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Evans C.T.,Hines Veterans Administration Hospital | Evans C.T.,Northwestern University | Safdar N.,William S. Middleton Memorial Veterans Hospital | Safdar N.,University of Wisconsin - Madison
Clinical Infectious Diseases | Year: 2015

Clostridium difficile is the most frequently identified cause of nosocomial diarrhea and has been associated with epidemics of diarrhea in hospitals and long-term care facilities. The continued increase in C. difficile infection (CDI) suggests that it has surpassed other pathogens in causing healthcare-associated infections. The Centers for Disease Control and Prevention recently identified CDI as an "urgent threat" in its recent report on antibiotic resistance threats in the United States, highlighting the need for urgent and aggressive action to prevent this infection. The impact of antibiotics as a risk factor for new-onset CDI is well established; however, recognizing classes of antibiotics with the highest risks and reducing unnecessary antibiotic use are important strategies for prevention of CDI and subsequent recurrence. In addition, the recognition of the community as an important setting for onset of CDI presents a challenge and is an area for future research. © 2015 Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015.


Kemp J.J.,University of Wyoming | Lickel J.J.,William S. Middleton Memorial Veterans Hospital | Deacon B.J.,University of Wyoming
Behaviour Research and Therapy | Year: 2014

Although the chemical imbalance theory is the dominant causal explanation of depression in the United States, little is known about the effects of this explanation on depressed individuals. This experiment examined the impact of chemical imbalance test feedback on perceptions of stigma, prognosis, negative mood regulation expectancies, and treatment credibility and expectancy. Participants endorsing a past or current depressive episode received results of a bogus but credible biological test demonstrating their depressive symptoms to be caused, or not caused, by a chemical imbalance in the brain. Results showed that chemical imbalance test feedback failed to reduce self-blame, elicited worse prognostic pessimism and negative mood regulation expectancies, and led participants to view pharmacotherapy as more credible and effective than psychotherapy. The present findings add to a growing literature highlighting the unhelpful and potentially iatrogenic effects of attributing depressive symptoms to a chemical imbalance. Clinical and societal implications of these findings are discussed. © 2014 Elsevier Ltd.


Craig W.A.,University of Wisconsin - Madison | Andes D.R.,University of Wisconsin - Madison | Stamstad T.,William S. Middleton Memorial Veterans Hospital
Antimicrobial Agents and Chemotherapy | Year: 2010

MX-2401 is a novel lipopeptide (amphomycin analog) with a broad-spectrum bactericidal activity against Gram-positive organisms. We used murine thigh and lung infection models in neutropenic and normal mice to characterize the in vivo pharmacokinetic/pharmacodynamic (PK/PD) activities of MX-2401. The compound (2.5 to 40 mg/kg of body weight) demonstrated linear PK characterized by an area under the concentrationtime curve (AUC) of 228 to 3,265 μg·h/ml and half-lives of 5.7 to 8.8 h. MICs ranged from 0.25 to 2 μg/ml. The in vivo postantibiotic effect was prolonged (8.5 h with Staphylococcus aureus and 10.3 to 12.3 with Streptococcus pneumoniae). MX-2401 exhibited dose-dependent in vivo activity against various strains of S. pneumoniae and S. aureus; penicillin and macrolide resistance in the pneumococci and methicillin resistance in the staphylococci had no impact on the antimicrobial activity of the drug. To determine which PK/PD index correlated best with MX-2401 activity, dose fractionation studies over a 72-hour period were performed. The maximum concentration of drug in serum divided by the MIC (Cmax/MIC) correlated best with the efficacy for both S. aureus and S. pneumoniae. Static doses required free-drug Cmax/MIC values of 0.683 to 1.06. Free-drug 72-h AUC/MIC values for the static dose were in the range of 7.49 to 32.3 and were less than expected. The drug showed modest enhancement in activity in the presence of white blood cells (1.7- to 3.4-fold). The potency of the drug in the lung was only marginally lower than in the thigh (1.3- to 1.9-fold). Based on its PK/PD profile, MX-2401 appears to be a promising new lipopeptide agent for treatment of infections by Gram-positive bacteria, including those induced by antibiotic-resistant pathogens. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Safdar N.,William S. Middleton Memorial Veterans Hospital | Safdar N.,University of Wisconsin - Medical School | O'Horo J.C.,Mayo Medical School | Maki D.G.,University of Wisconsin - Medical School
Journal of Hospital Infection | Year: 2013

Background: Arterial catheters are essential in critical care for haemodynamic and blood gas monitoring. The risk of infection remains ill defined. Aims: To delineate the incidence, pathogenesis and risk factors for arterial catheter-related bloodstream infection (BSI). Methods: Arterial catheters in two randomized trials in 1998-2000 were studied prospectively. One trial studied the effect of a 1% chlorhexidine-75% alcohol solution for cutaneous antisepsis for intravascular catheters, and the other trial studied the efficacy of a chlorhexidine-impregnated sponge dressing, both for prevention of catheter-related BSI. At catheter removal, skin of the insertion site, catheter segments, hub and infusate were cultured quantitatively in all cases. Catheter-related BSI was confirmed by concordance between isolates from the catheter and from blood cultures by restriction-fragment DNA subtyping. Risk factors for arterial catheter-related BSI were determined using univariate analysis. Findings: Of 834 arterial catheters studied (3273 catheter-days), 109 (13%) were colonized and 11 caused bacteraemia (1.3%, 3.4 per 1000 catheter-days). The majority of catheter-related BSIs were acquired extraluminally from skin of the insertion site (63%). The risk of arterial catheter-related BSI was comparable with that for short-term non-cuffed central venous catheters (2.7%, 5.9 per 1000 CVC-days). Conclusion: In patients in intensive care with cryptogenic sepsis or bacteraemia, arterial catheter-related BSI must also be suspected and excluded. The most common route of infection is extraluminal; as such, novel technologies shown to prevent bloodstream infection with CVCs, such as chlorhexidine for cutaneous antisepsis and chlorhexidine-impregnated dressings, may also be of benefit with arterial catheters. © 2013.


Koopmann M.C.,William S. Middleton Memorial Veterans Hospital | Kudsk K.A.,William S. Middleton Memorial Veterans Hospital | Szotkowski M.J.,William S. Middleton Memorial Veterans Hospital | Rees S.M.,University of Wisconsin - Madison
Annals of Surgery | Year: 2011

Objective: To examine whether feeding tube placement into high-risk patients using a team-based protocol and electromagnetic tube tracking reduces complications associated with blind tube placement and to evaluate safety of blind tube placement in alert, low-risk patients. Background: Approximately 1•2million feeding tubes with stylets are placed annually in the US. Serious complications during placement exceed the rates of retained sponges and wrong site surgery. Several suggested solutions to the problem have been proposed but none completely eliminate the serious complications and many are neither cost-effective nor practical. Methods: In a retrospective, single center study, we compared complications after bedside feeding tube placement using a blind technique in 2005 to a hospital protocol mandating tube placement in high-risk patients by a Tube Team in 2007 using electromagnetic tracking. Outcome variables included airway placement, pneumothorax, death, and radiology resource utilization. Results: The Tube Team protocol eliminated airway tube placement (0 of 1154 vs. 20 of 1822, P < 0.001), pneumothorax (0/715 vs. 11/1822, P = 0.009), and all mortality whereas improving placement (83.9% success vs. 60.5%, P<0.001) in high-risk patients compared to the 2005 study. The number of X-rays obtained per tube (1.07 +/- 0.01 vs. 1.49 +/- 0.026, P < 0.001) and need for fluoroscopy (2.1% vs. 10.9%, P < 0.001) significantly dropped with the Tube Team. A final comparison was made to low-risk patients considered acceptable for blind tube placement in 2007 due to their alertness and ability to cooperate and provide feedback during tube placement. Although no mortality occurred during blind placement in low risk, alert patients, blind placement resulted in significantly increased airway placement (3/143, p = 0.001) and pneumothorax (2 of 143, P = 0.01) compared to the Tube Team protocol. Most patients who would have required fluoroscopic placement of feeding tube due to failed blind technique had successful placement by the Team avoiding fluoroscopy. Conclusion: Feeding tube placement by a dedicated team using electromagnetic tracking eliminates the morbidity and mortality of this common hospital procedure. Blind placement is not acceptable in awake, alert patients. Copyright © 2011 by Lippincott Williams & Wilkins.

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