Open label comparative trial of mono versus dual antibiotic therapy for Typhoid Fever in adults

Abstract

BackgroundEmerging 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.MethodsAn 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.Results105 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.ConclusionsCombined therapy of third-generation cephalosporins and azithromycin for TF may surpass monotherapy in terms of FCT and time to elimination of bacteremia.Trial registrationTrial registration number: NCT02224040.

The epidemiology of typhoid fever in the Dhulikhel area, Nepal: A prospective cohort study

“…As resistance to ampicillin, trimethoprim-sulphamethoxazole, and chloramphenicol was generally low, the use of older medications may be required to curb resistance to newer antibiotics. Another approach might be the administration of dual antibiotic therapy which was reported to shorten fever clearance time, and shorten the duration of bacteremia [ 21 ][ 22 ]…”

“…Although the official WHO webpage still claims "paratyphoid" fever to be a milder disease, clinical features of TF, caused by either Salmonella Typhi or Paratyphi, have been reported to be similar by some studies in locals and travelers[ 22 ] [ 13 ] [ 23 ]. Patients infected by either serovar did indeed have a similar clinical presentation, with the exception of arthralgia, which was much more common in infections caused by Salmonella Typhi.…”

A review of clinical profile, complications and antibiotic susceptibility pattern of extensively drug-resistant (XDR) Salmonella Typhi isolates in children in Karachi.

“…We can infer that these two antibiotics may have synergic action against XDR-Enteric fever. This synergism among various antibiotics has been observed in MDR Enteric fever also (26).…”

A review of clinical profile, complications and antibiotic susceptibility pattern of extensively drug resistant (XDR) Salmonella Typhi isolates in children in Karachi.

“…This nding is consistent with other studies, which also found better cure rates with Azithromycin and Meropenem (20,21) Seventy six patients (48%) were successfully treated wth combination of Azithromycin and Meropenum.We found synergistic effect of Azithromycin and Meropenum in achieving fever defervescence. Synergism among various antibiotics have been observed in MDR Enteric fever also (22). Eight children were cured on single drugs although they were resistant to those antibiotics.…”