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Wolie ZT, Roberts JA, Gilchrist M, McCarthy K, Sime FB. Current practices and challenges of outpatient parenteral antimicrobial therapy: a narrative review. J Antimicrob Chemother 2024; 79:2083-2102. [PMID: 38842523 PMCID: PMC11368434 DOI: 10.1093/jac/dkae177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2024] Open
Abstract
Extended hospitalization for infection management increases inpatient care costs and the risk of healthcare-associated adverse events, including infections. The growing global demand for healthcare, the diminishing availability of hospital beds and an increasing patient preference for care within their own home have been the primary drivers of the expansion of hospital-in-the-home programmes. Such programmes include the use of IV antimicrobials in outpatient settings, known as outpatient parenteral antimicrobial therapy (OPAT). However, OPAT practices vary globally. This review article aims to describe the current OPAT practices and challenges worldwide. OPAT practice begins with patient evaluation and selection using eligibility criteria, which requires collaboration between the interdisciplinary OPAT team, patients and caregivers. Depending on care requirements, eligible patients may be enrolled to various models of care, receiving medication by healthcare professionals at outpatient infusion centres, hospital clinics, home visits or through self-administration. OPAT can be used for the management of many infections where an effective oral treatment option is lacking. Various classes of parenteral antimicrobials, including β-lactams, aminoglycosides, glycopeptides, fluoroquinolones and antifungals such as echinocandins, are used globally in OPAT practice. Despite its benefits, OPAT has numerous challenges, including complications from medication administration devices, antimicrobial side effects, monitoring requirements, antimicrobial instability, patient non-adherence, patient OPAT rejection, and challenges related to OPAT team structure and administration, all of which impact its outcome. A negative outcome could include unplanned hospital readmission. Future research should focus on mitigating these challenges to enable optimization of the OPAT service and thereby maximize the documented benefits for the healthcare system, patients and healthcare providers.
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Affiliation(s)
- Zenaw T Wolie
- UQ Centre for Clinical Research, Faculty of Medicine, University of Queensland, Brisbane, QLD 4029, Australia
| | - Jason A Roberts
- UQ Centre for Clinical Research, Faculty of Medicine, University of Queensland, Brisbane, QLD 4029, Australia
- Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, Queensland, Australia
- Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane, QLD 4029, Australia
- Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, 30029 Nîmes, France
| | - Mark Gilchrist
- Department of Pharmacy/Infection, Imperial College Healthcare NHS Trust, London, UK
- Department of Infectious Diseases, Imperial College, London, UK
| | - Kate McCarthy
- Royal Brisbane Clinical School, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
- Department of Infectious Diseases, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
| | - Fekade B Sime
- UQ Centre for Clinical Research, Faculty of Medicine, University of Queensland, Brisbane, QLD 4029, Australia
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Versporten A, Bruyndonckx R, Adriaenssens N, Hens N, Monnet DL, Molenberghs G, Goossens H, Weist K, Coenen S. Consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in the community, European Union/European Economic Area, 1997-2017. J Antimicrob Chemother 2021; 76:ii45-ii59. [PMID: 34312660 PMCID: PMC8314111 DOI: 10.1093/jac/dkab177] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Objectives Data on consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials were collected from 30 EU/European Economic Area (EEA) countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of main subgroups of tetracyclines, sulphonamides and trimethoprim and other antibacterials. Methods For the period 1997–2017, data on consumption of tetracyclines (ATC group J01A), sulphonamides and trimethoprim (ATC group J01E), and other antibacterials (ATC group J01X) in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials was analysed based on ATC-4 subgroups and presented as trends, seasonal variation, presence of change-points and compositional changes. Results In 2017, consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in the community expressed in DDD per 1000 inhabitants per day varied considerably between countries. Between 1997 and 2017, consumption of tetracyclines did not change significantly, while its seasonal variation significantly decreased over time. Consumption of sulphonamides and trimethoprim significantly decreased until 2006, and its seasonal variation significantly decreased over time. The consumption of other antibacterials showed no significant change over time or in seasonal variation. Conclusions Consumption and composition of tetracyclines, sulphonamides and trimethoprim, and other antibacterials showed wide variations between EU/EEA countries and over time. This represents an opportunity to further reduce consumption of these groups in some countries and improve the quality of their prescription.
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Affiliation(s)
- Ann Versporten
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
| | - Robin Bruyndonckx
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.,Interuniversity Institute for Biostatistics and statistical Bioinformatics (I-BIOSTAT), Data Science Institute, Hasselt University, Hasselt, Belgium
| | - Niels Adriaenssens
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.,Centre for General Practice, Department of Family Medicine & Population Health (FAMPOP), University of Antwerp, Antwerp, Belgium
| | - Niel Hens
- Interuniversity Institute for Biostatistics and statistical Bioinformatics (I-BIOSTAT), Data Science Institute, Hasselt University, Hasselt, Belgium.,Centre for Health Economic Research and Modelling Infectious Diseases, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
| | - Dominique L Monnet
- Disease Programmes Unit, European Centre for Disease Prevention and Control, Stockholm, Sweden
| | - Geert Molenberghs
- Interuniversity Institute for Biostatistics and statistical Bioinformatics (I-BIOSTAT), Data Science Institute, Hasselt University, Hasselt, Belgium.,Interuniversity Institute for Biostatistics and Statistical Bioinformatics (I-BIOSTAT), Catholic University of Leuven, Leuven, Belgium
| | - Herman Goossens
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
| | - Klaus Weist
- Disease Programmes Unit, European Centre for Disease Prevention and Control, Stockholm, Sweden
| | - Samuel Coenen
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.,Centre for General Practice, Department of Family Medicine & Population Health (FAMPOP), University of Antwerp, Antwerp, Belgium
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Palms DL, Jacob JT. Close Patient Follow-up Among Patients Receiving Outpatient Parenteral Antimicrobial Therapy. Clin Infect Dis 2021; 70:67-74. [PMID: 30810165 DOI: 10.1093/cid/ciz150] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2018] [Accepted: 02/22/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Outpatient parenteral antimicrobial therapy (OPAT) programs allow patients to receive intravenous treatment in the outpatient setting. We developed a predictive model of 30-day readmission among hospitalized patients discharged on OPAT from 2 academic medical centers with a dedicated OPAT clinic for management. METHODS A retrospective medical records review was performed and logistic regression was used to assess OPAT and other outpatient clinic follow-up in conjunction with age, sex, pathogen, diagnosis, discharge medication, planned length of therapy, and Charlson comorbidity score. We hypothesized that at least 1 follow-up visit at the Emory OPAT clinic would reduce the risk for hospital readmission within 30 days. RESULTS Among 755 patients, 137 (18%) were readmitted within 30 days. Most patients (73%) received outpatient follow-up care at Emory Healthcare within 30 days of discharge or prior to readmission, including 52% of patients visiting the OPAT clinic. The multivariate logistic regression model indicated that a follow-up OPAT clinic visit was associated with lower readmission compared to those who had no follow-up visit (odds ratio, 0.10 [95% confidence interval, .06-.17]) after adjusting for infection with enterococci, Charlson score, discharge location, and county of residence. CONCLUSIONS These results can inform potential interventions to prevent readmissions through OPAT clinic follow-up and to further assess factors associated with successful care transitions from the inpatient to outpatient setting.
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Affiliation(s)
- Danielle L Palms
- Department of Epidemiology, Rollins School of Public Health, Emory University
| | - Jesse T Jacob
- Department of Epidemiology, Rollins School of Public Health, Emory University.,Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
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Goossens LMA, Vemer P, Rutten-van Mölken MPMH. The risk of overestimating cost savings from hospital-at-home schemes: A literature review. Int J Nurs Stud 2020; 109:103652. [PMID: 32569827 DOI: 10.1016/j.ijnurstu.2020.103652] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 05/08/2020] [Accepted: 05/12/2020] [Indexed: 02/02/2023]
Abstract
BACKGROUND The concept of hospital-at-home means that home treatment is provided to patients who would otherwise have been treated in the hospital. This may lead to lower costs, but estimates of savings may be overstated if inpatient hospital costs are priced incorrectly. OBJECTIVE The objective of this study was to evaluate the quality of cost analyses of hospital-at-home studies for acute conditions published from 1996 through 2019 and to present an overview of evidence. DESIGN Literature review DATA SOURCES: The PubMed and NHS EED databases were searched. REVIEW METHODS The overall quality of studies was evaluated based on Quality of Health Economic Studies (QHES) score, design, sample size, alignment of cost calculation with study perspective, time horizon, use of tariffs or real resource use and clarity of calculations. Furthermore, we systematically assessed whether cost savings were likely to be overestimated, based on criteria about the costing of inpatient hospital days, informal care costs and bias. RESULTS We identified 48 studies. The average QHES score was 60 out of a maximum of 100 points. Almost all studies violated one or more criteria for the risk of overestimation of cost savings. The most frequent problems were the use of average unit prices per inpatient day (not taking into account the decreasing intensity of care) and biased designs. Most studies found cost differences in favour of hospital-at-home; the range varied from savings of €8773 to a cost increase of €2316 per patient. CONCLUSION Overall quality of studies was not good, with some exceptions. Many cost savings were probably overestimated.
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Affiliation(s)
- Lucas M A Goossens
- Erasmus School for Health Policy & Management, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam 3000, the Netherlands.
| | - Pepijn Vemer
- Erasmus School for Health Policy & Management, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam 3000, the Netherlands; Department of Pharmacotherapy, Epidemiology & Economics, University of Groningen, P.O. Box 196, 9700 AD, Groningen, the Netherlands
| | - Maureen P M H Rutten-van Mölken
- Erasmus School for Health Policy & Management, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam 3000, the Netherlands
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Erba A, Beuret M, Daly ML, Khanna N, Osthoff M. OPAT in Switzerland: single-center experience of a model to treat complicated infections. Infection 2019; 48:231-240. [PMID: 31828605 DOI: 10.1007/s15010-019-01381-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Accepted: 12/03/2019] [Indexed: 11/25/2022]
Abstract
PURPOSE Outpatient parenteral antimicrobial therapy (OPAT) programmes are established in the minority of Swiss hospitals. We aimed to study the OPAT programme at the University Hospital Basel during a 3-year period to evaluate safety and outcome. METHODS All patients treated in the OPAT programme between 2015 and 2017 were included in the study. Demographic, clinical and OPAT outcome data were extracted from the hospital information system. Differences between treatment periods were analysed and risk factors for readmission and adverse events identified. RESULTS In total, 462 patients were enrolled from 2015 to 2017. Patient numbers and total treatment days increased by 68% and 116%, respectively. Indications included many complicated infections such as bone and joint (23%) and intravascular infections (13%). Of the identified Gram-negative bacteria, 25% produced extended spectrum beta-lactamases. The percentage of antibiotics administrated with an elastomeric device increased from 11% in 2015 to 29% in 2017, whereas the use of once-daily antimicrobials (such as ceftriaxone) declined. Adverse events were rare (n = 67; 14.6%) including only two severe catheter-related events. Cure was noted in 98% of patients. 30-day unplanned readmission occurred in 46 (10.0%) patients, and intravascular infections and a higher Charlson comorbidity index were identified as independent predictors. CONCLUSION This study demonstrates the successful implementation of a formal OPAT programme in a Swiss tertiary care hospital. Careful selection of patients and monitoring during treatment are crucial to avoid frequent readmissions. Hence, our data call for an expansion of OPAT services in Switzerland in the near future.
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Affiliation(s)
- Andrea Erba
- Division of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland
| | - Michelle Beuret
- Division of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland
| | - Mary-Louise Daly
- Medical Outpatient Clinic, University Hospital Basel, Basel, Switzerland
| | - Nina Khanna
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
| | - Michael Osthoff
- Division of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
- Department of Clinical Research, University of Basel, Basel, Switzerland.
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Boese CK, Lechler P, Frink M, Hackl M, Eysel P, Ries C. Cost-analysis of inpatient and outpatient parenteral antimicrobial therapy in orthopaedics: A systematic literature review. World J Clin Cases 2019; 7:1825-1836. [PMID: 31417928 PMCID: PMC6692268 DOI: 10.12998/wjcc.v7.i14.1825] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 06/21/2019] [Accepted: 06/27/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Increasing numbers of total joint arthroplasties and consecutive revision surgery are associated with the risk of periprosthetic joint infections (PPJI). Treatment of PPJI is complex and associated with immense socio-economic burden. One treatment aspect is parenteral antiinfective therapy, which usually requires an inpatient setting [Inpatient parenteral antibiotic therapy (IPAT)]. An alternative is outpatient parenteral treatment [Outpatient parenteral antibiotic therapy (OPAT)]. To conduct a health economic cost-benefit analysis of OPAT, a detailed cost analysis of IPAT and OPAT is required. So far, there is a lack of knowledge on the health economic effects of IPAT and OPAT for PPJI.
AIM To review an economic comparison of IPAT and OPAT.
METHODS A systematic literature review was performed through Medline following the PRISMA guidelines.
RESULTS Of 619 identified studies, 174 included information of interest and 21 studies were included for quantitative analysis of OPAT and IPAT costs. Except for one study, all showed relevant cost savings for OPAT compared to IPAT. Costs for IPAT were between 1.10 to 17.34 times higher than those for OPAT.
CONCLUSION There are only few reports on OPAT for PPJI. Detailed analyses to support economic or clinical guidelines are therefore limited. There is good clinical evidence supporting economic benefits of OPAT, but more high quality studies are needed for PPJI.
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Affiliation(s)
- Christoph Kolja Boese
- Department of Orthopaedic and Trauma Surgery, University Hospital of Cologne, Cologne 50931, Germany
| | - Philipp Lechler
- Clinic for Trauma and Hand Surgery, Kreiskliniken, Altötting 84503, Germany
- Center for Orthopaedics and Trauma Surgery, University Hospital Giessen and Marburg, Marburg 35043, Germany
| | - Michael Frink
- Center for Orthopaedics and Trauma Surgery, University Hospital Giessen and Marburg, Marburg 35043, Germany
| | - Michael Hackl
- Department of Orthopaedic and Trauma Surgery, University Hospital of Cologne, Cologne 50931, Germany
| | - Peer Eysel
- Department of Orthopaedic and Trauma Surgery, University Hospital of Cologne, Cologne 50931, Germany
| | - Christian Ries
- Department of Orthopaedic and Trauma Surgery, University Hospital of Cologne, Cologne 50931, Germany
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Sriskandarajah S, Hobbs J, Roughead E, Ryan M, Reynolds K. Safety and effectiveness of 'hospital in the home' and 'outpatient parenteral antimicrobial therapy' in different age groups: A systematic review of observational studies. Int J Clin Pract 2018; 72:e13216. [PMID: 29920884 DOI: 10.1111/ijcp.13216] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 05/09/2018] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE The aim of this study was .to systematically review the published literature of observational studies evaluating the safety and effectiveness of hospital in the home (HITH) and outpatient parenteral antimicrobial therapy (OPAT) in the general population, older people and children. STUDY DESIGN The review included retrospective studies and prospective studies performed on HITH and OPAT within different age groups. Only the studies that analysed the safety and effectiveness of HITH and OPAT were included for review. DATA SOURCES A literature search of electronic databases CINAHL, Web of Science, PubMed and SCOPUS from 1997 to 2016 was performed. DATA SYNTHESIS Forty-four studies met the inclusion criteria. Five studies were undertaken on HITH within the general population, 26 studies were undertaken on OPAT within the general population, 8 studies were on HITH and OPAT for older people and 5 studies were on OPAT with children. More than 88% of the studies reported a cure or treatment success rate of greater than 80%. Adverse events with drugs ranged from 0% to 30.2%; adverse events with vascular access devices ranged from 0% to 29%; readmission rate varied from 1% to 26%; mortality varied from 0% to 27.5%. CONCLUSIONS This review quantifies the rates of success and harm in real world practice, and demonstrates that while most patients experience treatment success, adverse events may be high in some groups. However, the methodologies used to measure these parameters were inconsistent and some demographic groups had only a small number of studies.
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Affiliation(s)
- Shanthy Sriskandarajah
- Medical Device Research Institute, College of Science and Engineering, Flinders University, Adelaide, SA, Australia
| | - Jodie Hobbs
- Medical Device Research Institute, College of Science and Engineering, Flinders University, Adelaide, SA, Australia
| | - Elizabeth Roughead
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia
| | - Melissa Ryan
- Medical Device Research Institute, College of Science and Engineering, Flinders University, Adelaide, SA, Australia
| | - Karen Reynolds
- Medical Device Research Institute, College of Science and Engineering, Flinders University, Adelaide, SA, Australia
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Theocharis G, Barbas SG, Spiropoulos T, Stamouli PE, Perdikis DN, Falagas ME. Patient house calls in Attica and Thessaloniki, Greece (2005-2015): a model for out-of-hospital multispecialty emergency medicine. BMC Health Serv Res 2018; 18:304. [PMID: 29703193 PMCID: PMC5923023 DOI: 10.1186/s12913-018-3111-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 04/11/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The SOS-doctors are a network of physicians who perform house-call visits in the areas of Attica and Thessaloniki, Greece. METHODS Patients requesting medical services by the SOS doctors during the period 1/1/2005 - 31/12/2015 were eligible for inclusion in this retrospective analysis. RESULTS During this period 335, 212 home visits were performed. Females used this service more frequently compared to males (60.5% versus 39.5%). Among the age-groups, patients aged over 75 years made 56.6% of all house calls. Fewer phone requests were recorded during autumn than in winter (21.1% versus 29.1%). Infections were the most common cause of house-visits (29%), followed by cardiovascular diseases (10.3%), musculoskeletal (9.1%), gastrointestinal (6.3%) and neurological disorders (3.7%). An increasing demand for radiology at home was observed, starting at 352 calls in 2009 and reaching 2230 in 2015. Finally, 9.2% of patients were advised to be admitted into a hospital. CONCLUSION A shift towards older age, but not the oldest old (> 90 years), and acute conditions was observed during the study period. The study confirms that home visits retain a significant role in the modern health care systems.
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Affiliation(s)
- George Theocharis
- SOS doctors, Athens, Greece.,Department of Medicine, "Euroclinic" General Clinic, Athens, Greece
| | | | | | - Petroula E Stamouli
- Department of Applied Mathematical and Physical Sciences, National Technical University of Athens, Athens, Greece
| | - Dimitrios N Perdikis
- Department of Applied Mathematical and Physical Sciences, National Technical University of Athens, Athens, Greece
| | - Matthew E Falagas
- Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, 151 23, Marousi, Greece. .,Department of Medicine, Henry Dunant Hospital Center, Athens, Greece. .,Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA.
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Psaltikidis EM, Silva END, Bustorff-Silva JM, Moretti ML, Resende MR. Economic evaluation of outpatient parenteral antimicrobial therapy: a systematic review. Expert Rev Pharmacoecon Outcomes Res 2017; 17:355-375. [PMID: 28776441 DOI: 10.1080/14737167.2017.1360767] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Outpatient parenteral antimicrobial therapy (OPAT) consists of providing antimicrobial therapy by parenteral infusion without hospitalization. A systematic review was performed to compare OPAT and hospitalization as health care modalities from an economic perspective. Areas covered: We identified 1455 articles using 13 electronic databases and manual searches. Two independent reviewers identified 35 studies conducted between 1978 and 2016. We observed high heterogeneity in the following: countries, infection site, OPAT strategies and outcomes analyzed. Of these, 88% had a retrospective observational design and one was a randomized trial. With respect to economic analyses, 71% of the studies considered the cost-consequences, 11% cost minimization, 6% cost-benefit, 6% cost-utility analyses and 6% cost effectiveness. Considering all 35 studies, the general OPAT cost saving was 57.19% (from -13.03% to 95.47%). Taking into consideration only high-quality studies (6 comparative studies), the cost saving declined by 16.54% (from -13.03% to 46.86%). Expert commentary: Although most studies demonstrate that OPAT is cost-effective, the magnitude of this effect is compromised by poor methodological quality and heterogeneity. Economic assessments of the issue are needed using more rigorous methodologies that include a broad range of perspectives to identify the real magnitude of economic savings in different settings and OPAT modalities.
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Affiliation(s)
- Eliane Molina Psaltikidis
- a Health Technology Assessment Department , Clinical Hospital of State University of Campinas , Campinas , Brazil.,b School of Medical Sciences , State University of Campinas , Campinas , Brazil
| | | | - Joaquim Murray Bustorff-Silva
- a Health Technology Assessment Department , Clinical Hospital of State University of Campinas , Campinas , Brazil.,d Surgery Department, School of Medical Sciences , State University of Campinas , Campinas , Brazil
| | - Maria Luiza Moretti
- e Division of Infectious Diseases, Internal Medicine Department, School of Medical Sciences , State University of Campinas , Campinas , Brazil
| | - Mariângela Ribeiro Resende
- a Health Technology Assessment Department , Clinical Hospital of State University of Campinas , Campinas , Brazil.,e Division of Infectious Diseases, Internal Medicine Department, School of Medical Sciences , State University of Campinas , Campinas , Brazil
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Eliadi I, Tsoumi G, Kampouropoulou O, Theofanis V, Mantzourani M, Samarkos M. Characterization of the medical admissions in a tertiary Greek hospital. Eur J Intern Med 2017; 40:e15-e16. [PMID: 28119030 DOI: 10.1016/j.ejim.2017.01.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2017] [Accepted: 01/18/2017] [Indexed: 10/20/2022]
Affiliation(s)
- Irene Eliadi
- 1st Department of Medicine, Laikon Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece
| | - Georgia Tsoumi
- 1st Department of Medicine, Laikon Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece
| | - Olga Kampouropoulou
- 1st Department of Medicine, Laikon Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece
| | - Vasileios Theofanis
- 1st Department of Medicine, Laikon Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece
| | - Marina Mantzourani
- 1st Department of Medicine, Laikon Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece
| | - Michael Samarkos
- 1st Department of Medicine, Laikon Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece.
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Mitchell ED, Czoski Murray C, Meads D, Minton J, Wright J, Twiddy M. Clinical and cost-effectiveness, safety and acceptability of community intra venous antibiotic service models: CIVAS systematic review. BMJ Open 2017; 7:e013560. [PMID: 28428184 PMCID: PMC5775457 DOI: 10.1136/bmjopen-2016-013560] [Citation(s) in RCA: 79] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
OBJECTIVE Evaluate evidence of the efficacy, safety, acceptability and cost-effectiveness of outpatient parenteral antimicrobial therapy (OPAT) models. DESIGN A systematic review. DATA SOURCES MEDLINE, EMBASE, CINAHL, Cochrane Library, National Health Service (NHS) Economic Evaluation Database (EED), Research Papers in Economics (RePEc), Tufts Cost-Effectiveness Analysis (CEA) Registry, Health Business Elite, Health Information Management Consortium (HMIC), Web of Science Proceedings, International Pharmaceutical Abstracts, British Society for Antimicrobial Chemotherapy website. Searches were undertaken from 1993 to 2015. STUDY SELECTION All studies, except case reports, considering adult patients or practitioners involved in the delivery of OPAT were included. Studies combining outcomes for adults and children or non-intravenous (IV) and IV antibiotic groups were excluded, as were those focused on process of delivery or clinical effectiveness of 1 antibiotic over another. Titles/abstracts were screened by 1 reviewer (20% verified). 2 authors independently screened studies for inclusion. RESULTS 128 studies involving >60 000 OPAT episodes were included. 22 studies (17%) did not indicate the OPAT model used; only 29 involved a comparator (23%). There was little difference in duration of OPAT treatment compared with inpatient therapy, and overall OPAT appeared to produce superior cure/improvement rates. However, when models were considered individually, outpatient delivery appeared to be less effective, and self-administration and specialist nurse delivery more effective. Drug side effects, deaths and hospital readmissions were similar to those for inpatient treatment, but there were more line-related complications. Patient satisfaction was high, with advantages seen in being able to resume daily activities and having greater freedom and control. However, most professionals perceived challenges in providing OPAT. CONCLUSIONS There were no systematic differences related to the impact of OPAT on treatment duration or adverse events. However, evidence of its clinical benefit compared with traditional inpatient treatment is lacking, primarily due to the dearth of good quality comparative studies. There was high patient satisfaction with OPAT use but the few studies considering practitioner acceptability highlighted organisational and logistic barriers to its delivery.
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Affiliation(s)
- E D Mitchell
- Centre for Health Services Research, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | - C Czoski Murray
- Centre for Health Services Research, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | - D Meads
- Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | - J Minton
- Department of Infection and Travel Medicine, Leeds Teaching Hospitals NHS Trust, St James's Hospital, Leeds, UK
| | - J Wright
- Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | - M Twiddy
- Centre for Health Services Research, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
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Oral Parenteral Antimicrobial Therapy Administration in a Homeless Population. JOURNAL OF INFUSION NURSING 2017; 39:81-5. [PMID: 26934162 DOI: 10.1097/nan.0000000000000165] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to treat serious infections. Patients who identify themselves as homeless may receive OPAT less often, and little is known about their treatment outcomes. The purpose of this study was to describe challenges, treatment completion rates, and cost savings of OPAT in homeless patients discharged from a public safety-net hospital.
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Minton J, Murray CC, Meads D, Hess S, Vargas-Palacios A, Mitchell E, Wright J, Hulme C, Raynor DK, Gregson A, Stanley P, McLintock K, Vincent R, Twiddy M. The Community IntraVenous Antibiotic Study (CIVAS): a mixed-methods evaluation of patient preferences for and cost-effectiveness of different service models for delivering outpatient parenteral antimicrobial therapy. HEALTH SERVICES AND DELIVERY RESEARCH 2017. [DOI: 10.3310/hsdr05060] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
BackgroundOutpatient parenteral antimicrobial therapy (OPAT) is widely used in most developed countries, providing considerable opportunities for improved cost savings. However, it is implemented only partially in the UK, using a variety of service models.ObjectivesThe aims of this research were to (1) establish the extent of OPAT service models in England and identify their development; (2) evaluate patients’ preferences for different OPAT service delivery models; (3) assess the cost-effectiveness of different OPAT service delivery models; and (4) convene a consensus panel to consider our evidence and make recommendations.MethodsThis mixed-methods study included seven centres providing OPAT using four main service models: (1) hospital outpatient (HO) attendance; (2) specialist nurse (SN) visiting at home; (3) general nurse (GN) visiting at home; and (4) self-administration (SA) or carer administration. Health-care providers were surveyed and interviewed to explore the implementation of OPAT services in England. OPAT patients were interviewed to determine key service attributes to develop a discrete choice experiment (DCE). This was used to perform a quantitative analysis of their preferences and attitudes. Anonymised OPAT case data were used to model cost-effectiveness with both Markov and simulation modelling methods. An expert panel reviewed the evidence and made recommendations for future service provision and further research.ResultsThe systematic review revealed limited robust literature but suggested that HO is least effective and SN is most effective. Qualitative study participants felt that different models of care were suited to different types of patient and they also identified key service attributes. The DCE indicated that type of service was the most important factor, with SN being strongly preferred to HO and SA. Preferences were influenced by attitudes to health care. The results from both Markov and simulation models suggest that a SN model is the optimal service for short treatment courses (up to 7 days). Net monetary benefit (NMB) values for HO, GN and SN services were £2493, £2547 and £2655, respectively. For longer treatment, SA appears to be optimal, although SNs provide slightly higher benefits at increased cost. NMB values for HO, GN, SN and SA services were £8240, £9550, £10,388 and £10,644, respectively. The simulation model provided useful information for planning OPAT services. The expert panel requested more guidance for service providers and commissioners. Overall, they agreed that mixed service models were preferable.LimitationsRecruitment to the qualitative study was suboptimal in the very elderly and ethnic minorities, so the preferences of patients from these groups might not be represented. The study recruited from Yorkshire, so the findings may not be applicable nationally.ConclusionsThe quantitative preference analysis and economic modelling favoured a SN model, although there are differences between sociodemographic groups. SA provides cost savings for long-term treatment but is not appropriate for all.Future workFurther research is necessary to replicate our results in other regions and populations and to evaluate mixed service models. The simulation modelling and DCE methods used here may be applicable in other health-care settings.FundingThe National Institute for Health Research Health Service and Delivery Research programme.
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Affiliation(s)
- Jane Minton
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | | | - David Meads
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | - Stephane Hess
- Institute of Transport Studies, University of Leeds, Leeds, UK
| | | | | | - Judy Wright
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | - Claire Hulme
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | | | | | - Philip Stanley
- Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
| | - Kate McLintock
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | | | - Maureen Twiddy
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
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Chung EK, Beeler CB, Muloma EW, Osterholzer D, Damer KM, Erdman SM. Development and implementation of a pharmacist-managed outpatient parenteral antimicrobial therapy program. Am J Health Syst Pharm 2016; 73:e24-33. [PMID: 26683676 DOI: 10.2146/ajhp150201] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
PURPOSE The development and implementation of a pharmacist-managed outpatient parenteral antimicrobial therapy (OPAT) program in a county teaching hospital are described. SUMMARY A pharmacist-managed OPAT program was developed and implemented at a county teaching hospital to provide consistent evaluation, approval, and monitoring of patients requiring OPAT for the treatment of infection. The developmental and implementation stages of the OPAT program included (1) a needs assessment, (2) the identification of resources necessary for program operation, (3) delineation of general OPAT program operations and activities of individual OPAT clinicians, (4) the development of patient selection criteria, including a plan of care algorithm, and (5) acquisition of administrative support to approve the program. In this program, the OPAT pharmacist plays an integral role in the management and oversight of OPAT patients, working under a collaborative agreement with infectious diseases physicians. The OPAT pharmacist assists with appropriate patient and regimen selection, confirmation of orders on discharge, assuring that laboratory tests for safety surveillance are performed and evaluated, performing routine monitoring for adverse events and line complications, and assuring the removal of the vascular access device upon the completion of OPAT. CONCLUSION The OPAT program provides structured monitoring, patient follow-up, and led to improvements in patient outcome with minimization of treatment and line-related adverse events.
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Affiliation(s)
- Eun Kyoung Chung
- Eun Kyoung Chung, Pharm.D., Ph.D., is Assistant Professor, Clinical Pharmacy/Pharmacotherapy, Department of Pharmacy, Kyung Hee University College of Pharmacy, Seoul, South Korea; at the time of writing she was a graduate student, Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafeyette, IN. Cole B. Beeler, M.D., is Infectious Diseases Fellow, Indiana University School of Medicine, Indianapolis; at the time of writing he was Chief Internal Medical Resident, Eskenazi Health (formerly Wishard Health Services), Indianapolis. Eva W. Muloma, M.D., is Infectious Diseases Physician, Indiana University Medical Group, and Co-Director, Outpatient Parenteral Antimicrobial Therapy (OPAT) Program, Eskenazi Health. Danielle Osterholzer, M.D., is Infectious Diseases Faculty, Hurley Medical Center, Flint, MI; at the time of writing she was Assistant Clinical Professor of Medicine and Pediatrics, Division of Infectious Diseases, Indiana University School of Medicine, and Section Chief of Infectious Diseases, Eskenazi Health. Kendra M. Damer, Pharm.D., is Associate Professor, Department of Pharmacy Practice, Butler University College of Pharmacy and Health Sciences, Indianapolis; at the time of writing she was Assistant Professor of Pharmacy Practice, Butler University College of Pharmacy and Health Sciences, and Infectious Diseases Clinical Pharmacy Specialist, Eskenazi Health. Sharon M. Erdman, Pharm.D., is Clinical Professor, Department of Pharmacy Practice, Purdue University College of Pharmacy, and Infectious Diseases Clinical Pharmacist and Co-Director, OPAT Program, Eskenazi Health
| | - Cole B Beeler
- Eun Kyoung Chung, Pharm.D., Ph.D., is Assistant Professor, Clinical Pharmacy/Pharmacotherapy, Department of Pharmacy, Kyung Hee University College of Pharmacy, Seoul, South Korea; at the time of writing she was a graduate student, Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafeyette, IN. Cole B. Beeler, M.D., is Infectious Diseases Fellow, Indiana University School of Medicine, Indianapolis; at the time of writing he was Chief Internal Medical Resident, Eskenazi Health (formerly Wishard Health Services), Indianapolis. Eva W. Muloma, M.D., is Infectious Diseases Physician, Indiana University Medical Group, and Co-Director, Outpatient Parenteral Antimicrobial Therapy (OPAT) Program, Eskenazi Health. Danielle Osterholzer, M.D., is Infectious Diseases Faculty, Hurley Medical Center, Flint, MI; at the time of writing she was Assistant Clinical Professor of Medicine and Pediatrics, Division of Infectious Diseases, Indiana University School of Medicine, and Section Chief of Infectious Diseases, Eskenazi Health. Kendra M. Damer, Pharm.D., is Associate Professor, Department of Pharmacy Practice, Butler University College of Pharmacy and Health Sciences, Indianapolis; at the time of writing she was Assistant Professor of Pharmacy Practice, Butler University College of Pharmacy and Health Sciences, and Infectious Diseases Clinical Pharmacy Specialist, Eskenazi Health. Sharon M. Erdman, Pharm.D., is Clinical Professor, Department of Pharmacy Practice, Purdue University College of Pharmacy, and Infectious Diseases Clinical Pharmacist and Co-Director, OPAT Program, Eskenazi Health
| | - Eva W Muloma
- Eun Kyoung Chung, Pharm.D., Ph.D., is Assistant Professor, Clinical Pharmacy/Pharmacotherapy, Department of Pharmacy, Kyung Hee University College of Pharmacy, Seoul, South Korea; at the time of writing she was a graduate student, Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafeyette, IN. Cole B. Beeler, M.D., is Infectious Diseases Fellow, Indiana University School of Medicine, Indianapolis; at the time of writing he was Chief Internal Medical Resident, Eskenazi Health (formerly Wishard Health Services), Indianapolis. Eva W. Muloma, M.D., is Infectious Diseases Physician, Indiana University Medical Group, and Co-Director, Outpatient Parenteral Antimicrobial Therapy (OPAT) Program, Eskenazi Health. Danielle Osterholzer, M.D., is Infectious Diseases Faculty, Hurley Medical Center, Flint, MI; at the time of writing she was Assistant Clinical Professor of Medicine and Pediatrics, Division of Infectious Diseases, Indiana University School of Medicine, and Section Chief of Infectious Diseases, Eskenazi Health. Kendra M. Damer, Pharm.D., is Associate Professor, Department of Pharmacy Practice, Butler University College of Pharmacy and Health Sciences, Indianapolis; at the time of writing she was Assistant Professor of Pharmacy Practice, Butler University College of Pharmacy and Health Sciences, and Infectious Diseases Clinical Pharmacy Specialist, Eskenazi Health. Sharon M. Erdman, Pharm.D., is Clinical Professor, Department of Pharmacy Practice, Purdue University College of Pharmacy, and Infectious Diseases Clinical Pharmacist and Co-Director, OPAT Program, Eskenazi Health
| | - Danielle Osterholzer
- Eun Kyoung Chung, Pharm.D., Ph.D., is Assistant Professor, Clinical Pharmacy/Pharmacotherapy, Department of Pharmacy, Kyung Hee University College of Pharmacy, Seoul, South Korea; at the time of writing she was a graduate student, Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafeyette, IN. Cole B. Beeler, M.D., is Infectious Diseases Fellow, Indiana University School of Medicine, Indianapolis; at the time of writing he was Chief Internal Medical Resident, Eskenazi Health (formerly Wishard Health Services), Indianapolis. Eva W. Muloma, M.D., is Infectious Diseases Physician, Indiana University Medical Group, and Co-Director, Outpatient Parenteral Antimicrobial Therapy (OPAT) Program, Eskenazi Health. Danielle Osterholzer, M.D., is Infectious Diseases Faculty, Hurley Medical Center, Flint, MI; at the time of writing she was Assistant Clinical Professor of Medicine and Pediatrics, Division of Infectious Diseases, Indiana University School of Medicine, and Section Chief of Infectious Diseases, Eskenazi Health. Kendra M. Damer, Pharm.D., is Associate Professor, Department of Pharmacy Practice, Butler University College of Pharmacy and Health Sciences, Indianapolis; at the time of writing she was Assistant Professor of Pharmacy Practice, Butler University College of Pharmacy and Health Sciences, and Infectious Diseases Clinical Pharmacy Specialist, Eskenazi Health. Sharon M. Erdman, Pharm.D., is Clinical Professor, Department of Pharmacy Practice, Purdue University College of Pharmacy, and Infectious Diseases Clinical Pharmacist and Co-Director, OPAT Program, Eskenazi Health
| | - Kendra M Damer
- Eun Kyoung Chung, Pharm.D., Ph.D., is Assistant Professor, Clinical Pharmacy/Pharmacotherapy, Department of Pharmacy, Kyung Hee University College of Pharmacy, Seoul, South Korea; at the time of writing she was a graduate student, Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafeyette, IN. Cole B. Beeler, M.D., is Infectious Diseases Fellow, Indiana University School of Medicine, Indianapolis; at the time of writing he was Chief Internal Medical Resident, Eskenazi Health (formerly Wishard Health Services), Indianapolis. Eva W. Muloma, M.D., is Infectious Diseases Physician, Indiana University Medical Group, and Co-Director, Outpatient Parenteral Antimicrobial Therapy (OPAT) Program, Eskenazi Health. Danielle Osterholzer, M.D., is Infectious Diseases Faculty, Hurley Medical Center, Flint, MI; at the time of writing she was Assistant Clinical Professor of Medicine and Pediatrics, Division of Infectious Diseases, Indiana University School of Medicine, and Section Chief of Infectious Diseases, Eskenazi Health. Kendra M. Damer, Pharm.D., is Associate Professor, Department of Pharmacy Practice, Butler University College of Pharmacy and Health Sciences, Indianapolis; at the time of writing she was Assistant Professor of Pharmacy Practice, Butler University College of Pharmacy and Health Sciences, and Infectious Diseases Clinical Pharmacy Specialist, Eskenazi Health. Sharon M. Erdman, Pharm.D., is Clinical Professor, Department of Pharmacy Practice, Purdue University College of Pharmacy, and Infectious Diseases Clinical Pharmacist and Co-Director, OPAT Program, Eskenazi Health
| | - Sharon M Erdman
- Eun Kyoung Chung, Pharm.D., Ph.D., is Assistant Professor, Clinical Pharmacy/Pharmacotherapy, Department of Pharmacy, Kyung Hee University College of Pharmacy, Seoul, South Korea; at the time of writing she was a graduate student, Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafeyette, IN. Cole B. Beeler, M.D., is Infectious Diseases Fellow, Indiana University School of Medicine, Indianapolis; at the time of writing he was Chief Internal Medical Resident, Eskenazi Health (formerly Wishard Health Services), Indianapolis. Eva W. Muloma, M.D., is Infectious Diseases Physician, Indiana University Medical Group, and Co-Director, Outpatient Parenteral Antimicrobial Therapy (OPAT) Program, Eskenazi Health. Danielle Osterholzer, M.D., is Infectious Diseases Faculty, Hurley Medical Center, Flint, MI; at the time of writing she was Assistant Clinical Professor of Medicine and Pediatrics, Division of Infectious Diseases, Indiana University School of Medicine, and Section Chief of Infectious Diseases, Eskenazi Health. Kendra M. Damer, Pharm.D., is Associate Professor, Department of Pharmacy Practice, Butler University College of Pharmacy and Health Sciences, Indianapolis; at the time of writing she was Assistant Professor of Pharmacy Practice, Butler University College of Pharmacy and Health Sciences, and Infectious Diseases Clinical Pharmacy Specialist, Eskenazi Health. Sharon M. Erdman, Pharm.D., is Clinical Professor, Department of Pharmacy Practice, Purdue University College of Pharmacy, and Infectious Diseases Clinical Pharmacist and Co-Director, OPAT Program, Eskenazi Health.
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Mujal A, Sola J, Hernandez M, Villarino MA, Baylina M, Tajan J, Oristrell J. Safety and effectiveness of outpatient parenteral antimicrobial therapy in older people. J Antimicrob Chemother 2016; 71:1402-7. [DOI: 10.1093/jac/dkv478] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Accepted: 12/14/2015] [Indexed: 12/23/2022] Open
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Outpatient parenteral antimicrobial therapy. CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY 2014; 24:9-11. [PMID: 24421785 DOI: 10.1155/2013/205910] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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MacKenzie M, Rae N, Nathwani D. Outcomes from global adult outpatient parenteral antimicrobial therapy programmes: A review of the last decade. Int J Antimicrob Agents 2014; 43:7-16. [DOI: 10.1016/j.ijantimicag.2013.09.006] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Accepted: 09/21/2013] [Indexed: 12/16/2022]
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