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

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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.

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Most cited references 47

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Understanding the mechanisms and drivers of antimicrobial resistance.

Alison Holmes, Luke Moore, Arnfinn Sundsfjord … (2016)

To combat the threat to human health and biosecurity from antimicrobial resistance, an understanding of its mechanisms and drivers is needed. Emergence of antimicrobial resistance in microorganisms is a natural phenomenon, yet antimicrobial resistance selection has been driven by antimicrobial exposure in health care, agriculture, and the environment. Onward transmission is affected by standards of infection control, sanitation, access to clean water, access to assured quality antimicrobials and diagnostics, travel, and migration. Strategies to reduce antimicrobial resistance by removing antimicrobial selective pressure alone rely upon resistance imparting a fitness cost, an effect not always apparent. Minimising resistance should therefore be considered comprehensively, by resistance mechanism, microorganism, antimicrobial drug, host, and context; parallel to new drug discovery, broad ranging, multidisciplinary research is needed across these five levels, interlinked across the health-care, agriculture, and environment sectors. Intelligent, integrated approaches, mindful of potential unintended results, are needed to ensure sustained, worldwide access to effective antimicrobials.

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Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data.

Thomas Van Boeckel, Sumanth Gandra, Ashvin Ashok … (2014)

Antibiotic drug consumption is a major driver of antibiotic resistance. Variations in antibiotic resistance across countries are attributable, in part, to different volumes and patterns for antibiotic consumption. We aimed to assess variations in consumption to assist monitoring of the rise of resistance and development of rational-use policies and to provide a baseline for future assessment. With use of sales data for retail and hospital pharmacies from the IMS Health MIDAS database, we reviewed trends for consumption of standard units of antibiotics between 2000 and 2010 for 71 countries. We used compound annual growth rates to assess temporal differences in consumption for each country and Fourier series and regression methods to assess seasonal differences in consumption in 63 of the countries. Between 2000 and 2010, consumption of antibiotic drugs increased by 36% (from 54 083 964 813 standard units to 73 620 748 816 standard units). Brazil, Russia, India, China, and South Africa accounted for 76% of this increase. In most countries, antibiotic consumption varied significantly with season. There was increased consumption of carbapenems (45%) and polymixins (13%), two last-resort classes of antibiotic drugs. The rise of antibiotic consumption and the increase in use of last-resort antibiotic drugs raises serious concerns for public health. Appropriate use of antibiotics in developing countries should be encouraged. However, to prevent a striking rise in resistance in low-income and middle-income countries with large populations and to preserve antibiotic efficacy worldwide, programmes that promote rational use through coordinated efforts by the international community should be a priority. US Department of Homeland Security, Bill & Melinda Gates Foundation, US National Institutes of Health, Princeton Grand Challenges Program. Copyright © 2014 Elsevier Ltd. All rights reserved.

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Drug-resistant enteric fever worldwide, 1990 to 2018: a systematic review and meta-analysis

Annie J. Browne, Bahar H. Kashef Hamadani, Emmanuelle A P Kumaran … (2020)

Background Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention. Methods We performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I 2 statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance. Findings We identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified. Interpretation Drug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice. Trial registration PROSPERO CRD42018029432.

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Author and article information

Journal

Journal ID (nlm-ta): Clin Infect Dis

Journal ID (iso-abbrev): Clin Infect Dis

Journal ID (publisher-id): cid

Title: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America

Publisher: Oxford University Press (US )

ISSN (Print): 1058-4838

ISSN (Electronic): 1537-6591

Publication date Collection: 01 November 2020

Publication date (Electronic): 01 December 2020

Publication date PMC-release: 01 December 2020

Volume: 71

Issue: Suppl 3 , Surveillance for Enteric Fever in Asia Project (SEAP) — Phase II

Pages: S276-S284

Affiliations

[1 ] Department of Pediatrics and Child Health, Aga Khan University , Karachi, Pakistan

[2 ] Department of Pathology and Laboratory Medicine, Aga Khan University , Karachi, Pakistan

[3 ] Applied Epidemiology, Sabin Vaccine Institute , Washington, DC, USA

[4 ] Kharadar General Hospital , Karachi, Pakistan

[5 ] Infectious Diseases and Geographic Medicine, Stanford University , Stanford, California, USA

[6 ] National Foundation for the Centers for Disease Control and Prevention , Atlanta, Georgia, USA

[7 ] Global Immunization Division, Centers for Disease Control and Prevention , Atlanta, Georgia, USA

[8 ] Child Health Research Foundation, Department of Microbiology, Dhaka Shishu (Children) Hospital , Bangladesh

Author notes

Correspondence: Samir K. Saha, Child Health Research Foundation, SEL Huq Skypark, 23/2 Khilji Road, Block-B (Mirpur Road), Mohammadpur Dhaka, 1207, Bangladesh ( Samir@ 123456chrfbd.org ).

Article

Publisher ID: ciaa1323

DOI: 10.1093/cid/ciaa1323

PMC ID: 7705872

PubMed ID: 33258934

SO-VID: 4d092055-94e4-4ac6-a3e6-9437b7ac89a1

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date: 01 December 2020

Page count

Pages: 9

Funding

Funded by: Bill and Melinda Gates Foundation, DOI 10.13039/100000865;

Award ID: INV-008335

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

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Abstract

Background

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Conclusions

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Point-Of-Care Testing for AMR

Most cited references 47

Understanding the mechanisms and drivers of antimicrobial resistance.

Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data.

Drug-resistant enteric fever worldwide, 1990 to 2018: a systematic review and meta-analysis

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