scholarly journals The activity of ceftazidime-avibactam against gram-negative bacteria – pathogens of wound burn infection

MediAl ◽  
2019 ◽  
pp. 70-73
Author(s):  
N. A. Gordinskaya ◽  
E. V. Sabirova ◽  
N. V. Abramova
Keyword(s):  
Thermal Injury ◽  
Antimicrobial Agents ◽  
High Efficiency ◽  
Common Mechanism ◽  
Gram Negative Bacteria ◽  
Beta Lactam ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Lactam Ring

Introduction. The most common mechanism for the resistance of gram-negative bacteria to various classes of antimicrobial agents, including carbapenems, is the production of beta-lactamases, enzymes that destroy the beta-lactam ring. Purpose of the study. To analyze the activity of ceftazidime/avibactam against pseudomonads and Klebsiella isolated in patients with severe thermal injury. Materials and methods. We analyzed 2553 isolates – pathogens of wound burn infection in patients with thermal injury treated in 2018–2019. Results and discussion. Phenotypically, 72,8% of the analyzed P. aeruginosa were resistant to carbapenems, while 56,3% of carbapenemresistant strains produce group Vim metal-beta-lactamases. Analysis of the effectiveness of ceftazidime/avibactam against P. aeruginosa showed its high efficiency, more than half of the strains (55,3%) were sensitive to the drug. The studied K. pneumoniae phenotypically in 63,1% were carbapenem-resistant. Among K. pneumoniae resistant to carbapenems, 89,3% of the strains revealed genes of serine KPC or OXA-48 like carbapenemases. In vitro ceftazidime/avibactam was active against two-thirds (72,7%) of K. pneumoniae strains. Сonclusions. 1. Gram-negative microorganisms occupy 30,2% of the etiological structure of a wound burn infection. 2. Phenotypically 72,8% of Pseudomonas aeruginosa are resistant to carbapenems, 56,3% of them produce metal beta-lactamases. 3. 63,1% of Klebsiella pneumoniae isolated in patients with thermal injury are resistant to carbapenems, 89,3% of them carry cattle or OXA-48 genes like carbapenemases. 4. Ceftazidime / avibactam in vitro showed activity against P. aeruginosa and K. pneumoniae, with 55,3% and 72,7% of the strains, respectively, being sensitive.

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

scholarly journals PREVALENCE OF CEPHALOSPORIN-RESISTANT GRAM-NEGATIVE BACILLI FROM CLINICAL SAMPLES

2016 ◽  
pp. 176
Author(s):  
Kavi Aniis ◽  
Rajamanikandan Kcp ◽  
Arvind Prasanth D
Keyword(s):  
Clinical Samples ◽  
Beta Lactamase ◽  
Bacterial Isolates ◽  
Beta Lactam ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Lactam Ring ◽  
Esbl Producers

<p>ABSTRACT<br />Objective: Beta-lactams are the group of antibiotics that contain a ring called as “beta-lactam ring,” which is responsible for the antibacterial activity.<br />The presence of resistance among Gram-negative organisms is due to the production of beta-lactamases enzymes that hydrolysis the beta-lactam ring<br />thereby conferring resistance to the organism. This study is undertaken to determine the prevalence of extended-spectrum beta-lactamase (ESBL)<br />producing Gram-negative organism from clinical samples.<br />Methods: A total of 112 clinical samples were taken for this study. The combined disc synergistic test (CDST) was used for the phenotypic detection<br />of ESBL producers from the clinical samples. The genotypic identification of ESBL producers was carried out by alkaline lysis method by isolation of<br />plasmid DNA.<br />Result: A total of 87 bacterial isolates were isolated and identified. Among them, Klebsiella (41%) was the predominant organism followed by<br />Escherichia coli (33%), Proteus (10%), Pseudomonas (10%), and Serratia (6%). Among the various bacterial isolates, Klebsiella showed a higher<br />percentage of resistance. The CDST showed that 8 isolates of Klebsiella, 3 isolates of E. coli, and 1 isolate of Pseudomonas were found to be ESBL<br />producers. The genotypic confirmation showed that the two bacterial isolates, namely, Klebsiella and E. coli were found to possess temoniera (TEM)<br />gene which was the 400-500 bp conferring resistance to the antibiotics.<br />Conclusion: The results of this study suggest that early detection of ESBL producing Gram-negative organism is a very important step in planning the<br />therapy of patient in Hospitals. CDST continues to be a good indicator in the detection of ESBL producers.<br />Keywords: Beta-lactamases, Gram-negative bacilli, Extended-spectrum beta-lactamase, Resistance, Combined disc synergistic test.</p><p> </p>

scholarly journals Susceptibility trends of ceftolozane/tazobactam and comparators when tested against European Gram-negative bacterial surveillance isolates collected during 2012–18

2020 ◽  
Vol 75 (10) ◽  
pp. 2907-2913 ◽  
Author(s):  
Helio S Sader ◽  
Cecilia G Carvalhaes ◽  
Leonard R Duncan ◽  
Robert K Flamm ◽  
Dee Shortridge
Keyword(s):  
Eastern Europe ◽  
Active Compound ◽  
Western Europe ◽  
Antimicrobial Agents ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Systemic Infections

Abstract Background The Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) monitors the in vitro activity of ceftolozane/tazobactam and numerous antimicrobial agents against Gram-negative bacteria worldwide. Objectives To evaluate the activity of ceftolozane/tazobactam and resistance trends among Pseudomonas aeruginosa and Enterobacterales isolates in Europe between 2012 and 2018. Methods P. aeruginosa (7503) and Enterobacterales (30 582) isolates were collected from 53 medical centres in 26 countries in Europe and the Mediterranean region and tested for susceptibility by reference broth microdilution method in a central laboratory. MIC results were interpreted using EUCAST criteria. Results Ceftolozane/tazobactam was the most active compound tested against P. aeruginosa isolates after colistin, with overall susceptibility rates of 94.1% in Western Europe and 80.9% in Eastern Europe. Moreover, ceftolozane/tazobactam retained activity against 75.2% and 59.2% of meropenem-non-susceptible P. aeruginosa isolates in Western and Eastern Europe, respectively. Tobramycin was the third most active compound tested against P. aeruginosa, with susceptibility rates of 88.6% and 70.9% in Western and Eastern Europe, respectively. Ceftolozane/tazobactam was active against 94.5% of all Enterobacterales and 96.1% of meropenem-susceptible isolates from Western Europe. In Eastern Europe, ceftolozane/tazobactam was active against 79.4% of Enterobacterales overall and 86.2% of meropenem-susceptible isolates. Discussion Antimicrobial susceptibility rates for agents commonly used to treat serious systemic infections varied widely among nations and geographic regions and were generally lower in Eastern Europe compared with Western Europe. Ceftolozane/tazobactam demonstrated potent activity against P. aeruginosa, including MDR strains, and retained activity against most meropenem-susceptible Enterobacterales causing infection in European medical centres.

scholarly journals SPS-neutralization in tissue samples for efficacy testing of antimicrobial peptides

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Gabrielle Sherella Dijksteel ◽  
Peter H. Nibbering ◽  
Magda M. W. Ulrich ◽  
Esther Middelkoop ◽  
Bouke K. H. L. Boekema
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Antimicrobial Agents ◽  
Ex Vivo ◽  
Residual Activity ◽  
Gram Negative Bacteria ◽  
Tissue Samples ◽  
Gram Negative ◽  
Viable Bacteria

Abstract Background Accurate determination of the efficacy of antimicrobial agents requires neutralization of residual antimicrobial activity in the samples before microbiological assessment of the number of surviving bacteria. Sodium polyanethol sulfonate (SPS) is a known neutralizer for the antimicrobial activity of aminoglycosides and polymyxins. In this study, we evaluated the ability of SPS to neutralize residual antimicrobial activity of antimicrobial peptides [SAAP-148 and pexiganan; 1% (wt/v) in PBS], antibiotics [mupirocin (Bactroban) and fusidic acid (Fucidin) in ointments; 2% (wt/wt))] and disinfectants [2% (wt/wt) silver sulfadiazine cream (SSD) and 0.5% (v/v) chlorhexidine in 70% alcohol]. Methods Homogenates of human skin models that had been exposed to various antimicrobial agents for 1 h were pipetted on top of Methicillin-resistant Staphylococcus aureus (MRSA) on agar plates to determine whether the antimicrobial agents display residual activity. To determine the optimal concentration of SPS for neutralization, antimicrobial agents were mixed with PBS or increasing doses of SPS in PBS (0.05–1% wt/v) and then 105 colony forming units (CFU)/mL MRSA were added. After 30 min incubation, the number of viable bacteria was assessed. Next, the in vitro efficacy of SAAP-148 against various gram-positive and gram-negative bacteria was determined using PBS or 0.05% (wt/v) SPS immediately after 30 min incubation of the mixture. Additionally, ex vivo excision wound models were inoculated with 105 CFU MRSA for 1 h and exposed to SAAP-148, pexiganan, chlorhexidine or PBS for 1 h. Subsequently, samples were homogenized in PBS or 0.05% (wt/v) SPS and the number of viable bacteria was assessed. Results All tested antimicrobials displayed residual activity in tissue samples, resulting in a lower recovery of surviving bacteria on agar. SPS concentrations at ≥0.05% (wt/v) were able to neutralize the antimicrobial activity of SAAP-148, pexiganan and chlorhexidine, but not of SSD, Bactroban and Fucidin. Finally, SPS-neutralization in in vitro and ex vivo efficacy tests of SAAP-148, pexiganan and chlorhexidine against gram-positive and gram-negative bacteria resulted in significantly higher numbers of CFU compared to control samples without SPS-neutralization. Conclusions SPS was successfully used to neutralize residual activity of SAAP-148, pexiganan and chlorhexidine and this prevented an overestimation of their efficacy.

scholarly journals DESIGN, SYNTHESIS, DOCKING STUDIES AND BIOLOGICAL EVALUATION OF 2-PHENYL-3-(SUBSTITUTED BENZO[d] THIAZOL-2-YLAMINO)-QUINAZOLINE-4(3H)-ONE DERIVATIVES AS ANTIMICROBIAL AGENTS

2018 ◽  
Vol 10 (10) ◽  
pp. 57
Author(s):  
Pooja Pisal ◽  
Meenakshi Deodhar ◽  
Amol Kale ◽  
Ganesh Nigade ◽  
Smita Pawar
Keyword(s):  
Antimicrobial Agents ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Spectral Studies ◽  
Gram Negative Bacteria ◽  
Significant Activity ◽  
Fusion Reactions ◽  
Gram Positive ◽  
Gram Negative

Objective: A new series 2-phenyl-3-(substituted benzo[d] thiazol-2-ylamino)-quinazoline-4(3H)-one was prepared by the fusion method by reacting 2-phenyl benzoxazine with 2-hydrazino benzothiazole and it was evaluated for their antimicrobial activity against gram positive, gram negative bacteria and fungi.Methods: Titled compounds were synthesized by fusion reactions. These compounds were evaluated by in vitro antibacterial and antifungal activity using the minimum inhibitory concentration and zone of inhibition methods. The synthesized compounds were characterized with the help of infrared, NMR and mass spectral studies. The benzothiazole moiety and the quinazoline ring have previously shown DNA gyrase inhibition and target related antibacterial activity. Thus, molecular docking studies of synthesized compounds were carried out (PDB: 3G75) to study the possible interaction of compounds with the target. The batch grid docking was performed to determine the probable.Results: These compounds showed significant activity against gram positive and gram negative bacteria as well against the fungi. The compound A5 was found to be active against B. subtilis, P aeruginosa and C. albican at 12.5 µg/ml MIC. The compound A3 was found to be active against all microbial strains selected at 25 and 12.5 µg/ml MIC.Conclusion: Though the relationship between the activities shown by these compounds in, the antimicrobial study is still to be established, the docking studies conducted found to be consistent with antimicrobial results. Thus the results indicate that the designed structure can be a potential lead as an antimicrobial agent.

scholarly journals In vitro activity of the siderophore cephalosporin, cefiderocol, against molecularly characterized, carbapenem-non-susceptible Gram-negative bacteria from Europe

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Christopher Longshaw ◽  
Davide Manissero ◽  
Masakatsu Tsuji ◽  
Roger Echols ◽  
Yoshinori Yamano
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Similar Proportion ◽  
Gram Negative Bacteria ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Gene Profiles ◽  
Carbapenemase Gene

Abstract Objectives Many carbapenem-resistant (CR) Gram-negative (GN) pathogens exhibit MDR, meaning few therapeutic options are available for CR-GN infections. Cefiderocol, a siderophore cephalosporin, has demonstrated in vitro efficacy against CR-GN bacteria. In the SIDERO-CR-2014–2016 surveillance study, European clinical isolates comprising carbapenem-non-susceptible (CarbNS) Enterobacterales and MDR non-fermenters were tested against cefiderocol and comparators. Methods Cefiderocol MICs were determined using iron-depleted CAMHB, and comparators using CAMHB, per recommended CLSI methodology. Carbapenemase gene profiles were determined using PCR. Results Isolates (N = 870) from 23 European countries comprised CarbNS Enterobacterales (n = 457), MDR Pseudomonas aeruginosa (n = 177) and MDR Acinetobacter baumannii (n = 236). The most common carbapenemases were KPC (52%), OXA-48-like (19%), VIM (14%) and NDM (8%) in Enterobacterales, VIM (41%) in P. aeruginosa and OXA-23-like (57%) and OXA-24/40-like (37%) in A. baumannii. Most carbapenemase-producing isolates (65%) co-carried ESBLs. Approximately half of P. aeruginosa isolates were negative for carbapenemases, compared with 10% of Enterobacterales and 3% of A. baumannii. A similar proportion of Enterobacterales were susceptible to cefiderocol (81.6%; 79.0% of VIM producers; 51.4% of NDM producers; based on EUCAST breakpoint values) compared with comparator antimicrobial agents, including colistin (76.4%; 93.5% of VIM producers; 78.4% of NDM producers) and ceftazidime/avibactam (76.6%; 1.6% of VIM producers; 2.7% of NDM producers). Of P. aeruginosa isolates, 98.3% were susceptible to cefiderocol (100% of VIM producers), similar to colistin (100%). Against A. baumannii, 94.9% had cefiderocol MIC ≤2 mg/L and 93.6% of isolates were susceptible to colistin. Conclusions Cefiderocol demonstrated potent activity against CarbNS and MDR GN bacteria, including non-fermenters and a wide variety of MBL- and serine-β-lactamase-producing strains.

Catalyst Free and Energy Economical Synthesis of Thiazole Derivatives Bearing Azo Imine Linkage with Imidazole as Antimicrobial Agents

2019 ◽  
Vol 16 (3) ◽  
pp. 284-290
Author(s):  
Nayan M. Panchani ◽  
Hitendra S. Joshi
Keyword(s):  
Antibacterial Activity ◽  
Room Temperature ◽  
Antimicrobial Agents ◽  
Fungal Infections ◽  
Gram Negative Bacteria ◽  
Thiazole Derivatives ◽  
Microbial Diseases ◽  
Gram Negative ◽  
In Vitro Antibacterial Activity

Background:Several strategies have been reported for the synthesis of thiazole derivatives.Methods:However, many of these methods suffer from several drawbacks. Several modifications have been made to counter these problems. Here, we have synthesized a new series of 2-(2-((1HImidazol- 4-yl)methylene)hydrazinyl)-4-(4-substitutedphenyl)thiazoles without using the catalyst at room temperature.Results:The structures of synthesized compounds have been confirmed by spectral analysis, such as Mass, IR, 1H NMR and 13C NMR. All synthesized compounds were screened for in vitro antibacterial activity against some gram-positive and gram-negative bacteria.Conclusion:The thiazole derivatives, with a pharmacologically potent group, discussed in this article may provide valued therapeutic important in the treatment of microbial diseases, especially against bacterial and fungal infections.

Characterization of eight beta-lactamases of Gram-negative bacteria

1982 ◽  
Vol 152 (2) ◽  
pp. 567-571
Author(s):  
T Sawai ◽  
M Kanno ◽  
K Tsukamoto
Keyword(s):  
Assay Method ◽  
Gram Negative Bacteria ◽  
Beta Lactam ◽  
Ph Optimum ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Beta Lactam Antibiotics ◽  
R Plasmids ◽  
Ph Stat ◽  
Species Specific

Eight kinds of beta-lactamases produced by gram-negative bacteria were characterized by the following properties: molecular weight, isoelectric point, pH optimum, molecular activity, immunochemical reactivity, and kinetic parameters with respect to twelve kinds of common beta-lactam antibiotics. These beta-lactamases included two types of penicillinases mediated by R plasmids and six kinds of species-specific cephalosporinases. To determine a reliable value of the kinetic parameter, Km, we introduced a continuous and acidimetric assay method of beta-lactamase activity with a pH stat.

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