ANAEROBIC ENDOCARDITIS: IS IT MISSED?

148

during the second eruption of chickenpox. Palm of left hand; bullous lesions with central necrosis on the right wrist; plantar side of left foot.

Case 1 : skin lesions

2 Case

A 7-year-old boy with acute lymphatic leukaemia in the first relapse, was being treated with vincristine, L-asparaginase, and prednisone. Chickenpox developed despite administration of zoster immunoglobulin 15 days earlier. He was treated with acyclovir (25 mg/kg i.v. per day in three doses) for 7 days. The disease ran a mild course without general illness, and not more than 60 skin lesions developed. Cytostatic therapy was discontinued except for one dose of methotrexate with citrovorum factor rescue, because of a rapid rise in peripheral blood lymphoblasts. 2 weeks after the onset of the chickenpox induction was tried with cytarabine (1000 mglm2per day i.v. for 12 days) and 6-thioguanine (75 per day orally) followed by 2 days of doxorubicin (40 mg/m i.v.). After 3 weeks of pancytopenia, remission was diag-

mf/m2

nosed. At that time, 7 weeks after the varicella, some bullous lesions developed on the head and neck, and then spread to the arms and trunk. The lesions were unlike chickenpox, being larger and irregularly shaped with a slightly haemorrhagic border and bottom. The fluid in the bullae was clear. Culture yielded varicellazoster virus; no antibody response against this virus had occurred. Because of the child’s poor general condition and the occurrence of convulsions of unknown origin, it was decided to treat him again with acyclovir. He died within 12 h after this treatment was started.

Necropsy was not permitted. These two patients developed a similar atypical skin rash caused by varicella-zoster virus, after treatment with acyclovir and very high dosages of cytotoxic and immunosuppressive drugs. Neither patient had antibodies against varicella-zoster virus. The intensive and immunosuppressive treatment had probably interfered with cellular and humoral immune responses. It is unlikely that the early antiviral treatment, meant that the amount of antigen was too low for an adequate immune response, since at the onset of the rash there is normally already some antibody production. Moreover, animal experiments have shown that if the interval between the challenge with herpesvirus and the start of treatment with acyclovir is longer than 24 h antibody production is not prevented. After treatment with acyclovir a recurrent varicella-zoster virus infection can be expected, in the absence of an adequate immune response, since animals experiments (unpublished) have shown that ganglia cannot be cleared of virus even with prompt and prolonged treatment with acyclovir.

cytotoxic

It might be advisable to give these patients zoster immunoglobulin during episodes of intensive chemotherapy, to prevent dissemination of virus from ganglia. M. H. Departments of Paediatrics, Infectious Diseases, and Virology, University Hospital, 2333 AA Leiden, Netherlands

VAN

WEEL-SIPMAN

J. W. M. VAN DER MEER J. DE KONING J. VERSTEEG

ANAEROBIC ENDOCARDITIS: IS IT MISSED?

SIR,-The diagnosis of mixed bacterial endocarditis is difficult, especially when one of the organisms is a fastidious anaerobe and the

patient has already started antibiotic therapy, making culture techniques unrewarding. In these circumstances gas-liquid chromatography (GLC) and indirect immunofluorescent assay (IF Al may be helpful. To illustrate this we report a case of Streptococciis vir/dans endocarditis whose response to therapy was poor. Further examination of blood cultures by GLC and IFA provided evidence that Bacteroides fragilis was an additional infecting organism requiring specific treatment. Without the application of these techniques the diagnosis would not have been possible. A 14-year-old boy was admitted to hospital with fever, dyspnoea, and signs of cardiac failure with evidence of severe mitral and aortic valve regurgitation. Blood cultures taken on admission grew "viridans streptococci" later identified as Strep. mitior, sensitive to penicillin. Treatment was started with penicillin 2 megaunits 4-hourly, diuretics, and digoxin. After a week of therapy, he had recurrent episodes of pulmonary oedema which necessitated an emergency operation at which both mitral and aortic valves were replaced with xenografts. No organisms were isolated from the removed valves. Gentamicin 80 mg 8-hourly was added. Postoperatively, the patient made a reasonable recovery at first. His serum showed good inhibitory and cidal titres against the Strep. mitior. 10 days later, however, he had respiratory distress, tachycardia (200 min), pyrexia (39-5°), and signs of aortic regurgitation, necessitating a second operation where the aortic prosthesis was found to have partly dehisced and had to be replaced. 1. Editorial Gas chromatographic diagnosis of infection Lancet 1980; ii: 513-14 2 Kasper DL, Fiddian AP, Tabaqchali S Rapid diagnosis of Bacteroides infections by in-

direct immunofluorescent assay of clinical specimens. Lancet 1979;

i:

239-42

149

Further blood cultures were taken. Gram-stained smears of the blood at 36 h showed scanty gram-negative (GN) rods, in four out of six bottles, which failed to grow on subculture. A generalised toxic erythematous rash compatible with penicillin hypersensitivity had also developed. Treatment was changed to cefuroxime I -5g8-hourly and amikacin 500 mg 8-hourly. Although the initial presumptive diagnosis was that this organism might be an aerobic opportunistic GN bacillus, the possibility that it could be an anaerobic GN rod was also considered, so GLC was done on 2 ml of blood from each of the blood culture bottles, from control uninoculated, and from inoculated blood culture bottles with no growth after 48 h using standard methods for the detection of short chain fatty acids.3 The chromatograms showed significant quantities of acetic, propionic, butyric, and succinic acids in the bottles in which GN rods had been seen, indicating the presence of anaerobic GN rods. The control bottles, apart from small amounts of acetic and lactic acid, were negative. IFA of smears from the positive blood culture bottles were tested with the pooled antisera of Bacteroides spp and anticapsular serum There was positive fluorescence with both antisera iden-

reported.2

tifying the organism as B. fragilis. Metronidazole was given intravenously (500 mg 8-hourly) for 24 h followed by metronidazole suppoositories 1 g twice daily which maintained serum levels of peak 26 -4 and trough 24-33 mg/l. Amikacin was stopped. The dosages of cefuroxime and metronidazole were halved after 3 weeks. Therapy was continued for 6 weeks. The patient now made an uneventful recovery and was discharged after 7 weeks. In the rapid diagnosis of anaerobic infections, the use of GLC to detect short-chain fatty acids in specimens of pus is now well documented,l3-5but its value in blood cultures is not yet well established,6,7 We previously reported the development and use of IFA in the rapid diagnosis of Bacteroicks infections,2but IFA has not been applied to blood culture before. In this patient, using both techniques, the diagnosis was made within 2 h. In most series of endocarditis, 20-30% are culture-negative, and these cases have worse prognosis. 8Although, Bacteroides spp have formed a small proportion of the causative organisms reported, particularly in mixed bacterial infections,10 some may have been missed. B. fragilis is resistant to the penicillins and aminoglycosides, usually given for treatment, thus more frequent use of GLC and IFA on blood cultures might be fruitful.

Anticapsular serum was kmdly provided by Dr D

Departments of Medical Microbiology, Cardiology, and Cardiothoracic Surgery, St Bartholomew’s Hospital, London EC 1

L.

Kasper.

SOAD TABAQCHALI A. R. WILLS T. RIORDAN S. O. BANIM G. M. REES

HYPERSENSITIVITY REACTION TO CHLORBUTOL-PRESERVED HEPARIN

SIR,-Allergic reactions to heparin are rare, and are usually attributed to heparin itself or to impurities. Hypersensitivity reactions to preservatives in heparin are even rarer. A 26-year-old woman taking anticoagulants subsequent to a mitral valve replacement for rheumatic heart disease, was transferred to our department 2 days after a normal vaginal delivery because she JG, Thadepali H, Onderdonk AB Rapid diagnosIs of anaerobic infections by direct gas liquid chromatograhy of clinical specimens J Clin Invest 1976; 57: 478-84 4 Phillips, KD, Tearle PV, Willis, AT Rapid diagnosis of anaerobic infections by gas liquid chromatography of clinical material J Clin Path 1976, 29: 428-30 5. Tabaqchali S, Fiddian AP, Atkinsoin P Recent techniques in the investigation and diagnosis of anaerobic infections J Infect 1979; 1: suppl 1, 13-22 6. Wust J Presumptive diagnosis of anaerobic bacteraemia by Gas Liquid Chromatography of blood cultures J Clin Microbiol 1977, 6: 586-90. 7 Sondag JE, Ali M, Murray PR Rapid presumptive identification of anaerobes in blood cultures by gas-liquid chromatography J Clin Microibiol 1980, 11: 274-77. 8 Editorial Culture negative endocarditis Lancet 1977; ii: 1164-65 9 Editorial Infective endocarditis with negative blood cultures Br Med J 1979, ii 4. 10 Nastro LJ, Finegold SM Endocarditis due to anaerobic Gram-negative bacilli Am J Medicine 1973; 54: 482-96 3 Gorbach SL, Mayhew JW, Bartlett

febrile and had a red, indurated eruption on both thighs, thought to be erysipelas. She had a purulent vaginal discharge and we noted a raised erythematous rash, with well defined margins, over the anterior and lateral aspects of both thighs. 2 days before her delivery, warfarin had been replaced by chlorbutol-preserved heparin administered subcutaneously in all four limbs,, and we suspected a hypersensitivity reaction to heparin. On careful examination of recent injection sites, red indurated areas were noted was

both arms also. Culture of the vaginal discharge grew Escherichia coli and the patient became afebrile on cephalothin treatment. The heparin injections were replaced by oral warfarin. The rash disappeared completely after a week. Intradermal skin testing with preservative-free heparin produced no response, while a 0 5% solution of chlorbutol (and O. 15070 chlorocresol) induced positive skin reactions. Macrophage migration was significantly inhibited by the patient’s lymphocytes; the mast cell degranulation test was negative. Chlorocresol and chlorbutol are common preservatives in pharmaceutical products. Adverse effects attributed to chlorocresol include contact sensitisationand delayed local hypersensitivityand systemic anaphylactoid3reactions to injections of heparin preserved with chlorocresol. We have not found any description of a similar allergic reaction to chlorbutol. Chlorbutol is often included in sedative compounds and antipruritic powders and its antibacterial and antifungal properties make it a suitable preservative for eye and nose drops and for a variety of injectables. Toxic effects of chlorbutol include hypotension, dyspnoea, and stupor. 4,5 A three-year survey, during which time over 30 000 million units of heparin with chlorbutol had been used 6 worldwide, revealed no reports of allergic reactions. Our patient was treated for 5 days with heparin preserved with chlorbutol (Leo) and erythema appeared at each injection site. The skin tests and other investigations confirm that a cellular type of delayed hypersensitive reaction to chlorbutol had developed. The positive immunological tests to chlorbutol and chlorocresol suggest previous contact with chlorocresol. The two molecules are very different, and cross-reactivity seems unlikely. We suggest that, if an allergic reaction develops during treatment with heparin, consideration should be given to the preservative as the responsible agent. Preservative-free preparations of heparin can be safely used. on

S. DUX S. PITLIK G. PERRY J. B. ROSENFELD

of Internal Medicine C, Beilinson Medical Centre, Petah Tiqva, Israel, and Tel Aviv University Sackler School of Medicine

Department

SEVERE CORNEAL INFECTION IN A CONTACT LENS WEARER

SIR,-The use of contact lenses both for therapeutic and cosmetic reasons, has been increasing rapidly. In the early days contact lenses

only in the daytime but lately continuous-wear soft lenses have been introduced. Continuously worn soft contact lens increase the risk of physical and physiological changes in the cornea,? but few major complictions have been reported. 8,9 We report here a case of an almost blinding bilateral corneal infection associated with soft contact lenses. were worn

1. Fisher AA Contact dermatitis, 2nd ed Philadelphia. Lea and Febiger, 1972: 374 2 Hancock BW, Naysmith A Hypersensitivity to chlorocresol preserved heparin Br Med J 1975; iii 746 3. Ainley EJ, Mackie IG, MacArthur D Adverse reaction to chlorocresol preserved heparin Lancet 1977; i 705 4 Barody T, Chinwah PM, Graham GG, Wade DN, Williams KM Chlorbutol toxicity and dependence. Med J Austr 1979,i 288 5 Valentour JC, Sunshine I Chlorbutol poisoning Report of a fatal case Z Rechtsmedizin 1975, 77: 61 6 Marsh BT. Preservatives in heparin Lancet 1977, i 860

Binder- The physiologic effects Ophthalmology 1980, 87: 745-49

7. Perry S. 8

of extended

wear

soft contact lenses.

Cooper RL, Constable IJ. Infective keratitis in soft contact lens wearers. Br J Ophthal 1977; 61: 250-54.

9. Landholt E, Wiesmann E. Eine Epidemie von Pseudomonas-Keratitiden bei von Dauerkontaktlinsen Klin Mbl Augenheilk 1979, 174: 788-91

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