The clinical Spectrum of Viridans Group Streptococci infections in paediatric patients at a tertiary hospital

Background: Viridans Group Streptococci (VGS) are often considered organisms of low virulence; however, infection can result in clinically significant sepsis and life-threatening complications in paediatric patients. Objectives: This study aimed to describe the spectrum of clinical presentation of VGS bacteraemia in paediatric patients, to analyse risk factors, and to describe the antibiotics resistance patterns of VGS. Method: Cultures of VGS in paediatric patients admitted to Chris Hani Baragwanath Academic Hospital in 2019 were identified through National Health Laboratory Service. Data were extracted from archived clinical records and analysed. Sepsis scores were calculated at the time of bacteraemia. Results: A total of 133 cultures were identified; 64 (48.1%) polymicrobial cultures and no records 4 (0.03%) were excluded; 65 (48.9%) were analysed. The median age was 1.5 months (range 0.03 to 168, interquartile range [IQR]: 0.3–13.25), 27/65 (42%) were neonates. The median duration of hospitalisation was 7 days (IQR: 3–21). The commonest diagnoses were neonatal sepsis 30.8% (n = 20) and pneumonia 28% (n = 18). The systemic inflammatory response syndrome (SIRS) score was ≥ 2 in 57% (16/28) patients; paediatric sequential organ failure assessment (pSOFA) score was 2 in 10/24 (42%). Fifty-seven (88%) patients were discharged; three (5%) required ICU admission and 8/65 (12.3%) died. Malnutrition was present in 50% of patients who died. Cephalosporins and penicillin had sensitivity of 89% and 55%, respectively. Conclusion: Viridans Group Streptococci bacteraemia was common in neonates, and pneumonia was a common presentation in this cohort. The VGS bacteraemia was associated with morbidity and deaths in this cohort. Contribution: The VGS should be considered a significant organism when cultured from sterile sites and routine antibiotic susceptibility testing should be performed. Prospective studies are recommended

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 plasmidand 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.http://www.plosone.orgdm2022Medical Microbiolog

Antimicrobial Susceptibility Patterns of Selected Bacteraemic Isolates from South African Public Sector Hospitals, 2010

We report on antimicrobial susceptibility surveillance data for six key bloodstream pathogens (Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus) identified in public sector hospitals in South Africa during 2010. Major findings include the accelerated emergence of carbapenem resistance among K. pneumoniae and Enterobacter species, with overall susceptibility rates of 98% and 96% for ertapenem, and above 99% for meropenem and imipenem. Levels of resistance among P. aeruginosa and A. baumannii remain high in all centres, with few changes since 2009. Large decreases in piperacillin-tazobactam susceptibility rates were noted at three institutions, probably related to methodological issues. S. aureus remains a major pathogen countrywide, with between 30-60% of isolates resistant to cloxacillin [methicillin-resistant S. aureus (MRSA)]. Ongoing surveillance for antimicrobial resistance is vital, and the use of a centralised data extraction system may aid in this.http://www.sajei.co.za/index.php/SAJE

Prevalence and trends of staphylococcus aureus bacteraemia in hospitalized patients in South Africa, 2010 to 2012: laboratory-based surveillance mapping of antimicrobial resistance and molecular epidemiology.

CAPRISA, 2015.Abstract available in pdf

National sentinel site surveillance for antimicrobial resistance in Klebsiella pneumoniae isolates in South Africa, 2010 - 2012

BACKGROUND. The increasing rates of antimicrobial resistance observed in the nosocomial pathogen Klebsiella pneumoniae are of major public health concern worldwide. Objectives. To describe the antibiotic susceptibility profiles of K. pneumoniae isolates from bacteraemic patients submitted by sentinel laboratories in five regions of South Africa from mid-2010 to mid-2012. Molecular methods were used to detect the most commonly found extended-spectrum beta-lactamase (ESBL) and carbapenemase resistance genes. METHODS. Thirteen academic centres serving the public healthcare sector in Gauteng, KwaZulu-Natal, Free State, Limpopo and Western Cape provinces submitted K. pneumoniae isolates from patients with bloodstream infections. Vitek 2 and MicroScan instruments were used for organism identification and susceptibility testing. Multiplex polymerase chain reactions (PCRs) were used to detect blaCTX-M, blaSHV and blaTEM genes in a proportion of the ESBL isolates. All isolates exhibiting reduced susceptibility to carbapenems were PCR tested for blaKPC and blaNDM-1 resistance genes. RESULTS. Overall, 68.3% of the 2 774 isolates were ESBL-positive, showing resistance to cefotaxime, ceftazidime and cefepime. Furthermore, 46.5% of all isolates were resistant to ciprofloxacin and 33.1% to piperacillin-tazobactam. The major ESBL genes were abundantly present in the sample analysed. Most isolates (95.5%) were susceptible to the carbapenems tested, and no isolates were positive for blaKPC or blaNDM-1. There was a trend towards a decrease in susceptibility to most antibiotics. CONCLUSION. The high proportion of ESBL-producing K. pneumoniae isolates observed, and the prevalence of ESBL genes, are of great concern. Our findings represent a baseline for further surveillance in SA, and can be used for policy and treatment decisions.http://www.samj.org.zaam201

Potential of Minimally Invasive Tissue Sampling for Attributing Specific Causes of Childhood Deaths in South Africa: A Pilot, Epidemiological Study

Background. Current estimates for causes of childhood deaths are mainly premised on modeling of vital registration and limited verbal autopsy data and generally only characterize the underlying cause of death (CoD). We investigated the potential of minimally invasive tissue sampling (MITS) for ascertaining the underlying and immediate CoD in children 1 month to 14 years of age. Methods. MITS included postmortem tissue biopsies of brain, liver, and lung for histopathology examination; microbial culture of blood, cerebrospinal fluid (CSF), liver, and lung samples; and molecular microbial testing on blood, CSF, lung, and rectal swabs. Each case was individually adjudicated for underlying, antecedent, and immediate CoD by an international multidisciplinary team of medical experts and coded using the International Classification of Diseases, Tenth Revision (ICD-10). Results. An underlying CoD was determined for 99% of 127 cases, leading causes being congenital malformations (18.9%), complications of prematurity (14.2%), human immunodeficiency virus/AIDS (12.6%), diarrheal disease (8.7%), acute respiratory infections (7.9%), injuries (7.9%), and malignancies (7.1%). The main immediate CoD was pneumonia, sepsis, and diarrhea in 33.9%, 19.7%, and 10.2% of cases, respectively. Infection-related deaths were either an underlying or immediate CoD in 78.0% of cases. Community-acquired pneumonia deaths (n = 32) were attributed to respiratory syncytial virus (21.9%), Pneumocystis jirovecii (18.8%), cytomegalovirus (15.6%), Klebsiella pneumoniae (15.6%), and Streptococcus pneumoniae (12.5%). Seventy-one percent of 24 sepsis deaths were hospital-acquired, mainly due to Acinetobacter baumannii (47.1%) and K. pneumoniae (35.3%). Sixty-two percent of cases were malnourished. Conclusions. MITS, coupled with antemortem clinical information, provides detailed insight into causes of childhood deaths that could be informative for prioritization of strategies aimed at reducing under-5 mortality

Unraveling Specific Causes of Neonatal Mortality Using Minimally Invasive Tissue Sampling: An Observational Study

Background. Postmortem minimally invasive tissue sampling (MITS) is a potential alternative to the gold standard complete diagnostic autopsy for identifying specific causes of childhood deaths. We investigated the utility of MITS, interpreted with available clinical data, for attributing underlying and immediate causes of neonatal deaths. Methods. This prospective, observational pilot study enrolled neonatal deaths at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. The MITS included needle core-biopsy sampling for histopathology of brain, lung, and liver tissue. Microbiological culture and/or molecular tests were performed on lung, liver, blood, cerebrospinal fluid, and stool samples. The “underlying” and “immediate” causes of death (CoD) were determined for each case by an international panel of 12–15 medical specialists. Results. We enrolled 153 neonatal deaths, 106 aged 3–28 days. Leading underlying CoD included “complications of prematurity” (52.9%), “complications of intrapartum events” (15.0%), “congenital malformations” (13.1%), and “infection related” (9.8%). Overall, infections were the immediate or underlying CoD in 57.5% (n = 88) of all neonatal deaths, including the immediate CoD in 70.4% (58/81) of neonates with “complications of prematurity” as the underlying cause. Overall, 74.4% of 90 infection-related deaths were hospital acquired, mainly due to multidrug-resistant Acinetobacter baumannii (52.2%), Klebsiella pneumoniae (22.4%), and Staphylococcus aureus (20.9%). Streptococcus agalactiae was the most common pathogen (5/15 [33.3%]) among deaths with “infections” as the underlying cause. Conclusions. MITS has potential to address the knowledge gap on specific causes of neonatal mortality. In our setting, this included the hitherto underrecognized dominant role of hospital-acquired multidrug-resistant bacterial infections as the leading immediate cause of neonatal deaths

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 (HIC). 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 hospitalised infants < 60 days postnatal age with sepsis (August 2018-February 2021). 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 g (IQR: 990-1692). Only a minority had high risk criteria, such as being born < 28 weeks, 19% (24/127), or birth weight < 1000 g, 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-enrolment 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

Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria

Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria