gemifloxacin and Pneumococcal-Infections

This review focuses on the activity of gemifloxacin, a new respiratory fluoroquinolone, against the two most important bacterial pathogens associated with lower respiratory tract infections, namely Streptococcus pneumoniae and Haemophilus influenzae.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple; Fluoroquinolones; Gemifloxacin; Haemophilus Infections; Haemophilus influenzae; Humans; Naphthyridines; Pneumococcal Infections; Streptococcus pneumoniae

Community-acquired lower respiratory tract infections (LRTIs) are more prevalent in the elderly than in children and younger adults and form a significant proportion of all consultations and hospital admissions in this older age group. Furthermore, in a world of increasing life expectancy the trend seems unlikely to be reversed. Antimicrobial treatment of community-acquired pneumonia (CAP) must cover Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, and in many circumstances should also cover the intracellular (atypical) pathogens. In contrast, acute exacerbations of chronic bronchitis (AECB) are mainly associated with H. influenzae and S. pneumoniae and not with atypical bacteria: in severe cases, other Gram-negative bacteria may be involved. Frequently in LRTIs, the aetiology of the infection cannot be identified from the laboratory specimens and treatment has to be empirical. In such situations it is important to not only to use an antibiotic that covers all likely organisms, but also one that has good activity against these organisms given the local resistance patterns. Gemifloxacin is a new quinolone antibiotic that targets pneumococcal DNA gyrase and topoisomerase IV and is highly active against S. pneumoniae including penicillin-, macrolide- and many ciprofloxacin-resistant strains, as well as H. influenzae and the atypical pathogens. In clinical trials in CAP and AECB, gemifloxacin has been shown to be as effective a range of comparators and demonstrated an adverse event profile that was in line with the comparator agents. In one long-term study in AECB significantly more patients receiving gemifloxacin than clarithromycin remained free of recurrence after 26 weeks. The improved potency, broad spectrum of activity and proven clinical and bacteriological efficacy and safety profile should make it a useful agent in the 21st century battle against community-acquired LRTIs.

Topics: Anti-Bacterial Agents; Bronchitis; Chlamydophila Infections; Community-Acquired Infections; Fluoroquinolones; Gemifloxacin; Gram-Negative Bacterial Infections; Haemophilus Infections; Humans; Legionnaires' Disease; Moraxellaceae Infections; Naphthyridines; Pneumococcal Infections; Pneumonia, Bacterial; Pneumonia, Mycoplasma; Staphylococcal Infections

Levofloxacin, levorotatory isomer of ofloxacine, is the only FQ3G on the belgian market since the middle of 2000 and is a little more efficient than the FQ2G against S. pneumoniae. The FQ4G are in vitro active against the common and atypic respiratory pathogenes and significantly more efficient against the Gram positive cocci, principally against S. pneumoniae. Their long duration of action allows one oral administration a day sufficient to obtain bactericidal levels in the serum. Their secondary effects are located principally at the level of digestive tract, neurologic system or cutaneous area. In the U.S.A., several FQ4G (clina-, grepa-, spar-, trova-floxacin) were withdrawn from use after observance of severe toxicity, while there were being administrated on a large scale. Furthermore, two of these "respiratory" FQ4G (gemi- and moxi-floxacin) should reinforced our therapeutic armoury, moxifloxacin as of 2002 and gemifloxacin as of 2004. The position of FQ3G and 4G are in discussion. In the case of pneumonia acquired in the community and confirmed by X-Ray, our recommendation is to administer a new FQ at the first choice if the patient is allergic to penicillin, debilitated or if a penicillin resistant S. pneumoniae suspected (epidemiology, recent antibiotherapy) and at the second choice if it is resistance to penicillin or to macrolide, in case of atypic pneumonia. Today, the majority of the pneumonia acquired outside the hospital is empirically treated with a betalactam (oral or intravenous), with or without macrolide. The new FQ are important drugs. One must avoid overprescription which leads to bacterial resistance (especially S. pneumoniae).

Topics: Administration, Oral; Anti-Infective Agents; Aza Compounds; Belgium; Biological Availability; Drug Monitoring; Drug Resistance; Fluoroquinolones; Gemifloxacin; Humans; Intestinal Absorption; Levofloxacin; Moxifloxacin; Naphthyridines; Ofloxacin; Patient Selection; Pneumococcal Infections; Quinolines; Respiratory Tract Infections; Streptococcus pneumoniae; Time Factors; Treatment Outcome

The ability to identify agents with the optimal combination of potency, pharmacokinetics and pharmacodynamics should help to maximize bacteriological cure and thus minimize the potential for selection and spread of resistance. Gemifloxacin demonstrated excellent correlation between efficacy and the AUC0-24h/MIC ratio whereas there was little correlation with time above MIC. Thus, gemifloxacin is similar to other quinolones in that it is the amount of drug present, not the frequency of administration, that determines antibacterial effect. In a neutropenic murine thigh model of infection, caused by Gram-negative bacilli, a AUC0-24h/MIC ratio of approximately 100 was necessary to protect >90% of the animals, which is similar to data reported previously for other quinolones. However, in order to achieve the same protection in an immunocompetent murine infection caused by Streptococcus pneumoniae, the AUC-24h/MIC ratio was approximately 25. The magnitude of this AUC0-24h/MIC ratio did not alter for strains exhibiting penicillin or macrolide resistance. Importantly, when gemifloxacin was examined against strains of S. pneumoniae with well-characterized ciprofloxacin resistance (including mutations in gyrase, parC and parE as well as efflux strains) there was little impact on the in vivo efficacy. Overall, the data showed a trend towards a decrease in the AUC0-24h/MIC ratio for these more resistant strains. The lower AUC0-24h/MIC ratio was especially noticeable for the efflux mutants suggesting that the quinolone efflux mechanism may be down-regulated in vivo and may be of minimal relevance to the clinical activity of gemifloxacin against S. pneumoniae. The efficacy of gemifloxacin, in comparison with other oral agents used to treat respiratory infections, has also been evaluated in a rat model using doses, and therefore AUC0-24h/MIC ratios, that approximate those in man. These data confirm the excellent activity of gemifloxacin against strains of Haemophilus influenzae and S. pneumoniae, including those demonstrating penicillin, macrolide and quinolone resistance.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Area Under Curve; Drug Resistance, Microbial; Fluoroquinolones; Gemifloxacin; Haemophilus Infections; Haemophilus influenzae; Humans; Mice; Microbial Sensitivity Tests; Naphthyridines; Pneumococcal Infections; Rats; Streptococcus pneumoniae

The incidence of penicillin resistance in pneumococci is increasing in the USA, having risen from <5% before 1989 to >35% in 1997. There has also been a shift in the ratio of intermediate to high-level resistance from 3 or 4:1 to 2 or 1:1. Multidrug resistance and resistance to macrolides and fluoroquinolones in pneumococci is also a matter of concern. The implications for empirical treatment of respiratory tract infections are considerable. The potential of quinolones with activity against respiratory pathogens including pneumococci must be preserved by careful antimicrobial prescribing.

Topics: Adult; Aged; Anti-Infective Agents; Community-Acquired Infections; Drug Resistance, Microbial; Female; Fluoroquinolones; Gemifloxacin; Humans; Male; Middle Aged; Naphthyridines; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae

The objective of this study was to determine serum bactericidal titers (SBT, the highest dilution of serum showing no growth) and the serum bactericidal activity (SBA, i.e. duration of SBT greater than 1:2) as well as the serum bactericidal rate of gemifloxacin and clarithromycin after single doses in healthy male volunteers against Streptococcus pneumoniae. Strains tested had various degrees of susceptibility to penicillin as well as different susceptibility to quinolones due to a different QRDR mutation pattern (parC, gyrA). Serum samples from volunteers (n = 12) who had received a single oral dose of either 320 mg gemifloxacin or 500 mg clarithromycin in an open-label crossover study were obtained over a 24-hour period. SBA was determined, using the microdilution method. SBA of wildtype strains for gemifloxacin ranged from 8.9 to 15.4 h (mean 12.6 h). For gemifloxacin, 2 strains with solitary gyrA mutation had an SBA from 4.5 to 4.7 h (median 4.5 h). One of the 2 strains with a single QRDR mutation in parC displayed an SBA of 4.5 h, comparable to the gyrA mutation strains, whereas the second strain had a nearly twice as long SBA of 8.9 h. Two strains with two mutations (parC and gyrA) did not display any SBA. For clarithromycin, the duration of SBA ranged from 11.3 to 15.5 h (mean 13.6 h) for 6 of the 12 strains with an MIC < or = 0.06 mg/L (no SBA was found for the remaining strains, with an MIC of 0.25 mg/L or higher). In conclusion, a correlation between individual serum concentrations and SBA was found for both antibiotics.

Topics: Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Clarithromycin; Cross-Over Studies; DNA Mutational Analysis; DNA, Bacterial; Drug Resistance, Bacterial; Drug Therapy, Combination; Fluoroquinolones; Gemifloxacin; Humans; Male; Middle Aged; Naphthyridines; Pneumococcal Infections; Quinolones; Streptococcus pneumoniae

An open-label, non-comparative study assessed the clinical and bacteriological efficacy of gemifloxacin (320 mg, once-daily for 7 days) in lower respiratory tract infections (LRTI). Patients with acute exacerbation of chronic bronchitis (AECB, n=261) or community-acquired pneumonia (CAP, n=216) were enrolled into the study. Clinical success rates at follow-up (days 21-28) in the intent-to-treat (ITT) population were high, 83.1% in AECB patients (95% CI: 77.9, 87.4) and 82.9% in CAP patients (95% CI: 77.0, 87.5). High bacteriological success rates were achieved (bacteriological ITT population), 91.2% (52/57) in AECB patients (95% CI: 80.0, 96.7) and 77.9% (60/77) in CAP patients (95% CI: 66.8, 86.3). Gemifloxacin was well tolerated with a low incidence of adverse events. Gemifloxacin treatment resulted in high clinical and bacteriological success rates and is a well-tolerated therapy for the treatment of LRTIs.

Topics: Adult; Aged; Anti-Infective Agents; Bronchitis; Chronic Disease; Community-Acquired Infections; Drug Administration Schedule; Female; Fluoroquinolones; Gemifloxacin; Gram-Negative Bacterial Infections; Haemophilus Infections; Humans; Klebsiella Infections; Male; Middle Aged; Naphthyridines; Pneumococcal Infections; Pneumonia, Bacterial; Staphylococcal Infections; Treatment Failure

This study aimed to evaluate the antimicrobial susceptibility profiles of 364 Streptococcus pneumoniae isolates and studied the genotypes of S. pneumoniae with high level beta-lactam resistance in Taiwan. Clonal complexes related to Spain(23F)-1, Taiwan(19F)-14, and Taiwan(23F)-15 were responsible for the spread of isolates with high beta-lactam resistance.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactams; Genotype; Humans; Microbial Sensitivity Tests; Pneumococcal Infections; Serotyping; Streptococcus pneumoniae; Taiwan

The fitness cost of the genes responsible for resistance to fluoroquinolones in clinical isolates of Streptococcus pneumoniae were estimated in vitro in a common genetic background. Naturally occurring parC, parE, and gyrA loci containing mutations in the quinolone-resistance-determining regions were introduced by transformation into S. pneumoniae strain R6 individually and in combinations. The fitness of these transformants was estimated by pairwise competition experiments with a common R6 strain. On average, single par and gyr mutants responsible for low-level MIC resistance (first-step resistance) impose a fitness burden of approximately 8%. Some of these mutants engender no measurable cost, while one, a parE mutant, reduces the fitness of these bacteria by more than 40%. Most interestingly, the addition of the second par or gyr mutations required for clinically significant, high-MIC fluoroquinolone resistance does not increase the fitness burden imposed by these single genes and can even reduce it. We discuss the implications of these results for the epidemiology of fluoroquinolone resistance and the evolution of acquired resistance in treated patients.

Topics: DNA Gyrase; DNA Topoisomerase IV; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Mutation; Pneumococcal Infections; Streptococcus pneumoniae; Transformation, Bacterial

The potential for resistance development in Streptococcus pneumoniae secondary to exposure to gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin at various levels was examined at high inoculum (10(8.5) to 10(9) log10 CFU/ml) over 96 h in an in vitro pharmacodynamic (PD) model using two fluoroquinolone-susceptible isolates. The pharmacokinetics of each drug was simulated to provide a range of free areas under the concentration-time curves (fAUC) that correlated with various fluoroquinolone doses. Potential first (parC and parE)- and second-step (gyrA and gyrB) mutations in isolates with raised MICs were identified by sequence analysis. PD models simulating fAUC/MICs of 51 andgatifloxacin>moxifloxacin=gemifloxacin, which may be related to structural differences within the class.

Topics: Area Under Curve; Aza Compounds; Drug Resistance, Bacterial; Fluoroquinolones; Gatifloxacin; Gemifloxacin; Levofloxacin; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Ofloxacin; Pneumococcal Infections; Quinolines; Streptococcus pneumoniae

Molecular characterization of fluoroquinolone-resistant Streptococcus pneumoniae in Canada was conducted from 1997 to 2005. Over the course of the study, 205 ciprofloxacin-resistant isolates were evaluated for ParC and GyrA quinolone resistance-determining region (QRDR) substitutions, substitutions in the full genes of ParC, ParE, and GyrA, reserpine sensitivity, and serotype and by pulsed-field gel electrophoresis. Rates of ciprofloxacin resistance of S. pneumoniae increased significantly, from less than 1% in 1997 to 4.2% in 2005. Ciprofloxacin resistance was greatest in people >64 years of age and least in those <16 years of age. Significant increases were also noted in rates of resistance to gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin, to the current rates of 1.6%, 1.0%, 1.1%, and 1.0%, respectively. The most common genotype observed consisted of QRDR substitutions in GyrA (Ser81Phe) and ParC (Ser79Phe). Substitutions outside the QRDR of GyrA, ParC, and ParE were not associated with fluoroquinolone resistance in this study. Overall, 21% of isolates were reserpine-sensitive and were thus assumed to be efflux positive. The ciprofloxacin-resistant isolates belonged to 35 different serotypes, but 10 (19F, 11A, 23F, 6B, 22F, 12F, 6A, 14, 9V, and 19A) accounted for 72% of all isolates. The majority of the isolates were found to be genetically unrelated by pulsed-field gel electrophoresis. Within the observed clusters, there was considerable genetic heterogeneity with regard to fluoroquinolone resistance mechanisms and serotypes. Continued surveillance and molecular analysis of fluoroquinolone-resistant S. pneumoniae in Canada are essential for appropriate empirical treatment of infections and early detection of novel resistance mechanisms.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Aza Compounds; Bacterial Proteins; Canada; Child; Child, Preschool; Ciprofloxacin; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Fluoroquinolones; Gatifloxacin; Gemifloxacin; Genotype; Humans; Infant; Infant, Newborn; Levofloxacin; Middle Aged; Moxifloxacin; Naphthyridines; Ofloxacin; Pneumococcal Infections; Quinolines; Serotyping; Streptococcus pneumoniae

This study used Monte Carlo simulations to assess the potential for attainment of pharmacodynamic targets with the fluoroquinolones garenoxacin, gemifloxacin, and moxifloxacin against Streptococcus pneumoniae in serum and epithelial lining fluid (ELF) from hospitalized patients with community-acquired pneumonia (CAP).. Data on the free AUC over 24 hours (fAUC(0-24)), a measure of drug exposure, were derived from previously described population pharmacokinetic models for therapeutic doses of the 3 fluoroquinolones. MIC distribution data for S pneumoniae were obtained from the Canadian Respiratory Organism Susceptibility Study. These data were used to produce the ratio of fAUC(0-24) to the MIC(90) (fAUC(0-24)/MIC(90)), a pharmacodynamic predictor of bacterial eradication. Monte Carlo simulations were used to analyze the potential for garenoxacin 400 mg QD, gemifloxacin 320 mg QD, and moxifloxacin 400 mg QD to achieve target fAUC(0-24)/MIC(90) ratios of 30, 40, 100, and 120 against S pneumoniae in serum and ELF from hospitalized patients with CAP. Target ratios of 30 and 40 were used to assess the probability of bacterial eradication, while ratios of 100 and 120 were used to assess the probability of preventing development of resistance.. Monte Carlo simulations indicated that all 3 fluoroquinolones had a high probability (>90%) of attaining target fAUC(0-24)/MIC(90) ratios of 30 and 40 against S pneumoniae in both serum and ELF. Garenoxacin 400 mg QD was associated with a >95% probability of achieving target fAUC(0-24)/MIC(90) ratios of 100 and 120 in both serum and ELF. Both gemifloxacin 320 mg QD and moxifloxacin 400 mg QD were associated with high probabilities of attaining fAUC(0-24)/MIC(90) ratios of 100 and 120 in ELF (>95%); the probability of gemifloxacin and moxifloxacin attaining these targets in serum ranged from 78.3% to 88.0%.. Based on these simulations, garenoxacin 400 mg QD, gemifloxacin 320 mg QD, and moxifloxacin 400 mg QD appeared likely to achieve target serum and ELF concentrations against S pneumoniae in hospitalized patients with CAP, with a low potential to select for resistance.

Topics: Anti-Bacterial Agents; Area Under Curve; Aza Compounds; Community-Acquired Infections; Fluoroquinolones; Gemifloxacin; Humans; Monte Carlo Method; Moxifloxacin; Naphthyridines; Pneumococcal Infections; Quinolines; Respiratory Mucosa

A dose-decreasing immunocompetent sepsis mouse model was used to evaluate the in vivo effect of levofloxacin, moxifloxacin and gemifloxacin, using a ciprofloxacin/levofloxacin susceptible serotype 6B strain (ciprofloxacin MIC: 1 mg/l) and two resistant serotype 14 and 19F strains with gyrA and parC point mutations (ciprofloxacin MICs of 32 and 64 mg/l, respectively). Significant higher in vivo activity was found for moxifloxacin and gemifloxacin than for levofloxacin against strains 1 and 2, and for gemifloxacin versus moxifloxacin or levofloxacin against strain 3. Gemifloxacin treatment resulted in 100% survival against strains 1 and 2(AUC0-24 h/MIC of 30 and 62) but against strain 3, survival was 60-80% (AUC0-24 h/MIC of 93). Similar AUC0-24 h/MIC values produced different therapeutic results suggesting that in vitro parameters other than the MIC could influence efficacy predictions based on in vitro susceptibility tests (MICs) or pharmacodynamic parameters (AUC0-24 h/MIC).

Topics: Animals; Anti-Infective Agents; Aza Compounds; Ciprofloxacin; Disease Models, Animal; DNA Gyrase; DNA Topoisomerase IV; Drug Resistance, Bacterial; Female; Fluoroquinolones; Gemifloxacin; Levofloxacin; Mice; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Ofloxacin; Pneumococcal Infections; Point Mutation; Quinolines; Sepsis; Streptococcus pneumoniae; Treatment Outcome

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Humans; Ireland; Naphthyridines; Pneumococcal Infections; Population Surveillance; Respiratory Tract Infections; Streptococcus pneumoniae; United Kingdom

An in vitro pharmacodynatnic modeling apparatus (PDMA) generated specific bacterial kill profiles for single-dose regimens of gatifloxacin (GT), gemifloxacin (GM), moxifloxacin (MX) and levofloxacin (LV) against isolates of Streptococcus pneumoniae with specific QRDR profiles: SP-WT (no modifications); SP-C (changes in parC); and SP-AC (changes in both parC and gyrA). No differences in 3-log reduction time or total log reduction were observed among the four agents for SP-WT; however, LV failed to achieve a 3-log reduction in SP-C and SP-AC, and total log reduction after 12 hrs was minimal compared to the other agents. GM and MX required less time for 3-log reduction of SP-AC compared to GT, but total log reductions in SP-AC were similar among the three newer quinolone agents (GM > MX > GT). The study isolates with QRDR modifications greatly reduced LV activity. GM and MX maintained the greatest degree of activity against all study isolates and their activity was not adversely influenced by the genetic modifications in SP-C and SP-AC. The dual targeting characteristic of GM was also assessed, but did not offer significant advantages relative to MX and GT.

Topics: Analysis of Variance; Aza Compounds; Culture Media; DNA Gyrase; DNA Topoisomerase IV; Drug Resistance, Bacterial; Fluoroquinolones; Gatifloxacin; Gemifloxacin; Humans; Levofloxacin; Microbial Sensitivity Tests; Moxifloxacin; Mutation; Naphthyridines; Ofloxacin; Pharmacogenetics; Pneumococcal Infections; Probability; Quinolines; Reference Values; Regression Analysis; Sensitivity and Specificity; Streptococcus pneumoniae

The in vitro susceptibility to trovafloxacin and gemifloxacin of Streptococcus pneumoniae strains exhibiting decreased susceptibility to ciprofloxacin (MIC > or =2 microg/ml; 30 strains with intermediate resistance [MIC 2 microg/ml] and 43 strains with complete resistance [MIC > or =4 microg/ml]) was determined. Seventy-three strains collected in a surveillance study carried out from May 1996 to April 1997 in Spain (prior to commercialisation of trovafloxacin and gemifloxacin) from patients with respiratory tract infections were tested. The antibacterial activity of gemifloxacin was affected to a lesser extent than that of trovafloxacin by the increase in the MIC of ciprofloxacin, with gemifloxacin showing significantly (P< or =0.001) better antibacterial activity than trovafloxacin in all ciprofloxacin MIC categories (MIC50/MIC90 values of 0.015/0.03, 0.015/0.06, 0.03/0.06 and 0.12/0.25 microg/ml for gemifloxacin vs. 0.12/0.12, 0.12/1, 0.25/0.5 and 2/4 microg/ml for trovafloxacin in the 2, 4, 8 and > or =16 microg/ml ciprofloxacin MIC categories, respectively). Nine (12.3%) of these 73 strains exhibited decreased susceptibility to trovafloxacin (> or =2 microg/ml), whereas all strains were inhibited by 0.25 microg/ml of gemifloxacin.

Topics: Anti-Infective Agents; Ciprofloxacin; Drug Resistance, Microbial; Fluoroquinolones; Gemifloxacin; Humans; Microbial Sensitivity Tests; Naphthyridines; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae

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.

Topics: Animals; Anti-Infective Agents; Fluoroquinolones; Gemifloxacin; Haemophilus Infections; Haemophilus influenzae; Male; Naphthyridines; Pneumococcal Infections; Rats; Rats, Sprague-Dawley; Respiratory Tract Infections

Nine penicillin-resistant Streptococcus pneumoniae clinical isolates from Northern Ireland, resistant to ciprofloxacin (MICs, 2 to 64 microg/ml) through topoisomerase- and/or reserpine-sensitive efflux mechanisms, were highly susceptible to gemifloxacin (MICs, 0.03 to 0. 12 microg/ml). Two strains (requiring a ciprofloxacin MIC of 64 microg/ml) carried known quinolone resistance mutations in parC, parE, and gyrB, resulting in S79F, D435V, and E474K changes, respectively. Thus, gemifloxacin is active against clinical strains exhibiting altered topoisomerase and efflux phenotypes.

Topics: Anti-Infective Agents; Ciprofloxacin; DNA Topoisomerases, Type I; Drug Resistance, Microbial; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines; Northern Ireland; Penicillin Resistance; Phenotype; Pneumococcal Infections; Reverse Transcriptase Polymerase Chain Reaction; Streptococcus pneumoniae