Department of Laboratory Medicine, E-Da Hospital, Kaohsiung, Taiwan.
Department of Parasitology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
BMC Microbiol. 2023 Jul 5;23(1):178. doi: 10.1186/s12866-023-02926-6.
Non-typeable Haemophilus influenzae (NTHi) has become the major cause of invasive H. influenzae diseases in the post-H. influenzae type b vaccine era. The emergence of multidrug-resistant (MDR) NTHi is a growing public health problem. Herein, we investigated the molecular basis of MDR in NTHi. The isolated NTHi were subjected to antimicrobial susceptibility testing for 12 agents. Whole genome and plasmid sequencing were conducted and analyzed to identify significant genetic variations and plasmid-encoded genes conferred antibiotic resistance.
Thirteen (50%) MDR NTHi isolates were obtained; of these, 92.3% were non-susceptible to ampicillin, 30.8% to amoxicillin-clavulanate, 61.5% to cefuroxime, 61.5% to ciprofloxacin/levofloxacin, 92.3% to trimethoprim-sulfamethoxazole, 30.8% to tetracycline, and 7.7% to azithromycin. Eight ampicillin-resistant isolates were β-lactamase positive; of these, 6 carried bla and 2 carried bla, whereas 4 were β-lactamase negative. Genetic variations in mrdA, mepA, and pbpG were correlated with amoxicillin-clavulanate non-susceptibility, whereas variations in ftsI and lpoA conferred cefuroxime resistance. Five variations in gyrA, 2 in gyrB, 3 in parC, 1 in parE, and 1 in the parC-parE intergenic region were associated with levofloxacin/ciprofloxacin non-susceptibility. Among these genes, 8 variations were linked to high-level levofloxacin resistance. Six variations in folA were associated with trimethoprim-sulfamethoxazole resistance. Plasmid-bearing tet(B) and mef(A) genes were responsible for tetracycline and azithromycin resistance in 4 and 1 MDR isolates, respectively.
This study clarified the molecular epidemiology of MDR in NTHi. This can benefit the monitoring of drug resistance trends in NTHi and the adequate medical management of patients with NTHi infection.
在乙型流感嗜血杆菌（Hib）疫苗时代后，非分型流感嗜血杆菌（NTHi）已成为侵袭性流感嗜血杆菌病的主要病因。多重耐药（MDR）NTHi 的出现是一个日益严重的公共卫生问题。在此，我们研究了 NTHi 中 MDR 的分子基础。对分离的 NTHi 进行了 12 种药物的药敏试验。进行了全基因组和质粒测序，并对其进行了分析，以鉴定具有抗生素耐药性的显著遗传变异和质粒编码基因。
共获得 13 株（50%）MDR NTHi 分离株；其中，92.3%对氨苄西林不敏感，30.8%对阿莫西林-克拉维酸不敏感，61.5%对头孢呋辛不敏感，61.5%对环丙沙星/左氧氟沙星不敏感，92.3%对复方磺胺甲噁唑不敏感，30.8%对四环素不敏感，7.7%对阿奇霉素不敏感。8 株氨苄西林耐药株为β-内酰胺酶阳性；其中 6 株携带 bla，2 株携带 bla，而 4 株为β-内酰胺酶阴性。mrdA、mepA 和 pbpG 的基因变异与阿莫西林-克拉维酸不敏感相关，ftsI 和 lpoA 的变异导致头孢呋辛耐药。gyrA 中有 5 个变异，gyrB 中有 2 个变异，parC 中有 3 个变异，parE 中有 1 个变异，parC-parE 基因间区中有 1 个变异与左氧氟沙星/环丙沙星不敏感相关。在这些基因中，有 8 个变异与高水平左氧氟沙星耐药相关。folA 中有 6 个变异与复方磺胺甲噁唑耐药相关。携带 tet(B)和 mef(A)基因的质粒分别导致 4 株和 1 株 MDR 分离株对四环素和阿奇霉素耐药。
本研究阐明了 NTHi 中 MDR 的分子流行病学。这有助于监测 NTHi 耐药趋势，并对 NTHi 感染患者进行适当的医疗管理。
