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 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 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.

scholarly journals In vivo emergence of resistance to cefiderocol in an XDR Pseudomonas aeruginosa and an MDR Citrobacter koseri after prolonged therapy: a case report.

2020 ◽  
Author(s):  
Carolina Grande Perez ◽  
Evelyne Maillart ◽  
Véronique Yvette Miendje Deyi ◽  
Te Din Daniel Huang ◽  
Prochore Kamgang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Class A ◽  
Stewardship Program ◽  
Class D ◽  
Emergence Of Resistance

Abstract The non-fermenters, e.g. Pseudomonas aeruginosa, and the extended spectrum β-lactamases or carbapenemases producing enterobacteriaceae represent a serious threat for patients admitted in Intensive Care Units (ICUs). News antibiotics have been developed to treat multidrug resistant bacteria. However, treatment emerging resistance has been shown for many of these newest antibiotics. Cefiderocol, a siderophore-antibiotic, has been developed to overcome most of the resistance mechanisms and shows great efficacy against most multi-drug resistant and extensively drug resistant Gram-negative bacteria, including the non-fermenters. We report the case of a patient abundantly treated with antibiotics. He received 158 days of antibiotherapy on 230 hospitalization days, including a six-week course of cefiderocol, in 14 different treatment lines. The patient developed a Pseudomonas aeruginosa (MIC: 8 µg/ml, GES type ESBL) and a Citrobacter koseri (MIC: 16 µg/ml, CTX-M group 9 type class A β-lactamase and a class D OXA-1 oxacillinase) resistant to cefiderocol. This antibiotic should be used with caution to preserve its efficacy, within a strict antimicrobial stewardship program.

scholarly journals Selection of medications in comorbidity

2020 ◽  
Vol 10 (1) ◽  
pp. 57-60
Author(s):  
F. I. Belialov
Keyword(s):  
Adverse Effects ◽  
Positive Influence ◽  
Comorbid Disease ◽  
New Classification ◽  
Drug Classification ◽  
Class A ◽  
Class D ◽  
Class B ◽  
Comorbid Diseases ◽  
Selection Of

New classification divides medications on five classes by influence on comorbid diseases and conditions and rates drug’s effects as favourable (A), possible (B), neutral (C), undesirable (D), and unfavourable (X). Class A includes drugs used in treatment of comorbid disease, class B embraced drugs with positive influence, class C includes drugs without significant influence or contradictory influence, class D consist of drugs with possible nonsevere adverse effects, and class X includes drugs with severe adverse effects. The more universal drug classification according to influence on comorbid diseases can include and unite other classifications. Classification may help unify marks of positive and negative influences drugs on comorbidity and help practitioners in selection of effective and safe treatment.

scholarly journals In VitroandIn VivoProperties of BAL30376, a β-Lactam and Dual β-Lactamase Inhibitor Combination with Enhanced Activity against Gram-Negative Bacilli That Express Multiple β-Lactamases

2011 ◽  
Vol 55 (4) ◽  
pp. 1510-1519 ◽  
Author(s):  
Malcolm G. P. Page ◽  
Clothilde Dantier ◽  
Eric Desarbre ◽  
Bérangère Gaucher ◽  
Klaus Gebhardt ◽  
...  
Keyword(s):  
Clavulanic Acid ◽  
Stenotrophomonas Maltophilia ◽  
Multidrug Resistant ◽  
Triple Combination ◽  
Class A ◽  
Link Type ◽  
Class D ◽  
Class C ◽  
Inhibitor Combination ◽  
Lactamase Inhibitor

ABSTRACTBAL30376 is a triple combination comprising a siderophore monobactam,BAL19764; a novel bridged monobactam,BAL29880, which specifically inhibits class C β-lactamases; and clavulanic acid, which inhibits many class A and some class D β-lactamases. The MIC90was ≤4 μg/ml (expressed as the concentration ofBAL19764) for most species of theEnterobacteriaceaefamily, including strains that produced metallo-β-lactamases and were resistant to all of the other β-lactams tested. The MIC90forStenotrophomonas maltophiliawas 2 μg/ml, for multidrug-resistant (MDR)Pseudomonas aeruginosait was 8 μg/ml, and for MDRAcinetobacterandBurkholderiaspp. it was 16 μg/ml. The presence of the class C β-lactamase inhibitorBAL29880contributed significantly to the activity ofBAL30376against strains ofCitrobacter freundii,Enterobacterspecies,Serratia marcescens, andP. aeruginosa. The presence of clavulanic acid contributed significantly to the activity against many strains ofEscherichia coliandKlebsiella pneumoniaethat produced class A extended-spectrum β-lactamases. The activity ofBAL30376against strains with metallo-β-lactamases was largely attributable to the intrinsic stability of the monobactamBAL19764toward these enzymes. Considering its three components,BAL30376was unexpectedly refractory toward the development of stable resistance.

scholarly journals AmpD Is Required for Regulation of Expression of NmcA, a Carbapenem-Hydrolyzing β-Lactamase ofEnterobacter cloacae

2001 ◽  
Vol 45 (10) ◽  
pp. 2908-2915 ◽  
Author(s):  
Thierry Naas ◽  
Sandrine Massuard ◽  
Fabien Garnier ◽  
Patrice Nordmann
Keyword(s):  
Amino Acid ◽  
Enterobacter Cloacae ◽  
Genetic System ◽  
Amino Acid Identity ◽  
Wild Type ◽  
Regulation Of Expression ◽  
Class A ◽  
Induction Process ◽  
Resistant Mutants ◽  
Do So

ABSTRACT To further elucidate the induction process of the carbapenem-hydrolyzing β-lactamase of Ambler class A, NmcA,ampD genes of the wild-type (WT) strain and of ceftazidime-resistant mutants of Enterobacter cloacaeNOR-1 were cloned and tested in transcomplementation experiments. Ceftazidime-resistant E. cloacae NOR-1 mutants exhibited derepressed expression of the AmpC-type cephalosporinase and of the carbapenem-hydrolyzing β-lactamase NmcA. The ampD genes of Escherichia coli andE. cloacae WT NOR-1 transcomplemented the ceftazidime-resistant E. cloacae NOR-1 mutants to the WT level of β-lactamase expression, while the mutatedampD alleles of E. cloacaeNOR-1 failed to do so. The deduced E.cloacae NOR-1 WT AmpD protein exhibited 95 and 91% amino acid identity with the E. cloacaeO29 and E. cloacae 14 WT AmpD proteins, respectively. Of the 12 ceftazidime-resistant E.cloacae NOR-1 strains, 3 had AmpD proteins with amino acid changes, while the others had truncated AmpD proteins. Most of these mutations were located outside the conserved regions that link the AmpD proteins to the cell wall hydrolases. AmpD fromE. cloacae NOR-1 is involved in the regulation of expression of both β-lactamases (NmcA and AmpC), suggesting that structurally unrelated genes may be under the control of an identical genetic system.

scholarly journals In Vitro and In Vivo Activities of AM-112, a Novel Oxapenem

2003 ◽  
Vol 47 (5) ◽  
pp. 1652-1657 ◽  
Author(s):  
Conor E. Jamieson ◽  
Peter A. Lambert ◽  
Iain N. Simpson
Keyword(s):  
Clavulanic Acid ◽  
Enterobacter Cloacae ◽  
Penicillin Binding Proteins ◽  
Class A ◽  
Sepsis Model ◽  
Class D ◽  
Class C ◽  
Lactamase Inhibitor

ABSTRACT AM-112 [(1′R,5R,6R)-3-(4-amino-1,1-dimethyl-butyl)-6-(1′-hydroxyethyl)oxapenem-3-carboxylate] is a novel oxapenem compound which possesses potent β-lactamase-inhibitory properties. Fifty-percent inhibitory concentrations (IC50s) of AM-112 for class A enzymes were between 0.16 and 2.24 μM for three enzymes, compared to IC50s of 0.008 to 0.12 μM for clavulanic acid. Against class C and class D enzymes, however, the activity of AM-112 was between 1,000- and 100,000-fold greater than that of clavulanic acid. AM-112 had affinity for the penicillin-binding proteins (PBPs) of Escherichia coli DC0, with PBP2 being inhibited by the lowest concentration of AM-112 tested, 0.1 μg/ml. Ceftazidime was combined with AM-112 at 1:1 and 2:1 ratios in MIC determination studies against a panel of β-lactamase-producing organisms. These studies demonstrated that AM-112 was effective at protecting ceftazidime against extended-spectrum β-lactamase-producing strains and derepressed class C enzyme producers, reducing ceftazidime MICs by 16- and 2,048-fold. Similar results were obtained when AM-112 was combined with ceftriaxone, cefoperazone, or cefepime in a 1:2 ratio. Protection of ceftazidime with AM-112 was maintained against Enterobacter cloacae P99 and Klebsiella pneumoniae SHV-5 in a murine intraperitoneal sepsis model. The 50% effective dose of ceftazidime against E. cloacae P99 and K. pneumoniae SHV-5 was reduced from >100 and 160 mg/kg of body weight to 2 and 33.6 mg/kg, respectively, when it was combined with AM-112 at a 1:1 ratio. AM-112 demonstrates potential as a new β-lactamase inhibitor.

Acquisition and Transmission of Carbapenemase-Producing (blaKPC-2) Enterobacter cloacae in a Highly Frequented Outpatient Clinic

2020 ◽  
Author(s):  
Sabrina Klein ◽  
Sébastien Boutin ◽  
Isabel Späth ◽  
Christoph Kimmich ◽  
Juliane Brandt ◽  
...  
Keyword(s):  
Outpatient Clinic ◽  
Enterobacter Cloacae ◽  
Multidrug Resistant ◽  
Outpatient Department ◽  
Outpatient Clinics ◽  
Multidrug Resistant Organisms

Abstract The role of outpatient clinics as a potential transmission ground for multidrug-resistant organisms has not been adequately investigated. Here, we report a transmission cluster of blaKPC-2-positive Enterobacter cloacae among patients treated in a highly frequented outpatient department.

scholarly journals The Impact of Multidrug-Resistant Organisms on Outcomes in Patients With Diabetic Foot Infections

2020 ◽  
Vol 7 (5) ◽  
Author(s):  
Oryan Henig ◽  
Jason M Pogue ◽  
Emily Martin ◽  
Umar Hayat ◽  
Mahmoud Ja’ara ◽  
...  
Keyword(s):  
Propensity Score ◽  
Diabetic Foot ◽  
Medical Center ◽  
Conditional Logistic Regression ◽  
Generation Cephalosporin ◽  
Multidrug Resistant ◽  
Diabetic Foot Infections ◽  
Increased Risk ◽  
Multidrug Resistant Organisms ◽  
The Impact

Abstract Background Multidrug-resistant organisms (MDROs) are important diabetic foot infection (DFI) pathogens. This study evaluated the impact of DFIs associated with MDRO pathogens (DFI-MDRO) on clinical outcomes. Methods Adults admitted to Detroit Medical Center from January 2012 to December 2015 with culture-positive DFI were included. Associations between outcomes and DFI-MDRO (evaluated as a single group that included methicillin-resistant Staphylococcus aureus [MRSA], vancomycin-resistant enterococci, Enterobacteriaceae resistant to third-generation cephalosporin [3GCR-EC], Acinetobacter baumannii, and Pseudomonas aeruginosa) were analyzed. Outcomes included above- and below-knee lower extremity amputation (LEA), readmissions, and mortality within a year after DFI. A propensity score predicting the likelihood of having DFI-MDRO was computed by comparing patients with DFI-MDRO with patients with DFI with non-MDRO pathogens (DFI-non-MDRO). Using conditional logistic regression, DFI-MDRO was analyzed as an independent variable after patients in the MDRO and non-MDRO groups were matched by propensity score. Results Six hundred forty-eight patients were included, with a mean age ± SD of 58.4 ± 13.7. Most patients in the cohort presented with chronic infection (75%). DFI-MDRO occurred in greater than one-half of the cohort (n = 364, 56%), and MRSA was the most common MDRO (n = 224, 62% of the DFI-MDRO group). In propensity-matched analyses, DFI-MDRO was not associated with 1-year LEA or readmissions, but was associated with recurrent DFI episodes (odds ratio, 2.1; 95% confidence interval, 1.38–3.21). Conclusions DFI-MDRO was associated with a 2-fold increased risk of recurrent DFI compared with patients with DFI-non-MDRO.

scholarly journals In VitroActivity of Delafloxacin against Clinical Neisseria gonorrhoeae Isolates and Selection of Gonococcal Delafloxacin Resistance

2016 ◽  
Vol 60 (5) ◽  
pp. 3106-3111 ◽  
Author(s):  
Olusegun O. Soge ◽  
Stephen J. Salipante ◽  
David No ◽  
Erin Duffy ◽  
Marilyn C. Roberts
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Spontaneous Mutation ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Content Type ◽  
Resistant Mutants ◽  
Reference Strains ◽  
Selection Of

ABSTRACTWe evaluated thein vitroactivity of delafloxacin against a panel of 117Neisseria gonorrhoeaestrains, including 110 clinical isolates collected from 2012 to 2015 and seven reference strains, compared with the activities of seven antimicrobials currently or previously recommended for treatment of gonorrhea. We examined the potential for delafloxacin to select for resistant mutants in ciprofloxacin-susceptible and ciprofloxacin-resistantN. gonorrhoeae. We characterized mutations in thegyrA,gyrB,parC, andparEgenes and the multidrug-resistant efflux pumps (MtrC-MtrD-MtrE and NorM) by PCR and sequencing and by whole-genome sequencing. The MIC50, MIC90, and MIC ranges of delafloxacin were 0.06 μg/ml, 0.125 μg/ml, and ≤0.001 to 0.25 μg/ml, respectively. The frequency of spontaneous mutation ranged from 10−7to <10−9. The multistep delafloxacin resistance selection of 30 daily passages resulted in stable resistant mutants. There was no obvious cross-resistance to nonfluoroquinolone comparator antimicrobials. A mutant with reduced susceptibility to ciprofloxacin (MIC, 0.25 μg/ml) obtained from the ciprofloxacin-susceptible parental strain had a novel Ser91Tyr alteration in thegyrAgene. We also identified new mutations in thegyrAand/orparCandparEgenes and the multidrug-resistant efflux pumps (MtrC-MtrD-MtrE and NorM) of two mutant strains with elevated delafloxacin MICs of 1 μg/ml. Although delafloxacin exhibited potentin vitroactivity againstN. gonorrhoeaeisolates and reference strains with diverse antimicrobial resistance profiles and demonstrated a low tendency to select for spontaneous mutants, it is important to establish the correlation between these excellentin vitrodata and treatment outcomes through appropriate randomized controlled clinical trials.

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