Antimicrobial resistance and clonality of Staphylococcus aureus causing bacteraemia in children admitted to the Manhiça District Hospital, Mozambique, over two decades

Funding Information: The authors thank the families and their children who participated in the study. We are grateful to the CISM and MDH staff for collecting and processing data; and the District Health Authorities for their collaboration in the research activities on-going in the Manhiça District. We acknowledge Manuela Oliveira (FMV/UL, Portugal) for access to PFGE facility. Special thanks for the CISM Bacteriology and Molecular Biology laboratory technicians for sample processing. We thank Sultuane Givá for their invaluable work in the microbiological laboratory. Funding Information: CISM receives core funding from “Agencia Española de Cooperacion Internacional para el Desarollo (AECID).” MG was supported by grant 145278, from Fundação Calouste Gulbenkian “Calouste Gulbenkian Foundation.” Additional support was provided by Fundação para a Ciência e a Tecnologia (FCT, Portugal) through funds to GHTM (UID/04413/2020). This study was partly supported by funds from PATH through to the pneumonia and pneumococcus surveillance study (GAT.770-790-01350-LPS), Bill & Melinda Gates Foundation through Center for Vaccine Development, University of Maryland School of Medicine, the United States Agency for International Development mission in Mozambique through to Fixed Obligation grant no. AID-656-F-12-00001, under RFA-656-12-000003, and the “Child Health and Mortality Prevention Surveillance-CHAMPS” through Bill & Melinda Gates Foundation under the grant OPP1126780, subcontract SC00003286. ISGlobal acknowledges support from the grant CEX2018-000806-S funded by MCIN/AEI/10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Program.” Publisher Copyright: Copyright © 2023 Garrine, Costa, Messa, Massora, Vubil, Ácacio, Nhampossa, Bassat, Mandomando and Couto.

Background: Staphylococcus aureus is one of the main causes of bacteraemia, associated with high mortality, mainly due to the occurrence of multidrug resistant (MDR) strains. Data on antibiotic susceptibility and genetic lineages of bacteraemic S. aureus are still scarce in Mozambique. The study aims to describe the antibiotic susceptibility and clonality of S. aureus isolated from blood cultures of children admitted to the Manhiça District Hospital over two decades (2001–2019). Methods: A total of 336 S. aureus isolates detected in blood cultures of children aged <5 years were analyzed for antibiotic susceptibility by disk diffusion or minimal inhibitory concentration, and for the presence of resistance determinants by PCR. The clonality was evaluated by SmaI-PFGE, spa typing, and MLST. The SCCmec element was characterized by SCCmec typing. Results: Most S. aureus (94%, 317/336) were resistant to at least one class of antibiotics, and one quarter (25%) showed a MDR phenotype. High rates of resistance were detected to penicillin (90%) and tetracycline (48%); followed by erythromycin/clindamycin (25%/23%), and co-trimoxazole (11%), while resistance to methicillin (MRSA strains) or gentamicin was less frequent (≤5%). The phenotypic resistance to distinct antibiotics correlated well with the corresponding resistance determinants (Cohen’s κ test: 0.7–1.0). Molecular typing revealed highly diverse clones with predominance of CC5 (17%, 58/336) and CC8 (16%), followed by CC15 (11%) and CC1 (11%). The CC152, initially detected in 2001, re-emerged in 2010 and became predominant throughout the remaining surveillance period, while other CCs (CC1, CC5, CC8, CC15, CC25, CC80, and CC88) decreased over time. The 16 MRSA strains detected belonged to clones t064-ST612/CC8-SCCmecIVd (69%, 11/16), t008-ST8/CC8-SCCmecNT (25%, 4/16) and t5351-ST88/CC88-SCCmecIVa (6%, 1/16). Specific clonal lineages were associated with extended length of stay and high in-hospital mortality. Conclusion: We document the circulation of diverse MDR S. aureus causing paediatric bacteraemia in Manhiça district, Mozambique, requiring a prompt recognition of S. aureus bacteraemia by drug resistant clones to allow more targeted clinical management of patients.