QUINOLONE RESISTANCE AMONG ESCHERICHIA COLI AND KLEBSIELLA PNEUMONIAE BACTERIA ISOLATED AT RAFIDIA AND AN-NAJAH NATIONAL UNIVERSITY HOSPITALS IN NABLUS DISTRICT: PROSPECTIVE CROSS-SECTIONAL STUDY

Khatatbeh, Marah

QUINOLONE RESISTANCE AMONG ESCHERICHIA COLI AND KLEBSIELLA PNEUMONIAE BACTERIA ISOLATED AT RAFIDIA AND AN-NAJAH NATIONAL UNIVERSITY HOSPITALS IN NABLUS DISTRICT: PROSPECTIVE CROSS-SECTIONAL STUDY

Date

2024-10-24

Authors

Khatatbeh, Marah

Publisher

An-Najah National University

Abstract

Background: Among several bacterial genera, quinolone resistance has become more prevalent in recent years. This was clear among common nosocomial pathogens such as Escherichia coli and Klebsiella pneumoniae. While quinolones are a valuable part of the current antimicrobial treatment options, growing quinolone resistance poses a threat to their continued efficacy. Objectives: First, this study aimed to determine the prevalence of resistance of E. coli and K. pneumoniae to quinolone antibiotics (ciprofloxacin and levofloxacin) at two major hospitals in Nablus District, Rafidia and An-Najah National University Hospital. Second, the association of resistance to these antibiotics with various demographic and clinical findings was examined. Third, mechanisms of quinolone resistance among E. coli and K. pneumoniae were determined through resistance gene detection by PCR. Methodology: A cross-sectional study design was selected. A total of 219 bacterial isolates (169 isolates of E. coli and 50 isolates of K. pneumoniae) were collected from the first of June 2023 to the last day of September 2023, from all patients infected with those bacterial species. The included bacteria in this study were isolated from patients admitted to the two mentioned Hospitals during the study period. Types of bacteria were already identified by the VITEK 2 system (BioMérieux) in the two mentioned hospitals. Resistance of the included bacteria to ciprofloxacin and levofloxacin was determined by the disk diffusion method. In addition, multiplex PCR was used for detection of resistant genes in order to determine quinolone resistance mechanisms among 118 resistant strains. The detected mechanisms and genes were target modification (qnrA, qnrB, and qnrS genes), enzymatic modification (aac(6’)-Ib-cr gene), and efflux pump mechanism (QepA, OqxA, and OqxB genes). Association of quinolone resistance with clinical symptoms, demographic information, and other risk factors were evaluated. Results: Relatively high frequencies of ciprofloxacin resistance (46.1%) and levofloxacin resistance (47.9%) were found among E. coli isolates. Higher resistance frequency of ciprofloxacin (70%) and levofloxacin (68%) among K. pneumoniae isolates were detected. Escherichia coli and K. pneumoniae ciprofloxacin resistant bacteria isolated at An-Najah National University Hospital (60% and 92.9%, respectively) were significantly higher (P= 0.000 and P= 0.001, respectively) than that of the isolates obtained from Rafidia Hospital (37.3% and 40.9%, respectively). Ciprofloxacin resistance among E. coli isolated from the general surgery unit was significantly higher than that of the emergency ward (54.5%; P=0.002) and the outpatients (36.9%; P= 0.016). However, E. coli levofloxacin resistance frequency in the intensive care unit was significantly higher than that of the outpatients (49.2%; P=0.018), emergency (45.5%; P=0.022), and general surgery (42.9%; P=0.037). Escherichia coli isolation rate from urine (80%) was significantly higher than that of wound swabs (76.3%; P=0.013). Furthermore, K. pneumoniae isolation rate from urine (20%) was significantly higher than that of wound swabs (23.7%; P=0.036). Escherichia coli ciprofloxacin resistance was significantly higher (P=0.008) in male isolates (53.6%) than in female isolates (36.3%). Escherichia coli isolated from patients over 65 years of age had the highest levofloxacin resistance frequency (62.5%), which was also significantly (P= 0.007) higher than that of the 40–65-year age group. Escherichia coli ciprofloxacin resistant bacterium isolated from patients with urinary catheters (91.7%) had a significantly higher frequency than that of hypertension patients (85.5%; P=0.013), diabetes mellitus patients (84.8%; P=0.017), cancer patients (81.9%; P=0.022), and hepatic cirrhosis patients (64.1%; P=0.028). However, K. pneumoniae ciprofloxacin resistant bacterium isolated from hepatic cirrhosis patients (77.8%) had a significantly higher frequency than that of hypertension patients (65.2%; P=0.003), cancer patients (61.9%; P=0.019), and diabetes mellitus patients (58.9%; P=0.032). Frequency of levofloxacin resistant E. coli isolated from diabetes mellitus patients (89.1%) was significantly higher than that of hypertension patients (76.3%; P=0.013), cancer patients (73.6%; P=0.016), patient with the urinary catheter (77.8%; P=0.021), and hepatic cirrhosis patients (51.3%; P=0.028). On the other hand, levofloxacin resistant K. pneumoniae isolated from diabetes mellitus patients (71.8%) had a significantly higher frequency than that of hypertension patients (56.5%; P=0.009), cancer patients (52.4%; P=0.016), hepatic cirrhosis patients (59.3%; P=0.023), and patient with the urinary catheter (48%; P=0.031). With respect to the quinolone resistance mechanisms, the efflux pump among E. coli isolates was the most predominant (43.3%) with OqxA (23.5%) being the most common gene, followed by enzymatic modification by Aac(6’)-Ib-cr enzyme (29.6%) and target modification mechanism (26%) in which the QnrS gene was the most common (13.6%). Similarly, the efflux pump mechanism of quinolones resistance among K. pneumoniae isolates was also the most common (37.8%) with the OqxA gene exhibiting the highest frequency (27%), followed by enzymatic modification by Aac(6’)-Ib-cr enzyme (32.4%) and target modification mechanism (29.7%) with QnrS and QnrB being the most commonly detected genes (10.8%). Conclusion: Our findings showed high rates of ciprofloxacin and levofloxacin resistance among E. coli and K. pneumoniae isolates, also a high percentage of the efflux pump mechanism with OqxA being the most common gene, followed by enzymatic modification by Aac(6’)-Ib-cr enzyme and target modification mechanism in which the QnrS gene was the most common. We emphasize that it is necessary to perform an antibiotic susceptibility test before choosing a prescription. Monitoring the rates of resistance in the nations clinical facilities should be a greater priority for the relevant government health departments.