New Classification and Update on the Quinolone Antibiotics DANA E. KING, M.D., ROBB MALONE, PHARM.D., and SANDRA H.

LILLEY, PHARM.D. East Carolina University School of Medicine, Greenville, North Carolina The newer fluoroquinolones have broad-spectrum bactericidal activity, excellent oral bioavailability, good tissue penetration and favorable safety and tolerability profiles. A new four-generation classification of the quinolone drugs takes into account the expanded antimicrobial spectrum of the more recently introduced fluoroquinolones and their clinical indications. First-generation drugs (e.g., nalidixic acid) achieve minimal serum levels. Second-generation quinolones (e.g., ciprofloxacin) have increased gram-negative and systemic activity. Thirdgeneration drugs (e.g., levofloxacin) have expanded activity against grampositive bacteria and atypical pathogens. Fourth-generation quinolone drugs (currently only trovafloxacin) add significant activity against anaerobes. The quinolones can be differentiated within classes based on their pharmacokinetic properties. The new classification can help family physicians prescribe these drugs appropriately. (Am Fam Physician 2000;61:2741-8.) With the increasing number of available quinolone antibiotics, prescribing these drugs has become a challenge. Compared with older quinolones such as norfloxacin (Noroxin) and ciprofloxacin (Cipro), the newer agents have an expanded antimicrobial spectrum and new indications. The most recently released agents have significant antimicrobial activity against gram-positive streptococci, atypical pathogens and anaerobes. The new classification of quinolone antibiotics by generation can help family physicians prescribe these agents appropriately and evaluate new drugs as they are introduced.1 Recently released fluoroquinolone agents have The original quinolone antibiotics included broader antimicrobial activity, nalidixic acid (NegGram), cinoxacin (Cinobac) and including coverage against oxolinic acid (no longer available in the United gram-positive streptococci and States). The addition of fluoride to the original atypical pathogens. quinolone antibiotic compounds yielded a new class of drugs, the fluoroquinolones, which have a broader antimicrobial spectrum and improved pharmacokinetic properties.2 Enhanced antimicrobial activity has extended the use of the fluoroquinolones beyond the traditional indications for quinolone antibiotics in the treatment of urinary tract infections. The fluoroquinolones are effective in a wider variety of infectious diseases, including skin and respiratory infections.3 Because of their excellent safety and tolerability, they have become popular alternatives to penicillin and cephalosporin derivatives in the treatment of various infections. Overview of Fluoroquinolones

9 The advisory recommended that trovafloxacin therapy be reserved for infections judged to be life. the U. despite subinhibitory concentrations. confusion and dizziness).or limb-threatening. Concern about the adverse effects of quinolones on joints is based primarily on experimental evidence in young animals. more serious but less common side effects are vomiting and diarrhea.10 In contrast to aminoglycosides and beta-lactams. In one study. such as pneumonia.7 Side Effects The most common adverse The most common adverse effects of the effects of fluoroquinolones fluoroquinolones are nausea.5 Other tract and include nausea. The antibacterial effect continues for approximately two to three hours after bacteria are exposed to these drugs. some fluoroquinolones are active against dormant and replicating bacteria.S. Because tissue and fluid concentrations often exceed the serum drug concentration.The fluoroquinolones are broad-spectrum antibiotics with particular activity against gram-negative organisms.11. The fluoroquinolones are bactericidal antibiotics that act by specifically targeting DNA gyrase.000 children who received ciprofloxacin. However. involve the gastrointestinal which occur in 3 to 6 percent of recipients. especially Pseudomonas aeruginosa. Bacterial Resistance Gram-positive and gram-negative bacteria have been reported to be resistant to quinolones.4-6 Fluoroquinolones are usually well tolerated. The duration of the postantibiotic effect may be increased with longer bacterial drug exposure and higher drug concentrations. they can have serious adverse effects. These agents are well absorbed when given orally. vomiting and diarrhea. with few side effects.8 In June 1999. these antibiotics are particularly useful for certain infections. central nervous system effects (headache. phototoxicity (more common with lomefloxacin [Maxaquin] and sparfloxacin [Zagam]). Food and Drug Administration (FDA) issued a public health advisory warning about the risk of liver toxicity with trovafloxacin after 14 cases of acute liver failure were associated with its use. The accumulation of several bacterial mutations (DNA gyrase and bacterial permeability) has been associated with the development of very high minimum inhibitory . decreased outer membrane permeability or the development of efflux mechanisms.5 Fluoroquinolones exhibit a postantibiotic effect following bacterial exposure to inhibitory concentrations. cardiotoxicity (sparfloxacin) and hepatotoxicity (trovafloxacin [Trovan]). with treatment initiated only in the inpatient setting and when the benefits of trovafloxacin outweigh the risks. no arthropathies were observed in more than 1. These drugs are not recommended for use in patients younger than 18 years or in pregnant or lactating women.12 This resistance appears to be the result of one of three mechanisms: alterations in the quinolone enzymatic targets (DNA gyrase). however.

This resistance mechanism is shared with antimicrobial agents structurally unrelated to the quinolones. Some infectious disease specialists have become concerned about the overuse of fluoroquinolones. this agent has the broadest spectrum of activity of the currently available quinolones. Trovafloxacin is the fluoroquinolone with the most potent anaerobic activity. the newest fluoroquinolones have enhanced activity against gram-positive bacteria with only a minimal decrease in activity against gram-negative bacteria. Family physicians should always follow the principle of using the drug with the narrowest spectrum and the least toxicity. Six new fluoroquinolones have been introduced in the United States during the past five years. overuse is quite easy.6. such as the beta-lactams. Enterobacteriaceae species and P. Sparfloxacin has even greater activity against Mycoplasma species. and grepafloxacin (Rexar) and trovafloxacin were introduced in 1997.1. Cross-resistance among the quinolones is expected. including activity against Bacteroides species. Because of the broad spectrum and oral availability of these agents. as well as good activity against Mycoplasma and Chlamydia species. aureus and Enterococcus species. Levofloxacin (Levaquin) and sparfloxacin became available in 1996. tetracyclines and chloramphenicol (Chloromycetin). S.15 Sparfloxacin has a further expanded spectrum of activity that includes some activity against anaerobes. As a result. Compared with ciprofloxacin (the prototypical agent of the original fluoroquinolones). the bacterial susceptibility and pharmacokinetic profiles of each quinolone should be considered in determining the effectiveness of specific agents.6.7 The first fluoroquinolones were widely used because they were the only orally administered agents available for the treatment of serious infections caused by gram-negative organisms.2 Broadened Antimicrobial Activity The original fluoroquinolone agents were introduced in the late 1980s. aeruginosa. ciprofloxacin became the most frequently used antibiotic throughout the world.16 .11 Resistance to quinolones can also develop because of alterations in bacterial permeability and the development of efflux pumps. as well as a wide range of indications. pneumoniae.13 Their expanded gram-positive activity is especially important because it includes significant activity against Streptococcus pneumoniae. but the extent to which the minimum inhibitory concentration is affected varies from agent to agent. grepafloxacin was voluntarily withdrawn because of the possibility of torsades de pointes occurring with its use.14. In December 1999. Shortly thereafter.11 Levofloxacin has enhanced activity against S. Therefore.concentrations to ciprofloxacin in isolates of Staphylococcus aureus. Gatifloxacin (Tequin) and moxifloxacin (Avelox) became available in early 2000. including Pseudomonas species.

2.3 Consequently.18 . ciprofloxacin.17 Significant hepatic disease may increase the elimination halflife of trovafloxacin.5 Distribution of the fluoroquinolones into respiratory tract tissues and fluids is of particular interest because of the activity of these agents against common respiratory pathogens. because of the formation of insoluble drug cationic chelate complexes in the gastrointestinal tract. bronchial. 43 percent is excreted unchanged in the feces. lomefloxacin.18 Approximately 50 percent of a trovafloxacin dose is conjugated in the liver. Dosage adjustments are required in patients with mild to moderate cirrhosis.or twice-daily dosing. magnesium. lung. nasal. gall bladder. enoxacin (Penetrex). may be as much as 25 times higher than serum drug concentrations. The quinolones vary with respect to the relative contribution of renal and nonrenal pathways for their elimination. Because sucralfate (Carafate) contains aluminum. such as ciprofloxacin and ofloxacin (Floxin). prostate. norfloxacin. calcium. the oral route is generally preferred in most situations.6 Renal and nonrenal (gastrointestinal or hepatic) mechanisms are responsible for the elimination of nalidixic acid. 4. administering the usual dose at an extended interval is recommended. Peak serum concentrations obtained after oral administration are very near those achieved with intravenous administration. Consequently.3. these agents are especially useful in treating urinary tract infections. Because the fluoroquinolones have a large volume of distribution. it can also reduce absorption of the quinolones.4-6 Urine drug concentrations of some fluoroquinolones. bile and genital tract tissues. cinoxacin. and hospitalized patients should be switched from intravenous to oral formulations as soon as oral medications can be tolerated.5. Only ofloxacin and levofloxacin are exclusively eliminated by the kidney. Trovafloxacin is eliminated primarily by hepatic mechanisms. Penetration is particularly high in renal. Absorption of orally administered fluoroquinolones is significantly decreased when these agents are coadministered with aluminum.17 The long half-lives of the newer fluoroquinolones allow once. They are rapidly and almost completely absorbed from the gastrointestinal tract. moxifloxacin and sparfloxacin. In most instances. Adequate spacing of administration times has not been determined. No data are available on patients with severe liver disease. gatifloxacin. Trovafloxacin penetrates noninflamed meninges and may have a future role in the treatment of bacterial meningitis. and coadministration of quinolones and sucralfate should be avoided. Dosage adjustments based on estimated creatinine clearance values must be made for the agents with significant renal elimination. they concentrate in tissues at levels that often exceed serum drug concentrations.10 The problem can be overcome largely by administering products containing these metal ions at least four hours before or two hours after oral administration of a fluoroquinolone.Clinically Important Pharmacokinetic Parameters The newer fluoroquinolone antibiotics also have improved pharmacokinetic parameters compared with the original quinolones. iron or zinc.

However. TABLE 1 Classification of Quinolone Antibiotics Classification Agents First Antimicrobial spectrum General clinical indications* Uncomplicated Nalidixic acid Gram-negative . dosage adjustment based on age alone is not recommended.Increased serum fluoroquinolone concentrations have been noted in the elderly. The usual cause is the somewhat decreased volume of distribution and decreased renal function in older persons.

some grampositive organisms (including Staphylococcus aureus but not Streptococcus pneumoniae) and some atypical pathogens Same as for secondgeneration agents plus expanded grampositive coverage (penicillin-sensitive and penicillin-resistant S. pelvic infections *--These indications may not correlate with those labeled by the U. skin and soft tissue infections Third generation Levofloxacin (Levaquin) Sparfloxacin (Zagam) Gatifloxacin (Tequin) Moxifloxacin (Avelox) Acute exacerbations of chronic bronchitis.and thirdgeneration agents (excluding complicated urinary tract infections and pyelonephritis) plus intra. 9. 11 through 13 and 19. second. prostatitis. Information from references 1. New Classification of Quinolones Fourth generation Trovafloxacin Same as for third(Trovan) generation agents plus broad anaerobic coverage . Food and Drug Administration.abdominal infections. nosocomial pneumonia. sexually transmitted diseases.S. community-acquired pneumonia Same as for first-. pneumoniae) and expanded activity against atypical pathogens urinary tract infections Second generation Uncomplicated and complicated urinary tract infections and pyelonephritis. 5 through 7.generation (NegGram) Cinoxacin (Cinobac) Norfloxacin (Noroxin) Lomefloxacin (Maxaquin) Enoxacin (Penetrex) Ofloxacin (Floxin) Ciprofloxacin (Cipro) organisms (but not Pseudomonas species) Gram-negative organisms (including Pseudomonas species).

cinoxacin (Cinobac). gramnegative bacterial infections Infectious diarrhea Typhoid fever Prostatitis Acute sinusitis Ciprofloxacin Ciprofloxacin Ciprofloxacin Norfloxacin. moxifloxacin (Avelox). gatifloxacin Lower respiratory tract Lomefloxacin. levofloxacin. ciprofloxacin. chronic bronchitis moxifloxacin. trovafloxacin (Trovan)* Complicated urinary tract infections and pyelonephritis Norfloxacin.11-13.S. gatifloxacin (Tequin). a significant new group of pathogens is added to the coverage. trovafloxacin* Acute exacerbations of Levofloxacin. levofloxacin (Levaquin). TABLE 2 Indications for Quinolone Antibiotics Labeled by the U. enoxacin (Penetrex). lomefloxacin. ciprofloxacin. ciprofloxacin (Cipro). ofloxacin.1 Drugs in each group are similar in antimicrobial activity. gatifloxacin. trovafloxacin* infections Urethral and cervical gonococcal infections Norfloxacin. gatifloxacin. ciprofloxacin. trovafloxacin* Ciprofloxacin.The new classification of quinolone antibiotics takes into account the expanded antimicrobial spectrum of the newer fluoroquinolones and their clinical indications (Tables 11. lomefloxacin (Maxaquin). tract infections norfloxacin (Noroxin).9. ofloxacin. Food and Drug Administration Indications Agents Uncomplicated urinary Nalidixic acid (NegGram). ciprofloxacin. ofloxacin. ofloxacin (Floxin). Introduced in 1997. trovafloxacin* chlamydial and gonnococcal infections Bone and joint infections.19 and 220). trovafloxacin* . gatifloxacin. trovafloxacin* Urethral and cervical Ofloxacin. ofloxacin. sparfloxacin (Zagam). this classification is a useful tool for physicians to use when empirically prescribing these drugs or evaluating new agents introduced to the market. levofloxacin.5-7. enoxacin. enoxacin. levofloxacin. trovafloxacin* infections (limited) Skin and skin-structure Ofloxacin. With each successive generation.

2-6.or limb-threatening infections. headache (3 to 44 percent of recipients).Community-acquired pneumonia Intra-abdominal infections Levofloxacin. The drugs can be further differentiated based on available formulations.9 Information from Drug facts and comparisons: loose-leaf information service. moxifloxacin. With some exceptions. sparfloxacin.5 Oral (Maxaquin) hours .19 TABLE 3 Distinguishing Characteristics of Quinolone Antibiotics Class and agent Halflife* Dosage Significant Route of adjustment adverse administration required effects† Significant drug interactions‡ First generation Nalidixic acid 60 to Oral (NegGram) 90 minutes Cinoxacin (Cinobac) 1.14.3 to 5. significant adverse effects and significant drug interactions (Table 3). required dosage adjustments in renal or hepatic disease. Louis: Facts and Comparisons. trovafloxacin* Trovafloxacin* Gynecologic and pelvic Trovafloxacin* infections Nosocomial pneumonia Trovafloxacin* *--Treatment with trovafloxacin is reserved for life. gatifloxacin. Wolters Kluwer Company.5 hours Oral Renal impairment Renal impairment Lomefloxacin 7 to 8.1 to 2. agents in the four fluoroquinolone classes can also be grouped by their clinical indications.10.17.15. Warfarin (Coumadin) Second generation Norfloxacin (Noroxin) 2.7 hours Oral Renal impairment Renal impairment Hypersensitivity (fewer than 3 percent of recipients) Warfarin.8. cyclosporine (Sandimmune) Phototoxicity. 2000:1280-93. St.

intravenous Renal impairment Sparfloxacin (Zagam) 21 hours Oral Renal impairment . QTinterval prolongation. including class I antiarrhythmics. theophylline. vomiting. theophylline. torsades des pointes Drugs that prolong the QT interval. cisapride (Propulsid). cyclosporine. bismuth subsalicylate. Warfarin.4 Oral.6 percent of recipients). glyburide (Micronase) Headache. nausea (5. intravenous Renal or Insomnia (13 hepatic percent of impairment recipients) (patients with severe disease) Renal impairment Ciprofloxacin 3 to 5.§ pentamidine (Pentam) and Third generation Levofloxacin (Levaquin) 6 hours Oral.3 to 7 Oral hours Renal or hepatic impairment (patients with advanced cirrhosis) Phototoxicity (mild) Warfarin.abdominal pain (11 percent). abdominal pain caffeine. (Cipro) hours intravenous Nausea. diarrhea Phototoxicity (8 percent of recipients). ranitidine (Zantac). phenothiazines. tricyclic antidepressants. nausea (6. caffeine Warfarin Ofloxacin (Floxin) 5 to 8 hours Oral.6 percent) Enoxacin (Penetrex) 3.

calcium and zinc.21. insomnia. First Generation The first-generation agents include cinoxacin and nalidixic acid. Ciprofloxacin is the most potent fluoroquinolone against P. †--All quinolones cause nausea. Second-generation agents include ciprofloxacin. antacids containing aluminum or magnesium. ‡--All quinolones interact with sucralfate (Carafate). These agents are not recommended for use in patients with poor renal function because of significantly decreased urine concentrations.22 . cisapride will be available only to patients who meet specific clinical eligibility criteria for a limited-access protocol. candidal vaginitis (1 to 10 percent) *--Half-lives are significantly increased for renally eliminated compounds.8 (Trovan) hours Alatrofloxacin (Trovan IV) Oral Intravenous Dizziness (2. Information from references 2 through 6. 2000. use of these drugs has been restricted to the treatment of uncomplicated urinary tract infections. 10. Compared with first-generation drugs and considered as a group. intravenous 12 hours Oral Renal impairment Hepatic impairment Hepatic impairment (patients with mild to moderate cirrhosis) QT-interval prolongation Same as for sparfloxacin Same as for sparfloxacin Fourth generation Trovafloxacin 7. 14. §--As of July 14. sexually transmitted diseases. these agents have broader clinical applications in the treatment of complicated urinary tract infections and pyelonephritis. Cinoxacin and nalidixic acid require more frequent dosing than the newer quinolones. citrate (Bicitra) severe hepatotoxicity (rare). iron. and they are more susceptible to the development of bacterial resistance. headache and dizziness (3 percent or more of recipients). as well as some gram-positive and atypical pathogen coverage. 17 and 19. tendon rupture and cartilage damage are considered a possible effect of any quinolone. selected pneumonias and skin infections. Because minimal serum levels are achieved.erythromycin Gatifloxacin (Tequin) Moxifloxacin (Avelox) 7 hours Oral. citric to 11 percent of acidsodium recipients). which are the oldest and least often used quinolones.4 Morphine. 8.10 Second Generation The second-generation quinolones have increased gram-negative activity. norfloxacin and ofloxacin. lomefloxacin. 15.2. enoxacin. aeruginosa.

Sparfloxacin carries a significant risk of phototoxicity. it should be stressed that S. It also retains activity against Pseudomonas species comparable to that of ciprofloxacin.20 Levofloxacin (the more active component of the ofloxacin racemic mixture12. moxifloxacin and sparfloxacin. pneumoniae. phenothiazines and class I antiarrhythmics.19 Although the third-generation quinolones retain broad gram-negative coverage. Gatifloxacin also has FDA-labeled indications for urinary tract infections and gonorrhea.Because of its good penetration into bone. Although the FDA has labeled some second-generation quinolones for the treatment of lower respiratory tract infections and acute sinusitis.17. Fourth Generation Trovafloxacin.12. Third Generation The third-generation quinolones currently include levofloxacin. such as tricyclic antidepressants. particularly penicillin-sensitive and penicillin-resistant S. Because of their expanded antimicrobial spectrum.21.23 Grepafloxacin. These agents are separated into a third class because of their expanded activity against gram-positive organisms. However. Consequently. Ciprofloxacin and ofloxacin are the most widely used second-generation quinolones because of their availability in oral and intravenous formulations and their broad set of FDA-labeled indications. Of the second-generation agents. pneumoniae is frequently resistant to agents in this class.21) and gatifloxacin are available in oral and intravenous formulations. levofloxacin does not affect the QT interval. adds significant antimicrobial activity against anaerobes while maintaining the gram-positive and gramnegative activity of the third-generation quinolones. they are less active than ciprofloxacin against Pseudomonas species. which are their primary FDA-labeled indications. secondgeneration quinolones are not the drugs of first choice for lower respiratory tract infections and acute sinusitis. currently the only member of the fourth-generation class.18 .6. gatifloxacin. the FDA recommends that all of these drugs should be avoided in patients who are taking drugs that are known to prolong the QT interval. ofloxacin has the greatest activity against Chlamydia trachomatis. sparfloxacin and moxifloxacin have been reported to cause prolongation of the QT interval. acute sinusitis and acute exacerbations of chronic bronchitis. and atypical pathogens such as Mycoplasma pneumoniae and Chlamydia pneumoniae. orally administered ciprofloxacin is a useful alternative to parenterally administered antibiotics for the treatment of osteomyelitis caused by susceptible organisms. third-generation quinolones are useful in the treatment of community-acquired pneumonia. gatifloxacin has not.24 In contrast.

Septra) for the treatment of uncomplicated urinary tract infections or doxycycline (Vibramycin) for the treatment of acute exacerbations of chronic bronchitis.9 Final Comment Fluoroquinolones are more expensive than first-line agents such as trimethoprimsulfamethoxazole (Bactrim. the drug was originally labeled by the reserved for inpatient treatment FDA for the treatment of a wide spectrum of of life. hepatotoxicity.18 Because of concern about infections. this agent should be published. trovafloxacin therapy should be reserved for life. the use of orally administered fluoroquinolones (when indicated) instead of intravenously administered antibiotics may provide significant advantages in terms of reduced hospitalization or home health care costs. intravenous formulation. The average wholesale costs of orally and intravenously administered quinolones are provided in Table 4. Although the findings of Because of the risk of hepatic few clinical trials on trovafloxacin have been toxicity. TABLE 4 Cost of Fluoroquinolone Therapy Agent Usual dosage Norfloxacin (Noroxin) 400 mg twice daily orally Lomefloxacin (Maxaquin) 400 mg per day orally Enoxacin (Penetrex) 200 to 400 mg twice daily orally Ofloxacin (Floxin) 200 to 400 mg twice daily orally 400 mg every 12 hours intravenously Ciprofloxacin (Cipro) 250 to 750 mg twice daily orally 400 mg every 12 hours intravenously Levofloxacin (Levaquin) 250 to 500 mg per day orally 500 mg every 24 hours intravenously Cost* $ 68 66 62 to 65 75 to 94 158 68 to 80 180 69 to 81 119 .Trovafloxacin is the Trovafloxacin is available in an oral tablet and as fluoroquinolone with the most the prodrug alatrofloxacin (Trovan IV) in an potent anaerobic activity. However.or limb-threatening infectious diseases. and the drug should be taken for no longer than 14 days.or limb-threatening infections requiring inpatient treatment (hospital or long-term care facility).

SANDRA H... He completed a family practice residency at the University of Maryland School of Medicine.D. Address correspondence to Dana E.. he was a pharmacotherapy resident in primary care in the Department of Family Medicine at East Carolina University School of Medicine. Greenville.C. ROBB MALONE.D. N. PHARM. Dr. 2000. King.. Cost to the patient will be higher.C.C. N. depending on prescription filling fee. He received his doctor of pharmacy degree from the UNC at Chapel Hill School of Pharmacy. Charleston. SC 29425. Dr.D. Lilley received her pharmacy degree from the UNC at Chapel Hill School of Pharmacy and is a certified pharmacotherapy specialist. The authors thank Susan Loftin and Julie Calder for technical assistance in the preparation of the manuscript.: Medical Economics Data. Medical University of South Carolina. Greenville. and a faculty development fellowship at the University of North Carolina (UNC) at Chapel Hill School of Medicine. he was associate professor at East Carolina University School of Medicine. is outpatient pharmacist and diabetes care specialist at UNC Hospitals. is associate professor of family medicine and head of the clinical pharmacy section of the Department of Family Medicine at East Carolina University School of Medicine.D. PHARM. M. Charleston. Department of Family Medicine. Chapel Hill. Reprints are not available from the authors. Lexington. She is also a clinical associate professor at the UNC at Chapel Hill School of Pharmacy and associate director of pharmacy education for the Eastern Area Health Education Center. based on average wholesale prices in Red book. M.J. Previously. KING. is associate professor of family medicine at the Medical University of South Carolina. REFERENCES Sparfloxacin (Zagam) Gatifloxacin (Tequin) . N. LILLEY. Baltimore. Previously. King received his medical degree from the University of Kentucky College of Medicine. N. 295 Calhoun St.200 mg per day orally 67 400 mg per day orally 70 400 mg every 24 hours intravenously 114 Moxifloxacin (Avelox) 400 mg per day orally 87 Trovafloxacin (Trovan) 100 to 200 mg per day orally 59 to 72 Alatrofloxacin (Trovan IV) 200 mg every 24 hours intravenously 111 *--Estimated cost to the pharmacist (rounded to the nearest dollar) for 10 days of oral therapy or three days of intravenous treatment. Montvale. The Authors DANA E..

Quinolones: a practical review of clinical uses. Quinolone activity against anaerobes: microbiological aspects.746. 1999.htm. 9.. Clin Geriatr 1998. Lietman PS. June 9. Public health advisory. 17. Ernst EJ. Sparfloxacin and levofloxacin. 7. Acar JF. Clin Infect Dis 1997. 2000:1280-93. J Fam Pract 1996. Clin Infect Dis 1996. Owens RC. Hecht DW. Food and Drug Administration. Schacht P. .42:15-7. Drugs 1995. Ensberg M.fda. Pharmacotherapy 1999. Goldstein FW.19:21-34. Trovafloxacin: an overview. 12.22(suppl 1):1-11. Overview of the fluoroquinolone antibiotics. Emphasis on joint evaluation. Gootz TD.6(8):53-8. Chysky V. 16. Ambrose PG. 14. 8. 11. Clin Microbiol Rev 1989. Arcieri G. Med Lett Drugs Ther 1997.39(suppl B):1-14.23(suppl 1):S2-8. Trovan (trovafloxacin/alatrofloxacin mesylate). and drug interactions. 61:269-72.45(suppl 3):59-64. Echols R. Louis: Facts and Comparisons. Stevens R. Pharmacotherapy 1993.42:69-78. Self T. 103(6):67-70. Retrieved March 22. Stein GE. Infection 1991. Med Lett Drugs Ther 2000. The quinolones.: Pfizer Inc. Stein GE. Borcherding SM. from the World Wide Web: http://www. 19. In vitro susceptibility of anaerobes to quinolones in the United States. New York. Reitan JF. 18. 13.24(suppl 1):S67-73. Amsden GW. 2000. Drug facts and comparisons: loose-leaf information service. Use of newer fluoroquinolones in the elderly. Brighty KE. Havlichek DH. Hooper DC.39:41-4. 6. Garey KW.19:289-96. Kapila K. 3. The chemistry and biological profile of trovafloxacin. Stein GE. New generations of quinolones: with particular attention to levofloxacin. dosing considerations. 21.23(suppl 1):S19-24. Wexler HM. Fitton A. 20. Wolters Kluwer Company. Newer oral antimicrobials for resistant respiratory tract pathogens.1. Clin Pharmacokinet 1992. Norrby SR.13:4S-17S. Just PM. 5. 1998. N. Safety of ciprofloxacin in children: worldwide clinical experience based on compassionate use.2:378-424. Milkovich G. Nightingale CH. Trends in bacterial resistance to fluoroquinolones. Pharmacokinetics and pharmacodynamics of newer fluoroquinolones. 49(suppl 2):76-80. An overview of their pharmacology. Conn Med 1997. Drugs 1993. news/trovan/trovan-advisory. Community-acquired pneumonia: is there a preferred therapy? Med/Pharm Forum 1998. Wolfson JS. Which show the most promise? Postgrad Med 1998. Klepser ME.Y. Levofloxacin and trovafloxacin: the next generation of fluoroquinolones? Am J Health Syst Pharm 1997.54:2569-84. St. Ernst ME. 15. 2. 22.May:17-22. J Antimicrob Chemother 1997. Safety and tolerability of fluoroquinolones. Appelbaum PC. Gatifloxicin and moxifloxacin: two new fluoroquinolones. Fluoroquinolone antimicrobial agents. Clin Infect Dis 1996. Hullmann R. Quintiliani R. 10. Trovan (trovafloxacin) [Package insert]. Nicholas RA. Corley CR.

transmitted or reproduced in any medium. Fluoroquinolone toxicities. stored. Copyright © 2000 by the American Academy of Family Physicians. printed. This material may not otherwise be downloaded.: Rhône-Poulenc Rorer Pharmaceuticals Inc. Contact for copyright questions and/or permission requests. Pa. Collegeville.49(suppl 2):15963. copied. Lietman PS. non-commercial reference. Drugs 1995. whether now known or later invented. A person viewing it online may make one printout of the material and may use that printout only for his or her personal. An update. . 24. 1997. This content is owned by the AAFP.. except as authorized in writing by the AAFP. Zagam (sparfloxacin) [Product information].23.

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