John W. Ahern

A survey of once-daily dosage tobramycin therapy in patients with cystic fibrosis.

The purpose of this study was to quantify the prevalence of once‐daily dosage of tobramycin (ODDT) among Cystic Fibrosis Foundation‐accredited care centers and affiliated programs (CFFACCs) and characterize the ODDT approaches used by these institutions. An anonymous cross‐sectional survey of CFFACCs was performed using an electronic survey tool. This tool was electronically mailed to the program directors. Eighty‐four out of 195 institutions completed the survey (response rate = 43%). Fifty‐one (61%) of 84 centers reported using ODDT. Of those 51 institutions, 34 (67%) use a dosage of 10 mg/kg/dose. Serum creatinine was measured routinely in 51 centers (100%) with weekly monitoring being used in 40 centers (78%). Audiometric evaluation was performed routinely in 22 (43%) centers with annual assessment performed in 14 (64%) of these 22 centers. In conclusion, a majority of responding institutions use ODDT. The most common reported dosage is 10 mg/kg. Serum creatinine was routinely measured in all institutions with weekly assessment being the most common frequency. Audiometic assessment is routinely performed in <50% of centers. Of the institutions performing audiograms routinely, annual assessment is the most common frequency. Pediatr Pulmonol. 2009; 44:325–329.

Experience with vancomycin in patients receiving slow low-efficiency dialysis

Background Slow low-efficiency dialysis (SLED) is an emerging dialytic strategy for managing acute renal failure. There is no published data describing how SLED effects the pharmacokinetics of vancomycin. Methods A prospective pharmacokinetic evaluation of vancomycin was performed in critically ill medical and surgical patients with acute renal failure who required IV vancomycin and concurrent SLED therapy. Patients received vancomycin 15 mg/kg by actual body weight. Serum drug concentrations were evaluated at 6, 12, and 24 hours postinfusion. Patient-specific vancomycin pharmacokinetic parameters were determined from serum concentrations to calculate a maintenance dosage regimen. Results Mean ± SD half-life, volume of distribution, and systemic clearance, were 43.1 hours ± 21.6 hours, 0.84 L/kg ± 0.17 L/kg, and 24.3 mL/min ± 8.39 mL/min, respectively. Vancomycin dosing intervals ranged from 24 to 72 hours. Conclusion The elimination half-life of vancomycin was variable and prolonged in patients receiving SLED therapy. An initial vancomycin dose of 15 mg/kg is recommended for patients receiving SLED. Given the variability of the vancomycin half-life during SLED, a vancomycin serum concentration should be obtained 24 hours following the initial dose.

Potential Influence of Antisecretory Therapy on the Development of Candida-Associated Intraabdominal Infection

Background: Concerns surrounding the potential extra gut complication of gastric acid suppression are becoming increasingly realized. Objective: To determine whether chronic antisecretory treatment with a proton pump inhibitor (PPI) or histamine2-receptor antagonist (H2RA) is associated with the presence of Candida spp. in cases of complicated intraabdominal infection. Methods: We conducted a case-controlled study of adult surgical intensive care unit patients with complicated intraabdominal infection during a 5-year period. Exclusion criteria consisted at primary peritonitis, diagnosis of intraabdominal infection more than 72 hours before hospital admission, or a stay in the intensive care unit of less than 72 hours. Patients were categorized into either the antisecretory group (H2RA or PPI therapy prior to admission) or control group (no prior antisecretory therapy). Results: One hundred eighteen patients met inclusion criteria. Chronic antisecretory (n = 41) and control (n = 77) patients were similar except in median age (69.0 vs 59.0 y; p = 0.026) and preadmission antibiotic use (36.6% vs 15.6%; p = 0.010). The 2 groups had a similar proportion of patients with Candida (30.3% vs 32.1%; p = 0.857); the cultures included C, albicans, C. glabrata, and C. parapsilosis. Yeast was recovered more often in patients diagnosed with community-acquired intraabdominal infection and in patients who had used PPIs before hospital admission (p = 0.066). Additionally, Candida was cultured more often in antisecretory patients with a history ol prior abdominal surgery than in control patients (91.7% vs 62.5%; p = 0.066). Conclusions: No significant difference was found in the number of patients in the antisecretory and control groups from whom peritoneal Candida was recovered. However, patients with prior abdominal surgery and those in the community with chronic PPI use may be predisposed to Candida-associated intraabdominal infections.

Colistin: Potential for Dosage Error

TO THE EDITOR—We read with interest the article by Dalfino et al [1] that evaluated a high-dose extended-interval colistin dosage regimen for critically ill patients. Colistin is experiencing resurgence in use given the rise in multidrug-resistant infections [2]. As a result, studies that provide outcome data to support clinical dosage regimens are valuable. From a safety perspective, the variability that exists with product nomenclature and dose needs to be highlighted [3]. Colistin is available in 2 salt forms, colis-tin sulfate and colistimethate sodium (CMS) [4].Relative to the sulfate salt, CMS is safer when given parenterally [2]. On administration, CMS is hydrolyzed to colistin, which is the base component that is responsible for antibacterial activity [4]. Confusion frequently surrounds colistin dosage because of the lack of a universal dose unit (international units vs milligrams) [3, 4]. This dose variability is further complicated by differences in product labeling, which can express the dosage in terms of salt or base [3, 4]. In the United States, the dosage of all Food and Drug Administration–approved CMS for injection products is defined in terms of the colistin base and not the salt [5]. The base is to be expressed in milligrams [5]. Following a recent fatality with colistin, a National Alert Network communication reminded clinicians that colis-tin should only be prescribed in terms of base activity and to be cognizant of references that refer to the dose in terms of international units or milligrams of CMS [5]. A dose that is based on CMS will yield a dose that is 2.5 times higher than if calculated on the basis of the base [5]. Dalfino et al [1] used a dosage regimen based on CMS. It expressed the CMS activity in international units. A loading dose of 9 million IUs was followed by a maintenance dose of 4.5 million IUs every 12 hours. To safely prescribe this regimen in the United States, the dosage would need to be converted from CMS to milligrams of colistin base activity, using the following equivalency: 30 000 IUs = 1 mg of colistin base [6]. This would produce a loading dose of 300 mg of colistin base, followed by a maintenance dose of 150 mg of colistin base every 12 hours. From a medication safety perspective, there is a need to standardize product labeling (milligrams vs international units; dosage using salt vs dosage using base) for colistin products [2–4]. However, …

Use of Longitudinal Surveillance Data to Assess the Effectiveness of Infection Control in Critical Care

A simple method for quantifying nosocomial infection and colonization with multidrug-resistant organisms is described. This method is applied to the intensive care unit of an academic medical center where longitudinal surveillance data have been used to assess the impact of infection control interventions and antibiotic use.

Development of a pediatric pocket-sized guide for antimicrobial therapy.

Approximately 35% of hospitalized children receive antimicrobials.[1][1] The pharmacokinetic and pharmacodynamic properties of these agents are highly variable in children and dependent on postconceptional age, chronological age, and weight.[2][2] As a result, medication therapy in children is

Remembering the past: creatinine clearance and drug dosage adjustment.

TO THE EDITOR: In a recent publication, Brown et al. suggests using a functional creatinine clearance (CrCl) range to guide drug dosage adjustment for renally eliminated drugs. This range uses an upper and lower uncorrected CrCl estimate (mL/min) that is calculated from the Cockcroft-Gault (CG) equation using ideal body weight and total body weight respectively. Other investigators have also evaluated several weight relationships and adjustment factors to determine which approach optimizes the predictive performance of this equation. In the midst of these ongoing efforts, it is instructional for practitioners to recall some of the earlier literature that has expressed concern with using weight in the CG calculation to derive an uncorrected CrCl (mL/min) for the purpose of renal drug dosage adjustment. In 1976, Hull and Sarubbi published a nomogram that determined gentamicin dosage using a CrCl that was derived from age, weight, and serum creatinine (SCr). A subsequent commentary questioned the ability of this nomogram to accurately calculate maintenance doses for large or small patients based on the observation that the CrCl was not corrected to body size (uncorrected). Spyker and Guerrant emphasized that the frequency of drug administration or dosage interval depends not only on renal function (clearance) but also on distribution volume (Vd), which together determine drug half-life. The uncorrected CrCl would address clearance (CL) but would not account for Vd, which also influences the rate of drug elimination (Ke) indicated by the relationship Ke = CL/ Vd. As a result, the authors postulated that the uncorrected CrCl could possibly overor underestimate gentamicin maintenance doses for large and small patients, respectively, as their Vd would not be considered. To address this situation, Spyker and Guerrant proposed correcting CrCl to standard body size (mL/min per 70 kg or 1.73 m). This “corrected CrCl” would adjust for differences in Vd in patients of different sizes so that drug elimination could be correctly inferred from the nomogram. Sarubbi and Hull subsequently developed an amikacin dosage nomogram that incorporated corrected CrCl and reported slight but nonsignificant improvement in the correlation between predicted and observed concentrations relative to the uncorrected CrCl. A recent review states there is a lack of clarity around the optimal index of renal function for drug dosage adjustment. The weight containing CG equation (uncorrected) is often used by the pharmaceutical industry as a method for renal dosage adjustments. However, in 1988, D’Angio et al expressed concerns over using this version of the CG equation for renal drug dosage adjustment. Using hypothetical examples to illustrate pharmacokinetic concepts, D’Angio et al reminded readers that an uncorrected CrCl should not be used to compare elimination rates of renally cleared medications in patients of differing sizes because of differences in Vds. For such comparisons, D’Angio et al recommended a CrCl that is corrected to an average weight of 72 kg by multiplying the original CG formula by 72/body weight. This removes weight from the equation and simplifies the expression for males to (140 − Age)/SCr, which has units of mL/min/72 kg. Unfortunately, drug product information often does not specify whether CrCl should be corrected to 70 kg. In 1997, McCormack et al mentioned that standard dosage references often implicitly assume normal renal function is 100 to 120 mL/min/72 kg. McCormack et al added that empirical dosage adjustments should be based on a comparison between a weight corrected CrCl and a “normal” CrCl for a 72-kg man (100-120 mL/min). This allows for an apple-to-apple comparison of elimination rates (patient to standard reference) as the patient’s CrCl will be “corrected” to the size assumed by the reference. This permits comparison of elimination rates as both clearances are operating within identical Vds ensuring that both CL/Vd ratios are in proper proportion. In 2008, Dersch and McCromack reemphasized the concepts expressed by McCormack et al and added that the corrected CrCl is a relative CrCl and serves as a relative measure of renal function as it compares renal function from a specific individual with a reference point that defines “normal” renal function as 100 to 120 mL/min/72 kg. The functional range for creatinine clearance that has been proposed by Brown et al has intuitive appeal. However, this report did not address the pharmacokinetic concerns that have been raised by several authors over the past 30 years in regards to using weight in the CG equation. Therefore, it would seem prudent to exercise caution in using the original CG equation with weight if the intent is to compare renal function for the purpose of dosage modification. In addition, the functional creatinine clearance that is proposed by Brown et al requires knowledge of the patient’s weight and height (to determine ideal body 508746 AOPXXX10.1177/1060028013508746Ahern and PossidenteAnnals of Pharmacotherapy research-article2013

Electronic evaluation of residency applicants using Microsoft SharePoint

The 2005 ASHP accreditation standards for postgraduate year 1 (PGY1) pharmacy residency programs require that programs develop a formal procedure to evaluate program applicants.[1][1] The purpose of this process is to ensure that candidates have the baseline knowledge, skills, attitudes, and

Risk Factors for Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia Despite Treatment With Vancomycin

Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia despite treatment with vancomycin is not uncommon. Factors that contribute to vancomycin failure remain poorly understood. A retrospective case-control study was performed to examine factors associated with persistent MRSA bacteremia. All episodes of MRSA bacteremia from 1998 to 2004 were reviewed. Case patients had at least 1 positive blood culture drawn 5 or more days after beginning vancomycin. Two controls for each case were randomly selected with negative blood cultures within 48 hours of starting vancomycin. Of 251 MRSA bloodstream infections, 20 patients met the case definition. The median number of foreign devices, an intravascular device or septic phlebitis as a site of infection, and a maximum vancomycin minimum inhibitory concentration of 2 μg/mL were significantly associated with persistent bacteremia. In a multivariate model, only the number of foreign devices present at the onset of the bacteremia was found to be an independent predictor.

Development of a Gentamicin and Tobramycin Dosing Strategy in the Neonatal Intensive Care Unit

OBJECTIVE To evaluate the ability of a neonatal aminoglycoside dosing nomogram to produce peak serum concentrations greater than 6 mg/L and trough serum concentrations less than 1.5 mg/L. METHODS Neonates admitted to the Intensive Care Unit who received gentamicin or tobramycin were included if they met the following dosing criteria: Patients < 28 weeks postconceptional age (PCA) received 2.5 mg/kg every 24 hours, those 28–34 weeks PCA received 2.5 mg/kg every 16 hours, and neonates ≥ 35 weeks PCA received 2.5 mg/kg every 12 hours. Serum gentamicin or tobramycin concentrations were obtained and mean patient pharmacokinetic values from this group were used to predict concentrations that would have resulted if the following dosing strategy were used: 4 mg/kg every 36 hours in patients < 29 weeks PCA and 3.5 mg/kg every 24 hours in those ≥ 29 weeks. These doses were then prospectively evaluated in a separate group of neonates. RESULTS Two-hundred sixty one peak serum concentrations were obtained in patients ...