Outbreak of Ceftazidime Resistance Due to a Novel Extended-Spectrum β-Lactamase in Isolates from Cancer Patients

Naumovski, Louie; Quinn, John P.; Miyashiro, Deborah; Patel, Maitraya; Bush, Karen; Singer, Susan B.; Graves, Donna; Palzkill, Tim; Arvin, Ann M.

doi:10.1128/aac.37.2.375

Cited by 51 publications

(92 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The Lys-39 mutation (characterizing the TEM-2 enzyme) is frequent among extended-spectrum ␤-lactamases, being present in TEM-3, TEM-7, TEM-8, TEM-11, TEM-13, TEM-14, TEM-16, TEM-18, and TEM-24 (11,19). Such frequency is higher than expected if the low frequency of TEM-2 among the (11).…”

Section: Discussionmentioning

confidence: 56%

“…The change Arg-1643Ser has been found previously in TEM-5, TEM-7, TEM-8, TEM-9, TEM-10, TEM-12, TEM-24, and TEM-26 (6,11,19). Dramatic changes in the hydrolysis of ceftazidime and aztreonam occurred when we introduced the mutation Ser-164.…”

Section: Discussionmentioning

confidence: 80%

“…This effect could be increased by the higher promoter strength of the natural bla TEM-2 gene from Tn1 (7). The change Glu-1043Lys was identified previously in TEM-3, TEM-4, TEM-6, TEM-8, TEM-9, TEM-14, TEM-15, TEM-16, TEM-17, TEM-18, TEM-24, and TEM-26 (6,11,19), and the change Glu-2403Lys was identified in TEM-5, TEM-10, and TEM-24 (6,11). These changes at positions 104 and 240 consistently decreased susceptibility to ceftazidime and aztreonam.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Single amino acid replacements at positions altered in naturally occurring extended-spectrum TEM beta-lactamases

Blázquez

Morosini

Negri

et al. 1995

Antimicrob Agents Chemother

View full text Add to dashboard Cite

By directed mutagenesis, we constructed a set of seven TEM-1 derivatives containing single replacements in each one of the amino acids substituted in naturally occurring extended-spectrum TEM ␤-lactamases. The exact contribution of each mutation to the resistance phenotype was determined. In addition, mutant enzyme production and stabilities were studied. Five of seven mutations determined to some extent variations in cephalosporin and/or monobactam activity. Dramatic changes in the hydrolysis of ceftazidime and aztreonam occurred when a serine was at position 164. Changes at positions 104, 238, and 240 showed more leaky variation in activity towards cephalosporins and aztreonam. Replacements at positions 237 and 265 caused no variation in susceptibility to cephalosporins. Interestingly, the change from Gln to Lys at position 39 found in TEM-2, classically considered a neutral change, slightly but consistently increased the MIC of ceftazidime and aztreonam. The in vitro construction of mutations appearing in naturally occurring TEM-␤-lactamases, studied in the same genetic context, may help to understand the evolution of extended-spectrum ␤-lactamases.The production of TEM-type ␤-lactamases is the most prevalent mode of resistance to ␤-lactam antibiotics. TEM-1 ␤-lactamase is considered a broad-spectrum enzyme because it hydrolyzes both penicillins and cephalosporins (4). TEM-1, however, cannot efficiently inactivate new extended-spectrum cephalosporins, such as cefotaxime and ceftazidime, and monobactams, such as aztreonam. Molecular variants of TEM-1, termed extended-spectrum ␤-lactamases, emerged and disseminated probably as a consequence of the introduction of these extended-spectrum ␤-lactam antibiotics.After years of intensive study of molecular variations involved in substrate profile alterations of TEM enzymes, it is now known that clinically resistant variants are the result of amino acid substitutions in one of several well-defined positions or of combinations of two to five of these substitutions (for a review, see reference 11). Figure 1 shows the modified positions in these resistant variants and the amino acids by which they are substituted in naturally occurring TEM-type ␤-lactamases. For each position, the replacement is with a particular amino acid, the only exception being Arg-164, which can be replaced by either Ser or His. Several authors constructed TEM-1 derivatives containing some of the abovedescribed single mutations by either oligonucleotide-directed mutagenesis (10, 30) or subcloning of fragments containing those mutations (28). Biochemical and microbiological studies have been performed with some of these mutants. Nevertheless, none of these publications includes a comparative study of the variations in ␤-lactamase phenotype and stability resulting from all seven single mutations corresponding to the seven positions modified in naturally occurring ␤-lactamases. In addition, the microbiological activities were, in each one of these studies, measured in a different genetic context (prom...

show abstract

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Single amino acid replacements at positions altered in naturally occurring extended-spectrum TEM beta-lactamases

Blázquez

Morosini

Negri

et al. 1995

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Although Cotton et al (4) had described an outbreak due to horizontal transmission between patients, ESBL can also arise from selection in individual microbiota. The use of cephalosporins, mainly ceftazidime, has been indicated as one of the major risk factors for acquisition of ESBL (7,18,21,25). Lucet et al (15) pointed other risk factors for ESBL acquisition which are associated with the severity of illness of patient requiring long stay in intensive care units and presence of catheters.…”

Section: Introductionmentioning

confidence: 99%

Extended-spectrum beta-lactamases in Klebsiella spp and Escherichia coli obtained in a Brazilian teaching hospital: detection, prevalence and molecular typing

Freitas¹,

Machado²,

Soares³

et al. 2003

Braz. J. Microbiol.

View full text Add to dashboard Cite

His study was performed to compare the methods of detection and to estimate the prevalence of extendedspectrum β-lactamases (ESBL) among Klebsiella spp and E. coli in a university hospital in southern Brazil. We also used a molecular typing method to evaluate the genetic correlation between isolates of ESBL K. pneumoniae. Production of ESBL was investigated in 95 clinical isolates of Klebsiella spp and Escherichia coli from Hospital de Clínicas de Porto Alegre, using Kirby-Bauer zone diameter (KB), double-disk diffusion (DD), breakpoint for ceftazidime (MIC CAZ), increased zone diameter with clavulanate (CAZ/CAC) and ratio of ceftazidime MIC/ceftazidime-clavulanate MIC (MIC CAZ/CAC). Molecular typing was performed by DNA macrorestriction analysis followed by pulsed-field gel electrophoresis. The KB method displayed the highest rates of ESBL (up to 70% of Klebsiella and 59% of E. coli), contrasting with all the other methods (p < 0.05). The confirmatory methods (DD, MIC CAZ, CAZ/CAC and MIC CAZ/CAC) showed a range of ESBL production from 8 to 13% for E. coli and from 33 to 40% for Klebsiella species. Therefore, the KB method was useful only as a screening method as it provided several false positive results. Molecular typing of 17 ESBL K. pneumoniae indicated that the isolates had no clonal relation. We found a good correlation among the confirmatory methods for ESBL detection although the methods which evaluate inhibition of the β-lactamase by clavulanate appeared to be more specific. The high prevalence of ESBL Klebsiella in our hospital is probably due to individual selection of resistant strains rather than the transmission of a common strain.

show abstract

“…At present, at least 67 TEM-derived and 12 SHV-derived ESBLs have been described (e.g. Jacoby & Medeiros, 1991;Naumovski et al, 1992). More ESBLs are being added to the list, e.g.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of extended-spectrum β-lactamase-producing Gram-negative bacteria in septicaemic neonates in a tertiary care hospital

Jain

Roy

Gupta

et al. 2003

Journal of Medical Microbiology

152

View full text Add to dashboard Cite

The present study was undertaken to investigate the high incidence of multiresistant Gram-negative bacilli causing neonatal septicaemia. Samples of neonatal blood from 728 suspected cases were obtained in brain heart infusion broth with sodium polyanethol sulfonate. All Gram-negative rods isolated were subsequently subjected to routine antimicrobial susceptibility testing and tests for extended-spectrum â-lactamase (ESBL) production, as per NCCLS recommendations. ESBL was detected in 86·6 % of Klebsiella spp., 73·4 % of Enterobacter spp. and 63·6 % of Escherichia coli strains. It was also observed that 74·4-80·9 % of these ESBL producers were resistant to cefotaxime and 47·6-59·5 % were resistant to ceftazidime in routine susceptibility testing. Some ESBL producers (36·3-61·5 %) were found to be susceptible to either or both cephalosporins used in this study. It is concluded that indiscriminate use of third-generation cephalosporins may be responsible for the selection of ESBL-producing multiresistant strains in the neonatal intensive-care unit (NICU).

show abstract

Outbreak of Ceftazidime Resistance Due to a Novel Extended-Spectrum β-Lactamase in Isolates from Cancer Patients

Cited by 51 publications

References 0 publications

Single amino acid replacements at positions altered in naturally occurring extended-spectrum TEM beta-lactamases

Single amino acid replacements at positions altered in naturally occurring extended-spectrum TEM beta-lactamases

Extended-spectrum beta-lactamases in Klebsiella spp and Escherichia coli obtained in a Brazilian teaching hospital: detection, prevalence and molecular typing

Prevalence of extended-spectrum β-lactamase-producing Gram-negative bacteria in septicaemic neonates in a tertiary care hospital

Contact Info

Product

Resources

About