Posts filed under ‘Resistencia bacteriana’

Commentary – A Unified Numbering Scheme for Class C β-Lactamases

Antimicrob. Agents Chemother. March 2020 V.64 N.3

A standard numbering scheme has been proposed for class C β-lactamases. This will significantly enhance comparison of biochemical and biophysical studies performed on different members of this class of enzymes and facilitate communication in the field.

FULL TEXT

https://aac.asm.org/content/64/3/e02247-19.abstract?etoc

PDF

https://aac.asm.org/content/aac/64/3/e02247-19.full.pdf

 

February 25, 2020 at 10:44 am

A Standard Numbering Scheme for Class C β-Lactamases

Antimicrob. Agents Chemother. March 2020 V.64 N.3

Unlike for classes A and B, a standardized amino acid numbering scheme has not been proposed for the class C (AmpC) β-lactamases, which complicates communication in the field. Here, we propose a scheme developed through a collaborative approach that considers both sequence and structure, preserves traditional numbering of catalytically important residues (Ser64, Lys67, Tyr150, and Lys315), is adaptable to new variants or enzymes yet to be discovered and includes a variation for genetic and epidemiological applications.

FULL TEXT

https://aac.asm.org/content/64/3/e01841-19.abstract?etoc

PDF

https://aac.asm.org/content/aac/64/3/e01841-19.full.pdf

 

February 25, 2020 at 10:43 am

Emergence of Ceftriaxone Resistance during a Case of Pneumococcal Meningitis with Fatal Evolution

Antimicrob. Agents Chemother. March 2020 V.64 N.3

We report a case of a 62-year-old man treated for Streptococcus pneumoniae meningitis by ceftriaxone and dexamethasone. After neurological improvement, neurological degradation by vasculitis occurred, despite effective concentrations of ceftriaxone in the serum and cerebrospinal fluid (CSF). S. pneumoniae with increased MICs to third-generation-cephalosporins (3GC) was isolated from the ventricular fluid 10 days after the isolation of the first strain. Isolate analysis showed that a mutation in the penicillin-binding protein 2X (PBP2X) has occurred under treatment.

This Journal section presents a real, challenging case involving a multidrug-resistant organism. The case authors present the rationale for their therapeutic strategy and discuss the impact of mechanisms of resistance on clinical outcome. An expert clinician then provides a commentary on the case.

FULL TEXT

https://aac.asm.org/content/64/3/e01958-19.abstract?etoc

PDF

https://aac.asm.org/content/aac/64/3/e01958-19.full.pdf

 

 

Antimicrob. Agents Chemother. March 2020 V.64 N.3

Case Commentary: Delayed Cerebral Vasculitis Associated with the Development of Ceftriaxone-Resistant Pneumococcal Meningitis

Mizrahi and colleagues present a well-described case of the emergence of drug resistance in Streptococcus pneumoniae meningitis during therapy with ceftriaxone monotherapy with a low bactericidal concentration in the cerebrospinal fluid. Adherence to international guidelines could possibly have prevented the emergence of this resistant isolate and the adverse outcome.

FULL TEXT

https://aac.asm.org/content/64/3/e02251-19.abstract?etoc

PDF

https://aac.asm.org/content/aac/64/3/e02251-19.full.pdf

 

February 25, 2020 at 10:41 am

Editorial – The End of Coagulase-Negative Staphylococci? A Micro-Comic Strip

Journal of Clinical Microbiology March 2020 V.58 N.3

With improved identification of bacteria using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), it has become common to identify staphylococci to the species level (1). This has led to a better understanding of the appropriate susceptibility testing methods for the staphylococcus species, which, in turn, makes specification of staphylococci more important….

FULL TEXT

https://jcm.asm.org/content/58/3/e02080-19?etoc

PDF

https://jcm.asm.org/content/jcm/58/3/e02080-19.full.pdf

February 25, 2020 at 10:17 am

Public Health Efforts Can Impact Adoption of Current Susceptibility Breakpoints, but Closer Attention from Regulatory Bodies Is Needed.

J Clin Microbiol. February 27, 2019 V.57 N.3

McKinnell JA1,2,3, Bhaurla S4, Marquez-Sung P4, Pucci A4, Baron M4, Kamali T4, Bugante J4, Schwartz B4, Balter S4, Terashita D4, Butler-Wu S5, Gunzenhauser J4, Hindler J4, Humphries RM3.

Abstract

Microbiological testing, including interpretation of antimicrobial susceptibility testing results using current breakpoints, is crucial for clinical care and infection control. Continued use of obsolete Enterobacteriaceae carbapenem breakpoints is common in clinical laboratories. The purposes of this study were (i) to determine why laboratories failed to update breakpoints and (ii) to provide support for breakpoint updates. The Los Angeles County Department of Public Health conducted a 1-year outreach program for 41 hospitals in Los Angeles County that had reported, in a prior survey of California laboratories, using obsolete Enterobacteriaceae carbapenem breakpoints. In-person interviews with hospital stakeholders and customized expert guidance and resources were provided to aid laboratories in updating breakpoints, including support from technical representatives from antimicrobial susceptibility testing device manufacturers. Forty-one hospitals were targeted, 7 of which had updated breakpoints since the prior survey. Of the 34 remaining hospitals, 27 (79%) assumed that their instruments applied current breakpoints, 17 (50%) were uncertain how to change breakpoints, and 10 (29%) lacked resources to perform a validation study for off-label use of the breakpoints on their systems. Only 7 hospitals (21%) were familiar with the FDA/CDC Antibiotic Resistance Isolate Bank. All hospitals launched a breakpoint update process; 16 (47%) successfully updated breakpoints, 12 (35%) received isolates from the CDC in order to validate breakpoints on their systems, and 6 (18%) were planning to update within 1 year. The public health intervention was moderately successful in identifying and overcoming barriers to updating Enterobacteriaceae carbapenem breakpoints in Los Angeles hospitals. However, the majority of targeted hospitals continued to use obsolete breakpoints despite 1 year of effort. These findings have important implications for the quality of patient care and patient safety. Other public health jurisdictions may want to utilize similar resources to bridge the patient safety gap, while manufacturers, the FDA, and others determine how best to address this growing public health issue.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425187/pdf/JCM.01488-18.pdf

February 18, 2020 at 9:55 am

Infections Caused by Carbapenem-Resistant Enterobacteriaceae: An Update on Therapeutic Options.

Front Microbiol. January 30, 2019

Sheu CC1,2, Chang YT2,3, Lin SY2,3, Chen YH2,4,5, Hsueh PR6,7.

Abstract

Carbapenems are considered as last-resort antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. With the increasing use of carbapenems in clinical practice, the emergence of carbapenem-resistant pathogens now poses a great threat to human health. Currently, antibiotic options for the treatment of carbapenem-resistant Enterobacteriaceae (CRE) are very limited, with polymyxins, tigecycline, fosfomycin, and aminoglycosides as the mainstays of therapy. The need for new and effective anti-CRE therapies is urgent. Here, we describe the current understanding of issues related to CRE and review combination therapeutic strategies for CRE infections, including high-dose tigecycline, high-dose prolonged-infusion of carbapenem, and double carbapenem therapy. We also review the newly available antibiotics which have potential in the future treatment of CRE infections: ceftazidime/avibactam, which is active against KPC and OXA-48 producers; meropenem/vaborbactam, which is active against KPC producers; plazomicin, which is a next-generation aminoglycoside with in vitro activity against CRE; and eravacycline, which is a tetracycline class antibacterial with in vitro activity against CRE. Although direct evidence for CRE treatment is still lacking and the development of resistance is a concern, these new antibiotics provide additional therapeutic options for CRE infections. Finally, we review other potential anti-CRE antibiotics in development: imipenem/relebactam and cefiderocol. Currently, high-dose and combination strategies that may include the new β-lactam/β-lactamase inhibitors should be considered in severe CRE infections to maximize treatment success. In the future, when more treatment options are available, therapy for CRE infections should be individualized and based on molecular phenotypes of resistance, susceptibility profiles, disease severity, and patient characteristics. More high-quality studies are needed to guide effective treatment for infections caused by CRE

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363665/pdf/fmicb-10-00080.pdf

February 18, 2020 at 9:54 am

β-lactam/β-lactamase inhibitor combinations: an update.

Medchemcomm. August 17, 2018  V.9 N.9 P.1439-1456.

Tehrani KHME1, Martin NI1,2.

Abstract

Antibiotic resistance caused by β-lactamase production continues to present a growing challenge to the efficacy of β-lactams and their role as the most important class of clinically used antibiotics. In response to this threat however, only a handful of β-lactamase inhibitors have been introduced to the market over the past thirty years. The first-generation β-lactamase inhibitors (clavulanic acid, sulbactam and tazobactam) are all β-lactam derivatives and work primarily by inactivating class A and some class C serine β-lactamases. The newer generations of β-lactamase inhibitors including avibactam and vaborbactam are based on non-β-lactam structures and their spectrum of inhibition is extended to KPC as an important class A carbapenemase. Despite these advances several class D and virtually all important class B β-lactamases are resistant to existing inhibitors. The present review provides an overview of recent FDA-approved β-lactam/β-lactamase inhibitor combinations as well as an update on research efforts aimed at the discovery and development of novel β-lactamase inhibitors.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151480/pdf/MD-009-C8MD00342D.pdf

February 18, 2020 at 9:53 am

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