Levofloxacin: Uses
Levofloxacin is used orally or IV for the treatment of respiratory tract infections (acute bacterial exacerbations of chronic bronchitis, acute maxillary sinusitis, community-acquired pneumonia, nosocomial pneumonia), uncomplicated or complicated skin and skin structure infections, uncomplicated or complicated urinary tract infections, acute pyelonephritis, and chronic prostatitis caused by susceptible organisms.
Levofloxacin also is used in the treatment of travelers' diarrhea and pelvic inflammatory disease. In addition, levofloxacin is recommended as an alternative agent for the treatment of gonorrhea, nongonococcal urethritis, or urogenital chlamydial infections; for the treatment of active tuberculosis; for postexposure prophylaxis following suspected or confirmed exposure to aerosolized anthrax spores (inhalational anthrax) or for treatment of inhalational anthrax; and for the treatment or prophylaxis of plague. In the absence of factors that may interfere with absorption of an orally administered drug (e.g., vomiting), IV levofloxacin does not provide a higher degree of efficacy nor more potent antimicrobial activity than an equivalent dosage of oral levofloxacin.
Therefore, IV levofloxacin generally is reserved for patients who cannot tolerate or are unable to take an oral dosage form or in whom the IV route offers a clinical advantage. Prior to initiation of levofloxacin therapy, appropriate specimens should be obtained for identification of the causative organism(s) and in vitro susceptibility tests.
Levofloxacin therapy may be started pending results of susceptibility tests, but should be discontinued and other appropriate anti-infective therapy substituted if the organism is found to be resistant to levofloxacin. In vitro susceptibility tests should be repeated periodically during levofloxacin therapy to assess effectiveness of the drug and to detect emergence of levofloxacin-resistant strains, which may develop during therapy with the drug.
Because resistant strains of Pseudomonas aeruginosa have developed during fluoroquinolone therapy, in vitro susceptibility tests are particularly important when levofloxacin is used in the treatment of infections caused by this organism.
Respiratory Tract Infections
Levofloxacin is used in adults for the treatment of acute bacterial exacerbations of chronic bronchitis, acute maxillary sinusitis, community-acquired pneumonia (CAP), and nosocomial pneumonia caused by susceptible organisms.
Acute Exacerbations of Chronic Bronchitis
Levofloxacin is used in adults for the treatment of acute bacterial exacerbations of chronic bronchitis caused by susceptible Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, Staphylococcus aureus, or Streptococcus pneumoniae. In controlled clinical studies in adults with acute bacterial exacerbations of chronic bronchitis, levofloxacin was as effective as therapy with cefaclor or cefuroxime. Levofloxacin therapy generally resulted in bacterial cure rates of 95-97% in patients with acute bacterial exacerbations of chronic bronchitis. The most prevalent pathogens in these studies were H. influenzae, H. parainfluenzae, M. catarrhalis, and S. pneumoniae.
Acute Sinusitis
Levofloxacin is used in adults for the treatment of acute maxillary sinusitis caused by susceptible H. influenzae, M. catarrhalis, or S. pneumoniae. In one open study in adults with acute maxillary sinusitis, therapy with levofloxacin or amoxicillin and clavulanate potassium resulted in clinical success rates of 87-88%.
Community-acquired Pneumonia
Levofloxacin is used in adults for the treatment of CAP1, 21 caused by susceptible Chlamydia pneumoniae, H. influenzae, H. parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, M. catarrhalis, Mycoplasma pneumoniae, S. aureus, or S. pneumoniae (including penicillin-resistant strains [penicillin MIC =2mcg/mL).
In one controlled clinical study in adults with CAP, a regimen that included IV and/or oral administration of levofloxacin was as effective as a regimen that included IV ceftriaxone and/or oral cefuroxime. Levofloxacin generally resulted in clinical success (cure or improvement) 5-7 days following completion of therapy in 93-95% of adults with CAP. In controlled clinical studies, presumptive bacteriologic eradication 5-7 days following completion of therapy was evident in 98% of patients with H. influenzae infection, 95% of those with H. parainfluenzae infection, 100% of those with K. pneumoniae infection, 94% of those with M. catarrhalis infection, 88% of those with S. aureus infection, and 95% of those with S. pneumoniae infection.
Clinical success rate 5-7 days following completion of therapy in patients with atypical pneumonia caused by C. pneumoniae, M. pneumoniae, or L. pneumoniae was 96, 96, or 70%, respectively. Data on the efficacy of levofloxacin in adults with CAP due to S. pneumoniae has been obtained from 8 clinical studies. In these studies, levofloxacin therapy resulted in clinical success (cure or improvement) in 98% of the 250 levofloxacin-treated patients with CAP due to S. pneumoniae. Infection due to penicillin-resistant S. pneumoniae was documented in 18 levofloxacin-treated patients in these studies; evaluation of 15 of these patients who completed therapy indicates that levofloxacin is effective in patients with infection due to penicillin-resistant S. pneumoniae (clinical success rate 100%). Some clinicians, including the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA), suggest that fluoroquinolones with enhanced activity against S. pneumoniae (e.g., gatifloxacin, levofloxacin, moxifloxacin) are drugs of choice for the treatment of CAP in adults.
However, there is disagreement over the role of these drugs in the outpatient treatment of CAP. The IDSA recommends monotherapy with these oral fluoroquinolones as one of several possible regimens for empiric outpatient treatment of acute CAP in immunocompetent adults, but the ATS suggests that these agents not be used for outpatient treatment of CAP in immunocompetent adults without cardiopulmonary disease or other modifying factors that would increase the risk of multidrug-resistant S. pneumonia. To limit emergence of fluoroquinolone-resistant strains, the US Centers for Disease Control and Prevention (CDC) suggest that use of these oral fluoroquinolones in the outpatient treatment of CAP be reserved for when other anti-infectives are ineffective or cannot be used or when highly penicillin-resistant S. pneumoniae (penicillin MIC greater than or equal to 2 mcg/mL) are identified as the cause of infection.
Nosocomial Pneumonia
Levofloxacin is used in adults for the treatment of nosocomial pneumonia caused by susceptible H. influenzae, Escherichia coli, K. pneumoniae, Serratia marcescens, Ps. aeruginosa, S. aureus (oxacillin-susceptible strains only), or S. pneumoniae. If the infection is known or suspected of being caused by Ps. aeruginosa, concomitant therapy with an antipseudomonal b-lactam anti-infective is recommended. In a multicenter, randomized, open-label study in adults with clinical and radiologically documented nosocomial pneumonia, patients were randomized to receive a 7- to 15-day regimen of IV levofloxacin (750 mg once daily) following by oral levofloxacin (750 mg once daily) or IV imipenem and cilastatin sodium (500-1000 mg every 6-8 hours) followed by oral ciprofloxacin (750 mg every 12 hours).
Patients with documented Ps. aeruginosa infections received adjunctive therapy with ceftazidime or piperacillin and tazobactam sodium (for those receiving levofloxacin) or an aminoglycoside (for those receiving the comparator regimen); those with suspected oxacillin-resistant S. aureus (ORSA; previously known as methicillin-resistant S. aureus or MRSA) received concomitant vancomycin. The overall clinical success rate 3-15 days after completion of therapy was 58.% for those receiving levofloxacin and 60.% for those receiving the comparator regimen; the overall microbiologic eradication rate was 66. and 60.%, respectively.
Skin and Skin Structure Infections
Levofloxacin is used in adults for the treatment of mild to moderate uncomplicated skin and skin structure infections caused by susceptible S. aureus or S. pyogenes (group A b-hemolytic streptococci). The drug has been effective in the treatment of abscesses, cellulitis, furuncles, impetigo, pyoderma, and wound infections. In 2 controlled studies, oral levofloxacin was as effective as oral ciprofloxacin in the treatment of mild to moderate skin infections caused by susceptible bacteria, mainly S. aureus and S. pyogenes. Levofloxacin resulted in a bacteriologic cure rate of 93.2-97.5% in patients with mild to moderate skin and skin structure infections. Levofloxacin also is used in adults for the treatment of complicated skin and skin structure infections caused by susceptible S. aureus (oxacillin-susceptible strains), Enterococcus faecalis, S. pyogenes, or Proteus mirabilis.
Urinary Tract Infections and Prostatitis
Uncomplicated Urinary Tract Infections
Levofloxacin is used in adults for the treatment of mild to moderate uncomplicated urinary tract infections (UTIs) caused by susceptible E. coli, K. pneumoniae, or S. saprophyticus.
Complicated Urinary Tract Infections
Levofloxacin is used in adults for the treatment of mild to moderate complicated UTIs caused by susceptible E. faecalis, Enterobacter cloacae, E. coli, K. pneumoniae, P. mirabilis, or Ps. aeruginosa and mild to moderate acute pyelonephritis caused by susceptible E. coli. In controlled clinical studies, levofloxacin therapy was as effective as ciprofloxacin or lomefloxacin in the treatment of complicated UTIs or pyelonephritis. In one study in adults with complicated UTIs, bacterial eradication 5-9 days following completion of therapy was evident in 93% of patients with E. coli infection, 97% of those with K. pneumoniae infection, and 90% of those with P. mirabilis infection.
Prostatitis
Levofloxacin is used in adults for the treatment of chronic prostatitis caused by susceptible E. coli, E. faecalis, or S. epidermidis. In one double-blind controlled study, adults with prostatitis were randomized to receive a 28-day regimen of oral levofloxacin (500 mg once daily) or ciprofloxacin (500 mg twice daily). The overall microbiologic eradication rate 5-18 days after completion of treatment was 75% in those who received levofloxacin and 76.% in those who received ciprofloxacin. In those with infections caused by E. coli, E. faecalis, or S. epidermidis, the eradication rate was 93.3,72.2 or 81.8%, respectively, in those who received levofloxacin and 81., or 78.%, respectively, in those who received ciprofloxacin.
GI Infections
Travelers' Diarrhea
Oral levofloxacin is used in the treatment of travelers' diarrhea. The principal cause of travelers' diarrhea is infection with enterotoxigenic E. coli, but other infectious agents (e.g., Shigella, Salmonella, Campylobacter spp, Vibrio parahaemolyticus) also have been associated with the disease.
Treatment of travelers' diarrhea depends on the severity of the illness. In individuals with mild to moderate disease, replacement therapy with oral fluids and electrolytes may be sufficient, although therapy with nonspecific or antimotility agents (e.g., bismuth subsalicylate, loperamide) may be useful for temporary relief of associated symptoms (e.g., abdominal cramps, diarrhea). Travelers who develop diarrhea with at least 3 loose stools in an 8-hour period, especially if associated with nausea, vomiting, abdominal cramps, fever, or bloody stools, may benefit from short-term treatment with an anti-infective agent. An effective anti-infective agent can shorten a typical 3- to 5-day illness to 1-1. days. When use of an anti-infective agent is indicated for treatment of travelers' diarrhea, ciprofloxacin, levofloxacin, norfloxacin, or ofloxacin generally is recommended. Some clinicians suggest that azithromycin can be used as an alternative agent in children and pregnant women and may be a drug of choice for travelers in areas with a high prevalence of Campylobacter resistant to fluoroquinolones (e.g., Thailand).
Co-trimoxazole also can be used for the treatment of travelers' diarrhea in children and pregnant women who cannot receive fluoroquinolones; however, resistance to co-trimoxazole has been reported in many areas. Efficacy of anti-infective therapy may depend on the etiologic agent and its susceptibility to anti-infectives. Nausea and vomiting without diarrhea should not be treated with anti-infectives. Travelers should consult a physician, rather than attempt self-medication, if the diarrhea is severe or fails to respond to several days of therapy, the stools contain blood and/or mucus, fever with shaking chills occurs, or dehydration and persistent diarrhea develop.
Because travelers' diarrhea is a relatively nonthreatening illness that is usually mild and self-limiting and can be effectively treated and because of the risks of widespread use of prophylactic anti-infectives (e.g., potential adverse drug reactions, selection of resistant organisms, increased susceptibility to infections caused by these or other organisms), the US Centers for Disease Control (CDC) and most experts recommend that anti-infectives not be used prophylactically by most individuals traveling to areas of risk. In addition, although controlled studies have indicated that various anti-infectives when taken prophylactically have been 52-95% effective in preventing travelers' diarrhea in several developing areas of the world, efficacy depends on resistance patterns of pathogenic bacteria in each travel area, and such information seldom is available.
While fluoroquinolone resistance for bacteria causing travelers' diarrhea currently is least common, this could change as use of these drugs increases worldwide. The CDC states that although use of anti-infectives for prophylaxis of travelers' diarrhea in certain high-risk groups (e.g., travelers with immunosuppression or immunodeficiency) may seem reasonable, currently there are no specific data to support such prevention in these populations. (For information on prophylaxis of travelers' diarrhea in HIV-infected individuals, see Travelers' Diarrhea under Uses: GI Infections, in Ciprofloxacin 8:12.18.)
Anti-infectives that have been used for prophylaxis of travelers' diarrhea are not effective in preventing diarrhea caused by viral or parasitic infections, and use of such prophylaxis may give a false sense of security to the traveler about the risk associated with consuming certain local foods and beverages. The principal preventive measure is prudent dietary practices. If prophylaxis is used, ciprofloxacin, levofloxacin, norfloxacin, or ofloxacin can be given for a maximum of 3 weeks.
Gonorrhea and Associated Infections
Levofloxacin is one of several drugs of choice recommended for the treatment of uncomplicated gonorrhea and is one of several alternatives recommended for the treatment of disseminated gonococcal infection in adults and adolescents. The CDC states that uncomplicated cervical, urethral, or rectal gonorrhea in adults and adolescents may be treated with a single IM dose of ceftriaxone, a single oral dose of cefixime, or a single oral dose of certain fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) given in conjunction with an anti-infective regimen effective for presumptive treatment of chlamydia (e.g., a single dose of oral azithromycin or a 7-day regimen of oral doxycycline).
For the treatment of disseminated gonococcal infections in adults and adolescents, the CDC recommends a multiple-dose regimen of IM or IV ceftriaxone or, alternatively, a multiple-dose parenteral regimen of certain IV cephalosporins (cefotaxime, ceftizoxime), certain IV fluoroquinolones (ciprofloxacin, levofloxacin), or IM spectinomycin. However, fluoroquinolones should not be used for the treatment of gonococcal infections acquired in Asia or the Pacific islands (including Hawaii) and may be inadvisable for infections acquired in other areas where Neisseria gonorrhoeae with quinolone resistance have been reported (including California). For additional information on current recommendations for the treatment of gonorrhea and associated infections.
Nongonococcal Urethritis
The CDC recommends oral levofloxacin as an alternative agent for the treatment of nongonococcal urethritis. The CDC currently considers a single oral dose of azithromycin or a 7-day regimen of oral doxycycline the regimens of choice for the treatment of nongonococcal urethritis. Alternative regimens recommended by the CDC are a 7-day regimen of oral erythromycin base or ethylsuccinate or a 7-day regimen of oral ofloxacin or oral levofloxacin.
Patients treated for nongonococcal urethritis should be instructed to abstain from sexual intercourse until 7 days after initiation of treatment and to return for evaluation if symptoms persist or recur after completion of therapy; symptoms alone (without documentation of signs or laboratory evidence of urethral inflammation) are not sufficient basis for retreatment. Patients with persistent or recurrent urethritis who were not compliant with the treatment regimen or were reexposed to untreated sexual partner(s) should be retreated with the initial regimen. If the patient has recurrent and persistent urethritis, was compliant with the regimen, and reexposure can be excluded, the CDC recommends a 7-day regimen of oral erythromycin base or ethylsuccinate given in conjunction with a single 2-g dose of oral metronidazole.
Chlamydial Infections
Although levofloxacin has not been evaluated in clinical trials for the treatment of chlamydial infections, the CDC states that the drug can be considered an alternative agent for the treatment of urogenital chlamydial infections. The CDC currently considers a single oral dose of azithromycin or a 7-day regimen of oral doxycycline the regimens of choice for the treatment of urogenital chlamydial infections in adults and adolescents and recommends a 7-day regimen of oral erythromycin base or ethylsuccinate or a 7-day regimen of oral ofloxacin or oral levofloxacin as alternative regimens.
Pelvic Inflammatory Disease
Oral or IV levofloxacin is recommended for use in the treatment of acute pelvic inflammatory disease (PID). When a parenteral regimen is indicated for the treatment of PID, the CDC generally recommends a regimen of IV cefotetan or IV cefoxitin given in conjunction with IV or oral doxycycline or a regimen of IV clindamycin given in conjunction with IV or IM gentamicin; however, a regimen of IV levofloxacin given with or without IV metronidazole is one of several alternative parenteral regimens. When an oral regimen is indicated for the treatment of PID, oral levofloxacin with or without oral metronidazole is one of several regimens recommended by the CDC. Although fluoroquinolones are effective against both N. gonorrhoeae and C. trachomatis, metronidazole usually is included in fluoroquinolone regimens to provide coverage for anaerobes. For further information on treatment of PID.
Mycobacterial Infections
Treatment of Active Tuberculosis
Fluoroquinolones, including levofloxacin, have been used in multiple-drug regimens for the treatment of active tuberculosis in patients with infections caused by Mycobacterium tuberculosis resistant to first-line agents and in patients intolerant of some first-line agents.
Although the potential role of fluoroquinolones and the optimal length of therapy have not been fully defined, the CDC, ATS, and IDSA state that use of fluoroquinolones as alternative agents for the treatment of active tuberculosis can be considered in patients with relapse, treatment failure, or M. tuberculosis resistant to isoniazid and/or rifampin or when first-line drugs cannot be tolerated. It has been theorized that adding a fluoroquinolone to a first-line multiple-drug regimen possibly may enhance the bactericidal efficacy of the regimen, prevent development of resistance, or shorten the duration of treatment needed; however, the CDC, ATS, and IDSA state that fluoroquinolones should not be considered first-line agents for the treatment of tuberculosis caused by M. tuberculosis susceptible to first-line agents.
Although there is clinical experience with several fluoroquinolones in the treatment of tuberculosis, the ATS, CDC, and IDSA recommend use of gatifloxacin, levofloxacin, or moxifloxacin as second-line agents and, on the basis of cumulative experience, these experts suggest that levofloxacin may be the preferred oral fluoroquinolone when use of one of these drugs is considered necessary in the treatment of the disease.
When an alternative regimen is indicated for the treatment of active tuberculosis because of drug resistance or intolerance and when rifampin cannot be used (e.g., because of rifampin-resistant strains), the CDC, ATS, and IDSA suggest that a regimen of isoniazid, ethambutol, and a fluoroquinolone given for 12-18 months (with pyrazinamide given during at least the first 2 months) can be considered. For the treatment of pulmonary tuberculosis caused by isoniazid-resistant M. tuberculosis (with or without resistance to streptomycin), these experts suggest that adding a fluoroquinolone to a 6-month regimen of rifampin, ethambutol, and pyrazinamide can be considered for patients who have extensive disease.
For the treatment of pulmonary tuberculosis caused by isoniazid- and rifampin-resistant strains (with or without resistance to streptomycin), an 18- to 24-month regimen of a fluoroquinolone, ethambutol, pyrazinamide, a parenteral agent (e.g., streptomycin, amikacin, kanamycin, capreomycin) with or without another alternative agent can be considered. When the infection is caused by strains resistant to isoniazid, rifampin, ethambutol, and/or pyrazinamide (with or without streptomycin resistance), a 24-month regimen of a fluoroquinolone, ethambutol or pyrazinamide (if active), a parenteral agent (e.g., streptomycin, amikacin, kanamycin, capreomycin), and 2 other alternative agents can be considered.
The most recent CDC, ATS, and IDSA recommendations for the treatment of tuberculosis should be consulted for more specific information.
Anthrax
The US Working Group on Civilian Biodefense suggests that, based on in vitro data, oral levofloxacin can be considered an alternative agent for postexposure prophylaxis following suspected or confirmed exposure to aerosolized anthrax spores (inhalational anthrax) when oral ciprofloxacin and oral doxycycline are unavailable. These experts also suggest that oral levofloxacin can be considered an alternative for the treatment of inhalational anthrax when a parenteral regimen is not available (e.g., when there are supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting).
Although the CDC and other experts (e.g., US Working Group on Civilian Biodefense) recommend that treatment of inhalational anthrax be initiated with a multiple-drug parenteral regimen that includes ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective, use of these parenteral regimens may not be possible if large numbers of individuals require treatment in a mass casualty setting and it may be necessary to use an oral regimen. IV levofloxacin was included in some multiple-drug parenteral regimens that were used for the initial treatment of several patients who developed inhalational anthrax following bioterrorism-related exposures to Bacillus anthracis spores that occurred in the US during September and October 2001.
Although there are no animal or human studies to date evaluating use of levofloxacin for treatment or prophylaxis of anthrax and fluoroquinolones other than ciprofloxacin currently are not included in CDC's recommended regimens, in vitro evidence suggests that other fluoroquinolones would be as effective as ciprofloxacin in treating anthrax. For additional information on treatment of anthrax and recommendations for prophylaxis following exposure to anthrax spores.
Plague
Fluoroquinolones (e.g., ciprofloxacin, levofloxacin, ofloxacin) have been suggested as alternative agents for the treatment of plague caused by Yersinia pestis and also have been recommended for postexposure prophylaxis following a high risk exposure to Y. pestis, including exposure in the context of biologic warfare or bioterrorism. The recommendation for use of fluoroquinolones for treatment or prophylaxis of plague is based on results of in vitro and animal testing.
Although human studies are not available, results of in vitro studies indicate that levofloxacin is active against Y. pestis. For the treatment of plague, IM streptomycin (or IM or IV gentamicin) generally is considered the regimen of choice. Alternative drugs recommended for the treatment of plague when aminoglycosides are not used include IV doxycycline, IV chloramphenicol (drug of choice for plague meningitis), an IV fluoroquinolone (e.g., ciprofloxacin, levofloxacin), or co-trimoxazole (may be less effective than other alternatives).
However, an oral regimen of doxycycline (or tetracycline) or a fluoroquinolone (e.g., ciprofloxacin, levofloxacin, ofloxacin) may be substituted when the patient's condition improves or when a parenteral regimen is unavailable (e.g., when there are supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting); oral chloramphenicol is considered an alternative in these situations.
In the context of biologic warfare or bioterrorism, some experts (e.g., the US Working Group on Civilian Biodefense, US Army Medical Research Institute of Infectious Diseases) recommend that asymptomatic individuals with exposure to plague aerosol or asymptomatic individuals with household, hospital, or other close contact (within about 2 m) with an individual who has pneumonic plague receive an oral anti-infective regimen for postexposure prophylaxis; however, any exposed individual who develops a temperature of 38.°C or higher or new cough should promptly receive a parenteral anti-infective for treatment of the disease.
If postexposure prophylaxis is indicated, these experts recommend a regimen of oral doxycycline (or tetracycline) or an oral fluoroquinolone (e.g., ciprofloxacin, levofloxacin, ofloxacin); oral chloramphenicol is considered an alternative. For additional information on use of fluoroquinolones for treatment or prophylaxis of plague.
Ophthalmic Infections
For use of levofloxacin in the topical treatment of ophthalmic infections caused by susceptible organisms.