Antimicrobial resistance and antimicrobial stewardship in South Africa: a survey of healthcare workers in academic and nonacademic hospitals.

Objective: Antimicrobial stewardship programmes (ASPs) facilitate appropriate antimicrobial use and require contextualization for optimal functioning. We aimed to investigate perceptions of and antimicrobial resistance (AMR) and ASPs among healthcare workers in academic and nonacademic hospitals. Design: Cross-sectional survey. Setting: Three academic (Charlotte Maxeke Johannesburg Academic, Inkosi Albert Luthuli, Tygerberg) and three nonacademic hospitals (Leratong, Prince Mshiyeni Memorial, and Paarl) in South Africa from January to June 2022. Participants: Doctors, nurses, and pharmacists. Methods: Voluntary questionnaire using Google Forms, encompassing AMR, ASPs, and selected discipline-specific components. Results: Participants comprised 79 doctors (50 academic), 178 nurses (169 academic), and 21 pharmacists (18 academic) and were female predominant. AMR was a problem in academic hospitals (74.7% vs 51.2%, p 0.004); 73.5% overall reported inappropriate antimicrobial use as a major contributor. Adequate education on antimicrobials occurred in only 36.4% overall. Microbiological testing guided therapy more often in nonacademic settings (80.0% vs 50.2%, p <0.001). In both settings, antimicrobial availability drove selection in 48.2%. Overall, ASPs improved patient care (89.8%) and reduced antimicrobial use (86.9%), although felt to override prescriber autonomy in academic settings (29.4% vs 7.5%, p 0.007), mainly among nurses. Only 50.2% reported successful local ASPs. A minority of pharmacists (20.0%) reported sufficient hospital support for ASPs. Education, involvement of infection control staff, and inclusion of nurses in ASPs were most impactful on AMR. Conclusion: Selected healthcare worker perspectives differ by category and setting and can be targeted to improve ASPs. Further studies should target a higher number of clinical staff in both settings.

Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study.

Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole-resistant Candida spp. isolates in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe the epidemiology, Candida spp. distribution, treatment, and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalized infants <60 days postnatal age with sepsis (August 2018-February 2021). A total of 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28-34), and median birth weight was 1270 gr (interquartile range [IQR]: 990-1692). Only a minority had high-risk criteria, such as being born <28 weeks, 19% (24/127), or birth weight <1000 gr, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%), and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole-resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrollment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines.

Our study describes neonates from low- and middle-income countries with neonatal invasive candidiasis (NIC). Most of them were outside the groups considered at high risk for NIC described in high-income countries. Candida spp. epidemiology was also different. The mortality was high (22%). Further research in these settings is required.

Microbe Mail: A microbiology and infectious diseases podcast for clinicians and students.

Microbe Mail medical podcast is an audio-only informal educational platform, which addresses widespread topics in medical microbiology and infectious diseases (ID), with a particular focus on low- and middle-income settings. Podcasting has become a common form of informal learning in healthcare education and for continual professional development (CPD). Contribution: In this article, we discuss the development of the Microbe Mail podcast, its informal microbiology and ID education impact in the 2 years since commencement and future directions to improve uptake in Africa and low- and middle-income countries.

Molecular characterisation of Acinetobacter baumannii isolates from bloodstream infections in a tertiary-level hospital in South Africa.

Acinetobacter baumannii is an opportunistic pathogen and causes various infections in patients. This study aimed to describe the clinical, epidemiological and molecular characteristics of A. baumannii isolated from BCs in patients at a tertiary-level hospital in South Africa. Ninety-six isolates from bloodstream infections were collected. Clinical characteristics of patients were recorded from patient files. Organism identification and AST was performed using automated systems. PCR screening for the mcr-1 to mcr-5 genes was done. To infer genetic relatedness, a dendrogram was constructed using MALDI-TOF MS. All colistin-resistant isolates (n = 9) were selected for WGS. The patients were divided into three groups, infants (<1 year; n = 54), paediatrics (1-18 years; n = 6) and adults (≥19 years; n = 36) with a median age of 13 days, 1 and 41 years respectively. Of the 96 A. baumannii bacteraemia cases, 96.9% (93/96) were healthcare-associated. The crude mortality rate at 30 days was 52.2% (48/92). The majority of the isolates were multidrug-resistant (MDR). All isolates were PCR-negative for the mcr-1 to mcr-5 genes. The majority of the isolates belonged to cluster 1 (62/96) according to the MALDI-TOF MS dendrogram. Colistin resistance was confirmed in nine A. baumannii isolates (9.4%). The colistin-resistant isolates belonged to sequence type (ST) 1 (5/6) and ST2 (1/6). The majority of ST1 isolates showed low SNP diversity (≤4 SNPs). All the colistin-resistant isolates were resistant to carbapenems, exhibited an XDR phenotype and harboured the bla OXA-23 gene. The bla NDM gene was only detected in ST1 colistin-resistant isolates (n = 5). The lpsB gene was detected in all colistin-resistant isolates as well as various efflux pump genes belonging to the RND, the MFS and the SMR families. The lipooligosaccharide OCL1 was detected in all colistin-resistant ST1 and ST2 isolates and the capsular polysaccharide KL3 and KL17 were detected in ST2 and ST1 respectively. This study demonstrated a 9.4% prevalence of colistin-resistant ST1 and ST2 A. baumannii in BC isolates. The detection of the lpsB gene indicates a potential threat and requires close prospective monitoring.

Acinetobacter baumannii complex, national laboratory-based surveillance in South Africa, 2017 to 2019.

OBJECTIVE: We aimed to provide an analysis of A. baumannii complex (ABC) isolated from blood cultures in South Africa. MATERIALS AND METHODS: ABC surveillance was conducted from 1 April 2017 to 30 September 2019 at 19 hospital sites from blood cultures of any age and sex. Organism identification was performed using the MALDI-TOF MS and antimicrobial susceptibility testing (AST), MicroScan Walkaway System. We confirmed colistin resistance with Sensititre, FRCOL panel, and selected for whole-genome sequencing. RESULTS: During the study period, we identified 4822 cases of ABC, of which 2152 cases were from 19 enhanced surveillance sites were reported during the enhanced surveillance period (1 August 2018 to 30 September 2019). Males accounted for 54% (2611/4822). Of the cases with known age, 41% (1968/4822) were infants (< 1-year-old). Seventy-eight percent (1688/2152) of cases had a known hospital outcome, of which 36% (602/1688) died. HIV status was known for 69% (1168/1688) of cases, and 14% (238/1688) were positive. Eighty-two percent (1389/1688) received antimicrobial treatment in admission. Three percent (35/1389) of cases received single colistin. Four percent (75/2033) were resistant to colistin. At least 75% of the isolates (1530/2033) can be classified as extensively drug-resistant (XDR), with resistance to most antibiotics except for colistin. The majority, 83% (20/24), of the colistin-resistant isolates were of the sequence type (ST) 1. Resistance genes, both plasmid- and chromosomal- mediated were not observed. Although all isolates had, nine efflux pump genes related to antimicrobial resistance. CONCLUSION: Our surveillance data contributed to a better understanding of the natural course of A. baumannii disease, the patient characteristics among infants, and the level of resistance. At least two-thirds of the isolates were extensively drug-resistant, and four percent of isolates were resistant to colistin.

Case-fatality and sequelae following acute bacterial meningitis in South Africa, 2016 through 2020.

OBJECTIVES: Providing country-specific estimates of case fatality and sequelae from bacterial meningitis (BM) is important to evaluate and monitor progress toward the World Health Organization's roadmap to "defeating meningitis by 2030". METHODS: From 2016-2020, GERMS-SA conducted enhanced surveillance at 26 hospitals across South Africa. Episodes of laboratory-confirmed BM due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis were included. Risk factors for in-hospital death and sequelae at hospital discharge among survivors were analyzed. RESULTS: Of 12,717 invasive bacterial infections reported nationally, 39% (4980) were from enhanced surveillance sites, including 4159 pneumococcal, 640 H. influenzae, and 181 meningococcal infections. BM accounted for 32% (1319/4159) of pneumococcal, 21% (136/640) of H. influenzae, and 83% (151/181) of meningococcal invasive diseases. Clinical data were available for 91% (1455/1606) of BM: 26% (376/1455) were aged <5 years, 50% (726/1455) were female, and 62% (723/1171) with known HIV results, were HIV-infected. In-hospital case fatality was 37% (534/1455), and 24% (222/921) of survivors had adverse sequelae. Risk factors for death included altered mental status, HIV infection, and comorbidities. Risk factors for adverse sequelae included altered mental status and antimicrobial nonsusceptibility. CONCLUSION: BM in South Africa has a high case fatality, and adverse sequelae frequently occur among survivors. Those with comorbidities (including HIV) are at the highest risk.

Comparison of carbapenem minimum inhibitory concentrations of Oxacillin-48-like Klebsiella pneumoniae by Sensititre, Vitek 2, MicroScan, and Etest.

OBJECTIVES: The aim of this laboratory-based study was to compare carbapenem MICs yielded by Sensititre, Vitek 2, MicroScan WalkAway plus and Etest for Oxacillin (OXA)-48-like Klebsiella pneumoniae isolates. METHODS: Analysis was performed for categorical agreement for ertapenem, meropenem, and imipenem, and the proportion of isolates with MICs ≤8µg/mL and the MIC50/MIC90 for meropenem and imipenem, from a convenience sample of 82 deduplicated blood culture OXA-48-like K. pneumoniae isolates. RESULTS: The proportion of isolates testing susceptible to ertapenem by Etest (19/82, 23.1%) differed from Sensititre/Vitek (0/82) and MicroScan (2/82, 2.4%) (p < 0.001 for all). For meropenem, the proportion of isolates susceptible by Etest (31/82, 37.8%) differed from Sensititre/Vitek (16/82, 19.5%) (p = 0.015). There was variation in the proportion of isolates that tested imipenem susceptible when comparing Sensititre (9/82, 11%) and Vitek (8/82, 9.8%) to MicroScan (27/82, 32.9%), p = 0.001 and p < 0.001, respectively, Sensititre and Vitek to Etest (45/82, 54.9%), p < 0.001 for both, and MicroScan to Etest, p = 0.007. The proportion of isolates with meropenem MICs ≤8µg/mL with Sensititre and Vitek differed significantly from Etest, 58.5% and 85.4%, respectively, p < 0.001. A 2-fold difference between the Sensititre and Vitek meropenem and imipenem MIC at which ≥50% of isolates were inhibited compared to the MicroScan, and a 4-fold difference compared to Etest, was present. CONCLUSIONS: Substantial variability in carbapenem MICs for OXA-48-like carbapenemase-producing Enterobacterales isolates by the four methods was demonstrated. Performance characteristics verification of MIC methods in use for the predominant carbapenemase-producing Enterobacterales type is required by laboratories to optimize the accuracy of carbapenem reporting.

Comparison of Zinc Concentrations in the Broth of Commercial Automated Susceptibility Testing Devices (Vitek 2, MicroScan, BD Phoenix, and Sensititre).

Up to 4-fold differences in zinc concentrations have been observed in commercial broth routinely utilized for susceptibility testing via manual broth microdilution. Herein, we report the concentration of zinc in the broth of common automated susceptibility testing (AST) platforms (Vitek, MicroScan, BD Phoenix, and Sensititre). For AST platforms with lyophilized broth contents (Vitek and MicroScan), wells were rehydrated with appropriate diluent, and contents were aliquoted out for zinc assay. Aliquots from the manufacturer-specific broth (premade cation-adjusted Mueller-Hinton broth [caMHB]) for BD Phoenix and Sensititre were also assayed by inductively coupled plasma mass spectrometry. Up to a 10-fold difference in zinc concentrations was observed across the 4 platforms (MicroScan: 0.46 mg/L; BD Phoenix: 1.16 mg/L; Vitek: 1.22 mg/L; Sensititre: 4.49 mg/L). Attention should be given to the supraphysiologic and variable zinc concentrations observed in broth used in automated platforms and the subsequent implications for susceptibility testing of metallo-ß-lactamase (MBL)-harboring isolates. This variability also hampers efforts to develop a standardized method to uniformly reduce zinc concentrations in broth and mimic physiologic zinc conditions. IMPORTANCE Growing data on the impact of extracellular zinc concentration on metallo-ß-lactamase-mediated resistance has shed light on the importance of susceptibility testing media. However, there are no studies documenting the amount of zinc in commonly utilized automated susceptibility testing (AST) platforms. This study reveals supraphysiologic zinc concentrations as well as large zinc variability among AST platforms and highlights the challenges this raises in the development of zinc-limited media.

Incidence of candidemia and prevalence of azole-resistant candidemia at a tertiary South African hospital - A retrospective laboratory analysis 2016-2020.

Background: Candidemia is associated with high morbidity and mortality. The epidemiology of candidemia has changed globally over the past 20 years. South African surveillance demonstrated a shift in epidemiology from Candida albicans to non-albicans species including Candida parapsilosis and Candida auris. Hospital-level candidemia incidence from South Africa has not been reported previously. Methods: We performed a retrospective laboratory-based analysis of blood cultures with confirmed causative agents of candidemia. Ward type, department, gender and admission to critical care units were captured. Data were analysed in Microsoft Excel, Statistical Package for the Social Sciences (SPSS) and Epitools. Results: The incidence of candidemia during the study period was 2.87 per 1000 admissions. The total proportion of non-albicans species causing candidemia was 425/618 (69.7%). Overall, 65.4% of candidemia cases occurred in non-critical care units. There was a significant increase in the proportion of C. auris isolates between 2016 and 2020 (p < 0.001). Isolation of C. auris was associated with admission to critical care units (p < 0.001, odds ration [OR] 3.856, 95% confidence interval [CI]: 2.360-6.300). The proportion of azole-resistant candidemia cases increased from 21/53 (39.6%) in 2016 to 41/59 (69.5%) in 2020 (p = 0.002). Conclusion: The incidence of candidemia remained stable over the five-year study period. However, the proportion of C. auris isolates increased significantly during the study period as did the overall proportion of azole-resistant candidemia. Antifungal stewardship and continued hospital-level surveillance are imperative.

Clinical and laboratory features of patients with Candida auris cultures, compared to other Candida, at a South African Hospital.

INTRODUCTION: Multidrug resistant Candida auris is an emerging threat worldwide. It has been identified in Africa, however, there is minimal data available comparing C. auris to other Candida species in Africa. METHODOLOGY: Retrospective, case control study at a tertiary South African Hospital. Clinical and laboratory features of patients with positive C. auris clinical cultures from 1 January 2015 to 31 August 2018 were compared to patients who cultured C. albicans and C. glabrata. RESULTS: Forty-five clinical cases with C. auris cultures were identified. The median age was 32 years (IQR = 26-46). The median duration of hospital stay was 64 days (IQR = 39-88) and median time from admission to diagnosis 35 days (IQR = 21-53). Indwelling devices and previous antibiotic exposure were found to be significant risk factors. All C. auris isolates were susceptible to amphotericin B and micafungin. Patients treated with amphotericin B alone, had a higher mortality (73.33%, n = 11/15) than patients treated with an echinocandin (54.55%, n = 6/11), however this was not statistically significant. All C. auris isolates were healthcare associated with 80% (n = 36/45) acquired in ICU. The 30-day all-cause in-patient mortality was 42% (n = 19/45) for C. auris, 36% (n = 16/45) for C. albicans and 53% (n = 24/45) for C. glabrata. CONCLUSIONS: C. auris is an emerging multi drug resistant threat in South Africa. Improved access to echinocandins and improvement of infection prevention and control strategies are imperative to prevent further morbidity and mortality due to this pathogen.

Antibiotic Discovery and Resistance: The Chase and the Race.

The history of antimicrobial resistance (AMR) evolution and the diversity of the environmental resistome indicate that AMR is an ancient natural phenomenon. Acquired resistance is a public health concern influenced by the anthropogenic use of antibiotics, leading to the selection of resistant genes. Data show that AMR is spreading globally at different rates, outpacing all efforts to mitigate this crisis. The search for new antibiotic classes is one of the key strategies in the fight against AMR. Since the 1980s, newly marketed antibiotics were either modifications or improvements of known molecules. The World Health Organization (WHO) describes the current pipeline as bleak, and warns about the scarcity of new leads. A quantitative and qualitative analysis of the pre-clinical and clinical pipeline indicates that few antibiotics may reach the market in a few years, predominantly not those that fit the innovative requirements to tackle the challenging spread of AMR. Diversity and innovation are the mainstays to cope with the rapid evolution of AMR. The discovery and development of antibiotics must address resistance to old and novel antibiotics. Here, we review the history and challenges of antibiotics discovery and describe different innovative new leads mechanisms expected to replenish the pipeline, while maintaining a promising possibility to shift the chase and the race between the spread of AMR, preserving antibiotic effectiveness, and meeting innovative leads requirements.

Trends in the epidemiology of urinary tract infections in pregnancy at a tertiary hospital in Johannesburg: Are contemporary treatment recommendations appropriate?

BACKGROUND: Urinary tract infections (UTIs) are common during pregnancy and are associated with maternal and foetal complications. Empiric antibiotic choices in pregnancy require consideration of efficacy and safety, resulting in limited oral options. With rapidly evolving antibiotic resistance, surveillance to guide empiric treatment recommendations is essential. METHODS: A retrospective analysis of urine culture isolates from the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) Obstetrics Department for 1 January 2015 to 31 December 2020 was performed. RESULTS: The top 3 pathogens were Escherichia coli, Enterococcus faecalis and Klebsiella pneumoniae. For E. coli susceptibility to cefuroxime declined (95% to 81%, p < 0.0001). Similarly, the E. coli extended spectrum beta-lactamase rate increased from 5% to 10% (p = 0.04). E. coli susceptibility to nitrofurantoin (93%) and fosfomycin (96%) remained high. In 2019, carbapenem-resistant K. pneumoniae emerged. Ampicillin susceptibility was high amongst the E. faecalis isolates. Amoxicillin-clavulanate demonstrated high levels of activity against the top 3 uropathogens. CONCLUSION: The Essential Drug List recommended antibiotics for lower UTIs, nitrofurantoin and fosfomycin, are appropriate empiric options for E. coli, the most common uropathogen in the CMJAH obstetric population. The high rate of E. faecalis susceptibility to nitrofurantoin reported from other Gauteng tertiary obstetric patients, suggests that nitrofurantoin will provide adequate empiric cover for a large proportion of UTIs. However, the determination of the E. faecalis nitrofurantoin and fosfomycin susceptibility rates in the CMJAH obstetric population will provide useful data. Periodic surveillance at the various levels of antenatal care in different regions of South Africa and the determination of risk factors for infections with resistant uropathogens is needed.

The potential impact of the COVID-19 pandemic on global antimicrobial and biocide resistance: an AMR Insights global perspective.

The COVID-19 pandemic presents a serious public health challenge in all countries. However, repercussions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on future global health are still being investigated, including the pandemic's potential effect on the emergence and spread of global antimicrobial resistance (AMR). Critically ill COVID-19 patients may develop severe complications, which may predispose patients to infection with nosocomial bacterial and/or fungal pathogens, requiring the extensive use of antibiotics. However, antibiotics may also be inappropriately used in milder cases of COVID-19 infection. Further, concerns such as increased biocide use, antimicrobial stewardship/infection control, AMR awareness, the need for diagnostics (including rapid and point-of-care diagnostics) and the usefulness of vaccination could all be components shaping the influence of the COVID-19 pandemic. In this publication, the authors present a brief overview of the COVID-19 pandemic and associated issues that could influence the pandemic's effect on global AMR.

Epidemiology of Culture-confirmed Candidemia Among Hospitalized Children in South Africa, 2012-2017.

BACKGROUND: We aimed to describe the epidemiology of candidemia among children in South Africa. METHODS: We conducted laboratory-based surveillance among neonates (≤28 days), infants (29 days to <1 year), children (1-11 years) and adolescents (12-17 years) with Candida species cultured from blood during 2012-2017. Identification and antifungal susceptibility of viable isolates were performed at a reference laboratory. We used multivariable logistic regression to determine the association between Candida parapsilosis candidemia and 30-day mortality among neonates. RESULTS: Of 2996 cases, neonates accounted for 49% (n = 1478), infants for 27% (n = 806), children for 20% (n = 589) and adolescents for 4% (n = 123). The incidence risk at tertiary public sector hospitals was 5.3 cases per 1000 pediatric admissions (range 0.39-119.1). Among 2943 cases with single-species infections, C. parapsilosis (42%) and Candida albicans (36%) were most common. Candida auris was among the 5 common species with an overall prevalence of 3% (n = 47). Fluconazole resistance was more common among C. parapsilosis (55% [724/1324]) versus other species (19% [334/1737]) (P < 0.001). Of those with known treatment (n = 1666), 35% received amphotericin B deoxycholate alone, 32% fluconazole alone and 30% amphotericin B deoxycholate with fluconazole. The overall 30-day in-hospital mortality was 38% (n = 586) and was highest among neonates (43% [323/752]) and adolescents (43% [28/65]). Compared with infection with other species, C. parapsilosis infection was associated with a reduced mortality among neonates (adjusted odds ratio 0.41, 95% confidence interval: 0.22-0.75, P = 0.004). CONCLUSIONS: Candidemia in this setting mainly affected neonates and infants and was characterized by fluconazole-resistant C. parapsilosis with no increased risk of death.

A retrospective analysis of community-onset bloodstream infections at a tertiary-care academic hospital in South Africa. Are current empiric antimicrobial practices appropriate?

Background: Community-onset bloodstream infection (CO-BSI) is associated with substantial morbidity and mortality. Knowledge of locally prevalent pathogens and antimicrobial susceptibility patterns can promptly guide appropriate empiric therapy and improve outcomes. Objectives: We sought to determine the epidemiology of CO-BSI, the blood culture positivity rate and the contamination rate. We also sought to establish appropriateness of current empiric antimicrobial therapy practices. Methods: We retrospectively analyzed blood cultures taken from January 2015 to December 2019 at the emergency departments (EDs) of a tertiary-care academic hospital in South Africa using extracted laboratory data. Results: The overall positivity rate of blood cultures taken at the EDs was 15% (95% confidence interval [CI], 0.15-0.16) and the contamination rate was 7% (95% CI, 0.06-0.07). Gram-positive bacteria predominated in the pediatric cohort: neonates, 52 (54%) of 96; infants, 57 (52%) of 109; older children, 63 (61%) of 103. Methicillin-susceptible Staphylococcus aureus was the predominant pathogen among older children: 30 (35%) of 85. Escherichia coli was the most common pathogen isolated among adults and the elderly: 225 (21%) of 1,060 and 62 (29%) of 214, respectively. Among neonates, the susceptibility of E. coli and Klebsiella pneumoniae to the combination of ampicillin and gentamicin was 17 (68%) of 25. Among adults, the susceptibility of the 5 most common pathogens to amoxicillin-clavulanate was 426 (78%) of 546 and their susceptibility to ceftriaxone was 481 (85%) of 565 (P = .20). The prevalence of methicillin-resistant S. aureus, extended-spectrum ß-lactamase-producing and carbapenem-resistant Enterobacterales were low among all age groups. Conclusions: Review of blood culture collection techniques is warranted to reduce the contamination rate. High rates of resistance to currently prescribed empiric antimicrobial agents for CO-BSI warrants a re-evaluation of local guidelines.

Comparative sensitivity of 1,3 beta-D-glucan for common causes of candidaemia in South Africa.

Culture-based diagnosis of candidaemia suffers poor sensitivity and prolonged turnaround time. The 1,3-beta-D-glucan (BDG) assay is a non-culture-based broad fungal antigen with rapid turnaround time. To assess overall, species-specific and population-specific sensitivity of the BDG assay for candidaemia, to determine if the BDG assay is able to detect candidaemia prior to blood culture collection, and to evaluate the performance of the assay for the detection of Candida auris candidaemia. A retrospective review of all blood cultures (BC) with C albicans, C parapsilosis, C glabrata, C krusei and C auris was performed. A corresponding BDG result (Fungitell® ) within 10 days of the BC was sought on the laboratory information system. Overall sensitivity of the assay was 79% (95% CI 73-85; 173/218). Per species sensitivity was 81% (95% CI 72-90; 66/81) for C albicans, 72% (61-83; 60/83) for C parapsilosis, 90% (95% CI 79-100; 27/30) for C glabrata, 71% (95% CI 43-99; 10/14) C auris and 100% (10/10) for C krusei. No statistically significant difference in sensitivity between species was noted (P = .093). The assay demonstrated 92% (59/64) sensitivity in neonatal ICU (P = .047) compared to 94% (15/16) in surgery, 81% (59/73) in adult ICUs and 71% (15/21) in Oncology. BDG results were positive up to 10 days prior to blood culture collection with no significant difference in detection rate (P = .563). BDG results were positive up to 10 days prior to blood culture collection. BDG when collected a mean of 2.5 days (range 1-10 days) prior to blood culture collection were positive.

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.

Federation of Infectious Diseases Societies of Southern Africa guideline: Recommendations for the detection, management and prevention of healthcare-associated Candida auris colonisation and disease in South Africa.

Candida auris has been detected at almost 100 South African hospitals, causing large outbreaks in some facilities, and this pathogen now accounts for approximately 1 in 10 cases of candidaemia. The objective of this guideline is to provide updated, evidence-informed recommendations outlining a best-practice approach to prevent, diagnose and manage C. auris disease in public- and private-sector healthcare settings in South Africa. The 18 practical recommendations cover five focus areas: laboratory identification and antifungal susceptibility testing, surveillance and outbreak response, infection prevention and control, clinical management and antifungal stewardship.

Evaluation of the RESIST-4 O.K.N.V immunochromatographic lateral flow assay for the rapid detection of OXA-48, KPC, NDM and VIM carbapenemases from cultured isolates.

PURPOSE: This study aimed to evaluate the performance of the RESIST-4 O.K.N.V immunochromatographic lateral flow assay for the detection of OXA-48, KPC, NDM and VIM carbapenemases in 100 clinical Enterobacteriaceae isolates using solid culture media. METHODOLOGY: In total, 100 clinical Enterobacteriaceae isolates with characterized ß-lactamase enzymes (OXA-48 n=46, KPC n =4, NDM n =43 and VIM n =10) were evaluated using the RESIST-4 O.K.N.V assay. The assay was also evaluated using carbapenem-sensitive control strains and confirmed non-carbapenemase-producing Enterobacteriaceae clinical isolates resistant to carbapenems. Inter-rater agreement of the test was evaluated by four different users who tested 11 randomly selected isolates daily over 3 days. RESULTS: Overall accuracy of the assay was 99.5  %. For the detection of KPC, OXA-48 and its variants and VIM the assay correctly identified 100  % of the isolates when compared to PCR. Initial performance for NDM detection was sensitivity=95.3 %, specificity=100  %. Two PCR positive Providencia rettgeri isolates rendered false negative results on the assay. Retesting from a carbapenem zone of inhibition rendered a positive result for both isolates increasing the sensitivity to 100  %. No false positive results or cross reactions were detected. CONCLUSION: The RESIST-4 O.K.N.V is reliable, sensitive and specific for the detection of OXA-48, KPC, NDM and VIM carbapenemases. Further evaluation on improving NDM detection in organisms from the Proteeae tribe is warranted to determine optimal test conditions.