ro13-9904 and Paratyphoid-Fever

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.. To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials.. 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.. 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.. 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.. 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 2. 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.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Cefixime; Ceftriaxone; Cephalosporins; Child; Chloramphenicol; Ciprofloxacin; Fluoroquinolones; Humans; Monobactams; Ofloxacin; Pakistan; Paratyphoid Fever; Recurrence; Typhoid Fever

Enteric fever, a systemic illness, is caused by Salmonella enterica serovar Typhi or S. enterica serovar Paratyphi A, B or C. The organism is transmitted to humans by the faecal oral route and is endemic in countries with poor sanitation and lacking clean drinking water. There are around 27 million individuals infected with S. Typhi worldwide annually. Enteric fever is a particular problem in travellers to endemic areas, especially those visiting friends and relatives. Currently, the two main vaccines recommended for travellers are the Vi polysaccharide vaccine and the oral Ty21a vaccine. These internationally licensed vaccines are safe and effective against S. Typhi. However, there is currently no commercially available vaccine against S. Paratyphi, which is increasingly reported as a cause of enteric fever. Vaccine uptake and taking appropriate precautions are poor in travellers visiting friends and relatives abroad; this problem requires addressing. Ciprofloxacin is no longer recommended for empirical treatment of infection because of increasing reports of resistance, especially from South Asia. Ceftriaxone and azithromycin are currently the most commonly used antimicrobials for empirical treatment of enteric fever but resistance to both these agents is emerging.

Topics: Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Drug Resistance; Humans; Paratyphoid Fever; Salmonella paratyphi A; Salmonella paratyphi B; Salmonella paratyphi C; Salmonella typhi; Travel; Typhoid Fever; Typhoid-Paratyphoid Vaccines

Enteric fever, caused by Salmonella Typhi and Salmonella Paratyphi A, is the leading cause of bacterial febrile disease in South Asia.. Individual data from 2092 patients with enteric fever randomized into 4 trials in Kathmandu, Nepal, were pooled. All trials compared gatifloxacin with 1 of the following comparator drugs: cefixime, chloramphenicol, ofloxacin, or ceftriaxone. Treatment outcomes were evaluated according to antimicrobial if S. Typhi/Paratyphi were isolated from blood. We additionally investigated the impact of changing bacterial antimicrobial susceptibility on outcome.. Overall, 855 (41%) patients had either S. Typhi (n = 581, 28%) or S. Paratyphi A (n = 274, 13%) cultured from blood. There were 139 (6.6%) treatment failures with 1 death. Except for the last trial with ceftriaxone, the fluoroquinolone gatifloxacin was associated with equivalent or better fever clearance times and lower treatment failure rates in comparison to all other antimicrobials. However, we additionally found that the minimum inhibitory concentrations (MICs) against fluoroquinolones have risen significantly since 2005 and were associated with increasing fever clearance times. Notably, all organisms were susceptible to ceftriaxone throughout the study period (2005-2014), and the MICs against azithromycin declined, confirming the utility of these alternative drugs for enteric fever treatment.. The World Health Organization and local government health ministries in South Asia still recommend fluoroquinolones for enteric fever. This policy should change based on the evidence provided here. Rapid diagnostics are urgently required given the large numbers of suspected enteric fever patients with a negative culture.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Child; Drug Resistance, Multiple, Bacterial; Female; Fluoroquinolones; Gatifloxacin; Humans; Male; Microbial Sensitivity Tests; Nepal; Ofloxacin; Paratyphoid Fever; Salmonella paratyphi A; Salmonella typhi; Treatment Failure; Treatment Outcome; Typhoid Fever; Young Adult

Fifty-nine adult Filipino patients suffering from typhoid fever documented by blood culture were randomly allocated to one of three different drug regimens. Nineteen patients received 3 g ceftriaxone iv once daily for three days. Twenty patients received 4 g ceftriaxone iv once daily for three days and 20 patients received oral chloramphenicol 3 g daily in divided doses for two days followed by 2 g daily for 12 days. Eighteen patients were cured (95%) with 3 g of ceftriaxone for three days. All patients receiving 4 g ceftriaxone per day for three days or chloramphenicol for 14 days were cured. In the ceftriaxone groups two patients developed typhoid fever 30 and 45 days respectively after completion of treatment and one further patient had evidence of reinfection. Three patients relapsed within 15 to 17 days in the chloramphenicol group. Fever subsided in most patients between six and eight days, with three patients having a prolonged and moderate fever for 11 days in the ceftriaxone groups. This study suggests that a short treatment of three days of typhoid fever with ceftriaxone (3 or 4 g once daily) is adequate and not hazardous as far as relapses are concerned.

Topics: Adolescent; Adult; Ceftriaxone; Chloramphenicol; Female; Humans; Male; Middle Aged; Paratyphoid Fever; Recurrence; Typhoid Fever

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.. 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.. 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.

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Drug Resistance, Bacterial; Female; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Pakistan; Paratyphoid Fever; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever

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.. 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.. 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.. 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.

Topics: Anti-Bacterial Agents; Azithromycin; Bangladesh; Ceftriaxone; Child; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Paratyphoid Fever; Salmonella paratyphi A; Salmonella typhi; 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.

Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Confusion; Humans; Hypotension; Male; Meningism; Pancytopenia; Paratyphoid Fever; Pneumonia; Salmonella typhi; Typhoid Fever

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.. 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.. 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.

Topics: Aged; Amino Acid Substitution; Anti-Bacterial Agents; Azithromycin; Cefotaxime; Ceftriaxone; Ciprofloxacin; DNA Gyrase; Drug Resistance, Bacterial; High-Throughput Nucleotide Sequencing; Humans; Male; Microbial Sensitivity Tests; Paratyphoid Fever; Salmonella paratyphi A; Treatment Failure

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bacteremia; Ceftriaxone; Diagnosis, Differential; Diarrhea; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Paratyphoid Fever; Recurrence; Salmonella paratyphi A; Travel Medicine

We report six cases of Salmonella enterica serotype Paratyphi A infections in travelers returning from Myanmar. In 2015, 31 cases of paratyphoid fever were reported in Japan, and 54.8% of those traveled to Myanmar. Among them, six patients presented to our hospital. They had traveled to Myanmar from July 2014 to August 2015 for business purposes. All six isolates were phage type 1, and they were resistant to nalidixic acid.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Myanmar; Paratyphoid Fever; Salmonella paratyphi A; Travel

In Asia, Salmonella Paratyphi A is an emerging infection, and travelers are increasingly at risk. During October 2009-November 2009, an outbreak in S. Paratyphi A infection was noted in Israeli travelers returning from Nepal.. An outbreak investigation included a standardized exposure questionnaire admitted to all patients and medical chart abstraction. Isolates were tested for antimicrobial susceptibility and pulsed-field gel electrophoresis (PFGE).. During 1 October 2009-30 November 2009, 37 Israeli travelers returning from Nepal were diagnosed with S. Paratyphi A bacteremia. All 37 case isolates had an identical pattern on PFGE, and all were nalidixic acid resistant. Only 1 food venue was frequented by all the outbreak cases, with the largest number of exposures occurring around the Jewish New Year. All patients recovered without complications. Time to defervescence in 17 patients treated with ceftriaxone and azithromycin combination was 3.2 days (± 1.7), whereas in 13 cases treated with ceftriaxone monotherapy, the time to defervescence was 6.6 days (± 1.8; P < .001).. A point-source, "Paratyphoid Mary"-like outbreak was identified among Israeli travelers to Nepal. Combination Ceftriaxone-Azithromycin therapy may provide a therapeutic advantage over monotherapy, and merits further clinical trials.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Disease Outbreaks; Drug Therapy, Combination; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Israel; Male; Microbial Sensitivity Tests; Molecular Typing; Nepal; Paratyphoid Fever; Salmonella paratyphi A; Surveys and Questionnaires; Travel; Young Adult

We report here a case of recurrent paratyphoid fever A with hepatitis A co-infection in a patient with chronic hepatitis B. A 26-year-old male patient, who was a hepatitis B virus carrier, was co-infected with Salmonella enterica serovar Paratyphi A and hepatitis A virus. The recurrence of the paratyphoid fever may be ascribed to the coexistence of hepatitis B, a course of ceftriaxone plus levofloxacin that was too short and the insensitivity of paratyphoid fever A to levofloxacin. We find that an adequate course and dose of ceftriaxone is a better strategy for treating paratyphoid fever. Furthermore, the co-infection of paratyphoid fever with hepatitis A may stimulate cellular immunity and break immunotolerance. Thus, the administration of the anti-viral agent entecavir may greatly improve the prognosis of this patient with chronic hepatitis B, and the episodes of paratyphoid fever and hepatitis A infection prompt the use of timely antiviral therapy.

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Coinfection; Drug Resistance, Bacterial; Hepatitis A; Hepatitis A virus; Hepatitis B, Chronic; Humans; Levofloxacin; Male; Paratyphoid Fever; Recurrence; Salmonella paratyphi A

Limited information is available regarding the clinical efficacy of azithromycin for the treatment of enteric fever due to fluoroquinolone-resistant Salmonella Typhi and Salmonella Paratyphi among travelers returning to their home countries.. We report a case of a 52-year-old Japanese man who returned from India, who developed a fever of 39°C with no accompanying symptoms 10 days after returning to Japan from a 1-month business trip to Delhi, India. His blood culture results were positive for Salmonella Paratyphi A. He was treated with 14 days of ceftriaxone, after which he remained afebrile for 18 days before his body temperature again rose to 39°C with no apparent symptoms. He was then empirically given 500 mg of azithromycin, but experienced clinical and microbiological failure of azithromycin treatment for enteric fever due to Salmonella Paratyphi A. However, the minimum inhibitory concentration (MIC) of azithromycin was not elevated (8 mg/L). He was again given ceftriaxone for 14 days with no signs of recurrence during the follow-up.. There are limited data available for the treatment of enteric fever using azithromycin in travelers from developed countries who are not immune to the disease, and thus, careful follow-up is necessary. In our case, the low azithromycin dose might have contributed the treatment failure. Additional clinical data are needed to determine the rate of success, MIC, and contributing factors for success and/or failure of azithromycin treatment for both Salmonella Typhi and Salmonella Paratyphi infections.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteremia; Ceftriaxone; Humans; India; Japan; Male; Middle Aged; Paratyphoid Fever; Salmonella paratyphi A; Travel; Treatment Failure

We report a case of recurrent, multifocal Salmonella enterica serotype Paratyphi A breast abscesses, resistant to ciprofloxacin, which relapsed despite surgery, aspiration and multiple courses of antibiotics, including co-trimoxazole and azithromycin. The patient was cured after a prolonged course of intravenous ceftriaxone.

Topics: Abscess; Administration, Oral; Adult; Anti-Bacterial Agents; Azithromycin; Breast Diseases; Ceftriaxone; Ciprofloxacin; Drug Resistance, Bacterial; Female; Humans; Infusions, Intravenous; Paratyphoid Fever; Recurrence; Salmonella paratyphi A; Suction; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Endocarditis; Humans; Male; Paratyphoid Fever; Salmonella paratyphi A

Paratyphoid fever is an acute infection caused by Salmonella paratyphi A, B or C. The disease is transmitted from person to person by fecal-oral way. Typical for typhoid fever are splenomegaly, bradycardia, fever, constipation or mild diarrhoea oftten associated with abdominal tenderness. We present the case of patient who was infected by Salmonella paratyphi C while his travelling in Asia.

Topics: Adult; Amoxicillin; Ceftriaxone; Ciprofloxacin; Drug Combinations; Drug Therapy, Combination; Humans; Male; Paratyphoid Fever; Salmonella paratyphi A; Sulfamethizole; Travel; Trimethoprim

A case of Salmonella paratyphi A infection was diagnosed late in a patient treated for febrile pneumonia after his returning from India. This case was remarkable in two aspects: first, it illustrated the reemergence of S.paratyphi A infections in people having traveled to India, with increasing fluoroquinolone resistance, and second the difficulty of diagnosing this disease, since the patient was initially treated for pneumonia and flu-like syndrome. Salmonella typhi or paratyphi infections should be evoked in case of persistent fever in patients having traveled to endemic areas, even if digestive signs are absent. Furthermore, choosing an empiric antibiotic treatment with fluoroquinolones could lead to treatment failure if the patient traveled in a country where fluoroquinolone resistance is high, as in Asia and especially in India.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Bangladesh; Ceftriaxone; Drug Resistance, Multiple, Bacterial; Endemic Diseases; Fluoroquinolones; Humans; India; Ketolides; Male; Paratyphoid Fever; Pneumonia, Bacterial; Salmonella paratyphi A; Travel

Topics: Adult; Azithromycin; Ceftriaxone; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Humans; India; Male; Microbial Sensitivity Tests; Paratyphoid Fever; Recurrence; Salmonella paratyphi A; Travel

Topics: Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Ciprofloxacin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Paratyphoid Fever; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever; United Kingdom

This report describes a case of ciprofloxacin treatment failure in a patient with enteric fever caused by Salmonella enterica serotype Paratyphi A. The organism was isolated from a blood culture from a patient who was treated with oral ciprofloxacin (500 mg every 12 h) for 13 days. The organism showed reduced susceptibility to ciprofloxacin (MIC 0.75 microg ml-1) and was resistant to nalidixic acid. The patient was then placed on intravenous ceftriaxone (1 g every 12 h) and responded within 3 days. The patient was discharged after 9 days on ceftriaxone with no relapse on follow-up. This case adds to the increasing incidence of treatment failures with ciprofloxacin in typhoid fever caused by typhoid salmonellae with reduced susceptibility to ciprofloxacin. It also highlights the inadequacy of current laboratory methods for fluoroquinolone susceptibility testing in adequately predicting in vivo activity of ciprofloxacin against typhoid salmonellae and supports calls for new guidelines for fluoroquinolone susceptibility testing of these organisms.

Topics: Adolescent; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Ciprofloxacin; Drug Resistance, Bacterial; Female; Humans; Microbial Sensitivity Tests; Nalidixic Acid; Paratyphoid Fever; Salmonella paratyphi A; Treatment Failure

A 31-year-old Nepali man was admitted to the intensive care unit with a 3-day history of fever associated with four-limb weakness, followed by difficulty in swallowing. The patient came from Nepal 20 days before admission. On examination the patient was conscious and appeared ill, with a temperature of 38.0 degrees C. His four limbs were weak (grades 2-3) and he was areflexic with mild facial weakness and absent gag reflex. Brain CT and MRI were normal. Cerebrospinal fluid analysis showed high protein. A neurophysiologic study showed data consistent with motor axonal polyradiculopathy. The patient was diagnosed with Guillain-Barré syndrome (GBS), and intravenous immunoglobulin (0.4 g/kg day for 5 days) was administered. On the third hospitalization day, the patient developed respiratory failure for which he was intubated and mechanically ventilated. On the same day, blood samples grew Salmonella paratyphi A (S. paratyphi A), which was sensitive to ceftriaxone. The patient was then diagnosed with GBS associated with S. paratyphi A, and treated with ceftriaxon (2 g administered intravenously, daily for 10 days). On the eleventh hospitalization day the patient was weaned from ventilator and extubated successfully. Subsequently, the patient improved, his fever subsided, and he regained muscle power satisfactorily.

Topics: Adult; Ceftriaxone; Electrodiagnosis; Guillain-Barre Syndrome; Humans; Immunization, Passive; Male; Neurologic Examination; Paratyphoid Fever; Salmonella paratyphi A

We report a case of fulminant hepatic failure associated with Salmonella paratyphi A infection, in a 29-year-old patient who was admitted to the intensive care unit (ICU) with fever of two days, headache and vomiting followed by behavioural changes and disorientation. On examination, the patient appeared acutely ill, agitated, confused, and deeply jaundiced. Temperature 38.5 degrees of C, pulse 92/min, blood pressure 130/89 mmHg. Both samples of blood grew S. paratyphi A, which was sensitive to ceftriaxone and ciprofloxacin. Ceftriaxon was administered with high-dose dexamethasone. Two weeks after treatment with ceftriaxon, the patient was discharged in satisfactory condition.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Ceftriaxone; Ciprofloxacin; Dexamethasone; Glucocorticoids; Humans; Liver Failure, Acute; Male; Paratyphoid Fever; Salmonella paratyphi A

A case of pyrexia from abroad presenting to the emergency department is discussed. The causes of such pyrexia are outlined and the investigations are described. We stress that vaccination is not foolproof from acquiring an infection from abroad.

Topics: Adult; Anorexia; Anti-Bacterial Agents; Bradycardia; Ceftriaxone; Communicable Disease Control; Contact Tracing; Disease Notification; Emergency Treatment; England; Female; Fever of Unknown Origin; Humans; Incidence; Microbial Sensitivity Tests; Pakistan; Paratyphoid Fever; Risk Factors; Salmonella paratyphi A; Travel; Vaccination; Vomiting

Topics: Adult; Animals; Blastocystis Infections; Ceftriaxone; Ciprofloxacin; Drug Resistance, Microbial; Drug Resistance, Multiple; Humans; Male; Metronidazole; Paratyphoid Fever; Salmonella paratyphi A; Species Specificity; Travel; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Amoxicillin; Ceftriaxone; Child; Diarrhea; Drug Therapy, Combination; Humans; Male; Paratyphoid Fever; Salmonella paratyphi A

Pharmacokinetic properties of ceftriaxone, such as sustained tissue drug levels over 24 hours after a single injection; good penetration of the antibiotic into cells; significant biliary excretion as active unchanged compound and high potency against S. typhi, should make it possible to significantly shorten the treatment of typhoid fever. To test this hypothesis a pilot, open study was initiated. 17 adult patients suffering from uncomplicated typhoid or paratyphoid fever, documented by blood culture, were treated with 4g ceftriaxone once daily for three days (4 patients) or two days (15 patients). The cure rate of 17 assessable patients was 94.2% (one failure). One possible relapse was observed two months after treatment. It is to be noted that no patient in the study suffered from a severe form of the disease.

Topics: Adolescent; Adult; Aged; Ceftriaxone; Female; Humans; Kinetics; Male; Middle Aged; Paratyphoid Fever; Salmonella paratyphi A; Salmonella paratyphi B; Typhoid Fever