Making a case for outpatient parenteral antimicrobial therapy (OPAT).

In the wake of the COVID-19 pandemic, and its negative impact on both acute and elective care and decline in available inpatient resources, there is an imperative to maximize safe and effective alternatives to inpatient hospital care. Properly governed outpatient parenteral antimicrobial therapy (OPAT) services embed the principles of antimicrobial stewardship (AMS) (including use of early oral therapy) and support admission avoidance and early discharge for a growing range of patient groups with complex infections through well-organized multidisciplinary team working. Expansion of OPAT aligns with the UK's national strategy to deliver care closer to home and cost-effectively maximize use of inpatient resources. OPAT serves as an exemplar to other ambulatory services and presents opportunities for developing and assuring AMS strategies within the rapidly developing hospital-at-home and virtual ward environments.

Healthcare-associated infections among neonates and children in Pakistan: findings and the implications from a point prevalence survey.

BACKGROUND: Healthcare-associated infections (HAIs) increase morbidity, mortality and costs. The overall prevalence of HAIs is greater in low- and middle-income countries due to poor resources and infrastructure, with the incidence of HAIs greater among neonates and children. There is a need to understand the current situation in Pakistan including key drivers to improve future care. METHODS: Point prevalence survey (PPS) of HAIs in the children's wards of 19 public sector secondary- and tertiary-care hospitals of Pakistan and associated key drivers. RESULTS: A total of 1147 children were included in the PPS. 35.7% were neonates with 32.8% aged >1-5 years. 35.2% were admitted to the intensive care units (ICUs). Peripheral, central venous and urinary catheters were present in 48%, 2.9% and 5.6% of the patients, respectively. A total of 161 HAIs from various pathogens were observed in 153 cases, giving a prevalence of 13.3%. The majority of HAIs were caused by Staphylococcus aureus (31.7%) followed by Klebsiella pneumoniae (22.9%) and Escherichia coli (17.4%). Bloodstream infections were identified in 42 cases followed by lower-respiratory-tract infections in 35. Increased length of hospital stays and being admitted to the ICU, 'rapidly fatal' patients under the McCabe and Jackson criteria, central and peripheral catheterization, and invasive mechanical ventilation were, associated with higher HAIs (P<0.001). 99.7% of HAI patients fully recovered and were discharged from the hospital. CONCLUSION: There is a high prevalence of HAIs among neonates and children admitted to health facilities in Pakistan. Infection prevention and control measures should be implemented to help prevent future HAIs.

Factors influencing the stewardship activities of Antimicrobial Management Teams: a national cross-sectional survey.

BACKGROUND: The link between inappropriate antibiotic prescribing and the global threat of antimicrobial resistance is well documented. International strategies recommend antimicrobial stewardship (AMS) programmes, with improvement interventions to safeguard antibiotics. AIM: This study sought to systematically evaluate the impact of multi-professional Antimicrobial Management Team (AMT) staff resource availability on stewardship activities. METHODS: We conducted an on-line, cross-sectional survey of AMTs in each regional Health Board and the national specialist hospital in Scotland (N = 15). Responses were analysed descriptively, exploring observed relationships between variables to identify patterns. FINDINGS: Results highlighted apparent variation in the levels of AMT resource availability across Scotland, not directly influenced by Health Board size, with some larger Health Boards having proportionately poorer AMT resource allocation. However, the range and frequency of activities to support AMS was not directly linked to either Health Board size or staff resource allocation, indicating a more complex inter-relationship between factors. CONCLUSIONS: There is apparent inequity in staff resource available for AMTs across Scotland, with significantly lower resource allocation in comparison with recommendations from other international studies. However, considering these survey findings with our earlier qualitative research indicates that leadership style and team member enthusiasm may be as, if not more, influential than resource availability on the scope of AMT activities. These findings have international relevance for hospital service managers considering the recruitment, training and ongoing support of AMTs, in order to maximize impact from a limited resource.

Outpatient parenteral antimicrobial therapy (OPAT) versus inpatient care in the UK: a health economic assessment for six key diagnoses.

OBJECTIVES: To compare costs associated with different models of outpatient parenteral antimicrobial therapy (OPAT) delivery with costs of inpatient (IP) care across key infection groups managed via OPAT in the UK. DESIGN: A cost-minimisation design was used due to evidence of similarities in patient and treatment outcomes between OPAT and IP care. A bottom-up approach was undertaken for the evaluation of OPAT associated costs. The British Society of Antimicrobial Chemotherapy National Outcomes Registry System was used to determine key infection diagnoses, mean duration of treatment and most frequent antibiotics used. SETTING: Several OPAT delivery settings were considered and compared with IP care. INTERVENTIONS: OPAT models considered were OP clinic model, nurse home visits, self (or carer)-administration by a bolus intravenous, self-administration by a commercially prefilled elastomeric device, continuous intravenous infusion of piperacillin with tazobactam or flucloxacillin with elastomeric device as OP once daily and, specifically for bone and joint and diabetic foot infections, complex outpatient oral antibiotic therapies. RESULTS: Base case and a range of scenario results showed all evaluated OPAT service delivery models to be less costly than IP stay of equivalent duration. The extent of savings varied by OPAT healthcare delivery models. Estimated OPAT costs as a proportion of IP costs were estimated at 0.23-0.53 (skin and soft-tissue infections), 0.34-0.46 (complex urinary tract infections), 0.23-0.51 (orthopaedic infections), 0.24-0.42 (diabetic foot infections) 0.40-0.56 (exacerbations of bronchiectasis) and 0.25-0.42 (intra-abdominal infections). Partial or full complex oral antibiotic therapies in orthopaedic or diabetic foot infections costs were estimated to be 0.13-0.26 of IP costs. Main OPAT costs were associated with staff time and antimicrobial medications. CONCLUSIONS: OPAT is a cost-effective use of National Health Service resources for the treatment of a range of infections in the UK in patients who can be safely managed in a non-IP setting.

From 'OPAT' to 'COpAT': implications of the OVIVA study for ambulatory management of bone and joint infection.

Bone and joint infection contributes significantly to clinical activity within outpatient parenteral antimicrobial therapy (OPAT) services. The OVIVA (oral versus intravenous antibiotics for bone and joint infection) randomized study has challenged the practice of prolonged intravenous therapy, because non-inferiority of oral antibiotic therapy was demonstrated, thereby implying that early transition to oral therapy is an appropriate alternative to prolonged intravenous therapy. We examine the caveats to the study and discuss the implications for OPAT practice, highlighting the importance of careful oral antibiotic selection with attention to bioavailability, bone penetration, drug interactions, compliance and toxicity monitoring. We emphasize that ambulatory antibiotic therapy (whether intravenous or oral) in this patient group requires expert multidisciplinary management, monitoring and follow-up, and ideally should be undertaken within existing OPAT or, more accurately, complex outpatient antibiotic therapy (COpAT) services.

Paradoxical upgrading reaction in extra-pulmonary tuberculosis: association with vitamin D therapy.

SETTING: Glasgow, Scotland, UK. BACKGROUND: Paradoxical reactions in tuberculosis (TB) are a notable example of our incomplete understanding of host-pathogen interactions during anti-tuberculosis treatment. OBJECTIVES: To determine risk factors for a TB paradoxical reaction, and specifically to assess for an independent association with vitamin D use. DESIGN: Consecutive human immunodeficiency virus (HIV) negative adult patients treated for extra-pulmonary TB were identified from an Extended Surveillance of Mycobacterial Infections database. In our setting, vitamin D was variably prescribed for newly diagnosed TB patients. A previously published definition of paradoxical TB reaction was retrospectively applied to, and data on all previously described risk factors were extracted from, centralised electronic patient records. The association with vitamin D use was assessed using multivariate logistic regression. RESULTS: Of the 249 patients included, most had TB adenopathy; 222/249 had microbiologically and/or histologically confirmed TB. Vitamin D was prescribed for 57/249 (23%) patients; 37/249 (15%) were classified as having paradoxical reactions. Younger age, acid-fast bacilli-positive invasive samples, multiple disease sites, lower lymphocyte count and vitamin D use were found to be independent risk factors. CONCLUSION: We speculate that vitamin D-mediated signalling of pro-inflammatory innate immune cells, along with high antigenic load, may mediate paradoxical reactions in anti-tuberculosis treatment.

Restrictive antibiotic stewardship associated with reduced hospital mortality in gram-negative infection.

INTRODUCTION: : Antimicrobial stewardship has an important role in the control of Clostridium difficile infection (CDI) and antibiotic resistance. An important component of UK stewardship interventions is the restriction of broad-spectrum beta-lactam antibiotics and promotion of agents associated with a lower risk of CDI such as gentamicin. While the introduction of restrictive antibiotic guidance has been associated with improvements in CDI and antimicrobial resistance, evidence of the effect on outcome following severe infection is lacking. METHODS: : In 2008, Glasgow hospitals introduced a restrictive antibiotic guideline. A retrospective before/after study assessed outcome following Gram-negative bacteraemia in the 2-year period around implementation. RESULTS: : Introduction of restrictive antibiotic guidelines was associated with a reduction in utilization of ceftriaxone and co-amoxiclav and an increase in amoxicillin and gentamicin. Approximately 1593 episodes of bacteremia were included in the study. The mortality over 1-year following Gram-negative bacteraemia was lower in the period following guideline implementation (RR 0.852, P = 0.045). There was no evidence of a difference in secondary outcomes including ITU admission, length of stay, readmission, recurrence of bacteraemia and need for renal replacement therapy. There was a fall in CDI (RR 0.571, P = 0.014) and a reduction in bacterial resistance to ceftriaxone and co-amoxiclav but no evidence of an increase in gentamicin resistance after guideline implementation. CONCLUSION: : Restrictive antibiotic guidelines were associated with a reduction in CDI and bacterial resistance but no evidence of adverse outcomes following Gram-negative bacteraemia. There was a small reduction in one year mortality.

Daptomycin for the treatment of osteomyelitis and orthopaedic device infections: real-world clinical experience from a European registry.

Osteomyelitis is a serious infection predominantly caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Orthopaedic device-related infections are complex and require a careful combination of surgical intervention and antimicrobial therapy. Daptomycin, a cyclic lipopeptide, effectively penetrates soft tissue and bone and demonstrates rapid concentration-dependent bactericidal activity against Gram-positive pathogens. This retrospective, non-interventional study evaluated clinical outcomes in patients with osteomyelitis or orthopaedic device infections treated with daptomycin from the European Cubicin® Outcomes Registry and Experience (EU-CORE(SM)) study. Patients were treated between January 2006 and April 2012, with follow-up to 2014. Clinical outcomes were assessed as success (cured or improved), failure or non-evaluable. Of 6,075 patients enrolled, 638 (median age, 63.5 years) had primary infections of osteomyelitis or orthopaedic device infections, 224 had non-prosthetic osteomyelitis, 208 had osteomyelitis related to a permanent or temporary prosthetic device, and 206 had orthopaedic device infections. The most commonly isolated pathogen was S. aureus (214 [49.1 %]; 24.8 % were MRSA). Overall, 455 (71.3 %) patients had received previous antibiotic therapy. Patients underwent surgical interventions, including tissue (225 [35.3 %]) and bone (196 [30.7 %]) debridement, as part of their treatment. Clinical success rates were 82.7 % and 81.7 % in S. aureus and coagulase-negative staphylococcal infections. Adverse events (AEs) and serious AEs assessed as possibly related to daptomycin were observed in 6.7 % and 1.9 % of patients, respectively. Daptomycin was discontinued by 5.5 % of patients due to AEs and 10 (1.6 %) deaths were reported. In conclusion, daptomycin was effective and safe in patients with osteomyelitis or orthopaedic device infections.

How is income generated by outpatient parenteral antibiotic treatment (OPAT) in the UK? Analysis of payment tariffs for cellulitis.

OBJECTIVES: We determined the available mechanisms to generate income from outpatient parenteral antimicrobial therapy (OPAT) in the UK and calculated the revenue generated from treatment of an episode of cellulitis. METHODS: Revenue was calculated for patients receiving treatment for cellulitis as an inpatient and for patients receiving OPAT by a series of different payment pathways. Selected established OPAT services in Northern Ireland, Scotland and Wales, where Payment-by-Results (PbR) does not operate, were contacted to determine individual national funding arrangements. RESULTS: In England, a traditional inpatient episode for uncomplicated cellulitis requiring 7 days of treatment generated £1361 of revenue, while OPAT generated revenue ranging from £773 to £2084 for the same length of treatment depending on the payment pathway used. Treatment using OPAT to avoid admission entirely generated £2084, inpatient admission followed by transfer to a virtual OPAT ward at day 2 generated £1361 and inpatient admission followed by discharge from hospital to OPAT at day 2 generated £773. In Northern Ireland, Scotland and Wales block contracts were used and no income was calculable for an individual episode of cellulitis. CONCLUSIONS: No single funding mechanism supports OPAT across the UK. In England, revenue generated by OPAT providers from treatment of cellulitis varied with the OPAT payment pathway used, but equalled or exceeded the income generated from equivalent inpatient care. Cost savings for OPAT and reuse of released inpatient beds will increase revenue further. A single OPAT tariff is proposed.

Outpatient parenteral antimicrobial therapy and antimicrobial stewardship: challenges and checklists.

Outpatient parenteral antimicrobial therapy (OPAT) has become, for many countries, an established form of healthcare delivery. At the same time, there have been calls to ensure the prudent use of the existing antimicrobial armamentarium. For OPAT, this presents a dilemma. On one hand, stewardship principles look for the most effective agent with minimal collateral effects. In OPAT, whilst the aims of the service are similar, convenience of dosing to optimize early hospital discharge or admission avoidance may take precedence over an agent's spectrum of activity. This brief article aims to highlight the importance and explore the challenges of antimicrobial stewardship in the context of OPAT. Within the UK, the safe and effective use of antimicrobials is modelled around the IDSA/Society for Healthcare Epidemiology of America stewardship practice guidelines with local customization where appropriate. Current UK stewardship practice principles were compared with published good practice recommendations for OPAT to identify how OPAT could support the broader antimicrobial stewardship agenda. It is essential that antimicrobial stewardship teams should understand the challenges faced in the non-inpatient setting and the potential benefits/lower risks associated with avoided admission or shortened hospital stay in this population. Within its limitations, OPAT should practise stewardship principles, including optimization of intravenous to oral switch and the reporting of outcomes, healthcare-associated infections and re-admission rates. OPAT should report to the antimicrobial stewardship team. Ideally the OPAT team should be formally represented within the stewardship framework. A checklist has been proposed to aid OPAT services in ensuring they meet their stewardship agenda.

Economic evaluation of treatment for MRSA complicated skin and soft tissue infections in Glasgow hospitals.

In the UK, methicillin-resistant Staphylococcus aureus (MRSA)-associated skin and soft tissue infections (SSTIs) are predominantly managed in the hospital using intravenous (IV) glycopeptides. We set out to explore the potential for and relative healthcare costs of earlier hospital discharge through switch to oral antibiotic therapy (linezolid or rifampicin and doxycycline) or continuation of IV therapy (teicoplanin) via an outpatient parenteral antimicrobial therapy (OPAT) service. Over 16 months, 173 patients were retrospectively identified with MRSA SSTI, of whom 82.8 % were treated with IV therapy. Thirty-seven patients were potentially suitable for earlier discharge with outpatient therapy. The model assumed 3 days of inpatient management and a maximum of 14 days of outpatient therapy. For the status quo, where patients received only inpatient care with IV therapy, hospital costs were calculated at £12,316 per patient, with 97 % of costs accounted for by direct bed day costs. The mean total cost savings achievable through OPAT or oral therapy was estimated to be £6,136 and £6,159 per patient treated, respectively. A significant proportion of patients with MRSA SSTI may be suitable for outpatient management with either oral therapy or via OPAT, with the potential for significant reduction in healthcare costs.

Risk of venous thromboembolism in patients treated for bacterial infection in the community with outpatient parenteral antimicrobial therapy.

BACKGROUND: It is recommended that venous thromboembolism (VTE) prophylaxis be considered for patients receiving outpatient parenteral antimicrobial therapy (OPAT), but there is no published data to quantify VTE risk in this patient group. AIM AND METHOD: The aim of this retrospective cohort study was to establish VTE incidence in patients managed through an OPAT service and assess utility of a common VTE prediction score normally used for inpatients. Consecutive episodes of OPAT between May 2009 and May 2012 were included. Patients on long-term anti-coagulants, those with an established indication for extended, outpatient VTE prophylaxis (i.e. patients referred to OPAT following hip or knee arthroplasty) were excluded. The Padua VTE Prediction Score was retrospectively applied to the cohort. The primary outcome was incidence of symptomatic VTE during or up to 90 days after completion of OPAT treatment. RESULTS: There were 780 included patient episodes; 105 (13.5%) patients had a Padua VTE risk score >3; no patients received pharmacological VTE prophylaxis during OPAT treatment. During or up to 90 days following OPAT, two proximal lower limb DVTs were diagnosed, giving VTE incidence of 2/780 (0.26%, 95% CI: 0.03-0.92%), and there were eight deaths of which none were suspected to be related to VTE. There was one intracranial haemorrhage associated death. CONCLUSION: This retrospective cohort study found a low incidence of VTE in OPAT patients, and does not support routine application of inpatient VTE prophylaxis algorithms to patients treated for infection in the community.

Missed opportunities for HIV diagnosis: a three-year audit in the West of Scotland.

BACKGROUND: National specialty guidelines for HIV testing aim to increase diagnosis and reduce late presentation. An audit of new HIV diagnoses in Glasgow was performed to assess local performance against these guidelines and estimate the proportion of patients presenting who had previous missed opportunities for diagnosis. METHODS: A retrospective case note review of 339 patients diagnosed from September 2008 to September 2011 was performed. Documented past medical history was assessed for HIV clinical indicator conditions prior to HIV diagnosis and prior review by medical services. RESULTS: Ninety (26%) individuals had at least one documented clinical indicator condition prior to HIV diagnosis, of whom 80 had prior contact with at least one speciality. This group also had a lower mean nadir CD4 count (258 cells/cmm versus 393 cells/cmm, p = <0.005) and were more likely to be severely immunocompromised at diagnosis, with a CD4 count below 50 cells/cmm (31% versus 9%, p = <0.005). AIDS-defining illnesses were also more common (31% versus 8%, p ≤ 0.005) as was HIV-related mortality (p ≤ 0.005). CONCLUSION: Additional support and training are required to increase adherence to HIV-testing guidelines within primary and secondary care in order to prevent ongoing late presentation with both individual clinical and public health implications.

Outpatient parenteral antibiotic therapy: principles and practice.

Outpatient parenteral antimicrobial therapy (OPAT) refers to the administration of a parenteral antimicrobial in a non inpatient or ambulatory setting with the explicit aim of facilitating admission avoidance or early discharge. Whilst OPAT has predominantly been the domain of the infection specialist, the internal medicine specialist has a key role in service development and delivery as a component of broader ambulatory care initiatives such as "hospital at home". Main drivers for OPAT are patient welfare, reduction of risk of health care associated infection and cost-effective use of hospital resources. The safe practice of OPAT is dependent on a team approach with careful patient selection and antimicrobial management with programmed and adaptable clinical monitoring and assessment of outcome. Gram-positive infections, including cellulitis, bone and joint infection, bacteraemia and endocarditis are key infections potentially amenable to OPAT whilst resistant Gram-negative infections are of increasing importance. Ceftriaxone, teicoplanin, daptomycin and ertapenem lend themselves well to OPAT due to daily (or less frequent) bolus administration, although any antimicrobial may be administered if the patient is trained to administer and/or an appropriate infusion device is employed. Clinical experience from NHS Greater Glasgow and Clyde is presented to illustrate the key principles of OPAT as practised in the UK. Increasingly complex patients with multiple medical needs, the relative scarcity of inpatient resources and the broader challenge of ambulatory care and "hospital at home" will ensure the internal medicine specialist will have a key role in the future development of OPAT.

Management of suspected Lyme borreliosis: experience from an outpatient parenteral antibiotic therapy service.

OBJECTIVES: Lyme borreliosis (LB) is the most common human tick-borne infection in Europe and the USA. In this study we set out to analyse the outcome of patients treated for Lyme disease via outpatient parenteral antibiotic therapy (OPAT) and the appropriateness of this treatment using current guidelines. METHODS: This was a retrospective review of all patients with suspected LB managed via OPAT in Glasgow in 2000-11. RESULTS: Of 72 patients treated for suspected LB, 35 patients (49%) were treated in accordance with guidelines and 36 (50%) were treated with no specific guidelines. A definite improvement was seen in 20 patients (28%). Adverse reactions were documented in 29 (40%) patients with neutropenia, and mild liver function derangement was most commonly observed. CONCLUSION: These results show the complexity of translating well-substantiated regimens from clinical trials to actual clinical practice. OPAT was an effective way of administering parenteral therapy for Lyme disease but should not be undertaken lightly due to the rate of adverse events and low rates of success in certain patient groups seen in this study. In view of this, stricter criteria for inclusion to OPAT in line with published guidance should be applied to minimize patient harm and optimize success.

Q fever in military and paramilitary personnel in conflict zones: case report and review.

We present the case of a 44-year-old civilian security officer medically evacuated from Iraq with acalculous cholecystitis and Guillain-Barré syndrome and subsequently found to have acute Q fever. The presenting features of Q fever in military and related personnel deployed to Iraq and Afghanistan are reviewed and the use of PCR in early diagnosis of Q fever is discussed. The atypical presentation in this case encourages clinicians to have a low threshold for considering Q fever as part of the differential diagnosis in soldiers and related personnel returning from these areas of high endemicity.

Self-administration of outpatient parenteral antibiotic therapy and risk of catheter-related adverse events: a retrospective cohort study.

Despite increasing use, limited data has been published comparing safety of different outpatient parenteral antimicrobial therapy (OPAT) models. Potential risks of self-administration at home include venous access device infection and other line complications. This study aims to investigate rates and predictors of intravenous access device complications in a large OPAT cohort. This is a retrospective cohort study of all uses of midlines, peripherally inserted central catheters (PICCs) and tunnelled central venous catheters (TCVCs) with univariate and multivariate (logistic regression) analysis of factors associated with line infections (LIs) and with other line events (OLEs). On univariate analysis, line infections were associated with length of line use, female sex and TCVC lines (compared to midlines). Patients self-administering OPAT in the home had a non-significantly lower rate of LIs. On multivariate analysis only duration of line use was a significant predictor of LIs-OR 1.012 (95%CI 1.001-1.023). For OLEs, multivariate analysis suggested that only line type and use of flucloxacillin were significant explanatory variables. In this cohort, there is no evidence that self-administration of OPAT is associated with higher rates of venous access device complications after controlling for confounding variables.