Phenotypic variation of Salmonella in host tissues delays eradication by antimicrobial chemotherapy.

Antibiotic therapy often fails to eliminate a fraction of transiently refractory bacteria, causing relapses and chronic infections. Multiple mechanisms can induce such persisters with high antimicrobial tolerance in vitro, but their in vivo relevance remains unclear. Using a fluorescent growth rate reporter, we detected extensive phenotypic variation of Salmonella in host tissues. This included slow-growing subsets as well as well-nourished fast-growing subsets driving disease progression. Monitoring of Salmonella growth and survival during chemotherapy revealed that antibiotic killing correlated with single-cell division rates. Nondividing Salmonella survived best but were rare, limiting their impact. Instead, most survivors originated from abundant moderately growing, partially tolerant Salmonella. These data demonstrate that host tissues diversify pathogen physiology, with major consequences for disease progression and control.

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.

Linking epidemiological and genomic data in cases of enteric fever in England to inform clinical management and public health action.

OBJECTIVES: To explore the feasibility of linking data from enhanced surveillance patient questionnaires from each enteric fever case in England with genome sequencing data, including antimicrobial resistance (AMR) profiles, from the corresponding isolate of typhoidal salmonellae. METHODS: After linking data we interrogated the merged dataset and assessed the utility of passive surveillance data to match and monitor antimicrobial treatment regimens in enteric fever patients with the AMR profiles of the infectious agent. RESULTS: A high proportion of cases were given antibiotics (n = 1230/1415; 86.9%); half of the cases stated the class of antibiotic they were given (n = 630/1239) and half were prescribed cephalosporins (n = 316/630). Reported treatment with a combination of antibiotics increased with symptom severity. Nearly half of isolates (n = 644/1415; 45.5%) had mutations conferring resistance to ciprofloxacin. Based on genome-derived AMR profiles, typhoidal salmonellae isolates inferred to be susceptible to the recommended first-line antimicrobials were twice as likely to be isolated from individuals residing in the least deprived areas compared with the most deprived (n = 26/169; 15.4% versus n = 32/442; 7.2%). CONCLUSIONS: Due to the high proportion of missing data obtained from patient interviews, we recommend a more transparent and systematic approach to recording the antibiotic prescription details by healthcare professionals in primary and secondary care. A more robust approach to data capture at this point in the care pathway would enable us to audit inconsistencies in the prescribing algorithms across England and ensure equitable treatment across all sections of society. Integrating prescribing data with the genome-derived AMR profiles of the causative agent at the individual patient level provides an opportunity to monitor the impact of treatment on clinical outcomes, and to promote best practice in real time.

Typhoid fever in children in Goroka, Papua New Guinea.

BACKGROUND: Typhoid is endemic in many low-income countries, including in Papua New Guinea. This study aimed to describe the burden and clinical features of typhoid in children in a provincial hospital, to describe environmental conditions that lead to typhoid, and to document the antibiotic sensitivity of Salmonella spp. in the Eastern Highlands Province. METHODS: A combined retrospective and prospective study of children admitted to with clinical features of typhoid to the Goroka Hospital throughout 2022. RESULTS: The study included 98 children, of which 54% were female. The median age was 8 (IQR 5-10.6) years. Over 60% of the patients were from Goroka District, the peri-urban area encompassing the town and surrounds. Ninety-four percent (92) of the patients used a pit latrine as a toilet and only 28% had access to treated water. Neuropsychiatric symptoms were common (60%), as was leukopenia (48%), thrombocytopenia (52%) and anaemia (42%). Thirty-seven patients had positive blood cultures for Salmonella typhi; all isolates were sensitive to third-generation cephalosporins, pefloxacin, ampicillin, trimethoprim and sulfamethoxazole, and only 54% sensitive to chloramphenicol. The median duration of hospitalisation was 6 days (IQR). There were no deaths. CONCLUSION: Prompt public health actions are needed to reduce the burden of typhoid infection in the Papua New Guinea. The conjugate typhoid vaccine should be considered in the highlands region, where typhoid is most endemic.

An Unusual Hematological Complication of Typhoid Fever Case Report.

Typhoid fever is caused by Salmonella species. The most common hematological complications described are anemia and disseminated intravascular coagulation. Splenic infarction is an unusual complication of typhoid fever, and this presentation is rarely described. We report the case of a young female who presented with complaints of severe left upper quadrant pain after being diagnosed with typhoid fever. Computed tomography (CT) revealed multiple wedge-shaped splenic infarcts. She was treated with antibiotics and was also started on antiplatelets. She had a complete recovery with this management, and antiplatelets were tapered off on subsequent visits.

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.

Case of Carbapenem-Resistant Salmonella Typhi Infection, Pakistan, 2022.

Salmonella Typhi infection in a patient in Pakistan initially responded to standard treatment but failed to respond to subsequent treatment. The first strain was susceptible to carbapenems and azithromycin; subsequent strains harbored the NDM-5 gene. Treatment with a combination of intravenous meropenem and colistin was successful. Carbapenem-resistant Salmonella Typhi emergence will hinder treatment.

Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi.

Salmonella Typhi is the primary causative agent of typhoid fever; an acute systemic infection that leads to chronic carriage in 3-5% of individuals. Chronic carriers are asymptomatic, difficult to treat and serve as reservoirs for typhoid outbreaks. Understanding the factors that contribute to chronic carriage is key to development of novel therapies to effectively resolve typhoid fever. Herein, although we observed no distinct clustering of chronic carriage isolates via phylogenetic analysis, we demonstrated that chronic isolates were phenotypically distinct from acute infection isolates. Chronic carriage isolates formed significantly thicker biofilms with greater biomass that correlated with significantly higher relative levels of extracellular DNA (eDNA) and DNABII proteins than biofilms formed by acute infection isolates. Importantly, extracellular DNABII proteins include integration host factor (IHF) and histone-like protein (HU) that are critical to the structural integrity of bacterial biofilms. In this study, we demonstrated that the biofilm formed by a chronic carriage isolate in vitro, was susceptible to disruption by a specific antibody against DNABII proteins, a successful first step in the development of a therapeutic to resolve chronic carriage.

A pattern of antibiotic drug resistance of Salmonella Typhi and Salmonella Paratyphi among children with enteric fever in a tertiary care hospital in Lahore, Pakistan.

AIM: To establish the pattern of antibiotic resistance and assess the frequency of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Salmonella Typhi and Salmonella Paratyphi among children with enteric fever. METHODS: This cross-sectional study was carried out in the Department of Pediatrics, Sharif Medical City Hospital, Lahore, from July 2020 to January 2021. The study involved patients aged between 0 to 15 years who attended our outpatient department or were admitted to the ward with the suspicion of typhoid fever. A convenience sample of patients with blood cultures positive for S. Typhi and S. Paratyphi was enrolled. RESULTS: Of the 105 participants, 70 (66.7%) were male. The mean age was 8.48±4.18 years, and the most affected age group was 6-10 years (n=46, 43.8%). Among the cultured organisms, 95 (90.5%) isolates were S. Typhi and 10 (9.5%) were S. Paratyphi A. Antibiotic resistance was highest against ampicillin (n=91, 86.7%), and all of the isolates were sensitive to imipenem and meropenem. Twenty-three (21.9%) cultured organisms were MDR and 54 (56.8%) were XDR. CONCLUSION: An alarming antibiotic drug resistance pattern was observed among children with enteric fever in Lahore. The lowest resistance was noted for azithromycin, meropenem, and imipenem. Our findings warrant the immediate implementation of tailored antibiotic stewardship and infection control strategies.

Cefotaxime in Enteric Fever: Therapeutic Reappraisal.

Enteric fever is one of the most common infectious diseases in the economically developing world and this bacterial infection is the common most cause of fever in travelers to these endemic areas. Even after the availability and deployment of preventive measures like vaccination against Salmonella typhi (S. typhi) and sanitation practices; effective treatment is paramount to reduce the associated morbidity and mortality. Cephalosporins are antimicrobials belonging to the ß-lactam class with established efficacy, pharmacokinetic, and safety profile by virtue of which, they belong to the group of antibiotics most commonly utilized in clinical practice. They have a broadspectrum of activity against various gram-positive and gram-negative bacteria. Like penicillin, they belong to the ß-lactam class of drugs. Amid such a scenario of rising antimicrobial resistance, a broad-spectrum antibiotic like cefotaxime is a real bliss. Distinctive properties of cefotaxime like broad-spectrum of activity, bactericidal action, stability against the common resistance-causing mechanisms, and good safety profile make it a reliable choice in the therapy landscape of enteric fever. It delivers desired efficacy in such difficult-to-treat scenarios at a manageable tolerability profile. Cefotaxime and ceftriaxone have a comparable spectrum of antimicrobial activity, but both differ in terms of pharmacokinetics. Considering the published literature, cefotaxime seems to be a dependable option for the management of typhoid owing to its effectiveness against S. typhi bundled with an acceptable tolerability profile.

Complicated multi-drug resistant typhoid fever with cerebral oedema, diffuse encephalitis and fungal infection of the oral cavity: A case report.

Enteric fever is a highly fatal infectious disease that can present with extensive symptoms that renders diagnosis quite risky. Multi-drug resistant Salmonella typhi infection has become endemic in third world countries and has been routinely associated with catastrophic complications and even death, with diagnostic and therapeutic impedance. Typhoid fever is known to cause life-threatening cerebral complications. We report the case of a 16-year-old male who presented to us with a high-grade fever, watery diarrhoea, altered level of consciousness, and a mixed dark-coloured crusted oral lesion. Blood workup showed neutropenia, lymphocytopenia, thrombocytopenia, transaminitis, and hyponatraemia. Blood culture grew multi-drug resistant Salmonella Typhi. CT scan of the brain showed diffuse cerebral oedema, while EEG was consistent with the diagnosis of diffuse encephalitis. The patient responded well to culture-sensitive antibiotics, while the oral lesion showed a dramatic response to presumptive antifungal treatment. We discuss the compositions available to date on typhoid-associated encephalitis and the connection of fungal infection in this specific case attempting to promote awareness regarding possible unorthodox presentations of enteric fever.

Pan Drug-Resistant Salmonella Serovar Typhi Septicaemia In A Child: A Case Report.

Typhoid fever, caused by Salmonella enterica serovar Typhi, is a common cause of febrile illness, especially in lower middle-income countries. The only known reservoirs of this infection are humans, and it is prevalent in areas with limited availability of clean drinking water and sanitary conditions. Lately, extensively drug-resistant Salmonella ser. Typhi (XDR S. Typhi) has emerged as one of Pakistan's most challenging public health concerns. Here, we report a case of relapsed typhoid fever in a child, in whom the isolate was found to be resistant to meropenem and azithromycin.

Extensively drug-resistant typhoid fever; it's not that simple: a case report.

Multi-drug resistant strains of Salmonella typhi (S. typhi) has remained endemic in developing countries for the last two decades. With irrational use of antibiotics, an extensively drug-resistant (XDR) strain of S. typhi, sensitive only to Carbapenems and Azithromycin, has evolved which was first reported in Sindh, Pakistan, in 2018. Most of the cases of XDR S. typhi infection treated with antibiotics improve without any complications. Failure to respond to appropriate antibiotics should raise the suspicion of visceral abscesses. Splenic abscess is a rare complication of S. typhi infection. A patient with splenic abscess due to XDR S. typhi has been reported who responded to prolonged antibiotic treatment. We report the case of a young boy from Peshawar with multiple splenic abscesses due to XDR S. typhi which did not respond to percutaneous aspiration and culture-guided antibiotics for two weeks. Eventually, he had to undergo splenectomy. He has remained afebrile since then.

Typhoid fever control in the 21st century: where are we now?

PURPOSE OF REVIEW: Momentum for achieving widespread control of typhoid fever has been growing over the past decade. Typhoid conjugate vaccines represent a potentially effective tool to reduce the burden of disease in the foreseeable future and new data have recently emerged to better frame their use-case. RECENT FINDINGS: We describe how antibiotic resistance continues to pose a major challenge in the treatment of typhoid fever, as exemplified by the emergence of azithromycin resistance and the spread of Salmonella Typhi strains resistant to third-generation cephalosporins. We review efficacy and effectiveness data for TCVs, which have been shown to have high-level efficacy (≥80%) against typhoid fever in diverse field settings. Data from randomized controlled trials and observational studies of TCVs are reviewed herein. Finally, we review data from multicountry blood culture surveillance studies that have provided granular insights into typhoid fever epidemiology. These data are becoming increasingly important as countries decide how best to introduce TCVs into routine immunization schedules and determine the optimal delivery strategy. SUMMARY: Continued advocacy is needed to address the ongoing challenge of typhoid fever to improve child health and tackle the rising challenge of antimicrobial resistance.

Clinical profiles and antimicrobial resistance patterns of invasive Salmonella infections in children in China.

Invasive Salmonella infections result in a significant burden of disease including morbidity, mortality, and financial cost in many countries. Besides typhoid fever, the clinical impact of non-typhoid Salmonella infections is increasingly recognized with the improvement of laboratory detection capacity and techniques. A retrospective multicenter study was conducted to analyze the clinical profiles and antimicrobial resistance patterns of invasive Salmonella infections in hospitalized children in China during 2016-2018. A total of 130 children with invasive Salmonella infections were included with the median age of 12 months (range: 1-144 months). Seventy-nine percent of cases occurred between May and October. Pneumonia was the most common comorbidity in 33 (25.4%) patients. Meningitis and septic arthritis caused by nontyphoidal Salmonella (NTS) infections occurred in 12 (9.2%) patients and 5 (3.8%) patients. Patients < 12 months (OR: 16.04) and with septic shock (OR: 23.4), vomit (OR: 13.33), convulsion (OR: 15.86), C-reactive protein (CRP) ≥ 40 g/L (OR: 5.56), and a higher level of procalcitonin (PCT) (OR: 1.05) on admission were statistically associated to an increased risk of developing meningitis. Compared to 114 patients with NTS infections, 16 patients with typhoid fever presented with higher levels of CRP and PCT (P < 0.05). The rates of resistance to ampicillin, sulfamethoxazole/trimethoprim, ciprofloxacin, and ceftriaxone among Salmonella Typhi and NTS isolates were 50% vs 57.3%, 9.1% vs 24.8%, 0% vs 11.2%, and 0% vs 9.9%, respectively. NTS has been the major cause of invasive Salmonella infections in Chinese children and can result in severe diseases. Antimicrobial resistance among NTS was more common.

Typhoid fever presenting with gastric ulcer bleeding.

BACKGROUND: Enteric fever is a systemic disease caused by Salmonella enterica serovar Typhi or Salmonella enterica serovar Paratyphi, characterized by high fever and abdominal pain. Most patients with enteric fever improve within a few days after antibiotic treatment. However, some patients do not recover as easily and develop fatal life-threatening complications, including intestinal hemorrhage. Lower gastrointestinal bleeding has been reported in 10% of cases. However, upper gastrointestinal bleeding has rarely been reported in patients with enteric fever. We present a case of gastric ulcer hemorrhage caused by enteric fever. CASE PRESENTATION: A 32-year-old woman, complaining of fever lasting four days and right upper quadrant pain and melena that started one day before admission, consulted our hospital. Abdominal computed tomography revealed mild hepatomegaly and gastroscopy revealed multiple active gastric ulcers with flat black hemorrhagic spots. The melena of the patient stopped on the third day. On the fifth admission day, she developed hematochezia. At that time, Salmonella enterica serovar Typhi was isolated from the blood culture. The antibiotic regimen was switched to ceftriaxone. Her hematochezia spontaneously resolved the following day. Finally, the patient was discharged on the 12th admission day without clinical symptoms. However, her fever recurred one month after discharge, and she was readmitted and Salmonella enterica serovar Typhi was confirmed again via blood culture. She was treated with ceftriaxone for one month, and was discharged without complications. CONCLUSION: Our case showed that although rare, active gastric ulcers can develop in patients with enteric fever. Therefore, upper and lower gastrointestinal bleeding should be suspected in patients with enteric fever, especially showing relapsing bacteremia.

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.

Molecular characterization of the severe falciparum malaria with typhoid co-infection: A case report.

Malaria and typhoid co-infections can be a serious public health issue in tropical countries leading to incorrect diagnosis due to overlapping clinical presentations of malaria and typhoid and hence, causing a delay in implementing the appropriate treatment regimen for these concurrent infections. This study reports a case of six-year-old female child co-infected with severe malaria (Plasmodium falciparum) and typhoid (Salmonella typhi) diagnosed by rapid malaria antigen test (RMAT) and blood culture respectively. Further, analysis of the chloroquine resistance gene Pfcrt for the falciparum demonstrated the presence of K76T mutant allele in pfcrt gene with high IC50 (150nM) for chloroquine (CQ) drug. The present case highlights the significance of timely identification and treatment of co-infections and also provides information about the circulating P. falciparum clinical strains.

Extended-spectrum Beta-lactamases Encoding Genes among Salmonella Enterica serovar Typhi Isolates in Patients with Typhoid Fever from four Academic Medical Centers Lagos, Nigeria.

BACKGROUND: There is scarce information about the occurrence of extended-spectrum ß-lactamases (ESBLs) in Salmonella enterica serovar Typhi (S. Typhi) from patients with typhoid fever. OBJECTIVE: To study the antimicrobial resistance and ESBL encoding genes among S. Typhi isolates in aforesaid patients from Lagos, Nigeria. METHODS: S. Typhi isolates were collected from blood samples of typhoid fever patients from 4 academic medical centers in Lagos, Nigeria. The identification of isolates and their antibiotic susceptibility testing were performed by standard bacteriological techniques and disc diffusion method, respectively. The production of ESBLs was investigated using combination disk test (CDT) and polymerase chain reaction (PCR). RESULTS: A total of 27 S. Typhi isolates was collected. All isolates were susceptible to imipenem and nitrofurantoin. Fifteen (55.6%) isolates were multidrug-resistant (MDR). The CDT test showed 11 (40.7%) ESBL producer isolates. However, the PCR revealed a higher occurrence rate for ESBL producers (66.7%, n = 18/27). The ESBL genes were as follows: blaCTX-M (37.0%, n = 10/27), blaSHV (18.5%, n = 5/27), and blaTEM (44.4%, n = 12/27). All ESBL positive S. Typhi isolates were MDR. CONCLUSIONS: This study showed the emergence of ESBL-harboring S. Typhi in patients with typhoid fever from Nigeria.