Concentrations Of Gatifloxacin Research Articles

Concentration-dependent changes in the susceptibility and killing of Staphylococcus aureus in an in vitro dynamic model that simulates normal and impaired gatifloxacin elimination

To demonstrate the impact of normal (NEK) and impaired elimination kinetics (IEK) of gatifloxacin on its ability to protect from losses in the susceptibility of Staphylococcus aureus, a clinical isolate of methicillin-resistant S. aureus at a starting inoculum of 10 8 cfu/ml was exposed to 3 days of quinolone dosing. A series of monoexponential pharmacokinetic profiles with half-lives of 7 h (NEK) and 31 h (IEK) were simulated over 32- and 8-fold ranges of the 24 h area under the concentration-time curve (AUC 24)-to-MIC ratio, respectively. The simulated AUC 24/MICs were designed to provide peak concentrations ( C maxs) close to the MIC, between the MIC and the mutant prevention concentration (MPC), i.e., within the mutant selection window (MSW), and above the MPC. With both NEK and IEK simulations, significant increases in MIC were observed at those AUC 24/MICs that correspond to gatifloxacin concentrations within the MSW over most of the dosing interval (>25%). No such increases were observed at the smallest AUC 24/MIC (10 h with NEK and 20 h with IEK) when the simulated C maxs were close to the MIC, with minimal if any bacterial killing, and at the highest AUC 24/MICs (310 and 160 h, respectively) when gatifloxacin concentrations exceeded the MPC over most of the dosing interval, with maximal antimicrobial effect. These ‘protective’ AUC 24/MIC ratios correspond to 135% of the usual gatifloxacin clinical dose (400 mg NEK) and 60% of the loading and maintenance doses (400 mg, then 200 mg IEK). This study predicts different protective potentials of gatifloxacin in IEK and NEK against staphylococcal resistance and supports the MSW concept.

Serum Bactericidal Activity of the Methoxyfluoroquinolones Gatifloxacin and Moxifloxacin against Clinical Isolates of Staphylococcus Species: Are the Susceptibility Breakpoints Too High?

Healthy volunteers received a single dose of gatifloxacin and moxifloxacin (400 mg each), and serum samples were obtained from these volunteers over a 24-h period. Prolonged (> or =12 h) serum bactericidal activity (SBA) was observed for both agents against staphylococcal isolates with minimum inhibitory concentrations (MICs) of gatifloxacin of < or =0.5 mug/mL. In strains with gatifloxacin MICs of 1.0 mug/mL, SBA was observed for < or =6 h, and, for isolates with gatifloxacin MICs of 2.0 mug/mL, little or no SBA was observed for either drug. The relative lack of SBA against less susceptible strains of staphylococci suggests that the current susceptibility breakpoint concentration (MIC, 2.0 mug/mL) for these methoxyfluoroquinolones against Staphylococcus is too high.

Determination of gatifloxacin in human serum and urine by high-performance liquid chromatography with ultraviolet detection

A simple and sensitive HPLC method for the determination of gatifloxacin concentrations in human serum and urine was developed and validated. Serum proteins were removed by ultrafiltration through a filtering device after adding a displacing agent. Urine samples were diluted with mobile phase prior to injection. Separation was achieved with a C18 reverse-phase column and gatifloxacin concentrations were determined using ultraviolet detection. The quantitation limits of the assay were 100 ng/ml in serum and 1.0 μg/ml in urine. The assay method was successfully applied to a pharmacokinetic study of gatifloxacin in healthy volunteers.

Gatifloxacin and moxifloxacin: an in vitro susceptibility comparison to levofloxacin, ciprofloxacin, and ofloxacin using bacterial keratitis isolates

Purpose We compared the in vitro susceptibility patterns and the minimum inhibitory concentrations (MICs) of gatifloxacin (GAT) and moxifloxacin (MOX) (fourth-generation fluoroquinolones) to ciprofloxacin (CIP) and ofloxacin (OFX) (second-generation fluoroquinolones) and levofloxacin (LEV; third-generation fluoroquinolone) using bacterial keratitis isolates. The goal was to determine whether the fourth-generation fluoroquinolones offer any advantages over the second- and third-generation fluoroquinolones. Design Experimental laboratory investigation. In contrast to an epidemiologic prevalence study, this study was designed to compare the relative susceptibility of each bacterial group to different fluoroquinolones by deliberate selection of representative isolates that were both susceptible and resistant to second-generation fluoroquinolones. Methods In retrospect, the MICs of 177 bacterial keratitis isolates were determined to CIP, OFX, LEV, GAT, and MOX using E tests. A relative susceptibility analysis was performed for each bacterial group that included separate bacterial groups that were resistant to second-generation fluoroquinolones. The NCCLS susceptibility patterns and the MICs were compared statistically. Comparing MICs, the antibiotic with the lower MICs has greater antibacterial activity. Results For most keratitis isolates, there were no susceptibility differences among the five fluoroquinolones. The fourth-generation fluoroquinolones did, however, demonstrate increased susceptibility for Staphylococcus aureus isolates that were resistant to CIP, LEV and OFX. In general, CIP demonstrated the lowest MICs for gram-negative bacteria. The MICs for fourth-generation fluoroquinolones were statistically lower than the second-generation fluoroquinolones for all gram-positive bacteria tested. Comparing the two fourth-generation fluoroquinolones, MOX demonstrated lower MICs for most gram-positive bacteria, whereas GAT demonstrated lower MICs for most gram-negative bacteria. Conclusions Based on in vitro testing, the fourth-generation fluoroquinolones may offer some advantages over those currently available for the treatment of bacterial keratitis. Clinical studies will be required to confirm these results.

Inhibitory Activities of Quinolones against DNA Gyrase of Chlamydia pneumoniae

The gyrA and gyrB genes of Chlamydia pneumoniae TW-183 were cloned, and their proteins were purified by use of a fusion system with a maltose-binding protein. The 50% inhibitory concentrations of garenoxacin, sparfloxacin, moxifloxacin, gatifloxacin, and levofloxacin were 10.1, 47.5, 39.6, 64.2, and 156.9 microg/ml, respectively, and the MICs against C. pneumoniae TW-183 were 0.008, 0.016, 0.063, 0.125, and 0.25 microg/ml, respectively.

Bioavailability of gatifloxacin by gastric tube administration with and without concomitant enteral feeding in critically ill patients

Sequential intravenous-to-oral antimicrobial therapy with highly bioavailable antiinfective agents such as the fluoroquinolones may improve patient safety and decrease cost of infection management. However, physiologic changes associated with critical illness may alter drug absorption, distribution, and clearance, and concomitant enteral feeding may decrease fluoroquinolone bioavailability. We evaluated the effect of critical illness and concomitant gastric tube feeding on gatifloxacin bioavailability. Prospective, randomized, single-dose, two-way crossover, pharmacokinetic study. SETTINGA tertiary, level-one, trauma center. Sixteen critically ill patients (baseline Acute Physiology and Chronic Health Evaluation II score >or=16) tolerating enteral nutrition administered by gastric tube (NG) for >or=12 hrs were randomized to receive gatifloxacin concurrently with continuous tube feeding or with interrupted tube feeds. Patients with renal insufficiency or those receiving concomitant fluoroquinolone therapy or postpyloric feeding were excluded. Patients received gatifloxacin 400 mg either by the intravenous or NG route followed by the alternative dosage form after a 72-hr washout period. Serial serum gatifloxacin concentrations (from 5 mins to 24 hrs) were analyzed using a validated high-performance liquid chromatography method. Bioavailability was determined as the ratio of NG/intravenous area under the concentration-time curve (AUC infinity ) measured by the trapezoidal method. Although there was no difference in the bioavailability between NG (AUC infinity : 38.0 [range 20.1 to 48.5] microg x h/mL) and intravenous (AUC infinity : 39.5 [range 24.1 to 63.1] microg x h/mL, p =.60) gatifloxacin (bioavailability: 98.5% [range 61.1% to 119.7%]), a wide variability was observed in three of eight patients (>30% reduction in bioavailability). Concomitant gastric tube feeding did not affect gatifloxacin bioavailability (interrupted tube feeds: 98.5% [range 61.1% to 119.7%]; continuous tube feeding: 109.0% [range 86.2% to 142.1%]; p =.42). Neither a period nor differential carryover effect was observed. Although concomitant tube feeding did not affect gatifloxacin bioavailability, critical illness resulted in significant variability that may complicate the role of gatifloxacin in sequential intravenous-to-oral therapy. More research is needed to identify those patients in whom gatifloxacin bioavailability is reduced and for whom an empirical increase in gatifloxacin dose should be considered.

Vitreous and aqueous penetration of orally administered gatifloxacin in humans.

To investigate the penetration of gatifloxacin, a novel extended-spectrum fourth-generation fluoroquinolone antibiotic, into the vitreous and aqueous humor after oral administration. A prospective, nonrandomized study of 24 consecutive patients scheduled for pars plana vitrectomy between September 2001 and May 2002 at the Cullen Eye Institute. Aqueous, vitreous, and serum samples were obtained and analyzed from 24 patients after administration of two 400-mg gatifloxacin tablets taken 12 hours apart before the operation. Assays were performed using high-performance liquid chromatography. Mean +/- SD gatifloxacin concentrations in serum (n = 23), vitreous (n = 23), and aqueous (n = 11) were 5.14 +/- 1.36 micro g/mL, 1.34 +/- 0.34 micro g/mL, and 1.08 +/- 0.54 micro g/mL respectively. Mean +/- SD sampling times after oral administration of the second gatifloxacin tablet for serum, vitreous, and aqueous were 3.2 +/- 1.0 hours, 4.0 +/- 1.0 hours, and 3.9 +/- 1.1 hours, respectively. The percentages of serum gatifloxacin concentration achieved in the vitreous and aqueous were 26.17% and 21.02%, respectively. Mean inhibitory vitreous and aqueous MIC(90 ) levels were achieved against many pathogens, including Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Propionibacterium acnes, Haemophilus influenzae, Escherichia coli, Bacillus cereus, Proteus mirabilis, and other organisms. Orally administered gatifloxacin achieves therapeutic levels in the noninflamed human eye, and the activity spectrum appropriately encompass the bacterial species most frequently involved in the various causes of endophthalmitis. Because of its broad-spectrum coverage, low MIC(90) levels for the organisms of concern, and good tolerability, gatifloxacin represents a major advance in the prophylaxis or treatment of postoperative, posttraumatic, and bleb-associated bacterial endophthalmitis.

Single and multi-step resistance selection study in Streptococcus pneumoniae comparing ceftriaxone with levofloxacin, gatifloxacin and moxifloxacin

Attempts were made to select resistant pneumococcal mutants by sequential subculturing of 12 clinically isolated pneumococci, [four were penicillin sensitive (MIC) 0.03–0.06 mg/l, four penicillin intermediate (MIC 0.25–0.5 mg/l) and four penicillin resistant (MIC 2–4 mg/l)] in sub-inhibitory concentrations of ceftriaxone, levofloxacin, gatifloxacin and moxifloxacin. Subculturing in gatifloxacin, levofloxacin, moxifloxacin and ceftriaxone selected 12 mutants (12/12), 10 mutants (10/12), 10 mutants (10/12) and three mutants (3/12), respectively. DNA sequencing of the quinolone-resistant mutants showed that most strains had mutations in GyrA at E85 or S81. This in vitro mutation study demonstrates a clear distinction between the low frequency of development of resistance with ceftriaxone exposure as opposed to the high frequency with quinolone exposure.

Inhibitory activities of quinolones against DNA gyrase and topoisomerase IV of Enterococcus faecalis.

We have cloned the DNA gyrase and topoisomerase IV genes of Enterococcus faecalis to examine the actions of quinolones against E. faecalis genetically and enzymatically. We first generated levofloxacin-resistant mutants of E. faecalis by stepwise selection with increasing drug concentrations and analyzed the quinolone resistance-determining regions of gyrA and parC from the resistant mutants. Isogenic mutants with low-level resistance contained a mutation in gyrA, whereas those with higher levels of resistance had mutations in both gyrA and parC. These results suggested that gyrA is the primary target for levofloxacin in E. faecalis. We then purified the recombinant DNA gyrase and topoisomerase IV enzymes of E. faecalis and measured the in vitro inhibitory activities of quinolones against these enzymes. The 50% inhibitory concentrations (IC(50)s) of levofloxacin, ciprofloxacin, sparfloxacin, tosufloxacin, and gatifloxacin for DNA gyrase were found to be higher than those for topoisomerase IV. In conflict with the genetic data, these results indicated that topoisomerase IV would be the primary target for quinolones in E. faecalis. Among the quinolones tested, the IC(50) of sitafloxacin (DU-6859a), which shows the greatest potency against enterococci, for DNA gyrase was almost equal to that for topoisomerase IV; its IC(50)s were the lowest among those of all the quinolones tested. These results indicated that other factors can modulate the effect of target affinity to determine the bacterial killing pathway, but the highest inhibitory actions against both enzymes correlated with good antienterococcal activities.

Interference of Sub-Inhibitory Concentrations of Gatifloxacin on Various Determinants of Bacterial Virulence

The physico-chemical characteristics of the molecular array on the outermost surface of bacteria modulate various bacterial functions which, when expressed in the human environment, constitute important determinants of bacterial virulence.The present study investigated the ability of subinhibitory concentrations of gatifloxacin to interfere with various virulence determinants of Escherichia coli and with the adhesiveness of Staphylococcus aureus. The adhesiveness of S. aureus and E. coli to human epithelial cells was inhibited at gatifloxacin concentrations down to 1/32 and 1/64 the minimum inhibitory concentration (MIC). Sub-MICs of gatifloxacin down to 1/8-MIC significantly reduced hemagglutination and hydrophobicity, which are correlated with fimbriation and provide clues relating to the physico-chemical characteristics of the outer surface of bacteria. Swarming (motility) was reduced at concentrations down to 1/8 MIC. Phagocytosis was not affected but killing significantly increased from 1/8 to 1/2 MIC.The respiratory bursts of neutrophils investigated by a chemiluminescence procedure were not modified. The interpolation of these pharmacodynamic findings with pharmacokinetic curves indicates that the effect of sub-MIC concentrations of gatifloxacin can engender activity, prolonging antimicrobial effects on virulence determinants over 30 hours after the antimicrobial concentration has fallen below the MIC.

Gatifloxacin: a review of its use in the management of bacterial infections.

Gatifloxacin is an 8-methoxy fluoroquinolone antibacterial agent. The drug has a broader spectrum of antibacterial activity than the older fluoroquinolones (e.g. ciprofloxacin) and shows good activity against many Gram-positive and Gram-negative pathogens, atypical organisms and some anaerobes. Notably, gatifloxacin is highly active against both penicillin-susceptible and -resistant strains of Streptococcus pneumoniae, a common causative pathogen in community-acquired pneumonia (CAP), acute sinusitis and acute bacterial exacerbations of bronchitis. Gatifloxacin is absorbed well from the gastrointestinal tract (oral bioavailability is almost 100%). Therefore, patients can be switched from intravenous to oral therapy without an adjustment in dosage. High concentrations of gatifloxacin are achieved in plasma and target tissues/fluids. Gatifloxacin has a long plasma elimination half-life, thus allowing once-daily administration. Few clinically significant interactions between gatifloxacin and other drugs have been reported. In patients with CAP, clinical response rates in recipients of intravenous/oral gatifloxacin 400 mg/day ranged from 86.8 to 98.0% and rates of bacterial eradication ranged from 83.1 to 100% (up to 28 days post-treatment). Gatifloxacin showed efficacy similar to that of amoxicillin/clavulanic acid, ceftriaxone (with or without erythromycin) with or without stepdown to clarithromycin, levofloxacin or clarithromycin. Gatifloxacin was as effective as clarithromycin or amoxicillin/clavulanic acid, and was significantly more effective (in terms of clinical response; p < 0.035) than 7 to 10 days' treatment with cefuroxime axetil in the treatment of acute exacerbations of chronic bronchitis. In acute sinusitis, gatifloxacin showed clinical efficacy similar to that of clarithromycin, trovafloxacin or amoxicillin/clavulanic acid. Genitourinary infections were also successfully treated with gatifloxacin. Gatifloxacin is generally well tolerated. Its tolerability profile was broadly similar to those of comparator agents in comparative trials. The most common adverse events are gastrointestinal symptoms (oral formulation) and injection site reactions. Gatifloxacin has an extended spectrum of antibacterial activity and provides better coverage of Gram-positive organisms (e.g. S. pneumoniae) than some older fluoroquinolones. The drug has favourable pharmacokinetic properties, is administered once daily and is at least as well tolerated as other fluoroquinolones. Gatifloxacin is a useful addition to the fluoroquinolones currently available for use in the clinical setting and has an important role in the management of adult patients with various bacterial infections. As with other fluoroquinolones, careful control of gatifloxacin usage in the community is important in order to prevent the emergence of bacterial resistance and thus preserve the clinical value of this agent.

In vitro activity of gatifloxacin compared with gemifloxacin, moxifloxacin, trovafloxacin, ciprofloxacin and ofloxacin against uropathogens cultured from patients with complicated urinary tract infections

Minimum inhibitory concentrations (MICs) of gatifloxacin were compared with those of gemifloxacin, moxifloxacin, trovafloxacin, ciprofloxacin and ofloxacin using an agar dilution method for 400 uropathogens cultured from the urine of urological patients with complicated and/or hospital-acquired urinary tract infections (UTI). The collection of strains was made up of Enterobacteriaceae (34.5%), enterococci (31.5%), staphylococci (21.2%) and non-fermenting bacteria (12.8%). The antibacterial activity of the three newer fluoroquinolones, gatifloxacin, gemifloxacin, and moxifloxacin, were similar, but showed some drug specific differences. Gemifloxacin was most active against Escherichia coli, but less so against Proteus mirabilis. In this series all isolates of E. coli were inhibited at a MIC of 0.25 mg/l gatifloxacin and moxifloxacin and by 0.125 mg/l gemifloxacin. The MIC distribution of all fluoroquinolones showed a bimodal distribution for staphylococci, enterococci and Pseudomonas aeruginosa. The two modes for P. aeruginosa were 1 and 64 mg/l for gemifloxacin and moxifloxacin and 0.5 and 64 mg/l for gatifloxacin. For staphylococci the two modes were 0.125 and 2 mg/l for gatifloxacin, 0.03 and 4 mg/l for gemifloxacin, and 0.03 and 2 mg/l for moxifloxacin; for enterococci, 0.25 and 16 mg/l for gatifloxacin, 0.06 and 2 mg/l for gemifloxacin, and 0.25 and 8 mg/l for moxifloxacin. Compared with trovafloxacin the MICs were similar, but the newer fluoroquinolones were more active than ciprofloxacin and ofloxacin against Gram-positive bacteria. Of the newer fluoroquinolones gatifloxacin had the highest rate of renal excretion and could be considered a promising alternative fluoroquinolone agent for the treatment of UTI.

Pharmacodynamics of gatifloxacin in experimental models of pneumococcal meningitis.

The alarming increase of bacterial resistance has had a serious impact on treatment practices for patients with meningitis and has prompted investigation of other possibly effective antibiotic regimens with agents, such as gatifloxacin and trovafloxacin, that have excellent activity against Streptococcus pneumoniae. The use of fluoroquinolones in children has been limited by studies that report chondrotoxicity in young animals. Gatifloxacin, a new fluoroquinolone, was recently tested in a rabbit model of cephalosporin-resistant pneumococcal meningitis. In these studies, animals were infected with a ceftriaxone-resistant (minimal inhibitory concentration [MIC], 4 microg/mL; minimal bactericidal concentration [MBC], 4 microg/mL) and gatifloxacin-susceptible (MIC, 0.125 microg/mL; MBC, 0.25 microg/mL) strain of S. pneumoniae and were treated with either a single- or divided-dose regimen of gatifloxacin. Results from these studies are reviewed and compared with data from other studies that used a similar rabbit model of pneumococcal meningitis. Overall, it was found that the bacteriologic efficacy of gatifloxacin against S. pneumoniae was as effective as that of conventional regimens. Bactericidal activity of gatifloxacin was correlated with the area under the time-concentration curve-to-MBC ratio; maximal activity was achieved when gatifloxacin concentrations exceeded the MBC for the entire dosing interval.

Bactericidal Activity of Gatifloxacin (AM-1155) against Pseudomonas aeruginosa and Enterococcus faecalis in an in vitro Bladder Model Simulating Human Urinary Concentrations after Oral Administration

The bactericidal activity of gatifloxacin, a new 6-fluoro-8-methoxy quinolone, was determined in a dynamic in vitro model mimicking complicated lower urinary tract infection. Strains of Pseudomonas aeruginosa and Enterococcus faecalis with different susceptibility were exposed to changing gatifloxacin concentrations, simulating human urinary concentrations afer oral treatment with 200 mg twice daily for 3 consecutive days. Bacterial numbers of P. aeruginosa (minimal inhibitory concentrations, MIC: ≤ 32 μg/ml) and of E. faecalis (MIC: 16 μg/ml) were reduced to undetectable levels during exposure. For the strains with lower susceptibility, gatifloxacin showed bactericidal activity, but eradication was not complete. Thus, in a complicated urinary tract infection model, breakpoint MICs of gatifloxacin for uropathogenic organisms were presumed to range from 16 to 32 μg/ml. At least 86% of recent clinical isolates of P. aeruginosa and E. faecalis were inhibited at its breakpoint MIC. These results suggest that gatifloxacin may be useful in the treatment of urinary tract infections.

Determination of gatifloxacin in human serum and urine by HPLC

Asensitive and specific HPLC method for gatifloxacin applicable to serum and urine of volunteers was developed. The method can be operated unattended in over-night runs. It uses reversedphase HPLC with fluorimetric detection. Trovafloxacin serves as internal standard. With a detection limit of 0.03 mgL−1 the method was sensitive enough to measure serum concentrations of gatifloxacin in healthy volunteers for 48 hours after a single oral dose of 400 mg. There was excellent agreement with results obtained by a microbiological assay.

Concentrations of gatifloxacin in plasma and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy.

The concentrations of gatifloxacin achieved after a single 400 mg oral dose were measured in plasma, epithelial lining fluid (ELF), alveolar macrophages (AMs) and bronchial mucosa (BM) using a microbiological assay. Fourteen patients undergoing fibre-optic bronchoscopy were studied. Mean plasma, ELF, AMs and BM concentrations, respectively, at 2, 4 and 12 h were as follows: 2 h: 3.96 mg/L, 6.00 mg/L, 69.10 mg/L, 6.24 mg/kg; 4 h: 3.22 mg/L, 6.16 mg/L, 77.32 mg/L, 5.32 mg/kg; 12 h: 1.74 mg/L, 2.98 mg/L, 61.95 mg/L, 3.00 mg/kg. These concentrations exceed the MIC(90)s for common respiratory pathogens such as Streptococcus pneumoniae (0.5 mg/L), Haemophilus influenzae (0.013 mg/L), Moraxella catarrhalis (0.05 mg/L), Chlamydia pneumoniae (0.125 mg/L) and Mycoplasma pneumoniae (0.06 mg/L).

In vitro antimicrobial activity and penetration rate into sputum of gatifloxacin, a novel 6-fluoro-8-methoxy quinolone, and its therapeutic efficacy in respiratory infections.

The in vitro antimicrobial activity of gatifloxacin against clinical isolates of pathogenic bacteria was evaluated. Minimum inhibitory concentrations of gatifloxacin, ofloxacin, ciprofloxacin, tosufloxacin, sparfloxacin, and rifampicin against 20 strains each of methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa, 18 strains of Enterobacter cloacae, 15 strains each of Streptococcus Pneumoniae and Moraxella catarrhalis, 12 strains of Haemophilus influenzae, 18 strains of Mycobacterium intracellulare, and 22 strains each of Mycobacterium tuberculosis and Mycobacterium avium were determined. The minimum inhibitory concentrations90's of gatifloxacin against the above species were 0.12, 8, <==0.06, 0.5, 2, 2, <==0.06, 0.39, 0.05, 0.013, 2, 0.5, and 4 &mgr;g/ml, respectively. Gatifloxacin was four times as active as ofloxacin against methicillin-susceptible and -resistant Staphylococcus aureus, and as active as ofloxacin against Enterobacteriaceae and Pseudomonas aeruginosa. Gatifloxacin was as active as tosufloxacin and sparfloxacin against Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae. The antimycobacterial activity of gatifloxacin was similar to that of sparfloxacin. Five patients with chronic respiratory infections and one patient with acute pneumonia received 100-400 mg/day of gatifloxacin orally for 5-12 days (mean, 8.17 days). The clinical effects were excellent in one patient and good in five. One strain of Haemophilus influenzae was eradicated and one strain of Pseudomonas aeruginosa persisted after therapy. Adverse reactions were mild and improved after completion of therapy. In one patient with chronic bronchitis, the maximum sputum concentrations 2-4 h after oral administration of 150 mg of gatifloxacin on days 1 and 6 were 0.88 and 1.45 &mgr;g/ml, respectively, and in serum the values were 0.84 and 1.24 &mgr;g/ml, respectively. Thus it was found that gatifloxacin possesses potent activity against respiratory pathogens (including Mycobacteriaceae), and shows good penetration rate into sputum, and that it can be used as the drug of first choice in the treatment of respiratory tract infections.