ANTIMICROBIAL AGENTS

AND

CHEMOTHERAPY, Mar. 1991,

p.

Vol. 35, No. 3

423-429

0066-4804/91/030423-07$02.00/0 Copyright C) 1991, American Society for Microbiology

Activity of Temafloxacin against Respiratory Pathogens ROBERT N. SWANSON,t* DWIGHT J. HARDY,t DANIEL T. W. CHU, NATHAN L. SHIPKOWITZ, AND JACOB J. CLEMENT Anti-Infective Research Division, Abbott Laboratories, Abbott Park, Illinois 60064-3500 Received 18 September 1990/Accepted 20 December 1990

The activity of the quinolone temafloxacin against respiratory pathogens was compared with those of ciprofloxacin and ofloxacin. MICs for 90% of strains tested indicated that temafloxacin was at least two- to fourfold more potent than the other two quinolones against Staphylococcus aureus, Streptococcus pneumoniae, and Legionella pneumophila. Temafloxacin had potency equal to that of ciprofloxacin and was twofold more active than ofloxacin against Streptococcus pyogenes, Moraxella catarrhalis, and Bordetella pertussis. Against Haemophilus influenzae and Klebsiella pneumoniae, temafloxacin was four- and twofold less potent than ciprofloxacin, respectively. When administered orally in mouse protection tests against S. aureus, S. pneumoniae, and S. pyogenes, temafloxacin was at least eight times more potent than ciprofloxacin and was two to four times more active than ofloxacin. Against H. influenzae, temafloxacin was as active as ofloxacin and was two times less active than ciprofloxacin following oral administration in mice. In treating L. pneumophila in guinea pigs and H. influenzae otitis media in gerbils, temafloxacin and ofloxacin were more effective than ciprofloxacin. Against S. pneumoniae otitis media in gerbils, temafloxacin and ciprofloxacin were more active than ofloxacin. Following subcutaneous administration in mice, temafloxacin achieved higher lung levels than ciprofloxacin or ofloxacin did.

subcutaneously against S. pneumoniae and Streptococcus pyogenes (13). The improved in vivo activity seen in this study appeared to be due, in part, to the improved pharmacokinetics of temafloxacin following oral and parenteral administration. These findings suggest that temafloxacin may be effective in treating lower respiratory tract infections, including those caused by S. pneumoniae. In the present study we characterized, in vitro and in mouse protection tests, the activity of temafloxacin against bacteria frequently associated with respiratory tract infections. In addition, temafloxacin was evaluated against experimental legionellosis and otitis media caused by S. pneumoniae and H. influenzae. In all tests the efficacy of temafloxacin was compared with those of ciprofloxacin and ofloxacin.

Temafloxacin is a new fluoroquinolone with broad-spectrum potency and favorable pharmacokinetics. Previously, it has been reported that temafloxacin is active against a wide range of bacteria and that it is effective in treating both gram-positive and gram-negative infections in mice (2, 4, 8, 13, 18, 19). Temafloxacin also is well absorbed in humans, with a mean peak level in serum of 3.3 ,ug/ml and a serum elimination half-life of 6.8 h following a single oral dose of 400 mg (17). Like most of the new fluoroquinolones, temafloxacin has substantial activity against many of the classic respiratory pathogens, including Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, Staphylococcus aureus, and Legionella pneumophila. Current clinical data indicate that the new quinolones can be successfully used to treat acute exacerbations of chronic bronchitis and other lower respiratory tract infections caused by these bacteria. In treating these conditions, the rates of cure or improvement for ciprofloxacin, ofloxacin, enoxacin, and pefloxacin range from 70 to 100% (23-25). However, the use of these new quinolones in treating bronchopulmonary infections appears to be limited by their reduced in vitro activity against Streptococcus pneumoniae, one of the most frequently isolated bacteria from community-acquired respiratory tract infections. Clinical and bacteriological relapses in S. pneumoniae-infected patients receiving quinolones have been reported; and in one study the rate of persistence, recurrence, or reinfection because of pneumococcus in quinolonetreated patients was 67% (5, 24). Temafloxacin is reported to be at least as active as ciprofloxacin in vitro against streptococci, and in mouse protection tests it is two- to eightfold more potent than ciprofloxacin when administered orally or

MATERIALS AND METHODS

Bacterial strains. The bacteria used in this study were clinical isolates, strains from the Abbott Laboratories culture collection, or strains from the American Type Culture Collection, Rockville, Md. All bacteria were identified by standard procedures at Abbott Laboratories and were maintained frozen at -60°C. Antimicrobial agents. Temafloxacin, ciprofloxacin, ofloxacin, and erythromycin were synthesized at Abbott Laboratories. Ampicillin was purchased from Parke-Davis (Morris Plains, N.J.). Stock solutions of quinolones for in vitro susceptibility testing were prepared in water. Other antibacterial agents were prepared according to the instructions of the manufacturer. For animal testing, all compounds were prepared in sterile injectable water. Susceptibility testing. MICs were determined by the standard twofold dilution method in agar with 1 x 104 CFU per spot as the inoculum or by the broth microdilution method with 5 x 105 CFU per ml as the inoculum (16). S. aureus and K. pneumoniae were tested in Mueller-Hinton agar, while streptococci and M. catarrhalis were tested in MuellerHinton agar supplemented with 5% (vol/vol) sheep blood. H.

Corresponding author. t Present address: Pfizer Pharmaceuticals, 235 East 42nd Street, New York, NY 10017. t Present address: Clinical Microbiology Laboratories, University of Rochester Medical Center, Rochester, NY 14642. *

423

424

SWANSON ET AL.

influenzae was tested in Mueller-Hinton agar supplemented with 3% lysed horse blood and 0.001% NAD. Streptococci and H. influenzae were incubated for 20 to 24 h. L. pneumophila was tested in buffered yeast extract broth (1) and buffered charcoal yeast extract agar and incubated for 48 h. Bordetella pertussis was tested in Bordet-Gengou agar supplemented with 15% (vol/vol) sheep blood and incubated for 72 h. Mycoplasma pneumoniae was tested by a previously described tube dilution method in SP-4 broth (22) with 104 to 105 color-changing units per ml used as the inoculum. Incubation for all tests was at 35°C in ambient air. Time-kill studies. The bactericidal kinetics of temafloxacin, ciprofloxacin, and ofloxacin against S. pneumoniae and S. pyogenes were determined in Mueller-Hinton broth supplemented with 3% (vol/vol) lysed horse blood and brain heart infusion broth (BHIB), respectively. Briefly, colonies from overnight cultures were suspended in sterile saline and adjusted to match a 0.5 McFarland turbidity standard. Adjusted bacterial suspensions were further diluted in growth medium and added to 50-ml flasks containing 10 ml of broth to yield final cell densities of approximately 105 to 106 CFU/ml. Compounds were added to flasks before inoculation to achieve the final desired concentrations for testing. Separate flasks without antibacterial agents served as controls for growth. At designated time intervals after exposure to drugs, 0.5-ml aliquots of cultures were aseptically removed, serially diluted in 10-fold increments in saline, and plated (0.1 ml) in duplicate onto drug-free agar. To eliminate the effect of drug carry-over, a minimum of a 1:100 dilution was used for plating. At 24 h only, 0.1-ml aliquots of undiluted cultures and cultures diluted 1:10 were plated to detect viable counts of 100

60

70

46.3

,

0.5

0.008 1.8 0.008 2.6 0.008 0.8

10

0

20

30

40

50

ED,(ms/kg/day) FIG. 1. Activities of temafloxacin, ofloxacin, and ciprofloxacin when administered orally in mouse protection tests. ED50, Median 50% effective dose.

was two- to fourfold more active than ciprofloxacin or ofloxacin. Against H. influenzae type b, temafloxacin was as potent as ciprofloxacin or ofloxacin when administered subcutaneously and was as active as ofloxacin and twofold less active than ciprofloxacin when administered orally. Legionellosis in guinea pigs. Bacterial counts from the lungs of treated and untreated L. pneumophila-infected guinea pigs are given in Table 4. When administered intraperitoneally at 15 mg/kg/day (7.5 mg/kg per injection, twice a day) for 2 days, temafloxacin reduced bacterial counts by 5.36 log CFU. At the same dose, ciprofloxacin and ofloxacin reduced lung counts by 4.22 and 4.87 log CFU, respectively. When administered at 1.5 mg/kg/day, temafloxacin lowered bacterial counts by 4.89 log CFU, as compared with a 1.17 log CFU reduction with ciprofloxacin and a 3.58 log CFU reduction with ofloxacin. None of the quinolones significantly lowered bacterial counts when they were given at 0.15 mg/kg/day. Erythromycin lactobionate had no significant activity in this model. H. influenzae otitis media in gerbils. Bacterial counts from the middle ear fluid of treated and untreated gerbils with H. influenzae otitis media are presented in Table 5. Oral treatment with temafloxacin, ciprofloxacin, or ofloxacin at doses of as low as 10 mg/kg/day reduced bacterial counts by 5.82 to 6.10 log CFU. At 2 mg/kg/day, temafloxacin reduced bacterial counts by 3.05 log CFU, as compared with a 4.27 log

CFU reduction in ofloxacin-treated gerbils. Ciprofloxacin did not lower bacterial counts at this dose. All three quinolones were more active in this model than ampicillin was, which was effective only at 50 mg/kg/day.

24

The MICs against S. pneumoniae ATCC 6303 were as follows: temafloxacin, 0.25 ,ug/ml; ciprofloxacin, 1.0 p.g/ml; and ofloxacin, 0.5 ,ug/ml. a

10649

Streptococcus

O Temafloxacin hydrochloride * Ofloxacin

3.3

aureus

Log decrease in viable counts after exposure

Compound

., .I>10

ANTIMICROB. AGENTS CHEMOTHER.

MIC BACTERIA Staphylococcus 0.06 1.2 aureus 10649

0.12 0.12

Streptococcus pneuoniae

0.2 5 0.50 _

6303

0.5

pyogenes

0.5 0.5

Haenophilw influenzae 1435

E Ciprofloxacin

3.7

4.1

1

Streptococcus C203

Ol Temafloxacin hydrochloride * Ofloxacin

j34.8

0.008 0.3

0.006 0.4 0.008 0.3 0

10

20

30

40

50

ED,(mgJkgtday) FIG. 2. Activities of temafloxacin, ofloxacin, and ciprofloxacin when administered subcutaneously in mouse protection tests. ED50, Median 50% effective dose.

VOL. 35, 1991

TEMAFLOXACIN AGAINST RESPIRATORY PATHOGENS

TABLE 4. Activities of temafloxacin, ciprofloxacin, and ofloxacin against L. pneumophila ATCC 33152 pneumonia in guinea pigsa Compound Compound

Temafloxacin

TABLE 6. Activities of temafloxacin, ciprofloxacin, and ofloxacin against S. pneumoniae ATCC 6303 otitis media in gerbils'

MIC (,ug/ml)

Dose (mg/kg/day)"

Log CFU ± SE)C (mean

0.03

15 1.5 0.15

3.07 0.81d 3.57 0.30d 7.95 ± 0.17

Compound Compound

Temafloxacin

MIC (jig/ml)

Dose (mg/

kg/day)b

Log CFU (mean ± SE)C

eatv Negative

0.25

250

sl.30 ± 0.00d 1.68 ± 0.37

100

50

10

Ciprofloxacin

0.03

Ofloxacin

0.06

Erythromycin lactobionate

1

Untreated controls

15 1.5 0.15

4.23 + 0.21d 7.28 0.28d 8.18 ± 0.14

15 1.5 0.15

3.58 ± 0.12d 4.85 0.45d 7.88 ± 0.39

50 5

7.60 ± 0.64 8.30 ± 0.10

0

8.43 ± 0.07

a The lungs of L. pneumophila-infected guinea pigs contained 7.9 log CFU of bacteria at the start of therapy. b Antibiotics were administered intraperitoneally twice a day for 2 days. Geometric mean CFU in two lungs. d Significantly different from untreated controls at P = 0.05.

S. pneumoniae otitis media in gerbils. Bacterial counts from the middle ear fluid of treated and untreated S. pneumoniaeinfected gerbils are given in Table 6. At oral doses of 10 mg/kg/day, temafloxacin lowered bacterial counts to essentially undetectable levels in three of four animals. Ciprofloxacin at this dose reduced bacterial counts by 2.67 log CFU, but it did not clear the infection in any animals. Ofloxacin at 10 mg/kg/day was not effective. Ampicillin was the most

TABLE 5. Activities of temafloxacin, ciprofloxacin, and

ofloxacin against H. influenzae ATCC 43095 otitis media in gerbils' Compound

Temafloxacin

~MIC

Dose

0.015

Negative cultures

s1.30 ± oo0d s1.30 ± oo0d 4.35 1.29d

100 100

50 10 2

s1.30 + 0.00d 1.58 0.19d 7.20 ± 0.06

75 50 0

50 10 2

1.43 0.12d s1.30 ± 000d 3.13 1.83d

50 100 0

50

51.30 ± oo0d

100

10 2

7.00 ± 0.28 7.27 ± 0.15

0 0

0

7.40 ± 0.11

0

50 10 2

Ciprofloxacin

Ofloxacin

Ampicillin Untreated controls

0.015

0.030

0.25

Log

CFU

(p.g/m) (mg/g/day) (lig/ml) (mg/kg/day)b

(mean

±SE)'

427

0

aThe middle ears of H. influenzae-infected gerbils contained 3.3 log CFU of bacteria at the start of therapy. b Antibiotics were administered orally twice a day for 2 days. c Geometric mean CFU per middle ear. The minimum number of bacteria detected by this method was 1.30 log CFU per ear. d Significantly different from untreated controls at P = 0.05.

Ciprofloxacin

Ofloxacin

250

1

0.5

Untreated controls

0.03

0.20d

75

75

'1.30 ± 0.00d

100

50

'1.30

0.00d

100

10

2.33

0.47d

0

250

s1.30

100

10

± 0.ood 1.90 ± 0.60d 5.27 ± 0.20

50 10 2

s1.30 ± 0.00d s1.30 ± 0.00d s1.30 + 0.00d

100 100

0

5.00 ± 0.35

50

Ampicillin

1.50

cultures

75

0

100

0

a The middle ears of S. pneumoniae-infected gerbils contained 3.8 log CFU of bacteria at the start of therapy. b Antibiotics were administered orally twice a day for 2 days. Geometric mean CFU per middle ear. The minimum number of bacteria detected by this method was 1.30 log CFU per ear. dSignificantly different from untreated controls at P = 0.05.

active antibiotic in this test, with a 100% cure rate at doses of as low as 2 mg/kg/day. Pharmacokinetics in mice. The pharmacokinetics of temafloxacin, ciprofloxacin, and ofloxacin following a single subcutaneous injection of 25 mg/kg are shown in Table 7. Temafloxacin and ofloxacin achieved higher concentrations in serum and had longer serum half-lives than did ciprofloxacin. Peak lung concentrations occurred 0.5 h after injection and were higher for temafloxacin and ofloxacin. From 1 to 3 h after antibiotic administration the lung levels of temafloxacin were 1.7 to 2.0 times higher than those of the other quinolones. Pharmacokinetics in guinea pigs. The concentrations of temafloxacin, ciprofloxacin, and ofloxacin in serum were determined after a single intraperitoneal administration of 7.5 mg/kg in guinea pigs. All three quinolones reached maximum levels in the serum within 0.5 h after injection. Temafloxacin achieved a peak level in serum of 4.0 ,ug/ml and had a serum half-life of 1.0 h. Ofloxacin had a peak level in serum of 4.3 ,ug/ml and a serum half-life of 0.9 h. The peak concentration of ciprofloxacin in serum was 1.5 ,ug/ml, and the serum half-life was 1.3 h. DISCUSSION

The three fluoroquinolones evaluated in this study had potent activities against gram-negative respiratory pathogens. The MIC90s of temafloxacin against M. catarrhalis, H. influenzae, B. pertussis, and K. pneumoniae ranged from 0.03 to 0.12 ,ug/ml. The MIC90s of ofloxacin against the same bacteria also ranged from 0.03 to 0.12 jig/ml, while the MIC90s of ciprofloxacin were 0.008 to 0.06 ,ug/ml. These results are in agreement with the findings of numerous other studies (2, 4, 13, 18, 19). Because of their excellent in vitro activities and pharmacokinetics, these quinolones are able to achieve peak concentrations in the serum and bronchial

428

ANTIMICROB. AGENTS CHEMOTHER.

SWANSON ET AL.

TABLE 7. Pharmacokinetics of temafloxacin, ciprofloxacin, and ofloxacin in mice after a single subcutaneous administration of 25 mg/kg Concn in serum (,ug/ml) or lungs (,ug/g) at the following time (h) p.i.:

4/2 (h)0 8 24 6 3 2 t1

AUC

hIml)b

Compound

Sample

Temafloxacin

Serum Lung

8.0 14.3

4.7 8.4

2.0 3.2

0.8 1.4

0.3 0

0.2 0

0 0

1.3 0.7

9.1 10.2

Ciprofloxacin

Serum Lung

5.1 8.0

1.4 4.3

0.4 1.8

0 0.8

0 0

0 0

0 0

0.4 0.7

1.4 6.5

Ofloxacin

Serum Lung

7.6 12.0

5.6 4.5

3.5 1.6

1.0 0

0.3 0

0.1 0

0 0

1.2 0.5

11.6 5.0

a

b

qLg

1/2,

Serum or lung half-life. AUC, Area under the curve.

secretions which are much higher than the MICs for these bacteria (24). This suggests that these agents would be effective in treating lower respiratory tract infections caused by the gram-negative pathogens listed above, and this has been confirmed by clinical trials (23-25). Based on data from the present study, temafloxacin can be expected to demonstrate similar clinical effectiveness. Against L. pneumophila, temafloxacin was two- to fourfold more potent in vitro than ciprofloxacin or ofloxacin was. The MIC90 of temafloxacin in broth was 0.03 ,ug/ml, as compared with 0.06 p.g/ml for ciprofloxacin and ofloxacin. In agar the MIC90s of temafloxacin, ciprofloxacin, and ofloxacin were 0.25, 1.0, and 0.5 p.g/ml, respectively. In treating experimental legionellosis in guinea pigs, temafloxacin was as effective as ofloxacin and was more effective than ciprofloxacin. All three of the quinolones were significantly more active than erythromycin lactobionate, an antibiotic of choice in treating this disease. It should be noted that the potency of erythromycin in this model likely would have been improved by more frequent dosing, e.g., four times a day instead of twice a day, or by lowering the infecting dose. Guinea pigs had a high number of bacteria, 8 x 107 CFU, in their lungs at the time therapy was started. Other studies have shown that many of the new quinolones, including ciprofloxacin, ofloxacin, pefloxacin, difloxacin, and lomefloxacin, are effective in treating L. pneumophila pneumonia in guinea pigs (6, 9, 10, 14, 15, 20, 21). Few data exist concerning the use of quinolones in treating human legionellosis, and the potential value of these antibiotics for this indication may ultimately depend on pharmacological properties such as tissue distribution and intracellular penetration into alveolar macrophages. The three quinolones evaluated in the present study were less active against gram-positive respiratory pathogens. Temafloxacin was the most potent against staphylococci and streptococci, with MIC90s of 0.12 to 1 ,ug/ml. The MIC%0s of ciprofloxacin and ofloxacin against these bacteria were 0.25 to 2.0 ,ug/ml. Against S. pneumoniae the MIC90 of temafloxacin was 0.25 ,ug/ml, while the MIC90s of ciprofloxacin and ofloxacin were 2.0 Vig/ml. In patients with pneumococcal infection, it is unlikely that orally administered ciprofloxacin or ofloxacin would be able to achieve levels greatly exceeding these MICs for extended periods of time (24). Temafloxacin, because of its favorable pharmacokinetic profile in humans and fourfold greater potency against S. pneumoniae, would be more likely to achieve levels in serum and tissue greater than the MIC. Following a single subcutaneous dose of 25 mg/kg in mice, the concentrations of temafloxacin in the serum and lungs exceeded the MIC90 against S. pneu-

moniae (0.5 jig/ml) for 3 h. Levels of ciprofloxacin exceeded the MIC90 (2 ,ug/ml) for only 0.5 h in sera and 1 h in the lungs. Ofloxacin achieved concentrations higher than the MIC%0 (2.0 ,ug/ml) for 2 h in sera and 1 h in the lungs. Thus, therapeutic concentrations of temafloxacin were present in the lungs of mice 2 h longer than they were in mice treated with ciprofloxacin or ofloxacin. Against S. aureus, S. pneumoniae, and S. pyogenes infected in mice, temafloxacin was 2 to 11 times more potent than ciprofloxacin and 2 to 4 times more potent than ofloxacin. Temafloxacin was also more effective than ciprofloxacin and ofloxacin in treating S. pneumoniae otitis media in gerbils. Bedos et al. (3) reported that the antipneumococcal activity of temafloxacin is equal to or greater than that of erythromycin and comparable to that of amoxicillin in a mouse pneumonia model. The in vitro and in vivo potencies of temafloxacin, along with its greater lung penetration in mice, suggests that this antibacterial agent may be useful in treating lower respiratory tract infections caused by gram-positive bacteria. ACKNOWLEDGMENTS We acknowledge the technical expertise of Ken Jarvis, Michael Mitten, Jill Beyer, Dena Hensey, Nancy Ramer, and Thomas Hutch, along with the statistical evaluation provided by Richard Rode. We also thank Robert Fulghum, East Carolina University, for assisting in the development of the otitis media model. REFERENCES 1. Barbaree, J. M., A. Sanchez, and G. N. Sanden. 1983. Tolerance of Legionella species to sodium chloride. Curr. Microbiol. 9:1-5. 2. Barry, A. L., and R. N. Jones. 1989. In-vitro activities of temafloxacin, tosufloxacin (A-61827) and five other fluoroquinolone agents. J. Antimicrob. Chemother. 23:527-535. 3. Bedos, J. P., B. Regnier, and J. J. Pocidalo. 1989. Antipneumococcal activity of temafloxacin in a murine pneumonia model. Rev. Infect. Dis. ll(Suppl. 5):S1228-S1229. 4. Chin, N. X., V. M. Figueredo, A. Novelli, and H. C. Neu. 1988. In vitro activity of temafloxacin, a new difluoro quinolone antimicrobial agent. New Antimicrob. Agents 7:58-63. 5. Davies, B. J., and F. P. V. Maesen. 1987. Respiratory infections: clinical experiences with the new quinolones. Pharm. Weekbl.

9(Suppl.):53-57. 6. Dournon, E., P. Rajagopalan, J. L. Vilde, and J. J. Pocidalo. 1986. Efficacy of pefloxacin in comparison with erythromycin in the treatment of experimental guinea pig legionellosis. J. Antimicrob. Chemother. 17(Suppl. B):41-48. 7. Fernandes, P. B., D. T. W. Chu, R. R. Bower, K. P. Jarvis, N. R. Ramer, and N. L. Shipkowitz. 1986. In vivo evaluation of A-56619 (difloxacin) and A-56620: new aryl-fluoroquinolones. Antimicrob. Agents Chemother. 29:201-208.

VOL. 35, 1991

TEMAFLOXACIN AGAINST RESPIRATORY PATHOGENS

8. Fernandes, P. B., and R. N. Swanson. 1988. Correlation of in vitro activities of the fluoroquinolones to their in vivo efficacies. Drugs Exp. Clin. Res. 24:375-378. 9. Fernandes, P. B., R. N. Swanson, and D. T. W. Chu. 1988. Relative in vivo potency of new fluoroquinolones against two intracellular pathogens, Salmonella typhimurium and Legionella pneumophila. Rev. Infect. Dis. 10(Suppl. 1):S117. 10. Fitzgeorge, R. B., D. H. Gibson, R. Jepras, and A. Baskerville. 1985. Studies on ciprofloxacin therapy of experimental Legionnaires' disease. J. Infect. 10:194-203. 11. Fulghum, R. S., J. E. Brinn, A. M. Smith, H. J. Daniel III, and P. J. Loesche. 1982. Experimental otitis media in gerbils and chinchillas with Streptococcus pneumoniae, Haemophilus influenzae, and other aerobic and anaerobic bacteria. Infect. Immun. 36:802-810. 12. Hamilton, M. A., R. C. Russo, and R. V. Thurston. 1977. Trimmed Spearman-Karber method for estimating median lethal concentrations in toxicity bioassays. Environ. Sci. Technol. 11:714-719. 13. Hardy, D. J., R. N. Swanson, D. M. Hensey, N. R. Ramer, R. R. Bower, C. W. Hanson, and P. B. Fernandes. 1987. Comparative antibacterial activities of temafloxacin hydrochloride (A-62254) and two reference fluoroquinolones. Antimicrob. Agents Chemother. 31:1768-1774. 14. Havlichek, D., D. Pohlod, and L. Saravolatz. 1987. Comparison of ciprofloxacin and rifampicin in experimental Legionella pneumophila pneumonia. J. Antimicrob. Chemother. 20:875-881. 15. Kohno, S., K. Yamaguchi, Y. Dohtsu, H. Koga, T. Hayashi, M. Hirota, A. Saito, and K. Hara. 1988. Efficacy of NY-198 against experimental Legionnaires disease. Antimicrob. Agents Chemother. 32:1427-1429. 16. National Committee for Clinical Laboratory Standards. 1985. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A. National Committee for Clinical Laboratory Standards, Villanova, Pa.

429

17. Nye, K., Y. G. Shi, J. M. Andrews, J. P. Ashby, and R. Wise. 1989. The in-vitro activity, pharmacokinetics and tissue penetration of temafloxacin. J. Antimicrob. Chemother. 24:415-424. 18. Rolston, K., B. LeBlanc, G. Gooch, D. H. Ho, and G. P. Bodey. 1989. In vitro activity of PD117558 and temafloxacin. Rev. Infect. Dis. 11(Suppl. 5):S927-S928. 19. Rolston, K. V. I., D. H. Ho, B. LeBlanc, G. Gooch, and G. P. Bodey. 1988. Comparative in vitro activity of the new difluoroquinolone temafloxacin (A-62254) against bacterial isolates from cancer patients. Eur. J. Clin. Microbiol. 7:684-686. 20. Saito, A., H. Koga, H. Shigeno, K. Watanabe, K. Mori, S. Kohno, Y. Shigeno, Y. Suzuyama, K. Yamaguchi, M. Hirota, and K. Hara. 1986. The antimicrobial activity of ciprofloxacin against Legionella species and the treatment of experimental Legionella pneumonia in guinea pigs. J. Antimicrob. Chemother. 18:251-260. 21. Saito, A., K. Sawatari, Y. Fukuda, M. Nagasawa, H. Koga, A. Tomonaga, H. Nakazato, K. Fujita, Y. Shigeno, Y. Suzuyama, K. Yamaguchi, K. Izumikawa, and K. Hara. 1985. Susceptibility of Legionella pneumophila to ofloxacin in vitro and in experimental Legionella pneumonia in guinea pigs. Antimicrob. Agents Chemother. 28:15-20. 22. Senterfit, L. B. 1983. Antibiotic susceptibility testing of mycoplasmas, p. 397-401. In S. Razin and J. G. Tully (ed.), Methods in mycoplasmatology, vol. 2. Academic Press, Inc., New York. 23. Shah, P., and K. Frech. 1986. Overview of clinical experience with quinolones, p. 29-43. In A. Percival (ed.), Quinolonestheir future in clinical practice. Royal Society of Medicine Services International Congress and Symposium no. 14. Royal Society of Medicine Services Ltd., London. 24. Thys, J. P., F. Jacobs, and S. Motte. 1989. Quinolones in the treatment of lower respiratory tract infections. Rev. Infect. Dis. ll(Suppl. 5):S1212-S1219. 25. Wolfson, J. S., and D. C. Hooper. 1989. Fluoroquinolone antimicrobial agents. Clin. Microbiol. Rev. 2:378-424.

Activity of temafloxacin against respiratory pathogens.

The activity of the quinolone temafloxacin against respiratory pathogens was compared with those of ciprofloxacin and ofloxacin. MICs for 90% of strai...
1MB Sizes 0 Downloads 0 Views