XXXX Treatment Outcomes in Relation to Treatment, Initial and Acquired Second-Line Drug Resistance.

@entity1 @entity6371 @entity3284 @entity2887 @entity378 @entity734
BACKGROUND:    Resistance to @entity734 ( @entity734 ) develops during treatment of multidrug-resistant (MDR) @entity378 ( @entity378 ), but the impact on treatment outcome has not been determined. OBJECTIVES:    To determine the relationship with treatment outcomes of (1) initial versus acquired drug resistance and (2) treatment regimens. METHODS:    @entity6371 @entity1 starting @entity734 treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to @entity2887 and second-line injectables (SLI), and (2) treatment regimens. RESULTS:    Of 1,244 @entity6371 @entity1 , 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain @entity6371 , 69.7% with initial resistance to either a @entity3284 or SLI, 37.5% with acquired resistance to a @entity3284 or SLI, 29.3% with @entity378 , and 13.0% with acquired @entity378 (P<0.0001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of proven effective drugs increased from  <=1 to >= 5 (P<0.0001 for trend); while acquired drug resistance decreased from 12%-16% range, depending on the drug, down to 0%-2% (P<0.0001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (CL 0.56,0.69) for each increment in drug resistance and increased 2.1-fold (1.40,3.18) for each additional effective drug, controlling for differences between programs and @entity1 . Specific treatment, @entity1 and program variables were also associated with treatment outcome. CONCLUSION:    Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.
