title: Sulfa use, dihydropteroate synthase mutations, and Pneumocystis jirovecii pneumonia.
abstract: A systematic review was conducted to examine the associations in Pneumocystis jirovecii pneumonia (PCP) patients between dihydropteroate synthase (DHPS) mutations and sulfa or sulfone (sulfa) prophylaxis and between DHPS mutations and sulfa treatment outcome. Selection criteria included study populations composed entirely of PCP patients and mutation or treatment outcome results for all patients, regardless of exposure status. Based on 13 studies, the risk of developing DHPS mutations is higher for PCP patients receiving sulfa prophylaxis than for PCP patients not receiving sulfa prophylaxis (p < 0.001). Results are too heterogeneous (p < 0.001) to warrant a single summary effect estimate. Estimated effects are weaker after 1996 and stronger in studies that included multiple isolates per patient. Five studies examined treatment outcome. The effect of DHPS mutations on treatment outcome has not been well studied, and the few studies that have been conducted are inconsistent even as to the presence or absence of an association.
authors.affiliation: Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, North Carolina 27599-7435, USA. meshnick@email.unc.edu
authors.forename: Cheryl R
authors.initials: CR
authors.lastname: Stein
authors.forename: Charles
authors.initials: C
authors.lastname: Poole
authors.forename: Powel
authors.initials: P
authors.lastname: Kazanjian
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004094:Dihydropteroate Synthase / Q000235:genetics*; D025141:Drug Resistance, Fungal; D006801:Humans; D009154:Mutation; D045363:Pneumocystis carinii / Q000187:drug effects* / Q000201:enzymology; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000890:Anti-Infective Agents; D013449:Sulfonamides; D004094:Dihydropteroate Synthase