CAMPYLOBACTER CHOLECYSTITIS

1092 similar to the National Collection of Type Cultures strain 11168 except that it was sensitive to metronidazole; this type is commonly found in patients with acute enteritis. After 5 days’ treatment with erythromycin and a further lapse of a few days another midstream urine on June 30 was sterile. Serum taken 12 days after the patient’s first complaint showed an agglutination titre against a formolised suspension for his own organism of 1 in 160 (weak at 1 in 320). This had fallen to 1 in 10 (weak at 1 in 20) in serum taken 10 weeks after the start of his illness. Campylobacter urinary infections may be being missed: these organisms are not normally sought in urine and unless special search is made they will not be found. We thank Dr M. B. Skirrow, Worcester sistance and advice in this case. The Surgery, Station Approach, Frinton on Sea, Essex

Pathology Laboratory, St. Mary’s Hospital, Colchester, Essex

Royal Infirmary,

for his

JOHN S. DAVIES JOHN B. PENFOLD

SIR,-The association of meningism with enteric infections caused by Salmonella or Shigella is well recognised, but I can find no reports of an association between meningism and Campylobacterjejuni enteritis. I describe here two cases. A 29-year-old postal officer gave an 8 h history of fever, severe occipital headache, photophobia, nausea, and vague lower abdominal pain but with no other bowel symptoms. His wife had had diarrhoea on the previous day. The patient was febrile (38.4°C) with neck stiffness on full flexion, but Kernig’s sign was negative. The rest of the clinical examination was normal. His white cell count was 18.2x 109/1 (81% neutrophils, 17% lymphocytes, 2% monocytes). The cerebrospinal fluid (c.s.F.) was clear, colourless, and under normal pressure, with normal protein 0-3g/1 and glucose 3.8 mmol/1. The c.s.F. contained no white or red cells and stained deposit showed no organisms. Bacterial culture of the c.s.F. was negative but viral studies were not done. Blood cultures set up on admission were also negative. Urine analysis, serum electrolytes, and blood-urea were normal. 2 days after admission he had watery diarrhcea containing blood and mucus, and fxcal culture yielded C. jejuni but no other enteric bacterial, parasitic, or viral pathogens were identified. He made an uneventful recovery with symptomatic treatment. A 7-year-old-boy gave a 12 h history of retro-orbital headache, photophobia, dizziness, nausea, and colicky abdominal pain but with no other bowel symptoms. His 5-year-old brother had had a similar illness on the previous day. The patient was febrile (38.5°C) with slight neck stiffness but Kernig’s sign was negative. The rest of the clinical examination was normal. The white-cell count was 13.7 X 109/1 (89% neutrophils, 9% lymphocytes, 2% monocytes). The c.s.F. was clear, colourless, and under normal pressure with normal protein 0.15 g/1 and glucose 4.0 mmol/1. The c.s.F. contained no white or red cells, stained deposit showed no organisms, and bacterial and viral cultures were negative. Blood cultures and throat swab cultures taken on admission were negative. Urine analysis, serum electrolytes, and blood-urea were normal. 3 days after admission of the patient he passed soft bloodstained fseces from which C. jejuni was isolated. No other enteric bacterial, viral, or parasitic pathogens were identified. He made an uneventful recovery with symptomatic treatment. C. jejuni Krugman, S., Ward, R., Katz, S. Louis, 1977. p. 303.

L. Infectious Diseases of

tal, Liverpool, for permission to report these two cases. Regional Public Health Laboratory, Fazakerley Hospital, Liverpool L9 7AL

Children; St.

E. P. WRIGHT

CAMPYLOBACTER CHOLECYSTITIS

as-

MENINGISM ASSOCIATED WITH CAMPYLOBACTER JEJUNI ENTERITIS

1.

isolated from his brother who also had diarrhoea and also from the family puppy which was apparently healthy. Circumstantial evidence in these two cases suggests a possible association between C. jejuni and meningism. C. jejuni is being increasingly recognised as a cause of acute enteritis as indicated in your editoriaF, and C. jejuni should be considered, in addition to other enteric agents, in patients with meningism. I thank Dr H. E. Parry, infectious diseases unit, Fazakerley Hospi-

was

SIR,- There are few reports of infections caused by campylobacters outside the gastrointestinal tract. We describe here a case of campylobacter cholecystitis. A 52-year-old woman, with no medical history, was admitted to hospital on July 27, 1978, with fever of 10 days’ duration and worsening abdominal pain. On July 15 she had eaten with her family at a restaurant and during the night after this meal indigestion had started with slight fever, continuing the next day with nausea, vomiting, and diarrhoea. Her husband and son had also had diarrhoea, but they recovered spontaneously after 2 days. Our patient, however, remained weak with anorexia. The diarrhcea and abdominal pain increased. Symptomatic therapy was of no help and a relapsing fever developed with peaks of39°C. On admission to hospital, she was in good general condition, but reported 3 kg weight loss. Abdominal palpation revealed a mass in the right hypochondrium. A plain X-ray of the abdomen revealed a large calcified stone in the right hypochondrium. Intravenous pyelography was normal. Intravenous cholangiography revealed a gallbladder abnormality with patent bileducts. Her leucocyte-count was 11 800/ul with 69% neutrophils. Biochemical data were normal except for a rise of , 1 9 lutamyl transpeptidase 54 U/l (normal 4-18) and a total bilirubin of 1.25 mg/dl (normal ≤1.00). Urine examination was normal. An operation for acute empyematous cholecystitis was done on July 28. The gallbladder was hydropic (15 cm on 6 cm) and contained two giant gallstones and a seropurulent fluid. Anatomo-pathological examination confirmed an acute ulcerative recurrence of a chronic cholecystitis. Chloramphenicol 1 g twice daily was administered at the onset of operation and stopped 5 days later. The patient recovered uneventfully. Blood, bile, and stool were cultured. From the bile we isolated, after 5 days culture on thioglycollate broth in pure culture, Campylobacter jejuni. Routine culture of the bile for aerobes and anaerobes was negative. Blood taken on admission remained sterile on culture. Stools cultured by filtration technique3 7 days after surgery (and 2 days after chloramphenicol had been withdrawn) were also positive for C. jejuni. Repeat stool culture, 1 month later, was negative. Formolised suspensions of bacteria were used for detecting agglutinins in patient’s sera. Two sera, one obtained 2 weeks after the beginning of the disease and the other 1 month later, contained specific agglutinins to a titre of 1/1280 against the homologous antigen. The serotype was determined bv hwmagglutination using boiled antigen. When placed in contact with four different hyperimmune rabbit sera to two strains of C. jejuni (Z2 and Ed.) and two C. fetus strains (serotype 0, and O2) the antigens prepared with the strain isolated from the stools and that isolated from bile were agglutinated by antiserum Z2 (titres 1:1024 for both) and not by antisera Ed., 0,

or02’ To

our

knowledge this

is the second

published case’ of cam-

2. Lancet, 1978, ii, 135. 3. Butzler, J P., and others J. Pediat. 1973, 82, 318 4 Schwartz, R , and others.Am.J. Gastroent. 1966,

45, 366

1093

pylobacter cholecystitis. It demonstrates that the intestine was the source of the infection which spread to the gallbladder. Since C.

jejuni was isolated from the bile in pure culture it is this microorganism may play a role in acute cho-

possible that lecystitis.

BX’e thank Prof. J. P. Butzler

(Brussels) for the serology and serotyp-

ing of the strains. Departments of Microbiology and Surgery, Stuivenberg Hospital, 2000 Antwerp, Belgium

A. MERTENS M. DE SMET

like concentrations of nitrazepam, plasma levels fall to less than 10 c of the effective level within about 12 h. Significant drug accumulation does not occur on long-term administration in recommended dosage. These characteristics, which are not shared by most hypnotics, make chlormethiazole a valuable drug for use in the elderly; it is relatively free from hangover effects and other adverse reactions and it has been shown to be as effective as or superior to existing medication in the treatment of insomnia.7,8 We suggest that the criticisms made by Hession et al. should more appropriately be levelled at other hypnotics rather than at chlormethiazole which is rarely associated with withdrawal symptoms when used in the correct

dosage. USES AND ABUSES OF CHLORMETHIAZOLE

SIR,-Dr Hession and his colleagues (May 5, p. 953) have drawn attention to the dependence which can result from the prolonged use of chlormethiazole and to the psychiatric disorders which may develop upon its withdrawal. The doses prescribed in the first patients they describe, however, were far in excess of the recommended dosage. Doctors should be aware of possible dangers of overdosage of drugs, especially when they are administered to the elderly, but Hession’s recommendation’ that "information about the dangers of this drug should be sent out to all doctors as a matter of urgency" is quite unjustified on the evidence provided. All hypnotics are liable to produce the side-effects of dependence and hangover. These in turn are related to the size of dose and to accumulation of the drug in the body, and they vary from one drug to another. Dependence results both from effects on mood and also from a continual demand for the drug in order to avoid the insomnia and nightmares that follow the cessation of therapy. Accumulation occurs when residual amounts of the drug remain in the body and are not cleared before the next dose. Hangover is characterised by persistence of pharmacological activity into the next day, and the intensity and duration of this effect is also related to the half-life of the drug. The dangers of barbiturates are well recognised since they produce marked dependence, accumulation, and hangover effects and they have been largely replaced by other hypnotics, particularly the benzodiazepines. Nitrazepam is the most widely prescribed and its clinical efficacy as a hypnotic has been well established as equal to that of the barbiturates. Moreover, reports of dependence and of death from overdosage are rare, and the drug retains its hypnotic effect on prolonged dosage. Hangover effects, however, are marked because of the long half-life (about 30 h); even after a single dose in young people impairment of psychomotor performance is found the following dayI.2 and these effects are greater in the elderly because the ageing brain is more sensitive. This, together with the high blood and tissue levels which result from repeated administration, makes nitrazepam an unsuitable hypnotic for long-term use in the elderly who may present with a variety of neuropsychiatric manifestations.4 There is also evidence that treatment after prolonged use of nitrazepam as a night sedative, produces marked withdrawal symptoms.5 Thus to avoid hangover effect after single dose administration and the cumulative effects (confusion, ataxia, and worsened mental condition) resulting from long-term administration, the "ideal" hypnotic should have a short half-life. Of the hypnotics commonly prescribed chlormethiazole has a half-life which is one of the shortest (about 4 h6). Plasma concentrations reach the effective level rapidly after oral dosing and, un-

Departments of Geriatric Medicine and Clinical Pharmacology, University College Hospital Medical School, London WC1

A. N. EXTON-SMITH A. E. M. MCLEAN

years this unit has been using chlormeththe main drug in conventional detoxification therapy to counter alcohol-withdrawal syndrome, and I have treated more than a thousand chronic alcoholics with oral chlormethiazole over the past three years. Chlormethiazole is potentially a safe drug for routine use for a short period for inpatient management of alcohol-withdrawal syndrome. We use the following dosage schedule: chlormethiazole edisylate (’Heminevrin’) capsules equivalent to 192 mg base per capsule three three times a day for 3 days, two three times a day for 2 days, and one three times a day for 1 day. The total average dose is thus about 8 mg chlormethiazole base tailed off over a period of 6 consecutive days. The drug is well tolerated and does not precipitate any untoward or alarming reactions; its use on an outpatient basis, however, is not advised. Chronic alcoholics may acquire hyperprolactinxmia with impotence and hypogonadism,9.1O biochemical hypothyroidism," and hypercortisolaemia,12 and hepatic microsomal enzymes may be induced as a result of chronic drinking." Interestingly, chlormethiazole, when given to chronic alcoholics, does not raise serum-prolactin concentrations as phenothiazines, butyrophenones, and so on do; on the contrary, it lowers prolactin levels significantly.-14 It does not interfere with thyroid function,15 nor does it affect serum-cortisol (unpublished) and it has no effect on hepatic microsomal enzymes. 16 In view of these observations, chlormethiazole seems to be an ideal drug to treat alcohol-withdrawal syndrome. It is the wrong use of a right drug which was responsible for the reactions reported by Hession et al.

SIR,-For several

iazole

as

Elmdene Alcoholic Treatment

Bexley Hospital, Bexley, Kent DA5

2BW

Unit,

SISIR K.

MAJUMDAR

cessation of

1. 2

Walters, A. J., Lader, M. H. Nature, 1971, 229, 637. Malpas, A., Rowan, A. J., Joyce, C. R. B., Scott, D. F. Br. med. J. 1970, ii, 762. 3. Castleden, C. M., George, C. F., Marcer, D., Hallett, C. ibid. 1977, i, 10. 4. Grimley Evans, J., Jarvis, E. H. ibid. 1972, ii, 487. 5. Adam, K., Adamson, L., Brezinová, V., Hunter, W. M., Oswald, I. ibid. 1976, i, 1558. 6 Witts, D. J., Bowhay, A. A., Garland, M., McLean, A. E. M., Exton-Smith, A. N. Age Ageing, (in the press).

SiR,-In alcoholics and patients with other unstable personalities any sedative-hypnotic drug can lead to dependence1.2 with the risk of psychological and physical abstinence symptoms. Chlormethiazole is no exception, especially when used without regard to correct indication-a finding stressed by a 7 8

Grunstein, J A. H. Mod Geriat. 1971, 1, 472. Dehlin, O., Falkheden, T, Gatzinska, R. Nordqvist, P Clin Ther. 1978, 2,

41. 9 Majumdar, S. K. Lancet, 1978, i, 101 10 Majumdar, S. K Practitioner in the press). 11 Goldberg, M Lancet, 1962, n, 746. 12 Smals, A., Kloppenborg. P. ibid. 1977, i, 1369. 13 Gelehrter, T D. New Engl J Med. 1976, 294, 589. 14 Majumdar, S K, Shaw, G. K, Thomson, A D Br. 15 Majumdar, S K Pharmatherapeutica. 1978. 2, 67. 16. Majumdar, S K. ibid. p. 27 1. Glatt, M. M Br med.J 1957, i, 164. 2 Glatt, M. M. ibid. 1958, ii, 1100

med. J. 1978, ii,

1266.