zithromax 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

Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention.. We performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I. We identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified.. Drug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice.. PROSPERO CRD42018029432.

Topics: Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Global Health; Humans; Paratyphoid Fever; Prevalence; Salmonella paratyphi A; Salmonella typhi; 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

Review status: Current question - no update intended. Azithromycin treatments are included in the review: Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). (Thaver D, Zaidi AKM, Critchley JA, Azmatullah A, Madni SA, Bhutta ZA. Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD004530. DOI: 10.1002/14651858.CD004530.pub3.)   This latter review is being updated, and will be published in late 2011.Enteric fever (typhoid and paratyphoid fever) is potentially fatal. Infection with drug-resistant strains of the causative organism Salmonella enterica serovar Typhi or Paratyphi increases morbidity and mortality. Azithromycin may have better outcomes in people with uncomplicated forms of the disease.. To compare azithromycin with other antibiotics for treating uncomplicated enteric fever.. In August 2008, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 3), MEDLINE, EMBASE, LILACS, and mRCT. We also searched conference proceedings, reference lists, and contacted researchers and a pharmaceutical company.. Randomized controlled trials comparing azithromycin with other antibiotics for treating children and adults with uncomplicated enteric fever confirmed by cultures of S. Typhi or Paratyphi in blood and/or stool.. Both authors independently extracted data and assessed the risk of bias. Dichotomous data were presented and compared using the odds ratio, and continuous data were reported as arithmetic means with standard deviations and were combined using the mean difference (MD). Both were presented with 95% confidence intervals (CI).. Seven trials involving 773 participants met the inclusion criteria. The trials used adequate methods to generate the allocation sequence and conceal allocation, and were open label. Three trials exclusively included adults, two included children, and two included both adults and children; all were hospital inpatients. One trial evaluated azithromycin against chloramphenicol and did not demonstrate a difference for any outcome (77 participants, 1 trial). When compared with fluoroquinolones in four trials, azithromycin significantly reduced clinical failure (OR 0.48, 95% CI 0.26 to 0.89; 564 participants, 4 trials) and duration of hospital stay (MD -1.04 days, 95% CI -1.73 to -0.34 days; 213 participants, 2 trials); all four trials included people with multiple-drug-resistant or nalidixic acid-resistant strains of S. Typhi or S. Paratyphi. We detected no statistically significant difference in the other outcomes. Compared with ceftriaxone, azithromycin significantly reduced relapse (OR 0.09, 95% CI 0.01 to 0.70; 132 participants, 2 trials) and not other outcome measures. Few adverse events were reported, and most were mild and self limiting.. Azithromycin appears better than fluoroquinolone drugs in populations that included participants with drug-resistant strains. Azithromycin may perform better than ceftriaxone.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Child; Humans; Paratyphoid Fever; Randomized Controlled Trials as Topic; Typhoid Fever

Enteric fever (typhoid and paratyphoid fever) is potentially fatal. Infection with drug-resistant strains of the causative organism Salmonella enterica serovar Typhi or Paratyphi increases morbidity and mortality. Azithromycin may have better outcomes in people with uncomplicated forms of the disease.. To compare azithromycin with other antibiotics for treating uncomplicated enteric fever.. In August 2008, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 3), MEDLINE, EMBASE, LILACS, and mRCT. We also searched conference proceedings, reference lists, and contacted researchers and a pharmaceutical company.. Randomized controlled trials comparing azithromycin with other antibiotics for treating children and adults with uncomplicated enteric fever confirmed by cultures of S. Typhi or Paratyphi in blood and/or stool.. Both authors independently extracted data and assessed the risk of bias. Dichotomous data were presented and compared using the odds ratio, and continuous data were reported as arithmetic means with standard deviations and were combined using the mean difference (MD). Both were presented with 95% confidence intervals (CI).. Seven trials involving 773 participants met the inclusion criteria. The trials used adequate methods to generate the allocation sequence and conceal allocation, and were open label. Three trials exclusively included adults, two included children, and two included both adults and children; all were hospital inpatients. One trial evaluated azithromycin against chloramphenicol and did not demonstrate a difference for any outcome (77 participants, 1 trial). When compared with fluoroquinolones in four trials, azithromycin significantly reduced clinical failure (OR 0.48, 95% CI 0.26 to 0.89; 564 participants, 4 trials) and duration of hospital stay (MD -1.04 days, 95% CI -1.73 to -0.34 days; 213 participants, 2 trials); all four trials included people with multiple-drug-resistant or nalidixic acid-resistant strains of S. Typhi or S. Paratyphi. We detected no statistically significant difference in the other outcomes. Compared with ceftriaxone, azithromycin significantly reduced relapse (OR 0.09, 95% CI 0.01 to 0.70; 132 participants, 2 trials) and not other outcome measures. Few adverse events were reported, and most were mild and self limiting.. Azithromycin appears better than fluoroquinolone drugs in populations that included participants with drug-resistant strains. Azithromycin may perform better than ceftriaxone.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Child; Humans; Paratyphoid Fever; Randomized Controlled Trials as Topic; Typhoid Fever

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.. 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).. 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.. 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.. ClinicalTrials.gov (NCT02324751 and NCT02192008).

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Ciprofloxacin; Female; Humans; Male; Middle Aged; Paratyphoid Fever; Treatment Outcome; Typhoid Fever; United Kingdom; Young Adult

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

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

Topics: Anti-Bacterial Agents; Azithromycin; Dengue; Diagnosis, Differential; Doxycycline; Drug Resistance, Bacterial; Endemic Diseases; Humans; Malaria; Paratyphoid Fever; Polysaccharides, Bacterial; Salmonella paratyphi A; Salmonella typhi; Travel-Related Illness; Typhoid Fever; Typhoid-Paratyphoid Vaccines

Topics: Azithromycin; Humans; Paratyphoid Fever; 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

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

In Japan azithromycin (AZM) has been used to treat enteric fever caused by bacteria with resistance to fluoroquinolones; however, the dose, length of treatment and effectiveness of AZM among Japanese patients with enteric fever is unclear. We studied 5 Japanese adults and 1 Japanese child with enteric fever (4 had typhoid fever and 2 had paratyphoid fever) who were treated with oral AZM. The treatment regimens were: 1,000 mg as a single or in 2 divided doses on the 1st day, followed by 500 mg as a single dose daily for 5-6 additional days, or 500 mg as a single dose daily for 10 days. The minimum inhibitory concentrations (MICs) for AZM against 5 causative organisms were investigated with an E-test. Good clinical results were observed in the 5 adult patients but treatment failure was seen in the 1 child patient with typhoid fever; no adverse reactions were found. MICs of AZM were 4 microg/ml against S. Typhi in 2 patients, 8 microg/ml against S. Typhi in 2 patients, and 32 microg/ml against S. Paratyphi A in 1 patient. Our findings indicate AZM may be a reasonable choice for treatment of Japanese adult patients with enteric fever.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Child; Dose-Response Relationship, Drug; Female; Humans; Japan; Male; Microbial Sensitivity Tests; Paratyphoid Fever; Typhoid Fever

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: Anti-Bacterial Agents; Azithromycin; Bacteriological Techniques; Blood; Feces; Humans; Japan; Paratyphoid Fever; Quinolones; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever

The prevalence of Salmonella enterica serotype Paratyphi A infection is increasing, and multidrug resistance is a well-recognized problem. Resistance to fluoroquinolones is common and leads to more frequent use of newer agents like azithromycin. We report the first case of azithromycin resistance and treatment failure in a patient with S. Paratyphi A infection.

Topics: Azithromycin; Drug Resistance, Bacterial; Humans; Male; Middle Aged; Paratyphoid Fever; Salmonella paratyphi A; Treatment Failure

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

The therapeutic alternatives available for use against ciprofloxacin-resistant enteric fever isolates in an endemic area are limited. The antibiotics currently available are the quinolones, third-generation cephalosporins and conventional first-line drugs. In this study, the MICs of various newer drugs were determined for 31 ciprofloxacin-resistant enteric fever isolates (26 Salmonella enterica serovar Typhi and 5 S. enterica serovar Paratyphi A). MICs for ciprofloxacin, ofloxacin, gatifloxacin, levofloxacin, cefotaxime, cefixime, cefepime and azithromycin were determined using Etest strips and the agar dilution method. By Etest, all of the ciprofloxacin-resistant isolates had ciprofloxacin MICs >/=32 mug ml(-1). S. Typhi showed MIC(90) values of 0.50, 0.25 and 0.38 mug ml(-1) for cefixime, cefotaxime and cefepime, respectively. For the cephalosporins, a negligible difference in MIC(90) and MIC(50) values for S. Typhi and S. Paratyphi A was observed. A single isolate of S. Typhi showed a high azithromycin MIC of 64 mug ml(-1). The MIC(90) value for azithromycin in S. Typhi and S. Paratyphi was 24 mug ml(-1). Gatifloxacin demonstrated lower resistance (80.8 %) compared with the other quinolones (92-100 %) in S. Typhi. The rise in MIC levels of these antimicrobials is a matter for serious concern.

Topics: Anti-Bacterial Agents; Azithromycin; Cephalosporins; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Paratyphoid Fever; Quinolones; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever