Ampicillin-Resistant Non-β-Lactamase-Producing <i>Haemophilus influenzae</i> in Spain: Recent Emergence of Clonal Isolates with Increased Resistance to Cefotaxime and Cefixime

Antimicrobial Agents and Chemotherapy - Tập 51 Số 7 - Trang 2564-2573 - 2007
Silvia García-Cobos1, José Antonio Lepe1,2, Edurne Lázaro3, Federico Román1, Emilia Cercenado4, César Garcı́a-Rey5, María Pérez‐Vázquez1, Jesús Oteo1, Francisco J. de Abajo3
1Antibiotic Laboratory, Bacteriology Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
2Consejo Superior de Investigaciones Científicas, Madrid, Spain
3División de Farmacovigilancia, Agencia Española del Medicamento, Madrid, Spain
4Microbiology Department, Hospital Gregorio Marañón, Madrid, Spain
5GlaxoSmithKline S.A., Madrid, Spain

Tóm tắt

ABSTRACT The sequence of the ftsI gene encoding the transpeptidase domain of penicillin-binding protein 3 (PBP 3) was determined for 354 nonconsecutive Haemophilus influenzae isolates from Spain; 17.8% of them were ampicillin susceptible, 56% were β-lactamase nonproducing ampicillin resistant (BLNAR), 15.8% were β-lactamase producers and ampicillin resistant, and 10.4% displayed both resistance mechanisms. The ftsI gene sequences had 28 different mutation patterns and amino acid substitutions at 23 positions. Some 93.2% of the BLNAR strains had amino acid substitutions at the Lys-Thr-Gly (KTG) motif, the two most common being Asn526 to Lys (83.9%) and Arg517 to His (9.3%). Amino acid substitutions at positions 377, 385, and 389, which conferred cefotaxime and cefixime MICs 10 to 60 times higher than those of susceptible strains, were found for the first time in Europe. In 72 isolates for which the repressor acrR gene of the AcrAB efflux pump was sequenced, numerous amino acid substitutions were found. Eight isolates with ampicillin MICs of 0.25 to 2 μg/ml showed changes that predicted the early termination of the acrR reading frame. Pulsed-field gel electrophoresis analysis demonstrated that most BLNAR strains were genetically diverse, although clonal dissemination was detected in a group of isolates presenting with increased resistance to cefotaxime and cefixime. Background antibiotic use at the community level revealed a marked trend toward increased amoxicillin-clavulanic acid consumption. BLNAR H. influenzae strains have arisen by vertical and horizontal spread and have evolved to adapt rapidly to the increased selective pressures posed by the use of oral penicillins and cephalosporins.

Từ khóa


Tài liệu tham khảo

10.1128/JCM.44.5.1645-1649.2006

Bell, S. M., and D. Plowman. 1980. Mechanisms of ampicillin resistance in Haemophilus influenzae from respiratory tract. Lanceti:279-280.

10.1093/infdis/160.5.810

10.1128/AAC.25.6.706

10.1128/JCM.42.2.524-529.2004

Campos, J., and J. A. Sáez-Nieto. 2001. Gram-negative infections: Haemophilus and other clinically relevant gram-negative coccobacilli, p. 557-580. In N. Cimolai (ed.), Laboratory diagnosis of bacterial infections. Marcel Dekker, Inc., New York, NY.

Performance standards for antimicrobial susceptibility testing fifteenth edition 2005

10.1128/AAC.46.7.2208-2218.2002

10.1128/AAC.41.2.292

10.1128/jcm.32.10.2382-2386.1994

10.1126/science.7542800

10.1093/jac/dki167

10.1007/s150100050026

10.1128/JCM.36.12.3629-3635.1998

10.1016/S0140-6736(05)17907-0

10.1128/AAC.48.5.1509-1514.2004

10.1093/jac/dkl142

10.1089/107662903764736337

10.1093/jac/dkl310

10.1128/AAC.48.5.1630-1639.2004

10.1128/JCM.40.3.1063-1066.2002

10.1128/AAC.00960-06

10.1128/AAC.45.11.3226-3228.2001

10.1128/AAC.17.1.80

10.1093/jac/dkg474

10.1093/infdis/165-Supplement_1-S107

10.1128/iai.55.11.2585-2589.1987

10.1128/AAC.26.2.235

10.1128/AAC.1.4.283

10.1128/AAC.25.6.747

10.1128/AAC.49.5.1965-1972.2005

10.1128/AAC.01316-05

10.1128/JCM.33.9.2233-2239.1995

10.1016/S0140-6736(05)70770-4

10.1007/s10156-003-0278-Y

10.1128/AAC.45.6.1693-1699.2001

Guidelines for ATC classification and DDD assignment 2005

Thông tin
Thông tin xuất bản

Antimicrobial Agents and Chemotherapy

Tập 51 Số 7

2564-2573

Thông tin tác giả