Extensively drug-resistant Salmonella Typhi leading to relapsed urinary tract infection: A case report.

Salmonella enterica serotype Typhi (S Typhi) associated urinary tract infections are exceedingly rare, accounting for less than 1% of cases. Such infections have known to occur in immune-compromised or individuals with urogenital structural abnormalities. With the emergence of extensively drug resistant S Typhi strains in Pakistan, the management of its various unique presentations poses therapeutic challenges. We report the first documented case of a 74 years old male patient presenting with relapsed urinary tract infection secondary to extensively drug resistant S Typhi.

Salmonella enterica serotype Choleraesuis: a rare pathogen isolated from perianal abscess.

Infections with non-typhoidal salmonella (NTS) most commonly cause localised infections such as cutaneous abscesses in humans and are a leading source of foodborne illness. Here, we present a unique case of NTS Choleraesuis in a perianal abscess in an immunocompetent patient without any comorbidities.A woman in her late 40s was diagnosed with a perianal abscess with an unknown origin of infection. The patient has undergone an incision and drainage. Her pus culture and sensitivity report yielded Salmonella enterica serotype Choleraesuis. Then, the patient recovered after treatment with intravenous antibiotics and supportive treatment.We present an unusual case of S. enterica serotype Choleraesuis, which is rarely reported as a causative agent of perianal abscess in India. This case has been reported for its rarity in India.

Source tracking of extensively drug resistant Salmonella Typhi in food and raw vegetables using molecular approaches.

INTRODUCTION: Extensively drug resistant (XDR) strains of the Salmonella lineages have been reported to spread from Africa to South Asia. XDR strains are resistant to fluoroquinolones, chloramphenicol, co-trimoxazole, and ampicillin, resulting in treatment failure. The objectives of this study included the investigation of transmission of S. Typhi lineages and the identification of the potentially contaminated sources of the XDR typhoid outbreak from different urban areas by using molecular techniques. METHODOLOGY: Environmental samples, including food samples, were collected from different towns and the susceptibility of each isolate to the antimicrobial agents was examined. Molecular identification of different Salmonella lineages including S. Typhi, S. Paratyphi A, H58, and XDR was carried out through multiplex PCR. RESULTS AND CONCLUSIONS: A total of 328 environmental samples including raw vegetables, water, and bakery items were collected. More than half of the tested samples (64%) found harboring Salmonella spp. The Salmonella was confirmed through PCR amplification of species-specific markers that showed the presence of S. Typhi (40%), S. Paratyphi A (8%), H58 (7%), and XDR S. Typhi (6%). Raw vegetables had the highest number of Salmonella spp., indicating consumption of raw vegetables as a possible source of salmonellosis. XDR status was also affirmed through phenotypic antimicrobial susceptibility testing.

Estimating the subnational prevalence of antimicrobial resistant Salmonella enterica serovars Typhi and Paratyphi A infections in 75 endemic countries, 1990-2019: a modelling study.

BACKGROUND: Enteric fever, a systemic infection caused by Salmonella enterica serovars Typhi and Paratyphi A, remains a major cause of morbidity and mortality in low-income and middle-income countries. Enteric fever is preventable through the provision of clean water and adequate sanitation and can be successfully treated with antibiotics. However, high levels of antimicrobial resistance (AMR) compromise the effectiveness of treatment. We provide estimates of the prevalence of AMR S Typhi and S Paratyphi A in 75 endemic countries, including 30 locations without data. METHODS: We used a Bayesian spatiotemporal modelling framework to estimate the percentage of multidrug resistance (MDR), fluoroquinolone non-susceptibility (FQNS), and third-generation cephalosporin resistance in S Typhi and S Paratyphi A infections for 1403 administrative level one districts in 75 endemic countries from 1990 to 2019. We incorporated data from a comprehensive systematic review, public health surveillance networks, and large multicountry studies on enteric fever. Estimates of the prevalence of AMR and the number of AMR infections (based on enteric fever incidence estimates by the Global Burden of Diseases study) were produced at the country, super-region, and total endemic area level for each year of the study. FINDINGS: We collated data from 601 sources, comprising 184 225 isolates of S Typhi and S Paratyphi A, covering 45 countries over 30 years. We identified a decline of MDR S Typhi in south Asia and southeast Asia, whereas in sub-Saharan Africa, the overall prevalence increased from 6·0% (95% uncertainty interval 4·3-8·0) in 1990 to 72·7% (67·7-77·3) in 2019. Starting from low levels in 1990, the prevalence of FQNS S Typhi increased rapidly, reaching 95·2% (91·4-97·7) in south Asia in 2019. This corresponded to 2·5 million (1·5-3·8) MDR S Typhi infections and 7·4 million (4·7-11·3) FQNS S Typhi infections in endemic countries in 2019. The prevalence of third-generation cephalosporin-resistant S Typhi remained low across the whole endemic area over the study period, except for Pakistan where prevalence of third-generation cephalosporin resistance in S Typhi reached 61·0% (58·0-63·8) in 2019. For S Paratyphi A, we estimated low prevalence of MDR and third-generation cephalosporin resistance in all endemic countries, but a drastic increase of FQNS, which reached 95·0% (93·7-96·1; 3·5 million [2·2-5·6] infections) in 2019. INTERPRETATION: This study provides a comprehensive and detailed analysis of the prevalence of MDR, FQNS, and third-generation cephalosporin resistance in S Typhi and S Paratyphi A infections in endemic countries, spanning the last 30 years. Our analysis highlights the increasing levels of AMR in this preventable infection and serves as a resource to guide urgently needed public health interventions, such as improvements in water, sanitation, and hygiene and typhoid fever vaccination campaigns. FUNDING: Fleming Fund, UK Department of Health and Social Care; Wellcome Trust; and Bill and Melinda Gates Foundation.

Typhoidal salmonella disease in Mukuru informal settlement, Nairobi Kenya; carriage, diversity, and antimicrobial resistant genes.

INTRODUCTION: Multiple studies have shown that typhoid fever is endemic in developing countries characterized by poor hygiene. A unique way of Salmonella Typhi (S.Typhi) pathogenicity is establishing a persistent, usually asymptomatic carrier state in some infected individuals who excrete large numbers of bacteria in faeces. This study aimed to determine the isolation rate of S.Typhi from blood and stool samples among cases and asymptomatic individuals in the Mukuru informal settlement and identify antibiotic resistance patterns within the same population. MATERIALS AND METHODS: We recruited 1014 outpatient participants presenting with typhoid-like symptoms in selected health centres in Nairobi, Kenya. Bacterial isolation was done on Xylose Lysine Deoxycholate agar (XLD) and Mac Conkey agar (Oxoid), followed by standard biochemical tests. Identification was done using API20E, and S.Typhi was confirmed by serotyping using polyvalent antisera 0-9 and monovalent antisera d. The Kirby-Bauer disc diffusion method was used to test the antimicrobial susceptibility of S.Typhi isolates, while Multi-Drug Resistant (MDR) strains were characterized using conventional PCR. RESULTS: Of 1014 participants, 54 (5%) tested positive for S.Typhi. Thirty-eight (70%) of the S.Typhi isolated were from stool samples, while sixteen (30%) were from blood. Three (0.2%) of the isolates were from asymptomatic carriers. Of the 54 S.Typhi isolates, 20 (37%) were MDR. Resistance to ciprofloxacin and nalidixic acid was 43% and 52%, respectively. Resistance to amoxicillin-clavulanic acid (a beta-lactam inhibitor) was 2%. The BlaTEM-1 gene was present in 19/20 (95%) MDR isolates. CONCLUSION: MDR S.Typhi is prevalent in Mukuru Informal settlement. The sharp increase in nalidixic acid resistance is an indication of reduced susceptibility to fluoroquinolones, which are currently the recommended drugs for the treatment of typhoid fever. This study highlights the need for effective antimicrobial stewardship and routine surveillance of antimicrobial resistance (AMR) to inform policy on the prevention and control of MDR Typhoid disease.

Sensorineural hearing loss as an atypical presentation of typhoid fever: A case report.

Typhoid fever, also known as enteric fever, is a multisystemic infection primarily caused by Salmonella enterica serotype Typhi, and less commonly by Salmonella enterica serotypes Paratyphi A, B, and C. The classic presentation includes fever, malaise, diffuse abdominal pain, and constipation. If left untreated, typhoid fever can progress to delirium, obtundation, intestinal haemorrhage, bowel perforation, and death within a month of onset. However, the clinical course can deviate from the classic stepladder fever pattern, which now occurs in as few as 12% of cases.1 In this report, we describe an atypical presentation as sensorineural hearing loss in an otherwise healthy young male.

Evaluating the relationship between ciprofloxacin prescription and non-susceptibility in Salmonella Typhi in Blantyre, Malawi: an observational study.

BACKGROUND: Ciprofloxacin is the first-line drug for treating typhoid fever in many countries in Africa with a high disease burden, but the emergence of non-susceptibility poses a challenge to public health programmes. Through enhanced surveillance as part of vaccine evaluation, we investigated the occurrence and potential determinants of ciprofloxacin non-susceptibility in Blantyre, Malawi. METHODS: We conducted systematic surveillance of typhoid fever cases and antibiotic prescription in two health centres in Blantyre, Malawi, between Oct 1, 2016, and Oct 31, 2019, as part of the STRATAA and TyVAC studies. In addition, blood cultures were taken from eligible patients presenting at Queen Elizabeth Central Hospital, Blantyre, as part of routine diagnosis. Inclusion criteria were measured or reported fever, or clinical suspicion of sepsis. Microbiologically, we identified Salmonella enterica serotype Typhi (S Typhi) isolates with a ciprofloxacin non-susceptible phenotype from blood cultures, and used whole-genome sequencing to identify drug-resistance mutations and phylogenetic relationships. We constructed generalised linear regression models to investigate associations between the number of ciprofloxacin prescriptions given per month to study participants and the proportion of S Typhi isolates with quinolone resistance-determining region (QRDR) mutations in the following month. FINDINGS: From 46 989 blood cultures from Queen Elizabeth Central Hospital, 502 S Typhi isolates were obtained, 30 (6%) of which had either decreased ciprofloxacin susceptibility, or ciprofloxacin resistance. From 11 295 blood cultures from STRATAA and TyVAC studies, 241 microbiologically confirmed cases of typhoid fever were identified, and 198 isolates from 195 participants sequenced (mean age 12·8 years [SD 10·2], 53% female, 47% male). Between Oct 1, 2016, and Aug 31, 2019, of 177 typhoid fever cases confirmed by whole-genome sequencing, four (2%) were caused by S Typhi with QRDR mutations, compared with six (33%) of 18 cases between Sept 1 and Oct 31, 2019. This increase was associated with a preceding spike in ciprofloxacin prescriptions. Every additional prescription of ciprofloxacin given to study participants in the preceding month was associated with a 4·2% increase (95% CI 1·8-7·0) in the relative risk of isolating S Typhi with a QRDR mutation (p=0·0008). Phylogenetic analysis showed that S Typhi isolates with QRDR mutations from September and October, 2019, belonged to two distinct subclades encoding two different QRDR mutations, and were closely related (4-10 single-nucleotide polymorphisms) to susceptible S Typhi endemic to Blantyre. INTERPRETATION: We postulate a causal relationship between increased ciprofloxacin prescriptions and an increase in fluoroquinolone non-susceptibility in S Typhi. Decreasing ciprofloxacin use by improving typhoid diagnostics, and reducing typhoid fever cases through the use of an efficacious vaccine, could help to limit the emergence of resistance. FUNDING: Wellcome Trust, Bill & Melinda Gates Foundation, and National Institute for Health and Care Research (UK).

Case Report: A Case of Complicated Typhoid Fever with Rhabdomyolysis and Hemophagocytic Lymphohistiocytosis.

Typhoid fever can have diverse extra-intestinal complications including encephalitis, Guillain-Barré syndrome, endocarditis, myocarditis, osteomyelitis, renal abscess, and splenic abscesses. Secondary hemophagocytic lymphohistiocytosis with rhabdomyolysis is a rare complication of typhoid fever. Here, we present the case of an adolescent with typhoid fever complicated by rhabdomyolysis and hemophagocytic lymphohistiocytosis.

Prevalence and antimicrobial resistance profile of Salmonella typhi infection in Iraq, 2019-2021.

INTRODUCTION: Salmonella typhi could infect the intestinal tract and the bloodstream or invade body organs and secrete endotoxins. It is endemic in developing countries. It is increasingly evolving antimicrobial resistance to several commonly used antimicrobial agents. MATERIALS AND METHODS: A cross-sectional study was done at Iraqi Communicable Disease Control Center, where all confirmed cases of Salmonella typhi are reported, for a period 2019-2021. All demographic, epidemiological and clinical characteristics of patients, comorbidities, type of samples, distribution of S. typhi by age and gender, time distribution in each year and profile of bacterial resistance and sensitivity to antibiotics were gathered and analysed. RESULTS: Most samples were taken from blood. The mean age of cases during 2019, 2020 and 2021 was 18.7 ± 6.5, 17.7 ± 14.1 and 17.3 ± 12.8. Males constituted 56.7%, 58.5% and 39.8%, respectively. Some cases had comorbidities. Most cases had headache and fever. Some of them had nausea, diarrhoea, vomiting and epigastric pain. The age and sex were significantly associated with years of reporting. The most months of case reporting were June-July (2019 and 2021), Jan. -Feb. (2020). There was an obvious increase in S. typhi resistance to ceftriaxone (92.2%, 86.1%, 88.8%) and ampicillin (77.1%, 76.9%, 81.27%). There was a gradual increase in sensitivity to tetracycline (83.1%, 88.1%, 94%), cotrimoxazole (86.7%, 86.1%, 92.2%), ciprofloxacin (78.3%, 90.1%, 87.8%) and cefixime (77.7%, 72.3%, 72.7%). CONCLUSIONS: There was a sharp rise in resistance rates of the S. typhi in Iraq (during 2019-2021) to ceftriaxone and ampicillin, while there were highest sensitivity rates to imipenem, aztreonam and chloramphenicol. The following recommendations were made: (1) Improvement of general hygiene and food safety measures. (2) Emphasis on vaccination and surveillance of Salmonella infection. (3) Rational use of appropriate antibiotics through implementation of treatment guidelines. (5) Educate communities and travelers about the risks of S. typhi and its preventive measures.

Interrogating Salmonella Typhi biofilm formation and dynamics to understand antimicrobial resistance.

AIMS: Salmonella Typhi biofilm-mediated infections are globally rising. Due to the emergence of drug resistance antibiotics did not show effective results against S. Typhi biofilm. Therefore, there is an urgent need for an in-depth interrogation of S. Typhi biofilm to understand its formation kinetics, compositions, and surface charge value. METHODS: This study utilized the S. Typhi MTCC-733 strain from a microbial-type culture collection in India. The S. Typhi biofilm was formed on a glass slide in a biofilm development apparatus. Typhoidal biofilm analysis was done with the help of various assays such as a crystal violet assay, SEM analysis, FTIR analysis, Raman analysis, and zeta potential analysis. KEY FINDING: This article contained a comprehensive assessment of the typhoid biofilm formation kinetics, biofilm compositions, and surface charge which revealed that cellulose was a major molecule in the typhoidal biofilm which can be used as a major biofilm drug target against typhoidal biofilm. SIGNIFICANCE: This study provided interrogations about typhoidal biofilm kinetics which provided ideas about the biofilm composition. The cellulose molecule showed a major component of S. Typhi biofilm and it could potentially involved in drug resistance, and offer a promising avenue for developing a new antibiofilm therapeutic target to conquer the big obstacle of drug resistance. The obtained information can be instrumental in designing novel therapeutic molecules in the future to combat typhoidal biofilm conditions effectively for overcoming antibiotic resistance against bacterial infection Salmonella.

Clinico-Microbiological Correlation in Salmonella Endophthalmitis: Case Series and Review of Literature.

PURPOSE: To report two rare cases of Salmonella endogenous endophthalmitis in an immunocompromised premature baby and an immunocompetent adult and do a brief literature review of related cases. Diagnosis in both cases was confirmed only after the pathogen grew from ocular samples, in the absence of clear signs of enteric fever. METHODS: Retrospective analysis of medical and microbiology records. RESULTS: Both of our cases of Salmonella endophthalmitis had poor visual outcome, despite timely and aggressive management and irrespective of immune status of the patient. Salmonella infection being a rare cause of endophthalmitis was not initially suspected as the adult had minimal systemic symptoms 2 weeks before presentation, while the preterm baby was still on milk feeds. These were just two microbiologically confirmed cases of Salmonella endophthalmitis at our institute over the past 10 years, though enteric fever due to Salmonella species is endemic in Asian countries. CONCLUSIONS: Salmonella endophthalmitis, though rare, leads to poor visual outcomes despite early recognition and aggressive management and may be confused with other infections or non-infectious entities such as necrotizing retinoblastoma in babies, in the absence of clear systemic signs of the disease.

Detection of Salmonella typhi Isolates and Ceftriaxone Strains Harbouring CTX-M-15 Gene.

OBJECTIVE: To determine blaCTX-M-15(Cefotaxime-Munich) gene amongst the extensively drug resistant (XDR) Salmonella typhi (S. typhi) isolates by quantitative Polymerase Chain Reaction (qPCR). STUDY DESIGN: Observational, cross-sectional study. Place and Duration of the Study: PNS Shifa Hospital and Bahria University of Health Sciences (BUHS), from January to June 2022. METHODOLOGY: All the patients clinically suspected of enteric fever, whose blood culture specimens yielded growth of S. typhi were included in this study. These samples were confirmed by serotyping and biochemical reactions. The ceftriaxone resistance was evaluated by antibiotic susceptibility test according to CLSI 2020 guidelines, whereas blaCTX-M-15 gene was detected by (PCR) using gene-specific primers. RESULTS: Out of 149 S. typhi isolates, 87.2% were confirmed XDR S. typhi resistant to ceftriaxone (CRO). Among these, 83.9% harboured blaCTX-M-15 gene. CONCLUSION: There was a very high frequency of XDR S. typhi harbouring blaCTX-M-15 in Karachi, Pakistan. KEY WORDS: blaCTX-M-15, Salmonella typhi, Third generation cephalosporin, Typhoid fever, Extensively drug resistant.

Clinical and antimicrobial susceptibility profile of typhoid fever in children in the era of antibiotic resistance.

Enteric fever remains a significant public health problem in low- and middle-income countries with further challenges from emerging antimicrobial resistance. Our prospective study evaluated the current clinical and antimicrobial susceptibility profile of enteric fever in 88 children and compared it to previously established literature. Enteric fever usually presents with nonspecific signs and symptoms, with predominant respiratory complaints. A paradigm shift in the antimicrobial sensitivity pattern has been noted, with increasing resistance for first-line antibiotics and older antibiotics such as ampicillin, cotrimoxazole, and chloramphenicol showing good sensitivity. Thus, the introduction of the latter merits consideration.

Defying the odds: Determinants of the antimicrobial response of Salmonella Typhi and their interplay.

Salmonella Typhi, the invasive serovar of S. enterica subspecies enterica, causes typhoid fever in healthy human hosts. The emergence of antibiotic-resistant strains has consistently challenged the successful treatment of typhoid fever with conventional antibiotics. Antimicrobial resistance (AMR) in Salmonella is acquired either by mutations in the genomic DNA or by acquiring extrachromosomal DNA via horizontal gene transfer. In addition, Salmonella can form a subpopulation of antibiotic persistent (AP) cells that can survive at high concentrations of antibiotics. These have reduced the effectiveness of the first and second lines of antibiotics used to treat Salmonella infection. The recurrent and chronic carriage of S. Typhi in human hosts further complicates the treatment process, as a remarkable shift in the immune response from pro-inflammatory Th1 to anti-inflammatory Th2 is observed. Recent studies have also highlighted the overlap between AP, persistent infection (PI) and AMR. These incidents have revealed several areas of research. In this review, we have put forward a timeline for the evolution of antibiotic resistance in Salmonella and discussed the different mechanisms of the same availed by the pathogen at the genotypic and phenotypic levels. Further, we have presented a detailed discussion on Salmonella antibiotic persistence (AP), PI, the host and bacterial virulence factors that can influence PI, and how both AP and PI can lead to AMR.

Phage-antibiotic synergism against Salmonella typhi isolated from stool samples of typhoid patients.

BACKGROUND: Typhoid fever is a fatal disease in humans that is caused by Salmonella typhi. S. typhi infections need immediate antibiotic therapy, and their extensive use has led to multidrug-resistant (MDR) pathogens. The use of bacteriophages is becoming a new way to treat these resistant bacteria. This research was directed to bacteriophage isolation against S. typhi and to determine phage-antibiotic synergism. AIMS: To isolate bacteriophages targeting S. typhi, the causative agent of typhoid fever, and investigate their potential synergistic effects when combined with antibiotics. STUDY DESIGN: A cross-sectional study. METHODS: The Widal test was positive; twenty diarrheal stool samples were taken, and for confirmation of S. typhi, different biochemical tests were performed. The disc-diffusion technique was used to determine antimicrobial resistance, and the double agar overlay method was used for bacteriophage isolation from sewage water against S. typhi. To test antibiotic-phage synergism, the S. typhi bacteria was treated by phages together with varying antibiotic concentrations. RESULTS: Eleven samples were positive for S. typhi with black colonies on SS-agar. These were catalase and MR positive with alkali butt on TSI. Clear plaques were observed after the agar overlay. Isolated phages were stable at various pH and temperature levels. Synergism was observed on agar plate. The zone was enlarged when phages were combined with bacterial lawn culture and ciprofloxacin disk. Bacterial growth inhibition had a significant p-value of 0.03 in titration plates, with the phage-ciprofloxacin combination being more effective than the phage and antibiotic alone. CONCLUSION: The study highlights the synergistic effects of isolated bacteriophages with antibiotics, which are not only effective against S. typhi infection but also decrease antibiotic resistance.

Typhoid spondylodiscitis of the cervical spine.

Spinal infection comprises pyogenic and non-pyogenic spondylodiscitis. This condition may manifest with non-specific clinical symptoms, elevated infective parameters and imaging findings that are difficult to distinguish. The cornerstone of a definitive diagnosis and subsequent successful treatment lies in tissue analysis through culture and histopathological studies. In this context, we present a case of Salmonella pyogenic spondylodiscitis affecting the C5/C6 vertebrae, complicated by Salmonella bacteraemia and characterised by mechanical neck pain that curtails daily activities and overall functioning, although without neurological deficits. The uniqueness of this case stems from its occurrence in an immunocompetent individual from a non-endemic area, with no identifiable sources of Salmonella infection or preceding gastrointestinal symptoms.

Case Report: An Imported Case of Typhoid Fever Combined with Rhabdomyolysis and Multiple Organ Lesions in China.

Here, we report a case of blood culture-confirmed typhoid fever, rhabdomyolysis, and multiple organ damage that arrived in our country from overseas. A 23-year-old male patient presented at our hospital with fever and muscle pain; the condition progressed rapidly. Six days after the onset of symptoms, the patient developed rhabdomyolysis and liver/kidney damage; levels of creatine kinase (CK; maximum peak: 729,869 U/L) and myoglobin (> 3,000 ng/mL) were extremely high, although the extent of renal damage was relatively mild. Blood culture showed Salmonella typhi. The patient received a combination of meropenem and levofloxacin anti-infective therapy, as well as fluid and nutritional metabolic support. He gradually recovered and was discharged after two negative blood cultures. This case highlights the fact that typhoid-induced rhabdomyolysis is a serious, life-threatening disease and that the levels of CK and myoglobin are useful indicators for evaluating typhoid-induced rhabdomyolysis. Clinicians should remain vigilant regarding travel-related illnesses associated with enteric fever.

Trends in antimicrobial resistance amongst Salmonella Paratyphi A isolates in Bangladesh: 1999-2021.

BACKGROUND: Typhoid and paratyphoid remain common bloodstream infections in areas with suboptimal water and sanitation infrastructure. Paratyphoid, caused by Salmonella Paratyphi A, is less prevalent than typhoid and its antimicrobial resistance (AMR) trends are less documented. Empirical treatment for paratyphoid is commonly based on the knowledge of susceptibility of Salmonella Typhi, which causes typhoid. Hence, with rising drug resistance in Salmonella Typhi, last-line antibiotics like ceftriaxone and azithromycin are prescribed for both typhoid and paratyphoid. However, unlike for typhoid, there is no vaccine to prevent paratyphoid. Here, we report 23-year AMR trends of Salmonella Paratyphi A in Bangladesh. METHODS: From 1999 to 2021, we conducted enteric fever surveillance in two major pediatric hospitals and three clinics in Dhaka, Bangladesh. Blood cultures were performed at the discretion of the treating physicians; cases were confirmed by culture, serological and biochemical tests. Antimicrobial susceptibility was determined following CLSI guidelines. RESULTS: Over 23 years, we identified 2,725 blood culture-confirmed paratyphoid cases. Over 97% of the isolates were susceptible to ampicillin, chloramphenicol, and cotrimoxazole, and no isolate was resistant to all three. No resistance to ceftriaxone was recorded, and >99% of the isolates were sensitive to azithromycin. A slight increase in minimum inhibitory concentration (MIC) is noticed for ceftriaxone but the current average MIC is 32-fold lower than the resistance cut-off. Over 99% of the isolates exhibited decreased susceptibility to ciprofloxacin. CONCLUSIONS: Salmonella Paratyphi A has remained susceptible to most antibiotics, unlike Salmonella Typhi, despite widespread usage of many antibiotics in Bangladesh. The data can guide evidence-based policy decisions for empirical treatment of paratyphoid fever, especially in the post typhoid vaccine era, and with the availability of new paratyphoid diagnostics.

Assessing the global risk of typhoid outbreaks caused by extensively drug resistant Salmonella Typhi.

Since its emergence in 2016, extensively drug resistant (XDR) Salmonella enterica serovar Typhi (S. Typhi) has become the dominant cause of typhoid fever in Pakistan. The establishment of sustained XDR S. Typhi transmission in other countries represents a major public health threat. We show that the annual volume of air travel from Pakistan strongly discriminates between countries that have and have not imported XDR S. Typhi in the past, and identify a significant association between air travel volume and the rate of between-country movement of the H58 haplotype of S. Typhi from fitted phylogeographic models. Applying these insights, we analyze flight itinerary data cross-referenced with model-based estimates of typhoid fever incidence to identify the countries at highest risk of importation and sustained onward transmission of XDR S. Typhi. Future outbreaks of XDR typhoid are most likely to occur in countries that can support efficient local S. Typhi transmission and have strong travel links to regions with ongoing XDR typhoid outbreaks (currently Pakistan). Public health activities to track and mitigate the spread of XDR S. Typhi should be prioritized in these countries.