In vitro activity of the antimalarial, antibiotic drugs fosmidomycin and clindamycin against clinical isolates of bacterial bloodstream infections in febrile, hospitalized Ghanaian children.

BACKGROUND: The clinical and laboratory distinction between malaria and bacterial blood stream infections in patients with undifferentiated fever remains challenging. Misclassification may result in ineffective treatment with the risk of progression of disease and subsequent morbidity and mortality. A pragmatic solution is the use of multi-disease treatments effective against both malaria and the clinically most relevant bacterial pathogens. Fosmidomycin and clindamycin are two antibiotics that have demonstrated high efficacy in treating malaria. A multi-drug combination treatment of fosmidomycin, clindamycin, and artesunate has been evaluated for the treatment of malaria. To further explore whether fosmidomycin and clindamycin could be used in combined anti-malarial, anti-bacterial broad-spectrum chemotherapeutic treatment, the in vitro anti-bacterial activity of fosmidomycin and clindamycin was assessed against clinically relevant bacterial pathogens responsible for blood stream infections in sub-Saharan African children.

METHODS: In vitro drug susceptibility testing was performed using clinical isolates of bacterial bloodstream infections from febrile, hospitalized children in Ghana. Isolates included the most common bacteria responsible for bloodstream infections in sub-Saharan African children, comprising Klebsiella pneumoniae, Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus, and non-typhoidal Salmonella (NTS). Minimum Inhibitory Concentrations of fosmidomycin and clindamycin were determined using the agar dilution method.

RESULTS: The findings of in vitro antimicrobial susceptibility testing demonstrated that all tested strains showed susceptibility to at least one of the antibiotics tested. Gram-negative strains demonstrated susceptibility to fosmidomycin (100%) but resistance to clindamycin, while gram-positive strains showed the opposite pattern: susceptibility to clindamycin (100%) but resistance to fosmidomycin.

CONCLUSIONS: The results underscore the potential of combining fosmidomycin and clindamycin in antimalarial treatment regimens as a multi-disease treatment strategy, particularly for febrile children. Such an approach would target both Plasmodium falciparum and the clinically most relevant bacterial pathogens, addressing one of the most important diagnostic and treatment challenges faced in malaria-endemic regions.