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Two hundred four strains of Streptococcus pneumoniae isolated in Hong Kong from January 1993 to May 1995 were analyzed for their antibiotic susceptibilities and epidemiological patterns. The ages of the patients from whom the strains were isolated from 1 month to 93 years (median, 53 years); the male-to-female ratio was 2.8, with a predominance of males in the pediatric group. Fifty-nine (28.9%) strains showed reduced penicillin susceptibility, including 40 (19.6%) with frank penicillin resistance (MIC > 1 microgram/ml). Tetracycline resistance alone was found in 28.4% of strains. Isolates with reduced penicillin susceptibility were more common in children than adults (40 versus 23.9%, P = 0.02), and penicillin resistance rates were significantly higher in hospitalized patients than in outpatients (39.5 versus 12.5%; p < 0.001). Penicillin resistance was significantly associated with resistance to ceftriaxone, erythromycin, and tetracycline (P < 0.01) but not with ofloxacin or vancomycin (P = 0.5). Among eight different patterns of resistance to three or more antibiotics, the commonest one (14.2%) was multiple resistance to penicillin, chloramphenicol, ceftriaxone, erythromycin, and tetracycline. Emergence of multiple-antibiotic-resistant S. pneumoniae reflects changes in the pneumococcus itself and the general indiscriminate use of antibiotics in treatment of respiratory infections in Hong Kong.