New Classification and Update on the Quinolone Antibiotics

SUVASISH KUMAR SAHA

M. Pharm (DU)

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. Third-
generation drugs (e.g., levofloxacin) have expanded activity against gram-
positive 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

The fluoroquinolones are broad-spectrum antibiotics with particular activity against

gram-negative organisms, especially Pseudomonas aeruginosa. These agents are well
absorbed when given orally. Because tissue and fluid concentrations often exceed the
serum drug concentration, these antibiotics are particularly useful for certain infections,
such as pneumonia.4-6 Fluoroquinolones are usually well tolerated, with few side effects.
However, they can have serious adverse effects.7

Side Effects The most common adverse

The most common adverse effects of the effects of fluoroquinolones
fluoroquinolones are nausea, vomiting and diarrhea, involve the gastrointestinal
which occur in 3 to 6 percent of recipients.5 Other tract and include nausea,
more serious but less common side effects are vomiting and diarrhea.
central nervous system effects (headache, confusion
and dizziness), phototoxicity (more common with
lomefloxacin [Maxaquin] and sparfloxacin [Zagam]), cardiotoxicity (sparfloxacin) and
hepatotoxicity (trovafloxacin [Trovan]).

Concern about the adverse effects of quinolones on joints is based primarily on

experimental evidence in young animals. These drugs are not recommended for use in
patients younger than 18 years or in pregnant or lactating women. In one study, however,
no arthropathies were observed in more than 1,000 children who received ciprofloxacin.8

In June 1999, the U.S. 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.9 The advisory recommended that trovafloxacin
therapy be reserved for infections judged to be life- or limb-threatening, with treatment
initiated only in the inpatient setting and when the benefits of trovafloxacin outweigh the
risks.

The fluoroquinolones are bactericidal antibiotics that act by specifically targeting DNA
gyrase.10 In contrast to aminoglycosides and beta-lactams, some fluoroquinolones are
active against dormant and replicating bacteria.5 Fluoroquinolones exhibit a postantibiotic
effect following bacterial exposure to inhibitory concentrations. The antibacterial effect
continues for approximately two to three hours after bacteria are exposed to these drugs,
despite subinhibitory concentrations. The duration of the postantibiotic effect may be
increased with longer bacterial drug exposure and higher drug concentrations.

Bacterial Resistance
Gram-positive and gram-negative bacteria have been reported to be resistant to
quinolones.11,12 This resistance appears to be the result of one of three mechanisms:
alterations in the quinolone enzymatic targets (DNA gyrase), decreased outer membrane
permeability or the development of efflux mechanisms.
The accumulation of several bacterial mutations (DNA gyrase and bacterial permeability)
has been associated with the development of very high minimum inhibitory
concentrations to ciprofloxacin in isolates of Staphylococcus aureus, Enterobacteriaceae
species and P. aeruginosa.11

Resistance to quinolones can also develop because of alterations in bacterial permeability

and the development of efflux pumps. This resistance mechanism is shared with
antimicrobial agents structurally unrelated to the quinolones, such as the beta-lactams,
tetracyclines and chloramphenicol (Chloromycetin).

Cross-resistance among the quinolones is expected, but the extent to which the minimum
inhibitory concentration is affected varies from agent to agent. Therefore, the bacterial
susceptibility and pharmacokinetic profiles of each quinolone should be considered in
determining the effectiveness of specific agents.2

Broadened Antimicrobial Activity

The original fluoroquinolone agents were introduced in the late 1980s. Shortly thereafter,
ciprofloxacin became the most frequently used antibiotic throughout the world.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,
including Pseudomonas species.

Some infectious disease specialists have become concerned about the overuse of
fluoroquinolones. Because of the broad spectrum and oral availability of these agents,
overuse is quite easy. 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. Levofloxacin (Levaquin) and sparfloxacin became available in 1996, and
grepafloxacin (Rexar) and trovafloxacin were introduced in 1997. Gatifloxacin (Tequin)
and moxifloxacin (Avelox) became available in early 2000. In December 1999,
grepafloxacin was voluntarily withdrawn because of the possibility of torsades de pointes
occurring with its use.

Compared with ciprofloxacin (the prototypical agent of the original fluoroquinolones),

the newest fluoroquinolones have enhanced activity against gram-positive bacteria with
only a minimal decrease in activity against gram-negative bacteria.6,13 Their expanded
gram-positive activity is especially important because it includes significant activity
against Streptococcus pneumoniae.1,11

Levofloxacin has enhanced activity against S. pneumoniae, S. aureus and Enterococcus

species, as well as good activity against Mycoplasma and Chlamydia species.14,15
Sparfloxacin has a further expanded spectrum of activity that includes some activity
against anaerobes. Sparfloxacin has even greater activity against Mycoplasma species.
Trovafloxacin is the fluoroquinolone with the most potent anaerobic activity, including
activity against Bacteroides species. As a result, this agent has the broadest spectrum of
activity of the currently available quinolones, as well as a wide range of indications.6,16

Clinically Important Pharmacokinetic Parameters

The newer fluoroquinolone antibiotics also have improved pharmacokinetic parameters

compared with the original quinolones. They are rapidly and almost completely absorbed
from the gastrointestinal tract. Peak serum concentrations obtained after oral
administration are very near those achieved with intravenous administration.3
Consequently, the oral route is generally preferred in most situations, and hospitalized
patients should be switched from intravenous to oral formulations as soon as oral
medications can be tolerated.

Absorption of orally administered fluoroquinolones is significantly decreased when these

agents are coadministered with aluminum, magnesium, calcium, iron or zinc, because of
the formation of insoluble drug cationic chelate complexes in the gastrointestinal tract.3,10
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.
Because sucralfate (Carafate) contains aluminum, it can also reduce absorption of the
quinolones. Adequate spacing of administration times has not been determined, and
coadministration of quinolones and sucralfate should be avoided.

Because the fluoroquinolones have a large volume of distribution, they concentrate in

tissues at levels that often exceed serum drug concentrations. Penetration is particularly
high in renal, lung, prostate, bronchial, nasal, gall bladder, bile and genital tract tissues.4-6
Urine drug concentrations of some fluoroquinolones, such as ciprofloxacin and ofloxacin
(Floxin), may be as much as 25 times higher than serum drug concentrations.
Consequently, these agents are especially useful in treating urinary tract infections.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. Trovafloxacin penetrates noninflamed meninges and may have a future role in
the treatment of bacterial meningitis. 4,17

The long half-lives of the newer fluoroquinolones allow once- or twice-daily dosing. The
quinolones vary with respect to the relative contribution of renal and nonrenal pathways
for their elimination. Only ofloxacin and levofloxacin are exclusively eliminated by the
kidney.2,5,6 Renal and nonrenal (gastrointestinal or hepatic) mechanisms are responsible
for the elimination of nalidixic acid, cinoxacin, norfloxacin, ciprofloxacin, enoxacin
(Penetrex), lomefloxacin, gatifloxacin, moxifloxacin and sparfloxacin. Dosage
adjustments based on estimated creatinine clearance values must be made for the agents
with significant renal elimination. In most instances, administering the usual dose at an
extended interval is recommended.
Trovafloxacin is eliminated primarily by hepatic mechanisms.18 Approximately 50
percent of a trovafloxacin dose is conjugated in the liver; 43 percent is excreted
unchanged in the feces.17 Significant hepatic disease may increase the elimination half-
life of trovafloxacin. Dosage adjustments are required in patients with mild to moderate
cirrhosis. No data are available on patients with severe liver disease.18

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

New Classification of Quinolones

The new classification of quinolone antibiotics takes into account the expanded
antimicrobial spectrum of the newer fluoroquinolones and their clinical indications
(Tables 11,5-7,9,11-13,19 and 220). Introduced in 1997, this classification is a useful tool for
physicians to use when empirically prescribing these drugs or evaluating new agents
introduced to the market.1 Drugs in each group are similar in antimicrobial activity. With
each successive generation, a significant new group of pathogens is added to the
coverage.

TABLE 2
Indications for Quinolone Antibiotics Labeled by the U.S. Food and Drug
Administration
Indications Agents
Uncomplicated urinary Nalidixic acid (NegGram), cinoxacin (Cinobac),
tract infections norfloxacin (Noroxin), lomefloxacin (Maxaquin),
enoxacin (Penetrex), ofloxacin (Floxin), ciprofloxacin
(Cipro), levofloxacin (Levaquin), gatifloxacin
(Tequin), trovafloxacin (Trovan)*
Complicated urinary Norfloxacin, lomefloxacin, enoxacin, ofloxacin,
tract infections and ciprofloxacin, levofloxacin, gatifloxacin
pyelonephritis
Lower respiratory tract Lomefloxacin, ofloxacin, ciprofloxacin, trovafloxacin*
infections (limited)
Skin and skin-structure Ofloxacin, ciprofloxacin, levofloxacin, trovafloxacin*
infections
Urethral and cervical Norfloxacin, enoxacin, ofloxacin, ciprofloxacin,
gonococcal infections gatifloxacin, trovafloxacin*
Urethral and cervical Ofloxacin, trovafloxacin*
chlamydial and
gonnococcal infections
Bone and joint Ciprofloxacin
infections, gram-
negative bacterial
infections
Infectious diarrhea Ciprofloxacin
Typhoid fever Ciprofloxacin
 Prostatitis Norfloxacin, ofloxacin, trovafloxacin*
Acute sinusitis Ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin
(Avelox), trovafloxacin*
Acute exacerbations of Levofloxacin, sparfloxacin (Zagam), gatifloxacin,
chronic bronchitis moxifloxacin, trovafloxacin*
Community-acquired Levofloxacin, sparfloxacin, gatifloxacin, moxifloxacin,
pneumonia trovafloxacin*
Intra-abdominal Trovafloxacin*
infections
Gynecologic and pelvic Trovafloxacin*
infections
Nosocomial pneumonia Trovafloxacin*
*--Treatment with trovafloxacin is reserved for life- or limb-threatening infections.9
Information from Drug facts and comparisons: loose-leaf information service. St. Louis:
Facts and Comparisons, Wolters Kluwer Company, 2000:1280-93.

With some exceptions, agents in the four fluoroquinolone classes can also be grouped by
their clinical indications. The drugs can be further differentiated based on available
formulations, required dosage adjustments in renal or hepatic disease, significant adverse
effects and significant drug interactions (Table 3).2-6,8,10,14,15,17,19

TABLE 3
Distinguishing Characteristics of Quinolone Antibiotics
Dosage Significant Significant
Class and Half- Route of adjustment adverse drug
agent life* administration required effects† interactions‡
First generation
Nalidixic acid 60 to Oral Renal Warfarin
(NegGram) 90 impairment (Coumadin)
minutes
Cinoxacin 1.1 to Oral Renal Hypersensitivity
(Cinobac) 2.7 impairment (fewer than 3
hours percent of
recipients)
Second generation
Norfloxacin 2.3 to Oral Renal Warfarin,
(Noroxin) 5.5 impairment cyclosporine
 hours (Sandimmune)
Lomefloxacin 7 to 8.5 Oral Renal Phototoxicity,
(Maxaquin) hours impairment headache (3 to
44 percent of
recipients),
abdominal pain
(11 percent),
nausea (5.6
percent)
Enoxacin 3.3 to 7 Oral Renal or Phototoxicity Warfarin,
(Penetrex) hours hepatic (mild) ranitidine
impairment (Zantac),
(patients bismuth
with subsalicylate,
advanced theophylline,
cirrhosis) caffeine
Ofloxacin 5 to 8 Oral, Renal or Insomnia (13 Warfarin
(Floxin) hours intravenous hepatic percent of
impairment recipients)
(patients
with severe
disease)
Ciprofloxacin 3 to 5.4 Oral, Renal Nausea, Warfarin,
(Cipro) hours intravenous impairment vomiting, theophylline,
abdominal pain caffeine,
cyclosporine,
glyburide
(Micronase)
Third generation
Levofloxacin 6 hours Oral, Renal Headache,
(Levaquin) intravenous impairment nausea (6.6
percent of
recipients),
diarrhea
Sparfloxacin 21 Oral Renal Phototoxicity (8 Drugs that
(Zagam) hours impairment percent of prolong the QT
recipients), QT- interval,
interval including class I
prolongation, antiarrhythmics,
torsades des tricyclic
pointes antidepressants,
 phenothiazines,
cisapride
(Propulsid),§
pentamidine
(Pentam) and
erythromycin
Gatifloxacin 7 hours Oral, Renal Same as for
(Tequin) intravenous impairment sparfloxacin
Moxifloxacin 12 Oral Hepatic QT-interval Same as for
(Avelox) hours impairment prolongation sparfloxacin
Fourth generation
Trovafloxacin 7.8 Oral Hepatic Dizziness (2.4 Morphine, citric
(Trovan) hours Intravenous impairment to 11 percent of acidsodium
Alatrofloxacin (patients recipients), citrate (Bicitra)
(Trovan IV) with mild to severe
moderate hepatotoxicity
cirrhosis) (rare), candidal
vaginitis (1 to
10 percent)
*--Half-lives are significantly increased for renally eliminated compounds.
†--All quinolones cause nausea, insomnia, headache and dizziness (3 percent or more of recipients);
tendon rupture and cartilage damage are considered a possible effect of any quinolone.
‡--All quinolones interact with sucralfate (Carafate), antacids containing aluminum or magnesium,
iron, calcium and zinc.
§--As of July 14, 2000, cisapride will be available only to patients who meet specific clinical
eligibility criteria for a limited-access protocol.
Information from references 2 through 6, 8, 10, 14, 15, 17 and 19.

First Generation
The first-generation agents include cinoxacin and nalidixic acid, which are the oldest and
least often used quinolones. Because minimal serum levels are achieved, use of these
drugs has been restricted to the treatment of uncomplicated urinary tract infections.

Cinoxacin and nalidixic acid require more frequent dosing than the newer quinolones,
and they are more susceptible to the development of bacterial resistance. These agents are
not recommended for use in patients with poor renal function because of significantly
decreased urine concentrations.2,10

Second Generation
The second-generation quinolones have increased gram-negative activity, as well as some
gram-positive and atypical pathogen coverage. Compared with first-generation drugs and
considered as a group, these agents have broader clinical applications in the treatment of
complicated urinary tract infections and pyelonephritis, sexually transmitted diseases,
selected pneumonias and skin infections.

Second-generation agents include ciprofloxacin, enoxacin, lomefloxacin, norfloxacin and

ofloxacin. Ciprofloxacin is the most potent fluoroquinolone against P. aeruginosa.21,22
Because of its good penetration into bone, orally administered ciprofloxacin is a useful
alternative to parenterally administered antibiotics for the treatment of osteomyelitis
caused by susceptible organisms.

Although the FDA has labeled some second-generation quinolones for the treatment of
lower respiratory tract infections and acute sinusitis, it should be stressed that S.
pneumoniae is frequently resistant to agents in this class. Consequently, second-
generation quinolones are not the drugs of first choice for lower respiratory tract
infections and acute sinusitis.

Of the second-generation agents, ofloxacin has the greatest activity against Chlamydia
trachomatis.

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.

Third Generation
The third-generation quinolones currently include levofloxacin, gatifloxacin,
moxifloxacin and sparfloxacin. These agents are separated into a third class because of
their expanded activity against gram-positive organisms, particularly penicillin-sensitive
and penicillin-resistant S. pneumoniae, and atypical pathogens such as Mycoplasma
pneumoniae and Chlamydia pneumoniae.6,12,19 Although the third-generation quinolones
retain broad gram-negative coverage, they are less active than ciprofloxacin against
Pseudomonas species.

Because of their expanded antimicrobial spectrum, third-generation quinolones are useful

in the treatment of community-acquired pneumonia, acute sinusitis and acute
exacerbations of chronic bronchitis, which are their primary FDA-labeled indications.
Gatifloxacin also has FDA-labeled indications for urinary tract infections and
gonorrhea.20 Levofloxacin (the more active component of the ofloxacin racemic
mixture12,21) and gatifloxacin are available in oral and intravenous formulations.

Sparfloxacin carries a significant risk of phototoxicity.21,23 Grepafloxacin, sparfloxacin

and moxifloxacin have been reported to cause prolongation of the QT interval;
gatifloxacin has not. However, 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, such
as tricyclic antidepressants, phenothiazines and class I antiarrhythmics.24 In contrast,
levofloxacin does not affect the QT interval.
Fourth Generation
Trovafloxacin, currently the only member of the fourth-generation class, adds significant
antimicrobial activity against anaerobes while maintaining the gram-positive and gram-
negative activity of the third-generation quinolones. It also retains activity against
Pseudomonas species comparable to that of
ciprofloxacin.17,18 Trovafloxacin is the
fluoroquinolone with the most
Trovafloxacin is available in an oral tablet and as potent anaerobic activity.
the prodrug alatrofloxacin (Trovan IV) in an Because of the risk of hepatic
intravenous formulation. Although the findings of toxicity, this agent should be
few clinical trials on trovafloxacin have been reserved for inpatient treatment
published, the drug was originally labeled by the of life- or limb-threatening
FDA for the treatment of a wide spectrum of infections.
infectious diseases.18 Because of concern about
hepatotoxicity, trovafloxacin therapy should be
reserved for life- or limb-threatening infections requiring inpatient treatment (hospital or
long-term care facility), and the drug should be taken for no longer than 14 days.9

Final Comment

Fluoroquinolones are more expensive than first-line agents such as trimethoprim-

sulfamethoxazole (Bactrim, Septra) for the treatment of uncomplicated urinary tract
infections or doxycycline (Vibramycin) for the treatment of acute exacerbations of
chronic bronchitis. However, 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. The average
wholesale costs of orally and intravenously administered quinolones are provided in
Table 4.

TABLE 4
Cost of Fluoroquinolone Therapy
Agent Usual dosage Cost*
Norfloxacin (Noroxin) 400 mg twice daily orally $ 68
Lomefloxacin (Maxaquin) 400 mg per day orally 66
Enoxacin (Penetrex) 200 to 400 mg twice daily orally 62 to 65
Ofloxacin (Floxin) 200 to 400 mg twice daily orally 75 to 94
 400 mg every 12 hours intravenously 158
Ciprofloxacin (Cipro) 250 to 750 mg twice daily orally 68 to 80
400 mg every 12 hours intravenously 180
Levofloxacin (Levaquin) 250 to 500 mg per day orally 69 to 81
500 mg every 24 hours intravenously 119
Sparfloxacin (Zagam) 200 mg per day orally 67
Gatifloxacin (Tequin) 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, based on average wholesale prices in Red
book. Montvale, N.J.: Medical Economics Data, 2000. Cost to the patient will be higher,
depending on prescription filling fee.

The authors thank Susan Loftin and Julie Calder for technical assistance in the
preparation of the manuscript.

The Authors

DANA E. KING, M.D.,

is associate professor of family medicine at the Medical University of South Carolina,
Charleston. Previously, he was associate professor at East Carolina University School of
Medicine, Greenville, N.C. Dr. King received his medical degree from the University of
Kentucky College of Medicine, Lexington. He completed a family practice residency at
the University of Maryland School of Medicine, Baltimore, and a faculty development
fellowship at the University of North Carolina (UNC) at Chapel Hill School of Medicine.

ROBB MALONE, PHARM.D.,

is outpatient pharmacist and diabetes care specialist at UNC Hospitals, Chapel Hill, N.C.
Previously, he was a pharmacotherapy resident in primary care in the Department of
Family Medicine at East Carolina University School of Medicine. He received his doctor
of pharmacy degree from the UNC at Chapel Hill School of Pharmacy.

SANDRA H. LILLEY, PHARM.D.,

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. 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,
Greenville, N.C. Dr. Lilley received her pharmacy degree from the UNC at Chapel Hill
School of Pharmacy and is a certified pharmacotherapy specialist.
Address correspondence to Dana E. King, M.D., Department of Family Medicine,
Medical University of South Carolina, 295 Calhoun St., Charleston, SC 29425.
Reprints are not available from the authors.

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