scholarly journals Pseudomonas aeruginosa LasA Protease in Treatment of Experimental Staphylococcal Keratitis

2004 ◽  
Vol 48 (5) ◽  
pp. 1681-1687 ◽  
Author(s):  
Irina S. Barequet ◽  
Guy J. Ben Simon ◽  
Mary Safrin ◽  
Dennis E. Ohman ◽  
Efrat Kessler
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Rabbit Model ◽  
Treatment Protocols ◽  
Methicillin Resistant ◽  
Clinical Scores ◽  
Lasa Protease ◽  
Late Treatment ◽  
Intrastromal Injection ◽  
Staphylococcus Simulans

ABSTRACT LasA protease is a staphylolytic endopeptidase secreted by Pseudomonas aeruginosa. We have examined the effectiveness of LasA protease in the treatment of staphylococcal keratitis caused by methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates in a rabbit model. Keratitis was induced by intrastromal injection of the bacteria. The eyes were treated topically, and the efficacy of LasA protease was compared to those of lysostaphin (a staphylolytic protease secreted by Staphylococcus simulans) and vancomycin. When treatment was initiated early (4 h) after infection, practically all of the MSSA- and MRSA-infected corneas were sterilized by LasA protease, and its efficacy in eradicating the bacteria was comparable to those of lysostaphin and vancomycin. By contrast, most of the control corneas were heavily infected, with median values of 4.5 × 106 (MSSA) and 5 × 105 (MRSA) CFU/cornea (P < 0.001). When treatment was initiated late (10 h) after infection, LasA protease reduced the numbers of CFU in both MSSA- and MRSA-infected corneas by 3 to 4 orders of magnitude compared to the numbers of CFU for the controls (median values, 1,380 and 30 CFU/cornea, respectively, for the treated animals compared to 1.2 × 106 and 5 × 105 CFU/cornea for the respective controls [P = 0.001]), and it was more effective than vancomycin in eradicating MRSA cells (P = 0.02). In both the early- and the late-treatment protocols, the clinical scores for eyes treated with LasA protease were significantly lower than those for the eyes of the corresponding controls and comparable to those for the lysostaphin- and vancomycin-treated eyes. We conclude that LasA protease is effective in the treatment of experimental S. aureus keratitis in rabbits and may have potential for the treatment of disease in humans.

scholarly journals Lysostaphin Treatment of Experimental Methicillin-Resistant Staphylococcus aureus Aortic Valve Endocarditis

1998 ◽  
Vol 42 (6) ◽  
pp. 1355-1360 ◽  
Author(s):  
Michael W. Climo ◽  
Roberto L. Patron ◽  
Beth P. Goldstein ◽  
Gordon L. Archer
Keyword(s):  
Staphylococcus Aureus ◽  
Aortic Valve ◽  
Rabbit Model ◽  
Once Daily ◽  
Methicillin Resistant ◽  
Bacterial Counts ◽  
Immunological Reactions ◽  
The Mean ◽  
Staphylococcus Simulans ◽  
Better Than

ABSTRACT The emergence of clinical isolates of methicillin-resistantStaphylococcus aureus with reduced susceptibility to vancomycin has prompted a search for new and novel therapeutic agents active against S. aureus. Lysostaphin, a peptidase produced by Staphylococcus simulans, specifically cleaves the glycine-glycine bonds unique to the interpeptide cross-bridge of theS. aureus cell wall. The effectiveness of various regimens of dosing with intravenous lysostaphin was compared to that of vancomycin in the rabbit model of aortic valve endocarditis caused by a clinical methicillin-resistant S. aureus isolate. All animals were treated for a total of 3 days. The most active regimen, lysostaphin given three times daily, produced sterile vegetations in 10 of 11 treated rabbits, with a mean reduction in vegetation bacterial counts of 8.5 log10 CFU/g compared to the counts in the untreated controls. In contrast, vancomycin given twice daily sterilized no vegetations and reduced vegetation bacterial counts by only 4.8 log10 CFU/g. Lysostaphin given once daily was less effective, reducing mean vegetation bacterial counts by only 3.6 log10 CFU/g, but the combination of lysostaphin once daily and vancomycin twice daily reduced the mean vegetation bacterial density by 7.5 log10 CFU/g, a result that was significantly better than that for either regimen alone (P < 0.05). Lysostaphin was well tolerated by the rabbits, with no evidence of immunological reactions following up to 9 weeks of intravenous administration. We conclude that lysostaphin given alone or in combination with vancomycin is more effective in the treatment of experimental methicillin-resistant S. aureus aortic valve endocarditis than vancomycin alone.

scholarly journals Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model

2015 ◽  
Vol 59 (12) ◽  
pp. 7571-7580 ◽  
Author(s):  
Wei-Tao Jia ◽  
Qiang Fu ◽  
Wen-Hai Huang ◽  
Chang-Qing Zhang ◽  
Mohamed N. Rahaman
Keyword(s):  
Staphylococcus Aureus ◽  
Bioactive Glass ◽  
Calcium Sulfate ◽  
Rabbit Model ◽  
Local Delivery ◽  
Methicillin Resistant ◽  
Content Type ◽  
Borate Bioactive Glass ◽  
Phosphate Buffered Saline

ABSTRACTThere is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TECin vitroand to cure methicillin-resistantStaphylococcus aureus(MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC.

scholarly journals Improved Protection in a Rabbit Model of Community-Associated Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia upon Neutralization of Leukocidins in Addition to Alpha-Hemolysin

2016 ◽  
Vol 60 (10) ◽  
pp. 6333-6340 ◽  
Author(s):  
Binh An Diep ◽  
Vien T. M. Le ◽  
Zehra C. Visram ◽  
Harald Rouha ◽  
Lukas Stulik ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Human Monoclonal Antibody ◽  
Rabbit Model ◽  
Passive Immunization ◽  
Severe Pneumonia ◽  
Phagocytic Cells ◽  
Methicillin Resistant ◽  
Content Type ◽  
Alpha Hemolysin ◽  
Full Protection

ABSTRACTCommunity-associated methicillin-resistantStaphylococcus aureus(CA-MRSA), especially the USA300 pulsotype, is a frequent cause of skin and soft tissue infections and severe pneumonia. Despite appropriate antibiotic treatment, complications are common and pneumonia is associated with high mortality.S. aureusstrains express multiple cytotoxins, including alpha-hemolysin (Hla) and up to five bicomponent leukocidins that specifically target phagocytic cells for lysis. CA-MRSA USA300 strains carry the genes for all six cytotoxins. Species specificity of the leukocidins greatly contributes to the ambiguity regarding their role inS. aureuspathogenesis. We performed a comparative analysis of the leukocidin susceptibility of human, rabbit, and mouse polymorphonuclear leukocytes (PMNs) to assess the translational value of mouse and rabbitS. aureusmodels. We found that mouse PMNs were largely resistant to LukSF-PV, HlgAB, and HlgCB and susceptible only to LukED, whereas rabbit and human PMNs were highly sensitive to all these cytotoxins. In the rabbit pneumonia model with a USA300 CA-MRSA strain, passive immunization with a previously identified human monoclonal antibody (MAb), Hla-F#5, which cross-neutralizes Hla, LukSF-PV, HlgAB, HlgCB, and LukED, provided full protection, whereas an Hla-specific MAb was only partially protective. In the mouse USA300 CA-MRSA pneumonia model, both types of antibodies demonstrated full protection, suggesting that Hla, but not leukocidin(s), is the principal virulence determinant in mice. As the rabbit recapitulates the high susceptibility to leukocidins characteristic of humans, this species represents a valuable model for assessing novel, cytotoxin-targeting anti-S. aureustherapeutic approaches.

scholarly journals Ceftobiprole Is Superior to Vancomycin, Daptomycin, and Linezolid for Treatment of Experimental Endocarditis in Rabbits Caused by Methicillin-Resistant Staphylococcus aureus

2009 ◽  
Vol 54 (2) ◽  
pp. 610-613 ◽  
Author(s):  
P. Tattevin ◽  
L. Basuino ◽  
D. Bauer ◽  
B. A. Diep ◽  
H. F. Chambers
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Group ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Rabbit Model ◽  
Laboratory Strain ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
High Affinity

ABSTRACT Beta lactam agents are the most active drugs for the treatment of streptococci and methicillin-susceptible Staphylococcus aureus endocarditis. However, methicillin-resistant S. aureus (MRSA) is resistant to all beta lactam agents licensed to date, and alternative treatments are limited. Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the penicillin binding protein that mediates the methicillin resistance of staphylococci and is active against MRSA. Ceftobiprole was compared to vancomycin, daptomycin, and linezolid in a rabbit model of MRSA aortic valve endocarditis caused by the homogeneously methicillin-resistant laboratory strain COL. Residual organisms in vegetations were significantly fewer in ceftobiprole-treated rabbits than in any other treatment group (P < 0.05 for each comparison). In addition, the numbers of organisms in spleens and in kidneys were significantly lower in ceftobiprole-treated rabbits than in linezolid- and vancomycin-treated animals (P < 0.05 for each comparison). Anti-MRSA beta lactam agents such as ceftobiprole may represent a significant therapeutic advance over currently available agents for the treatment of MRSA endocarditis.

scholarly journals Multimicrobial Pneumonia during the Early Stages of a Global Pandemic

2021 ◽  
Vol 8 (6) ◽  
Author(s):  
Jalal H ◽  
◽  
Henriksen G ◽  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Acute Infection ◽  
Standard Of Care ◽  
Antibiotic Use ◽  
Lung Parenchyma ◽  
Community Acquired Pneumonia ◽  
Methicillin Resistant ◽  
Global Pandemic

Community-acquired pneumonia is an acute infection of lung parenchyma which causes local and systemic inflammatory changes via cytokines. Several bacteria and viruses are responsible for this type of pneumonia, and the most common bacterial cause is Streptococcus pneumoniae. The classic symptoms are cough, fever, and pleuritic chest pain. In the Winter of 2020, a new strain of coronavirus known as SARS-CoV-2 spread throughout the world and was responsible for a global pandemic that transformed the way we live our lives. A 93-year old female presented to the hospital with respiratory distress and was found to have not only COVID-19 pneumonia but also superimposed Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa pneumonia. Following the most up-to-date guidelines, she was determined to have community-acquired pneumonia. Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa are uncommon causes of communityacquired pneumonia. She was treated with the standard of care at the time, which included vancomycin, piperacillin-tazobactam, and hydroxychloroquine. This case highlights the rarity of this specific presentation of community acquired pneumonia in regards to microbial etiology. It showcases that patients may develop certain diseases despite not having any risk factors. A major takeaway point is that apt decision making is a critical and time sensitive matter when determining whether a bacterial co-infection is present since it can affect patient outcomes. Since co-infections are relatively infrequent, antibiotic use in COVID-19 positive patients needs to be tailored accordingly. At the same time, it is crucial to keep in mind that co-infections are associated with increased severity of COVID-19 as well as poorer outcomes.

scholarly journals Diabetic Foot Infections: Local Prevalence of and Case–Control Study of Risk Factors for Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa

2020 ◽  
Vol 7 (10) ◽  
Author(s):  
Justin J Kim ◽  
Alison Lydecker ◽  
Rohini Davé ◽  
Jacqueline T Bork ◽  
Mary-Claire Roghmann
Keyword(s):  
Risk Factors ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Diabetic Foot ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Case Control Study ◽  
Case Control ◽  
Methicillin Resistant ◽  
Diabetic Foot Infections ◽  
Control Study

Abstract We identified deep diabetic foot infections by culture and conducted a case–control study examining the risk factors for moderate to severe methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PsA) diabetic foot infections. Our MRSA prevalence was lower than literature values; PsA was higher. Gangrene may be predictive of Pseudomonas infection.

Sign in / Sign up

Export Citation Format

Share Document