Best practices: Appropriate use of the new ß-lactam/ß-lactamase inhibitor combinations, ceftazidime-avibactam and ceftolozane-tazobactam in South Africa.

Antibiotic stewardship of hospital-acquired infections because of difficult-to-treat resistant (DTR) Gram-negative bacteria is a global challenge. Their increasing prevalence in South Africa has required a shift in prescribing in recent years towards colistin, an antibiotic of last resort. High toxicity levels and developing resistance to colistin are narrowing treatment options further. Recently, two new ß-lactam/ß-lactamase inhibitor combinations, ceftazidime-avibactam and ceftolozane-tazobactam were registered in South Africa, bringing hope of new options for management of these life-threatening infections. However, with increased use in the private sector, increasing levels of resistance to ceftazidime-avibactam are already being witnessed, putting their long-term viability as treatment options of last resort, in jeopardy. This review focuses on how these two vital new antibiotics should be stewarded within a framework that recognises the resistance mechanisms currently predominant in South Africa's multi-drug and DTR Gram-negative bacteria. Moreover, the withholding of their use for resistant infections that can be treated with currently available antibiotics is a critical part of stewardship, if these antibiotics are to be conserved in the long term.

Epidemiologic Shift in Candidemia Driven by Candida auris, South Africa, 2016-20171.

Candida auris is an invasive healthcare-associated fungal pathogen. Cases of candidemia, defined as illness in patients with Candida cultured from blood, were detected through national laboratory-based surveillance in South Africa during 2016-2017. We identified viable isolates by using mass spectrometry and sequencing. Among 6,669 cases (5,876 with species identification) from 269 hospitals, 794 (14%) were caused by C. auris. The incidence risk for all candidemia at 133 hospitals was 83.8 (95% CI 81.2-86.4) cases/100,000 admissions. Prior systemic antifungal drug therapy was associated with a 40% increased adjusted odds of C. auris fungemia compared with bloodstream infection caused by other Candida species (adjusted odds ratio 1.4 [95% CI 0.8-2.3]). The crude in-hospital case-fatality ratio did not differ between Candida species and was 45% for C. auris candidemia, compared with 43% for non-C. auris candidemia. C. auris has caused a major epidemiologic shift in candidemia in South Africa.

Plasmid-mediated resistance and virulence mechanisms in the private health sector in KwaZulu-Natal, South Africa: An investigation of methicillin resistant Staphylococcus aureus (MRSA) clinical isolates collected during a three month period.

OBJECTIVES: Due to the lack of information on the plasmid content of MRSA strains in South Africa (SA), this study investigated the resistance and virulence mechanisms of 27 clinical isolates from the private health care sector over a period of 3 months. METHODS: Plasmids were extracted and the presence of MRSA confirmed by the presence of mecA. The isolates were subjected to antimicrobial susceptibility testing and molecular characterization of common resistance encoding genes and frequently encountered virulence factors by PCR using plasmid DNA as the template. The genetic relatedness between the isolates was determined by pulsed field gel electrophoresis (PFGE). RESULTS: All isolates were plasmid positive, and displayed ampillicin, ciprofloxacin, gentamicin, rifampicin, tetracycline, erythromycin, and clindamycin resistance. They were all fully susceptible to daptomycin, linezolid, vancomycin, tigecycline and fusidic acid. Multidrug resistance (MDR) was found in 74.1% (20/27) of the MRSA isolates. The frequency of the resistance and virulence genes ranged from 100% to 0%. PFGE analysis revealed 10 pulsotypes, designated A-J, which showed correlation with resistance profile of the isolates in each group. Of note, 85.2% (23/27) of the isolates clustered into six major PFGE types giving an indication of similar circulating MRSA clones. CONCLUSIONS: This study highlights the genetic diversity and resistance mechanisms in MRSA strains from the private health sector in SA hence the need for implementing effective infection control programs.

First detection of human dirofilariasis in South Africa.

Humans are occasionally inadvertently infected with dirofilariae, the zoonotic nematodes. We report two cases of human dirofilariasis in South Africa, an area apparently non-endemic for this infection. Dirofilariasis is frequently misdiagnosed, so increased awareness of this entity in areas that are non-endemic is essential for prevention of inappropriate investigations and invasive therapy.

NDM-1-producing Enterobacteriaceae from South Africa: moving towards endemicity?

We describe 4 patients infected with NDM-1 Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens from South Africa that co-produced SHV-12, CTX-M-3, and CTX-M-15 and were positive for qnrS, qnrA, aac(6')-Ib-cr, rmtF, rmtC, and armA. Plasmids belonged to IncN, IncA/C replicon types with ccdAB and vagC/D addiction factors. Local and imported cases of NDM-producing bacteria co-exist within South Africa.