In-vitro activity of gatifloxacin against Chlamydia trachomatis and Chlamydia pneumoniae
Patricia M. Roblin and
Margaret R. Hammerschlag*
Division of Infectious Diseases, Department of Pediatrics, State University of New
York, Health Science Center at Brooklyn, Brooklyn, New York 11203, USA
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Abstract
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We compared the activity of gatifloxacin, a new quinolone, ofloxacin and
erythromycin against five isolates of Chlamydia trachomatis and 20 isolates of Chlamydia pneumoniae, including TW183 and clinical isolates from the USA and Japan.
Testing was done in cycloheximide-treated HEp-2 cells. Gatifloxacin was slightly less active
against C. trachomatis and slightly more active against C. pneumoniae than
ofloxacin, with MICs at which 90% of the isolates had no inclusions and minimal chlamydicidal
concentrations at which 90% of the isolates had no inclusions after passage of 0.25 mg/L.
Gatifloxacin was less active than erythromycin for both species.
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Introduction
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Chlamydiaspp. are important human pathogens. Chlamydia trachomatis is
the most frequent sexually transmitted infection in the United States, responsible for over three
million cases of cervicitis and urethritis per year.1 Chlamydia pneumoniae is a frequent cause of community-acquired respiratory tract
infection including pneumonia and bronchitis in adults and children.2,3 Quinolones have attracted interest as
potential therapy for both sexually transmitted infections and community-acquired respiratory
tract infections because they are active against a wide range of pathogens responsible for these
diseases. Ofloxacin is currently recommended by the Centers for Disease Control as an
alternative regimen for the treatment of genital C. trachomatis infections in adults.1 We previously reported that several quinolones, including
ofloxacin, levofloxacin, grepafloxcin, sparfloxacin, trovafloxacin and moxifloxacin have
significant activity against C. pneumoniae in vitro.
4
,5
,6
,7 We tested a new 8-methoxyquinolone,
gatifloxacin, for activity against C. trachomatisand C. pneumoniae in
comparison with ofloxacin and erythromycin.
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Materials and methods
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Gatifloxacin (Bristol Myers Squibb, Wallingford, CT, USA), ofloxacin (Ortho
Pharmaceuticals, Raritan, NJ, USA) and erythromycin were supplied as powders and solubilized
according to instructions from the manufacturers. Five strains of C. trachomatis were
tested, E Bour (ATCC VR-3483), F IC-CAL-3 (ATCC VR-346), H UW-43/CX, (ATCC
VR-879), J UW-36/CX (ATCC VR-885) and L2434Bu (ATCC VR-902B). All were
obtained from the ATCC. Twenty strains of C. pneumoniae were tested: TW-183 and
AR39 (Washington Research Foundation, Seattle, WA, USA), 10 clinical isolates from
Brooklyn, T2023 (ATCC VR1356), T2043 (ATCC VR1355), T2337, T2219, BAL14, BAL15,
BAL16, BAL37, BAL48, BAL62, a clinical isolate from Japan, J-21 (ATCC VR1435), CDC8
from Atlanta, W6805 from Wisconsin and five isolates from a multicentre pneumonia treatment
study (379CBD, 327JM, 40DEF, 473GET, 284JL).
Susceptibility testing of C. trachomatis and C. pneumoniae was performed
in cell culture using HEp-2 cells grown in 96-well microtiter plates.7 Each well was inoculated with 0.1 mL of the test strain diluted to yield 103 to 104
inclusion-forming units (IFU) per mL, centrifuged at 1700g for 1 h and incubated at
35°C for 1 h. Wells were then aspirated and overlaid with 0.2 mL of medium containing 1
mg/L of cycloheximide and serial two-fold dilutions of the test drug. After incubation at
35°C for 72 h, cultures were fixed and stained for inclusions with fluorescein-conjugated
anti-body to the lipopolysaccharide genus antigen (Pathfinder, Kallestad Diagnostics, Chaska,
MN, USA). The MIC was the lowest antibiotic concentration at which no inclusions were seen.
The minimal bactericidal concentration (MBC) was determined by aspirating the
antibiotic-containing medium, washing wells twice with phosphate buffered saline and adding
antibiotic-free medium. Cultures were frozen at 70°C, thawed, passed on to new
cells, incubated for 72 h then fixed and stained as above. The MBC was the lowest antibiotic
concentration which resulted in no inclusions after passage. All tests were run in triplicate.
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Results and discussion
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The MICs and MBCs for all five strains of C. trachomatiswere 0.25 mg/L of
gatifloxacin, 0.125 mg/L of ofloxacin and 0.03 mg/L of erythromycin. The MICs and MBCs for C. pneumoniae are given in the Table. Gatifloxacin was slightly
less active against C. trachomatis, and slightly more active against C. pneumoniae than ofloxacin but
less active than erythromycin against both species
The MICs of gatifloxacin against C. pneumoniae were very consistent from strain to
strain, especially in view of the wide geographic distribution of the isolates tested. Data on the
activity of gatifloxacin against Chlamydia spp. are limited. Miyashita et al.8 tested gatifloxacin against three strains of C.
trachomatis,five strains of C. pneumoniae, including TW 183 and AR 39
and two strains of Chlamydia psittaci. The MICs for all three species ranged from 0.063
to 0.125 mg/L. The MICs for C. pneumoniae TW 183 and AR39 were 0.063 mg/L,
which is four-fold more active than our results with these strains. This difference may be within
the standard error of the test. They also tested 25 recent clinical isolates and the MIC90 and MBC90 were 0.125 mg/L, which is not significantly different from our
results with American clinical isolates. The MIC90 and MBC90 of
ofloxacin against C. pneumoniae were 0.5 and 1 mg/L, respectively, which are almost
exactly the values we found (MIC90 and MBC90 0.5 mg/L). Miyashita et al.8 also evaluated the efficacy of treatment with
gatifloxacin and other antibiotics on survival in a mouse model of C. psittaci
pneumonia. The survival of mice treated with 5 mg/kg of gatifloxacin was significantly higher
than that seen with ofloxacin. Wise et al.9 tested
gatifloxacin against three strains of C. trachomatis and C. pneumoniaeTW-183. The MICs and MBCs ranged from 0.06 to 0.12 mg/L, which was two- to four-fold
more active than we found for C. trachomatis and TW-183.
The 1998 Guidelines for the Treatment of Sexually Transmitted Diseases lists ofloxacin as
an alternative regimen for the treatment of uncomplicated genital C. trachomatis
infection in adolescents and adults.1 Ofloxacin is similar in
efficacy to doxycycline and azithromycin, but is more expensive and offers no advantage with
regard to dosing and the length of treatment.1 Based on its
in-vitro activity and pharmacokinetics10, gatifloxacin
should have equivalent efficacy to ofloxacin for treatment of C. trachomatis infections.
There are no published studies that have assessed the efficacy of any quinolone for the
treatment of C. pneumoniae infection that have utilized culture.4,5 The diagnosis was based on serology
alone, thus microbiological efficacy could not be assessed. We treated three patients with culture
documented C. pneumoniae infection (bronchitis and pneumonia) with grepafloxacin.
Although grepafloxacin has an MIC90 and MBC90 of 0.5 mg/L against C. pneumoniae,two of three patients remained culture-positive and symptomatic despite
2 weeks of treatment with the drug.7 Prospective studies of
gatifloxacin for the treatment of genital chlamydia infections and community-acquired
pneumonia utilizing culture of C. trachomatis and C. pneumoniae will
determine the role of gatifloxacin in the treatment of these infections.
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Notes
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* Correspondence address. Department of Pediatrics, Box 49, SUNY
Health Science Center at Brooklyn, 450 Clarkson Avenue, Brooklyn, NY 11203-2098, USA. Tel:
+1-718-245-4075; Fax: +1-718-245-2118; E-mail: mhammerschlag{at}pol.net 
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Received 11 October 1998;
returned 22 February 1999; revised 18 March 1999;
accepted 23 May 1999