Gatifloxacin and Moxifloxacin: An In Vitro

Susceptibility Comparison to Levofloxacin,

Ciprofloxacin, and Ofloxacin Using Bacterial
Keratitis Isolates
REGIS P. KOWALSKI, MS, [M]ASCP, DEEPINDER K. DHALIWAL, MD,
LISA M. KARENCHAK, BS, [M]ASCP, ERIC G. ROMANOWSKI, MS, FRANCIS S. MAH, MD,
DAVID C. RITTERBAND, MD, AND Y. JEROLD GORDON, MD
PURPOSE:

We compared the in vitro susceptibility

patterns and the minimum inhibitory concentrations
(MICs) of gatifloxacin (GAT) and moxifloxacin (MOX)
(fourth-generation fluoroquinolones) to ciprofloxacin
(CIP) and ofloxacin (OFX) (second-generation fluoroquinolones) and levofloxacin (LEV; third-generation fluoroquinolone) using bacterial keratitis isolates. The goal
was to determine whether the fourth-generation fluoroquinolones offer any advantages over the second- and
third-generation fluoroquinolones.
DESIGN: Experimental laboratory investigation. In contrast to an epidemiologic prevalence study, this study was
designed to compare the relative susceptibility of each
bacterial group to different fluoroquinolones by deliberate selection of representative isolates that were both
susceptible and resistant to second-generation fluoroquinolones.
METHODS: In retrospect, the MICs of 177 bacterial
keratitis isolates were determined to CIP, OFX, LEV,
GAT, and MOX using E tests. A relative susceptibility
analysis was performed for each bacterial group that
included separate bacterial groups that were resistant to
Accepted for publication March 4, 2003.
InternetAdvance publication at ajo.com June 27, 2003.
From the Charles T. Campbell Ophthalmic Microbiology Laboratory,
University of Pittsburgh, Pittsburgh, Pennsylvania (R.P.K., D.K.D.,
L.M.K., E.G.R., F.S.M. Y.J.G.), and New York Eye and Ear Infirmary,
New York, New York (D.C.R.).
This work was suppoorted by The Eye and Ear Foundation of
Pittsburgh, Pittsburgh, PA, a core grant for Vision Research EY 08098
and Research to Prevent Blindness. The second author (D.K.D.) was
granted travel support for the 2002 European Congress of Cataract And
Refractive Surgery, Nice, France, by Alcon (Fort Worth, Texas).
Data from this study have been presented at the 2002 ARVO meeting
in Ft. Lauderdale, Florida; the 2002 European Cataract and Refractive
Surgery meeting in Nice, France; and the 2002 OMIG meeting in
Orlando, Florida.
Inquires to Regis P. Kowalski, MS, [M]ASCP, The Eye and Ear
Institute Bldg., Ophthalmic Microbiology, Room 642, 203 Lothrop
Street, Pittsburgh, PA 15213; fax (412) 647-5331; e-mail: kowalskirp@
msx.upmc.edu

500

2003 BY

second-generation fluoroquinolones. The NCCLS susceptibility patterns and the MICs were compared statistically. Comparing MICs, the antibiotic with the lower
MICs has greater antibacterial activity.
RESULTS: For most keratitis isolates, there were no
susceptibility differences among the five fluoroquinolones. The fourth-generation fluoroquinolones did,
however, demonstrate increased susceptibility for Staphylococcus aureus isolates that were resistant to CIP, LEV
and OFX. In general, CIP demonstrated the lowest MICs
for gram-negative bacteria. The MICs for fourth-generation fluoroquinolones were statistically lower than the
second-generation fluoroquinolones for all gram-positive
bacteria tested. Comparing the two fourth-generation
fluoroquinolones, MOX demonstrated lower MICs for
most gram-positive bacteria, whereas GAT demonstrated
lower MICs for most gram-negative bacteria.
CONCLUSIONS: Based on in vitro testing, the fourthgeneration fluoroquinolones may offer some advantages
over those currently available for the treatment of bacterial keratitis. Clinical studies will be required to confirm these results. (Am J Ophthalmol 2003;136:
500 505. 2003 by Elsevier Inc. All rights reserved.)

HE USE OF THE SECOND-GENERATION FLUORO-

quinolones ciprofloxacin and ofloxacin has provided

successful medical coverage for the treatment of
bacterial keratitis.1,2 These fluoroquinolones provide excellent activity against the most frequent gram-positive
and gram-negative ocular pathogens. Antibiotic resistance
of Staphylococcus aureus3 and Pseudomonas aeruginosa4 keratitis isolates to the second-generation fluoroquinolones
has increased the interest in the fourth-generation fluoroquinolones for future coverage of bacterial keratitis.
Moxifloxacin and gatifloxacin are two fourth-generation
fluoroquinolones that are approved for systemic therapy and
are undergoing development for topical ophthalmic therapy.

ELSEVIER INC. ALL

RIGHTS RESERVED.

0002-9394/03/$30.00
doi:10.1016/S0002-9394(03)00294-0

In this in vitro study, the fourth-generation fluoroquinolones (moxifloxacin and gatifloxacin) were compared with
the second-generation fluoroquinolones (ciprofloxacin and
ofloxacin) and a third-generation fluoroquinolone levofloxacin. Although this report labels levofloxacin as a
third-generation fluoroquinolone, controversy still exists
on whether levofloxacin is a second-generation fluoroquinolone because the chemical structure is the same as the
active structure of ofloxacin. The minimum inhibitory
concentrations were determined for bacterial keratitis
isolates to the five fluoroquinolones, and the cumulative
susceptibilities and minimum inhibitory concentrations
were compared to determine whether the fourth-generation fluoroquinolones offered any advantages over the
second- and third-generation fluoroquinolones.

DESIGN
THE IN VITRO SUSCEPTIBILITIES AND MINIMUM INHIBITORY

concentrations of ciprofloxacin, ofloxacin, levofloxacin,

moxifloxacin, and gatifloxacin were compared in a retrospective laboratory study using bacteria isolated from
clinical cases of keratitis.

METHODS
THE MINIMUM INHIBITORY CONCENTRATIONS (g/ml) OF

177 bacterial keratitis isolates were determined to ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, and gatifloxacin using E tests. The bacterial isolates tested
represent the major pathogens that are implicated in
infectious keratitis and were selected based on the most
recently isolated for each bacterial group. All bacterial
isolates were collected from the cornea. The number
chosen to be tested was arbitrary and bacterial groups that
had less than 10 isolates were not part of the study (that is,
Enterococcus, Bacillus, Beta-hemolytic Streptococcus, Proteus,
Escherichia coli, etc.). The isolates were collected anonymously
from January 1993 through June 2001 by the Charles T.
Campbell Ophthalmic Microbiology Laboratory and stored at
76 degrees Celsius (University of Pittsburgh, Pittsburgh,
PA, Institutional Review Board no. 000943). The bacterial
groups, when applicable, were designated as fluoroquinolone
resistant or susceptible based on disk diffusion susceptibility
testing to ciprofloxacin and ofloxacin. Selection of resistance
to ciprofloxacin and ofloxacin was desired to test any possible
advantage for moxifloxacin and gatifloxacin. The isolates
included 25 isolates of Staphylococcus aureus that were resistant to ciprofloxacin and ofloxacin; 25 isolates of Staphylococcus aureus that were susceptible to ciprofloxacin and
ofloxacin; 10 isolates of coagulase negative Staphylococcus that
were resistant to ciprofloxacin and ofloxacin; 10 isolates of
coagulase negative Staphylococcus that were susceptible to
ciprofloxacin and ofloxacin; 20 isolates of Streptococcus pneumoniae; 20 isolates of Streptococcus viridans; 25 isolates of
Pseudomonas aeruginosa that were susceptible to ciprofloxacin
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COMPARISON

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and ofloxacin; 12 isolates of Pseudomonas aeruginosa that were

resistant to ciprofloxacin and ofloxacin; 10 isolates of Serratia
marcescens; 10 isolates of Hemophilus species; and 10 isolates of
Moraxella species. The ciprofloxacin-resistant isolates of
Pseudomonas aeruginosa were obtained through the New York
Eye & Ear Infirmary, New York, New York (D.C.R.) and
represent all the isolates collected before June 2001. No
ciprofloxacin-resistant Pseudomonas aeruginosa had been isolated from the cornea in Pittsburgh, Pennsylvania. The
antibiotic susceptibility of each bacterial isolate was determined by comparing the minimum inhibitory concentration
of each to the National Committee of Clinical Laboratory
Standards (NCCLS) for each fluoroquinolone antibiotic.5
The standards are based on the safe achievable concentrations of antibiotic in the serum. There are no standards for
topical ocular therapy that represent the concentrations of
antibiotics in the ocular tissue but the serum standards can be
used to interpret susceptibility if it is assumed the antibiotic
concentrations in the ocular tissues are equal or greater than
the antibiotic concentrations in the serum. For an isolate to
be susceptible to ciprofloxacin, the minimum inhibitory
concentration was to be less than or equal to 1 g/ml. For an
isolate to be susceptible to ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin, the minimum inhibitory concentration was to be less than or equal to 2 g/ml. For the
cumulative antibiotic susceptibility of each bacterial group,
the number of susceptible isolates was divided by the number
of susceptible and nonsusceptible isolates. The susceptibility
patterns were statistically analyzed with either the chisquared test or the Monte Carlo randomization test.
The data analysis was determined for each bacterial
group and does not represent an epidemiologic study of the
entire population because some minor bacterial groups
were not included (that is, Enterococcus, Bacillus, Betahemolytic Streptococcus, Proteus, E. coli, and so forth). The
minimum inhibitory concentrations (g/ml) were analyzed nonparametrically as discrete data using the KruskalWallis test. The analysis ranked all the minimum
inhibitory concentrations from the lowest to highest and
compared the antibiotics by analysis of variance
(ANOVA) of the ranks (not the actual minimum inhibitory concentrations) using Duncans multiple comparisons
at P .05 significance. The minimum inhibitory concentrations of the Staphylococcus aureus (second-generation
resistant and susceptible) and coagulase negative Staphylococcus (second-generation resistant and susceptible) groups
were compared nonparametrically with the Mann-Whitney two-sample test. Comparing minimum inhibitory concentrations, the antibiotic with the lower minimum
inhibitory concentrations has greater antibacterial activity.

RESULTS
TABLE 1 SUMMARIZES THE DESCRIPTIVE STATISTICS OF THE

minimum inhibitory concentrations (g/ml) and susceptibility results of 177 keratitis isolates to gatifloxacin, moxiFLUOROQUINOLONES

501

TABLE 1. Descriptive Statistics of Minimum Inhibitory Concentrations (MIC) (g/ml) for Bacterial Keratitis Isolates to
Fluoroquinolone Antibiotics
n

Median

MIC90

Mode

Staphylococcus aureus-Fluoroquinolone susceptible

Moxifloxacin
25
0.032
0.047
0.032, 0.047
Gatifloxacin
25
0.094
0.22
0.064
Levofloxacin
25
0.19
0.38
0.19
Ciprofloxacin
25
0.38
0.5
0.38
Ofloxacin
25
0.5
0.75
0.5
Staphylococcus aureusFluoroquinolone resistant
Moxifloxacin
25
1.5
4.0
1.0, 1.5
Gatifloxacin
25
4.0
12.0
3.0
Levofloxacin
25
16.0
32.0
16.0, 32.0
Ciprofloxacin
25
64.0
128.0
64.0
Ofloxacin
25
64.0
64.0
64.0
coagulase negative StaphylococcusFluoroquinolone susceptible
Moxifloxacin
10
0.064
0.125
0.064
Gatifloxacin
10
0.125
0.19
0.094
Levofloxacin
10
0.19
0.19
0.19
Ciprofloxacin
10
0.22
0.38
0.19, 0.38
Ofloxacin
10
0.5
0.75
0.38, 0.5
coagulase negative StaphylococcusFluoroquinolone resistant
Moxifloxacin
10
2.5
3.0
3.0
Gatifloxacin
10
3.0
3.0
3.0
Levofloxacin
10
64.0
64.0
64.0
Ciprofloxacin
10
64.0
64.0
64.0
Ofloxacin
10
64.0
64.0
64.0
Streptococcus pneumoniae
Moxifloxacin
20
0.125
0.19
0.19
Gatifloxacin
20
0.22
0.25
0.25
Levofloxacin
20
0.75
1.0
0.75
Ciprofloxacin
20
0.75
2.0
0.38
Ofloxacin
20
2.0
4.0
1.5, 2.0
Streptococcus viridans group
Moxifloxacin
20
0.125
0.19
0.19
Gatifloxacin
20
0.25
0.38
0.38
Levofloxacin
20
0.75
1.0
1.00
Ciprofloxacin
20
1.0
4.0
0.25, 0.5, 1.0, 2.0
Ofloxacin
20
2.0
4.0
4.0
Pseudomonas aeruginosaFluoroquinolone susceptible
Moxifloxacin
25
0.5
0.75
0.25, 0.5
Gatifloxacin
25
0.25
0.38
0.19, 0.38
Levofloxacin
25
0.38
0.5
0.25, 0.38
Ciprofloxacin
25
0.094
0.125
0.094
Ofloxacin
25
0.75
1.5
0.5, 1.0
Pseudomonas aeruginosaFluoroquinolone resistant are resistant to all generations of fluoroquinolones
Serratia marcescens
Moxifloxacin
10
0.25
0.38
0.38
Gatifloxacin
10
0.25
0.38
0.25
Levofloxacin
10
0.19
0.25
0.19
Ciprofloxacin
10
0.064
0.094
0.064
Ofloxacin
10
0.5
0.75
0.5

Susceptibility

100%
100%
100%
100%
100%
68%
8%
0%
0%
0%
100%
100%
100%
100%
100%
50%
40%
10%
0%
0%
100%
100%
95%
85%
70%
100%
100%
100%
60%
55%
100%
100%
100%
100%
100%

100%
100%
100%
100%
100%

Continued on next page.

floxacin, levofloxacin, ciprofloxacin, and ofloxacin. Table

2 details the statistical comparisons of the antibiotic
susceptibilities and antibacterial activities of the second502

AMERICAN JOURNAL

generation, third-generation, and fourth-generation fluoroquinolones. In general, little difference was observed in
the susceptibility results between the second- and thirdOF

OPHTHALMOLOGY

SEPTEMBER 2003

TABLE 1. Descriptive Statistics of Minimum Inhibitory Concentrations (MIC) (g/ml) for Bacterial Keratitis Isolates to
Fluoroquinolone Antibiotics (Continued)

Haemophilus species
Moxifloxacin
Gatifloxacin
Levofloxacin
Ciprofloxacin
Ofloxacin
Moraxella species
Moxifloxacin
Gatifloxacin
Levofloxacin
Ciprofloxacin
Ofloxacin

Median

MIC90

Mode

Susceptibility

10
10
10
10
10

0.039
0.017
0.024
0.014
0.05

0.19
0.064
0.032
0.032
0.125

0.016, 0.023, 0.19

0.008
0.016
0.012
0.047

100%
100%
100%
100%
100%

10
10
10
10
10

0.047
0.032
0.047
0.032
0.125

0.047
0.032
0.064
0.064
0.19

0.047
0.032
0.064
0.032
0.125

100%
100%
100%
100%
100%

n the number of isolates tested; median the middle MIC value in the ordered array of MIC values; MIC90 the MIC that inhibits 90%
of bacterial isolates tested; mode the MIC value occurring with the greatest frequency; susceptibility is the cumulative susceptibility of the
isolates to the antibiotics based on the NCCLS serum standards.

TABLE 2. The Statistical Comparison of In Vitro Susceptibility and Antibacterial Activity Among Second-, Third-, and FourthGeneration Fluoroquinolones
Susceptibility

Gram-positive bacteria
S. aureusFQ susceptible
S. aureusFQ resistant
coag neg StaphylococcusFQ susceptible
coag neg StaphylococcusFQ resistant
Streptococcus pneumoniae
Streptococcus viridans group
Gram-negative bacteria
Pseudomonas aeruginosa-FQ susceptible
Pseudomonas aeruginosa-FQ resistant
Serratia marcescens
Haemophilus species
Moraxella species

Antibacterial Activity*

CO
OC
CO
CO
CO

All
All
All
All

CGLMO
(All resistant)
CLGMO
C G M O, G L M O,
CLMO
GCMLO

All equal

L
L
L
L
L

M
M
M
M
M

equal
equal (All resistant)
equal
equal

G
G
G
G
G

All equal
M (P 0.01) G L O C
All equal
All equal
M G L C, L C O,
M G (P 0.03) O
M G L (P 0.01) C O

MGLCO

Second Generation: ciprofloxacin (C), ofloxacin (O); third-generation: levofloxacin (L); fourth-generation: moxifloxacin (M), gatifloxacin (G).
FQ fluoroquinolone, susceptible or resistant as determined by disk diffusion testing.
*Comparing MICs, the antibiotic with the lower MICs has greater antibacterial activity.

generation fluoroquinolones compared with the fourthgeneration fluoroquinolones for most ocular bacterial
pathogens. Either they were all equally susceptible (Staphylococcus aureusfluoroquinolone susceptible, coagulase
negative Staphylococcusfluoroquinolone susceptible, coagulase negative Staphylococcusfluoroquinolone resistant,
Pseudomonas aeruginosafluoroquinolone susceptible, Serratia marcescens, Haemophilus species, Moraxella species)
or equally resistant (Pseudomonas aeruginosafluoroquinolone resistant). There were important differences for
VOL. 136, NO. 3

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specific bacterial groups, however; the fourth-generation

fluoroquinolones demonstrated greater susceptibility
than second- and third-generation fluoroquinolones (moxifloxacin for Staphylococcus aureusfluoroquinolone resistant, P .01; moxifloxacin and gatifloxacin for
Streptococcus pneumoniae compared with ofloxacin, P
.03). Finally, the Streptococcus viridans group demonstrated greater susceptibility (P .01) to gatifloxacin,
moxifloxacin, and levofloxacin than to ciprofloxacin and
ofloxacin.
FLUOROQUINOLONES

503

second one in the DNA gyrase gene, it was also predictable

that these fluoroquinolones would provide better coverage
against gram-positive bacteria that were already resistant
to current fluoroquinolones that only required a single
mutation to establish resistance.6 9 In this study, there was
a significant increase in the fourth-generation fluoroquinolones minimum inhibitory concentrations for second-generation fluoroquinolone resistant Staphylococcus isolates
compared with susceptible isolates. This may represent the
presence of a single mutation. It must be noted, however,
that other mechanisms of fluoroquinolone resistance also
exist and include efflux mechanisms, altered porin diffusion channels, and possibly plasmid-mediated transfer of
resistance.10 12
In contrast to gram-positive bacteria, the fourth-generation fluoroquinolones (moxifloxacin, gatifloxacin) offered
no apparent advantages over current fluoroquinolones
(levofloxacin, ofloxacin, or ciprofloxacin) for the treatment of gram-negative ocular bacterial pathogens. Engineering the side chains of the fluoroquinolone core
molecule for enhanced gram-positive activity actually
resulted in a slight elevations in minimum inhibitory
concentrations for gram-negative bacteria. In this study,
we determined that when second-generation fluoroquinolone resistance occurred in Pseudomonas aeruginosa, resistance was consistent across all five fluoroquinolones.
The results of our study were similar to our previous in
vitro study13 examining endophthalmitis isolates (82.8%
gram-positive, 17.2% gram-negative, n 93). The fourthgeneration fluoroquinolones were more potent (lower minimum inhibitory concentrations) than the second- and
third-generation fluoroquinolones for gram-positive bacteria but comparable for gram-negative bacteria. The study
concluded that the fourth-generation fluoroquinolones
may prove beneficial in topical surgical prophylaxis to
prevent endophthalmitis.
The role of antibiotic potency (lower minimum inhibitory concentrations) must be further investigated. From a
microbiological point of view, a low minimum inhibitory
concentration to an antibiotic would offer two theoretical
advantages: (1) more effective killing of a bacterium as
lethal tissue levels exceed the minimum inhibitory concentration and (2) reduced selection for resistance because
sublethal dosing is less likely. Minor differences in minimum inhibitory concentrations among fluoroquinolones
may be less important clinically, however, as long as
effective antibiotic tissue concentrations remain high. In a
previous study,14 we demonstrated this point using time
kill studies by exposing Staphylococcus aureus and Pseudomonas aeruginosa with low varying minimum inhibitory
concentrations to steady-state higher concentrations of
ciprofloxacin, ofloxacin, and levofloxacin. There were no
differences in killing rates of the tested fluoroquinolones.
This would be expected from concentration dependent
fluoroquinolone antibiotics. Clinical efficacy is a function
of low minimum inhibitory concentrations and other

In contrast to the limited differences of susceptibilities

between the fourth-generation fluoroquinolones and earlier generations, there were major differences in minimum
inhibitory concentrations for most of the ocular bacterial
species tested (Tables 1, 2). The minimum inhibitory
concentrations of the fourth-generation fluoroquinolones
(moxifloxacin, gatifloxacin) were statistically lower in all
cases compared with levofloxacin and ciprofloxacin for
gram-positive bacteria. In contrast, ciprofloxacin demonstrated the lowest minimum inhibitory concentrations
against gram-negative bacteria.
Direct comparison of the two fourth-generation fluoroquinolones (moxifloxacin vs gatifloxacin) demonstrated
equivalent susceptibilities for all bacterial groups except for
Staphylococcus aureusfluoroquinolone resistant, for
which moxifloxacin demonstrated increased susceptibility
(P .01). The minimum inhibitory concentrations of
moxifloxacin were statistically lower than gatifloxacin for
all gram-positive bacteria tested except coagulase negative
Staphylococcusfluoroquinolone resistant, for which moxifloxacin was statistically equivalent to gatifloxacin. The
minimum inhibitory concentrations of gatifloxacin were
statistically lower than moxifloxacin for most gram-negative bacteria tested (Pseudomonas aeruginosafluoroquinolone susceptible, Hemophilus species and Moraxella species).
Gatifloxacin and moxifloxacin demonstrated equivalent
minimum inhibitory concentrations against the gramnegative bacterium, Serratia marcescens.
For both gatifloxacin and moxifloxacin, the minimum
inhibitory concentrations were statistically higher for the
second-generation fluoroquinolone resistant Staphylococci
than for the second-generation fluoroquinolone susceptible Staphylococci (Staphylococcus aureus, P .00001;
coagulase negative Staphylococcus, P .0002).

DISCUSSION
THE SUCCESSFUL INTRODUCTION OF THE FOURTH-GENER-

ation fluoroquinolones, gatifloxacin (Tequin; Bristol-Meyers Squibb Company, Princeton, New Jersey, USA) and
moxifloxacin (Avelox; Bayer Corporation, West Haven,
Connecticut, USA) for the treatment of systemic infections has led to eager anticipation in ophthalmology for
their future application to the topical treatment of bacterial keratitis. In this in vitro study, we assessed their
potential role to fulfill this function. Because the fourthgeneration fluoroquinolones were specifically developed to
compete with the beta lactams as primary agents in the
systemic treatment of acute gram-positive respiratory infections (for example, S. pneumoniae), it came as no
surprise that the minimum inhibitory concentrations were
lower than the second-generation fluoroquinolones against
gram-positive pathogens. Furthermore, because fourthgeneration fluoroquinolones require two mutations to establish resistance, one in the topoisomerase IV and a
504

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OPHTHALMOLOGY

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additional variables that include antibiotic tissue concentration, concentration of antibiotic used, dosing regimen,
solubility, toxicity, allergenicity, and patient compliance.
The actual clinical efficacy of these newer fluoroquinolones remains to be defined by the results of clinical trials for
the treatment of bacterial keratitis and conjunctivitis.
The introduction of the fourth-generation fluoroquinolones will require the treating ophthalmologist to make
choices about the appropriate use of these newer drugs.
Ophthalmologists will be faced with at least three options:
(1) use fourth-generation fluoroquinolones exclusively, (2)
use all generations of fluoroquinolones interchangeably
depending on other factors (for example, cost), and (3)
continue to use older second- and third-generation fluoroquinolones and reserve the fourth-generation fluoroquinolones for culture-proven resistant organisms only.
Valid arguments can be made to support both options 1
and 3. Arguments in favor of option 1 include the
following: (1) with the widespread practice of empirical
therapy, fourth-generation fluoroquinolones are the best,
most potent drugs available to rapidly clear infections and
prevent vision loss; (2) preoperative patients deserve the
best to prevent endophthalmitis; (3) these antibiotics are
less likely to select for resistance; and (4) continued use of
older fluoroquinolones may reduce the time of usefulness of
fourth-generation fluoroquinolones by increased selection
of second-generation fluoroquinolone-resistant mutants
with one step mutations already in place. Arguments in
favor of option 3 include the following: (1) current
fluoroquinolones are still doing an excellent job for most
ocular infections and surgical prophylaxis, (2) current
fluoroquinolones are likely to be cheaper than newer
fluoroquinolones and thereby offer a way to hold down
rising health care costs, and (3) selection of resistance by
current fluoroquinolones can be reduced by patient and
doctor education (avoid long-term use and tapering dose
regimens).
Although options 1 and 3 remain possible choices,
reality may be dictated by a number of influential factors
that will result in option 2, namely, the simultaneous use
of all generations of fluoroquinolones. Some of the defining
factors will include current practice patterns and the
inertia associated with inducing change; the success of
pharmaceutical marketing pressures to influence physician
choice; cost determinations that will affect HMO, hospital
formulary, and physician choices; and scientific data from
basic research studies and clinical trials that will persuade
experts in the field to recommend one drug over another.
In conclusion, the fourth-generation fluoroquinolones,
gatifloxacin and moxifloxacin, offer some advantages over
the second- and third-generation fluoroquinolones. Our in
vitro studies demonstrate that they provide greater antibacterial activity against gram-positive keratitis isolates
and appear to cover many second-generation fluoroquin-

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olone-resistant Staphylococcus isolates. Their role in clinical practice remains to be defined, and resistance will
inevitably result from overuse. The proven value of initial
culture and susceptibility testing for corneal infections has
long been recognized in ophthalmology as the best guide
for appropriate antibiotic therapy. A greater utilization of
this practice would optimize patient care and, it is hoped,
curtail the development of resistance to the newer fluoroquinolones by allowing for their more judicious use.

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