The main objective of this cross-sectional study was to investigate the prevalence of beta-lactam (cephalosporins or carbapenems) or colistin resistant bacteria. Those were isolated from urine samples in two private polyclinics located in the Sfax region, in southern Tunisia. From September 2021 to August 2022, 116 strains resistant to β-lactams or colistin were isolated, identified by MALDI-TOF, and their antibiotic susceptibility was assessed by disk diffusion method. Resistance genes were detected by real-time PCR, standard PCR, and sequencing. The results revealed that the 116 strains consisted predominantly of Enterobacteriaceae (92.2 %) and non-fermenting bacteria (7.8 %). Among these strains, 21 (18.1 %) were resistant to carbapenems, three (2.7 %) to colistin, including two strains of Klebsiella pneumoniae (1.7 %) exhibiting resistance to both carbapenems and colistin. In Enterobacteriaceae, blaCTX-A, blaSHV, and blaTEM were found in 79.5 %, 46.7 %, and 40.2 % of strains, respectively. For these strains, the minimum inhibitory concentrations (MICs) of imipenem and ertapenem ranged from >32 to 6 μg/mL and > 32 to 2 μg/mL, respectively, with blaOXA-48 and blaNDM detected in 21.7 % and 19.6 % of isolates, respectively. Seven A. baumannii isolates resistant to imipenem and meropenem (MICs >32 μg/mL and 8 μg/mL, respectively) carried blaOXA-23 (n = 5) and blaOXA-24 (n = 2). In addition, mutations in the mgrB gene conferring colistin resistance were identified in two isolates. Two K. pneumoniae were colistin-resistant and carried the blaOXA-48 gene. These results highlight the urgency of developing new strategies for the identification and surveillance of pathogenic strains in humans to effectively combat this growing public health threat in Tunisia.
Urinary tract infections (UTIs) are a significant public health concern. In 2019, approximately 404.61 million cases of UTIs were reported globally, with a particularly high incidence among women (Yang et al., 2022). These infections are mainly induced by gram-negative bacteria with the prevalence of Enterobacteriaceae such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and K. aerogenes (Flores-Mireles et al., 2015).
The production of β-lactamases is a primary mechanism of antibiotic resistance in Gram-negative bacteria. Multidrug-resistant bacteria were initially treated with third-generation cephalosporins (C3Gs), but the emergence of resistance led to the use of carbapenems, which are generally more effective against both Gram-positive and Gram-negative bacteria (Meletis, 2016). Currently, the emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) in the population is a major and widespread health problem (Dziri et al., 2020).
The spread of CRE, frequently calls into question the effectiveness of carbapenem therapies as a last resort treatment to combat multidrug-resistant (MDR) organisms. In gram-negative bacteria, carbapenemases have been frequently described worldwide (Dziri et al., 2020). Currently, more than 350 types of carbapenemase enzymes have been characterised, with a prevalence of KPC, NDM, VIM, IMP, and OXA type (Dziri et al., 2020). The metallo-β-lactamase enzyme NDM-1, which was first identified in New Delhi in 2009, helps bacteria hydrolyse all antibiotics belonging to the β-lactam family, with the exception of monobactam (Yong et al., 2009). The presence and distribution of isolates producing NDM-1 has been documented in several countries, including the United States, the United Kingdom, France, Africa, and Australia (Chen et al., 2011). In Tunisia, this gene was found to be disseminated in all regions of the country, within the hospital environment and in the community (Mansour et al., 2019). Since OXA-48 carbapenemases were first isolated in Turkey in 2001, they have been frequently reported throughout the world (Mhaya et al., 2020a). The blaOXA-48 gene is predominant in Europe, particularly in France, Spain, and Switzerland. Additionally, North African countries, particularly Tunisia, Egypt and Libya, as well as in various countries in the Middle East consist of that predominance (Boyd et al., 2022).
The spread of carbapenemase-producing A. baumannii in clinical settings has become a significant threat to public health. This resistance is most commonly mediated by oxacillinases, such as OXA-23, OXA-24 and OXA-58 (Ramirez et al., 2020). The class B β-lactamase gene blaNDM has also been reported in A. baumannii. A concerning characteristic of blaNDM is its location on mobile genetic elements, facilitating its transfer between different bacterial species (Berrazeg et al., 2014).
The emergence and spread of carbapenemase-producing bacteria requires clinicians to introduce colistin for the treatment of infections caused by pathogens (Berglund, 2019). Resistance to colistin is induced following a modification of lipopolysaccharides (LPS), causing a reduction in the negative charge of LPS, which consequently reduces its affinity for this antibiotic. Mutations in two-part regulatory systems, such as mutations occuring in the mgrB, phoP/Q, pmrA/B, pmrC and crrABC genes, or through plasmid-mediated resistance genes (mcr-1 to mcr-10) are at the base of these changes (Moffatt et al., 2019).
Our study aimed to evaluate the prevalence of ESBLs, carbapenemases, and colistin resistance in Gram-negative bacteria isolated from urine samples. These samples were collected from two polyclinics in the Sfax region of southern Tunisia between September 2021 and August 2022. In addition, antibiotic resistance profile were analyzed and mechanisms responsible for this resistance were identified.
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