Usefulness of betalactam therapy for community-acquired pneumonia in the era of drug-resistant Streptococcus pneumoniae: A randomized study of amoxicillin-clavulanate and ceftriaxone

Empirical antibiotic therapy of community-acquired pneumonia (CAP) has been complicated by the worldwide emergence of penicillin resistance among Stre ptococcus pneumoniae. The impact of this resistance on the outcome of patie nts hospitalized for CAP, empirically treated with betalactams, has not bee n evaluated in a randomized study. We conducted a prospective, randomized t rial to assess the efficacy of amoxicillin-clavulanate (2 g/200 mg/8 hr) an d ceftriaxone (1 g/24 hr) in a cohort of patients hospitalized for moderate -to-severe CAP. Three-hundred seventy-eight patients were randomized to rec eive amoxicillin-clavulanate (184 patients) or ceftriaxone (194 patients). Efficacy was assessed on Day 2, after completion of therapy and at long ter m follow-up. There were no significant differences in outcomes between trea tment groups, both in intention-to-treat and per-protocol analysis, Overall mortality was 10.3% for amoxicillin-clavulanate and 8.8% for ceftriaxone ( NS), There were 116 evaluable patients with proven pneumococcal pneumonia, Rates of high-level penicillin resistance (MIC of penicillin greater than o r equal to2 mug/mL) were similar in the two groups (8.2 and 10.2%). Clinica l efficacy at the end of therapy was 90.6% for amoxicillin-clavulanate and 88.9% for ceftriaxone (95% C.I. of the difference: -9.3 to + 12.7%). No dif ferences in outcomes were attributable to differences in penicillin suscept ibility of pneumococcal strains. Sequential i.v./oral amoxicillin-clavulana te and parenteral ceftriaxone were equally safe and effective for the empir ical treatment of acute bacterial pneumonia, including penicillin and cepha losporin-resistant pneumococcal pneumonia. The use of appropriate betalacta ms in patients with penumococcal pneumonia and in the overall CAP populatio n, is reliable at the current level of resistance.