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8.6 Antibiotic treatment for Typhoid Fever
a Children with typhoid fever should be treated with a luoroquinolone i.e. ciproloxacin, gatiloxacin, oloxacin, and perloxacin as a irst line treatment for
7–10 days. — Ciproloxacin: orally 15 mgkg per dose twice daily for 7–10 days.
Strong recommendation; moderate quality evidence
b If the response to treatment is poor, consider drug-resistant typhoid and treat with a second line antibiotic like 3rd generation cephalosporins or azithromycin.
— Cetriaxone IV: 80 mgkg per day for 5–7 days OR
— Azithromycin: 20 mgkg per day for 5–7 days
Strong recommendation, moderate quality evidence
c Where drug resistance to antibiotics among salmonella isolates is known, follow the national guidelines according to local susceptibility data.
Strong recommendation, moderate quality evidence
he panel noted that patterns of antimicrobial resistance to salmonella isolates are constantly changing, making continuous surveillance of resistance levels critical for
clinicians to keep abreast of treatment options. Currently, nalidixic acid resistance is very common and widespread across many countries and there is increasing
resistance to ciproloxacin. his trend in antibiotic resistance to luoroquinolones may have implications on the efectiveness of ciproloxacin in some countries, which
may require use of alternative luoroquinolone determined by local susceptibility data.
It was also noted that the duration of treatment varied from 7 to15 days in the RCTs studies that were reviewed making it diicult to draw a conclusive decision
about duration. However, it was clear that treatment required at least ≥ 7 days of irst line antibiotics.
8.6.1 Evidence and summary of findings
First line antibiotics, including beta-lactams and chloramphenicol, have gradually become less useful with increasing drug resistance. Studies of antibiotic resistance
since 1989 in the Indian subcontinent and China have shown that 50–80 of all Salmonella typhi isolates were multidrug resistant MDR [Lee 2000]. he choice
of antibiotics for enteric fever has been based on studies of the prevalence of MDR Salmonella typhi and paratyphi.
A Cochrane review evaluated luoroquinolone antibiotics for treating enteric fever in children and adults compared with other antibiotics, diferent luoroquinolones,
and diferent durations of luoroquinolone treatment [haver, 2008]. he review included 38 trials; 22 had unclear allocation concealment and 34 did not use
blinding. Only four trials exclusively included children, seven had both adults and children, and three studied outpatients. here are no conclusive data to make irm
recommendations regarding the superiority of luoroquinolones over irst line
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antibiotics i.e. chloramphenicol, ampicillin, amoxicillin or cephalosporins i.e. ceixime, cetriaxone in children. However, there is a general trend in favour of using
luoroquinolones as irst line treatment, and either 3rd generation cephalosporins or azithromycin as second line antibiotics for enteric fever due to the rising level of
resistance in many parts of the world.
In children, there was a high proportion of nalidixic acid-resistant strains; older luoroquinolones increased clinical failures compared with azithromycin OR 2.67,
95 CI 1.16 to 6.11; 125 participants, one trial, with no diferences using newer luoroquinolones 285 participants, one trial. Fluoroquinolones and ceixime were
not statistically signiicantly diferent 82 participants, one trial.Trials comparing diferent durations of luoroquinolone treatment also were not statistically
signiicantly diferent 889 participants, nine trials. Norloxacin had more clinical failures than other luoroquinolones 417 participants, ive trials.
Indirect evidence from the adults showed that there is:
n
Moderate quality evidence that luoroquinolones are superior to chloramphenicol in reducing relapse and duration of hospital stay
see GRADE table A7.24 .
n
Low quality evidence that luoroquinolones are superior to amoxicillin or ampicillin in reducing clinical or microbiological failure
see GRADE table A7.25
.
n
Low quality evidence that luoroquinolones are superior to cetriaxone in reducing clinical failure in settings of low nalidixic acid resistance
see GRADE table A7.25
.
n
Moderate quality evidence that azithromycin is superior to luoroquinolones in reducing clinical failures in settings of high nalidixic acid resistance
see GRADE table A7.26
. here was a wide range of diferent durations of therapy compared in several trials,
and the trials for each comparison were small – mostly with small sample sizes and lacking considerably in statistical power. he review found only two trials that
compared a short-course regimen 7 days or less with a long-course regimen more than 7 days. Clinical failure, microbiological failure, and relapse rates were low in
both arms, but the data were not suicient to make any conclusion.
8.6.2 Benefits and risks
Benefits Although there was no diference in the clinical failure in patients without MDR
when luoroquinolones are compared with irst line antibiotics, there was a clear beneit in favour of luoroquinolones in fever clearance, microbiological failure, and
relapse. here is also a clear beneit of using luoroquinolones over chloramphenicol; reduced relapse rate and convalescent faecal carriage 298 patients in three studies
with RR 0.17, 95 CI 0.04 to 0.70; and reduced risk of treatment failure given increasing frequency of participants with MDR.
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