Abstract
Antimicrobial resistance (AMR) in Vibrio cholerae represents a major threat to cholera control efforts in Africa. However, data on the geographic distribution of AMR patterns in the Democratic Republic of the Congo (DRC) remain limited and fragmented. This study aimed to describe the geographic heterogeneity of AMR profiles among V. cholerae O1 isolates from three cholera hotspot provinces in eastern DRC and to identify associated determinants. We conducted a repeated analytical cross-sectional study including 3,676 V. cholerae O1 isolates obtained from 25,421 stool samples collected between 2007 and 2023 by the National Cholera Reference Laboratory in Goma, across three eastern DRC provinces (North Kivu, South Kivu, and Tanganyika). Antimicrobial resistance patterns were analyzed using two complementary approaches: (i) a generalized linear mixed-effects model (GLMM) with a random intercept for health zones to quantify spatial heterogeneity through the intraclass correlation coefficient (ICC) and to test Province × Serotype interactions using likelihood ratio tests; and (ii) Firth’s penalized logistic regression, restricted to the common period 2021–2022, to estimate adjusted odds ratios (aORs) for erythromycin resistance while addressing quasi-complete separation. Analyses were performed using R version 4.3.3. Resistance was nearly universal to ampicillin (99.8%), chloramphenicol (100%), cotrimoxazole (100%), and nalidixic acid (99.9%), while no resistance was detected to tetracycline, doxycycline, norfloxacin, or azithromycin. Only erythromycin resistance showed marked geographic heterogeneity, with a clear north-to-south gradient (28.2% in North Kivu, 65.4% in South Kivu, and 86.5% in Tanganyika; p < 0.001) and extreme within-province variability (0–97.9% across health zones). Health zone-level variation accounted for 56.7% of the total variance (ICC = 0.567). After adjustment for temporal effects, geographic differences remained significant, with higher odds of erythromycin resistance in South Kivu (adjusted OR = 1.93; 95% CI: 1.31–2.85; p = 0.001) and Tanganyika (adjusted OR = 4.02; 95% CI: 1.89–9.27; p < 0.001). AMR among V. cholerae in the DRC is characterized by near-universal resistance to historically used antibiotics, while susceptibility to doxycycline and azithromycin remains preserved. The marked geographic gradient in erythromycin resistance, substantial within-province heterogeneity, and significant Province × Serotype interaction highlights the need for surveillance at the health zone level to guide locally adapted cholera treatment strategies.
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