External validity and clinical usefulness of a risk prediction model for 30 day unplanned hospitalization in patients receiving outpatient parenteral antimicrobial therapy.

OBJECTIVES: Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to treat a variety of infections. However, hospital readmissions remain relatively common. We examined the external validity and clinical usefulness of a previously derived risk prediction model for 30 day unplanned hospitalization in patients receiving OPAT. METHODS: A retrospective cohort study was conducted at two large teaching hospitals in the UK. The design comprised quasi-external temporal validation on patients from the same OPAT setting as the model development, and broader external validation on patients from a different setting. The model predictors were age, prior hospitalizations in the preceding 12 months, Charlson comorbidity score, concurrent IV antimicrobial therapy, type of infection and mode of OPAT treatment. Discriminative ability, calibration and clinical usefulness were assessed. RESULTS: Data from 2578 OPAT patients were analysed. The rates of 30 day unplanned hospitalization were 11.5% (123/1073), 12.9% (140/1087) and 25.4% (106/418) in the model derivation, temporal validation and broader external validation cohorts, respectively. The discriminative ability of the prediction model was adequate on temporal validation (c-statistic 0.75; 95% CI: 0.71-0.79) and acceptable on broader validation (c-statistic 0.67; 95% CI: 0.61-0.73). In both external cohorts, the model displayed excellent calibration between observed and predicted probabilities. Decision curve analysis showed increased net benefit across a range of meaningful risk thresholds. CONCLUSIONS: A simple risk prediction model for unplanned readmission in OPAT patients demonstrated reproducible predictive performance, broad clinical transportability and clinical usefulness. This model may help improve OPAT outcomes through better identification of high-risk patients and provision of tailored care.

West Nile Virus Infection in Travelers Returning to United Kingdom from South Africa.

West Nile virus (WNV) is an arthropod-transmitted flavivirus that causes West Nile fever and may infrequently cause neuroinvasive disease in humans. We present 2 cases of confirmed WNV infection, 1 of severe encephalitis and 1 of mild febrile illness, in a couple returning to the United Kingdom from South Africa.

Outpatient parenteral antimicrobial therapy (OPAT) in the UK: a cross-sectional survey of acute hospital trusts and health boards.

This study reviews the current OPAT service provision in the UK and evaluates concordance with the national OPAT practice guidelines (standards of care). We conducted a survey of acute hospital trusts and health boards in the UK regarding OPAT practices between June and September 2017. 165 (93%) of the 178 acute hospital trusts/health boards that were contacted responded to the survey. 100 (61%) indicated they had an OPAT service. Ten (10%) OPAT services did not involve an infection specialist. Bone and joint infections, and skin and soft-tissue infections were the most common conditions treated. Most OPAT services (74%) hold weekly multidisciplinary meetings/virtual ward rounds to review patient's progress. 73% had a dedicated OPAT database. We identified variations in practice and concordance with the national OPAT good practice guidelines. In an era of increasing demand for home-based care, further studies are required to identify the optimal configuration of OPAT services with regards to quality and patient safety.

Clinical efficacy, cost analysis and patient acceptability of outpatient parenteral antibiotic therapy (OPAT): a decade of Sheffield (UK) OPAT service.

Outpatient parenteral antimicrobial therapy (OPAT) has evolved relatively slowly in the UK. This study describes the OPAT service based in a large UK teaching hospital in Sheffield, and examines the clinical efficacy, patient acceptability and costs saved over a 10-year period. Data on 3812 episodes of OPAT administered between January 2006 and January 2016 were retrieved from a prospectively maintained electronic database. This study compared the real costs of the OPAT service with estimated costs of conventional inpatient care for these patient episodes, and analysed patient feedback questionnaires that were administered randomly between January 2014 and January 2015. A wide range of infections were managed during the 10-year period. Skin and soft tissue infections accounted for 57% of OPAT episodes. The total number of bed-days saved was 49,854. A successful outcome (cure or improvement) was found in 3357 (88%) episodes. Re-admission occurred in 265 (7%) episodes. The rates of healthcare-associated infections were low: 15 intravenous-line-related infections were recorded (0.3 per 1000 OPAT patient-days). Patient acceptance and satisfaction with OPAT were high. OPAT cost 15%, 39%, 40% and 44% of inpatient costs for an infectious diseases unit, national average costs, other departments (non-infectious diseases unit), and the minimum national average costs for each diagnostic category, respectively. This study shows that OPAT is safe, clinically efficacious and acceptable for treating a wide range of infections with high levels of patient satisfaction and substantial cost savings.

Prediction of Outcome From Adult Bacterial Meningitis in a High-HIV-Seroprevalence, Resource-Poor Setting Using the Malawi Adult Meningitis Score (MAMS).

Background: Acute bacterial meningitis (ABM) in adults residing in resource-poor countries is associated with mortality rates >50%. To improve outcome, interventional trials and standardized clinical algorithms are urgently required. To optimize these processes, we developed and validated an outcome prediction tool to identify ABM patients at greatest risk of death. Methods: We derived a nomogram using mortality predictors derived from a logistic regression model of a discovery database of adult Malawian patients with ABM (n = 523 [65%] cerebrospinal fluid [CSF] culture positive). We validated the nomogram internally using a bootstrap procedure and subsequently used the nomogram scores to further interpret the effects of adjunctive dexamethasone and glycerol using clinical trial data from Malawi. Results: ABM mortality at 6-week follow-up was 54%. Five of 15 variables tested were strongly associated with poor outcome (CSF culture positivity, CSF white blood cell count, hemoglobin, Glasgow Coma Scale, and pulse rate), and were used in the derivation of the Malawi Adult Meningitis Score (MAMS) nomogram. The C-index (area under the curve) was 0.76 (95% confidence interval, .71-.80) and calibration was good (Hosmer-Lemeshow C-statistic = 5.48, df = 8, P = .705). Harmful effects of adjunctive glycerol were observed in groups with relatively low predicted risk of poor outcome (25%-50% risk): Case Fatality Rate of 21% in the placebo group and 52% in the glycerol group (P < .001). This effect was not seen with adjunctive dexamethasone. Conclusions: MAMS provides a novel tool for predicting prognosis and improving interpretation of ABM clinical trials by risk stratification in resource-poor settings. Whether MAMS can be applied to non-HIV-endemic countries requires further evaluation.

High mortality amongst adolescents and adults with bacterial meningitis in sub-Saharan Africa: an analysis of 715 cases from Malawi.

UNLABELLED: Mortality from bacterial meningitis in African adults is significantly higher than those in better resourced settings and adjunctive therapeutic interventions such as dexamethasone and glycerol have been shown to be ineffective. We conducted a study analysing data from clinical trials of bacterial meningitis in Blantyre, Malawi to investigate the clinical parameters associated with this high mortality. METHODS: We searched for all clinical trials undertaken in Blantyre investigating bacterial meningitis from 1990 to the current time and combined the data from all included trial datasets into one database. We used logistic regression to relate individual clinical parameters to mortality. Adults with community acquired bacterial meningitis were included if the CSF culture isolate was consistent with meningitis or if the CSF white cell count was >100 cells/mm(3) (>50% neutrophils) in HIV negative participants and >5 cells/mm(3) in HIV positive participants. Outcome was measured by mortality at discharge from hospital (after 10 days of antibiotic therapy) and community follow up (day 40). RESULTS: Seven hundred and fifteen episodes of bacterial meningitis were evaluated. The mortality rate was 45% at day 10 and 54% at day 40. The most common pathogens were S.pneumoniae (84% of positive CSF isolates) and N.meningitidis (4%). 607/694 (87%) participants tested were HIV antibody positive. Treatment delays within the hospital system were marked. The median presenting GCS was 12/15, 17% had GCS<8 and 44.9% had a seizure during the illness. Coma, seizures, tachycardia and anaemia were all significantly associated with mortality on multivariate analysis. HIV status and pneumococcal culture positivity in the CSF were not associated with mortality. Adults with community acquired bacterial meningitis in Malawi present with a severe clinical phenotype. Predictors of high mortality are different to those seen in Western settings. Optimising in-hospital care and minimising treatment delays presents an opportunity to improve outcomes considerably.

Epstein-barr virus coinfection in cerebrospinal fluid is associated with increased mortality in Malawian adults with bacterial meningitis.

Mortality from adult bacterial meningitis exceeds 50% in sub-Saharan Africa. We postulated that-particularly in individuals infected with human immunodeficiency virus (HIV)-herpes simplex virus, varicella zoster virus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in the cerebrospinal fluid (CSF) contribute to poor outcome. CSF from 149 Malawian adults with bacterial meningitis and 39 controls were analyzed using polymerase chain reaction. EBV was detected in 79 of 149 bacterial meningitis patients. Mortality (54%) was associated with higher CSF EBV load when adjusted for HIV (P = .01). CMV was detected in 11 of 115 HIV-infected patients, 8 of whom died. The mechanisms by which EBV and CMV contribute to poor outcome require further investigation.

Eumycetoma of the hand caused by Leptosphaeria tompkinsii and refractory to medical therapy with voriconazole.

We report on the first case of eumycetoma caused by the organism Leptosphaeria tompkinsii to be diagnosed and possibly acquired within the United Kingdom. Conventional culture of fungal grains and surgical tissue specimens was negative and the diagnosis was achieved using panfungal polymerase chain reaction and sequencing technology. Despite limited surgical resection and prolonged antifungal therapy with voriconazole, the patient developed progressive disease with mycetoma bone involvement. This case highlights the usefulness of molecular diagnostic techniques in eumycetoma where organisms may fail to grow with conventional culture or be difficult to identify morphologically. It also reminds us that eumycetoma is a difficult infection to treat and despite optimism regarding the efficacy of the newer triazole antifungals in this condition, treatment failures may still occur.

Glycerol adjuvant therapy in adults with bacterial meningitis in a high HIV seroprevalence setting in Malawi: a double-blind, randomised controlled trial.

BACKGROUND: Southern Africa has a high incidence of bacterial meningitis in adults, often associated with HIV co-infection. Mortality exceeds 50%, even with appropriate antibiotic therapy, and is not improved with corticosteroids. Glycerol adjuvant therapy reduces long-term morbidity in bacterial meningitis in children, and its use is being promoted. We aimed to assess the effectiveness of glycerol as an adjuvant therapy for adults with bacterial meningitis in Africa. METHODS: The study was done in two phases. First, in an open-label dose-finding study, 45 adult patients with symptoms, signs, and cerebrospinal fluid findings consistent with bacterial meningitis received either 50 mL, 75 mL, or 100 mL of glycerol four times a day for 4 days. We then did a randomised, double-blind, placebo-controlled trial of oral glycerol in adults with bacterial meningitis. Patients with clinical and cerebrospinal fluid findings suggestive of bacterial meningitis were randomly assigned in blocks of 12 by use of a random number list produced by an independent statistician to receive either glycerol or an equivalent volume of sugar solution. Glycerol and placebo were indistinguishable by colour or taste. The primary outcome was mortality at 40 days, with secondary outcomes including disability and mortality restricted to pneumococcal disease. All patients were analysed for the primary outcome excluding those who were lost to follow-up. This trial is registered at controlled-trials.com, number ISRCTN70121840. FINDINGS: 75 mL glycerol four times a day was the highest tolerated dose, and was used for the main study. 265 patients were assigned treatment: 137 glycerol and 128 placebo. The trial was stopped early on the advice of the data and safety monitoring board after a planned interim analysis. By day 40, 61 (49%) of 125 patients in the placebo group and 86 (63%) of 136 in the glycerol group had died (adjusted odds ratio 2.4, 95% CI 1.3-4.2, p=0.003). There was no benefit from glycerol for death and disability by day 40, and glycerol did not improve death and disability by day 40 or death at day 40 in patients with proven bacterial disease or pneumococcal disease. Two serious adverse events occurred that were possibly due to the study drug. INTERPRETATION: Oral glycerol therapy cannot be recommended as an adjuvant therapy in adults with bacterial meningitis in resource-poor settings with a high HIV prevalence. FUNDING: Meningitis Research Foundation.