Olga Robledo

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

Increase in serotype 19A prevalence and amoxicillin non-susceptibility among paediatric Streptococcus pneumoniae isolates from middle ear fluid in a passive laboratory-based surveillance in Spain, 1997-2009

BackgroundConjugate vaccines, such as the 7-valent conjugate vaccine (PCV7), alter serotype nasopharyngeal carriage, potentially increasing cases of otitis media by non-vaccine serotypes.MethodsAll 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.ResultsA 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.ConclusionsIn 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.

Variations in serotypes and susceptibility of adult non-invasive Streptococcus pneumoniae isolates between the periods before (May 2000–May 2001) and 10 years after (May 2010–May 2011) introduction of conjugate vaccines for child immunisation in Spain

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 (P<0.001) 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% (P<0.001), mainly due to increases in serotypes 19A (294.1% increase; P<0.001) 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 (P<0.001). 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.

Serotype Distribution and Susceptibility of Streptococcus pneumoniae Isolates from Pleural Fluid in Spain from 1997 to 2008

ABSTRACT 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 (R2 ≥ 0.600; P ≤ 0.002). The incidence of serotypes 1 and 19A showed increasing trends (R2 ≥ 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.

Susceptibility of Recently Collected Spanish Pneumococci Nonsusceptible to Oral Penicillin from Serotypes Not Included in the 7-Valent Conjugate Vaccine

ABSTRACT 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 <33%/≤6.0% (erythromycin and oral cephalosporins with defined breakpoints), 85.1%/11.9% (amoxicillin), and 96.0%/52.2% (cefotaxime), respectively. Low susceptibility to common oral β-lactams was also found in serotypes 11A (95.5% susceptibility to cefotaxime and erythromycin) and 35B.

Susceptibility of pneumococci causing meningitis in Spain and prevalence among such isolates of serotypes contained in the 7-valent pneumococcal conjugate vaccine

1. Ramesh E, Raghunathan R, Manian RD et al. Synthesis and antibacterial property of quinolines with potent DNA gyrase activity. Bioorg Med Chem 2009; 17: 660–6. 2. Waites KB, Taylor-Robinson D. Mycoplasma and Ureaplasma. In: Murray PR, ed. Manual of Clinical Microbiology. Washington, DC: ASM Press, 2007; 1004–20. 3. Morozumi MS, Iwata K, Hasegawa K et al. Increased macrolide resistance of Mycoplasma pneumoniae in pediatric patients with community-acquired pneumonia. Antimicrob Agents Chemother 2008; 52: 348–50. 4. Clyde WA Jr. Mycoplasma pneumoniae infections of man. In: Tully JG, Whitcomb RF, eds. The Mycoplasmas II. Human and Animal Mycoplasmas. New York: Academic Press, 1979; 275–306. 5. Kenny GE. Mycoplasmas. In: Balows A, Hausler WJ Jr, Herrmann KL, eds. Manual of Clinical Microbiology. Washington, DC: ASM Press, 1991; 478–82. 6. Domagala JM. Structure-activity and structure-side-effect relationships for the quinolone antibacterials. J Antimicrob Chemother 1994; 33: 685–706.