Susceptibility of Newly Established Mouse Strain MPS to <i>Mycoplasma pneumoniae</i> Infection

Sasaki, Yuko; Ogura, Atuo; Nakayama, Kazue; Noguchi, Yoko; Matsuno, Kumiko; Saito, Manabu

doi:10.1111/j.1348-0421.1991.tb01553.x

Cited by 5 publications

(2 citation statements)

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“…In groups treated with 15 mg/kg twice daily for 2.5 days, hamsters were sacrificed on day 9 after infection. In groups treated with 15 mg/kg twice daily for 5 (17). M. pneumoniae was not recovered from the plates with the 100 and 10-1 dilutions after azithromycin therapy because of the high concentration of azithromycin remaining in the medium, so colony counts for all therapeutic courses were determined with plates with dilutions of 10-2 or 10-3.…”

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In vitro and in vivo activities of macrolides against Mycoplasma pneumoniae

Ishida

Kaku

Irifune

et al. 1994

Antimicrob Agents Chemother

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We investigated the in vitro and in vivo activities of macrolides against Mycoplasma pneumoniae. In vitro MICs of azithromycin, erythromycin, clarithromycin, and roxithromycin were determined. Azithromycin was the most potent antimicrobial agent tested in vitro. Its MIC for 90%o of the strains was 0.00024 ,ug/ml. MICs for 90%o of the strains of erythromycin, clarithromycin, and roxithromycin were 0.0156, 0.0078, and 0.03125 ,ug/mI, respectively. In vivo activities were assessed in a pulmonary infection model with Syrian golden hamsters. We evaluated the in vivo effects on reduction of viable M. pneumoniae cell counts and on reduction of microscopic and macroscopic histopathologies for azithromycin, erythromycin, and clarithromycin given at 10 mg/kg once daily for 1 and 3 days and given at 15 mg/kg twice daily for 2.5 and 5 days. Mycoplasma pneumoniae is a major cause of pneumonia and accounts for as many as 20% of the total number of cases of pneumonia (6). The recommended therapy is erythromycin, which is efficacious in reducing the duration of symptoms (19). Recently, it has been suggested that new macrolides (8, 10), such as azithromycin, clarithromycin, and roxithromycin, may be used more frequently for respiratory tract infections because of their improved potencies and pharmacokinetic parameters compared with those of erythromycin (10). Azithromycin is a new azalide antibiotic (7, 15) that differs from erythromycin by a methyl-substituted nitrogen at position 9a within the macrocyclic ring. This modification has resulted in improved potency against gram-negative bacteria. Moreover, azithromycin proved to be superior to erythromycin in a mouse pneumococcal model because of these improved pharmacokinetic parameters (1).In this study we evaluated the in vitro antimycoplasmal activities of azithromycin, erythromycin, clarithromycin, and roxithromycin. We also tested the in vivo antimycoplasmal efficacies of azithromycin, erythromycin, and clarithromycin in courses of 10 mg/kg once daily for 1 or 3 days or 15 mg/kg twice daily for 2.5 or 5 days by using an experimental pulmonary infection model with Syrian golden hamsters (2). Organisms. Forty clinically isolated strains of M. pneumoniae obtained from 1988 to 1992 at Nagasaki University Hospital and three standard strains, FH, Mac, and M129, which were supplied by M. F. Barile (Food and Drug Administration, Bethesda, Md.), were used for in vitro tests, and the virulent strain M129 at passage level 12 was used for experimental mycoplasmal pneumonia in Syrian golden hamsters.MIC determinations. MICs were determined by using a modified broth microdilution method (12, 22, 23) with modified Chanock broth medium (3), which consisted of seven parts PPLO broth without crystal violet (Difco Laboratories, Detroit, Mich.), 2 parts uninactivated horse serum, 1 part 25% fresh yeast extract, 1% glucose, and 0.002% phenol red adjusted to pH 7.8 with 1 N sodium hydroxide. Inocula were 10 CFU/ml. The plates, sealed with plate sealers, were incubated at 37°C in air. In each case...

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In vitro and in vivo activities of macrolides against Mycoplasma pneumoniae

Ishida

Kaku

Irifune

et al. 1994

Antimicrob Agents Chemother

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“…Each group consisted of five 6-week-old male Syrian golden hamsters weighing about 100 g each (Japan SLC, Shizuoka, Japan). Animals were anesthetized by intraperitoneal injection of ketamine (Sankyo Co., Ltd.) and infected by the intratracheal intubation method described previously (3) Lungs were removed aseptically, and the viable M. pneumoniae cells per lung were counted by the method described previously (14). Some colonies were used for identification of M. pneumoniae by a growth-inhibition test with anti-M. pneumoniae rabbit serum and by their hemadsorption properties (5).…”

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In vitro and in vivo activities of sparfloxacin against Mycoplasma pneumoniae

Kaku

Ishida

Irifune

et al. 1994

Antimicrob Agents Chemother

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The in vitro and in vivo activities of sparfloxacin against Mycoplasma pneumoniae were compared with those of erythromycin, levofloxacin, ofloxacin, and minocycline. The MICs of sparfloxacin, erythromycin, levofloxacin, ofloxacin, and minocycline for 90%7o of the 43 M. pneumoniae strains tested were 0.063, 0.016, 0.5, 1, and 0.5 ,ug/ml, respectively. In the experimental pulmonary M. pneumoniae infection model in Syrian golden hamsters, sparfloxacin was as eflective as erythromycin when orally administered at 15 mg/kg twice daily for 5 days and more eflective than erythromycin when orally administered at 10 mg/kg once daily for 5 days. Sparfloxacin was more elfective than levofloxacin and ofloxacin in both dosing regimens. The peak concentrations of sparfloxacin in hamster sera after administration of single oral doses of 15 mg/kg were almost the same as those in human sera after administration of single oral doses of 200 mg (the usual clinical dose), and the half-life of sparfloxacin in hamster serum was shorter than that in human serum after administration of a single oral dose of 200 mg. These results suggest that sparfloxacin may be clinically useful for the treatment of M. pneumonwae infections.Mycoplasma pneumoniae is a major causative organism of pneumonia and accounts for about 20% of total pneumonia infections (6). The recommended therapeutic drug against M. pneumoniae infections is now erythromycin, which is efficacious in shortening the duration of symptoms (15). However, an increase in the number of mutants resistant to erythromycin has been reported (11). So, new chemotherapeutic drugs have been desired for the treatment of mycoplasmal infections. New quinolones (18) with a broad spectrum of activity against gram-positive and gram-negative bacteria have been developed during the past decade, and some of them have been reported to be active against M. pneumoniae (1, 2,8,12,17). In particular, the in vitro activity of sparfloxacin (10) (17) with modified Chanock broth medium (4) consisting of 7 parts PPLO broth without crystal violet (Difco Laboratories, Detroit, Mich.), 2 parts uninactivated horse serum, 1 part 25% fresh yeast extract, 1% glucose, and 0.002% phenol red and adjusted to pH 7.8 and inocula of 105 CFU/ml. The plates, sealed with plate sealers, were then incubated at 37°C in air. In each case, when the color of the medium of the drug-free control changed from red to yellow, the minimal concentration of drug preventing the color change was defined as the MIC (17).Assessment of in vivo activities. The in vivo activities of drugs were assessed in a pulmonary M. pneumoniae infection model using Syrian golden hamsters (1,3,16). Each group consisted of five 6-week-old male Syrian golden hamsters weighing about 100 g each (Japan SLC, Shizuoka, Japan). Animals were anesthetized by intraperitoneal injection of ketamine (Sankyo Co., Ltd.) and infected by the intratracheal intubation method described previously (3)

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