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

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.

2020 ◽  
Vol 6 (3) ◽  
pp. FSO438 ◽  
Author(s):  
Ann A Elshamy ◽  
Khaled M Aboshanab

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.


2009 ◽  
Vol 53 (6) ◽  
pp. 2450-2454 ◽  
Author(s):  
Inácio Mandomando ◽  
Dinis Jaintilal ◽  
Maria J. Pons ◽  
Xavier Vallès ◽  
Mateu Espasa ◽  
...  

ABSTRACT The antimicrobial susceptibility and mechanisms of resistance of 109 Shigella and 40 Salmonella isolates from children with diarrhea in southern Mozambique were assessed. The susceptibility to seven antimicrobial agents was tested by disk diffusion, and mechanisms of resistance were searched by PCR or colorimetric method. A high proportion of Shigella isolates were resistant to chloramphenicol (Chl) (52%), ampicillin (Amp) (56%), tetracycline (Tet) (66%), and trimethoprim-sulfamethoxazole (Sxt) (84%). Sixty-five percent of the isolates were multidrug resistant. Shigella flexneri isolates were more resistant than those of Shigella sonnei to Amp (66% versus 0.0%, P < 0.001) and Chl (61% versus 0.0%, P < 0.001), whereas S. sonnei isolates presented higher resistance to Tet than S. flexneri isolates (93% versus 64%, P = 0.02). Resistance among Salmonella isolates was as follows: Tet and Chl, 15% each; Sxt, 18%; and Amp, 25%. Only 3% of Salmonella isolates were resistant to nalidixic acid (Nal), and none to ciprofloxacin or ceftriaxone (Cro). Among Salmonella isolates, multiresistance was found in 23%. Among Shigella isolates, antibiotic resistance was related mainly to the presence of oxa-1-like β-lactamases for Amp, dfrA1 genes for Sxt, tetB genes for Tet, and Chl acetyltransferase (CAT) activity for Chl. Among Salmonella isolates, resistance was conferred by tem-like β-lactamases for Amp, floR genes and CAT activity for Chl, tetA genes for Tet, and dfrA1 genes for Sxt. Our data show that Shigella isolates are resistant mostly to the most available, inexpensive antibiotics by various molecular mechanisms but remain susceptible to ciprofloxacin, Cro, and Nal, which is the first line for empirical treatment of shigellosis in the country.


2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Guido Granata ◽  
Nicola Petrosillo

The global rise of multidrug-resistant gram-negative bacteria represents an increasing threat to patient safety. From the first observation of a carbapenem-resistant gramnegative bacteria a global spread of extendedspectrum beta-lactamases and carbapenemases producing <em>Klebsiella</em> <em>pneumoniae</em> has been observed. Treatment options for multidrug-resistant <em>K. pneumoniae</em> are actually limited to combination therapy with some aminoglycosides, tigecycline and to older antimicrobial agents. Unfortunately, the prevalence of colistin-resistant and tigecycline- resistant <em>K. pneumoniae</em> is increasing globally. Infection due to colistin-resistant <em>K. pneumoniae</em> represents an independent risk factor for mortality. Resistance to colistin in <em>K. pneumoniae</em> may be multifactorial, as it is mediated by chromosomal genes or plasmids. The emergence of transmissible, plasmidmediated colistin resistance is an alarming finding. The absence of new agents effective against resistant Gram-negative pathogens means that enhanced surveillance, compliance with infection prevention procedures, and antimicrobial stewardship programs will be required to limit the spread of colistinresistant <em>K. pneumoniae</em>.


2017 ◽  
Vol 38 (03) ◽  
pp. 311-325 ◽  
Author(s):  
George Zhanel ◽  
Nina Clark ◽  
Joseph Lynch

AbstractBacteria within the genus Acinetobacter (principally A. baumannii-calcoaceticus complex [ABC]) are gram-negative coccobacilli that may cause nosocomial infections in critically ill or debilitated patients (particularly ventilator-associated pneumonia and infections of the bloodstream, urinary tract, and wounds). Treatment of Acinetobacter infections is difficult, as Acinetobacter spp. are intrinsically resistant to multiple antimicrobial agents, and have a remarkable ability to acquire new resistance determinants via mechanisms that include plasmids, transposons, integrons, and resistance islands. Since the 1990s, global resistance to antimicrobials has escalated dramatically among ABC. Global spread of multidrug-resistant (MDR)-A. baumannii strains reflects dissemination of a few clones between hospitals, geographic regions, and continents; excessive use of antibiotics amplifies this spread. Many isolates are resistant to all antimicrobials except colistin (polymyxin E) and tigecycline, and some infections are untreatable with existing antimicrobial agents. Antimicrobial resistance poses a serious threat to treat or prevent infections due to ABC. Strategies to curtail environmental colonization with MDR-ABD will require aggressive infection control efforts and cohorting of infected patients. Thoughtful antibiotic strategies are essential to limit the spread of MDR-ABC. Optimal therapy will likely require combination antimicrobial therapy of existing antibiotics as well as development of novel antibiotic classes.


Author(s):  
Divya Chauhan ◽  
Santwana Verma ◽  
Ravi Verma ◽  
Garima Sharma

The spread of resistance among coagulase negative Staphylococci against major drugs is alarming as it limits the treatment options for serious infections. Resistance to linezolid in these organisms is emerging and further compounded by being observed in multidrug resistant strains. It is the only antibiotic available as an oral formulation for resistant Staphylococcal infections and due to the presence of a novel structure and unique mechanism of action, it does not display cross resistance with other classes of antimicrobial agents. However, the widespread use of Linezolid has gradually turned the impending fear of emergence of resistance against this novel drug into a reality. Herein we report a case of sepsis due to methicillin resistant Staphylococcus haemolyticus in a 16-year-old male child found resistant to linezolid, rarely reported from Sub Himalayan region of Indian sub-continent.


2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.


Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2888 ◽  
Author(s):  
Buthaina Jubeh ◽  
Zeinab Breijyeh ◽  
Rafik Karaman

The discovery of antibiotics has created a turning point in medical interventions to pathogenic infections, but unfortunately, each discovery was consistently followed by the emergence of resistance. The rise of multidrug-resistant bacteria has generated a great challenge to treat infections caused by bacteria with the available antibiotics. Today, research is active in finding new treatments for multidrug-resistant pathogens. In a step to guide the efforts, the WHO has published a list of the most dangerous bacteria that are resistant to current treatments and requires the development of new antibiotics for combating the resistance. Among the list are various Gram-positive bacteria that are responsible for serious healthcare and community-associated infections. Methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and drug-resistant Streptococcus pneumoniae are of particular concern. The resistance of bacteria is an evolving phenomenon that arises from genetic mutations and/or acquired genomes. Thus, antimicrobial resistance demands continuous efforts to create strategies to combat this problem and optimize the use of antibiotics. This article aims to provide a review of the most critical resistant Gram-positive bacterial pathogens, their mechanisms of resistance, and the new treatments and approaches reported to circumvent this problem.


2020 ◽  
Vol 8 (2) ◽  
pp. 191 ◽  
Author(s):  
Despoina Koulenti ◽  
Elena Xu ◽  
Andrew Song ◽  
Isaac Yin Sum Mok ◽  
Drosos E. Karageorgopoulos ◽  
...  

Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the pharmacokinetics, safety profile, and efficacy of these drugs, aiming to provide a comprehensive review to the involved stakeholders.


2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Mark J. DiNubile

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.


Sign in / Sign up

Export Citation Format

Share Document