Levofloxacin: High-dose, short-course for bacterial infection

28 April, 2019

Associate Professor Panpit Suwangool
Bangkok Hospital, Thailand

Levofloxacin is a well-established antibacterial for respiratory and urinary tract infections.1 Levofloxacin is active against some penicillin- and macrolide- resistant pathogens including Streptococcus pneumoniae – the most common causative pathogen for community-acquired pneumonia. The high-dose, short-course regimen of levofloxacin (750 mg) has concentration-dependent bactericidal activity and reduces the emergence of resistance.1,2

Associate Professor Panpit Suwangool – infectious disease expert of Bangkok Hospital – shares insights into this high-dose, short-course regimen of levofloxacin.


Q1. In your opinion, how does the high dose levofloxacin reduce the emergence of resistance?

The rapid emergence of bacterial resistance with high use fluoroquinolone is of great concern. Levofloxacin demonstrates concentration-dependent bactericidal activity.1,2 Several studies have shown that high dose regimens of levofloxacin are more effective – with therapeutic outcome most closely related to the ratio of the area under the concentration-time curve (AUC) to the minimum inhibitory concentration (MIC) for the pathogen; a high ratio of peak plasma concentration (Cmax) to MIC has also been associated with prevention of the emergence of resistance.2-4


Q2. What are the principles of prescribing levofloxacin 500 mg and 750 mg?

Increasing the levofloxacin dose from 500 mg to 750 mg depends on the dose-dependent pharmacokinetic/pharmacodynamic (PK/PD) of levofloxacin.4 In a multicenter, randomised controlled trial comparing levofloxacin dosages of 750 mg per day for 5 days with 500 mg per day for 10 days for the treatment of mild-to-severe community-acquired pneumonia (CAP), the clinical success rates were 92.4% (n=198) for the 750-mg group and 91.1% (n=192) for the 500-mg group (95% confidence interval, -7.0 – 4.4); the microbiologic eradication rates were 93.2% and 92.4% in the 750-mg and 500-mg groups, respectively.2

Taking of the advantage of its PK/PD properties, this short-course, high-dose regimen reduces the total amount of drug to which pathogens are unnecessarily exposed, thereby limiting the development of resistance.2


Q3. What are the indications for levofloxacin monotherapy and combination therapy? What are the mechanisms of drug combinations? In clinical practice, when would you recommend a regimen that combines levofloxacin with other antibiotics?

Indications for levofloxacin monotherapy include: Known susceptible infection e.g., community-acquired pneumonia, bacterial sinusitis, urinary tract infection; and suspected bacterial or atypical infections.1 Meanwhile, indications for levofloxacin combination therapy are: Suspected multidrug-resistance infections e.g., hospital-acquired pneumonia and ventilator-acquired pneumonia; and critically ill septic patients.1

The initial use of combination therapy broadens the empiric coverage provided by two antimicrobial agents with different spectra of activity and aims to improve clinical outcomes with the synergistic effect of the combination i.e., more rapid killing of the pathogen.5 Combination therapy also provides protection against emergence of resistance. A majority of published data have shown no or very low mortality with the use of combination therapy as compared to monotherapy.6 However, while combination therapy may be beneficial, antibiotic treatment should be deescalated when susceptibility results are known.5


Q4. Newer quinolones such as sitafloxacin and prulifloxacin have been developed in the recent years. How does this affect the use of levofloxacin in clinical practice and the selection of antibiotic therapy?

Prulifloxacin is as active as levofloxacin and has broad spectrum antimicrobial activity against both gram negative and Gram positive bacteria.7

Sitafloxacin is very active active against many Gram negative bacteria and anaerobes including strains resistant to other fluoroquinolones.8 It is also active against Klebsiella pneumoniae and Escherichia coli with extended-spectrum beta lactamases (ESBL), and carbapenem-resistant Acinetobacter baumannii.9 Moreover, sitafloxacin is currently the only oral antibiotic active against A. baumannii. As such, sitafloxacin is superior to both levofloxacin and prulifloxacin in bacterial infections due to ESBL-producing bacteria and A. baumannii.


Q5. What is your opinion on the US Food and Drug Administration (USFDA) warning about the association of fluoroquinolones with disabling side effects involving tendons, muscles, joints, nerves, and the central nervous system? What are the risk factors associated with FQ-induced tendinopathy/tendon rupture?

A systematic review evaluating 16 observational studies has reported rare occurrence of fluoroquinolone-induced tendinopathy and tendon rupture, although concomitant corticosteroids increase the risk for this complication.10

Central nervous system (CNS) and gastrointestinal (GI)-related adverse events are more common with the use of fluoroquinolones as compared to the use of other antimicrobials.11 The most commonly reported adverse events were nausea, vomiting, diarrhoea, headache, dizziness, and rash.11 While common central nervous system (CNS)-related side effects associated with the use of fluoroquinolones include dizziness and insomnia, other more severe drug reaction of convulsion and psychosis seemed to be associated with other underlying conditions and the use of other drugs unrelated to fluoroquinolones.12


  1. Anderson VR and Perry CM. Drugs 2008;68:535-565.
  2. Dunbar LM, et al. Clin Infect Dis 2003;37:752-760.
  3. Preston SL, et al. JAMA 1998;279:125-129.
  4. Lister PD. Diagn Microbiol Infect Dis 2002;44:43-49.
  5. Tamma PD, et al. Clin Microbiol Rev 2012;25:450-470.
  6. Paul M, et al. Cochrane Database Syst Rev 2014;7:CD003344.
  7. Rafailidis PI, et al. Int J Antimicrob Agents 2011;37:283-290.
  8. Anderson DL. Drugs Today (Barc) 2008;44:489-501.
  9. Tantisiriwat W and Linasmita P. J Med Assoc Thai 2017;100:469-478.
  10. Stephenson AL, et al. Drug Saf 2013;36:709-721.
  11. Tandan M, et al. Int J Antimicrob Agents 2018;52:529-540.
  12. Mandell L and Tillotson G. Can J Infect Dis 2002;13:54-61.