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

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.

2001 ◽  
Vol 45 (6) ◽  
pp. 1923-1927 ◽  
Author(s):  
Arthur L. Barry ◽  
Peter C. Fuchs ◽  
Steven D. Brown

ABSTRACT In vitro susceptibility tests were performed to document the inhibitory activities of three nonfluorinated quinolone (NFQ) compounds (PGE 9262932, PGE 9509924, and PGE 4175997) compared to those of ciprofloxacin, levofloxacin, and trovafloxacin against 3,030 bacterial isolates. The spectra of the NFQ agents included most gram-positive species as well as quinolone-susceptibleEnterobacteriaceae. Ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus strains were inhibited by the NFQ series at ≤1.0 μg/ml. The NFQ compounds were not very active against Pseudomonas aeruginosa and most other nonfermentative gram-negative bacilli. Against other species, the potency of the NFQ agents was similar to that of trovafloxacin. Continued investigation of the NFQ compounds seems to be warranted.


2004 ◽  
Vol 48 (8) ◽  
pp. 2831-2837 ◽  
Author(s):  
Mizuyo Kurazono ◽  
Takashi Ida ◽  
Keiko Yamada ◽  
Yoko Hirai ◽  
Takahisa Maruyama ◽  
...  

ABSTRACT ME1036, formerly CP5609, is a novel parenteral carbapenem with a 7-acylated imidazo[5,1-b]thiazole-2-yl group directly attached to the carbapenem moiety of the C-2 position. The present study evaluated the in vitro activities of ME1036 against clinical isolates of gram-positive and gram-negative bacteria. ME1036 displayed broad activity against aerobic gram-positive and gram-negative bacteria. Unlike other marketed β-lactam antibiotics, ME1036 maintained excellent activity against multiple-drug-resistant gram-positive bacteria, such as methicillin-resistant staphylococci and penicillin-resistant Streptococcus pneumoniae (PRSP). The MICs of this compound at which 90% of isolates were inhibited were 2 μg/ml for methicillin-resistant Staphylococcus aureus (MRSA), 2 μg/ml for methicillin-resistant coagulase-negative staphylococci, and 0.031 μg/ml for PRSP. In time-kill studies with six strains of MRSA, ME1036 at four times the MIC caused a time-dependent decrease in the numbers of viable MRSA cells. The activity of ME1036 against MRSA is related to its high affinity for penicillin-binding protein 2a, for which the 50% inhibitory concentration of ME1036 was approximately 300-fold lower than that of imipenem. In conclusion, ME1036 demonstrated a broad antibacterial spectrum and high levels of activity in vitro against staphylococci, including β-lactam-resistant strains.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Salu Rai ◽  
Uday Narayan Yadav ◽  
Narayan Dutt Pant ◽  
Jaya Krishna Yakha ◽  
Prem Prasad Tripathi ◽  
...  

In Nepal, little is known about the microbiological profile of wound infections in children and their antimicrobial susceptibility patterns. Total of 450 pus/wound swab samples collected were cultured using standard microbiological techniques and the colonies grown were identified with the help of biochemical tests. The antimicrobial susceptibility testing was performed by Kirby-Bauer disc diffusion technique. Methicillin-resistantStaphylococcus aureusisolates were detected by using cefoxitin disc and confirmed by determining minimum inhibitory concentrations (MIC) of oxacillin. 264 (59%) samples were culture positive. The highest incidence of bacterial infections was noted in the age group of less than 1 year (76%). Out of 264 growth positive samples, Gram-positive bacteria were isolated from 162 (61%) samples and Gram-negative bacteria were found in 102 (39%) samples.Staphylococcus aureus(99%) was the predominant Gram-positive bacteria isolated andPseudomonas aeruginosa(44%) was predominant Gram-negative bacteria. About 19% ofS. aureusisolates were found to be methicillin-resistant MIC of oxacillin ranging from 4 μg/mL to 128 μg/mL. Among the children of Nepal, those of age less than 1 year were at higher risk of wound infections by bacteria.Staphylococcus aureusfollowed byPseudomonas aeruginosawere the most common bacteria causing wound infections in children.


2021 ◽  
Vol 9 (2) ◽  
pp. 64-70
Author(s):  
Ahmed A. Al-Naqshbandi ◽  
Hedy A. Hassan ◽  
Mahmoud A. Chawsheen ◽  
Haval H. Abdul Qader

Wound infection with antibiotic-resistant bacteria can extend a patients’ debility and increase the expense of treatment in the long term; therefore, careful management of patients with wound infections is necessary to avoid complications. The usage of antimicrobial agent is a major factor in resistance development. This study aims to understand the causes of wound infections, as well as the criteria for diagnosing them for more sensible antibiotic prescribing. Samples from 269 wound patients were collected, and cultured for bacterial growth. Gram stain technique, bacterial identification via VITEK 2 compact system were investigated in this study. Gram negative bacteria accounted for 59.15% of the total isolates, while pathogenic gram positive bacteria accounted for 40.85% of total isolates. Escherichia coli and Pseudomonas aeruginosa are the dominant pathogenic gram negative bacteria in wounds, while Staphylococcus aureus, and Staphylococcus epidermidis are the dominant pathogenic gram positive bacteria. Pseudomonas aeruginosa showed 100% resistance to the majority of antibiotic tested, including Ampicillin, Amoxicillin/Clavulanic Acid, Aztreona, Ceftriaxone, and others. Staphylococcus aureus and Staphylococcus epidermidis are 100% resistant to Ampicillin, Ceftriaxone, and Cefotaxime. For more efficient antibiotic prescriptions, the causative microorganisms, and their current susceptibility patterns need to be mandated for testing before prescribing any antibiotics to patients. Prescriptions are frequently based solely on general information about the antibiotic's function, rather than on individual response variation to the pathogen and the antibiotic. Particularly when the common pathogens in this study show multidrug resistance in wounds.


1997 ◽  
Vol 41 (10) ◽  
pp. 2282-2285 ◽  
Author(s):  
Y Adachi ◽  
K Nakamura ◽  
Y Kato ◽  
N Hazumi ◽  
T Hashizume ◽  
...  

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.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Soek Sin Teh ◽  
Gwendoline Cheng Lian Ee ◽  
Siau Hui Mah ◽  
Yoke Keong Yong ◽  
Yang Mooi Lim ◽  
...  

Thein vitrocytotoxicity tests on the extracts ofMesua beccariana,M. ferrea, andM. congestifloraagainst Raji, SNU-1, HeLa, LS-174T, NCI-H23, SK-MEL-28, Hep-G2, IMR-32, and K562 were achieved using MTT assay. The methanol extracts ofMesua beccarianashowed its potency towards the proliferation of B-lymphoma cell (Raji). In addition, only the nonpolar to semipolar extracts (hexane to ethyl acetate) of the threeMesuaspecies indicated cytotoxic effects on the tested panel of human cancer cell lines. Antioxidant assays were evaluated using DPPH scavenging radical assay and Folin-Ciocalteu method. The methanol extracts ofM. beccarianaandM. ferreashowed high antioxidant activities with low EC50values of 12.70 and 9.77 μg/mL, respectively, which are comparable to that of ascorbic acid (EC50 = 5.62 μg/mL). Antibacterial tests were carried out using four Gram positive and four Gram negative bacteria onMesua beccarianaextracts. All the extracts showed negative results in the inhibition of Gram negative bacteria. Nevertheless, methanol extracts showed some activities against Gram positive bacteria which areBacillus cereus, methicillin-sensitiveStaphylococcus aureus(MSSA), and methicillin-resistantStaphylococcus aureus(MRSA), while the hexane extract also contributed some activities towardsBacillus cereus.


2003 ◽  
Vol 47 (8) ◽  
pp. 2615-2618 ◽  
Author(s):  
Conor E. Jamieson ◽  
Peter A. Lambert ◽  
Iain N. Simpson

ABSTRACT Four novel oxapenem compounds (i.e., AM-112, AM-113, AM-114, and AM-115) were investigated for their β-lactamase inhibitory activity against a panel of isolated class A, C, and D enzymes, which included expanded-spectrum β-lactamase enzymes (ESBLs). The oxapenems were potent β-lactamase inhibitors. Activity varied within the group, with AM-113 and AM-114 proving to be the most active compounds. The 50% inhibitory concentrations for these agents were up to 100,000-fold lower than that of clavulanic acid against class C and D enzymes. As a group, the oxapenems were more potent than clavulanic acid against enzymes from all classes. The ability of these compounds to protect ceftazidime from hydrolysis by β-lactamase-producing strains was evaluated by MIC tests that combined ceftazidime and each oxapenem in a 1:1 or 2:1 ratio. The oxapenems markedly reduced the MICs for ceftazidime against class C hyperproducing strains and strains producing TEM- and SHV-derived ESBLs. There was little difference between the activity of 1:1 and 2:1 combinations of ceftazidime and oxapenem. The oxapenems failed to enhance the activity of ceftazidime against derepressed AmpC-producing Pseudomonas aeruginosa strains.


2013 ◽  
Vol 57 (10) ◽  
pp. 4653-4655 ◽  
Author(s):  
P. Cottagnoud ◽  
M. Cottagnoud ◽  
F. Acosta ◽  
A. Stucki

ABSTRACTCeftaroline is a new cephalosporin with bactericidal activity against resistant Gram-positive organisms, including methicillin-resistantStaphylococcus aureus(MRSA) and penicillin-resistantStreptococcus pneumoniae, as well as common Gram-negative organisms. This study tested the prodrug, ceftaroline fosamil, against a penicillin-sensitive and a penicillin-resistant strain ofS. pneumoniaein an experimental rabbit meningitis model. The penetration of ceftaroline into inflamed meninges was approximately 14%. Ceftaroline fosamil was slightly superior to ceftriaxone against the penicillin-sensitive strain and significantly superior to the combination of ceftriaxone and vancomycin against the penicillin-resistant strain.


2008 ◽  
Vol 52 (5) ◽  
pp. 1653-1662 ◽  
Author(s):  
Laura Lawrence ◽  
Paul Danese ◽  
Joe DeVito ◽  
Francois Franceschi ◽  
Joyce Sutcliffe

ABSTRACT Rx-01_423 and Rx-01_667 are two members of the family of oxazolidinones that were designed using a combination of computational and medicinal chemistry and conventional biological techniques. The compounds have a two- to eightfold-improved potency over linezolid against serious gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant streptococci, and vancomycin-resistant enterococci. This enhanced potency extends to the coverage of linezolid-resistant gram-positive microbes, especially multidrug-resistant enterococci and pneumococci. Compounds from this series expand the spectrum compared with linezolid to include fastidious gram-negative organisms like Haemophilus influenzae and Moraxella catarrhalis. Like linezolid, the Rx-01 compounds are bacteriostatic against MRSA and enterococci but are generally bactericidal against S. pneumoniae and H. influenzae.


2019 ◽  
Vol 13 (03) ◽  
pp. 245-250 ◽  
Author(s):  
Balaji Veeraraghavan ◽  
Aruna Poojary ◽  
Chaitra Shankar ◽  
Anurag Kumar Bari ◽  
Seema Kukreja ◽  
...  

Introduction: Tigecycline Evaluation and Surveillance Trail (TEST) study is an on-going global surveillance. The study was performed to determine the susceptibility of common pathogens to tigecycline and comparator antibiotics by broth microdilution (BMD) at two tertiary care centres in India from 2015 to 2017. Methodology: Total of 989 isolates collected from various clinical specimens between January 2015 and September 2017 from two centres in India were included. BMD was performed to determine the minimum inhibitory concentration (MIC) for tigecycline and comparator antibiotics. Results: Among Gram-negative bacteria, susceptibility to tigecycline was lowest among Klebsiella spp. being 84% while others such as E. coli, Enterobacter spp., Serratia spp. and H. influenzae showed susceptibility of 98%, 95%, 98% and 100% respectively. Overall, 99 isolates among Enterobacteriaceae (E. coli, Klebsiella spp. and Enterobacter spp.) were ESBL producers, susceptible to tigecycline. Among the 101 meropenem resistant Enterobacteriaceae, 85 were susceptible to tigecycline (84%). Among the Gram-positive bacteria, S. aureus and Enterococcus spp. were 99% and 98% susceptible to tigecycline respectively. Among 68 MRSA isolates in the study, 66 (97%) were susceptible to tigecycline. Seven vancomycin resistant E. faecalis were isolated and all were susceptible to tigecycline. Conclusion: Tigecycline has retained activity over both Gram-positive and Gram-negative organisms with MIC values comparable to global reports. About 98% of the MDR Gram-positive and Gram-negative bacteria in the study are susceptible to tigecycline. With increased incidence of extensively drug resistant organisms, tigecycline is a potential reserve drug.


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