![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, January 1999, p. 178-180, Vol. 43, No. 1
Microbiology Department,
Received 26 May 1998/Returned for modification 22 July
1998/Accepted 5 October 1998
A nationwide susceptibility surveillance study of beta-hemolytic
streptococcal isolates from pharyngeal swabs obtained in 11 Spanish
hospitals between May 1996 and April 1997 against 12 antibiotics was
carried out. Of the isolates 86% (786 of 914 isolates) were group A
and 8.4% (77 of 914 isolates) were group C. No resistance was found to
Penicillin remains the drug of
choice in the treatment of streptococcal pharyngitis
(3), although communications increasingly report treatment failure frequencies of up to 30% (2, 4). This has been attributed to copathogenicity with
In vitro penicillin resistance has not yet been described in group A
beta-hemolytic streptococci (Streptococcus pyogenes) (3, 7, 8). Resistance to macrolides is more common but remains at <5% among group A streptococci in most countries of the
world (8). In recent years, erythromycin resistance
frequencies in Spain have ranged from 1 to 10% (3, 6, 15).
As more data are gradually accumulated on antimicrobial agent use and resistance in the community (10, 17), careful surveillance is required (8).
The aim of this study was to describe the susceptibility of
beta-hemolytic streptococci in a nationwide antimicrobial surveillance study carried out in Spain. Included in this prospective surveillance study were all consecutive clinical isolates of beta-hemolytic streptococci from pharyngeal swabs collected between May 1996 and April
1997 at 11 hospital centers selected on the basis of geographical location.
Once a month at each center the isolates, after being kept at Susceptibility testing was performed by a semiautomated microdilution
method (microtiter plates were manufactured by Accumed International,
East Grinstead, United Kingdom) following the guidelines of the
National Committee for Clinical Laboratory Standards (11), with antimicrobials commonly used in empiric therapy in Spain (penicillin, amoxicillin, amoxicillin clavulanate, cefixime,
cefaclor, cefuroxime, cefotaxime, ceftriaxone, erythromycin,
azithromycin, clarithromycin, and ciprofloxacin). The breakpoints
employed for the calculations of percentages of antimicrobial
resistance are shown in a footnote to Table 1 (11).
Haemophilus influenzae ATCC 49247, Streptococcus
pneumoniae ATCC 49619, Staphylococcus aureus ATCC
29213, and Escherichia coli ATCC 25922 were used as control
strains. The mechanism of resistance by S. pyogenes to erythromycin was evaluated with a double diffusion disk test, as
described elsewhere (18), with erythromycin (15 µg) and
clindamycin (2 µg) disks placed 20 mm apart onto 5% defibrinated
horse blood agar and incubated overnight at 35°C in a 5% carbon
dioxide atmosphere (14).
Statistical analysis of data was performed by the chi-square test, with
the Yates correction when necessary. The data were analyzed with
Epi-Info version 6.04 (5).
A total of 914 isolates of beta-hemolytic streptococci were obtained,
of which 86% (786 isolates) were group A, 8.4% (n = 77) were group C, 4.5% (n = 41) were group G, and
1.1% (n = 10) were group F. The two most common groups
(A and C) exhibited the same in vitro susceptibility (i.e., MIC at
which 90% of the isolates were inhibited [MIC90], MIC
range, and resistance prevalence) to Table 1 shows the in vitro susceptibility
of the 786 S. pyogenes isolates. All This study reveals an increase in erythromycin resistance prevalence in
Spain (27%) compared to the resistance rates of up to 10% found in
previous studies (3, 6, 15), which is due in part to the use
of different breakpoints for erythromycin in the present study and in
the previous ones. Were the breakpoint ( When a cutoff value of In this study fewer group A isolates were obtained in summer (91 of 786 isolates [11.6%]) than in other seasons, for which the frequency
ranged from 28 to 30%. Seasonal variations have been previously
described in Spain (13), and lower isolation rates in summer
have been noted. The frequency of macrolide-resistance exhibited a
seasonal pattern, being 13.2, 25.0, 31.7, and 31.3% in summer, autumn,
winter, and spring, respectively (P < 0.001). Antibiotic consumption patterns may contribute to resistance
seasonality. In Spain community antibiotic consumption accounts for
90% of total consumption, and 17% of it is consumption of macrolides (1). Another possible explanation is the existence of a
seasonal clone variation of new phenotypes with respect to virulence
and antibiotic susceptibility.
Figure 1 shows the erythromycin MIC
distribution. With respect to S. pyogenes erythromycin
resistance phenotypes (18), 93% (198 of 213 isolates) of
strains belong to phenotype M (presumed efflux, with low-level
resistance to erythromycin and susceptibility to clindamycin), as was
found in previous studies in our country (6, 14), 6% (13 of
213 isolates) belong to the constitutive phenotype, and 1% (2 of 213 isolates) belong to the inducible phenotype. The increase in macrolide
resistance observed is due to the M phenotype, with
cross-resistance between C14 (erythromycin and
clarithromycin) and C15 (azithromycin) macrolides.
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Antimicrobial Resistance of 914 Beta-Hemolytic
Streptococci Isolated from Pharyngeal Swabs in Spain: Results of a
1-Year (1996-1997) Multicenter Surveillance Study
ABSTRACT
Top
Abstract
Text
References
-lactam antibiotics, but significant differences (P < 0.001) with respect to lack of susceptibility to macrolides were found between groups (27% for group A and 12% for group C) and
between seasons (13.2% in summer and 31.7% in winter). Most of these
isolates displayed the M phenotype (low-level resistance to
erythromycin and susceptibility to clindamycin).
TEXT
Top
Abstract
Text
References
-lactamase-producing microorganisms, generating doubt as
to the use of penicillin as empiric treatment in recurrent
infections (2). Instead, other antibiotics not subject to
inactivation by -lactamases, i.e., amoxicillin clavulanate,
oral cephalosporins, or erythromycin, are favored by some, the latter
being considered the drug of choice in penicillin-allergic patients
(2).
70°C,
were thawed, seeded onto an enriched transport medium, incubated
overnight at 35 to 37°C, and shipped to a central laboratory (Instituto Valenciano de Microbiología, Valencia, Spain), where confirmation of identification and serogroup typing (as group A, C, F,
or G) with an immunoagglutination test (Streptest; Murex, Chantillon,
France) were performed.
-lactam antibiotics and to
ciprofloxacin but not to macrolides. The percentages of isolates
that were nonsusceptible (intermediate strains plus resistant strains)
to macrolides were 27.1% (213 of 786 isolates) for group A and
11.7% (9 of 77 isolates) for group C (P = 0.001).
-lactam antibiotics
exhibited similar in vitro activities, with MIC90s of <1
µg/ml. The penicillins and parenteral cephalosporins exhibited
similar activities with respect to MIC90, MIC range, and
resistance prevalence. With respect to oral cephalosporins, only
cefixime showed MIC of >1 µg/ml (for 8 of 786 strains). Macrolides
elicited resistance by around 27% of the isolates, as stated above,
with MIC90 values ranging from 4 µg/ml (of erythromycin
or clarithromycin) to 8 µg/ml (of azithromycin). The
MIC90 of ciprofloxacin was 1 µg/ml.
TABLE 1.
MIC90, range of MICs, and susceptibility for
786 isolates of S. pyogenes obtained from pharyngeal
exudate samples
8 µg/ml) (12)
employed in the previous studies (3, 6, 15) used, the
erythromycin resistance prevalence in this study would be 6.1%.
1 µg/ml was used for highly resistant
strains (3, 13) resistance was found in only 3% of strains isolated in 1991 and 1992 (3) or 4.7% of those isolated in 1994 (13). The overall erythromycin resistance frequency of 27% is due in part to an increase in the isolation rate of very highly
resistant strains; 6.1% of the isolates had MIC of 8 µg/ml, contrasted with 1% of those examined in 1991 and 1992 (3). This may be explained in part by the confirmed increase of macrolide use in Spain (1) as well as in other countries (16, 17, 19). This phenomenon has also been suggested to occur in the case
of S. pneumoniae (9).
View larger version (16K):
[in a new window]
FIG. 1.
Erythromycin MIC distribution.
Careful surveillance is required (8) for streptococcal
isolates in countries where macrolide antibiotics are frequently prescribed (10) or high resistance rates for macrolides
exist (as in Spain), as these antibiotics are the most widely used
alternatives to oral -lactams in the empiric treatment of
streptococcal pharyngitis.
| |
ACKNOWLEDGMENTS |
|---|
This study was supported by a grant from SmithKline Beecham Pharmaceuticals, Madrid, Spain.
| |
FOOTNOTES |
|---|
* Corresponding author. Mailing address: Departamento Médico, SmithKline Beecham Pharmaceuticals, Valle de la Fuenfría, 3, 28034 Madrid, Spain. Phone: 34-91-3345275. Fax: 34-91-3345141. E-mail: lorenzo.aguilar-alfaro{at}sb.com.
Composed of M. Gobernado and N. Diosdado, La Fe Hospital, Valencia;
E. Bouza and E. Cercenado, Gregorio Marañón Hospital, Madrid; A. Gutierrez and A. García, La Paz Hospital,
Madrid; R. Cisterna and A. Morla, Basurto Hospital, Bilbao; E. Perea and L. Martínez, Virgen Macarena Hospital, Seville;
M. de la Rosa and A. Martínez-Brocal, Virgen de las Nieves
Hospital, Granada; M. Casal and A. Ibarra, Reina Sofía
Hospital, Córdoba; I. Trujillano, Clinico Universitario Hospital,
Salamanca; R. Gómez-Lus and M. C. Rubio, Clinico
Universitario Hospital, Zaragoza; A. C. Gómez-García and F. J. Blanco-Palenciano, Infanta
Cristina Hospital, Badajoz; C. García-Riestra and I. Rodríguez, Xeral de Galicia Hospital, Santiago de Compostela;
C. Gimeno and D. Navarro, Instituto Valenciano de
Microbiología, Valencia; and A. Torrellas, J. J. Granizo, R. Moreno, and R. Dal-Ré, SmithKline Beecham
Pharmaceuticals, Madrid, Spain.
| |
REFERENCES |
|---|
|
Top
Abstract
Text
References
|
|---|
| 1. | Baquero, F., and the Task Force of the General Direction for Health Planning of the Spanish Ministry of Health. 1996. Antibiotic resistance in Spain: what can be done? Clin. Infect. Dis. 23:819-823[Medline]. |
| 2. | Bass, J. W. 1991. Antibiotic management of group A streptococcal pharyngotonsillitis. Pediatr. Infect. Dis. J. 10:543-549. |
| 3. |
Betriu, C.,
A. Sánchez,
M. Gómez,
A. Cruceyra, and J. J. Picazo.
1993.
Antibiotic susceptibility of group A streptococci: a 6-year follow-up study.
Antimicrob. Agents Chemother.
37:1717-1719 |
| 4. | Bisno, A. L. 1995. Streptococcus pyogenes, p. 1786-1798. In G. L. Mandell, J. E. Bennet, and I. R. Dolin (ed.), Principles and practice of infectious diseases. Churchill Livingstone, Inc., New York, N.Y. |
| 5. | Dean, A., J. Dean, D. Coulombier, K. Brendel, D. Smith, A. Burton, R. Dicker, K. Sullivan, R. Fagan, and T. Arner. 1994. Epi-Info version 6.04: a word processing, database and statistics program for epidemiology on microcomputers. Centers for Disease Control and Prevention, Atlanta, Ga. |
| 6. |
García-Bermejo, I.,
J. Cacho,
B. Orden,
J. I. Alós, and J. L. Gómez-Garcés.
1998.
Emergence of erythromycin-resistant, clindamycin-susceptible Streptococcus pyogenes isolates in Madrid, Spain.
Antimicrob. Agents Chemother.
42:989-990 |
| 7. | Gerber, M. A. 1995. Antibiotic resistance in group A streptococci. Pediatr. Clin. N. Am. 42:539-551[Medline]. |
| 8. | Kaplan, E. L. 1997. Recent evaluation of antimicrobial resistance in beta-hemolytic streptococci. Clin. Infect. Dis. 24(Suppl. 1):S89-S92. |
| 9. | Liñares, J., R. Pallarés, T. Alonso, L. Pérez, J. Ayats, F. Gudiol, P. F. Viladrich, and R. Martin. 1992. Trends in antimicrobial resistance of clinical isolates of Streptococcus pneumoniae in Bellvitge Hospital, Barcelona, Spain (1979-1990). Clin. Infect. Dis. 15:99-105[Medline]. |
| 10. | Maruyama, S., H. Yoshioka, K. Fujita, M. Takimoto, and Y. Satake. 1979. Sensitivity of group A streptococci to antibiotics: prevalence of resistance to erythromycin in Japan. Am. J. Dis. Child. 133:1143-1145[Abstract]. |
| 11. | National Committee for Clinical Laboratory Standards. 1997. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 4th ed. Approved standard M7-A4. National Committee for Clinical Laboratory Standards, Wayne, Pa. |
| 12. | National Committee for Clinical Laboratory Standards. 1992. Performance standards for antimicrobial susceptibility testing; fourth informational supplement. Document M100-S4. National Committee for Clinical Laboratory Standards, Villanova, Pa. |
| 13. | Orden, B., R. Martínez, A. López, and A. Franco. 1996. Resistencia antibiotica a eritromicina, clindamicina y tetraciclina de 573 cepas de Streptococcus pyogenes (1992-1994). Enferm. Infecc. Microbiol. Clin. 14:86-89[Medline]. |
| 14. | Orden, B., E. Pérez-Trallero, M. Montes, and R. Martínez. 1988. Erythromycin resistance of Streptococcus pyogenes in Madrid. Pediatr. Infect. Dis. J. 17:470-473. |
| 15. | Pérez-Trallero, E., J. M. García, and M. Urbieta. 1989. Erythromycin resistance in streptococci. Lancet ii:444-445. |
| 16. |
Phillips, G.,
D. Parratt,
G. V. Orange,
I. Harper,
H. McEwan, and N. Young.
1990.
Erythromycin-resistant Streptococcus pyogenes.
J. Antimicrob. Chemother.
25:723-724 |
| 17. |
Seppälä, H.,
T. Klaukka,
J. Vuopio-Varkila,
A. Muotiala,
H. Helenius,
K. Lager, and P. Huovinen.
1997.
The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland.
N. Engl. J. Med.
337:441-446 |
| 18. |
Seppälä, H.,
A. Nissinen,
Q. Yu, and P. Huovinen.
1993.
Three different phenotypes of erythromycin-resistant Streptococcus pyogenes in Finland.
J. Antimicrob. Chemother.
32:885-891 |
| 19. |
Zackrisson, G.,
L. Lind,
K. Roos, and P. Larson.
1988.
Erythromycin resistant -hemolytic streptococci group A in Göteborg, Sweden.
Scand. J. Infect. Dis.
20:419-420[Medline].
|
This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clin. Vaccine Immunol. | Clin. Microbiol. Rev. |
|---|---|
| J. Clin. Microbiol. | ALL ASM JOURNALS |
