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

MRSA Nasal Carriage Patterns and the Subsequent Risk of Conversion between Patterns, Infection, and Death.

2013

Gupta K, Martinello RA, Young M, Strymish J, Cho K, Lawler E.

Source

The National Center for Occupational Health and Infection Control (COHIC), Office of Public Health, Department of Veterans Affairs, Gainesville, Florida, United States of America ; Department of Medicine, Veterans Affairs Boston Health Care System, West Roxbury, Massachusetts, United States of America ; Massachusetts Veterans Epidemiology Research and Information Center, Jamaica Plain, Massachusetts, United States of America ; Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.

Abstract

BACKGROUND:

Patterns of methicillin-resistant S. aureus (MRSA) nasal carriage over time and across the continuum of care settings are poorly characterized. Knowledge of prevalence rates and outcomes associated with MRSA nasal carriage patterns could help direct infection prevention strategies. The VA integrated health-care system and active surveillance program provides an opportunity to delineate nasal carriage patterns and associated outcomes of death, infection, and conversion in carriage.

METHODS/FINDINGS:

We conducted a retrospective cohort study including all patients admitted to 5 acute care VA hospitals between 2008-2010 who had nasal MRSA PCR testing within 48 hours of admission and repeat testing within 30 days. The PCR results were used to define a baseline nasal carriage pattern of never, intermittently, or always colonized at 30 days from admission. Follow-up was up to two years and included acute, long-term, and outpatient care visits. Among 18,038 patients, 91.1%, 4.4%, and 4.6% were never, intermittently, or always colonized at the 30-day baseline. Compared to non-colonized patients, those who were persistently colonized had an increased risk of death (HR 2.58; 95% CI 2.18;3.05) and MRSA infection (HR 10.89; 95% CI 8.6;13.7). Being in the non-colonized group at 30 days had a predictive value of 87% for being non-colonized at 1 year. Conversion to MRSA colonized at 6 months occurred in 11.8% of initially non-colonized patients. Age >70 years, long-term care, antibiotic exposure, and diabetes identified >95% of converters.

CONCLUSIONS:

The vast majority of patients are not nasally colonized with MRSA at 30 days from acute hospital admission. Conversion from non-carriage is infrequent and can be risk-stratified. A positive carriage pattern is strongly associated with infection and death. Active surveillance programs in the year following carriage pattern designation could be tailored to focus on non-colonized patients who are at high risk for conversion, reducing universal screening burden.

PLOSOne

Continuous high-dose vancomycin combination therapy for methicillin-resistant staphylococcal prosthetic hip infection: a prospective cohort study.

OCt 2012

Dubée V, Zeller V, Lhotellier L, Kitzis MD, Ziza JM, Mamoudy P, Desplaces N.

Source

Service de Médecine Interne et Rhumatologie, Paris, France.

Abstract

Few data are available on treatment and outcome of methicillin-resistant (MR) staphylococcal prosthetic joint infections. Vancomycin remains the treatment of choice for these infections, but its efficacy and safety in bone-and-joint infections are insufficiently documented. We conducted a prospective cohort study on 60 patients treated between November 2002 and December 2008 for chronic MR staphylococcal (44 S. epidermidis, nine other coagulase-negative Staphylococcus and seven S. aureus) prosthetic hip infections (PHIs). Twenty-two patients had previously undergone surgery for their PHI and 21 had previously received antibiotics. All patients had surgery (exchange arthroplasty for 58 patients, resection arthroplasty for two) and received an antibiotic regimen combining high-dose continuous intravenous vancomycin infusion (target serum concentration 30-40 mg/L) with another antibiotic for 6 weeks, followed by an additional 6 weeks of oral intake. Two years after surgery, infection was considered cured in 41 (68%) patients and only two relapses occurred after one-stage exchange arthroplasty. Nineteen (32%) patients experienced nephrotoxicity that was generally mild (RIFLE class R for 14 patients, class I for four patients and class F for one patient) and most often reversible. Continuous high-dose intravenous vancomycin combination therapy is an effective, feasible and reasonably safe treatment of chronic MR staphylococcal PHI.

Wiley Online

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