Methicillin-resistant Staphylococcus aureus - induced thrombo-inflammatory response is reduced with timely antibiotic administration.

Jan 2013

Franks Z, Campbell RA, Vieira de Abreu A, Holloway JT, Marvin JE, Kraemer BF, Zimmerman GA, Weyrich AS, Rondina MT.

Source

Matthew T. Rondina, MD, University of Utah, Department of Internal Medicine, 50 North Medical Drive, Room 4B120, SLC, Utah 84132, USA, Tel.: +1 801 581 7818, Fax: +1 801 585 1393, E-mail: matthew.rondina@hsc.utah.edu.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA ) induces a pro-thrombotic and pro-inflammatory milieu. Although timely antibiotic administration in MRSA sepsis may improve outcomes by arresting bacterial growth, the effects of antibiotics on mitigating injurious thrombo-inflammatory cellular responses remains unexplored. Using a newly developed human whole blood model and an in vivo mouse model of MRSA infection, we examined how antibiotics inhibit MRSA induced thrombo-inflammatory pathways. Human whole blood was inoculated with MRSA. Thrombin generation and inflammatory cytokine synthesis was measured in the presence or absence of linezolid and vancomycin. C57BL/6 mice were injected with MRSAand the effect of vancomycin administration was examined. MRSA accelerated thrombin generation in a time- and concentration-dependent manner and induced the release of cytokines, including interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1. The increase in thrombin generation and inflammatory responses was mediated through the synthesis of tissue factor and cytokines, respectively, and the release of microparticles. The early administration of antibiotics restored normal thrombin generation patterns and significantly reduced the synthesis of cytokines. In contrast, when antibiotic administration was delayed, thrombin generation and cytokine synthesis were not significantly reduced. In mice infected with MRSA, early antibiotic administration reduced thrombin anti-thrombin complexes and cytokine synthesis, whereas delayed antibiotic administration did not. These data provide novel mechanistic evidence of the importance of prompt antibiotic administration in infectious syndromes.

Schattauer

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

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

Matched-Cohort DNA Microarray Diversity Analysis of Methicillin Sensitive and Methicillin Resistant Staphylococcus aureus Isolates from Hospital Admission Patients.

2012

Ruffing U, Akulenko R, Bischoff M, Helms V, Herrmann M, von Müller L.

Source

Institute of Medical Microbiology and Hygiene, Saarland University Medical Center, Homburg/Saar, Germany.

Abstract

As genotyping of S. aureus is important for epidemiologic research and for hygiene management, methods are required for standardized fast and easily applicable evaluation of closely related epidemic strains with high prevalence in hospitals. In this single centre matched control study we compared a new commercially available DNA microarray (IdentiBAC) with standard spa-typing for S. aureus genotyping. Included in the study was a subgroup of 46 MRSA and matched 46 MSSA nasal isolates of the Saarland University Medical Center collected during a state-wide admission prevalence screening. Microarray (MA) and also spa-typing could easily differentiate the genetically diverse MSSA group. However, due to the predominance of CC5/t003 in the MRSA group a sufficient subtyping required analysis of more complex genetic profiles as was shown here by the MA comprising a total number of 334 different hybridization probes. The genetic repertoire of the MRSA group was characterized by more virulence genes as compared to the MSSA group. The standard evaluation of MA results by the original software into CCs, agr-, SCCmec- and capsule-types was substituted in the present study by implementation of multivariate subtyping of closely related CC5 isolates using three different bioinformatic methods (splits graph, cluster dendrogram, and principal component analysis). Each method used was applicable for standardized and highly discriminative subtyping with high concordance. We propose that the identified S. aureus subtypes with characteristic virulence gene profiles are presumably associated also with virulence and pathogenicity in vivo; however, this remains to be analyzed in future studies. MA was superior to spa-typing for epidemiologic and presumably also provide functional respectively virulence associated characterization of S. aureus isolates. This is of specific importance for the hospital setting. In future, MA could become a new standard test for S. aureus typing in combination with multivariate bioinformatic analysis.

PubMed

A case of refractory deep incisional surgical site infection due to methicillin-resistant Staphylococcus aureus(MRSA) and successfully treated with oral linezolid.

Nov 2012

[Article in Japanese]

Matsumoto H, Kawabata R, Kishimoto T, Yamamoto E, Kimura Y, Imamura H, Yamamoto T, Takemoto H, Fukunaga M,Ohzato H.

Source

Dept. of Surgery, Sakai City Hospital.

Abstract

We report a case of methicillin-resistant Staphylococcus aureus(MRSA) surgical site infection successfully treated with linezolid. A 66-year-old man had undergone total gastrectomy for gastric cancer after neoadjuvant chemotherapy. Three days after the operation, he was diagnosed with deep incisional surgical site infection due to MRSA, and wound care was started. After discharge, he received adjuvant chemotherapy and wound care, but the wound had not healed in 10 months. We started treatment with oral linezolid and nutritional support, and the wound was fully healed 12 months after the operation. Antibiotic treatment with oral linezolid may be effective for refractory deep incisional surgical site infection due to MRSA in outpatients.

PierOnline

Incidence and seasonal distribution of methicillin-resistant Staphylococcus aureus in adult outpatients at a clinic in Buenos Aires province: period 2006 to 2011

Oct 2012

[Article in Spanish]

Verón MT, Ojeda MG, Avino F, Spelzzini A, Barboza AL, Petrozzino Y.

Source

Servicio de Infectología y Microbiología Clínica, Clínica Privada Independencia. Luis María Drago 5681 (1605) Munro, Provincia de Buenos Aires, Argentina. E-mail: mtveron@gmail.com.

Abstract

In the last decade there was a significant growth of community-acquired methicillin-resistant Staphylococcus aureus(ca-MrSa). We herein describe the annual incidence, seasonal distribution, antimicrobial resistance and phenotypes of MrSain adult outpatients. From january 2006 to december 2011, 173 strains of S. aureus were studied, 77 (45 %) of which wereMrSa. The annual incidence per 100 processed materials increased from 0.13 in 2006 to 0.62 in 2011 due to the oxacillin-resistant phenotype, showing peaks in springsummer until december 2008 and subsequent peaks in autumn-winter. The antimicrobial resistance profile was: erythromycin 24 (31 %), clindamycin 22 (29 %), gentamicin 23 (30 %), ciprofloxacin 13 (17 %), trimethoprim-sulfamethoxazole 3 (4 %), chloramphenicol 2 (3 %), rifampicin 2 (3 %), and minocycline 0. Sixteen phenotypes were identified; the oxacillin-resistant phenotype being the most common, accounting for 53 % (41 isolates) and exhibiting an increase ranging from 31 % to 65 %. The empirical treatment of infections was changed and prevention measures were implemented among contacts.

PubMed

Long-Term Risk for Readmission, Methicillin-resistant Staphylococcus aureus (MRSA) Infection, and Death among MRSA-Colonized Veterans.

Dec 2012

Quezada Joaquin NM, Diekema DJ, Perencevich EN, Bailey G, Winokur PL, Schweizer ML.

Source

Division of Infectious Diseases.

Abstract

Background: 

While numerous studies assessed outcomes of MRSA colonization over the short term, little is known about longer-term outcomes after discharge. An assessment of long-term outcomes could inform the utility of various MRSA prevention approaches.Methods: A matched cohort study was performed among Veterans Affairs (VA) patients screened for MRSA colonization between the years 2007 and 2009 and followed to evaluate outcomes until 2010. Cox proportional hazard models were used to evaluate the association between MRSA colonization and long-term outcomes such as infection-related readmission, and crude mortality.Results: 404 veterans were included, 206 of whom were MRSA carriers and 198 who were non-carriers. There were no culture-proven MRSA infections on readmission among the non-carriers, but 13% of MRSA-carriers were readmitted with culture proven MRSA infections on readmission  MRSA carriers were significantly more likely to be readmitted, be readmitted more than once due to proven or probable MRSA infections, and be readmitted within 90 days of discharge compared to non-carriers. Infection-related readmission (adjusted hazard ratio [AHR] =4.07; 95% confidence interval [CI]: 2.16, 7.67) and mortality (AHR=2.71; 95% CI: 1.87, 3.91) were significantly higher amongMRSA carriers compared to non-carriers, after statistically adjusting for potential confounders

Conclusions: 

Among a cohort of VA patients, MRSA carriers are at high risk of infection-related readmission, MRSA infection and mortality compared to non-carriers. Non- carriers are at very low risk of subsequent MRSA infection. Future studies should address whether interventions such as nasal or skin decolonization could result in improved outcomes for MRSA carriers.

Antimicrobial Agents and Chemotherapy