Songmee Bae

Nasal colonization by four potential respiratory bacteria in healthy children attending kindergarten or elementary school in Seoul, Korea

A longitudinal analysis was carried out of the colonization by four potential respiratory pathogens - Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus - in 165 healthy children (aged 3-7 years) attending three kindergartens and 417 healthy children (aged 7-10 years) attending an elementary school in Seoul, Korea, by four consecutive examinations over 1 year. The prevalence of nasal carriers of one or more of four bacteria was found to be higher in younger children (≤7 years) (mean 68.6%) than that in older children (mean 46.8%). The mean rates of nasal carriage of Strep. pneumoniae, H. influenzae, M. catarrhalis and Staph. aureus were 16.8, 18.9, 20.2 and 18.2%, respectively. Colonization by Strep. pneumoniae, H. influenzae and M. catarrhalis was higher in pre-school children (28.6, 32.4 and 35.0%, respectively) than in school children (12.2, 13.6 and 14.3%, respectively). Carriage trends differed with age, with Strep. pneumoniae, H. influenzae and M. catarrhalis colonization decreasing with age but Staph. aureus colonization increasing. Positive associations of co-occurrence between Strep. pneumoniae, H. influenzae and M. catarrhalis were evident, with a significant negative association evident between Staph. aureus and the other three bacteria. A better understanding of the colonization and interaction of potential respiratory pathogens may be important for predicting changes in bacterial ecology and for designing control strategies that target bacterial colonization in upper respiratory tract infections.

Prevalence of serotype and multidrug-resistance of Streptococcus pneumoniae respiratory tract isolates in 265 adults and 36 children in Korea, 2002-2005.

In total, 301 isolates of Streptococcus pneumoniae collected from patients with respiratory tract infections admitted at primary clinics during 2002-2005 were tested for multidrug-resistance (MDR) phenotypes and their serotypes in Korea. The predominant serotypes were 19F, 19A, 23F, 11A, 3, 6A, and 6B, accounting for 67.8% of all isolates. Their serotype coverage by 23-valent polysaccharide vaccine and 7-valent conjugation vaccine was 73.1% and 39.2%, respectively. For the application of Clinical and Laboratory Standards Institutes new breakpoint for penicillin, the resistance rate of penicillin was 27.9% (but the penicillin resistance was 80.4% based on the previous breakpoint for penicillin of Clinical and Laboratory Standards Institute). Actually, the full resistance rate was only 4.0% (minimum inhibitory concentration >or=8 mg/L). Resistances to erythromycin, clindamycin, and tetracycline were very high (82.9%, 79.4%, and 71.7%, respectively). Especially, 56.1% of all the isolates were MDR, defined as resistant to three or more of the following agents: penicillin, erythromycin, clindamycin, cefotaxime, tetracycline, and levofloxacin. MDR strains were relatively associated with serotypes 19F, 19A, 23F, and 11A, accounting for 58.0% of the isolates. Their serotype coverage by 23-valent polysaccharide vaccine and 7-valent conjugation vaccine was 79.5% and 45.9%, respectively. Levofloxacin, as a representative fluoroquinolone, was active against 88.2% of all MDR isolates. Of particular concern was the high prevalence of MDR pneumococci in non-PCV7 serotypes with an MDR serotype 19A, 11A, 3, and 6A being mostly responsible. It would be prudent to consider more efficient protective strategies for people at high risk for pneumococcal diseases in regions with a high prevalence of MDR pneumococci.

Changes in serotype prevalence and antimicrobial resistance among invasive Streptococcus pneumoniae isolates in Korea, 1996-2008.

We investigated changes in serotypes and antimicrobial susceptibilities among 386 isolates of invasive Streptococcus pneumoniae collected from numerous hospitals in Korea from 1996 to 2008. Serotypes 19F (9.8 %), 23F (8.3 %), 19A (7.8 %), 6A (7.5 %), 3 (7.3 %), 9V (6.5 %), 6B (6.2 %), 14 (4.9 %), 1 (3.9 %), 11A (3.9 %) and 4 (3.1 %) represented 69.2 % of all isolates. While the overall proportion of PCV7 serotypes was stable over time, we observed modest decreases in children <5 years old and in adults ≥65 years old between 1996-1999 and 2007-2008. An increased prevalence of non-PCV7 serotypes in these age groups was primarily attributable to an increase in serotypes 3, 6A and 19A. Most invasive S. pneumoniae isolates showed high resistance rates to erythromycin (74.9 %), tetracycline (71.1 %) and clindamycin (61.7 %). Between 1996-2003 and 2004-2008, non-susceptibility rates to cefotaxime and multi-drugs (three or more classes) in PCV7 serotypes showed a declining trend, while in non-PCV7 serotypes there was an increasing trend. Non-PCV7 serotypes 6A and 19A, which mostly exhibited multidrug-resistant phenotypes (69.0 % and 76.7 % respectively), increased between 1996-2003 and 2004-2008. Although PCV7 was introduced in Korea in November 2003, pneumococcal vaccination has not been included in the national child vaccination programme. Our results provide details of serotype occurrence that will be useful when adoption of universal pneumococcal vaccination in Korea is being considered.

High prevalence of multiresistance in levofloxacin-nonsusceptible Streptococcus pneumoniae isolates in Korea

Korea exhibits the highest rates of multidrug resistance among Streptococcus pneumoniae. The increasing use of levofloxacin has raised concern about the dissemination of levofloxacin resistance in dominant multidrug-resistant (MDR) clones of our pneumococcal population. A total of 50 levofloxacin-nonsusceptible S. pneumoniae (MIC, ≥4 μg/mL) collected from a multihospital network from 1996 to 2006 were analyzed for serotype, antibiotic resistance profile, quinolone resistance-determining region mutation, and multilocus sequence type. Most levofloxacin-nonsusceptible S. pneumoniae (94.0%) exhibited an MDR phenotype. This phenotype was closely associated with a limited number of epidemic MDR clones that are well-known key agents of the global spread of antimicrobial resistance in S. pneumoniae. However, the clonal dissemination of levofloxacin-nonsusceptible S. pneumoniae was rare. Levofloxacin-nonsusceptible clones with nonvaccine serotypes increased during the post-vaccine era in this study. This result suggests that Korean clinicians must be aware of the levofloxacin resistance trend and need to be more prudent for the first choice of fluoroquinolone for empiric treatment of respiratory tract infections in clinical setting. Moreover, the emergence of new clones and their variations may be more frequently associated with resistance under this selective pressure, such as the introduction of a 7-valent pneumococcal conjugate vaccine into our community.

Cluster of Serogroup W-135 Meningococcal Disease in 3 Military Recruits

We describe a group of 3 cases of invasive meningococcal disease that occurred in a military training camp in April 2011. All three patients were hospitalized. Ultimately, two patients recovered and one died. One patient had meningitis, one patient had septicemia and meningitis, and the other had no definite septicemia or meningitis. Neisseria meningitidis serogroup W-135 was detected in the serum and cerebrospinal fluid (CSF) of all patients by real-time polymerase chain reaction. In the one case of mortality, two strains were isolated from the patients blood and CSF. Using multilocus sequence typing analysis, these strains were identified as a novel sequence type, ST-8912. Special attention is required for the meningococcal disease in military camp because the military personnels are in high risk of contact transmission. Graphical Abstract

Prevalent Multidrug-resistant Nonvaccine Serotypes in Pneumococcal Carriage of Healthy Korean Children Associated with the Low Coverage of the Seven-valent Pneumococcal Conjugate Vaccine

Objectives Our previous longitudinal multicenter-based carriage study showed that the average carriage rate of Streptococcus pneumoniae was 16.8% in 582 healthy children attending kindergarten or elementary school in Seoul, Korea. We assessed serotype-specific prevalence and antimicrobial resistance among colonizing pneumococcal isolates from young children in the era of low use of the seven-valent pneumococcal conjugate vaccine (PCV7). Methods Serotypes were determined by an agglutination test with specific antisera or by a multiplex polymerase chain reaction (PCR) assay. An antimicrobial susceptibility test was performed with broth microdilution in Korean 96-well panels from Dade-MicroScan (Sacramento, CA, USA). Results Pneumococcal colonization patterns were dynamic and longterm persistent carriage was rare, which indicated a sequential turnover of pneumococcal strains. Of the 369 pneumococci (except for 23 killed isolates), 129 (34.9%) isolates were PCV7 vaccine serotypes (VTs); 213 (57.8%) isolates were nonvaccine serotypes (NVTs); and the remaining 27 (7.2%) isolates were nontypable (NT). The highest rates of multidrug resistance (MDR) were observed in VTs (86.0%; 111/129 isolates) and NVTs (70.0%; 149/213 isolates). Conclusion This study overall showed the frequent carriage of VTs and NVTs with MDR in healthy children attending kindergarten or elementary school. Efforts should be directed toward reducing the extensive prescription of antibiotics and using new broader vaccines to reduce the expansion of MDR strains of NVTs in our community.

Serotype distribution and β-lactam resistance in Haemophilus influenzae isolated from patients with respiratory infections in Korea.

Haemophilus influenzae is a frequent causative bacterial pathogen of respiratory tract infections. Resistance to β-lactam antibiotics has been a significant clinical problem in treatment for H. influenzae respiratory infections. This study describes the serotype, antibiotic resistance and distribution of TEM-1 or ROB-1 β-lactamase in H. influenzae isolates from local private hospitals from 2002 to 2004. Among the 100 H. influenzae respiratory isolates, only 7% were identified as serotypes a, b, e, and f, with the remaining 93% being nontypeable. Resistance to ampicillin, cefaclor, and tetracycline was 57%, 46%, and 16%, respectively. All strains were susceptible to azithromycin and ciprofloxacin, whereas amoxicillin/clavulanate, cefotaxime, and imipenem exhibited reduced susceptibilities of 99%, 99%, and 91%, respectively. All 57 ampicillinresistant strains (minimum inhibitory concentration, MIC≥4 μg/ml) were β-lactamase-positive and possessed the TEM-1 type β-lactamase. One β-lactamase-positive amoxicillin/clavulanate-resistant isolate that was resistant to ampicillin (MIC>128 μg/ml) had the TEM-1 type β-lactamase and not susceptible to cefaclor and cefotaxime. Analysis of penicillin binding protein 3 revealed six residues (Asp-350, Met-377, Ala-502, Asn-526, Val-547, and Asn-569) that were substituted by Asn, Ile, Val, Lys, Ile, and Ser, respectively.

High prevalence of nasal carriage of β-lactamase-negative ampicillin-resistant Haemophilus influenzae in healthy children in Korea

This study investigated the carriage of antimicrobial resistant Haemophilus influenzae in 582 healthy children attending kindergarten or elementary school at four intervals over a 9-month period in Seoul, Korea. Diverse colonization patterns and a lower level of long-term persistent carriage by H. influenzae status were evident in this study. Colonizing H. influenzae isolates showed a high rate of resistance to β-lactams including ampicillin (51·9%), cefaclor (52·1%), and amoxicillin/clavulanate (16·3%). Based on the ampicillin resistance mechanism, H. influenzae isolates were categorized as β-lactamase-negative, ampicillin-susceptible (BLNAS) (48·1%), β-lactamase-positive, ampicillin-resistant (BLPAR) (22·6%), β-lactamase-negative, ampicillin-resistant (BLNAR) (22·8%), and β-lactamase-positive, amoxicillin/clavulanate-resistant (BLPACR) strains (6·5%). This study provides the first evidence of a high prevalence (22·8%) of BLNAR strains of H. influenzae nasal carriage in healthy children attending kindergarten or the first 2 years of elementary school in Korea. The high carriage of these resistant strains in overcrowded urban settings may create reservoirs for development of H. influenzae-resistant strains.