Organ and tissue donation depends on non-transplant clinicians to identify and timeously refer potential donors and to counsel families compassionately about the prognosis at end of life. Organ donation referral is often felt to be beyond the capacity of district-level hospital services. In this case series, we report on four referrals from a geographically remote, public sector district-level hospital, and review the identification, referral and consent process of potential donors after brain death, and also donors after circulatory death. For the one successfully consented donor we report on the donor work-up and management, and the outcome of the organ recovery and organ allocation process.

BACKGROUND: The increasing prevalence of antibiotic resistance is a major threat to public health. Primary care, where 80% of antibiotics are consumed, is a pivotal setting to direct antimicrobial stewardship (AMS) efforts. However, the ideal model to improve antibiotic prescribing in primary care in low-resource settings is not known OBJECTIVE: To implement a multidisciplinary audit and feedback AMS intervention with the aim to improve appropriate antibiotic prescribing at primary care level METHODS: The intervention was implemented and monitored in 10 primary care centres of the Cape Town metropole between July 2017 and June 2019. The primary and secondary outcome measures were monthly adherence to a bundle of antibiotic quality process measures and monthly antibiotic consumption, respectively. Multidisciplinary audit and feedback meetings were initiated and integrated into facility clinical meetings. Two Excel tools were utilised to automatically calculate facility audit scores and consumption. Once a month, 10 antibiotic prescriptions were randomly selected for a peer review audit by the team. The prescriptions were audited for adherence to a bundle of seven antibiotic process measures using the standard treatment guidelines (STG) and Essential Medicines List (EML) as standard. Concurrently, primary care pharmacists monitored monthly antibiotic consumption by calculating defined daily doses (DDDs) per 100 prescriptions dispensed. Adherence and consumption feedback were regularly provided to the facilities. Learning collaboratives involving representative multidisciplinary teams were held twice-yearly. Pre-, baseline and post-intervention periods were defined as 6 months before, first 6 months and last 6 months of the study, respectively RESULTS: The mean overall adherence increased from 19% (baseline) to 47% (post intervention) (p<0.001). Of the 2 077 prescriptions analysed, 33.7% had an antibiotic prescribed inappropriately. No diagnosis had been captured in patient notes, and the antibiotic chosen was not according to the STG and EML in 30.1% and 31.7% of cases, respectively. Seasonal variation was observed in prescribing adherence, with significantly lower adherence in winter and spring months (adjusted odds ratio 0.60). A reduction of 12.9 DDDs between the pre- and post-intervention periods (p=0.0084) was documented, which represented a 19.3% decrease in antibiotic consumption CONCLUSION: The study demonstrated that peer reviewed audit and feedback is an effective AMS intervention to improve antibiotic prescribing in primary care in a low-resource setting. The intervention, utilising existing resources and involving multidisciplinary engagement, may be incorporated into existing quality improvement processes at facility level, to ensure sustainable change

Blood cultures are an important diagnostic and antibiotic stewardship tool to aid in treatment, monitoring and prognosis of patients with infection. This guideline is intended to update our 2010 guideline on the optimal use of blood cultures. Since then, there have been significant changes to the definitions of sepsis, guidance on the number of blood cultures recommended per draw, central and peripheral line blood cultures, advances in mitigating culture contamination, updates on the indications for blood cultures, and guidance on performance of follow-up cultures.

A previously healthy 10-year-old girl, living in a sheep-farming community in South Africa with exposure to dogs, presented to her local hospital with generalised tonic-clonic seizures. The initial clinical assessment and laboratory work-up were unremarkable. When she presented with further seizures 6 months later, attempts to arrange neuroimaging and specialist assessment were unsuccessful owing to restrictions on routine healthcare services during the SARS-CoV-2 nationwide lockdown. Subsequently, 11 months after her first presentation, she developed focal neurological signs suggestive of raised intracranial pressure. A brain computed tomography scan revealed a left-sided cerebral cyst and imminent tonsillar herniation. An emergency burr-hole procedure was performed to relieve the raised intracranial pressure, followed by definitive neurosurgical excision of cysts. Hydatid protoscolices and hooklets were seen on microscopy of cyst fluid, and treatment with albendazole and praziquantel was initiated. While her infection was treated successfully, long-term sequelae including permanent blindness and hemiparesis could potentially have been prevented with early neuroimaging and surgical intervention.

The newer beta-lactam-inhibitor combination (BLIC) antibiotics are available in South Africa (SA) for the treatment of carbapenem-resistant Enterobacterales infections. We describe the successful use of ceftazidime-avibactam (CA) for the treatment of a child with persistent carbapenem-resistant Serratia marcescens bacteraemia, and the challenges faced using this lifesaving antibiotic, including access to susceptibility testing, procurement process, cost and complexity of deciding when, how and for how long to use it. Furthermore, the burden of carbapenem resistance is increasing in SA, and inappropriate use of CA and other newer BLIC antibiotics, such as ceftolozane-tazobactam, will inevitably endanger their longevity. A careful balance must be struck between removing unnecessary obstacles and delays in initiating these antibiotics for life-threatening infections, and additional antimicrobial stewardship-guided interventions aimed at preserving their therapeutic use.

Advances in DNA sequencing technologies and computational tools over the past few years have led to vast improvements in the metagenomic analysis of the human microbiota. While this has also significantly improved our understanding of the role of the host-microbiome interaction in health and disease, the current clinical expectation is that testing, particularly of the gastrointestinal biome, can be used to diagnose, manage and treat patients. The authors outline the available technologies and highlight current limitations of these techniques to address this clinical demand. Through understanding the limitations of and need for more research and data collection, one can improve the appropriate utilisation and interpretation, as well as the current rational clinical application of these techniques.

The legal regulation of faecal microbiota transplantation (FMT) in South Africa (SA) is currently unclear. The purpose of this article, the first of three in a series, is to explore the nature, role and clinical application of FMT in SA in order to determine, from a legal perspective, the appropriate regulatory pathways governing FMT as a procedure that may combine approaches for the treatment of drugs, human tissue for transplantation, or clinical treatment as part of the practice of medicine. FMT has been shown to be a novel, safe and effective treatment for recurrent Clostridioides difficile infection (CDI). Stool banks are instrumental in enabling access to FMT for patients and clinicians and help to catalyse research in the microbiome. However, the regulatory landscape in SA remains unclear. Microbial therapies such as FMT are necessary, especially in a time of rising microbiome-associated inflammatory diseases and increasing resistance to traditional antibiotics. FMT is now considered as part of the standard of care for recurrent CDI overseas, but is currently only being used for research purposes in a minority of clinical cases of CDI in SA. This article, which lays the foundation for consideration of this question in three parts, suggests that the relevant regulatory system would depend on the categorisation of human stool as tissue, the exact composition of the FMT, how it is administered to patients, and the relevant levels of manipulation of the stool for FMT-derived products.

The purpose of this article, the last in a series of three exploring the legal framework for the regulation of faecal microbiota transplantation (FMT) in South Africa (SA), is to determine the regulatory framework that applies to microbial-based treatments involving a level of manipulation that exceeds that of basic stool transplantation, e.g. processed FMT-derived products in capsule form. The article highlights the legal requirements for the registration of these products as biological medicines in SA law. Although human stool banks are not regulated in terms of the National Health Act 61 of 2003 (NHA) and regulations, the earlier articles point out that human stool fits the definition of human tissue and human biological material as defined by the NHA. For this reason, stool banks should be considered tissue banks in terms of the NHA and regulations. Healthcare practitioners and researchers involved in FMT banking and transplantation should strive to comply with these regulations in the absence of clear legal direction at present.

Faecal microbiota transplantation (FMT) has been shown to be an effective treatment for recurrent Clostridioides difficile infection. The purpose of this article, the second of a series of three articles, is to explore the legal framework governing human FMT in South Africa (SA). FMT involves different modes of administration that require different regulatory considerations. The focus of this article is to explore the legal classification of human stool as tissue in terms of the National Health Act 61 of 2003, as well as the regulation of human stool banks as tissue banks. The article concludes with specific recommendations aimed at improving the current regulatory vacuum relating to the regulation of FMT in SA.

The systemic fluoroquinolones (FQs) have recently been reported to be associated with significant side-effects in susceptible individuals. This has prompted the Food and Drug Administration (FDA) in the USA and the European Medicines Agency (EMA) to issue warnings regarding their use. The FQs should not be used for common bacterial infections, such as urinary tract infections, travellers' diarrhoea and upper and lower respiratory tract infections, unless it is not possible to use another oral agent. There are situations, however, in which these agents are not only effective, but their benefit outweighs the risk. These include the management of conditions such as acute prostatitis, typhoid fever, prosthetic joint infections, multidrug-resistant tuberculosis, certain hospital-acquired infections and situations where the organism is susceptible to FQs, which could then be administered orally. Alternatively, the patient would have to be admitted to hospital for parenteral therapy.

BACKGROUND: Colistin is an old antibiotic that has been reintroduced as salvage therapy in hospitalised patients because it is frequently the only agent active against Gram-negative bacteria. Various guidelines for colistin administration have led to confusion in establishing the appropriate dose, which has potential for adverse consequences including treatment failure or toxicity. The emergence and spread of colistin resistance has been documented in South Africa (SA), but no local information exists on how and why colistin is used in hospitals, and similarly, compliance with current dosing guidelines is unknown. OBJECTIVES: To evaluate the current utilisation of colistin in SA hospitals, in order to identify stewardship opportunities that could enhance the appropriate use of this antibiotic. METHODS: Electronic patient records of adult patients on intravenous (IV) colistin therapy for >72 hours in four private hospitals were retrospectively audited over a 10-month period (1 September 2015 - 30 June 2016). The following data were recorded: patient demographics, culture and susceptibility profiles, diagnosis, and indication for use. Compliance with six colistin process measures was audited: obtaining a culture prior to initiation, administration of a loading dose, administration of the correct loading dose, adjustments to maintenance dose according to renal function, whether colistin was administered in combination with another antibiotic, and whether de-escalation following culture and sensitivity results occurred. Outcome measures included effects on renal function, overall hospital mortality, intensive care unit length of stay (LoS), and hospital LoS. RESULTS: Records of 199 patients on IV colistin were reviewed. There was 99.0% compliance with obtaining a culture prior to antibiotic therapy, 93.5% compliance with prescription of a loading dose, and 98.5% compliance regarding prescription of colistin in combination with another agent. However, overall composite compliance with the six colistin stewardship process measures was 82.0%. Non-compliance related to inappropriate loading and maintenance doses, lack of adjustment according to renal function and lack of de-escalation following culture sensitivity was evident. Significantly shorter durations of treatment were noted in patients who received higher loading doses (p=0.040) and in those who received maintenance doses of 4.5 MU twice daily v. 3 MU three times daily (p=0.0027). In addition, compared with patients who survived, more patients who died received the 3 MU three times daily maintenance dose (p=0.0037; phi coefficient 0.26). CONCLUSIONS: The study identified multiple stewardship opportunities to optimise colistin therapy in hospitalised patients. Urgent implementation of a stewardship bundle to improve colistin utilisation is warranted.

Abstract Two bacteria, namely Bacillus subtilis and Pseudomonas aeruginosa were exposed to different concentrations of diesel to increase their adaptation to the fossil fuel, and were used for the degradation of diesel-biodiesel blends. The biodegradation rate was evaluated using the redox indicator 2,6-dichlorophenol indophenol (DCPIP) test and gravimetric analysis. The preliminary exposure of cells to diesel proved to improve their biodegradation capacities, and exposure to a higher concentration (70%) of diesel resulted in maximum biodegradation of up to 58.38 g and 1.78 g of degraded oil per CFU/mL (1010) for P. aeruginosa and B. subtilis respectively. It was found that the adapted cells preferably used diesel in the blend. P. aeruginosa and B. subtilis exhibited different adaptation capabilities and biodegradation behaviour. Biodiesel stimulated the biodegradation of the diesel-biodiesel blends by non-adapted cells only; the adapted cells exhibited a different behaviour.

Antibiotic resistance has increased worldwide to the extent that it is now regarded as a global public health crisis. Interventions to reduce excessive antibiotic prescribing to patients can reduce resistance and improve microbiological and clinical outcomes. Therefore, although improving outpatient antibiotic use is crucial, few data are provided on the key interventional components and the effectiveness of antibiotic stewardship in the primary care setting, in South Africa. The reasons driving the excessive prescription of antibiotics in the community are multifactorial but, perhaps most importantly, the overlapping clinical features of viral and bacterial infections dramatically reduce the ability of GPs to distinguish which patients would benefit from an antibiotic or not. As a consequence, the need for tools to reduce diagnostic uncertainty is critical. In this regard, besides clinical algorithms, a consensus of collaborators in European and UK consortia recently provided guidance for the use of C-reactive protein point-of-care testing in outpatients presenting with acute respiratory tract infections (ARTIs) and/or acute cough, if it is not clear after proper clinical assessment whether antibiotics should be prescribed or not. A targeted application of stewardship principles, including diagnostic stewardship as described in this review, to the ambulatory setting has the potential to affect the most common indications for systemic antibiotic use, in that the majority (80%) of antibiotic use occurs in the community, with ARTIs the most common indication.

The polymyxin antibiotic colistin is an antibiotic of last resort for the treatment of extensively drug-resistant Gram-negative bacteria, including carbapenemase-producing Enterobacteriaceae. The State of the World's Antibiotics report in 2015 highlighted South Africa (SA)'s increasing incidence of these 'superbugs' (3.2% of Klebsiella pneumoniae reported from SA were carbapenemase producers), and in doing so, underscored SA's increasing reliance on colistin as a last line of defence. Colistin resistance effectively renders such increasingly common infections untreatable.

BACKGROUND: Inappropriate use of antibiotics for non-severe upper respiratory tract infections (URTIs), most of which are viral, significantly adds to the burden of antibiotic resistance. Since the introduction of pneumococcal conjugate vaccines in South Africa in 2009, the relative frequency of the major bacterial pathogens causing acute otitis media (AOM) and acute bacterial rhinosinusitis (ABRS) has changed RECOMMENDATIONS: Since URTIs are mostly viral in aetiology and bacterial AOM and ABRS frequently resolve spontaneously, these recommendations include diagnostic criteria to assist in separating viral from bacterial causes and hence select those patients who do not require antibiotics. Penicillin remains the drug of choice for tonsillopharyngitis and amoxicillin the drug of choice for both AOM and ABRS. A dose of 90 mg/kg/d is recommended for children, which should be effective for pneumococci with high-level penicillin resistance and will also cover most infections with Haemophilus influenzae. Amoxicillin-clavulanate (in high-dose amoxicillin formulations available for both children and adults) should be considered the initial treatment of choice in patients with recent antibiotic therapy with amoxicillin (previous 30 days) and with resistant H. influenzae infections pending the results of studies of local epidemiology (β-lactamase production >15%). The macrolide/azalide class of antibiotics is not recommended routinely for URTIs and is reserved for β-lactam-allergic patients CONCLUSION: These recommendations should facilitate rational antibiotic prescribing for URTIs as a component of antibiotic stewardship. They will require updating when new information becomes available, particularly from randomised controlled trials and surveillance studies of local aetiology and antibiotic susceptibility patterns