Should we use combination therapy for typhoid?

PLoS Negl Trop Dis 12(4): e0006380

Contributed by Dr Sowmya Sridharan

Typhoid fever remains an important cause of AFI in many part of India. An open-label, comparative trial was conducted Nepal to evaluate the role of combination therapy in culture-confirmed TF cases. Patients were allocated to one of four study arms:

  1. hospitalized patients received either intravenous ceftriaxone or a combination of ceftriaxone and oral azithromycin
  2. outpatients received either oral azithromycin or a combination of oral azithromycin and cefixime

The primary outcome evaluated was fever clearance time (FCT) and the secondary outcomes included duration of bacteremia.

Among the 105 blood culture-confirmed patients included in the trial, FCT was significantly shorter for the combination therapy group (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.

The advantage of this trial is that it includes patients with multidrug resistant typhoid similar to our setting. The trial is not randomized, the doses of azithromycin used were low and after 48 hours of therapy the inpatient group was discharged on oral antibiotics, the details of which are not provided.