Interactions of Methicillin Resistant Staphylococcus aureus USA300 and Pseudomonas aeruginosa in Polymicrobial Wound Infection.

2013

Pastar I, Nusbaum AG, Gil J, Patel SB, Chen J, Valdes J, Stojadinovic O, Plano LR, Tomic-Canic M, Davis SC.

Source

Department of Dermatology and Cutaneous Surgery, Wound Healing and Regenerative Medicine Research Program, University of Miami Miller School of Medicine, Miami, Florida, United States of America.

Abstract

Understanding the pathology resulting from and polymicrobial wound infections is of great importance due to their ubiquitous nature, increasing prevalence, growing resistance to antimicrobial agents, and ability to delay healing. Methicillin-resistantUSA300 is the leading cause of community-associated bacterial infections resulting in increased morbidity and mortality. We utilized a well-established porcine partial thickness wound healing model to study the synergistic effects of USA300 and on wound healing. Wound re-epithelialization was significantly delayed by mixed-species biofilms through suppression of keratinocyte growth factor 1. showed an inhibitory effect on USA300 growth while both species co-existed in cutaneous wounds . Polymicrobial wound infection in the presence of resulted in induced expression of USA300 virulence factors Panton-Valentine leukocidin and α-hemolysin. These results provide evidence for the interaction of bacterial species within mixed-species biofilms and for the first time, the contribution of virulence factors to the severity of polymicrobial wound infections.

PubMed

Impact of Methicillin Resistant Staphylococcus aureus Contact Isolation Units on Medical Care.

2013

Masse V, Valiquette L, Boukhoudmi S, Bonenfant F, Talab Y, Carvalho JC, Alarie I, Carrier N, Farand P.

Source

Infectious Diseases Division, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada.

Abstract

BACKGROUND:

Patient isolation using contact precautions has gained widespread use to halt MRSA transmission, however supportive data is scarce and concerns regarding patient safety and satisfaction have been raised. At our institution, MRSApatients are isolated on a dedicated ward (cohort isolation), rather than in separate rooms. Our objectives were (1) to determine the proportion of bedside medical visits to patients on an isolation ward, (2) to quantify complications in those patients and (3) to determine if those complications are related to isolation and if they can be prevented.

METHODS:

This retrospective case-control study was performed on the two sites of a tertiary teaching hospital in Sherbrooke, QC, Canada. We matched MRSA patients with an admission diagnosis of heart failure or chronic obstructive pulmonary disease to similar non-isolated controls. The proportion of bedside visits was ascertained through the number of progress notes with subjective elements or with a physical examination. Complications were sought through an extensive file review, and events were analysed according to Baker's CAES causality and preventability scales.

RESULTS:

Overall, 111 patient pairs were analysed (35 with heart failure and 76 with COPD). Isolated patients received less bedside visits (subjective notes/1,000 patient-days: 849.6 983.3, p = 0,001). Attending physicians (454.5 451.4, p = 0,02) and residents (347.0 416.9, p = 0.01) are responsible for this discrepancy, while medical students appear to visit isolated and non-isolated patients equally (116.5 114.9, p = 0.90). Isolated patients showed a tendency towards longer stay and more preventable complications, although no difference in the total number of complications was observed.

CONCLUSION:

Isolated patients have less documented care that suggests less bedside visits from the medical staff, which could hamper the therapeutical relationship. Further studies are needed to explain this finding.

PubMed

Predictive factors for early mortality among patients with methicillin-resistant Staphylococcus aureusbacteraemia.

Feb 2013

Gasch O, Camoez M, Domínguez MA, Padilla B, Pintado V, Almirante B, Lepe JA, Lagarde M, Ruiz de Gopegui E, Martínez JA, Montejo M, Torre-Cisneros J, Arnáiz A, Goenaga MA, Benito N, Rodríguez-Baño J, Pujol M; on behalf of the REIPI/GEIH Study Groups.

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Source

Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain.

Abstract

OBJECTIVES:

A high proportion of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia die within a few days of the onset of infection. However, predictive factors for early mortality (EM) have barely been examined. The aim of this study was to determine the predictive factors for EM in patients with MRSA bacteraemia.

METHODS:

All episodes of MRSA bacteraemia were prospectively followed in 21 Spanish hospitals from June 2008 to December 2009. Epidemiology, clinical data, therapy and outcome were recorded. All MRSA strains were analysed in a central laboratory. Mortality was defined as death from any cause occurring in the 30 days after the onset of MRSAbacteraemia. EM was defined as patients who died within the first 2 days, and late mortality (LM) for patients who died after this period. Multivariate analyses were performed by using logistic regression models.

RESULTS:

A total of 579 episodes were recorded. Mortality was observed in 179 patients (31%): it was early in 49 (8.5%) patients and late in 130 (22.5%). Independent risk factors for EM were [OR (95% CI)] initial Pitt score >3 [3.99 (1.72-3.24)], previous rapid fatal disease [3.67 (1.32-10.24)], source of infection lower respiratory tract or unknown [3.76 (1.31-10.83) and 2.83 (1.11-7.21)], non-nosocomial acquisition [2.59 (1.16-5.77)] and inappropriate initial antibiotic therapy [3.59 (1.63-7.89)]. When predictive factors for EM and LM were compared, inappropriate initial antibiotic therapy was the only distinctive predictor of EM, while endocarditis and lower respiratory tract sources both predicted LM.

CONCLUSIONS:

In our large cohort of patients several factors were related to EM, but the only distinctive predictor of EM was inappropriate initial antibiotic therapy.

Oxford - Journal of Antimicrobial Chemotherapy

Draft Genome Sequence of the Methicillin-Resistant Staphylococcus aureus Isolate MRSA-M2.

2013

Harro JM, Daugherty S, Bruno VM, Jabra-Rizk MA, Rasko DA, Shirtliff ME.

Source

Department of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, Maryland, USA.

Abstract

We report the draft genome sequence of a methicillin-resistant strain of Staphylococcus aureus, designated MRSA-M2. This clinical isolate was obtained from an osteomyelitis patient undergoing treatment at the University of Texas Medical Branch (Galveston, TX). This strain is an ST30, spa type T019, agr III strain and has been utilized as a model S. aureus strain in a number of proteomic, transcriptomic, and animal model studies.

PubMed

Laboratory Maintenance of Methicillin-Resistant Staphylococcus aureus (MRSA).

Feb 2013

Vitko NP, Richardson AR.

Source

Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina.

Abstract

Staphylococcus aureus is an important bacterial pathogen in the hospital and community settings, especially Staphylococcus aureus clones that exhibit methicillin-resistance (MRSA). Many strains of S. aureus are utilized in the laboratory, underscoring the genetic differences inherent in clinical isolates. S. aureus grows quickly at 37°C with aeration in rich media (e.g., BHI) and exhibits a preference for glycolytic carbon sources. Furthermore, S. aureus has a gold pigmentation, exhibits β-hemolysis, and is catalase and coagulase positive. The four basic laboratory protocols presented in this unit describe how to culture S. aureus on liquid and solid media, how to identify S. aureus strains as methicillin resistant, and how to generate a freezer stock of S. aureus for long-term storage. Curr. Protoc. Microbiol.

Full Text

Wiley Online

Predicting High Prevalence of Community Methicillin-Resistant Staphylococcus aureus Strains in Nursing Homes.

Mar 2013

Murphy CR, Hudson LO, Spratt BG, Quan V, Kim D, Peterson E, Tan G, Evans K, Meyers H, Cheung M, Lee BY, Mukamel DB, Enright MC, Whealon M, Huang SS.

Source

Division of Infectious Diseases and Health Policy Research Institute, University of California, Irvine, School of Medicine, Irvine, California.

Abstract

We assessed characteristics associated with community-associated methicillin-resistant Staphylococcus aureus(CA-MRSA) carriage among residents of 22 nursing homes. Of MRSA-positive swabs, 25% (208/824) were positive for CA-MRSA. Median facility CA-MRSA percentage was 22% (range, 0%-44%). In multivariate models, carriage was associated with age less than 65 years (odds ratio, 1.2; [Formula: see text]) and Hispanic ethnicity (odds ratio, 1.2; [Formula: see text]). Interventions are needed to target CA-MRSA.

PubMed

Controlled Multicenter Evaluation of a Bacteriophage Based Method for the Rapid Detection of Staphylococcusaureus in Positive Blood Cultures.

Feb 2013

Bhowmick T, Mirrett S, Reller LB, Price C, Qi C, Weinstein MP, Kirn TJ.

Source

UMDNJ-Robert Wood Johnson Medical School, 1 Robert Wood Johnson Place, New Brunswick, NJ 08901.

Abstract

Staphylococci are a frequent cause of bloodstream infections (BSIs). Appropriate antibiotic treatment for BSIs may be delayed because conventional laboratory testing methods take 48-72 hours to identify and characterize isolates from positive blood cultures. We evaluated a novel assay based on bacteriophage amplification that identifies S. aureus and differentiates between methicillin-susceptible and methicillin-resistant S. aureus (MSSA and MRSA, respectively) in samples taken directly from signal positive BACTEC™ blood culture bottles within 24 hours of positive signal, with results available within 5 hours. The performance of the MicroPhage KeyPath™ MRSA/MSSA Blood Culture Test was compared to conventional identification and susceptibility testing methods. At four sites, we collectively tested a total of 1165 specimens of which 1116 were included in our analysis. Compared to standard methods, the KeyPath™ MRSA/MSSA Blood Culture Test demonstrated a sensitivity, specificity, positive predictive value and negative predictive value of 91.8%, 98.3%, 96.3% and 96.1%, respectively for correctly identifying S. aureus. Of those correctly identified as S. aureus (n=334), 99.1% were correctly categorized as either MSSA or MRSA. Analysis of a subset of the data revealed that the KeyPath™ MRSA/MSSA Blood Culture Test delivered results a median of 30 hours sooner than conventional methods (a median of 46.9 hours vs a median of 16.9 hours). Although the sensitivity of the test in detecting S. aureus-positive samples is not high, its accuracy in determining methicillin resistance and susceptibility among positives is very high. These characteristics may enable earlier implementation of appropriate antibiotic treatment for many S. aureus BSI patients. (Subsets of these results were presented at the 2010 ICAAC meeting in Boston, MA and the 2011 ASM meeting in New Orleans).

PubMed

Prevalence and characterization of Methicillin-resistant Staphylococcus aureus isolated from retail meat and humans in Georgia.

Jan 2013

Jackson CR, Davis JA, Barrett JB.

Source

Bacterial Epidemiology and Antimicrobial Resistance Research Unit, USDA-ARS, Russell Research Center, Athens, GA 30605.

Abstract

There is increasing interest in the presence of Staphylococcus aureus, specifically methicillin-resistant S. aureus (MRSA), on retail meat products. In this study, staphylococci were isolated from retail pork and retail beef in Georgia and MRSA from the products were compared to human MRSA from the same geographic area using broth microdilution antimicrobial susceptibility testing, Multilocus sequence typing (MLST), spa typing, SCCmec typing, and Pulsed-Field Gel Electrophoresis (PFGE). S. aureus was isolated from 45% (45/100) of pork products and 63% (63/100) of beef products; mecA was detected in S. aureus from both pork (3/100; 3%) and beef (4/100; 4%). Fifty percent (50/100) of human S. aureus also contained mecA. Multidrug resistance was detected among MRSA from all sources. All MRSA (n=57) were SCCmec type IV and nine different spa types were present among the isolates (t002, t008, t012, t024, t179, t337, t548, t681, and t1062). Four sequence types (ST5, ST8, ST9, and ST30) were detected using MLST; the majority of MRSA were ST8 followed by ST5. One retail beef MRSA was ST8, while the remaining three were ST5. In retail pork MRSA, ST5, ST9, and ST30 were observed. The majority of human MRSA were ST8. Thirty-seven MRSA isolates were pvl+, one of which was a retail beefMRSA. Using PFGE, MLST, and spa typing, three retail beef MRSA were identical in PFGE pattern, ST, and spa type to two human clonal MRSA (USA100 and USA300). One additional retail beef MRSA had a similar PFGE pattern to a human MRSAisolate, whereas none of the retail pork MRSA had similar PFGE patterns to human MRSA. This data suggests that the retail beef samples were contaminated from a human source possibly during processing of the meat and may present a source ofMRSA to consumers and others who handle raw meat.

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

Abscess Volume and Ultrasound Characteristics of Community-Associated Methicillin-Resistant Staphylococcus aureus Infection.

Jan 2013

Mistry RD, Marin JR, Alpern ER.

Source

From the *Department of Pediatrics, University of Pennsylvania School of Medicine, and Division of Emergency Medicine, Children's Hospital of Philadelphia, Philadelphia; and †University of Pittsburgh School of Medicine, Division of Pediatric Emergency Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA.

Abstract

BACKGROUND:

Skin abscesses may vary in volume and inflammation based on organism, although this has not been evaluated using emergency ultrasonography (EUS).

OBJECTIVE:

The objective of this study was to examine the utility of EUS in discerning skin abscess volume and inflammation by infecting organism.

METHODS:

This was a secondary analysis of prospectively enrolled subjects 2 months to 19 years presenting for a skin abscess. Subjects with a prior drainage procedure, multiple lesions, incomplete EUS measurements, or lack of an abscess culture were excluded. Abscess cavity dimensions in the x, y, and z planes and signs of local inflammation (cobblestoning, hyperechoic, or thickened dermis) were determined. Abscess volume was calculated using the ellipsoid formula: 4/3 π · (rx) · (ry) · (rz).

RESULTS:

One hundred eighty-eight subjects met the inclusion criteria. Mean age was 7.7 ± 6.2 years; 39.9% were male. The gluteal region was most commonly involved (33.0%), and lesions were present for a mean 4.2 days (95% confidence interval [CI], 3.8-4.6 days). Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from 125 (66.5%); methicillin-sensitive S. aureus (21.8%) was most common among non-MRSA lesions. Abscess volume was smaller in MRSA (1.12 cm) compared with non-MRSA (2.46 cm) lesions (mean difference, -1.33 cm; 95% CI, -2.21 to -0.47 cm). No differences betweenMRSA and non-MRSA lesions were present for EUS signs of inflammation. When adjusting for age, duration of lesion, and spontaneous drainage, smaller abscess volumes were associated with MRSA infection (odds ratio, 0.83; 95% CI, 0.71-0.97). Using an optimal threshold value of 1.32 cm, sensitivity and specificity for non-MRSA lesion were 50.8% and 81.5%, respectively.

CONCLUSIONS:

Methicillin-resistant S. aureus infection is statistically negatively associated with abscess volume, although of limited predictive ability. Findings using EUS suggest that MRSA does not differ from other organisms with respect to size and inflammation. Clinicians should not consider unique treatment for the presence of MRSA abscess based on these EUS findings.

PubMed

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