Antimicrobial Agents and Chemotherapy, February 1999, p. 357-359, Vol. 43, No. 2
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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
Fernando
Baquero,1
José Angel
García-Rodríguez,2
Juan
García de
Lomas,3
Lorenzo
Aguilar,4,* and
The
Spanish Surveillance Group for Respiratory
Pathogens
Microbiology Department, Ramón y Cajal
Hospital,1 and
Medical Department,
SmithKline Beecham Pharmaceuticals,4 Madrid,
Microbiology Department, University Hospital,
Salamanca,2 and
Instituto Valenciano
de Microbiología, Valencia,3 Spain
Received 22 May 1998/Returned for modification 7 August
1998/Accepted 12 November 1998
 |
ABSTRACT |
A nationwide susceptibility surveillance of 1,113 Streptococcus pneumoniae isolates was carried out and found
the following percentages of resistance: cefuroxime, 46%; penicillin,
37%; macrolides, 33%; aminopenicillins, 24%; cefotaxime, 13%; and
ceftriaxone, 8%. A significant (P < 0.05)
seasonality pattern for 
-lactam antibiotics was observed. Resistance
to macrolides was higher (P < 0.05) in
middle-ear samples. Higher percentages of resistance to cefuroxime and
macrolides were observed among penicillin-intermediate and -resistant
strains, whereas high frequencies of resistance to aminopenicillins and
expanded-spectrum cephalosporins were observed only among
penicillin-resistant strains.
| |
TEXT |
Resistance to penicillin among
Streptococcus pneumoniae strains is increasing, with
geographical variations (2, 6), making it important to
conduct surveillance studies (1). In Spain penicillin
resistance increased from 6% (1979) to 44% (1989) (5).
Penicillin resistance in S. pneumoniae is often associated with resistance to other antibiotics, such as erythromycin (4, 5).
The aim of this study was to describe the susceptibility of S. pneumoniae in a nationwide antimicrobial surveillance prospective study. All consecutive clinical isolates collected (between May 1996 and April 1997) from patients with community-acquired infections at 14 hospital centers selected on the basis of geographical location were included.
At each center, isolates kept at 
70°C were thawed once a month,
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 the identities of
isolates were confirmed by conventional tests and criteria. Isolates
were kept frozen at 70°C in duplicate until antimicrobial susceptibility testing was performed.
Susceptibility testing was performed by using a semiautomated
microdilution method in Mueller-Hinton broth supplemented with 3%
lysed horse blood according to the guidelines of the National Committee
for Clinical Laboratory Standards (NCCLS) (9), with a final
inoculum of 5 × 105 CFU/ml, and cultures were
incubated 24 h at 35°C under a 5% carbon dioxide atmosphere,
with antimicrobials commonly used in empiric therapy in Spain (Table
1). Haemophilus influenzae ATCC 49247, S. pneumoniae ATCC 49619, Staphylococcus aureus ATCC
29213, and Escherichia coli ATCC 25922 were used as control
strains. The mechanism of resistance to erythromycin was evaluated by
using a double diffusion disk test as described elsewhere
(13), 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 under a 5% carbon dioxide atmosphere
(10).
Statistical analysis of data was performed by the chi-square test, with
the Yates correction when necessary and correction for multiple
comparisons (Bonferroni's method).
In vitro susceptibilities are shown in Table
1. Forty percent of isolates were
penicillin susceptible, 24% showed intermediate resistance to
penicillin, and 36% were penicillin resistant. Extended-spectrum cephalosporins, amoxicillin-clavulanate, and ciprofloxacin exhibited the highest activities (MIC at which 90% of the isolates are inhibited [MIC90] 
2 µg/ml), whereas macrolides, cefaclor,
cefixime, and cefuroxime exhibited the lowest activities
(MIC90 
8 µg/ml). The prevalence of resistance was
around 10% for extended-spectrum cephalosporins, 25% for
aminopenicillins, >30% for penicillin and macrolides, and 46% for
cefuroxime. Among the oral antibiotics, amoxicillin-clavulanate
exhibited the highest intrinsic activity (MIC90 = 2 µg/ml) and the lowest prevalence of resistant strains (25.5%).
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TABLE 1.
In vitro activities of antimicrobial
agentsa against 1,113 S. pneumoniae
isolates classified by penicillin susceptibility, and proportions of
fully resistant strains
|
|
Resistance to both macrolides and cefuroxime was markedly increased in
strains showing intermediate resistance to penicillin compared with
that in penicillin-susceptible strains (51 versus 6% for macrolides
and 40 versus 0% for cefuroxime); this phenomenon was not observed
with amoxicillin (with or without clavulanate), cefotaxime, or
ceftriaxone. Increases in resistance to aminopenicillins and
extended-spectrum cephalosporins were observed only when
penicillin-intermediate and -resistant strains were compared.
Cefuroxime resistance increased again in the penicillin-resistant
strains compared with that in the penicillin-intermediate strains (100 versus 40%, respectively). Penicillin-intermediate and -resistant
strains showed the same level of resistance to macrolides (51 to 53%).
Middle-ear isolates exhibited the highest (P < 0.05)
percentage of resistance to macrolides (49%) compared with isolates of other origins. Sixty-nine percent of pediatric samples were middle-ear isolates. As described previously (3), pediatric isolates
exhibit higher resistance to penicillin compared with isolates from
internal medicine patients (50 versus 37%); however, there were no
significant differences between medical wards.
Seasonal variations in pneumococcal infections have been documented
(7). In this 1-year surveillance study, the overall distribution of isolates by season was 10.3% in the spring of 1996, 13.5% in the summer of 1996, 25.7% in the autumn of 1996, 32.1% in
the winter of 1996 to 1997, and 18.6% in the spring of 1997. Statistically significant (P < 0.05) differences were
found with respect to seasonal rates, with higher rates of resistance to all -lactams in summer and winter. Penicillin resistance rates of
41, 31, 43, and 30% were seen in summer, autumn, winter, and spring,
respectively. No seasonality was observed for macrolide resistance rates.
Penicillin resistance among pneumococci has increased in Spain since
1989, from 44% in a previous national survey (5) to 60% in
this study when penicillin-intermediate and -resistant strains are
included. This increase is attributable to an increase in isolates in
the penicillin-resistant category: 36.5% in the present study versus
15.3% in 1989 (5). Furthermore, 58% resistance was found
in a study carried out in Madrid on isolates from children with
invasive pneumococcal infection between 1989 and 1993; only 14% of the
isolates exhibited intermediate resistance (12).
With respect to erythromycin resistance, an increase was identified
between 1989 (5) and 1996 to 1997 (10 versus 33.7%, respectively). This increase was due to an increase in the more highly
resistant strains (MIC 8 µg/ml) from 1990 (8) to 1996 to 1997 (9.4 versus 25.8%, respectively). In this study, the most common erythromycin resistance phenotype found was the constitutive phenotype (98.4%; 369 of 375 isolates); the M phenotype was found in
1.3% (5 strains), and the inducible phenotype was shown only in 1 strain. Interestingly, all five M phenotype isolates came from a single
hospital (Insular Hospital, Las Palmas, Spain). Significant differences
(P < 0.001) in M phenotype prevalence were found
between this hospital (31%; 5 M phenotype isolates among 16 erythromycin-resistant isolates) and others (0%).
It has been suggested that the selective pressure of the local pattern
of antibiotic consumption, together with the spread of resistant clones
(11), may account for the spread of antibiotic resistance.
The consumption of antibiotics has increased in areas where increases
in S. pneumoniae resistance have been described (8). In Spain, community antibiotic consumption accounts for 90% of total antibiotic consumption; 50% of this consists of
penicillins, 17% consists of macrolides, and 13% consists of oral
cephalosporins (2). Antibiotic consumption may be one of the
reasons for the seasonal variation in penicillin resistance observed in
this study.
Increases in resistance, together with significant local differences in
resistance patterns, make local susceptibility surveillance a must in
order to establish guidelines for the empiric treatment of
respiratory-tract infections.
| |
ACKNOWLEDGMENTS |
This study has been 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.
The members of the Spanish Surveillance Group for Respiratory
Pathogens are T. Jiménez de Anta and F. Marco, Clinic i
Provincial Hospital, Barcelona; E. Bouza and E. Cercenado, Gregorio
Marañón Hospital, Madrid; R. Gómez-Lus and
M. C. Rubio, University Hospital, Zaragoza; M. Gobernado and
N. Diosdado, La Fe Hospital, Valencia; I. Trujillano, University
Hospital, Salamanca; C. García Riestra and I. Rodríguez, Xeral de Galicia Hospital, Santiago de Compostela; M. de la Rosa and A. Martínez-Brocal, Virgen de las Nieves
Hospital, Granada; A. Gutierrez and A. García, La Paz Hospital,
Madrid; A. M. Martín Sánchez and F. Cañas,
Insular Hospital, Las Palmas; E. Perea and L. Martínez, Virgen
Macarena Hospital, Seville; G. Prats and F. Sanchez, Santa Creu i San
Pau Hospital, Barcelona; M. Casal and A. Ibarra, Reina Sofia Hospital,
Córdoba; R. Cisterna and A. Morla, Basurto Hospital, Bilbao;
A. C. Gómez-García and F. J. Blanco-Palenciano, Infanta Cristina Hospital, Badajoz; 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.
| |
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Antimicrobial Agents and Chemotherapy, February 1999, p. 357-359, Vol. 43, No. 2
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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