Post-antibiotic and post-antibiotic sub-MIC effects of gentamicin, sophoraflavanone G, and their combination against a clinical isolate of Staphylococcus aureus

2010 ◽  
Vol 4 (5) ◽  
pp. 821-826 ◽  
Author(s):  
Ruhollah Mirjani ◽  
Fatemeh Rafii ◽  
Mohammad Sharifzadeh ◽  
Massoud Amanlou ◽  
Ahmad R. Shahverdi
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Fold Increase ◽  
Dependent Manner ◽  
Combination Methods ◽  
Antibiotic Effect ◽  
Short Term Exposure ◽  
Drug Determination ◽  
Dosing Intervals

Abstract Background: Post-antibiotic effect (PAE) defines the potential of a drug to delay re-growth of a bacterial population after short-term exposure and removal of a drug. Determination of the PAE is recommended in preclinical evaluation of all new antimicrobial agents, because it influences optimal antimicrobial dosing intervals. Objective: Evaluate the PAE and PA-SME of gentamicin and sophoraflavanone G against Staphylococcus aureus (S. aureus) itself and in combination. Methods: A spectrophotometric method was used to determine the PAE and PA-SME. Results: Sophoraflavanone G and gentamicin, showed considerable PAE and PA-SME at the tested concentrations against S. aureus. The increased duration of PAE caused by sophoraflavanone G and gentamicin was dosedependent. In addition, sophoraflavanone G at sub-MIC concentrations enhanced the PAE and PA-SME of gentamicin in a dose-dependent manner. The highest enhancing effect was observed for gentamicin at the synergistic MIC and 1/2 the synergistic MIC levels against S. aureus 0.03 μg/mL (30 ng/mL) of sophoraflavanone G (with PAE=55 minutes). It enhanced the post-antibiotic sub-MIC effect (PA-SME) duration of gentamicin at concentrations of 4 μg/mL from 15 minutes to 80 minutes (a six-fold increase). Conclusion: Sophoraflavanone G is promising for the preparation of an effective therapeutic formulation against gentamicin-resistant S. aureus.

scholarly journals Antimicrobial, Antibiofilm, and Anti-persister Activities of Penfluridol Against Staphylococcus aureus

2021 ◽  
Vol 12 ◽  
Author(s):  
Yaqian Liu ◽  
Pengfei She ◽  
Lanlan Xu ◽  
Lihua Chen ◽  
Yimin Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Atp Release ◽  
Drug Repurposing ◽  
Skin Wound ◽  
Clinical Settings ◽  
Dependent Manner ◽  
Acute Peritonitis ◽  
Opportunistic Human Pathogen ◽  
Long Acting

Staphylococcus aureus has increasingly attracted global attention as a major opportunistic human pathogen owing to the emergence of biofilms (BFs) and persisters that are known to increase its antibiotic resistance. However, there are still no effective antimicrobial agents in clinical settings. This study investigated the antimicrobial activity of penfluridol (PF), a long-acting antipsychotic drug, against S. aureus and its clinical isolates via drug repurposing. PF exhibited strong bactericidal activity against S. aureus, with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 4–8 and 16–32 μg/ml, respectively. PF could significantly inhibit biofilm formation and eradicate 24 h preformed biofilms of S. aureus in a dose-dependent manner. Furthermore, PF could effectively kill methicillin-resistant S. aureus (MRSA) persister cells and demonstrated considerable efficacy in a mouse model of subcutaneous abscess, skin wound infection, and acute peritonitis caused by MRSA. Notably, PF exerted almost no hemolysis activity on human erythrocytes, with limited cytotoxicity and low tendency to cause resistance. Additionally, PF induced bacterial membrane permeability and ATP release and further caused membrane disruption, which may be the underlying antibacterial mechanism of PF. In summary, our findings suggest that PF has the potential to serve as a novel antimicrobial agent against S. aureus biofilm- or persister-related infections.

scholarly journals Differential effects of antibiotics on neutrophils exposed to lipoteichoic acid derived from Staphylococcus aureus

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Marquerita Algorri ◽  
Annie Wong-Beringer
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Lipoteichoic Acid ◽  
Neutrophil Function ◽  
Exposure Level ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Persistent Bacteremia ◽  
Neutrophil Survival

Abstract Background Persistent bacteremia occurs in at least 30% of patients with Staphylococcus aureus bloodstream infection (SAB) and may be attributable to a dysregulated host immune response. Neutrophils interact with a variety of S. aureus microbial factors, including lipoteichoic acid (LTA), to activate phagocytic function in a concentration-dependent manner. Antibiotics have been shown to exert both direct antimicrobial action as well as immunomodulatory effects. In this study, we compared the effects of different anti-staphylococcal antibiotics on LTA-mediated immune activation of neutrophils. Methods Neutrophils obtained from healthy volunteers were exposed to two levels of LTA (1 and 10 μg/ml) with or without addition of antibiotics from different pharmacologic classes (vancomycin, daptomycin, ceftaroline). Neutrophil function was assessed by examining phagocytic response, activation (CD11b, CD62L expression), Toll-like receptor-2 expression, cell survival and apoptosis, and CXCL8 release. Results Differential LTA-mediated antibiotic effects on neutrophil function were observed primarily at the high LTA exposure level. Ceftaroline in the presence of 10 μg/ml LTA had the most prominent effects on phagocytosis and CD11b and CD62L expression, with trends towards increased neutrophil survival and preservation of CXCL8 release when compared to daptomycin and vancomycin with the latter significantly dampening PMN CXCL8 release. Conclusions Select antimicrobial agents, such as ceftaroline, exert immunostimulatory effects on neutrophils exposed to S. aureus LTA, which when confirmed in vivo, could be leveraged for its dual immunomodulatory and antibacterial actions for the treatment of persistent SAB mediated by a dysregulated host response.

Determination of Antimicrobial Potentials of Ethanol Extract of Combretum dolichopentalum Leaves by Total Dehydrogenase Activity Assay

2017 ◽  
Vol 8 ◽  
pp. 27-40
Author(s):  
Favour Ntite Ujowundu
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Dehydrogenase Activity ◽  
Antimicrobial Agents ◽  
Ethanol Extract ◽  
Bactericidal Effect ◽  
Salmonella Typhi ◽  
Vaginal Swab ◽  
Dependent Manner ◽  
Streptococcus Pneumonia

The viability of microorganisms can be determined by the total dehydrogenase activity (DHA). Thus, a reduction in total dehydrogenase activity is an indication of the bactericidal effect of plant extract. The antimicrobial potentials of ethanol extract of Combretum dolichopentalum (EECD) leaves on microbial isolates from stool, degenerated wound, and high vaginal swab were determined by the total dehydrogenase activity. The microbial cells were standardized in a spectrophotometer to an optical density of 0.70 at 420 nm and used as standardized cell suspension (inoculum) in the dehydrogenase assay. The results obtained indicated that EECD leaves were effective antimicrobial agents against Escherichia coli, Staphylococcus aureus, Salmonella typhi and Streptococcus pneumonia isolates. Threshold inhibitory concentrations of the extracts showed that EECD leaves inhibited dehydrogenase activity in all the organisms in a dose dependent manner. At 355.78 μg/ml, EECD leaves achieved an IC50against E. coli, and at 349.42 µg/ml and 843.80 µg/ml EECD obtained an IC50against Streptococcus pneumonia and Staphylococcus aureus respectively. Also, at 2270.68 μg/ml EECD leaves eliminated 100 % S. typhi to achieve 100 % inhibiting concentration. C. dolichopentalum makes a promising drug with bactericidal effect especially against Escherichia coli and Salmonella typhi.

scholarly journals Bidirectional alterations in antibiotics susceptibility in Staphylococcus aureus - Pseudomonas aeruginosa dual-species biofilm

2018 ◽  
Author(s):  
Elena Y. Trizna ◽  
Maria N. Yarullina ◽  
Diana R. Baidamshina ◽  
Farida S. Akhatova ◽  
Elvira V. Rozhina ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Efficacy ◽  
Antimicrobial Agents ◽  
Fold Increase ◽  
Antimicrobial Treatment ◽  
Mixed Infections ◽  
Similar Increase ◽  
Efficient Treatment ◽  
Antibiotics Susceptibility ◽  
Efficacy Of Treatment

ABSTRACTWhile in biofilms bacteria are embedded into an extracellular matrix which forms inaccessible barrier for antimicrobials thereby drastically increasing the concentrations of antibiotics required for treatment. Here we show that the susceptibility of S. aureus and P. aeruginosa to antibiotics in mixed biofilms significantly differs from monoculture biofilms depending on both conditions and chosen antimicrobial agents. While S. aureus could completely avoid vancomycin, ampicillin and ceftriaxone by embedding into the biofilm of P. aeruginosa, the very same consortium was characterized by 10–fold increase in susceptibility to broad-spectrum antimicrobials like ciprofloxacin and aminoglycosides compared to monocultures. These data clearly indicate that efficient treatment of biofilm-associated mixed infections requires antimicrobials active against both pathogens, since the interbacterial antagonism would enhance the efficacy of treatment. Moreover, similar increase in antibiotics efficacy was observed when P. aeruginosa suspension was added to the mature S. aureus biofilm, compared to S. aureus monoculture, and vice versa. These findings open promising perspectives to increase the antimicrobial treatment efficacy of the wounds infected with nosocomial pathogens by the transplantation of the skin residential microflora.

scholarly journals In Vitro Activities of Ceftobiprole, Tigecycline, Daptomycin, and 19 Other Antimicrobials against Methicillin-Resistant Staphylococcus aureus Strains from a National Survey of Belgian Hospitals

2006 ◽  
Vol 50 (8) ◽  
pp. 2680-2685 ◽  
Author(s):  
Olivier Denis ◽  
Ariane Deplano ◽  
Claire Nonhoff ◽  
Marie Hallin ◽  
Raf De Ryck ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Therapeutic Potential ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Methicillin Resistant ◽  
Excellent Activity ◽  
Agar Dilution

ABSTRACT The in vitro activities of 22 antimicrobial agents, including ceftobiprole, daptomycin, and tigecycline, against 511 methicillin-resistant Staphylococcus aureus (MRSA) isolates from 112 Belgian hospitals were studied by using the CLSI agar dilution method. Isolates were characterized by pulsed-field gel electrophoresis (PFGE) analysis and by PCR detection of determinants of resistance to aminoglycosides, macrolides-lincosamides-streptogramins, and tetracyclines. A representative set of isolates with different PFGE genotypes was further characterized by multilocus sequence typing, determination of staphylococcal cassette chromosome mec (SCCmec) type, and multiplex PCR for toxic shock syndrome type 1 (TSST-1) and Panton-Valentine leukocidin genes. MRSA isolates belonged to nine epidemic MRSA clones, of which sequence type 45 (ST45)-SCCmec IV and ST8-SCCmec IV were predominant, accounting for 49 and 20% of isolates, respectively. The distribution of antimicrobial resistance and TSST-1 genes was strongly linked to clonal types. Ceftobiprole, daptomycin, and tigecycline showed high activity against all isolates of these sporadic and epidemic MRSA clones, as indicated by MIC90s of 2 mg/liter, 0.5 mg/liter, and 0.25 mg/liter, respectively. The MIC distribution of daptomycin and tigecycline was not different in isolates with decreased susceptibility to glycopeptides or tetracyclines, respectively. Ceftobiprole MICs were not correlated with oxacillin and cefoxitin MICs. These data indicate excellent activity of the newly developed agents ceftobiprole, daptomycin, and tigecycline against MRSA isolates recently recovered from hospitalized patients in Belgium, supporting their therapeutic potential for nosocomial MRSA infections.

scholarly journals Inhibitory Activity of Levofloxacin against MDR Staphylococcus aureus and Pseudomonas aeruginosa Clinical Isolates

2019 ◽  
Vol 6 (1) ◽  
pp. 25
Author(s):  
Lisa Nathalie ◽  
Lindawati Alimsardjono ◽  
Isnaeni Isnaeni
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Minimum Inhibitory Concentration ◽  
Antimicrobial Agents ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Bacterial Concentration ◽  
Important Species ◽  
One Step

Introduction: Staphylococcus  aureus  and  Pseudomonas  aeruginosa  are the most dangerous  and important species among  their genus.  These  bacteria  are often  resistant  to  many  classes  of antimicrobial  agents;  which  make difficulties in selecting appropriate drug to treat infections. Multidrug-resistance occurs readily in hospitals for which antimicrobials  agents  were   used  widely. Objective: The  aims  of  this  study  was  to  determine  minimum  inhibitory concentration  (MIC) and  minimum bacterial  concentration  (MBC) of levofloxacin  against 22 multidrug  resistant- clinical (MDR) strains of Staphylococcus aureus and Pseudomonas aeruginosa isolated from patients pus and urine in hospital. Methods: Determination of the MIC was performed by macro-dilution broth assay as recommended by Clinical and Laboratory Standards Institute (CLSI), while the MBC was determined one-step further after the MIC determination. Results: It was found that MIC of the levofloxacin were (0.3 ± 0.0) - >0.5 µg/mL and (0.2 ± 0.1) - (1.0 ±0.0)µg/mL against S. aureus from pus and urine, respectively.  In addition, higher MICs were yielded against P. aeruginosa, (1.0 ± 0.0) - >8.0 µg/mL and (0.7 ± 0.3) - (3.0 ± 1.2) µg/mL for pus and urine isolates respectively. Similar to MICs, the MBCs against P. aeruginosa were higher than S. aureus, (0.6 ± 0.0) - > 4.0 µg/mL and (0.3 ± 0.0) - >8.0 µg/mL isolated from pus and urine respectively, (2.0 ± 0.6) - > 8.0 µg/mL and (3.0 ± 1.2) - >7.0 µg/mL against P. aeruginosa from pus and urine respectively. Conclusion: The levofloxacin was still susceptible as bacteriostatic against isolates from both body fluids, but not bactericidal towards all isolates.

scholarly journals Identification and Characterization of SirA, an Iron-Regulated Protein from Staphylococcus aureus

1999 ◽  
Vol 181 (5) ◽  
pp. 1436-1443 ◽  
Author(s):  
Jon H. Heinrichs ◽  
LaVette E. Gatlin ◽  
Charles Kunsch ◽  
Gil H. Choi ◽  
Mark S. Hanson
Keyword(s):  
Staphylococcus Aureus ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Genomic Sequence ◽  
Iron Acquisition ◽  
Bacterial Species ◽  
Dependent Manner ◽  
Dyad Symmetry ◽  
Siderophore Transport

ABSTRACT The acquisition of iron by pathogenic bacteria is often a crucial step in establishing infection. To accomplish this, many bacteria, including Staphylococcus aureus, produce low-molecular-weight iron-chelating siderophores. However, the secretion and transport of these molecules in gram-positive organisms are poorly understood. The sequence, organization, and regulation of genes involved in siderophore transport are conserved among gram-negative bacteria. We used this information to identify a putative siderophore transport locus from an S. aureus genomic sequence database. This locus contains three predicted open reading frames with a high degree of homology to genes involved in siderophore uptake in several bacterial species, in particular the cbrlocus of the plant pathogen Erwinia chrysanthemi. The first gene in the locus, which we have designated sir for staphylococcal iron regulated, encodes a putative lipoprotein with a molecular mass of 37 kDa. The open reading frame is preceded by a 19-bp region of dyad symmetry with homology for operator sequences controlling iron-regulated expression of genes in other bacteria. Fur titration experiments indicate that this region of dyad symmetry is sufficient for Fur-dependent regulation in Escherichia coli. The expression of this gene was repressed, in a dose-dependent manner, by the addition of iron to the S. aureus culture medium. sir-encoded proteins may be involved in iron acquisition in vivo and therefore may be targets for antimicrobial agents.

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