Sleiman Ahmad, Abdelkhalek Pascal, Doumat George, Atallah Frida, Hamadeh Lama, Moussa Pamela, Bou Akl Imad, Dbaibo Ghassan, Araj George F, Kanj Souha S, Mahfouz Rami, Matar Ghassan M, Kanafani Zeina A, Abou Fayad Antoine G
Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Center for Infectious Diseases Research, American University of Beirut, Beirut, Lebanon.
Front Med (Lausanne). 2023 Feb 1;10:1001476. doi: 10.3389/fmed.2023.1001476. eCollection 2023.
The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Secondary bacterial infections are associated with unfavorable outcomes in respiratory viral infections. This study aimed at determining the prevalence of secondary bacterial infections in COVID-19 patients admitted at a tertiary medical center in Lebanon.
From May till November, 2020, a total of 26 Gram-negative isolates were recovered from 16 patients during the course of their COVID-19 infection with being the most prevalent. The isolates were assessed for their antimicrobial susceptibility by broth microdilution against 19 antimicrobial agents from different classes. Whole genome sequencing of 13 isolates allowed the mining of antimicrobial resistance (AMR) determinants as well as mobile genetic elements and sequence types (ST). Finally, broth microdilution with three different efflux pump inhibitors [theobromine, conessine and PheArg-β-naphthylamide (PAβN)] was done.
Antimicrobial susceptibility testing showed that out of the 26 Gram-negative isolates, 1 (4%) was extensively drug resistant and 14 (54%) were multi-drug resistant (MDR). Whole genome sequencing results revealed a plethora of AMR determinants among the 13 sequenced isolates. Moreover, the 9 Enterobacterales and 4 sequenced isolates belonged to 9 and 2 different ST, respectively. Using a variety of efflux pump inhibitors we demonstrated that only PAβN had a significant effect when combined with levofloxacin, and the latter regained its activity against two isolates.
The identification of carbapenem and colistin resistant Gram-negative bacilli causing secondary bacterial infections in critical patients diagnosed with COVID-19 should be of high concern. Additionally, it is crucial to monitor and track AMR, post-COVID pandemic, in order to better understand the effect of this disease on AMR exacerbation.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）已在全球范围内传播。继发性细菌感染与呼吸道病毒感染的不良结局相关。本研究旨在确定黎巴嫩一家三级医疗中心收治的COVID-19患者中继发性细菌感染的患病率。
2020年5月至11月期间，在16例COVID-19感染患者病程中，共分离出26株革兰阴性菌，其中[具体细菌名称未给出]最为常见。采用肉汤微量稀释法对这些分离株进行19种不同类别的抗菌药物敏感性评估。对13株分离株进行全基因组测序，以挖掘抗菌药物耐药性（AMR）决定因素以及移动遗传元件和序列类型（ST）。最后，使用三种不同的外排泵抑制剂[可可碱、康丝碱和苯丙氨酸精氨酸-β-萘酰胺（PAβN）]进行肉汤微量稀释试验。
抗菌药物敏感性测试显示，在26株革兰阴性菌分离株中，1株（4%）为广泛耐药，14株（54%）为多重耐药（MDR）。全基因组测序结果显示，在13株测序分离株中存在大量AMR决定因素。此外,9株肠杆菌科细菌和4株[具体细菌名称未给出]测序分离株分别属于9种和2种不同的ST。使用多种外排泵抑制剂，我们证明只有PAβN与左氧氟沙星联合使用时有显著效果，且左氧氟沙星对2株[具体细菌名称未给出]分离株恢复了活性。
在确诊为COVID-19的重症患者中，鉴定出导致继发性细菌感染的耐碳青霉烯和耐黏菌素革兰阴性杆菌应引起高度关注。此外，在COVID大流行后监测和追踪AMR至关重要，以便更好地了解这种疾病对AMR加剧的影响。
