Table 5.
Multivariable Logistic Regression Analysis of the Association of Treatment Outcome With Drug Resistance Pattern and Effective Drug Treatment Among Patients With Multidrug-Resistant Tuberculosis With Known Outcomes, Controlling for Country, Patient, and Program Characteristics
| Variable by Categorya | Adjusted OR (95% CI) for Treatment Success (Ordinal Categories)b | P Value |
|---|---|---|
| Drug resistance pattern | ||
| Initial and acquired resistance to SLIs and FQs in 5 main categories | ||
| Plain MDR tuberculosis, no acquired resistance | Reference | <.001 (trend) |
| Initial pre-XDR tuberculosis | 0.43 (.36–0.52) | |
| Acquired pre-XDR tuberculosis | 0.18 (.14–.28) | |
| Initial XDR tuberculosis | 0.08 (.04–.14) | |
| Acquired XDR tuberculosis | 0.04 (.02–.08) | |
| Initial and acquired resistance to SLIs and FQs in all 9 categories | ||
| Plain MDR tuberculosis, no acquired resistance | Reference | <.001 (trend) |
| Initial pre-XDR tuberculosis | ||
| Initial SLI resistance | 0.62 (.56–.69) | |
| Initial FQ resistance | 0.38 (.30–.48) | |
| Acquired pre-XDR tuberculosis | ||
| Acquired SLI resistance | 0.24 (.18–.32) | |
| Acquired FQ resistance | 0.14 (.10–.22) | |
| Initial XDR tuberculosis | 0.10 (.06–.16) | |
| Acquired XDR tuberculosis | ||
| Initial MDR tuberculosis with acquired SLI and FQ resistance | 0.06 (.02–.10) | |
| Initial pre-XDR tuberculosis with acquired SLI resistance | 0.04 (.02–.08) | |
| Initial pre-XDR tuberculosis with acquired FQ resistance | 0.02 (.00–.06) | |
| Drug treatmentc | ||
| No. of effective drugs in patient's treatment, mean | ||
| 0–1 | Reference | <.001 (trend) |
| 2 | 2.10 (1.40–3.18) | |
| 3 | 3.06 (1.64–5.68) | |
| 4 | 4.44 (1.94–10.12) | |
| 5–6 | 6.44 (2.30–18.04) | |
| Pyrazinamided | ||
| Effective | 1.28 (.80–2.04) | .31 |
| Not effective or not used | Reference | Reference |
| Unknown | 1.92 (1.21–3.04) | .005 |
| Ethambutol | ||
| Effective | 1.71 (1.14–2.58) | .009 |
| Not effective or not used | ||
| Any SLI | ||
| Effective | 2.76 (1.72–4.44) | <.001 |
| Not effective or not used | ||
| Any FQ | ||
| Effective | 3.88 (2.39–6.30) | <.001 |
| Not effective or not used | ||
| Thioamidese | ||
| Effective | 1.57 (1.03–2.42) | .04 |
| Not effective or not used | ||
| Para-aminosalicylic acid | ||
| Effective | 0.92 (.59–1.42) | .70 |
| Not effective or not used | ||
| Patient characteristics | ||
| Illicit drug use | ||
| Yes | 0.20 (.05–.77) | .02 |
| No | Reference | Reference |
| Unknown | 1.30 (.74–2.31) | .36 |
| HIV infection | ||
| Yes | 0.72 (.39–1.32) | .29 |
| No | Reference | Reference |
| Unknown | 0.50 (.22–1.13) | .10 |
| Extent of cavitary disease on chest radiograph | ||
| None | Reference | Reference |
| Unilateral | 1.22 (.78–1.91) | .38 |
| Bilateral | 0.53 (.33–.85) | .009 |
| Body mass index category | ||
| Underweight (<18.5 kg/m2) | Reference | <.001 (trend) |
| Normal weight (18.5–25.0 kg/m2) | 2.11 (1.51–2.94) | |
| Overweight (>25.0 kg/m2) | 4.46 (2.30–8.64) | |
| Program characteristicsf | ||
| GLC | ||
| GLC approved | 3.74 (2.01–6.93) | <.001 |
| Did not apply to the GLCg | ||
| Routine hospitalization | ||
| Routine hospitalization | 1.03 (.59–1.78) | .92 |
| Mixed | 4.02 (1.73–9.32) | .001 |
| Routine ambulatory treatment | Reference | Reference |
| No. of hospitalizations | ||
| 0 | Reference | <.001 (trend) |
| 1 | 0.41 (.30–.56) | |
| 2 | 0.16 (.08–.30) | |
Abbreviations: CI, confidence interval; FQ, fluoroquinolone; GLC, Green Light Committee; HIV, human immunodeficiency virus; MDR, multidrug-resistant; OR, odds ratio; SLI, second-line injectable drug; XDR, extensively drug-resistant.
a Pre-XDR tuberculosis was defined as MDR tuberculosis with additional resistance to any FQ or any SLI but not to both groups of drugs; XDR tuberculosis, as MDR tuberculosis with additional resistance to both any FQ and any SLI; initial SLI resistance, as resistance to any of the SLIs (kanamycin, amikacin, capreomycin) at initial diagnosis of MDR tuberculosis; and initial FQ resistance, as resistance to any FQ at initial diagnosis of MDR tuberculosis.
b Variables with a natural ordering in sequential response categories are modeled as ordinal variables if the logit plot of the levels of the variables versus treatment outcome was linear or close to linear. The first OR in the series represents the relative change in odds per step in the series. Values >1 indicate successful outcomes. Values <1 indicate poor outcomes.
c Mean number of effective drugs per day until sputum culture conversion or censoring, with “effective” defined according to Centers for Disease Control and Prevention (CDC) drug susceptibility testing (DST) results. The number of effective drugs and drug resistance patterns were colinear with the set of individual effective drugs; therefore, the “base model” with drug resistance patterns and number of effective drugs does not include the set of individual effective drugs, whereas the model with the set of individual effective drugs does not include drug resistance pattern and number of effective drugs.
d Phenotypic DST for pyrazinamide and pncA gene sequencing have not yet been completed; therefore, the effectiveness of pyrazinamide is based on all available DST results, including both CDC results and those from laboratories at the participating sites all of which used the Mycobacterial Growth Indicator Tube 960 method.
e Thioamides include ethionamide and prothionamide, analyzed together as the same drug.
f Both GLC approval and routine hospitalization were colinear with country; therefore, the model with GLC and routine hospitalization does not include country. The model with country does not include GLC approval and routine hospitalization. Otherwise, the same covariates were statistically significant in both models.
g These countries did not apply to the GLC because they were too affluent (South Korea and Taiwan) or because the specific drug products provided by the GLC were not registered in the country (South Africa and Thailand) and could not be imported.