scholarly journals Interactions of Ceftobiprole with β-Lactamases from Molecular Classes A to D

2007 ◽  
Vol 51 (9) ◽  
pp. 3089-3095 ◽  
Author(s):  
Anne Marie Queenan ◽  
Wenchi Shang ◽  
Malgosia Kania ◽  
Malcolm G. P. Page ◽  
Karen Bush
Keyword(s):  
Functional Groups ◽  
Hydrolytic Stability ◽  
Enterobacter Cloacae ◽  
Class A ◽  
Extended Spectrum ◽  
Class D ◽  
The Family ◽  
Class B ◽  
The Common ◽  
Antibacterial Spectrum

ABSTRACT The interactions of ceftobiprole with purified β-lactamases from molecular classes A, B, C, and D were determined and compared with those of benzylpenicillin, cephaloridine, cefepime, and ceftazidime. Enzymes were selected from functional groups 1, 2a, 2b, 2be, 2d, 2e, and 3 to represent β-lactamases from organisms within the antibacterial spectrum of ceftobiprole. Ceftobiprole was refractory to hydrolysis by the common staphylococcal PC1 β-lactamase, the class A TEM-1 β-lactamase, and the class C AmpC β-lactamase but was labile to hydrolysis by class B, class D, and class A extended-spectrum β-lactamases. Cefepime and ceftazidime followed similar patterns. In most cases, the hydrolytic stability of a substrate correlated with the MIC for the producing organism. Ceftobiprole and cefepime generally had lower MICs than ceftazidime for AmpC-producing organisms, particularly AmpC-overexpressing Enterobacter cloacae organisms. However, all three cephalosporins were hydrolyzed very slowly by AmpC cephalosporinases, suggesting that factors other than β-lactamase stability contribute to lower ceftobiprole and cefepime MICs against many members of the family Enterobacteriaceae.

scholarly journals Ceftazidime-avibactam

2021 ◽  
Vol 34 (Suppl 1) ◽  
pp. 38-40
Author(s):  
Mayra Matesanz ◽  
José Mensa ◽  
Keyword(s):  
Enterobacter Cloacae ◽  
Generation Cephalosporin ◽  
Multidrug Resistant ◽  
Class A ◽  
Class D ◽  
Multidrug Resistant Organisms ◽  
Resistant Mutants ◽  
Colonization Period ◽  
Antibacterial Spectrum ◽  
Selection Of

Ceftazidime is a 3rd generation cephalosporin active against Pseudomonas aeruginosa. Avibactam is an inhibitor of class A, C and some class D β-lactamases. The antibacterial spectrum of ceftazidime-avibactam covers 95% of P. aeruginosa isolates and >99% of enterobacteria, including strains carrying extended-spectrum β-lactamases (ESBLs). Selection of resistant mutants in Klebsiella pneumoniae and Enterobacter cloacae strains producing KPC-3 or KPC-2 after exposure to ceftazidime-avibactam has been described by the appearance of one or more amino acid changes in the Ω-loop of the β-lactamase. These strains usually regain susceptibility to meropenem. There is evidence of a shorter multidrug-resistant organisms colonization period in patients treated with this antimicrobial, which could be beneficial in the treatment of infections caused by bacteria carrying ESBLs or carbapenemases.

scholarly journals Interactions of β-Lactamases with Sanfetrinem (GV 104326) Compared to Those with Imipenem and with Oral β-Lactams

1998 ◽  
Vol 42 (5) ◽  
pp. 1168-1175 ◽  
Author(s):  
Gioia S. Babini ◽  
Meifang Yuan ◽  
David M. Livermore
Keyword(s):  
Functional Group ◽  
Klebsiella Oxytoca ◽  
Enterobacter Cloacae ◽  
Proteus Vulgaris ◽  
Morganella Morganii ◽  
Full Activity ◽  
Class A ◽  
Extended Spectrum ◽  
Class B ◽  
Hydrolysis Of

ABSTRACT Sanfetrinem is a trinem β-lactam which can be administered orally as a hexatil ester. We examined whether its β-lactamase interactions resembled those of the available carbapenems, i.e., stable to AmpC and extended-spectrum β-lactamases but labile to class B and functional group 2f enzymes. The comparator drugs were imipenem, oral cephalosporins, and amoxicillin. MICs were determined for β-lactamase expression variants, and hydrolysis was examined directly with representative enzymes. Sanfetrinem was a weak inducer of AmpC β-lactamases below the MIC and had slight lability, with ak cat of 0.00033 s−1 for theEnterobacter cloacae enzyme. Its MICs for AmpC-derepressedE. cloacae and Citrobacter freundii were 4 to 8 μg/ml, compared with MICs of 0.12 to 2 μg/ml for AmpC-inducible and -basal strains; MICs for AmpC-derepressed Serratia marcescens and Morganella morganii were not raised. Cefixime and cefpodoxime were more labile than sanfetrinem to theE. cloacae AmpC enzyme, and AmpC-derepressed mutants showed much greater resistance; imipenem was more stable and retained full activity against derepressed mutants. Like imipenem, sanfetrinem was stable to TEM-1 and TEM-10 enzymes and retained full activity against isolates and transconjugants with various extended-spectrum TEM and SHV enzymes, whereas these organisms were resistant to cefixime and cefpodoxime. Sanfetrinem, like imipenem and cefixime but unlike cefpodoxime, also retained activity against Proteus vulgaris and Klebsiella oxytoca strains that hyperproduced potent chromosomal class A β-lactamases. Functional group 2f enzymes, including Sme-1, NMC-A, and an unnamed enzyme fromAcinetobacter spp., increased the sanfetrinem MICs by up to 64-fold. These enzymes also compromised the activities of imipenem and amoxicillin but not those of the cephalosporins. The hydrolysis of sanfetrinem was examined with a purified Sme-1 enzyme, and biphasic kinetics were found. Finally, zinc β-lactamases, including IMP-1 and the L1 enzyme of Stenotrophomonas maltophilia, conferred resistance to sanfetrinem and all other β-lactams tested, and hydrolysis was confirmed with the IMP-1 enzyme. We conclude that sanfetrinem has β-lactamase interactions similar to those of the available carbapenems except that it is a weaker inducer of AmpC types, with some tendency to select derepressed mutants, unlike imipenem and meropenem.

scholarly journals Cyclic Boronates Inhibit All Classes of β-Lactamases

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Samuel T. Cahill ◽  
Ricky Cain ◽  
David Y. Wang ◽  
Christopher T. Lohans ◽  
David W. Wareham ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Bacterial Infections ◽  
Binding Mode ◽  
Gram Negative ◽  
Content Type ◽  
Class A ◽  
Class D ◽  
Dual Action ◽  
The Common ◽  
Continued Use

ABSTRACT β-Lactamase-mediated resistance is a growing threat to the continued use of β-lactam antibiotics. The use of the β-lactam-based serine-β-lactamase (SBL) inhibitors clavulanic acid, sulbactam, and tazobactam and, more recently, the non-β-lactam inhibitor avibactam has extended the utility of β-lactams against bacterial infections demonstrating resistance via these enzymes. These molecules are, however, ineffective against the metallo-β-lactamases (MBLs), which catalyze their hydrolysis. To date, there are no clinically available metallo-β-lactamase inhibitors. Coproduction of MBLs and SBLs in resistant infections is thus of major clinical concern. The development of “dual-action” inhibitors, targeting both SBLs and MBLs, is of interest, but this is considered difficult to achieve due to the structural and mechanistic differences between the two enzyme classes. We recently reported evidence that cyclic boronates can inhibit both serine- and metallo-β-lactamases. Here we report that cyclic boronates are able to inhibit all four classes of β-lactamase, including the class A extended spectrum β-lactamase CTX-M-15, the class C enzyme AmpC from Pseudomonas aeruginosa, and class D OXA enzymes with carbapenem-hydrolyzing capabilities. We demonstrate that cyclic boronates can potentiate the use of β-lactams against Gram-negative clinical isolates expressing a variety of β-lactamases. Comparison of a crystal structure of a CTX-M-15:cyclic boronate complex with structures of cyclic boronates complexed with other β-lactamases reveals remarkable conservation of the small-molecule binding mode, supporting our proposal that these molecules work by mimicking the common tetrahedral anionic intermediate present in both serine- and metallo-β-lactamase catalysis.

scholarly journals Characterization of beta-lactamase gene blaPER-2, which encodes an extended-spectrum class A beta-lactamase.

1996 ◽  
Vol 40 (3) ◽  
pp. 616-620 ◽  
Author(s):  
A Bauernfeind ◽  
I Stemplinger ◽  
R Jungwirth ◽  
P Mangold ◽  
S Amann ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Beta Lactamase ◽  
Reading Frame ◽  
Beta Lactamases ◽  
Class A ◽  
Extended Spectrum ◽  
The Family ◽  
Extended Spectrum Beta Lactamases ◽  
Lactamase Gene

Plasmidic extended-spectrum beta-lactamases of Ambler class A are mostly inactive against ceftibuten. Salmonella typhimurium JMC isolated in Argentina harbors a bla gene located on a plasmid (pMVP-5) which confers transferable resistance to oxyiminocephalosporins, aztreonam, and ceftibuten. The beta-lactamase PER-2 (formerly ceftibutenase-1; CTI-1) is highly susceptible to inhibition by clavulanate and is located at a pI of 5.4 after isoelectric focusing. The blaPER-2 gene was cloned and sequenced. The nucleotide sequence of a 2.2-kb insert in vector pBluescript includes an open reading frame of 927 bp. Comparison of the deduced amino acid sequence of PER-2 with those of other beta-lactamases indicates that PER-2 is not closely related to TEM or SHV enzymes (25 to 26% homology). PER-2 is most closely related to PER-1 (86.4% homology), an Ambler class A enzyme first detected in Pseudomonas aeruginosa. An enzyme with an amino acid sequence identical to that of PER-1, meanwhile, was found in various members of the family Enterobacteriaceae isolated from patients in Turkey. Our data indicate that PER-2 and PER-1 represent a new group of Ambler class A extended-spectrum beta-lactamases. PER-2 so far has been detected only in pathogens (S. typhimurium, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis) isolated from patients in South America, while the incidence of PER-1-producing strains so far has been restricted to Turkey, where it occurs both in members of the family Enterobacteriaceae and in P. aeruginosa.

scholarly journals Genetic Diversity, Biochemical Properties, and Detection Methods of Minor Carbapenemases in Enterobacterales

2021 ◽  
Vol 7 ◽  
Author(s):  
Rémy A. Bonnin ◽  
Agnès B. Jousset ◽  
Cécile Emeraud ◽  
Saoussen Oueslati ◽  
Laurent Dortet ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Multidrug Resistant ◽  
Biochemical Properties ◽  
Amino Acid Sequences ◽  
Detection Methods ◽  
Gram Negative ◽  
Class A ◽  
Class D ◽  
Class B ◽  
Encoding Genes

Gram-negative bacteria, especially Enterobacterales, have emerged as major players in antimicrobial resistance worldwide. Resistance may affect all major classes of anti-gram-negative agents, becoming multidrug resistant or even pan-drug resistant. Currently, β-lactamase-mediated resistance does not spare even the most powerful β-lactams (carbapenems), whose activity is challenged by carbapenemases. The dissemination of carbapenemases-encoding genes among Enterobacterales is a matter of concern, given the importance of carbapenems to treat nosocomial infections. Based on their amino acid sequences, carbapenemases are grouped into three major classes. Classes A and D use an active-site serine to catalyze hydrolysis, while class B (MBLs) require one or two zinc ions for their activity. The most important and clinically relevant carbapenemases are KPC, IMP/VIM/NDM, and OXA-48. However, several carbapenemases belonging to the different classes are less frequently detected. They correspond to class A (SME-, Nmc-A/IMI-, SFC-, GES-, BIC-like…), to class B (GIM, TMB, LMB…), class C (CMY-10 and ACT-28), and to class D (OXA-372). This review will address the genetic diversity, biochemical properties, and detection methods of minor acquired carbapenemases in Enterobacterales.

Endolymphatic SAC Surgery for Menière's Disease

1983 ◽  
Vol 92 (2) ◽  
pp. 113-118 ◽  
Author(s):  
Gershon J. Spector ◽  
Peter G. Smith
Keyword(s):  
Meniere’S Disease ◽  
Menière’S Disease ◽  
Meniere's Disease ◽  
Ménière’S Disease ◽  
Menière's Disease ◽  
Class A ◽  
Class D ◽  
Class B ◽  
Ménière's Disease

An endolymphatic-mastoid Silastic shunt procedure was performed in 122 cases of Menière's disease having a mean follow-up period of three years. In accordance with American Academy of Ophthalmology and Otolaryngology 1972 criteria, there were 43 % class A, 20% class B, 21% class C, and 17% class D results. Analysis of 35 recent cases having a mean follow-up period of nine months revealed 57% class A, 25% class B, 9% class C, and 9% class D results. Sixteen percent of the patients who experienced classes A, B or C results complained of other fluctuating symptoms which were not relieved by surgery. Moreover, three new eases of otolithic crisis were found in the postoperative group. Seven of ten patients who experienced a class A or B result had either a recrudescence of their vertigo or a significant decrement in hearing in response to a postoperative salt-loading test. It is concluded that the surgical success rate decreases with time and that the procedure appears to alter the symptom complex but does not cure Menière's disease.

scholarly journals In Vitro Activity of Cefiderocol against Multi-Drug Resistant Carbapenemase-Producing Gram-Negative Pathogens

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S376-S376 ◽  
Author(s):  
Sandra Boyd ◽  
Karen Anderson ◽  
Valerie Albrecht ◽  
Davina Campbell ◽  
Maria S Karlsson ◽  
...  
Keyword(s):  
Vitro Activity ◽  
Burkholderia Cepacia Complex ◽  
Uptake System ◽  
Drug Resistant ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Class A ◽  
Class D ◽  
Class B

Abstract Background Few options remain for treatment of infections caused by multi-drug resistant (MDR), carbapenemase-producing gram-negative pathogens. Cefiderocol (CFDC; Shionogi & Co. Ltd), is a novel parenteral siderophore cephalosporin that enters the bacterial cell through the iron–siderophore uptake system. Here we report on the in vitro activity of CFDC against a set of well-characterized MDR gram-negative isolates collected by the Centers for Disease Control and Prevention. Methods Minimum inhibitory concentrations (MIC) values for CFDC in iron-depleted cation-adjusted Mueller Hinton broth were determined using reference broth microdilution. Study isolates (n = 315) included Enterobacteriaceae (59%), Pseudomonas aeruginosa (19%), Acinetobacter baumannii (17%), Stenotrophomonas maltophilia (4%), and Burkholderia cepacia complex (1%). Of these, 229 (73%) were carbapenemase-producers including Ambler Class A- (37%), Class B- (29%) and Class D- type (29%) enzymes. The remaining isolates included 51 β-lactam-resistant isolates that were non-carbapenemase-producers, and 35 β-lactam-susceptible isolates. Results were interpreted using suggested CFDC breakpoints of Sensitive ≤4 μg/mL and Resistant ≥16 μg/mL. Results The majority of the isolates (90.8%) were categorized as CFDC susceptible; the percentage of isolates with a CFDC MIC ≤4 μg/mL among Enterobacteriaceae, P. aeruginosa, and A. baumannii was 87.5%, 100%, and 89%, respectively. Percentage of isolates with a CFDC MIC ≤4 μg/mL that harbored a carbapenemase of the Class A-, Class B-, and Class D-type was 91.8%, 74.8%, 98.0%, respectively. By applying suggested breakpoints, 12 isolates were categorized as intermediate and 17 as resistant. The resistant isolates included 11 NDM-, 2 OXA-23- and 4 KPC-positive organisms. Conclusion Cefiderocol showed potent activity against MDR gram-negative pathogens including Class A, B, and D carbapenemase-producing isolates. Of note, all P. aeruginosa, including Class B metallo-β-lactamase producers, were susceptible to CFDC. Disclosures All authors: No reported disclosures.

scholarly journals Characterization of CIA-1, an Ambler Class A Extended-Spectrum β-Lactamase from Chryseobacterium indologenes

2011 ◽  
Vol 56 (1) ◽  
pp. 588-590 ◽  
Author(s):  
Takehisa Matsumoto ◽  
Mika Nagata ◽  
Nau Ishimine ◽  
Kenji Kawasaki ◽  
Kazuyoshi Yamauchi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Reference Strain ◽  
Content Type ◽  
Chryseobacterium Indologenes ◽  
Esbl Gene ◽  
Class A ◽  
Extended Spectrum ◽  
Class B ◽  
Lactamase Gene

ABSTRACTAn Ambler class A β-lactamase gene,blaCIA-1, was cloned from the reference strainChryseobacterium indologenesATCC 29897 and expressed inEscherichia coliBL21. TheblaCIA-1gene encodes a novel extended-spectrum β-lactamase (ESBL) that shared 68% and 60% identities with the CGA-1 and CME-1 β-lactamases, respectively.blaCIA-1-like genes were detected from clinical isolates. In addition to the metallo-β-lactamase IND of Ambler class B,C. indologeneshas a class A ESBL gene,blaCIA-1, located on the chromosome.

scholarly journals Systematic comparison of three commercially available combination disc tests and zCIM for carbapenemase detection in Enterobacterales isolates

2021 ◽  
Author(s):  
Janko Sattler ◽  
Anne Brunke ◽  
Axel Hamprecht
Keyword(s):  
Infection Control ◽  
Patient Treatment ◽  
Diagnostic Strategy ◽  
Class A ◽  
Molecular Tests ◽  
Class D ◽  
Great Performance ◽  
Class B ◽  
Overall Performance ◽  
Sensitivity Specificity

Detection of carbapenemases in Enterobacterales is crucial for patient treatment and infection control. Among others, combination disk tests (CDT) with different inhibitors (e.g. EDTA) and variations of the carbapenem inactivation method (CIM) are recommended by EUCAST or CLSI and are used by many laboratories as they are relatively inexpensive. In this study, we compare three commercially available CDT, faropenem disc testing (FAR) and the zinc supplemented CIM test (zCIM) for detection of carbapenemase-producing Enterobacterales (CPE). Rosco KPC/MBL and OXA-48 Confirm Kit (ROS-CDT), Liofilchem KPC&MBL&OXA-48 disc kit (LIO-CDT), Mastdiscs Combi Carba plus (MAST-CDT), FAR and zCIM were challenged with 106 molecularly characterized CPE and 47 non-CPE. Sensitivity/specificity was 86% (CI 78-92%)/98% (CI 89-100%) for MAST-CDT and ROS-CDT, 96% (CI 91-99%)/87% (CI 74-95%) for LIO-CDT and 99% (CI 95-100%)/81% (CI 67-91%) for FAR compared to 98% (CI 93-100%)/100% (CI 92-100%) for zCIM. The CDT showed great performance differences depending on the carbapenemase class, with MAST-CDT and LIO-CDT best detecting class B, ROS-CDT class A and LIO-CDT class D carbapenemases. Conclusion : The overall performance of commercially available CDTs was good but varied greatly for different carbapenemases and between manufacturers, compared with FAR and zCIM which performed well for all carbapenemase types. For reliable carbapenemase detection CDT should preferably not be used as the sole test, but can be part of a diagnostic strategy when combined with other assays (e.g. CIM-based, immunochromatographic or molecular tests).

scholarly journals Capacitação Profissional na Geração de Resíduos Sólidos de Serviço de Saúde em Ambiente Hospitalar

UNICIÊNCIAS ◽  
2021 ◽  
Vol 24 (2) ◽  
pp. 146-150
Author(s):  
Huama Monteiro de Brito ◽  
Marcelo Dias de Souza ◽  
Patrícia Paz da Costa ◽  
Géssica Lataliza de Menezes ◽  
Flavia Machado Coelho ◽  
...  
Keyword(s):  
Experimental Study ◽  
Health Services ◽  
Hospital Environment ◽  
Environmental Damage ◽  
Mato Grosso ◽  
Class A ◽  
Qualified Person ◽  
Class D ◽  
Professional Employees ◽  
The Common

O trabalho teve como objetivo analisar a geração de resíduos comuns do Hospital São Luiz de Cáceres do Estado de Mato Grosso, em relação à capacitação dos funcionários no local de trabalho. Trata-se de estudo de intervenção, analítico, experimental de resíduos de serviços de saúde. A realização da capacitação foi no ano de 2017, em que foram abordados cinco pontos de geração no hospital, tendo como prioridade a quantidade de resíduos gerados em cada ponto, sendo quantificados e analisados antes e após a capacitação profissional dos colaboradores. Os resultados demonstraram que os resíduos comuns gerados no local estão sendo descartados de forma incorreta, pois foram observados resíduos da classe A nas lixeiras de classe D, sendo que mesmo com a capacitação, a segregação ainda continuou sendo realizada de forma incorreta por alguns profissionais. Portanto, em função de danos financeiros e ambientais, pode-se dizer que é de suma importância que os profissionais sejam capacitados por uma pessoa qualificada. É necessária uma pessoa capacitada para se responsabilizar pelo PGRSS, SCIH e gestores, aplicando treinamento de capacitação e monitorando diretamente o manejo dos resíduos sólidos gerados no ambiente hospitalar.   Palavras-chave: Lixo Hospitalar. Segregação. Gerenciamento de Resíduos.   Abstract The work aimed to analyze the common residues generation of Hospital São Luiz de Cáceres of the state of Mato Grosso, in relation to the employees training in the workplace. This is an intervention, analytical and experimental study of health services residues. The training was carried out in 2017, in which five generation points were added, having as priority the amount of residues generated in each point, being quantified and advanced and after the professional employees training. The results showed that the common residues generated at the site is being disposed of incorrectly, because class A residues were observed in class D dumps, being that even with the training, the segregation still continued to be performed incorrectly by some professionals. Therefore, due to the financial and environmental damage, it can be said that it is extremely important that professionals are trained by a qualified person. A trained person is required to be responsible for the PGRSS, SCIH and managers, applying training and monitoring directly the solid residues management in the hospital environment.   Keywords: Hospital Garbage. Segregation. Residues Management.

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