Carbapenem-resistantAcinetobacter baumannii: diversity of resistant mechanisms and risk factors for infection

2011 ◽  
Vol 140 (1) ◽  
pp. 137-145 ◽  
Author(s):  
Y. J. KIM ◽  
S. I. KIM ◽  
Y. R. KIM ◽  
K. W. HONG ◽  
S. H. WIE ◽  
...  
Keyword(s):  
Risk Factors ◽  
Efflux Pump ◽  
Clinical Epidemiology ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Apache Ii Score ◽  
Mechanisms Of Resistance ◽  
High Apache ◽  
Carbapenem Resistant ◽  
Clonal Spread

SUMMARYCarbapenem-resistantAcinetobacter baumannii(CRAB) are an increasing infectious threat in hospitals. We investigated the clinical epidemiology of CRAB infectionsvs. colonization in patients, and examined the mechanisms of resistance associated with elevated minimum inhibitory concentrations (MICs) for carbapenems. From January to June 2009, 75 CRAB strains were collected. CRAB infection was significantly associated with malignancy and a high APACHE II score. The most dominant resistance mechanism was ISAba1preceding OXA-51, producing strains with overexpression of efflux pump. Strains carryingblaOXA-23-like enzymes had higher carbapenem MICs than those carryingblaOXA-51-like enzymes; however, the presence of multiple mechanisms did not result in increased resistance to carbapenems. There was no difference in the resistance mechanisms in strains from infected and colonized patients. The majority of strains were genetically diverse by DNA macrorestriction although there was evidence of clonal spread of four clusters of strains in patients.

scholarly journals Characterization of resistance mechanisms of Enterobacter cloacae Complex co-resistant to carbapenem and colistin

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shixing Liu ◽  
Renchi Fang ◽  
Ying Zhang ◽  
Lijiang Chen ◽  
Na Huang ◽  
...  
Keyword(s):  
Lipid A ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Resistance Mechanisms ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
Horizontal Spread

Abstract Background The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains. Results This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found. Conclusions This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.

scholarly journals Molecular Epidemiology and Characterization of Carbapenem-Resistant Klebsiella pneumoniae Isolated from Urine at a Teaching Hospital in Taiwan

2021 ◽  
Vol 9 (2) ◽  
pp. 271
Author(s):  
Yuarn-Jang Lee ◽  
Chih-Hung Huang ◽  
Noor Andryan Ilsan ◽  
I-Hui Lee ◽  
Tzu-Wen Huang
Keyword(s):  
Klebsiella Pneumoniae ◽  
Teaching Hospital ◽  
Efflux Pump ◽  
Resistance Mechanisms ◽  
Pcr Analysis ◽  
Carbapenem Resistant ◽  
High Prevalence ◽  
Antimicrobial Susceptibility Tests ◽  
Susceptibility Tests ◽  
Tract Infections

Urinary tract infections (UTIs) are common in clinics and hospitals and are associated with a high economic burden. Enterobacterium Klebsiella pneumoniae is a prevalent agent causing UTIs. A high prevalence of carbapenem-resistant K. pneumoniae (CRKP) has emerged recently and is continuing to increase. Seventeen urinary CRKP isolates collected at a teaching hospital in Taiwan from December 2016 to September 2017 were analyzed to elucidate their drug resistance mechanisms. Two-thirds of the isolates were obtained from outpatients. Antimicrobial susceptibility tests demonstrated multidrug resistance in all the isolates. Multilocus sequence typing analysis showed high diversity among the isolates. PCR analysis demonstrated the presence of carbapenemases in three isolates. All isolates carried at least one other extended-spectrum β-lactamase, including TEM, DHA, and CTX-M. Fifteen isolates contained mutations in one of the outer membrane porins that were assessed. The expression levels of the acrB and/or oqxB efflux pump genes, as determined by qRT-PCR, were upregulated in 11 isolates. Six isolates might have utilized other efflux pumps or antimicrobial resistance mechanisms. These analyses demonstrated a highly diverse population and the presence of complex resistance mechanisms in urinary isolates of K. pneumoniae.

scholarly journals Resistance Mechanisms of Multiresistant Pseudomonas aeruginosa Strains from Germany and Correlation with Hypermutation

2007 ◽  
Vol 51 (11) ◽  
pp. 4062-4070 ◽  
Author(s):  
B. Henrichfreise ◽  
I. Wiegand ◽  
W. Pfister ◽  
B. Wiedemann
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Type Ii ◽  
Mechanisms Of Resistance ◽  
Resistance Determinants ◽  
Class 1 ◽  
Mutator Strains ◽  
Multiresistant Strains

ABSTRACT In this study, we analyzed the mechanisms of multiresistance for 22 clinical multiresistant and clonally different Pseudomonas aeruginosa strains from Germany. Twelve and 10 strains originated from cystic fibrosis (CF) and non-CF patients, respectively. Overproduction of the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was studied. Furthermore, loss of OprD, alterations in type II topoisomerases, AmpC overproduction, and the presence of 25 acquired resistance determinants were investigated. The presence of a hypermutation phenotype was also taken into account. Besides modifications in GyrA (91%), the most frequent mechanisms of resistance were MexXY-OprM overproduction (82%), OprD loss (82%), and AmpC overproduction (73%). Clear differences between strains from CF and non-CF patients were found: numerous genes coding for aminoglycoside-modifying enzymes and located, partially in combination with β-lactamase genes, in class 1 integrons were found only in strains from non-CF patients. Furthermore, multiple modifications in type II topoisomerases conferring high quinolone resistance levels and overexpression of MexAB-OprM were exclusively detected in multiresistant strains from non-CF patients. Correlations of the detected phenotypes and resistance mechanisms revealed a great impact of efflux pump overproduction on multiresistance in P. aeruginosa. Confirming previous studies, we found that additional, unknown chromosomally mediated resistance mechanisms remain to be determined. In our study, 11 out of 12 strains and 3 out of 10 strains from CF patients and non-CF patients, respectively, were hypermutable. This extremely high proportion of mutator strains should be taken into consideration for the treatment of multiresistant P. aeruginosa.

Quinoline resistance mechanisms in Plasmodium falciparum: the debate goes on

Parasitology ◽  
1997 ◽  
Vol 114 (7) ◽  
pp. 125-136 ◽  
Author(s):  
S. A. WARD ◽  
P. G. BRAY ◽  
S. R. HAWLEY
Keyword(s):  
Efflux Pump ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Food Vacuole ◽  
Drug Binding ◽  
Drug Uptake ◽  
Cross Resistance ◽  
Parasite Resistance ◽  
Therapeutic Success ◽  
Drug Binding Site

Despite considerable therapeutic success with the antimalarial 4-aminoquinolines such as chloroquine, there is serious doubt about the future of this drug class due mainly to the development and spread of parasite resistance throughout endemic areas. In this article we review the possible biochemical and molecular basis of resistance. Based on our current understanding we have considered the possibility of developing strategies which may allow the aminoquinolines to once again be used effectively against P. falciparum. Our conclusions are that drug resistance is the result of a reduced rate of drug uptake which in turn reduces the amount of drug available to bind the target. The basis for this reduced accumulation could be an altered pH gradient making the food vacuole more alkaline or the parasite cytosol more acidic, an efflux pump removing drug directly from the membrane or any other process which will reduce the rate of drug uptake. Central to the effectiveness of this resistance mechanism is the transient availability of a high affinity, low capacity drug binding site (possibly haem) within the parasite. Resistance reversers such as verapamil influence the apparent Ka for this drug binding phenomenon via an increased drug uptake rate. We demonstrate that by chemical modification of the aminoquinolines, producing predictable alterations in their physicochemical properties, that it is possible to minimise the verapamil sensitive component of resistance and reduce significantly cross-resistance patterns without loss in absolute activity. Based on these views we suggest that the aminoquinoline antimalarials still have a role to play in the cheap, safe and effective chemotherapy of falciparum malaria.

scholarly journals Resistance in Staphylococcus Aureus: The Never-Ending Story

2016 ◽  
Vol 33 (3) ◽  
pp. 153-162
Author(s):  
Jovan Orlović ◽  
Biljana Miljković-Selimović ◽  
Marina Dinić ◽  
Ljiljana Ristić
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Mechanisms Of Resistance ◽  
Antibacterial Drugs ◽  
Ongoing Effort ◽  
Growth And Reproduction

Summary Combating Staphylococcus aureus (S. aureus) infections using antibacterial drugs is actually an ongoing effort to overcome resistance mechanism of this microorganism. In this paper, we discussed (1) the mechanisms of resistance to some of the most commonly used antimicrobial agents in the treatment of S. aureus: methicillin, vancomicyn and quinolones. In addition, (2) efflux pump mechanisms involved in maintaining homeostasis in the presence of compounds that inhibit S. aureus growth and reproduction, as well as mechanisms of resistance to a number of antibiotics, have been reviewed.

scholarly journals Some approaches to new antibacterial agents

2007 ◽  
Vol 79 (12) ◽  
pp. 2143-2153 ◽  
Author(s):  
John B. Bremner
Keyword(s):  
Bacterial Resistance ◽  
Efflux Pump ◽  
Transmembrane Protein ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Target Site ◽  
Resistant Bacteria ◽  
General Strategy ◽  
Dual Action ◽  
Hybrid Drugs

Bacteria use a number of resistance mechanisms to counter the antibacterial challenge, and one of these is the expression of transmembrane protein-based efflux pumps which can pump out antibacterials from within the cells, thus lowering the antibacterial concentration to nonlethal levels. For example, in S. aureus, the NorA pump can pump out the antibacterial alkaloid berberine and ciprofloxacin. One general strategy to reduce the health threat of resistant bacteria is to block a major bacterial resistance mechanism at the same time as interfering with another bacterial pathway or target site. New developments of this approach in the context of dual-action prodrugs and dual-action (or hybrid) drugs in which one action is targeted at blocking the NorA efflux pump and the second action at an alternative bacterial target site (or sites) for the antibacterial action are discussed. The compounds are based on a combination of 2-aryl-5-nitro-1H-indole derivatives (as the NorA efflux pump blocking component) and derivatives of berberine. General design principles, syntheses, antibacterial testing, and preliminary work on modes of action studies are discussed.

scholarly journals Impact of an Intervention to Control Imipenem-Resistant Acinetobacter baumannii and Its Resistance Mechanisms: An 8-Year Survey

2021 ◽  
Vol 11 ◽  
Author(s):  
Lida Chen ◽  
Pinghai Tan ◽  
Jianming Zeng ◽  
Xuegao Yu ◽  
Yimei Cai ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acinetobacter Baumannii ◽  
Bacterial Resistance ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Multi Drug Resistance ◽  
Minimal Inhibitory Concentrations ◽  
Resistance Rates ◽  
The Impact

BackgroundThis study aimed to examine the impact of an intervention carried out in 2011 to combat multi-drug resistance and outbreaks of imipenem-resistant Acinetobacter baumannii (IRAB), and to explore its resistance mechanism.MethodsA total of 2572 isolates of A. baumannii, including 1673 IRAB isolates, were collected between 2007 and 2014. An intervention was implemented to control A. baumannii resistance and outbreaks. Antimicrobial susceptibility was tested by calculating minimal inhibitory concentrations (MICs), and outbreaks were typed using pulsed-field gel electrophoresis (PFGE). Resistance mechanisms were explored by polymerase chain reaction (PCR) and whole genome sequencing (WGS).ResultsFollowing the intervention in 2011, the resistance rates of A. baumannii to almost all tested antibiotics decreased, from 85.3 to 72.6% for imipenem, 100 to 80.8% for ceftriaxone, and 45.0 to 6.9% for tigecycline. The intervention resulted in a decrease in the number (seven to five), duration (8–3 months), and departments (five to three) affected by outbreaks; no outbreaks occurred in 2011. After the intervention, only blaAMPC (76.47 to 100%) and blaTEM–1 (75.74 to 96.92%) increased (P < 0.0001); whereas blaGES–1 (32.35 to 3.07%), blaPER–1 (21.32 to 1.54%), blaOXA–58 (60.29 to 1.54%), carO (37.50 to 7.69%), and adeB (9.56 to 3.08%) decreased (P < 0.0001). Interestingly, the frequency of class B β-lactamase genes decreased from 91.18% (blaSPM–1) and 61.03% (blaIMP–1) to 0%, while that of class D blaOXA–23 increased to 96.92% (P < 0.0001). WGS showed that the major PFGE types causing outbreaks each year (type 01, 11, 18, 23, 26, and 31) carried the same resistance genes (blaKPC–1, blaADC–25, blaOXA–66, and adeABC), AdeR-S mutations (G186V and A136V), and a partially blocked porin channel CarO. Meanwhile, plasmids harboring blaOXA–23 were found after the intervention.ConclusionThe intervention was highly effective in reducing multi-drug resistance of A. baumannii and IRAB outbreaks in the long term. The resistance mechanisms of IRAB may involve genes encoding β-lactamases, efflux pump overexpression, outer membrane porin blockade, and plasmids; in particular, clonal spread of blaOXA–23 was the major cause of outbreaks. Similar interventions may also help reduce bacterial resistance rates and outbreaks in other hospitals.

scholarly journals Characterization of IncHI1B Plasmids Encoding Efflux Pump TmexCD2-ToprJ2 in Carbapenem-Resistant Klebsiella variicola, Klebsiella quasipneumoniae, and Klebsiella michiganensis Strains

2021 ◽  
Vol 12 ◽  
Author(s):  
Yujiao Wang ◽  
Bo Zhu ◽  
Min Liu ◽  
Xiutao Dong ◽  
Jianping Ma ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Health Concern ◽  
Close Monitoring ◽  
Carbapenem Resistant ◽  
Resistance Nodulation Division ◽  
Tertiary Hospitals ◽  
Severe Infections

Tigecycline serves as one of the last-resort antibiotics to treat severe infections caused by carbapenem-resistant Enterobacterales. Recently, a novel plasmid-mediated resistance-nodulation-division (RND)-type efflux pump gene cluster, TmexCD1-ToprJ1, and its variants, TmexCD2-ToprJ2 and TmexCD3-ToprJ3, encoding tetracyclines and tigecycline resistance, were revealed. In this study, we reported three TmexCD2-ToprJ2-harboring Klebsiella species strains, collected from two teaching tertiary hospitals in China, including one K. quasipneumoniae, one K. variicola, and one K. michiganensis. The three strains were characterized by antimicrobial susceptibility testing (AST), conjugation assay, WGS, and bioinformatics analysis. AST showed that K. variicola and K. quasipneumoniae strains were resistant to tigecycline with MIC values of 4μg/ml, whereas the K. michiganensis was susceptible to tigecycline with an MIC value of 1μg/ml. The TmexCD2-ToprJ2 clusters were located on three similar IncHI1B plasmids, of which two co-harbored the metallo-β-lactamase gene blaNDM-1. Conjugation experiments showed that all three plasmids were capable of self-transfer via conjugation. Our results showed, for the first time, that this novel plasmid-mediated tigecycline resistance mechanism TmexCD2-ToprJ2 has spread into different Klebsiella species, and clinical susceptibility testing may fail to detect. The co-occurrence of blaNDM-1 and TmexCD2-ToprJ2 in the same plasmid is of particular public health concern as the convergence of “mosaic” plasmids can confer both tigecycline and carbapenem resistance. Its further spread into other clinical high-risk Klebsiella clones will likely exacerbate the antimicrobial resistance crisis. A close monitoring of the dissemination of TmexCD-ToprJ encoding resistance should be considered.

scholarly journals Prevalence and mechanisms of carbapenem resistance  among  Klebsiella aerogenes  in a tertiary hospital in China

2020 ◽  
Author(s):  
Luxiang Liu ◽  
Jingjing Quan ◽  
Dongdong Zhao ◽  
Weichao Liao ◽  
Jiaojian Lv ◽  
...  
Keyword(s):  
Intensive Care ◽  
Efflux Pump ◽  
Carbapenem Resistance ◽  
Clonal Diversity ◽  
Tertiary Hospital ◽  
Molecular Characteristics ◽  
Klebsiella Aerogenes ◽  
Carbapenem Resistant ◽  
Efflux Pump Inhibition ◽  
Clonal Spread

Abstract Background: Klebsiella aerogenes has emerged as one of the most important nosocomial pathogens for patients in intensive care units (ICU) in recent years. This study aims to evaluated the prevalence and molecular characteristics of clinical carbapenem-resistant K. aerogenes (CRKA) isolates in a tertiary hospital in China.Results: Twenty CRKA were identified among all the isolates, with the rate of 5.5% (20/364). Six CRKA isolates produced KPC-2 and 1 CRKA isolate produced NDM-1. PFGE and MLST indicated that the 20 CRKA strains were clonal diversity. All the bla KPC-2 gene and bla NDM-1 gene were located on plasmids and all the plasmids with bla KPC-2 and bla NDM-1 genes could successfully transferred to EC600 or J53. Twelve of 13 CRKA strains without any carbapenemase genes were positive for efflux pump inhibition test.Conclusion: Overall, the prevalence of CRKA in the tertiary hospital in Zhejiang Province of China is 5.5%. Only 35% of CRKA produce carbapenemase and efflux pumps might play an important role in the carbapenem resistance of K. aerogenes. It is necessary to strengthen the surveillance of carbapenem resistance in the hospital to prevent the horizontal and clonal spread of CRKA.

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