Occurrence and predictors of laboratory abnormalities during outpatient parenteral antimicrobial therapy - A multicenter cohort study to inform laboratory test monitoring.

OBJECTIVES: Evidence on the optimal frequency of laboratory testing during outpatient parenteral antimicrobial therapy (OPAT) is lacking. Therefore, we investigated how often and when laboratory abnormalities occur during OPAT and which factors are associated with these abnormalities. METHODS: We performed a multicenter cohort study in four Dutch hospitals among adult patients receiving OPAT and collected routinely obtained laboratory test results. Incidence and incidence rates were calculated for various laboratory abnormalities. Survival analysis was performed to visualize the time to the first occurrence of laboratory abnormalities and Poisson regression analysis to compare the number of abnormalities in the first and second 30 OPAT days among patients receiving OPAT for ≥60 days. Predictors were identified using a multivariable Cox proportional hazard regression model. RESULTS: 45.1% of 1152 included patients developed laboratory abnormalities, but only 2% led to OPAT discontinuation. Hepatotoxicity was most common (33.9 events/1000 OPAT days), with a time-dependent decrease in the occurrence of the first hepatotoxic event, while hypokalemia was rare (1.7 events/1000 OPAT days). In the subgroup of patients receiving ≥60 days of OPAT, nephrotoxicity was more common in days 31-60. We observed partly toxicity-specific associations between antibiotic type, concomitant medication, baseline laboratory values, patient characteristics, and the occurrence of laboratory abnormalities. CONCLUSIONS: While laboratory abnormalities are frequently observed during OPAT, they rarely lead to discontinuation of OPAT. Specific patient, treatment and laboratory characteristics were associated with the occurrence of laboratory abnormalities. Based on our results, we recommend a more personalized laboratory monitoring policy with less blood sampling.

Effectiveness and safety of Ceftolozane/Tazobactam administered in continuous infusion through elastomeric pumps in OPAT regimen: a case series.

PURPOSE: This study aimed to present real-life data on the use, effectiveness, and safety of administering Ceftolozane/Tazobactam (C/T) through elastomeric pumps (EP) in the outpatient setting. METHODS: This case series study was conducted from January 2022 to July 2023 in a large University Hospital in Rome, Italy. Patients receiving continuous infusion of C/T via EP were included up to a follow-up period of 90 days after the end of antibiotic therapy. The primary endpoint was the infection's clinical cure rate. Secondary endpoints were adverse events attributable to continuous home infusion of Ceftolozane/Tazobactam via elastomeric pumps. RESULTS: Seven patients received C/T continuously infused via EP and were included in the final analysis. Three patients suffered from prosthetic joint infection (n = 3/7; 43%), two patients from osteomyelitis (n = 2/7; 29%), one patient from otomastoiditis (n = 1/7; 15%) and one from pneumonia (n = 1/7; 15%). All infection were sustained by P. aeruginosa. Five strains had MDR-type susceptibility profiles (n = 5/7; 71%) and two of these were DTR (n = 2/7; 29%). The infection cure rate reached 86% (n = 6/7). Two patients reported a complication related to the vascular catheter for drug infusion (n = 2/7; 29%). CONCLUSIONS: Continuous infusion of Ceftolozane/Tazobactam by elastomeric pumps has been shown to be safe and effective in practice representing a viable option of intravenous treatment in outpatient setting for infection sustained by P. aeruginosa especially for multidrug-resistant strains.

Early Oral Step-Down Versus Continued Intravenous Antibiotic Treatment of Complicated Intra-Abdominal Infection.

Background: Complicated intra-abdominal infections (cIAIs) require a combined tactic, of source control and antimicrobial therapy. This study aimed to evaluate the safety and efficacy of oral step-down antimicrobial therapy in cIAIs after initial intravenous (IV) antimicrobial therapy. Methods: This retrospective cohort study included hospitalized adult patients diagnosed with a cIAI who received more than seven days of IV therapy from March 2017 to October 2021. Exclusion criteria included primary/peritoneal dialysis-related peritonitis, necrotizing pancreatitis, fistulizing inflammatory bowel disease, or upper gastrointestinal tract infection. Patients were assigned into two groups: IV-only or oral step-down therapy. The primary outcome was infection recurrence, defined as re-initiation of antimicrobial agents after a treatment-free period of more than or equal to three days. Secondary outcomes included treatment escalation, repeat source control procedure, treatment-related complications, and all-cause mortality. Results: The cohort consisted of 248 patients (199 IV-only and 49 oral step-down). Patients receiving IV-only therapy had a shorter median antimicrobial duration than the oral step-down group (13 vs. 23 d; p <0.0001). Infection recurrence occurred in 26 (13.1%) and 6 (12.2%) patients in the IV-only and oral step-down groups, respectively (p = 0.88). Treatment escalation, repeat source control, and 28-day mortality were similar between groups. Oral step-down therapy resulted in more adverse drug events (10.2% vs. 3.0%; p = 0.04). Discussion: Transition to oral step-down after initial IV therapy had a similar rate of infection recurrence as IV-only therapy but was associated with a longer duration of antimicrobial therapy and an increased rate of adverse drug reactions. Larger randomized non-inferiority studies are needed to confirm this approach.

The Infusion of Piperacillin/Tazobactam with an Elastomeric Device: A Combined 24-H Stability Study and Drug Solution Flow Rate Analysis.

Bacterial respiratory tract infections (e.g., in patients with cystic fibrosis) may be treated with the intravenous infusion of a piperacillin/tazobactam (P/T) solution through an elastomeric device. In the present work, we combined a 24-h drug stability study with an assessment of the drug solution flow rate during an in vitro simulated infusion. Experiments were performed in triplicate with two excipient-free generic P/T solutions and an excipient-containing proprietary P/T solution in saline (all 50/6.25 mg/mL) released from an elastomeric infusion device at 32 °C. The P/T solutions' stability was assessed by an HPLC-UV assay, pH and osmolality measurements, a visual assessment, and particle counting. Before these analyses, a forced degradation study was performed. To assess the flow rate, a precision scale was used to weigh the solution collected at the infusion line outlet. The stability criteria were <10% degradation and a flow rate within ± 15% of the nominal value over the 24-h infusion period: all three P/T solutions were found to be stable. The actual flow rate was lower than the expected flow rate; this difference was probably due to the drug solution's high viscosity and must be taken into account in clinical use.

Outpatient parenteral antibiotic therapy (OPAT) through elastomeric continuous infusion pumps in a real-life observational study: Characteristics, safety, and efficacy analysis.

INTRODUCTION: This study aimed to present real-life data on the use, efficacy, and safety of administering antibiotic therapy through portable elastomeric pumps (pEP) in the outpatient setting. METHODS: This retrospective observational cohort study was conducted from January 2020 to May 2023 in a large academic hospital in Rome, Italy. All patients receiving antibiotic therapy via pEP were included up to a follow-up period of 90 days after the end of antibiotic therapy. The primary outcome was the treatment response. Secondary endpoints were adverse events attributable to the drug administered, the vascular catheter, or the infection itself. RESULTS: Of the 490 patients referred to our outpatient parenteral antibiotic therapy (OPAT) unit, 94 (19.2%) received antibiotic therapy via pEP and were included in the final analysis. The most frequently treated infections were those involving bone and prosthetics, including spondylodiscitis (n=27; 28.8%). Most infections were due to Pseudomonas aeruginosa (n=55; 48.3%). Cefepime (n=32; 34.0%), piperacillin/tazobactam (n=29; 30.9%), ceftolozane/tazobactam (n=7; 7.5%), and oxacillin (n=7; 7.5%) were the most frequently administered antibiotics. The infection cure rate reached 88.3% (n=83). 12 patients (12.8%) reported adverse events, of which half (6.4%) were drug-related and half (6.4%) were line-related. CONCLUSIONS: OPAT through portable elastomeric infusion pumps proved to be safe and effective. It also contributed to the reduction of healthcare costs, fully respecting the principles of personalized medicine. This strategy has emerged as a promising tool for antibiotic stewardship and infection control.

A Qualitative Review of Patient Feedback for the OPAT (Outpatient Antimicrobial Therapy) Service in Bristol.

Outpatient parenteral antimicrobial therapy (OPAT) aims to deliver intravenous antimicrobials to medically stable patients with complex infections outside of a hospital setting. There is good evidence to demonstrate the safety and efficacy of OPAT in the literature. Anecdotally, the feedback from patients has been positive, but only a few studies evaluate this topic in detail. The aim of this qualitative study was to examine patients' experiences with and feedback on the OPAT service in Bristol, United Kingdom, which was established in 2021. A total of 92 patient feedback surveys were reviewed retrospectively, and thematic analysis was undertaken. Feedback from OPAT patients in our centre was overwhelmingly positive. The key themes identified were benefits to the patients, their friends, and family, and positive feedback about OPAT staff. The mean overall satisfaction score for OPAT was 9.6 out of 10. Areas to improve included communication between the OPAT and parent teams, improving OPAT capacity, and expansion of the service.

Outpatient Parenteral Antimicrobial Therapy in a Safety Net Hospital: Opportunities for Improvement.

Background: Outpatient parenteral antimicrobial therapy (OPAT) is a safe and cost-effective transitional care approach administered via different delivery models. No standards exist for appropriate OPAT program staffing. We examined outcomes of patients receiving OPAT via different care models to identify strategies to improve safety while reducing health care overuse. Methods: Retrospective demographic, clinical, and outcome data of patients discharged with OPAT were reviewed in 2 periods (April-June 2021 and January-March 2022; ie, when staffing changed) and stratified by care model: self-administered OPAT, health care OPAT, and skilled nursing facility OPAT. Results: Of 342 patients, 186 (54%) received OPAT in 2021 and 156 (46%) in 2022. Hospital length of stay rose from 12.4 days to 14.3 in 2022. In a Cox proportional hazards regression model, visits to the emergency department (ED) within 30 days of OPAT initiation (hazard ratio, 1.76; 95% CI, 1.13-2.73; P = .01) and readmissions (hazard ratio, 2.34; 95% CI, 1.22-4.49; P = .01) increased in 2022 vs 2021, corresponding to decreases in OPAT team staffing. Higher readmissions in the 2022 cohort were for reasons unrelated to OPAT (P = .01) while readmissions related to OPAT did not increase (P = .08). Conclusions: In a well-established OPAT program, greater health care utilization-length of stay, ED visits, and readmissions-were seen during periods of higher staff turnover and attrition. Rather than blunt metrics such as ED visits and readmissions, which are influenced by multiple factors besides OPAT, our findings suggest the need to develop OPAT-specific outcome measures as a quality assessment tool and to establish optimal OPAT program staffing ratios.

Quantifying the Time to Administer Outpatient Parenteral Antimicrobial Therapy: A Missed Opportunity to Compensate for the Value of Infectious Diseases.

Outpatient parenteral antimicrobial therapy (OPAT) relies on substantial uncompensated provider time. In this study of a large academic OPAT program, the median amount of unbilled OPAT management time was 27 minutes per week, per OPAT course. These data should inform benchmarks in pursuing novel payment approaches for OPAT.

Head-to-head comparison of multi-dose oritavancin and dalbavancin for complicated infections: A propensity score-matched analysis.

BACKGROUND: Oritavancin and dalbavancin are long-acting lipoglycopeptide antibiotics approved for the treatment of skin and skin structure infections. Recently, they have been used for outpatient antimicrobial therapy for complicated infections. No head-to-head studies exist for this purpose. OBJECTIVE: To compare outcomes of patients treated with multiple doses of oritavancin or dalbavancin for complicated infections. PATIENTS AND METHODS: This was a single-centre, retrospective cohort study evaluating adult patients who received two or more doses of lipoglycopeptides for complicated infections from February 2019 through December 2022. Patients receiving oritavancin were compared to dalbavancin after propensity score-matching. The primary endpoint was clinical success at 90 days. Other endpoints included: 30-day re-admission, 30-day mortality, adverse drug reactions (ADRs), and changes in white blood cell count and inflammatory markers after the first dose. RESULTS: After exclusions and propensity score-matching, 131 matched pairs (N = 262) were included in the analysis. Most patients were receiving lipoglycopeptide therapy for osteomyelitis. There was no significant difference in clinical success at 90 days in patients who received oritavancin compared to those who received dalbavancin (99 [76%] vs. 103 [79%], respectively; P = 0.556). There was no significant difference in secondary endpoints, however, there was a trend towards higher incidence of ADRs oritavancin compared to dalbavancin (9 [7%] vs. 2 [2%], respectively; P = 0.060) which led to more treatment discontinuation. CONCLUSION: There was no significant difference in efficacy between multi-dose oritavancin and dalbavancin for the treatment of complicated infections. Both agents were generally well tolerated; however, dalbavancin may be better tolerated when long-term treatment is warranted.

Exploring patients' perspectives: a mixed methods study on Outpatient Parenteral Antimicrobial Therapy (OPAT) experiences.

BACKGROUND: Outpatient Parenteral Antimicrobial Therapy (OPAT), an alternative to inpatient intravenous antibiotic therapy, has shown benefits in international studies such as increased patient satisfaction. Because OPAT has been used only sporadically in Germany so far, no structured results on patients' experiences and concerns regarding OPAT have yet been available. This study therefore aims to explore the experiences of OPAT patients in a pilot region in Germany. METHODS: This is an observational study in a German pilot region, including a survey of 58 patients on their experiences with OPAT, and in-depth interviews with 12 patients (explanatory-sequential mixed-methods design). RESULTS: Patients reported that they were satisfied with OPAT. That a hospital discharge was possible and anti-infective therapy could be continued in the home environment was rated as being particularly positive. In the beginning, many patients in the interviews were unsure about being able to administer the antibiotic therapy at home on their own. However, healthcare providers (doctors and pharmacy service provider staff) were able to allay these concerns. Patients appreciated regular contact with care providers. There were suggestions for improvement, particularly concerning the organization of the weekly check-up appointments and the provision of information about OPAT. CONCLUSIONS: Patients were generally satisfied with OPAT. However, the treatment structures in Germany still need to be expanded to ensure comprehensive and high-quality OPAT care. TRIAL REGISTRATION: NCT04002453, https://www. CLINICALTRIALS: gov/ , (registration date: 2019-06-21).

Evaluation of health-related quality of life in patients receiving outpatient parenteral antimicrobial therapy (OPAT) in a UK setting.

BACKGROUND: Studies assessing the benefits of outpatient parenteral antimicrobial therapy (OPAT) have paid less attention to patient-centered factors such as patients' experiences and their health-related quality of life (HRQoL). RESEARCH DESIGN AND METHODS: Prospective before-and-after quasi-experimental study enrolled adult patients receiving OPAT at a tertiary hospital in Derbyshire, UK, between October 2022 and October 2023. Consenting patients completed paired EQ-5D-3 L questionnaires before OPAT initiation and upon completion of therapy or 30 days after its commencement (whichever occurred first). Changes and predictors of change in HRQoL indicators and associations with clinical outcomes (treatment failure, adverse events, and 30-day unplanned readmission) were examined. RESULTS: Health state index and visual analogue scale (EQ VAS) scores of 162 enrolled patients at baseline were significantly lower than the UK population averages, but the patients experienced significant improvements in both scores and in four EQ-5D dimensions (mobility, self-care, usual activities, and pain/discomfort). Baseline health index and EQ VAS scores were significant independent predictors of positive changes in HRQoL scores. CONCLUSIONS: OPAT is associated with improved patient-reported quality of life and facilitates early return to work or school. Nevertheless, it is crucial to closely monitor patients with a lower baseline quality of life to optimize their overall OPAT experience.

Outpatient parenteral antimicrobial therapy (OPAT) in Germany: insights and clinical outcomes from the K-APAT cohort study.

PURPOSE: Outpatient parenteral antimicrobial therapy (OPAT) offers several key advantages, including enhanced patient quality of life, reduced healthcare costs, and a potential reduction of nosocomial infections. It is acknowledged for its safety and effectiveness. This study provides the first systematic clinical data for Germany, where OPAT has not yet been widely adopted. The aim is to establish a foundational reference point for further research and integration of OPAT into the German healthcare system. METHODS: This prospective observational study descriptively analyses data obtained from a cohort of patients receiving OPAT. Both in- and outpatients from all medical specialties could be recruited. Patients administered the anti-infective medications themselves at home using elastomeric pumps. RESULTS: 77 patients received OPAT, with a median duration of 15 days and saving 1782 inpatient days. The most frequently treated entities were orthopaedic infections (n = 20, 26%), S. aureus bloodstream infection (n = 16, 21%) and infectious endocarditis (n = 11, 14%). The most frequently applied drugs were flucloxacillin (n = 18, 23%), penicillin G (n = 13, 17%) and ceftriaxone (n = 10; 13%). Only 5% of patients (n = 4) reported to have missed more than one outpatient dose (max. 3 per patient). Only one catheter-related adverse event required medical intervention, and there were no catheter-related infections. CONCLUSION: The study demonstrates that OPAT can be safely conducted in Germany. In preparation for its broader implementation, crucial next steps include creating medical guidelines, fostering interdisciplinary and inter-sectoral communication, as well as creating financial and structural regulations that facilitate and encourage the adoption of OPAT. TRIAL REGISTRATION NUMBER: NCT04002453.

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.

Supportive care needs of adults living with a peripherally inserted central catheter (PICC) at home: a qualitative content analysis.

BACKGROUND: Peripherally inserted central catheters (PICCs) are common vascular access devices inserted for adults undergoing intravenous treatment in the community setting. Individuals with a PICC report challenges understanding information and adapting to the device both practically and psychologically at home. There is a lack of research investigating the supportive care needs of individuals with a PICC to inform nursing assessment and the provision of additional supports they may require to successfully adapt to life with a PICC. The aim of this study was to identify the supportive care needs of adults with cancer or infection living with a PICC at home. METHOD: Qualitative, semi-structured interviews were used to identify supportive care needs of adults living with a PICC at home. Participants were recruited from cancer and infectious diseases outpatient units. Two researchers independently analysed transcripts using content analysis. RESULTS: A total of 15 participants were interviewed (30-87 years old). There were 5 males and 10 females interviewed, 9 participants had a cancer diagnosis and most lived in a metropolitan area. Many participants lived with a partner/spouse at home and three participants had young children. Participants identified supportive care needs in the following eight categories (i (i) Adapting daily life (ii) Physical comfort (iii) Self-management (iv) Emotional impact (v) Information content (vi) Understanding information (vii) Healthcare resources and (viii) Social supports. CONCLUSIONS: Adults living with a PICC at home report a broad range of supportive care needs. In addition to practical and information needs, health consumers may also require support to accept living with a device inside their body and to assume responsibility for the PICC. These findings may provide nurses with a greater understanding of individual needs and guide the provision of appropriate supports.

The success rate and complications of midline catheters in pediatric outpatient parenteral antibiotic therapy (OPAT).

The use of outpatient parenteral antimicrobial therapy (OPAT) for children has several advantages, including reduced length of hospital stay and costs. A reliable vascular access is key to delivering safe and effective pediatric OPAT. In recent years, midline catheters (MC) have been increasingly used for short-term intravenous antibiotic therapy in children. However, there are no studies investigating the use of MCs in the OPAT setting. The main aim of this paper was to evaluate the success and complications of using MCs for pediatric OPAT. This was a retrospective cohort study from a tertiary academic pediatric hospital. All MCs inserted at the hospital and used for OPAT were eligible for study inclusion. The primary objective was to describe the percentage of patients able to complete OPAT without the need for additional venous access. Forty-one MCs were included in the study. Patient mean (SD) age was 5.9 (4.9) years. In 31 cases (76%, 95% CI 62-86%), the iv therapy could be successfully completed using only the MC. Imbalances between the groups suggested unfavorable outcome for saphenous vein catheters as well as for shorter and smaller-sized catheters. Fourteen patients (34%) were subjected to a MC-related complication. Pain on injection in the MC was the most frequent complication (n = 10, 24%).    Conclusion: Midline catheters could be an alternative to central venous access for pediatric OPAT. Avoiding saphenous vein insertion and using longer and larger-sized catheters could increase MC success rate. No severe MC-related complication was found. Further randomized studies comparing different catheter types are needed. What is Known: • For selected patients, pediatric outpatient parenteral antimicrobial therapy (OPAT) is safe and provides health-economic, psychosocial, and medical advantages compared to in-hospital care. • A reliable venous access is one of the key factors to the success of OPAT, but this can be a challenge in children. What is New: • Using midline catheters, 76% of patients could complete their intended iv therapy without the need for additional venous access. Avoiding saphenous vein insertion and using longer and larger-sized catheters could increase the success rate. • Thirty-four percent of catheters were subject to some kind of complication, the most common being pain on injection in the catheter.

NOTICE OF DUPLICATE PUBLICATION: "Stability of meropenem in portable elastomeric infusion devices: which protocol should be implemented in clinical practice?"

The American Society for Microbiology (ASM) and Microbiology Spectrum are withdrawing the article mentioned below as it is an inadvertent duplicate publication: Esteban-Cartelle B, Serrano DR, Pérez Menéndez-Conde C, Vicente-Oliveros N, Álvarez-Díaz A, Abete JF, Martín-Dávila P. 2024. Stability of meropenem in portable elastomeric infusion devices: which protocol should be implemented in clinical practice? Microbiol Spectr 12:e02063-23. https://doi.org/10.1128/spectrum.02063-23. This article was accidentally published twice in the journal due to a technical error, and there are no ethical or integrity concerns regarding the original published article. The duplicate version of the article has been withdrawn to correct the scholarly record. The original published article and its content are not affected by this withdrawal and can be found here: https://journals.asm.org/doi/10.1128/spectrum.02064-23 The American Society for Microbiology apologizes to the authors and its readers for the technical error and the inconvenience this may have caused. The authors agreed with the publication of this notice.