William Peppard

Clostridium difficile Enteritis: An Early Postoperative Complication in Inflammatory Bowel Disease Patients After Colectomy

Clostridium difficile, the leading cause of hospital-acquired diarrhea, is known to cause severe colitis. C. difficile small bowel enteritis is rare (14 case reports) with mortality rates ranging from 60 to 83%. C. difficile has increased in incidence particularly among patients with inflammatory bowel disease. This case series of six patients from 2004 to 2006 is the largest in the literature. All patients received antibiotics before colectomies for ulcerative colitis and developed severe enteritis that was C. difficile toxin positive. Three patients underwent ileal pouch anal anastomosis and loop ileostomy. Four of the six patients had C. difficile colitis before colectomy. Presenting symptoms were high volume watery ileostomy output followed by ileus in five of six patients. Four of the six patients presented with fever and elevated WBC. Five of the six developed complications requiring further surgery or prolonged hospitalization. Patients were treated with intravenous hydration and metronidazole then converted to oral metronidazole and/or vancomycin. None of the patients died. A high suspicion of C. difficile enteritis in patients with inflammatory bowel disease and history of C. difficile colitis may lead to more rapid diagnosis, aggressive treatment, and improved outcomes for patients with C. difficile enteritis.

Safety and Efficacy of Prophylactic Anticoagulation in Patients with Traumatic Brain Injury

BACKGROUND Patients with traumatic brain injury (TBI) are at high risk for venous thromboembolism (VTE), but physicians are cautious with chemical prophylaxis in these patients because of concern about exacerbating intracranial hemorrhage. We hypothesized that early use of chemical thromboprophylaxis would reduce VTE incidence without increasing intracranial hemorrhage. STUDY DESIGN Records of all patients admitted with a TBI to a Level I trauma center from 2006 to 2008 were reviewed. TBI was defined as intracranial hemorrhage, hematoma, contusion, or diffuse axonal injury with a head Abbreviated Injury Scale score >2. Patients were excluded if they were discharged or died within 72 hours of admission. Chemical prophylaxis was defined as subcutaneous or intravenous unfractionated heparin or low molecular weight heparin before any VTE diagnosis. Progression of TBI was defined by worsening CT findings. VTE was defined as deep venous thrombosis or pulmonary embolus confirmed by radiology reports. Primary outcomes were progression of hemorrhage and VTE events. RESULTS Eight hundred and twelve of the 1,258 patients admitted to the trauma center with a TBI met study criteria. Chemical thromboprophylaxis was given to 49.5% (n = 402). Mean head Abbreviated Injury Scale score was 3.4 in both groups. One hundred and sixty-nine patients started prophylaxis within 48 hours and 242 patients began within 72 hours. Patients receiving chemical prophylaxis had a lower incidence of VTE (1% versus 3%; p = 0.019). Although not statistically significant, they also had a lower rate of injury progression, 3% versus 6% (p = 0.055). CONCLUSIONS Use of chemical thromboprophylaxis in TBI patients with a stable or improved head CT after 24 hours substantially reduces the incidence of VTE and does not increase the risk of progression of intracranial hemorrhage.

Linezolid for the treatment of drug-resistant infections.

Multidrug-resistant pathogens have become increasingly common in contemporary healthcare. Specific to Gram-positive pathogens, methicillin-resistant Staphylococcus aureus (MRSA) is of particular concern, as it has been associated with increased hospital length of stay, higher healthcare expenditures and poorer outcomes. To date, linezolid is the first and only oxazolidinone approved by the US FDA for the treatment of infections caused by Gram-positive pathogens, including MRSA. This article will serve as a comprehensive review of linezolid, including an overview of the current market and its in vitro activity, with an in-depth review of its pharmacokinetic and pharmacodynamic profile. Emphasis will be placed on clinical data for the drug, both on- and off-label. The article will conclude with a brief overview of linezolid’s pharmacoeconomic implications and safety profile, followed by a commentary and 5-year prospective analysis remarking on the future of the antimicrobial field as it relates to MRSA.

Pharmacologic options for CNS infections caused by resistant Gram-positive organisms

Infectious disease continues to evolve, presenting new and challenging clinical situations for practitioners. Specific to device-related and neurosurgical-related CNS infections, Gram-positive organisms are of growing concern. Current Infection Disease Society of America guidelines for the treatment of CNS infections offer little direction after conventional therapy, consisting of vancomycin, has failed or the patient has demonstrated intolerance. A review of literature evaluating alternative therapies, specifically linezolid, quinupristin/dalfopristin, daptomycin and tigecycline, will be presented. Interpretations of these data are offered followed by a brief presentation of future therapies, including oritavancin, telavancin, dalbavancin, ceftobiprole and iclaprim, all of which possess potent Gram-positive activity.

Role of linezolid in the treatment of complicated skin and soft tissue infections

Staphylococcus aureus is the most common cause of complicated skin and soft tissue infections (cSSTIs). Antibiotic choices for these infections continue to evolve. History has seen penicillin progress to antistaphylococcal penicillins and cephalosporins, but these drugs are now giving way to drugs that are effective against methicillin-resistant S. aureus (MRSA). While vancomycin has been the gold standard to treat MRSA infections, newer therapeutic options have been developed over the last 5 years. These include quinupristin–dalfopristin, daptomycin, tigecycline and linezolid, which is the focus for this review. Linezolid is efficacious in the treatment of cSSTIs (including diabetic foot infections) caused by Gram-positive organisms (including MRSA), with a well-defined safety profile and straightforward dosing. It is also approved for nosocomial pneumonia, community-acquired pneumonia and uncomplicated skin and skin structure infections. Linezolid has an oral and parenteral formulation, which are equivalent. The oral formulation has the potential to offer economic benefits as compared with other therapies. Currently, there are only a few new antibiotics in development with MRSA activity. The proper use of all antibiotics, including these newer agents, is increasingly important if we are to slow the evolution of microbial resistance.

Early Trophic Enteral Nutrition Is Associated With Improved Outcomes in Mechanically Ventilated Patients With Septic Shock A Retrospective Review

Purpose: Current guidelines provide weak recommendations for starting enteral nutrition (EN) in patients with septic shock (on vasopressor support). Outcomes of patients receiving EN in septic shock on vasopressor support have not been well studied. We hypothesize that early trophic EN in mechanically ventilated patients with septic shock is associated with improved outcomes. Methods: Single-center retrospective study of mechanically ventilated patients admitted with septic shock to identify patients receiving (1) no EN, (2) <600 kcal/d within 48 hours, and (3) ≥600 kcal/d within 48 hours. Outcomes studied included in-hospital mortality, length of intensive care unit stay (LOS), duration of mechanical ventilation (DOMV), and complications of feeding intolerance. Results: Sixty-six patients were identified. In all, 15 received no EN, 37 received <600 kcal/d, and 14 received ≥600 kcal/d EN daily. Median LOS was 12, 5, and 13 days, respectively. The LOS was lower in patients receiving <600 kcal/d when compared to either no EN (P < .001) or those receiving ≥600 kcal/d (P < .001). Median DOMV was lower in patients receiving <600 kcal/d (median 3, P < .001) as compared to no EN (median 7, P < .001) or those receiving ≥600 kcal/d (median 7.5, P < .001). Mortality was not different. There were no significant complications among groups. Conclusion: In patients with septic shock, those receiving <600 kcal/d EN within 48 hours had lower DOMV and LOS when compared to those who did not receive EN or those who received ≥600 kcal/d. These observations provide strong justification for prospective evaluation of the effect of early trophic EN in patients with septic shock.

Implementation of Polymerase Chain Reaction to Rule Out Clostridium difficile Infection Is Associated With Reduced Empiric Antibiotic Duration of Therapy

Purpose The polymerase chain reaction (PCR) test has higher sensitivity and a faster turnaround time than the enzyme immunoassay (EIA) for identification of Clostridium difficile, although the clinical implications of these variables are not well described. Methods Inpatients with a negative EIA (n = 79) or PCR (n = 87) test were retrospectively evaluated. Patients were excluded if they had a positive EIA or PCR test during the same hospitalization or if they were currently receiving treatment for C. difficile infection (CDI) prior to admission. The primary outcome was empiric CDI antibiotic duration of therapy associated with each test method. Results Empiric CDI antibiotic duration of therapy was 2.31 (95% confidence interval [CI], 1.48–3.15) days for the EIA group and 0.88 (0.45–1.33) days for the PCR group (P = .007). Number of diagnostic laboratory tests performed per patient were 2.73 (2.64–2.83) and 1.16 (1.04–1.28) tests, respectively (P < .001). Conclusion Use of the PCR test to rule out CDI was associated with reduced duration of empiric CDI antibiotic therapy and fewer diagnostic laboratory tests performed per patient. When combined with fewer diagnostic laboratory tests performed per patient and shorter duration of contact isolation, the higher acquisition cost of the PCR test was offset, resulting in cost neutrality. These findings provide additional data to support the routine use of the PCR test.

Evidence based approach to the treatment of community-associated methicillin-resistant Staphylococcus aureus

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have increased dramatically over the last two decades. The types of infections can range from complicated skin and skin structure infections (cSSSI) to pneumonia and endocarditis. Oral antimicrobial therapy, such as trimethoprim-sulfamethoxazole, clindamycin, long-acting tetracyclines, or linezolid may provide enhanced benefit to those with uncomplicated cutaneous lesions when used in conjunction with incision and drainage in an outpatient setting. However, resistance, susceptibilities, patient-specific circumstances, and adverse effects can impact a healthcare professional’s choice of antibiotics. In patients with complicated infections requiring hospitalization or parenteral treatment, vancomycin remains the drug of choice, even though increased resistance and decreased efficacy have crept into clinical practice. Linezolid, quinupristin/dalfopristin, daptomycin, and tigecycline are alternative intravenous agents for the treatment of CA-MRSA. Investigational agents such as dalbavancin, telavancin, oritivancin, iclaprim, ceftobiprole, ceftaroline, and others may expand our therapeutic armamentarium for the treatment of infections caused by CA-MRSA in the future.

Pharmacist involvement on a rapid response team

Purpose. The effect of a pharmacist on a rapid response team (RRT) was investigated. Methods. This study evaluated 234 patients before and 157 patients after pharmacist involvement on an RRT. The primary outcome was time to medication administration, with a goal turnaround time of less than 30 minutes. Secondary outcomes included most frequently used medications, readmissions to the intensive care unit (ICU) within 48 hours, number of rapid responses that resulted in ICU admission, length of hospital stay, and survival to hospital discharge. Additionally, pharmacist interventions were tracked in the postinterventional group. Results. The preinterventional group screened 326 rapid response events, of which 234 were included for analysis; during the postinterventional phase, 256 rapid response events were evaluated, of which 157 were included. The primary outcome, median time to medication administration from central pharmacy, was lower in the postinterventional group compared with the preinterventional group (32.0 minutes versus 64.5 minutes, p = 0.004). ICU admission rates following rapid response were not significantly different between the two groups. Additionally, there were no significant differences between rates of medical emergency and survival to hospital discharge. The most common medications administered were metoprolol and naloxone. Pharmacists provided documentation for 90 of 157 (57%) patient cases. In the 90 cases with documentation, 18 (20% of patients) had documented pharmacist interventions, including dosing assistance for 8 cases (44% of interventions). Conclusion. The addition of a pharmacist to an RRT reduced time to medication administration, helped improve medication accessibility, and helped optimize medication selection and dosing.

New developments in the treatment of acute bacterial skin and skin structure infections: considerations for the effective use of dalbavancin.

Dalbavancin, an intravenous glycopeptide, was approved by the US Food and Drug Administration in May 2014 for use in adult patients with acute bacterial skin and skin structure infections. The recommended dosing regimen for effective use of dalbavancin is 1,000 mg followed by a 500 mg dose after 1 week. Two multinational, identically designed, non-inferiority trials, DISCOVER 1 and 2, demonstrated similar early clinical success with dalbavancin compared to vancomycin with an option to switch to oral linezolid. In a recently published non-inferiority trial, a single-dose regimen of dalbavancin was compared to the traditional two-dose administration and was found to have a non-inferior clinical response. In the aforementioned trials, dalbavancin was well tolerated, with patients experiencing transient adverse events of mild to moderate severity. The prolonged half-life, excellent skin and soft tissue penetration, bactericidal activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus, and convenient dosing make dalbavancin a reasonable option for the treatment of acute bacterial skin and skin structure infections in adult patients who have tried and failed other therapies.