R.A. Seaton

Faecal transplant for recurrent Clostridium difficile-associated diarrhoea: a UK case series

BACKGROUND Clostridium difficile-associated diarrhoea (CDAD) is an increasingly common and life threatening consequence of modern medical practice. Recurrent disease is seen in up to one-third of patients and there is no consensus on optimal therapy. Restoration of normal colonic flora addresses the underlying pathogenic mechanism in CDAD. METHODS We describe the use of nasogastrically administered faecal transplant in the treatment of 15 patients with recurrent CDAD. Retrospective case note review was used to review the success and safety of therapy. RESULTS Of 15 patients treated using this technique, 11 were cured of CDAD. Two patients required a further course of metronidazole after transplantation and one patient required a second treatment. One patient had recurrence of CDAD 4 weeks after treatment following a course of broad-spectrum antibiotics. No adverse events were noted. CONCLUSION In our experience, this technique is an effective and safe treatment for recurrent CDAD. Faecal transplantation via a nasogastric tube could be considered in patients with refractory relapsing CDAD.

Daptomycin: rationale and role in the management of skin and soft tissue infections

The emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) and glycopeptide tolerance in S. aureus has underlined the importance of the newer anti-MRSA agents, particularly in the management of complicated skin and soft tissue infections (cSSTIs). The novel cyclic lipopeptide antibiotic daptomycin shows marked in vitro cidality against MRSA compared with both vancomycin and linezolid. Although comparative studies in cSSTIs have demonstrated non-inferiority with vancomycin and semi-synthetic penicillins, data from both clinical trials and observational studies suggest in vivo cidality as evidenced by rapid resolution of clinical signs of local inflammation and reduced duration of therapy. Overall success in SSTI post-marketing studies is >90%, and >88% in MRSA-infected patients, with no difference in the outcome observed between those with complicated versus uncomplicated infections. When used at licensed doses (4-6 mg/kg), daptomycin is safe and effective in SSTIs with significant muscle toxicity occurring in only 0.4% to 2.5% of patients. Clinical failure in daptomycin-treated SSTIs is associated with severity of infection (creatinine clearance <30 mL/min, intensive care unit stay and sepsis syndrome). Higher dosing at 6 mg/kg (with increased dosing interval in renal failure) should be considered in such patients as well as those at risk of bacteraemia, osteomyelitis, diabetic foot infection and in situations where there is more rapid drug clearance, such as infections complicating intravenous drug use and thermal burns. Once-daily dosing allows ease of use in both hospital and outpatient settings and may facilitate early discharge or avoided admission in some patient groups with SSTIs. Clinical experience to date suggests potential economic advantages associated with earlier hospital discharge and shorter duration of therapy, although further detailed cost-effectiveness comparisons are required to validate these observations in different healthcare settings.

Outpatient parenteral antibiotic therapy (OPAT) for bone and joint infections: experience from a UK teaching hospital-based service

OBJECTIVES We describe failure rates of 198 patients with bone and joint infection (BJI), including prosthetic joint infection and diabetic foot osteomyelitis, managed through the Glasgow centre for outpatient parenteral antibiotic therapy (OPAT) over a period of 4 years. Outcomes following initial intravenous antimicrobial therapy and a median follow-up time of 60 weeks are described. PATIENTS AND METHODS A prospectively maintained registry of all patients attending OPAT was examined for cases of BJI. Once identified, patient case records were reviewed and data extracted. Diagnosis, demographics, microbiology and treatment were recorded, and case records were examined for evidence of failing initial prescribed OPAT therapy and up to 24 months of follow-up. RESULTS One hundred and ninety-eight cases of BJI were identified. The overall success rate following initial OPAT was 86.4%, with a range from 71.8% success rate for diabetic foot or stump infection (DFI) to 100% for metalwork-related infection. The failure rate over the follow-up period was 29.8%. Factors associated with poor initial outcome included older age, methicillin-resistant Staphylococcus aureus infection and DFI, factors that continued to explain failure up to 24 months in multivariate survival analysis. CONCLUSIONS For the majority of conditions, BJI can be successfully managed through OPAT. Identification of those likely to respond less well, including older patients, those with DFI and those with infections by resistant organisms, may encourage enhanced vigilance and consideration of newer or more aggressive treatments in these subgroups of patients.

Risk factors for failure of outpatient parenteral antibiotic therapy (OPAT) in infective endocarditis

Objectives To identify risk factors for failure of outpatient antibiotic therapy (OPAT) in infective endocarditis (IE). Patients and methods We identified IE cases managed at a single centre over 12 years from a prospectively maintained database. ‘OPAT failure’ was defined as unplanned readmission or antibiotic switch due to adverse drug reaction or antibiotic resistance. We analysed patient and disease-related risk factors for OPAT failure by univariate and multivariate logistic regression. We also retrospectively collected follow-up data on adverse disease outcome (defined as IE-related death or relapse) and performed Kaplan–Meier survival analysis up to 36 months following OPAT. Results We identified 80 episodes of OPAT in IE. Failure occurred in 25/80 episodes (31.3%). On multivariate analysis, cardiac or renal failure [pooled OR 7.39 (95% CI 1.84–29.66), P = 0.005] and teicoplanin therapy [OR 8.69 (95% CI 2.01–37.47), P = 0.004] were independently associated with increased OPAT failure. OPAT failure with teicoplanin occurred despite therapeutic plasma levels. OPAT failure predicted adverse disease outcome up to 36 months (P = 0.016 log-rank test). Conclusions These data caution against selecting patients with endocarditis for OPAT in the presence of cardiac or renal failure and suggest teicoplanin therapy may be associated with suboptimal OPAT outcomes. Alternative regimens to teicoplanin in the OPAT setting should be further investigated.

Penicillium marneffei infection presenting as an immune reconstitution inflammatory syndrome in an HIV patient.

We describe a case of Penicillium marneffei infection acquired in Thailand, manifesting as an immune reconstitution inflammatory syndrome (IRIS) in a Caucasian man with advanced HIV-related immunosuppression (CD4 72 cells/mm3). Initial presentation was consistent with Pneumocystis jirovecii pneumonia, and empirical co-trimoxazole resulted in clinical improvement. One month after initiating antiretroviral therapy (ART), an enlarging scaly lesion on his forehead and erythematous nodules on his face, trunk and limbs developed. P. marneffei was isolated from a skin aspirate. Response to antifungal therapy was complicated by drug interactions but cure was complete after four months of treatment. Few cases of IRIS associated with P. marneffei have been reported.

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.

Hospitalised adult patients with Suspected 2009 H1N1 Infection at Regional Infectious Diseases Units in Scotland – Most had alternative final diagnoses

The misdiagnosis of serious illness during the current flu pandemic has been highlighted in your journal by Payne et al, and others have raised their concern. We have reviewed 110 cases of ‘‘query H1N1’’ presenting to our Infectious Diseases service and have found a variety of alternative diagnoses, some of which required significantly different management. Human pandemic Influenza A (H1N1) virus has spread globally during 2009. On the 25th April the first 2 cases confirmed in Europe were in our region, the West of Scotland, United Kingdom. Subsequently suspected and confirmed cases surged throughout the UK. Information regarding the clinical spectrum and risk factors for severe illness are still emerging. The clinical case definition, indications for hospital admission and therapeutic intervention are continually being refined as more experience in managing these patients is gained. In order to add to the growing body of clinical experience in managing this novel infection worldwide, this case series describes the clinical presentation and outcome of all adult patients admitted to the Infectious Diseases units in the West of Scotland with suspected H1N1 infection, during the first three months of the global pandemic. In the West of Scotland, the two regional infectious diseases units at Gartnavel General Hospital in Glasgow and at Monklands District General hospital in Airdrie, serve the populations of Lanarkshire, Forth Valley, and Greater Glasgow and Clyde Health Boards (population approx 1.9 million). Between April and July 2009, all adult patients in the West of Scotland requiring hospitalization for confirmed or suspected H1N1 infection were transferred to one of these two Regional Infectious Diseases unit for isolation and treatment, unless their condition merited direct admission to intensive care. The case definition was a pyrexia 38 C or history of fever AND two or more of the following symptoms: cough, sore throat, headache, rhinorrhoea, limb/ joint pain.

Outpatient parenteral antimicrobial therapy (OPAT) and the general physician.

Outpatient parenteral antimicrobial therapy (OPAT) refers to outpatient or community-based management of an infection via the administration of an intravenous (IV) antimicrobial without an overnight hospital stay. Patients may be managed without admission or may transition to OPAT following hospitalisation. By minimising hospital stay, OPAT is increasingly recognised as a cost-efficient and acceptable management strategy for a variety of selected patients requiring either short- or medium-to long-term parenteral therapy in the UK (Table ​(Table11).1–5 This short article outlines good practice recommendations and highlights OPAT management of infections commonly encountered by physicians with acute medical duties. Table 1. Characteristics of recently published UK OPAT service cohorts.

Daptomycin in synovial fluid during treatment of methicillin-resistant Staphylococcus aureus septic arthritis

3 Kielstein JT, Engbers C, Bode-Bö ger SM et al. Dosing of daptomycin in intensive care unit patients with acute kidney injury undergoing extended dialysis—a pharmacokinetic study. 5 Goedecke VA, Clajus C, Burkhardt O et al. Pharmacokinetics and dialysate levels of daptomycin given intravenously in a peritoneal dialysis patient. 7 Martens-Lobenhoffer J, Kielstein JT, Oye C et al. Validated high performance liquid chromatography-UV detection method for the determination of daptomycin in human plasma. 8 Hermsen ED, Hovde LB, Hotchkiss JR et al. Increased killing of staphylococci and streptococci by daptomycin compared with cefazolin and vancomycin in an in vitro peritoneal dialysate model. Sir, Methicillin-resistant Staphylococcus aureus (MRSA) osteoarticular infections present a therapeutic challenge, requiring the adequate removal of infected materials and antibiotic penetration to give therapeutic concentrations at the infection site. Daptomycin, a cyclic lipopeptide antibiotic with a broad spectrum of activity against Gram-positive organisms including MRSA, is an emerging therapy in osteoarticular infection. However, to our knowledge, there are no data on daptomycin osteoarticular tissue penetration. Herein, we report therapeutic intra-articular concentrations in a case of daptomycin-treated MRSA septic arthritis. A 41-year-old man with haemoglobin S/C disease (a sickle-cell disorder) and asymptomatic, antiretroviral-therapy-naive HIV infection presented with a hot, swollen left knee. A long complicated history of recurrent MRSA infection involving his left hip, femur and knee followed an infected total hip replacement 6 years previously. Despite a Girdlestone procedure, extensive chronic osteomyelitis had developed. Prolonged suppressive antibiotic therapy was associated with a 3 year period free of overt infection. Knee aspiration revealed thick pus and MRSA susceptible to vancomycin, teicoplanin, sodium fusidate, tetracyclines, linezolid and daptomycin, but resistant to rifampicin, trimethoprim and clin-damycin. The MIC of daptomycin was 0.38 mg/L by Etest. Antibiotic options were limited by previous hepatotoxicity with glycopeptides and peripheral neuropathy with linezolid. Arthroscopic washout of the joint was performed and 6 mg/kg daptomycin was used in combination with 500 mg of oral sodium fusidate 8 hourly. On day 14 of daptomycin therapy, the left knee was aspirated and samples were collected for culture and daptomycin concentration quantification. A simultaneously drawn serum sample was also obtained for daptomycin concentration. Synovial fluid was serosanguineous, not blood stained and culture was negative. Samples for daptomy-cin assay collected in glass and plastic containers were assayed for the presence of daptomycin, as previously described. 1 Daptomycin serum concentration was 12.9 mg/L and synovial fluid concentrations were 9.0 mg/L (glass) …

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.