title: [In vitro and in vivo activities of panipenem against penicillin-resistant Streptococcus pneumoniae].
abstract: Efficacy of panipenem/betamipron (PAPM/BP) against experimental pneumonia caused by penicillin-resistant Streptococcus pneumoniae (PRSP: MIC of benzylpenicillin, > or = 1.56 micrograms/ml) in mice was compared with those of imipenem/cilastatin (IPM/CS), meropenem (MEPM), cefozopran (CZOP), ceftriaxone (CTRX), ampicillin (ABPC), and vancomycin (VCM). The infection was induced by inoculating a PRSP clinical isolate, 9601 (serotype 6) or 10,693 (serotype 19), into ddY male mice intranasally. Drugs were administered subcutaneously at doses of 0.4, 2, and 10 mg/kg, 18, 26, 42, and 50 hours post-infection. Viable cell counts in the lungs were determined 66 hours post-infection. PAPM/BP showed the greatest efficacy against the infections among tested drugs. MICs of PAPM against PRSP 9601 and 10,693 were both 0.125 microgram/ml, which were superior to those of IPM (0.25 and 0.5 microgram/ml, respectively), MEPM (0.5 and 1 microgram/ml, respectively), CZOP (2 and 1 microgram/ml, respectively), CTRX (both 1 microgram/ml), ABPC (both 4 micrograms/ml), and VCM (0.5 and 0.25 microgram/ml, respectively). These results suggest that the potent in vivo activity of PAPM/BP reflects the potent in vitro activity of PAPM. MICs of PAPM, IPM, MEPM, and CZOP against clinical isolates, penicillin-susceptible S. pneumoniae (PSSP: MIC of benzylpenicillin, < or = 0.05 microgram/ml), penicillin-intermediate S. pneumoniae (PISP: MIC of benzylpenicillin, 0.1-0.78 microgram/ml), and PRSP, were tested by an agar dilution method. MIC90s of the drugs against the PSSP, PISP, and PRSP were as follows: PAPM, 0.012, 0.05, and 0.39 microgram/ml; IPM, < or = 0.006, 0.1, and 0.78 microgram/ml; MEPM, 0.05, 0.39, and 1.56 micrograms/ml; and CZOP, 0.2, 0.78, and 6.25 micrograms/ml, respectively. Thus, PAPM showed the most potent activity among tested drugs against clinical isolates of PISP and PRSP.
authors.affiliation: Biological Research Laboratories, Sankyo Co., Ltd., 2-58 Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fukuoka
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Abe
authors.forename: S
authors.initials: S
authors.lastname: Ohya
mesh_terms: D000667:Ampicillin / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002443:Ceftriaxone / Q000494:pharmacology / Q000627:therapeutic use; D002511:Cephalosporins / Q000494:pharmacology / Q000627:therapeutic use; D015377:Cilastatin / Q000494:pharmacology / Q000627:therapeutic use; D000077728:Cilastatin, Imipenem Drug Combination; D004195:Disease Models, Animal; D004338:Drug Combinations; D004351:Drug Resistance; D015378:Imipenem / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D000077731:Meropenem; D051379:Mice; D008815:Mice, Inbred Strains; D010403:Penicillin Resistance; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D013845:Thienamycins / Q000494:pharmacology* / Q000627:therapeutic use*; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use*; D000097586:Cefozopran
chemical_list: D000667:Ampicillin; D002443:Ceftriaxone; D002511:Cephalosporins; D015377:Cilastatin; D000077728:Cilastatin, Imipenem Drug Combination; D004338:Drug Combinations; D015378:Imipenem; D000077731:Meropenem; D013845:Thienamycins; D014640:Vancomycin; D015091:beta-Alanine; D000097586:Cefozopran; C075316:panipenem-betamipron