scholarly journals Class D β-Lactamases: Are They All Carbapenemases?

2014 ◽  
Vol 58 (4) ◽  
pp. 2119-2125 ◽  
Author(s):  
Nuno T. Antunes ◽  
Toni L. Lamoureaux ◽  
Marta Toth ◽  
Nichole K. Stewart ◽  
Hilary Frase ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Clinical Importance ◽  
Kinetic Studies ◽  
Resistance Pattern ◽  
Content Type ◽  
Narrow Spectrum ◽  
Class D ◽  
Life Threatening

ABSTRACTCarbapenem-hydrolyzing class D β-lactamases (CHDLs) are enzymes of the utmost clinical importance due to their ability to produce resistance to carbapenems, the antibiotics of last resort for the treatment of various life-threatening infections. The vast majority of these enzymes have been identified inAcinetobacterspp., notably inAcinetobacter baumannii. The OXA-2 and OXA-10 enzymes predominantly occur inPseudomonas aeruginosaand are currently classified as narrow-spectrum class D β-lactamases. Here we demonstrate that when OXA-2 and OXA-10 are expressed inEscherichia colistrain JM83, they produce a narrow-spectrum antibiotic resistance pattern. When the enzymes are expressed inA. baumanniiATCC 17978, however, they behave as extended-spectrum β-lactamases and confer resistance to carbapenem antibiotics. Kinetic studies of OXA-2 and OXA-10 with four carbapenems have demonstrated that their catalytic efficiencies with these antibiotics are in the same range as those of some recognized class D carbapenemases. These results are in disagreement with the classification of the OXA-2 and OXA-10 enzymes as narrow-spectrum β-lactamases, and they suggest that other class D enzymes that are currently regarded as noncarbapenemases may in fact be CHDLs.

scholarly journals N-Acetylcysteine Selectively Antagonizes the Activity of Imipenem in Pseudomonas aeruginosa by an OprD-Mediated Mechanism

2015 ◽  
Vol 59 (6) ◽  
pp. 3246-3251 ◽  
Author(s):  
Jerónimo Rodríguez-Beltrán ◽  
Gabriel Cabot ◽  
Estela Ynés Valencia ◽  
Coloma Costas ◽  
German Bou ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Outer Membrane ◽  
Bacterial Species ◽  
Outer Membrane Proteins ◽  
Antibiotic Activity ◽  
Simultaneous Treatment ◽  
Content Type ◽  
Sds Page

ABSTRACTThe modulating effect ofN-acetylcysteine (NAC) on the activity of different antibiotics has been studied inPseudomonas aeruginosa. Our results demonstrate that, in contrast to previous reports, only the activity of imipenem is clearly affected by NAC. MIC and checkerboard determinations indicate that the NAC-based modulation of imipenem activity is dependent mainly on OprD. SDS-PAGE of outer membrane proteins (OMPs) after NAC treatments demonstrates that NAC does not modify the expression of OprD, suggesting that NAC competitively inhibits the uptake of imipenem through OprD. Similar effects on imipenem activity were obtained withP. aeruginosaclinical isolates. Our results indicate that imipenem-susceptibleP. aeruginosastrains become resistant upon simultaneous treatment with NAC and imipenem. Moreover, the generality of the observed effects of NAC on antibiotic activity was assessed with two additional bacterial species,Escherichia coliandAcinetobacter baumannii. Caution should be taken during treatments, as the activity of imipenem may be modified by physiologically attainable concentrations of NAC, particularly during intravenous and nebulized regimes.

scholarly journals Inactivation of the Pseudomonas -Derived Cephalosporinase-3 (PDC-3) by Relebactam

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Melissa D. Barnes ◽  
Christopher R. Bethel ◽  
Jim Alsop ◽  
Scott A. Becka ◽  
Joseph D. Rutter ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Gram Negative ◽  
Content Type ◽  
Life Threatening ◽  
Lactamase Inhibitor

ABSTRACT Pseudomonas aeruginosa is a prevalent and life-threatening Gram-negative pathogen. Pseudomonas -derived cephlosporinase (PDC) is the major inducible cephalosporinase in P. aeruginosa . In this investigation, we show that relebactam, a diazabicyclooctane β-lactamase inhibitor, potently inactivates PDC-3, with a k 2 / K of 41,400 M −1 s −1 and a k off of 0.00095 s −1 . Relebactam restored susceptibility to imipenem in 62% of multidrug-resistant P. aeruginosa clinical isolates, while only 21% of isolates were susceptible to imipenem-cilastatin alone. Relebactam promises to increase the efficacy of imipenem-cilastatin against P. aeruginosa .

scholarly journals National Surveillance of Antimicrobial Susceptibility of Bacteremic Gram-Negative Bacteria with Emphasis on Community-Acquired Resistant Isolates: Report from the 2019 Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART)

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Po-Yu Liu ◽  
Yu-Lin Lee ◽  
Min-Chi Lu ◽  
Pei-Lan Shao ◽  
Po-Liang Lu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Gram Negative Bacteria ◽  
National Surveillance ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Carbapenem Resistant

ABSTRACT A multicenter collection of bacteremic isolates of Escherichia coli (n = 423), Klebsiella pneumoniae (n = 372), Pseudomonas aeruginosa (n = 300), and Acinetobacter baumannii complex (n = 199) was analyzed for susceptibility. Xpert Carba-R assay and sequencing for mcr genes were performed for carbapenem- or colistin-resistant isolates. Nineteen (67.8%) carbapenem-resistant K. pneumoniae (n = 28) and one (20%) carbapenem-resistant E. coli (n = 5) isolate harbored blaKPC (n = 17), blaOXA-48 (n = 2), and blaVIM (n = 1) genes.

scholarly journals Precision Medicine and Mysteries in Clinical Microbiology: Rationalizing Epidemiology, Genotype, and Phenotype To Guide Therapeutics

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Federico Perez ◽  
Robert A. Bonomo
Keyword(s):  
Escherichia Coli ◽  
Health Care ◽  
Pseudomonas Aeruginosa ◽  
High Risk ◽  
Precision Medicine ◽  
Clinical Microbiology ◽  
Whole Genome ◽  
Content Type ◽  
Rational Combination ◽  
Synergy Testing

ABSTRACT Whole-genome sequencing (WGS) using MinION was used to characterize high-risk clones of Escherichia coli and Klebsiella pneumoniae harboring blaNDM-5, blaOXA-181, and blaCTX-M-15, as well as Pseudomonas aeruginosa harboring blaNDM, in a patient who received health care in India. Synergy testing demonstrated the activity of aztreonam and ceftazime-avibactam in combination. This case illustrates a “precision medicine” approach where deeper understanding of the genotype through WGS and of the phenotype through synergy testing formed the basis for rational combination therapy.

scholarly journals Challenging Antimicrobial Susceptibility and Evolution of Resistance (OXA-681) during Treatment of a Long-Term Nosocomial Infection Caused by a Pseudomonas aeruginosa ST175 Clone

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Jorge Arca-Suárez ◽  
Pablo Fraile-Ribot ◽  
Juan Carlos Vázquez-Ucha ◽  
Gabriel Cabot ◽  
Marta Martínez-Guitián ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Nosocomial Infection ◽  
Resistance Mechanisms ◽  
Cross Resistance ◽  
The Novel ◽  
Content Type ◽  
Narrow Spectrum ◽  
Extended Spectrum

ABSTRACT Selection of extended-spectrum mutations in narrow-spectrum oxacillinases (e.g., OXA-2 and OXA-10) is an emerging mechanism for development of in vivo resistance to ceftolozane-tazobactam and ceftazidime-avibactam in Pseudomonas aeruginosa. Detection of these challenging enzymes therefore seems essential to prevent clinical failure, but the complex phenotypic plasticity exhibited by this species may often lead to their underestimation. The underlying resistance mechanisms of two sequence type 175 (ST175) P. aeruginosa isolates showing multidrug-resistant phenotypes and recovered at early and late stages of a long-term nosocomial infection were evaluated. Whole-genome sequencing (WGS) was used to investigate resistance genomics, whereas molecular and biochemical methods were used for characterization of a novel extended-spectrum OXA-2 variant selected during therapy. The metallo-β-lactamase blaVIM-20 and the narrow-spectrum oxacillinase blaOXA-2 were present in both isolates, although they differed by an inactivating mutation in the mexB subunit, present only in the early isolate, and in a mutation in the blaOXA-2 β-lactamase, present only in the final isolate. The new OXA-2 variant, designated OXA-681, conferred elevated MICs of the novel cephalosporin–β-lactamase inhibitor combinations in a PAO1 background. Compared to OXA-2, kinetic parameters of the OXA-681 enzyme revealed a substantial increase in the hydrolysis of cephalosporins, including ceftolozane. We describe the emergence of the novel variant OXA-681 during treatment of a nosocomial infection caused by a Pseudomonas aeruginosa ST175 high-risk clone. The ability of OXA-681 to confer cross-resistance to ceftolozane-tazobactam and ceftazidime-avibactam together with the complex antimicrobial resistance profiles exhibited by the clinical strains harboring this new enzyme argue for maintaining active surveillance on emerging broad-spectrum resistance in P. aeruginosa.

scholarly journals In VitroSusceptibility of Characterized β-Lactamase-Producing Strains Tested with Avibactam Combinations

2014 ◽  
Vol 59 (3) ◽  
pp. 1789-1793 ◽  
Author(s):  
Henry Li ◽  
Mark Estabrook ◽  
George A. Jacoby ◽  
Wright W. Nichols ◽  
Raymond T. Testa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Broad Spectrum ◽  
Enterobacter Cloacae ◽  
Gram Negative ◽  
Content Type ◽  
Extended Spectrum ◽  
Lactamase Inhibitor

ABSTRACTAvibactam, a broad-spectrum β-lactamase inhibitor, was tested with ceftazidime, ceftaroline, or aztreonam against 57 well-characterized Gram-negative strains producing β-lactamases from all molecular classes. Most strains were nonsusceptible to the β-lactams alone. Against AmpC-, extended-spectrum β-lactamase (ESBL)-, and KPC-producingEnterobacteriaceaeorPseudomonas aeruginosa, avibactam lowered ceftazidime, ceftaroline, or aztreonam MICs up to 2,048-fold, to ≤4 μg/ml. Aztreonam-avibactam MICs against a VIM-1 metallo-β-lactamase-producingEnterobacter cloacaeand a VIM-1/KPC-3-producingEscherichia coliisolate were 0.12 and 8 μg/ml, respectively.

scholarly journals New Small Plasmid HarboringblaKPC-2in Pseudomonas aeruginosa

2016 ◽  
Vol 60 (5) ◽  
pp. 3211-3214 ◽  
Author(s):  
Renata Galetti ◽  
Leonardo Neves Andrade ◽  
Michael Chandler ◽  
Alessandro de Mello Varani ◽  
Ana Lúcia Costa Darini
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Inverted Repeat ◽  
Sequence Type ◽  
Small Plasmid ◽  
Content Type ◽  
Complete Sequencing ◽  
Genetic Context

ABSTRACTThe aim of this study was to characterize the genetic context ofblaKPC-2inPseudomonas aeruginosasequence type 244 from Brazil. TheblaKPC-2gene was detected in a new small plasmid, pBH6. Complete sequencing revealed that pBH6 was 3,652 bp long and included the Tn3resolvase and Tn3inverted repeat (IR), a partial copy of ISKpn6, and a putativeoriregion but norepgenes. pBH6 replicated stably intoEscherichia colistrain DH10B andP. aeruginosastrain PAO.

scholarly journals Pseudomonas aeruginosa AlgU Contributes to Posttranscriptional Activity by IncreasingrsmAExpression in amucA22Strain

2016 ◽  
Vol 198 (13) ◽  
pp. 1812-1826 ◽  
Author(s):  
Sean D. Stacey ◽  
Christopher L. Pritchett
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Laboratory Strain ◽  
Immunocompromised Patients ◽  
Chronic Infections ◽  
Rnase Protection ◽  
Content Type ◽  
Mutant Strains ◽  
Life Threatening ◽  
Severe Infections

ABSTRACTPseudomonas aeruginosathrives in multiple environments and is capable of causing life-threatening infections in immunocompromised patients. RsmA is a posttranscriptional regulator that controls virulence factor production and biofilm formation. In this study, we investigated the expression and activity ofrsmAand the protein that it encodes, RsmA, inP. aeruginosamucAmutant strains, which are common in chronic infections. We determined that AlgU regulates a previously unknownrsmApromoter inP. aeruginosa. Western blot analysis confirmed that AlgU controlsrsmAexpression in both a laboratory strain and a clinical isolate. RNase protection assays confirmed the presence of tworsmAtranscripts and suggest that RpoS and AlgU regulatersmAexpression. Due to the increased amounts of RsmA inmucAmutant strains, a translational leader fusion of the RsmA target,tssA1, was constructed and tested inmucA,algU,retS,gacA, andrsmAmutant backgrounds to examine posttranscriptional activity. From these studies, we determined that RsmA is active inmucA22mutants, suggesting a role for RsmA inmucAmutant strains. Taken together, we have demonstrated that AlgU controlsrsmAtranscription and is responsible for RsmA activity inmucAmutant strains. We propose that RsmA is active inP. aeruginosamucAmutant strains and that RsmA also plays a role in chronic infections.IMPORTANCEP. aeruginosacauses severe infections in immunocompromised patients. The posttranscriptional regulator RsmA is known to control virulence and biofilm formation. We identify a newrsmApromoter and determine that AlgU is important in the control ofrsmAexpression. MutantmucAstrains that are considered mucoid were used to confirm increasedrsmAexpression from the AlgU promoter. We demonstrate, for the first time, that there is RsmA activity in mucoidP. aeruginosastrains. Our work suggests that RsmA may play a role during chronic infections as well as acute infections.

scholarly journals Regional Resistance Surveillance Program Results for 12 Asia-Pacific Nations (2011)

2013 ◽  
Vol 57 (11) ◽  
pp. 5721-5726 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
Myrna Mendoza ◽  
Kirnpal K. Banga Singh ◽  
Mariana Castanheira ◽  
Jan M. Bell ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Streptococcus Pneumoniae ◽  
South Korea ◽  
Geographic Region ◽  
Asia Pacific ◽  
Surveillance Program ◽  
Broth Microdilution ◽  
Content Type

ABSTRACTThe Regional Resistance Surveillance program monitored susceptibility rates and developing resistance by geographic region, including 12 Asia-Pacific (APAC) countries. Reference broth microdilution methods for susceptibility/interpretations were applied, processing 5,053 strains. AmongStaphylococcus aureusisolates (37% methicillin-resistantS. aureus[MRSA], highest in South Korea [73%]), linezolid (LZD), tigecycline (TIG), and vancomycin were 100% active, but 33 and 34% of strains were levofloxacin (LEV) or macrolide resistant, respectively.Streptococcus pneumoniaewas most resistant to β-lactams and macrolides (45%) but was LZD, LEV, and TIG susceptible (>98%). Extended-spectrum β-lactamase (ESBL) phenotype rates inEscherichia coliandKlebsiellaspp. were 48 and 47%, respectively, and were highest in Taiwan, at 75 to 91%. The best anti-ESBL-phenotype agents were amikacin (81 to 96% susceptible), colistin (COL; >98%), TIG (>98%), and carbapenems (81 to 97%).Pseudomonas aeruginosashowed ≥20% resistance to all drugs except COL (99% susceptible). In conclusion, endemic evolving antimicrobial resistances in APAC nations show compromised roles for many commonly used antimicrobials.

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