- Autores: BUSTAMANTE R., CÁRDENAS A., CHABÉ M., DURAN L., GEORGE C., GUERRERO J., HUANG L., Matos O, MILLER R. F., PONCE C. A., VARGAS S. L.
- Ano de Publicação: 2017
- Journal: Antimicrobial Agents and Chemotherapy
- Link: http://aac.asm.org/content/early/2016/11/08/AAC.01290-16.short?rss=1&cited-by=yes&legid=aac;AAC.01290-16v1
Mutations in the Dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii associate with failure of sulfa prophylaxis. They can develop by selection in patients receiving sulfa drugs, or be acquired via person-to-person transmission. DHPS mutations raise concern about decreasing efficacy of sulfa drugs, the main available therapeutic tool for Pneumocystis pneumonia (PCP).
The prevalence of Pneumocystis DHPS mutations was examined in Pneumocystis isolates from 56 sulfa-prophylaxis-naive adults with first-episode of PCP from 2002-2010 in Santiago, Chile. Their clinical history was reviewed to analyze the effect of these mutations on response to trimethoprim-sulfamethoxazole (TMP-SMZ) therapy and outcome. Mutant genotypes occurred in 22(48%) of 46 HIV-infected, and in 5(50%) of 10 HIV-uninfected patients. Compared to patients with wild type genotype, those with mutant genotypes were more likely to experience sulfa treatment-limiting adverse reactions, and, to have a twice-longer duration of mechanical ventilation if mechanically ventilated. Specific genotypes did not associate with death, which occurred in none of the HIV-infected, and in 50% of non-HIV-infected patients. Chile has a high prevalence of DHPS mutations presumably acquired through inter-human transmission because patients were not on sulfa prophylaxis.
Results contrast with the low prevalence observed in other Latin American countries with similar usage of sulfa drugs suggesting additional sources of resistant genotypes may be possible. The twice-longer duration of mechanical ventilation in patients with mutant DHPS genotypes may suggest decreased efficacy of TMP-SMZ and warrant collaborative studies to recognize the relevance of DHPS mutations, and further research to increase therapeutic options for PCP.