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.

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.

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

The estimated burden of fungal disease in South Africa

Background. With a population of 56.5 million, over 7 million persons living with HIV, one of the world's highest rates of tuberculosis (TB) and a large proportion of the population living in poverty, South Africa (SA)'s fungal disease burden is probably substantial and broad in scope.Objectives. To estimate the burden of fungal disease in SA.Methods. Using total and at-risk populations and national, regional and occasionally global data, we estimated the incidence and prevalence of the majority of fungal diseases in SA.Results. Estimates for the annual incidence of HIV-related life-threatening fungal disease include cryptococcal meningitis (8 357 cases), Pneumocystis pneumonia (4 452 cases) and endemic mycoses (emergomycosis, histoplasmosis and blastomycosis, with 100, 60 and 10 cases per year, respectively). We estimate 3 885 cases of invasive aspergillosis annually. The annual burden of candidaemia and Candida peritonitis is estimated at 5 421 and 1 901 cases, respectively. The epidemic of pulmonary TB has probably driven up the prevalence of chronic pulmonary aspergillosis to 99 351 (175.8/100 000), perhaps the highest in the world. Fungal asthma probably affects >100 000 adults. Mucosal candidiasis is common, with an annual prevalence estimated at 828 666 and 135 289 oral and oesophageal cases, respectively, complicating HIV infection alone (estimates in other conditions not made), and over a million women are estimated to be affected by recurrent vulvovaginal candidiasis each year. Tinea capitis in children is common and conservatively estimated at >1 000 000 cases. The inoculation mycoses sporotrichosis, chromoblastomycosis and eumycetoma occur occasionally (with 40, 40 and 10 cases estimated, respectively). Overall, we estimate that over 3.2 million South Africans are afflicted by a fungal disease each year (7.1% of the population).Conclusions. Significant numbers of South Africans are estimated to be affected each year by fungal infections, driven primarily by the syndemics of HIV, TB and poverty. These estimates emphasise the need for better epidemiological data, and for improving the diagnosis and management of these diseases

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.

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.

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.

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.