# Molecular Analysis of Tigecycline Resistance in Carbapenem-Resistant Enterobacterales (CRE) in Mthatha and Surrounding Hospitals

## TL;DR

This study analyzed tigecycline resistance in carbapenem-resistant bacteria from South African hospitals, finding that tet(X) genes were not the main cause and highlighting risk factors like antibiotic exposure.

## Contribution

The study identifies risk factors for tigecycline resistance in CRE and clarifies that tet(X) genes are not the primary resistance mechanism in this region.

## Key findings

- 7.2% of CRE isolates were resistant to tigecycline, primarily in Klebsiella species.
- tet(X) genes were not identified as the main mechanism of tigecycline resistance.
- Risk factors include age, antibiotic pre-exposure, prolonged hospitalization, and invasive procedures.

## Abstract

Background: The emergence of carbapenem-resistant Enterobacterales is prevalent and poses a significant threat to health systems worldwide. This study aimed to conduct a molecular analysis of tigecycline resistance in 100 CRE isolates from Mthatha Hospital and surrounding hospitals. Methods: A retrospective study among patients who attended Nelson Mandela Academic Hospital (NMAH) and Mthatha Regional Hospital (MRH), Eastern Cape, South Africa. Enterobacterales isolates were identified using the Vitek2® system (bioMérieux); an E-test was performed on 100 CRE isolates according to the manufacturer’s instructions. PCR assays for rapid detection of tet(X) and its variants, including tet(X1) and tet(X2), and high-level tigecycline resistance genes tet(X3), tet(X4), and tet(X5) were developed. Results: The results show a notably high prevalence of CRE infections in neonatal, male surgical, and maternal and pediatric wards, predominantly driven by Klebsiella species (53.4%), followed by Enterobacter species (20.5%) and then Escherichia coli (6.7%), and 7.2% of CRE isolates were resistant to tigecycline (E-test). In this study, tet(X) genes were not identified as the primary mechanism of tigecycline resistance. The risk factors associated with tigecycline resistance in CRE include age, pre-exposure to antibiotics, prolonged hospitalization, and undergoing invasive procedures, indicated by strong r = 0.9501. Conclusions: CRE gradually evolves, posing a significant threat to patients of all ages; early detection of carbapenemase production in clinical infections, carriage states, or both is essential to prevent hospital-based outbreaks.