Faculty Opinions recommendation of Decreasing in vitro susceptibility of clinical Staphylococcus aureus isolates to vancomycin at the New York Hospital: quantitative testing redux.

2012 ◽  
Author(s):  
George Sakoulas
Keyword(s):  
New York ◽  
Staphylococcus Aureus ◽  
In Vitro Susceptibility ◽  
York Hospital

Systematic analysis and integrative discovery of active-site subpocket-specific dehydroquinate synthase inhibitors combating antibiotic-resistant Staphylococcus aureus infection

2018 ◽  
Vol 16 (06) ◽  
pp. 1850027
Author(s):  
Quanfeng Liu ◽  
Liping Li ◽  
Fei Xu
Keyword(s):  
Staphylococcus Aureus ◽  
Active Site ◽  
Shikimate Pathway ◽  
In Vitro Susceptibility ◽  
Systematic Analysis ◽  
Antibiotic Resistant ◽  
Enzyme Active Site ◽  
Specific Inhibitors ◽  
Dehydroquinate Synthase

Shikimate pathway plays an essential role in the biosynthesis of aromatic amino acids in various plants and bacteria, which consists of seven key enzymes and they are all attractive targets for antibacterial agent development due to their absence in humans. The Staphylococcus aureus dehydroquinate synthase (SaDHQS) is involved in the second step of shikimate pathway, which catalyzes the NAD[Formula: see text]-dependent conversion of 3-deoxy-D-arabino-heptulosonate-7-phosphate to dehydroquinate via multiple steps. The enzyme active site can be characterized by two spatially separated subpockets 1 and 2, which represent the reaction center of substrate adduct with NAD[Formula: see text] nicotinamide moiety and the assistant binding site of NAD[Formula: see text] adenine moiety, respectively. In silico virtual screening is performed against a biogenic compound library to discover SaDHQS subpocket-specific inhibitors, which were then tested against both antibiotic-sensitive and antibiotic-resistant S. aureus strains by using in vitro susceptibility test. The activity profile of hit compounds has no considerable difference between the antibiotic-sensitive and -resistant strains. The subpocket 1-specific inhibitors exhibit a generally higher activity than subpocket 2-specific inhibitors, and they also hold a strong selectivity between their cognate and noncognate subpockets. Dynamics and energetics analyses reveal that the SaDHQS active site prefers to interact with amphipathic and polar inhibitors by forming multiple hydrogen bonds and van der Waals packing at the complex interfaces of the two subpockets with their cognate inhibitors.

Increase in the in vitro susceptibility of Staphylococcus aureus to antimicrobial agents in the presence of Candida albicans

1979 ◽  
Vol 25 (4) ◽  
pp. 429-435 ◽  
Author(s):  
J. deRepentigny ◽  
R. Lévesque ◽  
L. G. Mathieu
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Candida Albicans ◽  
Inhibitory Activity ◽  
Antimicrobial Agents ◽  
Mixed Cultures ◽  
Alpha Toxin ◽  
In Vitro Susceptibility ◽  
Pure Cultures

In experiments with mixed cultures of Staphylococcus aureus and Candida albicans both in the absence and in the presence of 5-fluorocytosine (5-FC), we have observed that (1) there is an inhibition of S. aureus growth in mixed cultures with C. albicans in media supplemented with 1 μg/mL of 5-FC and that 5-FC has no effect on staphylococci in pure cultures; (2) this inhibition occurred with clinically isolated and laboratory strains and could be reversed by specific metabolites; (3) Staphylococcus aureus was inhibited by filtrates of C. albicans cultures treated with 5-FC and this seemed to be favored by some C. albicans filterable product which can affect the cell wall and the permeability of the staphylococcal cells since they become sensitive to 5-FC; (4) nine other commonly used antimicrobials showed an increased inhibitory activity against S. aureus in mixed cultures with C. albicans; and (5) there is a decrease in the number of precipitating antigens of S. aureus and of the activity of alpha toxin when this species was grown with both C. albicans and 5-FC. Our results indicate that the susceptibility of some species to antimicrobials could be significantly modified in the presence of other species. One cannot exclude that a similar phenomenon could happen in hosts under treatment with antibiotics against infection.

scholarly journals Transposon Disruption of the Complex I NADH Oxidoreductase Gene (snoD) in Staphylococcus aureus Is Associated with Reduced Susceptibility to the Microbicidal Activity of Thrombin-Induced Platelet Microbicidal Protein 1

2006 ◽  
Vol 188 (1) ◽  
pp. 211-222 ◽  
Author(s):  
Arnold S. Bayer ◽  
Peter McNamara ◽  
Michael R. Yeaman ◽  
Natalie Lucindo ◽  
Tiffanny Jones ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Complex I ◽  
Enzyme Inhibitor ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Gene Products ◽  
Chromosomal Dna ◽  
In Vitro Susceptibility ◽  
Ph Tolerance ◽  
Platelet Microbicidal Protein

ABSTRACT The cationic molecule thrombin-induced platelet microbicidal protein 1 (tPMP-1) exerts potent activity against Staphylococcus aureus. We previously reported that a Tn551 S. aureus transposon mutant, ISP479R, and two bacteriophage back-transductants, TxA and TxB, exhibit reduced in vitro susceptibility to tPMP-1 (tPMP-1r) compared to the parental strain, ISP479C (V. Dhawan, M. R. Yeaman, A. L. Cheung, E. Kim, P. M. Sullam, and A. S. Bayer, Infect. Immun. 65:3293-3299, 1997). In the current study, the genetic basis for tPMP-1r in these mutants was identified. GenBank homology searches using sequence corresponding to chromosomal DNA flanking Tn551 mutant strains showed that the fourth gene in the staphylococcal mnh operon (mnhABCDEFG) was insertionally inactivated. This operon was previously reported to encode a Na+/H+ antiporter involved in pH tolerance and halotolerance. However, the capacity of ISP479R to grow at pH extremes and in high NaCl concentrations (1 to 3 M), coupled with its loss of transmembrane potential (ΔΨ) during postexponential growth, suggested that the mnh gene products are not functioning as a secondary (i.e., passive) Na+/H+ antiporter. Moreover, we identified protein homologies between mnhD and the nuo genes of Escherichia coli that encode components of a complex I NADH:ubiquinone oxidoreductase. Consistent with these data, exposures of tPMP-1-susceptible (tPMP-1s) parental strains (both clinical and laboratory derived) with either CCCP (a proton ionophore which collapses the proton motive force) or pieracidin A (a specific complex I enzyme inhibitor) significantly reduced tPMP-induced killing to levels seen in the tPMP-1r mutants. To reflect the energization of the gene products encoded by the mnh operon, we have renamed the locus sno (S. aureus nuo orthologue). These novel findings indicate that disruption of a complex I enzyme locus can confer reduced in vitro susceptibility to tPMP-1 in S. aureus.

ID: 49: STUDY OF MINIMUM INHIBITORY CONCENTRATION OF CEFAZOLIN FOR METHICILLIN SENSITIVE STAPHYLOCOCCUS AUREUS AND CORRELATION WITH OXACILLIN SUSCEPTIBILITY

2016 ◽  
Vol 64 (4) ◽  
pp. 954.2-954
Author(s):  
C Quarshie ◽  
J Koirala ◽  
V Sundareshan
Keyword(s):  
Staphylococcus Aureus ◽  
Standard Deviation ◽  
Minimum Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Medical Center ◽  
Generation Cephalosporin ◽  
In Vitro Susceptibility ◽  
Suitable Alternative ◽  
High Level

BackgroundCefazolin, a first generation cephalosporin, has been used for the treatment of Methicillin Sensitive Staphylococcus aureus (MSSA) infections since the 1970s. There have now been reported cases of failed therapy with cefazolin. High-level β-lactamase producing strains of S. aureus can inactivate the susceptible β-lactam (cefazolin) at a rate high enough to overcome its antibacterial effect. These strains typically have a high Minimum Inhibitory Concentration (MIC) for cefazolin when a large inoculum is used. About 20% of MSSA isolates have been shown to have a substantial inoculum effect suggesting that cefazolin treatment might be associated with clinical failure in serious MSSA infections. The minimum inhibition concentration (MIC) for cefazolin is not provided on all standard sensitivity panels and susceptibility is extrapolated from the report on oxacillin. The goal of this study was to analyze the MIC of cefazolin for MSSA isolates to determine the correlation of cefazolin susceptibility and in vitro susceptibility of oxacillin. We also evaluated the MIC of alternative antibiotics as part of this study for use in patients that might be allergic to penicillin.MethodThirty two isolates of MSSA were randomly selected from repositories of isolates at Memorial Medical Center hospital's microbiology department from 2015. The isolates were from patients with a wide variety of diagnoses, including bacteremia, osteomyelitis and wound infections. S. aureus ATCC 29213 was used as controls. MICs were determined by a Kirby Bauer method for cefazolin and Epsilometer test for other antibiotics that were studied. Inocula were standardized using optical density measurements, with determinations of CFU/ml to determine the inoculum concentrations. IN addition to cefazolin, we obtained the MIC for daptomycin, oxacillin, ceftaroline and telavancin as well.ResultsOf the thirty two MSSA isolates tested, 100% were susceptible to cefazolin. The mean zone of inhibition (ZOI) was 29.18 with standard deviation of 3.67 for cefazolin (29–35 mm ZOI with ATCC strains of MSSA) . All the isolates were susceptible to Oxacillin with mean MIC of 0.7735 with standard deviation of 0.30. Daptomycin, ceftaroline and telavancin were 100% susceptible with mean MIC of 0.27, 0.25, and 0.07, respectively. All isolates were studied for the alternate antibiotics and no resistance was noted.ConclusionThe MIC of cefazolin for MSSA determined by in vitro susceptibility to oxacillin was entirely in the susceptible range with 100% correlation. Daptomycin, ceftaroline and telavancin are suitable alternative antibiotics for treatment of patients with infections due to MSSA in whom anti-staphylococcal penicillins cannot be used due to penicillin allergic, intolerance, and/or non-availability since there is not much resistance to these antibiotics in MSSA.

Sign in / Sign up

Export Citation Format

Share Document