Juan García-de-Lomas

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.

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.

Antimicrobial Resistance among Respiratory Pathogens in Spain: Latest Data and Changes over 11 Years (1996-1997 to 2006-2007)

ABSTRACT A nationwide multicenter susceptibility surveillance study (Susceptibility to the Antimicrobials Used in the Community in España [SAUCE] project), SAUCE-4, including 2,559 Streptococcus pneumoniae, 2,287 Streptococcus pyogenes, and 2,736 Haemophilus influenzae isolates was carried out from May 2006 to June 2007 in 34 Spanish hospitals. Then, the results from SAUCE-4 were compared to those from all three previous SAUCE studies carried out in 1996-1997, 1998-1999, and 2001-2002 to assess the temporal trends in resistance and the phenotypes of resistance over the 11-year period. In SAUCE-4, on the basis of the CLSI breakpoints, penicillin (parenteral, nonmeningitis breakpoint) and cefotaxime were the antimicrobials that were the most active against S. pneumoniae (99.8% and 99.6%, respectively). Only 0.9% of isolates had a penicillin MIC of ≥2 μg/ml. In S. pyogenes, nonsusceptibility to erythromycin was observed in 19.4% of isolates. Among the H. influenzae isolates, a β-lactamase-positive prevalence of 15.7% was found. A statistically significant temporal decreasing trend over the 11-year period was observed for nonsusceptibility (from 60.0% to 22.9%) and resistance (from 36.5% to 0.9%) to penicillin and for the proportion of erythromycin-resistant isolates of S. pneumoniae of the macrolide-lincosamide-streptogramin B (MLSB) phenotype (from 98.4% to 81.3%). A similar trend was observed for the prevalence of ampicillin resistance (from 37.6% to 16.1%), β-lactamase production (from 25.7% to 15.7%), and β-lactamase-negative ampicillin resistance (BLNAR) in H. influenzae (from 13.5% to 0.7%). Among erythromycin-resistant isolates of S. pyogenes, a significant increasing trend in the prevalence of MLSB was observed (from 7.0% to 35.5%). SAUCE-4 confirms a generalized decline in the resistance of the main respiratory pathogens to the antimicrobials as well as a shift in their resistance phenotypes.

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.

Performance of the Binax NOW Streptococcus pneumoniae Urinary Antigen Assay for Diagnosis of Pneumonia in Children with Underlying Pulmonary Diseases in the Absence of Acute Pneumococcal Infection

ABSTRACT The performance of the Binax NOW immunochromatographic test for detecting Streptococcus pneumoniae antigen in urine specimens from 103 children presenting underlying pulmonary diseases with no recent pneumococcal infection was assessed. Our data indicate that this assay is unlikely to be useful for discriminating between children with and without pneumococcal pneumonia.

A large percentage of the Spanish population under 30 years of age is not protected against hepatitis A

A seroepidemiological study was conducted to assess the seroprevalence of hepatitis A (HAV) antibodies in the Spanish general population in 1992–93. A total of 2744 subjects (1337 men and 1437 women) in the 5–59 years age range were stratified by gender and age (5–12, 13–19, 20–29, 30–39, 40–49, 50–59 years). The presence of total anti‐HAV antibodies was investigated using a commercial enzyme immunoassay. Fifty‐five percent (95% CI: 53.5–57.2%) of the subjects were positive for anti‐HAV antibodies, the age‐standardized anti‐HAV prevalence being 65.4%. Prevalence of seropositive subjects increased with increasing age (χ2 = 996,17; P < 0.0001), being 11%, 25% and 54% for the 5–12, 13–19 and 20–29 age groups respectively. The results from this study showed a remarkable decline in seroprevalence rates among children, adolescents and young adults. The large number of susceptible subjects in these groups of the population has public health implications in a country with intermediate HAV prevalence. J. Med. Virol. 60:363–366, 2000.

Increasing telithromycin resistance among Streptococcus pyogenes in Europe

OBJECTIVES To assess changes in macrolide and ketolide resistance among Streptococcus pyogenes in Europe and to examine the relationship of resistance to antimicrobial usage. METHODS Clinical S. pyogenes isolates were collected from Denmark, Finland, France, Germany, Italy, Netherlands, Norway, Spain, Sweden, UK, Croatia, Hungary, Poland, Slovak Republic and Slovenia during 2002-03 (n = 2165) and 2004-05 (n = 2333). Resistance to telithromycin (MIC > or = 2) and erythromycin (MIC > or = 0.5) was determined by CLSI broth microdilution. Changes in resistance over time and the relationship of resistance to antimicrobial use (European Surveillance of Antimicrobial Consumption data) were assessed. Telithromycin-resistant isolates were characterized by PFGE to determine genetic relatedness and by PCR to detect mef(A), erm(A) and erm(B). RESULTS The erythromycin resistance rate during 2004-05 (11.6%) was similar to 2002-03 (10.4%). The proportion of macrolide-resistant isolates with the constitutive MLS(B) phenotype increased from 29.3% (2002-03) to 45.7% (2004-05). Telithromycin resistance increased from 1.8% in 2002-03 to 5.2% in 2004-05. For Western Europe, associations of telithromycin and erythromycin resistance, respectively, were found with azithromycin use (R2 = 0.52 and 0.60), clarithromycin use (R2 = 0.76 and 0.85) and total macrolide/lincosamide use (R2 = 0.75 and 0.69). For Eastern Europe, associations of antimicrobial use with resistance were not apparent. The 162 telithromycin-resistant isolates comprised 42 PFGE patterns with 68.5% in eight major PFGE groups. The erm(B) gene was detected in 155 of the 162 telithromycin-resistant isolates. CONCLUSIONS Significant increases in telithromycin resistance occurred from 2002-03 to 2004-05 in Europe. Macrolide use appears to be a factor in the emergence of ketolide resistance among S. pyogenes in Western Europe.

Activities of Six Different Quinolones against Clinical Respiratory Isolates of Streptococcus pneumoniae with Reduced Susceptibility to Ciprofloxacin in Spain

ABSTRACT Six quinolones were tested on 817 consecutive pneumococcal isolates for which ciprofloxacin MICs were high (≥2 μg/ml); the isolates had been collected during two recent Spanish surveillance studies. For strains for which the ciprofloxacin MIC was ≥4 μg/ml, the MICs at which 90% of the isolates tested against gemifloxacin, moxifloxacin, gatifloxacin, sparfloxacin, levofloxacin, and ofloxacin were inhibited were 0.25, 1, 1, 1, 4 and 16 μg/ml, respectively, and the corresponding prevalences of resistance were 0, 1, 4.5, 9.5, 8.4 and 23%. The proportion of isolates for which the ciprofloxacin MIC is high has increased over time.

Is Sexual Transmission an Important Pattern for Herpes Simplex Type 2 Virus Seroconversion in the Spanish General Population

Herpes simplex type 2 (HSV‐2) seroprevalence within a community is determined by sexual and perinatal transmission from mother to baby, the two main sources of virus shedding. A seroepidemiological study of HSV‐2 was undertaken on a representative sample (n = 3974) of the Spanish population to assess indirectly the relative relevance of these two transmisssion routes. The sample comprised 1922 men and 2052 women in the age range 5–59 years, stratified by sex and age (5–12, 13–19, 20–29, 30–39, 40–49, and 50–59 years). Sera were screened for HSV‐2 specific Ig G antibodies by an enzyme‐linked immunoabsorbent assay based on recombinant glycoprotein G2 (gG2). The overall prevalence of antibodies to HSV‐2 was 3.6% (95% CI: 3.1–4.2%). Prevalence by gender did not differ: males (3.6%; 95% CI: 2.8–4.6%) and females (3.6%; 95% CI: 2.8–4.5%). There were no significant differences between age groups with respect to seropositivity rates. Detection of HSV‐2 antibodies was not associated with increasing age, as is expected for a sexually transmitted disease. The fact that seroprevalence rates among the different age groups did not differ suggests that the virus is not circulating in the general population and may be restricted to risk groups only. Similar positivity rates found in the group of females of childbearing age and in the youngest population indicate that perinatal viral shedding is the main source of HSV‐2 seroconversion in the Spanish population. J. Med. Virol. 59:194–197, 1999.