I72 Let ters to the Edi tor

2. Wheeler AP, Clark RG. Campylobacter bacteraemia, cholecystitis and the Acquired Immunodeficieney Syndrome Ann Intern Med I986; xos: 804.

3. Smibert RM. The genus Campylobacter. Ann Rev Microbiol I978; 3z: 673-709. 4. ScmidtU, Chmel H, Kaminski Z, Sen P. The Clinical Spectrum of Campylobacter fetus

Infection: Report of five cases and review of the literature. Q J Med I98O; 49:43r-442. 5. Perlman DM, Ampel NM, Schifman RB et al. Persistent Campylobacterjejuni Infection in

patients infected with human immunodeficiency virus (HIV). Ann Intern Med ~988 ; xo8: 540-546 •

Idiosyncratic reaction to nebulised ribavirin

Accepted for publication 28 September x989

Sir, Cosgrove et al. ( j 7 Infect I989; x9: 85-87) have reported a probable idiosyncratic reaction to nebulised ribavirin in an artificially ventilated neonate. T h e authors kindly sent us a copy of their manuscr ipt (which originally described their generally favourable experience with ribavirin in a number of ventilated neonates) and this case was repor ted by us at that t ime to both the U .K . Commit tee on Safety of Medicines and U.S. Food and Drug Administrat ion, as a probable adverse reaction to the drug.

Ribavirin is used widely throughout the world for the t reatment of viral bronchiolitis, and appears to be extremely safe; in a recent review of an estimated 26 ooo t reatments administered in the U.S.A. over 2~ year period 1 the reported adverse reaction rate was found to be 0"07 % ; none of the reported reactions was considered to be serious, the commonest being minor skin rashes and mild, transient bronchospasm. An abrupt fall in oxygenation on initiating t reatment has not previously been described al though a recent report ment ioned an infant with congenital heart disease who had an unexplained cardiorespiratory collapse on the ventilator shortly after starting ribavirin ;2 no further details were given.

I t is interesting that dramatic changes in oxygenation in the baby reported by Cosgrove et al. (I989) had already been documented prior to initiation of ribavirin therapy; none the less, the recurrence of hypoxia on four separate challenges seems to confirm the association with ribavirin administration. I t is, however, difficult to suggest the mechanism involved. In theory, severe bronchospasm could have been the cause, but it is unlikely that this would resolve immediately on withdrawing the drug, as stated. Indeed, the instantaneous improvement reported on halting ribavirin administrat ion is more suggestive of a mechanical problem and I wonder if the authors had excluded the possibility of a blocked filter in the circuit or some other impediment to the free flow of oxygen to the infant.

Seaton and Johnson have recently reported statistically significant (albeit clinically modest) rises in systemic blood pressure (BP) during administrat ion of nebulised r ibav i r in ) This effect is in accord with the results of animal pharmacological studies (unpublished data on file, Viratek) which demonstrated modest , transient rises in systemic BP after intravenous administrat ion of ribavirin. We have no data on the effects of ribavirin on pulmonary arterial pressure. As it stands the known pharmacological effect of ribavirin in increasing systemic BP slightly should have reduced the degree of r ight-to-left shunt via a septal defect and patent ductus arteriosus, and thereby have improved oxygenation in this particular baby. Previous studies have shown significant improvement in oxygenation on ribavirin therapy compared with placebo, in both previously healthy infants 4 and those with underlying cardiopulmonary disease)

T h e causative mechanism of this reported reaction therefore remains undetermined. We would fully endorse Cosgrove et al.'s call for careful recording and report ing of

Let ters to the Edi tor 173

any suspected reaction to ribavirin, as with any relatively new medicine; it is only in this way that a comprehensive side-effect profile can be compiled and appropriate warnings included in the product literature.

Viratek Inc., I C N Biomedicals, N . J . C. Snell Lincoln Road, Cressex Estate, High Wycombe, H P I 2 3XJ , U.K.

R e f e r e n c e s

i. Janai H, Zaleska M, Marks M et al. National surveillance of ribavirin utilisation over two and a half years. Proc i6th Int Congress of Chemother, Jerusalem, June I989; p. i i i .

2. Sharland M, Whitehouse N, Qureshi S. Ribavirin in respiratory syncytial virus infection. Arch Dis Child I989; 64: 425.

3. Seaton E, Johnson G. Unexpected blood pressure increase associated with aerosolised ribavirin. Pediatr Res I988; 23: 38IA.

4. Breese Hall C, McBride J, Walsh E et al. Aerosolised ribavirin treatment of infants with respiratory syncytial virus infection. N Engl J Med I983 ; 3o8: I443-7.

5. Breese Hall C, McBride J, Gala C et al. Ribavirin treatment of respiratory syncytial viral infection in infants with underlying cardiopulmonary disease. J A M A I985; 254: 3047-305 I.

E l i m i n a t i o n h a l f - l i f e o f a m p h o t e r i c i n B

Accepted for publication I9 October I989

Sir, The clinical use of amphotericin B (AmB) is now a matter of concern to general physicians and surgeons because it is no longer an infrequently prescribed medication reserved to specialists in infectious diseases. This has come about because: (I) a rise in the frequency of systemic fungal infections has followed advances in medical and surgical therapies that preserve more and more patients with host defences crippled by diseases and the broadaxe therapies applied to them; (2) some 36 years after its d i s cove ry /AraB remains the most effective agent for treating systemic mycoses; and (3) AmB may be the most toxic antimicrobial agent used in systemic therapy.

Because the frequency of dosing appears to be an important determinant of toxicity, the elimination half-life of AmB from the blood may be clinically relevant. Published data on this point are sparse. In a report published in I958, 2 the half-life of AmB in the blood was said to be about 24 h but supportive data were not provided.

More recentlyfl the terminal half-life for elimination of AmB was calculated to be approximately I5 days in two adult patients with disseminated histoplasmosis. It is a value of doubtful relevance to setting dosing intervals because no account was taken of phases of disappearance from the blood that differ in rates of elimination. Moreover, the frequency of dosing differed in the two patients and the periods of administration of AraB were not specified.

Starke et al. 4 studied five premature children and five older children. The half-life of AraB in the serum varied from 7 to 693 h, variations that probably had little to do with dosage but probably reflected the relative immaturity of metabolic and excretory capabilities as well as variations in periods of infusion.

We made three separate series of measurements of the disappearance of AraB from the blood during the course of uniform treatment of a 65-year-old white man referred for care of persistent, progressive coccidioidomycosis of his left elbow. One week after