When first line treatment of neonatal infection is not enough: blood culture and resistance patterns in neonates requiring second line antibiotic therapy in Bangui, Central African Republic.

BACKGROUND: Infectious diseases account for the third most common cause of neonatal deaths. Globally, antibiotic resistance (ABR) has been increasingly challenging neonatal sepsis treatment, with 26 to 84% of gram-negative bacteria resistant to third-generation cephalosporins. In sub-Saharan Africa, limited evidence is available regarding the neonatal microbiology and ABR. To our knowledge, no studies have assessed neonatal bacterial infections and ABR in Central-African Republic (CAR). Therefore, this study aimed to describe the pathogens isolated and their specific ABR among patients with suspected antibiotic-resistant neonatal infection admitted in a CAR neonatal unit. METHODS: This retrospective cohort study included neonates admitted in the neonatal unit in Bangui, CAR, from December 2018 to March 2020, with suspected antibiotic-resistant neonatal infection and subsequent blood culture. We described the frequency of pathogens isolated from blood cultures, their ABR prevalence, and factors associated with fatal outcome. RESULTS: Blood cultures were positive in 33 (26.6%) of 124 patients tested (17.9% for early-onset and 46.3% for late-onset infection; p = 0.002). Gram-negative bacteria were isolated in 87.9% of positive samples; with most frequently isolated bacteria being Klebsiella pneumoniae (39.4%), Escherichia coli (21.2%) and Klebsiella oxytoca (18.2%). All tested bacteria were resistant to ampicillin. Resistance to third-generation cephalosporins was observed in 100% of tested Klebsiella pneumoniae, 83.3% of isolated Klebsiella oxytoca and 50.0% of tested Escherichia coli. None of the tested bacteria were resistant to carbapenems. Approximately 85.7 and 77.8% of gram-negative tested bacteria were resistant to first-line (ampicillin-gentamicin) and second-line (third-generation cephalosporins) treatments, respectively. In hospital mortality, adjusted for blood culture result, presence of asphyxia, birth weight and sex was higher among neonates with positive blood culture (adjusted relative risk [aRR] = 2.32; 95% confidence interval [CI] = 1.17-4.60), male sex (aRR = 2.07; 95% CI = 1.01-4.26), asphyxia (aRR = 2.42; 95% CI = 1.07-5.47) and very low birth weight (1000-1499 g) (aRR = 2.74; 95% CI = 1.3-5.79). CONCLUSION: Overall, 77.8% of confirmed gram-negative neonatal infections could no longer effectively be treated without broad-spectrum antibiotics that are not routinely used in sub-Saharan Africa referral hospitals. Carbapenems should be considered an option in hospitals with surveillance and antibiotic stewardship.

2003-2019: explosive spread of enterobacteria producing extended-spectrum beta-lactamases in Bangui Central African Republic.

INTRODUCTION: the spread of enterobacteria producing extended-broad-spectrum beta-lactamases (ESBL) is a global public health-problem. In a study carried in 2003-2005 at the Pasteur Institute in Bangui, 450 enterobacteria were identified in clinical isolates, of which 17 were ESBL (prevalence: 3.78%). The aim of this study was to update this data. METHODS: from May 2018 to April 2019, a total of 941 enterobacteria were isolated and identified under identical conditions of recruitment and with the same techniques used in the previous study: phenotypic identification using Api 20E strips (bioMérieux SA, Marcy-l'Etoile, France) and antimicrobial drug susceptibility using the disk diffusion method (Bio-Rad antibiotic discs, Marnes la Coquette, France). Resistance genes were identified by polymerase chain reaction (PCR) and sequencing. RESULTS: from May 2018 to April 2019, a total of 941 enterobacteria were isolated of which 478 were ESBL, thus amounting to a prevalence of 50.80%. The genetic profiles of the bla CTX-M resistance genes exhibited the emergence of the CTX-M28 variant (CTX-M1 group) and variants of the M2 and M9 groups. There was also a notable increase, from 35 to 64%, in the ESBL with a bla SHV gene. CONCLUSION: this study documents a 13 fold increase in the prevalence of ESBL derived from clinical isolates of the bacteriology laboratory of the Institute Pasteur in Bangui, by comparing its data with that of the publication by Frank et al. 2006. Together with this increase a significant diversification of the circulating CTX-M resistance genes was noticed.

Vitamin C levels in a Central-African mother-infant cohort: Does hypovitaminosis C increase the risk of enteric infections?

In the MITICA (Mother-to-Infant TransmIssion of microbiota in Central-Africa) study, 48 mothers and their 50 infants were followed from delivery to 6 months between December 2017 and June 2019 in Bangui (Central-African Republic). Blood tests and stool analyses were performed in mothers at delivery, and their offspring at birth, 11 weeks and 25 weeks. Stool cultures were performed in specific growth media for Salmonella, Shigella, E. coli, Campylobacter, Enerobacter, Vibrio cholerae, Citrobacter and Klebsiella, as well as rotavirus, yeasts and parasitological exams. The median vitamin C levels in mothers at delivery were 15.3 µmol/L (inter-quartile-range [IQR] 6.2-27.8 µmol/L). In infants, the median vitamin C levels at birth were 35.2 µmol/L (IQR 16.5-63.9 µmol/L). At 11 and 25 weeks, the median vitamin C levels were 41.5 µmol/L (IQR 18.7-71.6 µmol/L) and 18.2 µmol/L (IQR 2.3-46.6 µmol/L), respectively. Hypovitaminosis C was defined as seric vitamin C levels <28 µmol/L and vitamin C deficiency was defined as vitamin C levels <11 µmol/L according to the WHO definition. In mothers, the prevalence of hypovitaminosis-C and vitamin C deficiency at delivery was 34/45 (75.6%) and 19/45 (42.2%), respectively. In infants, the prevalence of hypovitaminosis-C and vitamin C deficiency at 6 months was 18/33 (54.6%) and 11/33 (33.3%), respectively. Vitamin C levels in mothers and infants were correlated at birth (Spearman's rho = 0.5; P value = 0.002), and infants had significantly higher levels of vitamin C (median = 35.2 µmol/L; IQR 16.5-63.9 µmol/L), compared to mothers (median = 15.3 µmol/L; IQR 6.2-27.8 µmol/L; P value <0.001). The offspring of vitamin C-deficient mothers had significantly lower vitamin C levels at delivery (median = 18.7 µmol/L; IQR 13.3-30.7 µmol/L), compared to the offspring of non-deficient mothers (median = 62.2 µmol/L; IQR 34.6-89.2 µmol/L; P value <0.001). Infants with hypovitaminosis-C were at significantly higher risk of having a positive stool culture during the first 6 months of life (adjusted OR = 5.3, 95% CI 1.1; 26.1; P value = 0.038).

Seventh Pandemic Vibrio cholerae O1 Sublineages, Central African Republic.

Four cholera outbreaks were reported in the Central African Republic during 1997-2016. We show that the outbreak isolates were Vibrio cholerae O1 serotype Inaba from 3 seventh pandemic El Tor sublineages originating from West Africa (sublineages T7 and T9) or the African Great Lakes Region (T10).