Abstract
Klebsiella pneumoniae is a clinically relevant pathogen and a frequent cause of hospital-acquired (HA) and community-acquired (CA) urinary tract infections (UTI). The increased resistance of this pathogen is leading to limited therapeutic options. To investigate the epidemiology, virulence, and antibiotic resistance profile of K. pneumoniae in urinary tract infections, we conducted a multicenter retrospective study for a total of 81 isolates (50 CA-UTI and 31 HA-UTI) in Portugal. The detection and characterization of resistance and virulence determinants were performed by molecular methods (PCR, PCR-based replicon typing, and multilocus sequence typing (MLST)). Out of 50 CA-UTI isolates, six (12.0%) carried β-lactamase enzymes, namely blaTEM-156 (n = 2), blaTEM-24 (n = 1), blaSHV-11 (n = 1), blaSHV-33 (n = 1), and blaCTX-M-15 (n = 1). All HA-UTI were extended-spectrum β-lactamase (ESBL) producers and had a multidrug resistant profile as compared to the CA-UTI isolates, which were mainly resistant to ciprofloxacin, levofloxacin, tigecycline, and fosfomycin. In conclusion, in contrast to community-acquired isolates, there is an overlap between virulence and multidrug resistance for hospital-acquired UTI K. pneumoniae pathogens. The study is the first to report different virulence characteristics for hospital and community K. pneumoniae pathogens, despite the production of β-lactamase and even with the presence of CTX-M-15 ESBL, a successful international ST15 clone, which were identified in both settings. This highlights that a focus on genomic surveillance should remain a priority in the hospital environment.
Highlights
The clonal relatedness of the multidrug resistance (MDR) CTX-M-15 ESBL K. pneumoniae producers, including one isolate identified in the community setting, was investigated by multilocus sequence typing (MLST)
The present study demonstrates that fosfomycin, an older antimicrobial agent, should be considered to be an emerging treatment option for difficult-to-treat hospital-acquired urinary tract infections caused by K. pneumoniae uropathogens, including MDR isolate multidrugs, but caution should be applied for its use as an alternative agent for outpatient therapy of UTIs
In 2018, we reported that the ST11 that belongs to the CC258 group, one of the most threating MDR Gram-negative bacterias circulating in nosocomial settings worldwide [51], has been replaced by the ST14 clone Klebsiella pneumoniae carbapenemases (KPC)-3 carbapenemase-producing K. pneumoniae isolates [14]
Summary
The Gram-negative Klebsiella pneumoniae is a clinically relevant pathogen that has the propensity to acquire multidrug resistance (MDR), limiting the therapeutic options for treating related infections such as pneumonia, liver abscess, meningitis, bloodstream infections, and urinary tract infections (UTIs) [1].K. pneumoniae is the second most frequent etiological agent involved in community-acquired (CA) UTIs [2,3], and it is one of the top three pathogens of international concern documented in the 2017 World Health Organization’s (WHO) Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics [4].Extended-spectrum β-lactamases (ESBL) are bacterial enzymes that confer resistance against a number of commonly used classes of β-lactam antibiotics [5]. The Gram-negative Klebsiella pneumoniae is a clinically relevant pathogen that has the propensity to acquire multidrug resistance (MDR), limiting the therapeutic options for treating related infections such as pneumonia, liver abscess, meningitis, bloodstream infections, and urinary tract infections (UTIs) [1]. The emergence of antimicrobial resistance, as Klebsiella pneumoniae carbapenemases (KPC) and cefotaximases (CTX-M) enzymes production, additional to the rapid worldwide spread of K. pneumoniae ESBL producers is posing a serious threat to global health [6], despite the implementation of local and national guidelines [7] as well as the development innovative approaches that are being considered for therapeutics [8]. We previously reported a high prevalence of virulence determinants on multidrug-resistant sequence type (ST) KPC-3 carbapenemase K. pneumoniae [14] and detailed the possibility of this microorganism preceding difficult-to-treat and fatal infections, including those caused by other Gram-negative pathogens, such as A. baumannii [15]. Despite the recent interest in this relationship, the interplay between resistance and virulence in K. pneumoniae clinical isolates remains poorly understood [9], and to our knowledge, the pathogenic potential of K. pneumoniae in urinary tract infections, especially in the community setting, and its resistance profile have not yet been characterized
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