Background Multi-drug resistant organisms are an increasingly important cause of neonatal sepsis. Aim This study aimed to review neonatal sepsis caused by multi-drug resistant Enterobacteriaceae (MDRE) in neonates in Johannesburg, South Africa. Methods This was a cross sectional retrospective review of MDRE in neonates admitted to a tertiary neonatal unit between 1 January 2013 and 31 December 2015. Results There were 465 infections in 291 neonates. 68.6% were very low birth weight (< 1500 g). The median age of infection was 14.0 days. Risk factors for MDRE included prematurity ( p = 0.01), lower birth weight ( p = 0.04), maternal HIV infection ( p = 0.02) and oxygen on day 28 ( p < 0.001). The most common isolate was Klebsiella pneumoniae (66.2%). Total MDRE isolates increased from 0.39 per 1000 neonatal admissions in 2013 to 1.4 per 1000 neonatal admissions in 2015 ( p < 0.001). There was an increase in carbapenem-resistant Enterobacteriaceae (CRE) from 2.6% in 2013 to 8.9% in 2015 ( p = 0.06). Most of the CRE were New Delhi metallo—β lactamase- (NDM) producers. The all-cause mortality rate was 33.3%. Birth weight ( p = 0.003), necrotising enterocolitis ( p < 0.001) and mechanical ventilation ( p = 0.007) were significantly associated with mortality. Serratia marcescens was isolated in 55.2% of neonates that died. Conclusions There was a significant increase in MDRE in neonatal sepsis during the study period, with the emergence of CRE. This confirms the urgent need to intensify antimicrobial stewardship efforts and address infection control and prevention in neonatal units in LMICs. Overuse of broad- spectrum antibiotics should be prevented.

ObjectiveTo gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR).DesignA web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns.Setting39 NNUs from 12 countries.PatientsAny neonate admitted to one of the participating NNUs.InterventionsThis was an observational cohort study.ResultsThe number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions <32 weeks ranged from 0% to 19%, and the majority of units (26/39, 66%) use Essential Medicines List ‘Access’ antimicrobials as their first-line treatment in neonatal sepsis. Cephalosporin resistance rates in Gram-negative isolates ranged from 26% to 84%, and carbapenem resistance rates ranged from 0% to 81%. Glycopeptide resistance rates among Gram-positive isolates ranged from 0% to 45%.ConclusionAMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally.

Introduction Candida auris is a multidrug-resistant fungal pathogen endemic in South African hospitals. Materials and methods We tested bloodstream C. auris isolates that were submitted to a reference laboratory for national laboratory-based surveillance for candidaemia, 2016-2017. We confirmed species identification by phenotypic/molecular methods. We tested susceptibility to amphotericin B, anidulafungin, caspofungin, micafungin, itraconazole, posaconazole, voriconazole, fluconazole and flucytosine using broth microdilution (BMD) and Etest. We interpreted minimum inhibitory concentrations (MICs) using tentative breakpoints. We sequenced the genomes of a subset of isolates and compared to the C. auris B8441 reference strain. Results Of 400 C. auris isolates, 361 (90%) were resistant to at least one antifungal agent, 339 (85%) to fluconazole alone (MIC of ≥32 mg/L), 19 (5%) to fluconazole and amphotericin B (MIC ≥2 mg/L) and one (0.3%) to amphotericin B alone. Two (0.5%) isolates from a single patient were pan-resistant (fluconazole, amphotericin B, echinocandins). Of 93 isolates selected for whole genome sequencing, 78 clustered in clade III including the pan-resistant isolates, 13 in clade I and two in clade IV. Eighty-four of these (91%) were resistant to at least one antifungal agent; both resistant and susceptible isolates had mutations. The common substitutions identified across the different clades were VF125AL, Y132F, K177R, N335S, E343D in ERG11 ; N647T in MRR1; A651P, A657V, S195G in TAC1b; S639P in FKS1; and S58T in ERG3 genes. Conclusions Most South African C. auris isolates were resistant to azoles, though resistance to polyenes and echinocandins was less common. We observed mutations in resistance genes even in phenotypically-susceptible isolates.

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