RESUMEN
To determine the incidence of antimicrobial-resistant emerging pathogens, Clostridium difficile, and its associated risk factors in tertiary care setups of Pakistan. This cross-sectional prospective study was conducted from January 2019 to December 2020, to determine the prevalence and antimicrobial resistance patterns of C. difficile strains isolated from 450 stool specimens of patients suffering from diarrhea hospitalized in tertiary care hospitals in Peshawar, Pakistan. The stool samples of the patients were processed for culture and detection of toxin A and toxin B by enzyme-linked immunosorbent assay (ELISA) and tpi PCR. The drug sensitivity test was performed for antibiotics including ampicillin, cefixime, cefepime, amoxicillin, nalidixic acid, sulpha/TMP (SXT), chloramphenicol, metronidazole, vancomycin, ciprofloxacin, levofloxacin, and imipenem. Of 450 stool specimens, 108 (24%) were positive for C. difficile by stool culture, whereas 115 (25.5%) were only positive for C. difficile toxins based on ELISA and PCR (128 (28.6%). Of 108, 90.7% (n = 98) isolates were resistant to one antibiotic, and 90 (83.4%) were resistant to three or more antimicrobials. The highest resistance rates were found against penicillin (83.3%) followed by amoxicillin (70%), nalidixic acid (61%), and metronidazole (38%), and the lowest resistance was found against vancomycin (6.4%) and imipenem (3.7%). CDI was statistically significantly correlated with increased age, use of antibiotics, abdominal surgeries, use of proton pump inhibitors and H2a, and presence of comorbidities. The high frequency of C. difficile in Peshawar, Pakistan, indicates that CDI is an important nosocomial infection in different hospitals. The results will be helpful for clinicians to redesign control and therapeutic strategies in hospitals.
RESUMEN
Background: The IL-12/IFN-γ axis pathways play a vital role in the control of intracellular pathogens such as Salmonella typhi. Objective: The study is aimed at using whole exome sequencing (WES) to screen out genetic defects in IL-12/IFN-γ axis in patients with recurrent typhoid fever. Methods: WES using next-generation sequencing was performed on a single patient diagnosed with recurrent typhoid fever. Following alignment and variant calling, exomes were screened for mutations in 25 genes that are involved in the IL-12/IFN-γ axis pathway. Each variant was assessed by using various bioinformatics mutational analysis tools such as SIFT, Polyphen2, LRT, MutationTaster, and MutationAssessor. Results: Out of 25 possible variations in the IL-12/IFN-γ axis genes, only 2 probable disease-causing mutations were identified. These variations were rare and include mutations in IL23R and ZNFX I. Other pathogenic mutations were found, but they were not considered likely to cause disease based on various mutation predictors. Conclusion: Applying WES to the patient with recurrent typhoid fever detects variants that are not much important as other genes in the IL-12/IFN-γ axis. Results of the current study suggest that a large population sizes would be needed to examine the functional relevance of IL-12/IFN-γ axis genes with recurrent typhoid fever.
