scholarly journals A Primer on AmpC β-Lactamases: Necessary Knowledge for an Increasingly Multidrug-resistant World

2019 ◽  
Vol 69 (8) ◽  
pp. 1446-1455 ◽  
Author(s):  
Pranita D Tamma ◽  
Yohei Doi ◽  
Robert A Bonomo ◽  
J Kristie Johnson ◽  
Patricia J Simner ◽  
...  
Keyword(s):  
Observational Studies ◽  
Treatment Options ◽  
Enterobacter Cloacae ◽  
Multidrug Resistant ◽  
Effective Management ◽  
Mechanisms Of Resistance ◽  
Management Approaches ◽  
Species Specific ◽  
Third Generation Cephalosporins

Abstract Understanding the nuances of AmpC β-lactamase–mediated resistance can be challenging, even for the infectious diseases specialist. AmpC resistance can be classified into 3 categories: (1) inducible chromosomal resistance that emerges in the setting of a β-lactam compound, (2) stable derepression due to mutations in ampC regulatory genes, or (3) the presence of plasmid-mediated ampC genes. This review will mainly focus on inducible AmpC resistance in Enterobacteriaceae. Although several observational studies have explored optimal treatment for AmpC producers, few provide reliable insights into effective management approaches. Heterogeneity within the data and inherent selection bias make inferences on effective β-lactam choices problematic. Most experts agree it is prudent to avoid expanded-spectrum (ie, third-generation) cephalosporins for the treatment of organisms posing the greatest risk of ampC induction, which has best been described in the context of Enterobacter cloacae infections. The role of other broad-spectrum β-lactams and the likelihood of ampC induction by other Enterobacteriaceae are less clear. We will review the mechanisms of resistance and triggers resulting in AmpC expression, the species-specific epidemiology of AmpC production, approaches to the detection of AmpC production, and treatment options for AmpC-producing infections.

scholarly journals Immunotherapy in Adrenocortical Carcinoma: Predictors of Response, Efficacy, Safety, and Mechanisms of Resistance

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 304
Author(s):  
Marta Araujo-Castro ◽  
Eider Pascual-Corrales ◽  
Javier Molina-Cerrillo ◽  
Teresa Alonso-Gordoa
Keyword(s):  
Adrenocortical Carcinoma ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Mechanisms Of Resistance ◽  
Response Efficacy ◽  
Predictors Of Response ◽  
Primary Endpoints ◽  
Tumor Mutational Burden

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options in the advanced stages. Immunotherapy offers hope for altering the orthodox management of cancer, and its role in advanced ACC has been investigated in different studies. With the aim clarifying the role of immunotherapy in ACC we performed a comprehensive review about this topic focusing on the predictors of response, efficacy, safety, and the mechanisms of resistance. Five clinical trials with four immune checkpoint inhibitors (pembrolizumab, avelumab, nivolumab, and ipilimumab) have investigated the role of immunotherapy in advanced ACC. Despite, the different primary endpoints used in these studies, the reported rates of overall response rate and progression free survival were generally poor. Three main potential markers of response to immunotherapy in ACC have been described: Expression of PD-1 and PD-L1, microsatellite instability and tumor mutational burden. However, none of them has been validated in prospective studies. Several mechanisms of ACC immunoevasion may be responsible of immunotherapy failure, and a greater knowledge of these mechanisms might lead to the development of new strategies to overcome the immunotherapy resistance. In conclusion, although currently the role of immunotherapy is limited, the identification of immunological markers of response and the implementation of strategies to avoid immunotherapy resistance could improve the efficacy of this therapy.

scholarly journals Shifting Gears: The Future of Polymyxin Antibiotics

Antibiotics ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 42 ◽  
Author(s):  
Lenhard ◽  
Bulman ◽  
Tsuji ◽  
Kaye
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Carbapenem Resistant ◽  
The Future ◽  
Important Addition ◽  
Future Strategy ◽  
Future Utility ◽  
A Current

The manuscripts contained in this special edition of Antibiotics represent a current review of the polymyxins as well as highlights from the 3rd International Polymyxin Conference, which was held in Madrid, Spain, April 25 to 26, 2018. The role of the polymyxin antibiotics has evolved over time based on the availability of alternative agents. After high rates of nephrotoxicity caused the drug class to fall out of favor, polymyxins were once against utilized in the 21st century to combat drug-resistant pathogens. However, the introduction of safer agents with activity against drug-resistant organisms has brought the future utility of polymyxins into question. The present review investigates the future niche of polymyxins by evaluating currently available and future treatment options for difficult-to-treat pathogens. The introduction of ceftazidime-avibactam, meropenem-vaborbactam and plazomicin are likely to decrease polymyxin utilization for infections caused by Enterobacteriaceae. Similarly, the availability of ceftolozane-tazobactam will reduce the use of polymyxins to counter multidrug-resistant Pseudomonas aeruginosa. In contrast, polymyxins will likely continue be an important option for combatting carbapenem-resistant Acinetobacter baumannii until better options become commercially available. Measuring polymyxin concentrations in patients and individualizing therapy may be a future strategy to optimize clinical outcomes while minimizing nephrotoxicity. Inhaled polymyxins will continue to be an adjunctive option for pulmonary infections but further clinical trials are needed to clarify the efficacy of inhaled polymyxins. Lastly, safer polymyxin analogs will potentially be an important addition to the antimicrobial armamentarium.

scholarly journals Noninferior Antibiotics: When Is “Not Bad” “Good Enough”?

2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Mark J. DiNubile
Keyword(s):  
Nursing Home ◽  
Clinical Practice ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Chronically Ill ◽  
Multidrug Resistant ◽  
Everyday Clinical Practice ◽  
Novel Treatment ◽  
Efficacious Treatment

Abstract Novel treatment options are urgently needed for patients with serious multidrug-resistant infections seen increasingly in routine everyday clinical practice, both in the hospital and nursing home as well as in the clinic and office setting. Unfortunately, the problem is no longer confined to chronically ill, repeatedly hospitalized patients. This essay explores the role of noninferiorly studies in addressing the pressing need for new antimicrobial agents to combat the emerging “superbugs”, calling attention to the nuances of interpreting their sometimes less-than-straightforward results. The overriding aim is not to find better antibiotics for routinely treatable infections but to identify safe and efficacious treatment options where none presently exist.

scholarly journals A review on bacterial resistance to carbapenems: epidemiology, detection and treatment options

2020 ◽  
Vol 6 (3) ◽  
pp. FSO438 ◽  
Author(s):  
Ann A Elshamy ◽  
Khaled M Aboshanab
Keyword(s):  
Public Health ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Mechanisms Of Resistance ◽  
Carbapenem Resistant ◽  
Public Health Threat ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenems are a class of antimicrobial agents reserved for infections caused by multidrug-resistant microorganisms. The emergence of carbapenem resistance has become a serious public health threat. This type of antimicrobial resistance is spreading at an alarming rate, resulting in major outbreaks and treatment failure of community-acquired and nosocomial infections caused by the clinically relevant carbapenem-producing Enterobacteriaceae or carbapenem-resistant Enterobacteriaceae. This review is focused on carbapenem resistance, including mechanisms of resistance, history and epidemiology, phenotypic and genotypic detection in the clinically relevant bacterial pathogens and the possible treatment options available.

scholarly journals Multidrug-resistant Neisseria gonorrhoeae with reduced cefotaxime susceptibility is increasingly common in men who have sex with men, Amsterdam, the Netherlands

2009 ◽  
Vol 14 (37) ◽  
Author(s):  
H JC de Vries ◽  
J J van der Helm ◽  
M F Schim van der Loeff ◽  
A P van Dam
Keyword(s):  
The Netherlands ◽  
Neisseria Gonorrhoeae ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Considerable Proportion ◽  
Third Generation ◽  
Sexually Transmitted ◽  
Sex With Men ◽  
Third Generation Cephalosporins ◽  
Multiple Antibiotics

Antimicrobial resistance is an increasing problem in Neisseria gonorrhoeae (NG) treatment. Presently, third-generation parenteral cephalosporins, like ceftriaxone and cefotaxime, are the first option. Resistance to oral, but not to parenteral, third-generation cephalosporins has been reported previously. We analysed the microbial susceptibility (as minimum inhibitory concentration - MIC) of NG cultures obtained from high-risk visitors of the largest Dutch outpatient clinic for sexually transmitted infections (STI) in Amsterdam, the Netherlands. Among 1,596 visitors, we identified 102 patients with at least one NG isolate with reduced susceptibility to cefotaxime (0.125 μg/ml < MIC ≤ 0.5 μg/ml). The percentage of NG isolates with reduced susceptibility to cefotaxime rose from 4.8% in 2006 to 12.1% in 2008 (chi2 17.5, p<0.001). With multivariate logistic regression, being a man who has sex with men (MSM) was significantly associated with reduced susceptibility to cefotaxime (p<0.001). Compared to susceptible NG isolates, those with decreased susceptiblity to cefotaxime were more often resistant also to penicillin (16.5% vs. 43.3%), tetracycline (21.5% vs. 68.9%) and ciprofloxacin (44.4% vs. 90.0%, all p<0.001). The increased prevalence of NG strains with reduced susceptibility to cefotaxime among MSM may herald resistance to third-generation parenteral cephalosporins. A considerable proportion of these strains show resistance to multiple antibiotics which could limit future NG treatment options.

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 Dual Role of gnaA in Antibiotic Resistance and Virulence in Acinetobacter baumannii

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Qingye Xu ◽  
Tao Chen ◽  
Biyong Yan ◽  
Linyue Zhang ◽  
Borui Pi ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Capsular Polysaccharide ◽  
Treatment Options ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Bacterial Virulence ◽  
Content Type ◽  
Evolution Experiment

ABSTRACT Acinetobacter baumannii is an important Gram-negative pathogen in hospital-related infections. However, treatment options for A. baumannii infections have become limited due to multidrug resistance. Bacterial virulence is often associated with capsule genes found in the K locus, many of which are essential for biosynthesis of the bacterial envelope. However, the roles of other genes in the K locus remain largely unknown. From an in vitro evolution experiment, we obtained an isolate of the virulent and multidrug-resistant A. baumannii strain MDR-ZJ06, called MDR-ZJ06M, which has an insertion by the ISAba16 transposon in gnaA (encoding UDP-N-acetylglucosamine C-6 dehydrogenase), a gene found in the K locus. The isolate showed an increased resistance toward tigecycline, whereas the MIC decreased in the case of carbapenems, cephalosporins, colistin, and minocycline. By using knockout and complementation experiments, we demonstrated that gnaA is important for the synthesis of lipooligosaccharide and capsular polysaccharide and that disruption of the gene affects the morphology, drug susceptibility, and virulence of the pathogen.

scholarly journals Genomic Insights Into Last-Line Antimicrobial Resistance in Multidrug-Resistant Staphylococcus and Vancomycin-Resistant Enterococcus

2021 ◽  
Vol 12 ◽  
Author(s):  
Adrianna M. Turner ◽  
Jean Y. H. Lee ◽  
Claire L. Gorrie ◽  
Benjamin P. Howden ◽  
Glen P. Carter
Keyword(s):  
Molecular Mechanisms ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Vancomycin Resistant Enterococcus ◽  
Human Pathogens ◽  
Mechanisms Of Resistance ◽  
Global Spread ◽  
Vancomycin Resistant ◽  
Emergence Of Resistance

Multidrug-resistant Staphylococcus and vancomycin-resistant Enterococcus (VRE) are important human pathogens that are resistant to most clinical antibiotics. Treatment options are limited and often require the use of ‘last-line’ antimicrobials such as linezolid, daptomycin, and in the case of Staphylococcus, also vancomycin. The emergence of resistance to these last-line antimicrobial agents is therefore of considerable clinical concern. This mini-review provides an overview of resistance to last-line antimicrobial agents in Staphylococcus and VRE, with a particular focus on how genomics has provided critical insights into the emergence of resistant clones, the molecular mechanisms of resistance, and the importance of mobile genetic elements in the global spread of resistance to linezolid.

Conventional and contemporary management approaches for the treatment of vestibular schwannomas: Microsurgery versus radiosurgery, a literature review

2004 ◽  
Vol 4 (1) ◽  
pp. 39-45
Author(s):  
K. Hickey
Keyword(s):  
Treatment Options ◽  
Cranial Nerves ◽  
Vestibular Schwannomas ◽  
Treatment Modalities ◽  
The Past ◽  
Close Proximity ◽  
Technical Advances ◽  
Management Approaches ◽  
Contemporary Management

The management of intracerebral tumours has always provided us with a challenge when deciding upon the best treatment approach. However, when such tumours are benign and located in close proximity to critical structures, tumour management becomes all the more challenging.The treatment of vestibular schwannomas has always posed such problems because of their anatomical proximity to critical structures such as the brainstem and several cranial nerves. Through a comprehensive literature appraisal, this article evaluates the problems associated with conventional treatment options and discusses how technical advances over the past decades have affected disease management and therefore impacted on the range and type of treatment modalities employed. In addition, it highlights the role of alternative contemporary approaches in the management of vestibular schwannomas.

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