Serum interleukin levels and antibiotic resistance in children with urinary tract infection

Urinary tract infections (UTIs) have a significant impact on a large number of individuals each year and can result in severe health complications. Annually, symptomatic UTIs lead to seven million patients seeking medical care in the outpatient department and one million visiting the emergency department. in 2019, there were an estimated 404.61 million cases and 236,790 deaths reported worldwide. About 1380 urine samples and 100 serum samples were collected from patients attending Imam Kadumia Medical City (IKMC). The urine samples were analyzed using the VITEK-2 technology. One extensively drug-resistant (XDR) strain was subjected to whole-genome sequencing (WGS) for genome study. At the same time, serum IL-6 and IL-8 were measured in children with newly diagnosed, untreated urinary tract infections documented by a positive urine culture. IL-6 and IL-8 were determined by the enzyme-linked immunosorbent assay (ELISA) technique. Significant elevation in serum IL-6 and IL-8 levels was observed in patients with a urinary tract infection compared to the control group. These levels are crucial in the acute phase of infection, suggesting that these cytokines are essential for developing and manifesting UTIs; this highlights the importance of monitoring these levels during the infection's acute phase. The incidence of urinary tract infections among patients who visited IKMC in 2022 was 62.17%, indicating a significant occurrence. E. coli had the highest prevalence of enteric bacterial isolates, accounting for 21.045%, whereas Morganella and Salmonella had the lowest incidence at 0.07%. UTIs were most prevalent in infants under the age of one. The isolated organisms exhibited significant heterogeneity in their response to antibiotics. Imipenem (71.91%) and nitroxoline (79.95%) were the most efficient antibiotics against most bacteria. However, rifampicin, ceftriaxone, norfloxacin, and doxycycline showed significant resistance rates of 76.57%, 72.49%, 71.33%, and 70.16%, respectively. A single XDR bacterium was sent for whole genome sequencing (WGS) to discover the genetic diversity using next-generation sequencing (NGS) technology and facilitate an in-depth genomic analysis of a clinically significant pathogen. Focusing on a single isolate allowed for comprehensive characterization of resistance mechanisms, including the identification of specific resistance genes and plasmid profiles, which is essential for understanding the molecular basis of XDR phenotypes. The bacteria were identified as K. pneumoniae, with a sequencing type of ST437 and a serotype of K36:O2. The K. pneumoniae bacteria were identified as XDR due to the presence of 56 resistance genes that make them resistant to all types of antibiotics, including macrolides, aminoglycosides, fosfomycin, glycopeptides, disinfecting agents, phenicols, sulfonamides, trimethoprim, quinolones, tetracycline, vancomycin, and β-lactams. Furthermore, over 100 virulence genes belonging to several virulence categories, such as immune evasion, adherence, iron absorption, antiphagocytosis, regulation, efflux pump, nutritional factor, toxin, bile resistance, manganese uptake, and surface protein anchoring, were identified. The genome analysis using plasmidfinder software found 15 plasmids, namely ColKP3, ColpVC, IncFIB(K), IncFIB(pQil), IncFII, IncFII(K), IncX3, rep14a, rep17, rep18a, rep18b, rep2, repUS15, repUS43, and repUS7. These plasmids exhibited an 81% overlap with the reference accession number. A total of 10,293 single nucleotide polymorphisms (SNPs) were identified in our isolate. Among these, 6,936 were transition mutations, and 3,357 were transversion mutations. Additionally, there were 61 insertions and 71 deletions. These mutations resulted in 3,707 protein frameshifts and 909 silent mutations