Department of Microbiology and Immunology, Faculty of Pharmacy, Al Azhar University, Assiut Branch, Assiut, 71526, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Al Khalifa Al Ma'moun St., Abbassia, Cairo, Egypt.
Sci Rep. 2021 Oct 11;11(1):20136. doi: 10.1038/s41598-021-99230-y.
Among bacterial species implicated in hospital-acquired infections are the emerging Pan-Drug Resistant (PDR) and Extensively Drug-Resistant (XDR) Acinetobacter (A.) baumannii strains as they are difficult to eradicate. From 1600 clinical specimens, only 100 A. baumannii isolates could be recovered. A high prevalence of ≥ 78% resistant isolates was recorded for the recovered isolates against a total of 19 tested antimicrobial agents. These isolates could be divided into 12 profiles according to the number of antimicrobial agents to which they were resistant. The isolates were assorted as XDR (68; 68%), Multi-Drug Resistant (MDR: 30; 30%), and PDR (2; 2%). Genotypically, the isolates showed three major clusters with similarities ranging from 10.5 to 97.8% as revealed by ERIC-PCR technique. As a resistance mechanism to fluoroquinolones (FQs), target site mutation analyses in gyrA and parC genes amplified from twelve selected A. baumannii isolates and subjected to sequencing showed 12 profiles. The selected isolates included two CIP-susceptible ones, these showed the wild-type profile of being have no mutations. For the ten selected CIP-resistant isolates, 9 of them (9/10; 90%) had 1 gyrA/1 parC mutations (Ser 81 → Leu mutation for gyrA gene and Ser 84 → Leu mutation for parC gene). The remaining CIP-resistant isolate (1/10; 10%) had 0 gyrA/1 parC mutation (Ser 84 → Leu mutation for parC gene). Detection of plasmid-associated resistance genes revealed that the 86 ciprofloxacin-resistant isolates carry qnrA (66.27%; 57/86), qnrS (70.93%; 61/86), aac (6')-Ib-cr (52.32%; 45/86), oqxA (73.25%; 63/86) and oqxB (39.53%; 34/86), while qepA and qnrB were undetected in these isolates. Different isolates were selected from profiles 1, 2, and 3 and qnrS, acc(6,)-ib-cr, oqxA, and oqxB genes harbored by these isolates were amplified and sequenced. The BLAST results revealed that the oqxA and oqxB sequences were not identified previously in A. baumannii but they were identified in Klebsiella aerogenes strain NCTC9793 and Klebsiella pneumoniae, respectively. On the other hand, the sequence of qnrS, and acc(6,)-ib-cr showed homology to those of A. baumannii. MDR, XDR, and PDR A. baumannii isolates are becoming prevalent in certain hospitals. Chromosomal mutations in the sequences of GyrA and ParC encoding genes and acquisition of PAFQR encoding genes (up to five genes per isolate) are demonstrated to be resistance mechanisms exhibited by fluoroquinolones resistant A. baumannii isolates. It is advisable to monitor the antimicrobial resistance profiles of pathogens causing nosocomial infections and properly apply and update antibiotic stewardship in hospitals and outpatients to control infectious diseases and prevent development of the microbial resistance to antimicrobial agents.
在医院获得性感染中涉及的细菌种类包括新兴的泛耐药（PDR）和广泛耐药（XDR）鲍曼不动杆菌（A.）菌株，因为它们很难消除。从 1600 份临床标本中，仅回收了 100 株 A. 鲍曼不动杆菌分离株。回收的分离株对总共测试的 19 种抗菌药物的耐药率均≥78%。这些分离株可根据对它们耐药的抗菌药物数量分为 12 种类型。根据 ERIC-PCR 技术，这些分离株分为三个主要聚类，相似度为 10.5%至 97.8%。作为对氟喹诺酮类药物（FQs）的耐药机制，对从 12 株选定的 A. 鲍曼不动杆菌分离株扩增的 gyrA 和 parC 基因进行的靶位突变分析，并进行测序显示 12 种类型。所选分离株包括两个 CIP 敏感的分离株，它们显示出没有突变的野生型。对于 10 个选定的 CIP 耐药分离株，其中 9 个（9/10；90%）有 1 个 gyrA/1 个 parC 突变（gyrA 基因的丝氨酸 81→亮氨酸突变和 parC 基因的丝氨酸 84→亮氨酸突变）。剩下的一个 CIP 耐药分离株（1/10；10%）有 0 个 gyrA/1 个 parC 突变（parC 基因的丝氨酸 84→亮氨酸突变）。检测质粒相关的耐药基因显示，86 株环丙沙星耐药分离株携带 qnrA（66.27%；57/86）、qnrS（70.93%；61/86）、aac（6'）-Ib-cr（52.32%；45/86）、oqxA（73.25%；63/86）和 oqxB（39.53%；34/86），而这些分离株中未检测到 qepA 和 qnrB。从谱 1、2 和 3 中选择不同的分离株，并扩增和测序这些分离株携带的 qnrS、acc(6,)-ib-cr、oqxA 和 oqxB 基因。BLAST 结果表明，oqxA 和 oqxB 序列以前未在 A. 鲍曼不动杆菌中鉴定，但在肺炎克雷伯菌 NCTC9793 和肺炎克雷伯菌中分别鉴定。另一方面，qnrS 和 acc(6,)-ib-cr 的序列与 A. 鲍曼不动杆菌的序列具有同源性。MDR、XDR 和 PDR A. 鲍曼不动杆菌分离株在某些医院越来越普遍。GyrA 和 ParC 基因编码序列的染色体突变以及获得多达每个分离株 5 个 PAFQR 编码基因被证明是氟喹诺酮类耐药 A. 鲍曼不动杆菌分离株的耐药机制。建议监测引起医院感染的病原体的抗菌药物耐药谱，并在医院和门诊中正确应用和更新抗生素管理，以控制传染病并防止微生物对抗菌药物的耐药性发展。
