scholarly journals Genetic traceability of Staphylococcus aureus strains isolated from primiparous dairy cows mastitis, humans and environment in the Northeast region of Brazil

2021 ◽  
Vol 51 (4) ◽  
Author(s):  
Amanda Thaís Ferreira Silva ◽  
José Givanildo da Silva ◽  
Breno Bezerra Aragão ◽  
Núbia Michelle Vieira da Silva ◽  
Priscylla Carvalho Vasconcelos ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Dairy Cows ◽  
Dairy Herds ◽  
Beta Lactam ◽  
Beta Lactams ◽  
High Genetic Diversity ◽  
Northeast Region ◽  
Intramammary Infections ◽  
D Value

ABSTRACT: This research aimed to investigate the genotypic relatedness of 18 Staphylococcus aureus strains isolated from intramammary infections in primiparous cows and extramammary sites on five dairy herds by rep-PCR using RW3A primers, and by PFGE using the endonuclease SmaI. The isolates were also evaluated in vitro for the susceptibility against beta-lactam antimicrobials drugs (penicillin and oxacillin), considering that beta-lactams are frequently used for treating staphylococcal intrammamary infections. The rep-PCR typing was highly discriminatory (D value= 0.9804) and a total of 15 patterns were detected. The PFGE method was also highly discriminatory (D value= 0.9667) and a total of 13 patterns were observed. A total of 15 out of 18 (83%) isolates were resistant to penicillin and one out of 18 (6%) to oxacillin. In conclusion, these findings confirmed the occurrence of a high genetic diversity of S. aureus strains at the herds and the presence of clonally-related strains only at the same herd, emphasizing a variety of genotypic profiles among the isolates.

scholarly journals Addition of Ceftaroline to Daptomycin after Emergence of Daptomycin-Nonsusceptible Staphylococcus aureus during Therapy Improves Antibacterial Activity

2012 ◽  
Vol 56 (10) ◽  
pp. 5296-5302 ◽  
Author(s):  
Warren E. Rose ◽  
Lucas T. Schulz ◽  
David Andes ◽  
Rob Striker ◽  
Andrew D. Berti ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Membrane Damage ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Bacterial Killing ◽  
Content Type ◽  
Cell Membrane Damage

ABSTRACTAntistaphylococcal beta-lactams enhance daptomycin activity and have been used successfully in combination for refractory methicillin-resistantStaphylococcus aureus(MRSA) infections. Ceftaroline possesses MRSA activity, but it is unknown if it improves the daptomycin potency comparably to other beta-lactams. We report a complex patient case of endocarditis who was treated with daptomycin in combination with ceftaroline, which resulted in clearance of a daptomycin-nonsusceptible strain. Anin vitropharmacokinetic/pharmacodynamic model of renal failure was used to simulate the development of daptomycin resistance and evaluate the microbiologic effects of daptomycin plus ceftaroline treatment. Combination therapy with daptomycin and ceftaroline restored daptomycin sensitivityin vivoand resulted in clearance of persistent blood cultures. Daptomycin susceptibilityin vitrowas increased in the presence of either ceftaroline or oxacillin. Daptomycin at 6 mg/kg of body weight every 48 h was bactericidal in the model but resulted in regrowth and daptomycin resistance (MIC, 2 to 4 μg/ml) with continued monotherapy. The addition of ceftaroline at 200 mg every 12 h after the emergence of daptomycin resistance enhanced bacterial killing. Importantly, daptomycin plus ceftaroline as the initial combination therapy produced rapid and sustained bactericidal activity and prevented daptomycin resistance. Bothin vivo- andin vitro-derived daptomycin resistance resulted in bacteria with more fluid cell membranes. After ceftaroline was added in the model, fluidity was restored to the level of the initialin vivoisolate. Daptomycin-resistant isolates required high daptomycin exposures (at least 10 mg/kg) to optimize cell membrane damage with daptomycin alone. Ceftaroline combined with daptomycin was effective in eliminating daptomycin-resistant MRSA, and these results further justify the potential use of daptomycin plus beta-lactam therapy for these refractory infections.

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 Comparative Activities of Telavancin Combined with Nafcillin, Imipenem, and Gentamicin against Staphylococcus aureus

2013 ◽  
Vol 57 (6) ◽  
pp. 2678-2683 ◽  
Author(s):  
Steven N. Leonard ◽  
Megan E. Supple ◽  
Ronak G. Gandhi ◽  
Meghna D. Patel
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Utility ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Once Daily ◽  
Content Type ◽  
Resistant Strains ◽  
Synergy Test ◽  
Time Kill

ABSTRACTBeta-lactams enhance the killing activity of vancomycin. Due to structural and mechanistic similarities between vancomycin and telavancin, we investigated the activity of telavancin combined with nafcillin and imipenem compared to the known synergistic combination of telavancin and gentamicin. Thirty strains ofStaphylococcus aureus, 10 methicillin-susceptibleS. aureus(MSSA), 10 methicillin-resistantS. aureus(MRSA), and 10 heterogeneously vancomycin-intermediateS. aureus(hVISA), were tested for synergy by time-kill methodology. Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in anin vitropharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of 10 mg/kg of body weight of telavancin once daily alone and combined with 2 g nafcillin every 4 h, 500 mg imipenem every 6 h, or 5 mg/kg gentamicin once daily over 72 h. In the synergy test, 67% of strains displayed synergy with the combination of telavancin and gentamicin, 70% with telavancin and nafcillin, and 63% with telavancin and imipenem. In the PK/PD model, the activities of all three combinations against MRSA and hVISA were superior to all individual drugs alone (P≤ 0.002) and were similar to each other (P≥ 0.187). The activities of all three combinations against MSSA were generally similar to each other except for one strain where the combination of telavancin and imipenem was superior to all other regimens (P≤ 0.011). The activity of the combination of telavancin and beta-lactam agents was similar to that of telavancin and gentamicin againstS. aureus, including resistant strains. Because beta-lactam combinations are less likely to be nephrotoxic than telavancin plus gentamicin, these beta-lactam combinations may have clinical utility.

scholarly journals β-Lactam Combinations with Vancomycin Show Synergistic Activity against Vancomycin-SusceptibleStaphylococcus aureus, Vancomycin-IntermediateS. aureus(VISA), and Heterogeneous VISA

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Kieu-Nhi Tran ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Single Agent ◽  
Synergistic Activity ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Content Type ◽  
Fold Reduction ◽  
Mrsa Strains ◽  
Time Kill

ABSTRACTIncreasing utilization of vancomycin due to the high prevalence of methicillin-resistantStaphylococcus aureus(MRSA) infections has led to the emergence of vancomycin-intermediateS. aureus(VISA) and heterogeneous VISA (hVISA) strains.In vitrodata suggest the potential for potent synergy between several beta-lactams and vancomycin. The objective of this study is to evaluate the synergy between beta-lactams and vancomycin against MRSA that is vancomycin susceptible, vancomycin-susceptibleStaphylococcus aureus(VSSA), hVISA, and VISA. Fifty randomly selected clinical MRSA strains with various susceptibility levels to vancomycin were evaluated for vancomycin alone and vancomycin in combination with various concentrations of cefazolin (CFZ), cefepime (FEP), ceftaroline (CPT), and nafcillin (NAF). The potential for synergy was assessed by 24-h time-kill studies. Beta-lactams reduced vancomycin MIC values against all strains (4- to 16-fold reduction). In time-kill studies against MRSA, CFZ, FEP, CPT, and NAF all demonstrated similar degrees of killing at 24 h, and all showed synergistic activity with vancomycin against VSSA, hVISA, and VISA. Each of these combinations was also superior to any single agent against isolates of all three phenotypes, and each was bactericidal (P< 0.001 for all comparisons). All single-agent exposures demonstrated no activity at 24 h. The combination of vancomycin and beta-lactams significantly improved antibacterial activity against VSSA, hVISA, and VISA strains compared to the activity of any agent alone, supporting the potential use of vancomycin–beta-lactam combination therapy in infections caused by MRSA. Further clinical research is warranted to investigate the synergy of vancomycin against theseStaphylococcusstrains.

scholarly journals In Vitro Selection of High-Level Beta-Lactam Resistance in Methicillin-Susceptible Staphylococcus aureus

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 637
Author(s):  
Vladimir Gostev ◽  
Olga Kalinogorskaya ◽  
Ksenia Ivanova ◽  
Ekaterina Kalisnikova ◽  
Irina Lazareva ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
In Vitro Selection ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Disk Diffusion Test ◽  
Amoxicillin Clavulanate ◽  
High Level ◽  
Derivatives Of ◽  
Selection Of

Selective pressure of beta-lactams is thought to be responsible for mutation selection in methicillin-susceptible Staphylococcus aureus (MSSA). We used next-generation sequencing to compare the genomes of beta-lactamase-positive (SA0707) and -negative (SA0937) MSSA isolates with their derivatives obtained after selection with oxacillin, ceftaroline, or meropenem. Selection with oxacillin and ceftaroline caused a rapid and significant (6–8 times) increase in the minimum inhibitory concentration (MICs) of oxacillin, penicillin, amoxicillin/clavulanate, and ceftaroline against the derivatives of both isolates, associated with growth impairment. Selection with meropenem caused a limited increase in the MICs of all beta-lactams against both isolates. During the initial stages of selection (after 5–15 passages), mutations were detected only in some reads, which indicated the heterogeneity of the population; however, during the later stages, either the population reversed to the wild type or fixation of the mutation was observed in the entire population. Selection with different beta-lactams caused diverse mutational events, but common mutations were detected in gdpP, all penicillin-binding proteins, cell wall regulators (vraST, graR), and deletions in the promoter region of pbp4. Therefore, the disk diffusion test with cefoxitin does not reveal resistance associated with these mechanisms in some cases, which can lead to the failure of beta-lactam therapy.

scholarly journals Triple oral beta-lactam containing therapy for Buruli ulcer treatment shortening

2018 ◽  
Author(s):  
María Pilar Arenaz Callao ◽  
Rubén González del Río ◽  
Ainhoa Lucía Quintana ◽  
Charles J. Thompson ◽  
Alfonso Mendoza-Losana ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Amoxicillin Clavulanate ◽  
Low Toxicity ◽  
Potential Use ◽  
Ulcer Treatment

ABSTRACTThe potential use of clinically approved beta-lactams for Buruli ulcer (BU) treatment was investigated with representative classes analyzed in vitro for activity against Mycobacterium ulcerans. Beta-lactams tested were effective alone and displayed a strong synergistic profile in combination with antibiotics currently used to treat BU, i.e. rifampicin and clarithromycin; this activity was further potentiated in the presence of the beta-lactamase inhibitor clavulanate. In addition, quadruple combinations of rifampicin, clarithromycin, clavulanate and beta-lactams resulted in multiplicative reductions in their minimal inhibitory concentration (MIC) values. The MIC of amoxicillin against a panel of clinical isolates decreased more than 200-fold within this quadruple combination. Amoxicillin/clavulanate formulations are readily available with clinical pedigree, low toxicity, and orally and pediatric available; thus, supporting its potential inclusion as a new anti-BU drug in current combination therapies.

scholarly journals Development and Evaluation of a Sensitive Bacteriophage-Based MRSA Diagnostic Screen

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 631
Author(s):  
Matthew Brown ◽  
Wendy Hahn ◽  
Bryant Bailey ◽  
Alex Hall ◽  
Gema Rodriguez ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Low Cost ◽  
Cross Reactivity ◽  
Luciferase Reporter ◽  
Bacillus Species ◽  
Beta Lactam ◽  
Negative Results ◽  
Supportive Role ◽  
Lactam Antibiotic

Engineered luciferase reporter bacteriophages provide specific, sensitive, rapid and low-cost detection of target bacteria and address growing diagnostic needs in multiple industries. Detection of methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization and antibiotic susceptibility play a critical supportive role in preventing hospital-acquired infections and facilitating antibiotic stewardship. We describe the development and evaluation of a novel phage-based MRSA diagnostic screen for nasal swab specimens. The screen utilizes two luciferase reporter phages capable of recognizing genetically-diverse Staphylococcus aureus. The beta-lactam antibiotic cefoxitin is included to differentiate between resistant (MRSA) and susceptible organisms. The screen positively identified 97.7% of 390 clinical MRSA isolates at low bacterial concentrations. At higher inoculums, 93.5% of 123 clinical non-MRSA Staphylococcus aureus yielded appropriate negative results. Although cross-reactivity of the phage cocktail was observed with other staphylococcal and bacillus species, these false positives were absent under selective conditions. MRSA remained detectable in the presence of 38 distinct competing species and was accurately identified in 100% of 40 spiked nasal specimens. Thus, this six-hour screen sensitively detected MRSA both in vitro and in human nasal matrix.

scholarly journals Dalbavancin, Vancomycin and Daptomycin Alone and in Combination with Cefazolin against Resistant Phenotypes of Staphylococcus aureus in a Pharmacokinetic/Pharmacodynamic Model

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 696 ◽  
Author(s):  
Jacinda C. Abdul-Mutakabbir ◽  
Razieh Kebriaei ◽  
Kyle C. Stamper ◽  
Zain Sheikh ◽  
Philip T. Maassen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Inhibitory Concentration ◽  
Pharmacodynamic Model ◽  
In Vitro Tests ◽  
Beta Lactam ◽  
Fold Reduction ◽  
The One ◽  
Time Kill

The most efficacious antimicrobial therapy to aid in the successful elimination of resistant S. aureus infections is unknown. In this study, we evaluated varying phenotypes of S. aureus against dalbavancin (DAL), vancomycin (VAN), and daptomycin (DAP) alone and in combination with cefazolin (CFZ). The objective of this study was to observe whether there was a therapeutic improvement in adding a beta-lactam to a glycopeptide, lipopeptide, or a lipoglycopeptide. We completed a series of in vitro tests including minimum inhibitory concentration testing (MIC) of the antimicrobials in combination, time-kill analysis (TKA), and a 168 h (7-day) one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model on two daptomycin non-susceptible (DNS), vancomycin intermediate S. aureus strains (VISA), D712 and 6913. Results from our MIC testing demonstrated a minimum 2-fold and a maximum 32-fold reduction in MIC values for DAL, VAN, and DAP in combination with CFZ, in contrast to either agent used alone. The TKAs completed on four strains paralleled the enhanced activity demonstrated via the combination MICs. In the one-compartment PK/PD models, the combination of DAP plus CFZ or VAN plus CFZ resulted in a significant (p < 0.001) improvement in bactericidal activity and overall reduction in CFU/ml over the 7-day period. While the addition of CFZ to DAL improved time to bactericidal activity, DAL alone demonstrated equal and more sustained overall activity compared to all other treatments. The use of DAL alone, with or without CFZ and the combinations of VAN or DAP with CFZ appear to result in increased bactericidal activity against various recalcitrant S. aureus phenotypes.

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