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Levofloxacin

A Review of its Use in the Treatment of Bacterial Infections in the United States

Drugs volume 63, pages 2769–2802 (2003)Cite this article

Summary

Abstract

Levofloxacin (Levaquin®) is a fluoroquinolone antibacterial agent with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and atypical respiratory pathogens. It is active against both penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae. The prevalence of S. pneumoniae resistance to levofloxacin is <1% overall in the US.

A number of randomised comparative trials in the US have demonstrated the efficacy of levofloxacin in the treatment of infections of the respiratory tract, genitourinary tract, skin and skin structures. Sequential intravenous to oral levofloxacin 750mg once daily for 7–14 days was as effective in the treatment of nosocomial pneumonia as intravenous imipenem/cilastatin 500–1000mg every 6–8 hours followed by oral ciprofloxacin 750mg twice daily in one study. In patients with mild to severe community-acquired pneumonia (CAP), intravenous and/or oral levofloxacin 500mg once daily for 7–14 days achieved clinical and bacteriological response rates similar to those with comparator agents, including amoxicillin/clavulanic acid, clarithromycin, azithromycin, ceftriaxone and/or cefuroxime axetil and gatifloxacin. A recent study indicates that intravenous or oral levofloxacin 750mg once daily for 5 days is as effective as 500mg once daily for 10 days, in the treatment of mild to severe CAP. Exacerbations of chronic bronchitis and acute maxillary sinusitis respond well to treatment with oral levofloxacin 500mg once daily for 7 and 10–14 days, respectively.

Oral levofloxacin was as effective as ofloxacin in uncomplicated urinary tract infections and ciprofloxacin or lomefloxacin in complicated urinary tract infections. In men with chronic bacterial prostatitis treated for 28 days, oral levofloxacin 500mg once daily achieved similar clinical and bacteriological response rates to oral ciprofloxacin 500mg twice daily. Uncomplicated skin infections responded well to oral levofloxacin 500mg once daily for 7–10 days, while in complicated skin infections intravenous and/or oral levofloxacin 750mg for 7–14 days was at least as effective as intravenous ticarcillin/clavulanic acid (± switch to oral amoxicillin/clavulanic acid) administered for the same duration.

Levofloxacin is generally well tolerated, with the most frequently reported adverse events being nausea and diarrhoea; in comparison with some other quinolones it has a low photosensitising potential and clinically significant cardiac and hepatic adverse events are rare.

Conclusion: Levofloxacin is a broad-spectrum antibacterial agent with activity against a range of Gram-positive and Gram-negative bacteria and atypical organisms. It provides clinical and bacteriological efficacy in a range of infections, including those caused by both penicillin-susceptible and -resistant strains of S. pneumoniae. Levofloxacin is well tolerated, and is associated with few of the phototoxic, cardiac or hepatic adverse events seen with some other quinolones. It also has a pharmacokinetic profile that is compatible with once-daily administration and allows for sequential intravenous to oral therapy. The recent approvals in the US for use in the treatment of nosocomial pneumonia and chronic bacterial prostatitis, and the introduction of a short-course, high-dose regimen for use in CAP, further extend the role of levofloxacin in treating bacterial infections.

Pharmacodynamic Properties

Levofloxacin is the L-isomer of the racemate ofloxacin. It inhibits bacterial DNA gyrase and topoisomerase IV. Levofloxacin has a broad spectrum of activity against Gram-positive and Gram-negative aerobic bacteria and atypical bacteria, but limited activity against most anaerobic bacteria.

Levofloxacin is active against Streptococcus pneumoniae (including penicillin-resistant strains [MIC value for penicillin ≥2 mg/L]) and methicillin-susceptible Staphylococcus aureus, with minimum concentrations required to inhibit the growth of 90% of strains (MIC90) in the range 1.0–2.0 mg/L and 0.25–0.5 mg/ L, respectively. The percentages of Gram-positive clinical isolates that were susceptible to levofloxacin and gatifloxacin were similar, but were higher with levofloxacin than ciprofloxacin. Levofloxacin has only limited in vitro activity against enterococci; however, it is indicated in infections caused by susceptible strains of E. faecalis.

Levofloxacin is highly active against Haemophilus influenzae (MIC90 0.008–0.12 mg/L), Moraxella catarrhalis (MIC90 ≤0.03–0.06 mg/L) and also shows activity against the Enterobacteriaceae (MIC90 ≤2.0 mg/L for most isolates). The susceptibility rates of Pseudomonas aeruginosa to levofloxacin were 62–74% compared with 63–80% for ciprofloxacin, in studies performed in North America. Levofloxacin also shows good activity against the atypical respiratory pathogens Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella spp. (MIC90 ≤0.5, 1.0 and 0.03 mg/L, respectively).

Surveillance programmes in the US have found that resistance to levofloxacin among respiratory pathogens, including S. pneumoniae, remains low overall (≤1%). The activity of levofloxacin is concentration-dependent, and area under the plasma concentration-time curve (AUC)/MIC ratios of >100–125 and >30 are predictors of clinical and bacteriological efficacy against Gram-negative bacteria and S. pneumoniae, respectively. In patients receiving a once-daily dosage of oral levofloxacin 500mg, an AUC/MIC ratio >30 for S. pneumoniae is achieved 99% of the time. Levofloxacin shows a postantibiotic effect against a range of bacteria.

Pharmacokinetic Properties

Levofloxacin is rapidly absorbed after oral administration. The absolute bioavailability is approximately 99% and its pharmacokinetics are linear over the dosage range 500–1000mg once daily for multiple-dose administration. The oral and intravenous routes are considered interchangeable. It has low plasma protein binding (24–38%) and a volume of distribution of 76–102L. Tissue distribution is extensive, with concentrations in most tissues (including the lung, prostate gland and skin) exceeding those in plasma and being many times higher than the MICs of common pathogenic bacteria at these sites. The concentrations of levofloxacin in lung tissue homogenate, epithelial lining fluid and alveolar macrophages are up to 5-, 3- and 23-fold greater than those in plasma, and the prostate/plasma penetration ratio is up to 4.

Levofloxacin undergoes only limited metabolism and the main route of excretion is through the kidneys, with 64–102% of a dose being recovered unchanged in the urine. The mean terminal elimination half-life is approximately 6–9 hours. Clearance of levofloxacin is reduced in renal impairment and dosage modifications are necessary for patients with creatinine clearance <50 mL/min.

The pharmacokinetics of levofloxacin are not significantly altered by age, sex or in patients with HIV infection. Compared with those in healthy volunteers, levofloxacin peak plasma concentration and AUC values increased by approximately 10–30% in patients with community-acquired bacterial infections. The absorption of levofloxacin is reduced by concurrent administration of magnesium-or aluminium-containing antacids, sucralfate, iron or zinc preparations. No significant interactions between levofloxacin and theophylline or warfarin were observed in healthy volunteers; however, several case reports have suggested levofloxacin may reduce the metabolism and/or clearance of these agents in certain patients. No clinically significant interactions have been reported with cimetidine, ranitidine, probenecid, cyclosporin, digoxin, zidovudine or nelfinavir.

Therapeutic Efficacy

Randomised, comparative trials have confirmed the efficacy of oral and/or intravenous levofloxacin in the treatment of adults with infections of the respiratory tract, genitourinary tract, skin and skin structures using once-daily dosages of 250, 500 or 750mg depending on the indication. Treatment duration varied for different indications. Sequential intravenous to oral therapy has been used successfully in patients with pneumonia or complicated skin infections.

Respiratory tract infections: In a study in patients with nosocomial pneumonia, 7–15 days of therapy with sequential intravenous and oral levofloxacin 750mg once daily was as effective as intravenous imipenem/cilastatin 500–1000mg every 6–8 hours followed by oral ciprofloxacin 750mg twice daily. Clinical and bacteriological response rates were 58% and 67% in levofloxacin recipients and were both 61% in patients receiving the comparator. Most patients with P. aeruginosa infection received adjunctive therapy with ceftazidime or piperacillin/tazobactam (levofloxacin group) or an aminoglycoside (comparator regimen); clinical and bacteriological response rates were 65% and 59% with the levofloxacin regimen and 41% and 29% with the comparator.

Several well-designed comparative trials of the treatment of mild to severe community-acquired pneumonia (CAP) with intravenous and/or oral levofloxacin 500mg once daily for 7–14 days have been performed. In these studies clinical and bacteriological response rates were similar in recipients of levofloxacin (86–96% and 85–98%) and the comparator (83–96% and 75–98%). Comparators included amoxicillin/clavulanic acid, clarithromycin, gatifloxacin, ceftriaxone and/or cefuroxime axetil, azithromycin (plus ceftriaxone) or a sequential regimen of ceftriaxone plus erythromycin followed by amoxicillin/clavulanic acid plus clarithromycin. Levofloxacin was effective against CAP caused by common respiratory pathogens such as S. pneumoniae, H. influenzae, M. catarrhalis, M. pneumoniae, C. pneumoniae and Legionella spp.

Data from a recent study indicate that levofloxacin 750mg once daily for 5 days is as effective as levofloxacin 500mg once daily for 10 days in the treatment of patients with mild to severe CAP (oral or intravenous administration permissible with both regimens).

Seven days’ treatment with oral levofloxacin 500mg once daily achieved clinical response rates of 83–94% in patients with acute exacerbations of chronic bronchitis (AECB) compared with 80–93% of patients receiving comparators (cefuroxime axetil, clarithromycin, azithromycin or moxifloxacin). Bacteriological response rates were 68–96% for levofloxacin and 48–96% for the comparator groups.

In patients with acute maxillary sinusitis treatment for 10–14 days with oral levofloxacin 500mg once daily was as effective as oral amoxicillin/clavulanic acid 500mg three times daily or oral clarithromycin 500mg twice daily. Clinical response rates were 88–96% for levofloxacin and 87–94% for the comparator regimens. Bacteriological efficacy was not assessed in these trials.

Genitourinary tract infections: In urinary tract infections clinical and bacteriological response rates for oral levofloxacin ranged from 93–98% and 94–96% and those for comparator regimens from 89–97% and 92–94%. A 3-day course of levofloxacin 250mg once daily was as effective as ofloxacin 200mg twice daily in patients with uncomplicated urinary tract infections. Levofloxacin 250mg once daily for 7–10 days was as effective as ciprofloxacin 500mg twice daily for 10 days or lomefloxacin 400mg once daily for 7–10 days in patients with acute pyelonephritis and as effective as lomefloxacin 400mg once daily for 14 days in patients with complicated urinary tract infections.

In men with chronic bacterial prostatitis a 28-day course of oral levofloxacin 500mg once daily provided similar efficacy to oral ciprofloxacin 500mg twice daily administered for the same duration. Clinical response rates were 75% and 73% and bacteriological response rates 75% and 77% in levofloxacin and ciprofloxacin recipients. In patients infected with Escherichia coli bacteriological response rates were 93% with levofloxacin and 82% with ciprofloxacin.

Skin and skin structure infections: In three randomised, comparative studies of levofloxacin in uncomplicated skin and skin structure infections, oral levofloxacin 500mg was as effective as ciprofloxacin 500mg twice daily or gatifloxacin 400mg once daily (all administered for 7–10 days). In a trial involving patients with complicated infections, clinical response rates were similar with levofloxacin 750mg once daily (oral or intravenous administration for 7–14 days) and intravenous ticarcillin/clavulanic acid (3.1g every 4–6 hours with the option to switch to oral amoxicillin/clavulanic acid 875mg twice daily). The bacteriological response rate was higher with levofloxacin than the comparator regimen (84% vs 71% [95% CI for between-group difference; −24.3, −0.2]).

Tolerability

Levofloxacin is generally well tolerated. The majority of adverse events are transient and of mild to moderate severity. During phase III clinical trials in North America involving oral and/or intravenous dosages up to 750mg once daily, the incidence of adverse events considered related to levofloxacin was 6.3%, with the most frequently reported events being nausea (1.3%), diarrhoea, vaginitis, abdominal pain and insomnia (all ≤1%). Treatment was discontinued in 4.0% of patients because of adverse events. The type of adverse events seen with 750mg daily is similar to that with lower dosages.

Levofloxacin was as well tolerated as ciprofloxacin, ofloxacin, gatifloxacin, lomefloxacin and moxifloxacin in comparative clinical trials. It was also at least as well tolerated as a range of agents from other antibacterial classes used as comparators. In patients with sinusitis oral levofloxacin was associated with a significantly lower incidence of adverse events than oral amoxicillin/clavulanic acid or clarithromycin.

Levofloxacin has a low potential for causing phototoxic reactions (incidence 0.03%). Tendon disorders, severe liver toxicity and symptomatic hypoglycaemia or hyperglycaemia are rare with levofloxacin, as are clinically significant cardiac adverse events. Although prolongation of the QTC interval has been reported, few cases of torsade de pointes have occurred (<1 report per million prescriptions in the US).

Dosage and Administration

Levofloxacin is available as intravenous and oral preparations and patients may be switched between formulations without altering the dosage. In the US all dosage regimens are based on once-daily administration.

Levofloxacin 500mg once daily is the current recommended dosage for patients with AECB (administered for 7 days), acute maxillary sinusitis (10–14 days) and uncomplicated skin and skin structure infections (7–10 days). In patients with CAP, dosages of either 500mg once daily for 7–14 days or 750mg once daily for 5 days are recommended. For complicated and uncomplicated urinary tract infections 250mg once daily for 10 days or 3 days, respectively, should be used. A dosage of 750mg once daily for 7–14 days is recommended for patients with nosocomial pneumonia or complicated skin and skin structure infections. In patients with chronic bacterial prostatitis the recommended dosage is 500mg once daily for 28 days. Levofloxacin is approved for the treatment of infections caused by susceptible strains of common pathogens associated with each condition. In the case of nosocomial pneumonia involving P. aeruginosa, combination therapy with an antipseudomonal β-lactam is advised.

Modification of the dosage is required in patients with renal impairment (creatinine clearance <50 mL/min). Levofloxacin is contraindicated in patients aged under 18 years and women who are pregnant or breastfeeding. Caution should be used in those patients with risk factors for QTC prolongation or disorders that predispose them to seizures, and in diabetic patients receiving concomitant antihyperglycaemic agents. Caution is also required when administering levofloxacin concurrently with theophylline, warfarin and nonsteroidal anti-inflammatory drugs. Antacids and sucralfate should not be taken within 2 hours of levofloxacin adminstration.

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Notes

  1. Use of tradenames is for product identification purposes only and does not imply endorsement.

References

  1. Hurst M, Lamb HM, Scott LJ, et al. Levofloxacin: an updated review of its use in the treatment of bacterial infections. Drugs 2002; 62(14): 2127–67

    PubMed  CAS  Google Scholar 

  2. Zhanel GG, Ennis K, Vercaigne L, et al. A critical review of the fluoroquinolones: focus on respiratory tract infections. Drugs 2002; 62(1): 13–59

    PubMed  CAS  Google Scholar 

  3. Hooper DC. Mode of action of fluoroquinolones. Drugs 1999; 58 Suppl. 2: 6–10

    PubMed  CAS  Google Scholar 

  4. Ortho-McNeil Pharmaceutical Inc. Levaquin (levofloxacin) tablets; Levaquin (levofloxacin) injection; Levaquin (levofloxacin in 5% dextrose) injection; prescribing information. Raritan (NJ): Ortho-McNeil Pharmaceutical Inc., 2003 Oct

    Google Scholar 

  5. National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard — sixth edition (M7-A6). MIC testing supplemental tables M100-S13 (M7). National Committee for Clinical Laboratory Standards, 2003;23 (2)

  6. White RL, Enzweiler KA, Friedrich LV, et al. Comparative activity of gatifloxacin and other antibiotics against 4009 clinical isolates of Streptococcus pneumoniae in the United States during 1999–2000. Diagn Microbiol Infect Dis 2002 Jul; 43(3): 207–17

    PubMed  CAS  Google Scholar 

  7. Diekema DJ, Jones RN, Rolston KVI. Antimicrobial activity of gatifloxacin compared to seven other compounds tested against Gram-positive organisms isolated at 10 cancer-treatment centers. Diagn Microbiol Infect Dis 1999; 34: 37–43

    PubMed  CAS  Google Scholar 

  8. Hoban DJ, Doern GV, Fluit AC, et al. Worldwide prevalence of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the SENTRY Antimicrobial Surveillance Program, 1997–1999. Clin Infect Dis 2001; 32 (Suppl. 2): S81–93

    PubMed  CAS  Google Scholar 

  9. Sahm DF, Weaver MK, Flamm RK, et al. Rates of antimicrobial resistance among clinical isolates of Streprococcus pneumoniae in the United States: results from the TRUST 7 (2002–2003) surveillance study [abstract no. 201 plus poster]. 41st Annual Meeting IDSA; 2003 Oct 9–12; San Diego

  10. Rolston KV, Frisbee-Hume S, LeBlanc BM, et al. Antimicrobial activity of a novel des-fluoro (6) quinolone, garenoxacin (BMS-284756), compared to other quinolones, against clinical isolates from cancer patients. Diagn Microbiol Infect Dis 2002 Oct; 44(2): 187–94

    PubMed  CAS  Google Scholar 

  11. Blondeau JM, Laskowski R, Bjarnason J, et al. Comparative in vitro activity of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin against 4151 Gram-negative and Gram-positive organisms. Int J Antimicrob Agents 2000; 14: 45–50

    PubMed  CAS  Google Scholar 

  12. Deshpande LM, Jones RN. Antimicrobial activity of advanced-spectrum fluoroquinolones tested against more than 2000 contemporary bacterial isolates of species causing community-acquired respiratory tract infections in the United States (1999). Diagn Microbiol Infect Dis 2000; 37: 139–42

    PubMed  CAS  Google Scholar 

  13. Biedenbach DJ, Barrett MS, Croco MA, et al. BAY 12-8039, a novel fluoroquinolone: activity against important respiratory tract pathogens. Diagn Microbiol Infect Dis 1998; 32: 45–50

    PubMed  CAS  Google Scholar 

  14. Biedenbach DJ, Jones RN. The comparative antimicrobial activity of levofloxacin tested against 350 clinical isolates of streptococci. Diagn Microbiol Infect Dis 1996; 25: 47–51

    PubMed  CAS  Google Scholar 

  15. Kirby JT, Mutnick AH, Jones RN, et al. Geographic variations in garenoxacin (BMS284756) activity tested against pathogens associated with skin and soft tissue infections: report from the SENTRY Antimicrobial Surveillance Program (2000). Diagn Microbiol Infect Dis 2002 Aug; 43(4): 303–9

    PubMed  CAS  Google Scholar 

  16. Deshpande LM, Diekema DJ, Jones RN. Comparative activity of clinafloxacin and nine other compounds tested against 2000 contemporary clinical isolates from patients in United States hospitals. Diagn Microbiol Infect Dis 1999; 35: 81–8

    PubMed  CAS  Google Scholar 

  17. Zhanel GG, Palatnick L, Nichol KA, et al. Antimicrobial resistance in respiratory tract Streptococcus pneumoniae isolates: results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002. Antimicrob Agents Chemother 2003 Jun; 47(6): 1867–74

    PubMed  CAS  Google Scholar 

  18. Hoban D, Waites K, Felmingham D. Antimicrobial susceptibility of community-acquired respiratory tract pathogens in North America in 1999–2000: findings of the PROTEKT Surveillance Study. Diagn Microbiol Infect Dis 2003 Apr; 45(4): 251–9

    PubMed  CAS  Google Scholar 

  19. Gordon KA, Beach ML, Biedenbach DJ. Antimicrobial susceptibility patterns of β-hemolytic and viridans group streptococci: report from the SENTRY Antimicrobial Surveillance Program (1997–2000). Diagn Microbiol Infect Dis 2002 Jun; 43(2): 157–62

    PubMed  CAS  Google Scholar 

  20. Zhanel GG, Palatnick L, Nichol KA, et al. Antimicrobial resistance in Haemophilus influenzae and Moraxella catar-rhalis respiratory tract isolates: results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002. Antimicrob Agent Chemother 2003; 47(6): 1875–81

    CAS  Google Scholar 

  21. Karlowsky JA, Kelly LJ, Thornsberrry C, et al. Susceptibility to fluoroquinolones among commonly isolated Gram-negative bacilli in 2000: TRUST and TSN data for the United States. Tracking Resistance in the United States Today. The Surveillance Network. Int J Antimicrob Agents 2002; 19(1): 21–31

    PubMed  CAS  Google Scholar 

  22. Burgess DS, Nathisuwan S. Cefepime, piperacillin/tazobactam, gentamicin, ciprofloxacin, and levofloxacin alone and in combination against Pseudomonas aeruginosa. Diagn Microbiol Infect Dis 2002 Sep; 44(1): 35–41

    PubMed  CAS  Google Scholar 

  23. Visalli MA, Jacobs MR, Appelbaum PC. Determination of activities of levofloxacin, alone and combined with gentamicin, ceftazidime, cefpirome, and meropenem, against 124 strains of Pseudomonas aeruginosa by checkerboard and time-kill methodology. Antimicrob Agents Chemother 1998; 42: 953–5

    PubMed  CAS  Google Scholar 

  24. Fish DN, Choi MK, Jung R. Synergic activity of cephalosporins plus fluoroquinolones against Pseudomonas aeruginosa with resistance to one or both drugs. J Antimicrob Chemother 2002 Dec; 50(6): 1045–9

    PubMed  CAS  Google Scholar 

  25. Howard W, Biedenbach DJ, Jones RN. Comparative antimicrobial spectrum and activity of the desfluoroquinolone BMS284756 (T-3811) tested against non-fermentative Gram-negative bacilli. Clin Microbiol Infect 2002 Jun; 8(6): 340–4

    PubMed  CAS  Google Scholar 

  26. Zhanel GG, Palatnick L, Smith H, et al. ABT-492 demonstrates potent activity against Canadian lower respiratory tract infection pathogens isolated in 2001–2002 [abstract plus poster]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego, 185

  27. Hoban DJ, Biedenbach DJ, Mutnick AH, et al. Pathogen occurrence and susceptibility patterns associated with pneumonia in hospitalized patients in North America: results of the SENTRY Antimicrobial Surveillance Study (2000). Diagn Microbiol Infect Dis 2003 Apr; 45(4): 279–85

    PubMed  CAS  Google Scholar 

  28. Jones RN, Pfaller MA. In vitro activity of newer fluoroquinolones for respiratory tract infections and emerging patterns of antimicrobial resistance: data from the SENTRY Antimicrobial Surveillance Program. Clin Infect Dis 2000; 31 Suppl. 2: S16–23

    PubMed  CAS  Google Scholar 

  29. Thornsberry C, Karlowsky JA, Weaver MK, et al. Current view of antimicrobial susceptibility among common gram-negative pathogens: 2003 TRUST surveillance data [abstract 222 plus poster]. 41st Annual Meeting of IDSA; 2003 Oct 9–12; San Diego

  30. Thornsberry C, Sahm DF, Weaver MK, et al. Antimicrobial susceptibilities of common pathogens causing nosocomial pneumonia: 2001–2003 TRUST surveillance. 43rd Inter-science Conference on Antimicrobial Agents and Chemotherapy; 2003 Sep 14–17; Chicago

  31. Appelbaum PC. Quinolone activity against anaerobes. Drugs 1999; 58 Suppl.: 60–4

    PubMed  CAS  Google Scholar 

  32. Wexler HM, Molitoris E, Molitoris D, et al. In vitro activity of levofloxacin against a selected group of anaerobic bacteria isolated from skin and soft tissue infections. Antimicrob Agents Chemother 1998; 42: 984–6

    PubMed  CAS  Google Scholar 

  33. Goldstein EJ, Citron DM, Hudspeth M, et al. Trovafloxacin compared with levofloxacin, ofloxacin, ciprofloxacin, azithro-mycin and clarithromycin against unusual aerobic and anaerobic human and animal bite-wound pathogens. J Antimicrob Chemother 1998; 41: 391–6

    PubMed  CAS  Google Scholar 

  34. Credite KL, Jacobs MR, Appelbaum PC. Time-kill studies of the antianaerobe activity of garenoxacin compared with those of nine other agents. Antimicrob Agents Chemother 2003 Apr; 47(4): 1399–402

    Google Scholar 

  35. Hoellman DB, Kelly LM, Jacobs MR. Comparative antianaerobic activity of BMS 284756. Antimicrob Agents Chemother 2001; 45(2): 589–92

    PubMed  CAS  Google Scholar 

  36. Zhanel GG, Laing NM, Decorby M, et al. Pharmacodynamic (PD) activity of fluoroquinolones (FQ) in a mixed infection simulating an artificial bowel: effect of eradicating Bacteroides fragilis [poster no. A145]. 103rd American Society for Microbiology General Meeting; 2002 May 19–23; Salt Lake City

  37. Horn R, Lavallée J, Robson HG. Susceptibility of the Bacteroides fragilis group to garenoxacin (BMS284756), other quinolones and standard antianaerobic agents [abstract no. E-60 plus poster 60]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego

  38. Wilcox MH, Fawley W, Freeman J, et al. In vitro activity of new generation fluoroquinolones against genotypically distinct and indistinguishable Clostridium difficile isolates. J Antimicrob Agents Chemother 2000; 46: 551–5

    CAS  Google Scholar 

  39. Donskey CJ, Chowdhry TK, Hecker MT, et al. Effect of antibiotic therapy on the density of vancomycin resistant enterococci in the stool of colonized patients. N Engl J Med 2000; 343(26): 1925–32

    PubMed  CAS  Google Scholar 

  40. Miller M, Cohen E, Consolacion N, et al. Control of hyperendemic nosocomial C. difficile-associated diarrhea by substitution of cephalosporins with ticar/clav & fluoroquinolones in the hospital formulary [abstract no. K-1369 plus poster]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego

  41. Rao GG, Mahankali Rao CS, Starke I. Clostridium difficile-associated diarrhoea in patients with community-acquired lower respiratory infection being treated with levofloxacin compared with β-lactam-based therapy. J Antimicrob Chemother 2003; 51: 697–701

    CAS  Google Scholar 

  42. Hammerschlag MR, Qumei KK, Roblin PM. In vitro activities of azithromycin, clarithromycin, L-ofloxacin, and other antibiotics against Chlamydia pneumoniae. Antimicrob Agents Chemother 1992; 36(7): 1573–4

    PubMed  CAS  Google Scholar 

  43. Critchley IA, Jones ME, Heinze PD, et al. In vitro activity of levofloxacin against contemporary clinical isolates of Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae from North America and Europe. Clin Microbiol Infect 2002 Apr; 8(4): 214–21

    PubMed  CAS  Google Scholar 

  44. Waites KB, Crabb DM, Bing X, et al. In vitro susceptibilities to and bactericidal activities of garenoxacin (BMS-284756) and other antimicrobial agents against human mycoplasmas and ureaplasmas. Antimicrob Agents Chemother 2003 Jan; 47(1): 161–5

    PubMed  CAS  Google Scholar 

  45. Roblin PM, Hammerschlag MR. In Vitro Activity of a New Antibiotic, NVP-PDF386 (VRC4887), against Chlamydia pneumoniae. Antimicrob Agents Chemother 2003 Apr; 47(4): 1447–8

    PubMed  CAS  Google Scholar 

  46. Piddock LJV. Mechanisms of fluoroquinolone resistance: an update 1994–1998. Drugs 1999; 58 Suppl. 2: 11–8

    PubMed  CAS  Google Scholar 

  47. Thornsberry C, Sahm DF, Kelly LJ, et al. Regional trends in antimicrobial resistance among clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella cat-arrhalis in the United States: results from the TRUST Surveillance Program, 1999–2000. Clin Infect Dis 2002; 34 Suppl. 1: S4–16

    PubMed  Google Scholar 

  48. Karlowsky JA, Jones ME, Thornsberry C, et al. Trends in antimicrobial susceptibilities among Enterobacteriaceae isolated from hospitalized patients in the United States from 1998 to 2001. Antimicrob Agents Chemother 2003 May; 47(5): 1672–80

    PubMed  CAS  Google Scholar 

  49. Felmingham D, Reinert RR, Hirakata Y, et al. Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and compatative in vitro activity of the ketolide, telithromycin. J Antimicrob Chemother 2002 Sep; 50 Suppl. S1: 25–37

    PubMed  CAS  Google Scholar 

  50. Karlowsky JA, Thornsberry C, Jones ME, et al. Factors associated with relative rates of antimicrobial resistance among Streptococcus pneumoniae in the United States: results from the TRUST Surveillance Program (1998–2002). Clin Infect Dis 2003 Apr 15; 36(8): 963–70

    PubMed  Google Scholar 

  51. Ho PL, Yung RWH, Tsang DNC, et al. Increasing resistance of Streptococcus pneumoniae to fluoroquinolones: results of a Hong Kong multicentre study in 2000. J Antimicrob Chemother 2001; 48: 659–65

    PubMed  CAS  Google Scholar 

  52. Chen DK, McGeer A, de Azavedro JC, et al. Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. N Engl J Med 1999; 341: 233–9

    PubMed  CAS  Google Scholar 

  53. Ferraro M, Brown S, Harding I. Prevalence of fluoroquinolone resistance amongst Streptococcus pneumoniae isolated in the United States during the winter of 2000–01 [abstract no. C2-650]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego, 97

  54. Pfaller MA, Jones RN. Gatifloxacin phase IV surveillance trial (TeqCES study) utilizing 5000 primary care physician practices: report of pathogens isolated and susceptibility patterns in community-acquired respiratory tract infections. Diagn Microbiol Infect Dis 2002 Sep; 44(1): 77–84

    PubMed  CAS  Google Scholar 

  55. Sahm DF, Peterson DE, Critchley IA, et al. Analaysis of ciprofloxacin activity against Streptococcus pneumoniae after 10 years of use in the United States. Antimicrob Agents Chemother 2000; 44(9): 2521–4

    PubMed  CAS  Google Scholar 

  56. Smith HJ, Nichol KA, Palatnick L, et al. In vitro activity of ABT-492 against ciprofloxacin-resistant Streptococcus pneumoniae compared to eight other drugs [abstract plus poster]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego, 184

  57. Bozdogan B, Kelly L, Jacobs MR, et al. Activity of DK-507k, a new fluoroquinolone, against quinolone non-susceptible Streptococcus pneumoniae compared to ciprofloxacin, levoflox-acin, moxifloxacin, gatifloxacin, and sitafloxacin [abstract plus poster]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego, 189

  58. Davidson RJ, MacKenzie H, Forward K, et al. Comparative activity of new generation fluoroquinolones against S. pneumoniae with documented topoisomerase IV (parC) and DNA gyrase (gyrA) mutations [abstract no. 825]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco

  59. Bast DJ, De Azavedo JCS, Duncan C, et al. Activity of newer fluoroquinolones against isolates of Streptococcus pneumoniae with increasing resistance to ciprofloxacin [abstract no. 1490]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco, 264

  60. Zhanel GG, Roberts D, Waltky A, et al. Pharmacodynamic activity of fluoroquinolones against ciprofloxacin-resistant Streptococcus pneumoniae. J Antimicrob Chemother 2002; 49: 807–12

    PubMed  CAS  Google Scholar 

  61. Jorgensen JH, Weigel LM, Ferraro MJ, et al. Activities of newer fluoroquinolones against Streptococcus pneumoniae clinical isolates including those with mutations in the gyrA, parC, and parE loci. Antimicrob Agents Chemother 1999; 43: 329–34

    PubMed  CAS  Google Scholar 

  62. Klepser ME, Ernst EJ, Petzold CR, et al. Comparative bactericidal activities of ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin against Streptococcus pneumoniae in a dynamic in vitro model. Antimicrob Agents Chemother 2001; 45(3): 673–8

    PubMed  CAS  Google Scholar 

  63. Drageon HB, Juvin ME, Bryskier A. Relative potential for selection of fluoroquinolone-resistant Streptococcus pneumoniae strains by levofloxacin: comparison with ciprofloxacin, sparfloxacin and ofloxacin. J Antimicrob Chemother 1999; 43 Suppl. C: 55–9

    Google Scholar 

  64. Fukuda H, Hiramatsu K. Primary targets of fluoroquinolones in Streptococcus pneumoniae. Antimicrob Agents Chemother 1999; 43: 410–2

    PubMed  CAS  Google Scholar 

  65. Davies TA, Pankuch GA, Dewasse BE, et al. In vitro development of resistance to five quinolones and amoxicillinclavu-lanate in Streptococcus pneumoniae. Antimicrob Agents Chemother 1999; 43: 1177–82

    PubMed  CAS  Google Scholar 

  66. Kelly, LA, Thornsberry C, Jones ME, et al. Multidrag-resistant pneumococci isolated in the US: 1997–2001 TRUST Surveillance [abstract no. C2-2109]. Proceeedings of the 41st Inter-science Conference on Antimicrobial Agents and Chemotherapy; 2001 Dec 16–19; Chicago, 142

  67. Sahm, DF, Thornsberry C, Jones ME, et al. Antimicrobial susceptibility of Enterobacteriaceae and Pseudomonas aeruginosa from inpatient infections in the U.S.: 1999–2002 TRUST surveillance [abstract plus poster]. Annual Meeting Society for Critical Care Medicine (SCCM); 2003 Jan 30; San Antonio (TX)

  68. Karlowsky JA, Draghi DC, Jones ME, et al. Surveillance for antimicrobial susceptibility among clinical isolates of Pseudomonas aeruginosa and Acinetobacter baumannii from hospitalized patients in the United States, 1998 to 2001. Antimicrob Agents Chemother 2003 May; 47(5): 1681–8

    PubMed  CAS  Google Scholar 

  69. Preston SL, Drasano GL, Berman AL, et al. Pharmacodynamics of levofloxacin: a new paradigm for early clinical trials. JAMA 1998; 279(2): 125–9

    PubMed  CAS  Google Scholar 

  70. Forrest A, Nix DE, Ballow CH, et al. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother 1993; 37(5): 1073–81

    PubMed  CAS  Google Scholar 

  71. Nightingale CH, Grant EM, Quintiliani R. Pharmacodynamics and pharmacokinetics of levofloxacin. Chemotherapy 2000; 46 Suppl. 1: 6–14

    PubMed  CAS  Google Scholar 

  72. Ibrahim KH, Hovde LB, Ross G, et al. Microbiologic effectiveness of time- or concentration-based dosing strategies in Streptococcus pneumoniae. Diagn Microbiol Infect Dis 2002 Nov; 44(3): 265–71

    PubMed  CAS  Google Scholar 

  73. Lister PD. Pharmacodynamics of 750 mg and 500 mg doses of levofloxacin against ciprofloxacin-resistant strains of Streptococcus pneumoniae. Diagn Microbiol Infect Dis 2002 Sep; 44(1): 43–9

    PubMed  CAS  Google Scholar 

  74. Drusano GL, Preston SL, Corrado M, et al. Target attainment analysis for levofloxacin (L) 750mg IV daily for nosocomial pneumonia using Monte Carlo simulation for common Gram-negative pathogens [abstract no. A-638]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego

  75. Preston SL, Drusano GL, Corrado M, et al. Pharmacodynamic analysis of levofloxacin (L) 750 mg IV daily for nosocomial pneumonia [abstract plus poster]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego

  76. West M, Boulanger BR, Fogarty C, et al. Levofloxacin compared with imipenem/cilastatin followed by ciprofloxacin in adult patients with nosocomial pneumonia: a multicenter, prospective, randomized, open-label study. Clin Ther 2003; 25(2): 485–506

    PubMed  CAS  Google Scholar 

  77. Preston SL, Redell M, Chien SC, et al. Evaluation of the target attainment rate of levofloxacin and ciprofloxacin for intensive care unit patients. Proceedings of the 10th International Congress on Infectious Diseases; 2002 Mar 11–14; Singapore

  78. Pankuch GA, Jacobs MR, Appelbaum PC. Antipneumococcal activity of grepafloxacin compared to that of other agents by time-kill methodology. Antimicrob Agents Chemother 1998; 42(5): 1263–5

    PubMed  CAS  Google Scholar 

  79. Fuchs PC, Barry AL, Brown SD. Streptococcus pneumoniae killing rate and post-antibiotic effect of levofloxacin and ciprofloxacin. J Chemother 1997; 9(6): 391–3

    PubMed  CAS  Google Scholar 

  80. Pendland SL, Diaz-Linares M, Garey KW, et al. Bactericidal activity and postantibiotic effect of levofloxacin against anaerobes. Antimicrob Agents Chemother 1999; 43: 2547–9

    PubMed  CAS  Google Scholar 

  81. Spangler SK, Lin G, Jacobs MR, et al. Postantibiotic effect of levofloxacin against pneumococci. Drugs 1999; 58 Suppl. 2: 378–80

    CAS  Google Scholar 

  82. Credito KL, Clark CL, Jacobs MR, et al. Post-antibiotic effect (PAE) of gemifloxacin (SB 265805) compared with five other quinolones against pneumococci [abstract no. 537]. 39th Inter-science Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco, 21

  83. Spangler SK, Bajaksouzian S, Jacobs MR, et al. Postantibiotic effects of grepafloxacin compared to those of five agents against 12 Gram-positive and -negative bacteria. Antimicrob Agents Chemother 2000; 44: 186

    PubMed  CAS  Google Scholar 

  84. Smith RP, Baltch AL, Ritz W, et al. Postantibiotic effect (PAE) measurement for levofloxacin and four other antibiotics against Legionella pneumophila, using mathematical modeling of the growth curve [abstract no. A109]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24–27; San Diego, 34

  85. Chien S-C, Rogge MC, Gilscon LG, et al. Pharmacokinetic profile of levofloxacin following once-daily 500-milligram oral or intravenous doses. Antimicrob Agents Chemother 1997; 41(10): 2256–60

    PubMed  CAS  Google Scholar 

  86. Lubasch A, Keller I, Borner K, et al. Comparative pharmacokinetics of ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, trovafloxacin, and moxifloxacin after single oral administration in healthy volunteers. Antimicrob Agents Chemother 2000; 44: 2600–3

    PubMed  CAS  Google Scholar 

  87. Chien S-C, Wong FA, Fowler CL, et al. Double-blind evaluation of the safety and pharmacokinetics of multiple oral once-daily 750-milligram and 1-gram doses of levofloxacin in healthy volunteers. Antimicrob Agents Chemother 1998; 42: 885–8

    PubMed  CAS  Google Scholar 

  88. Chow AT, Fowler C, Williams RR, et al. Safety and pharmacokinetics of multiple 750-milligram doses of intravenous levofloxacin in healthy volunteers. Antimicrob Agents Chemother 2001; 45(7): 2122–5

    PubMed  CAS  Google Scholar 

  89. Amsden GW, Graci DM, Cabelus LJ, et al. A randomized, crossover design study of the pharmacology of extended-spectrum fluoroquinolones for pneumococcal infections. Chest 1999; 116: 115–9

    PubMed  CAS  Google Scholar 

  90. Noel GJ, Abels R, Minton N, et al. Effects of three fluoroquinolones (FQs) on QTc intervals in healthy volunteers [abstract]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Dec 16–19; Chicago, 639a

  91. Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet 1997; 32(2): 101–19

    PubMed  CAS  Google Scholar 

  92. Lee L-J, Hafkin B, Lee I-D, et al. Effect of food and sucralfate on levofloxacin after a single oral dose of 500 mg in male and female subjects. American Society for Microbiology [abstract no. A40]. 35th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1995 Sep 17–20; San Francisco, 8

  93. Langtry HD, Lamb HM. Levofloxacin: its use in infections of the respiratory tract, skin, soft tissues and urinary tract. Drugs 1998; 56(3): 487–515

    PubMed  CAS  Google Scholar 

  94. Taira K, Koga H, Kohno S. Accumulation of a newly developed fluoroquinolone, OPC-17116, by human polymorphonuclear leukocytes. Antimicrob Agents Chemother 1993; 37: 1877–81

    PubMed  CAS  Google Scholar 

  95. Gaja M, Higa F, Yamashiro T, et al. Penetration of levofloxacin, a new quinolone antibacterial agent, into human neutrophils. Chemotherapy 1992; 40: 64–7

    CAS  Google Scholar 

  96. Smith RP, Baltch AL, Franke MA, et al. Levofloxacin penetrates human monocytes and enhances intracellular killing of Staphylococcus aureus and Pseudomonas aeruginosa. J Antimicrob Chemother 2000; 45: 483–8

    PubMed  CAS  Google Scholar 

  97. Chow AT, Chen A, Lattime H, et al. Penetration of levofloxacin into skin tissue after oral administration of 750 mg once-daily doses. J Clin Pharm Ther 2002; 27: 143–50

    PubMed  CAS  Google Scholar 

  98. Gotfried MH, Danziger LH, Rodvold KA. Steady-state plasma and intrapulmonary concentrations of levofloxacin and ciprofloxacin in healthy adult subjects. Chest 2001; 119: 1114–22

    PubMed  CAS  Google Scholar 

  99. Rodvold KA, Danziger LH, Gotfried MH. Steady-state plasma and bronchopulmonary concentrations of intravenous levofloxacin and azithromycin in healthy adults. Antimicrob Agents Chemother 2003 Aug; 47(8): 2450–7

    PubMed  CAS  Google Scholar 

  100. Drusano GL, Preston SL, Gotfried MH, et al. Levofloxacin penetration into epithelial lining fluid as determined by population pharmacokinetic modeling and Monte Carlo simulation. Antimicrob Agents Chemother 2002; 46(2): 586–9

    PubMed  CAS  Google Scholar 

  101. Drusano GL, Preston SL, Gotfried MH, et al. The penetration of 750 mg of levofloxacin administered intravenously into the epithelial lining fluid (ELF). Proceedings of the 10th International Congress on Infectious Diseases; 2002 Mar 11–14; Singapore

  102. Kahn JB, Wiesinger BA, North D, et al. The penetration of levofloxacin (LVFX) into the prostate [abstract no. 250]. Clin Infect Dis 1998; 27: 967

    Google Scholar 

  103. Yamashita M, Sawada K, Chokyu H, et al. Prostatic tissue levels of levofloxacin [in Japanese]. Chemotherapy 1992; 40 Suppl. 3: 203–9

    Google Scholar 

  104. Drusano GL, Preston SL, Van Guilder M, et al. A population pharmacokinetic analysis of the penetration of the prostate by levofloxacin. Antimicrob Agents Chemother 2000; 44: 2046–51

    PubMed  CAS  Google Scholar 

  105. Rodvold KA, Danziger LH, Gotfried MH, et al. Steady-state plasma and bronchopulmonary concentrations of intravenous levofloxacin and azithromycin in healthy adult subjects. Antimicrob Agents Chemother 2003 Aug; 47(8): 2450–7

    PubMed  CAS  Google Scholar 

  106. Nagai H, Yamasaki T, Masuda M, et al. Penetration of levofloxacin into bronchoalveolar lavage fluid. Drugs 1993; 45 Suppl. 3: 259

    Google Scholar 

  107. Nakamori Y, Tsuboi E, Narui K, et al. Sputum penetration of levofloxacin and its clinical efficacy in patients with chronic lower respiratory tract infections [in Japanese]. Jpn J Antibiot 1992; 45: 539–47

    PubMed  CAS  Google Scholar 

  108. Okazaki O, Kojima C, Hakusui H, et al. Enantioselective disposition of ofloxacin in humans. Antimicrob Agents Chemother 1991; 35(10): 2106–9

    PubMed  CAS  Google Scholar 

  109. Gisclon LG, Curtin CR, Chien SC, et al. The pharmacokinetics (PK) of levofloxacin (LVFX) in subjects with renal impairment, and in subjects receiving hemodialysis or continuous ambulatory peritoneal dialysis [abstract no. A13]. 36th Inter-science Conference on Antimicrobial Agents and Chemotherapy; 1996 Sep 15–18; New Orleans

  110. Sowinski KM, Lucksiri A, Kays MB, et al. Levofloxacin pharmacokinetics in ESRD and removal by the cellulose acetate high performance-210 hemodialyzer. Am J Kidney Dis 2003 Aug; 42(2): 342–9

    PubMed  CAS  Google Scholar 

  111. Kees F, Hansen E, Bucher M, et al. Pharmacokinetics of levofloxacin in patients during continuous venovenous hemofiltration. Antiinfect Drugs Chemother 2000; 17(1): 77

    Google Scholar 

  112. Traunmüller F, Thalhammer-Scherrer R, Locker G, et al. Single-dose pharmacokinetics of levofloxacin during continuous venovenous hemofiltration (CVVH) [abstract no. MoP247]. Clin Microbiol Infect 2000; 6 Suppl. 1: 203

    Google Scholar 

  113. Malone RS, Fish DN, Abraham E, et al. Pharmacokinetics of levofloxacin and ciprofloxacin during continuous renal replacement therapy in clinically ill patients. Antimicrob Agents Chemother 2001; 45(10): 2949–54

    PubMed  CAS  Google Scholar 

  114. Rogge MC, Chien S-C, Holland ML. Single-dose pharmacokinetics of levofloxacin: influence of age and gender [abstract]. 5th International Symposium on New Quinolones; 1994 Aug; Singapore

  115. Goodwin SD, Gallis HA, Chow AT, et al. Pharmacokinetics and safety of levofloxacin in patients with human immunodeficiency virus infection. Antimicrob Agents Chemother 1994; 38(4): 799–804

    PubMed  CAS  Google Scholar 

  116. Chien SC, Chow AT, Rogge MC, et al. Pharmacokinetics and safety of oral levofloxacin in human immunodeficiency virus-infected individuals receiving concomitant zidovudine. Antimicrob Agents Chemother 1997; 41(8): 1765–9

    PubMed  CAS  Google Scholar 

  117. Piscitelli SC, Spooner K, Baird B, et al. Pharmacokinetics and safety of high-dose and extended-interval regimens of levofloxacin in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 1999; 43(9): 2323–7

    PubMed  CAS  Google Scholar 

  118. Preston SL, Drusano GL, Berman AL, et al. Levofloxacin population pharmacokinetics and creation of a demographic model for prediction of individual drug clearance in patients with serious community-acquired infection. Antimicrob Agents Chemother 1998; 42(5): 1098–104

    PubMed  CAS  Google Scholar 

  119. Rebuck JA, Fish DN, Abraham E. Pharmacokinetics of intravenous and oral levofloxacin in critically ill adults in a medical intensive care unit. Pharmacotherapy 2002 Oct; 22(10): 1216–25

    PubMed  CAS  Google Scholar 

  120. Shiba K, Sakai O, Shimada J, et al. Effects of antacids, ferrous sulfate, and ranitidine on absorption of DR-3355 in humans. Antimicrob Agents Chemother 1992; 36(10): 2270–4

    PubMed  CAS  Google Scholar 

  121. Okimoto N, Niki YSR. Effect of levofloxacin on serum concentration of theophylline. Chemotherapy 1992; 40 Suppl. 3: 68–74

    CAS  Google Scholar 

  122. Gisclon LG, Curtin CR, Fowler CL, et al. Absence of a pharmacokinetic interaction between intravenous theophylline and orally administered levofloxacin [abstract no. A39]. 35th Inter-science Conference on Antimicrobial Agents and Chemotherapy; 1995 Sep 17–20; San Francisco

  123. Nakamura H, Ohtsuka T, Enomoto H, et al. Effect of levofloxacin on theophylline clearance during theophylline and clari-thromycin combination therapy. Ann Pharmacother 2001; 35: 691–3

    PubMed  CAS  Google Scholar 

  124. Liao S, Palmer M, Fowler CA, et al. Absence of an effect of levofloxacin on warfarin pharmacokinetics and anticoagulation in male volunteers [abstract no. A42]. 35th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1995 Sep 17–20; San Francisco, 8

  125. Gheno G, Cinetto L. Levofloxacin-warfarin interaction [letter]. Eur J Clin Pharmacol 2001; 57: 427

    PubMed  CAS  Google Scholar 

  126. Jones CB, Fugate SE. Levofloxacin and warfarin interaction. Ann Pharmacother 2002 Oct; 36(10): 1554–7

    PubMed  Google Scholar 

  127. Yamreudeewong W, Lower DL, Kilpatrick DM, et al. Effect of levofloxacin coadministration on the international normalized ratios during warfarin therapy. Pharmacotherapy 2003 Mar; 23(3): 333–8

    PubMed  CAS  Google Scholar 

  128. Gaitonde MD, Mendes P, House ESA, et al. The effects of cimetidine and probenecid on the pharmacokinetics of levofloxacin (LVFX) [abstract no. A41]. 35th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1995 Sep 17–20; San Francisco, 8

  129. Capone D, Carrano R, Gentile A, et al. Pharmacokinetic interaction between tacrolimus and levofloxacin in kidney transplant recipients [abstract]. Nephrol Dial Transplant 2001; 16(6): A207

    Google Scholar 

  130. Chien S-C, Rogge MC, Williams RR, et al. Absence of a pharmacokinetic interaction between digoxin and levofloxacin. J Clin Pharm Ther 2002; 27: 7–12

    PubMed  CAS  Google Scholar 

  131. Villani P, Viale P, Signorini L, et al. Pharmacokinetic evaluation of oral levofloxacin in human immunodeficiency virus-infected subjects receiving concomitant antiretroviral therapy. Antimicrob Agents Chemother 2001; 45(7): 2160–2

    PubMed  CAS  Google Scholar 

  132. Hautamaki D, Kureishi A, Warner J, et al. Five day moxiflox-acin compared to 7 day levofloxacin therapy in the treatment of acute exacerbations of chronic bronchitis (AECB) [abstract]. Am J Respir Crit Care Med 2001; 163(5): A771

    Google Scholar 

  133. Kahn JB, Wiesenger BA, Olson WH, et al. Levofloxacin vs. ceftriaxone sodium and erythromycin in the treatment of patients with community-acquired pneumonia at high risk of mortality [poster]. Proceedings of the 7th International Symposium of New Quinolones; 2001 Jun 10–12; Edinburgh, 115

  134. Tennenberg AM, Khashab MM, Wiesenger BA, et al. Prospective evaluation of levofloxacin in a study of community acquired Legionnaires’ disease. American Thoracic Society (ATS) Meeting 2003; May 16–18; Seattle (WA)

  135. Lode H, Mauch H, Schafer V, et al. Influence of levofloxacin compared with clarithromycin on the infection-free interval in patients with chronic bronchitis [abstract no. P1122]. 13th European Congress of Clinical Microbiology and Infectious Diseases; 2003 May 10–13; Glasgow

  136. Dunbar LM, Wunderink RG, Habib MP, et al. High-dose, short-course levofloxacin for community-acquired pneumonia: a new treatment paradigm. Clin Infect Dis 2003; 37: 761–3

    Google Scholar 

  137. Ortho-McNeil Pharmaceutical Inc. Levaquin receives FDA approval for five-day treatment of community-acquired pneumonia [online]. Available from URL: http://www.orthomcneil.com/news [Accessed 2003 Oct 29]

  138. Ortho-McNeil Pharmaceutical Inc. Nosocomial pneumonia indication approved for LEVAQUIN(R) [media release]. 2002

  139. Kahn JB, Oross MP, Wu S-C, et al. Levofloxacin in the treatment of pneumonia due to Pseudomonas aeruginosa. Chest 2002 Oct; 122 Suppl.: 164 plus poster presented at Chest 2002 Nov 2–7; San Diego

    Google Scholar 

  140. Carbon C, Ariza H, Rabie WJ, et al. Comparative study of levofloxacin and amoxycillin/clavulanic acid in adults with mild-to-moderate community-acquired pneumonia. Clin Microbiol Infect 1999; 5(12): 724–32

    CAS  Google Scholar 

  141. Gotfried MH, Dattani D, Riffer E, et al. A controlled, double-blind, multicenter study comparing clarithromycin extended-release tablets with levofloxacin tablets in the treatment of community-acquired pneumonia. Clin Ther 2002; 24: 736–51

    PubMed  CAS  Google Scholar 

  142. File Jr TM, Segreti J, Dunbar L, et al. A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with community-acquired pneumonia. Antimicrob Agents Chemother 1997; 41(9): 1965–72

    PubMed  CAS  Google Scholar 

  143. Frank E, Liu J, Kinasewitz G, et al. A multicenter, open-label, randomized comparison of levofloxacin and azithromycin plus ceftriaxone in hospitalized adults with moderate to severe community-acquired pneumonia. Clin Ther 2002 Aug; 24(8): 1292–308

    PubMed  CAS  Google Scholar 

  144. Sullivan JG, McElroy AD, Honsinger RW, et al. A double-blind, randomized study of safety and efficacy: treating community-acquired pneumonia with once-daily gatifloxacin vs once-daily levofloxacin. J Respir Dis 1999; 20(11): S49–59

    Google Scholar 

  145. Wiesinger BA, Kahn JB, Williams RR, et al. Efficacy of levofloxacin in the treatment of community-acquired pneumonia due to penicillin- and macrolide-resistant Streptococcus pneumoniae [abstract no. P404]. J Antimicrob Chemother 1999; 44 Suppl. A: 130

    Google Scholar 

  146. Kahn JB, Wiesenger BA, Drucker LM, et al. Cumulative clinical trial experience with levofloxacin in pneumococcal bacteremia [abstract no. 8.21 plus poster]. 6th International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones (ICAMS-KO-6); 2002 Jan 23–26; Bologna

  147. Fogarty CM, Greenberg RN, Dunbar L, et al. Effectiveness of levofloxacin for adult community-acquired pneumonia caused by macrolide-resistant Streptococcus pneumoniae: integrated results from four open-label, multicenter, phase III clinical trials. Clin Therapeutics 2001; 23(3): 425–39

    CAS  Google Scholar 

  148. Davidson R, Cavalcanti R, Brunton JL, et al. Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N Engl J Med 2002; 346(10): 747–50

    PubMed  Google Scholar 

  149. Urban C, Rahman N, Zhao X, et al. Fluoroquinolone-resistant Streptococcus pneumoniae associated with levofloxacin therapy. J Infect Dis 2001; 184: 794–8

    PubMed  CAS  Google Scholar 

  150. Anderson KB, Tan JS, File TMJr, et al. Emergence of levoflox-acin-resistant pneumococci in immunocompromised adults after therapy for community-acquired pneumonia. Clin Infect Dis 2003 Aug 1; 37(3): 376–81

    PubMed  Google Scholar 

  151. Rittenhouse BE, Stinnett AA, Dulisse B, et al. Evaluating the costs of levofloxacin and ceftriaxone in inpatient adults with community-acquired pneumonia. Pharmacol Ther 1999; 24(4): 169–79

    Google Scholar 

  152. Rittenhouse BE, Stinnett AA, Dulisse B, et al. An economic evaluation of levofloxacin versus cefuroxime axetil in the outpatient treatment of adults with community-acquired pneumonia. Am J Manag Care 2000; 6(3): 381–9

    PubMed  CAS  Google Scholar 

  153. Rai S, Farag B, Mifune Y, et al. Levofloxacin vs. ceftriaxone/ azithromycin in the treatment of community-acquired pneumonia: a length of stay comparison [abstract no. P1123]. 13th European Congress of Clinical Microbiology and Infectious Diseases; 2003 May 10–13; Glasgow

  154. Richerson MA, Ambrose PG, Quintiliani R, et al. Pharmacoeconomic evaluation of alternative antibiotic regimens in hospitalized patients with community-acquired pneumonia. Infect Dis Clin Pract 1998; 7(5): 227–33

    Google Scholar 

  155. Palmer CS, Zhan C, Elixhauser A, et al. Economic assessment of the community-acquired pneumonia intervention trial employing levofloxacin. Clin Ther 2000; 22(2): 250–64

    PubMed  CAS  Google Scholar 

  156. Habib MP, Gentry LO, Rodriguez-Gomez G, et al. Multicenter, randomized study comparing efficacy and safety of oral levofloxacin and cefaclor in treatment of acute bacterial exacerbations of chronic bronchitis. Infect Dis Clin Pract 1998; 7(2): 101–9

    Google Scholar 

  157. Amsden GW, Baird IM, Simon S, et al. Efficacy and safety of azithromycin vs levofloxacin in the outpatient treatment of acute bacterial exacerbations of chronic bronchitis. Chest 2003 Mar; 123(3): 772–7

    PubMed  CAS  Google Scholar 

  158. Davies BI, Maesen FP. Clinical effectiveness of levofloxacin in patients with acute purulent exacerbations of chronic bronchitis: the relationship with in-vitro activity. J Antimicrob Chemother 1999; 43 Suppl. C: 83–90

    PubMed  CAS  Google Scholar 

  159. Shah PM, Maesen FP, Dolmann A, et al. Levofloxacin versus cefuroxime axetil in the treatment of acute exacerbation of chronic bronchitis: results of a randomized, double-blind study. J Antimicrob Chemother 1999; 43: 529–39

    PubMed  CAS  Google Scholar 

  160. Masterton RG, Burley CJ. Randomized, double-blind study comparing 5- and 7-day regimens of oral levofloxacin in patients with acute exacerbation of chronic bronchitis. Int J Antimicrob Agents 2001; 18: 503–12

    PubMed  CAS  Google Scholar 

  161. Adelglass J, DeAbate CA, McElvaine P, et al. Comparison of the effectiveness of levofloxacin and amoxicillin-clavulanate for the treatment of acute sinusitis in adults. Otolaryngol Head Neck Surg 1999; 120: 320–7

    PubMed  CAS  Google Scholar 

  162. Adelglass J, Jones TM, Ruoff G, et al. A multicenter, investigator-blinded, randomized comparison of oral levofloxacin and oral clarithromycin in the treatment of acute bacterial sinusitis. Pharmacotherapy 1998; 18(6): 1255–63

    PubMed  CAS  Google Scholar 

  163. Lasko B, Lau CY, Saint-Pierre C, et al. Efficacy and safety of oral levofloxacin compared with clarithromycin in the treatment of acute sinusitis in adults: a multicentre, double-blind, randomized study. Canadian Sinusitis Study Group. J Int Med Res 1998; 26: 281–91

    PubMed  CAS  Google Scholar 

  164. Bundrick W, Heron SP, Ray P. Levofloxacin versus ciprofloxacin in the treatment of chronic bacterial prostatitis: a randomized double-blind multicenter study. Urology 2003; 62(3): 537–41

    PubMed  Google Scholar 

  165. Nickel JC, Downey J, Clark J, et al. Levofloxacin treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men: a randomized placebo controlled multicenter trial [abstract no. 104]. J Urology 2003; 169 Suppl.: 27

    Google Scholar 

  166. Lipsky BA. Prostatitis and urinary tract infection in men: what’s new; what’s true? Am J Med 1999; 106: 327–34

    PubMed  CAS  Google Scholar 

  167. Richard GA, DeAbate CA, Ruoff GE, et al. A double-blind, randomized trial of the efficacy and safety of short-course, once-daily levofloxacin versus ofloxacin twice daily in uncomplicated urinary tract infections. Infect Dis Clin Pract 2000; 9: 323–9

    Google Scholar 

  168. Klimberg IW, Cox II CE, Fowler CL, et al. A controlled trial of levofloxacin and lomefloxacin in the treatment of complicated urinary tract infection. Urology 1998; 51(4): 610–5

    PubMed  CAS  Google Scholar 

  169. Richard GA, Klimberg IN, Fowler CL, et al. Levofloxacin versus ciprofloxacin versus lomefloxacin in acute pyelonephritis. Urology 1998; 52: 51–5

    PubMed  CAS  Google Scholar 

  170. Nichols RL, Smith JW, Gentry LO, et al. Multicenter, randomized] study comparing levofloxacin and ciprofloxacin for uncomplicated skin and skin structure infections. South Med J 1997; 90(12): 1193–200

    PubMed  CAS  Google Scholar 

  171. Nicodemo AC, Robledo JA, Jasovich A, et al. A multicentre, double-blind, randomised study comparing the efficacy and safety of oral levofloxacin versus ciprofloxacin in the treatment of uncomplicated skin and skin structure infections. Int J Clin Pract 1998; 52(2): 69–74

    PubMed  CAS  Google Scholar 

  172. Tarshis GA, Miskin BM, Jones TM, et al. Once-daily oral gatifloxacin versus oral levofloxacin in treatment of uncomplicated skin and soft tissue infections: double-blind, multicenter, randomized study. Antimicrob Agents Chemother 2001; 45(8): 2358–62

    PubMed  CAS  Google Scholar 

  173. Graham DR, Talan DA, Nichols RL, et al. Once-daily, high-dose levofloxacin versus ticarcillin-clavulanate alone or followed by amoxicillin-clavulanate for complicated skin and skin-structure infections: a randomized, open-label trial. Clin Infect Dis 2002 Aug 15; 35(4): 381–9

    PubMed  CAS  Google Scholar 

  174. Wiesenger BA, Noel GJ, Tennenberg AM, et al. The safety of high-dose (750-mg qd) levofloxacin [poster]. Proceedings of the 10th International Congress on Infectious Diseases; 2002 Mar 11–14; Singapore

  175. Lipsky BA, Baker CA. Fluoroquinolone toxicity profiles: a review focusing on newer agents. Clin Infect Dis 1999; 28: 352–64

    PubMed  CAS  Google Scholar 

  176. Boccumini LE, Fowler CL, Campbell TA, et al. Photoreaction potential of orally administered levofloxacin in healthy subjects. Ann Pharmacother 2000; 34: 453–8

    PubMed  CAS  Google Scholar 

  177. Stahlmann R, Lode H. Toxicity of quinolones. Drugs 1999; 58 Suppl. 2: 37–42

    PubMed  CAS  Google Scholar 

  178. Lewis JR, Gums JG, Dickensheets DL. Levofloxacin-induced bilateral Achilles tendonitis. Ann Pharmacother 1999; 33: 792–5

    PubMed  CAS  Google Scholar 

  179. Connelly S, Bayliff C, Mehta S. Levofloxacin-induced bilateral Achilles tendinopathy. Can J Hosp Pharm 2002 Jun; 55: 212–4

    Google Scholar 

  180. Haddow LJ, Chandra Sekhar M, Hajela V, et al. Spontaneous Achilles tendon rupture in patients treated with levofloxacin. J Antimicrob Chemother 2003 Mar; 51(3): 747–8

    PubMed  CAS  Google Scholar 

  181. Kahn JB. Latest industry information on the safety profile of levofloxacin in the US. Chemotherapy 2001; 47 Suppl. 3: 32–7

    PubMed  CAS  Google Scholar 

  182. Harding I, Simpson I. Levofloxacin: low potential for hepato-biliary adverse reactions [abstract no. P851]. Clin Microbiol Infect 2001; 7 Suppl. S1: 164

    Google Scholar 

  183. Schwalm J-D, Lee CH. Acute hepatitis associated with oral levofloxacin therapy in a hemodialysis patient. CMAJ 2003 Apr 1; 168(7): 847–8

    PubMed  Google Scholar 

  184. Menzies DJ, Dorsainvil PA, Cunha BA, et al. Severe and persistent hypoglycemia due to gatifloxacin interaction with oral hypoglycemic agents. Am J Med 2002; 113: 232

    PubMed  Google Scholar 

  185. O’Hare M, Simpson IN. Levofloxacin: low potential for cardiovascular adverse reactions. Clin Microbiol Infect 2001; 7 Suppl. 1: 164–5

    Google Scholar 

  186. Sadek M, Bharadwaj R, Cohen H, et al. The effects of intravenous levofloxacin on the electrocardiographic QT interval. Pharmacotherapy 2002 Oct; 22: 1327–8

    Google Scholar 

  187. Samaha FF. QTC interval prolongation and polymorphic ventricular tachycardia in association with levofloxacin [letter]. Am J Med 1999; 107: 528–9

    PubMed  CAS  Google Scholar 

  188. Frothingham R. Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxi-floxacin. Pharmacotherapy 2001; 21(12): 1468–72

    PubMed  CAS  Google Scholar 

  189. Noel GJ, Natarajan J, Chien S, et al. Effects of three fluoroquinolones on QT interval in healthy adults after single doses. Clin Pharmacol Ther 2003 Apr; 73(4): 292–303

    PubMed  CAS  Google Scholar 

  190. Paltoo B, O’Donoghue S, Moussavi MS. Levofloxacin induced polymorphic ventricular tachycardia with normal QT interval. PACE 2001; 24: 895–7

    PubMed  CAS  Google Scholar 

  191. Weiss LR. Open-label, randomized comparison of the efficacy and tolerability of clarithromycin, levofloxacin, and cefuroxime axetil in the treatment of adults with acute bacterial exacerbations of chronic bronchitis. Clin Ther 2002 Sep; 24(9): 1414–25

    PubMed  CAS  Google Scholar 

  192. Bartlett JG, Dowell SF, Mandell LA, et al. Practice guidelines for the management of community-acquired pneumonia in adults. Clin Infect Dis 2000; 31(2): 347–82

    PubMed  CAS  Google Scholar 

  193. American Thoracic Society. Guidelines for the management of adults with community-acquired pneumonia; diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Resp Crit Care Med 2001; 163: 1730–54

    Google Scholar 

  194. Campbell Jr GD. The role of antimicrobial therapy in acute exacerbations of chronic bronchitis. Am J Med Sci 1999; 318(2): 84–8

    PubMed  Google Scholar 

  195. Craven DE, De Rosa FG, Thornton D. Nosocomial pneumonia: emerging concepts in diagnosis, management, and prophylaxis. Curr Opin Crit Care 2002; 8: 421–9

    PubMed  Google Scholar 

  196. American Thoracic Society. Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventative strategies: a consensus statement. Am J Resp Crit Care Med 1996; 153: 1711–25

    Google Scholar 

  197. Chastre J, Fagon J-Y. Ventilator-associated pneumonia. Am J Respir Crit Care Med 2002; 165: 867–903

    PubMed  Google Scholar 

  198. Beringer PM, Wong-Beringer A, Rho JR. Economic aspects of antibacterial adverse effects. Pharmacoeconomics 1998; 13 (1 Pt 1): 35–49

    Google Scholar 

  199. Schaeffer AJ. The expanding role of fluoroquinolones. Am J Med 2002 Jul 8; 113 Suppl. 1A: 45S–54S

    PubMed  CAS  Google Scholar 

  200. Bjerklund Johansen TE, Grüneberg RN, Guibert J, et al. The role of antibiotics in the treatment of chronic prostatitis: a consensus statement. Eur Urol 1998; 34: 457–66

    PubMed  CAS  Google Scholar 

  201. Bertino Jr J, Fish D. The safety profile of the fluoroquinolones. Clin Ther 2000; 22: 798–817

    PubMed  CAS  Google Scholar 

  202. Bayer Pharmaceuticals Corporation. Avelox (moxifloxacin hydrochloride) tablets; Avelox I.V. (moxifloxacin hydrochloride in sodium chloride injection): prescribing information. West Hacen (CT): Bayer Pharmaceuticals Corporation, 2003 Mar

    Google Scholar 

  203. Bristol-Myers Squibb Company. Tequin (gatifloxacin) tablets; injection: prescribing information. Princeton (NJ): Bristol-Myers Squibb Company, 2002 Dec

    Google Scholar 

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Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 1311, New Zealand

    Katherine F. Croom & Karen L. Goa

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  1. Katherine F. Croom
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  2. Karen L. Goa
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Correspondence to Katherine F. Croom.

Additional information

Various sections of the manuscript reviewed by: J.M. Blondeau, Department of Clinical Microbiology, Royal University Hospital, Saskatoon, Saskatchewan, Canada; D.N. Fish, Department of Pharmacy Practice, Colorado Health Sciences Center, Denver, Colorado, USA; D.R.P. Guay, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA; M.P. Habib, Pulmonary Section, Veterans Affairs Medical Center, Tucson, Arizona, USA; P.B. Iannini, Department of Medicine, Danbury Hospital, Danbury, Connecticut, USA; S.L. Preston, Clinical Pharmacology Studies Unit, Albany Medical College, Albany, New York, USA; J.A. Ramirez, Department of Medicine, University of Louisville, Louisville, Kentucky, USA; K.A. Rodvold, Department of Pharmacy Practice, University of Illinois, Chicago, Illinois, USA.

Data Selection

Sources: Medical literature published in any language since 1998 on levofloxacin, identified using Medline and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: Medline search terms were ‘levofloxacin’. EMBASE search terms were ‘levofloxacin’ or ‘DR 3355’. AdisBase search terms were ‘levofloxacin’ or ‘DR-3355’. Searches were last updated 10 November 2003.

Selection: Studies in patients with bacterial infections who received levofloxacin. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Acute exacerbations of chronic bronchitis, acute sinusitis, antibacterials, chronic bacterial prostatitis, community-acquired pneumonia, genitourinary tract infections, levofloxacin, nosocomial pneumonia, pharmacodynamics, pharmacokinetics, respiratory tract infections, skin and skin structure infections, therapeutic use, urinary tract infections.

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Croom, K.F., Goa, K.L. Levofloxacin. Drugs 63, 2769–2802 (2003). https://doi.org/10.2165/00003495-200363240-00008

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Keywords

  • Levofloxacin
  • Gatifloxacin
  • Nosocomial Pneumonia
  • Clinical Response Rate
  • Cefuroxime Axetil