scholarly journals In vitro evaluation of BO-3482, a novel dithiocarbamate carbapenem with activity against methicillin-resistant staphylococci.

1997 ◽  
Vol 41 (10) ◽  
pp. 2282-2285 ◽  
Author(s):  
Y Adachi ◽  
K Nakamura ◽  
Y Kato ◽  
N Hazumi ◽  
T Hashizume ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clostridium Difficile ◽  
Proteus Mirabilis ◽  
Gram Negative Bacteria ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Gram Negative ◽  
Methicillin Resistant ◽  
Beta Lactam Antibiotics

BO-3482, a dithiocarbamate carbapenem, inhibited clinical isolates of methicillin-resistant staphylococci (MRS) at 6.25 microg/ml (MIC at which 90% of isolates tested are inhibited [MIC90]), while the MIC90 of imipenem was > 100 microg/ml. BO-3482 was generally less active than imipenem against methicillin-susceptible Staphylococcus aureus, streptococci, enterococci, and gram-negative bacteria, although BO-3482 showed better activity (MIC90) than imipenem against Enterococcus faecium, Haemophilus influenzae, Proteus mirabilis, and Clostridium difficile. The affinities (50% inhibitory concentrations) of BO-3482 for penicillin-binding protein (PBP) PBP 2' of MRS and PBP 5 of E. faecium (both PBPs have low affinities for ordinary beta-lactam antibiotics) were 3.8 and 20 microg/ml, respectively, reflecting the greater activity of BO-3482 against MRS than against E. faecium.

Protein expression profiles in methicillin-resistant Staphylococcus aureus (MRSA) under effects of subminimal inhibitory concentrations of imipenem

2019 ◽  
Vol 366 (15) ◽  
Author(s):  
Jichun Wang ◽  
Junrui Wang ◽  
Yanyan Wang ◽  
Peng Sun ◽  
Xiaohui Zou ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cellular Proliferation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Expression Profiles ◽  
Gram Negative Bacteria ◽  
Beta Lactam ◽  
Gram Negative ◽  
Methicillin Resistant

ABSTRACT Imipenem is a beta-lactam antibiotic mainly active against gram-negative bacterial pathogens and also could cause cell wall impairment in methicillin-resistant Staphylococcus aureus(MRSA). However, related antibacterial mechanisms of imipenem on MRSA and mixed infections of MRSA and gram-negative bacteria are relatively poorly revealed. This study was to identify proteins in the MRSA response to subminimal inhibitory concentrations (sub-MICs) of imipenem treatment. Our results showed that 240 and 58 different expression proteins (DEPs) in sub-MICs imipenem-treated S3 (a standard MRSA strain) and S23 (a clinical MRSA strain) strains were identified through the isobaric tag for relative and absolute quantitation method when compared with untreated S3 and S23 strains, respectively, which was further confirmed by multiple reactions monitoring. Our result also demonstrated that expressions of multiple DEPs involved in cellular proliferation, metabolism and virulence were significantly changed in S3 and S23 strains, which was proved by gene ontology annotations and qPCR analysis. Further, transmission electron microscopy and scanning electron microscopy analysis showed cell wall deficiency, cell lysis and abnormal nuclear mitosis on S23 strain. Our study provides important information for understanding the antibacterial mechanisms of imipenem on MRSA and for better usage of imipenem on patients co-infected with MRSA and other multidrug-resistant gram-negative bacteria.

scholarly journals Specific interaction between beta-lactams and soluble penicillin-binding protein 2a from methicillin-resistant Staphylococcus aureus: development of a chromogenic assay.

1996 ◽  
Vol 40 (9) ◽  
pp. 2075-2079 ◽  
Author(s):  
S Roychoudhury ◽  
R E Kaiser ◽  
D N Brems ◽  
W K Yeh
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Methicillin Resistant ◽  
Chromogenic Assay ◽  
Enzymatic Acylation

We investigated the enzymatic acylation of penicillin-binding protein 2a (PBP 2a) from methicillin-resistant Staphylococcus aureus by beta-lactams. Using a purified, soluble form of the protein (PBP 2a'), we observed beta-lactam-induced in vitro precipitation following first-order kinetics with respect to protein concentration. We used electrospray mass ionization spectrometry to show that the protein precipitate predominantly contained PBP 2a', with the beta-lactam bound to it in a 1:1 molar ratio. Using nitrocefin, a chromogenic beta-lactam, we confirmed the correlation between PBP 2a' precipitation and its beta-lactam-dependent enzymatic acylation by monitoring the absorbance associated with the precipitate. Finally, dissolving the precipitate in urea, we developed a simple in vitro chromogenic assay to monitor beta-lactam-dependent enzymatic acylation of PBP 2a'. This assay represents a significant improvement over the traditional radioactive penicillin-binding assay.

scholarly journals In Vitro Pharmacodynamic Studies of L-749,345 in Comparison with Imipenem and Ceftriaxone against Gram-Positive and Gram-Negative Bacteria

1998 ◽  
Vol 42 (9) ◽  
pp. 2365-2370 ◽  
Author(s):  
Inga Odenholt ◽  
Elisabeth Löwdin ◽  
Otto Cars
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Comparative Studies ◽  
Gram Negative Bacteria ◽  
Postantibiotic Effect ◽  
Gram Positive ◽  
Gram Negative ◽  
Methicillin Resistant ◽  
Gram Negative Organisms

ABSTRACT L-749,345 is a new parenteral carbapenem with a very long half-life similar to that of ceftriaxone. The aim of the present study was to investigate different pharmacodynamic parameters of L-749,345 in comparison with those of ceftriaxone and imipenem. The following studies were performed: (i) comparative studies of the MICs of L-749,345, imipenem, and ceftriaxone for 70 strains of gram-positive and gram-negative bacteria; (ii) comparative studies of the rate of killing of gram-positive and gram-negative bacteria by L-749,345, imipenem, and ceftriaxone; (iii) studies of the postantibiotic effects of L-749,345, imipenem, and ceftriaxone; and (iv) studies of the postantibiotic sub-MIC effects of L-749,345, imipenem, and ceftriaxone. Significantly lower MICs of L-749,345 compared with those of ceftriaxone were found for all gram-negative organisms except Haemophilus influenzae. The MICs of L-749,345 were similar to those of imipenem for all organisms except Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus, for which the MICs of L-749,345 were higher. A concentration-dependent killing of methicillin-resistant S. aureus but not methicillin-susceptible strains was noted for both L-749,345 and imipenem. All three of the investigated drugs exhibited a postantibiotic effect against the gram-positive strains but exhibited no postantibiotic effect against the gram-negative strains.

scholarly journals Ceftobiprole Is Superior to Vancomycin, Daptomycin, and Linezolid for Treatment of Experimental Endocarditis in Rabbits Caused by Methicillin-Resistant Staphylococcus aureus

2009 ◽  
Vol 54 (2) ◽  
pp. 610-613 ◽  
Author(s):  
P. Tattevin ◽  
L. Basuino ◽  
D. Bauer ◽  
B. A. Diep ◽  
H. F. Chambers
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Group ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Rabbit Model ◽  
Laboratory Strain ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
High Affinity

ABSTRACT Beta lactam agents are the most active drugs for the treatment of streptococci and methicillin-susceptible Staphylococcus aureus endocarditis. However, methicillin-resistant S. aureus (MRSA) is resistant to all beta lactam agents licensed to date, and alternative treatments are limited. Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the penicillin binding protein that mediates the methicillin resistance of staphylococci and is active against MRSA. Ceftobiprole was compared to vancomycin, daptomycin, and linezolid in a rabbit model of MRSA aortic valve endocarditis caused by the homogeneously methicillin-resistant laboratory strain COL. Residual organisms in vegetations were significantly fewer in ceftobiprole-treated rabbits than in any other treatment group (P < 0.05 for each comparison). In addition, the numbers of organisms in spleens and in kidneys were significantly lower in ceftobiprole-treated rabbits than in linezolid- and vancomycin-treated animals (P < 0.05 for each comparison). Anti-MRSA beta lactam agents such as ceftobiprole may represent a significant therapeutic advance over currently available agents for the treatment of MRSA endocarditis.

Cefotaxime and amikacin: results of in vitro and in vivo studies against Gram-negative bacteria and Staphylococcus aureus

1980 ◽  
Vol 6 (suppl A) ◽  
pp. 55-61 ◽  
Author(s):  
J. Klastersky ◽  
H. Gaya ◽  
S. H. Zinner ◽  
C. Bernard ◽  
J-C. Ryff ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
In Vivo Studies ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
And Staphylococcus Aureus

scholarly journals Species-Specific Sensitivity of Coagulase-Negative Staphylococci to Single Antibiotics and Their Combinations

2011 ◽  
Vol 60 (2) ◽  
pp. 155-161 ◽  
Author(s):  
GRAŻYNA SZYMAŃSKA ◽  
MAGDALENA SZEMRAJ ◽  
ELIGIA M. SZEWCZYK
Keyword(s):  
University Hospital ◽  
Hospital Environment ◽  
Beta Lactam ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Beta Lactam Antibiotics ◽  
Resistant Strains ◽  
Staphylococcus Hominis ◽  
Species Specific

The activity of beta-lactam antibiotics (oxacillin, cloxacillin, cephalotin), vancomycin, gentamicin and rifampicin applied in vitro individually and in combination against 37 nosocomial methicillin-resistant strains of coagulase-negative staphylococci (CNS) was assessed to demonstrate the heterogeneity of this group of bacteria and estimate the chance of the efficacy of such therapy. The strains belonged to four species: Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus cohnii, Staphylococcus hominis. They originated from a hospital environment and from the skin of medical staff of the intensive care unit of a paediatric ward at a university hospital. All strains were methicillin-resistant, according to CLSI standards, but individual strains differed in MIC(ox) values. Susceptibility to other tested antibiotics was also characteristic for the species. The increased susceptibility to antibiotics in combinations, tested by calculating the fractional inhibitory concentration (FIC) index, concerned 26 out of 37 investigated strains and it was a feature of a particular species. Combinations of vancomycin and cephalotin against S. epidermidis and oxacillin with vancomycin were significant, as well as cephalotin and rifampicin in growth inhibition of multiresistant S. haemolyticus strains.

scholarly journals Combination antibiotic therapy versus monotherapy in the treatment of acute exacerbations of chronic obstructive pulmonary disease: an open-label randomized trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Phuong Nguyen Thi Thu ◽  
Minh Ngo Thị Huong ◽  
Ngan Tran Thi ◽  
Hoi Nguyen Thanh ◽  
Khue Pham Minh
Keyword(s):  
Clinical Success ◽  
Chronic Obstructive ◽  
Gram Negative Bacteria ◽  
Beta Lactam ◽  
Open Label ◽  
Obstructive Pulmonary Disease ◽  
Gram Negative ◽  
Copd Exacerbations ◽  
Beta Lactam Antibiotics ◽  
Acute Exacerbations

Abstract Background The role of antibiotics in the treatment of chronic obstructive pulmonary disease (COPD) exacerbations and their effectiveness in combination have not been clearly established. To determine whether using a combination of fluoroquinolones and beta-lactams improves the clinical and microbiological efficacy of antibiotics on day 20 of treatment, we conducted an open-label randomized trial based on clinical outcomes, microbiological clearance, spirometry tests, and signs of systemic inflammation in patients hospitalized with acute exacerbations of COPD. Methods We enrolled 139 subjects with COPD exacerbations, defined as acute worsening of respiratory symptoms leading to additional treatment. Patients were divided randomly into two groups: 79 patients using beta-lactam antibiotics alone and 60 using beta-lactam antibiotics plus fluoroquinolones. Clinical and microbiological responses, spirometry tests, symptom scores, and serum C-reactive protein (CRP) levels were evaluated. Results Clinical success, lung function, and symptoms were similar in patients with or without fluoroquinolone administration on days 10 and 20. Combination therapy was superior in terms of microbiological outcomes and reduction in serum CRP value. Although equivalent to monotherapy in terms of clinical success, the combination showed superiority in terms of microbiological success and a decrease in CRP. The combination therapy group had a higher microbiological success rate with gram-negative bacteria than the monotherapy group with Pseudomonas aeruginosa (100% vs. 33.3%, respectively) and Acinetobacter baumanii (100% vs. 20%, respectively) (P < 0.05). Conclusions Concomitant use of fluoroquinolone and beta-lactam antibiotics for bacterial infections during COPD exacerbations caused by gram-negative bacteria appear to be effective and should be applied in clinical practice.

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