Clinical Evaluation of Ethambutol in Pulmonary Tuberculosis

Donomae, I; Yamamoto, Kazuo

doi:10.1111/j.1749-6632.1966.tb45528.x

Cited by 40 publications

(16 citation statements)

References 5 publications

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“…In one study, Japanese patients were treated with two different doses of ethambutol administered either concomitantly with isoniazid or as monotherapy (35). Unfortunately, in that study, our attempts at population PK analysis led to rather imprecise estimates of SCL, very different from PK parameters in recent population PK publications (80,110); thus, estimates of AUC are less precise.…”

Section: Ethambutolmentioning

confidence: 99%

An Oracle: Antituberculosis Pharmacokinetics-Pharmacodynamics, Clinical Correlation, and Clinical Trial Simulations To Predict the Future

Pasipanodya

Gumbo

2011

Antimicrob Agents Chemother

107

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Antimicrobial pharmacokinetic-pharmacodynamic (PK/PD) science and clinical trial simulations have not been adequately applied to the design of doses and dose schedules of antituberculosis regimens because many researchers are skeptical about their clinical applicability. We compared findings of preclinical PK/PD studies of current first-line antituberculosis drugs to findings from several clinical publications that included microbiologic outcome and pharmacokinetic data or had a dose-scheduling design. Without exception, the antimicrobial PK/PD parameters linked to optimal effect were similar in preclinical models and in tuberculosis patients. Thus, exposure-effect relationships derived in the preclinical models can be used in the design of optimal antituberculosis doses, by incorporating population pharmacokinetics of the drugs and MIC distributions in Monte Carlo simulations. When this has been performed, doses and dose schedules of rifampin, isoniazid, pyrazinamide, and moxifloxacin with the potential to shorten antituberculosis therapy have been identified. In addition, different susceptibility breakpoints than those in current use have been identified. These steps outline a more rational approach than that of current methods for designing regimens and predicting outcome so that both new and older antituberculosis agents can shorten therapy duration.Advances in the treatment of tuberculosis (TB) have suffered from a lack of scientific imagination. A century ago, TB research was the true cutting edge of medical innovation (65,90,97). Unfortunately, while scientific knowledge for the therapy of most diseases virtually exploded, we and others in the TB world still use dated paradigms and language. In the meantime, the pandemic shows no signs of subsiding. In 2008, there were 8.9 to 9.9 million incident cases of TB; prevalence was 9.6 to 13.3 million cases, and 1.8 million people died from TB (107). "Short-course chemotherapy" is actually long. Longterm mortality, morbidity, relapse, and resistance emergence are still problems even after "successful" therapy (20,77,78,93). Indeed, while it often said that the therapy has a 95% success rate under directly observed therapy (DOTS) programs, a look at high-TB-burden countries with good DOTS programs reveals cure rates for pulmonary TB of only 34 to 76%, and those are under study conditions (1, 103). Recently, the efficacy of DOTS itself has been challenged (14, 103). Clearly, the traditional approaches have not succeeded in eradicating TB. It is time to take a different road.

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Section: Ethambutolmentioning

confidence: 99%

An Oracle: Antituberculosis Pharmacokinetics-Pharmacodynamics, Clinical Correlation, and Clinical Trial Simulations To Predict the Future

Pasipanodya

Gumbo

2011

Antimicrob Agents Chemother

107

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“…According to experiences obtained so far the ocular toxicity of EMB manifests itself by two types of Walsh's retrobulbar neuritis [7,9,17,37,49]. The problem of ocular toxicity of EMB was given great at tention.Itwas ascertained that it depended on the dose [9,17,20,37], With a prescribed dosage of EMB its incidence is less than 1 %> [7]. However, it is alleged that subjective visual troubles precede the objectively ascer tainable alterations [9].…”

Section: Discussionmentioning

confidence: 99%

“…It was intro duced more intensively into clinical practice after the conference organ ized by the New York Academy of Sciences in 1965. Useful information was presented at this conference regarding the drug, its anti-bacterial effect [21,50], pharmacology [8,45], toxicity [16,37,47] as well as clinical efficiency [2,4,10,13,17,20,26,33,47]. The American Tho racic Society [1] stated that it was a drug which replaced PAS safely and efficiently in patients who did not tolerate the latter.…”

mentioning

confidence: 99%

“…The American Tho racic Society [1] stated that it was a drug which replaced PAS safely and efficiently in patients who did not tolerate the latter. This opinion was drawn from the first American [3,20,59] and Japanese [17] clini cally controlled trials in which EMB was tested in monotherapy as well as in combination with INH in comparison with INH-PAS. Certain pap ers published in Europe after 1965 range EMB by its efficiency with the so-called 'great' anti-tuberculosis drugs [29,35,39,43].…”

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confidence: 99%

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Ethambutol in Therapy of Complicated Tuberculosis

Tousek¹,

Papezová²

1973

Chemotherapy

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The authors administered ethambutol (EMB) in doses of 25 mg/kg body weight daily for 2 months and 15 mg/kg body weight in another period to 55 patients of whom they have assessed only 50. These are patients who could be followed up for at least 3 months. 46 of them had pulmonary tuberculosis, 2 basilar meningitis, 1 tuberculosis of bones and joints and 1 specific adnexitis. Patients were in question whose common feature lay in difficult curability owing to the resistance of tubercle bacilli (48%), hepatic lesion (63%), intolerance of drugs (50%) and serious superposed diseases (46%). EMB was combined with one or two efficient drugs that could be applied. Therapeutic results were assessed in all patients whose therapy lasted at least 4 months (4–21 months, average 8 months). Patients who excreted tubercle bacilli were rendered negative. Negativity was obtained sooner if the drug combination contained RAMP. Radiologically, once aggravation of the cavernous process ensued. EMB was discontinued once after 14 days and once after 21 months of treatment owing to increasing values of the liver function tests. The first woman patient had had epidemic hepatitis and showed an allergic reaction to SM and VM, the other patient recovered from a severe hepatic lesion with icterus after MZA. The treatment was twice interrupted for fear of a possible damage to sight after degenerative alterations had been ascertained on the eyeground after 2 and 4 months of therapy but they did not fall within the aspect of retrobuloar Walsh’s neuritis. Tolerance of EMB was very good, no subjective troubles were ascertained.

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“…Controlled clinical trials (1,8) have shown its effectiveness in the treatment of tuberculosis, especially in combination with other antituberculosis drugs (2,21). There, have been no clinical trials with EMB in the treatment of mycobacterial infections other than tuberculosis and only a few reports about the usefulness of EMB in the treatment of infections caused by Mycobacterium avium (10,28) and Mycobacterium marinum (29).…”

mentioning

confidence: 99%

Ethambutol MICs and MBCs for Mycobacterium avium complex and Mycobacterium tuberculosis

Heifets¹,

Iseman²,

Lindholm-Levy³

1986

Antimicrob Agents Chemother

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We determined the MICs of ethambutol for both Mycobacterium avium and Mycobacterium tuberculosis strains by using broth dilution (7H12 broth, radiometric method) and agar dilution (7H111 agar) methods. We found the MICs to be much lower in liquid than in solid medium. The broth-determined MICs for susceptible M. tuberculosis and most of the M. avium strains were comparable to the levels in blood of patients, being lower than the peak levels. We propose that the MICs, determined radiometrically in 7H12 broth, be considered as tentative criteria for susceptibility testing of M. avium isolates in future clinical trials. The use of these values instead of critical concentrations should also be considered as an alternative to the conventional susceptibility testing method in chemotherapy of tuberculosis. Ethambutol produced bactericidal effects against both M. tuberculosis and M. avium, and the MIC/MBC ratios were in the same range for both species when MICs and MBCs were tested in 7H12 brQth by conventional sampling and plating.

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Clinical Evaluation of Ethambutol in Pulmonary Tuberculosis

Cited by 40 publications

References 5 publications

An Oracle: Antituberculosis Pharmacokinetics-Pharmacodynamics, Clinical Correlation, and Clinical Trial Simulations To Predict the Future

An Oracle: Antituberculosis Pharmacokinetics-Pharmacodynamics, Clinical Correlation, and Clinical Trial Simulations To Predict the Future

Ethambutol in Therapy of Complicated Tuberculosis

Ethambutol MICs and MBCs for Mycobacterium avium complex and Mycobacterium tuberculosis

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