Risk factors for systemic vancomycin exposure following administration of oral vancomycin for the treatment of Clostridium difficile infection.

OBJECTIVE: To identify risk factors for systemic exposure to vancomycin (VAN) following administration of oral vancomycin (POV) for the treatment of Clostridium difficile infection (CDI). DESIGN: Prospective, observational, single-center case series. SETTING: Academic medical center. PATIENTS: Hospitalized patients with suspected or confirmed CDI who received POV for at least 5 days. INTERVENTION: Random VAN serum levels were obtained on days 5, 10, and weekly thereafter in patients treated for ≥ 5 days with POV without concomitant intravenous VAN. MEASUREMENTS AND RESULTS: Of 117 random VAN serum levels from 85 patients, 58 patients (68.2%) had one or more detectable (≥ 0.05 µg/ml) levels and 15 (17.6%) of 85 patients had one or more levels > 2.5 µg/ml. Risk factors for detectable VAN exposure following administration of POV included POV dosages > 500 mg/day (odds ratio [OR] 35.83, 95% confidence interval [CI] 7.56-169.8), the presence of severe CDI (OR 4.11, 95% CI 2.76-10.83, p=0.028), intensive care unit (ICU) admission (OR 3.80, 95% CI 1.02-14.21, p=0.032), and the administration of POV ≥ 10 days (OR 6.71, 95% CI 1.81-24.83, p=0.0025). Risk factors for exposure to serum VAN concentrations > 2.5 µg/ml included the presence of gastrointestinal (GI) pathology (OR 5.22, 95% CI 3.45-18.3, p=0.031), ICU admission (OR 3.21, 95% CI 1.40-10.28, p=0.022), the use of VAN retention enemas (OR 4.73, 95% CI 2.42-20.39, p=0.036), and having a creatinine clearance ≤ 50 ml/minute or undergoing hemodialysis or continuous renal replacement therapy (OR 4.03, 95% CI 1.26-12.84, p=0.039). CONCLUSIONS: Serum VAN levels were detected in 58 (68.2%) of 85 patients receiving POV for CDI. Risk factors for systemic exposure to VAN following administration of POV included ICU admission; VAN dosages > 500 mg/day; administration ≥ 10 days or as retention enemas; and the presence of severe CDI, renal dysfunction, or inflammatory conditions of the GI tract. Unique to our study, we identified ICU admission and the concomitant use of VAN retention enemas to be significant risk factors for systemic exposure to VAN.

Proton pump inhibitor-associated pneumonia: Not a breath of fresh air after all?

Over the past two decades, proton pump inhibitors (PPIs) have emerged as highly effective and relatively safe agents for the treatment of a variety of gastrointestinal disorders. Unfortunately, this desirable pharmacological profile has also contributed to superfluous and widespread use in both the inpatient and outpatient settings. While generally well-tolerated, research published over the last decade has associated these agents with increased risks of Clostridium difficile disease, fractures likely due to calcium malabsorption and both community-acquired (CAP) and hospital-acquired pneumonias (HAP). The mechanism behind PPI-associated pneumonia may be multifactorial, but is thought to stem from compromising the stomach's "acid mantle" against gastric colonization of acid-labile pathogenic bacteria which then may be aspirated. A secondary postulate is that PPIs, through their inhibition of extra-gastric H(+)/K(+)-ATPase enzymes, may reduce the acidity of the upper aerodigestive tract, thus resulting in increased bacterial colonization of the larynx, esophagus and lungs. To date, several retrospective case control studies have been published looking at the association between PPI use and CAP. Some studies found a temporal relationship between PPI exposure and the incidence of pneumonia, but only two could define a dose-response relationship. Furthermore, other studies found an inverse correlation between duration of PPI use and risk of CAP. In terms of HAP, we reviewed two retrospective cohort studies and one prospective study. One retrospective study in a medical ICU found no increased association of HAP in PPI-exposed patients compared to no acid-lowering therapy, while the other in cardiothoracic surgery patients showed a markedly increased risk compared to those receiving H(2)RAs. The one prospective study in ICU patients showed an increased risk of HAP with PPIs, but not with H(2)RAs. In conclusion, the current literature shows a slight trend toward an association between PPI use and pneumonia and an increased risk with PPIs over H(2)RAs, but the findings are not consistent across all studies. Larger controlled trials still need to be done to better identify the risk that PPIs impart towards patients contracting CAP or HAP. Until these are completed, we will have to continue to extrapolate across smaller controlled trials to predict the associated risks in our respective patient populations. In the interim, it appears prudent to limit the use of PPIs to situations where they are clinically indicated and, in such cases, use them at the lowest effective dose. In the case of prescribing for stress ulcer prophylaxis in ICU patients, perhaps H(2)RAs should be used as the preferred agents over PPIs.

Stability of extemporaneously prepared acetylcysteine 1% and 10% solutions for treatment of meconium ileus.

PURPOSE: The stability of extemporaneously prepared acetylcysteine 1% and 10% solutions for treatment of meconium ileus was evaluated. METHODS: Acetylcysteine 1% (10-mg/mL) and 10% (100-mg/mL) solutions were prepared by mixing 3 and 10 mL, respectively, of commercially available 20% acetylcysteine solution with a sufficient quantity of bacteriostatic 0.9% sodium chloride for injection to make a final volume of 60 mL. Three identical samples of each concentration were prepared, placed in 2-oz amber plastic prescription bottles, and stored at 20-25 °C. Samples were assayed in duplicate using high-performance liquid chromatography and inspected for changes in color, odor, and pH immediately after preparation and at 7, 14, 30, 60, and 90 days. Stability was defined as retention of at least 90% of the initial concentration. RESULTS: At least 90% of the initial concentration of acetylcysteine was retained in both formulations for 60 days. No appreciable change from the initial pH occurred in the acetylcysteine 1% or 10% solution during the first 60 days, but there was a notable change in pH after 90 days in both formulations. Neither solution was stable at day 90. There was no detectable change in color at 90 days; however, the odor of hydrogen sulfide was more pungent than on previous study days. CONCLUSION: Extemporaneously prepared solutions of acetylcysteine 1% (10 mg/mL) and 10% (100 mg/mL) prepared with bacteriostatic 0.9% sodium chloride for injection were stable for at least 60 days when stored in plastic amber bottles at room temperature.

Needs assessment analysis for vitamin K antagonist anticoagulation in the resource-constrained setting of Eldoret, Kenya.

OBJECTIVES: To assess the frequency of indications for vitamin K antagonist (VKA) therapy in the inpatient and outpatient setting in Eldoret, Kenya, and to describe the strategies used for managing these conditions. METHODS: All inpatient admissions during a 1.5-month period were prospectively assessed for any indications for VKA therapy by clinical pharmacy staff. For the outpatient assessment, the files of all patients receiving care in the outpatient adult cardiology clinic within the previous 6 months were identified and evaluated for indications for VKA therapy. For patients identified with an indication for VKA therapy, additional information was collected, including the VKA indication, pharmacologic management, and any other risk-modifying conditions. RESULTS: In the primary analysis, 20 of the 554 patients admitted to the public adult wards (3.61% [95% CI 2.14-5.08]) were candidates for VKA therapy. Of the 168 outpatient cardiology clinic charts reviewed, 72 patients (42.8% [37.96-47.76]) had indications for VKA therapy. In the secondary analysis, 70% of the inpatient population and 93% of the outpatient population received suboptimal VKA therapy. Of these patients in need of VKA therapy, 53.3% were on aspirin therapy only and 33.7% were not receiving any pharmacologic therapy. CONCLUSION: As developing countries begin to address the growing burden of chronic diseases, a commensurate focus on providing infrastructure for comprehensive cardiovascular care, including an organized VKA monitoring service, needs to occur.