scholarly journals Characterization of a Novel Plasmid in Serratia marcescens Harboring blaGES-5 Isolated from a Nosocomial Outbreak in Japan

2021 ◽  
Author(s):  
Noriko Nakanishi ◽  
Shoko Komatsu ◽  
Tomotada Iwamoto ◽  
Ryohei Nomoto
Keyword(s):  
Serratia Marcescens ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Clinical Settings ◽  
Nosocomial Outbreak ◽  
Nosocomial Pathogen ◽  
Surveillance Programs ◽  
Comparative Genetic Analysis ◽  
Unique Plasmid

Serratia marcescens is a nosocomial pathogen with carbapenem resistance, limiting the availability of effective treatment options. In this study, we performed molecular characterization of GES-5 carbapenemase-producing S. marcescens isolated from an outbreak in Japan. Comparative genetic analysis revealed that the blaGES-5–encoding plasmid p2020-O-9 is a unique plasmid contributing towards carbapenem resistance. Furthermore, this study highlights the necessity of surveillance programs for monitoring novel, along with commonly occurring carbapenemases in clinical settings.

scholarly journals Molecular Characterization of Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates from Egyptian Patients

2020 ◽  
Author(s):  
Reem M Hassan ◽  
Sherifa T Salem ◽  
Saly Ismail Mostafa Hassan ◽  
Asmaa Hegab ◽  
Yasmine S Elkholy
Keyword(s):  
Acinetobacter Baumannii ◽  
Molecular Characterization ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Common Mechanism ◽  
Carbapenem Resistant ◽  
Egyptian Patients ◽  
Global Threat

Abstract Acinetobacter baumannii (A. baumannii) represents a global threat owing to its ability to resist most of the currently available antimicrobial agents. Moreover, emergence of carbapenem resistant A. baumannii (CR-AB) isolates limits the available treatment options. Enzymatic degradation by variety of ß-lactamases, have been identified as the most common mechanism of carbapenem resistance in A. baumannii. The alarming increase in the prevalence of CR-AB necessitates continuous screening and molecular characterization to appreciate the problem. The present study was performed to assess the prevalence and characterize carbapenemases among 206 CR-AB isolated from various clinical specimens collected from different intensive care units at Kasr Al-Aini Hospital. All isolates were confirmed to be A. baumannii by detection of the blaOXA-51-like gene. Molecular screening of 13 common Ambler class bla carbapenemases genes in addition to insertion sequence (IS-1) upstream OXA-23 was performed by using four sets of multiplex PCR, followed by identification using gene sequencing technology. Among the investigated genes, the prevalence of blaOXA-23, and blaOXA-58 were 77.7%, and 1.9%, respectively. The ISAba1 was detected in 10% of the blaOXA-23 positive isolates. The prevalence of metallo-β-lactamases (MBLs) studied; blaNDM-1, blaSPM, blaVIM, blaSIM-1 were 11.7%, 6.3%, 0.5%, and 0.5% respectively. One of class A; bla KPC was detected in 10.7% of the investigated isolates. blaOXA-24/40, blaIMP, blaGES, blaVEB and blaGIM were not detected in any of the studied isolates. Moreover, 18.4% of the isolates have shown to harbor two or more of the screened bla genes. We concluded that the most prevalent type of ß-lactamases genes among CR-AB isolates collected from Egyptian patients were blaOXA-23 followed by blaNDM-1 and blaKPC.

scholarly journals β-Cyclodextrin/Isopentyl Caffeate Inclusion Complex: Synthesis, Characterization and Antileishmanial Activity

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4181
Author(s):  
Carine S. F. Marques ◽  
Nathalia S. Barreto ◽  
Simone S. C. de Oliveira ◽  
André L. S. Santos ◽  
Marta H. Branquinha ◽  
...  
Keyword(s):  
Inclusion Complex ◽  
Marked Improvement ◽  
Treatment Options ◽  
Molar Ratio ◽  
Clinical Settings ◽  
Drug Solubility ◽  
Proliferation Assay ◽  
Solubility Profile ◽  
Ft Ir

Isopentyl caffeate (ICaf) is a bioactive ester widely distributed in nature. Our patented work has shown promising results of this molecule against Leishmania. However, ICaf shows poor solubility, which limits its usage in clinical settings. In this work, we have proposed the development of an inclusion complex of ICaf in β-cyclodextrin (β-CD), with the aim to improve the drug solubility, and thus, its bioavailability. The inclusion complex (ICaf:β-CD) was developed applying three distinct methods, i.e., physical mixture (PM), kneading (KN) or co-evaporation (CO) in different molar proportions (0.25:1, 1:1 and 2:1). Characterization of the complexes was carried out by thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and molecular docking. The ICaf:β-CD complex in a molar ratio of 1:1 obtained by CO showed the best complexation and, therefore, was selected for further analysis. Solubility assay showed a marked improvement in the ICaf:β-CD (CO, 1:1) solubility profile when compared to the pure ICaf compound. Cell proliferation assay using ICaf:β-CD complex showed an IC50 of 3.8 and 2.7 µg/mL against L. amazonesis and L. chagasi promastigotes, respectively. These results demonstrate the great potential of the inclusion complex to improve the treatment options for visceral and cutaneous leishmaniases.

scholarly journals Molecular characterization of carbapenem-resistant Acinetobacter baumannii clinical isolates from Egyptian patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0251508
Author(s):  
Reem M. Hassan ◽  
Sherifa T. Salem ◽  
Saly Ismail Mostafa Hassan ◽  
Asmaa Sayed Hegab ◽  
Yasmine S. Elkholy
Keyword(s):  
Acinetobacter Baumannii ◽  
Molecular Characterization ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Common Mechanism ◽  
Carbapenem Resistant ◽  
Egyptian Patients ◽  
Global Threat

Acinetobacter baumannii (A. baumannii) represents a global threat owing to its ability to resist most of the currently available antimicrobial agents. Moreover, emergence of carbapenem resistant A. baumannii (CR-AB) isolates limits the available treatment options. Enzymatic degradation by variety of ß-lactamases, have been identified as the most common mechanism of carbapenem resistance in A. baumannii. The alarming increase in the prevalence of CR-AB necessitates continuous screening and molecular characterization to appreciate the problem. The present study was performed to assess the prevalence and characterize carbapenemases among 206 CR-AB isolated from various clinical specimens collected from different intensive care units at Kasr Al-Aini Hospital. All isolates were confirmed to be A. baumannii by detection of the blaOXA-51-like gene. Molecular screening of 13 common Ambler class bla carbapenemases genes in addition to insertion sequence (IS-1) upstream OXA-23 were performed by using four sets of multiplex PCR, followed by identification using gene sequencing technology. Among the investigated genes, the prevalence of blaOXA-23, and blaOXA-58 were 77.7%, and 1.9%, respectively. The ISAba1 was detected in 10% of the blaOXA-23 positive isolates. The prevalence of metallo-β-lactamases (MBLs) studied; blaNDM-1, blaSPM, blaVIM, blaSIM-1 were 11.7%, 6.3%, 0.5%, and 0.5% respectively. One of class A; bla KPC was detected in 10.7% of the investigated isolates. blaOXA-24/40, blaIMP, blaGES, blaVEB and blaGIM were not detected in any of the studied isolates. Moreover, 18.4% of the isolates have shown to harbor two or more of the screened bla genes. We concluded that the most prevalent type of ß-lactamases genes among CR-AB isolates collected from Egyptian patients were blaOXA-23 followed by blaNDM-1 and blaKPC.

scholarly journals Discovery and characterization of New Delhi metallo-β-lactamase-1 inhibitor peptides that potentiate meropenem-dependent killing of carbapenemase-producing Enterobacteriaceae

2020 ◽  
Vol 75 (10) ◽  
pp. 2843-2851 ◽  
Author(s):  
Misha I Kazi ◽  
Blair W Perry ◽  
Daren C Card ◽  
Richard D Schargel ◽  
Hana B Ali ◽  
...  
Keyword(s):  
Biochemical Characterization ◽  
Treatment Options ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
New Delhi ◽  
Mammalian Cell Lines ◽  
Starting Point ◽  
Direct Binding ◽  
New Compounds

Abstract Objectives Metallo-β-lactamases (MBLs) are an emerging class of antimicrobial resistance enzymes that degrade β-lactam antibiotics, including last-resort carbapenems. Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are increasingly prevalent, but treatment options are limited. While several serine-dependent β-lactamase inhibitors are formulated with commonly prescribed β-lactams, no MBL inhibitors are currently approved for combinatorial therapies. New compounds that target MBLs to restore carbapenem activity against CPE are therefore urgently needed. Herein we identified and characterized novel synthetic peptide inhibitors that bound to and inhibited NDM-1, which is an emerging β-lactam resistance mechanism in CPE. Methods We leveraged Surface Localized Antimicrobial displaY (SLAY) to identify and characterize peptides that inhibit NDM-1, which is a primary carbapenem resistance mechanism in CPE. Lead inhibitor sequences were chemically synthesized and MBCs and MICs were calculated in the presence/absence of carbapenems. Kinetic analysis with recombinant NDM-1 and select peptides tested direct binding and supported NDM-1 inhibitor mechanisms of action. Inhibitors were also tested for cytotoxicity. Results We identified approximately 1700 sequences that potentiated carbapenem-dependent killing against NDM-1 Escherichia coli. Several also enhanced meropenem-dependent killing of other CPE. Biochemical characterization of a subset indicated the peptides penetrated the bacterial periplasm and directly bound NDM-1 to inhibit enzymatic activity. Additionally, each demonstrated minimal haemolysis and cytotoxicity against mammalian cell lines. Conclusions Our approach advances a molecular platform for antimicrobial discovery, which complements the growing need for alternative antimicrobials. We also discovered lead NDM-1 inhibitors, which serve as a starting point for further chemical optimization.

scholarly journals Characterization of a Nosocomial Outbreak Caused by a Multiresistant Acinetobacter baumannii Strain with a Carbapenem-Hydrolyzing Enzyme: High-Level Carbapenem Resistance inA. baumannii Is Not Due Solely to the Presence of β-Lactamases

2000 ◽  
Vol 38 (9) ◽  
pp. 3299-3305 ◽  
Author(s):  
Germán Bou ◽  
Gonzalo Cerveró ◽  
M. Angeles Domínguez ◽  
Carmen Quereda ◽  
Jesús Martínez-Beltrán
Keyword(s):  
Acinetobacter Baumannii ◽  
Carbapenem Resistance ◽  
Pulsed Field Gel Electrophoresis ◽  
Nosocomial Outbreak ◽  
Chromosomal Dna ◽  
Penicillin Binding Proteins ◽  
Class D ◽  
High Level ◽  
Genotype A

From February to November 1997, 29 inpatients at Ramón y Cajal Hospital, Madrid, Spain, were determined to be either colonized or infected with imipenem- and meropenem-resistant Acinetobacter baumannii (IMRAB) strains (MICs, 128 to 256 μg/ml). A wide antibiotic multiresistance profile was observed with IMRAB strains. For typing IMRAB isolates, pulsed-field gel electrophoresis was used. For comparative purposes, 30 imipenem- and meropenem-susceptible A. baumannii (IMSAB) strains isolated before, during, and after the outbreak were included in this study. The molecular-typing results showed that the outbreak was caused by a single IMRAB strain (genotype A). By cloning experiments we identified a class D β-lactamase (OXA-24) encoded in the chromosomal DNA of this IMRAB strain which showed carbapenem hydrolysis. Moreover, the outer membrane profile of the IMRAB strain showed a reduction in the expression of two porins at 22 and 33 kDa when compared with genetically related IMSAB isolates. In addition no efflux mechanisms were identified in the IMRAB strains. In summary, we report here the molecular characterization of a nosocomial outbreak caused by one multiresistant A. baumannii epidemic strain that harbors a carbapenem-hydrolyzing enzyme. Although alterations in the penicillin-binding proteins cannot be ruled out, the reduction in the expression of two porins and the presence of this OXA-derived β-lactamase are involved in the carbapenem resistance of the epidemic nosocomial IMRAB strain.

scholarly journals Prevalence and Carbapenem Resistance of Acinetobacter baumannii and Other Than A. baumannii Isolates From Intensive Care Units (ICUs) and non-ICUs

2020 ◽  
Vol 41 (S1) ◽  
pp. s356-s357
Author(s):  
Tomasz Kasperski ◽  
Biophage Pharma S.A. Kraków ◽  
Agnieszka Chmielarczyk ◽  
Monika Pomorska-Wesolowska ◽  
Dorota Romaniszyn ◽  
...  
Keyword(s):  
Intensive Care ◽  
Inhibitory Concentration ◽  
Carbapenem Resistance ◽  
Diagnostic Methods ◽  
Clinical Settings ◽  
Gram Negative Bacteria ◽  
Carbapenem Resistant ◽  
Therapeutic Problem ◽  
Hospital Associated Infections ◽  
Very High

Background:Acinetobacter spp are gram-negative bacteria that have emerged as a leading cause of hospital-associated infections, most often in the intensive care unit (ICU) setting. This is particularly important in Poland, where the prevalence of A. baumannii in various types of infections, including bloodstream infection (BSI), pneumonia, skin and soft-tissue infection (SSTI), and urinary tract infection (UTI) is higher than in neighboring countries. Recently, other Acinetobacter spp, including A. lwoffii or A. ursingii, have been found to be clinically relevant. In Poland, we have also observed a very rapid increase in antimicrobial resistance, significantly faster for A. baumannii than for other nosocomial pathogens. Methods: A study was conducted in 12 southern Polish hospitals, including 3 ICUs, from January 1 to December 31, 2018. Only adult hospitalized patients were included. Strains were identified using the MALDI-TOF method. Carbapenem resistance was determined using the minimum inhibitory concentration (MIC). Results: During the study, 194 strains belonging to the Acinetobacter genus were isolated. A. baumannii was the dominant species, 88.1% (n = 171), and 23 isolates (11.9%) were other Acinetobacter spp: A. ursingii (n = 5), A. lwofii (n = 4), A. haemolyticus (n = 4), A. junii (n = 3), A. radioresistens (n = 2), A. bereziniae (n = 2), and A. johnsonii (n = 2). Moreover, 15 Acinetobacter strains were collected from ICUs. The most Acinetobacter strains were isolated from SSTIs (n = 115) from non-ICU settings. Non–A. baumannii strains were also most frequently isolated from SSTIs; they constituted 11.3% of all Acinetobacter strains from this type of infection (n = 13). The total Acinetobacter prevalence was 2.6%, whereas the prevalence in the ICU setting was 7%. Acinetobacter prevalence in SSTIs was 10.4%. In pneumonia, Acinetobacter prevalence was 18.6% for ICUs (n = 13) and 2.7% for non-ICUs (n = 46). Strains from UTIs were isolated only with the non-ICU setting, and their prevalence was 0.7% (n = 14). More than half of the tested strains (52.1%) were resistant to carbapenems, but all non–A. baumannii strains were susceptible. The highest resistance to carbapenems was among strains from pneumonia cases in ICUs (58.3%) and resistance among all strains isolated from ICU was 50%. However, even higher resistance was noted among SSTI strains from non-ICUs (61.7%). Conclusions: Increasingly, more than A. baumannii, other species among Acinetobacter strains are isolated from patients hospitalized in Polish hospitals. To assess the significance of non–A. baumannii spp in clinical settings, precise species identification is needed. Therefore, the diagnostic methods used must be improved. Carbapenem-resistant A. baumannii infections are the biggest problem in pneumonia patients in ICUs and in SSTI patients in other hospital departments. Carbapenem resistance occurs in a very high percentage of A. baumannii strains; among non–A. baumannii strains it is not yet a therapeutic problem.Funding: NoneDisclosures: None

scholarly journals S. pseudintermedius and S. aureus lineages with transmission ability circulate as causative agents of infections in pets for years

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Laura Ruiz-Ripa ◽  
Carmen Simón ◽  
Sara Ceballos ◽  
Carmelo Ortega ◽  
Myriam Zarazaga ◽  
...  
Keyword(s):  
Treatment Options ◽  
Companion Animals ◽  
Clinical History ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Antimicrobial Resistance Profile ◽  
Causative Agents ◽  
Veterinary Hospital ◽  
Coagulase Positive Staphylococci

Abstract Background Staphylococcus pseudintermedius (SP) and Staphylococcus aureus (SA) are common colonizers of companion animals, but they are also considered opportunistic pathogens, causing diseases of diverse severity. This study focused on the identification and characterization of 33 coagulase-positive staphylococci isolated from diseased pets (28 dogs and five cats) during 2009–2011 in a veterinary hospital in Spain in order to stablish the circulating lineages and their antimicrobial resistance profile. Results Twenty-eight isolates were identified as SP and five as SA. Nine methicillin-resistant (MR) isolates (27%) carrying the mecA gene were detected (eight MRSP and one MRSA). The 55% of SP and SA isolates were multidrug-resistant (MDR). MRSP strains were typed as ST71-agrIII-SCCmecII/III-(PFGE) A (n=5), ST68-agrIV-SCCmecV-B1/B2 (n=2), and ST258-agrII-SCCmecIV-C (n=1). SP isolates showed resistance to the following antimicrobials [percentage of resistant isolates/resistance genes]: penicillin [82/blaZ], oxacillin [29/mecA] erythromycin/clindamycin [43/erm(B)], aminoglycosides [18–46/aacA-aphD, aphA3, aadE], tetracycline [71/tet(M), tet(K)], ciprofloxacin [29], chloramphenicol [29/catpC221], and trimethoprim-sulfamethoxazole [50/dfrG, dfrK]. The dfrK gene was revealed as part of the radC-integrated Tn559 in two SP isolates. Virulence genes detected among SP isolates were as follow [percentage of isolates]: siet [100], se-int [100], lukS/F-I [100], seccanine [7], and expB [7]. The single MRSA-mecA detected was typed as t011-ST398/CC398-agrI-SCCmecV and was MDR. The methicillin-susceptible SA isolates were typed as t045-ST5/CC5 (n=2), t10576-ST1660 (n=1), and t005-ST22/CC22 (n=1); the t005-ST22 feline isolate was PVL-positive and the two t045-ST45 isolates were ascribed to Immune Evasion Cluster (IEC) type F. Moreover, the t10576-ST1660 isolate, of potential equine origin, harbored the lukPQ and scneq genes. According to animal clinical history and data records, several strains seem to have been acquired from different sources of the hospital environment, while some SA strains appeared to have a human origin. Conclusions The frequent detection of MR and MDR isolates among clinical SP and SA strains with noticeable virulence traits is of veterinary concern, implying limited treatment options available. This is the first description of MRSA-ST398 and MRSP-ST68 in pets in Spain, as well the first report of the dfrK-carrying Tn559 in SP. This evidences that current transmissible lineages with mobilizable resistomes have been circulating as causative agents of infections among pets for years.

Characterization of carbapenem resistance mechanisms inKlebsiella pneumoniaeandin vitrosynergy of the colistin–meropenem combination

2014 ◽  
Vol 27 (5) ◽  
pp. 277-282 ◽  
Author(s):  
Lakshmana Gowda Krishnappa ◽  
Mohammed Ali M. Marie ◽  
Yazeed A. Al Sheikh
Keyword(s):  
Carbapenem Resistance ◽  
Resistance Mechanisms

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.

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