Stigmasterol: An adjuvant for beta lactam antibiotics against beta-lactamase positive clinical isolates

Steroids ◽  
2017 ◽  
Vol 128 ◽  
pp. 68-71 ◽  
Author(s):  
Tong Woei Yenn ◽  
Muhammad Arslan Khan ◽  
Nur Amiera Syuhada ◽  
Leong Chean Ring ◽  
Darah Ibrahim ◽  
...  
1985 ◽  
Vol 51 (5-6) ◽  
pp. 600-602
Author(s):  
J. L. Hoekstra ◽  
A. W. Houben ◽  
E. E. Stobberingh ◽  
C. P. A. van Boven

1999 ◽  
Vol 10 (2) ◽  
pp. 128-133 ◽  
Author(s):  
Ross J Davidson ◽  
Canadian Bacterial Surveillance Network ◽  
Donald E Low

OBJECTIVE: To determine the prevalence of antimicrobial resistance in clinical isolates ofStreptococcus pneumoniae, Haemophilus influenzaeandMoraxella catarrhalisfrom medical centres across Canada.METHODS: Fifty laboratories from across Canada were asked to collect up to 25 consecutive clinical isolates ofS pneumoniae,H influenzaeandM catarrhalisat some time between September 1994 and May 1995, and then again between September and December of 1996. A total of 2364S pneumoniae, 575H influenzaeand 200M catarrhalissamples were collected.H influenzaeandM catarrhalisisolates were tested for the production of beta-lactamase.S pneumoniaeisolates were characterized as penicillin susceptible, intermediately resistant or high level penicillin-resistant. Minimal inhibitory concentrations (MICs) were determined using a microbroth dilution technique described by the National Committee of Clinical Laboratory Standards.RESULTS: Between the two collection periods, there was a significant increase in highly penicillin-resistantS pneumoniaefrom 2.1% to 4.4% (P<0.05) and an increase in intermediately penicillin-resistant strains from 6.4% to 8.9% (P<0.05). A significant increase in high level penicillin-resistantS pneumoniaewas noted among paediatric isolates. No significant difference in the susceptibilities of comparator agents was detected. A significant increase in the number of beta-lactamase producingH influenzae, 34% to 43% (P<0.05) was observed. Ninety-five per cent ofM catarrhalisisolates were beta-lactamase producers in both time periods.CONCLUSIONS: During the course of this study, the incidence of penicillin resistance inS pneumoniaedoubled. As a result of this increase, infections due to this organism in sites where poor penetration of beta-lactam antibiotics occur may become increasingly difficult to manage.


2020 ◽  
Vol 4 ◽  
pp. 86
Author(s):  
Liam Shaw

Introduction. Antimicrobial resistance (AMR) is a worrying and confusing problem for both patients and medical professionals. It is often difficult for non-specialists to understand how different antibiotics are related to one another. Here, I use experimental data from hundreds of thousands of clinical isolates to infer relationships between antibiotics and represent them with simple diagrams. Methods. The minimum inhibitory concentration (MIC) of a bacterial isolate for a given antibiotic is defined as the lowest concentration that prevents visible growth. Measuring MICs for multiple antibiotics using the same isolate implicitly records the relationships of the antibiotics for a given species. The basic principle is that antibiotics with similar mechanisms of action should give rise to similar mechanisms of resistance, so should have correlated MICs across large numbers of isolates. This information can then be used to calculate distances between antibiotics based on pairwise correlations of their rank-ordered MICs. I apply this approach to a large historical AMR surveillance dataset (the Pfizer ATLAS surveillance dataset, 2004-2017). Results. I demonstrate that clustering antibiotics in this way allows a simple visual comparison of how similar antibiotics are to each other based on their efficacy within a species. The resulting visualizations broadly recapitulate antibiotic classes. They also clearly show the dramatic effects of combining beta-lactam antibiotics with beta-lactamase inhibitors, as well as highlighting antibiotics which have unexpected correlations in MICs that are not predicted from their chemical similarities alone. Conclusion. Large AMR surveillance datasets can be used in a hypothesis-free manner to show relationships between antibiotics based on their real-world efficacy.


1998 ◽  
Vol 42 (4) ◽  
pp. 550-552 ◽  
Author(s):  
S. Mattar ◽  
L. Sanchez ◽  
D. Perez ◽  
A. Arango ◽  
R. Parodi ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Shamshul Ansari ◽  
Rabindra Dhital ◽  
Sony Shrestha ◽  
Sangita Thapa ◽  
Ram Puri ◽  
...  

Introduction. Pseudomonas aeruginosais the most frequently isolated organism as it acts as the opportunistic pathogen and can cause infections in immunosuppressed patients. The production of different types of beta-lactamases renders this organism resistant to many commonly used antimicrobials. Therefore, the aim of this study was to document the antibiotic resistance rate inPseudomonas aeruginosaisolated from different clinical specimens.Methods. Pseudomonas aeruginosarecovered was identified by standard microbiological methods. Antibiotic susceptibility testing was performed by modified Kirby-Bauer disc diffusion method following Clinical and Laboratory Standard Institute (CLSI) guidelines and all the suspected isolates were tested for the production of ESBLs, MBLs, and AmpC.Results.Out of total (178) isolates, 83.1% were recovered from the inpatient department (IPD). Majority of the isolates mediated resistance towards the beta-lactam antibiotics, while nearly half of the isolates were resistant to ciprofloxacin. Most of the aminoglycosides used showed resistance rate up to 75% but amikacin proved to be better option. No resistance to polymyxin was observed. ESBLs, MBLs, and AmpC mediated resistance was seen in 33.1%, 30.9%, and 15.7% isolates, respectively.Conclusions. Antibiotic resistance rate and beta-lactamase mediated resistance were high. Thus, regular surveillance of drug resistance is of utmost importance.


2010 ◽  
Vol 4 (04) ◽  
pp. 239-242 ◽  
Author(s):  
Supriya Upadhyay ◽  
Malay Ranjan Sen ◽  
Amitabha Bhattacharjee

Introduction: Infections caused by Pseudomonas aeruginosa are difficult to treat as the majority of isolates exhibit varying degrees of beta-lactamase mediated resistance to most of the beta-lactam antibiotics. It is also not unusual to find a single isolate that expresses multiple β-lactamase enzymes, further complicating the treatment options. Thus the present study was designed to investigate the coexistence of different beta-lactamase enzymes in clinical isolates of P. aeruginosa. Methodology: A total of 202 clinical isolates of P. aeruginosa were tested for the presence of AmpC beta-lactamase, extended spectrum beta-lactamase (ESBL) and metallo beta-lactamase (MBL) enzyme. Detection of AmpC beta-lactamase was performed by disk antagonism test and a modified three-dimensional method, whereas detection of ESBL was done by the combined disk diffusion method per Clinical and Laboratory Standards Institute (CLSI) guidelines and MBL were detected by the Imipenem EDTA disk potentiation test. Results: A total of 120 (59.4%) isolates were confirmed to be positive for AmpC beta-lactamase. Among them, 14 strains (7%) were inducible AmpC producers. Co-production of AmpC along with extended spectrum beta-lactamase and metallo beta-lactamase was reported in 3.3% and 46.6% isolates respectively. Conclusion: The study emphasizes the high prevalence of multidrug resistant P. aeruginosa producing beta-lactamase enzymes of diverse mechanisms. Thus proper antibiotic policy and measures to restrict the indiscriminative use of cephalosporins and carbapenems should be taken to minimize the emergence of this multiple beta-lactamase producing pathogens.


2019 ◽  
Author(s):  
Philippe Colson ◽  
Lucile Pinault ◽  
Said Azza ◽  
Nicholas Armstrong ◽  
Eric Chabriere ◽  
...  

ABSTRACTEnzymatic proteins with a metallo-beta-lactamase (MBL) fold have been essentially studied in bacteria for their activity on beta-lactam antibiotics. However, the MBL fold is ancient and highly conserved, and these proteins are capable of cleaving a broad range of substrates. It has recently been shown that MBLs are present in a wide array of cellular organisms, including eukaryotes and archaea. We show here that Tupanvirus deep ocean, a giant virus, also encodes a protein with a MBL fold. Phylogeny showed its clustering with transfer ribonucleases (RNases) and the presence of orthologs in other giant viruses, mainly those harboring the largest sets of translation components. In addition, it suggests an ancient origin for these genes and a transfer between giant viruses and Acanthamoeba spp., a host of many giant viruses. Biologically, after its expression in Escherichia coli, the tupanvirus protein was found to hydrolyse nitrocefin, a chromogenic beta-lactam. We also observed an hydrolysis of penicillin G (10 μg/mL) and detected the metabolite of penicillin G hydrolysis, benzylpenilloic acid. This was inhibited by sulbactam, a beta-lactamase inhibitor. In addition, we tested the degradation of single-stranded DNA, double-stranded DNA, and RNAs, and observed a strong activity on RNAs from seven bacteria with G+C varying from 42% to 67%, and from Acanthamoeba castellanii, the tupanvirus host. This was not inhibited by sulbactam or ceftriaxone. RNase activity was estimated to be 0.45±0.15 mU/mg using a fluorescence-based assay. Our results still broaden the range of hosts of MBL fold proteins and demonstrate that such protein can have dual beta-lactamase/nuclease activities. We suggest that they should be annotated according to this finding to avoid further confusion.


2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Mojgan Sabet ◽  
Ziad Tarazi ◽  
David C. Griffith

ABSTRACT Resistance to beta-lactams has created a major clinical issue. QPX7728 is a novel ultrabroad-spectrum cyclic boronic acid beta-lactamase inhibitor with activity against both serine and metallo-beta-lactamases developed to address this resistance for use in combination with beta-lactam antibiotics. The objective of these studies was to evaluate the activity of QPX7728 in combination with multiple beta-lactams against carbapenem-resistant Klebsiella pneumoniae isolates in a neutropenic mouse thigh infection model. Neutropenic mice were infected with strains with potentiated beta-lactam MICs of ≤2 mg/liter in the presence of 8 mg/liter QPX7728. Two strains of carbapenem-resistant K. pneumoniae were tested with aztreonam, biapenem, cefepime, ceftazidime, ceftolozane, and meropenem alone or in combination with 12.5, 25, or 50 mg/kg of body weight of QPX7728 every 2 hours for 24 hours. Treatment with all beta-lactams alone either was bacteriostatic or allowed for bacterial growth. The combination of QPX7728 plus each of these beta-lactams produced bacterial killing at all QPX7728 doses tested. Overall, these data suggest that QPX7728 administered in combination with different partner beta-lactam antibiotics may have utility in the treatment of bacterial infections due to carbapenem-resistant K. pneumoniae.


1996 ◽  
Vol 40 (11) ◽  
pp. 2488-2493 ◽  
Author(s):  
P Mugnier ◽  
P Dubrous ◽  
I Casin ◽  
G Arlet ◽  
E Collatz

A clinical strain of Pseudomonas aeruginosa, PAe1100, was found to be resistant to all antipseudomonal beta-lactam antibiotics and to aminoglycosides, including gentamicin, amikacin, and isepamicin. PAe1100 produced two beta-lactamases, TEM-2 (pI 5.6) and a novel, TEM-derived extended-spectrum beta-lactamase called TEM-42 (pI 5.8), susceptible to inhibition by clavulanate, sulbactam, and tazobactam. Both enzymes, as well as the aminoglycoside resistance which resulted from AAC(3)-IIa and AAC(6')-I production, were encoded by an 18-kb nonconjugative plasmid, pLRM1, that could be transferred to Escherichia coli by transformation. The gene coding for TEM-42 had four mutations that led to as many amino acid substitutions with respect to TEM-2: Val for Ala at position 42 (Ala42), Ser for Gly238, Lys for Glu240, and Met for Thr265 (Ambler numbering). The double mutation Ser for Gly238 and Lys for Glu240, which has so far only been described in SHV-type but not TEM-type enzymes, conferred concomitant high-level resistance to cefotaxime and ceftazidime. The novel, TEM-derived extended-spectrum beta-lactamase appears to be the first of its class to be described in P. aeruginosa.


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