When should you prescribe amoxicillin clavulanate?
One of the focuses of bpac programmes this year has been on the rational use of antibiotics. We have had many letters
from our readers about different scenarios of antibiotic use, with a large proportion relating to the use of amoxicillin
clavulanate. It appears that there is a lack of clarity surrounding the indications for its use.
Overview
Amoxicillin clavulanate is an important and effective broad spectrum antibiotic that is used widely in general practice.
The problem is not that it does not work, but rather the more it is used, the higher the likelihood that bacteria will
become resistant to this drug. Most infections can be successfully treated with other types of antibiotics and amoxicillin
clavulanate needs to be reserved for specific indications when it is really needed.
The most common first-line indications for amoxicillin clavulanate are for human or animal bites or clenched fist injuries
and for diabetic foot infections. Common second-line indications (after treatment failure with a narrow spectrum antibiotic)
include mild acute pyelonephritis and acute sinusitis.
Amoxicillin clavulanate is now a first-line treatment for acute pyelonephritis. For more information, see the latest edition of our handbook, "Antibiotics: Choices for common infections", bpacnz.
While use of amoxicillin clavulanate in New Zealand is reducing, prescribing figures are still high compared to other
countries. Amoxicillin clavulanate is familiar, it works well and it potentially saves a patient from having to return
to their doctor after treatment failure. However convenience for an individual has to be weighed against preventing bacterial
resistance for the entire community. Every time you think about prescribing amoxicillin clavulanate, consider whether
an alternative would be better.
Your clinical scenarios answered
Is it appropriate to prescribe amoxicillin clavulanate with roxithromycin for the treatment of
community acquired pneumonias?
Management of pneumonia is possible in the community when symptoms are not severe, and when the available care for an
individual is satisfactory. The choice of which oral antibiotics to use is generally made on empiric grounds to cover
the most likely causative organisms.
Community acquired pneumonia (CAP) is most commonly caused by Streptococcus pneumoniae. Even when showing relative
resistance in vitro, at standard or high doses, amoxicillin is the most active available oral β-lactam antibiotic against S.
pneumoniae.
The addition of the β-lactamase inhibitor clavulanic acid (as in amoxicillin clavulanate) adds nothing to the activity
of amoxicillin versus S. pneumoniae but is associated with increased adverse effects such as diarrhoea.
Neither amoxicillin nor amoxicillin clavulanate cover the atypical organisms, Mycoplasma pneumoniae, Chlamydia pneumoniae or Legionella
sp.
Most guidelines therefore suggest using amoxicillin as monotherapy for CAP with the addition of a macrolide or a tetracycline
if there is high clinical suspicion of atypical pneumonia or if there is lack of clinical response in 24 – 48 hours:
- Amoxicillin* 1
g three times per day, for seven days
- + /-
- Erythromycin 500 mg four times per day
or
- Roxithromycin 300 mg once per day
or
- Doxycycline 200 mg stat then 100 mg once per day
Treatment with amoxicillin clavulanate is appropriate for post viral/influenza pneumonia, where Staphlococcus aureus is
often implicated, and to cover anaerobes in aspiration pneumonia.
H. influenzae and M. catarrhalis, although associated with exacerbations of COPD, are uncommon causes
of CAP and therefore the extra cover provided by amoxicillin clavulanate is unnecessary.
The treatment guidelines for CAP cover a range of clinical scenarios from treating relatively well people at home to
those who are critically ill and require hospitalisation. The recommended regimens for hospitalised patients with poor
prognostic indicators differ from those appropriate for community level management.
Bibliography:
Bjerre L, Verheij T, Kochen M. Antibiotics for community acquired pneumonia in adult outpatients. Cochrane Database
Syst Rev 2004;2:CD002109.
British Thoracic Society. BTS guidelines for the management of community acquired pneumonia in adults: update 2009.
Thorax 2009;64(Suppl III):iii1-iii55.
Cregin RG. Current management issues associated with community-acquired pneumonia. J Pharm Pract 2003;16(5):324–34.
Low DE. Treatment of community-acquired pneumonia. CMAJ 2008;179(12):1269-71.
NHS Clinical Knowledge Summaries. Community acquired pneumonia. Available from: www.cks.nhs.uk
SIGN. Community management of lower respiratory tract infection in adults: a national clinical guideline. Scottish Intercollegiate
Guidelines Network, 2002. Available from: www.sign.ac.uk
Stocks N, Turnbridge J, Crockett A. Lower respiratory tract infections and community acquired pneumonia in adults. Aus
Fam Physician 2004;33(5):297-301.
Woodhead M, Blasi F, Ewig S, et al. Guidelines for the management of adult lower respiratory tract infections. European
Respiratory Society, 2005. Available from: http://dev.ersnet.org
In some clinics, pelvic inflammatory disease (PID) is treated empirically with doxycycline and
amoxicillin clavulanate. Is this ideal?
The majority of cases of PID are sexually acquired. Approximately two-thirds of cases are associated with chlamydia
and/or gonorrhoea. Vaginal flora such as those present with bacterial vaginosis and Mycoplasma genitalium are also associated
with PID.1,2
Non-sexually acquired PID is rare but may arise after procedures that breach the protective cervical barrier such as
interuterine device insertion, dilation and curettage and surgical termination of pregnancy. In terms of management, guidelines
do not differentiate between these groups.
Treatment protocols are designed to reflect the common microbiological aetiologies and patterns of resistance. Amoxicillin
clavulanate was traditionally used as part of a treatment regimen for PID, however due to increased resistance, it is
no longer recommended. Resistance of N. gonorrhoea to penicillin is through two separate mechanisms: β-lactamase
resistance, which can be countered by the use of amoxicillin clavulanate, or by altered penicillin binding proteins which
results in resistance to amoxicillin clavulanate. Between April and June 2008 over 80% of isolates of N. gonorrhoea in
New Zealand were found to have this second mechanism of resistance, making them resistant to amoxicillin clavulanate.1
A suggested regimen for PID is:2,3
- Doxycycline 100 mg twice per day for 14 days
- or azithromycin 1 g stat (for chlamydia)
- And ceftriaxone 250 mg IM stat (for gonorrhoea)
- And metronidazole 400 mg twice per day for 14 days (for vaginal flora)
It is recommended that patients should be followed up at 72 hours and then four to six weeks post treatment.
N.B. In our Antibiotic report/express audit, May 2009, we gave advice that mild to moderate
non-sexually acquired PID should be treated with amoxicillin clavulanate and doxycycline. However in practice, all PID
is treated the same. Amoxicillin clavulanate is not indicated and the regimen of doxycycline, ceftriaxone and metronidazole
should be used.
References:
- ESR. Antimicrobial resistance among Neisseria gonorrhoeae April to June 2008. Public Health Surveillance. 2008. Available
from
www.surv.esr.cri.nz/antimicrobial/neisseria_gonorrhoeae.php (Accessed
September 2009).
- Sweet RL. Treatment strategies for pelvic inflammatory disease. Expert Opin Pharmacother 2009;10(5):823-37.
- Dayan L. Pelvic inflammatory disease. Aus Fam Phys 2006;35(11):858-62. Available from
http://www.racgp.org.au/afp/200611/12508
What is the appropriate antibiotic(s) to use for perianal cellulitis to prevent abscess formation
in adults? In view of the fact that anaerobic organisms are likely to be involved amoxicillin clavulanate is often used.
Perianal cellulitis is most commonly seen in young children and is mainly associated with group A streptococcus. In
adults, this type of perianal cellulitis is very unlikely, however there are clinical situations where adults, usually
males, present with signs of perianal pre-abscess.
There is a lack of evidence about the best early treatment to prevent the formation of an abscess. Isolates of abscess
pus are commonly polymicrobial. Therefore if considering empirical treatment of a pre-abscess a broad spectrum antibiotic
should be used. In this case amoxicillin clavulanate 500/125 mg three times per day for five to seven days, is appropriate.
This regimen does not cover N. gonorrhoea, so depending on the patient’s history, rectal swabs for gonorrhoea
may be considered.
ACKNOWLEDGEMENT Thank you to Assoc. Prof Mark Thomas, Infectious Disease
Specialist, Dr Celia Devenish, Obstetrician and Gynaecologist and Dr Jill McIlraith, GP and Sexual Health
Clinician for expert guidance in developing this document.
Once an abscess has formed, even if non-fluctuant, the recommended treatment is incision and drainage. In patients with
no confounding risk factors (e.g. immunosuppression), antibiotics are of no benefit. The action of antibiotics is impaired
by the abscess environment and their use has no effect on long-term prognosis such as fistulae.1