Maharjan Anu, Dhungel Binod, Bastola Anup, Thapa Shrestha Upendra, Adhikari Nabaraj, Banjara Megha Raj, Lekhak Binod, Ghimire Prakash, Rijal Komal Raj
Central Department of Microbiology, Tribhuvan University, Kirtipur, Kathmandu 44618, Nepal.
Sukraraj Tropical and Infectious Disease Hospital, Teku, Kathmandu 44600, Nepal.
Infect Dis Rep. 2021 Apr 21;13(2):388-400. doi: 10.3390/idr13020037.
Enteric fever, a systemic infection caused by Typhi and Paratyphi is one of the most common infections in developing countries such as Nepal. Aside from irrational practices of antibiotic use, mutations in chromosomal genes encoding DNA gyrase and Topoisomerase IV and by plasmid mediated quinolone resistant (PMQR) genes are suggested mechanisms for the development of resistance to nalidixic acid and reduced susceptibility to ciprofloxacin. Regardless of high endemicity of enteric fever in Nepal, there is paucity of studies on prevalence and drug-resistance of the pathogen. Therefore, this study aimed to assess the antibiotic susceptibility pattern of isolates and determine the minimum inhibitory concentration of ciprofloxacin.
A total of 1298 blood samples were obtained from patients with suspected enteric fever, attending Sukraraj Tropical and Infectious Disease Hospital (STIDH) during March-August, 2019. Blood samples were inoculated immediately into BACTEC culture bottles and further processed for isolation and identification of Typhi and Paratyphi. Axenic cultures of the isolates were further subjected to antimicrobial susceptibility testing (AST) by using the modified Kirby-Bauer disc diffusion method based on the guidelines by CLSI. The minimum inhibitory concentration (MIC) of ciprofloxacin was determined by agar-dilution method.
Out of 1298 blood cultures, 40 (3.1%) were positive for spp. among which 29 (72.5%) isolates were . Typhi and 11 (27.5%) isolates were . Paratyphi A. In AST, 12.5% (5/40), 15% (6/40) and 20% (8/40) of the isolates were susceptible to nalidixic acid, ofloxacin and levofloxacin, respectively, whereas none of the isolates were susceptible to ciprofloxacin. The MIC value for ciprofloxacin ranged from 0.06-16 µg/mL in which, respectively, 5% (2/40) and 52.5% (21/40) of the isolates were susceptible and resistant to ciprofloxacin. None of the isolates showed multidrug-resistance (MDR) in this study.
This study showed high prevalence of quinolone-resistant spp., while there was marked re-emergence of susceptibilities to traditional first option drugs. Hence, conventional first-line-drugs and third-generation cephalosporins may find potential usage as the empirical drugs for enteric fever. Although our reporting was free of MDR strains, extensive surveillance, augmentation of diagnostic facilities and treatment protocol aided by AST report are recommended for addressing the escalating drug-resistance in the country.
伤寒热是由伤寒杆菌和副伤寒杆菌引起的一种全身性感染，是尼泊尔等发展中国家最常见的感染之一。除了抗生素使用的不合理做法外，编码DNA旋转酶和拓扑异构酶IV的染色体基因突变以及质粒介导的喹诺酮耐药（PMQR）基因被认为是对萘啶酸产生耐药性和对环丙沙星敏感性降低的机制。尽管尼泊尔伤寒热的流行率很高，但关于该病原体的流行情况和耐药性的研究却很少。因此，本研究旨在评估分离株的抗生素敏感性模式，并确定环丙沙星的最低抑菌浓度。
2019年3月至8月期间，从苏克拉拉杰热带和传染病医院（STIDH）疑似伤寒热患者中采集了1298份血样。血样立即接种到BACTEC培养瓶中，并进一步进行处理以分离和鉴定伤寒杆菌和副伤寒杆菌。根据CLSI指南，使用改良的 Kirby-Bauer 纸片扩散法对分离株的无菌培养物进行进一步的抗菌药物敏感性试验（AST）。通过琼脂稀释法测定环丙沙星的最低抑菌浓度（MIC）。
在1298份血培养中，40份（3.1%）对 spp.呈阳性，其中29份（72.5%）分离株为伤寒杆菌，11份（27.5%）分离株为副伤寒杆菌A。在AST中，分别有12.5%（5/40）、15%（6/40）和20%（8/40）的分离株对萘啶酸、氧氟沙星和左氧氟沙星敏感，而没有分离株对环丙沙星敏感。环丙沙星的MIC值范围为0.06 - 16 µg/mL，其中分别有5%（2/40）和52.5%（21/40）的分离株对环丙沙星敏感和耐药。在本研究中，没有分离株显示出多重耐药（MDR）。
本研究显示喹诺酮耐药的 spp.流行率很高，而对传统首选药物的敏感性明显重新出现。因此，传统的一线药物和第三代头孢菌素可能作为伤寒热的经验性药物有潜在用途。尽管我们的报告中没有MDR菌株，但建议进行广泛监测、增加诊断设施以及借助AST报告制定治疗方案，以应对该国不断升级的耐药性问题。
