ISSUE No. 42 The international newsletter on the control of diarrhoea1 diseases are really needed. Third, in some coun- Drugs and childhood diarrhoea tries, widespread use of antimicrobials has led to high levels of antibiotic resistance - this means that the antibiotics are no Oral rehydration therapy should be the commonly used to treat diarrhoea, explain- longer effective. On page 5, DD describes priority treatment for childhood diarrhoea. ing why they are not appropriate for acute how antibiotic resistance develops and why Ninety five per cent of acute childhood diarrhoea in children. The next two issues it is a serious problem. diarrhoea, whatever the cause, can be suc- will include reviews of antimotility drugs cessfully treated with ORT and continued and adsorbents. Working together feeding, and does not require treatment To reduce inappropriate use of drugs for with drugs. Despite widespread promotion Unnecessary prescribing diarrhoea, a co-ordinated response is of this message, doctors continue to Unnecessary prescribing has several needed. This involves legislation, training prescribe ineffective, expensive and important disadvantages. First, giving and education of doctors and the public, unnecessary drugs to treat diarrhoea; powerful drugs to small children does not and ensuring that messages about drug families continue to ask their doctors for stop the diarrhoea, may cause dangerous treatment for diarrhoea are consistent. The them or buy them over the counter from side effects and can result in families article on page 7 describes the coordinated pharmacists; and manufacturers continue neglecting to rehydrate and feed a sick approach being taken in Peru, where the to promote and market a wide range of child. Second, drugs are expensive for Ministry of Health, health professionals anti-diarrhoeals. In many countries, drugs families and for the health system. The and activists are working together to tackle are used more than ORT to treat diarrhoea resources saved by reducing unnecessary the problem of widespread over-use of (see pages 6 and 7). On pages 2, 3 and 4, prescribing could-be better-used in other anti-hiarrhoeal drugs in children. DD reviews some of the antibiotics most ways and the drugs saved for when they KME, WAMC and KA Use of ORS and druas for diarrhoea _ it? 60 50 40 30 20 10 0 c Africa Americas South East East Western Asia Mediterranean Pacific n ORS use rate Drug use rate Information from 140 household surveys in 47 countries, up to 1989 Source: WHO Programme for Control of Diarrhoea1 Diseases Seventh Programme Report (1988-l 989) WHOICDDl90.34 In this issue: 0 Drugreviews and resources 0 Antibiotic resistance Appropriate Health Resources & Technologies Action Group Ltd 0 Reports from Peru, Pakistan and Indonesia Dialogue on Diarrhoea, issue 42, September 1990. Published quarterly by AHRTAG, 1 London Bridge Street, London SE1 9SG, UK. 1 Drugs and diarrhoea In most cases of childhood diarrhoea, drugs are The role of some antibiotics in treating unnecessary and inappropriate. The WHO CDD shigellosis is well established, but not all antibiotics are equally effective. Some programme has reviewed the literature on the early uncontrolled studies reported good efficacy and side effects of the most widely used results from treating shigellosis with oral drugs. In this issue DD previews the information aminoglycosides. Others showed bacterial and clinical cure rates of less than 50 per available on three types of antimicrobial agents - cent, and two suggested that streptomycin neomycin, streptomycin and hydroxyquinolines. and neomycin were no better in shigellosis therapy than simple supportive care. A double blind trial comparing neomycin 1 Diarrhoea can be caused by: with ampicillin provided further evidence Neomycin of the ineffectiveness of non-absorbable 8 0 Viruses - mostly rotavirus antibiotics such as neomycin in shigellosis Nzmycin, an antibiotic contained in 0 Bacteria - virtually all are Gram- treatment. many oral anti-diarrhoeal preparations, negative aerobic pathogens Studies have also shown that antibiotic has not been proved to be effective in the 0 Protozoa - especially Cryptosporidia, therapy can actually prolong the carrier treatment of acute diarrhoea. Neomycin Giardia and amoeba state in Salmonella gastroenteritis, and given by mouth has been associated with clinical relapse may be more frequent in 2 Antibiotics are, in general, only useful for toxic effects on the gut and may worsen patients treated with antibiotics. Placebo or prolong diarrhoea. Widespread use bacteria. lltey are ineffective for viruses and have very limited value for protozoa, controlled trials of neomycin, ampicillin, of antibiotics such as neomycin can and amoxycillin have confirmed that these increase antimicrobial resistance. Oral e.g. tetracycline is partly eflective for amoeba. There are, however, anti- antibiotics are ineffective in treating preparations containing neomycin are protozoals for amoeba and Giardia. Salmonella gastroenteritis. not recommended for use in the treat- ment of diarrhoea. 3 Antibiotics are ineffective for many food Adverse effects poisoning Salmonella. i%y are not prac- Neomycin can damage the structure of the Formulations tical for other bacterial diarrhoeas, except gut and interfere with its normal function. Neomycin is an aminoglycoside antibiotic cholera and shigellosis, because one can- It can cause malabsorption of fats, sugars used either alone or in combination with not determine clinically what bacten’um and calcium. After as little as three days, intestinal adsorbents, antimotility agents, is involved, if any, and thus what destruction of the microvilli lining the sur- antibiotic to give. or other antibiotics*. face of the small intestine can appear; and after seven days, invasion of the sub- Pharmacology duce enterotoxin. Widespread use of mucosal layer of the small bowel by Neomycin is classified as non-absorbable neomycin may therefore not only increase wsinophilic white cells has been Observed. - most of a dose given by mouth is the frequency of antibiotic resistant micro- Controlled trials have demonstrated that excreted unchanged in the stool, although organisms, but may also help bacteria that extended courses of neomycin prolonged some absorption does occur in the cause diarrhoea through enterotoxin to sur- the duration of diarrhoea. gastrointestinal tract. What is absorbed is vive and spread. When given by injection, amino- primarily excreted in the urine. glycosides are known to produce toxic Efficacy effects on the kidneys and ears. Because How it works Studies of neomycin in acute diarrhoea (of neomycin is usually given by mouth in Neomycin is rapidly bactericidal (it kills unknown aetiology) have reported ‘cure’ diarrhoea treatment and is poorly and inhibits reproduction of bacteria rates ranging from 50-100 per cent. absorbed, these complications are uncom- quickly). It is active against most aerobic However, none included placebo controls, mon, but there have been reports of toxic Gram-negative organisms (see box) and and since most acute diarrhoeas are self- effects with prolonged therapy or high staphylococci, but resistant strains of limiting, these reports of ‘cures’ are not doses, especially when kidney function is Escherichia colt, Klebsiella, Proteus, meaningful. already impaired. Shigella, and Salmonella are common. One double blind, placebo-controlled Streptococci and Gram-positive bacilli are trial (see box, page 4) of neomycin in acute Source: the text on pages 2 to 4 has been also largely resistant. diarrhoea indicated that neomycin may adapted by DD from draft material prepared The mechanism of resistance of Gram- actually increase the severity and prolong by the Control of Diarrhoeal Diseases Pro- gramme of the World Health Organization negative organisms to neomycin can also the duration of the disease. There are no reported trials assessing neomycin in the (WHO). A series of nine reviews is in confer resistance to other antibiotics (see preparation covering drugs commonly used page 5). These resistance factors, which treatment of diarrhoea caused by enterotoxigenic , entero-adherent, entero- in the treatment of diarrhoea. They will be can be transferred between bacteria, can grouped in three sections: antimicrobials, haemorrhagic or entero-invasive E. coli. sometimes also convey the ability to pro- antimotility drugs and adsorbents, and Some uncontrolled clinical observations published together as a WHO publication have reported good response of EPEC entitled l7re rational use of drugs in the *With all drug preparations it is important infections to neomycin therapy, but others management of acute diarrhoea in children, to look carefully at the contents or ingre- have noted little difference between to be available early in 1991 from: dients as well as the brand name. neomycin and supportive therapy alone. CDD/WHO, 1211 Geneva 27, Switzerland. 2 Dialogue on Diarrhoea, issue 42, September 1990. Published quarterly by AHRTAG, 1 London Bridge Street, London SE1 9SG, UK. Drugs and diarrhoea Formulations and drug interactions Neomycin is usually sold in combination with a variety of adsorbents or other antibiotics. None of these combination pro- ducts has been shown to be effective in clinical trials. The hydroxyquinolines con- tained in many of them have been withdrawn and prohibited in many coun- tries because of their dangerous effect on the nervous system, while kaolin and pec- tin components can interfere with the absorption of certain