Pneumocystis jiroveciidihydropteroate synthase gene mutations in a group of HIV-negative immunocompromised patients withPneumocystispneumonia.
The purpose of this study was to investigate dihydropteroate synthase (DHPS) mutations and their clinical context in non-HIV-infected patients withPneumocystispneumonia (PCP). DHPS genes in respiratory samples collected from HIV-negative patients with PCP presented between January 2008 and April 2011 were amplified by polymerase chain reaction (PCR) and sequenced. Basic clinical data from the medical records of the patients were also reviewed. The most common point mutations, which result in Thr55Ala and Pro57Ser amino acid substitutions, were not detected in thePneumocystis jiroveciisampled from the HIV-negative patients. Two other point mutations, which result in nonsynonymous mutation, Asp90Asn and Glu98Lys, were identified inP. jiroveciifrom two patients. Among the patients, the levels of lactate dehydrogenase (LDH), C-reactive protein (CRP) and plasma (1-3) β-D-glucan were elevated in 75, 92.31 and 42.86% of patients, respectively. The percentage of circulating lymphocytes was significantly lower in non-survivors than in survivors [4.2%, interquartile range (IQR) 2.4-5.85 versus 10.1%, IQR 5.65-23.4; P=0.019]. The neutrophil proportion in bronchoalveolar lavage fluid (BALF) was significantly higher in non-survivors than in survivors (49.78±27.67 versus 21.33±15.03%; P=0.047). Thirteen patients had received adjunctive corticosteroids (1 mg/kg/day prednisone equivalent) and nine (69.23%) of them eventually experienced treatment failure. No common DHPS gene mutations ofP. jiroveciiwere detected in the HIV-negative PCP patients. However, other mutations did exist, the significance of which remains to be further identified. The elevation of neutrophil counts in BALF and reduction of the number of lymphocytes in peripheral blood may be associated with poor outcome. The efficacy of adjunctive steroid therapy in HIV-negative patients withP. jiroveciiinfection requires further investigation.
Department of Pulmonary Medicine, First Hospital, Peking University, Beijing 100034, P.R. China.
Yingjiao
Y
Long
Department of Pulmonary Medicine, First Hospital, Peking University, Beijing 100034, P.R. China.
Cheng
C
Zhang
Department of Pulmonary Medicine, First Hospital, Peking University, Beijing 100034, P.R. China.
Li
L
Su
Department of Pulmonary Medicine, First Hospital, Peking University, Beijing 100034, P.R. China.
Chengli
C
Que
Pneumocystis jirovecii; dihydropteroate synthase gene; drug resistance; mutation