BACKGROUND Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Streptococcus pneumoniae continues to be the most important causative agent in CAP. OBJECTIVE This article reviews options for the empiric treatment of pneumococcal pneumonia in Turkey based on local epidemiologic data. METHODS This was a retrospective review of studies evaluating antimicrobial susceptibility patterns among clinical isolates of S pneumoniae in Turkey from 2000 onward. Relevant studies were identified through literature searches of both Turkish (Ulakbim and Pleksus) and international (MEDLINE) databases using the search terms S pneumoniae and Turkey. Only antibiotics likely to be used in pneumococcal pneumonia were evaluated. The minimum concentration required to inhibit 90% of isolates (MIC(90)) for each antibiotic was obtained by averaging all reported values to arrive at a single value for the entire country. RESULTS The MIC(90) for penicillin was 1 g/mL; among all isolates of S pneumoniae, 6.4% were penicillin resistant and 30.9% showed intermediate susceptibility. The MIC(90)s and overall rates of resistance (combined intermediate susceptibility and resistance) for the other antibiotics studied were as follows: cefaclor, 4 microg/mL (26.3%); cefuroxime, 2 microg/mL (15.4%); ceftriaxone, 0.25 microg/mL (0.75%); imipenem, 0.06 microg/mL (0%); erythromycin, 2 microg/mL (13.9%); clarithromycin, 2 microg/mL (13.7%); azithromycin, 2 microg/mL (13.8%); telithromycin, 0.06 microg/mL (no published breakpoints); trimethoprim-sulfamethoxazole, 4 microg/mL (63.8%); tetracycline, 16 microg/mL (24.6%); ciprofloxacin, 2 microg/mL (no published breakpoints); ofloxacin, 2 microg/mL (4%); levofloxacin, 1 microg/mL (0%); gemifloxacin, 0.06 microg/mL (no published breakpoints); and moxifloxacin, 0.06 microg/mL (0%). Penicillin G, at standard parenteral doses, has been shown to achieve concentrations above the MIC for >40% to 100% of the dosing interval, depending on the MIC of the isolate. Based on pharmacodynamic studies, the MIC(90) for penicillin in Turkey should easily be exceeded with the use of penicillin G 3 mU QID. In vitro, susceptibility is generally greater to amoxicillin than to penicillin, with average amoxicillin MIC values approximately 1 dilution lower than those for penicillin. Amoxicillin's better pharmacodynamic/pharmacokinetic properties relative to penicillin make it a reasonable option for the treatment of CAP. In pharmacodynamic studies, amoxicillin 1 g TID achieved and maintained serum concentrations of 2 to 4 microg/mL for at least 40% of the dosing interval. A new formulation of amoxicillin/clavulanate given 2000/125 mg BID is expected to eradicate isolates of S pneumoniae at an amoxicillin MIC < or = 4 microg/mL. CONCLUSIONS Based on data from Turkish surveillance studies performed from 2000 onward, high-dose parenteral penicillin G and parenteral/oral amoxicillin may be initial choices for the empiric treatment of uncomplicated pneumococcal pneumonia in Turkey. If these agents cannot be used for any reason, other options include parenteral cefuroxime, ceftriaxone, cefotaxime, newer quinolones, macrolides, and telithromycin. Due to elevated rates of resistance in Turkey, trimethoprim-sulfamethoxazole and tetracyclines are not recommended for empiric use in these infections.