Ceftriaxone resistant Salmonella enterica serovar Paratyphi A identified in a case of enteric fever: first case report from Pakistan.

BACKGROUND: Enteric fever is an acute systemic infectious disease associated with substantial morbidity and mortality in low- and middle-income countries (LMIC), with a global burden of 14.3 million cases. Cases of enteric fever or paratyphoid fever, caused by Salmonella enterica serovar Paratyphi A (S. Para A) have been found to rise in many endemic and non-endemic countries. Drug resistance is relatively uncommon in S. Para A. Here we report a case of paratyphoid fever caused by ceftriaxone resistant S. Para A from Pakistan. CASE PRESENTATION: A 29-year-old female presented with a history of fever, headache, and shivering. Her blood culture revealed a S. Para A isolate (S7), which was resistant to ceftriaxone, cefixime, ampicillin and ciprofloxacin. She was prescribed oral Azithromycin for 10 days, which resulted in resolution of her symptoms. Two other isolates of S. Para A (S1 and S4), resistant to fluoroquinolone were also selected for comparison. DST and whole genome sequencing was performed for all three isolates. Sequence analysis was performed for identification of drug resistance and phylogeny. Whole Genome Sequencing (WGS) of S7 revealed the presence of plasmids, IncX4 and IncFIB(K). blaCTX-M-15 and qnrS1 genes were found on IncFIB(K). The gyrA S83F mutation conferring fluoroquinolone resistance was also found present. Multi-locus sequence typing (MLST) showed the S7 isolate to belong to ST129. S1 and S4 had the gyrA S83Y and S83F mutations respectively. CONCLUSIONS: We highlight the occurrence of plasmid-mediated ceftriaxone resistant strain of S. Para A. This is of significance as ceftriaxone is commonly used to treat paratyphoid fever and resistance in S. Para A is not known. Continuous epidemiological surveillance is required to monitor the transmission and spread of antimicrobial resistance (AMR) among Typhoidal Salmonellae. This will guide treatment options and preventive measures including the need for vaccination against S. Para A in the region.

Treatment of enteric fever (typhoid and paratyphoid fever) with cephalosporins.

BACKGROUND: Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first-line antimicrobials. Resistance patterns vary in different locations and are changing over time. Fluoroquinolone resistance in South Asia often precludes the use of ciprofloxacin. Extensively drug-resistant strains of enteric fever have emerged in Pakistan. In some areas of the world, susceptibility to old first-line antimicrobials, such as chloramphenicol, has re-appeared. A Cochrane Review of the use of fluoroquinolones and azithromycin in the treatment of enteric fever has previously been undertaken, but the use of cephalosporins has not been systematically investigated and the optimal choice of drug and duration of treatment are uncertain. OBJECTIVES: To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the WHO ICTRP and ClinicalTrials.gov up to 24 November 2021. We also searched reference lists of included trials, contacted researchers working in the field, and contacted relevant organizations. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in adults and children with enteric fever that compared a cephalosporin to another antimicrobial, a different cephalosporin, or a different treatment duration of the intervention cephalosporin. Enteric fever was diagnosed on the basis of blood culture, bone marrow culture, or molecular tests. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were clinical failure, microbiological failure and relapse. Our secondary outcomes were time to defervescence, duration of hospital admission, convalescent faecal carriage, and adverse effects. We used the GRADE approach to assess certainty of evidence for each outcome. MAIN RESULTS: We included 27 RCTs with 2231 total participants published between 1986 and 2016 across Africa, Asia, Europe, the Middle East and the Caribbean, with comparisons between cephalosporins and other antimicrobials used for the treatment of enteric fever in children and adults. The main comparisons are between antimicrobials in most common clinical use, namely cephalosporins compared to a fluoroquinolone and cephalosporins compared to azithromycin. Cephalosporin (cefixime) versus fluoroquinolones Clinical failure, microbiological failure and relapse may be increased in patients treated with cefixime compared to fluoroquinolones in three small trials published over 14 years ago: clinical failure (risk ratio (RR) 13.39, 95% confidence interval (CI) 3.24 to 55.39; 2 trials, 240 participants; low-certainty evidence); microbiological failure (RR 4.07, 95% CI 0.46 to 36.41; 2 trials, 240 participants; low-certainty evidence); relapse (RR 4.45, 95% CI 1.11 to 17.84; 2 trials, 220 participants; low-certainty evidence). Time to defervescence in participants treated with cefixime may be longer compared to participants treated with fluoroquinolones (mean difference (MD) 1.74 days, 95% CI 0.50 to 2.98, 3 trials, 425 participants; low-certainty evidence). Cephalosporin (ceftriaxone) versus azithromycin Ceftriaxone may result in a decrease in clinical failure compared to azithromycin, and it is unclear whether ceftriaxone has an effect on microbiological failure compared to azithromycin in two small trials published over 18 years ago and in one more recent trial, all conducted in participants under 18 years of age: clinical failure (RR 0.42, 95% CI 0.11 to 1.57; 3 trials, 196 participants; low-certainty evidence); microbiological failure (RR 1.95, 95% CI 0.36 to 10.64, 3 trials, 196 participants; very low-certainty evidence). It is unclear whether ceftriaxone increases or decreases relapse compared to azithromycin (RR 10.05, 95% CI 1.93 to 52.38; 3 trials, 185 participants; very low-certainty evidence). Time to defervescence in participants treated with ceftriaxone may be shorter compared to participants treated with azithromycin (mean difference of -0.52 days, 95% CI -0.91 to -0.12; 3 trials, 196 participants; low-certainty evidence). Cephalosporin (ceftriaxone) versus fluoroquinolones It is unclear whether ceftriaxone has an effect on clinical failure, microbiological failure, relapse, and time to defervescence compared to fluoroquinolones in three trials published over 28 years ago and two more recent trials: clinical failure (RR 3.77, 95% CI 0.72 to 19.81; 4 trials, 359 participants; very low-certainty evidence); microbiological failure (RR 1.65, 95% CI 0.40 to 6.83; 3 trials, 316 participants; very low-certainty evidence); relapse (RR 0.95, 95% CI 0.31 to 2.92; 3 trials, 297 participants; very low-certainty evidence) and time to defervescence (MD 2.73 days, 95% CI -0.37 to 5.84; 3 trials, 285 participants; very low-certainty evidence). It is unclear whether ceftriaxone decreases convalescent faecal carriage compared to the fluoroquinolone gatifloxacin (RR 0.18, 95% CI 0.01 to 3.72; 1 trial, 73 participants; very low-certainty evidence) and length of hospital stay may be longer in participants treated with ceftriaxone compared to participants treated with the fluoroquinolone ofloxacin (mean of 12 days (range 7 to 23 days) in the ceftriaxone group compared to a mean of 9 days (range 6 to 13 days) in the ofloxacin group; 1 trial, 47 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Based on very low- to low-certainty evidence, ceftriaxone is an effective treatment for adults and children with enteric fever, with few adverse effects. Trials suggest that there may be no difference in the performance of ceftriaxone compared with azithromycin, fluoroquinolones, or chloramphenicol. Cefixime can also be used for treatment of enteric fever but may not perform as well as fluoroquinolones.  We are unable to draw firm general conclusions on comparative contemporary effectiveness given that most trials were small and conducted over 20 years previously. Clinicians need to take into account current, local resistance patterns in addition to route of administration when choosing an antimicrobial.

Clinical manifestations and microbiological features between indigenous and imported enteric fever in Taiwan, 2010-2020.

Previous studies had showed that indigenous clones of Salmonella Typhi and S. Paratyphi were originally imported from other countries in Taiwan. We presented the clinical manifestations and laboratory findings of indigenous and imported enteric fever cases in Taiwan in the current decade. We retrospectively reviewed typhoid and paratyphoid fever cases in two medical centers of Chang Gung Memorial Hospitals in 2010-2020. A total of 37 enteric fever cases including 24 typhoid fever and 13 paratyphoid fever were recorded. There were 20 indigenous cases, 16 imported cases, and one indetermined case. Splenomegaly and hepatitis were more frequent in typhoid fever than in paratyphoid fever (P < 0.05). Imported cases had more ciprofloxacin non-susceptibility rate (8/16, 50.0%) than indigenous cases (2/20, 10%). Indigenous ciprofloxacin non-susceptible S. Typhi isolates were found in 2018. One indigenous S. Paratyphi B isolate was multi-drug resistant (MDR) to chloramphenicol, ampicillin, and trimethoprim/sulfamethoxazole.

Genomic surveillance reveals international circulation and local transmission of Salmonella enterica serovars Typhi and Paratyphi A in Taiwan.

BACKGROUND/PURPOSE: Morbidity and mortality from typhoid and paratyphoid fever remain an important problem for public health authorities in developing countries. In countries with lower incidences, most cases occur in travelers who visit regions in which typhoid and paratyphoid fever are highly endemic. The aim was to evaluate the source and transmission dynamics of typhoid and paratyphoid fever in Taiwan by using genomic analysis. METHODS: During 2012-2019, 15 clinical isolates of Salmonella Typhi and S. Paratyphi A were collected. Demographic and clinical information of the infections were analyzed. We performed whole genome sequencing and evolutionary analysis on these isolates. RESULTS: Clinical and microbiological data from 7 S. Typhi and 8 S. Paratyphi A isolates in Taiwan showed epidemiological and bacterial genomic link to the infection in South and Southeast Asia. The Taiwanese typhoidal isolates also share highly similar genomes with those collected from UK, indicating global circulation of the typhoidal clones. Local transmission of the imported but indigenized international clones was observed. Mutations occurring at gyrA 83 aa, including S83Y and S83F, were identified in the ciprofloxacin-resistant strains. CONCLUSION: Due to the advance of global transportation and communication, the transmission mode of infectious disease has been modified. Domestic typhoid and paratyphoid fever caused by international resistant clones can occur in low-incidence countries. Genome analysis showed that the indigenous clone originally imported from other countries has been circulating in Taiwan for over a decade.

Prevalence of Enteric Fever Pathogens Isolated from Blood Culture at a Tertiary Care Centre.

INTRODUCTION: Typhoid fever and paratyphoid fever commonly called as enteric fever is a life-threatening illness caused by Salmonella serotype Typhi and Salmonella serotype Paratyphi, respectively. It is a major public health issue in underdeveloped and developing countries. The aim of the study is to find out the prevalence of enteric fever pathogens in blood culture of patients attending a tertiary care centre. METHODS: A descriptive cross-sectional study was conducted in 3483 blood samples of patients attending a tertiary care centre, with the history and symptoms suspicious of enteric fever during one year period from mid-September 2019 to mid-September 2020 after ethical approval from the institutional review committee. Isolates were identified by standard microbiological methods and tested for in vitro antibiotic susceptibility by modified kirby-bauer disc diffusion method. The obtained data was entered and analyzed in WHONET 5.6 program, point estimate at 95% was calculated along with frequency and proportion for binary data. RESULTS: In our study, enteric fever pathogens were isolated from 18 (0.51%) blood samples. Out of which, Salmonella Paratyphi A was isolated from 10 (8.19%) and Salmonella Typhi was isolated from 8 (6.55%) blood samples. Other serotypes were not isolated. Antimicrobial susceptibility test showed that salmonella species that was isolated were sensitive to most of the drugs. CONCLUSIONS: Prevalence of enteric fever pathogens was lesser compared to other studies. Varying degrees of antibiotic resistance among isolated enteric fever pathogens necessitates continuous surveillance of the susceptibility patterns. Prudent use of antimicrobials, active infection control practices and stringent antibiotic policy should be implemented to prevent emergence of antibiotic resistance and future outbreaks.

Salmonella Paratyphi B; Public Health and Parental Choice: When to Treat Asymptomatic Carriers of Infection?

BACKGROUND: Salmonella Paratyphi B (Paratyphoid B) is a rare infection and a notifiable disease in England. Disease is typically mild, and chronic carriage in children has been described in endemic countries. Almost all cases in England are imported, with very few cases of community transmission reported. METHODS: The aim of this work was to describe an unusual cluster of Paratyphoid B cases transmitted within England, examining clinical, epidemiologic and microbiologic data. Detailed phylogenetic analysis is presented to corroborate public health epidemiologic links between cases. RESULTS: One child had recently returned from an endemic area and had mild gastrointestinal symptoms. One year later, 2 other children with no travel history developed invasive disease requiring hospitalization. Epidemiologic links confirmed person-to-person spread between these three cases. All isolates of S. Paratyphi B (n = 93) received by the Gastrointestinal Bacteria Reference Unit between 2014 and 2019 were typed using whole genome sequencing. Three cases of Paratyphoid B were identified in the same geographical location over a 2-year period. S. Paratyphi B strains isolated from the stool and blood of the three cases were closely linked (0-5 single-nucleotide polymorphisms) using whole genome sequencing. CONCLUSIONS: This case series highlights the potential public health risks of paratyphoid B and the range of pediatric complications associated with this illness, especially in younger children. Although rare, chronic carriage of Paratyphoid B can lead to transmission in nonendemic areas and should be considered in all children presenting with signs of enteric fever even where there is no history of foreign travel.

Typhoid and paratyphoid fever: a clinical seminar.

Rationale for review: Enteric fever (EF) caused by Salmonella enterica subspecies enterica serovar Typhi (Salmonella Typhi) and S. Paratyphi (Salmonella Paratyphi) remains an important cause of infectious morbidity and mortality in many low-income countries and, therefore, still poses a major infectious risk for travellers to endemic countries. Main findings: Although the global burden of EF has decreased over the past two decades, prevalence of EF remains high in Asia and Africa, with the highest prevalence reported from the Indian subcontinent. These statistics are mirrored by data on travel-related EF. Widespread and increasing antimicrobial resistance has narrowed treatment options for travel-related EF. Ceftriaxone- and azithromycin-based therapies are commonly used, even with the emergence of extremely drug-resistant typhoid in Pakistan. Preventive measures among locals and travellers include provision of safe food and water and vaccination. Food and water precautions offer limited protection, and the efficacy of Salmonella Typhi vaccines is only moderate signifying the need for travellers to be extra cautious. Recommendations: Improvement in the diagnosis of typhoid with high degree of clinical suspicion, better diagnostic assays, early and accurate detection of resistance, therapy with appropriate drugs, improvements in hygiene and sanitation with provision of safe drinking water in endemic areas and vaccination among travellers as well as in the endemic population are keys to controlling typhoid. While typhoid vaccines are recommended for travellers to high-risk areas, moderate efficacy and inability to protect against Salmonella Paratyphi are limitations to bear in mind. Improved Salmonella Typhi vaccines and vaccines against Salmonella Paratyphi A are required.

Salmonella Typhi and Paratyphi A infections in Cambodian children, 2012-2016.

OBJECTIVES: Enteric fever remains an important diagnostic and treatment challenge in febrile children living in the tropics. In the context of a national Salmonella enterica serovar Paratyphi A outbreak, the objective of this retrospective study was to compare features of S. Typhi and S. Paratyphi A infections in Cambodian children. METHODS: Clinical and laboratory features were reviewed for 192 blood culture-confirmed children with S. Typhi and S. Paratyphi A infections presenting to a paediatric referral hospital in Siem Reap, 2012-2016. RESULTS: Children with S. Typhi infections were younger, were more likely to have chills and/or diarrhoea, and were more frequently hospitalized than those with S. Paratyphi A infections. Over three quarters (88.3%) of S. Typhi isolates were multidrug-resistant, compared to none of the S. Paratyphi A. CONCLUSIONS: In this small study of Cambodian children, S. Typhi infections were more severe than S. Paratyphi A infections. Antibiotic resistance limits treatment options for enteric fever in this population.

Isolation and Characterization of a Lytic Salmonella paratyphi Phage and Its Antibiofilm Activity Individually or Collaborative with Kanamycin Sulfate.

Salmonella is among the most serious of foodborne pathogens worldwide and distributed widely in the natural environment; in addition, it has caused severe medical problems and foodborne diseases. Bacterial biofilm was the multicellular community of microorganisms that attached to nonbiological and biological surfaces. Phages and their derivatives are ideal candidates for replacing and compensating antibiotic resistance problems in the future. In this study, a virulent phage of KM15 was isolated from pig slaughterhouse sump samples in Kunming, China. It belonged to the Siphoviridae family, and optimal growth temperature was 42°C, the pH of optimal preservation buffer was 6-7, optimal multiplicity of infection was 0.0001, and the genome size was 41,869 bp. The Salmonella paratyphi A and Salmonella paratyphi B have a broad spectrum of antibiotic resistance and were isolated from clinical patients in the First People's Hospital of Yunnan Province; fortunately, most of them can be lysed by phage KM15. Collaboration of phage KM15 and kanamycin sulfate has a better antibiofilm effect than KM15 and kanamycin sulfate alone, in low-concentration bacterial culture; KM15 has better antibiofilm effect than kanamycin sulfate in high-concentration bacterial culture. The data of this study provided a strong evidence of application of phage to reduce the growth of Salmonella biofilm, which was important for public health.

[Typhoid and paratyphoid fever]. / Typhus abdominalis und Paratyphus.

Typhoid fever and paratyphoid fever are systemic infectious diseases of global significance caused by Salmonella enterica subspecies enterica Serovar Typhi (short name: Salmonella Typhi) or Serovar Paratyphi (short name: Salmonella Paratyphi). The course of these fecal-orally transmitted diseases is mainly characterized by a high fever. Left untreated, the course of typhoid fever can be severe and lethal. The infection is almost always acquired outside of Europe (mainly in India) and is notifiable in Germany, Austria and Switzerland. Paratyphoid is an attenuated disease of typhoid fever caused by Salmonella Paratyphi. Available vaccines only protect against Salmonella Typhi. Antibiotic resistance reflects the situation in endemic countries and shows a worrying increase of multi-drug resistant isolates. Currently, third-generation cephalosporins such as ceftriaxone are recommended as first-line therapy; if sensitive to quinolones, fluoroquinolones such as ciprofloxacin may continue to be administered. Crucial preventive measures for travelers to endemic regions include consistent water and food hygiene as well as vaccination, whereby only protection rates of 50-70 % are achieved by currently available vaccines. In the light of increasing multi-drug resistance, a more effective conjugate vaccine against Salmonella Typhi with cross-reactivity against Salmonella Paratyphi is needed more than ever.

Salmonella enterica serovar Paratyphi A isolated from a hard-to-heal diabetic ulcer: a case report.

Chronically infected diabetic wounds have a polymicrobial aetiology. However, Salmonella Paratyphi A is a very rare cause of wound infection. A 76-year-old female patient with type II diabetes presented with a wound on the left leg of two months' duration. The wound was painful, erythematous and a thick, foul-smelling discharge was present. There was a history of delayed wound healing. Salmonella Paratyphi A and Pseudomonas aeruginosa were isolated from the wound tissue. The patient was treated with cefuroxime and cloxacillin empirically and following the antibiotic susceptibility testing (ABST) report, ciprofloxacin was given for 10 days. The wound was treated with multiple debridements and topical antiseptic. On follow-up, the patient remained afebrile with subsiding discharge from the ulcer. This is the first reported case of Salmonella Paratyphi A from an infected diabetic ulcer in Sri Lanka and it serves to further define the spectrum of illnesses caused by this uncommon pathogen.

Treatment responses to Azithromycin and Ciprofloxacin in uncomplicated Salmonella Typhi infection: A comparison of Clinical and Microbiological Data from a Controlled Human Infection Model.

BACKGROUND: The treatment of enteric fever is complicated by the emergence of antimicrobial resistant Salmonella Typhi. Azithromycin is commonly used for first-line treatment of uncomplicated enteric fever, but the response to treatment may be sub-optimal in some patient groups when compared with fluoroquinolones. METHODS: We performed an analysis of responses to treatment with azithromycin (500mg once-daily, 14 days) or ciprofloxacin (500mg twice-daily, 14 days) in healthy UK volunteers (18-60 years) enrolled into two Salmonella controlled human infection studies. Study A was a single-centre, open-label, randomised trial. Participants were randomised 1:1 to receive open-label oral ciprofloxacin or azithromycin, stratified by vaccine group (Vi-polysaccharide, Vi-conjugate or control Men-ACWY vaccine). Study B was an observational challenge/re-challenge study, where participants were randomised to challenge with Salmonella Typhi or Salmonella Paratyphi A. Outcome measures included fever clearance time, blood-culture clearance time and a composite measure of prolonged treatment response (persistent fever ≥38.0°C for ≥72 hours, persistently positive S. Typhi blood cultures for ≥72 hours, or change in antibiotic treatment). Both trials are registered with ClinicalTrials.gov (NCT02324751 and NCT02192008). FINDINGS: In 81 participants diagnosed with S. Typhi in two studies, treatment with azithromycin was associated with prolonged bacteraemia (median 90.8 hours [95% CI: 65.9-93.8] vs. 20.1 hours [95% CI: 7.8-24.3], p<0.001) and prolonged fever clearance times <37.5°C (hazard ratio 2.4 [95%CI: 1.2-5.0]; p = 0.02). Results were consistent when studies were analysed independently and in a sub-group of participants with no history of vaccination or previous challenge. A prolonged treatment response was observed significantly more frequently in the azithromycin group (28/52 [54.9%]) compared with the ciprofloxacin group (1/29 [3.5%]; p<0.001). In participants treated with azithromycin, observed systemic plasma concentrations of azithromycin did not exceed the minimum inhibitory concentration (MIC), whilst predicted intracellular concentrations did exceed the MIC. In participants treated with ciprofloxacin, the observed systemic plasma concentrations and predicted intracellular concentrations of ciprofloxacin exceeded the MIC. INTERPRETATION: Azithromycin at a dose of 500mg daily is an effective treatment for fully sensitive strains of S. Typhi but is associated with delayed treatment response and prolonged bacteraemia when compared with ciprofloxacin within the context of a human challenge model. Whilst the cellular accumulation of azithromycin is predicted to be sufficient to treat intracellular S. Typhi, systemic exposure may be sub-optimal for the elimination of extracellular circulating S. Typhi. In an era of increasing antimicrobial resistance, further studies are required to define appropriate azithromycin dosing regimens for enteric fever and to assess novel treatment strategies, including combination therapies. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02324751 and NCT02192008).

An adolescent with multi-organ involvement from typhoid fever.

Typhoid fever is usually a mild clinical disease, but it can have potentially serious complications. Here, we describe a case of an adolescent male who presented with severe illness and multi-organ involvement from typhoid fever. He required follow-up after discharge but eventually recovered. Clinicians should be aware of the spectrum of clinical manifestations as early recognition will improve monitoring and management of typhoid disease.

A systematic review of antimicrobial resistance of typhoidal Salmonella in India.

Background & objectives: The temporal trends in the development of antimicrobial resistance (AMR) among Salmonella Typhi and Salmonella Paratyphi in India have not been systematically reported. We aimed to systematically review the temporal AMR trends (phenotypic and molecular mechanisms) in bacterial isolates from patients with enteric fever over two decades in India. Methods: To identify trends in AMR in India, resistance patterns among 4611 individual S. Typhi isolates and 800 S. Paratyphi A isolates, reported from 1992 to 2017 in 40 publications, were analysed. Molecular resistance determinants were extracted from 22 publications and also reviewed in accordance with the PRISMA guidelines. Articles were sourced using a predefined search strategy from different databases. Results: The analyses suggested that multidrug-resistant (MDR) enteric fever was declining in India and being replaced by fluoroquinolone (FQ) resistance. Mutations in gyrA and parC were key mechanisms responsible for FQ resistance, whereas MDR was largely driven by resistance determinants encoded on mobile genetic elements (plasmids, transposons). Interpretation & conclusions: The results reflect the effect of antimicrobial pressure which has been driving AMR in typhoidal Salmonella in India. Understanding these trends is important in planning future approaches to therapy, which serve as a baseline for assessment of the impact of new typhoid conjugate vaccines against these resistant organisms.

Cardiac Involvement in Travelers with Enteric Fever.

Data regarding cardiac involvement in enteric fever among travelers are scarce. In this retrospective study, 59 patients were hospitalized with enteric fever during 2004-2017 and 28 had cardiac workups. Among those, four had evidence of cardiac involvement, including clinical myocarditis, electrocardiogram changes, or troponin elevation. Cardiac involvement was higher among patients infected with Salmonella Typhi than with Salmonella Paratyphi A (P = 0.08), with a significant relative risk of 6 (95% CI: 1.15-31.22, P = 0.03). Time from symptoms onset to effective treatment was longer for patients with cardiac involvement (13 versus 7.15 days, P < 0.05). It seems that cardiac involvement in enteric fever is not uncommon in travelers. Such involvement seems to be more common in patients with delay of effective treatment to the second week of illness. Although fatal or complicated cases are rare in travelers, the cardiac complication may be an important contributor to morbidity and mortality in this group.

Identifying the mechanism underlying treatment failure for Salmonella Paratyphi A infection using next-generation sequencing - a case report.

BACKGROUND: Salmonella is a notorious pathogen that causes gastroenteritis in humans and the emergence of resistance to third-generation cephalosporins and azithromycin have raised concern. There has been rare case of Salmonella Paratyphi A infection accompanied by spondylitis. Here, we report a case of initial antibiotic treatment failure in a Korean man with Salmonella Paratyphi A infection and conducted next-generation sequencing (NGS) to determine the cause of failure of initial treatment for Salmonella Paratyphi A infection. CASE PRESENTATION: A 70-year-old man was admitted to Chosun University Hospital with reported consistent low back pain with a history of having 5 days of chills and fever in another hospital a month ago. He was administered ceftriaxone (2 g daily) for 18 days including initial treatment to cover Salmonella enterica. The antimicrobial susceptibility test using MIC plate, found that the identified organism was resistant to ciprofloxacin and nalidixic acid. Moreover, the Salmonella Paratyphi A isolates were found to have an MIC > 16 mg/L for azithromycin, as he had resistance to both azithromycin and nalidixic acid, the treatment was switched to a combination of ciprofloxacin and cefotaxime. We carried out next-generation sequencing (NGS) to determine the cause of failure of initial treatment for Salmonella Paratyphi A infection. NGS showed that the amino acid substitution GyrA S83F and the expression of multiple RNA-family efflux pumps led to a high-level resistance to quinolone. No genes related to ceftriaxone resistance, such as CTX-M, CMY-2, or other extended-spectrum beta-lactamases were identified in Salmonella enterica Paratyphi A using NGS. The GyrA S83F mutation and the expression of multiple RNA-family efflux pumps may have contributed to the treatment failure of ceftriaxone, even though the MIC of the isolate to ceftriaxone was less than 1. CONCLUSION: This case involved a Salmonella Paratyphi A infection accompanied by spondylitis. To our knowledge, this is the first report to elucidate the mechanism underlying antimicrobial resistance using NGS.

Azithromycin Resistance in Clinical Isolates of Salmonella enterica Serovars Typhi and Paratyphi in Bangladesh.

OBJECTIVE: Salmonella enterica serovars Typhi and Paratyphi, the causative agents of typhoid and paratyphoid, are major threats in developing countries. The present study aimed to investigate the resistance pattern of 40 clinically isolated Salmonella enterica serovars Typhi (n = 33) and Paratyphi (n = 7) to commonly used antibiotics, particularly azithromycin. MATERIALS AND METHODS: The disc diffusion method was used to investigate the resistance pattern of the clinical isolates against selected antibiotics. Minimum inhibitory concentration (MIC) was determined by the broth dilution method. Plate-based assays were used for the detection of efflux pumps. RESULTS: It was observed that 95% of the test isolates were resistant to azithromycin and 100% were resistant to clindamycin. MIC values of azithromycin ranged between 32 and 128 µg mL-1. Although 90% of isolates contained efflux pump, none of the isolates was found to have the mef(A) gene, indicating that some other efflux pump(s) might be present. Macrolide resistance gene, erm(B), was present in 25 isolates (62.5%). Other resistance genes were absent. Plasmids were absent, but class 1 integrons were present in 80% of the isolates. CONCLUSIONS: The occurrence of macrolide resistance in clinical Salmonella enterica serovars Typhi and Paratyphi is of particular significance in Bangladesh where azithromycin is a commonly used drug against most diseases.