Volume 12, Number 5—May 2006
THEME ISSUE
Tuberculosis Special Section
Research
Isoniazid Preventive Therapy and Risk for Resistant Tuberculosis
Table 2
Studies comparing isoniazid treatment with no treatment in HIV-uninfected populations*
| Author, country, dates | Population | Intervention/comparison; blinding | Enrolled (n) INH/control | Follow-up; loss to follow-up; overall or INH vs. control | TB cases: culture positive/total (%) |
Definition of INH resistance | Resistant cases/total tested (% culture positive tested) |
Risk for resistant TB/1,000 |
||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| INH | Controls | INH | Controls | INH | Controls | RR (95% CI) | ||||||
| Ferebee, USA, 1957–NS (18) | Household contacts of TB patients | 12 mo INH, 4–7 mg/kg/day/placebo; double blind | 7,755/7,996 | <10 y; 5.2% vs. 4.9% during Rx | NS/86 | NS/215 | >50 colonies growth in 0.2 μg/mL INH | 2/10 NS | 2/31 NS | 2.22 | 1.73 | 1.28 (0.20–8.07) |
| Katz, USA, 1958–1964 (19) | Mental hospital patients with inactive lesions | 2 y INH, 300 mg daily/no treatment; not blind | 118/107 | <4 y post-Rx; 30.6% overall† | NS/9 | NS/10 | Resistance to >0.25 γ INH | 1/1 NS | 2/5 NS | 76.27 | 37.38 | 2.04 (0.52–8.08) |
| Horwitz, Greenland, 1956–1963 (20) | 76 villages | 2 × 13 wk INH, 400 mg twice weekly/0.1 mg INH; double blind | 4,174/3,907 | 6 y; NS | 123/238 (51.7) | 186/323 (57.6) | (a) > 1 colony at >0.32 μg/mL INH | (a) 2/46 | (a) 5/66 | (a) 2.48 | (a) 6.26 | (a) 0.40 (0.08–1.97) |
| (b) Equal to control tube at >0.32 μg/mL INH | (b) 2/46 (37) | (b) 1/66 (36) | (b) 2.48 | (b) 1.25 | (b) 1.98 (0.18–21.31) | |||||||
| Comstock, USA (Alaska), 1957–1964 (21) | Residents of 28 villages and 2 boarding schools | 12 mo INH, 300 mg§ daily/placebo; double blind | 3,047/3,017 | Med.: 69.3 mo (range 43–76 mo); 5.3% observed for <40 mo | NS/58 | NS/141 | NS | 4/20 NS | 1/50 NS | 3.81 | 0.93 | 4.07 (0.47–34.98) |
| Ferebee, USA, 1960–1967 (9) | Persons with inactive lesions | 12 mo INH, 5 m g/kg/day/placebo; NS | 701/714 | 5 y; 2.2% by 1967 | NS/18 | NS/49 | >50 colonies growth in 0.2 μg/mL INH | 2/5 NS | 2/25 NS | 10.27 | 5.49 | 1.87 (0.31–11.19) |
| Pamra, India, 1958–1968 (22) | X-ray screening attendees with inactive TB | 12 mo INH, 3–4 mg/kg/day/placebo; NS | 139/178 | <5 y post-Rx; 8.6% vs. 11.2% | 10/18 (55.6) | 57/76 (75) | Growth on 1 μg/mL INH | 3/9 (90) | 6/52 (91) | 43.17 | 49.27 | 0.88 (0.24–3.15) |
| Hong Kong Chest Service, Hong Kong, 1981–1987 (27) | Men with silicosis | 24 wk INH, 300 mg daily/placebo;double blind | 167/159 | 2–5 y; 15.8% at 5 y | 19/25 (76) | 29/36 (80.6) | >20 colonies in >1 culture at >0.2 mg/L INH | 5/19 (100) | 4/28 (97) | 39.39 | 32.35 | 1.22 (0.34–4.32) |
*INH, isoniazid; TB, tuberculosis; RR, relative risk; CI, confidence interval; NS, not stated; med., median; Rx, treatment.
†(a), definition of resistance as >1 colony growth at >0.32 μg/mL INH.
‡(b), definition of resistance as growth equal to control tube at >0.32 μg/mL INH.
§Children were given 5 mg/kg/day INH.
1Current affiliation: Department of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile


