A Historical Perspective
The article by Dr. elMoussaui et al (1) is a worthwhile attempt to
establish the optimal antibiotic duration for a common condition.
For this discussion it is worthwhile considering the case Group A
Streptococcus pyogenes (GAS). In the early 1950s the Streptococcal
Research Group based at the Francis E. Warren Air Force Base in Wyoming,
USA, published a series of articles on penicillin treatment and
prophylaxis for GAS. Their research was performed during GAS pharyngitis
epidemics at the base which were leading to hospitalization rates of 10-13
per 1000 men per week (2). They found that by using intramuscular (IM)
injections of procaine penicillin at admission, 48 hours, and 96 hours,
they could reduce the prevalence of culture positive GAS pharyngitis from
98.5% at admission to 3.1% 48 hours later. After a full course of
treatment, the prevalence at five weeks was 10.7% in the treated group
compared to 46.7% in the placebo group (2). In a subsequent trial
examining penicillin prophylaxis, they used the same dosing regimen to
show an absolute risk reduction of 3.94% (4.52% controls, 0.58% treated)
in the incidence of primary rheumatic fever (3). The latter trial is
regarded as the only properly randomized and controlled trial for the
prevention of primary rheumatic fever (4).
Future studies with benzathine penicillin would reveal that a single
900,000 unit IM dose could prevent nearly all cases of GAS pharyngitis for
up to twenty-one days (5).
These studies are noteworthy because they illustrate how a virulent
and deadly pathogen can be effectively treated with a relatively small
dose of antibiotics, thus calling into question the often arbitrary
duration of antibiotic treatment. A greater focus on antibiotic duration
in future randomised, controlled trials will be necessary to enable
medicine to better treat infectious disease and effectively minimise
resistance to antibiotics.
1. el Moussaoui R, de Borgie CA, van den Broek P, Hustinx WN,
Bresser P, van den Berk GE, Poley JW, van den Berg B, Krouwels FH, Bonten
MJ, Weenink C, Bossuyt PM, Speelman P, Opmeer BC, Prins JM. Effectiveness
of discontinuing antibiotic treatment after three days versus eight days
in mild to moderate-severe community acquired pneumonia: randomised,
double blind study. BMJ 2006;332:1355-7.
2. Brink WR, Rammelkamp Jr. CH, Denny FW, and Wannamaker LW. Effect
of Penicillin and Aureomycin on the Natural Course of Streptococcal
Tonsillitis and Pharyngitis. American Journal of Medicine 1951;10(3):300-
3. Wannamaker LW, Rammelkamp Jr. CH, Denny FW, Brink WR, Houser HB,
and Hahn EO. Prophylaxis of Acute Rheumatic Fever. American Journal of
4. Bisno AL, Gerber MA, Gwaltney Jr. JM, Kaplan EL, Schwartz RH.
Practice Guideline for the Diagnosis and Management of Group A
Streptococcal Pharyngitis. Clinical Infectious Diseases 2002;35:113-25.
5. Davis J, and Schmidt WC. Benzathine Penicillin G: Its
Effectiveness in the Prevention of Streptococcal Infections in a Heavily
Exposed Population. NEJM;256(8):339-42.
Competing interests: No competing interests