Antimicrobial Resistance in Typhoidal Salmonella: Surveillance for Enteric Fever in Asia Project, 2016–2019

Abstract

Background Clinicians have limited therapeutic options for enteric as a result of increasing antimicrobial resistance, and therefore typhoid vaccination is recommended as a preventive measure. As a part of the Surveillance for Enteric Fever in Asia Project (SEAP), we investigated the extent measured the burden of antimicrobial resistance (AMR) among confirmed enteric fever cases in Bangladesh, Nepal, and Pakistan. Methods From September 2016–September 2019, SEAP recruited study participants of all age groups from its outpatient, inpatient, hospital laboratory, laboratory network, and surgical sites who had a diagnosis of febrile illness that was either suspected or blood culture confirmed for enteric fever. Antimicrobial resistance of isolates was determined by disc diffusion using Clinical and Laboratory Standard Institute cut-off points. We reported the frequency of multidrug resistance (MDR)(resistance to ampicillin, cotrimoxazole, and chloramphenicol), extensive drug resistance (XDR) (MDR plus non-susceptible to fluoroquinolone and any 3rd generation cephalosporins), and fluoroquinolone (FQ) and azithromycin non-susceptibility. Results We enrolled 8,705 blood culture confirmed enteric fever cases: 4,873 (56%) from Bangladesh, 1,602 (18%) from Nepal and 2,230 (26%) from Pakistan. Of these, 7,591 (87%) were Salmonella Typhi and 1114 (13%) were S. Paratyphi. MDR S. Typhi was identified in 17% (701/4065) of isolates in Bangladesh, and 1% (19/1342) in Nepal. In Pakistan, 16 % (331/2084) of S. Typhi isolates were MDR, and 64% (1319/2074) were XDR. FQ nonsusceptibility among S. Typhi isolates was 98% in Bangladesh, 87% in Nepal, and 95% in Pakistan. Azithromycin non-susceptibility was detected in 77 (2%) in Bangladesh, 9 (.67%) in Nepal and 9 (.59%) isolates in Pakistan. In Pakistan, three (2%) S. Paratyphi isolates were MDR; no MDR S. Paratyphi was reported from Bangladesh or Nepal. Conclusions Although AMR against S. Paratyphi was low across the three countries, there was widespread drug resistance among S. Typhi, including FQ non-susceptibility and the emergence of XDR S. Typhi in Pakistan, limiting treatment options. As typhoid conjugate vaccine (TCV) is rolled out, surveillance should continue to monitor changes in AMR to inform policies and to monitor drug resistance in S. Paratyphi, for which there is no vaccine.

Enteric Fever: Diagnostic Dilemma Encountered in Domperidone-Induced Neuroleptic Malignant Syndrome

“…Third-generation cephalosporins such as ceftriaxone are recommended for commencing the treatment. However, in Pakistan, the majority of Salmonella Typhi isolates have developed antimicrobial resistance [12].…”

“…Physical examination and blood investigations like CPK and LDH [7] should be promptly performed to rule out extrapyramidal side effects of the offending agent. NMS can be treated with bromocriptine, dantrolene, amantadine, and there is some role for anticholinergics as well [7][8][9][10][11][12][13][14]. In cases of enteric fever, CNS complications must be ruled out in a timely manner before labeling the patient as having another illness due to drug side-effect profile.…”

Typhoid Conjugate Vaccine: An Urgent Tool to Combat Typhoid and Tackle Antimicrobial Resistance

“…Indeed, an outbreak caused by an extensively drug-resistant (XDR) strain of Salmonella Typhi was identified in Pakistan in 2016; XDR Salmonella Typhi is resistant to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, streptomycin, fluoroquinolones, and third-generation cephalosporins. Within 4 years of its detection, XDR Salmonella Typhi constituted >80% of the entire Salmonella Typhi population in Pakistan [ 10 ], and it has been detected in at least 10 countries [ 9 ]. For patients with uncomplicated XDR typhoid, azithromycin is the last option for an oral antimicrobial.…”

Persistence of first-line antibiotic-resistant typhoid fever among Pakistani children: a growing concern for regional antimicrobial stewardship

“…Multidrug-resistant (MDR) S. Typhi, defined as resistance to the three first-line antibiotics used to treat TF -ampicillin, chloramphenicol and cotrimoxazole, appeared in the 1970s and is now widespread globally. This is becoming extensively drug-resistant (XDR) S. Typhi (defined as MDR plus resistance to fluoroquinolones and third-generation cephalosporins), mainly through acquiring plasmids conferring antibiotic resistance via bacterial conjugation (commonly associated with the H-58 haplotype) (6,7). When an S. Typhi strain develops resistance by acquiring a promiscuous plasmid or undergoing genetic mutation consistent changes occur in the reported incidence of susceptibility to that antibiotic.…”

“…This first report of the emergence of confirmed cases of MDR S. Typhi from the only public hospital in its largest neighborhood identifies a grave public health concern. The rise in prevalence of MDR and, in some instances, XDR, S. Typhi that has been observed not only in Karachi but also in Hyderabad (6,9), the second-largest city in Sindh and situated 160 Km to the northeast of Karachi, constitutes a major humanitarian crisis. In 2018, of nearly 8,200 confirmed cases of TF in Sindh two-thirds were XDR, of which Karachi accounted for 69% (10).…”