Cutaneous hypersensitivity reactions due to thiacetazone in HIV-1 seropositive patients treated for tuberculosis

Nunn, Paul; Brindle, Richard; Wasunna, K.; Gilks, Charles F.; Omwega, M.; Were, John; MEd, Miller; Kibuga, D.; Gathua, Samuel; Imalingat, A; Lucas, Sebastian; McAdam, Keith P. W. J.

doi:10.1016/0140-6736(91)92447-a

Cited by 175 publications

(54 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another factor contributing to poor outcome may be that ethambutol is not as effective as rifampin in the continuation phase of therapy (16). Ethambutol replaced thiacetazone in regions of HIV endemicity because thiacetazone caused severe and often fatal adverse reactions in HIV-infected adults and children (3,22). There were concerns about the use of ethambutol for young children because of their inability to report the early symptoms of optic neuritis, the most important side effect, that can lead to blindness.…”

Section: Discussionmentioning

confidence: 99%

Low Levels of Pyrazinamide and Ethambutol in Children with Tuberculosis and Impact of Age, Nutritional Status, and Human Immunodeficiency Virus Infection

Graham

Bell

Nyirongo

et al. 2006

Antimicrob Agents Chemother

106

View full text Add to dashboard Cite

Recent pharmacokinetic studies that included children found that serum drug levels were low compared to those of adults for whom the same dosages were used. This study aimed to characterize the pharmacokinetics of pyrazinamide and ethambutol in Malawian children and to examine the impact of age, nutritional status, and human immunodeficiency virus (HIV) infection. We conducted a pharmacokinetic study of children treated for tuberculosis with thrice-weekly pyrazinamide (n ‫؍‬ 27; mean age, 5.7 years) and of a separate group of children treated with thrice-weekly ethambutol (n ‫؍‬ 18; mean age, 5.5 years) as portions of tablets according to national guidelines. Malnutrition and HIV infection were common in both groups. Blood samples were taken just prior to oral administration of the first dose, and subsequent samples were taken at intervals of 2, 3, 4, 7, 24, and 48 h after drug administration. Serum drug levels were low in all children for both drugs; in almost all cases, the maximum concentration of the drug in serum (C max ) failed to reach the MIC for Mycobacterium tuberculosis. The C max of pyrazinamide was significantly lower in younger children (<5 years) than in older children. The C max of pyrazinamide was also lower for HIV-infected children and children with severe malnutrition, but these differences did not reach statistical significance. No differences were found for ethambutol in relation to age, HIV infection, or malnutrition, but the C max was <2 mg/liter in all cases. Studies of pharmacokinetic parameters and clinical outcomes obtained by using higher dosages of drugs for treatment of childhood tuberculosis are needed, and recommended dosages may need to be increased.There are very few pharmacokinetic (PK) studies of antituberculosis (anti-TB) drugs in children (8). Dosages for children are based on weight and extrapolated from data from studies with adults, yet pharmacokinetics for children, especially young children, is likely to be different than for adults. Studies of ethambutol and pyrazinamide have found lower plasma drug levels and shorter half-lives in children than in adults using the same dosages, and the authors have suggested that dosages per kilogram of body weight need to be higher for children than for adults (36,37). Similar conclusions were drawn from a recent study of isoniazid pharmacokinetics in South African children (29).Until recently, the use of the same dosage recommendation as for adults may not have been an important issue, since studies that followed these schedules for children found that outcomes were very good and serious adverse events were rare (1,2,6,33,34). These data suggest that adequate levels of drug were being achieved within a range that was safe. Recent reports of outcomes for child TB, however, have found much poorer treatment response than earlier studies (5,15,20,23).

show abstract

Section: Discussionmentioning

confidence: 99%

Low Levels of Pyrazinamide and Ethambutol in Children with Tuberculosis and Impact of Age, Nutritional Status, and Human Immunodeficiency Virus Infection

Graham

Bell

Nyirongo

et al. 2006

Antimicrob Agents Chemother

106

View full text Add to dashboard Cite

show abstract

“…HIV-positive patients treated with the older regimens consisting of streptomycin, isoniazid, and thiacetazone during the early stages of the epidemic had higher death rates compared with those given rifampicin-containing regimens (Nunn et al 1991;Elliott and Foster 1996). The latter may offer survival advantages because of the broad-spectrum antibacterial activity of rifampicin in preventing other bacterial infections.…”

Section: Barriers To Effective and Appropriate Therapymentioning

confidence: 97%

Tuberculosis and Co-infection with the Human Immunodeficiency Virus

Zumla

Grange

2004

Tuberculosis

View full text Add to dashboard Cite

“…Allergic side effects (cutaneous hypersen sitivity, skin rashes [19]) were observed in some cases, leading to replacement of TAZ by EMB. Possibly the side effects of TAZ could also be avoided by replacing TAZ with the new and effective hydrazones of the PH22 type ( fig.…”

Section: In Vivo Activitiesmentioning

confidence: 99%

Development of Effective Drug Combinations for the Inhibition of Multiply Resistant Mycobacteria, Especially of the <i>Mycobacterium avium </i>Complex

Seydel¹,

Schaper²,

Rüsch-Gerdes³

1992

Chemotherapy

View full text Add to dashboard Cite

Rationally designed combinations of rifampicin (RAMP) and thiacetazone plus isonicotinic acid hydrazide and/or ethambutol are highly effective in the treatment of patients (including HIV-positive) infected with multiply resistant mycobacteria of the Mycobacterium avium complex (MAC). Clinical results are very promising. The high efficacy of these combinations is due to the synergistic potentiation of single-drug activities. As soon as rifabutin is marketed, it should replace RAMP in the combination treatment of patients with highly RAMP-resistant MAC bacteria.

show abstract

Cutaneous hypersensitivity reactions due to thiacetazone in HIV-1 seropositive patients treated for tuberculosis

Cited by 175 publications

References 11 publications

Low Levels of Pyrazinamide and Ethambutol in Children with Tuberculosis and Impact of Age, Nutritional Status, and Human Immunodeficiency Virus Infection

Low Levels of Pyrazinamide and Ethambutol in Children with Tuberculosis and Impact of Age, Nutritional Status, and Human Immunodeficiency Virus Infection

Tuberculosis and Co-infection with the Human Immunodeficiency Virus

Development of Effective Drug Combinations for the Inhibition of Multiply Resistant Mycobacteria, Especially of the <i>Mycobacterium avium </i>Complex

Contact Info

Product

Resources

About