Table 4. Retrospective cohorts- ADR and associated risk factors.
| Reference | Cohort description and numbers | Acquired isoniazid resistance (%) | Acquired rifamycin resistance (%) | Acquired MDR TB (%) | Risk factors associated with ADR |
|---|---|---|---|---|---|
| Chien, JAC 2013 [25] | Culture confirmed pulmonary TB without HIV co-infection (baseline MDR/XDR excluded) n = 2080 | WCFU 108/2080 (5.2) | WCFU 160/2080 (4.7) | WCFU 178/2080 (8.6) | -Age group 45–64 (OR 2.07, p = 0.01) -Smear positivity (OR 2.09, p = 0.01)—Self-administration of treatment/lack of DOT (OR 2.94, p = 0.01) |
| Driver, Clin Infect Dis, 2001 [26] | Drug sensitive at baseline n = 4571, Known relapses/recurrences at end of at least 6mths Rx n = 123, Known DST at relapse or recurrence n = 95 | WCFU 14/4571 (0.3) PS 14/4571 (0.3) | WCFU 21/4571 (0.5) PS 21/4571 (0.5) | WCFU 9/4571 (0.2) PS 9/4571 (0.2) | -HIV co-infection (risk factor for acquired RIF monoresistance) |
| Gelmanova, Bull WHO, 2007 [27] | Enrolled in DOT n = 260, Culture +ve, with known DST (baseline MDR at excluded) n = 207 | Not specified | Not specified | WCFU 15/207 (7.3) | -Substance abuse (HR 2.88, p = 0.04)-Treatment commenced in hospital setting (HR = 6.34, p = 0.02)—Hospitalisation later in treatment (HR = 6.26, p = 0.047) -Self-administration of Rx/lack of DOT (HR 0.25, p = 0.03) |
| Jasmer, AJRCCM, 2004 [28] | Drug sensitive cases of TB who started treatment with allocated DOT status n = 372, Had f/u cultures as part of post-treatment evaluation n = 330 | WC 2/372 (0.5) WCFU 2/330 (0.6) Details of which drugs resistance is acquired to not specified | None of the factors analysed were associated (see S4 Table) | ||
| Kim BMC ID 2008 [13] | INH resistant at baseline n = 39 | N/A | WCFU 2/39 (5.1) MR(H) 2/39 (5.1%) | WCFU 2/39 (5.1) MR(H) 2/39 (5.1) | -2 vs 3 drugs in continuation phase -Extensive radiological disease -Smear positivity |
| Li CID 2005 [29] | Confirmed TB with known DST, n = 2861 | Not specified | WCFU 10/2861 (0.3) | Not specified | -HIV infection aOR, 5.5; 95% CI, 1.4–21.5) Analysis restricted to CD4 count <100: Rifampicin-based (as opposed to rifabutin) regimens aHR 8.5; 95% CI, 1.03–70.9) Analysis restricted to HIV patients on rifampicin-based regimens: patients received intermittent dosing during IP HR 6.4; 95% CI, 1.1–38.44) aOR adjusted odds ratio aHR adjusted hazards ratio |
| Matthys, PLoS ONE, 2009 [11] | Admitted and remained inpatient in penitentiary hospital during treatment (baseline MDR excluded) n = 189 | WCFU 0/189 (0) PS 0/81 (0) MR(S/R/E) 0/20 | WCFU 6/189 (3.2) PS 0/81 (0) MR(H/S/E) 0/46 (0) PR(H+E/H+S/H+S+E) 6/61 (9.8) | WCFU 6/189 (3.2) PS 0/81 (0) MR(H/S/R/E) 0/47 (0) PR(H+E/H+S/H+S+E) 6/61 (9.8) | -Amplification of resistance occurred in 10.7% of those with polyresistance at baseline (vs 3.4% in the whole cohort) |
| Moulding IJTLD 2004 [30] | Drug sensitive at baseline n = 5337 | WC 25/5337 (0.47) Details of which drugs resistance is acquired to not specified | - Separate drug formulation as opposed to fixed dose combination-Private sector management | ||
| Porco CID 2012 [31] | Drug sensitive at baseline n = 33725 Repeat DST at follow up n = 1792 | WC 52/33725 (0.15) WCFU 52/1792 (2.9) PS 46/30 548 (0.15) MR(R) 6/138 (4.3) | WC 64/33725 (0.19) WCFU 64/1792 (3.5) PS 37/30 548 (0.1) MR(I) 27/3039 (0.9) | WC 49/33725 (0.1) WCFU 49/1792 (2.7) PS 16/30 548 (0.05) MR(H/R) 33/3177 (1) | Acquired INH resistance: -Initial rifampicin resistance (aOR 10.3 p<0.001] -HIV infection (aOR = 3.36, p = 0.01)Acquired rifampicin resistance:- Age per year (aOR 0.96, p = 0.002)-HIV infection (aOR = 9.39, p<0.001)-Initial resistance to isoniazid (aOR = 11.2, p<0.001)-Cavitatory disease in the absence of DOT (OR = 2.65, p 0.03) Acquired MDR:- Initial isoniazid resistance (aOR = 19.2p<0.001)- Initial rifampicin resistance (aOR = 35.9, p<0.001) -HIV infection (aOR = 5.07, p = 0.003) -Cavitatory disease in the absence of DOT (aOR = 2.65, p = 0.04) aOR = adjusted odds ratio |
| Quy IJTLD 2003 [32] | New smear +ve cases starting TB Rx n = 2901, Culture positive failure and relapse cases with repeat DST and identical ISS610 patterns compared with baseline (baseline MDR excluded)n = 62 | WC 3/2901 (0.1)WCFU 3/62 (4.8) ¥ | WC 18/2901 (0.6) WCFU 17/62 (2.7) ¥ | WC 18/2901 (0.6) WCFU 17/62 (2.7) ¥ | -Baseline drug resistance (OR 6.6, 95% CI 1.4–32) |
| Seung CID 2004 [33] | Enrolled in category 1 treatment regimen n = 2194, Culture positive cases with known DST (baseline MDR cases excluded) n = 1610 | WC 19/1610 (1.2) PS 9/1212 (0.7) MR(R/E/S) 6/191 (3.1) PR(R+E/R+S/R+E+S) 2/27 (7.4) | WC 31/1610 (1.9) PS 9/1212 (0.7) MR(H/E/S) 6/212 (2.8) PR(H+S/H+E/H+S+E) 16/153 (10.4) | WC 28/1610 (1.7) PS 8/1212 (0.7) MR 6/225 (2.7) PR 18/180 (10) | -Baseline drug resistance |
| Spellman 1988 AIDS [34] | TB patients with known DST (baseline MDR cases excluded) n = 739 | WC 2/739 (0.3) PS 2/682 (0.3) MR(S/R/Et) 0/23 (0) PR(S+E/S+Et) 0/5 (0) | WC 4/739 (0.5) PS 2/682 (0.3) MR(H/S/Et) 1/42 (2.4) PR(H+S/H+E/H+Et/H+Et+S/S+E/S+Et) 1/14 (7.1) | WC 2/739 (0.3) PS 2/682 (0.3) MR(H/S/R/Et) 1/65 (1.5)PR H+S/H+E/H+Et/H+Et+S/S+E/S+Et) 1 /14 (7.1) | -Baseline drug resistance |
| Weis, NEJM 1994 [35] | Culture confirmed TB (baseline MDR cases excluded), n = 957 | Not specified | Not specified | WC 47/957 (4.9) | -Self-administration of treatment/lack of DOT (p<0.001) |
| Yoshiyama IJTLD 2004 [15] | Culture positive cases (baseline MDR cases excluded) n = 1871, patients with repeat DST n = 704 Re-registered cases with DST n = 59 | WC 5/1871 (0.3) WCFU 5/704 (0.7) PS 1/1634 (0.06) MR(R) 4/43 (0.09) | WC 11/1871 ((0.6) WCFU 11/704 (1.6) PS 4/1634 ((0.2) MR(H) 7/107 (6.5) | WC 12/1871 (0.6) WCFU 12/704 ((1.7) PS 1/1634 (0.06) MR(H/R) 11/150 (7.3) | -Previous treatment failure-Baseline resistance—HIV co-infection |
| Yuen, PLoSONE 2013 [36] | Culture confirmed new cases with initial DST n = 51,223, Known genotype and follow up DST (n = 3696 for isoniazid, and n = 4005 for rifamycin) | WC 61/51223 (0.1) WCFU 61/3696 (1.7) | WC 50/51223 (0.1)WCFU 50/4005 (1.2) | Not specified | Acquired INH resistance -M. bovis (aPR = = 8.46, 95% CI 2.96–24.14)Acquired rifamycin resistance—M. bovis (aPR = 4.53, 95% CI 1.29–15.90) -Homeless (aPR = 2.21, 95% CI 1.08–4.52)-HIV co-infection (aPR 8.89, 95% CI 4.43–17.85) -Initial isoniazid resistance (aPR 10.37, 95% CI 5.65–19.00)—Extrapulmonary only disease (aPR 2.31, 95% CI 1.17–4.58) -Self-administered therapy/lack of DOT (aPR 2.52, 95% CI (1.01–6.30) -Initial ethambutol resistance (aPR 4.22, 95% CI (1.06–16.76) -Injecting drug use (aPR 4.09, 95% CI 1.66–10.10) -Age 45–64 (aPR 0.46, 95% CI 0.25–0.85),-Age>65 (aPR 0.14, 95% CI 0.03–0.58) aPR = adjusted prevalence ratio |
Abbreviations: WC whole cohort denominator known DST; WCFU denominator f/u DST; PS denominator initial pan-sensitivity; MR denominator initial monoresistance; PR denominator initial polyresistance.H isoniazid S Streptomycin R rifampicin E ethambutol Et ethioniamide DOT directly observed therapy IP intensive phase CP continuation phase Hb haemoglobin ART antiretroviral therapy BMI body mass index INH isoniazid PZA pyrazinamide R rifampin E ethambutol.
¥ADR data presented is not stratified by baseline monoresistance and polyresistance as this information cannot be ascertained from the paper