Treatment Of Uncomplicated Typhoid Fever Research Articles

Antimicrobial Resistance Profile of Salmonella enterica Serovar typhi Isolated from Human Clinical Samples in Ebonyi State, Nigeria

The emergence of resistance to the frequent use of empirical treatment of uncomplicated enteric fever caused by Salmonella enterica serovar Typhi is on the increase. This study was designed to determine the antimicrobial Resistance profile of Salmonella enterica serovar Typhi isolated from human clinical samples in Ebonyi State. A non-duplicated stool culture of Salmonella enterica serovar Typhi of patients diagnosed with typhoid fever at General Hospital Onicha Igboeze were collected from the hospital ward namely: A & E (n = 4), MS (n = 3), FS (n = 3), PD (n = 7), LW (n = 4), ORT (n = 1), LAB (n = 17), THE (n = 9), GOPD (n = 4), MM (n = 3). Antimicrobial studies of Salmonella enterica serovar Typhi were determined using the Kirby–Bauer disk diffusion method. The proportion of resistance ranges from 33 %-100% against colistin, cefepime, nalidixic acid, cefoxitin, amikacin, cefuroxime, and piperacillin-tazobactam but isolates were only susceptible to meropenem 100%. The use of antimicrobial agents for the treatment of Salmonella enterica serovar typhi infection should be guided with antimicrobial susceptibility testing, Nonetheless, the diversity of the Salmonella isolates as a result of the dissemination of these resistant genes is a call for concern and emphasizes a need for an extensive investigation for the presence of these genes in Ebonyi State as well as the implementation of strict antimicrobial policies in a bid to restrict the spread of these resistance genes and prevent the emergence of new resistant strains.

Typhoid Fever: Azithromycin vs. Ceftriaxone for the Treatment of Mild to Moderate Cases in Children

Background: Typhoid fever is a bacterial infection that can spread throughout the body, affecting many organs. Without prompt treatment, it can cause serious complications and can be fatal. It's caused by a bacterium called Salmonella typhi, In areas where there are few carriers of the typhoid bacterium, the disease is uncommon. It's also unusual to find places with sanitary water treatment and waste management systems. Nowadays both Azithromycin and Ceftriaxone are used for the treatment of mild to moderate cases in children.
 Objective: To assess the outcome of treatment of Acute Typhoid Fever with Azithromycin vs Ceftriaxone in Children with no other complication.
 Methods: This comparative study was carried out at tertiary hospital from January 2019 to January 2020. Where 200 patients coming to the hospital were initially screened in the outpatient department. During the study period, all children 5-18 years of age who, according to the outpatient department physician, had a diagnosis of typhoid fever were admitted to hospital. After admission to the ward, Among 200 patients, 100 patients treated with azithromycin (7 days of 10 mg/kg/day (maximum dose, 500 mg/day) and 100 patients treated with ceftriaxone were cured (P > .05).
 Results: During the study, majority belong to 5-10 years age group and 45% live in semipucca building followed by 60% drink Supply water without boiling and 80% cases were accustomed to solely home made food and outside of food. Clinical characteristics of azithromycin and ceftriaxone recipients who had typhoid fever and for whom blood cultures were positive where in azithromycin group mean duration of hospital stay was 9.8 days followed by 100 cases showed salmonella typhi positive.
 Whereas in Ceftriaxone group mean duration of hospital stay was 9.0 days followed by 100 cases showed positivity in salmonella typhi positive. In azithromycin group 90% were cured by day 7 followed by 86% were cured microbiologically, plus no relapse cases were found.
 Whereas in ceftriaxone case 80% were cured by day 7 followed by 78% were cured microbiologically, plus 5 relapse cases were found.
 Conclusion: Oral azithromycin given once daily appears to be beneficial in the treatment of uncomplicated typhoid fever in children. If these findings are verified, the agent could be a viable therapeutic option for typhoid fever, especially in developing nations where medical resources are limited.

The Outcome of Azithromycin and Ciprofloxacin for Treatment of Uncomplicated Typhoid Fever

Background: Enteric fever affects more than 11 million children and adults globally each year. Typhoid fever is treated with antibiotics. 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. Objective: To compare the outcome of azithromycin and ciprofloxacin for treatment of uncomplicated typhoid fever. Method: This comparative intervention was done at tertiary hospital where one hundred patients ranging in age from 5 to 25 years were enrolled in the study and randomly assigned to one of the two treatment groups. Group A constituted of 50 patients receiving azithromycin and group B constituted of the other 50 patients receiving ciprofloxacin. All patients underwent blood cultures or stool cultures from which S. typhi or S. paratyphi was isolated, and these subjects comprised the basis for analysis. Results: During the study, majority of the patients belonged to 5-15 years age group. 50% cases lived in semi pucca buildings followed by 70% drank supply water without boiling and 80% cases were accustomed to homemade food and outside food. Moreover, significance association was noticed in food habit and water source of the patients. In group A, 50 cases showed positivity in salmonella typhi and their mean duration of hospital stay was 10 days. Similarly, in group B, 50 cases showed positivity in salmonella typhi and mean duration of hospital stay was 9.0 days. In group A, 90% were cured by day 7 plus no relapse cases were found. In group B, 80% were cured by day 7. Mild-to- moderate adverse events, all of which were short-term and self-limited were reported equally in both treatment groups. Conclusion: Our results indicated that azithromycin and ciprofloxacin were similarly effective, both clinically and bacteriologically, against typhoid fever caused by both sensitive organisms and MDR S. typhi.

Efficacy of Oral Azithromycin in Treatment of Uncomplicated Enteric Fever in Children

Background: Enteric fever also known as (typhoid or paratyphoid fever) is a common systemic infection with increased incidence of morbidity and mortality with salmonella typhi and paratyphi. Azithromycin has shown better outcomes in children with uncomplicated disease. Objective: To determine the efficacy of Azithromycin in treatment of uncomplicated enteric fever in children. Study Design: Descriptive case series study Place and Duration of Study: Department of Pediatrics, Sir Ganga Ram Hospital Lahore, Pakistan from 21st August 2015 to 20th February 2016. Methodology: One hundred and sixty five cases were included. Patients received capsule/suspension of Azithromycin (10 mg/kg/day) OD for 7 days. Treatment was labelled as effective if both clinical and microbiological cure were observed. Results: Patients ranged between 2-12 years of age. Mean age of the patients was 6.45±2.39 year. There were 85 males (51.5%) and 80 females (48.5%) in this study. Mean duration of fever was 6.97±1.37 days. Clinical cure, microbiological cure and efficacy was 93.9%. Conclusion: Azithromycin to be effective and safe in treatment of enteric fever. We observed high cure rate of 93.9% without any serious side effects leading to the conclusion that azithromycin is an effective oral agent for treatment for enteric fever. Keywords: Enteric Fever, Azithromycin, Salmonella Typhi/Paratyphi

Study on the efficacy of ceftriaxone versus azithromycin for the treatment of uncomplicated enteric fever among the patients admitted in a tertiary level hospital

Background: Typhoid fever is a severe debilitating and potentially life threating illness. In Bangladesh, typhoid fever is a round the year problem which sometimes take epidemic proportions. The reasons behind such occurrences are unsafe water supply, defective sewage system and unhygienic food handling practice. This study aimed to compare the efficacy of ceftriaxone and azithromycin in the treatment of uncomplicated enteric fever.Methods: An observational study was conducted at the department of pharmacology in Dhaka medical college, Dhaka, Bangladesh. Data were collected from blood culture positive patients for Salmonella typhi and Salmonella paratyphi, who admitted in the Dhaka medical college and hospital, Dhaka during the period of July 2015 to June 2016. Data was collected by using a structured questioner, face to face interview, physical examination and investigation reports. Patients were hospitalized during the entire treatment period and at admission evaluation was made by history and physical examination in a structured format. Subjects ware asked regarding changes in symptoms and possible adverse effects of the study drugs. All patients were asked to return two weeks after completion of treatment for follow up. Blood culture of Salmonella typhi or Salmonella paratyphi were done in all cases. Total 91 patients were culture positive for either S. typhi or S. paratyphi which were finally studied.Results: During the study period out of 91 patients, 51 were receiving ceftriaxone and 40 were receiving azithromycin. Clinical cure was achieved in 46 patients (90%) of ceftriaxone group and in 31 patients (78%) in the azithromycin group. There were no significant differences of clinical cure between both treatment groups (p>0.05). Mean fever clearance time in ceftriaxone group was 3±1.4 days and was 4±1.6 days for azithromycin group. Difference in fever clearance time was statistically significant (p<0.05). No clinical relapses were detected in any study subject. No major side effects of both drugs occurred in any subject.Conclusions: These results indicated that both ceftriaxone and azithromycin were effective against enteric fever caused by sensitive organisms and multi drug resistant S. typhi and S. paratyphi. It is concluded that ceftriaxone is more effective and can be a convenient alternative for the treatment of enteric fever, especially in developing countries like us where medical resources are scarce.

CLINICAL EFFECTIVENESS OF AZITHROMYCIN VERSUS CIPROFLOXACIN IN THE TREATMENT OF UNCOMPLICATED ENTERIC FEVER IN CHILDREN;

ABSTRACT
 Objective: To compare the clinical effectiveness of oral azithromycin with oral ciprofloxacin in the treatment of uncomplicated enteric fever in children.
 Material and Methods: A randomized controlled trial was carried out in the Pediatric department of Khyber Teaching Hospital for which a sample size of 282 patients was determined using WHO calculator with 5% level of significance and 80% power of test (Two sided). Non-probability consecutive sampling technique was used for selection of children age 6 to 18 years and either gender. They were divided into two groups (141 in each) where Group A was treated with oral azithromycin while Group B with ciprofloxacin for 7 days. Clinical effectiveness was determined when the patient remained afebrile for more than 48 hours without antipyretics.
 Results: In group A, 128 children (90.78%) while in Group B, 105 (74.46%) children become clinically cure.
 Conclusion: Oral Azithromycin is more effective than oral Ciprofloxacin in the treatment of typhoid fever in children.

Oral Azithromycin Vs Intravenous Ceftriaxone in the Treatment of Enteric Fever: A Systematic Review and Meta-Analysis

Background: Typhoid fever, also known as enteric fever, is a severe systemic illness characterized by fever and gastrointestinal manifestations that commonly affects children and young adults. It is most prevalent in SouthCentral Asia, Southern Africa, and Southeast Asia. Alternative drugs for the treatment of enteric fever have been studied to decrease toxicity and increase compliance. Oral azithromycin has been proposed and is widely studied as a suitable treatment alternative. Objective: The objective of this study is to compare oral azithromycin with intravenous ceftriaxone in the treatment of uncomplicated typhoid fever in terms of cure, duration of fever, relapse, and adverse events. Methodology: A systematic review and meta-analysis were done with eligible studies taken from PUBMED, MEDLINE, and Cochrane Clinical Trial Registry. Six studies passed the eligibility criteria and were analyzed using Review Manager 5.3. Results: Azithromycin showed comparable results with ceftriaxone in terms of cure, duration of fever and adverse events. However, azithromycin proved superior in decreasing relapse. Conclusion: Azithromycin is comparable to ceftriaxone in the treatment of uncomplicated typhoid fever in terms of cure, duration of fever, and occurrence of adverse events. Azithromycin likewise had a lower incidence of relapse. Recommendations: We recommend conducting local trials in pediatric patients, to compare azithromycin with standard antibiotic regimen for typhoid fever, to help update local recommendations and expand choices for antibiotic use.

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

BackgroundThe 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.MethodsWe 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).FindingsIn 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.InterpretationAzithromycin at a dose of 500mg daily is an effective treatment for fully sensitive strains of S. Typhi but is associated with delayed treatment response and prolonged bacteraemia when compared with ciprofloxacin within the context of a human challenge model. Whilst the cellular accumulation of azithromycin is predicted to be sufficient to treat intracellular S. Typhi, systemic exposure may be sub-optimal for the elimination of extracellular circulating S. Typhi. In an era of increasing antimicrobial resistance, further studies are required to define appropriate azithromycin dosing regimens for enteric fever and to assess novel treatment strategies, including combination therapies.Trial registrationClinicalTrials.gov (NCT02324751 and NCT02192008).

UNCOMPLICATED TYPHOID FEVER

Objectives: Objectives of this study were To compare the clinical andbacteriological cure rates of azithromycin and ciprofloxacin in the treatment of uncomplicatedtyphoid fever and To determine any difference in the clinical and bacteriological cure rateswithin the two groups of study. Study Design: Quasi experimental study. Setting: Departmentof Medicine, DHQ/ Teaching Hospital Dera Ghazi Khan. Period: April 2016 to September 2016.Patients and Methods: A total of 60 patients including both males and females over 18 yearsof age were included in the study by Simple random probability sampling. Patients fulfilling theinclusion criteria were divided in two equal groups of 30 by using the random numbers table.First group was treated with azithromycin one gram on day one and then 500 mg daily for nextsix days. Second group was treated with ciprofloxacin 500mg twice daily for ten days. All thedata was analyzed by the computer programme SPSS. Frequency, percentages, mean valuesand standard deviations were calculated for age, sex, symptoms, signs, culture reports, clinicalcure rates and bacteriological cure rates. Results: Most common clinical feature was fevernoted in 100% patients followed by headache (86.6%) and nausea / vomiting (76.6%). Out of60, 52 (86.6%) patients were culture positive. In Azithromycin group clinical and bacteriologicalresponses were achieved in 93.3% and 92.3% respectively while in ciprofloxacin group theywere 96.6% and 96.15% respectively. There was no significant statistical difference between theclinical and bacteriological cure rates among two groups. Conclusion: Both ciprofloxacin andazithromycin are equally effective in the treatment of uncomplicated typhoid fever.

Antimicrobial susceptibility profile, treatment outcome and serotype distribution of clinical isolates of Salmonella enterica subspecies enterica: a 2-year study from Kerala, South India.

Background/purposeTyphoid and paratyphoid fever continue to be important causes of illness and death in parts of Asia, being associated with poor sanitation and consumption of unsafe food and water. Antimicrobial resistance has emerged to traditional first-line drugs, namely, the fluoroquinolones, as well as to third-generation cephalosporins, posing challenges to treatment. Azithromycin has proven to be an effective alternative for treatment of uncomplicated typhoid fever. The purpose of this study was to determine the antimicrobial susceptibility, clinical outcome and serotype distribution pattern of clinical isolates belonging to Salmonella enterica subspecies enterica.MethodologyAll clinical isolates of S. enterica obtained from blood, sterile body fluids, as well as stool and urine samples at Amrita Institute of Medical Sciences and Research Centre, Kerala, India, between August 2011 and July 2013 were included in the study and processed based on standard microbiology protocols.ResultsA total of 118 isolates of Salmonella were obtained during the study period. Out of these, 79 were of S. Typhi (66.95%), followed by isolates of S. Paratyphi A (22; 18.64%) and S. Typhimurium 12 (10.17%). Five isolates could not be identified further. There was 100% susceptibility to ceftriaxone in all S. enterica subspecies. Ciprofloxacin susceptibility was 32.91% for S. Typhi and 40.90% for S. Paratyphi A as determined by the disk diffusion method. The susceptibility profile of S. Typhi isolates to different antimicrobials was as follows: chloramphenicol (94.93%), ampicillin (77.21%), cotrimoxazole (75.94%) and azithromycin (78.48%). For S. Typhi, the minimum inhibitory concentration (MIC) of ciprofloxacin required to inhibit the growth of 50% of organisms was 0.5 μg/mL (intermediate) and MIC required to inhibit the growth of 90% of organisms was 1 μg/mL (resistant). S. Typhimurium was 100% susceptible to cotrimoxazole, ampicillin, ceftriaxone, chloramphenicol, ofloxacin and azithromycin. Susceptibility to ciprofloxacin was 66.66%. Patients from whom S. Typhimurium was isolated had comorbidities with documented risk. Of the 118 patients, 3 expired. Two had typhoid fever and were in sepsis at admission. One had S. Typhimurium and was suffering from multiple myeloma.ConclusionS. Typhi was the predominant isolate. All isolates were susceptible to ceftriaxone. Chloramphenicol susceptibility was >90%. No multidrug-resistant Salmonella strains were isolated. Susceptibility to ciprofloxacin for S. Typhi was 33%. Recovery rate was 97%.

Study comparing ceftriaxone with azithromycin for the treatment of uncomplicated typhoid fever in children of India

Introduction: The typhoid fever is one of the most common and serious infections in a developing country like India. An increase in the occurrence of typhoid fever in Indian children has stimulated the evaluation of alternative drugs for treatment in the Out Patient Department (OPD) without hospitalisation. Objective: To study the feasibility of using oral azithromycin for treating blood culture positive uncomplicated typhoid fever instead of intravenous ceftriaxone in a resource poor setting. Materials and Methods: We performed a randomised controlled trial to compare the efficacy and safety of azithromycin (20 mg/kg/day) as a once daily oral dose with intravenous ceftriaxone for 7 days for the treatment of uncomplicated typhoid fever in children and adolescents in India. A total of 124 children aged 3-18 years who were suspected to have typhoid fever were randomized and studied. Statistical analysis used: Data analysis was performed using Epi Info version 7 (Centers for Disease Control, Atlanta, GA.) and SPSS for Windows version 7.5 (SPSS, Inc., Chicago, Il.). Results: Our study showed that clinical cure was achieved in 30 (100%) of 30 patients in the azithromycin group and in 30 (88.2%) of 34 patients in the ceftriaxone group. The mean time taken for clearance of bacteraemia was longer in the azithromycin group than in the ceftriaxone. No patient who received azithromycin had a relapse as compared to 5 patients who received ceftriaxone. No serious side effects occurred in any subject under study. Conclusion: Oral azithromycin could be a convenient and cheap alternative for the treatment of typhoid fever, especially in children in developing countries where medical resources are scarce.

To Study the Effectiveness of Oral Azithromycin as Compared to Parenteral Ceftriaxone in the Treatment of Uncomplicated Enteric Fever

Aim This study aims to compare the effectiveness of oral azithromycin and intravenous ceftriaxone in the treatment of uncomplicated enteric fever in children aged between 2 and 12 years. Methods This prospective randomized open-labeled study was conducted in the Department of Pediatrics in a medical college of South India. A total of 126 children with proven enteric fever were randomized into two treatment groups. One group received oral azithromycin (20 mg/kg/d) and the other group received parenteral ceftriaxone (75 mg/kg/d), both of which were given for a duration of 7 days. The study population was observed for fever defervescence, duration of hospital stay, and relapse. Results The mean time for fever defervescence was 3.68 ± 2.109 and 4.08 ± 1.903 days in the azithromycin group and the ceftriaxone group, respectively. The mean duration of hospital stay was 7.35 ± 2.604 days in the azithromycin group and 9.44 ± 0.249 days in the ceftriaxone group. In the azithromycin group three children had treatment failure and had to crossover to ceftriaxone group. Among the four treatment failures in the ceftriaxone group, two cases relapsed within 4-week follow-up period. There was no relapse in the azithromycin group. Conclusion Oral azithromycin is as effective as intravenous ceftriaxone in treating uncomplicated typhoid fever in children with respect to fever defervescence, duration of hospital stay, and relapse.

To compare the effectiveness of oral azithromycin versus intravenous ceftriaxone for treating uncomplicated enteric fever

Objectives: To compare the clinical effectiveness of oral azithromycin versus intravenous (IV) ceftriaxone for treating uncomplicated enteric fever. Methods: Children aged 2-17 years with uncomplicated enteric fever and positive blood cultures for Salmonella typhi were included in the study. These were grouped as Group A (50 cases) and Group B (50 cases). Group A was given oral azithromycin 10 mg/kg/day once a day (azithromycin group) and Group B was given IV ceftriaxone 100 mg/kg/day in 2 divided doses (ceftriaxone group) for 6 and 7 days, respectively. Every day the child was examined, and the study results were assigned as a clinical and microbiological cure or failure. Results: A total of 100 patients in sex ratio of 1.2:1 (male:female) with uncomplicated enteric fever were enrolled in the study. Mean duration to become afebrile was less with azithromycin (2.72 days) as compared to ceftriaxone (5.52 days) treatment (p=0.000). 96% of the cases treated with azithromycin attained defervescence by the 5th day of treatment, but only 27% of cases treated with ceftriaxone attained defervescence by the 5th day of treatment. A clinical cure was earlier with azithromycin than with ceftriaxone treatment (p=0.027). Microbiological cure was achieved in 100% and 98% cases treated with azithromycin and ceftriaxone, respectively (p=0.5). Conclusion: Oral azithromycin was more efficacious in the treatment of uncomplicated enteric fever in children as compared to IV ceftriaxone.

A clinical trial of treatment of uncomplicated typhoid fever: efficacy of ceftriaxone-azithromycin combination

Background: Typhoid fever is a systemic infection caused by Gram-negative bacterium Salmonella enterica serovar typhi ( S. typhi ). It is a major health problem in India. It carries significant morbidity and mortality. Antimicrobial therapy is critical for the management of typhoid fever. Emergence of multidrug-resistant (MDR) and nalidixic acid-resistant (NAR) strains of S. typhi has complicated therapy by limiting treatment options. Hence, this study was conducted to evaluate the efficacy and safety profile of ceftriaxone and azithromycin combination therapy in uncomplicated typhoid fever. Methods: Adults patients of blood culture proven uncomplicated typhoid fever admitted in the medicine ward of Teerthanker Mahaveer Medical College and Research Centre were treated with ceftriaxone intravenously (2 g daily for 14 days) and azithromycin orally (500 mg daily for 7 days). Patients were clinically and bacteriologically evaluated during the study period and follow-up. Results: 96% cure rate was observed. No relapse was recorded. Conclusion: Ceftriaxone-azithromycin combination may be considered as an empirical therapy for treatment of uncomplicated typhoid fever in view of the emergence of MDR and NAR strains of S. typhi .

Gatifloxacin Versus Ofloxacin for the Treatment of Uncomplicated Enteric Fever in Nepal: An Open-Label, Randomized, Controlled Trial

BackgroundFluoroquinolones are the most commonly used group of antimicrobials for the treatment of enteric fever, but no direct comparison between two fluoroquinolones has been performed in a large randomised trial. An open-label randomized trial was conducted to investigate whether gatifloxacin is more effective than ofloxacin in the treatment of uncomplicated enteric fever caused by nalidixic acid-resistant Salmonella enterica serovars Typhi and Paratyphi A.Methodology and Principal FindingsAdults and children clinically diagnosed with uncomplicated enteric fever were enrolled in the study to receive gatifloxacin (10 mg/kg/day) in a single dose or ofloxacin (20 mg/kg/day) in two divided doses for 7 days. Patients were followed for six months. The primary outcome was treatment failure in patients infected with nalidixic acid resistant isolates. 627 patients with a median age of 17 (IQR 9–23) years were randomised. Of the 218 patients with culture confirmed enteric fever, 170 patients were infected with nalidixic acid-resistant isolates. In the ofloxacin group, 6 out of 83 patients had treatment failure compared to 5 out of 87 in the gatifloxacin group (hazard ratio [HR] of time to failure 0.81, 95% CI 0.25 to 2.65, p = 0.73). The median time to fever clearance was 4.70 days (IQR 2.98–5.90) in the ofloxacin group versus 3.31 days (IQR 2.29–4.75) in the gatifloxacin group (HR = 1.59, 95% CI 1.16 to 2.18, p = 0.004). The results in all blood culture-confirmed patients and all randomized patients were comparable.ConclusionGatifloxacin was not superior to ofloxacin in preventing failure, but use of gatifloxacin did result in more prompt fever clearance time compared to ofloxacin. Trial registration: ISRCTN 63006567 (www.controlled-trials.com).

A Single Blind Comparative Randomized Non-Inferior Multicenter Study for Efficacy and Safety of Levofloxacin versus Ciprofloxacin in the Treatment of Uncomplicated Typhoid Fever

Ciprofloxacin is currently the drug of choice for typhoid fever, but Salmonella typhi resistance to ciprofloxacin is increasing, while levofloxacin has been shown to be very effective in a few open studies. This study aimed to compare the efficacy, and safety of levofloxacin and ciprofloxacin for typhoid fever. From 110 patients with confirmed typhoid fever, 54 patients received oral levofloxacin 500 mg once daily with one drop out, while 56 received ciprofloxacin 500 mg twice daily for 7 days with two drop outs. Defervescence of fever was achieved on an average of 3 days after initiating levofloxacin and 5 days after starting ciprofloxacin and one microbiologically non confirmed typhoid fever relapse occurred in the levofloxacin group while two relapses with positive Salmonella microorganism occurred in the ciprofloxacin group. No carrier of Salmonella typhi was found in both groups at day 30. Adverse reactions were more pronounced in the ciprofloxacin group compared to the levofloxacin group. In conclusion, oral levofloxacin 500 mg once daily for one week showed faster fever clearance compared to ciprofloxacin 500 mg twice daily in typhoid fever in Indonesia, and less adverse reactions occurred with levofloxacin compared to ciprofloxacin. This electronic document is a “live” template. The various components of your paper (title, text, heads, etc.) are already defined on the style sheet, as illustrated by the portions given in this document.

A meta-analysis comparing the safety and efficacy of azithromycin over the alternate drugs used for treatment of uncomplicated enteric fever

Drug-resistant typhoid fever is a major clinical problem globally. Emergence of multidrug-resistant (MDR) S. Typhi has complicated therapy by limiting treatment options. A meta-analysis was planned to determine the strength of evidence supporting use of azithromycin over the alternate drugs available for treatment of uncomplicated typhoid fever. Studies were identified using electronic database such as MEDLINE and other data at the National Library of Medicine assessed using PUBMED search engine as well as Cochrane Clinical Trial Register. Randomized control trials (RCTs) comparing azithromycin with chloramphenicol, fluoroquinolones and cephalosporins in culture-proven enteric fever were included. Data was extracted and methodological quality was assessed. Risk ratio (RR) with 95% confidence intervals was estimated for the dichotomous outcomes and mean difference (MD) with 95% confidence was estimated for continuous data. Primary outcomes studied were clinical failure (CF), microbiological failure, and relapse. A total of seven RCTs involving 773 patients met with our inclusion criteria. In comparison to older fluoroquinolones, azithromycin is marginally better in reducing the chance of CF with RR 0.46 (95% CI 0.25-0.82), while in comparison to ceftriaxone, it significantly reduced the chance of relapse with RR 0.1 (95% CI 0.01- 0.76). There were no serious adverse events reported in any of the trials. Azithromycin can be recommended as a second-line drug in MDR typhoid fever, however, large trials involving pediatric age group patients are recommended to arrive at a definite conclusion.

Gatifloxacin versus chloramphenicol for uncomplicated enteric fever: an open-label, randomised, controlled trial

SummaryBackgroundWe aimed to investigate whether gatifloxacin, a new generation and affordable fluoroquinolone, is better than chloramphenicol for the treatment of uncomplicated enteric fever in children and adults.MethodsWe did an open-label randomised superiority trial at Patan Hospital, Kathmandu, Nepal, to investigate whether gatifloxacin is more effective than chloramphenicol for treating uncomplicated enteric fever. Children and adults clinically diagnosed with enteric fever received either gatifloxacin (10 mg/kg) once a day for 7 days, or chloramphenicol (75 mg/kg per day) in four divided doses for 14 days. Patients were randomly allocated treatment (1:1) in blocks of 50, without stratification. Allocations were placed in sealed envelopes opened by the study physician once a patient was enrolled into the trial. Masking was not possible because of the different formulations and ways of giving the two drugs. The primary outcome measure was treatment failure, which consisted of at least one of the following: persistent fever at day 10, need for rescue treatment, microbiological failure, relapse until day 31, and enteric-fever-related complications. The primary outcome was assessed in all patients randomly allocated treatment and reported separately for culture-positive patients and for all patients. Secondary outcome measures were fever clearance time, late relapse, and faecal carriage. The trial is registered on controlled-trials.com, number ISRCTN 53258327.Findings844 patients with a median age of 16 (IQR 9–22) years were enrolled in the trial and randomly allocated a treatment. 352 patients had blood-culture-confirmed enteric fever: 175 were treated with chloramphenicol and 177 with gatifloxacin. 14 patients had treatment failure in the chloramphenicol group, compared with 12 in the gatifloxacin group (hazard ratio [HR] of time to failure 0·86, 95% CI 0·40–1·86, p=0·70). The median time to fever clearance was 3·95 days (95% CI 3·68–4·68) in the chloramphenicol group and 3·90 days (3·58–4·27) in the gatifloxacin group (HR 1·06, 0·86–1·32, p=0·59). At 1 month only, three of 148 patients were stool-culture positive in the chloramphenicol group and none in the gatifloxacin group. At the end of 3 months only one person had a positive stool culture in the chloramphenicol group. There were no other positive stool cultures even at the end of 6 months. Late relapses were noted in three of 175 patients in the culture-confirmed chloramphenicol group and two of 177 in the gatifloxacin group. There were no culture-positive relapses after day 62. 99 patients (24%) experienced 168 adverse events in the chloramphenicol group and 59 (14%) experienced 73 events in the gatifloxacin group.InterpretationAlthough no more efficacious than chloramphenicol, gatifloxacin should be the preferred treatment for enteric fever in developing countries because of its shorter treatment duration and fewer adverse events.FundingWellcome Trust.

Efficacy and safety of azithromycin for uncomplicated typhoid fever: An open label non-comparative study

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.

An imported enteric fever caused by a quinolone-resistantSalmonella typhi

Recent reports indicate that nalidixic acid susceptibility correlates well with the clinical outcome of patients with Salmonella Typhi infection treated with quinolones. We report a case of enteric fever caused by S Typhi in which the isolate was resistant to nalidixic acid, but showed in vitro susceptibility to ciprofloxacin. Following treatment with ciprofloxacin, the clinical outcome was not satisfactory and the patient had a relapse. However, after using a higher dose of ciprofloxacin, the patient was cured. We recommend that all Salmonella systemic infections resistant to nalidixic acid with in vitro but decreased susceptibility to fluoroquinolones be treated with other antibiotics like third-generation cephalosporins or azithromycin. These patients should be closely followed up and observed for further relapse.