Improving antimicrobial treatment in terms of antimicrobial stewardship and health costs by an OPAT service.

PURPOSE: Outpatient parenteral antimicrobial therapy (OPAT) is a standard for antimicrobial therapy internationally. With this prospective cohort study, we aimed to assess the impact of an OPAT service as part of antimicrobial stewardship (AMS) and evaluate the safety and efficiency of the program while illuminating the financial benefit for the hospital. METHODS: Socio-demographic data, treatment regimen and outcomes were prospectively recorded for all patients assigned to the program of the OPAT unit of the University Hospital of Zurich between November 2018 and September 2022. RESULTS: In total, we recorded 303 OPAT assignments of which 260 resulted in effective OPAT episodes. The 260 OPAT episodes were further optimized toward the choice of antimicrobial agent (n = 18) and length of therapy (n = 6). Moreover, OPAT resulted in alteration of patient assessment and care led by AMS strategies in 247 of 260 episodes (95%). While the bed days saved per year increased consistently with time, a total of 3934 in-hospital treatment days were saved amounting to a cost saving of 9,835,000 CHF over 47 months. Adverse events were recorded in 46 cases whilst only two of these have been the reason for readmission during OPAT treatment. Clinical cure was noted in 77% (199/260) and was negatively associated with Charlson Comorbidity Index (CCI; OR per 1 unit higher 0.85 (95% CI 0.78-0.93)). CONCLUSION: This study demonstrates the impact of an OPAT service in the framework of AMS as well as its benefits for the hospital whilst preserving safety and efficacy for the patient's parenteral antimicrobial treatment.

Understanding the Decline of Incident, Active Tuberculosis in People With Human Immunodeficiency Virus in Switzerland.

BACKGROUND: People with human immunodeficiency virus type 1 (HIV-1) (PWH) are frequently coinfected with Mycobacterium tuberculosis (MTB) and at risk for progressing from asymptomatic latent TB infection (LTBI) to active tuberculosis (TB). LTBI testing and preventive treatment (TB specific prevention) are recommended, but its efficacy in low transmission settings is unclear. METHODS: We included PWH enrolled from 1988 to 2022 in the Swiss HIV Cohort study (SHCS). The outcome, incident TB, was defined as TB ≥6 months after SHCS inclusion. We assessed its risk factors using a time-updated hazard regression, modeled the potential impact of modifiable factors on TB incidence, performed mediation analysis to assess underlying causes of time trends, and evaluated preventive measures. RESULTS: In 21 528 PWH, LTBI prevalence declined from 15.1% in 2001% to 4.6% in 2021. Incident TB declined from 90.8 cases/1000 person-years in 1989 to 0.1 in 2021. A positive LTBI test showed a higher risk for incident TB (hazard ratio [HR] 9.8, 5.8-16.5) but only 10.5% of PWH with incident TB were tested positive. Preventive treatment reduced the risk in LTBI test positive PWH for active TB (relative risk reduction, 28.1%, absolute risk reduction 0.9%). On population level, the increase of CD4 T-cells and reduction of HIV viral load were the main driver of TB decrease. CONCLUSIONS: TB specific prevention is effective in selected patient groups. On a population level, control of HIV-1 remains the most important factor for incident TB reduction. Accurate identification of PWH at highest risk for TB is an unmet clinical need.

Human Streptococcal Necrotizing Fasciitis Histopathology Mirrored in a Murine Model.

Streptococcal necrotizing fasciitis (NF) causes high morbidity and mortality despite state-of-the-art therapy. Low incidence and rapid disease progression, necessitating immediate initiation of therapy, have proven challenging aspects for setting up prospective randomized trials. This has resulted in little therapeutic progress over the past decade. The validation of reliable murine NF models to study both pathogenesis and optimized therapeutic regimens of streptococcal NF are thus essential. In this study, we characterized a murine NF model and compared the pathology with an in-depth tissue analysis of streptococcal NF in patients. We found that the streptococcal murine NF model closely reflected all histologic characteristics encountered in human streptococcal NF. This murine NF model helps understanding of human NF pathology better in a time-dependent manner and will allow studying novel therapeutic options in the future.

Therapeutic Drug Monitoring of Daptomycin: A Retrospective Monocentric Analysis.

BACKGROUND: Daptomycin dose is adjusted to body weight and renal function and is usually not guided by therapeutic drug monitoring. Daptomycin plasma concentration measurement was established at our institution in January 2009 and is now increasingly being used. The aim of this study was to describe and characterize variability in daptomycin exposure during routine clinical therapy. METHODS: We collected daptomycin plasma concentrations that were measured at our institution during the period January 2009-July 2012. Additional clinical and demographic data and their association with daptomycin exposure were tested by a multilevel linear regression analysis. RESULTS: A total of 332 daptomycin plasma concentrations were determined in 86 patients. Sixty-six percent (n = 218) of all determinations were trough concentrations (Cmin), and 34% (n = 114) were peak concentrations (Cmax). Cmin ranged 2-68 mg/L (median, 16.7 mg/L), and Cmax 20-236 mg/L (median, 66.2 mg/L). A significant positive association of total dose, albumin, creatinine and a significant negative association of dose interval and intermittent hemodialysis with Cmin were found in the regression analysis. Total dose and intensive care unit (ICU) stay were significantly associated with Cmax (P < 0.05). However, only 28% (P < 0.005) of Cmin variability and 8% (P = 0.08) of Cmax variability were explained by the factors included in the analysis. CONCLUSIONS: Daptomycin plasma concentrations are often unpredictable as shown by highly variable drug exposure that is only partially explained by dose administered and underlying renal function.

Rapid antimicrobial susceptibility testing in patients with bacteraemia due to Enterobacterales: an implementation study.

AIMS OF THE STUDY: The goal of this descriptive study was to assess the performance as well as the extent of the clinical impact of rapid automated antimicrobial susceptibility testing in patients with bacteraemia due to Enterobacterales. We also aimed to analyse how rapid automated antimicrobial susceptibility testing influences clinical decision-making. METHODS: This single-centre study conducted at the University Hospital of Zurich included data from all consecutive patients with Enterobacterales bacteraemia from November 2019 to October 2020. There was no control group. The primary outcome was the effect of rapid automated antimicrobial susceptibility testing on antibiotic therapy (no adjustment, escalation to a broader-spectrum antibiotic or de-escalation to a narrower-spectrum antibiotic). Rapid automated antimicrobial susceptibility testing results were further compared to susceptibility tests using European Committee on Antimicrobial Susceptibility Testing (EUCAST) standard methods and erroneous results were noted. Additionally, we investigated turnaround times for rapid automated antimicrobial susceptibility testing and routine diagnostic testing. RESULTS: We analysed 106 patients with 116 episodes of bacteraemia due to Enterobacterales, with Escherichia coli and Klebsiella pneumoniae being the most frequent isolates. Almost 8% of pathogens were multidrug resistant. Rapid automated antimicrobial susceptibility testing showed category agreement in 98.4% of all interpretable cases. A significant reduction of more than 20 h in turnaround times could be achieved with rapid automated antimicrobial susceptibility testing compared to the routine diagnostic workflow. In the majority of cases, rapid automated antimicrobial susceptibility testing had no effect, given that the empirical therapy was already correct or circumstances did not allow for de-escalation. In 38.8% of cases, antimicrobial therapy was adjusted, whereas eight cases were de-escalated based on rapid automated antimicrobial susceptibility testing alone. CONCLUSIONS: Rapid automated antimicrobial susceptibility testing may be a valuable and safe way to accelerate diagnosis. In particular, time to suitable therapy can be shortened in cases of incorrect therapy. However, physicians are reluctant to de-escalate antibiotic therapy based on rapid automated antimicrobial susceptibility testing alone, limiting its impact in everyday clinics. To further explore the potential of rapid automated antimicrobial susceptibility testing, a stringent/compulsory antibiotic stewardship programme would be a valuable next step.