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This study explored the serotype distribution and antibiotic susceptibility of adult non-invasive Streptococcus pneumoniae isolates received in the Spanish Reference Laboratory for Pneumococci immediately prior to introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in June 2001 (May 2000-May 2001) and 10 years afterwards (May 2010-May 2011). Serotyping was performed by Quellung reaction and/or dot-blot assay, and minimum inhibitory concentrations (MICs) were determined by agar dilution. Clinical and Laboratory Standards Institute (CLSI) breakpoints were used for susceptibility interpretation. A total of 1274 isolates were identified (650 in the first period and 624 in the second period). PCV7 serotypes (as a group) showed a decrease (P0.001) from 43.2% in the first period to 13.9% in the second period, with MIC(90) values (MIC for 90% of the organisms) of levofloxacin for the remaining PCV7 serotypes of 16 μg/mL. Inversely, non-PCV7 serotypes (as a group) increased from 56.8% to 86.1% (P0.001), mainly due to increases in serotypes 19A (294.1% increase; P0.001) and 15A (180.0% increase; P=0.005). Globally, non-susceptibility to penicillin decreased from 54.2% in the first period to 36.9% in the second period (P0.001). Serotype 19A became the most worrisome, with an increase (at least five dilutions) in MIC(90) for all β-lactams in the second period, with non-susceptibility increasing from 18.2% to 71.4% (P=0.003) for penicillin and from 0.0% to 38.1% (P=0.022) for amoxicillin. Cefditoren showed the highest intrinsic activity (lowest MIC(50)/MIC(90)) overall and also against serotype 19A. Continuous surveillance of serotype distribution and antibiotic susceptibility among adult non-invasive isolates is necessary to detect emerging serotypes and to continuously assess the intrinsic activity of highly active oral antibiotics such as levofloxacin and cefditoren and of parenteral antibiotics such as cefotaxime.

The susceptibilities of pneumococci recently collected (up to June 2009) in Spain (500 isolates nonsusceptible to oral penicillin and 150 susceptible isolates) from serotypes not included in the conjugate vaccine were determined. Most nonsusceptible isolates (53.6%) belonged to serotype 19A. Susceptibility rates in serotype 19A penicillin-intermediate ( n = 201)/penicillin-resistant ( n = 67) isolates were

Background Conjugate vaccines, such as the 7-valent conjugate vaccine (PCV7), alter serotype nasopharyngeal carriage, potentially increasing cases of otitis media by non-vaccine serotypes. Methods All paediatric middle ear fluid (MEF) isolates received in the Spanish Reference Laboratory for Pneumococci through a passive, laboratory-based surveillance system from January 1997 to June 2009 were analysed. Data from 1997 to 2000 were pooled as pre-vaccination period. Trends over time were explored by linear regression analysis. Results A total of 2,077 isolates were analysed: 855 belonging to PCV7 serotypes, 466 to serotype 19A, 215 to serotype 3, 89 to serotype 6A and 452 to other serotypes (< 40 isolates each). Over time, there has been a decreasing trend for PCV7 serotypes (R2 = 0.944; p < 0.001, with significant decreasing trends for serotypes 19F, 14, 23F and 9V), and increasing trends for serotype 19A (R2 = 0.901; p < 0.001), serotype 3 (R2 = 0.463; p = 0.030) and other non-PCV7 serotypes (R2 = 0.877; p < 0.001), but not for serotype 6A (R2 = 0.311; p = 0.094). Considering all isolates, amoxicillin non-susceptibility showed an increasing trend (R2 = 0.528; p = 0.017). Regarding serotype 19A, increasing trends in non-susceptibility to penicillin (R2 = 0.726; p = 0.001), amoxicillin (R2 = 0.804; p < 0.001), cefotaxime (R2 = 0.546; p = 0.005) and erythromycin (R2 = 0.546; p = 0.009) were found, with amoxicillin non-susceptibility firstly detected in 2003 (7.4%) and increasing up to 38.0% in 2009. In PCV7 serotypes (which prevalence decreased from 70.7% during 1997-2000 to 10.6% in 2009) amoxicillin non-susceptibility rates showed an increasing trend (R2 = 0.702; p = 0.002). However, overall, amoxicillin non-susceptibility (≈25% in 2008-9) could be mainly attributed to serotype 19A (> 35% isolates) since PCV7 strains represented < 11% of total clinical isolates. Conclusions In contrast to reports on invasive pneumococcal strains, in MEF isolates the reduction in the prevalence of PCV7 serotypes was not associated with decreases in penicillin/erythromycin non-susceptibility. The high prevalence of serotype 19A among paediatric MEF isolates and the amoxicillin non-susceptibility found in this serotype are worrisome since amoxicillin is the most common antibiotic used in the treatment of acute otitis media. These data suggest that non-PCV7 serotypes (mainly serotype 19A followed by serotypes 3 and 6A) are important etiological agents of acute otitis media and support the added value of the broader coverage of the new 13-valent conjugate vaccine.

Trends in serotype incidence and susceptibility (1997 to 2008) of Spanish Streptococcus pneumoniae pleural isolates ( n = 831) were explored. Penicillin (oral) nonsusceptibility rates and the incidence of 7-valent pneumococcal conjugate vaccine (PCV-7) serotypes showed decreasing trends ( R 2 ≥ 0.600; P ≤ 0.002). The incidence of serotypes 1 and 19A showed increasing trends ( R 2 ≥ 0.759; P < 0.001), with no trends for serotype 3. Serotypes 19A, 1, and 3 represented 85% of pediatric isolates in 2008. In serotype 19A, the penicillin nonsusceptibility rate was 82.4% in 2008, associated with amoxicillin and cefotaxime nonsusceptibility in 21.4% of isolates. Inclusion of these serotypes in new vaccines offers the broadest coverage.

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

To study the influence of penicillin/amoxicillin non-susceptibility on the activity of third-generation cephalosporins, 430 consecutive penicillin non-susceptible Streptococcus pneumoniae 2007 isolates received in the Spanish Reference Pneumococcal Laboratory were tested. For comparative purposes, 625 penicillin-susceptible 2007 isolates were also tested. Susceptibility was determined by agar dilution using Mueller-Hinton agar supplemented with 5% sheep blood. Penicillin-susceptible strains were susceptible to amoxicillin, cefotaxime and ceftriaxone, 99.8% to cefpodoxime and 99.5% to cefdinir, and were inhibited by 0.12 microg/ml of cefditoren and 4 microg/ml of cefixime. Penicillin-intermediate strains were susceptible to cefotaxime and ceftriaxone, with50% susceptibility to cefdinir and cefpodoxime. The MIC(50) and MIC(90) values of cefditoren were 0.25 microg/ml and 0.5 microg/ml, respectively, whereas cefixime exhibited only marginal activity (MIC(90)=16 microg/ml). Penicillin-resistant strains were resistant to cefdinir and cefpodoxime, with 74.8% and 94.1% susceptibility to cefotaxime and ceftriaxone, respectively. Cefditoren MIC(50)/MIC(90) (0.5/1 microg/ml) were lower than cefotaxime and ceftriaxone. Among amoxicillin non-susceptible strains, susceptibility to cefdinir and cefpodoxime was10%, and susceptibility to cefotaxime decreased from 87.9% in the intermediate category to 63.0% in the resistant group. Cefditoren MIC(50)/MIC(90) (0.5/1 microg/ml) were lower than cefotaxime. In conclusion, the activity of cefixime, cefdinir and cefpodoxime was highly affected by penicillin/amoxicillin non-susceptibility, while parenteral third-generation cephalosporins exhibited higher intrinsic activity (MIC(90)=1 microg/ml for penicillin-resistant and 2 microg/ml for amoxicillin-resistant strains). Cefditoren exhibited one-dilution lower MIC(90) values for these strains, even against those of the most troublesome serotypes.

Objectives: To study the influence of resistance phenotypes (based on sentinel antibiotics: penicillin and amoxicillin with/without clavulanate) on the cefuroxime versus cefditoren susceptibility of Streptococcus pneumoniae and Haemophilus influenzae recovered from children with acute otitis media. Methods: Middle ear isolates (193 S. pneumoniae and 114 H. influenzae) received in the Spanish Reference Laboratory (Instituto de Salud Carlos III) were tested. Antimicrobial susceptibility to penicillin, amoxicillin with/without clavulanate, cefuroxime and cefditoren was determined by agar dilution using Mueller‐Hinton agar supplemented with 5% sheep blood for S. pneumoniae and Haemophilus Test Medium for H. influenzae. Strains were classified according to penicillin susceptibility (S. pneumoniae )o rb-lactamase production (H. influenzae). Results: The decrease in penicillin susceptibility of S. pneumoniae (from the susceptible to the resistant category) decreased amoxicillin and cefuroxime susceptibility rates from 100% to 34% and 0%, respectively. All pneumococcal strains were inhibited by 0.5 mg/L cefditoren, including those from penicillin-resistant serotypes 14, 23F, 6B and 9V with higher amoxicillin versus penicillin MICs. Susceptibility rates of b-lactamase-positive H. influenzae strains were 93.8% and 85.4% to amoxicillin/ clavulanate and cefuroxime, respectively. Resistance to amoxicillin/clavulanate (MIC � 8/4 mg/L) was 12.1% (8 out of 66) and 6.3% (3 out of 48) in b-lactamase-negative and -positive strains, respectively. All H. influenzae strains were inhibited by � 0.06 mg/L cefditoren. Conclusions: Susceptibility to sentinel b-lactams cannot predict activity of other members of the group. The addition of clavulanic acid to amoxicillin does not guarantee 100% coverage of H. influenzae, regardless of b-lactamase production.

The aim of this study was to evaluate the effects of penicillin, amoxicillin or erythromycin resistance on the in vitro activity of oral cephalosporins against Streptococcus pneumoniae pediatric isolates. A total of 282 pediatric isolates received during 2005 in the Spanish Reference Pneumococcal Laboratory were tested by agar dilution: 104 strains were penicillin-susceptible, 72 intermediate, and 106 resistant. Serotypes 9 and 14 were the most troublesome with10% susceptibility to oral cephalosporins. Cefditoren exhibited the highest intrinsic activity against penicillin/amoxicillin-resistant pneumococci, with MIC(90s )of 0.5 microg/ml, followed by cefotaxime (2 microg/ml), cefpodoxime (4 microg/ml), cefuroxime (16 microg/ml), and cefaclor/cefixime (or= 32 microg/ml), with 0% susceptibility to cefaclor, cefuroxime and cefpodoxime. Cefditoren 0.5 microg/ml inhibited 95.3%, 95.5%, and 98.6% of penicillin-, amoxicillin-, and erythromycin-resistant isolates, respectively. Susceptibility to oral cephalosporins shifted from90% in penicillin-susceptible isolates to approximately 38% for cefuroxime/cefpodoxime and approximately 7% for cefaclor in penicillin-intermediate, and to 0% in resistant isolates. Despite the different in vitro activity of oral cephalosporins, full resistance to penicillin or amoxicillin implied lack of susceptibility to all oral cephalosporins with defined CLSI breakpoints, rendering them inadequate as empirical treatment in countries with a high prevalence of penicillin resistance.