Etest ECVs/ECOFFs for Detection of Resistance in Prevalent and Three Nonprevalent Candida spp. to Triazoles and Amphotericin B and Aspergillus spp. to Caspofungin: Further Assessment of Modal Variability.

Susceptibility testing is an important tool in the clinical setting; its utility is based on the availability of categorical endpoints, breakpoints (BPs), or epidemiological cutoff values (ECVs/ECOFFs). CLSI and EUCAST have developed antifungal susceptibility testing, BPs, and ECVs for some fungal species. Although the concentration gradient strip bioMérieux Etest is useful for routine testing in the clinical laboratory, ECVs are not available for all agent/species; the lack of clinical data precludes development of BPs. We reevaluated and consolidated Etest data points from three previous studies and included new data. We defined ECOFFinder Etest ECVs for three sets of species-agent combinations: fluconazole, posaconazole, and voriconazole and 9 Candida spp.; amphotericin B and 3 nonprevalent Candida spp.; and caspofungin and 4 Aspergillus spp. The total of Etest MICs from 23 laboratories (Europe, the Americas, and South Africa) included (antifungal agent dependent): 17,242 Candida albicans, 244 C. dubliniensis, 5,129 C. glabrata species complex (SC), 275 C. guilliermondii (Meyerozyma guilliermondii), 1,133 C. krusei (Pichia kudriavzevii), 933 C. kefyr (Kluyveromyces marxianus), 519 C. lusitaniae (Clavispora lusitaniae), 2,947 C. parapsilosis SC, 2,214 C. tropicalis, 3,212 Aspergillus fumigatus, 232 A. flavus, 181 A. niger, and 267 A. terreus SC isolates. Triazole MICs for 66 confirmed non-wild-type (non-WT) Candida isolates were available (ERG11 point mutations). Distributions fulfilling CLSI ECV criteria were pooled, and ECOFFinder Etest ECVs were established for triazoles (9 Candida spp.), amphotericin B (3 less-prevalent Candida spp.), and caspofungin (4 Aspergillus spp.). Etest fluconazole ECVs could be good detectors of Candida non-WT isolates (59/61 non-WT, 4 of 6 species).

Method-Dependent Epidemiological Cutoff Values for Detection of Triazole Resistance in Candida and Aspergillus Species for the Sensititre YeastOne Colorimetric Broth and Etest Agar Diffusion Methods.

Although the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria are not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole, and voriconazole SYO and Etest MICs from 39 laboratories representing all continents for (method/agent-dependent) 11,171 Candida albicans, 215 C. dubliniensis, 4,418 C. glabrata species complex, 157 C.guilliermondii (Meyerozyma guilliermondii), 676 C. krusei (Pichia kudriavzevii), 298 C.lusitaniae (Clavispora lusitaniae), 911 C.parapsilosissensu stricto, 3,691 C.parapsilosis species complex, 36 C.metapsilosis, 110 C.orthopsilosis, 1,854 C.tropicalis, 244 Saccharomyces cerevisiae, 1,409 Aspergillus fumigatus, 389 A.flavus, 130 A.nidulans, 233 A.niger, and 302 A.terreus complex isolates. SYO/Etest MICs for 282 confirmed non-wild-type (non-WT) isolates were included: ERG11 (C. albicans), ERG11 and MRR1 (C. parapsilosis), cyp51A (A. fumigatus), and CDR2 and CDR1 overexpression (C. albicans and C. glabrata, respectively). Interlaboratory modal agreement was superior by SYO for yeast species and by the Etest for Aspergillus spp. Distributions fulfilling CLSI criteria for epidemiological cutoff value (ECV) definition were pooled, and we proposed SYO ECVs for S. cerevisiae and 9 yeast and 3 Aspergillus species and Etest ECVs for 5 yeast and 4 Aspergillus species. The posaconazole SYO ECV of 0.06 µg/ml for C. albicans and the Etest itraconazole ECV of 2 µg/ml for A. fumigatus were the best predictors of non-WT isolates. These findings support the need for method-dependent ECVs, as, overall, the SYO appears to perform better for susceptibility testing of yeast species and the Etest appears to perform better for susceptibility testing of Aspergillus spp. Further evaluations should be conducted with more Candida mutants.

Waterborne outbreak of gastroenteritis on the KwaZulu-Natal Coast, South Africa, December 2016/January 2017.

An unexpected increase in gastroenteritis cases was reported by healthcare workers on the KwaZulu-Natal Coast, South Africa, January 2017 with >600 cases seen over a 3-week period. A case-control study was conducted to identify the source and risk factors associated with the outbreak so as to recommend control and prevention measures. Record review identified cases and controls and structured-telephonic interviews were conducted to obtain exposure history. Stool specimens were collected from 20 cases along with environmental samples and both screened for enteric pathogens. A total of 126 cases and 62 controls were included in the analysis. The odds of developing gastroenteritis were 6.0 times greater among holiday makers than residents (95% confidence interval (CI) 2.0-17.7). Swimming in the lagoon increased the odds of developing gastroenteritis by 3.3 times (95% CI 1.06-10.38). Lagoon water samples tested positive for norovirus (NoV) GI.6, GII.3 and GII.6, astrovirus and rotavirus. Eleven (55%) stool specimens were positive for NoV with eight genotyped as GI.1 (n = 2), GI.5 (n = 3), GI.6 (n = 2), and GI.7 (n = 1). A reported sewage contamination event impacting the lagoon was the likely source with person-to-person spread perpetuating the outbreak. Restriction to swimming in the lagoon was apparently ineffective at preventing the outbreak, possibly due to inadequate enforcement, communication and signage strategies.

Multicenter Study of Method-Dependent Epidemiological Cutoff Values for Detection of Resistance in Candida spp. and Aspergillus spp. to Amphotericin B and Echinocandins for the Etest Agar Diffusion Method.

Method-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of either Candida or Aspergillus species with amphotericin B or echinocandins. In addition, reference caspofungin MICs for Candida spp. are unreliable. Candida and Aspergillus species wild-type (WT) Etest MIC distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341 Candida albicans, 113 C. dubliniensis, 1,683 C. glabrata species complex (SC), 709 C. krusei, 767 C. parapsilosis SC, 796 C. tropicalis, 1,637 Aspergillus fumigatus SC, 238 A. flavus SC, 321 A. niger SC, and 247 A. terreus SC isolates. Etest MICs from 15 laboratories (in Argentina, Europe, Mexico, South Africa, and the United States) were pooled to establish Etest ECVs. Anidulafungin, caspofungin, micafungin, and amphotericin B ECVs (in micrograms per milliliter) encompassing ≥97.5% of the statistically modeled population were 0.016, 0.5, 0.03, and 1 for C. albicans; 0.03, 1, 0.03, and 2 for C. glabrata SC; 0.06, 1, 0.25, and 4 for C. krusei; 8, 4, 2, and 2 for C. parapsilosis SC; and 0.03, 1, 0.12, and 2 for C. tropicalis The amphotericin B ECV was 0.25 µg/ml for C. dubliniensis and 2, 8, 2, and 16 µg/ml for the complexes of A. fumigatus, A. flavus, A. niger, and A. terreus, respectively. While anidulafungin Etest ECVs classified 92% of the Candida fks mutants evaluated as non-WT, the performance was lower for caspofungin (75%) and micafungin (84%) cutoffs. Finally, although anidulafungin (as an echinocandin surrogate susceptibility marker) and amphotericin B ECVs should identify Candida and Aspergillus isolates with reduced susceptibility to these agents using the Etest, these ECVs will not categorize a fungal isolate as susceptible or resistant, as breakpoints do.

Multicenter, International Study of MIC/MEC Distributions for Definition of Epidemiological Cutoff Values for Sporothrix Species Identified by Molecular Methods.

Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrixschenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 µg/ml; itraconazole, 2 and 2 µg/ml; posaconazole, 2 and 2 µg/ml; and voriconazole, 64 and 32 µg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 µg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii, as well as ECVs for S. globosa and S. mexicana These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.

A small proportion of community-associated methicillin-resistant Staphylococcus aureus bacteraemia, compared to healthcare-associated cases, in two South African provinces.

We compared the proportion of cases of community-associated and healthcare-associated methicillin-resistant Staphylococcus aureus (CA-MRSA and HA-MRSA, respectively) bacteraemia among patients at five hospitals in the Gauteng and Western Cape provinces in South Africa and described the molecular characteristics and antimicrobial susceptibility trends. This was a cross-sectional study using data collected by enhanced surveillance for S. aureus bacteraemia. A total of 2511 cases of S. aureus bacteraemia were identified from January 2013 to January 2016. Among 1914 cases of S. aureus, 557 (29.1%) cases were identified as MRSA infection. Forty-four cases (44/1914 [2.3%] of all S. aureus cases) were considered CA-MRSA infection and 513/1914 (26.8% of all cases) had HA-MRSA infection; the majority were neonates. CA-MRSA constituted 7.9% (44/557) of all cases of MRSA infection. Staphylococcus aureus isolates demonstrated significantly reduced susceptibility to the following classes of antimicrobial agents: macrolides, tetracyclines, aminoglycosides and cotrimoxazole, in 2015 compared to 2013 (p < 0.05). Of the 557 MRSA isolates, 484 (87%) were typed for SCCmec elements and spa types: the most common SCCmec type was type III (n = 236, 48.76%), followed by type IV (n = 144, 29.76%). The most common spa types were t037 (n = 229, 47.31%) and t1257 (n = 90, 18.60%). Of 28 isolates selected for multilocus sequence typing (MLST), the most common sequence types (STs) were ST239 and ST612 of clonal complex 8 (CC8) (n = 8 each) and a novel ST (ST4121) was obtained for one isolate. This study demonstrates that S. aureus bacteraemia is common in South African academic centres and characterised by HA-MRSA SCCmec types III and IV. A small proportion of CA-MRSA cases were caused by a few different sequence types.

Multicenter study of epidemiological cutoff values and detection of resistance in Candida spp. to anidulafungin, caspofungin, and micafungin using the Sensititre YeastOne colorimetric method.

Neither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established for Candida spp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable. Candida species wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007 Candida albicans, 186 C. dubliniensis, 3,188 C. glabrata complex, 119 C. guilliermondii, 493 C. krusei, 205 C. lusitaniae, 3,136 C. parapsilosis complex, and 1,016 C. tropicalis isolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing ≥97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 µg/ml for C. albicans, 0.12, 0.25, and 0.03 µg/ml for C. glabrata complex, 4, 2, and 4 µg/ml for C. parapsilosis complex, 0.5, 0.25, and 0.06 µg/ml for C. tropicalis, 0.25, 1, and 0.25 µg/ml for C. krusei, 0.25, 1, and 0.12 µg/ml for C. lusitaniae, 4, 2, and 2 µg/ml for C. guilliermondii, and 0.25, 0.25, and 0.12 µg/ml for C. dubliniensis. Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81 Candida isolates with identified fks mutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities of Candida spp. to caspofungin by reference methodologies is not recommended.

Evaluation of screening and treatment of cryptococcal antigenaemia among HIV-infected persons in Soweto, South Africa.

OBJECTIVES: We retrospectively evaluated clinic-based screening to determine the prevalence of cryptococcal antigenaemia and management and outcome of patients with antigenaemia. METHODS: Cryptococcal antigen (CrAg) screening of HIV-infected adults who attended the HIV clinic at Chris Hani Baragwanath Hospital was conducted over 19 months. Data collected from CrAg-positive patients included CD4 T-lymphocyte count at screening, prior or subsequent cryptococcal meningitis (CM), antifungal and antiretroviral treatment and outcome after at least 8 months. RESULTS: Of 1460 patients with no prior CM, 30 (2.1%) had a positive CrAg test. The prevalence of antigenaemia among patients with a CD4 count < 100 cells/µl and no prior CM was 2.8% (20 of 708). Of 29 evaluable CrAg-positive patients with no prior CM, 14 (48%) did not return for post-screening follow-up. Of these 14, five developed CM and one (7%) was known to be alive at follow-up. Of 15 patients who returned for follow-up, two already had evidence of nonmeningeal cryptococcosis. Overall, 11 received fluconazole, one did not and fluconazole treatment was unknown for three. Among these 15, one developed CM and 10 (67%) were known to be alive at follow-up. Overall, 18 (62%) of 29 CrAg-positive patients died or were lost to follow-up. Seven (0.5%) of 1430 CrAg-negative patients developed CM a median of 83 days post-screening (range 34 to 219 days). CONCLUSIONS: Loss to follow-up is the major operational issue relevant to scale-up of screen-and-treat. Patient outcomes may be improved by rapid access to CrAg results and focus on linkage to and retention in HIV care.

Cryptococcus neoformans-Cryptococcus gattii species complex: an international study of wild-type susceptibility endpoint distributions and epidemiological cutoff values for amphotericin B and flucytosine.

Clinical breakpoints (CBPs) are not available for the Cryptococcus neoformans-Cryptococcus gattii species complex. MIC distributions were constructed for the wild type (WT) to establish epidemiologic cutoff values (ECVs) for C. neoformans and C. gattii versus amphotericin B and flucytosine. A total of 3,590 amphotericin B and 3,045 flucytosine CLSI MICs for C. neoformans (including 1,002 VNI isolates and 8 to 39 VNII, VNIII, and VNIV isolates) and 985 and 853 MICs for C. gattii, respectively (including 42 to 259 VGI, VGII, VGIII, and VGIV isolates), were gathered in 9 to 16 (amphotericin B) and 8 to 13 (flucytosine) laboratories (Europe, United States, Australia, Brazil, Canada, India, and South Africa) and aggregated for the analyses. Additionally, 442 amphotericin B and 313 flucytosine MICs measured by using CLSI-YNB medium instead of CLSI-RPMI medium and 237 Etest amphotericin B MICs for C. neoformans were evaluated. CLSI-RPMI ECVs for distributions originating in ≥3 laboratories (with the percentages of isolates for which MICs were less than or equal to ECVs given in parentheses) were as follows: for amphotericin B, 0.5 µg/ml for C. neoformans VNI (97.2%) and C. gattii VGI and VGIIa (99.2 and 97.5%, respectively) and 1 µg/ml for C. neoformans (98.5%) and C. gattii nontyped (100%) and VGII (99.2%) isolates; for flucytosine, 4 µg/ml for C. gattii nontyped (96.4%) and VGI (95.7%) isolates, 8 µg/ml for VNI (96.6%) isolates, and 16 µg/ml for C. neoformans nontyped (98.6%) and C. gattii VGII (97.1%) isolates. Other molecular types had apparent variations in MIC distributions, but the number of laboratories contributing data was too low to allow us to ascertain that the differences were due to factors other than assay variation. ECVs may aid in the detection of isolates with acquired resistance mechanisms.

Cryptococcus neoformans-Cryptococcus gattii species complex: an international study of wild-type susceptibility endpoint distributions and epidemiological cutoff values for fluconazole, itraconazole, posaconazole, and voriconazole.

Epidemiological cutoff values (ECVs) for the Cryptococcus neoformans-Cryptococcus gattii species complex versus fluconazole, itraconazole, posaconazole, and voriconazole are not available. We established ECVs for these species and agents based on wild-type (WT) MIC distributions. A total of 2,985 to 5,733 CLSI MICs for C. neoformans (including isolates of molecular type VNI [MICs for 759 to 1,137 isolates] and VNII, VNIII, and VNIV [MICs for 24 to 57 isolates]) and 705 to 975 MICs for C. gattii (including 42 to 260 for VGI, VGII, VGIII, and VGIV isolates) were gathered in 15 to 24 laboratories (Europe, United States, Argentina, Australia, Brazil, Canada, Cuba, India, Mexico, and South Africa) and were aggregated for analysis. Additionally, 220 to 359 MICs measured using CLSI yeast nitrogen base (YNB) medium instead of CLSI RPMI medium for C. neoformans were evaluated. CLSI RPMI medium ECVs for distributions originating from at least three laboratories, which included ≥95% of the modeled WT population, were as follows: fluconazole, 8 µg/ml (VNI, C. gattii nontyped, VGI, VGIIa, and VGIII), 16 µg/ml (C. neoformans nontyped, VNIII, and VGIV), and 32 µg/ml (VGII); itraconazole, 0.25 µg/ml (VNI), 0.5 µg/ml (C. neoformans and C. gattii nontyped and VGI to VGIII), and 1 µg/ml (VGIV); posaconazole, 0.25 µg/ml (C. neoformans nontyped and VNI) and 0.5 µg/ml (C. gattii nontyped and VGI); and voriconazole, 0.12 µg/ml (VNIV), 0.25 µg/ml (C. neoformans and C. gattii nontyped, VNI, VNIII, VGII, and VGIIa,), and 0.5 µg/ml (VGI). The number of laboratories contributing data for other molecular types was too low to ascertain that the differences were due to factors other than assay variation. In the absence of clinical breakpoints, our ECVs may aid in the detection of isolates with acquired resistance mechanisms and should be listed in the revised CLSI M27-A3 and CLSI M27-S3 documents.

Adequacy of paediatric renal tract ultrasound requests and reports in a general radiology department.

BACKGROUND: According to current guidelines, US is the most important modality for imaging urinary tract infections (UTI) in children. OBJECTIVES: (1) To assess the adequacy of paediatric renal US requests and reports in a general radiology department, and correlate the request adequacy and the performing radiologist's experience with report adequacy. (2) To determine the yield of abnormal findings. MATERIALS AND METHODS: Retrospective review of renal US requests. The information was scored: requests 0-3 (3 as highest adequacy) and reports 0-21 (21 as highest adequacy). Correlation tests used included Spearman's correlation, Kruskal-Wallis test, Chi-square test of independence and Fisher exact test. RESULTS: Mean report adequacy score was 6.67/21. Trainees did 87% of all scans and performed better (score 6.76) than the staff radiologists (score 6.08). Hydronephrosis was the most common abnormality. There was no correlation between request or reporter rank and reporting adequacy. CONCLUSION: Renal US requests and reports are inadequate. To improve reporting standards for trainees and specialists, a renal ultrasound reporting template was designed for use.

MDCT in the diagnosis of small-bowel obstruction by a retained surgical swab.

We describe a case report of gossypiboma (retained surgical swab), a rare occurrence secondary to a previous open surgical procedure. The incidence has been estimated at between 1 in 100 to 5 000 surgical procedures.

Histopathological features in advanced abdominal pregnancies co-infected with SARS-CoV-2 and HIV-1 infections: A case evaluation.

Objectives: This study aims to provide a semi-qualitative histopathological report of the dual SARS-CoV-2 and HIV infected placentae in the third trimester of Advanced Abdominal Pregnancy (AAP). Study design: Four AAP placentae in the third trimester of pregnancy (two positive for HIV-1 and two positives for SARS-CoV-2) were histologically examined. Results: The SARS-CoV-2+ HIV+ placentae were dysmorphic in shape compared to the flattened disc-like shape noted in the SARS-CoV-2+HIV-, SARS-CoV-2-HIV+and SARS-CoV-2-HIV- placentae. Diffused syncytial knots and syncytial degeneration were observed in all placentae. Intermittent cytotrophoblast increase, perivillous and intravillous fibrin deposition, mononuclear inflammatory cells with widespread degeneration/necrosis of the syncytiotrophoblast and microcalcification were pronounced in the SARS-CoV-2+HIV+ compared to the SARS-CoV-2+HIV- placentae. Vascular pathological changes included thrombi, ectasis, mural hypertrophy and atherotic vessels. Conclusion: Elevated syncytial trophoblast injury, villitis, microcalcifications and mineralisation of the syncytial basement membrane in the AAP placentae may be due to SARS-CoV-2 viral transgression instead of HIV infection alone. Vascular malperfusion is suggestive of a hypoxic insult arising from a compensatory response to meet the fetal oxygen and nutrient demands of an AAP. Placentae from HIV infected women on antiretroviral treatment were characterised by vascular malperfusion.

COVID-19 response in South African communities: Screening, testing, tracing and movement modelling.

In South Africa (SA), the first case of COVID-19 was reported on 5 March 2020 from a traveller who had returned from Italy. Increases in COVID-19 cases and deaths necessitated the design and implementation of community screening, testing, and tracing as a control strategy. The SA government's plans to implement community-based screening, testing, contact tracing and movement modelling during the early phases of the COVID-19 pandemic presented both opportunities and challenges. In this article, we present our experiences, opportunities and lessons for community-based COVID-19 response, anchoring these efforts in the primary healthcare system.

Invasive fungal infections in a paediatric intensive care unit in a low-to middle-income country.

Background: Paediatric intensive care units (PICUs) are high-risk settings for healthcare-associated infections. Invasive fungal infection (IFI) is one of the common causes of healthcare-associated infections. Objectives: To describe the prevalence and short-term outcomes of children with IFI, and to offer a basis for the efficient prevention and treatment of IFI. Methods: A retrospective study was conducted in children under the age of 12 years over a two-year period. Participants were categorised according to pre-defined microbiology criteria into IFI if they had a positive culture from blood or other sterile sites. Data collected included demographics, invasive procedures, length of stay and mortality. Results: One thousand and forty-two children were admitted during the study period. Of the total, 56.8% (n=592) were male. Median length of stay was 18 days (mean±SE 18.6±8.9). IFI was identified in 35 cases per 1 000 admissions, with 77.7% of these infants under the age of one year. The mean length of stay was 18.6 days compared with 7.5 days for children with bacterial infections. The in-hospital mortality for invasive fungal infection was 36% compared with 16% for all admissions. Findings confirmed that colonisation was more prevalent than IFI. Conclusion: IFIs are common among infants, and these patients have a higher mortality rate and prolonged hospital stay. Therefore we recommend early diagnosis and timely treatment with high-performance antifungal drugs to improve the prognosis in children with IFI.

Leveraging epidemiology as a decision support tool during the COVID-19 epidemic in South Africa.

By May 2021, South Africa (SA) had experienced two 'waves' of COVID-19 infections, with an initial peak of infections reached in July 2020, followed by a larger peak of infections in January 2021. Public health decisions rely on accurate and timely disease surveillance and epidemiological analyses, and accessibility of data at all levels of government is critical to inform stakeholders to respond effectively. In this paper, we describe the adaptation, development and operation of epidemiological surveillance and modelling systems in SA in response to the COVID-19 epidemic, including data systems for monitoring laboratory-confirmed COVID-19 cases, hospitalisations, mortality and recoveries at a national and provincial level, and how these systems were used to inform modelling projections and public health decisions. Detailed descriptions on the characteristics and completeness of individual datasets are not provided in this paper. Rapid development of robust data systems was necessary to support the response to the SA COVID-19 epidemic. These systems produced data streams that were used in decision-making at all levels of government. While much progress was made in producing epidemiological data, challenges remain to be overcome to address gaps to better prepare for future waves of COVID-19 and other health emergencies.

Quinolone-resistant Salmonella Typhi in South Africa, 2003-2007.

In South Africa, for the years 2003-2007, the Enteric Diseases Reference Unit received 510 human isolates of Salmonella Typhi, of which 27 were nalidixic acid-resistant [minimum inhibitory concentrations (MICs) 128-512 microg/ml] with reduced susceptibility to ciprofloxacin (MICs 0.125-0.5 microg/ml). Pulsed-field gel electrophoresis analysis of 19 available isolates differentiated them into five DNA pattern types; multiple-locus variable-number tandem repeat analysis differentiated the isolates into 10 types. This level of genetic diversity suggested that resistant strains usually emerged independently of one another. A 16- to 32-fold decrease in nalidixic acid MIC and a 2- to 8-fold decrease in ciprofloxacin MIC, was observed in the presence of an efflux pump inhibitor. All isolates were negative by PCR screening for qnr genes. Seven resistant isolates were further analysed for mutations in the quinolone resistance-determining region of gyrA, gyrB, parC and parE. No amino-acid mutations were identified in GyrB and ParE; all isolates showed amino-acid mutations in both GyrA and ParC. We conclude that amino-acid mutations in GyrA and ParC in combination with active efflux of antibiotic out of the bacterial cell are the probable mechanisms conferring quinolone resistance.

National Neonatal Sepsis Task Force launch: Supporting infection prevention and surveillance, outbreak investigation and antimicrobial stewardship in neonatal units in South Africa.

Despite a substantial decline in childhood mortality rates in South Africa (SA), progress in neonatal mortality reduction has been much slower. Severe bacterial infections remain a leading cause of neonatal morbidity and a direct cause of 13.1% of neonatal deaths among babies >1 kg. The incidence of hospital-acquired infections, antimicrobial resistance and outbreaks of infections in SA neonatal units is substantial, and is possibly higher than the currently available estimates. The SA Neonatal Sepsis Task Force was launched in Port Elizabeth, SA, on 13 September 2019 to provide technical advice and guidance on surveillance for neonatal sepsis, infection prevention, case management, antimicrobial stewardship and containment of neonatal unit outbreaks.

A multisectoral investigation of a neonatal unit outbreak of Klebsiella pneumoniae bacteraemia at a regional hospital in Gauteng Province, South Africa.

BACKGROUND: Rates of healthcare-associated infections (HAIs) among babies born in developing countries are higher than among those born in resource-rich countries, as a result of suboptimal infection prevention and control (IPC) practices. Following two reported deaths of neonates with carbapenem-resistant Klebsiella pneumoniae bloodstream infections (BSIs), we conducted an outbreak investigation in a neonatal unit of a regional hospital in Gauteng Province, South Africa. OBJECTIVES: To confirm an outbreak of K. pneumoniae BSIs and assess the IPC programme in the neonatal unit. METHODS: We calculated total and organism-specific BSI incidence risks for culture-confirmed cases in the neonatal unit for baseline and outbreak periods. We conducted a clinical record review for a subset of cases with K. pneumoniae BSI that had been reported to the investigating team by the neonatal unit. An IPC audit was performed in different areas of the neonatal unit. We confirmed species identification and antimicrobial susceptibility, and used polymerase chain reaction for confirmation of carbapenemase genes and pulsed-field gel electrophoresis (PFGE) for typing of submitted clinical isolates. RESULTS: From January 2017 to August 2018, 5 262 blood cultures were submitted, of which 11% (560/5 262) were positive. Of 560 positive blood cultures, 52% (n=292) were positive for pathogenic organisms associated with healthcare-associated BSIs. K. pneumoniae comprised the largest proportion of these cases (32%; 93/292). The total incidence risk of healthcare-associated BSI for the baseline period (January 2017 - March 2018) was 6.8 cases per 100 admissions, and that for the outbreak period (April - September 2018) was 10.1 cases per 100 admissions. The incidence risk of K. pneumoniae BSI for the baseline period was 1.6 cases per 100 admissions, compared with 5.0 cases per 100 admissions during the outbreak period. Average bed occupancy for the entire period was 118% (range 101 - 133%), that for the baseline period was 117%, and that for the outbreak period was 121%. In a subset of 12 neonates with K. pneumoniae bacteraemia, the median (interquartile range (IQR)) gestational age at birth was 27 (26 - 29) weeks, and the median (IQR) birth weight was 1 100 (880 - 1 425) g. Twelve bloodstream and 31 colonising K. pneumoniae isolates were OXA-48-positive. All isolates were genetically related by PFGE analysis (89% similarity). Inadequate IPC practices were noted, including suboptimal adherence to aseptic technique and hand hygiene (57% overall score in the neonatal intensive care unit), with poor monitoring and reporting of antimicrobial use (pharmacy score 55%). CONCLUSIONS: Overcrowding and inadequate IPC and antimicrobial stewardship contributed to a large outbreak of BSIs caused by genetically related carbapenemase-producing K. pneumoniae isolates in the neonatal unit.