FACT

Antibiotic-based combination therapy fosmidomycin-artesunate-clindamycin for the concurrent treatment of severe malaria and bacterial blood stream infection in African children

01/09/2026 to 31/08/2031

Severe malaria is a major cause of preventable morbidity and mortality in endemic regions. 76% of all malaria deaths occur in children <5 years in SSA. While severe malaria constitutes a medical emergency, about one third of children diagnosed with severe malaria suffer from another life-threatening infection, most commonly systemic bacterial infections. Diagnostic differentiation is often not possible in resource limited settings. Ideally, empiric treatment for both aetiologies is warranted. However, often enough either antimalarial or antibiotic therapy is administered, putting the patient at an increased risk of death. Additionally, artemisinin partial resistant Plasmodium isolates constitute an increasing therapeutic challenge for currently recommended artesunate monotherapy. Finally, a high proportion of bacterial isolates with resistance against commonly used antibiotics poses a similar therapeutic challenge. To overcome the 1) lack of adequate initial coverage of antimalarial and antibacterial pathogens, 2) increase of artemisinin partial resistant Plasmodium, and 3) high incidence of antimicrobial drug-resistant bacterial pathogens, we develop an antibiotic-based combination therapy with fosmidomycin- artesunate-clindamycin (FACT) for the simultaneous treatment of severe malaria and bacterial bloodstream infections. FACT includes parenteral artesunate, the currently recommended treatment of severe malaria, coverage of gram-positive and anaerobic bacteria by clindamycin and gram-negative bacteria by fosmidomycin. Clindamycin and fosmidomycin also exert proven synergistic antimalarial activity even in artemisinin resistant isolates. Matching pharmacokinetic parameters and independent modes of action provide further protection against selection for antimalarial drug resistance. Based on previous clinical trials, this project targets the late clinical development of FACT in a Phase II and Phase III clinical trial for subsequent implementation in health services.