P Chethankumar, A Tejashree, Murthy Neetha S, Raghavendra Rao Morubagal
Microbiology, JSS Medical College and Hospital, JSS Academy of Higher Education and Research (JSSAHER), Mysore, IND.
Cureus. 2024 Aug 6;16(8):e66295. doi: 10.7759/cureus.66295. eCollection 2024 Aug.
The dwindling antibiotic reserve owing to augmented drug-resistant bacteria is a major handicap for treating physicians. , a gram-negative encapsulated member of family, is one such pathogenic bacteria. Carbapenemase-producing globally recognized as one of the most critical bacterial threats to public health due to its extremely limited treatment options. Carbapenem-resistant (CRKP) infections pose therapeutic challenges due to simultaneous resistance to various other groups of antibiotics. In this study, we have evaluated the synergistic effect of fosfomycinagainst CRKP isolates when used in combination with colistin by applying the Checkerboard method.
A laboratory-based prospective study was conducted in the Department of Microbiology, JSS Hospital, Mysuru, for a period of one year after obtaining ethical clearance. isolates obtained from clinical samples were screened for carbapenem resistance by the VITEK-2 compact system (bioMérieux, Marcy-l'Étoile, France). The minimum inhibitory concentration (MIC) of colistin and fosfomycin was individually ascertained by broth microdilution (BMD). Finally, the synergistic activity of the fosfomycin-colistin combination was determined by the BMD-based Checkerboard method.
Among the 50 CRKP isolates, 36 (72%) isolates showed synergism, eight (16%) isolates showed indifference and six (12%) isolates showed partial synergism, while none of them showed additivity and antagonism by the Checkerboard method. These results are found to be statistically significant (chi-square value of 116.204 and p-value of < 0.00001).
This study showed a promising in-vitro synergy between the drugs fosfomycin and colistin by Checkerboard BMD testing protocol. Colistin being a reserve antibiotic, monotherapy comes with the limitations of higher chances of resistance as well as toxicity, which can be overcome by combination therapy, thereby decreasing CRKP-associated mortality rates and delivering holistic patient benefit.
由于耐药菌增多导致抗生素储备减少，这对治疗医生来说是一个主要障碍。肺炎克雷伯菌是肠杆菌科的革兰氏阴性有荚膜成员，就是这样一种病原菌。产碳青霉烯酶肺炎克雷伯菌由于其治疗选择极其有限，被全球公认为对公共卫生最严重的细菌威胁之一。耐碳青霉烯肺炎克雷伯菌（CRKP）感染因对其他各类抗生素同时耐药而带来治疗挑战。在本研究中，我们通过棋盘法评估了磷霉素与黏菌素联合使用时对CRKP分离株的协同作用。
在获得伦理批准后，于迈索尔JSS医院微生物科进行了为期一年的基于实验室的前瞻性研究。通过VITEK-2 compact系统（法国马赛-埃托瓦勒生物梅里埃公司）对从临床样本中获得的肺炎克雷伯菌分离株进行碳青霉烯耐药性筛查。通过肉汤微量稀释法（BMD）分别确定黏菌素和磷霉素的最低抑菌浓度（MIC）。最后，通过基于BMD的棋盘法确定磷霉素 - 黏菌素组合的协同活性。
在50株CRKP分离株中，36株（72%）分离株表现出协同作用，8株（16%）分离株表现为无作用，6株（12%）分离株表现出部分协同作用，而通过棋盘法它们均未表现出相加作用和拮抗作用。这些结果具有统计学意义（卡方值为116.204，p值<0.00001）。
本研究通过棋盘BMD检测方案显示了磷霉素和黏菌素之间有前景的体外协同作用。黏菌素作为一种储备抗生素，单一疗法存在耐药机会增加以及毒性等局限性，联合治疗可克服这些问题，从而降低CRKP相关死亡率并为患者带来全面益处。
