(Aust Prescr 1994;17:55-6)
Letters, which may not necessarily be published in full, should be restricted to not more than 250 words. When relevant, comment on the letter is sought from the author. Due to production schedules, it is normally not possible to publish letters received in response to material appearing in a particular issue earlier than the second or third subsequent issue.
Use of amoxycillin trihydrate/potassium clavulanate
Editor, — In his article `The promotion of Augmentin' (Aust Prescr 1993;16:89), Dr P. Mansfield ranks several antibiotics for the treatment of otitis media. This ranking is in accordance with recommendations made by the Victorian Drug Usage Advisory Committee.1 Dr Mansfield seems to justify the ranking by citing Appelman et al.2 in stating that Augmentin `has no significant benefit over placebo in treating children over two years with acute otitis media'. The obvious inference we are meant to draw is that Augmentin is relatively ineffective and thus we ought not to expose our patients to the risk of drug-induced morbidity by using it. Thus, the first choice of the several antibiotics listed is amoxycillin, with Augmentin being placed last.But is not the effective principle in both preparations the same? As I understand it, potassium clavulanate has no deleterious effect on the actual bactericidal efficacy of amoxycillin. Thus, is it not the case that amoxycillin, on its own, ought also to have `no significant benefit over placebo'? How then can it be ranked first over the other antibiotics listed, while, when compounded with something to improve it, it ranks last? Is Dr Mansfield being just as `inappropriate' as he claims the pharmaceutical manufacturers are in their advertising?
I agree that as far as morbidity is concerned, there may be good cause to prefer one preparation over the other, but I think that the argument as stated does not follow the laws of logic. Or is there some reason why the amoxycillin trihydrate in Alphamox, Amoxil, Cilamox, Fisamox or Moxacin has better bactericidal properties than the amoxycillin trihydrate in Augmentin?
Perhaps he can enlighten us?
A.G.
Moskwa
Senior
Lecturer
School
of Pharmacy and Medical Sciences
University
of South Australia
Adelaide,
S.A.
R E F E R E N C E S
1. Victorian Drug Usage Advisory Committee. Antibiotic guidelines. 7th ed. Melbourne: Victorian Medical Postgraduate Foundation, 1992.
2.
Appelman CL, Claessen JQ, Touw Otten FW, Hordijk GJ, de Melker
RA. Co-amoxiclav in recurrent acute otitis media: placebo controlled study.
Br Med J 1991;303:1450-2.
Dr P. Mansfield, the author of the article, and
Dr M.L. Mashford, Chairman of the Antibiotic Guidelines Subcommittee of
the Victorian Drug Usage Advisory Committee, comment:
The aim of MaLAM's reports for Australian Prescriber is to hint
at the reasons for asking questions about drug promotion such as SmithKline
Beecham's claim that `When you need to be sure in otitis media and sinusitis,
you need Augmentin'. That promise of certainty is seductive, but real
life is complex and uncertain.
Augmentin is more effective than amoxycillin alone against beta-lactamaseproducing bacteria in vitro. However, our responsibility is to treat people, not Petri dishes. In otitis media and sinusitis, in vitro susceptibility does not predict clinical outcome.1,2 Around 76% of patients with otitis media will recover without an antimicrobial.1 In some of the remaining 24%, viral involvement will defeat any antimicrobial.1
The Victorian Drug Usage Advisory Committee's new 1994-95 edition of `Antibiotic Guidelines' still recommends amoxycillin for otitis media, but only when severe signs are present. A New South Wales Health Department Working Party has also recommended that amoxycillin be used.3 Perhaps the best evidence to support those recommendations is a British study which found that amoxycillin is better than placebo in the short term, but not in the medium or long term.4
Future clinical studies may enable us to identify which patients are most likely to benefit from antimicrobials rather than suffer adverse effects. Meanwhile, we can not `be sure' whom to treat with what. However, it is logical to prefer amoxycillin. Augmentin is more expensive and is associated with a 13% incidence of adverse effects.5 Because adverse effects cause more patients to prematurely cease courses of Augmentin6, it may be even less effective than amoxycillin.
R E F E R E N C E S
1. Giebink GS, Canafax DM, Kempthorne J. Antimicrobial treatment of acute otitis media. J Pediatr 1991;119:495-500.
2. Victorian Drug Usage Advisory Committee. Antibiotic guidelines. 7th ed. Melbourne: Victorian Medical Postgraduate Foundation, 1992.
3.
N.S.W. Health Department Working Party. Guidelines on the management of
paediatric middle ear disease. Med J Aust 1993;159(7
Suppl):1S-8S.
4. Burke P, Bain J, Robinson D, Dunleavey J. Acute
red ear in children: controlled trial of nonantibiotic treatment in general
practice. Br Med J 1991;303:558-62.
5. Neu HC, Wilson AP, Gruneberg RN. Amoxycillin/clavulanic acid: a review of its efficacy in over 38,500 patients from 1979 to 1992. J Chemother 1993;5:67-93.
6. Wald ER, Chiponis D, LedesmaMedina J. Comparative effectiveness of amoxycillin and amoxycillinclavulanate potassium in acute paranasal sinus infections in children: a doubleblind, placebocontrolled trial. Pediatrics 1986;77:795-800.
Editor, — In Australian Prescriber Vol. 16 No. 4, there are two letters by A.W. Hartwig (`Letters' Aust Prescr 1993;16:76). In a reply to one of these, regarding malaria prophylaxis, Drs I. Riley and A. Cooper state that `... doxycycline is sufficient to suppress P. falciparum but not other species'. In the very next letter, Dr A. Broomhead, after apparently confirming that `Doxycycline is indicated ... as chemoprophylaxis for malaria caused by P. falciparum', then states that `Doxycycline is only able to suppress malaria caused by P. vivax'.Are those not contradictory statements, or is it just that we are suffering from an epidemic of the `miller's beautiful daughter/beautiful miller's daughter' syndrome of A.W. Hartwig's first letter?
It is quite possible to use words to express unambiguously exactly what is meant. What are the word `suppress' and the placing of the word `only' meant to indicate?
In
`suppressing' the malarial parasites, does doxycycline actually kill P.
falciparum as opposed to `only' inhibiting the growth of P. vivax?
Or does it suppress `only' P.
vivax and not P. falciparum?
Could I please ask for clarification?
A.G.
Moskwa
Senior
Lecturer
School
of Pharmacy and Medical Sciences
University
of South Australia
Adelaide,
S.A.
Editor,
— In reply to the letter from Dr Hartwig (Aust Prescr 1993;16:76),
it has been mentioned that doxycycline 50 mg daily is sufficient to suppress
P.
falciparum but not other species, whereas in the letter from Dr A.
Broomhead the last line says `Doxycycline is only able to suppress malaria
caused by P. vivax.'
Dr A.S. Deshpande
Ahmedabad,
India
The following
response has been prepared by the Editor after consultation with Professor
K. Rieckmann, Army Malaria Research Unit, Professor I. Riley and Dr
A. Broomhead:
Certain terms have acquired specific meanings and are well established
in the literature of antimalarial chemotherapy and chemoprophylaxis.1
• Suppressive prophylaxis is the effective prevention of acute attacks of malaria by the action of drugs against the asexual blood forms only.
• Causal prophylaxis is the effective prevention of acute attacks of malaria by the action of drugs against the sporozoite or against the preerythrocytic stages.
Parasites can be present in the bloodstream, but not be detectable on light microscopy (subpatent infection) and not cause clinical malaria. A suppressive prophylactic can be effective but permit subpatent infection. Without the aid of more sensitive tests, evidence of subpatent infection can only be obtained when subjects experience `breakthrough' while still taking the drug or recrudescence after ceasing the drug.
Doxycycline acts against the asexual erythrocytic stages of P. falciparum and P. vivax. It has only slight activity against the preerythrocytic stages of P. vivax and has recently been shown not to be uniformly effective against the preerythrocytic stages of P. falciparum. As the drug is not active against the dormant tissue forms (hypnozoites) of P. vivax, relapse may occur after cessation of doxycycline prophylaxis.
A dose of 100 mg doxycycline daily can be expected to suppress both P. falciparum and P. vivax malaria by acting against asexual blood, but not tissue, forms. At a dose of 50 mg, P. falciparum is suppressed, but breakthroughs of P. vivax are known to occur.2 As chloroquine resistance in P. vivax is still rare, the combination of doxycycline and chloroquine is logical for travellers to areas where P. falciparum and P. vivax co-exist.
Hypnozoites
are not affected by either drug so relapses of P. vivax may occur
after therapy has been stopped. P.
vivax relapse can only be prevented by an 8-aminoquinoline such as
primaquine. This drug can be taken by travellers after return from overseas
if there has been a heavy exposure to malaria.
References
1. Desjardins RE, Doberstyn EB, Wernsdorfer WH. The treatment and prophylaxis of malaria. In: Wernsdorfer WH, McGregor I, editors. Malaria: principles and practice of malariology. Edinburgh: Churchill Livingstone, 1988:827-64.
2. Pang L, Limsomwong N, Singharaj P. Prophylactic treatment of vivax and falciparum malaria with lowdose doxycycline. J Infect Dis 1988;158:1124-7.
