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

Abstract

Abstract 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.

Keywords

• Antibiotic resistance
• Neonatal sepsis
• Neonatal infection
• Neonatal intensive care unit
• Blood culture
• Klebsiella