Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.

INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS: In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum ß-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). CONCLUSIONS: After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.

Evaluation of a point-of-care blood test for identification of Ebola virus disease at Ebola holding units, Western Area, Sierra Leone, January to February 2015.

Current Ebola virus disease (EVD) diagnosis relies on reverse transcription-PCR (RT-PCR) technology, requiring skilled laboratory personnel and technical infrastructure. Lack of laboratory diagnostic capacity has led to diagnostic delays in the current West African EVD outbreak of 2014 and 2015, compromising outbreak control. We evaluated the diagnostic accuracy of the EVD bedside rapid diagnostic antigen test (RDT) developed by the United Kingdom's Defence Science and Technology Laboratory, compared with Ebola virus RT-PCR, in an operational setting for EVD diagnosis of suspected cases admitted to Ebola holding units in the Western Area of Sierra Leone. From 22 January to 16 February 2015, 138 participants were enrolled. EVD prevalence was 11.5%. All EVD cases were identified by a positive RDT with a test line score of 6 or more, giving a sensitivity of 100% (95% confidence interval (CI): 78.2-100). The corresponding specificity was high (96.6%, 95% CI: 91.3-99.1). The positive and negative predictive values for the population prevalence were 79.0% (95% CI: 54.4-93.8) and 100% (95% CI: 96.7-100), respectively. These results, if confirmed in a larger study, suggest that this RDT could be used as a 'rule-out' screening test for EVD to improve rapid case identification and resource allocation.

Treating drug-resistant tuberculosis in an era of shorter regimens: Insights from rural South Africa.

BACKGROUND: Progressive interventions have recently improved programmatic outcomes in drug-resistant tuberculosis (DR-TB) care in South Africa (SA). Amidst these, a shorter regimen was introduced in 2017 with weak evidence, and has shown mixed results. Outcomes still fall short of national targets, and the coronavirus disease 2019 pandemic has undermined progress to date. OBJECTIVES: To describe the outcomes of participants treated for DR-TB using a shorter, compared with a longer, regimen in a deeply rural SA setting, and to explore other factors affecting these outcomes. METHODS: This retrospective cohort study describes outcomes in short and long DR-TB treatment regimens, over 5 years, at two rural treatment sites in SA. Characteristics were analysed for outcome correlates using multivariable logistic regression models. RESULTS: Of 282 treatment episodes, 62% were successful, with higher success in shorter (69%) compared with longer regimens (58%). Mortality was approximately 21% in both groups. Characteristics included high proportions of HIV co-infection (61%). Injectables (adjusted odds ratio (aOR) 3.00, 95% confidence interval (CI) 1.48 - 6.09), bedaquiline (aOR 3.16, 95% CI 1.36 - 7.35), increasing age (aOR 0.97, 95% CI 0.95 - 0.99) and HIV viraemia defined as final HIV-RNA viral load >1 000 copies/mL (aOR 0.16, 95% CI 0.07 - 0.37) were all significantly and independently associated with treatment success. Injectables (aOR 0.22, 95% CI 0.08 - 0.57), bedaquiline (aOR 0.05, 95% CI 0.01 - 0.19), increasing age (aOR 1.09, 95% CI 1.05 - 1.13), extra-pulmonary TB (aOR 8.15, 95% CI 1.62 - 41.03) and HIV viraemia (aOR 9.20, 95% CI 3.22 - 26.24) were all significantly and independently associated with mortality. CONCLUSION: In a rural context, treating DR-TB amid limited resources and a high burden of HIV co-infection, we found that after considering controls, a short regimen was no different to a longer regimen in terms of success or mortality. Therefore, by alleviating burdens on multiple stakeholders, a short regimen is likely to be favourable for rural patients, clinicians, and healthcare systems. Besides other previously described correlates of outcomes, HIV viraemia emerged as a novel marker for reliably predicting poor outcomes in DR-TB with HIV co-infection, and a pragmatic target for intervention.

Preparing healthcare facilities to operate safely and effectively during the COVID-19 pandemic: The missing piece in the puzzle.

The stated objective of the COVID-19 lockdown was to allow time to prepare healthcare facilities. Preparation must include administrative and environmental measures, which when combined with personal protective equipment, minimise the risk of the spread of infection to patients and healthcare workers (HCWs) in facilities, allowing HCWs to safely provide essential services during the pandemic and limit the indirect effects of COVID-19 caused by healthcare disruption. We present our model for facility preparation based on colour-coded zones, social distancing, hand hygiene, rapid triage and separate management of symptomatic patients, and attention to infection transmission prevention between HCWs in communal staff areas. This model specifically addresses the challenges in preparing a facility for COVID-19 in a low-resource setting and in rural areas. In addition, we include links to resources to allow workers in low-resource settings to prepare their facilities adequately.

Antibiotic use and resistance: Knowledge, attitudes and perceptions among primary care prescribers in South Africa.

BACKGROUND: Antibiotic resistance (ABR) is a major threat to global health, driven in part by inappropriate prescription of antibiotics in primary care. OBJECTIVES: To describe South African (SA) prescribers' knowledge of, attitudes to and perceptions of ABR. METHODS: We conducted a cross-sectional survey of knowledge of, attitudes to and perceptions of ABR among a convenience sample of primary healthcare providers in SA, the majority from the private sector. We used logistic regression to examine associations between knowledge and prescribing behaviours. RESULTS: Of 264 prescriber respondents, 95.8% (230/240) believed that ABR is a significant problem in SA and 66.5% (157/236) felt pressure from patients to prescribe antibiotics. The median knowledge score was 5/7, and scores were highest in respondents aged <55 years (p=0.0001). Prescribers with higher knowledge scores were more likely than those with lower scores to believe that to decrease ABR, narrow-spectrum antibiotics should be used (adjusted odds ratio (aOR) 1.29, 95% confidence interval (CI) 1 - 1.65) and more likely to report that explaining disease features that should prompt follow-up was a useful alternative to prescribing (aOR 1.47, 95% CI 1.058 - 2.04), and were less likely to report that antibiotics cannot harm the patient if they are not needed, so they prescribe when not necessary (aOR 0.57, 95% CI 0.38 - 0.84). CONCLUSIONS: Prescribers of antibiotics in the private sector in SA were aware of the problem of ABR, but felt pressure from patients to prescribe. Those with higher knowledge scores reported positive prescribing behaviours, suggesting that more education is needed to tackle the problem of ABR.

Sustained reduction in antibiotic consumption in a South African public sector hospital; Four year outcomes from the Groote Schuur Hospital antibiotic stewardship program.

BACKGROUND: Overuse of antibiotics has driven global bacterial resistance to the extent that we have entered a post-antibiotic era, where infections that were once easily treatable are now becoming untreatable. Efforts to control consumption have focused on antibiotic stewardship programmes (ASPs), aimed at optimising use. OBJECTIVE: To report antibiotic consumption and cost over 4 years from a public hospital ASP in South Africa (SA). METHODS: A comprehensive ASP comprising online education, a dedicated antibiotic prescription chart and weekly dedicated ward rounds was introduced at Groote Schuur Hospital, Cape Town, in 2012. Electronic records were used to collect data on volume and cost of antibiotics and related laboratory tests, and to determine inpatient mortality and 30-day readmission rates. These data were compared with a control period before the intervention. RESULTS: Total antibiotic consumption fell from 1 046 defined daily doses/1 000 patient days in 2011 (control period) to 868 by 2013 and remained at similar levels for the next 2 years. This was driven by reductions in intravenous antibiotic use, particularly ceftriaxone. Inflation-adjusted cost savings on antibiotics were ZAR3.2 million over 4 years. Laboratory tests increased over the same period with a total increased cost of ZAR0.4 million. There was no significant change in mortality or 30-day readmission rates. CONCLUSIONS: The effects of a comprehensive ASP on medical inpatients at a public sector hospital in SA were durable over 4 years, leading to a reduction in total antibiotic consumption without adverse effect. When increased laboratory costs were offset there was a net cost saving of ZAR2.8 million.

Appropriate use of the Xpert® MTB/RIF assay in suspected tuberculous meningitis.

We disagree with the recommendation by the World Health Organization to use Xpert(®) MTB/RIF on cerebrospinal fluid for the initial diagnosis of tuberculous meningitis (TBM). TBM is a devastating disease requiring empirical treatment even when the probability of disease is low. We suggest that a useful TBM diagnostic test needs a negative predictive value (NPV) of ⩾ 99% so that empirical treatment can be stopped safely. The NPV of Xpert is around 84%, making a negative test of limited value. While better tests are awaited, a composite score, possibly combining Xpert with clinical variables and with high NPV, should be constructed and validated prospectively.

Diagnostic accuracy of tuberculin skin test self-reading by HIV patients in a low-resource setting.

BACKGROUND: The World Health Organization recommends tuberculin skin tests (TSTs) where feasible to identify individuals most likely to benefit from isoniazid preventive therapy (IPT). The requirement for TST reading after 48-72 h by a trained nurse is a barrier to implementation and increases loss to follow-up. METHODS: Patients with human immunodeficiency virus (HIV) infection were recruited from a primary care clinic in South Africa and trained by a lay counsellor to interpret their own TST. The TST was placed by a nurse, and the patient was asked to return 2 days later with their self-reading result, followed by blinded reading by a trained nurse (reference). RESULTS: Of 227 patients, 210 returned for TST reading; 78% interpreted their test correctly: those interpreting it as negative were more likely to be correct (negative predictive value 93%) than those interpreting it as positive (positive predictive value 42%); 10/36 (28%) positive TST results were read as negative by the patient. CONCLUSIONS: Patients with HIV in low-resource settings can be trained to interpret their own TST. Those interpreting it as positive should return to the clinic within 48-72 h for confirmatory reading and IPT initiation; those with a negative interpretation can return at their next scheduled visit and initiate IPT at that time if appropriate.

False-positive Xpert® MTB/RIF assays in previously treated patients: need for caution in interpreting results.

Xpert(®) MTB/RIF is the initial diagnostic test of choice for tuberculosis (TB). It is not known if false-positive results are more common in previously treated patients. We report four patients with successful treatment for TB up to 5 years previously who presented with respiratory tract infection and were Xpert-positive, but had negative TB cultures and clinical improvement without anti-tuberculosis treatment. We hypothesise that the Xpert results were false-positive due to the presence of dead Mycobacterium tuberculosis bacilli in lungs and sputum. Further work is required to determine the specificity of Xpert in previously treated patients.

Emergency medical services--poor response time in the rural Eastern Cape.

Emergency medical services (EMS) throughout South Africa are of unequal quality owing to historical population inequalities and under-resourced EMS in rural areas. There are no data regarding the quality of ambulance services in the rural Eastern Cape. The assessment of EMS is not easy, but an assessment tool has been established. We prospectively audited the response time to ambulance requests from a community health centre in the rural Eastern Cape.