Douglas Slain

Clinical practice guidelines for antimicrobial prophylaxis in surgery

These guidelines were developed jointly by the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), the Surgical Infection Society (SIS), and the Society for Healthcare Epidemiology of America (SHEA). This work represents an update to the previously published ASHP Therapeutic Guidelines on Antimicrobial Prophylaxis in Surgery, as well as guidelines from IDSA and SIS. The guidelines are intended to provide practitioners with a standardized approach to the rational, safe, and effective use of antimicrobial agents for the prevention of surgical-site infections (SSIs) based on currently available clinical evidence and emerging issues. Prophylaxis refers to the prevention of an infection and can be characterized as primary prophylaxis, secondary prophylaxis, or eradication. Primary prophylaxis refers to the prevention of an initial infection. Secondary prophylaxis refers to the prevention of recurrence or reactivation of a preexisting infection. Eradication refers to the elimination of a colonized organism to prevent the development of an infection. These guidelines focus on primary perioperative prophylaxis.

Candida Endophthalmitis : Focus on Current and Future Antifungal Treatment Options

Candida endophthalmitis is a sight‐threatening manifestation of disseminated candidiasis. The occurrence of endogenous candida endophthalmitis in patients with candidemia has ranged from 0–45% in the published literature. In critically ill patients, it has even been associated with increased mortality. In recent years, use of newer antifungal therapies for invasive candidiasis has increased given the rise in infections with non‐albicans species of Candida. To identify current practices of the management of endogenous candida endophthalmitis and relevant antifungal drug research in this disease state, we conducted a MEDLINE search (1967–2006) and bibliographic search of the English‐language literature. Treatments for candida endophthalmitis have not been evaluated through well‐designed, well‐powered clinical trials. Data have mainly been presented in case reports, case series, animal studies, pharmacokinetic studies, and as small subsets of larger trials. Traditional systemic therapies have been amphotericin B with or without flucytosine or fluconazole. Cure rates with antifungal drugs alone appear to be much higher in patients with chorioretinitis than in endophthalmitis with vitreal involvement. Pars plana vitrectomy with or without intravitreal amphotericin B injections has been advocated particularly for patients with moderate‐to‐severe vitritis and substantial vision loss. Information on new antifungal agents for endophthalmitis is limited, despite increasing use in patients with candidemia. Voriconazole may be a particularly attractive agent to consider for infections with fluconazole‐resistant, voriconazole‐susceptible strains. The current patchwork of animal studies and small patient reports provide clinicians with some insight into the role of newer agents in the treatment of candida endophthalmitis. In general, it appears that chorioretinitis infections can be more readily cured with most systemic antifungal agents, whereas more aggressive treatment, often including vitrectomy with or without intravitreal antifungal administration, is needed for patients with endophthalmitis with vitritis.

Eighteen cases of liver injury following ingestion of Polygonum multiflorum

OBJECTIVES Polygonum multiflorum is a popular Chinese herbal medication. In this case series, we report on 18 otherwise healthy non-viral hepatitis patients who developed liver dysfunction following consumption of P. multiflorum alone. METHODS Concurrent and retrospective analysis was used in this study. The causality of P. multiflorum in liver injury was graded by the Council for International Organizations of Medical Sciences (CIOMS) toxicity scale. RESULTS From 2005 to 2012, 18 cases of hepatotoxicity potentially involving P. multiflorum. The median age was 42 years old (range from 18 to 63). Median time of onset of symptoms was 27 days (1-120). Prevailing clinical symptoms were fatigue, loss of appetite and jaundice. Sixteen patients had elevated level of total bilirubin (>21 mol/L); liver enzymes elevated markedly in all patients (ALT>40 U/L, AST>40 U/L, GGT>50 U/L), except for alkaline phosphatase which elevated only in nine patients. Based on the liver enzyme pattern, the type of liver injuries were hepatocellular according to CIOMS. In terms of causality, 14 of 18 patients were evaluated as being highly probable. All patients were responding well to P. multiflorum stoppage, and liver protective-supportive care. CONCLUSIONS P. multiflorum products can be associated with hepatotoxicity in otherwise healthy non-viral hepatitis infected patients, regardless of herbal processing.

Effect of High-Dose Vitamin C on the Steady-State Pharmacokinetics of the Protease Inhibitor Indinavir in Healthy Volunteers

Study Objective. To determine whether daily high‐dose vitamin C alters the steady‐state pharmacokinetics of indinavir, a protease inhibitor indicated for treatment of the human immunodeficiency virus type 1.

Lipid-Based Amphotericin B for the Treatment of Fungal Infections

The frequency of life‐threatening fungal infections has increased dramatically over the past few decades. For more than 30 years amphotericin B has been the standard treatment for systemic and deep‐seated fungal infections, primarily because of its broad spectrum of activity. Its usefulness is limited by a relatively high frequency of significant adverse events including infusion‐related reactions and nephrotoxicity. In an effort to overcome these side effects, a number of lipid‐based formulations were developed, each with its own composition and pharmacokinetic behavior. The clinical significance of these differences is unknown. Available clinical data suggest the formulations have a reduced propensity for causing nephrotoxicity. However, considering limited efficacy data, they should be reserved as second‐line therapy for patients who cannot tolerate or fail an adequate trial of conventional amphotericin B or cannot benefit from other antifungal agents.

Variability in activity of hepatic CYP3A4 in patients infected with HIV.

Study Objectives. To evaluate hepatic cytochrome P450 (CYP) 3A4 activity in patients infected with the human immunodeficiency virus (HIV) using the erythromycin breath test (ERMBT), and to examine the relationship of the ERMBT to plasma concentrations of indinavir and nelfinavir.

Impact of a Multimodal Antimicrobial Stewardship Program on Pseudomonas aeruginosa Susceptibility and Antimicrobial Use in the Intensive Care Unit Setting

Objective. To study the impact of our multimodal antibiotic stewardship program on Pseudomonas aeruginosa susceptibility and antibiotic use in the intensive care unit (ICU) setting. Methods. Our stewardship program employed the key tenants of published antimicrobial stewardship guidelines. These included prospective audits with intervention and feedback, formulary restriction with preauthorization, educational conferences, guidelines for use, antimicrobial cycling, and de-escalation of therapy. ICU antibiotic use was measured and expressed as defined daily doses (DDD) per 1,000 patient-days. Results. Certain temporal relationships between antibiotic use and ICU resistance patterns appeared to be affected by our antibiotic stewardship program. In particular, the ICU use of intravenous ciprofloxacin and ceftazidime declined from 148 and 62.5 DDD/1,000 patient-days to 40.0 and 24.5, respectively, during 2004 to 2007. An increase in the use of these agents and resistance to these agents was witnessed during 2008–2010. Despite variability in antibiotic usage from the stewardship efforts, we were overall unable to show statistical relationships with P. aeruginosa resistance rate. Conclusion. Antibiotic resistance in the ICU setting is complex. Multimodal stewardship efforts attempt to prevent resistance, but such programs clearly have their limits.

Review of the New Delayed‐Release Oral Tablet and Intravenous Dosage Forms of Posaconazole

The triazole antifungal posaconazole was first approved as an oral suspension formulation. Despite pharmacokinetic target attainment and clinical efficacy in premarketing trials, postmarketing analyses indicated unpredictable bioavailability resulting in subtherapeutic concentrations and reports of breakthrough fungal infections. The newly approved posaconazole delayed‐release tablet and intravenous formulations display more consistent bioavailability in the presence of concomitant disease states, medications, and dietary considerations that classically alter drug concentrations of the oral suspension. Both the delayed‐release tablet and intravenous formulation display a similar adverse‐effect profile to the oral suspension. The posaconazole delayed‐release oral tablet is not significantly affected by gastric acid suppression therapy, and the intravenous dosage form provides an option for patients who are intubated or unable to tolerate oral medications. Pharmacoeconomic considerations, particularly with intravenous posaconazole, will likely play a role in dosage form selection and frequency of use. Due to sustained, higher drug concentrations, the new posaconazole formulations hold promise for greater efficacy in antifungal prophylaxis and bring opportunity for further study in the treatment of invasive mycoses.

Plasma and Tissue Cefazolin Concentrations in Obese Patients Undergoing Cesarean Delivery and Receiving Differing Pre-Operative Doses of Drug

BACKGROUND Patients undergoing cesarean delivery typically receive a 1-g to 2-g dose of cefazolin as pre-operative antibacterial prophylaxis. This traditional dosage may not provide an adequate tissue concentration of cefazolin in obese patients during the peri-operative period. This study compared the tissue concentrations of prophylactic cefazolin administered as a either a 2-g or a 4-g dose prior to cesarean delivery in obese patients. METHODS Twenty obese patients (first trimester body mass index [BMI] >35) who underwent cesarean delivery completed this randomized study. Eleven patients received 2 g of cefazolin, and nine received 4 g. Blood and subcutaneous tissues were collected at the times of the incision and closure. Myometrial biopsies were collected at uterine closure. A cefazolin concentration threshold of 4 mcg/g for tissue samples was used as a surrogate adequate concentration. Plasma and tissue cefazolin concentrations were compared for the two doses. RESULTS Mean plasma, umbilical cord, and myometrial cefazolin concentrations were significantly higher in the 4-g treatment group (p<0.05). Subcutaneous incision site tissue obtained at time of incision creation also was significantly higher in the 4-g group than in the 2-g group (40.11±24.10 mcg/g vs. 18.36±6.68 mcg/g; p=0.0005). Subcutaneous tissue concentrations at closure were significantly different in the two dosage groups (34.89±17.42 mcg/g vs. 21.73±16.02 mcg/g; p=0.044). All tissue samples were above the target of 4 mcg/g. Body morphometry did not correlate with the variability in cefazolin tissue concentration. No surgical site infections, endometritis, or other adverse effects were observed. CONCLUSIONS Administering a prophylactic dose of 4 g of cefazolin produced blood and tissue cefazolin concentrations that were significantly higher than concentrations obtained from a 2-g dose in patients with BMIs between 35 and 60 kg/m(2) undergoing cesarean delivery. It is unclear if the larger cefazolin dose produces a more protective anti-infective effect than that obtained with the more traditional 2-g dose for cesarean delivery in obese patients.

A matched-control evaluation of an antifungal bundle in the intensive care unit at a university teaching hospital

Background Antimicrobial use bundles are becoming a common means of implementing antimicrobial stewardship initiatives in the hospital setting. Although the utility of these bundles has been described for many disease states, their adoption for antifungal therapy management is largely unknown. Objective Our objective was to assess the utility of an antifungal bundle protocol in limiting excessive use of echinocandins in the intensive-care inpatient setting. Methods In this matched-control evaluation, pre-protocol control patients were matched with each prospective patient in a 2:1 ratio using five demographic and clinical characteristics. The impact of the antifungal bundle protocol on caspofungin days of therapy, drug costs, and adherence to bundle criteria was assessed. Results A significant reduction in median days of caspofungin therapy (4.00 vs. 2.00 days, p = 0.001) was found in the bundle group. Most of this reduction in use was realized in the medical ICU (p = 0.002) as opposed to the surgical ICU (p = 0.188). Conclusions Use of an antifungal bundle approach appears to facilitate a reduction in caspofungin use in the ICU without adversely affecting patient outcomes. Further trials are needed to assess the utility of such bundles in providing antimicrobial stewardship for antifungal drug use.