, Volume 68, Issue 4, pp 535–565


A Review of its Use as a High-Dose, Short-Course Treatment for Bacterial Infection
Adis Drug Evaluation



Levofloxacin (Levaquin®) is a fluoroquinolone antibacterial that is the L-isomer of ofloxacin. A high-dose (750 mg) short-course (5 days) of once-daily levofloxacin is approved for use in the US in the treatment of community-acquired pneumonia (CAP), acute bacterial sinusitis (ABS), complicated urinary tract infections (UTI) and acute pyelonephritis (AP).

The broad spectrum antibacterial profile of levofloxacin means that monotherapy is often a possibility in patients with CAP at times when other agents may require combination therapy, although levofloxacin can be used in combination therapy when necessary. The high-dose, short-course levofloxacin regimen maximizes its concentration-dependent bactericidal activity and may reduce the potential for resistance to emerge. In addition, this regimen lends itself to better compliance because of the shorter duration of treatment and the convenient once-daily administration schedule.

Oral levofloxacin is rapidly absorbed and is bioequivalent to the intravenous formulation; importantly, patients can transition between the formulations, which results in more options in regards to the treatment regimen and the potential for patients with varying degrees of illness to be treated. Levofloxacin has good tissue penetration and an adequate concentration can be maintained in the urinary tract to treat uropathogens.

Levofloxacin is generally well tolerated and has good efficacy in the treatment of patients with CAP, ABS, complicated UTI and AP. The efficacy and tolerability of levofloxacin 500 mg once daily for 10 days in patients with CAP, ABS and UTIs is well established, and the high-dose, short-course levofloxacin regimen has been shown to be noninferior to the 10-day regimen in CAP and ABS, and to have a similar tolerability profile. Similarly, the high-dose, short-course levofloxacin regimen is noninferior to ciprofloxacin in patients with complicated UTI or AP. Thus, levofloxacin is a valuable antimicrobial agent that has activity against a wide range of bacterial pathogens; however, its use should be considered carefully so that the potential for resistance selection can be minimized and its usefulness in severe infections and against a range of penicillin- and macrolide-resistant pathogens can be maintained.

Pharmacodynamic Properties

Levofloxacin is the synthetic L-isomer of the racemic quinolone ofloxacin. It interferes with critical processes in the bacterial cell, such as DNA replication, transcription, repair and recombination, by inhibiting type II topoisomerases. Levofloxacin is active against a broad range of Gram-positive, Gram-negative and atypical bacteria that may be causative pathogens in community-acquired and nosocomial infections.

In general, levofloxacin shows good in vitro activity against clinically-relevant Gram-positive, -negative and atypical organisms. Levofloxacin is active against the Gram-positive penicillin-susceptible and -resistant strains of Streptococcus pneumoniae, the Gram-negative species Enterobacter cloacae and Proteus mirabilis, and the atypical organisms Chlamydophila pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae, with minimum concentrations required to inhibit the growth of 90% of strains (MIC90) of ≤2 mg/L. Levofloxacin is highly active against the Gram-negative species Haemophilus influenzae, H. parainfluenzae and Moraxella catarrhalis (MIC90 of ≤0.06 mg/L), including β-lactamase positive strains of H. influenzae and M. catarrhalis. The activity of levofloxacin against Gram-positive meticillin/oxacillin-susceptible Staphylococcus aureus is slightly reduced, with the MIC90 (≤4 mg/L) in the susceptible to intermediate range, and the activity of levofloxacin against the Gram-negative Escherichia coli (MIC90 ≤0.06 to >8 mg/L) and Pseudomonas aeruginosa (MIC90 0.5–64 mg/L) is variable.

Rates of S. pneumoniae resistance to levofloxacin have remained ≤1% in surveillance programmes undertaken in the US, Canada and worldwide; in penicillin-resistant isolates of S. pneumoniae, the rate of resistance to levofloxacin was ≤2.7%. Recent data suggest that the rate of levofloxacin resistance in S. pneumoniae in the US has decreased between 2004 and 2006. Levofloxacin resistance has not been identified in H. influenzae or M. catarrhalis in surveillance studies conducted up to 2005, but it has been identified in E. coli, P. aeruginosa and S. aureus.

As the activity of levofloxacin is concentration dependent, the most common predictor of microbiological and clinical efficacy is the area under the plasma concentration-time curve (AUC): MIC ratio. A ratio of >30 was used in some studies to predict in vivo activity, particularly against S. pneumoniae, but a higher ratio (>100) is suggested as being predictive of a bactericidal effect and thus reducing the potential of first-step mutations occurring. In simulated pharmacodynamic analyses of levofloxacin 750 mg, the probability of an AUC: MIC target of ≥30 being attained in the plasma was ≥97%.

Pharmacokinetic Properties

Following oral administration, levofloxacin is rapidly absorbed and maximum plasma concentrations are attained in 1–2 hours. The absolute bioavailability of levofloxacin is ≈99% and the oral solution or tablet formulations and intravenous formulation are bioequivalent. Plasma protein binding is low (≤38%). Levofloxacin is distributed throughout the body and the concentration in other tissues (e.g. epithelial lining fluid, alveolar cells or macrophages, paranasal sinuses mucosa and urine) can exceed that in the plasma 2–4 hours after administration.

The pharmacokinetics of levofloxacin are not affected by age, gender, race, HIV status or the presence of a serious community-acquired bacterial infection. However, gastrointestinal absorption of the drug can be reduced by magnesium- or aluminium-containing antacids, metal cations, such as iron and vitamin preparations with zinc, as well as sucralfate. The concomitant use of levofloxacin with a range of other drugs has not resulted in any clinically significant effects in a small number of formal drug interaction studies. Clinically significant effects, such as symptomatic hyperglycaemia and hypoglycaemia, have been reported with levofloxacin, usually in patients with diabetes mellitus receiving concomitant hypoglycaemic agents/insulin. Postmarketing experience includes reports that levofloxacin enhances the effects of warfarin.

Therapeutic Efficacy

The efficacy of oral and/or intravenous levofloxacin 750 mg once daily for 5 days has been established in randomized, well designed trials in adults with CAP, ABS, complicated UTI or AP. Levofloxacin 750 mg once daily for 5 days was noninferior to levofloxacin 500 mg once daily for 10 days in the treatment of adults with CAP and ABS infections according to the primary endpoint of clinical response rate 7–14 days after the end of treatment. Clinical and microbiological response rates in the clinically evaluable population of patients with CAP were 92.4% versus 91.1% and 93.2% versus 92.4% in those receiving the 750 mg dosage regimen versus the 500 mg dosage regimen. In patients with ABS, the corresponding response rates were 91.4% versus 88.6% and 91.5% versus 89.4%, respectively.

Levofloxacin 750 mg once daily for 5 days was noninferior to ciprofloxacin 400 mg or 500 mg twice daily for 10 days in the treatment of adults with complicated UTI or AP infections according to the primary endpoint of microbiological response (eradication) rate on day 15–22 of the study. The microbiological response rate in levofloxacin or ciprofloxacin recipients (all patients with complicated UTI or AP) in the co-primary endpoint populations was 79.8% versus 79.8% (modified intent-to-treat population) and 86% versus 89.2% (microbiologically evaluable population). Clinical response rates in the corresponding groups were 81.1% versus 80.1% and 86.4% versus 88.4%, respectively.


Levofloxacin is generally well tolerated in patients with respiratory or UTIs. In a pooled analysis of patients with respiratory infections, the most commonly reported treatment-emergent adverse events included nausea, headache, diarrhoea, insomnia, constipation, abdominal pain, dizziness, dyspepsia and vomiting; the incidence of drug-related adverse events was not significantly different between those receiving the levofloxacin 750 mg or 500 mg regimen. No clinically important adverse events that occurred were deemed to be drug related. Discontinuation of therapy because of drug-related adverse events occurred in <2% of patients with respiratory infections. The most common treatment-emergent adverse events in patients with complicated UTI or AP were similar to those observed in patients with respiratory infections.


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  1. 1.
    Jones RN, Fritsche TR, Sader HS, et al. Activity of garenoxacin, an investigational des-F(6)-quinolone, tested against pathogens from community-acquired respiratory tract infections, including those with elevated or resistant-level fluoroquinolone MIC values. Diagn Microbiol Infect Dis 2007 May; 58(1): 9–17PubMedCrossRefGoogle Scholar
  2. 2.
    Brown SD, Rybak MJ. Antimicrobial susceptibility of Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae collected from patients across the USA, in 2001–2002, as part of the PROTEKT US study. J Antimicrob Chemother 2004 Aug; 54 Suppl. 1: 17–15CrossRefGoogle Scholar
  3. 3.
    Doern GV, Brown SD. Antimicrobial susceptibility among community-acquired respiratory tract pathogens in the USA: data from PROTEKT US 2000–01. J Infect 2004 Jan; 48(1): 56–65PubMedCrossRefGoogle Scholar
  4. 4.
    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): 251–9PubMedCrossRefGoogle Scholar
  5. 5.
    Gordon KA, Sader HS, Jones RN. Contemporary re-evaluation of the activity and spectrum of grepafloxacin tested against isolates in the United States. Diagn Microbiol Infect Dis 2003 Sep; 47(1): 377–83PubMedCrossRefGoogle Scholar
  6. 6.
    Huband MD, Cohen MA, Zurack M, et al. In vitro and in vivo activities of PD 0305970 and PD 0326448, new bacterial gyrase/topoisomerase inhibitors with potent antibacterial activities versus multidrug-resistant gram-positive and fastidious organism groups. Antimicrob Agents Chemother 2007 Apr; 51(4): 1191–201PubMedCrossRefGoogle Scholar
  7. 7.
    Keating GM, Scott LJ. Moxifloxacin: a review of its use in the management of bacterial infections. Drugs 2004; 64(20): 2347–77PubMedCrossRefGoogle Scholar
  8. 8.
    File Jr TM. New insights in the treatment by levofloxacin. Chemotherapy 2004; 50 Suppl. 1: 22–8PubMedCrossRefGoogle Scholar
  9. 9.
    Croom KF, Goa KL. Levofloxacin: a review of its use in the treatment of bacterial infections in the United States. Drugs 2003; 63(24): 2769–802PubMedCrossRefGoogle Scholar
  10. 10.
    Levaquin® (levofloxacin tablets, oral solution, injection): US prescribing information. Raritan (NJ): Ortho-McNeil Pharmaceutical, Inc., 2008 JanGoogle Scholar
  11. 11.
    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): 2127–67PubMedCrossRefGoogle Scholar
  12. 12.
    Clinical and Laboratory Standards Institute. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard — seventh edition. Clinical and Laboratory Standards Institute Document M7-A7. Wayne (PA): Clinical and Laboratory Standards Institute, 2006 Jan: 26 (2)Google Scholar
  13. 13.
    Clinical and Laboratory Standards Institute. Performance standards for antimicrobial disk susceptibility tests. Approved standard — ninth edition. Clinical and Laboratory Standards Institute Document M2-A9. Wayne (PA): Clinical and Laboratory Standards Institute, 2006 Jan: 261Google Scholar
  14. 14.
    Huband MD, Brighty KE, Monohan R, et al. In vitro antibacterial activity of CE-156811, CP-919474, and CP-929898: novel hygromycin A analogs compared to levofloxacin and other antibacterial agents against 1220 recent clinical isolates [abstract no. F1-1963]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA), 230Google Scholar
  15. 15.
    Nilius AM, Shen LL, Hensey-Rudloff D, et al. In vitro antibacterial potency and spectrum of ABT-492, a new fluoroquinolone. Antimicrob Agents Chemother 2003 Oct; 47(10): 3260–9PubMedCrossRefGoogle Scholar
  16. 16.
    Fritsche TR, Sader HS, Jones RN. Potency and spectrum of garenoxacin tested against an international collection of skin and soft tissue infection pathogens: report from the SENTRY antimicrobial surveillance program (1999–2004). Diagn Microbiol Infect Dis 2007 May; 58(1): 19–26PubMedCrossRefGoogle Scholar
  17. 17.
    Goff DA, Dowzicky MJ. Prevalence and regional variation in meticillin-resistant Staphylococcus aureus (MRSA) in the USA and comparative in vitro activity of tigecycline, a glycylcycline antimicrobial. J Med Microbiol 2007 Sep; 56(9): 1189–95PubMedCrossRefGoogle Scholar
  18. 18.
    Jacobs MR, Felmingham D, Appelbaum PC, et al. The Alexander Project 1998–2000: susceptibility of pathogens isolated from community-acquired respiratory tract infection to commonly used antimicrobial agents. J Antimicrob Chemother 2003 Aug; 52(2): 229–46PubMedCrossRefGoogle Scholar
  19. 19.
    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): 963–70PubMedCrossRefGoogle Scholar
  20. 20.
    Sahm DF, Weaver MK, Flamm RK, et al. Rates of antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in the United States: results from the TRUST 7 (2002–2003) surveillance study [abstract no. 201 plus poster]. 41st Annual Meeting of the Infectious Diseases Society of America; 2003 Oct 9–12; San Diego (CA)Google Scholar
  21. 21.
    Davidson RJ, Melano R, Forward KR. Antimicrobial resistance among invasive isolates of Streptococcus pneumoniae collected across Canada. Diagn Microbiol Infect Dis 2007 Sep; 59(1): 75–80PubMedCrossRefGoogle Scholar
  22. 22.
    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 Feb; 14(1): 45–50PubMedCrossRefGoogle Scholar
  23. 23.
    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 Sep; 35(1): 81–8PubMedCrossRefGoogle Scholar
  24. 24.
    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): 187–94PubMedCrossRefGoogle Scholar
  25. 25.
    Biedenbach DJ, Toleman MA, Walsh TR, et al. Characterization of fluoroquinolone-resistant β-hemolytic Streptococcus spp. isolated in North America and Europe including the first report of fluoroquinolone-resistant Streptococcus dysgalactiae subspecies equisimilis: report from the SENTRY antimicrobial surveillance program (1997–2004).Diagn Microbiol Infect Dis 2006 Jun; 55(2): 119–27PubMedGoogle Scholar
  26. 26.
    Bouchillon S, Hackel M, Johnson J, et al. The carbapenem PZ-601 (SMP-601) has potent in vitro Gram-positive, Gram-negative and anaerobic bacterial activity (poster F1-343). 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar
  27. 27.
    Paterson DL, Adams J, Doi Y. In vitro activity of PZ-601 (SMP-601), a novel carbapenem, against extended-spectrum beta-lactamase producing organisms [poster no. F1-346]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar
  28. 28.
    Thornsberry C, Sahm DF, Kelly LJ, et al. Regional trends in antimicrobial resistance among clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States: results from the TRUST Surveillance Program, 1999–2000. Clin Infect Dis 2002 Mar 1; 34 Suppl. 1: S4–16PubMedCrossRefGoogle Scholar
  29. 29.
    Karlowsky JA, Thornsberry C, Critchley IA, et al. Susceptibilities to levofloxacin in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis clinical isolates from children: results from 2000–2001 and 2001–2002 TRUST studies in the United States. Antimicrob Agents Chemother 2003 Jun; 47(6): 1790–7PubMedCrossRefGoogle Scholar
  30. 30.
    Zhanel GG, Hisanaga TL, Laing NM, et al. Antibiotic resistance in Escherichia coli outpatient urinary isolates: final results from the North American Urinary Tract Infection Collaborative Alliance (NAUTICA). Int J Antimicrob Agents 2006 Jun; 27(6): 468–75PubMedCrossRefGoogle Scholar
  31. 31.
    Soriano F, Granizo JJ, Coronel P, et al. Antimicrobial susceptibility of Haemophilus influenzae, Haemophilus parainfluenzae and Moraxella catarrhalis isolated from adult patients with respiratory tract infections in four southern European countries. The ARISE project. Int J Antimicrob Agents 2004 Mar; 23(3): 296–9Google Scholar
  32. 32.
    Hansen GT, Blondeau JM. Comparison of the minimum inhibitory, mutant prevention and minimum bactericidal concentrations of ciprofloxacin, levofloxacin and garenoxacin against enteric Gram-negative urinary tract infection pathogens. J Chemother 2005 Oct; 17(5): 484–92PubMedGoogle Scholar
  33. 33.
    Jones RN, Sader HS, Beach ML. Contemporary in vitro spectrum of activity summary for antimicrobial agents tested against 18 569 strains non-fermentative Gram-negative bacilli isolated in the SENTRY antimicrobial surveillance program (1997–2001). Int J Antimicrob Agents 2003 Dec; 22(6): 551–6PubMedCrossRefGoogle Scholar
  34. 34.
    Pfaller MA, Sader HS, Fritsche TR, et al. Antimicrobial activity of cefepime tested against ceftazidime-resistant Gram-negative clinical strains from North American Hospitals: report from the SENTRY antimicrobial surveillance program (1998–2004). Diagn Microbiol Infect Dis 2006 Sep; 56(1): 63–8PubMedCrossRefGoogle Scholar
  35. 35.
    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): 214–21PubMedCrossRefGoogle Scholar
  36. 36.
    Dubois J, St-Pierre C. Comparative in vitro activity and post-antibiotic effect of gemifloxacin against Legionella spp. J Antimicrob Chemother 2000 Apr; 45 Suppl. 1: 41–6PubMedCrossRefGoogle Scholar
  37. 37.
    Stout JE, Sens K, Mietzner S, et al. Comparative activity of quinolones, macrolides and ketolides against Legionella species using in vitro broth dilution and intracellular susceptibility testing. Int J Antimicrob Agents 2005 Apr; 25(4): 302–7PubMedCrossRefGoogle Scholar
  38. 38.
    Roblin PM, Reznik T, Kutlin A, et al. In vitro activities of rifamycin derivatives ABI-1648 (Rifalazil, KRM-1648), ABI-1657, and ABI-1131 against Chlamydia trachomatis and recent clinical isolates of Chlamydia pneumoniae. Antimicrob Agents Chemother 2003 Mar; 47(3): 1135–6PubMedCrossRefGoogle Scholar
  39. 39.
    Kohlhoff SA, Roblin PM, Reznik T, et al. In vitro activity of a novel diaminopyrimidine compound, iclaprim, against Chlamydia trachomatis and C.pneumoniae. Antimicrob Agents Chemother 2004 May; 48(5): 1885–6PubMedCrossRefGoogle Scholar
  40. 40.
    Hammerschlag MR, Roblin PM. The in vitro activity of a new fluoroquinolone, ABT-492, against recent clinical isolates of Chlamydia pneumoniae [letter]. J Antimicrob Chemother 2004 Jul; 54(1): 281–2PubMedCrossRefGoogle Scholar
  41. 41.
    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): 161–5PubMedCrossRefGoogle Scholar
  42. 42.
    Waites KB, Crabb DM, Duffy LB. In vitro activities of ABT-773 and other antimicrobials against human mycoplasmas. Antimicrob Agents Chemother 2003 Jan; 47(1): 39–42PubMedCrossRefGoogle Scholar
  43. 43.
    Waites KB, Crabb DM, Duffy LB. Comparative in vitro susceptibilities and bactericidal activities of investigational fluoroquinolone ABT-492 and other antimicrobial agents against human mycoplasmas and ureaplasmas. Antimicrob Agents Chemother 2003 Dec; 47(12): 3973–5PubMedCrossRefGoogle Scholar
  44. 44.
    Duffy LB, Crabb DM, Bing X, et al. Bactericidal activity of levofloxacin against Mycoplasma pneumoniae [letter]. J Antimicrob Chemother 2003 Sep; 52(3): 527–8PubMedCrossRefGoogle Scholar
  45. 45.
    Dunbar LM, Wunderink RG, Habib MP, et al. High-dose, short-course levofloxacin for community-acquired pneumonia: a new treatment paradigm [published erratum appears in Clin Infect Dis 2003 Oct 15; 37 (8): 1147]. Clin Infect Dis 2003 Sep 15; 37(6): 752–60PubMedCrossRefGoogle Scholar
  46. 46.
    Doern GV, Richter SS, Miller A, et al. Antimicrobial resistance among Streptococcus pneumoniae in the United States: have we begun to turn the corner on resistance to certain antimicrobial classes. Clin Infect Dis 2005 Jul; 41(2): 139–48PubMedCrossRefGoogle Scholar
  47. 47.
    Felmingham D, Feldman C, Hryniewicz W, et al. Surveillance of resistance in bacteria causing community-acquired respiratory tract infections. Clin Microbiol Infect 2002; 8 Suppl. 2: 12–42PubMedCrossRefGoogle Scholar
  48. 48.
    Canton R, Morosini M, Enright MC, et al. Worldwide incidence, molecular epidemiology and mutations implicated in fluoroquinolone-resistant Streptococcus pneumoniae: data from the global PROTEKT surveillance programme. J Antimicrob Chemother 2003 Dec; 52(6): 944–52PubMedCrossRefGoogle Scholar
  49. 49.
    Higgins PG, Fluit AC, Milatovic D, et al. Mutations in GyrA, ParC, MexR and NfxB in clinical isolates of Pseudomonas aeruginosa. Int J Antimicrob Agents 2003 May; 21(5): 409–13PubMedCrossRefGoogle Scholar
  50. 50.
    DeRyke CA, Du X, Nicolau DP. Evaluation of bacterial kill when modelling the bronchopulmonary pharmacokinetic profile of moxifloxacin and levofloxacin against parC-containing isolates of Streptococcus pneumoniae. J Antimicrob Chemother 2006; 58(3): 601–9PubMedCrossRefGoogle Scholar
  51. 51.
    LaPlante KL, Rybak MJ, Tsuji B, et al. Fluoroquinolone resistance in Streptococcus pneumoniae: area under the concentration-time curve/MIC ratio and resistance development with gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin. Antimicrob Agents Chemother 2007 Apr; 51(4): 1315–20PubMedCrossRefGoogle Scholar
  52. 52.
    Sahm DF, Benninger MS, Evangelista AT, et al. Antimicrobial resistance trends among sinus isolates of Streptococcus pneumoniae in the United States (2001–2005). Otolaryngol Head Neck Surg 2007 Mar; 136(3): 385–9PubMedCrossRefGoogle Scholar
  53. 53.
    Davies TA, Yee C, Morrow B, et al. Continued decline in levofloxacin-resistance among U.S. Streptococcus pneumoniae collected in TRUST 10 (2006) [abstract no. C2-210]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar
  54. 54.
    Zhanel GG, Fontaine S, Adam H, et al. A review of new fluoroquinolones: focus on their use in respiratory tract infections. Treat Respir Med 2006; 5(6): 437–65PubMedCrossRefGoogle Scholar
  55. 55.
    Frei CR, Burgess DS. Pharmacodynamic analysis of ceftriaxone, gatifloxacin, and levofloxacin against Streptococcus pneumoniae with the use of Monte Carlo simulation. Pharma-cotherapy 2005 Sep; 25(9): 1161–7Google Scholar
  56. 56.
    Schentag JJ, Meagher AK, Forrest A. Fluoroquinolone AUIC break points and the link to bacterial killing rates. Part 2: human trials. Ann Pharmacother 2003 Oct; 37(10): 1478–88Google Scholar
  57. 57.
    Odenholt I, Cars O. Pharmacodynamics of moxifloxacin and levofloxacin against Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli: simulation of human plasma concentrations after intravenous dosage in an in vitro kinetic model. J Antimicrob Chemother 2006 Nov; 58(5): 960–5PubMedCrossRefGoogle Scholar
  58. 58.
    Noreddin AM, Hoban DJ, Zhanel GG. Comparison of gatifloxacin and levofloxacin administered at various dosing regimens to hospitalised patients with community-acquired pneumonia: pharmacodynamic target attainment study using North American surveillance data for Streptococcus pneumoniae. Int J Antimicrob Agents 2005 Aug; 26(2): 120–5PubMedCrossRefGoogle Scholar
  59. 59.
    Noreddin AM, Marras TK, Sanders K, et al. Pharmacodynamic target attainment analysis against Streptococcus pneumoniae using levofloxacin 500 mg, 750 mg and 1000 mg once daily in plasma (P) and epithelial lining fluid (ELF) of hospitalized patients with community acquired pneumonia (CAP). Int J Antimicrob Agents 2004 Nov; 24(5): 479–84PubMedCrossRefGoogle Scholar
  60. 60.
    Dalhoff A, Schmitz F J.In vitro antibacterial activity and pharmacodynamics of new quinolones. Eur J Clin Microbiol Infect Dis 2003 Apr; 22(4): 203–21PubMedGoogle Scholar
  61. 61.
    Felmingham D, White AR, Jacobs MR, et al. The Alexander Project: the benefits from a decade of surveillance. J Antimicrob Chemother 2005 Oct; 56 Suppl. 2: ii3–21PubMedCrossRefGoogle Scholar
  62. 62.
    Stein G, Schooley S, Nicolau D. Urinary bactericidal activity of levofloxacin (750 mg) against fluoroquinolone-resistant [abstract no. P1533]. Clin Microbiol Infect 2006 Apr 1; 12 (Suppl. 4)Google Scholar
  63. 63.
    Langtry HD, Lamb HM. Levofloxacin: its use in infections of the respiratory tract, skin, soft tissues and urinary tract. Drugs 1998 Sep; 56(3): 487–515PubMedCrossRefGoogle Scholar
  64. 64.
    Chow AT, Fowler C, Williams RR, et al. Safety and pharmaco-kinetics of multiple 750-milligram doses of intravenous levofloxacin in healthy volunteers. Antimicrob Agents Chemother 2001 Jul; 45(7): 2122–5PubMedCrossRefGoogle Scholar
  65. 65.
    Chien SC, 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 Apr; 42(4): 885–8PubMedGoogle Scholar
  66. 66.
    Gotfried MH, Danziger LH, Rodvold KA. Steady-state plasma and intrapulmonary concentrations of levofloxacin and cipro-floxacin in healthy adult subjects. Chest 2001 Apr; 119(4): 1114–22PubMedCrossRefGoogle Scholar
  67. 67.
    Sprandel KA, Schriever CA, Pendland SL, et al. Pharmacokinetics and pharmacodynamics of intravenous levofloxacin at 750 milligrams and various doses of metronidazole in healthy adult subjects. Antimicrob Agents Chemother 2004 Dec; 48(12): 4597–605PubMedCrossRefGoogle Scholar
  68. 68.
    Rodvold KA, Danziger LH, Gotfried MH. Steady-state plasma and bronchopulmonary concentrations of intravenous levofloxacin and azithromycin in healthy adults. Antimicrob Agents Chemother 2003; 47(8): 2450–7PubMedCrossRefGoogle Scholar
  69. 69.
    Capitano B, Mattoes HM, Shore E, et al. Steady-state intrapulmonary concentrations of moxifloxacin, levofloxacin, and azithromycin in older adults. Chest 2004 Mar; 125(3): 965–73PubMedCrossRefGoogle Scholar
  70. 70.
    Conte Jr JE, Golden JA, McIver M, et al. Intrapulmonary pharmacodynamics of high-dose levofloxacin in subjects with chronic bronchitis or chronic obstructive pulmonary disease. Int J Antimicrob Agents 2007 Nov; 30(5): 422–7PubMedCrossRefGoogle Scholar
  71. 71.
    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 Feb; 46(2): 586–9PubMedCrossRefGoogle Scholar
  72. 72.
    Pea F, Marioni G, Pavan F, et al. Penetration of levofloxacin into paranasal sinuses mucosa of patients with chronic rhinosinusitis after a single 500 mg oral dose. Pharmacol Res 2007 Jan; 55(1): 38–41PubMedCrossRefGoogle Scholar
  73. 73.
    Garraffo R, Lavrut T, Durant J, et al. In vivo comparative pharmacokinetics and pharmacodynamics of moxifloxacin and levofloxacin in human neutrophils. Clin Drug Invest 2005; 25(10): 643–50CrossRefGoogle Scholar
  74. 74.
    Poole M, Anon J, Paglia M, et al. A trial of high-dose, short-course levofloxacin for the treatment of acute bacterial sinusitis. Otolaryngol Head Neck Surg 2006 Jan; 134(1): 10–7PubMedCrossRefGoogle Scholar
  75. 75.
    Peterson J, Kaul S, Khashab M, et al. A double-blind, randomized comparison of levofloxacin 750mg once-daily for 5 days with ciprofloxacin 400/500mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis. Urology 2008; 71: 17–22PubMedCrossRefGoogle Scholar
  76. 76.
    Klausner HA, Brown P, Peterson J, et al. A trial of levofloxacin 750 mg once daily for 5 days versus ciprofloxacin 400 mg and/ or 500 mg twice daily for 10 days in the treatment of acute pyelonephritis. Curr Med Res Opin 2007; 22(11): 2637–45CrossRefGoogle Scholar
  77. 77.
    Dunbar LM, Khashab MM, Kahn JB, et al. Efficacy of 750-mg, 5-day levofloxacin in the treatment of community-acquired pneumonia caused by atypical pathogens. Curr Med Res Opin 2004 Apr; 20(4): 555–63PubMedCrossRefGoogle Scholar
  78. 78.
    Shorr AF, Khashab MM, Xiang JX, et al. Levofloxacin 750-mg for 5 days for the treatment of hospitalized fine risk class III/IV community-acquired pneumonia patients. Respir Med 2006 Dec; 100(12): 2129–36PubMedCrossRefGoogle Scholar
  79. 79.
    Shorr AF, Zadeikis N, Xiang JX, et al. A multicenter, randomized, double-blind, retrospective comparison of 5- and 10-day regimens of levofloxacin in a subgroup of patients aged ≥65 years with community-acquired pneumonia. Clin Ther 2005 Aug; 27(8): 1251–9PubMedCrossRefGoogle Scholar
  80. 80.
    File Jr TM, Milkovich G, Tennenberg AM, et al. Clinical implications of 750 mg, 5-day levofloxacin for the treatment of community-acquired pneumonia. Curr Med Res Opin 2004 Sep; 20(9): 1473–81PubMedCrossRefGoogle Scholar
  81. 81.
    Peterson J, Khashab MM, Fisher AC, et al. Sustained early resolution of community-acquired pneumonia symptoms following treatment with high-dose, short-course levofloxacin [abstract no. 421 plus poster]. 44th Annual Meeting of the Infectious Diseases Society of America; 2006 Oct 12–16; Toronto (ON)Google Scholar
  82. 82.
    Khashab MM, Xiang J, Kahn JB. Comparison of the adverse event profiles of levofloxacin 500 mg and 750 mg in clinical trials for the treatment of respiratory infections. Curr Med Res Opin 2006 Oct; 22(10): 1997–2006PubMedCrossRefGoogle Scholar
  83. 83.
    Wargo KA, Wargo NA, Eiland III EH. Maximizing pharmaco-dynamics with high-dose levofloxacin. Hosp Pharm 2005; 40(9): 777–87Google Scholar
  84. 84.
    Segreti J, House HR, Siegel RE. Principles of antibiotic treatment of community-acquired pneumonia in the outpatient setting. Am J Med 2005 Jul; 118 Suppl. 7A: 21–8SCrossRefGoogle Scholar
  85. 85.
    Shams WE, Evans ME. Guide to selection of fluoroquinolones in patients with lower respiratory tract infections. Drugs 2005; 65(7): 949–91PubMedCrossRefGoogle Scholar
  86. 86.
    Slavin RG, Spector SL, Bernstein IL, et al. The diagnosis and management of sinusitis: a practice parameter update. J Allergy Clin Immunol 2005 Dec; 116 Suppl. 6: S13–47PubMedCrossRefGoogle Scholar
  87. 87.
    Carson C, Naber KG. Role of fluoroquinolones in the treatment of serious bacterial urinary tract infections. Drugs 2004; 64(12): 1359–73PubMedCrossRefGoogle Scholar
  88. 88.
    Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007 Mar 1; 44 Suppl. 2: S27–72PubMedCrossRefGoogle Scholar
  89. 89.
    McCormack PL, Keating GM. Amoxicillin/clavulanic acid 2000mg/125mg extended release (XR): a review of its use in the treatment of respiratory tract infections in adults. Drugs 2005; 65(1): 121–36PubMedCrossRefGoogle Scholar
  90. 90.
    Rosenfeld RM, Andes D, Bhattacharyya, et al. Clinical practice guideline: adult sinusitis. Otolaryngol Head Neck Surg 2007; 137 Suppl.: 1–31PubMedCrossRefGoogle Scholar
  91. 91.
    Nickel JC. Management of urinary tract infections: historical perspective and current strategies: part 2. Modern management. J Urol 2005 Jan; 173(1): 27–32Google Scholar
  92. 92.
    Warren JW, Abrutyn E, Hebel JR, et al. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA). Clin Infect Dis 1999 Oct; 29(4): 745–58CrossRefGoogle Scholar
  93. 93.
    Bhavnani SM, Ambrose PG, Craig WA, et al. Outcomes evaluation of patients with ESBL- and non-ESBL-producing Escherichia coli and Klebsiella species as defined by CLSI reference methods: report from the SENTRY Antimicrobial Surveillance Program. Diagn Microbiol Infect Dis 2006 Mar; 54(3): 231–6PubMedCrossRefGoogle Scholar
  94. 94.
    Lee SY, Kotapati S, Kuti JL, et al. Impact of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella species on clinical outcomes and hospital costs: a matched cohort study. Infect Control Hosp Epidemiol 2006 Nov; 27(11): 1226–32PubMedCrossRefGoogle Scholar
  95. 95.
    Klossek JM, Federspil P. Update on treatment guidelines for acute bacterial sinusitis. Int J Clin Pract 2005 Feb; 59(2): 230–8PubMedCrossRefGoogle Scholar
  96. 96.
    Kallen AJ, Welch HG, Sirovich BE. Current antibiotic therapy for isolated urinary tract infections in women. Arch Intern Med 2006 Mar 27; 166(6): 635–9PubMedCrossRefGoogle Scholar
  97. 97.
    Yee YC, Evangelista AT, Obot-Tucker M, et al. Five-year surveillance (2003–2007) of anti-pneumococcal activity of oral agents recommended for the empirical treatment of community-acquired pneumonia (CAP) in adults [abstract no. C2-204]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar
  98. 98.
    Jones RN, Fritsche TR, Sader HS. Therapeutic options among broad-spectrum β-lactams for infections caused by levofloxacin-nonsusceptible Streptococcus pneumoniae. Diagn Microbiol Infect Dis 2005 Jun; 52(2): 129–33PubMedCrossRefGoogle Scholar
  99. 99.
    Blondeau JM. Current issues in the management of urinary tract infections: extended-release ciprofloxacin as a novel treatment option. Drugs 2004; 64(6): 611–28PubMedCrossRefGoogle Scholar
  100. 100.
    Tobramycin (for injection, USP): US prescribing information. Schaumburg (IL): American Pharmaceutical Partners, Inc., 2003 OctGoogle Scholar
  101. 101.
    Keam SJ, Croom KF, Keating GM. Gatifloxacin: a review of its use in the treatment of bacterial infections in the US. Drugs 2005; 65(5): 695–724PubMedCrossRefGoogle Scholar
  102. 102.
    Biaxin® Filmtab® (clarithromycin tablets, USP), Biaxin® XL Filmtab® (clarithromycin extended-release tablets), Biaxin® Granules (clarithromycin for oral suspension, USP): US prescribing information. North Chicago (IL): Abbott Laboratories, 2005 JanGoogle Scholar
  103. 103.
    Abbott Laboratories. Erythrocin® stearate (erythromycin stearate tablets, USP): US patient information [online]. Available from URL: http://www.rxabbott.com/pdf/erythrocin.pdf [Accessed 2007 Nov 12]
  104. 104.
    Vantin® (cefpodoxime proxetil tablets and cefpodoxime proxetil for oral suspension): US prescribing information. New York (NY): Pharmacia & Upjohn Company, 2007 AprGoogle Scholar
  105. 105.
    Rocephin® (ceftriaxone sodium for injection): US prescribing information. Nutley (NJ): Roche Laboratories Inc., 2007 JanGoogle Scholar
  106. 106.
    Hospira I. Gentamicin sulfate (injection): US professional information [online]. Available from URL: http://www.drugs.com/pro/gentamicin-sulfate.html [Accessed 2007 Nov 12]
  107. 107.
    Hospira I. Amikacin (injection, USP): US professional information [online]. Available from URL: http://www.drugs.com/pro/amikacin.html [Accessed 2007 Nov 12]

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Wolters Kluwer Health ¦ AdisMairangi Bay, North Shore, AucklandNew Zealand
  2. 2.Wolters Kluwer HealthConshohockenUSA

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