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.

Implementation and Operational Research: Feasibility of Using Tuberculin Skin Test Screening for Initiation of 36-Month Isoniazid Preventive Therapy in HIV-Infected Patients in Resource-Constrained Settings.

INTRODUCTION: The tuberculin skin test (TST) can be used to identify HIV-infected people who would benefit the most from long-term isoniazid preventive therapy (IPT). However, in resource-constrained settings, implementation of the TST can be challenging. The objectives of this study were to assess the feasibility of implementing the TST for IPT initiation and to estimate the proportion of TST-positive incidence among HIV-positive patients in 2 high tuberculosis and HIV burden settings. METHODS: Two prospective observational cohort studies were conducted under programmatic conditions in Mathare, an urban slum of Nairobi, Kenya, and in rural Shiselweni, Swaziland. HIV-positive adults with negative tuberculosis symptomatic screening underwent the TST. Those testing positive were started on 36-month IPT. RESULTS: Of 897 and 1021 patients screened in Mathare and Shiselweni, 550 and 696, respectively, were included. Median age was 38 years, 67.7% were female, and 86.8% were on antiretroviral therapy. Among TST-eligible participants, 88.0% (491/558) and 81.8% (694/848) accepted TST and 74.2% (414/558) and 77.1% (654/858) returned for test reading in Mathare and Shiselweni, respectively. The TST was positive in 49.8% (95% confidence interval: 44.9 to 54.6) in Mathare and 33.2% (95% confidence interval: 29.6 to 36.8) in Shiselweni. The 36-month IPT was accepted by 96.1% (198/206) patients in Mathare and 99.5% (216/217) in Shiselweni. IPT implementation at the clinics was managed with no additional staff or extra space. CONCLUSION: Implementing the TST for IPT initiation was feasible and acceptable in both urban and rural resource-constrained settings. This strategy allows patients who can benefit the most to receive long-term IPT and avoids unnecessarily treating a significant number of patients who do not stand to benefit.