The burden of sepsis in neonates due to Acinetobacter baumannii (A. baumannii) in developing countries is not well reported. The objective of this study was to determine prevalence of culture ...confirmed sepsis due to A. baumannii, antimicrobial susceptibility and case-fatality rates (CFR) due to this organism.
A retrospective review of medical and laboratory records of neonates admitted to a tertiary government hospital from a developing country was conducted. Records of neonates with positive microbiological cultures from blood or cerebrospinal fluid due to A. baumannii were reviewed for demographic characteristics, clinical presentation, laboratory findings, antibiotic susceptibility and outcome at hospital discharge.
There were 399 isolates of A. baumannii cultured from sterile sites, with a prevalence of 4.3/1000 live births or 22.8/1000 admissions, accounting for 13% of all culture confirmed sepsis. Majority of neonates were preterm (91%) with a mean gestational age and birth weight of 30 weeks and 1400 grams respectively. Antimicrobial susceptibility of isolates was 64% to cephalosporins, 21% to aminoglycosides and 17% were extremely-drug resistant (XDR), only susceptible to colistin. The CFR was 32%. Factors associated with mortality were presence of a central venous catheter prior to onset of sepsis (49% vs 31%, p = 0.03); need for mechanical ventilation (62% vs 36%, p = 0.005) and inotropic support (57% vs 17%, p < 0.001).
A. baumannii is a significant pathogen causing sepsis in neonates, with 17% of them being XDR. It is associated with high CFR. These findings highlight the need for strict enforcement of infection control and antibiotic stewardship practices.
To compare Candida species distribution and antifungal susceptibility at South African public- and private-sector hospitals.
From February 2009 through to August 2010, laboratory-based surveillance ...for candidaemia was undertaken at 11 public-sector hospitals and >85 private-sector hospitals across South Africa. A case was defined as a patient of any age admitted to a sentinel hospital with isolation of Candida species from blood culture. Viable isolates were identified and tested for antifungal susceptibility at a reference laboratory. Demographic and limited clinical data were abstracted from laboratory records.
In total, 2172 cases of candidaemia were detected. Among patients with available data, almost two-thirds were critically ill (719/1138, 63%). On multivariable analysis, neonates adjusted OR (aOR), 2.2; 95% CI, 1.5-3.1; P < 0.001 and patients diagnosed in Gauteng province (aOR, 1.9; 95% CI, 1.3-2.7; P < 0.001) or in the private sector (aOR, 1.9; 95% CI, 1.2-3.2; P = 0.008) were significantly more likely to be infected with Candida parapsilosis than any other Candida species. Of 531 C. parapsilosis isolates, only 199 (37%) were susceptible to fluconazole and voriconazole; 44% (123/282) of fluconazole-resistant isolates were voriconazole cross-resistant. Factors associated with fluconazole non-susceptible C. parapsilosis infection on multivariable analysis included diagnosis in Gauteng province (aOR, 4.2; 95% CI, 2.7-6.7; P < 0.001), an ICU (aOR, 2.3; 95% CI, 1.5-3.6; P < 0.001) or the private sector (aOR, 2.2; 95% CI, 1.4-3.5; P < 0.001).
The dominance of triazole non-susceptible C. parapsilosis limits the choice of antifungal agents for management of candidaemia among critically ill neonates, children and adults in resource-limited South African hospitals.
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.
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.
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.
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.
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.
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).
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.
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.
We aimed to describe the epidemiology of candidemia among children in South Africa.
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.
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).
Candidemia in this setting mainly affected neonates and infants and was characterized by fluconazole-resistant C. parapsilosis with no increased risk of death.
Pneumonia is the major contributor to under 5 childhood mortality globally. We evaluated the etiology of pneumonia amongst HIV-uninfected South African children enrolled into the Pneumonia Etiology ...Research for Child Health case-control study.
Cases, 1-59 months of age hospitalized with World Health Organization clinically defined severe/very severe pneumonia, were frequency-matched by age and season to community controls. Nasopharyngeal-oropharyngeal swabs were analyzed using polymerase chain reaction for 33 respiratory pathogens, and whole blood was tested for pneumococcal autolysin. Cases were also tested for Mycobacterium tuberculosis. Population etiologic fractions (EF) of pneumonia with radiologic evidence of consolidation/infiltrate were derived for each pathogen through Bayesian analysis.
Of the 805 HIV-uninfected cases enrolled based on clinical criteria, radiologically confirmed pneumonia was evident in 165 HIV-exposed, -uninfected, and 246 HIV-unexposed children. In HIV-exposed and HIV-unexposed children, respiratory syncytial virus was the most important pathogen with EFs of 31.6% 95% credible interval (CrI), 24.8%-38.8% and 36.4% (95% CrI, 30.5%-43.1%), respectively. M. tuberculosis contributed EFs of 11.6% (95% CrI, 6.1%-18.8%) in HIV-exposed and 8.3% (95% CrI, 4.5%-13.8%) in HIV-unexposed children, including an EF of 16.3% (95% CrI, 6.1%-33.3%) in HIV-exposed children ≥12 months of age. Bacteremia (3.0% vs. 1.6%) and case fatality risk (3.6% vs. 3.7%) were similar in HIV-exposed and HIV-unexposed children.
Vaccination strategies targeting respiratory syncytial virus should be prioritized for prevention of pneumonia in children. Furthermore, interventions are required to address the high burden of tuberculosis in the pathogenesis of acute community-acquired pneumonia in settings such as ours.
Summary
Introduction
The prevalence of azole resistance in C parapsilosis is very low in most parts of the world. However, South Africa has reported an exceptionally high prevalence of azole ...resistance in C parapsilosis strains isolated from candidaemia cases. We aimed to determine the possible molecular mechanisms of fluconazole resistance in C parapsilosis isolates obtained through surveillance at a large neonatal unit at a South African academic hospital.
Methods
We sequenced the ERG11 and MRR1 genes of C parapsilosis isolates recovered from cases of neonatal candidemia, followed by microsatellite genotyping. A total of 73 isolates with antifungal susceptibility results were analysed.
Results
Of these, 57 (78%) were resistant, 11 (15%) susceptible dose‐dependent and 5 (7%) susceptible. The most commonly identified amino acid substitution within the ERG11 gene was Y132F in 68% (39/57) of fluconazole‐resistant isolates and none in susceptible isolates. Three amino acid substitutions (R405K, G583R and A619V) and 1 nucleotide deletion at position 1331 were identified within MRR1 gene in 19 (26%) isolates. Microsatellite genotyping grouped isolates into four clusters (50 isolates). Cluster 1 accounted for 23% (17/73) of all cases, cluster 2 for 22% (16/73), cluster 3 for 14% (10/73) and cluster 4 for 10% (7/73). We found an association between cluster type and fluconazole resistance (P‐value = .004). Isolates harbouring the Y132F substitution were more likely to belong to a cluster than non‐Y132F isolates.
Conclusion
Fluconazole resistance in C parapsilosis strains from a single South African neonatal unit was associated with cluster type and predominantly driven by Y123F amino acid substitutions in the ERG11 gene.
BACKGROUNDGlobally, very few childhood deaths have been attributed to coronavirus disease 2019 (COVID-19). We evaluated clinical, microbiologic and postmortem histopathologic findings in childhood ...deaths in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified antemortem or postmortem. METHODSSurveillance of childhood deaths was ongoing during the initial COVID-19 outbreak in South Africa from April 14, 2020, to August 31, 2020. All children hospitalized during this time had a SARS-CoV-2 test done as part of standard of care. Postmortem sampling included minimally invasive tissue sampling (MITS) of lung, liver and heart tissue; blood and lung samples for bacterial culture and molecular detection of viruses (including SARS-CoV-2) and bacteria. The cause of death attribution was undertaken by a multidisciplinary team and reported using World Health Organization framework for cause of death attribution. RESULTSSARS-CoV-2 was identified on antemortem and/or postmortem sampling in 11.7% (20/171) of deceased children, including 13.2% (12/91) in whom MITS was done. Eighteen (90%) of 20 deaths with SARS-CoV-2 infection were <12 months age. COVID-19 was attributed in the causal pathway to death in 91.7% (11/12) and 87.5% (7/8) cases with and without MITS, respectively. Lung histopathologic features in COVID-19-related deaths included diffuse alveolar damage (n = 6, 54.5%), type 2 pneumocyte proliferation (n = 6, 54.5%) and hyaline membrane formation (n = 5, 36.4%). Culture-confirmed invasive bacterial disease was evident in 54.5% (6/11) of COVID-19 attributed deaths investigated with MITS. CONCLUSIONSCOVID-19 was in the causal pathway of 10.5% (18/171) of all childhood deaths under surveillance. The postmortem histopathologic features in fatal COVID-19 cases in children were consistent with reports on COVID-19 deaths in adults; although there was a high prevalence of invasive bacterial disease in the children.
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