Neoehrlichiosis in Symptomatic Immunocompetent Child, South Africa.

We describe a case of neoehrlichiosis in an immunocompetent child with acute febrile illness in South Africa. Neoehrlichiosis was diagnosed by PCR on 16S rDNA from bone marrow aspirate. Phylogenetic analysis indicated an organism closely related to Candidatus Neoehrlichia. Clinicians should be aware of possible ehrlichiosis even in immunocompetent patients.

Antimicrobial Resistance and Molecular Typing of Neisseria gonorrhoeae Isolates From the Eastern Cape Province in South Africa.

BACKGROUND: There is a paucity of Neisseria gonorrhoeae antimicrobial resistance data from resource-constrained settings because of the lack of diagnostic testing and limited scale of surveillance programs. This study aimed to determine the antimicrobial resistance profile of N. gonorrhoeae in the rural Eastern Cape province of South Africa. METHODS: Specimens for N. gonorrhoeae culture were obtained from men with urethral discharge and women with vaginal discharge attending primary health care facilities. Direct inoculation of the agar plates was performed followed by culture and drug susceptibility testing using the Etest at the laboratory. Whole-genome sequencing of the isolates was performed to identify resistance-determining variants. RESULTS: One hundred N. gonorrhoeae isolates were obtained. Most strains were nonsusceptible to ciprofloxacin (76%), tetracycline (75%), and penicillin G (72%). The gyrA S91F mutation was present in 68 of 72 ciprofloxacin-resistant isolates (94%), with concurrent parC mutations in 47 of 68 (69%); gyrA I250M was the only mutation in 4 other resistant strains. One azithromycin-resistant isolate was identified with a minimal inhibitory concentration (MIC) of 8.0 mg/L and the 23S rDNA gene mutation C2597T. The median MIC of cefixime was 0.016 mg/L (range, 0.016-0.064 mg/L), and that of ceftriaxone was 0.016 mg/L (range, 0.016 mg/L). Whole-genome sequencing showed 58 sequence types as revealed in N. gonorrhoeae sequence typing for antimicrobial resistance and 70 sequence types in N. gonorrhoeae multiantigen sequence typing. CONCLUSIONS: This study confirmed high rates of N. gonorrhoeae antimicrobial resistance to ciprofloxacin, penicillin G, and tetracycline in our setting. The MICs of cephalosporins are reassuring for ceftriaxone use in syndromic treatment regimens, but the identification of azithromycin resistance warrants further attention.

Cross-reactivity of a Histoplasma capsulatum antigen enzyme immunoassay in urine specimens from persons with emergomycosis in South Africa.

Histoplasma antigen detection in urine is a rapid diagnostic method for disseminated histoplasmosis, although cross-reactivity has been reported in specimens from patients with other thermally dimorphic fungal infections. We tested urine specimens, from persons with suspected invasive fungal infections, using a commercial monoclonal antibody Histoplasma enzyme immunoassay (EIA) at a South African national mycology reference laboratory from August 2014 through December 2018. Corresponding fungal culture and histopathology results were obtained from an electronic laboratory information system. In some cases, cultured fungal isolates were sent with the urine specimen for species-level identification by phenotypic and molecular methods. Cross-reactivity was confirmed using culture filtrates of several fungal pathogens. Of 212 referred cases, 41 (19%) were excluded since they had no recorded clinical history (n = 1), alternative diagnoses were confirmed (n = 2), or no fungal culture or histopathology results (n = 38). Eighty-seven of 212 (41%) had laboratory evidence of an invasive fungal disease, while 84 (40%) did not. Of the 87 cases, 37 (43%) were culture-confirmed mycoses: emergomycosis (n = 18), histoplasmosis (n = 8), sporotrichosis (n = 6), cryptococcosis (n = 2), talaromycosis (n = 1), and other fungi isolated (n = 2). The sensitivity and specificity of the EIA were calculated for two groups: culture-confirmed (n = 37) and histology-confirmed invasive fungal disease (n = 50). The sensitivity and specificity of the EIA for diagnosis of histoplasmosis compared to culture were 88% (7/8, 95%CI 47-100%) and 72% (21/29, 95%CI 53-87%), respectively, and for diagnosis of emergomycosis/histoplasmosis compared to histology was 83% (29/35, 95%CI 66-93%) and 93% (14/15, 95%CI 68-100%), respectively. Cross-reactions occurred in urine specimens of patients with Emergomyces africanus infection and in culture filtrates of E. africanus, T. marneffei and Blastomyces species. A commercial Histoplasma EIA had satisfactory accuracy for diagnosis of culture-confirmed histoplasmosis, but cross-reacted in urine specimens from patients with invasive disease caused by the closely-related pathogen, E. africanus and in culture filtrates of E. africanus and other related fungi. LAY SUMMARY: Emergomyces africanus and Histoplasma capsulatum are fungi that cause a multi-system disease among HIV-seropositive persons with a low CD4 cell count. Handling live cultures of these fungi to confirm a diagnosis requires specialized laboratory equipment and infrastructure which is infrequently accessible in low-resource settings. The features of the two diseases (i.e., disseminated histoplasmosis and emergomycosis) may be indistinguishable when infected tissue is prepared, stained, and examined under a microscope. Enzyme immunoassays (EIA) have been developed as rapid diagnostic tools for the detection of a cell wall component of H. capsulatum in urine specimens, although cross-reactions have been reported in specimens from patients with other fungal infections. We evaluated the accuracy of a commercial Histoplasma EIA to diagnose histoplasmosis and to assess cross-reactions in urine specimens from persons with emergomycosis and in cultures of E. africanus and related fungi. We report a sensitivity and specificity of 88% (95%CI 47-100%) and 72% (95%CI 53-87%) for diagnosis of histoplasmosis compared to culture and 83% (95%CI 66-93%) and 93% (95%CI 68-100%) for diagnosis of either histoplasmosis/emergomycosis compared to a diagnosis made by microscopic examination of infected tissue. The assay cross-reacted in urine specimens from patients with emergomycosis and in culture filtrates of related fungi. Although the EIA cross-reacted with other related fungi, this test can decrease the time to diagnosis and facilitate early treatment of emergomycosis and histoplasmosis in South Africa.

Corrigendum: Dangers of Clostridium perfringens food poisoning in psychiatric patients.

[This corrects the article DOI: 10.4102/sajpsychiatry.v25i0.1339.].

Dangers of Clostridium perfringens food poisoning in psychiatric patients.

Clostridium perfringens food poisoning can be fatal in patients with chronic constipation. We report the investigation and management of a probable outbreak of C. perfringens food poisoning among psychiatric patients in Cape Town, South Africa, in 2013.

Bloodstream infections at a tertiary level paediatric hospital in South Africa.

BACKGROUND: Bloodstream infection (BSI) in children causes significant morbidity and mortality. There are few studies describing the epidemiology of BSI in South African children. METHODS: A retrospective descriptive cohort study was conducted at a paediatric referral hospital in Cape Town, South Africa. The National Health Laboratory Service (NHLS) microbiology database was accessed to identify positive blood culture specimens during the period 2011-2012. Demographic and clinical details, antimicrobial management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the NHLS database. RESULTS: Of the 693 unique bacterial and fungal BSI episodes identified during the study period, 248 (35.8%) were community-acquired (CA), 371 (53.5%) hospital-acquired (HA) and 74 (10.7%) healthcare-associated (HCA). The overall risk was 6.7 BSI episodes per 1000 admissions. Escherichia coli, Staphylococcus aureus and Streptococcus pneumoniae were the most frequent causes of CA-BSI and Klebsiella pneumoniae, Acinetobacter baumanii and S.aureus were most commonly isolated in HA-BSI. On multivariable analysis, severe underweight, severe anaemia at the time of BSI, admission in the ICU at the time of BSI, and requiring ICU admission after BSI was diagnosed were significantly associated with 14-day mortality. CONCLUSION: This study adds to the limited literature describing BSI in children in Africa. Further studies are required to understand the impact that BSI has on the paediatric population in sub-Saharan Africa.

Laboratory-acquired infections of Salmonella enterica serotype Typhi in South Africa: phenotypic and genotypic analysis of isolates.

BACKGROUND: Workers in clinical microbiology laboratories are exposed to a variety of pathogenic microorganisms. Salmonella species is among the most commonly reported bacterial causes of laboratory-acquired infections. We report on three cases of laboratory-acquired Salmonella enterica serotype Typhi (Salmonella Typhi) infection which occurred over the period 2012 to 2016 in South Africa. METHODS: Laboratory investigation included phenotypic and genotypic characterization of isolates. Phenotypic analysis included standard microbiological identification techniques, serotyping and antimicrobial susceptibility testing. Genotypic analysis included the molecular subtyping methodologies of pulsed-field gel electrophoresis analysis, multilocus sequence typing and whole-genome sequencing (WGS); with WGS data analysis including phylogenetic analysis based upon comparison of single nucleotide polymorphism profiles of isolates. RESULTS: All cases of laboratory-acquired infection were most likely the result of lapses in good laboratory practice and laboratory safety. The following critical issues were highlighted. There was misdiagnosis and misreporting of Salmonella Typhi as nontyphoidal Salmonella by a diagnostic laboratory, with associated public health implications. We highlight issues concerning the importance of accurate fluoroquinolone susceptibility testing and interpretation of results according to updated guidelines. We describe potential shortcomings of a single disk susceptibility screening test for fluoroquinolone susceptibility and suggest that confirmatory minimum inhibitory concentration testing should always be performed in cases of invasive Salmonella infections. These antimicrobial susceptibility testing issues resulted in inappropriate ciprofloxacin therapy which may have been responsible for failure in clearance of pathogen from patients. Salmonella Typhi capsular polysaccharide vaccine was not protective in one case, possibly secondarily to a faulty vaccine. CONCLUSIONS: Molecular subtyping of isolates proved effective to investigate the genetic relatedness of isolates. Molecular subtyping data interpreted together with epidemiological data allowed us to pinpoint the most likely sources for our cases of laboratory-acquired infection.

A dimorphic fungus causing disseminated infection in South Africa.

BACKGROUND: The genus emmonsia contains three species that are associated with human disease. Emmonsia crescens and Emmonsia parva are the agents that cause adiaspiromycosis, and one human case of Emmonsia pasteuriana infection has been described. We report a fungal pathogen within the genus emmonsia that is most closely related to E. pasteuriana in human immunodeficiency virus (HIV)-infected adults in South Africa. METHODS: Between July 2008 and July 2011, we conducted enhanced surveillance to identify the cause of systemic, dimorphic fungal infections in patients presenting to Groote Schuur Hospital and other hospitals affiliated with the University of Cape Town, Cape Town, South Africa. DNA sequencing was used to identify pathogenic fungi. RESULTS: A total of 24 cases of dimorphic fungal infection were diagnosed, 13 of which were caused by an emmonsia species. All 13 patients were HIV-infected, with a median CD4+ T-cell count of 16 cells per cubic millimeter (interquartile range, 10 to 44), and all had evidence of disseminated fungal disease. Three patients died soon after presentation, but the others had a good response to a variety of antifungal agents and antiretroviral therapy. Phylogenetic analysis of five genes (LSU, ITS1-2, and the genes encoding actin, ß-tubulin, and intein PRP8) revealed that this fungus belongs in the genus emmonsia and is most closely related to E. pasteuriana. CONCLUSIONS: The findings suggest that these isolates of an emmonsia species represent a new species of dimorphic fungus that is pathogenic to humans. The species appears to be an important cause of infections in Cape Town.

Klebsiella pneumoniae bloodstream infections at a South African children's hospital 2006-2011, a cross-sectional study.

BACKGROUND: Klebsiella pneumoniae (KP) is a significant paediatric bloodstream pathogen in children. There is little data from Africa. In this study we describe the epidemiology of multi-drug resistant Klebsiella pneumoniae bloodstream infection (KPBSI) at Red Cross War Memorial Children's Hospital, Cape Town, South Africa. METHODS: We conducted a retrospective cross-sectional study of KPBSI from 1 January 2006 to 31 December 2011 using conventional descriptive and inferential statistical methods. RESULTS: Of 410 hospitalised children with laboratory confirmed KPBSI, 339 (83 %) were caused by extended-spectrum ß-lactamase (ESBL) producing isolates. The median age (IQR) was 5.0 (2-16) months, 212 (51.7 %) were male, 82 (20 %) were HIV-infected, and 241 (58.8 %) were moderately or severely underweight. The infection was hospital-acquired or healthcare-associated in 389 (95 %) children and community-acquired in 21 (5 %) children. Significant risk factors for ESBL-KPBSI included cephalosporin exposure in the 12 months prior to the KPBSI, adjusted risk ratio (aRR) 1.18 (95 % CI: 1.06-1.31); HIV infection, aRR 1.14 (1.04-1.25), and intravenous infusions for more than 3 days before the KPBSI, aRR 1.15 (95 % CI: 1.04-1.28). A total of 109 (26.6 %) children died within 30 days of the KPBSI, their median age was four (IQR 1-11) months. The median (IQR) time between KPBSI and death was three (1-9) days. HIV-infection, aRR 2.44(95 % CI: 1.59-3.74); skin erosions at the time of KPBSI, aRR 2.15 (95 % CI: 1.54-3.00); being in PICU at the time of the KPBSI, aRR 1.64 (95 % CI: 1.03-2.61) or needing PICU admission after developing KPBSI, aRR 1.72 (95 % CI: 1.10-2.70) were significant risk factors for death. CONCLUSION: ESBL-producing KP is an important cause of laboratory confirmed bloodstream infection in hospitalised children and is associated with high mortality.

Carbapenem-resistant Enterobacterales among hospitalized patients in Cape Town, South Africa: clinical and microbiological epidemiology.

Background: Carbapenem-resistant Enterobacterales (CRE) are a substantial problem in Cape Town. CRE epidemiology is largely unknown and mortality remains high. Objectives: To describe and characterize the clinical and microbiological epidemiology of CRE within Cape Town hospitals to better inform therapy with regard to current and novel antibiotics, as well as improve antimicrobial stewardship (AMS), and infection prevention and control (IPC). Methods: This prospective, multicentre study performed between 1 November 2020 and 30 November 2022, across three public and three private hospitals included hospitalized participants with CRE from clinical cultures. Participant demographics, clinical information and microbiology results were collected and analysed. Results: Ninety percent of participants were from public hospitals. The age distribution ranged from 7 days to 88 years. Notable risk factors for CRE infection included recent exposure to antibiotics, medical devices and surgery. The most prevalent species was Klebsiella pneumoniae. However, a higher proportion of Serratia marcescens compared with previous reports was identified. The detected carbapenemases were blaOXA-48-like (80%) and blaNDM (11%). With the exception of amikacin (63%), tigecycline (65%), colistin (95%) and ceftazidime/avibactam (87%), susceptibility to antibiotics was low. Conclusions: This study identified common risk factors for CRE infection and generated a description of carbapenemase enzymes, species distribution and antibiograms, enabling a better understanding of CRE epidemiology. This provides insights into transmission patterns and resistance determinants of CREs, beneficial to informing data-driven regional patient management, AMS and IPC strategies.

Carbapenem-resistant Klebsiella pneumoniae among hospitalized patients in Cape Town, South Africa: molecular epidemiology and characterization.

Background: The molecular epidemiology of carbapenem-resistant Enterobacterales in Cape Town remains largely unknown. Objectives: This study aimed to describe the molecular epidemiology, resistome, virulome and mobilome of carbapenem-resistant Klebsiella pneumoniae (CRKP) within Cape Town to guide therapy, antimicrobial stewardship and infection prevention and control practices. Methods: Eighty-five CRKP isolates from hospitalized patients underwent WGS as part of a prospective, multicentre, cross-sectional study, conducted between 1 November 2020 and 30 November 2022, across public-sector and private-sector hospitals in Cape Town, South Africa. Results: MLST revealed three novel types, ST6785, ST6786 and ST6787, while the most common were ST219, ST307, ST17, ST13 and ST2497. Different predominant clones were noted in each hospital. The most common carbapenemase gene was blaOXA-48-like, detected in 71% of isolates, with blaNDM detected in 5%. Notably, co-detection of two carbapenemase genes (blaOXA-48-like and blaNDM) occurred in 13% of isolates. The yersiniabactin siderophore was detected in 73% of isolates, and was most commonly associated with the ICEKp5 mobile element. All carbapenemases were located on plasmids. The genes blaOXA-181 and blaOXA-232 colocalized with a ColKP3 replicon type on assembled contigs in 83% and 100% of cases, respectively. Conclusions: CRKP epidemiology in Cape Town reflects institutionally dominant, rather than regional, clones. The most prevalent carbapenemase gene was blaOXA-48-like, in keeping with CRKP epidemiology in South Africa in general. Emerging clones harbouring both blaOXA-48-like and blaNDM, such as ST17, ST2497 and the novel ST6787, are a concern due to the limited availability of appropriate antimicrobial agents in South Africa.

Prospective antimicrobial stewardship interventions by multidisciplinary teams to reduce neonatal antibiotic use in South Africa: the Neonatal Antimicrobial Stewardship (NeoAMS) study.

BACKGROUND: Hospitalised neonates are vulnerable to infection and have high rates of antibiotic utilisation. METHODS: Fourteen South African neonatal units (seven public, seven private sector) assembled multidisciplinary teams involving neonatologists, microbiologists, pharmacists, and nurses to implement prospective audit and feedback neonatal antimicrobial stewardship (NeoAMS) interventions. The teams attended seven online training sessions. Pharmacists conducted weekday antibiotic prescription reviews in the neonatal intensive care unit and/or neonatal wards providing feedback to the clinical teams. Anonymised demographic and NeoAMS interventions data were aggregated for descriptive purposes and statistical analysis. FINDINGS: During the 20-week NeoAMS intervention in 2022, 565 neonates were enrolled. Pharmacists evaluated seven hundred antibiotic prescription episodes; rule-out sepsis (180; 26%) and culture-negative sepsis (138; 20%) were the most frequent indications for antibiotic prescription. For infection episodes with an identified pathogen, only 51% (116/229) of empiric treatments provided adequate antimicrobial coverage. Pharmacists recommended 437 NeoAMS interventions (0·6 per antibiotic prescription episode), with antibiotic discontinuation (42%), therapeutic drug monitoring (17%), and dosing (15%) recommendations most frequent. Neonatal clinicians' acceptance rates for AMS recommendations were high (338; 77%). Mean antibiotic length of therapy decreased by 24% from 9·1 to 6·9 days (0·1 day decrease per intervention week; p=0·001), with the greatest decline in length of therapy for culture-negative sepsis (8·2 days (95%CI 5·7-11·7) to 5·9 days (95% CI 4·6-7·5); p=0·032). INTERPRETATION: This neonatal AMS programme was successfully implemented in heterogenous and resource-limited settings. Pharmacist-recommended AMS interventions had high rates of clinician acceptance. The NeoAMS intervention significantly reduced neonatal antibiotic use, particularly for culture-negative sepsis. FUNDING: A grant from Merck provided partial support.

A citywide, clonal outbreak of Pseudomonas aeruginosa.

BACKGROUND: Outbreaks of community-acquired Pseudomonas aeruginosa are typically small and localized. We investigated an increase in community-acquired infections with P. aeruginosa in Cape Town, South Africa. METHODS: Cases were defined as P. aeruginosa isolated from any clinical sample, and "wild-type" as those susceptible to all antibiotics tested. The residential addresses of community-acquired wild-type cases were mapped. Whole-genome sequencing and multilocus sequence typing were used to determine clonality and identify virulence genes. A clinical study in a subset of patients with bloodstream infection compared demographic and clinical characteristics between sequence types (STs). RESULTS: The outbreak lasted 10 months from December 2016 to September 2017 with 3,321 documented cases. At the peak, cases reached 2.3-fold baseline rates. Cases were distributed widely across the city. Multilocus ST 303 was predominant during the outbreak. A total of 51 virulence genes were differentially present in ST303 compared with other STs, including genes involved in biofilm formation, iron uptake, and gut penetration. CONCLUSION: The investigation confirmed a citywide outbreak of P. aeruginosa. We identified a predominant outbreak-associated clone, ST303, which harbored genes that could contribute to virulence and survival in adverse environmental conditions such as those associated with drought.

The BinaxNOW pneumococcal antigen test: An adjunct for diagnosis of pneumococcal bacteraemia.

BACKGROUND: Culture remains the diagnostic standard for Streptococcus pneumoniae bacteraemia but is limited by time to identification, prior antibiotics and bacterial autolysis. Culture-independent methods for detecting S. pneumoniae include PCR and antigen tests. We evaluated an antigen test on blood culture broth for the rapid detection of S. pneumoniae bacteraemia. METHOD: We collected 212 signal-positive blood cultures, with gram-positive cocci in pairs, chains or with uncertain morphology. The BinaxNOW S. pneumoniae urinary antigen test, Gram stain, culture and lytA PCR were performed on all samples. Diagnostic accuracy of the antigen test and Gram stain with gram-positive cocci in pairs were compared with culture, polymerase chain reaction (PCR) and the composite of culture and PCR. RESULTS: Streptococcus pneumoniae was isolated in 26% of samples, 66% cultured other gram-positive organisms and 8% of samples had no growth. Sensitivity and negative predictive values of the antigen test were 100%, specificity and positive predictive values were 87% - 88% and 76% - 81%, but increased to 93% - 96% and 96% - 98% when applied to subsets with gram-positive cocci in pairs, or history compatible with respiratory illness or meningitis. Sensitivity (69% - 75%) and specificity (81%) of Gram stain (gram-positive cocci in pairs) were lower than the antigen test even when applied to the same subsets. CONCLUSION: Accurate and rapid diagnosis of S. pneumoniae bacteraemia is challenging. Specificity of this antigen test is limited by cross-reactivity with other gram-positive organisms, but could be improved if Gram stain morphology and clinical history are available. The antigen test is a useful adjunct for rapid diagnosis of S. pneumoniae bacteraemia.

Spectrum of Bacterial Colonization in Patients Hospitalized for Treatment of Multidrug-Resistant Tuberculosis.

This study investigated the bacterial colonization in patients admitted for treatment of drug-resistant tuberculosis in a specialized TB hospital. Identification and antimicrobial susceptibility testing of bacterial isolates (n = 62) from nasal, groin, and rectal swabs [patient cohort (n = 37)] were determined by the VITEK-MS system. Resistance gene analysis was by PCR and DNA sequencing. Molecular typing of Klebsiella pneumoniae isolates was by Multilocus Sequencing Typing (MLST). Patients (n = 13/37; 35%) were colonized by multidrug-resistant (MDR) bacteria (ESBL and MRSA) on admission. Of the 24 patients who were not colonized by MDR bacteria on admission, 46% (17/37) became colonized by MDR bacteria within 1 month of admission, mostly with ESBL-producing Enterobacteriales and resistance to aminoglycosides and fluoroquinolones. ESBL Escherichia coli (41/62; 66%) and K. pneumoniae (14/62; 23%) predominated. Genes encoding for ESBLs (blaCTX-M-14, blaCTX-M-15, blaSHV-28, blaOXA-1, and blaOXY-2) and plasmid-mediated quinolone resistant genes (qnrB1, qnrB4, and qnrB10) were detected. MLST revealed genetic diversity among the K. pneumoniae isolates from hospitalized patients. This study provides insight into bacterial pathogen colonization in hospitalized TB patients with the first occurrence of the qnrB4 and qnrB10 genes and co-expression of genes: qnrB4+aac(6')-lb-cr, qnrB10+aac(6')-lb-cr, qnrB4+qnrS1, and qnrB10+qnrS1 in fluoroquinolone-resistant E. coli isolates within South Africa. However, the source and colonization routes of these isolates could not be determined.

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.

Colonisation with extended spectrum beta-lactamase-producing and carbapenem-resistant Enterobacterales in children admitted to a paediatric referral hospital in South Africa.

INTRODUCTION: There are few studies describing colonisation with extended spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and carbapenem-resistant Enterobacterales (CRE) among children in sub-Saharan Africa. Colonisation often precedes infection and multi-drug-resistant Enterobacterales are important causes of invasive infection. METHODS: In this prospective cross-sectional study, conducted between April and June 2017, 200 children in a tertiary academic hospital were screened by rectal swab for EBSL-PE and CRE. The resistance-conferring genes were identified using polymerase chain reaction technology. Risk factors for colonisation were also evaluated. RESULTS: Overall, 48% (96/200) of the children were colonised with at least one ESBL-PE, 8.3% (8/96) of these with 2 ESBL-PE, and one other child was colonised with a CRE (0.5% (1/200)). Common colonising ESBL-PE were Klebsiella pneumoniae (62.5%, 65/104) and Escherichia coli (34.6%, 36/104). The most frequent ESBL-conferring gene was blaCTX-M in 95% (76/80) of the isolates. No resistance- conferring gene was identified in the CRE isolate (Enterobacter cloacae). Most of the Klebsiella pneumoniae isolates were susceptible to piperacillin/tazobactam (86.2%) and amikacin (63.9%). Similarly, 94.4% and 97.2% of the Escherichia coli isolates were susceptible to piperacillin/tazobactam and amikacin, respectively. Hospitalisation for more than 7 days before study enrolment was associated with ESBL-PE colonisation. CONCLUSION: Approximately half of the hospitalised children in this study were colonised with ESBL-PE. This highlights the need for improved infection prevention and control practices to limit the dissemination of these microorganisms.

Safety and effectiveness of colistin compared with tobramycin for multi-drug resistant Acinetobacter baumannii infections.

BACKGROUND: Nosocomial infections due to multi-drug resistant Acinetobacter baumannii are often treated with colistin, but there are few data comparing its safety and efficacy with other antimicrobials. METHODS: A retrospective cohort study of patients treated with colistin or tobramycin for A. baumannii infections in intensive care units (ICUs) at Groote Schuur hospital. Colistin was used for A. baumannii isolates which were resistant to all other available antimicrobials. In the tobramycin group, 53% of the isolates were only susceptible to tobramycin and colistin. We assessed ICU mortality, nephrotoxicity and time to the first negative culture. RESULTS: 32 patients, with similar admission APACHE scores and serum creatinine, were treated with each antimicrobial. There were no significant differences between the colistin and tobramycin groups in ICU mortality (p=0.54), nephrotoxicity (p=0.67), change in creatinine from baseline to highest subsequent value (p=0.11) and time to microbiological clearance (p=0.75). The hazard ratio for total in-hospital survival in patients treated with colistin compared to tobramycin was 0.43 (95% CI 0.19 to 0.99). CONCLUSION: Our study suggests that colistin and tobramycin have similar risks of nephrotoxicity and are equally efficacious. Colistin is an acceptable antibiotic for the treatment of A. baumannii infections when the organism is resistant to other available antimicrobials.

The accuracy of extended-spectrum beta-lactamase detection in Escherichia coli and Klebsiella pneumoniae in South African laboratories using the Vitek 2 Gram-negative susceptibility card AST-N255.

BACKGROUND: Phenotypic detection of extended-spectrum beta-lactamases (ESBLs) is based on the inhibition of ESBL enzymes by ß-lactamase inhibitors and on the comparison of cephalosporin activity with or without a ß-lactamase inhibitor. Many South African diagnostic laboratories rely on the Vitek 2 for automated susceptibility testing and for ESBL detection. However, the Gram-negative susceptibility card currently used locally (AST-N255) has been modified and its accuracy for ESBL detection is not known. METHODS: We randomly selected 50 isolates of Klebsiella pneumoniae and Escherichia coli from a collection of clinical bloodstream isolates from Groote Schuur Hospital from 2015 to 2016, including ESBL-producing and non-ESBL-producing strains. We used standardised phenotypic (disc diffusion and broth microdilution) and genotypic (conventional polymerase chain reaction (PCR) for blaCTX-M, blaSHV and blaTEM ) methods for detection of ESBLs. We compared ESBL detection by Vitek 2 to a composite reference standard comprising ESBL detection either by both phenotypic methods or by one phenotypic method together with genotypic detection. RESULTS: The sensitivity of Vitek 2 system for detection of ESBLs was 33/36 or 92% (78% - 97%) for E. coli, and 40/40 or 100% (91% - 100%) for K. pneumoniae, whilst specificity was 10/10 or 100% (72% - 100%) and 9/10 or 90% (60% - 98%), respectively. This is comparable with previous studies. CONCLUSION: Using a composite reference standard of the phenotypic and genotypic methods employed in this study, no Vitek-categorised ESBL E. coli or K. pneumoniae was found to be a non-ESBL with the exception of possible misinterpretation with K. pneumoniae SHV-hyper-producing isolates.

A ten-year review of ESBL and non-ESBL Escherichia coli bloodstream infections among children at a tertiary referral hospital in South Africa.

INTRODUCTION: There are few studies describing Escherichia coli (E. coli) bloodstream infection (BSI) among children in Africa, yet E.coli is increasing in importance as a cause of antibiotic resistant infection in paediatric settings. METHODS: In this retrospective, descriptive study aspects of E. coli BSI epidemiology are described over a 10-year period including incidence risk, risk factors for extended-spectrum ß-lactamase (ESBL)-producing E. coli BSI, antibiotic susceptibility of the bacterial isolates and outcome including risk factors for severe disease. RESULTS: There were 583 new E. coli BSI episodes among 217,483 admissions, an overall incidence risk of 2.7 events/1,000 hospital admissions. Of 455 of these E. coli BSI episodes that were analysed, 136 (29.9%) were caused by ESBL-producing isolates. Risk factors for ESBL-producing E. coli BSI included hospitalization in the 28-day period preceding E. coli BSI episodes, having an underlying chronic illness other than HIV infection at the time of the E. coli BSI and having a temperature of 38° Celsius or higher at the time of the E. coli BSI. None of the E. coli isolates were resistant to carbapenems or colistin. The mortality rate was 5.9% and admission to the intensive care unit was required in 12.3% of BSI episodes. Predictors of severe disease included age less than 1 month, hospitalization in the 28-day period preceding E. coli BSI and BSI without a definable focus. CONCLUSIONS: These findings extend our understanding of E. coli BSI in a sub-Saharan African setting, provide useful information that can guide empiric treatment choices for community- and hospital-acquired BSI and help inform prevention strategies.