Fluoroquinolones (FQs) are broad-spectrum second-line antimicrobial drugs commonly used in the treatment of tuberculosis (TB). Data on FQ resistance in the Khyber Pakhtunkhwa (KP) province of Pakistan, a high-burden country, are scarce. This study aimed to analyze the resistance to FQs in this specific geographic area. Samples were collected from 25 districts of KP from 2014 to 2019. Data regarding suspected TB patients were collected from their guardians or secondary caregivers. All the samples were subjected to decontamination and digestion processing. Drug susceptibility testing (DST) was performed according to the standard minimum inhibitory concentration for ofloxacin (OFX), levofloxacin (LEV), and moxifloxacin (MOX), taken as 2, 1, and 1 μg/mL, respectively. For the 5,759 clinical samples collected from 25 districts, DST was conducted for a total of 3,158 samples. Out of the total DSTs, the OFX profile was available for 2,983, MOX profile for 2,290, and LEV profile for 544 samples. OFX and LEV resistance was found to be evenly distributed and has remained the same for the past few years, whereas MOX resistance increased from 1% in 2017 to 4% in 2019. Among a total of 807 OFX-resistant isolates, 218 (27%) were observed to be monoresistant to OFX, whereas 589 (73%) isolates were resistant to OFX and at least one other anti-TB drug. Drug resistance to OFX was higher in multidrug-resistant TB (MDR-TB), that is, 428 (53%). It was concluded that resistance to MOX has been increasing, whereas OFX resistance is much higher in MDR cases. FQ resistance needs to be continuously monitored to avoid further side effects. This study provides useful information for better management of FQ resistance with reference to the global TB control program 2030.

中文翻译：

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巴基斯坦开伯尔普赫图赫瓦省结核分枝杆菌分离株对氟喹诺酮类药物的耐药性

氟喹诺酮类（FQs）是广谱二线抗菌药物，常用于治疗结核病（TB）。巴基斯坦开伯尔-普赫图赫瓦省 (KP) 是一个高负担国家，关于 FQ 抗性的数据很少。本研究旨在分析该特定地理区域对 FQ 的抗性。样本是从 2014 年到 2019 年从 KP 的 25 个地区收集的。有关疑似结核病患者的数据是从他们的监护人或二级照顾者那里收集的。所有样品均经过去污和消解处理。根据氧氟沙星（OFX）、左氧氟沙星（LEV）和莫西沙星（MOX）的标准最小抑菌浓度进行药敏试验（DST），分别取2、1和1 μg/mL。从25个区采集的5759份临床样本中，对总共 3,158 个样本进行了 DST。在所有 DST 中，OFX 配置文件可用于 2,983 个，MOX 配置文件用于 2,290 个，LEV 配置文件用于 544 个样本。发现 OFX 和 LEV 耐药性分布均匀，并且在过去几年保持不变，而 MOX 耐药性从 2017 年的 1% 增加到 2019 年的 4%。 在总共 807 个 OFX 耐药菌株中，218 个（27% ) 被观察到对 OFX 具有单一耐药性，而 589 (73%) 个分离株对 OFX 和至少一种其他抗结核药物具有耐药性。耐多药结核病 (MDR-TB) 对 OFX 的耐药性更高，为 428 (53%)。得出的结论是，对 MOX 的耐药性一直在增加，而在 MDR 病例中，OFX 耐药性要高得多。需要持续监测 FQ 抗性以避免进一步的副作用。