Molecular evaluation of drug resistance in clinical isolates of Salmonella enterica serovar Typhi from Pakistan

Afzal, Amna; Sarwar, Yasra; Ali, Aamir; Maqbool, Abbas; Salman, Muhammad; Habeeb, Muhammad Asif; Haque, Abdul

doi:10.3855/jidc.3154

Cited by 23 publications

(21 citation statements)

References 59 publications

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“…One study reported 6% (16 isolates) ceftriaxone resistance using microdilution testing [86]. The remaining 21 studies performed Kirby-Bauer disc diffusion testing; of those, only three studies, one with 43% (80 isolates) [87], one with 15% (630 isolates) [46] and one with 11% (300 isolates) resistance [88], determined ceftriaxone MICs. However, ceftriaxone resistance was not confirmed by MIC testing (agar dilution) in the two latter studies [46, 88].…”

Section: Resultsmentioning

confidence: 99%

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

Browne

Hamadani

Kumaran

et al. 2020

BMC Med

502

401

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BackgroundAntimicrobial 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.MethodsWe 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 I2 statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance.FindingsWe 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.InterpretationDrug-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 registrationPROSPERO CRD42018029432.

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Section: Resultsmentioning

confidence: 99%

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

Browne

Hamadani

Kumaran

et al. 2020

BMC Med

502

401

View full text Add to dashboard Cite

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“…Typhi resistance to ceftriaxone has been documented as emerging in Bangladesh and Kuwait for up to 15 years (Afzal et al, 2013). Indeed, a recent study in Pakistan and India concludes that 73.7% (n=80), 56.2%, and 52.5% of bacterial isolates had developed resistance to sulfonamide, ampicillin, or streptomycin, respectively (Afzal et al, 2013), with 58.7% of the overall isolates having multi-drug resistance. Resistant strains have also been observed in Kenya with resistance against cotrimoxazole in 66.7% (22 individuals) of the S .…”

Section: Introductionmentioning

confidence: 99%

Acetalated dextran encapsulated AR-12 as a host-directed therapy to control Salmonella infection

Hoang

Borteh

Rajaram

et al. 2014

International Journal of Pharmaceutics

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AR-12 has been evaluated in clinical trials as an anti-cancer agent but also has demonstrated host-directed, broad-spectrum clearance of bacteria. We have previously shown that AR-12 has activity in vitro against Salmonella enterica serovar Typhimurium and Francisella species by inducing autophagy and other host immune pathways. AR-12 treatment of S. Typhimurium-infected mice resulted in a 10-fold reduction in bacterial load in the liver and spleen and an increased survival time. However, AR-12 treatment did not protect mice from death, likely due poor formulation. In the current study, AR-12 was encapsulated in a microparticulate carrier formulated from the novel degradable biopolymer acetalated dextran (Ace-DEX) and subsequently evaluated for its activity in human monocyte-derived macrophages (hMDMs). Our results show that hMDMs efficiently internalized Ace-DEX microparticles (MPs), and that encapsulation significantly reduced host cell cytotoxicity compared to unencapsulated AR-12. Efficient macrophage internalization of AR-12 loaded MPs (AR-12/MPs) was further demonstrated by autophagosome formation that was comparable to free AR-12 and resulted in enhanced clearance of intracellular Salmonella. Taken together, these studies provide support that Ace-DEX encapsulated AR-12 may be a promising new therapeutic agent to control intracellular bacterial pathogens of macrophages by targeting delivery and reducing drug toxicity.

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“…3 With this burden, treating typhoid fever is huge challenge for health care provider in developing countries. Factors like nonspecific signs and symptoms 4 , variable yield of organism on blood culture 5 and finally drug resistance 6 are one by one increasing the complexity of managing this disease. Over the past three decades drug susceptibility against Salmonella Typhi and Paratyphi has been changed significantly.…”

Section: Introductionmentioning

confidence: 99%

Extended drug resistance in children with typhoid fever.

Anwar

Rais

Jamil

et al. 2020

TPMJ

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In developing countries, typhoid fever is mostly seen due to poor public health and low socioeconomic indices. Currently Pakistan is going through the largest outbreak of XDR typhoid fever which has resulted in increased morbidity and mortality especially in pediatric population. Objectives: To see the pattern of extended drug resistant typhoid fever in different areas of Karachi. Study Design: Cross sectional study. Setting: Department of pediatrics, Ziauddin Hospital (KDLB, NORTH, CLIFTON campus). Period: 6 months from October 2018 till March 2019. Material & Methods: All patients who presented with history of fever for 3 or more days with signs and symptoms of typhoid fever were recruited. For data collection a self-structured questionnaire was used. Age, gender, socioeconomic status, personal hygiene, water supply and sanitation were taken into account. Blood samples were sent for cultures. Salmonella isolates were tested for antibiotic susceptibility. Tested antimicrobials were ampicillin, TMP/SMX, cefixime, ceftriaxone, aztreonam, ciprofloxacin, azithromycin, meropenem. For data analysis SPSS version 22 was used. Results: Out of 415 patients, 235 had culture proven typhoid fever. Salmonella typhi was isolated in 94.4%of the patients and salmonella paratyphi was isolated in 5.57%. Of the 235, Males were 62% and females were 42.4%. Major determinants associated with acquiring salmonella infection were young age (74%), male sex (62%), middle and low socioeconomic status (83.8%), living in west district of Karachi (54.9%) and drinking line water (79.2%). Extended drug resistance was encountered in 69.5%. Most of the isolates were sensitive to meropenem and azithromycin (96.7 %, and 95.5% respectively). Ceftriaxone resistance was prevelant in all three districts of Karachi (p value <0.001), in different age groups 1-6yrs (98%), 7-12 yrs(91%), 13-18 yrs (100%) and in males(58%) predominantly. Conclusion: Karachi is facing an outbreak of XDR typhoid fever. Risk of acquiring extended drug resistant typhoid fever is increased in younger age group 1-6 yrs, males, west district of Karachi and poor socioeconomic status. Drinking unboiled water is identified as one of the major culprits. Actions should be taken at all health care levels to monitor the judicious use of antibiotics, and preventive strategies like safe water supply, improved sanitation along with typhoid vaccination are suggested to overcome this outbreak.

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Molecular evaluation of drug resistance in clinical isolates of Salmonella enterica serovar Typhi from Pakistan

Cited by 23 publications

References 59 publications

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

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

Acetalated dextran encapsulated AR-12 as a host-directed therapy to control Salmonella infection

Extended drug resistance in children with typhoid fever.

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