Lorenzo Aguilar

Antimicrobial Susceptibilities of 1,684 Streptococcus pneumoniae and 2,039 Streptococcus pyogenes Isolates and Their Ecological Relationships: Results of a 1-Year (1998–1999) Multicenter Surveillance Study in Spain

ABSTRACT A nationwide multicenter susceptibility surveillance study which included 1,684 Streptococcus pneumoniae and 2,039S. pyogenes isolates was carried out over 1 year in order to assess the current resistance patterns for the two most important gram-positive microorganisms responsible for community-acquired infections in Spain. Susceptibility testing was done by a broth microdilution method according to National Committee for Clinical Laboratory Standards M100-S10 interpretative criteria. ForS. pneumoniae, the prevalences of highly resistant strains were 5% for amoxicillin and amoxicillin-clavulanic acid; 7% for cefotaxime; 22% for penicillin; 31% for cefuroxime; 35% for erythromycin, clarithromycin, and azithromycin; and 42% for cefaclor. For S. pyogenes, the prevalence of erythromycin resistance was 20%. Efflux was encountered in 90% of S. pyogenes and 5% of S. pneumoniae isolates that exhibited erythromycin resistance. Erythromycin resistance was associated with clarithromycin and azithromycin in both species, regardless of phenotype. Despite the different nature of the mechanisms of resistance, a positive correlation (r = 0.612) between the two species in the prevalence of erythromycin resistance was found in site-by-site comparisons, suggesting some kind of link with antibiotic consumption. Regarding ciprofloxacin, the MIC was ≥4 μg/ml for 7% of S. pneumoniae and 3.5% of S. pyogenes isolates. Ciprofloxacin resistance (MIC, ≥4 μg/ml) was significantly (P < 0.05) associated with macrolide resistance in both S. pyogenes and S. pneumoniae and with penicillin nonsusceptibility in S. pneumoniae.

Antimicrobial Resistance of 1,113Streptococcus pneumoniae Isolates from Patients with Respiratory Tract Infections in Spain: Results of a 1-Year (1996–1997) Multicenter Surveillance Study

ABSTRACT A nationwide susceptibility surveillance of 1,113Streptococcus 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 β-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.

Importance of Local Variations in Antibiotic Consumption and Geographical Differences of Erythromycin and Penicillin Resistance in Streptococcus pneumoniae

ABSTRACT A geographical analysis of how commonly prescribed oral antibiotics are quantitatively and qualitatively responsible for the different local rates of erythromycin and penicillin resistance in Streptococcus pneumoniae in Spain is presented. From 1998 to 1999 a multicenter surveillance study yielded 1,684 consecutive S. pneumoniae isolates from community-acquired respiratory infections. Data on antibiotic sales in the retail market for the same period were gathered, and the corresponding defined doses per 1,000 inhabitants per day were calculated. Macrolides and β-lactams were considered separately. Macrolides were subdivided into thrice-, twice-, and once-a-day macrolides, and β-lactams were split into aminopenicillins and cephalosporins. Univariate Spearman nonparametric coefficients (R) were calculated, and variables proving to be significantly associated (P < 0.1) were entered into several multiple lineal regression models. Ample variation in both resistance rates and antibiotic consumption was seen. Multivariate analyses showed that integrated consumption of both macrolides and β-lactams accounted well for erythromycin (R2 = 0.722; P = 0.002) and penicillin (R2 = 0.706; P = 0.002) resistance. Macrolides were more important drivers for local differences in both erythromycin and penicillin resistance than β-lactams were. Consumption of once-a-day macrolides was key for local erythromycin resistance variations. Cephalosporins were slightly more important penicillin resistance drivers than aminopenicillins were.

Geographical and Ecological Analysis of Resistance, Coresistance, and Coupled Resistance to Antimicrobials in Respiratory Pathogenic Bacteria in Spain

ABSTRACT A multicenter susceptibility surveillance (the S.A.U.C.E. project) including 2,721 Streptococcus pneumoniae, 3,174 Streptococcus pyogenes, and 2,645 Haemophilus influenzae consecutive isolates was carried out in 25 hospitals all over Spain from November 2001 to October 2002 to evaluate the current epidemiology of resistance of the main bacteria involved in community-acquired respiratory tract infections. Susceptibility testing was performed in a single centralized laboratory by a broth microdilution method. The prevalence of resistant S. pneumoniae strains was 0.4% for cefotaxime, 4.4% for amoxicillin and amoxicillin-clavulanic acid, 25.6% for cefuroxime-axetil, 34.5% for erythromycin, clarithromycin, and azithromycin, and 36.0% for cefaclor. Phenotypes of resistance to erythromycin were MLSB (macrolide-lincosamide-streptogramin B) in 89.9% (gene ermB) and M (macrolide) in 9.7% of cases (gene mefA). No strain harbored both genes simultaneously. Serotypes 19, 6, 23, 14, and 3 were the most prevalent, accounting for 54.6% of the total isolates. Resistance to macrolides seems to be the most alarming point, since among penicillin-susceptible isolates it reached 15.1% compared to 55.8% among penicillin-resistant strains. Geographically, a number of regions had rates of erythromycin resistance above 40% (even higher in children). Resistance to erythromycin was also high in S. pyogenes isolates: mean regional 33.2%, beta-lactamase-producing H. influenzae were 20%, whereas 4.4% had a beta-lactamase-negative, ampicillin-resistant phenotype. We highlight the importance of different geographical frequencies of coresistance (associations of resistance to different drugs within the same species) and coupled resistance (association of resistance between different species) probably resulting from different local coselective events.

Pharmacoepidemiological Analysis of Provincial Differences between Consumption of Macrolides and Rates of Erythromycin Resistance among Streptococcus pyogenes Isolates in Spain

ABSTRACT The M phenotype is by far the most common mechanism of erythromycin resistance among Streptococcus pyogenes isolates in Spain. A geographic analysis of the relationship between within-country differences in the prevalence of M-type resistance to erythromycin in S. pyogenes and the level of consumption of 14- and 15-membered macrolides within different provinces was carried out. From 1998 to 1999, a nationwide multicenter surveillance study yielded 2,039 consecutive pharyngeal isolates of S. pyogenes. Data on antibiotic consumption for the same period were gathered from IMS Health, and the corresponding daily defined doses per 1,000 inhabitants per day were calculated according to the Anatomic Therapeutic Classification index. Macrolide use was subdivided into dosages given three times a day (TID), twice a day (BID), or once a day (OD). Spearman nonparametric correlation coefficients (R) were calculated, and variables proving to be significantly associated (P < 0.1) were introduced into a linear regression model. The total consumption of macrolides presented a significant correlation with the prevalence of resistance (R = 0.527; P = 0.032). Neither TID nor BID macrolide consumption showed significant correlations. Only OD consumption had a significance below 0.1. These data are consistent with the hypothesis that only the total consumption of macrolides influences the local rates of M-type erythromycin resistance in S. pyogenes, and subgroups of macrolides seem to have an additive rather than a selective effect by contributing to increasing the final amount of macrolides used. Local variations in total consumption were associated only with BID consumption (R = 0.849; P = 0.004). The simple linear regression with total macrolide consumption showed a considerable determination coefficient (R2 = 0.678; P = 0.006). The model explains up to 68% of the measured variation and is clearly better as a predictor of the prevalence of resistance than the mere mean is. By solving the regression equation, the resultant value of 2.2 defined doses per 1,000 inhabitants per day fits with the existence of a critical threshold of selective pressure.

Antimicrobial Susceptibilities of 1,730 Haemophilus influenzae Respiratory Tract Isolates in Spain in 1998-1999

ABSTRACT A β-lactamase prevalence of 23% was found among 1,730Haemophilus influenzae isolates. Ampicillin susceptibility was 70%, and 12% of β-lactamase-negative strains presented diminished susceptibility to ampicillin (BLNAR phenotype). Susceptibility of 90% was found for cefaclor and clarithromycin, whereas it was nearly 100% for cefotaxime, cefixime, azithromycin, and cefuroxime. Ciprofloxacin-resistant (0.1%) and β-lactamase-positive amoxicillin/clavulanate-resistant (BLPACR) phenotypes (0.1%) are anecdotal so far.

Seroepidemiology of Bordetella pertussis infections in the Spanish population: a cross-sectional study

A study was conducted on a representative sample (n=4084) of the Spanish population to assess the prevalence of antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA). A total of 1982 men and 2102 women aged 5-59 years were stratified by sex and age (5-12, 13-19, 20-29, 30-39, 40-49 and 50-59 years). Antibodies to PT were found in 46% samples and to FHA in 74% and increased with age (p<0.0001), ranging from 35% in the 5-12 year age group to 52% in the 50-59 year age group for anti-PT and from 65 to 80% for anti-FHA, respectively. As vaccine induced-immunity wanes over time, the observed age distribution of antibodies suggests that Bordetella pertussis infection is widespread in the Spanish population and that pertussis booster vaccination in adolescents and adults with the newly developed acellular vaccines, should be considered if it is deemed necessary to control the circulation of the organism.

Survey of emm Gene Sequences from Pharyngeal Streptococcus pyogenes Isolates Collected in Spain and Their Relationship with Erythromycin Susceptibility

ABSTRACT We conducted a nationwide survey of the variable 5′ emm (M protein gene) sequences from 614 pharyngeal Streptococcus pyogenes isolates susceptible (299 isolates) and resistant (315 isolates) to erythromycin that were isolated in Spain from 1996 to 1999. Almost 98% of these isolates had emm sequences in agreement with previously recorded M antigen association. We only identified a new 5′ emm sequence in 17 isolates. Nine different emm types accounted for 85% of the S. pyogenes isolates susceptible to erythromycin. By contrast, only 3 emm types accounted for 70% of the erythromycin-resistant isolates. Further characterization of these isolates by ribotyping and pulsed-field gel electrophoresis indicated that high frequency of erythromycin resistance in Spain is due to few clones.

In vitro activity of ceftaroline against Streptococcus pneumoniae isolates exhibiting resistance to penicillin, amoxicillin, and cefotaxime.

Ten to forty percent of bacteremic pneumococcal infections occur in hospitalized patients, with the respiratory tract being the main portal of entry ([2][1], [3][2]). Empirical therapy of hospital-acquired pneumonia should cover Streptococcus pneumoniae and methicillin-resistant Staphylococcus

Clinical and Bacteriological Efficacy in Treatment of Acute Exacerbations of Chronic Bronchitis with Cefditoren-Pivoxil versus Cefuroxime-Axetil

ABSTRACT A randomized, double-blind, double-dummy trial was performed comparing 200 mg of cefditoren-pivoxil twice daily for 5 days versus standard cefuroxime-axetil treatment (250 mg twice daily for 10 days) of Anthonisen type I or II acute exacerbations of chronic bronchitis. The modified intention-to-treat population included 541 patients. Patients were assessed during therapy, at the end of therapy (visit 3; primary evaluation time point), and at follow-up. Clinical success was obtained in 79.9% of the 264 patients included in the cefditoren-pivoxil group and in 82.7% of the 277 patients in the cefuroxime-axetil group (treatment difference, 95% confidence interval [CI]: −2.8, −9.7 to 3.6%). Treatment clinical effects were more clearly seen in sputum signs (decreasing volume and purulence from approximately 80% to approximately 10% of the patients). At the end of treatment, exploratory analysis of the per-pathogen bacteriological response showed 72.8% (of 103 isolates) in the cefditoren-pivoxil arm versus 67.0% (of 94 isolates) in the cefuroxime-axetil group (treatment difference; 95% CI: 5.8, −7.0 to 18.6%). Globally, the per-pathogen bacteriological response correlated well with clinical success: 83.5% of 164 baseline isolates from patients with a clinical success were eradicated or presumably eradicated, in contrast to only 3% of 33 isolates from patients with a clinical failure. Clinical success in patients infected with Haemophilus influenzae, the most frequent isolate, was 84% (of 50) and 82.5% (of 40) (treatment difference; 95% CI: 1.5, −14 to 17%) in the cefditoren-pivoxil versus the cefuroxime-axetil group. Although this study does not prove that either drug is better than a placebo, cefditoren-pivoxil and the standard 10-day cefuroxime-axetil course had similar point estimates of success in acute exacerbations of chronic bronchitis.