Abstract
Urinary tract infections (UTIs) are the most frequent hospital infections and among the most commonly observed community acquired infections. Alongside their clinical importance, they are notorious because the pathogens that cause them are prone to acquiring various resistance determinants, including extended-spectrum beta-lactamases (ESBL); plasmid-encoded AmpC β-lactamases (p-AmpC); carbapenemases belonging to class A, B, and D; qnr genes encoding reduced susceptibility to fluoroquinolones; as well as genes encoding enzymes that hydrolyse aminoglycosides. In Escherichia coli and Klebsiella pneumoniae, the dominant resistance mechanisms are ESBLs belonging to the CTX-M, TEM, and SHV families; p-AmpC; and (more recently) carbapenemases belonging to classes A, B, and D. Urinary Pseudomonas aeruginosa isolates harbour metallo-beta-lactamases (MBLs) and ESBLs belonging to PER and GES families, while carbapenemases of class D are found in urinary Acinetobacter baumannii isolates. The identification of resistance mechanisms in routine diagnostic practice is primarily based on phenotypic tests for the detection of beta-lactamases, such as the double-disk synergy test or Hodge test, while polymerase chain reaction (PCR) for the detection of resistance genes is mostly pursued in reference laboratories for research purposes. As the emergence of drug-resistant bacterial strains poses serious challenges in the management of UTIs, this review aimed to appraise mechanisms of resistance in relevant Gram-negative urinary pathogens, to provide a detailed map of resistance determinants in Croatia and the world, and to discuss the implications of these resistance traits on diagnostic approaches. We summarized a sundry of different resistance mechanisms among urinary isolates and showed how their prevalence highly depends on the local epidemiological context, highlighting the need for tailored interventions in the field of antimicrobial stewardship.
Highlights
Urinary Tract InfectionsUropathogenic bacteria possess a plethora of virulence factors involved in the pathogenesis (type I pili, type III pili, alginate, haemolysins, aerobactin, siderophores), but they primarily utilize fimbriae to mediate the attachment to the urinary epithelium and subsequent penetration [3,7]
Urinary tract infections (UTIs) are the most frequent hospital infections and among the most commonly observed community acquired infections
UTIs develop as a result of the presence and multiplication of microorganisms in the different parts of the urinary system, subsequently resulting in tissue invasion, inflammatory response, and various symptoms depending on the localization of the infection [3]
Summary
Uropathogenic bacteria possess a plethora of virulence factors involved in the pathogenesis (type I pili, type III pili, alginate, haemolysins, aerobactin, siderophores), but they primarily utilize fimbriae to mediate the attachment to the urinary epithelium and subsequent penetration [3,7] Following this initial step, the pathogens can migrate to the kidney (by using flagella) and cause pyelonephritis [8]. UTIs usually arise due to the ascendant spread of endogenic microbiota from the intestines Among adults, they are more frequently observed among woman due to shorter urethra, whereas in men UTIs are usually considered complicated and linked to prostatic hypertrophy or adenoma [8]. The whole group of secondary pathogens is rarely observed in uncomplicated UTIs, but are frequently isolated in complicated urinary tract infections, as well as from hospitalized patients [16]. This review aims to appraise mechanisms of resistance in Gram-negative urinary pathogens, provide a detailed map of resistance determinants in Croatia and put it within the global context for all relevant Gram-negative pathogens, and to discuss the implications of these resistance traits on clinical approaches and the choice of antimicrobial drugs
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