Antimicrobial Agents and Chemotherapy, December 2000, p. 3481-3482, Vol. 44, No. 12
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
LETTERS TO THE EDITOR
Influences of Different Factors on Prevalence of
Ciprofloxacin Resistance in Streptococcus pneumoniae in
Spain
 |
LETTER |
A role of the use of fluoroquinolones in the development of
resistance to ciprofloxacin in Streptococcus pneumoniae in
Canada has been recently suggested (2). We would like to
contribute support for this hypothesis from three different perspectives.
First, we compared the levels of prevalence of ciprofloxacin resistance
between macrolide- and 
-lactam-susceptible and nonsusceptible S. pneumoniae strains. Then, we looked at differences in
ciprofloxacin resistance among serotypes. Finally, ciprofloxacin
resistance of strains isolated from children was compared to that of
strains from adults. A total of 1,113 pneumococcal isolates were
collected from patients with community-acquired respiratory tract
infections in a 1-year period (1996-1997) in a nationwide Spanish
prospective multicenter surveillance study (1).
Susceptibility testing and breakpoints used followed NCCLS
recommendations (4). A breakpoint for resistance to
ciprofloxacin of 
4 µg/ml was used for this analysis, as a
ciprofloxacin breakpoint has not been approved for S. pneumoniae by NCCLS. Statistical significance was determined by
the 
2 test.
Using an MIC >2 µg/ml, 59 strains were resistant to ciprofloxacin
(5.3%). A significant difference in the prevalence of resistance to
ciprofloxacin was found between the macrolide-susceptible and nonsusceptible pneumococci (4 versus 8%; P < 0.01)
(Table 1). However, no differences in
ciprofloxacin resistance (around 5%) were related to whether the
strains were susceptible to amoxicillin, amoxicillin-clavulanic acid,
or cefuroxime. Despite being high, the penicillin odds ratio (OR) did
not reach statistical significance.
Ciprofloxacin resistance was more prevalent among ST-19 strains
(9.9%), nontypeable strains (9.3%), and ST-3 strains (9.1%) than in
other strains (ST-14, 6.7%; ST-9, 4.5%; ST-6, 1.8%; ST-23, 1.7%;
other serotypes, 3.3%).
No strains for which the MIC of ciprofloxacin was 4 µg/ml were
found among the 125 pneumococci from children, whereas there were 59 such strains among the 988 strains (6%) from adults. Interestingly, strains for which the MICs were 8 and 16 µg/ml accounted for 1.9 and 0.6% of the strains from adults. Using an MIC of 2 µg/ml for
ciprofloxacin resistance, 224 resistant strains (22.6%) were found
among those isolated from adults, in contrast with 9 strains (7.2%)
from children (OR, 3.78; 95% confidence interval [CI], 1.83 to 8.1;
P < 0.01).
The different prevalence of ciprofloxacin resistance in adults compared
to children, even when a lower breakpoint is used (lower levels of
resistance precede higher ones), appears to be consistent with the
hypothesis of a link between fluoroquinolone consumption (extremely low
in children, if any) and selection of resistance. Despite the fact that
ST-19, together with ST-6, is recognized as the most prevalent serotype
in children in Spain (3) and also the most prevalent
ciprofloxacin-resistant serotype in our study, no resistant ST-19
strains were found in children, which suggests that phenotypic
clusterization may be related to consumption as well. It is also
noteworthy that ST-3, which has always been considered susceptible to
penicillin and erythromycin, shows a high prevalence of ciprofloxacin
resistance. Another important factor to bear in mind is the potential
cross-selection of resistance to a drug by other, unrelated
antibiotics. Our data show a tendency for ciprofloxacin-resistant
pneumococci to cluster among the macrolide-nonsusceptible strains,
suggesting that macrolide usage could select for ciprofloxacin resistance as well. All the aforementioned should be seriously taken
into account in order to avoid the coselection of resistance and to
preserve the value of present or future empirical antibiotics for use
against community-acquired respiratory pathogens by using the therapy
more likely to eradicate multiresistant pathogens.
| |
FOOTNOTES |
*
Phone: 34 91 334 5275
Fax: 34 91 334 5141
E-mail: lorenzo.aguilar-alfaro{at}sb.com
E. Bouza, Madrid;
M. Casal, Córdoba; R. Cisterna, Bilbao; R. Dal-Ré; Madrid;
J. García-de-Lomas, Valencia; C. García-Riestra, Santiago de Compostela; J. A. García-Rodríguez,
Salamanca; M. Gobernado, Valencia; C. Gómez-García,
Badajoz; R. Gómez-Lus, Zaragoza; A. Gutiérrez, Madrid; T. Jiménez-de-Anta, Barcelona; M. Martín-Sánchez, Las
Palmas; E. Perea, Sevilla; G. Prats, Barcelona; M. de la Rosa, Granada;
and J. J. Granizo, Madrid.
| |
REFERENCES |
| 1.
|
Baquero, F.,
J. A. García-Rodríguez,
J. García-de-Lomas,
L. Aguilar, and the Spanish Surveillance Group for Respiratory Pathogens.
1999.
Antimicrobial resistance of 1,113 Streptococcus pneumoniae isolates from patients with respiratory tract infections in Spain: results of a 1-year (1996-1997) multicenter surveillance study.
Antimicrob. Agents Chemother.
43:357-359[Abstract/Free Full Text].
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| 2.
|
Chen, D. K.,
A. McGeer,
Joyce,
C. de Azavedo, and D. E. Low for the Canadian Bacterial Surveillance Network..
1999.
Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada.
N. Engl. J. Med.
341:233-239[Abstract/Free Full Text].
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Fenoll, A.,
I. Jado,
D. Vicioso,
A. Pérez, and J. Casal.
1998.
Evolution of Streptococcus pneumoniae serotypes and antibiotic resistance in Spain: update (1990 to 1996).
J. Clin. Microbiol.
36:3447-3454[Free Full Text].
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| 4.
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National Committee for Clinical Laboratory Standards.
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Approved standard M7-A4. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 4th ed.
NCCLS, Wayne, Pa.
|
| | | | |
C. García-Rey
L. Aguilar*
Medical Department
SmithKline Beecham Pharmaceuticals
Madrid, Spain
|
| | | | |
F. Baquero
Microbiology Department
Hospital Ramón y Cajal
Madrid, Spain
|
| | | | |
Spanish Surveillance Group for Respiratory Pathogens
|
Antimicrobial Agents and Chemotherapy, December 2000, p. 3481-3482, Vol. 44, No. 12
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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