zithromax and Typhoid-Fever

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.. 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.. Continued advocacy is needed to address the ongoing challenge of typhoid fever to improve child health and tackle the rising challenge of antimicrobial resistance.

Topics: Azithromycin; Child; Humans; Salmonella typhi; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccines, Conjugate

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 is a systemic infection caused by Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi A, B, and C. There is an emergence of Typhoid fever caused by extensively drug-resistant Salmonella Typhi strain called XDR S.Typhi. This strain is resistant to recommended first-line antibiotics and cephalosporins. WHO estimated 5274 cases of XDR S.Typhi in Karachi from November 2016 to December 2019. This study aims to determine clinical course, complications and response to treatment of XDR S.Typhi among the pediatric population coming to Indus Hospital.. We reviewed the records of children who had culture-proven XDR S.Typhi infection at Indus Hospital from July 2017 to December 2018. A pre-designed data abstraction form was used to record information about seasonality, demographic details, clinical features and course, treatment, complications and outcomes of the cases of XDR S.Typhi.. The records of 680 children were reviewed. The median (IQR) age of the patients was 5 (2-8) years. More than half (n = 391, 57.5%) of the patients were males. The outcomes were recorded in 270 (40%) patients. Out of these, 234 (86.7%) children got cured within 14 days, while a delayed response to antibiotics was noted in 32 (11.9%) children. Seventy-six (29%) children recovered on a combination of meropenem and azithromycin, 72 (27%) got cured on azithromycin alone, while 15 (6%) responded to meropenem alone.. Our review indicated that children under 5 years of age were affected more with XDR S.Typhi. Azithromycin alone or in combination with meropenem were effective antibiotics for treating XDR S.Typhi in children.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Female; Humans; Male; Pharmaceutical Preparations; Salmonella typhi; 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

Recent attempts at mapping Typhoid epidemiology have revealed an enormous burden of disease in developing countries. Countries hitherto believed to have a low incidence, such as the African subcontinent, on accurate mapping were found to have a significant burden of disease. Drug resistance, because of rampant overuse of antibiotics, has driven selection pressure to extensively drug-resistant typhoid becoming a reality in the Indian subcontinent. With widespread travel, importation of this variety of typhoid to nonendemic countries is likely to lead to outbreaks in a nonimmune population.. A strain of extensively drug-resistant Salmonella Typhi isolated in Pakistan in 2016 has been responsible for multiple outbreaks in Pakistan and multiple travel-related cases all over the world in United States, UK, and Australia. This novel strain belongs to H58 lineage harbouring a plasmid encoding additional resistance elements like blaCTX-M-15 and a qnrS fluoroquinolone resistance gene. This resistance pattern has rendered many therapeutic options like Ceftriaxone and Fluoroquinolones clinically inactive impacting care in endemic and traveller populations alike.. Changing epidemiology and drug resistance in typhoid indicates that it may be prudent to vaccinate nonimmune travellers travelling to typhoid endemic areas, especially the Indian subcontinent.

Topics: Anti-Bacterial Agents; Asia; Azithromycin; Ceftriaxone; Communicable Diseases, Imported; Drug Resistance, Multiple, Bacterial; Fluoroquinolones; Genes, Bacterial; Humans; Pakistan; Public Health; Salmonella typhi; Travel; Typhoid Fever

The burden of diarrheal diseases is very high, accounting for 1.7 to 5 billion cases per year worldwide. Typhoid fever (TF) and cholera are potentially life-threatening infectious diseases, and are mainly transmitted through the consumption of food, drink or water that have been contaminated by the feces or urine of subjects excreting the pathogen. TF is mainly caused by Salmonella typhi, whereas cholera is caused by intestinal infection by the toxin-producing bacterium Vibrio cholerae. These diseases typically affect low- and middle-income countries where housing is overcrowded and water and sanitation are poor, or where conflicts or natural disasters have led to the collapse of the water, sanitation and healthcare systems. Mortality is higher in children under 5 years of age. Regarding their geographical distribution, TF has a high incidence in sub-Saharan Africa, India and south-east Asia, while cholera has a high incidence in a few African countries, particularly in the Horn of Africa and the Arabian Peninsula. In the fight against these diseases, preventive measures are fundamental. With modern air travel, transmissible diseases can spread across continents and oceans in a few days, constituting a threat to global public health. Nowadays, people travel for many reasons, such as tourism and business. Several surveys have shown that a high proportion of travelers lack adequate information on safety issues, such as timely vaccination and prophylactic medications. The main objective of this overview is to provide information to help European travelers to stay healthy while abroad, and thus also to reduce the potential importation of these diseases and their consequent implications for public health and society. The preventive measures to be implemented in the case of travel to countries where these diseases are still endemic are well known: the adoption of safe practices and vaccinations. It is important to stress that an effective preventive strategy should be based both on vaccinations and on hygiene travel guidelines. Furthermore, the emergence of multidrug-resistant strains is becoming a serious problem in the clinical treatment of these diseases. For this reason, vaccination is the main solution.

Topics: Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Azithromycin; Bicarbonates; Cephalosporins; Cholera; Cholera Vaccines; Ciprofloxacin; Drinking Water; Drug Resistance, Bacterial; Endemic Diseases; Epidemics; Europe; Global Burden of Disease; Glucose; Humans; Idarubicin; Potassium Chloride; Prednisone; Ringer's Lactate; Sanitation; Sodium Chloride; Travel; Travel Medicine; Travel-Related Illness; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vidarabine

Typhoid fever is an important cause of morbidity and mortality in the developing world, particularly in children, but is infrequently observed in the developed world and can occur in patients without a significant travel history. Rhabdomyolysis as a complication has rarely been reported, and never in a child. A child with Salmonella enterica serovar Typhi septicemia, complicated by rhabdomyolysis, encephalopathy and pancreatitis is described and all 15 reported cases to date are summarized.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Female; Humans; Rhabdomyolysis; 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

Emergence of multidrug resistance and decreased ciprofloxacin susceptibility (DCS) in Salmonella enterica serovar Typhi in South Asia have rendered older drugs, including ampicillin, chloramphenicol, trimethoprim-sulphamethoxazole, ciprofloxacin, and ofloxacin, ineffective or suboptimal for typhoid fever. Ideally, treatment should be safe and available for adults and children in shortened courses of 5 days, cause defervescence within 1 week, render blood and stool cultures sterile, and prevent relapse. In this review of 20 prospective clinical trials that enrolled more than 1600 culture-proven patients, azithromycin meets these criteria better than other drugs. Among fluoroquinolones, which are more effective than cephalosporins, gatifloxacin appears to be more effective than ciprofloxacin and ofloxacin for patients infected with bacteria showing DCS. Ceftriaxone continues to be useful as a back-up choice, and chloramphenicol, despite its toxicity for bone marrow and history of plasmid-mediated resistance, is making a comeback in developing countries that show their bacteria to be susceptible to it.

Topics: Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Clinical Trials as Topic; Drug Resistance, Bacterial; Fluoroquinolones; Gatifloxacin; Humans; Salmonella typhi; Treatment Outcome; Typhoid Fever

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

Multidrug-resistant (MDR) Salmonella Typhi (resistant to chloramphenicol, ampicillin, and trimethoprim-sulphamethoxazole) and isolates with reduced susceptibility to fluoroquinolones (indicated by resistance to nalidixic acid, NaR) have caused epidemics and become endemic in southern Viet Nam during the 1990s. Short courses of ofloxacin have proved acceptable for treating MDR/NaS isolates of S. Typhi (ofloxacin MIC90 = 0.06 mg/l) causing uncomplicated disease. Ofloxacin (10-15 mg/kg/d) given for 2, 3, or 5 d cured >90% of patients with an average fever clearance time (FCT) of 4 d. Less than 3% of patients relapsed or had a positive post-treatment stool culture. In contrast, the response of NaR isolates (ofloxacin MIC90 = 0.5 mg/l) to such regimens is poor. For example, ofloxacin (20 mg/kg/d) given for 7 d cured only 75% of patients, with an FCT of 7 d, and 19% of patients had positive post-treatment faecal cultures. Currently available alternatives for NaR infections include ceftriaxone, cefixime, and azithromycin. These antimicrobials are reasonably effective but expensive. New, effective, and affordable regimens are needed to treat these NaR infections. Short courses of the new generation fluoroquinolones or combinations of the available antimicrobials are possible options.

Topics: Adolescent; Adult; Age Distribution; Aged; Anti-Infective Agents; Azithromycin; Cephalosporins; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Fluoroquinolones; Humans; Infant; Infant, Newborn; Middle Aged; Nalidixic Acid; Treatment Outcome; Typhoid Fever; Vietnam

Azithromycin and trimethoprim-sulfamethoxazole (SXT) are widely used to treat undifferentiated febrile illness (UFI). We hypothesized that azithromycin is superior to SXT for UFI treatment, but the drugs are noninferior to each other for culture-confirmed enteric fever treatment.. We conducted a double-blind, randomized, placebo-controlled trial of azithromycin (20 mg/kg/day) or SXT (trimethoprim 10 mg/kg/day plus sulfamethoxazole 50 mg/kg/day) orally for 7 days for UFI treatment in Nepal. We enrolled patients >2 years and <65 years of age presenting to 2 Kathmandu hospitals with temperature ≥38.0°C for ≥4 days without localizing signs. The primary endpoint was fever clearance time (FCT); secondary endpoints were treatment failure and adverse events.. From June 2016 to May 2019, we randomized 326 participants (163 in each arm); 87 (26.7%) had blood culture-confirmed enteric fever. In all participants, the median FCT was 2.7 days (95% confidence interval [CI], 2.6-3.3 days) in the SXT arm and 2.1 days (95% CI, 1.6-3.2 days) in the azithromycin arm (hazard ratio [HR], 1.25 [95% CI, .99-1.58]; P = .059). The HR of treatment failures by 28 days between azithromycin and SXT was 0.62 (95% CI, .37-1.05; P = .073). Planned subgroup analysis showed that azithromycin resulted in faster FCT in those with sterile blood cultures and fewer relapses in culture-confirmed enteric fever. Nausea, vomiting, constipation, and headache were more common in the SXT arm.. Despite similar FCT and treatment failure in the 2 arms, significantly fewer complications and relapses make azithromycin a better choice for empirical treatment of UFI in Nepal.. NCT02773407.

Topics: Anti-Bacterial Agents; Azithromycin; Double-Blind Method; Humans; Nepal; Trimethoprim, Sulfamethoxazole Drug Combination; Typhoid Fever

Multi-drug resistant Typhoid fever (resistant to previously used chloramphenicol, ampicillin, amoxicillin, and trimethoprim-sulfamethoxazole) has been commonly described in the South East Asia region and a recent report suggests that the salmonella typhi have reduced response to fluoroquinolones (nalidixic acid-resistant). The optimum treatment protocol for this type of serovar has not been established. This study compared different antimicrobial regimens for the treatment of uncomplicated typhoid fever which was conducted in the medicine ward of Dhaka Medical College Hospital (DMCH) and outdoor setting in private practice in Dhaka metropolitan city, Mymensingh and Sylhet town from January 2017 to December 2017. Bangladeshi adults with uncomplicated typhoid fever were included in this an open-label randomized controlled trial. Ciprofloxacin (20mg/kg of body weight/day for 14 days), azithromycin (20mg/kg/day for 14 days), and Cefixime (16mg/kg/day for 14 days) were compared. Of the 81 enrolled patients, 62 were eligible for analysis (61 S. enterica serovar Typhi, 1 Salmonella enterica serovar paratyphi A). Of the S enterica serovar Typhi isolates, 88.7% (55/62) were MDR and 93.5% (58/62) were nalidixic acid resistant (NAR). The clinical cure rate was 62% (13/21) with ciprofloxacin, 71% (15/21) with Cefixime, and 85% (17/20) with azithromycin (p=0.053). The mean (95% confidence interval [CI]) fever clearance time for patients treated with azithromycin (5.8 days [5.1 to 6.5 days]) was shorter than that for patients treated with cefixime (7.1 days [6.2 to 8.1 days]) and ciprofloxacin (8.2 days [7.2 to 9.2 days]) (p<0.001). All three antibiotics were well tolerated. A 7-day course of azithromycin can be successfully used in uncomplicated typhoid fever due to isolates of MDR S enterica serovar Typhi.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bangladesh; Cefixime; Ciprofloxacin; Humans; Microbial Sensitivity Tests; Salmonella typhi; 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

Emerging resistance to antibiotics renders therapy of Typhoid Fever (TF) increasingly challenging. The current single-drug regimens exhibit prolonged fever clearance time (FCT), imposing a great burden on both patients and health systems, and potentially contributing to the development of antibiotic resistance and the chronic carriage of the pathogens. The aim of our study was to assess the efficacy of combining third-generation cephalosporin therapy with azithromycin on the outcomes of TF in patients living in an endemic region.. An open-label, comparative trial was conducted at Dhulikhel Hospital, Nepal, between October 2012 and October 2014. Only culture-confirmed TF cases were eligible. Patients were alternately allocated to one of four study arms: hospitalized patients received either intravenous ceftriaxone or a combination of ceftriaxone and oral azithromycin, while outpatients received either oral azithromycin or a combination of oral azithromycin and cefexime. The primary outcome evaluated was FCT and the secondary outcomes included duration of bacteremia.. 105 blood culture-confirmed patients, of whom 51 were treated as outpatients, were eligible for the study. Of the 88 patients who met the inclusion criteria for FCT analysis 41 patients received a single-agent regimen, while 47 patients received a combined regimen. Results showed that FCT was significantly shorter for the latter (95 versus 88 hours, respectively, p = 0·004), and this effect was exhibited in both the hospitalized and the outpatient sub-groups. Repeat blood cultures, drawn on day 3, were positive for 8/47 (17%) patients after monotherapy, versus 2/51 (4%) after combination therapy (p = 0·045). No severe complications or fatalities occurred in any of the groups.. Combined therapy of third-generation cephalosporins and azithromycin for TF may surpass monotherapy in terms of FCT and time to elimination of bacteremia.. Trial registration number: NCT02224040.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Male; Middle Aged; Nepal; Typhoid Fever; 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

Undifferentiated febrile illness (UFI) includes typhoid and typhus fevers and generally designates fever without any localizing signs. UFI is a great therapeutic challenge in countries like Nepal because of the lack of available point-of-care, rapid diagnostic tests. Often patients are empirically treated as presumed enteric fever. Due to the development of high-level resistance to traditionally used fluoroquinolones against enteric fever, azithromycin is now commonly used to treat enteric fever/UFI. The re-emergence of susceptibility of Salmonella typhi to co-trimoxazole makes it a promising oral treatment for UFIs in general. We present a protocol of a randomized controlled trial of azithromycin versus co-trimoxazole for the treatment of UFI.. This is a parallel-group, double-blind, 1:1, randomized controlled trial of co-trimoxazole versus azithromycin for the treatment of UFI in Nepal. Participants will be patients aged 2 to 65 years, presenting with fever without clear focus for at least 4 days, complying with other study criteria and willing to provide written informed consent. Patients will be randomized either to azithromycin 20 mg/kg/day (maximum 1000 mg/day) in a single daily dose and an identical placebo or co-trimoxazole 60 mg/kg/day (maximum 3000 mg/day) in two divided doses for 7 days. Patients will be followed up with twice-daily telephone calls for 7 days or for at least 48 h after they become afebrile, whichever is later; by home visits on days 2 and 4 of treatment; and by hospital visits on days 7, 14, 28 and 63. The endpoints will be fever clearance time, treatment failure, time to treatment failure, and adverse events. The estimated sample size is 330. The primary analysis population will be all the randomized population and subanalysis will be repeated on patients with blood culture-confirmed enteric fever and culture-negative patients.. Both azithromycin and co-trimoxazole are available in Nepal and are extensively used in the treatment of UFI. Therefore, it is important to know the better orally administered antimicrobial to treat enteric fever and other UFIs especially against the background of fluoroquinolone-resistant enteric fever.. ClinicalTrials.gov, ID: NCT02773407 . Registered on 5 May 2016.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Clinical Protocols; Double-Blind Method; Drug Resistance, Bacterial; Female; Fever; Humans; Male; Middle Aged; Nepal; Research Design; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Typhoid Fever; Typhus, Epidemic Louse-Borne; Young Adult

Azithromycin is an effective treatment for uncomplicated infections with Salmonella enterica serovar Typhi and serovar Paratyphi A (enteric fever), but there are no clinically validated MIC and disk zone size interpretative guidelines. We studied individual patient data from three randomized controlled trials (RCTs) of antimicrobial treatment in enteric fever in Vietnam, with azithromycin used in one treatment arm, to determine the relationship between azithromycin treatment response and the azithromycin MIC of the infecting isolate. We additionally compared the azithromycin MIC and the disk susceptibility zone sizes of 1,640 S. Typhi and S. Paratyphi A clinical isolates collected from seven Asian countries. In the RCTs, 214 patients who were treated with azithromycin at a dose of 10 to 20 mg/ml for 5 to 7 days were analyzed. Treatment was successful in 195 of 214 (91%) patients, with no significant difference in response (cure rate, fever clearance time) with MICs ranging from 4 to 16 μg/ml. The proportion of Asian enteric fever isolates with an MIC of ≤ 16 μg/ml was 1,452/1,460 (99.5%; 95% confidence interval [CI], 98.9 to 99.7) for S. Typhi and 207/240 (86.3%; 95% CI, 81.2 to 90.3) (P < 0.001) for S. Paratyphi A. A zone size of ≥ 13 mm to a 5-μg azithromycin disk identified S. Typhi isolates with an MIC of ≤ 16 μg/ml with a sensitivity of 99.7%. An azithromycin MIC of ≤ 16 μg/ml or disk inhibition zone size of ≥ 13 mm enabled the detection of susceptible S. Typhi isolates that respond to azithromycin treatment. Further work is needed to define the response to treatment in S. Typhi isolates with an azithromycin MIC of >16 μg/ml and to determine MIC and disk breakpoints for S. Paratyphi A.

Topics: Adolescent; Azithromycin; Child; Female; Humans; Male; Microbial Sensitivity Tests; Salmonella enterica; Serogroup; Typhoid Fever; Young Adult

An intervention study was carried out in the department of paediatrics of Mymensingh Medical College Hospital, Mymensingh to compare the clinical efficacy of Azithromycin in the treatment of childhood typhoid fever with that of cefixime for a period of one year from January 2011 to December 2011. A total of 60 cases of typhoid fever were enrolled in to a randomized clinical trial and was divided into two groups. The inclusion criteria of the cases were: Documented fever for more than 4 days plus two or more of the following clinical features: toxic physical appearance, intestinal complaints, coated tongue, ceacal gurgling, hepatomegaly and splenomegaly, diarrhoea and constipation plus positive Widal test and/or blood culture positivity. Patients who had complication like GIT heamorrhage; intestinal perforaion and/or shock were excluded from the study. Data were collected in a structured questionnaire. Azithromycin was given at a dose of 10mg/kg/day for a period of 07 days Cefixime was given at a dose of 20mg/kg/day in two divided dose for 14 days. The mean time of defervesence was 4.05+1.14 days with azithromycin and 3.41+0.95 with cefixime respectively. The minimum defervesence time was 02 days and maximum defervesence time was 07 days. Clinical cure rate was 87% in azithromycin group and 93% in cefixime group. No serious adverse effect was noted related to azithromycin and cefixime therapy except nausea, vomiting, diarrhoea and jaundice. It was found that azithromycin is almost as effective as cefixime in the treatment of typhoid fever.

Topics: Anti-Bacterial Agents; Azithromycin; Cefixime; Child; Child, Preschool; Female; Humans; Male; Typhoid Fever

An open-labelled, non-comparative study was conducted in 117 children aged 2-12 years to evaluate the efficacy and safety of azithromycin (20mg/ kg/day for 6 days) for the treatment of uncomplicated typhoid fever. Of the patients enrolled based on a clinical definition of typhoid fever, 109 (93.1%) completed the study.Mean (SD) of duration of fever at presentation was 9.1(4.5) days. Clinical cure was seen in 102 (93.5%) subjects, while 7 were withdrawn from the study because of clinical deterioration. Mean day of response was 3.45±1.97. BACTEC blood culture was positive for Salmonella typhi in 17/109 (15.5%) and all achieved bacteriological cure. No serious adverse event was observed. Global well being assessed by the investigator and subjects was good in 95% cases which was done at the end of the treatment. Azithromycin was found to be safe and efficacious for the management of uncomplicated typhoid fever.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bacteremia; Child; Child, Preschool; Female; Humans; Male; Salmonella typhi; Treatment Outcome; Typhoid Fever

Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing.. We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day) versus azithromycin (20 mg/kg/day) as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam.. An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi).. We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94-118 hours for gatifloxacin versus 88-112 hours for azithromycin), (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80-1.26]). Overall treatment failure occurred in 13/145 (9%) patients in the gatifloxacin group and 13/140 (9.3%) patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43-2.0]). 96% (254/263) of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263) were multidrug resistant.. Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the cost of azithromycin in Vietnam.. Controlled-Trials.com ISRCTN67946944.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Child; Fluoroquinolones; Gatifloxacin; Humans; Microbial Sensitivity Tests; Salmonella; Species Specificity; Typhoid Fever

Isolates of Salmonella enterica serovar Typhi that are multidrug resistant (MDR, resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) and have reduced susceptibility to fluoroquinolones (nalidixic acid resistant, Na(r)) are common in Asia. The optimum treatment for infections caused by such isolates is not established. This study compared different antimicrobial regimens for the treatment of MDR/Na(r) typhoid fever. Vietnamese children and adults with uncomplicated typhoid fever were entered into an open randomized controlled trial. Ofloxacin (20 mg/kg of body weight/day for 7 days), azithromycin (10 mg/kg/day for 7 days), and ofloxacin (15 mg/kg/day for 7 days) combined with azithromycin (10 mg/kg/day for the first 3 days) were compared. Of the 241 enrolled patients, 187 were eligible for analysis (186 S. enterica serovar Typhi, 1 Salmonella enterica serovar Paratyphi A). Eighty-seven percent (163/187) of the patients were children; of the S. enterica serovar Typhi isolates, 88% (165/187) were MDR and 93% (173/187) were Na(r). The clinical cure rate was 64% (40/63) with ofloxacin, 76% (47/62) with ofloxacin-azithromycin, and 82% (51/62) with azithromycin (P = 0.053). The mean (95% confidence interval [CI]) fever clearance time for patients treated with azithromycin (5.8 days [5.1 to 6.5 days]) was shorter than that for patients treated with ofloxacin-azithromycin (7.1 days [6.2 to 8.1 days]) and ofloxacin (8.2 days [7.2 to 9.2 days]) (P < 0.001). Positive fecal carriage immediately posttreatment was detected in 19.4% (12/62) of patients treated with ofloxacin, 6.5% (4/62) of those treated with the combination, and 1.6% (1/62) of those treated with azithromycin (P = 0.006). Both antibiotics were well tolerated. Uncomplicated typhoid fever due to isolates of MDR S. enterica serovar Typhi with reduced susceptibility to fluoroquinolones (Na(r)) can be successfully treated with a 7-day course of azithromycin.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Blood Cell Count; Child; Child, Preschool; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Nalidixic Acid; Ofloxacin; Salmonella enterica; Treatment Outcome; Typhoid Fever

An intervention study was carried out in Paediatric wards for a period of one year from January 2003 to December 2003 to determine the efficacy and safety of azithromycin in the treatment of uncomplicated childhood typhoid fever. A total of 50 cases were enrolled in the study. The inclusion criteria of the cases were: documented fever for more than 7 days plus two or more of the following clinical features: toxic appearance, abdominal tenderness, hepatomegaly, splenomegaly, diarrhoea, constipation and coated tongue plus positive Widal test and/or blood culture positivity. Patients who had complication like gastrointestinal tract (GIT) haemorrhage; intestinal perforation and/or shock were excluded from the study. Data were collected in a structured questionnaire. Azithromycin was given at a dose of 10mg/kg /day for a period of 07 days. The time to defervescence was 3.82+/-1.49 days. The minimum defervescence time was 02 days and maximum was 07 days. Clinical cure rate was 94%. No serious adverse effect was noted related to azithromycin therapy except nausea, vomiting, and jaundice. Prior treatment with antibiotics did not affect defervescence time (P>0.05). Pre-treatment febrile period has got positive and linear correlation with clinical response (r = +0.593). It was found that once daily administration of oral azithromycin for seven days in the treatment of uncomplicated typhoid fever was effective and reasonably safe.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Female; Humans; Male; Treatment Outcome; Typhoid Fever

We studied 149 children and adolescents 3-17 years of age with clinical typhoid fever who were treated with either oral azithromycin (20 mg/kg per day; maximum dose, 1000 mg/day) or intravenous ceftriaxone (75 mg/day; maximum dose, 2.5 g/day) daily for 5 days. Blood and stool specimens were obtained for culture before the initiation of therapy and were repeated on days 4 and 8 of treatment. Isolation of Salmonella enterica serovar Typhi or S. enterica serovar Paratyphi from the initial culture was required for inclusion in the final analysis. S. Typhi was isolated from 68 patients, 32 of whom were receiving azithromycin. Cure was achieved in 30 (94%) of 32 patients in the azithromycin group and in 35 (97%) of 36 patients in the ceftriaxone group (P=NS). Mean time to clearance of bacteremia was longer in the azithromycin group than in the ceftriaxone group. No patient who received azithromycin had a relapse, compared with 6 patients who received ceftriaxone. A 5-day course of azithromycin was found to be an effective treatment for uncomplicated typhoid fever in children and adolescents.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Female; Humans; Male; Salmonella Infections; Salmonella paratyphi A; Salmonella typhi; Treatment Outcome; Typhoid Fever

To examine the efficacy and safety of short courses of azithromycin and ofloxacin for treating multidrug-resistant (MDR, i.e., resistant to chloramphenicol, ampicillin, and cotrimoxazole) and nalidixic acid-resistant enteric fever, azithromycin (1 g once daily for 5 days at 20 mg/kg/day) and ofloxacin (200 mg orally twice a day for 5 days at 8 mg/kg/day) were compared in an open randomized study in adults admitted to a hospital with uncomplicated enteric fever. A total of 88 blood culture-confirmed patients were enrolled in the study (86 with Salmonella enterica serovar Typhi and 2 with S. enterica serovar Paratyphi A). Of these, 44 received azithromycin and 44 ofloxacin. A total of 68 of 87 (78%) isolates were MDR serovar Typhi, and 46 of 87 (53%) were nalidixic acid resistant. The MIC(90) (range) of azithromycin was 8 (4 to 16) microgram/ml for the isolates. The MIC(90) (range) of ofloxacin for the nalidixic acid-sensitive isolates was 0.03 (0.015 to 0.06) microgram/ml and for the nalidixic acid-resistant isolates it was 0.5 (0.25 to 1.0) microgram/ml. There was no significant difference in the overall clinical cure rate with ofloxacin and azithromycin (38 of 44 [86.4%] versus 42 of 44 [95.5%]; P = 0.27) or in the patients infected with nalidixic acid-resistant typhoid (17 of 21 [81.0%] versus 24 of 25 [96.0%]; P = 0.16). However, patients with nalidixic acid-resistant typhoid treated with ofloxacin had a longer fever clearance time compared with those treated with azithromycin (174 [60 to 264] versus 135 [72 to 186] h; P = 0.004) and had positive fecal cultures after the end of treatment (7 of 17 [41%] versus 0 of 19 [0%]; P = 0.002). Both antibiotics were well tolerated. A 5-day course of azithromycin was effective for the treatment of enteric fever due to MDR and nalidixic-acid-resistant serovar Typhi, whereas the ofloxacin regimen chosen was less satisfactory for these strains.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Drug Resistance, Multiple; Female; Humans; Male; Nalidixic Acid; Ofloxacin; Outcome Assessment, Health Care; Pilot Projects; Typhoid Fever

A total of 108 children aged 4-17 years were randomized to receive 7 days of azithromycin (10 mg/kg/day; maximum, 500 mg/day) or ceftriaxone (75 mg/kg/day; maximum, 2.5 g/day), to assess the efficacy of the agents for the treatment of uncomplicated typhoid fever. Salmonella typhi was isolated from the initial cultures of blood samples from 64 patients. A total of 31 (91%) of the 34 patients treated with azithromycin and 29 (97%) of the 30 patients treated with ceftriaxone were cured (P>.05). All 64 isolates were susceptible to azithromycin and ceftriaxone. Of the patients treated with ceftriaxone, 4 subsequently had relapse of their infection. No serious side effects occurred in any study subject. Oral azithromycin administered once daily appears to be effective for the treatment of uncomplicated typhoid fever in children. If these results are confirmed, the agent could be a convenient alternative for the treatment of typhoid fever, especially in individuals in developing countries where medical resources are scarce.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Child; Child, Preschool; Female; Humans; Male; Salmonella typhi; Treatment Outcome; Typhoid Fever

To compare clinical and bacteriological efficacies of azithromycin and ciprofloxacin for typhoid fever, 123 adults with fever and signs of uncomplicated typhoid fever were entered into a randomized trial. Cultures of blood were positive for Salmonella typhi in 59 patients and for S. paratyphi A in 3 cases; stool cultures were positive for S. typhi in 11 cases and for S. paratyphi A in 1 case. Multiple-drug resistance (MDR; resistance to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole) was present in isolates of 21 of 64 patients with positive cultures. Of these 64 patients, 36 received 1 g of azithromycin orally once on the first day, followed by 500 mg given orally once daily on the next 6 days; 28 patients received 500 mg of ciprofloxacin orally twice daily for 7 days. Blood cultures were repeated on days 4 and 10 after the start of therapy, and stool cultures were done on days 4, 10, and 28 after the start of therapy. All patients in both groups improved during therapy and were cured. Defervescence (maximum daily temperatures of

Topics: Adolescent; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Ciprofloxacin; Drug Resistance, Microbial; Drug Resistance, Multiple; Female; Humans; Male; Microbial Sensitivity Tests; Typhoid Fever

To compare the clinical and bacteriological efficacies of azithromycin and chloramphenicol for treatment of typhoid fever, 77 bacteriologically evaluable adults, with blood cultures positive for Salmonella typhi or Salmonella paratyphi A susceptible to their assigned drugs, were entered into a randomized open trial at four hospitals in India. Forty-two patients were randomized to receive azithromycin 500 mg p.o. od for 7 days and 35 to receive chloramphenicol 2-3 g p.o. od in four divided doses for 14 days. Thirty-seven patients (88%) in the azithromycin group responded with clinical cure or improvement within 8 days and 30 patients (86%) in the chloramphenicol group responded with cure or improvement. By day 14 after the start of treatment, all patients treated with azithromycin and all except two of the patients treated with chloramphenicol (94%) were cured or improved. Blood cultures repeated on day 8 after start of therapy showed eradication of organisms in 100% of patients in the azithromycin group and 94% of patients in the chloramphenicol group. By day 14 the eradication rate in the chloramphenicol group had increased to 97%. Stool cultures on days 21 and 35 after start of treatment showed no prolonged faecal carriage of Salmonella spp. in either group. These results indicate that azithromycin given once daily for 7 days was effective therapy for typhoid fever in a region endemic with chloramphenicol-resistant S. typhi infection and was equivalent in effectiveness to chloramphenicol given to patients with chloramphenicol-susceptible infections.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Chloramphenicol; Drug Resistance, Microbial; Female; Humans; India; Male; Microbial Sensitivity Tests; Middle Aged; Salmonella paratyphi A; Salmonella typhi; Treatment Outcome; Typhoid Fever

Topics: Adult; Azithromycin; Humans; Treatment Outcome; Typhoid Fever

Extensively drug-resistant (XDR) typhoid fever is a threat to travelers to Pakistan. We describe a multicontinental case series of travel-acquired XDR typhoid fever to demonstrate the global spread of the problem and encourage preventive interventions as well as appropriate empiric antimicrobial use.. Cases were extracted from the GeoSentinel database, microbiologic laboratory records of two large hospitals in Toronto, Canada, and by invitation to TropNet sites. All isolates were confirmed XDR Salmonella enterica serovar Typhi (Salmonella typhi), with resistance to ampicillin, ceftriaxone, ciprofloxacin and trimethoprim-sulfamethoxazole.. Seventeen cases were identified in Canada (10), USA (2), Spain (2), Italy (1), Australia (1) and Norway (1). Patients under 18 years represented 71% (12/17) of cases, and all patients travelled to Pakistan to visit friends or relatives. Only one patient is known to have been vaccinated. Predominant symptoms were fever, abdominal pain, vomiting and diarrhoea. Antimicrobial therapy was started on Day 1 of presentation in 75% (12/16) of patients, and transition to a carbapenem or azithromycin occurred a median of 2 days after blood culture was drawn. Antimicrobial susceptibilities were consistent with the XDR S. typhi phenotype, and whole genome sequencing on three isolates confirmed their belonging to the XDR variant of the H58 clade.. XDR typhoid fever is a particular risk for travelers to Pakistan, and empiric use of a carbapenem or azithromycin should be considered. Pre-travel typhoid vaccination and counseling are necessary and urgent interventions, especially for visiting friends and relatives travelers. Ongoing sentinel surveillance of XDR typhoid fever is needed to understand changing epidemiology.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Carbapenems; Humans; Pakistan; Salmonella typhi; Travel; Typhoid Fever

Whole genome sequences of Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) and Salmonella enterica subspecies enterica serovar Paratyphi A (S. Paratyphi A) from pediatric settings were used to assess the emerging Antimicrobial Resistance (AMR). The high throughput sequences of twenty pediatric clinical isolates of S. Typhi and S. Paratyphi A were retrieved and were screened for prevalent Antimicrobial Resistance Genes (ARGs) and Virulent Factors (VF). The resistance data was compared with the reference strains of S. Typhi and S. Paratyphi A. AMR studies identified sul1, sul2, dfrA7, tem-1, AH(6)-Id and APH(3″)-Ib as common ARGs. VFs were identified to understand the level of pathogenicity. The most prevalent AMR genes in the sequenced genomes were detected in phenotypically azithromycin-resistant S. Typhi. Correlation with the global genomes projected a trend of concurrent resistance to macrolides, β lactams, fluoroquinolones (FQs), tetracyclines, ansamycins, and aminoglycosides. Traces of sulphonamide-resistance were observed indicating the emergence of a currently non-prevalent S. Typhi resistance that could be a future threat. Hence new antibiotic regimen to treat azithromycin-resistant S. Typhi should be formulated by avoiding the risks of aggravating sulphonamide resistance. The identified ARGs in genomes from paediatric isolates will aid future studies to design anti-bacterial compounds against S. Typhi and S. Paratyphi A.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Drug Resistance, Bacterial; Genomics; Humans; Microbial Sensitivity Tests; Salmonella paratyphi A; Salmonella typhi; Sulfanilamide; Typhoid Fever

To determine the antibacterial susceptibility pattern of bacteraemia isolates of Salmonella enterica serovar typhi and paratyphi.. The retrospective descriptive observational study was conducted at the Microbiology section of Dow Diagnostic Research and Reference Laboratory, and comprised blood culture reports from January 1, 2017, to Dec 30, 2020, which were screened for the presence of Salmonella typhi and paratyphi growth The frequency of the isolates and their antibiotic resistance patterns were analysed. Data was analysed using SPSS 20.. Of the 174,190 blood culture samples, 62,709(36%) were positive for bacterial growth. Salmonella were isolated in 8,689(13.8%) samples of which 8,041(92.5%) were Salmonella typhi, 529(6%) were Salmonella paratyphi A and 119(1.3%) were Salmonella paratyphi B. There was a drastic increase in resistance to third-generation cephalosporin in Salmonella typhi from 71(12.8%) in 2017 to 1,420(71%) in 2018, 2,850(74.6%) in 2019 and 1,251(77%) in 2020. All isolates were sensitive to meropenem and azithromycin.. A high number of extensively drug-resistant typhoid cases due to Salmonella typhi were found. All isolates were sensitive to meropenem and azithromycin.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteremia; Drug Resistance, Bacterial; Humans; Meropenem; Microbial Sensitivity Tests; Pakistan; Retrospective Studies; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever

This study aimed to evaluate the minimum inhibitory concentration (MIC) of azithromycin (AZM) in clinical isolates of extensively drug-resistant (XDR) Salmonella Typhi (i.e., resistant to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, fluoroquinolones, and third-generation cephalosporin) using the E-test versus the broth microdilution method (BMD). From January to June 2021, a retrospective cross-sectional study was carried out in Lahore, Pakistan. Antimicrobial susceptibility was performed initially by the Kirby-Bauer disk diffusion method for 150 XDR Salmonella enterica serovar Typhi isolates, and MICs of all the recommended antibiotics were determined by the VITEK 2 (BioMérieux) fully automated system using Clinical Laboratory Standard Institute (CLSI) 2021 guidelines. The E-test method was used to determine AZM MICs. These MICs were compared with the BMD, which is the method recommended by the CLSI but not adopted in routine laboratory reporting. Of 150 isolates, 10 (6.6%) were resistant by disk diffusion. Eight (5.3%) of these had high MICs against AZM by the E-test. Only three isolates (2%) were resistant by E-test, having an MIC of 32 μg/mL. All eight isolates had a high MIC by BMD with different MIC distributions, but only one was resistant, having an MIC of 32 μg/mL by BMD. The sensitivity, specificity, negative predictive value, positive predictive value, and diagnostic accuracy of the E-test method versus BMD were 98.65%,100%, 99.3%, 33.3%, and 98.6%, respectively. Similarly, the concordance rate was 98.6%, negative percent agreement was 100%, and positive percent agreement was 33%. The BMD is the most reliable approach for reporting AZM sensitivity in XDR S. Typhi compared with the E-test and disk diffusion methods. Potentially, AZM resistance in XDR S. Typhi is around the corner. Sensitivity patterns should be reported with MIC values, and if possible, higher values should be screened for the presence of any potential resistance genes. Antibiotic stewardship should be strictly implemented.

Topics: Anti-Bacterial Agents; Azithromycin; Cross-Sectional Studies; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Retrospective Studies; Salmonella typhi; Typhoid Fever

To calculate the frequency of positive blood culture in clinically diagnosed cases of enteric fever and antibiotic sensitivity patterns in culture-positive cases of S.typhi Study Design: Observational Study. Place and Duration of the Study: Department of Paediatrics Medicine, Services Hospital Lahore, from November 15th 2020 to May 15th 2021.. A total of 246 patients, fulfilling the definition of a suspected case of enteric fever were enrolled. Blood cultures were drawn on the spot. Antimicrobial sensitivity for 8 antimicrobial agents-Ampicillin, amoxicillin, chloramphenicol, cefixime, ceftriaxone, cefotaxime, ciprofloxacin, meropenem, and Azithromycin, were performed. A p-value of <0.05 was considered statistically significant.. Blood cultures were positive in 62 (25.2%), patients out of which 34 (54.9%) were females and 28 (45.1%) were males, of which, 58 were S. typhi and 4 were S. Paratyphi A or B. Cefixime was sensitive in 27.4% of patients and intermediate sensitivity was found in 3.2% of cases and 69.4% of cases were resistant, ceftriaxone was sensitive in 38.7% of cases and Azithromycin was sensitive in 96.7% of cases, whereas meropenem showed 100% sensitivity. Chloramphenicol and Ciprofloxacin were resistant in 80.6% and 27.3% of the cases respectively. Among isolates, 32.3% (20) were categorised as sensitive enteric fever; 64.5% (40) as MDR, and 3.2% (2) as XDR enteric fever.. MDR and XDR enteric fever are a major concern. For such cases, Azithromycin remains the best oral antibiotic with a sensitivity of up to 96.7%. Meropenem was sensitive in 100% of cases and was the only antibiotic with no documented resistance in this study.. Enteric fever, Salmonella, Antibiotic sensitivity, Blood culture, MDR, XDR, Azithromycin, Meropenem.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Cefixime; Ceftriaxone; Child; Chloramphenicol; Ciprofloxacin; Drug Resistance, Bacterial; Female; Humans; Male; Meropenem; Microbial Sensitivity Tests; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever

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.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Humans; Salmonella typhi; Sepsis; Serogroup; 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

Azithromycin is an alternative to treat invasive non-typhoidal Salmonella (iNTS) infections. We determined its epidemiological cut-off (ECOFF) and compared azithromycin susceptibility testing methods for iNTS.. We used EUCAST ECOFFinder to determine the minimum inhibitory concentrations (MIC; obtained by broth microdilution) ECOFF and corresponding disk zone diameters of 515 iNTS from blood cultures in Democratic Republic of Congo, Burkina Faso, Rwanda, and Cambodia. Transferable resistance mechanisms were determined by polymerase chain reaction. We compared azithromycin susceptibility testing by semi-automated broth microdilution (customized Sensititre panel; reference), agar dilution, gradient tests (bioMérieux, Liofilchem, HiMedia; read at 80% (MIC80%) and 100% inhibition (MIC100%)), and disk diffusion (Rosco, Oxoid, BD, Liofilchem) for 161 wild- and 198 non-wild-type iNTS.. Azithromycin MIC ECOFF was 16 mg/L corresponding to a 12 mm zone diameter; mphA was detected in 192/197 non-wild- and 0/47 wild-type iNTS. Categorical agreement was excellent (≥98%) for all methods. Essential agreement was very good for agar dilution (>90%) but moderate for gradient tests (MIC80%: 52% to 71% and MIC100%: 72% to 91%). Repeatability was good for all methods/brands. Interreader agreement was high for broth microdilution and agar dilution (all ≤1 twofold dilution difference) and disk diffusion (>96% ≤3 mm difference) but lower for gradient tests (MIC80% & MIC100%: 83% to 94% ≤1 twofold dilution difference).. Azithromycin ECOFF of iNTS was 16 mg/L, i.e. equal to Salmonella Typhi. Disk diffusion is an accurate, precise, and user-friendly alternative for agar dilution and broth microdilution. Reading gradient tests at 100% instead of 80% inhibition improved accuracy and precision.

Topics: Agar; Anti-Bacterial Agents; Azithromycin; Humans; Microbial Sensitivity Tests; Salmonella; Salmonella Infections; Typhoid Fever

The emergence of increasingly antimicrobial-resistant Salmonella enterica serovar Typhi (S Typhi) threatens to undermine effective treatment and control. Understanding where antimicrobial resistance in S Typhi is emerging and spreading is crucial towards formulating effective control strategies.. In this genomic epidemiology study, we sequenced the genomes of 3489 S Typhi strains isolated from prospective enteric fever surveillance studies in Nepal, Bangladesh, Pakistan, and India (between 2014 and 2019), and combined these with a global collection of 4169 S Typhi genome sequences isolated between 1905 and 2018 to investigate the temporal and geographical patterns of emergence and spread of antimicrobial-resistant S Typhi. We performed non-parametric phylodynamic analyses to characterise changes in the effective population size of fluoroquinolone-resistant, extensively drug-resistant (XDR), and azithromycin-resistant S Typhi over time. We inferred timed phylogenies for the major S Typhi sublineages and used ancestral state reconstruction methods to estimate the frequency and timing of international and intercontinental transfers.. Our analysis revealed a declining trend of multidrug resistant typhoid in south Asia, except for Pakistan, where XDR S Typhi emerged in 2016 and rapidly replaced less-resistant strains. Mutations in the quinolone-resistance determining region (QRDR) of S Typhi have independently arisen and propagated on at least 94 occasions, nearly all occurring in south Asia. Strains with multiple QRDR mutations, including triple mutants with high-level fluoroquinolone resistance, have been increasing in frequency and displacing strains with fewer mutations. Strains containing acrB mutations, conferring azithromycin resistance, emerged in Bangladesh around 2013 and effective population size of these strains has been steadily increasing. We found evidence of frequent international (n=138) and intercontinental transfers (n=59) of antimicrobial-resistant S Typhi, followed by local expansion and replacement of drug-susceptible clades.. Independent acquisition of plasmids and homoplastic mutations conferring antimicrobial resistance have occurred repeatedly in multiple lineages of S Typhi, predominantly arising in south Asia before spreading to other regions.. Bill & Melinda Gates Foundation.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Drug Resistance, Bacterial; Fluoroquinolones; Genomics; Humans; Prospective Studies; Quinolones; Salmonella typhi; Typhoid Fever

Enteric fever is predominantly managed as an outpatient condition in endemic settings but there is little evidence to support this approach in non-endemic settings. This study aims to review the outcomes of outpatients treated for enteric fever at the Hospital of Tropical Diseases in London, UK.. We conducted a retrospective analysis of all patients with confirmed enteric fever between August 2009 and September 2020. Demographic, clinical, laboratory and microbiological data were collected and compared between the inpatient and outpatient populations. Outcomes investigated were complicated enteric fever, treatment failure and relapse.. Overall, 93 patients (59% male, median age 31) were identified with blood and/or stool culture confirmed enteric fever and 49 (53%) of these were managed as outpatients. The commonest empirical treatment for outpatients was azithromycin (70%) and for inpatients was ceftriaxone (84%). Outpatients were more likely than inpatients to receive only one antibiotic (57% vs 19%, p < 0.01) and receive a shorter duration of antibiotics (median 7 vs 11 days, p <0.01). There were no cases of complicated disease or relapse in either the inpatient or outpatient groups. There was one treatment failure in the outpatient group. Azithromycin was well-tolerated with no reported side effects.. Our findings suggest that outpatient management of uncomplicated imported enteric fever is safe and effective with the use of oral azithromycin. Careful monitoring of patients is recommended as treatment failure can occur.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Female; Hospitals; Humans; London; Male; Outpatients; Recurrence; Retrospective Studies; Salmonella typhi; Typhoid Fever

To evaluate the antibiotic prescribing practice in pediatric patients for enteric fever, and to assess the need of developing and implementing the Antibiotic Stewardship Program (ASP) for the hospital. A prospective audit was completed in the pediatric ward of tertiary care hospital of Lahore for one year. Blood culture reports were collected from microbiology departed and clinical data were assessed regarding the choice of antibiotics, frequency, dosage and clinical outcome. All the statistics were analyzed using SPSS software and compared with the guidelines. Out of 157 cases hospitalized with suspicion of enteric fever, 137 cultures were positive for salmonella. Monotherapy of ceftriaxone (70%) was prescribed mostly as empirical therapy. About 20% of patients received a combination of antibiotics empirically. Susceptibility reports showed only 7 cases were of non-resistant typhoid, 15 multi-drug resistant and 115 extensively drug-resistant. Nearly 46% of patients were discharged earlier whose empirical therapy was changed either before or promptly after susceptibility reporting. Commonly used definitive antibiotics (32%) were a combination of azithromycin and meropenem. Inappropriate use of antibiotics was noted frequently as compared to the guidelines. However, recommendations themselves need to be reviewed as antibiotic resistance patterns are changing drastically.

Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Azithromycin; Child; Clinical Audit; Humans; Typhoid Fever

Systematic studies to estimate the disease burden of typhoid and paratyphoid in India are limited. Therefore, a multicenter study on the Surveillance of Enteric Fever in India was carried out to estimate the incidence, clinical presentation, and antimicrobial resistance (AMR) trend. The data presented here represent the national burden of AMR in Salmonella Typhi and Salmonella Paratyphi A.. Antimicrobial susceptibility testing was performed for S. Typhi and S. Paratyphi A (n = 2373) isolates collected prospectively during a 2-year period from November 2017 to January 2020.. Of 2373 Salmonella isolates, 2032 (85.6%) were identified as S. Typhi and 341 (14.4%) were S. Paratyphi A. Approximately 2% of S. Typhi were multidrug-resistant (MDR), whereas all 341 (100%) of S. Paratyphi A isolates were sensitive to the first-line antimicrobials. Among 98% of ciprofloxacin nonsusceptible isolates, resistance (minimum inhibitory concentration [MIC] >0.5 µg/mL) was higher in S. Typhi (37%) compared with S. Paratyphi A (20%). Azithromycin susceptibility was 99.9% and 100% with a mean MIC of 4.98 μg/mL for S. Typhi and 7.39 μg/mL for S. Paratyphi A respectively. Ceftriaxone was the only agent that retained 100% susceptibility. Moreover, beta-lactam/beta-lactamase inhibitors showed potent in vitro activity against the study isolates.. Data obtained from this systematic surveillance study confirms the declining trend of MDR Salmonella isolates from India. The higher prevalence of ciprofloxacin nonsusceptibility enforces to limit its use and adhere to the judicious usage of azithromycin and ceftriaxone for enteric fever management.

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

Global travel has led to intermittent importation of multidrug-resistant Salmonella enterica serovar Typhi into industrialized countries. We detected azithromycin-resistant Salmonella Typhi in Singapore, of which 2 isolates were likely locally acquired. Ongoing vigilance and surveillance to minimize the public health risk for this serious pathogen is needed.

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Microbial Sensitivity Tests; Salmonella typhi; Singapore; Typhoid Fever

The emergence and spread of antimicrobial resistance (AMR) pose a major threat to the effective treatment and control of typhoid fever. The ongoing outbreak of extensively drug-resistant Salmonella Typhi (S. Typhi) in Pakistan has left azithromycin as the only remaining broadly efficacious oral antimicrobial for typhoid in South Asia. Ominously, azithromycin-resistant S. Typhi organisms have been subsequently reported in Bangladesh, Pakistan, and Nepal.. Here, we aimed to understand the molecular basis of AMR in 66 S. Typhi organisms isolated in a cross-sectional study performed in a suburb of Chandigarh in Northern India using whole-genome sequencing and phylogenetic analysis.. We identified 7 S. Typhi organisms with the R717Q mutation in the acrB gene that was recently found to confer resistance to azithromycin in Bangladesh. Six out of the seven azithromycin-resistant S. Typhi isolates also exhibited triple mutations in gyrA (S83F and D87N) and parC (S80I) genes and were resistant to ciprofloxacin. These contemporary ciprofloxacin/azithromycin-resistant isolates were phylogenetically distinct from each other and from those reported from Bangladesh, Pakistan, and Nepal.. The independent emergence of azithromycin-resistant typhoid in Northern India reflects an emerging broader problem across South Asia and illustrates the urgent need for the introduction of typhoid conjugate vaccines in the region.

Topics: Anti-Bacterial Agents; Azithromycin; Bangladesh; Cross-Sectional Studies; Drug Resistance, Bacterial; Genotype; Humans; India; Microbial Sensitivity Tests; Nepal; Pakistan; Phylogeny; 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

Enteric fever caused by Salmonella enterica continues to be a major public health problem worldwide. In the last decade, ceftriaxone and azithromycin have become the drugs of choice for treating enteric fever caused by Nalidixic acid resistant Salmonella (NARS) enterica. This has led to reports of drug resistance to both drugs. Since enteric fever is endemic in India, accurate drug susceptibility surveillance is crucial to ensure empiric management of enteric fever is appropriate. The aim of this study is to evaluate the minimum inhibitory concentration (MIC) of ceftriaxone and azithromycin for blood culture isolates of NARS isolated at our centre.. This is a retrospective study conducted in a tertiary care center in Mumbai for blood culture isolates of NARS from 2016 to 2018. Isolates were tested for antimicrobial susceptibility testing (AST) against ceftriaxone and azithromycin using a manual broth microdilution method (BMD).. Of 155 blood culture isolates of NARS: S. Typhi (n = 112) and S. Paratyphi A (n = 43) were included in the study. 81.9% (127 / 155) isolates were susceptible, 6.4% (10 / 155) isolates were intermediate while 11.6% (18 / 155) isolates were resistant to ceftriaxone. 100% susceptibility of NARS was observed to azithromycin.. This study documents an alarming increase in resistance to ceftriaxone among NARS in Mumbai while azithromycin continues to be susceptible in vitro. It is essential to know MICs to understand epidemiological trends and choose appropriate treatment regimens for treating enteric fever.

Topics: Azithromycin; Ceftriaxone; Drug Resistance, Bacterial; Humans; India; Microbial Sensitivity Tests; Retrospective Studies; Salmonella enterica; Typhoid Fever

Outbreaks of acute undifferentiated febrile illness (AUFI) are common in Nepal, but the exact etiology or risk factors for them often go unrecognized. Diseases like influenza, enteric fever and rickettsial fevers account for majority of such outbreaks. Optimal diagnostic tests to inform treatment decisions are not available at the point-of-care. A proper epidemiological and clinical characterization of such outbreaks is important for appropriate treatment and control efforts.. An investigation was initiated as a response to increased presentation of patients at Patan Hospital from Chalnakhel locality in Dakchinkali municipality, Kathmandu with AUFI from June 10 to July 1, 2016. Focused group discussion with local inhabitants and the epidemiological curve of febrile patients at local primary health care centre confirmed the outbreak. The household-survey was conducted in the area with questionnaire administered on patients to characterize their illnesses and their medical records were reviewed. A different set of questionnaire was administered on the patients and controls to investigate the association with common risk factors. Water samples were collected and analyzed microbiologically.. Eighty one patients from 137 households suffered from febrile illness within 6 weeks window before the investigation. All the 67 sampled patients with acute fever had a generalized illness without a discernible focus of infection. Only 38% of the patients had received a clinical diagnosis while the rest were treated empirically without a diagnosis. Three patients had blood culture confirmed enteric fever. Forty-two (63%) patients had been administered antibiotics, most commonly, ofloxacin, cefixime or azithromycin with a mean fever clearance time of 4 days. There was no definite association between several risk factors and fever. Fecal contamination was noted in tap water samples.. Based on the pattern of illness, this outbreak was most likely a mixture of self-limiting viral infections and enteric fever. This study shows that even in the absence of a confirmed diagnosis, a detailed characterization of the illness at presentation and the recovery course can suggest the diagnosis and help in formulating appropriate recommendation for treatment and control.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Cefixime; Child; Disease Outbreaks; Female; Fever; Humans; Male; Middle Aged; Nepal; Ofloxacin; Risk Factors; Typhoid Fever; Virus Diseases; Young Adult

A strain of extensively drug-resistant (XDR)

Topics: Anti-Bacterial Agents; Azithromycin; Carbapenems; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Ontario; Pakistan; Salmonella enterica; Travel; Typhoid Fever; Whole Genome Sequencing

Non-typhoidal Salmonella (NTS) are a major cause of bloodstream infection (BSI) in sub-Saharan Africa. This study aimed to assess its longitudinal evolution as cause of BSI, its serotype distribution and its antibiotic resistance pattern in Kisantu, DR Congo.. As part of a national surveillance network, blood cultures were sampled in patients with suspected BSI admitted to Kisantu referral hospital from 2015-2017. Blood cultures were worked-up according to international standards. Results were compared to similar data from 2007 onwards.. In 2015-2017, NTS (n = 896) represented the primary cause of BSI. NTS were isolated from 7.6% of 11,764 suspected and 65.4% of 1371 confirmed BSI. In children <5 years, NTS accounted for 9.6% of suspected BSI. These data were in line with data from previous surveillance periods, except for the proportion of confirmed BSI, which was lower in previous surveillance periods. Salmonella Typhimurium accounted for 63.1% of NTS BSI and Salmonella Enteritidis for 36.4%. Of all Salmonella Typhimurium, 36.9% did not express the O5-antigen (i.e. variant Copenhagen). O5-negative Salmonella Typhimurium were rare before 2013, but increased gradually from then onwards. Multidrug resistance was observed in 87.4% of 864 NTS isolates, decreased ciprofloxacin susceptibility in 7.3%, ceftriaxone resistance in 15.7% and azithromycin resistance in 14.9%. A total of 14.2% of NTS isolates, that were all Salmonella Typhimurium, were multidrug resistant and ceftriaxone and azithromycin co-resistant. These Salmonella isolates were called extensively drug resistant. Compared to previous surveillance periods, proportions of NTS isolates with resistance to ceftriaxone and azithromycin and decreased ciprofloxacin susceptibility increased.. As in previous surveillance periods, NTS ranked first as the cause of BSI in children. The emergence of O5-negative Salmonella Typhimurium needs to be considered in the light of vaccine development. The high proportions of antibiotic resistance are worrisome.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Bacteremia; Ceftriaxone; Child; Child, Preschool; Ciprofloxacin; Congo; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Salmonella; Salmonella enteritidis; Salmonella Infections; Salmonella typhimurium; Serogroup; Typhoid Fever; Young Adult

A 5-year-old male child with blood culture confirmed typhoid fever presented with twitching over the left scapular region. Contrast computerized tomography and electroencephalogram were normal. Following treatment with azithromycin and clonazepam, the twitching subsided. Subsultus tendinum, a rare neurological complication of typhoid fever, resolves spontaneously with treatment.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Family; Humans; Male; Salmonella typhi; Typhoid Fever

Topics: Azithromycin; Humans; Paratyphoid Fever; Typhoid Fever

Antimicrobial resistance is an ongoing issue in the treatment of typhoid fever. Resistance to first-line antimicrobials and extensively drug resistant (XDR)

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Drug Resistance, Multiple, Bacterial; Membrane Transport Proteins; Microbial Sensitivity Tests; Pakistan; Plasmids; Point Mutation; Salmonella typhi; Typhoid Fever

Topics: Anti-Bacterial Agents; Australia; Azithromycin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Meropenem; Pakistan; Salmonella typhi; Travel; Typhoid Fever

With the rise in fluoroquinolone-resistant Salmonella Typhi and the recent emergence of ceftriaxone resistance, azithromycin is one of the last oral drugs available against typhoid for which resistance is uncommon. Its increasing use, specifically in light of the ongoing outbreak of extensively drug-resistant (XDR) Salmonella Typhi (resistant to chloramphenicol, ampicillin, cotrimoxazole, streptomycin, fluoroquinolones and third-generation cephalosporins) in Pakistan, places selective pressure for the emergence and spread of azithromycin-resistant isolates. However, little is known about azithromycin resistance in Salmonella, and no molecular data are available on its mechanism.. We conducted typhoid surveillance in the two largest pediatric hospitals of Bangladesh from 2009-2016. All typhoidal Salmonella strains were screened for azithromycin resistance using disc diffusion and resistance was confirmed using E-tests. In total, we identified 1,082 Salmonella Typhi and Paratyphi A strains; among these, 13 strains (12 Typhi, 1 Paratyphi A) were azithromycin-resistant (MIC range: 32-64 μg/ml) with the first case observed in 2013. We sequenced the resistant strains, but no molecular basis of macrolide resistance was identified by the currently available antimicrobial resistance prediction tools. A whole genome SNP tree, made using RAxML, showed that the 12 Typhi resistant strains clustered together within the 4.3.1.1 sub-clade (H58 lineage 1). We found a non-synonymous single-point mutation exclusively in these 12 strains in the gene encoding AcrB, an efflux pump that removes small molecules from bacterial cells. The mutation changed the conserved amino acid arginine (R) at position 717 to a glutamine (Q). To test the role of R717Q present in azithromycin-resistant strains, we cloned acrB from azithromycin-resistant and sensitive strains, expressed them in E. coli, Typhi and Paratyphi A strains and tested their azithromycin susceptibility. Expression of AcrB-R717Q in E. coli and Typhi strains increased the minimum inhibitory concentration (MIC) for azithromycin by 11- and 3-fold respectively. The azithromycin-resistant Paratyphi A strain also contained a mutation at R717 (R717L), whose introduction in E. coli and Paratyphi A strains increased MIC by 7- and 3-fold respectively, confirming the role of R717 mutations in conferring azithromycin resistance.. This report confirms 12 azithromycin-resistant Salmonella Typhi strains and one Paratyphi A strain. The molecular basis of this resistance is one mutation in the AcrB protein at position 717. This is the first report demonstrating the impact of this non-synonymous mutation in conferring macrolide resistance in a clinical setting. With increasing azithromycin use, strains with R717 mutations may spread and be acquired by XDR strains. An azithromycin-resistant XDR strain would shift enteric fever treatment from outpatient departments, where patients are currently treated with oral azithromycin, to inpatient departments to be treated with injectable antibiotics like carbapenems, thereby further burdening already struggling health systems in endemic regions. Moreover, with the dearth of novel antimicrobials in the horizon, we risk losing our primary defense against widespread mortality from typhoid. In addition to rolling out the WHO prequalified typhoid conjugate vaccine in endemic areas to decrease the risk of pan-resistant Salmonella Typhi strains, it is also imperative to implement antimicrobial stewardship and water sanitation and hygiene intervention to decrease the overall burden of enteric fever.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Bangladesh; DNA, Bacterial; Drug Resistance, Bacterial; Genotype; Hospitals, Pediatric; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Polymorphism, Single Nucleotide; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever; Whole Genome Sequencing

We describe a ceftriaxone-resistant

Topics: Abdominal Pain; Adult; Agglutination Tests; Anti-Bacterial Agents; Azithromycin; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Ceftriaxone; Denmark; Drug Resistance; Escherichia coli; Female; Fever; Humans; Meropenem; Microbial Sensitivity Tests; Pakistan; Plasmids; Polymerase Chain Reaction; Pregnancy; Salmonella typhi; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Travel; Typhoid Fever; Whole Genome Sequencing

: Azithromycin has been in use as an alternate treatment option for enteric fever even when the guidelines on the susceptibility testing were not available. There is lack of data on susceptibility and mechanisms of resistance of azithromycin in Salmonella Typhi and S. Paratyphi A. The aim of the present study was to determine the azithromycin susceptibility and resistance mechanisms in typhoidal salmonellae isolates archived in a tertiary care centre in north India for a period of 25 years.. : Azithromycin susceptibility was determined in 602 isolates of S. Typhi (469) and S. Paratyphi A (133) available as archived collection isolated during 1993 to 2016, by disc diffusion and E-test method.PCR was done for ereA, ermA, ermB, ermC, mefA, mphA and msrA genes from plasmid and genomic DNA and sequencing was done to detect mutations in acrR, rplD and rplV genes.. : Azithromycin susceptibility was seen in 437/469 [93.2%; 95% confidence interval (CI), 90.5 to 95.1%] isolates of S. Typhi. Amongst 133 isolates of S. Paratyphi A studied, minimum inhibitory concentration (MIC) of ≤16 mg/l was found in 102 (76.7%; 95% CI, 68.8 to 83.0). MIC value ranged between 1.5 and 32 mg/l with an increasing trend in MIC. : Azithromycin could be considered as a promising agent against typhoid fever on the basis of MIC distribution in India. However, due to emergence of resistance in some parts, there is a need for continuous surveillance of antimicrobial susceptibility and resistance mechanisms. There is also a need to determine the breakpoints for S. Paratyphi A.

Topics: Azithromycin; Bacterial Proteins; Drug Resistance, Bacterial; Humans; India; Mutation; Salmonella enterica; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever

The epidemiology of typhoid fever in South Asia has changed. Multi-drug resistant (MDR) Salmonella typhi ( S. typhi) is now frequently resistant to nalidixic acid and thus labelled NARST. Treatment failure with the use of fluoroquinolones has been widely noted, forcing clinicians to adopt alternative treatment strategies. In this observational study, we looked at various treatment regimens and correlated clinical and microbiological outcomes. In 146 hospitalised adults, the median minimum inhibitory concentration (MIC) for ciprofloxacin was 0.38 µg/mL with a median fever clearance time (FCT) of eight days (range = 2-35 days). Of the regimens used, gatifloxacin and azithromycin had a shorter FCT of six days compared to ceftriaxone (ten days; P < 0.001). Though mortality and relapse in our cohort was low, NARST seemed to correlate with mortality ( P = 0.006). Gatifloxacin or azithromycin clearly emerge as the drugs of choice for treatment of typhoid in South India.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Ciprofloxacin; Cohort Studies; Drug Resistance, Multiple, Bacterial; Female; Fluoroquinolones; Gatifloxacin; Hospitalization; Humans; India; Male; Microbial Sensitivity Tests; Nalidixic Acid; Recurrence; Salmonella typhi; Treatment Outcome; Typhoid Fever; Young Adult

Tropical infections form 20-30% of ICU admissions in tropical countries. Diarrheal diseases, malaria, dengue, typhoid, rickettsial diseases and leptospirosis are common causes of critical illness. Overlapping clinical features makes initial diagnosis challenging. A systematic approach involving (1) history of specific continent or country of travel, (2) exposure to specific environments (forests or farms, water sports, consumption of exotic foods), (3) incubation period, and (4) pattern of organ involvement and subtle differences in manifestations help in differential diagnosis and choice of initial empiric therapy. Fever, rash, hypotension, thrombocytopenia and mild derangement of liver function tests is seen in a majority of patients. Organ failure may lead to shock, respiratory distress, renal failure, hepatitis, coma, seizures, cardiac arrhythmias or hemorrhage. Diagnosis in some conditions is made by peripheral blood smear examination, antigen detection or detection of microbial nucleic acid by PCR. Tests that detect specific IgM antibody become positive only in the second week of illness. Initial therapy is often empiric; a combination of intravenous artesunate, ceftriaxone and either doxycycline or azithromycin would cover a majority of the treatable syndromes. Additional antiviral or antiprotozoal medications are required for some specific syndromes. Involving a physician specializing in tropical or travel medicine is helpful.

Topics: Artesunate; Azithromycin; Ceftriaxone; Child; Communicable Diseases; Critical Care; Dengue; Diagnosis, Differential; Doxycycline; Exanthema; Female; Fever; Geography; Humans; Intensive Care Units; Leptospirosis; Malaria; Male; Nervous System Diseases; Pregnancy; Shock, Hemorrhagic; Syndrome; Travel; Tropical Medicine; Typhoid Fever

Topics: Abducens Nerve Diseases; Adolescent; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Diplopia; Female; Humans; Methylprednisolone; Neuroprotective Agents; Typhoid Fever

From June 2018, onwards, there has been an upsurge of multi-resistant enteric infections in children admitted from various catchment areas of Abbasi Shaheed Hospital (ASH). This is a serious concern as very few antibiotics are available to treat the children. Children from June 2018 to September 2018 of age groups 5.7 ± 2.84 (range 1.6 to 11 years), referred to ASH, for admission, with clinical suspicion of enteric fever and having received a third generation injectable cephalosporin by a general practitioner, for 5 days or more, with no response, and continuation of fever, were included. A total number of 137 patients had culture proven salmonella typhi, of whom 61(44.52%) showed sensitivity only to meropenem, 45 (32.8%) to azithromycin,13(9.4%)to fosfomycin, 11(8.02%) to Amoxicillin/clavulanic acid, 5 patients showed sensitivity to ceftriaxone(3.64%) and one had sensitivity to amikacin. All patients were treated successfully for 10 days and discharged home. There were no reported complications at follow-up. Multi-Drug Resistance (MDR) enteric fever appears to be a major health concern in Karachi. Mass immunization with oral live attenuated Typhi 21a or injectable unconjugated Vi typhoid vaccine, rational use of antibiotics, improvement in public sanitation facilities, availability of clean drinking water, promotion of safe food handling practices and public health education are vital in the prevention of MDR enteric fever.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Cohort Studies; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Male; Meropenem; Pakistan; Salmonella typhi; Typhoid Fever

Typhoid fever remains a serious problem in many developing countries. Due to resistance to multiple first line drugs, azithromycin has evolved as an important drug in the treatment of typhoid. While therapy with azithromycin is highly effective, no clinically validated mean inhibitory concentration (MIC) break points or disc diffusion cutoff guidelines are available so far. We describe an Indian adult with clinical and microbiological failure to azithromycin despite low azithromycin MIC.

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Male; Microbial Sensitivity Tests; Salmonella typhi; Serogroup; Treatment Failure; Typhoid Fever; Young Adult

Enteric fever (typhoid and paratyphoid) remains a threat to British troops overseas and causes significant morbidity and mortality. We report the case of a soldier who developed typhoid despite appropriate vaccination and field hygiene measures, which began 23 days after returning from a deployment in Sierra Leone. The incubation period was longer than average, symptoms started 2 days after stopping doxycycline for malaria chemoprophylaxis and initial blood cultures were negative. The Salmonella enterica serovar Typhi eventually isolated was resistant to amoxicillin, co-amoxiclav, co-trimoxazole and nalidixic acid and had reduced susceptibility to ciprofloxacin. He was successfully treated with ceftriaxone followed by azithromycin, but 1 month later he remained fatigued and unable to work. The clinical and laboratory features of enteric fever are non-specific and the diagnosis should be considered in troops returning from an endemic area with a febrile illness. Multiple blood cultures and referral to a specialist unit may be required.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Cecum; Ceftriaxone; Humans; Lymphatic Diseases; Male; Mesentery; Military Personnel; Sierra Leone; Tomography, X-Ray Computed; Treatment Failure; Typhoid Fever; Typhoid-Paratyphoid Vaccines; United Kingdom

Decreased ciprofloxacin susceptibility (DCS) and multidrug resistance in typhoidal Salmonella isolates in areas of endemicity are significant therapeutic problems. Guidelines for azithromycin disc diffusion and MIC interpretive criteria for Salmonella enterica serovar Typhi were published recently by the Clinical and Laboratory Standards Institute in 2015. We investigated the antimicrobial susceptibility pattern of azithromycin in 100 isolates of Salmonella Typhi (n=80), Paratyphi A (n=18) and B (n=2) recovered from bloodstream infections from January 2013 to December 2015. Zone sizes were extrapolated against MIC values, and a scatter plot was constructed. The azithromycin MICs by Etest ranged from 2 to 16 µg ml-1, while the disc diffusion diameters were from 13 to 22 mm. We observed that the margin of the zone of inhibition around the azithromycin disc may not be very clear and therefore difficult to interpret and that there was wide variation in the zone sizes for the same MIC value in both serovars. DCS was observed in 85 % of Salmonella Typhi recovered (68/80) and in 15/18 (83.3 %) Paratyphi A isolates. Judicious use of azithromycin is advocated as an alternative oral agent in endemic areas where DCS is common.

Topics: Anti-Bacterial Agents; Azithromycin; Bacteremia; Ciprofloxacin; Drug Resistance, Bacterial; Humans; India; Microbial Sensitivity Tests; Salmonella paratyphi A; Salmonella paratyphi B; Salmonella typhi; Serogroup; Typhoid Fever

Antimicrobial susceptibility was analyzed for 354 typhoidal Salmonella isolates collected during 1999-2012 in the Netherlands. In 16.1% of all isolates and in 23.8% of all isolates that showed increased MICs for ciprofloxacin, the MIC for azithromycin was increased. This resistance may complicate empirical treatment of enteric fever.

Topics: Anti-Bacterial Agents; Azithromycin; Ciprofloxacin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Netherlands; Salmonella; Salmonella Infections; Travel; Typhoid Fever

Septic arthritis is a rare complication of typhoid fever. A 12-year-old boy without pre-existing disease attended a paediatric hospital in Cambodia with fever and left hip pain. A hip synovial fluid aspirate grew multidrug-resistant Salmonella enterica ser. Typhi with intermediate susceptibility to ciprofloxacin. Arthrotomy, 2 weeks of intravenous ceftriaxone and 4 weeks of oral azithromycin led to resolution of symptoms. The optimum management of septic arthritis in drug-resistant typhoid is undefined.

Topics: Anti-Bacterial Agents; Arthritis, Infectious; Azithromycin; Cambodia; Ceftriaxone; Child; Debridement; Drug Resistance, Multiple, Bacterial; Hip Joint; Humans; Male; Microbial Sensitivity Tests; Salmonella typhi; Synovial Fluid; Treatment Outcome; Typhoid Fever

A middle-aged woman presented with fever of 1-month duration along with bilateral knee joint pain, swelling and difficulty in walking for 2 weeks. The patient's Typhidot test was positive for IgM antibodies. Her Widal test was negative, and blood culture and synovial fluid culture were sterile. She was started on ceftriaxone, to which her fever initially responded. However, after 4 days of treatment her disease course was complicated by relapse of fever and acute respiratory distress syndrome (ARDS). This settled with respiratory support and addition of azithromycin. Following recovery from ARDS and fever, her persistent knee arthritis responded to intra-articular methyl prednisolone instillation.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Azithromycin; Female; Humans; Knee Joint; Middle Aged; Prednisolone; Respiratory Distress Syndrome; Typhoid Fever

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

As a consequence of multidrug resistance, clinicians are highly dependent on fluoroquinolones for treating the serious systemic infection typhoid fever. While reduced susceptibility to fluoroquinolones, which lessens clinical efficacy, is becoming ubiquitous, comprehensive resistance is exceptional. Here we report ofloxacin treatment failure in typhoidal patient infected with a novel, highly fluoroquinolone-resistant isolate of Salmonella enterica serovar Typhi. The isolation of this organism has serious implications for the long-term efficacy of ciprofloxacin and ofloxacin for typhoid treatment.

Topics: Adolescent; Amino Acid Sequence; Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; DNA Gyrase; Drug Resistance, Multiple, Bacterial; Fluoroquinolones; Humans; Male; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation; Nepal; Ofloxacin; Salmonella typhi; Treatment Failure; Typhoid Fever

Salmonella typi is a rare cause of chronic osteomyelitis in a non-sickle cell patient. The authors report the case of a 25-year-old gentleman with a history of typhoid fever and an infected skin nodule on his left forearm 5 years prior to the diagnosis. He was referred to our orthopaedic colleagues with chronic osteomyelitis and underwent debridement of the bone for which samples grew Salmonella typhi. He was commenced on intravenous ceftriaxone 2 g once daily for 6 weeks followed by oral azithromycin 500 mg once daily for a further 6 weeks. The purpose of this case report is to consider the possible mode for antibiotic resistance. In this patient, the authors believe that partial treatment of the typhoid fever 5 years prior to diagnosis of osteomyelitis enabled antibiotic resistance to ciprofloxacin. Furthermore, the authors believe that the infected nodule was the result of direct inoculation with the Salmonella organism which then acted as a focus for further infections.

Topics: Adult; Anti-Infective Agents; Azithromycin; Ciprofloxacin; Debridement; Drug Resistance, Microbial; Forearm; Humans; Male; Osteomyelitis; Radiography; Salmonella Infections; Salmonella typhi; Treatment Outcome; Typhoid Fever

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Humans; Male; Salmonella typhi; Treatment Failure; Typhoid Fever

Infections with Salmonella enterica serovar Typhi isolates that are multidrug resistant (MDR: resistant to chloramphenicol, ampicillin, trimethoprim-sulphamethoxazole) with intermediate ciprofloxacin susceptibility are widespread in Asia but there is little information from Cambodia. We studied invasive salmonellosis in children at a paediatric hospital in Siem Reap, Cambodia. Between 2007 and 2011 Salmonella was isolated from a blood culture in 162 children. There were 151 children with enteric fever, including 148 serovar Typhi and three serovar Paratyphi A infections, and 11 children with a non-typhoidal Salmonella infection. Of the 148 serovar Typhi isolates 126 (85%) were MDR and 133 (90%) had intermediate ciprofloxacin susceptibility. Inpatient antimicrobial treatment was ceftriaxone alone or initial ceftriaxone followed by a step-down to oral ciprofloxacin or azithromycin. Complications developed in 37/128 (29%) children admitted with enteric fever and two (1.6%) died. There was one confirmed relapse. In a sample of 102 serovar Typhi strains genotyped by investigation of a subset of single nucleotide polymorphisms, 98 (96%) were the H58 haplotype, the majority of which had the common serine to phenylalanine substitution at codon 83 in the DNA gyrase. We conclude that antimicrobial-resistant enteric fever is common in Cambodian children and therapeutic options are limited.

Topics: Adult; Age Distribution; Anti-Infective Agents; Azithromycin; Cambodia; Ceftriaxone; Child; Child Mortality; Child, Preschool; Ciprofloxacin; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Female; Haplotypes; Hospitals, Pediatric; Humans; Male; Microbial Sensitivity Tests; Polymorphism, Single Nucleotide; Retrospective Studies; Salmonella typhi; Treatment Outcome; Typhoid Fever

Enteric fever is caused by Salmonella enterica serovars Typhi and Paratyphi A, B and C. It is a significant public health issue in Pakistan, which is exacerbated by a high level of resistance some isolates display to drugs routinely used in treatment. Azithromycin may be a treatment option for such isolates.. We determined the minimum inhibitory concentrations (MICs) of Salmonella Typhi and Paratyphi isolates against azithromycin in an attempt to gauge its feasibility as a therapeutic option. The MICs were also compared with corresponding disc diffusion zone sizes to see if there was consistency between the two tests. We tested 45 Salmonella enterica isolates using E-tests for MIC detection and azithromycin discs with a concentration of 15µg/ml for disc diffusion testing.. Salmonella Typhi, Salmonella Paratyphi A, and Salmonella Paratyphi C isolates demonstrated MICs of 2-12mg/L against azithromycin, suggesting that the antibiotic could be used for therapeutic purposes. For Salmonella Paratyphi B, the MICs were 2-48 mg/L. The higher MIC indicates a need for caution when considering use of azithromycin for Salmonella Paratyphi B infections without first testing for the MIC. There was a close correlation between MICs and zone sizes which was statistically significant.. Our results indicate azithromycin is a potential therapeutic option for enteric fever. Standardized laboratory testing methods and interpretation for azithromycin against Salmonella enterica would allow laboratories to report upon this antibiotic with confidence.

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Microbial Sensitivity Tests; Pakistan; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever

Topics: Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Typhoid Fever

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

Typhoid fever is a systemic disease not endemic to South Dakota. We report a case of a young child, living in South Dakota since immigrating with his family as a refugee, who developed typhoid fever. Contact investigation failed to identify a source, suggesting that the infection was acquired abroad. The clinical presentation of typhoid is discussed, and the literature relevant to diagnosis, treatment and prevention is reviewed.

Topics: Analgesics, Non-Narcotic; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Child, Preschool; Emigrants and Immigrants; Humans; Male; Salmonella typhi; Typhoid Fever

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

The ex vivo cytokine response to lipopolysaccharide (LPS) of whole blood from patients with typhoid fever was investigated. Tumor necrosis factor (TNF)-alpha release by LPS-stimulated blood was found to be lower during acute typhoid fever than after a course of antimicrobial therapy (P

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Cytokines; DNA, Bacterial; Enzyme-Linked Immunosorbent Assay; Female; Fluoroquinolones; Humans; In Vitro Techniques; Interleukin-1; Lipopolysaccharides; Male; Polymerase Chain Reaction; Receptors, Interleukin-1; Salmonella typhi; Statistics, Nonparametric; Tumor Necrosis Factor-alpha; Typhoid Fever

Topics: Azithromycin; Blood; Culture Media, Conditioned; Humans; Microbial Sensitivity Tests; Salmonella typhi; Staphylococcus aureus; Typhoid Fever

Topics: Adult; Azithromycin; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Treatment Outcome; Typhoid Fever