Consequences of antibiotic resistance after preventive treatment with cotrimoxazole in HIV patients (CoTrimResist)

Cotrimoxazole preventive therapy (CPT) is recommended to prevent morbidity and mortality due to Pneumocystis jirovecii pneumonia (PJP) and other infections in HIV-positive patients with low immunity. 

Recent WHO guidelines widely expand the indication for CPT by advocating that CPT be continued indefinitely in setting with high prevalence of malaria and bacterial infections, and regardless of patient's CD4 counts and clinical stage. There is poor documentation to support this recommendation, since studies have shown prolonged CPT is associated with modestly reduced morbidity due to pneumonia, meningitis and malaria, but no corresponding reduction in mortality. Furthermore, no consideration has been given to the possible negative effect that prolonged CPT may lead to increasing multidrug-resistance among bacteria, especially gut microbes, which is a major emerging public health problem world-wide. 

Our previous studies in Tanzania showed that multidrug-resistant bacteria frequently cause bloodstream infections with resultant very high case-fatality rates. As genes encoding for multiple antibiotic resistance traits are transferred by plasmids together with resistance towards cotrimoxazole, prolonged CPT will likely favor the selection of carriage of multidrug-resistant gut bacteria.

Our aim is to assess whether prolonged CPT has negative or positive effects on the patient and the society.  

Randomised controlled clinical trial CoTrimResist (external link) was designed to assess whether prolonged CPT in HIV-positive patients results in increased fecal carriage of multi-drug resistant gut microbes or increased nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA). Secondary endpoints are morbidity (clinical events, hospitalizations) and mortality. Stool specimens, nasal swabs and clinical data were collected from persons attending voluntary counseling and testing facilities and HIV clinics in Dar es Salaam, Tanzania. 

The study may have important impact on public health in terms of assisting development of rational recommendations for CPT use, and may help prevent emerging antibiotic resistance.

Our collaborative partner institution on the project is Muhimbili National Hospital (external link) (MNH), Dar es Salaam, Tanzania.