Toyonaga Y

Nationwide survey of the development of drug-resistance in the pediatric field: drug sensitivity of Haemophilus influenzae in Japan

We evaluated the β-lactamase-producing ability and resistance to 20 antibacterial agents of 448 clinically isolated strains of Haemophilus influenzae accumulated from October 2000 to July 2001 (phase 1) and of 376 different strains accumulated from January to June 2004 (phase 2), from institutions that participated in a nationwide Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease. Between phase 1 and phase 2 the proportion of β-lactamase-negative ampicillin (ABPC)-susceptible (BLNAS) strains declined from 62.9% to 34.3%; the proportions of β-lactamase-positive ABPC-resistant (BLPAR) strains were 8.3% and 6.4% in phases 1 and 2, but the proportion of β-lactamase-negative ABPC-resistant (BLNAR) strains increased from 28.8% in phase 1 to 59.3% in phase 2. Comparison of the MIC90 values of the antibacterial agents for H. influenzae in phase 1 and phase 2 showed that cefcapene, cefpodoxime, ceftriaxone, panipenem, and clarithromycin kept the same level, while cefdinir, faropenem, and rokitamycin showed 2-fold to 8-fold decreases. With the exception of the above antibiotics, all of the other antibacterial agents tested showed 2-fold to 4-fold increases. The MIC90 values of the β-lactam drugs for BLNAR were 2-fold to 32-fold higher than the values for BLNAS. The proportion of BLNAR H. influenzae strains rose dramatically over the 3 years between phases 1 and 2. In relation to age, prior administration of antibacterial agents, and attendance at a day nursery as background factors, no significant differences between BLNAS and BLNAR were detected in phase 1. In the phase 2 survey, the proportion of BLNAR strains showed significant differences between children under 3 years and those aged 3 years or more, and there were also significant differences according to whether antibacterial agents, especially β-lactams, had been administered previously. No significant difference was found in resistant bacteria according to whether or not a child had attended a day nursery.

Genetic analysis of a pediatric clinical isolate of Moraxella catarrhalis with resistance to macrolides and quinolones

During the surveillance conducted in 2012 by the Drug-resistant Pathogen Surveillance Group in Pediatric Infectious Disease, we isolated a strain of Moraxella catarrhalis that demonstrated resistance to both macrolides and quinolones from a male pediatric patient aged 1.5 years who had developed acute bronchitis. Then we evaluated the susceptibility of this strain to different types of antibacterial agents and conducted a genetic analysis. The results of the susceptibility evaluation showed that the MIC values of azithromycin, clarithromycin, and rokitamycin were >64 μg/mL, >64 μg/mL, and 4 μg/mL, respectively; clearly demonstrating resistance to macrolides. The MIC values of the quinolones levofloxacin, tosufloxacin, and garenoxacin were 4 μg/mL, 2 μg/mL, and 1 μg/mL, respectively; indicating decreased susceptibility. The genetic analysis of this strain revealed one mutation in 23s rRNA with a replacement of adenine by thymine at nucleotide position 2330 (A2330T) and another mutation in gyrB at nucleotide position 1481 by replacement of adenine with guanine (A1481G) that caused a substitution of the 494 th asparagine acid by glycine, as being associated with the observed resistance to macrolides and quinolones, respectively. Similar to drug-resistant bacteria Streptococcus pneumoniae and Haemophilus influenzae, the prevalence of which has recently increased, the treatment of drug-resistant M. catarrhalis infections is considered difficult due to the development of resistance to different types of antibacterial agents. It is vital to maintain an unwavering focus on the trend toward an increasing number of drug-resistant M. catarrhalis strains and ensure the proper use of each antibacterial agent.

Nationwide survey of the development of drug-resistant pathogens in the pediatric field: drug sensitivity of Streptococcus pneumoniae in Japan.

We evaluated the resistance to 20 different antibacterial agents of 362 clinically isolated strains of Streptococcus pneumoniae accumulated from October 2000 to July 2001 (phase 1) and of 332 different strains accumulated from January to June 2004 (phase 2), from institutions throughout Japan that participated in the surveys carried out by the Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease. In phase 1, the proportions of penicillin-sensitive S. pneumoniae (PSSP), penicillin-insensitive S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP) were 35.4%, 34.8%, and 29.8%, respectively, and the proportions were almost the same in phase 2: 33.1%, 37.0%, and 29.8%, respectively. Comparison of the MIC90 values of the antibacterial agents for PRSP in phase 1 and phase 2 revealed that these values for cefditoren, cefpodoxime, cefdinir, faropenem, ceftriaxone, cefotaxime, meropenem, and vancomycin increased by twofold to fourfold during the 3 years between phase 1 and phase 2. However the MIC90 of rokitamycin increased more than fourfold. The proportion of S. pneumoniae that were PISP + PRSP remained almost constant over the 3 years between phase 1 and phase 2. The background factors of patient age, previous administration of antibacterial agents, and attendance at a day nursery were examined; we found that in phase 1, the proportion of PISP + PRSP was significantly higher than that of PSSP in patients under 4 years old who had previously received antibacterial agents, but no significant differences were found in any of these background factors in the phase 2 survey. No significant difference was found in the proportions of penicillin-resistant bacteria according to whether or not the child had attended a day nursery.

Nationwide survey of Streptococcus pneumoniae drug resistance in the pediatric field in Japan

Streptococcus pneumoniae is a major causative pathogen of pneumonia in children. The Drug‐Resistant Pathogen Surveillance Group in Pediatric Infectious Disease conducted a nationwide surveillance of S. pneumoniae in 2000–2001, 2004, 2007, 2010 and 2012, and investigated changes in drug resistance of S. pneumoniae.

Serotype replacement of Streptococcus pneumoniae due to seven-valent pneumococcal conjugate vaccine in Japan

This study examined the trends for the serotypes of S. pneumoniae that have caused infections before (2010) and after (2012) the introduction of PCV‐7 in Japan.

Nationwide survey of drug resistance of S. pneumoniae in the pediatric field in Japan

Streptococcus pneumoniae is a major causative pathogen of pneumonia in children. The Drug‐Resistant Pathogen Surveillance Group in Pediatric Infectious Disease conducted a nationwide surveillance of S. pneumoniae in 2000–2001, 2004, 2007, 2010 and 2012, and investigated changes in drug resistance of S. pneumoniae.