在坦桑尼亚社区环境中从感染 HIV 的成年人中分离的肺炎链球菌中，二氢叶酸还原酶基因的抗微生物药物耐药率高且存在多种突变。
High rate of antimicrobial resistance and multiple mutations in the dihydrofolate reductase gene among Streptococcus pneumoniae isolated from HIV-infected adults in a community setting in Tanzania.
机构信息
Department of Clinical Science, University of Bergen, Bergen, Norway; National Centre for Tropical Infectious Diseases, Department of Medicine, Haukeland University Hospital, Bergen, Norway; Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
出版信息
J Glob Antimicrob Resist. 2020 Sep;22:749-753. doi: 10.1016/j.jgar.2020.06.026. Epub 2020 Jul 9.
OBJECTIVES
The aim of this study was to characterize molecular mechanisms of resistance to trimethoprim and other antibiotics in Streptococcus pneumoniae isolates from HIV-infected adults in Dar es Salaam, Tanzania.
METHODS
A total of 1877 nasopharyngeal swabs were collected and screened for pneumococcal colonization from 537 newly diagnosed individuals with HIV at four clinic visits during a 1-year follow-up from 2017-2018 as part of the randomized clinical trial CoTrimResist (ClinicalTrials.gov ID: NCT03087890).
RESULTS
A total of 76 pneumococcal isolates were obtained. Of the 70 isolates that could be serotyped, 42 (60.0%) were vaccine serotypes included in pneumococcal conjugate vaccine 23 (PCV23). The majority of isolates (73.7%; 56/76) were non-susceptible to penicillin (MICs of 0.06-2μg/mL). Isolates were frequently resistant to co-trimoxazole (trimethoprim/sulfamethoxazole) (71.1%) but less so to azithromycin (22.4%), erythromycin (21.1%), chloramphenicol (18.4%), tetracycline (14.5%), clindamycin (10.5%) and levofloxacin (0%). Moreover, 26.3% were multidrug-resistant (resistant to ≥3 antibiotic classes). Vaccine-type pneumococci were resistant to more classes of antibiotics, were more frequently resistant to erythromycin, azithromycin, clindamycin and tetracycline, and had higher MICs to penicillin (median, 0.19μg/mL; range, 0.002-1.5μg/mL) compared with non-vaccine serotypes (median, 0.125μg/mL; range, 0.012-0.25μg/mL) (P=0.003). Co-trimoxazole-resistant isolates carried from 1 to 11 different mutations in the dihydrofolate reductase (DHFR) gene, most commonly Ile100Leu (100%), Glu20Asp (91.8%), Glu94Asp (61.2%), Leu135Phe (57.1%), His26Tyr (53.1%), Asp92Ala (53.1%) and His120Gln (53.1%).
CONCLUSION
Streptococcus pneumoniae isolated from HIV-diagnosed patients were frequently non-susceptible to penicillin and co-trimoxazole. Most isolates carried multiple mutations in DHFR.
目的
本研究旨在描述坦桑尼亚达累斯萨拉姆感染艾滋病毒的成年人中肺炎链球菌分离株对甲氧苄啶和其他抗生素耐药的分子机制。
方法
2017 年至 2018 年期间，在一项为期 1 年的随机临床试验 CoTrimResist（ClinicalTrials.gov ID：NCT03087890）中，从 537 名新诊断为 HIV 的个体的 4 次就诊中，共采集了 1877 份鼻咽拭子，筛查肺炎链球菌定植情况。
结果
共获得 76 株肺炎链球菌分离株。在 70 株可分型的分离株中，42 株（60.0%）为包括肺炎球菌结合疫苗 23 型（PCV23）在内的疫苗血清型。大多数分离株（73.7%；56/76）对青霉素（MIC 为 0.06-2μg/mL）不敏感。分离株经常对复方磺胺甲噁唑（trimethoprim/sulfamethoxazole）（71.1%）耐药，但对阿奇霉素（22.4%）、红霉素（21.1%）、氯霉素（18.4%）、四环素（14.5%）、克林霉素（10.5%）和左氧氟沙星（0%）的耐药性较低。此外，26.3%的分离株为多药耐药（对≥3 种抗生素类别耐药）。疫苗型肺炎球菌对更多类别的抗生素耐药，对红霉素、阿奇霉素、克林霉素和四环素的耐药性更频繁，对青霉素的 MIC 更高（中位数为 0.19μg/mL；范围为 0.002-1.5μg/mL），而非疫苗血清型（中位数为 0.125μg/mL；范围为 0.012-0.25μg/mL）（P=0.003）。复方磺胺甲噁唑耐药分离株在二氢叶酸还原酶（DHFR）基因中携带 1 至 11 种不同的突变，最常见的是 Ile100Leu（100%）、Glu20Asp（91.8%）、Glu94Asp（61.2%）、Leu135Phe（57.1%）、His26Tyr（53.1%）、Asp92Ala（53.1%）和 His120Gln（53.1%）。
结论
从艾滋病毒诊断患者中分离出的肺炎链球菌对青霉素和复方磺胺甲噁唑经常不敏感。大多数分离株携带多个 DHFR 突变。
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