In vitro activity of gemifloxacin (SB-265805) compared with 14 other antimicrobials against intestinal pathogens

We studied the in vitro activity of gemifloxacin (SB-265805) and 14 comparator antimicrobials against 288 recent isolates of enteropathogenic bacteria (106 Salmonella: spp., 32 Hafnia alvei, 22 Yersinia enterocolitica, 21 Shigella: spp., 16 Aeromonas: spp. and 91 Campylobacter jejuni). Gemifloxacin, the other fluoroquinolones and cefotaxime were very active against all microorganisms tested except for C. jejuni. Seventy-seven per cent of isolates of C. jejuni were inhibited by erythromycin < or =0.5 mg/L. Only one strain of C. jejuni was highly resistant to this antimicrobial agent. Of the compounds tested, gentamicin was the most active in vitro. The in vitro activity of the other antibiotics tested was variable. A quinolone could be a good choice for treating gastrointestinal infections when antimicrobial therapy is indicated. For C. jejuni, another antibiotic such as erythromycin should be considered.     

Comparative in vitro activity of older and newer fluoroquinolones against respiratory tract pathogens

The aim of this study was to evaluate the antibacterial activity of older (ciprofloxacin and ofloxacin) and newer (moxifloxacin, grepafloxacin, sparfloxacin and levofloxacin) fluoroquinolones. Minimal inhibitory concentrations (MICs) were determined, according to the NCCLS guidelines, against the following respiratory tract pathogens: penicillin-susceptible and -resistant Streptococcus pneumoniae, beta-lactamase-positive and beta-lactamase-negative Haemophilus influenzae and beta-lactamase-positive Moraxella catarrhalis. In addition, we evaluated the minimal bactericidal concentrations of the same antibiotics against all the pneumococci and the haemophili. Finally, the activity of ciprofloxacin, ofloxacin, sparfloxacin and moxifloxacin against 15 pneumococci were investigated by time-kill analysis. All fluoroquinolones tested exhibited a similar, good activity against H. influenzae and M. catarrhalis. Against S. pneumoniae, irrespective of penicillin susceptibility, moxifloxacin, grepafloxacin, sparfloxacin and levofloxacin exhibited excellent activity, better than ciprofloxacin and ofloxacin. Time-kill analysis showed that 99.9% killing of all strains was obtained after 24 h with moxifloxacin at 2 x MIC, whereas other antimicrobials obtained similar results at 4 x MIC. Moxifloxacin is characterized by an improved activity against respiratory pathogens, including penicillin-resistant and -susceptible S. pneumoniae. Its activity is not influenced by beta-lactamase production. These results suggest that moxifloxacin represents a promising alternative for treatment of respiratory tract infections.     

Comparative in vitro activity of a new quinolone, fleroxacin, against respiratory pathogens from patients with cystic fibrosis.

We evaluated fleroxacin, a newer fluoroquinolone, against isolates from sputum from patients with cystic fibrosis. These isolates included rough and mucoid Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli. Selected isolates were tested by the broth microdilution method to examine the influence of various pHs, inoculum sizes, and biological fluids (serum or sputum from patients with cystic fibrosis). Fleroxacin MICs for 50 and 90% of isolates of P. aeruginosa were 2.0 and 4 micrograms/ml, those for P. cepacia were 2 and 16 micrograms/ml, those for S. aureus were 0.5 and 1 microgram/ml, those for H. influenzae were 0.06 and 0.06 micrograms/ml, and those for E. coli were 0.01 and 0.03 micrograms/ml, respectively. Fleroxacin activity against mucoid P. aeruginosa was similar to the activities of enoxacin and ofloxacin but eightfold lower than that of ciprofloxacin. It was twofold more active than norfloxacin and enoxacin but was twofold less active than ciprofloxacin, ofloxacin, and nafcillin against S. aureus. Fleroxacin inhibitory activity against P. cepacia was two- to fourfold lower than that of ciprofloxacin but eightfold greater than those of the other quinolones tested. Alterations in pH, diluent, and inoculum size did not significantly affect fleroxacin activity. These results, combined with available pharmacokinetic and tissue distribution data, support the need for clinical evaluation of fleroxacin in pulmonary infections in patients with cystic fibrosis.     

In vitro activity of telithromycin against respiratory tract pathogens in comparison with other antimicrobial agents

This study was done to evaluate the in vitro activity of a new ketolide telithromycin in comparison with clarithromycin, erythromycin, moxifloxacin and levofloxacin against Streptococcus pneumoniae (n = 67), Haemophilus influenzae (n = 139), and Moraxella catarrhalis (n = 46)collected between January and June 2003 in Hong Kong. Among the H. influenzae isolates, 25.2% produced beta-lactamase, while 97.8% of M. catarrhalis isolates produced beta-lactamase. Half of the S. pneumoniae isolates were nonsusceptible to penicillin, and 90.9% of these strains were resistant to clarithromycin and erythromycin. One (1.5%) S. pneumoniae strain was resistant to levofloxacin (MIC = 8 mg/l) and all isolates were sensitive to moxifloxacin and telithromycin with MIC <1 mg/l. H. influenzae isolates were sensitive to all fluoroquinolones tested and 2.2% of H. influenzae were resistant to clarithromycin. M. catarrhalis isolates were sensitive except 1 strain which was resistant to levofloxacin (MIC = 4 mg/l) and moxifloxacin (8 mg/l). All M. catarrhalis strains were sensitive to telithromycin with MIC90 = 0.5 mg/l. Telithromycin demonstrated high activity and no resistance was found in all these major respiratory tract pathogens.     

In vitro activity of gemifloxacin (SB 265805; LB20304a) against human mycoplasmas

The in vitro activity of gemifloxacin, a new broad-spectrum fluoroquinolone, was compared with those of ciprofloxacin, erythromycin, azithromycin and doxycycline against 29 human respiratory or urogenital tract mycoplasmas. Gemifloxacin was highly active against all of the mycoplasma and ureaplasma species tested (MIC range 0.001-0.25 mg/L) and was 5- to 100-fold more active than ciprofloxacin. Doxycycline was less active than gemifloxacin against the mycoplasmas (MIC range 0.01-1 mg/L) but had similar activity against Ureaplasma urealyticum (MIC ranges 0.025-0.25 mg/L and 0.1-0. 25 mg/L, respectively). The macrolides, particularly azithromycin, were more active than gemifloxacin against Mycoplasma pneumoniae (MIC range 0.001-0.0025 mg/L) and Mycoplasma genitalium (0.0005-0. 001 mg/L) isolates but were less active against Mycoplasma fermentans and U. urealyticum and inactive against Mycoplasma hominis. Gemifloxacin may therefore be useful in the treatment of respiratory, urogenital or systemic mycoplasma infections in humans.     

In vitro antibacterial activity of gemifloxacin and comparator compounds against common respiratory pathogens

This study investigated the in vitro potency of the novel quinolone agent gemifloxacin (SB-265805), in comparison with other quionolones, beta-lactams, macrolides and trimethoprim- sulphamethoxazole, against a panel of common respiratory pathogens. This panel comprised recent clinical isolates of Streptococcus pneumoniae (n = 347), Haemophilus influenzae (n = 256) and Moraxella catarrhalis (n = 184). Overall, the quinolones were highly active against H. influenzae and were the most potent agents against M. catarrhalis. Gemifloxacin was the most potent quinolone tested against all three species and was four- to 512-fold more potent against pneumococci than trovafloxacin, grepafloxacin, levofloxacin, ciprofloxacin, ofloxacin, gentamicin, cefuroxime, penicillin, ampicillin, clarithromycin, azithromycin or trimethoprim- sulphamethoxazole. Against 19 ofloxacin-intermediate and 52 ofloxacin-resistant strains of S. pneumoniae, gemifloxacin retained activity, and was the only agent tested with MICs of < or =0.5 mg/L. The results of this study demonstrate the excellent in vitro antibacterial activity of gemifloxacin against pathogens commonly associated with respiratory tract infections and suggest that gemifloxacin has significant potential in the treatment of such infections, including those caused by pneumococci considered resistant to other quinolones.     

Antimicrobial activity of gemifloxacin (SB-265805), a newer fluoroquinolone, against clinical isolates of Neisseria gonorrhoeae, including fluoroquinolone-resistant isolates

Antimicrobial activity of gemifloxacin (SB-265805), a newly developed fluoroquinolone, to Japanese isolates of Neisseria gonorrhoeae was compared with those of various fluoroquinolones, including norfloxacin, ciprofloxacin, tosufloxacin, levofloxacin, sparfloxacin, and trovafloxacin. Among the fluoroquinolones tested, gemifloxacin was most active against N. gonorrhoeae isolates. The MIC90 values of gemifloxacin for 94 N. gonorrhoeae isolated from 1992 through 1993 and 100 isolated from 1996 through 1997 were 0.03 and 0.125 microg/ml, respectively. On the other hand, MIC90 values of the other fluoroquinolone for the 1992-1993 isolates and the 1996-1997 isolates ranged from 0.125 to 2 microg/ml and from 0.5 to 8 microg/ml, respectively. Gemifloxacin was also the most potent fluoroquinolone against 31 ciprofloxacin-resistant isolates with the ciprofloxacin MIC of 1 to 16 microg/ml, for which the gemifloxacin MIC50 and MIC90 values were 0.25 and 2 microg/ml, respectively. Moreover, the activity of gemifloxacin against fluoroquinolone-resistant gonococcal isolates containing multiple amino acid substitutions in both GyrA and ParC proteins was superior to those of the other compounds.     

Comparative in vitro activity of S-4661, a new parenteral carbapenem, and other antimicrobial agents against respiratory pathogens

The activity of S-4661, a new parenteral carbapenem antibiotic, was evaluated against 202 recent clinical isolates of respiratory pathogens. S-4661 was similar to or 2 times more active than imipenem, meropenem, and biapenem, and 8-128 times more active than ceftazidime against gram-positive bacteria. Against gram-negative bacteria, S-4661 was slightly less active than meropenem, but 2-8 times more active than the other agents. In particular, against Pseudomonas aeruginosa S-4661 showed the most potent activity. Thus it was found that S-4661 possesses a potent and well-balanced activity against respiratory pathogens.     

Pharmacokinetics and tolerability of gemifloxacin (SB-265805) after administration of single oral doses to healthy volunteers

Gemifloxacin (known as SB-265805 or LB-20304) is a potent, novel fluoroquinolone compound with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in healthy male volunteers after a single dose of 20, 40, 80, 160, 320, 600, or 800 mg. Multiple serum and urine samples were collected and analyzed for gemifloxacin using high-performance liquid chromatography with fluorescence detection. Safety assessments included vital signs, 12-lead electrocardiogram readings, hematology, clinical chemistry, urinalysis, and adverse-experience monitoring. Gemifloxacin was rapidly absorbed after all doses. Maximum concentrations of gemifloxacin in serum (C(max)) were achieved approximately 1 h after dosing, after which concentrations in serum declined in a biexponential manner. Values of C(max) and the area under the concentration-time curve in serum from 0 h to infinity (serum AUC(0-infinity)) increased linearly with dose. Serum AUC(0-infinity) values (mean +/- standard deviation) were 0.65+/-0.01, 1.28+/-0.22, 2.54+/-0.31, 5.48+/-1.24, 9.82+/-2.70, 24.4+/-7.1, and 31.4+/-7.6 microg. h/ml following 20-, 40-, 80-, 160-, 320-, 600-, and 800-mg doses, respectively. The terminal phase elimination half-life was independent of dose, with an overall mean of 7.4+/-2.0 h. The profiles indicated that the pharmacokinetic profile is suitable for a once-daily dosing regimen. Approximately 25 to 40% of the administered dose was excreted unchanged in the urine, and renal clearance (ca. 150 ml/min) was independent of dose. There were no significant changes in clinical chemistry, hematology, or urinalysis parameters, vital signs, or 12-lead electrocardiogram readings in subjects, irrespective of dose. The results of these studies support the further investigation of once-daily administration of gemifloxacin.     

In vitro activity of tosufloxacin, a new quinolone, against respiratory pathogens derived from cystic fibrosis sputum.

By using broth microdilution methods, the in vitro activity of tosufloxacin (A-64730), a new quinolone, was compared with those of other agents, including five quinolones, against geographically diverse cystic fibrosis sputum isolates obtained from 26 cystic fibrosis centers in the United States. These included Pseudomonas aeruginosa, conventional as well as especially resistant (ceftazidime, aztreonam, gentamicin, and/or tobramycin) isolates: Escherichia coli; Pseudomonas cepacia; Staphylococcus aureus; and Haemophilus influenzae. Tosufloxacin MICs for 50 and 90% of isolates of standard P. aeruginosa were 0.5 and 2.0 mg/liter, for resistant P. aeruginosa they were 4.0 and greater than 16.0 mg/liter, for E. coli they were less than or equal to 0.016 mg/liter, for P. cepacia they were 4.0 and 8.0 mg/liter, for S. aureus they were 0.063 and 0.063 mg/liter, and for H. influenzae they were less than or equal to 0.016 and 0.032 mg/liter, respectively. Tosufloxacin activities against standard and resistant strains of P. aeruginosa were similar to those of comparative quinolones. Against E. coli, tosufloxacin activity was similar to those of other quinolones. Against S. aureus, tosufloxacin activity was similar to those of trimethoprim-sulfamethoxazole and cephalexin, but tosufloxacin was more active than other agents. Against H. influenzae, tosufloxacin activity was similar to those of other quinolones. There was minor diminution of activity at pH 8.2 but major diminution of activity at pH 5.2 and at inoculum sizes of greater than or equal to 10(7) CFU/ml. Activity was unaffected by sputum but was enhanced by serum and by the omission of cation supplementation. Tosufloxacin has consistent activity against common cystic fibrosis pathogens. Its high degree of activity against S. aureus with activity maintained against P. aeruginosa and other gram-negative bacteria of interest suggests that further in vitro studies and assessment of activity in in vivo models of cystic fibrosis pulmonary infections are warranted.     

Comparative in vitro activity of gemifloxacin

Gemifloxacin is a new quinolone and, like moxifloxacin, trovafloxacin, grepafloxacin and clinafloxacin, is more potent in vitro than ciprofloxacin or ofloxacin against Gram-positive aerobes. Gemifloxacin was the most potent of the quinolones tested against streptococci and most ciprofloxacin-resistant pneumococci were susceptible to gemifloxacin. Gemifloxacin, like moxifloxacin, trovafloxacin, grepafloxacin and clinafloxacin, was more potent than ciprofloxacin or ofloxacin against all staphylococci and many ciprofloxacin-resistant isolates were susceptible to these quinolones. Against Gram-negative aerobes gemifloxacin was as potent as or slightly less potent than ciprofloxacin, and isolates resistant to ciprofloxacin were also resistant to gemifloxacin and to moxifloxacin, trovafloxacin and grepafloxacin. Gemifloxacin was also the most potent quinolone against Gram-positive anaerobes and fusobacteria but trovafloxacin was the most potent agent tested against other Gram-negative anaerobes.     

Development of in vitro susceptibility testing methods for gemifloxacin (formerly LB20304a or SB-265805), an investigational fluoronaphthyridone

Potent investigational fluoroquinolones require convenient, but accurate, diagnostic tests for initially applied clinical trials. For this purpose, gemifloxacin (formerly SB-265805, LB20304a) was tested by the reference dilution tests and standardized disk diffusion methods of the National Committee for Clinical Laboratory Standards (NCCLS) to establish interpretive criteria. For rapid-growing pathogens, 986 organisms were tested by broth microdilution MIC, and 5- and 10-microgram disk diffusion tests. Correlation (r) between 5- and 10-microgram disk zone diameters was 0.99 (y = -0.12 to 0.99x) and the preferred 5-microgram disk zone/MIC scattergram produced a regression of y = 14.8 to 0.41x (r = 0.93). At potential pharmacodynamics (Cmax = 1.3 micrograms/mL for 320 mg dose) validated breakpoints of < or = 0.5 microgram/mL for susceptible and > or = 2 micrograms/mL for resistant, correlate zones of > or = 17 mm and < or = 13 mm produced rare serious interpretive errors (0.1%) and 96.7% absolute categorical agreement. For 304 Streptococcus pneumoniae and 305 strains of other streptococci, the same breakpoints produced 100 and 99.1% categorical accuracy even when testing levofloxacin-resistant (MIC, > or = 4 micrograms/mL) strains. Interpretive breakpoints were proposed for Hemophilus influenzae (300 strains tested), with complete correlation between tests. Etest (AB BIODISK, Solna, Sweden) was compared in all experiments with the fastidious species and showed a trend toward higher values (twofold). Gemifloxacin in vitro susceptibility test methods seem to be accurate and with very acceptable intermethod agreement, supported by previously reported functional quality control guidelines.     

Review of the in vitro activity of gemifloxacin against gram-positive and gram-negative anaerobic pathogens

Published reports on the in vitro activity of gemifloxacin mesylate (SB 265805), a new fluoronaphthyridone, against anaerobic pathogens are reviewed here. The studies used a variety of media, inocula and antimicrobial agents. Using a proposed breakpoint of 0.5 mg/L, these studies showed that gemifloxacin had generally higher potency against Gram-positive anaerobes (Clostridium perfringens, all Peptostreptococcus spp.) and fusobacteria (Fusobacterium nucleatum, Fusobacterium necrophorum) and moderate but variable potency against Gram-negative anaerobes. Bacteroides stercoris, Bacteroides tectum and many Bacteroides fragilis isolates were inhibited by concentrations of < or =0.5 mg/L, while the other species of the B. fragilis group required higher concentrations for inhibition. Species variability was evident: Porphyromonas asaccharolytica, Porphyromonas canoris, Porphyromonas gingivalis, Porphyromonas macaccae, Prevotella heparinolytica and Prevotella intermedia were susceptible to 0.5 mg/L of gemifloxacin while most other Porphyromonas and Prevotella spp. were not. These data suggest that gemifloxacin may have a clinical role in the treatment of certain dental, head and neck and pleuropulmonary infections in which Gram-positive anaerobes, fusobacteria and some Prevotella and Porphyromonas spp. may predominate.     

头孢丙烯及其他4种抗生素对社区获得性呼吸道感染病原菌体外抗菌活性比较

目的 :调查头孢丙烯及其他 4种抗生素对社区获得性呼吸道感染细菌的体外抗菌活性。方法 :肺炎链球菌、流感嗜血杆菌和卡他莫拉菌用全自动细菌分析系统的革兰阳性菌鉴定卡GPI、奈瑟及嗜血杆菌鉴定卡NHI做最终鉴定。药物敏感性试验采用Etest方法测定MIC。结果 :共计测定了 15 5株肺炎链球菌、97株流感嗜血杆菌、2 0株卡他莫拉菌、12株苯唑西林敏感的金黄色葡萄球菌 ,19株 β 溶血链球菌的药物敏感性试验。结果表明肺炎链球菌对 5种常用抗生素的敏感率分别为 :头孢丙烯 90 .3%、头孢克罗 85 .2 % ,阿奇霉素 2 5 .8%、青霉素 80 .6 %、阿莫西林 克拉维酸为 94 .2 %。流感嗜血杆菌对头孢丙烯和头孢克罗敏感率均为 97.9%。结论 :头孢丙烯对社区获得性呼吸道感染的 5种主要病原菌均显示了很高的体外抗菌活性。     

In vitro activity of A-56619 (difloxacin), A-56620, and other new quinolone antimicrobial agents against genital pathogens.

The in vitro activities of two new carboxyquinolones, A-56619 (difloxacin) and A-56620, were compared with those of ciprofloxacin, norfloxacin, and ofloxacin against genital tract pathogens. All the quinolones were highly active against Neisseria gonorrhoeae. A-56619 had the lowest MICs against Chlamydia trachomatis (MIC range, 0.125 to 0.25 micrograms/ml) and Haemophilus ducreyi (MIC for 90% of isolates tested, 0.1 micrograms/ml).     

Pharmacodynamics of telithromycin In vitro against respiratory tract pathogens

Telithromycin (HMR 3647) is a new ketolide that belongs to a new class of semisynthetic 14-membered-ring macrolides which have expanded activity against multidrug-resistant gram-positive bacteria. The aim of the present study was to investigate different basic pharmacodynamic properties of this new compound. The following studies of telithromycin were performed: (i) studies of the rate and extent of killing of respiratory tract pathogens with different susceptibilities to erythromycin and penicillin exposed to a fixed concentration that corresponds to a dose of 800 mg in humans, (ii) studies of the rate and extent of killing of telithromycin at five different concentrations, (iii) studies of the rate and extent of killing of the same pathogens at three different inocula, (iv) studies of the postantibiotic effect and the postantibiotic sub-MIC effect of telithromycin, and (v) determination of the rate and extent of killing of telithromycin in an in vitro kinetic model. In conclusion, telithromycin exerted an extremely fast killing of all strains of Streptococcus pneumoniae both with static concentrations and in the in vitro kinetic model. A slower killing of the strains of Streptococcus pyogenes was noted, with regrowth in the kinetic model of a macrolide-lincosamide-streptogramin B-inducible strain. The strains of Haemophilus influenzae were not killed at all at a concentration of 0.6 mg/liter due to high MICs. A time-dependent killing was seen for all strains. No inoculum effect was seen for the strains of S. pneumoniae, with a 99.9% reduction in the numbers of CFU for all inocula at both 8 h and 24 h. The killing of the strains of S. pyogenes was reduced by 1 log(10) CFU at 8 h and 2 to 3 log(10) CFU at 24 h when the two lower inocula were used but not at all at 8 and 24 h when the highest inoculum was used. For both of the H. influenzae strains there was an inoculum effect, with 1 to 2 log(10) CFU less killing for the inoculum of 10(8) CFU/ml in comparison to that for the inoculum of 10(6) CFU/ml. Overall, telithromycin exhibited long postantibiotic effects and postantibiotic sub-MIC effects for all strains investigated.     

Contemporary evaluation of the in vitro activity and spectrum of cefdinir compared with other orally administered antimicrobials tested against common respiratory tract pathogens (2000-2002)

Cefdinir is an oral cephalosporin approved by the Food and Drug Administration in 1997 for the treatment of acute exacerbation of chronic bronchitis, pharyngitis-tonsillitis, community-acquired pneumonia, acute maxillary sinusitis, and uncomplicated skin and skin structure infections in adults and adolescents, and acute otitis media, pharyngitis-tonsillitis, and uncomplicated skin and skin structure infections in children. Although cefdinir showed similar activity to other cephalosporins in the early studies, very limited data has been generated over the last decade. In this report, we summarize the contemporary in vitro activity and spectrum of cefdinir in comparison to numerous other orally administrated antimicrobials available for treatment of community-acquired respiratory infections. A total of 8,326 non-duplicate recent clinical isolates, including Haemophilus influenzae (3,438), Moraxella catarrhalis (1,688), and Streptococcus pneumoniae (3,200), were collected from 35 medical centers in North America during 2000 through 2002, and susceptibility tested by reference broth microdilution methods. Pneumococcal susceptibility patterns for beta-lactams and macrolides were also analyzed according to the year of isolation and the age group of the patients. Cefdinir had the greatest activity against H. influenzae among the cephalosporins tested with susceptibility rates of 97.1 to 99.0%. All of the agents tested had complete or near complete activity against M. catarrhalis. Against S. pneumoniae, cefdinir and other cephalosporins showed similar susceptibility patterns, but improved rates were observed in 2002 (78.5-79.4%) when compared to the previous monitored period (71.8-74.5%). This increase in susceptibility was mainly because of a declining the occurrence of high-level penicillin resistance (MIC >/=2 microg/ml) across all age groups. Macrolide resistance also decreased among S. pneumoniae in 2002 when compared to 2000 through 2001; however, resistance to levofloxacin continued to increase from 0.9% in 2000 to 1.4% in 2002. These results indicate a significant change in emerging beta-lactam resistance patterns (including cefdinir) with a decrease possibly influenced by greater pneumococcal vaccine use in children and the elderly. These rates of increased susceptibility could sustain and enhance the clinical activity of orally administered beta-lactams such as cefdinir.     

Comparative in vivo activity of gemifloxacin in a rat model of respiratory tract infection

The in vivo efficacy of the novel quinolone gemifloxacin (SB-265805) was examined in a rat respiratory tract infection (RTI) model against four strains of Streptococcus pneumoniae and two strains of Haemophilus influenzae with varying susceptibilities to standard antimicrobial agents. Animals were infected intrabronchially to produce pneumonia and therapy with oral gemifloxacin, amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin or levofloxacin was started 24 h after infection. The doses administered were chosen to approximate in the rat the serum or tissue concentrations measured in humans following therapeutic dosing. Therapy continued once- or twice-daily for 3 days, and approximately 17 h after the end of therapy the lungs were excised for bacterial enumeration. Following infection with strains of S. pneumoniae, gemifloxacin produced a 3-5 log reduction in bacterial numbers compared with untreated animals. Gemifloxacin was as effective as amoxycillin- clavulanate, and was as potent or more potent than all other comparators. Notably, the quinolone agents trovafloxacin, ciprofloxacin, grepafloxacin and levofloxacin were significantly less effective (P < 0.01) than gemifloxacin: these agents reduced bacterial numbers by < or =3 log compared with untreated animals. Gemifloxacin produced a marked response against H. influenzae infection, reducing bacterial numbers significantly (P < 0.01) compared with untreated controls. Gemifloxacin was significantly more potent than cefuroxime and azithromycin. None of the other comparator agents was more potent than gemifloxacin. The excellent efficacy seen in these experimental models of RTI with S. pneumoniae and H. influenzae confirms the in vitro activity of gemifloxacin against these organisms. This indicates that gemifloxacin may be of significant benefit in the treatment of RTI.     

Comparative in vitro activity of carbapenem antibiotics against respiratory pathogens isolated in recent years

We investigated the antibacterial activity of 12 antibiotics, including 4 carbapenems, against 200 strains of respiratory pathogens isolated in 1997, and compared the results with those obtained in 1993. The strains examined were 38 strains of methicillin-susceptible Staphylococcus aureus (MSSA), 32 strains of methicillin-resistant S. aureus (MRSA), 22 strains of penicillin-susceptible Streptococcus pneumoniae (PSSP), 10 strains of penicillin-resistant S. pneumoniae (PRSP), 53 strains of Pseudomonas aeruginosa, 19 strains of Moraxella catarrhalis, and 26 strains of Haemophilus influenzae. In 1993, 100 strains were examined. The minimal inhibitory concentration data of the present study showed that imipenem and panipenem were more active than the other agents against gram-positive bacteria, and that meropenem and biapenem were more active than the other agents against gram-negative bacteria. By comparing these results with those obtained in 1993, it was found that increase of resistance to carbapenem antibiotics was not observed against all the strains tested in this study. Thus, it can be stated that carbapenem antibiotics retain their position as the drug of first choice for severe infections. Received: January 4, 1999 / Accepted: May 26, 1999