Targeting Macrophage Activation for the Prevention and Treatment of Staphylococcus aureus Biofilm Infections.

Jan 2013

Hanke ML, Heim CE, Angle A, Sanderson SD, Kielian T.

Source

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198.

Abstract

Biofilm infections often lead to significant morbidity due to their chronicity and recalcitrance to antibiotics. We have demonstrated that methicillin-resistant Staphylococcus aureus (MRSA) biofilms can evade macrophage (MΦ) antibacterial effector mechanisms by skewing MΦs toward an alternatively activated M2 phenotype. To overcome this immune evasion, we have used two complementary approaches. In the first, a proinflammatory milieu was elicited by local administration of classically activated M1 MΦs and in the second by treatment with the C5a receptor (CD88) agonist EP67, which invokes MΦ proinflammatory activity. Early administration of M1-activated MΦs or EP67 significantly attenuated biofilm formation in a mouse model of MRSA catheter-associated infection. Several proinflammatory mediators were significantly elevated in biofilm-infected tissues from MΦ- and EP67-treated animals, revealing effective reprogramming of the biofilm environment to a proinflammatory milieu. A requirement for MΦ proinflammatory activity was demonstrated by the fact that transfer of MyD88-deficient MΦs had minimal impact on biofilm growth. Likewise, neutrophil administration had no effect on biofilm formation. Treatment of established biofilm infections with M1-activated MΦs also significantly reduced catheter-associated biofilm burdens compared with antibiotic treatment. Collectively, these results demonstrate that targeting MΦ proinflammatory activity can overcome the local immune inhibitory environment created during biofilm infections and represents a novel therapeutic strategy.

PubMed

Pharmacoeconomic analysis of the treatment of methicillin-resistant Staphylococcus aureus with daptomycin or vancomycin

Pharmacoeconomic analysis of the treatment of methicillin-resistant Staphylococcus aureus with daptomycin or vancomycin

Dec 2012

[Article in Spanish]

Rubio-Terrés C, Rubio-Rodríguez D, Majos N, Grau S.

Source

Carlos Rubio Terrés, Health value, C/ Virgen de Aránzazu, 21. 5ºB, 28034, Madrid, Spain. crubioterres@healthvalue.org.

Abstract

Introduction. 

The increased morbidity, mortality and high costs associated with bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) is a major public health problem. Pharmacoeconomic analysis was performed to compare the efficiency of daptomycin (DAP) against vancomycin (VAN) in the treatment of this infection. 

Methods. 

Retrospective, deterministic and probabilistic cost-effectiveness analysis. The effectiveness of the treatments was estimated from the results of a randomized clinical trial, which compared DAP (6 mg / kg IV daily) and VAN (1 g IV every 12 hours), both with or without gentamicin (1 mg / kg IV every 8 hours). Resource utilization was estimated from the clinical trial of the drug datasheets and Spanish sources, the unit costs were obtained also from Spanish sources. Monte Carlo probabilistic analysis and deterministic analysis were performed. 

Results. 

The clinical trial cure rates were higher with DAP (44.4%, 95% CI 43.5 to 45.4%) than with VAN (31.8%, 95% CI 30.9 to 32.7%) not statistically significant (p = 0.2203) but with economic impact. With DAP would occur less costs due to treatment failure (rescue antibiotics, additional tests, prolonged hospital stay and adverse reactions) than with VAN. In the base case the average cost of disease per patient was € 12,329 to € 12,696 with DAP and VAN (difference of 367 €). DAP treatment was dominant (more effective, with lower costs than VAN) both in the deterministic and probabilistic analysis. In the Monte Carlo simulation, DAP was the most cost-effective treatment in 100% of the 10,000 simulations, for a willingness to pay € 12,000 per additional cure (approximate cost of MRSA bacteraemia episode). 

Conclusions. 

According to this model, daptomycin is more cost-effective than vancomycin in treating MRSA bacteremia. The higher cost of acquisition of daptomycin does not imply a higher cost of treating this infection.

PubMed

Study determines best treatment timeline for MRSA-related pneumonia

Paul Tinder

A recent study at Henry Ford Hospital found that while the national practice guideline for treating MRSA-related pneumonia is seven to 21 days, effective treatment time could be achieved in half that time.

Researchers determined that patients treated for eight to 13 days on a therapy of either vancomycin or linezolid antibiotics experienced the highest rate of survival. The study is thought to be the first to evaluate MRSA-related pneumonia’s length of treatment.

The study was presented on Friday at the San Diego-based meeting of the Infectious Diseases Society of America.

“Based on our study, clinicians can effectively treat their patients within eight to 13 days, thus minimizing patients’ exposure to antibiotics and their side effects,” Hadeel Zainah, the study’s lead author, said.

The retrospective study involved the evaluation of the medical charts of 115 patients who were hospitalized with MRSA pneumonia. The patients received either linezolid, vancomycin or both.

Forty-percent of the patients were treated from eight to 13 days, 27 percent were treated for 14 to 20 days, and 13.9 percent of patients received treatment for more than 20 days. Patients treated between 14 and 20 days and for more than 20 days experienced lower survival rates.

Thirty-two of the patients died after 28 days.

The study did not evaluate if treatment duration affected length of stay or whether one antibiotic was more effective than the other.

MRSA-related pneumonia is a respiratory illness that can follow a bout of influenza. Symptoms include fever, chills, shortness of breath, headache, sore throat and cough.

Vaccine News Daily

Methicillin-resistant Staphylococcus aureus (MRSA) in the Athlete.

Methicillin-resistant Staphylococcus aureus (MRSA) in the Athlete.

Int J Sports Med. 2009 Aug

D. E. RedziniakD. R. DiduchK. TurmanJ. HartT. L. GrindstaffJ. M. MacKnightD. J. Mistry

The Orthopedic and Sports Medicine Center, Department of Orthopedic Surgery, Annapolis 21409, USA. redziniak@verizon.net

Although once considered only a nosocomial pathogen, methicillin-resistant Staphylococcus aureus (MRSA) is a rapidly emerging, problematic infection in the community. Community acquired MRSA (CA-MRSA) is notably becoming more prevalent in athletic environments and unfortunately, can be easily transmitted via superficial abrasions and minor skin trauma. CA-MRSA infections are highly contagious and are associated with significant morbidity, with published reports of up to 70% of infected team members requiring hospitalization and intravenous antibiotics . Risk factors for athletic related environments include contact sports with repeated close physical contact with other competitors, open abrasions, and sharing of personal equipment. Failure to correctly diagnose and appropriately treat skin and soft tissue lesions infected with CA-MRSA may contribute to large scale MRSA infections in athletic environments. The purpose of this review article is to help sports medicine physicians prevent, identify, and treat MRSA skin and superficial soft tissue infections in athletic environments. Georg Thieme Verlag KG Stuttgart New York.

Thieme Connect