Exploring the Antimicrobial Resistance Profile of <i>Salmonella typhi</i> and Its Clinical Burden

• Main Authors: Muhammad Asghar (Author), Taj Ali Khan (Author), Marie Nancy Séraphin (Author), Lena F. Schimke (Author), Otavio Cabral-Marques (Author), Ihtisham Ul Haq (Author), Zia- (Author), Susana Campino (Author), Ihsan Ullah (Author), Taane G. Clark (Author)
• Format: Book
• Published: MDPI AG, 2024-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antibiotics13080765; 2079-6382
• Keywords: <i>Salmonella typhi</i>; clinical paradigm; antibiogram; drug resistance; typhoid fever; Therapeutics. Pharmacology; RM1-950
• Source: Antibiotics, Vol 13, Iss 8, p 765 (2024)

<b>Background</b>: Typhoid fever caused by <i>Salmonella enterica</i> serovar Typhi <i>(S. typhi)</i> continues to pose a significant risk to public health in developing countries, including Pakistan. This study investigated the epidemiological factors linked to suspected and confirmed <i>S. typhi</i> infections in Peshawar's hospital population. <b>Methodology</b>: A total of 5735 blood samples of patients with suspected enteric fever were collected from September 2022 to November 2023. <i>S. typhi</i> infection was confirmed using microbiological culture of blood samples, biochemical-based tests, and DNA-sequencing methods. Drug sensitivity testing on cultures was conducted as per the CLSI guidelines. Chi-square tests were used to analyze the clinical and epidemiologic characteristics of 5735 samples stratified by <i>S. typhi</i> infection status, and risk factors were assessed by applying logistic regression models to estimate odds ratios (ORs). <b>Results</b>: The number of confirmed typhoid fever cases in this hospital-based study population was 691 (/5735, 12.0%), more prevalent in males (447/3235 13.8%) and children (0-11 years) (429/2747, 15.6%). Compared to children, the risk of <i>S. typhi</i> infection was lower in adolescence (adjusted OR = 0.52; 95% CI: 0.42-0.66), adulthood (19-59 years; aOR = 0.30; 95% CI: 0.25-0.38), and older adulthood (aOR = 0.08; 95% CI: 0.04-0.18) (<i>p</i> < 0.001). Compared to males, the risk of <i>S. typhi</i> infection was lower in females (aOR = 0.67; 95% CI = 0.56-0.80; <i>p</i> = 0.002). Living in a rural residence (compared to urban) was associated with a higher risk of infection (aOR = 1.38; 95% CI: 1.16-1.63; <i>p</i> = 0.001), while access to a groundwater source (compared to municipal water supply) led to a lower risk (aOR = 0.56; 95% CI: 0.43-0.73; <i>p</i> = 0.002). Vaccination demonstrated a robust protective effect (aOR = 0.069; 95% CI = 0.04-0.11, <i>p</i> = 0.002). For those with typhoid infections, clinical biomarker analysis revealed the presence of leucopenia (65/691, 9.4%), thrombocytopenia (130/691, 18.8%), and elevated alanine aminotransferase (ALT) (402/691, 58.2%) and C-reactive protein (CRP) (690/691, 99.9%) levels. Worryingly, among the positive <i>S. typhi</i> isolates, there was a high prevalence of drug resistance (653/691), including multidrug-resistant (MDR 82/691, 11.9%) and extensively drug-resistant types (XDR, 571/691, 82.6%). <b>Conclusions</b>: This study highlights the importance of age, sex, locality, water source, and vaccination status in shaping the epidemiological landscape of <i>S. typhi</i> in the Peshawar district. It implies that expanding vaccination coverage to the broader population of Khyber Pakhtunkhwa province, particularly in the district of Peshawar, would be beneficial.