In vitro and in vivo activities of sparfloxacin against Mycoplasma pneumoniae

Abstract

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)

Emergence of Macrolide-Resistant Mycoplasma pneumoniae with a 23S rRNA Gene Mutation

“…The expansion of 14-ML, azithromycin, and telithromycin usage for RTI worldwide may increase ML-resistant M. pneumoniae. Further evaluation for new quinolones, such as sparfloxacin (10) and sitafloxacin, will be necessary in vivo and in vitro.…”

Penetration of Minocycline Hydrochloride into Lung Tissue and Sputum

“…MINO has been widely used for the treatment of various infections including those of the respiratory tract because it is active not only against common gram-positive and -negative microbes, but also against Mycoplasma, Chlamydia and Rickettsia [1][2][3]. It has been shown that MINO penetrates easily into the cell [4], but little is known of the ratio of penetration of MINO into lung tissue and sputum after intravenous infusion.…”

In Vitro Activity of Telithromycin (HMR3647), a New Ketolide, against Clinical Isolates of Mycoplasma pneumoniae in Japan

“…In vitro antimycoplasmal susceptibility tests have not been standardized; one was performed in this study by the broth microdilution method, which has been recently applied for several potent antibiotics for treatment of M. pneumoniae infections (6,8,9,12,14,15). M. pneumoniae isolates were grown to a concentration of 10 8 CFU/ml in modified Chanock broth medium (3) consisting of 7 parts pleuropneumonia-like organism (PPLO) broth without crystal violet (Difco Laboratories, Detroit, Mich.), 2 parts uninactivated horse serum, and 1 part a mixture of 25% fresh yeast extract, 1% glucose, and 0.002% phenol red adjusted to a pH of 7.8 with 1 N sodium hydroxide.…”

“…MIC 50 and MIC 90 were defined as the drug concentrations required to inhibit the growth of 50 and 90% of the total number of isolates tested, respectively (6,8,9,12,14,15). As a control for potential interactions between antibiotics, medium components, and pH, which could potentially affect the observed MICs, the American Type Culture Collection bacterial reference strain Staphylococcus aureus ATCC 29213 was inoculated into microtiter plates containing Chanock broth.…”