All India Institute of Medical Sciences, Department of Microbiology, New Delhi 110029, India.
All India Institute of Medical Sciences, Department of Microbiology, New Delhi 110029, India.
J Glob Antimicrob Resist. 2019 Jun;17:236-239. doi: 10.1016/j.jgar.2019.01.007. Epub 2019 Jan 15.
Pneumocystis pneumonia (PCP) remains a debilitating cause of death among HIV-infected patients. The combination trimethoprim/sulfamethoxazole (SXT) is the most effective anti-Pneumocystis treatment and prophylaxis. However, long-term use of this combination has raised alarms about the emergence of resistant organisms. This study was performed to investigate mutations in the dihydropteroate synthase (DHPS) gene and their clinical consequences in HIV-infected patients with PCP.
A total of 76 clinically suspected cases of PCP among HIV-seropositive adult patients from March 2014 to March 2017 were included. Clinical samples (bronchoalveolar lavage fluid and sputum) were investigated for the detection of Pneumocystis jirovecii using both microscopy and nested PCR. DHPS genotyping and mutational analyses were performed and the data were correlated with clinical characteristics.
Among the 76 enrolled HIV-positive patients, only 17 (22.4%) were positive for P. jirovecii. DHPS gene sequencing showed a novel nucleotide substitution at position 288 (Val96Ile) in three patients (3/12; 25.0%). Patients infected with the mutant P. jirovecii genotype had severe episodes of PCP, did not respond to SXT and had a fatal outcome (P=0.005). All three patients had a CD4 T-cell count <100 cells/μL, and two also had co-infections.
This study suggests that the emergence of a mutant P. jirovecii genotype is probably associated with drug resistance and mortality. The data also suggest that DHPS mutational analyses should be performed in HIV-seropositive patients to avoid treatment failure and death due to PCP. However, the role of underlying disease severity and co-morbidities should not be underestimated.
肺孢子菌肺炎（PCP）仍是 HIV 感染患者衰弱性死亡的原因。复方磺胺甲噁唑（SXT）是最有效的抗肺孢子菌治疗和预防药物。然而，这种联合用药的长期使用引发了对耐药生物出现的担忧。本研究旨在调查 HIV 感染合并 PCP 患者二氢叶酸合成酶（DHPS）基因的突变及其临床后果。
共纳入 2014 年 3 月至 2017 年 3 月期间 76 例 HIV 阳性成人疑似 PCP 患者。使用显微镜和巢式 PCR 检测临床样本（支气管肺泡灌洗液和痰液）中是否存在卡氏肺孢子虫。进行 DHPS 基因分型和突变分析，并将数据与临床特征相关联。
在纳入的 76 例 HIV 阳性患者中，仅有 17 例（22.4%）卡氏肺孢子虫阳性。DHPS 基因测序显示 3 例（3/12；25.0%）患者在 288 位核苷酸发生新的取代（Val96Ile）。感染突变型卡氏肺孢子虫的患者 PCP 病情严重，对 SXT 无反应且结局致死（P=0.005）。所有 3 例患者的 CD4 T 细胞计数均<100 个/μL，其中 2 例还存在合并感染。
本研究提示突变型卡氏肺孢子虫基因型的出现可能与耐药性和死亡率相关。数据还表明，DHPS 突变分析应在 HIV 阳性患者中进行，以避免因 PCP 导致治疗失败和死亡。然而，不应低估潜在疾病严重程度和合并症的作用。
