A.W. Lees

Toxicity from rifampicin plus isoniazid and rifampicin plus ethambutol therapy

Abstract One hundred and five patients with pulmonary tuberculosis diagnosed for the first time were treated with a combination of rifampicin 600 mg daily plus isoniazid 300 mg daily. Treatment was discontinued in 3 patients because of a violent hypersensitivity reaction: in 2 of these patients there were raised serum bilirubin and transaminase levels and in the other raised transaminase levels. Of the 105 patients some disturbance of liver function was noticed in 37 (35 per cent). Of these 37 patients 23 (22 per cent) had transient elevation of transaminase levels and 14 (13 per cent) had elevation of serum bilirubin and transaminase levels. Apart from 2 patients who, in addition, had a hypersensitivity reaction, disturbance of liver function was associated with little or no constitutional disturbance. Of 12 patients with elevated serum bilirubin not associated with a hypersensitivity reaction treatment was continued in 4; was stopped in 4 but later successfully reinstituted; was stopped in 2 and finally abandoned after drug rechallenge; and in 2 patients treatment was abandoned without re-challenge though in 1 of these treatment was successfully restarted after 5 months. A transient skin rash was noted in 8 (7·6 per cent) patients. 72 patients with previously treated pulmonary tuberculosis were retreated with a combination of rifampicin 600 mg daily plus ethambutol 25 mg per kilo body-weight daily reducing to 15 mg after two months. No generalised hypersensitivity reactions were noted. Of the 72 patients some disturbance of liver function was noted in 7 (10 per cent). Of these 7 patients, 6 had transient elevations of transaminases and 1 had elevation of serum bilirubin and transaminase levels which returned to normal with continuation of treatment. Two patients (3 per cent) developed a skin rash and treatment was discontinued for this reason in 1. One patient had optic neuritis: but since stopping ethambutol initial visual acuity has been regained though colour vision is still defective. Disturbance of liver function was notably more frequent with rifampicin plus isoniazid than with rifampicin plus ethambutol, but was usually transient and always easily manageable.

Jaundice after rifampicin

Summary The occurrence of jaundice in four patients in a group of 50 with pulmonary tuberculosis treated with 600 mg rifampicin and 300 mg isoniazid daily is reported. In one case, resumption of treatment after jaundice had disappeared provoked its re-appearance: an ethambutol-isoniazid regimen was then substituted, and progress was subsequently uneventful. In two cases, after jaundice had disappeared and liver function tests had returned to normal the rifampicin-isoniazid regimen was reinstituted: serum transaminase levels became elevated but eventually returned to normal. In the remaining case rifampicin-isoniazid treatment was continued despite the occurrence of jaundice: jaundice subsequently disappeared and liver function tests became normal. The daily dose of rifampicin varied from 7·6 mg per kg to 14 mg per kg bodyweight. Although none of these patients was seriously ill, evidence of hepato-toxicity should be looked for in patients treated with rifampicin, and especially in those who may initially have impaired liver function.

Endocarditis due to Torulopsis glabrata.

Abstract A 65-year-old woman had an abscess in the right lower peritoneal cavity from which Escherichia coli and a fungus thought to be Candida albicans were cultured. She fully regained her general health, but over the next two years had three episodes of pyrexia, rigors, and shock associated with Torulopsis glabrata septicaemia. Apart from these episodes her general health was excellent. She died suddenly from a massive pulmonary fungal embolus. Post-mortem examination showed that the source of the embolus was a fungal endocarditis. There was no ante or post mortem evidence of predisposing disease of the heart-valves, nor were cardiac murmurs indicating endocardial involvement detected.

Probenecid and rifampicin serum levels

Serum-levels of rifampicin were investigated in patients receiving rifampicin alone or with other antituberculosis drugs. 2 g of probenecid given 30 min before 300 mg of rifampicin did not result in raising serum levels to more than half those achieved with the standard 600 mg dose of rifampicin. Hence probenecid should not be used to reduce rifampicin dosage in antituberculosis therapy.

A comparison between ampicillin and tetracycline in purulent chronic bronchitis

Summary In a double-blind trial of ampicillin and tetracycline in chronic bronchitics with purulent sputum, 44 patients received ampicillin 1 g. per day for five days and 43 patients received tetracycline 1 g. per day for five days. Purulence of sputum was lessened in 37 (84 per cent.) of the 44 ampicillin patients and in 35 (81 per cent.) of the 43 tetracycline patients; but whereas the purulence was completely eliminated in only 19 (43 per cent.) of the tetracycline patients, it was eliminated completely in 28 (64 per cent.) of the ampicillin patients. H. influenz˦, Strep. pneumoni˦ and other potential pathogens disappeared from the sputum of patients in both series with approximately equal frequency.

ETHAMBUTOL PLUS ISONIAZID COMPARED WITH RIFAMPICIN PLUS ISONIAZID IN ANTITUBERCULOSIS CONTINUATION TREATMENT

Patients with bacteriologically positive pulmonary tuberculosis were treated initially for an average of three and a half months with isoniazid, rifampicin, and ethambutol and then a total of one years treatment was completed with either rifampicin plus isoniazid (R+I) or with ethambutol plus isoniazid (E+I). 63 patients in each continuation group were followed up for at least one year, and no relapses occurred. Continuation treatment with E+I was as effective and acceptable as that with R+I and was much less costly.

Oral orciprenaline, salbutamol and isoetharine compared

Abstract Orciprenaline, salbutamol and isoetharine hydrochloride in a porous plastic matrix tablet were compared in 21 patients with reversible airways obstruction. The bronchodilator effects of the 3 preparations were similar. Cardiovascular effects were negligible after the single dose of all 3 preparations by mouth.

Ethambutol in the retreatment of chronic pulmonary tuberculosis

Summary Ethambutol in a dosage of 25 mg/kg for two months and in a dosage of 15 mg/kg thereafter was used in the retreatment of 36 patients with chronic sputum positive pulmonary tuberculosis. In 32 of the 36 culture of respiratory secretions became negative after a period ranging from one month to six months. In 4 cases in which the patients left hospital against medical advice the sputum was still positive, but in all instances the organisms were susceptible to ethambutol when treatment was interrupted. There was no evidence of ocular toxicity or other unwanted effect from ethambutol nor was hypersensitivity observed. If further experience shows that ocular toxicity is not a serious hazard, and if no other toxic effects are seen, ethambutol may take its place as a highly suitable companion for isoniazid in initial treatment.