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Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in premature infants and is steadily rising in frequency. Patients who develop NEC have a very high mortality, illustrating the importance of developing novel prevention or treatment approaches. We and others have shown that NEC arises in part from exaggerated signaling via the bacterial receptor, Toll-like receptor 4 (TLR4) on the intestinal epithelium, leading to widespread intestinal inflammation and intestinal ischemia. Strategies that limit the extent of TLR4 signaling, including the administration of amniotic fluid, can reduce NEC development in mouse and piglet models. We now seek to test the hypothesis that a secretome derived from amnion-derived cells can prevent or treat NEC in preclinical models of this disease via a process involving TLR4 inhibition. In support of this hypothesis, we show that the administration of this secretome, named ST266, to mice or piglets can prevent and treat experimental NEC. The protective effects of ST266 occurred in the presence of marked TLR4 inhibition in the intestinal epithelium of cultured epithelial cells, intestinal organoids, and human intestinal samples ex vivo, independent of epidermal growth factor. Strikingly, RNA-seq analysis of the intestinal epithelium in mice reveals that the ST266 upregulates critical genes associated with gut remodeling, intestinal immunity, gut differentiation. and energy metabolism. These findings show that the amnion-derived secretome ST266 can prevent and treat NEC, suggesting the possibility of novel therapeutic approaches for patients with this devastating disease.

Background: Fungal prosthetic joint infections (PJIs) are rare and often associated with poor outcome; however, risk factors are not well described.Methods: This was a retrospective case control study among all patients with PJIs from 2006-2016 at two major academic centers. Each fungal PJI case was matched 1:1 with a bacterial PJI control by joint (hip, knee, shoulder) and year of diagnosis. We compared demographics, comorbidities, and clinical characteristics between cases and controls using chi square/Fisher's exact or Wilcoxon rank sum test. Independent risk factors were identified with multivariable logistic regression.Results: Forty-one fungal PJIs occurred over the study and 61% were due to Candida albicans. The hip was involved in 51.2% of cases, followed by the knee (46.3%). Compared to bacterial PJI, fungal PJI cases were more likely to have received antibiotics within the previous 3 months (70.7% vs 34%, P=.001), wound drainage lasting >5 days (48% vs 9%, P=.0002), had a lower median CRP (2.95 mg/dl vs 5.99, P=.013) and synovial fluid white blood cell count (13,953 cells/mm3 vs 33,198, P=.007), and a higher proportion of prior two-stage exchanges (82.9% vs 53.6%, P=.008). After controlling for center, prolonged wound drainage (OR, 7.3; 95% CI, 2.02-26.95) and recent antibiotics (OR, 3.4; 95% CI, 1.2-9.3) were significantly associated with fungal PJI.Conclusion: In our study, Candida albicans was the most common species in fungal PJIs and prolonged wound drainage and recent antibiotics were independent risk factors. These clinical characteristics may help providers anticipate fungal PJI and adjust management strategies.

Background In this study, we present our experience with community-acquired, culture-positive, non-tuberculous mycobacterial (NTM) infections of the hand and wrist and compare the clinical features, risk factors, diagnostic delays, and treatment outcomes among patients referred for surgical consultation at our institution over a five-year period. Methodology We retrospectively identified patients on chart review who were diagnosed with culture-positive, extrapulmonary, cutaneous NTM infections between January 1, 2014, and December 31, 2018. Only patients with community-acquired NTM infections of the hand and wrist were included. Patient demographics, risk factors, location, diagnostic delays, NTM species isolated, treatment modalities, and treatment outcomes were collected and analyzed. These variables were further compared between patients who participated in fishing-related activities and those who did not. Results A total of 10 patients were identified with community-acquired NTM infections of the hand or wrist. Of these patients, eight (80%) were male, and six (60%) had participated in fishing-related activities prior to the initial presentation. The majority of patients had

Objective An exploratory phase II, multicenter, open-label, clinical trial (NCT03687632) was conducted to evaluate the safety and effectiveness in treating persistent corneal epithelial defects (PEDs) with ST266, a proprietary novel multi-cytokine platform biologic solution secreted by cultured Amnion-derived Multipotent Progenitor (AMP) cells. Methods Subjects with a PED were treated with ST266 eye drops 4 times daily for 28 days, then followed for 1 week. Safety was assessed by monitoring of adverse events (AEs) and serious adverse events (SAEs). Efficacy was assessed by measuring the area of the PED by slit lamp biomicroscopy. Tolerability of ST266, percentage of eyes with complete healing, reduction in area of the epithelial defect, and maintenance of a reduction in the area of the epithelial defect 7 days after treatment were recorded. Results Thirteen patients were enrolled into the trial at one of eight sites. The first patient withdrew after 5 days. The remaining 12 patients with PEDs with median duration of 39 days (range = 12 to 393 days) completed treatment. Ten of the 12 eyes had been refractory to treatment with various conventional therapies prior to enrollment. After 28 days of treatment, there was a significant decrease in mean PED area compared with baseline (66.4% ± 35.3%, P = 0.001). At follow-up, 1 week after completion of treatment, on day 35, the PED area was further reduced by 78.8% ± 37.5% (P = 0.01) compared with baseline. During 28 days of treatment, 5 eyes (41.7%) had complete wound closure. There were no AEs of concern thought to be related to the drug, and no SAEs were noted. Conclusions In this trial, we found ST266 eye drops might promote corneal epithelization, thereby reducing the PED area, including in refractory cases in a wide range of etiologies. ST266 was well-tolerated by most patients.

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Routine identification of fungal pathogens from positive blood cultures by culture-based methods can be time-consuming, delaying treatment with appropriate antifungal agents. The GenMark Dx ePlex investigational use only blood culture identification fungal pathogen panel (BCID-FP) rapidly detects 15 fungal targets simultaneously in blood culture samples positive for fungi by Gram staining. We aimed to determine the performance of the BCID-FP in a multicenter clinical study. Blood culture samples collected at 10 United States sites and tested with BCID-FP at 4 sites were compared to the standard-of-care microbiological and biochemical techniques, fluorescence in situ hybridization using peptide nucleic acid probes (PNA-FISH) and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS)., Routine identification of fungal pathogens from positive blood cultures by culture-based methods can be time-consuming, delaying treatment with appropriate antifungal agents. The GenMark Dx ePlex investigational use only blood culture identification fungal pathogen panel (BCID-FP) rapidly detects 15 fungal targets simultaneously in blood culture samples positive for fungi by Gram staining. We aimed to determine the performance of the BCID-FP in a multicenter clinical study. Blood culture samples collected at 10 United States sites and tested with BCID-FP at 4 sites were compared to the standard-of-care microbiological and biochemical techniques, fluorescence in situ hybridization using peptide nucleic acid probes (PNA-FISH) and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). Discrepant results were analyzed by bi-directional PCR/sequencing of residual blood culture samples. A total of 866 clinical samples, 120 retrospectively and 21 prospectively collected, along with 725 contrived samples were evaluated. Sensitivity and specificity of detection of Candida species (C. albicans, C. auris, C. dubliniensis, C. famata, C. glabrata, C. guilliermondii, C. kefyr, C. krusei, C. lusitaniae, C. parapsilosis, and C. tropicalis) ranged from 97.1 to 100% and 99.8 to 100%, respectively. For the other organism targets, sensitivity and specificity were as follows: 100% each for Cryptococcus neoformans and C. gattii, 98.6% and 100% for Fusarium spp., and 96.2% and 99.9% for Rhodotorula spp., respectively. In 4 of the 141 clinical samples, the BCID-FP panel correctly identified an additional Candida species, undetected by standard-of-care methods. The BCID-FP panel offers a faster turnaround time for identification of fungal pathogens in positive blood cultures that may allow for earlier antifungal interventions and includes C. auris, a highly multidrug-resistant fungus.

Background/aim Inhibition of apoptosis is one of the hallmarks of cancer, and anti-apoptotic genes are often targets of genetic and epigenetic alterations. Cellular inhibitor of apoptosis 2 (cIAP2) has a role in degrading caspases by linking them to ubiquitin molecules, and is upregulated in triple-negative breast cancer (TNBC). Previous studies have demonstrated that cIAP2 may play a role in the epithelial-to-mesenchymal transition (EMT). Materials and methods Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, was administered to triple-negative breast cancer (TNBC) cells alone or in combination with epigallocatechin-3-gallate (EGCG), a DNA methyltransferase (DNMT) inhibitor isolated from green tea. Results The compounds were able to decrease the expression of cIAP2 while increasing the expression of pro-apoptotic caspase 7. There were also changes in histone modifications, suggesting a role of epigenetic mechanisms in these changes in expression of cIAP2. These changes resulted in an increase in apoptosis. SAHA and EGCG were also capable of limiting TNBC cell migration across a fibronectin (FN) matrix. Conclusion SAHA and EGCG reduce the metastatic potential of TNBC by inducing the apoptotic pathway.

Cutibacterium (formerly called Propionibacterium ) acnes is a human skin flora often implicated in orthopedic infections. The unique characteristics of this microorganism make the diagnosis of infection difficult. The diagnosis often is made based on clinical evidence, radiographic signs, and laboratory and/or surgical findings combined. Treatment often involves both pharmacologic and surgical methods. In addition, formation of biofilms and increased resistance to drugs exhibited by the microorganism can require combined antimicrobial therapy. Prophylactic measures are particularly important, but no single method has been shown to fully eliminate the risk of C acnes infections. Previous reports have focused on C acnes infections involving surgical implants or after certain orthopedic procedures, particularly in the shoulder and spine. This article reviews current clinical, diagnostic, and treatment principles for C acnes in orthopedics in general. [ Orthopedics . 2020; 43(1):52–61.]

Background PCR tests now outnumber antigen tests for the diagnosis of respiratory syncytial virus (RSV) infection in the US. Recent analyses have shown that the traditional 10% positivity threshold to define an RSV season by rapid antigen testing was inappropriate for real-time PCR testing, for which 3% positivity appeared more appropriate. Objective To respectively model antigen (10%) and PCR (3%) positivity thresholds at national and regional levels using a large dataset of RSV testing results from US hospital-affiliated laboratories. Study design From 2011–2016, 599 laboratories participated in a national RSV surveillance program (RSVAlert®). For laboratories with ≥10 tests for ≥30 weeks of a season, national and regional test numbers and positivity were summarized by test type overall, by season, and weekly within each season. Test type positivity thresholds were used to calculate season onset and offset. Results A seasonal average of 543,387 RSV tests was reported. PCR testing increased from 26% in 2011–2012 to 72% in 2015–2016. Overall, national positivity was 15.6% for antigen and 8.3% for PCR testing. National RSV season onsets and offsets were comparable using the 10% antigen and 3% PCR thresholds, but PCR-defined seasons generally started and ended later than antigen-defined seasons. Regionally, there were fewer outlier estimates of RSV season length when the predominant regional test type was used to define the season. Conclusion RSV positivity rates differed by test type, likely due to differential clinical use of the tests. These findings support the use of distinct positivity thresholds by test type.

The Army Physical Fitness Test (APFT), including timed push-ups, sit-ups, and run, assesses physical performance for the Army. Percent body fat is estimated using height and circumference measurements. The objectives of the study were to (a) compare the accuracy of height and circumference measurements to other, more accepted, body fat assessment methods and (b) determine the relationships between body composition and APFT results. Participants included Reserve Officer Training Corps (ROTC) cadets (n = 11 males, 2 females, 21.6 ± 3.5 years) from a midwestern university). At one visit, percent body fat was assessed using height and circumference measurements, air-displacement plethysmography, and bioelectrical impedance analysis. APFT results were provided by the ROTC director. All assessment methods for percent body fat were strongly associated (r ≥ 0.7, p0.01), implying that height and circumference measurement is a practical tool to estimate percent body fat of ROTC cadets. Total APFT score was not associated with any body fat assessment method. Push-up number was negatively associated with percent body fat by all assessment methods (r ≥ -0.8, p = 0.001), although run time was positively associated (r ≥ 0.6, p0.05). This suggests that percent body fat may be an important variable in determining or improving cardiovascular and muscular endurance, but not APFT performance.

Actinomyces, particularly Actinomyces israelii, may cause indolent, persistent infections or represent normal mucosal flora, leading to management dilemmas.Prompted by a refractory Actinomyces meyeri infection complicating AIDS, clinical data for all Actinomyces isolates at our hospital laboratory since 1998 were analyzed.A total of 140 cases had a positive result for Actinomyces cultures. Of 130 cases with adequate follow-up, 36 (28%) cases had end-organ or disseminated disease treated with prolonged antibiotics or surgery or both (Group 1). A. meyeri was more common than A. israelii (33% versus 8%; P0.05) in Group 1, particularly thoracic infections. Another 56 (43%) cases were considered local pathogens, treated with drainage only or short-course antibiotics (Group 2). Another 38 (29%) cases were deemed commensals (Group 3). Immunosuppression was less frequent in Group 1 versus Group 2 or 3 (P = 0.05) and human immunodeficiency virus or AIDS was uncommon. Foreign bodies or devices (Group 1 versus Group 2 or 3, P = 0.003) and alcoholism (Group 1 versus Group 2 or 3; P = 0.03) were associated with actinomycosis. Isolates from the central nervous system and musculoskeletal sites were more often treated as definitive disease; skin, abdominal or pelvic or single blood culture isolates were more likely commensals (all P0.05). Disease progression or recurrence did not occur in Groups 2 and 3, whereas Group 1 had complex and variable courses, including 2 deaths.In the absence of disseminated or end-organ disease, avoiding prolonged therapy for Actinomyces isolates was not associated with adverse outcomes. Alcoholism or foreign bodies were associated with actinomycosis. A. meyeri may be a more common cause of actinomycosis than previously recognized.

We describe a febrile adult returning to the U.S. from Nigeria. Malaria was diagnosed by rapid antigen testing, but recognition of invasive nontyphoidal Salmonella disease was delayed. While the moniker, “typhomalaria,” once used to describe an illness with features of malaria and typhoid fever, has fallen out of favor, it may nevertheless be a helpful reminder to clinicians that both infectious diseases can arise in the same patient. Blood cultures should be obtained routinely in febrile returning travelers from malaria-endemic regions, including those in whom the diagnosis of malaria has already been established.

Ceftolozane/tazobactam (C/T) was tested and compared against 93 nonfermenting, Gram-negative clinical isolates from cystic fibrosis specimens. Based on current breakpoints for intra-abdominal and urinary tract infections (which may not be appropriate for pulmonary infections), C/T was found to be the most active agent against P. aeruginosa (95.7% susceptible), followed by piperacillin/tazobactam (89.4% susceptible). For other Gram-negative pathogens included, C/T had varying activity.

Background Insufficient data exist for how long endoscopes can be stored after reprocessing. Concern about possible microbial colonization has led to various recommendations for reprocessing intervals among institutions, with many as short as 5 days. A significant cost savings could be realized if it can be demonstrated that endoscopes may be stored for as long as 21 days without risk of clinically significant contamination. Objective To demonstrate whether flexible endoscopes may be stored for as long as 21 days after reprocessing without colonization by pathogenic microbes. Design Prospective, observational study. Setting Tertiary care center. Endoscopes Four duodenoscopes, 4 colonoscopes, and 2 gastroscopes. Intervention Microbial testing of endoscope channels. Main Outcome Measurements Culture results at days 0, 7, 14, and 21. Results There were 33 positive cultures from 28 of the 96 sites tested (29.2% overall contamination rate). Twenty-nine of 33 isolates were typical skin or environmental contaminants, thus clinically insignificant. Four potential pathogens were cultured, including Enterococcus , Candida parapsilosis , α-hemolytic Streptococcus , and Aureobasidium pullulans ; all were likely clinically insignificant as each was only recovered at 1 time point at 1 site, and all grew in low concentrations. There were no definite pathogenic isolates. Limitations Single center. Conclusion Endoscopes can be stored for as long as 21 days after standard reprocessing with a low risk of pathogenic microbial colonization. Extension of reprocessing protocols to 21 days could effect significant cost savings.

Ceftolozane-tazobactam is a cephalosporin-β-lactamase inhibitor combination that exhibits potent in vitro activity against Pseudomonas aeruginosa , including strains that are resistant to other β-lactams. The emergence of ceftolozane-tazobactam resistance among clinical isolates of P. aeruginosa has rarely been described. Here we characterized ceftolozane-tazobactam-resistant P. aeruginosa strains recovered from a patient who was treated with this agent for 6 weeks for a recurrent wound infection. The results showed that the resistance was mediated by a single AmpC structural mutation.

The vast bacteriophage population harbors an immense reservoir of genetic information. Almost 2000 phage genomes have been sequenced from phages infecting hosts in the phylum Actinobacteria, and analysis of these genomes reveals substantial diversity, pervasive mosaicism, and novel mechanisms for phage replication and lysogeny. Here, we describe the isolation and genomic characterization of 46 phages from environmental samples at various geographic locations in the U.S. infecting a single Arthrobacter sp. strain. These phages include representatives of all three virion morphologies, and Jasmine is the first sequenced podovirus of an actinobacterial host. The phages also span considerable sequence diversity, and can be grouped into 10 clusters according to their nucleotide diversity, and two singletons each with no close relatives. However, the clusters/singletons appear to be genomically well separated from each other, and relatively few genes are shared between clusters. Genome size varies from among the smallest of siphoviral phages (15,319 bp) to over 70 kbp, and G+C contents range from 45-68%, compared to 63.4% for the host genome. Although temperate phages are common among other actinobacterial hosts, these Arthrobacter phages are primarily lytic, and only the singleton Galaxy is likely temperate.

Background Respiratory syncytial virus (RSV) produces annual epidemics that vary in the timing of season onset, peak, and duration by season and by geographic region. Recent analyses by the US Centers for Disease Control at the national level have demonstrated that polymerase chain reaction (PCR) testing has largely replaced rapid antigen testing as the predominant test type and that the traditional 10% positivity threshold for defining an RSV season based on antigen testing should not be applied to PCR testing, for which the comparable threshold for real-time surveillance was 3%. The aim of this study was to validate and model implementation of the antigen (10%) and PCR (3%) positivity thresholds at regional, state, and local levels in a large national dataset of RSV testing results from US hospitals. Methods RSV test results were obtained from 599 laboratories that participated from 2011 to 2016 in RSVAlert®, a national RSV surveillance program. For laboratories that provided consistent weekly data (≥10 tests for ≥30 weeks of a season), regional test numbers and positivity were summarized weekly by test type within each season. Season onset and offset were calculated for the 10 US Department of Health and Human Services (HHS) regions and 10 large states plus Hawaii based on (1) antigen only for all seasons, (2) PCR only for all seasons, and (3) the predominant test type used in a specific geography in a season (either antigen or PCR). Results An average of 543,340 RSV tests was reported each season. At the regional and state levels, there were fewer outlier estimates of RSV season length when the predominant regional test type was used to define the season (Figures 1 and 2). Exceptions were few and occurred with antigen testing data. Conclusion Overall, PCR positivity of 3% was comparable to antigen positivity of 10% at the regional and state levels. Local RSV season determination was most reliable when based on the predominant test type utilized. Funded by AstraZeneca Disclosures C. S. Ambrose, AstraZeneca: Employee, Salary and Stocks.

Background Reliable, simple methods to assess environmental contamination with Clostridioides difficile are needed for studies of terminal disinfection effectiveness and transmission of C. difficile from fomites. We compared two novel sampling methods for assessment of C. difficile contamination: (1) isopropanol wipe sampling with broth enrichment (IW), where alcohol wipes are used to sample surfaces followed by immersion in CDBB-TC broth and (2) ethanol-shock hand imprint sampling (HI), where surfaces are sampled by gloved hands moistened with ethanol hand sanitizer followed by imprinting hands on selective agar (CDBA-TC). Both methods allow for sampling of complex surfaces common in hospital environments. Methods We performed a laboratory simulation study using six 10-fold dilutions (101–106) of C. difficile spores from two strains sampled from fiberglass surfaces by IW and HI. We then performed a field study of 10 sites in 11 hospital rooms of patients with C. difficile infection (CDI) diagnosed < 48 hours prior to sampling. Results for the HI and IW method were quantitative and qualitative, respectively. We compared room contamination prevalence (total CFU per room by HI and sites positive/total sites per room) to the cycle crossing threshold (CT) from the diagnostic C. difficile PCR test (Cepheid) from the room occupant. Results The IW laboratory limit of detection was 101 spores compared with 104 spores for HI. In the field study, IW and HI detected C. difficile contamination in 9/11 (82%) rooms at 22/110 (20%) sites and 5/11 (45%) rooms at 22/110 (20%) sites, respectively (Table 1). Six rooms with no detection by the HI method had a lower median number of sites positive per room compared with the 5 rooms with ≥1 cfu (1 vs 6, P < 0.05) (Table 1). The most commonly contaminated sites were linens (53%), call bells (43%), toilets (40%), blood pressure cuffs (40%), over-bed tables (38%), and bedrails (30%) (Table 2). Higher tcdB CT was associated with a lower total room contamination prevalence (Figures 1 and 2). Conclusion Our data suggest that the IW method is more sensitive for detection of C. difficile in the hospital environment, but the HI method offers quantitation. The prevalence of hospital room contamination for CDI patients appears to correspond with their toxin burden as estimated by PCR. Disclosures All authors: No reported disclosures.

Exophiala oligosperma is an uncommon pathogen associated with human infections, predominantly in immunocompromised hosts. Case reports of clinical infections related to E. oligosperma have been limited to 6 prior publications, all of which have shown limited susceptibility to conventional antifungal therapies, including amphotericin B, itraconazole, and fluconazole. We describe the first case of an E. oligosperma induced soft-tissue infection successfully treated with a 3-month course of voriconazole without persisting lesions.

We report the development of a collaborative relationship between antimicrobial stewardship and clinical microbiology that incorporates stewardship practices into daily laboratory rounds. Antimicrobial stewardship involvement on rounds was a welcomed and effective initiative with substantial rates of intervention. New opportunities to positively impact use of antimicrobials and laboratory resources were realized.

We examine the relationship between goal setting and transfer of training as measured on a 360-degree survey collected 3 months after a 5-day leadership development program. Leaders set personal go...

Microbial growth in heating ventilation and air-conditioning (HVAC) systems with the subsequent contamination of indoor air is of increasing concern. Microbes and the subsequent biofilms grow easily within heat exchangers. A comparative study where heat exchangers fabricated from antimicrobial copper were evaluated for their ability to limit microbial growth was conducted using a full-scale HVAC system under conditions of normal flow rates using single-pass outside air. Resident bacterial and fungal populations were quantitatively assessed by removing triplicate sets of coupons from each exchanger commencing the fourth week after their installation for the next 30 weeks. The intrinsic biofilm associated with each coupon was extracted and characterized using selective and differential media. The predominant organisms isolated from aluminum exchangers were species of Methylobacterium of which at least three colony morphologies and 11 distinct PFGE patterns we found; of the few bacteria isolated from the copper exchangers, the majority were species of Bacillus. The concentrations and type of bacteria recovered from the control, aluminum, exchangers were found to be dependent on the type of plating media used and were 11,411-47,257 CFU cm(-2) per coupon surface. The concentration of fungi was found to average 378 CFU cm(-2). Significantly lower concentrations of bacteria, 3 CFU cm(-2), and fungi, 1 CFU cm(-2), were recovered from copper exchangers regardless of the plating media used. Commonly used aluminum heat exchangers developed stable, mixed, bacterial/fungal biofilms in excess of 47,000 organisms per cm(2) within 4 weeks of operation, whereas the antimicrobial properties of metallic copper were able to limit the microbial load affiliated with the copper heat exchangers to levels 99.97 % lower during the same time period.

Pulmonary mycetomas often occur in fibrocystic sarcoidosis. When this condition is complicated by hemoptysis, definitive surgery is usually precluded because of poor lung function. Intracavitary antifungal therapy has been described for the treatment of symptomatic pulmonary mycetomas. We report the first use of intracavitary voriconazole in the management of a Pseudallescheria angusta pulmonary mycetoma complicated by hemoptysis in a patient with fibrocystic sarcoidosis and renal transplant.

1. Co-chaired this panel, 2. Department of Surgery, University of Michigan, Ann Arbor, Michigan, 3. Department of Surgery, University of South Florida, Tampa, Florida, 4. Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, 5. Department of Surgery, Sinai Hospital/Johns Hopkins University, Baltimore, Maryland, 6. Department of Surgery, NYU School of Medicine, New York, New York, 7. PolyRemedy Inc., Mountain View, California, 8. Department of Wound Healing, Cardiff University, Cardiff, Wales, United Kingdom, 9. Department of Surgery, Johns Hopkins University, Baltimore, Maryland, 10. Institute for Tissue Regeneration, Repair, and Rehabilitation, Bay Pines VA Healthcare System, Bay Pines, Florida, 11. Division of Plastic Surgery, University of South Florida, Tampa, Florida, 12. Department of Surgery, University of Arizona, Tucson, Arizona, and 13. Barnes Jewish Hospital, Washington University, St. Louis, Missouri

Background: Preclinical animal studies with a fetal bovine dermal collagen matrix suggest that fibroblasts quickly populate the material. At the same time there is a rapid ingrowth of new blood vessels. In short, the matrix quickly becomes living tissue. Experience with bioengineered skin constructs and porcine small intestinal submucosal products suggest that the application of a scaffold or matrix may play a role in the healing of venous leg ulcerations in humans. Methods: A fetal bovine dermal collagen matrix (Primatrix) was applied to patients with long-standing venous leg ulcerations. Histologic examination pre and post application with trichrome staining was employed to differentiate matrix from native collagen. Comparisons between animal and human ulcers were made grossly and histologically. Results: In all patients there was rapid formation of granulation tissue with a decrease in the depth of the wound. This was followed by epithelialization and wound closure. The stimulatory effect persisted for approximately 1 month after which time a second matrix was applied. In contrast to the animal study the grafts exhibited “take” in only one of our patients. Histologic examination in both animals and humans suggests a stimulation of native collagen production as well as an initial incorporation of the Primatrix into the wound bed. Conclusion: Primatrix has demonstrated efficacy in preclinical studies and in a series of patients with venous leg ulcerations. The product may function as a scaffold for the ingrowth of cells essential to wound healing. Further investigation in a randomized controlled study setting is recommended. Acknowledgment: TEI Biosciences

Background.Colonization with vancomycin-resistantEnterococcus(VRE) is a risk factor for subsequent VRE bloodstream infection (BSI); however, risk factors for BSI among colonized patients have not been adequately described. We sought to determine the proportion of VRE-colonized patients who subsequently develop VRE BSI and to identify risk factors for VRE BSI among these patients.Methods.Records of 768 patients colonized with VRE from January 2002 through June 2005 were reviewed. The proportion of patients who developed VRE BSI was calculated, and the characteristics of these patients were compared, in a 2 : 1 ratio, with those of patients who did not develop VRE BSI. To identify risk factors for VRE BSI and for death, we used univariate logistic regression analysis and then multivariate logistic regression analysis. Using pulsed-field gel electrophoresis (PFGE), we compared the isolate recovered when the patient was colonized and the isolate recovered when the patient developed VRE BSI.Results.Of the 768 patients colonized with VRE, 31 (4.0%) developed VRE BSI. Multivariate analysis identified the following idependent risk factors for developing VRE BSI: infection of an additional body site other than blood (adjusted odds ratio [aOR], 3.9;P= .04), admission to the hospital from a long-term care facility (aOR, 12.6;P= .04), and receipt of vancomycin (aOR, 10.6;P< .001). The independent risk factors for death among patients colonized with VRE were immunosuppression (aOR, 12.9;P= .001 ) and VRE BSI (aOR, 9.1;P= .002). Of the 31 patients who developed VRE BSI, 23 (74%) had a pair of isolates representing VRE colonization and VRE BSI. For 19 (83%) of these 23 patients, the isolate representing BSI was genetically related to the isolate representing VRE colonization: 12 pairs of isolates (52%) had identical banding patterns, 5 had closely related patterns, and 2 had possibly related patterns.Conclusion.Of the 768 patients colonized with VRE, 31 (4.0%) usually developed VRE BSI due to a related strain. Independent risk factors for BSI among colonized patients were admission from a long-term care facility, infection of an additional body site, and exposure to vancomycin. Independent risk factors for death were immunosuppression and VRE BSI.