Insights into Acinetobacter baumannii: A review of microbiological, virulence, and resistance traits in a threatening nosocomial pathogen

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Being a multidrug-resistant and an invasive pathogen, Acinetobacter baumannii is one of the major causes of nosocomial infections in the current healthcare system. It has been recognized as an agent of pneumonia, septicemia, meningitis, urinary tract and wound infections, and is associated with high mortality. Pathogenesis in A. baumannii infections is an outcome of multiple virulence factors, including porins, capsules, and cell wall lipopolysaccharide, enzymes, biofilm production, motility, and iron-acquisition systems, among others. Such virulence factors help the organism to resist stressful environmental conditions and enable development of severe infections. Parallel to increased prevalence of infections caused by A. baumannii, challenging and diverse resistance mechanisms in this pathogen are well recognized, with major classes of antibiotics becoming minimally effective. Through a wide array of antibiotic-hydrolyzing enzymes, efflux pump changes, impermeability, and antibiotic target mutations, A. baumannii models a unique ability to maintain a multidrug-resistant phenotype, further complicating treatment. Understanding mechanisms behind diseases, virulence, and resistance acquisition are central to infectious disease knowledge about A. baumannii. The aims of this review are to highlight infections and disease-producing factors in A. baumannii and to touch base on mechanisms of resistance to various antibiotic classes

Bacterial pneumonia associated with multidrug-resistant Gram-negative pathogens: Understanding epidemiology, resistance patterns, and implications with COVID-19

The ongoing spread of antimicrobial resistance has complicated the treatment of bacterial hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Gram-negative pathogens, especially those with multidrug-resistant profiles, including Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Pseudomonas aeruginosa, and Acinetobacter spp., are an important culprit in this type of infections. Understanding the determinants of resistance in pathogens causing pneumonia is ultimately stressing, especially in the shadows of the COVID-19 pandemic, when bacterial lung infections are considered a top priority that has become urgent to revise. Globally, the increasing prevalence of these pathogens in respiratory samples represents a significant infection challenge, with major limitations of treatment options and poor clinical outcomes. This review will focus on the epidemiology of HAP and VAP and will present the roles and the antimicrobial resistance patterns of implicated multidrug-resistant (MDR) Gram-negative pathogens like carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Enterobacterales (CRE), as well as colistin-resistant Gram-negative pathogens and extended-spectrum β-lactamase (ESBL)-producing Enterobacterales. While emerging from the COVID-19 pandemic, perspectives and conclusions are drawn from findings of HAP and VAP caused by MDR Gram-negative bacteria in patients with COVID-19

The current burden of carbapenemases: Review of significant properties and dissemination among gram-negative bacteria

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Carbapenemases are β-lactamases belonging to different Ambler classes (A, B, D) and can be encoded by both chromosomal and plasmid-mediated genes. These enzymes represent the most potent β-lactamases, which hydrolyze a broad variety of β-lactams, including carbapenems, cephalosporins, penicillin, and aztreonam. The major issues associated with carbapenemase production are clinical due to compromising the activity of the last resort antibiotics used for treating serious infections, and epidemiological due to their dissemination into various bacteria across almost all geographic regions. Carbapenemase-producing Enterobacteriaceae have received more attention upon their first report in the early 1990s. Currently, there is increased awareness of the impact of nonfermenting bacteria, such as Acinetobacter baumannii and Pseudomonas aeruginosa, as well as other Gram-negative bacteria that are carbapenemase-producers. Outside the scope of clinical importance, carbapenemases are also detected in bacteria from environmental and zoonotic niches, which raises greater concerns over their prevalence, and the need for public health measures to control consequences of their propagation. The aims of the current review are to define and categorize the different families of carbapenemases, and to overview the main lines of their spread across different bacterial groups

The Collateral Effects of COVID-19 Pandemic on the Status of Carbapenemase-Producing Pathogens

The serious challenge of antimicrobial resistance continues to threaten public health and lingers in the era of the coronavirus disease 2019 (COVID-19), declared pandemic by the World Health Organization. While the pandemic has triggered the importance of infection control practices and preventive measures such as physical distancing, hand hygiene, travel reduction and quarantine, the ongoing alarm of antimicrobial resistance seems to accompany the pandemic too. Antimicrobial resistance has been fostered during COVID-19, possibly due to high rate of empirical antibiotic utilization in COVID-19 patients, increased use of biocides, and the disruption of proper healthcare for other conditions. Specifically, carbapenemase-producing Gram-negative bacteria have shown to cause secondary bacterial infections in patients hospitalized for COVID-19. Clinical and microbiological evidence of such infections is accumulating in different parts of the world. With the resilient nature of carbapenemases, their association with mortality, and the limited treatment options available, concerns regarding this group of antibiotic-hydrolyzing enzymes during the pandemic are expected to upsurge. While the additional burden carbapenemases exert on healthcare is worrisome, it remains hidden or abandoned among the various health consequences of the pandemic. The purpose of this minireview is to shed a light on carbapenemase-associated infections during such unprecedented time of COVID-19. A focused insight shall be made into carbapenemases, their implications for COVID-19 patients, and the features and consequences of co-infection, with a review of available evidence from pertinent literature. The importance of increased surveillance for carbapenemase-producers and optimizing their management in relation to the pandemic, shall be addressed as well

Heterogeneity of Carbapenem Resistance Mechanisms among Gram-Negative Pathogens in Lebanon: Results of the First Cross-Sectional Countrywide Study

© Copyright 2017, Mary Ann Liebert, Inc. 2017. Carbapenem-resistant Gram-negative pathogens have progressively disseminated to different countries worldwide, presenting a serious public health concern. The aims of this study were to determine the prevalence of carbapenem resistance in Gram-negative bacteria in Lebanon, to elucidate molecular mechanisms, and to identify genetic relatedness of incriminated strains. Carbapenem nonsusceptible Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas were collected from 11 Lebanese hospitals in 2012. Antimicrobial susceptibility was assessed with phenotypic tests, genes encoding carbapenemases were screened via PCR-sequencing, and genetic relatedness was examined by PGFE and ERIC-PCR. A total of 398 nonrepetitive carbapenem nonsusceptible isolates were studied, of which 44 were Enterobacteriaceae, 142 were A. baumannii, and 212 were Pseudomonas. Among Enterobacteriaceae, 70.4% carried blaOXA-48-like gene on IncL/M-type plasmids, while acquired AmpC cephalosporinases, extended-spectrum-β-lactamases, and efflux-pump were additional contributors to carbapenem resistance. Among A. baumannii, 90% produced OXA-23 and GES-11 and carried insertion sequence ISAba1 upstream and adjacent to blaOXA-23 and blaAcinetobacter-derived cephalosporinases. Among Pseudomonas, 16% harbored VIM-2, 4.2% IMP-2, and 1.4% IMP-1 metallo-β-lactamases. Fingerprint analysis indicated that the spread of OXA-48-like carbapenemases was mostly mediated by horizontal transfer, while OXA-23 and GES-11 diffusion in A. baumannii and VIM-2 diffusion in P. aeruginosa were primarily due to clonal dissemination. This study is the first nationwide investigation of carbapenem resistance in Lebanon, showing low level of resistance in Enterobacteriaceae, and higher levels in A. baumannii and Pseudomonas. With current changes in the region, continuous surveillance of carbapenem resistance is crucial

Surveillance of carbapenem non-susceptible gram negative strains and characterization of carbapenemases of classes A, B and D in a Lebanese hospital

© 2015, Lebanese Order of Physicians. All rights reserved. The production of carbapenem-hydrolyzing enzymes has been recognized as one of the most currently relevant resistance mechanisms in gram negative bacterial isolates, and is being detected in various countries. In Lebanon, carbapenem resistance was studied among gram negative pathogens collected from a university hospital from January to June of years 2011 and 2012. All isolates were subjected to phenotypic tests including antibiotic susceptibility, cloxacillin effect, modified Hodge test, and Etest® for metallo-β-lactamase detection. They were also subjected to genotyping by PCR sequencing to characterize β-lactamases. Between January and June 2011, 48 carbapenem non-susceptible strains were collected. Of these, one Klebsiella pneumoniae harbored OXA-48 and insertion sequence IS1999; four Acinetobacter baumannii harbored simultaneously OXA-23 and GES-11, and three Pseudomonas harbored VIM-2 carbapenemase. Between January and June 2012, 100 carbapenem non-susceptible strains were collected. Of these, one K. pneumoniae harbored simultaneously OXA-48, IS1999, and an acquired AmpC of the ACC group; four Serratia marcescens harbored OXA-48, while among eight A. baumannii, one strain co-harbored OXA-23 and GES-11, six harbored OXA-23 and one OXA-24. Fifteen P. aeruginosa and two Pseudomonas species harbored VIM-2; two P. aeruginosa strains produced IMP-1 and two others IMP-2. This epidemiological survey demonstrates the presence of carbapenemases of Ambler classes A, B, and D in a Lebanese hospital and indicates increase in the number and variety of such enzymes

Assessment of the performance of CHROMagar KPC and Xpert Carba-R assay for the detection of carbapenem-resistant bacteria in rectal swabs: First comparative study from Abu Dhabi, United Arab Emirates

© 2019 International Society for Antimicrobial Chemotherapy Objectives: The objective of this study was to evaluate the performance of CHROMagar™ KPC compared with Xpert® Carba-R assay for the detection of carbapenem-resistant bacterial isolates from rectal swabs. Methods: Rectal swabs were obtained from patients admitted to Cleveland Clinic Abu Dhabi (United Arab Emirates) over a period of 7 months and were screened for carbapenem resistance by either culture on CHROMagar KPC or carbapenemase production using the Xpert Carba-R molecular method. Further testing for carbapenem susceptibility of isolates recovered from CHROMagar KPC was performed using VITEK®2. Results: A total of 1813 rectal swabs were screened, of which 61 (3.4%) were positive for carbapenem resistance by either one or both methods. Both methods were equally efficient in detecting carbapenem resistance in 37/61 swabs (60.7%), mostly positive for Klebsiella pneumoniae (22 isolates), of which 40.9% (9/22) carried blaOXA-48-like and blaNDM. Xpert Carba-R assay detected 12 additional swabs with negative CHROMagar KPC culture and revealed additional carbapenemase-producing organisms carrying blaOXA-48-like and/or blaNDM. CHROMagar KPC recovered organisms in nine swabs not detected by the genotypic method, 44.4% of which were K. pneumoniae. Three swabs yielded false-positive results (carbapenem-susceptible organisms) by both methods. Sensitivity and specificity were, respectively, 75.4% and 99.8% for CHROMagar KPC and 80% and 99.8% for Xpert Carba-R. Conclusion: This comparative study of CHROMagar KPC versus Xpert Carba-R in rectal swabs showed a slightly higher sensitivity for the PCR-based method. Whilst CHROMagar KPC provides a less expensive screening method, Xpert Carba-R may be more accurate and faster

Potassium Ion Channels in Glioma: From Basic Knowledge into Therapeutic Applications

Ion channels, specifically those controlling the flux of potassium across cell membranes, have recently been shown to exhibit an important role in the pathophysiology of glioma, the most common primary central nervous system tumor with a poor prognosis. Potassium channels are grouped into four subfamilies differing by their domain structure, gating mechanisms, and functions. Pertinent literature indicates the vital functions of potassium channels in many aspects of glioma carcinogenesis, including proliferation, migration, and apoptosis. The dysfunction of potassium channels can result in pro-proliferative signals that are highly related to calcium signaling as well. Moreover, this dysfunction can feed into migration and metastasis, most likely by increasing the osmotic pressure of cells allowing the cells to initiate the “escape” and “invasion” of capillaries. Reducing the expression or channel blockage has shown efficacy in reducing the proliferation and infiltration of glioma cells as well as inducing apoptosis, priming several approaches to target potassium channels in gliomas pharmacologically. This review summarizes the current knowledge on potassium channels, their contribution to oncogenic transformations in glioma, and the existing perspectives on utilizing them as potential targets for therapy.The APC was funded by the Lebanese International University

Role of outer membrane permeability, efflux mechanism, and carbapenemases in carbapenem-nonsusceptible Pseudomonas aeruginosa from Dubai hospitals: Results of the first cross-sectional survey

© 2019 The Authors Objectives: Carbapenem resistance in Pseudomonas aeruginosa is growing and results from variable mechanisms. The objectives of the current study were to investigate mechanisms of carbapenem resistance and genetic relatedness of P. aeruginosa isolates recovered in Dubai hospitals. Methods: From June 2015 through June 2016, carbapenem-nonsusceptible P. aeruginosa were collected from 4 hospitals in Dubai, and subjected to antimicrobial susceptibility testing, molecular investigation of carbapenemases by PCR-sequencing, analysis of outer membrane porin OprD2 and multidrug efflux channel MexAB-OprM levels by qPCR, and fingerprinting by ERIC-PCR. Results: Out of 1969 P. aeruginosa isolated during the study period, 471 (23.9%) showed reduced carbapenem susceptibility. Of these, 37 were analyzed and 32% of them produced VIM-type metallo-β-lactamases, including VIM-2, VIM-30, VIM-31, and VIM-42, while GES-5 and GES-9 co-existed with VIM in 5.4% of isolates. Outer membrane impermeability was observed in 73% of isolates and 75.6% displayed overproduced MexAB-OprM. ERIC-PCR revealed one large clone including most carbapenemase-producing isolates indicating clonal dissemination. Conclusion: This is the first study on carbapenem-nonsusceptible P. aeruginosa from Dubai, incriminating VIM production as well as outer membrane permeability and efflux systems as resistance mechanisms. Further studies on carbapenem-nonsusceptible P. aeruginosa in Dubai are warranted for containment of such health hazard