8th July 2011, Volume 124 Number 1337

Diana Lennon, Melissa Kerdemelidis, Bruce Arroll, Norman Sharpe

We wish to highlight that oral amoxicillin is as valid a first-line treatment for GAS pharyngitis as oral penicillin V in the National Heart Foundation sore throat management guidelines for New Zealand.1,2

Oral penicillin V 500 mg bd for adults, and 20 mg/kg/day for children (in 2-3 divided doses) is long-established in the international literature and guidelines as first-line treatment for Group A Streptococcal pharyngitis.1,2 However, once-daily oral amoxicillin has emerged as a good alternative, with at least three studies3-5 finding ten-day oral courses of once-daily amoxicillin and penicillin V (2- to 4-times daily) to be equivalent for GAS pharyngitis. Further details of these studies can be seen in the National Heart Foundation’s sore throat guidelines.2 †

While it is very effective, oral penicillin has appreciable disadvantages. It is less palatable6,8 and needs to be given on an empty stomach, three or so times each day, all which can cause considerable difficulties for many patients and caregivers. Conversely with once-daily amoxicillin, although its evidence for GAS eradication comes from hundreds not thousands of patients,9 a single dose without coordinating around mealtimes will suit many patients and families and may help substantially improve adherence. Many families will find it more convenient to take the antibiotics with their food, and the amoxicillin option avoids trying to dose children with a worse-tasting medicine multiple times throughout the day while strictly on an empty stomach.

Once-daily amoxicillin has now been added as a treatment alternative in some other GAS sore throat treatment guidelines internationally, such as the American Academy of Pediatrics' Red Book10 and those of the American Heart Association.11

Oral amoxicillin can be given for 10 days at a dose of 750 mg once daily for children weighing <30 kg, and 1500 mg once daily for children weighing >30 kg2 (which equates to 15 ml per day of 250 mg/5 ml oral liquid, or three 250 or 500 mg capsules, depending on weight).

Previous communication in the Journal1 may have inadvertently understated the positive role of once-daily amoxicillin in GAS eradication and thus rheumatic fever control. As pointed out previously in the Journal,1 there is a need for some caution with amoxicillin and it will not be suitable for all cases of GAS pharyngitis. It should not be used when infectious mononucleosis (IM)/ Epstein Barr Virus (EBV) is suspected (see footnote *), or if a chance a patient may miss any daily dose (for those at high risk for rheumatic fever). However, amoxicillin still has some important advantages. In line with guidelines elsewhere,10,11 we encourage its use in the New Zealand epidemic setting12 alongside oral penicillin as the first-line options.


Note: These antibiotic recommendations only apply to symptomatic pharyngitis (not asymptomatic carriers of GAS).
Acknowledgement: Scott Metcalfe, PHARMAC, reviewed and helped revise earlier drafts.
Diana Lennon
Professor of Population Child & Youth Health / Paediatrician in Infectious Diseases
University of Auckland / Starship Children’s Hospital 
Auckland
d.lennon@auckland.ac.nz
Melissa Kerdemelidis
Public Health Medicine Registrar
Christchurch
Bruce Arroll
Professor and Head of General Practice & Primary Health Care 
University of Auckland 
Auckland
Norman Sharpe
Medical Director
The National Heart Foundation of New Zealand 
Auckland
Footnotes:
As pointed out previously in the Journal,1 there is a need for some caution with amoxicillin and it will not be suitable for all cases of GAS pharyngitis. It should not be given either:
  1. If there is doubt that it will be taken every day.13
This is due to the risk of rheumatic fever developing from improperly treated GAS pharyngitis theoretically in association with less frequent dosing schedules; or
  1. If infectious mononucleosis (IM)/ Epstein Barr Virus (EBV) rather than GAS is suspected as the cause of sore throat.14
Giving amoxicillin in infectious mononucleosis may cause a rash, with or without induced sensitivity to amoxicillin.1,2 If infectious mononucleosis is suspected, then erythromycin is safer than amoxicillin for treating pharyngitis. If a rash occurs in this setting, it is not inherantly harmful, and does not add to morbidity. It can be hard to diagnose infectious mononucleosis, although the triad of lymphadenopathy, splenomegaly and exudative pharyngitis in a febrile patient is often suspicious.15 Extreme tiredness may be an early sign in teenagers.
The table below may help practitioners diagnose suspected infectious mononucleosis16 ‡:
Table: Clinical manifestations of infectious mononucleosis in children and adults
Sign or symptom
Frequency (%)
age<4 yrs
age 4+ yrs
adults (range)
lymphadenopathy
fever
sore throat or tonsillopharyngitis
exudative tonsillopharyngitis
splenomegaly
heptomegaly
cough or rhinitis
rash
abdominal pain or discomfort
eyelid oedema
94
92
67
45
82
63
51
34
17
14
95
100
75
59
53
30
15
17
0
14
93-100
63-100
70-91
40-74
32-51
6-24
5-31
0-15
2-14
5-34
used with permission
By contrast, the clinical features of patients at high risk of GAS and developing subsequent rheumatic fever are in the sore throat guidelines’2 algorithms at http://www.nzma.org.nz/journal/122-1301/3746/algorithms.pdf (comprising risk factors and clinical signs) and Appendix F ‘Differential diagnosis of pharyngitis’ (page 47) of the sore throat guidelines.2
 Summaries of the comparative studies of oral penicillins in the treatment of GAS pharyngitis and their results3-5,17 can be found in a table in Appendix H, page 49, of the National Heart Foundation Group A Streptococal Sore Throat Management guidelines, available athttp://www.heartfoundation.org.nz/files/Rheumatic%20Fever%20Guideline%202.pdf A further study there found once-daily oral amoxicillin to be similar in efficacy to twice-daily oral amoxicillin for GAS pharyngitis.17 The three studies comparing oral once-daily amoxicillin with penicillin V3-5 contained 799 patients, and the study comparing once- with twice-daily amoxicillin17 had 652 participants.

Author Information

Diana Lennon, Professor of Population Child & Youth Health / Paediatrician in Infectious Diseases, University of Auckland / Starship Children’s Hospital, Auckland, Melissa Kerdemelidis, Public Health Medicine Registrar, Christchurch, Bruce Arroll, Professor and Head of General Practice & Primary Health Care, University of Auckland, Auckland, Norman Sharpe, Medical Director, The National Heart Foundation of New Zealand Auckland

Acknowledgements

Scott Metcalfe, PHARMAC, reviewed and helped revise earlier drafts.

Correspondence

Diana Lennon

Correspondence Email

d.lennon@auckland.ac.nz

References

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  2. National Heart Foundation of New Zealand, Cardiac Society of Australia and New Zealand. New Zealand guidelines for rheumatic fever: evidence-based, best practice guidelines on 2. Group A Streptococcal Sore Throat Management, 2008.http://www.heartfoundation.org.nz/files/Rheumatic%20Fever%20Guideline%202.pdf
  3. Shvartzman P, Tabenkin H, Rosentzwaig A, Dolginov F. Treatment of streptococcal pharyngitis with amoxycillin once a day. BMJ. 1993;306:1170-2.
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