Molecular epidemiology of Haemophilus influenzae strains isolated from patients with meningitis during 1999 to 2003

Keiko Hasegawa, Naoko Chiba, Reiko Kobayashi, Miyuki Morozumi, Satoshi Iwata, Keisuke Sunakawa, Kimiko Ubukata

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Abstract

A total of 535 Haemophilus influenzae strains from 226 Japanese institutions participating in the Nationwide Surveillance Study Group for Bacterial Meningitis were sent to our laboratory during 1999 to 2003. All strains were analyzed by PCR to identify the beta-lactam resistance genes, and their susceptibilities to beta-lactam agents were determined. These strains were classified into 6 genotype patterns and MIC90 values for ampicillin (ABPC): (i) beta-lactamase nonproducing, ABPC susceptible (BLNAS) strains and lacked all resistance genes (27.7% of isolates; MIC90, 0.5 microg/ml); (ii) beta-lactamase producing, ABPC resistant (BLPAR) strains (12.9%, 16 microg/ml); (iii) beta-lactamase nonproducing, ABPC resistant (Low-BLNAR) strains with a Asn526Lys amino acid substitution in ftsI gene encoding PBP3 (31.2%, 2 microg/ml); (iv) beta-lactamase nonproducing, ABPC resistant (BLNAR) strains with Ser385Thr and Asn526Lys substitutions in ftsI (17.2%, 8 microg/ml); (v) amoxicillin/clavlanic acid resistant (BLPACR I) strains, having beta-lactamase gene and a Asn526Lys amino acid substitution in ftsI (9.2%, 32 microg/ml); and (vi) amoxicillin/clavlanic acid resistant (BLPACR II), having beta-lactamase gene and ftsI substitutions as for BLNAR strains (1.9%, 64 microg/ml). All but 4 strains were serotype b. The prevalence of BLNAR strains has increased exponentially: 0% (n = 0/41) in 1999, 5.8% (n = 4/69) in 2000, 14.1% (n = 19/139) in 2001, 20.1% (n = 32/159) in 2002, and 29.1% (n = 37/127) in 2003. The MIC90s of BLNAR isolates except for ABPC were as follows: piperacillin, 0.125 microg/ml; ceftriaxone, 0.25 microg/ml; meropenem, 0.5 microg/ml; cefotaxime, 1 microg/ml; panipenem, 2 microg/ml; cefozopran, 16 microg/ml; and cefotiam, 64 microg/ml. To prevent such resistance from increasing, expedited vaccination, correct identification of the BLNAR molecularly, and the proper selection of proper antibiotics based on PK/PD must be taken.

Original languageEnglish
Pages (from-to)835-845
Number of pages11
JournalKansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases
Volume78
Issue number9
Publication statusPublished - 2004
Externally publishedYes

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Molecular Epidemiology
Haemophilus influenzae
beta-Lactamases
Meningitis
Genes
meropenem
Amoxicillin
Amino Acid Substitution
Cephalosporinase
Cefotiam
beta-Lactam Resistance
Piperacillin
Bacterial Meningitides
Acids
Cefotaxime
Ceftriaxone
beta-Lactams
Ampicillin
Vaccination
Genotype

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Molecular epidemiology of Haemophilus influenzae strains isolated from patients with meningitis during 1999 to 2003. / Hasegawa, Keiko; Chiba, Naoko; Kobayashi, Reiko; Morozumi, Miyuki; Iwata, Satoshi; Sunakawa, Keisuke; Ubukata, Kimiko.

In: Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases, Vol. 78, No. 9, 2004, p. 835-845.

Research output: Contribution to journalArticle

Hasegawa, Keiko ; Chiba, Naoko ; Kobayashi, Reiko ; Morozumi, Miyuki ; Iwata, Satoshi ; Sunakawa, Keisuke ; Ubukata, Kimiko. / Molecular epidemiology of Haemophilus influenzae strains isolated from patients with meningitis during 1999 to 2003. In: Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases. 2004 ; Vol. 78, No. 9. pp. 835-845.
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abstract = "A total of 535 Haemophilus influenzae strains from 226 Japanese institutions participating in the Nationwide Surveillance Study Group for Bacterial Meningitis were sent to our laboratory during 1999 to 2003. All strains were analyzed by PCR to identify the beta-lactam resistance genes, and their susceptibilities to beta-lactam agents were determined. These strains were classified into 6 genotype patterns and MIC90 values for ampicillin (ABPC): (i) beta-lactamase nonproducing, ABPC susceptible (BLNAS) strains and lacked all resistance genes (27.7{\%} of isolates; MIC90, 0.5 microg/ml); (ii) beta-lactamase producing, ABPC resistant (BLPAR) strains (12.9{\%}, 16 microg/ml); (iii) beta-lactamase nonproducing, ABPC resistant (Low-BLNAR) strains with a Asn526Lys amino acid substitution in ftsI gene encoding PBP3 (31.2{\%}, 2 microg/ml); (iv) beta-lactamase nonproducing, ABPC resistant (BLNAR) strains with Ser385Thr and Asn526Lys substitutions in ftsI (17.2{\%}, 8 microg/ml); (v) amoxicillin/clavlanic acid resistant (BLPACR I) strains, having beta-lactamase gene and a Asn526Lys amino acid substitution in ftsI (9.2{\%}, 32 microg/ml); and (vi) amoxicillin/clavlanic acid resistant (BLPACR II), having beta-lactamase gene and ftsI substitutions as for BLNAR strains (1.9{\%}, 64 microg/ml). All but 4 strains were serotype b. The prevalence of BLNAR strains has increased exponentially: 0{\%} (n = 0/41) in 1999, 5.8{\%} (n = 4/69) in 2000, 14.1{\%} (n = 19/139) in 2001, 20.1{\%} (n = 32/159) in 2002, and 29.1{\%} (n = 37/127) in 2003. The MIC90s of BLNAR isolates except for ABPC were as follows: piperacillin, 0.125 microg/ml; ceftriaxone, 0.25 microg/ml; meropenem, 0.5 microg/ml; cefotaxime, 1 microg/ml; panipenem, 2 microg/ml; cefozopran, 16 microg/ml; and cefotiam, 64 microg/ml. To prevent such resistance from increasing, expedited vaccination, correct identification of the BLNAR molecularly, and the proper selection of proper antibiotics based on PK/PD must be taken.",
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T1 - Molecular epidemiology of Haemophilus influenzae strains isolated from patients with meningitis during 1999 to 2003

AU - Hasegawa, Keiko

AU - Chiba, Naoko

AU - Kobayashi, Reiko

AU - Morozumi, Miyuki

AU - Iwata, Satoshi

AU - Sunakawa, Keisuke

AU - Ubukata, Kimiko

PY - 2004

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N2 - A total of 535 Haemophilus influenzae strains from 226 Japanese institutions participating in the Nationwide Surveillance Study Group for Bacterial Meningitis were sent to our laboratory during 1999 to 2003. All strains were analyzed by PCR to identify the beta-lactam resistance genes, and their susceptibilities to beta-lactam agents were determined. These strains were classified into 6 genotype patterns and MIC90 values for ampicillin (ABPC): (i) beta-lactamase nonproducing, ABPC susceptible (BLNAS) strains and lacked all resistance genes (27.7% of isolates; MIC90, 0.5 microg/ml); (ii) beta-lactamase producing, ABPC resistant (BLPAR) strains (12.9%, 16 microg/ml); (iii) beta-lactamase nonproducing, ABPC resistant (Low-BLNAR) strains with a Asn526Lys amino acid substitution in ftsI gene encoding PBP3 (31.2%, 2 microg/ml); (iv) beta-lactamase nonproducing, ABPC resistant (BLNAR) strains with Ser385Thr and Asn526Lys substitutions in ftsI (17.2%, 8 microg/ml); (v) amoxicillin/clavlanic acid resistant (BLPACR I) strains, having beta-lactamase gene and a Asn526Lys amino acid substitution in ftsI (9.2%, 32 microg/ml); and (vi) amoxicillin/clavlanic acid resistant (BLPACR II), having beta-lactamase gene and ftsI substitutions as for BLNAR strains (1.9%, 64 microg/ml). All but 4 strains were serotype b. The prevalence of BLNAR strains has increased exponentially: 0% (n = 0/41) in 1999, 5.8% (n = 4/69) in 2000, 14.1% (n = 19/139) in 2001, 20.1% (n = 32/159) in 2002, and 29.1% (n = 37/127) in 2003. The MIC90s of BLNAR isolates except for ABPC were as follows: piperacillin, 0.125 microg/ml; ceftriaxone, 0.25 microg/ml; meropenem, 0.5 microg/ml; cefotaxime, 1 microg/ml; panipenem, 2 microg/ml; cefozopran, 16 microg/ml; and cefotiam, 64 microg/ml. To prevent such resistance from increasing, expedited vaccination, correct identification of the BLNAR molecularly, and the proper selection of proper antibiotics based on PK/PD must be taken.

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