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07-1.21; P0.0001, I =75%). Susceptibility-guided therapy was superior to first-line clarithromycin-based triple therapy only when clarithromycin resistance exceeded 20% (RR, 1.18; 95% CI, 1.07-1.30; P=0.001, I =81%). Susceptibility-guided therapy was not more effective than empirical quadruple therapy (RR, 1.02; 95% CI, 0.92-1.13; P=0.759, I =80%). Three RCTs were performed exclusively among previously treated subjects, and were highly heterogeneous. Our findings suggest that susceptibility-guided treatment may be slightly superior