scholarly journals Epinecidin-1 Protects against Methicillin Resistant Staphylococcus aureus Infection and Sepsis in Pyemia Pigs

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 693
Author(s):  
Han-Ning Huang ◽  
Chieh-Yu Pan ◽  
Bor-Chyuan Su ◽  
Hung-Yi Wu ◽  
Jyh-Yih Chen
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Analysis ◽  
Diabetic Patients ◽  
Methicillin Resistant ◽  
Antibiotic Drug

Methicillin resistant Staphylococcus aureus (MRSA) may be found on the skin, nose, and throats of long-term hospitalized patients. While MRSA infections are usually minor, serious infections and death may occur in immunocompromised or diabetic patients, or after exposure of MRSA to blood. This report demonstrates that the antimicrobial peptide (AMP) epinecidin-1 (Epi-1) efficiently protects against MRSA infection in a pyemia pig model. We first found that Epi-1 exhibits bactericidal activity against MRSA. Next, pharmacokinetic analysis revealed that Epi-1 was stable in serum for 4 h after injection, followed by a gradual decrease. This pharmacokinetic profile suggested Epi-1 may bind serum albumin, which was confirmed in vitro. Harmful effects were not observed for doses up to 100 mg/kg body weight in pigs. When Epi-1 was supplied as a curative agent 30 min post-infection, MRSA-induced abnormalities in blood uric acid (UA), blood urea nitrogen (BUN), creatine (CRE), GOT, and GPT levels were restored to normal levels. We further showed that the bactericidal activity of Epi-1 was higher than that of the antibiotic drug vancomycin. Epi-1 significantly decreased MRSA counts in the blood, liver, kidney, heart, and lungs of infected pigs. Elevated levels of serum C reactive protein (CRP), proinflammatory cytokine IL6, IL1β, and TNFα were also attenuated by Epi-1 treatment. Moreover, the MRSA genes, enterotoxin (et)-A, et-B, intrinsic methicillin resistance A (mecA), and methicillin resistance factor A (femA), were significantly reduced or abolished in MRSA-infected pigs after treatment with Epi-1. Hematoxylin and eosin staining of heart, liver, lung, and kidney sections indicated that Epi-1 attenuated MRSA toxicity in infected pigs. A survival study showed that the pyemia pigs infected with MRSA alone died within a week, whereas the pigs post-treated with 2.5 mg/kg Epi-1 were completely protected against death. The present investigation, thus, demonstrates that Epi-1 effectively protects pyemia pigs against pathogenic MRSA without major toxic side effects.

scholarly journals ComparativeIn VitroActivities of Oritavancin, Dalbavancin, and Vancomycin against Methicillin-Resistant Staphylococcus aureus Isolates in a Nondividing State

2016 ◽  
Vol 60 (7) ◽  
pp. 4342-4345 ◽  
Author(s):  
Adam Belley ◽  
David Lalonde Seguin ◽  
Francis Arhin ◽  
Greg Moeck
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Antibacterial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Skin Structure ◽  
Persistent Infections ◽  
Time Kill

ABSTRACTAntibacterial agents that kill nondividing bacteria may be of utility in treating persistent infections. Oritavancin and dalbavancin are bactericidal lipoglycopeptides that are approved for acute bacterial skin and skin structure infections in adults caused by susceptible Gram-positive pathogens. Using time-kill methodology, we demonstrate that oritavancin exerts bactericidal activity against methicillin-resistantStaphylococcus aureus(MRSA) isolates that are maintained in a nondividing statein vitro, whereas dalbavancin and the glycopeptide vancomycin do not.

Treatment of Infection and Colonization Caused by Methicillin-Resistant Staphylococcus aureus

1991 ◽  
Vol 12 (01) ◽  
pp. 29-35 ◽  
Author(s):  
Henry F. Chambers
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Active Agent ◽  
Methicillin Resistant ◽  
Drug Of Choice ◽  
Serious Infections ◽  
Combination Regimens ◽  
Higher Doses

AbstractThe mechanism of methicillin resistance confers resistance to all available B-lactam antibiotics; consequently, B-lactam antibiotics have no role in therapy of methicillin-resistant Staphylococcus aureus (MRSA) infections. Vancomycin remains the drug of choice. Teicoplanin and daptomycin are two investigational antibiotics related to vancomycin in structure and in spectrum of activity. In clinical trials employing relatively low doses, neither was as effective as vancomycin. Trials at higher doses are on-going. Quinolones, ciprofloxacin in particular, have been used successfully to treat infections caused by MRSA; however, the usefulness of quinolones may be limited by the tendency of resistance to emerge during therapy. Quinolones probably should be used only in combination with another active agent, such as rifampin, when treating serious infections caused by MRSA. Other agents may be active in vitro against MRSA, but clinical data showing their effectiveness are lacking. Rifampin combination regimens appear most effectively to eradicate colonization with MRSA.

scholarly journals Importance of penicillinase production for activity of penicillin alone or in combination with sulbactam in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

1996 ◽  
Vol 40 (5) ◽  
pp. 1219-1224 ◽  
Author(s):  
B Fantin ◽  
J Pierre ◽  
N Castéla-Papin ◽  
L Saint-Julien ◽  
H Drugeon ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Synergistic Effect ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Limiting Factor ◽  
High Dose ◽  
Methicillin Resistant

The activity of penicillin, alone and in combination with sulbactam, against a heterogeneously methicillin-resistant, penicillinase-producing clinical isolate of Staphylococcus aureus and its penicillinase-negative derivative was investigated in vitro and in a rabbit experimental endocarditis model. Penicillin was significantly more effective than vancomycin against the penicillinase-negative derivative in vivo (P < 0.001), and it sterilized 25% of the vegetations. The combination of penicillin and sulbactam exhibited an in vivo synergistic effect on the penicillinase-producing strain (P < 0.01) but did not produce any advantage over treatment with vancomycin, even when a high dose of sulbactam was used (100 mg/kg of body weight every 6 h). This combination was significantly less effective against the penicillinase-producing strain than was penicillin alone against the penicillinase-negative derivative (P < 0.03). In addition, the most resistant subpopulation of the surviving bacteria, which grew on agar containing 16 micrograms of methicillin per ml, was detected in 5 of 6 animals treated with penicillin and a high dose of sulbactam against the penicillinase-producing strain compared with only 1 of 12 animals treated with penicillin alone against the penicillinase-negative derivative (P < 0.01). We conclude that penicillin is highly effective against penicillinase-negative methicillin-resistant S. aureus and that penicillinase production, rather than methicillin resistance, appears to be the limiting factor for the activity of the penicillin-sulbactam combination against penicillinase-producing, methicillin-resistant S. aureus.

scholarly journals Evaluation of Ceftaroline, Vancomycin, Daptomycin, or Ceftaroline plus Daptomycin against Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus in anIn VitroPharmacokinetic/Pharmacodynamic Model of Simulated Endocardial Vegetations

2014 ◽  
Vol 58 (6) ◽  
pp. 3177-3181 ◽  
Author(s):  
Brian J. Werth ◽  
Katie E. Barber ◽  
Cortney E. Ireland ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Active Agent ◽  
Minimum Concentration ◽  
Ceftaroline Fosamil ◽  
Methicillin Resistant ◽  
Content Type ◽  
Sustained Activity

ABSTRACTInfective endocarditis (IE) caused by methicillin-resistantStaphylococcus aureus(MRSA) with reduced susceptibility to vancomycin and daptomycin has few adequate therapeutic options. Ceftaroline (CPT) is bactericidal against daptomycin (DAP)-nonsusceptible (DNS) and vancomycin-intermediate MRSA, but supporting data are limited for IE. This study evaluated the activities of ceftaroline, vancomycin, daptomycin, and the combination of ceftaroline plus daptomycin against DNS MRSA in a pharmacokinetic/pharmacodynamic (PK/PD) model of simulated endocardial vegetations (SEVs). Simulations of ceftaroline-fosamil (600 mg) every 8 h (q8h) (maximum concentration of drug in serum [Cmax], 21.3 mg/liter; half-life [t1/2], 2.66 h), daptomycin (10 mg/kg of body weight/day) (Cmax, 129.7 mg/liter;t1/2, 8 h), vancomycin (1 g) q8h (minimum concentration of drug in serum [Cmin], 20 mg/liter;t1/2, 5 h), and ceftaroline plus daptomycin were evaluated against 3 clinical DNS, vancomycin-intermediate MRSA in a two-compartment,in vitro, PK/PD SEV model over 96 h with a starting inoculum of ∼8 log10CFU/g. Bactericidal activity was defined as a ≥3-log10CFU/g reduction from the starting inoculum. Therapeutic enhancement of combinations was defined as ≥2-log10CFU/g reduction over the most active agent alone. MIC values for daptomycin, vancomycin, and ceftaroline were 4 mg/liter, 4 to 8 mg/liter, and 0.5 to 1 mg/liter, respectively, for all strains. At simulated exposures, vancomycin was bacteriostatic, but daptomycin and ceftaroline were bactericidal. By 96 h, ceftaroline monotherapy offered significantly improved killing compared to other agents against one strain. The combination of DAP plus CPT demonstrated therapeutic enhancement, resulting in significantly improved killing versus either agent alone against 2/3 (67%) strains. CPT demonstrated bactericidal activity against DNS, vancomycin-intermediate MRSA at high bacterial densities. Ceftaroline plus daptomycin may offer more rapid and sustained activity against some MRSA in the setting of high-inoculum infections like IE and should also be considered.

scholarly journals Growing Resistance to Vancomycin among Methicillin Resistant Staphylococcus Aureus Isolates from Different Clinical Samples

2014 ◽  
Vol 52 (196) ◽  
pp. 977-981 ◽  
Author(s):  
Prakash Chandra Pahadi ◽  
Upendra Thapa Shrestha ◽  
Nabaraj Adhikari ◽  
Pradeep Kumar Shah ◽  
Ritu Amatya
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Control Measures ◽  
Clinical Samples ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Methicillin Resistant

Introduction: Methicillin resistant Staphylococcus aureus (MRSA), majorly associated with nosocomial and community infections worldwide, are emerging as resistant strains to many antibiotics narrowing down the efficacy of antimicrobial therapy. In order to investigate the changing resistant pattern of MRSA to empirical drugs, the study was carried out at KIST Medical College and Hospital, Nepal. It also aims to determine the minimum inhibitory concentration of vancomycin among MRSA. Methods: Altogether 3500 clinical samples including 1303 blood, 1489 urine and 708 body fluids were collected and processed. Isolated S. aureus were further screened for methicillin resistance by Kirby-Bauer disk diffusion technique using cefoxitin (30μg) disk. All MRSA were subjected to in vitro determination of MIC of vancomycin by agar dilution method as recommended by CLSI guidelines. Results: Total 287 S. aureus were isolated from the different clinical samples. Altogether 248 (86.41%) were found to be multidrug resistance (MDR) while 42 (14.63%) of the isolates were methicillin resistance with the highest prevalence in the age group of 16-30. All 42 (100%) MRSA isolates were resistant to ampicillin and penicillin followed by 41 (97.62%), 32 (76.19%), 31(73.81%), 29 (69.05%), 9 (21.43%) and seven (16.67%) to cefotaxime, gentamycin, cotrimoxazole, erythromycin, tetracycline and ciprofloxacin respectively. Although all MRSA strains were sensitive to vancomycin on disc diffusion, four isolates were intermediates in vitro determination of MIC of vancomycin. The break point for vancomycin was found to be 15mm. Conclusions: The increment in vancomycin MIC among MRSA is alarming. Strict control measures to prevent MRSA spread and a routine surveillance for VRSA must be incorporated in hospitals.  Keywords: mdr; mrsa; mic; visa; vrsa.

Sign in / Sign up

Export Citation Format

Share Document