scholarly journals Extended-Spectrum β-Lactamases in the 21st Century: Characterization, Epidemiology, and Detection of This Important Resistance Threat

2001 ◽  
Vol 14 (4) ◽  
pp. 933-951 ◽  
Author(s):  
Patricia A. Bradford

SUMMARY β-Lactamases continue to be the leading cause of resistance to β-lactam antibiotics among gram-negative bacteria. In recent years there has been an increased incidence and prevalence of extended-spectrum β-lactamases (ESBLs), enzymes that hydrolyze and cause resistance to oxyimino-cephalosporins and aztreonam. The majority of ESBLs are derived from the widespread broad-spectrum β-lactamases TEM-1 and SHV-1. There are also new families of ESBLs, including the CTX-M and OXA-type enzymes as well as novel, unrelated β-lactamases. Several different methods for the detection of ESBLs in clinical isolates have been suggested. While each of the tests has merit, none of the tests is able to detect all of the ESBLs encountered. ESBLs have become widespread throughout the world and are now found in a significant percentage of Escherichia coli and Klebsiella pneumoniae strains in certain countries. They have also been found in other Enterobacteriaceae strains and Pseudomonas aeruginosa. Strains expressing these β-lactamases will present a host of therapeutic challenges as we head into the 21st century.

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Po-Yu Liu ◽  
Yu-Lin Lee ◽  
Min-Chi Lu ◽  
Pei-Lan Shao ◽  
Po-Liang Lu ◽  
...  

ABSTRACT A multicenter collection of bacteremic isolates of Escherichia coli (n = 423), Klebsiella pneumoniae (n = 372), Pseudomonas aeruginosa (n = 300), and Acinetobacter baumannii complex (n = 199) was analyzed for susceptibility. Xpert Carba-R assay and sequencing for mcr genes were performed for carbapenem- or colistin-resistant isolates. Nineteen (67.8%) carbapenem-resistant K. pneumoniae (n = 28) and one (20%) carbapenem-resistant E. coli (n = 5) isolate harbored blaKPC (n = 17), blaOXA-48 (n = 2), and blaVIM (n = 1) genes.


2014 ◽  
Vol 59 (3) ◽  
pp. 1789-1793 ◽  
Author(s):  
Henry Li ◽  
Mark Estabrook ◽  
George A. Jacoby ◽  
Wright W. Nichols ◽  
Raymond T. Testa ◽  
...  

ABSTRACTAvibactam, a broad-spectrum β-lactamase inhibitor, was tested with ceftazidime, ceftaroline, or aztreonam against 57 well-characterized Gram-negative strains producing β-lactamases from all molecular classes. Most strains were nonsusceptible to the β-lactams alone. Against AmpC-, extended-spectrum β-lactamase (ESBL)-, and KPC-producingEnterobacteriaceaeorPseudomonas aeruginosa, avibactam lowered ceftazidime, ceftaroline, or aztreonam MICs up to 2,048-fold, to ≤4 μg/ml. Aztreonam-avibactam MICs against a VIM-1 metallo-β-lactamase-producingEnterobacter cloacaeand a VIM-1/KPC-3-producingEscherichia coliisolate were 0.12 and 8 μg/ml, respectively.


2017 ◽  
Vol 45 ◽  
pp. 4
Author(s):  
Ruben Horn Vasconcelos ◽  
Windleyanne Gonçalves Amorim Bezerra ◽  
Raul Antunes Silva Siqueira ◽  
Pedro Henrique Quintela Soares De Medeiros ◽  
Ricardo Barbosa Lucena ◽  
...  

Background: Rock pigeon (Columba livia) is an exotic and invasive species of the Columbidae family found in several cities around the world, including Brazilian cities, and close to humans. This species is found in large populations often in public locations, where people may have contact. Several studies have demonstrated the isolation of human pathogens from these birds. However, there are scarce studies describing infections by Gram-negative bacteria to which pigeons are susceptible. Therefore, this report aimed to describe a case of natural coinfection of Pseudomonas aeruginosa and Enteroaggregative Escherichia coli in a feral pigeon.Case: A sick feral pigeon was delivered at the Laboratory of Ornithological Studies, State University of Ceará, Fortaleza, Brazil. Due to poor prognosis, the individual was euthanized with ketamine via intravenous injection and submitted to necropsy, in which samples were collected for microbiological and histopathological procedure. The procedure was performed aseptically and samples were collected from intestine, liver, spleen, heart and lung. Bacterial isolation was performed with culture media selective for Gram negative bacteria and strains were identified biochemically. Histopathological examination was performed with conventional method and slides were stained with hematoxylin and eosin. DNA from E. coli isolates was extracted with simples boiling method and submitted to uniplex conventional polymerase chain reaction (PCR) to diagnose diarrheagenic pathotypes with specific primers for the following genes: aaiC, aatA, eaeA, stx1, stx2, eltB, estA and ipaH. Escherichia coli was isolated from the intestine, liver, spleen and lung, while Pseudomonas aeruginosa was present in liver, spleen and lung. E. coli strains from liver and spleen were positive for the aaiC gene, which is a diagnostic gene for Enteroaggregative Escherichia coli (EAEC) pathotype. Necropsy revealed the presence of several caseous lesions around the head of the bird, cellulitis in the abdominal region, hepatomegaly, splenomegaly, hemorrhagic intestine and pericarditis. Microscopical findings were most intense in liver and lung samples, presenting vascular and inflammatory alterations. Histopathological alterations indicated an acute presentation of the infections and several lesions in different organs, demonstrating the septicemic characteristic of the microorganisms involved in this case.Discussion: Both pathogens in this report were identified mostly in the same organs, which may indicate that there was an association in the pathogenesis. However, the entry routes of infection in this case may have been different, considering that Pseudomonas aeruginosa was not isolated from the intestine. The histopathological findings were not pathognomonic for either pathogen. However, some characteristic lesions were observed, such as cellulitis, which is commonly attributed to Escherichia coli. EAEC strains are human pathogens that cause acute and persistent diarrhea around the world. These microorganisms could be potentially transmitted to humans, as suggested by other studies with feral pigeons and enteric pathogens. However, the absence of reports of pigeon-transmitted diarrheagenic infections in humans may suggest that pigeons are only reservoirs of these pathogens. In addition, as this report demonstrates, these birds may also suffer from these infections. In conclusion, the free-living pigeon presented a natural occurring case of coinfection by Pseudomonas aeruginosa and Enteroaggregative Escherichia coli. Both are human opportunistic pathogens, and may have public health implications


2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110118
Author(s):  
Cosmina Zeana ◽  
Frank E. Palmieri ◽  
Vikas Gupta ◽  
Gang Ye ◽  
Peter Lao ◽  
...  

This study evaluated an antibiotic stewardship program (ASP) intervention aimed at reducing inpatient fluoroquinolone (FQ) use and examined its impact on ciprofloxacin susceptibilities of gram-negative bacteria in a large 611-bed community hospital. A two-step ASP intervention was implemented: an electronic medical record algorithm that prompted physicians to re-evaluate FQ use shortly after admission and changed institutional UTI/pneumonia guidelines that recommended options alternate to FQs for first-line empiric antibiotic therapy in 2010 and 2011 respectively. Between 2007 and 2017 FQ use and ciprofloxacin susceptibilities of all non-duplicate cultured isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa obtained ≥72 h after admission were reviewed. Ambulatory care isolates served as a comparison group. FQ utilization rates and relationships to ciprofloxacin susceptibility were evaluated using interrupted time series models. Over the 11-year period, FQ use decreased from 110.0 (2007) to 26.2 (2017) days of therapy/1000 days at risk ( p < 0.001). Compared to pre-intervention, the estimated (post-intervention) reduction in FQ utilization was 28.4 (95% CI: 10.9–46) days of therapy/1000 days at risk. Reduced FQ utilization was correlated with increase susceptibilities to ciprofloxacin of hospital onset isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis ( p < 0.02), and Pseudomonas aeruginosa ( p = 0.07). No significant susceptibility change was observed in the ambulatory care isolates. Persuasive interventions by an ASP successfully modified physicians’ inpatient empiric antibiotic use, produced a sustained reduction in FQ utilization rates and increased ciprofloxacin susceptibility to four commonly encountered gram-negative bacteria in a community hospital.


Author(s):  
Katharina Bach ◽  
Birgit Edel ◽  
Steffen Höring ◽  
Lucie Bartoničkova ◽  
Stefan Glöckner ◽  
...  

AbstractThe LAMP-based eazyplex® BloodScreen GN was evaluated for the detection of frequent Gram-negatives directly from positive blood culture (BC) bottles. A total of 449 BCs were analyzed. Sensitivities and specificities were 100% and 100% for Escherichia coli, 95.7% and 100% for Klebsiella pneumoniae, 100% and 100% for blaCTX-M, 100% and 100% for Klebsiella oxytoca, 100% and 99% for Proteus mirabilis, and 100% and 99.8% for Pseudomonas aeruginosa, respectively. The time to result ranged from 8 to 16 min, plus about 6 min for sample preparation. The eazyplex® BloodScreen GN is a reliable molecular assay for rapid BC testing.


Author(s):  
Zehra Edis ◽  
Samir Haj Bloukh ◽  
Hamed Abu Sara

New antibacterial agents are needed to overcome the increasing number of infectious diseases caused by pathogenic microorganisms due to the emergence of multi-drug resistant strains. &nbsp;In this context, halogens, especially Iodine is known since ages for its antimicrobial activity. Therefore, especially triiodides encapsulated in organometallic complexes can be helpful as new agents against microorganisms. The aims of this work was to study the biological activity of [Na(12-Crown-4)2]I3 against gram positive Streptococcus pyogenes, Streptococcus faecalis, the spore forming bacteria Bacillus subtilis and gram negative bacteria Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Klebsiella pneumoniae, as well as the yeast Candida albicans. The antimicrobial and antifungal activities of the triiodide were determined by zone of inhibition plate studies. [Na(12-Crown-4)2]I3 exhibited potent antimicrobial activity on gram positive Streptochocci and the yeast C. albicans. Furthermore, the gram negative bacteria P. aeruginosa and K. pneumoniae were less effectively inhibited, while E. coli and P. mirabilis proved to be even resistant.


Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 247
Author(s):  
Khaled S. M. Azab ◽  
Mohamed Ali Abdel-Rahman ◽  
Hussien H. El-Sheikh ◽  
Ehab Azab ◽  
Adil A. Gobouri ◽  
...  

The incidence of Extended-spectrum β-lactamase (ESBL)-encoding genes (blaCTX-M and blaTEM) among Gram-negative multidrug-resistant pathogens collected from three different countries was investigated. Two hundred and ninety-two clinical isolates were collected from Egypt (n = 90), Saudi Arabia (n = 162), and Sudan (n = 40). Based on the antimicrobial sensitivity against 20 antimicrobial agents from 11 antibiotic classes, the most resistant strains were selected and identified using the Vitek2 system and 16S rRNA gene sequence analysis. A total of 85.6% of the isolates were found to be resistant to more than three antibiotic classes. The ratios of the multidrug-resistant strains for Egypt, Saudi Arabia, and Sudan were 74.4%, 90.1%, and 97.5%, respectively. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa showed inconstant resistance levels to the different classes of antibiotics. Escherichia coli and Klebsiella pneumoniae had the highest levels of resistance against macrolides followed by penicillins and cephalosporin, while Pseudomonas aeruginosa was most resistant to penicillins followed by classes that varied among different countries. The isolates were positive for the presence of the blaCTX-M and blaTEM genes. The blaCTX-M gene was the predominant gene in all isolates (100%), while blaTEM was detected in 66.7% of the selected isolates. This work highlights the detection of multidrug-resistant bacteria and resistant genes among different countries. We suggest that the medical authorities urgently implement antimicrobial surveillance plans and infection control policies for early detection and effective prevention of the rapid spread of these pathogens.


2021 ◽  
Vol 22 (10) ◽  
pp. 5328
Author(s):  
Miao Ma ◽  
Margaux Lustig ◽  
Michèle Salem ◽  
Dominique Mengin-Lecreulx ◽  
Gilles Phan ◽  
...  

One of the major families of membrane proteins found in prokaryote genome corresponds to the transporters. Among them, the resistance-nodulation-cell division (RND) transporters are highly studied, as being responsible for one of the most problematic mechanisms used by bacteria to resist to antibiotics, i.e., the active efflux of drugs. In Gram-negative bacteria, these proteins are inserted in the inner membrane and form a tripartite assembly with an outer membrane factor and a periplasmic linker in order to cross the two membranes to expulse molecules outside of the cell. A lot of information has been collected to understand the functional mechanism of these pumps, especially with AcrAB-TolC from Escherichia coli, but one missing piece from all the suggested models is the role of peptidoglycan in the assembly. Here, by pull-down experiments with purified peptidoglycans, we precise the MexAB-OprM interaction with the peptidoglycan from Escherichia coli and Pseudomonas aeruginosa, highlighting a role of the peptidoglycan in stabilizing the MexA-OprM complex and also differences between the two Gram-negative bacteria peptidoglycans.


2020 ◽  
Author(s):  
Hanh N. Lam ◽  
Tannia Lau ◽  
Adam Lentz ◽  
Jessica Sherry ◽  
Alejandro Cabrera-Cortez ◽  
...  

ABSTRACTAntibiotic resistant bacteria are an emerging global health threat. New antimicrobials are urgently needed. The injectisome type III secretion system (T3SS), required by dozens of Gram-negative bacteria for virulence but largely absent from non-pathogenic bacteria, is an attractive antimicrobial target. We previously identified synthetic cyclic peptomers, inspired by the natural product phepropeptin D, that inhibit protein secretion through the Yersinia Ysc and Pseudomonas aeruginosa Psc T3SSs, but do not inhibit bacterial growth. Here we describe identification of an isomer, 4EpDN, that is two-fold more potent (IC50 4 μM) than its parental compound. Furthermore, 4EpDN inhibited the Yersinia Ysa and the Salmonella SPI-1 T3SSs, suggesting that this cyclic peptomer has broad efficacy against evolutionarily distant injectisome T3SSs. Indeed, 4EpDN strongly inhibited intracellular growth of Chlamydia trachomatis in HeLa cells, which requires the T3SS. 4EpDN did not inhibit the unrelated Twin arginine translocation (Tat) system, nor did it impact T3SS gene transcription. Moreover, although the injectisome and flagellar T3SSs are evolutionarily and structurally related, the 4EpDN cyclic peptomer did not inhibit secretion of substrates through the Salmonella flagellar T3SS, indicating that cyclic peptomers broadly but specifically target the injestisome T3SS. 4EpDN reduced the number of T3SS basal bodies detected on the surface of Y. enterocolitica, as visualized using a fluorescent derivative of YscD, an inner membrane ring with low homology to flagellar protein FliG. Collectively, these data suggest that cyclic peptomers specifically inhibit the injectisome T3SS from a variety of Gram-negative bacteria, possibly by preventing complete T3SS assembly.IMPORTANCETraditional antibiotics target both pathogenic and commensal bacteria, resulting in a disruption of the microbiota, which in turn is tied to a number of acute and chronic diseases. The bacterial type III secretion system (T3SS) is an appendage used by many bacterial pathogens to establish infection, but is largely absent from commensal members of the microbiota. In this study, we identify a new derivative of the cyclic peptomer class of T3SS inhibitors. These compounds inhibit the T3SS of the nosocomial ESKAPE pathogen Pseudomonas aeruginosa and enteropathogenic Yersinia and Salmonella. The impact of cyclic peptomers is specific to the T3SS, as other bacterial secretory systems are unaffected. Importantly, cyclic peptomers completely block replication of Chlamydia trachomatis, the causative agent of genital, eye, and lung infections, in human cells, a process that requires the T3SS. Therefore, cyclic peptomers represent promising virulence blockers that can specifically disarm a broad spectrum of Gram-negative pathogens.


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