscytalidium dimidiatum.

Neoscytalidium dimidiatum is a mold known to cause onychomycosis and dermatomycosis; however, it is an extremely rare cause of systemic infection. We report a case of pulmonary infection with Neoscytalidium dimidiatum in an immunocompromised patient and discuss in vitro susceptibility data from this case and previous literature.