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Antimicrobial Agents and Chemotherapy, May 2001, p. 1605-1606, Vol. 45, No. 5
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.5.1605-1606.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
LETTERS TO THE EDITOR
Emergence of Fluoroquinolone-Resistant Strains of Vibrio
cholerae O1 Biotype El Tor among Hospitalized Patients with
Cholera in Calcutta, India
 |
LETTER |
Ciprofloxacin and norfloxacin are broad-spectrum
fluoroquinolones and possess excellent activity against Vibrio
cholerae O1 and O139 serogroups (6). Clinical studies
have shown that these drugs are effective in treatment of cholera in
adults and children (2-4). For the past 11 years, we have
been monitoring the incidence of antibiotic susceptibility and
genotypic changes in V. cholerae isolates from cholera
patients admitted at the Infectious Diseases Hospital, Calcutta, India.
Here, we report the emergence of fluoroquinolone-resistant strains of
V. cholerae O1 Biotype El Tor among hospitalized patients with cholera.
Antimicrobial susceptibility analysis of V. cholerae strains
was performed by disk diffusion (1) on Mueller-Hinton agar (Difco, Detroit, Mich.) with commercial disks (HiMedia, Mumbai, India).
The following antibiotic disks were used: ciprofloxacin, 5 µg;
nalidixic acid, 30 µg; norfloxacin, 10 µg; and tetracycline, 30 µg. Characterization of strains as susceptible, intermediately resistant, or resistant was based on the size of the inhibition zone
according to the manufacturer's instructions. These zone size
interpretive criteria for susceptibility corresponded to MICs of 0.25, 0.06, and 0.06 µg/ml for nalidixic acid, norfloxacin, and
ciprofloxacin, respectively. Strains showing intermediate zones of
growth inhibition were classified as resistant on the basis of previous
MIC studies with V. cholerae (6).
We have reported considerable increases in fluoroquinolone resistance
among V. cholerae strains belonging to non-O1, non-O139 serogroups during 1996 (5). All the V. cholerae
strains of serogroup O1 isolated in or before 1994 are susceptible to
ciprofloxacin. From 1995, we have recorded progressive increases in
ciprofloxacin and norfloxacin resistance among V. cholerae
O1 strains, with the highest occurrences of 38.8% in 1999 and 25% in
2000, respectively (Table 1). To our
knowledge, this is the first report on such high incidence of
fluoroquinolone resistance among toxigenic V. cholerae O1
strains. The MICs of ciprofloxacin and norfloxacin for
ciprofloxacin-resistant V. cholerae strains ranged between 9 and >32 µg/ml and between 192 and >256 µg/ml, respectively, when
tested with the E-test strips on Mueller-Hinton agar (AB Biodisk,
Solna, Sweden). The incidence of nalidixic acid resistance among
V. cholerae O1 strains was low (<10%) before 1993 and
peaked during subsequent years (1999; 100%), as shown in the Table 1. Possibly, ciprofloxacin resistance might have emerged in direct response to the selective pressure exerted by nalidixic acid coupled with disproportionate use of fluoroquinolones in the clinical settings.
It is worth to mention here that the increase in the incidence of
nalidixic acid-resistant strains of V. cholerae O1 (probably
with a single mutation in gyrA and/or other related genes)
portended a further increase in the incidence of strains with
clinically significant resistance to fluoroquinolones (with two or more
mutations in the gyrA gene). We are in the process of
identifying the mutational "hot spots" in the quinolone
resistance-determining region.
An interesting observation in the present report is the low incidence
of quinolone resistance in the O139 serogroup. One possible elucidation
is the low frequency of nalidixic acid resistance among V. cholerae O139 strains (Table 1), and therefore the frequency of
double mutations, a prerequisite for fluoroquinolone resistance, is
low, as reflected by resistance O139 strains to fluoroquinolones.
In this study we encountered a higher incidence of V. cholerae O1 resistance to ciprofloxacin than to norfloxacin, which
is generally less potent than ciprofloxacin. The possible explanation for this counterintuitive result is (i) since ciprofloxacin is in
extensive use for all the bacterial infections in this part of the
world, conditions of high selective pressure would have forced the
mutant V. cholerae strains to multiply and establish themselves as the dominant population; continued selective pressure favored these progeny to have further mutations; (ii) ciprofloxacin and
norfloxacin breakpoints are not comparable, at least for V. cholerae strains (the MIC for 50% of the strains
[MIC50], MIC90, and MIC ranges need to be
determined for both drugs to prove this hypothesis); or (iii)
ciprofloxacin and norfloxacin accumulation kinetics might differ among
V. cholerae O1 strains. Additional, extensive studies are
needed to test these possibilities in order to determine the mechanisms
responsible for heterogeneous fluoroquinolone resistance among V. cholerae O1 strains.
Emergence of fluoroquinolone resistance in V. cholerae will
certainly complicate the therapeutic use of these drugs, and attention must be paid to this trend. Fortunately, V. cholerae O1 and
O139 strains are susceptible to tetracycline, which is an effective drug for treatment of cholera at the Infectious Disease Hospital.
| |
ACKNOWLEDGMENTS |
This work was supported in part by the Japan International
Cooperation Agency (JICA/NICED project 054-1061-E-O) and CSIR, India
[no. 37 (1019)/99/EMR-II].
| |
FOOTNOTES |
*
Fax: 91-33-350-5066 E-mail: gbnair{at}vsnl.com
| |
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| | | | |
Pallavi Garg
Sutapa Sinha
Rupa Chakraborty
S. K. Bhattacharya
G. Balakrish Nair
T. Ramamurthy*
National Institute of Cholera and Infectious Diseases
P-33, CIT Rd. Scheme XM, Beliaghata
Calcutta 700 010, India
|
| | | | |
Yoshifumi Takeda
National Institute of Infectious Diseases
Shinjuku-ku, Tokyo, Japan
|
Antimicrobial Agents and Chemotherapy, May 2001, p. 1605-1606, Vol. 45, No. 5
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.5.1605-1606.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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