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Three Part Question

In [children with tonsillitis], [how long should antibiotics be given]? [outcome]

Clinical Scenario

A 3 year old boy was brought to the ED because of a fever, sore throat and an inflamed and tender tonsils. A diagnosis of tonsillitis was made. What course of antibiotics should be prescribed to the child? Which is more effective, a short-course or long-course antibiotic?

Search Strategy

Ovid MEDLINE(R) 1948 to June Week 3 2011 and
Embase 1980 to 2011 Week 25 and
CINAHL

[tonsillitis.mp. OR exp Tonsillitis/]

AND

[exp Anti-Bacterial Agents/ OR antibiotic.mp. OR antibiotic*.mp.]

limit to (english language and humans and "all child (0 to 18 years)")

Search Outcome

655 papers were found in Medline, 619 in Embase and 94 results obtained from CINAHL.
Only 4 papers were relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Cohen R. Reinert P. De La Rocque F. Levy C. Boucherat M. Robert M. Navel M. Brahimi N. Deforche D. P 4/7/2011 USA	501 children (2 - 12 years old) were randomized to receive either Azithromycin 10mg/kg/day once daily for 3 days or Azithromycin 20mg/kg/day once daily for 3 days or penicillin V 45 mg/kg/day three times daily for 10 days	Prospective, randomized clinical trial	Microbiological response on Day 14	AZM 10 mg/kg significantly less (P= 0.0001) than the other two groups. 90% CI for the mean difference between AZM 20 mg/kg and penicillin V (4.1% - 15.9%)	One study arm was not blinded due to the nature of the dosage of medication. P values for baseline characteristics were not calculated
D.Adam et al 6/7/2011 Germany	1-18 year olds with established diagnosis of group A streptococcal tonsillopharyngitis clinically and microbilogically.	phase IV, randomized, open label, comparative, multicentre study	Clinical response at end of treatment (7-9 days post-treatment)	Cefuroxime axetil (97.2%) vs penicillin V (93.3%); P=0.001	This study is an arm or a larger study assessing several agents for the eradication of GABHS. A degree of subjectivity in the exclusion criteria. Blinding of patients and investigators were not possible. Study power calculation were done using a chi test which resulted in 1590patients in the penicillin arm vs 530 patients in the cefuroxime axetil arm. Discussion possibly bias.
			Microbiological response at end of treatment (7-9 days post-treatment)	Cefuroxime axetil (90.0%) vs penicillin V (84.1%); P=0.001
M.Falagas et al. 6/7/2011 USA	Eleven RCTs comparing short-course vs long-course treatment (5 with penicillin V, 4 with oral cephalosporins, 1 with intramuscular ceftriaxone, and 1 with clindamycin; 6 of the 11 were open label) were included. Age groups included 1-80 year olds.	Meta-analysis	5-7 days vs 10 days	microbilogical erdication less likely with 5-7 days treatment (8 RCTS, 1607 patients; Odds ratio: 0.49; 95% CI: 0.32-0.74; P=0.18). Similarly, microbiological erdication in trials involving mainly children and adolescents (<18 years old) were also significantly lower for 5-7 days treatment arm (6 RCTs, 1258 patients; OR, 0.63; 95% CI, 0.40-0.98, P=0.80). Clinical success less likely in short-course treatment arm (5 RCTs, 1217 patients; OR, 0.49; 95% CI, 0.25-0.96; P=0.18).	Only assessed studies comparing the same antimicrobial agents. The methodological quality of most RCTs included was not good, 6 of the 11 had an open-label design
			shorter(<7days) vs longer courses of treatment (2 days longer than shorter treatment arm)	Microbiological eradication was significantly less likely in patients treated with short-course antibacterial regimens compared with patients treated with long-course regimens (10 RCTs, 1827 patients; OR, 0.40; 95% CI 0.28-0.57, P=0.33)
Altamimi S. Khalil A. Khalaiwi KA. Milner R. Pusic MV. Al Othman MA. 8/7/2011 Saudi Arabia	20 RCTs were included in this review which investigated a total of 13,102 cases of GABHS throat infections (tonsillitis, pharyngitis, tonsillopharyngitis) in children and young adults ranging from 1 to 18 year olds (except one study that included adults up to 25 years old). All studies only included patients who were diagnosed with GABHS by rapid antigen detection test or throat culture. The selected papers compared a short-course of several different antibiotics (azithromycin (n=6), cefuroxime (n=3), erythromycin (n = 2), clarithromycin (n = 3), cefixime (n =1), amoxacillin (n = 1), amoxacillin/clavulanate (n = 2), penicillin V (n =1), cefprozil (n = 1), cefpodoxime (n = 1), jasomycin (n = 1), cefdinir (n = 1), ceftibutin (n = 1) and loracarbef (n = 1)) against the standard treatment of 10 day penicillin V.	Systematic Review	Time to fever resolution	Only reported in two studies. Both studies favored the short duration group. In the first study, the short duration group had a mean duration of fever of 2.04 days compared with 2.38 days in the standard duration group, while in the second study the durations were 2.82 days and 3.1 days, respectively (MD -0.30, 95% CI -0.45 to -0.14).
			Time to sore throat resolution	Only reported in one study. Mean duration of sore throat was 2.19 days (SD 0.81) in the short duration treatment group and 2.69 days (SD 1.13) in the standard duration treatment group (MD -0.50, 95% CI -0.78 to -0.22).
			Early clinical treatment failure (persistence in symptoms within the first 2 weeks of treatment completion)	19 study reported on this outcome. The short duration treatment group showed a lower risk of early clinical treatment failure (OR 0.80, 95% CI 0.67 to 0.94).
			Late clinical recurrance (recurrance of symptoms, after initial resolution, beyond the 2 weeks post treatment)	Thirteen studies assessed the risk of late clinical recurrence. The risk of late clinical recurrence was not statistically different between short duration and standard duration groups (OR 0.95, 95% CI 0.83 to 1.08).
			Early bacteriological treatment failure (persistence of the same strain of GABHS within the first 2 weeks after completion of treatment)	All included studies assessed this outcome. There was no significant difference in the risk of early bacteriological treatment failure between short duration and standard duration groups (OR 1.08, 95% CI 0.97 to 1.20).
			Late bacteriological recurrance (recurrance of thesame GABHS strain, after initial resolution, beyond the first 2 weeks after completion of treatment)	All studies assessed this outcome. The risk of late bacteriological recurrence was significantly worse in the short duration treatment groups (OR 1.31, 95% CI 1.16 to 1.48). However, when eliminating the studies of low-dose azithromycin (10mg/kg), which performedmuch worse than other short duration regimens (OR 3.62, 95% CI 2.66 to 4.92), the two treatment groups were no longer statistically different (OR 1.06, 95% CI 0.92 to 1.22).

Comment(s)

These papers are comparing short-courses of different antibiotics with the standard treatment of tonsillitis which is 10 days of penicillin V. More evidince exists comparing different antibiotics with the current gold standard but there aren't many recent evidence to compare between a shorter course of penicillin with the standard 10 day course.

Clinical Bottom Line

Shorter courses improves compliance and in most cases resolves symptoms and eradicates the organism. However, more often than not, it's not as effective as 10 day penicillin V course in terms of long term effects and recurrance rates.

References

1. Cohen R. Reinert P. De La Rocque F. Levy C. Boucherat M. Robert M. Navel M. Brahimi N. Deforche D. P Comparison of two dosages of azithromycin for three days versus penicillin V for ten days in acute group A streptococcal tonsillopharyngitis Pediatric Infectious Disease Journal 2002
2. D.Adam et al Comparison of short-course (5 day) cefuroxime axetil with a standard 10 day oral penicillin V regimen in the treatment of tonsillopharyngitis Journal of Antimicrobial Chemotherapy 2000
3. M.Falagas et al. Effectiveness and safety of short-course vs long-course antibiotic therapy for group a beta hemolytic streptococcal tonsillopharyngitis: a meta-analysis of randomized trials. Mayo Clinic Proceedings 2008
4. Altamimi S. Khalil A. Khalaiwi KA. Milner R. Pusic MV. Al Othman MA. Short versus standard duration antibiotic therapy for acute streptococcal pharyngitis in children. [Review] [38 refs] Cochrane Database of Systematic Reviews 2009