Clinical Pharmacology of Antibiotics.

Antimicrobial pharmacology and its effect on prescribing is quite complex. Selecting an antibiotic that will optimally treat an infection while minimizing adverse effects and the development of resistance is only the first step, as one must also consider the patient's individual pharmacokinetic alterations and the pharmacodynamic properties of the drug when prescribing it as well. Patients with CKD may have alterations in their protein binding, volumes of distribution, kidney clearance, and nonrenal clearance that necessitates antibiotic dose adjustments to prevent the development of toxicity. Knowledge of a drug's pharmacodynamics, defined as the relationship between drug exposure and antibacterial efficacy, provides some guidance regarding the optimal way to make dose adjustments. Different pharmacodynamic goals, such as maximizing the time that free (unbound) drug concentrations spend above the minimum inhibitory concentration (MIC) for time dependent drugs (e.g., ß-lactams) or maximizing the free peak-to-MIC ratio for concentration-dependent antibiotics (e.g., aminoglycosides), require different adjustment strategies; for instance, decreasing the dose while maintaining normal dosing frequency or giving normal (or even larger) doses less frequently, respectively. Patients receiving hemodialysis have other important prescribing considerations as well. The nephrologist or patient may prefer to receive antibiotics that can be administered intravenously toward the end of a dialysis session. Additionally, newer dialysis technologies and filters can increase drug removal more than originally reported. This review will discuss the place in therapy, mechanism of action, pharmacokinetic, pharmacodynamic, and other pharmacologic considerations encountered when prescribing commonly used antibiotics in patients with chronic kidney disease or ESKD.

Single dose oral ranolazine pharmacokinetics in patients receiving maintenance hemodialysis.

PURPOSE: Ranolazine is a novel anti-angina treatment approved in the United States for chronic stable angina. Ranolazine pharmacokinetics have not been studied previously in patients who receive maintenance hemodialysis. This study describes the pharmacokinetics of ranolazine and three major metabolites (CVT-2738, CVT-2512, CVT-2514) in patients receiving thrice weekly hemodialysis. METHODS: Eight participants receiving maintenance hemodialysis completed this prospective, open-label study (study identifier NCT01435174 at Clinicaltrials.gov). Three participants received a single tablet of ranolazine 500 mg (followed by an interim analysis), and five received 2 tablets of ranolazine 500 mg. Blood samples were collected over 65 h to determine the pharmacokinetic characteristics during and between hemodialysis sessions. Non-compartmental analysis was used to determine the individual pharmacokinetic parameters. RESULTS: Ranolazine off-hemodialysis elimination phase half-lives were 3.6 and 3.9 h for 500 mg and 1000 mg doses, respectively. The time to maximum concentration ranged from 2 to 18 hours and the average maximum concentration was 0.65 ± 0.27 mcg/mL and 1.18 ± 0.48 mcg/mL for ranolazine 500 mg and 1000 mg dose, respectively. The mean hemodialysis percent reduction ratio for the ranolazine 500 mg dose was 52.3 ± 8.1% and for the ranolazine 1000 mg dose was 69.2 ± 37.6%. CONCLUSIONS: Data on ranolazine dosing in patients receiving maintenance hemodialysis is almost non-existent. Given the extent of pharmacokinetic variability observed with the 500 mg and 1000 mg oral doses of ranolazine, neither can be recommended as a starting dose in patients receiving maintenance hemodialysis. Guided by the information gained form this study about the extent of hemodialytic drug clearance, further multi-dose clinical trials of ranolazine are needed to optimize therapeutic outcomes in this patient population.

Impact of Information Presentation Format on Preference for Total Knee Replacement Surgery.

OBJECTIVE: Patients have a poor understanding of outcomes related to total knee replacement (TKR) surgery, with most patients underestimating the potential benefits and overestimating the risk of complications. In this study, we sought to compare the impacts of descriptive information alone or in combination with an icon array, experience condition (images), or spinner on participants' preference for TKR. METHODS: A total of 648 members of an online arthritis network were randomized to 1 of 4 outcome presentation formats: numeric only, numeric with an icon array, numeric with a set of 50 images, or numeric with a functional spinner. Preferences for TKR were measured before and immediately after viewing the outcome information using an 11-point numeric rating scale. Knowledge was assessed by asking participants to report the frequency of each outcome. RESULTS: Participants randomized to the icon array, images, and spinner had stronger preferences for TKR (after controlling for baseline preferences) compared to those viewing the numeric only format (P < 0.05 for all mean differences). Knowledge scores were highest in participants randomized to the icon array; however, knowledge did not mediate the association between format and change in preference for TKR. CONCLUSION: Decision support at the point-of-care is being increasingly recognized as a vital component of care. Our findings suggest that adding graphic information to descriptive statistics strengthens preferences for TKR. Although experience formats using images may be too complex to use in clinical practice, icon arrays and spinners may be a viable and easily adaptable decision aid to support communication of probabilistic information.

Reducing Risks for Older Adults With an Interprofessional Community-Academic Partnership: A Case Study.

As the older adult population in the United States increases and diversifies, understanding and reducing risks for hospitalization and institutionalization can reduce burdens for this vulnerable population. Using evidence-based assessment tools to understand medical, psychosocial, pharmacologic, and functional status can aid an interprofessional team to best evaluate older adults at risk. By providing culturally competent care for a diversifying older adult demographic, attention to social determinants can improve health equity for this population. This article describes in a case study exemplar, how one such interprofessional collaborative practice program, Geriatric Outreach and Training with Care (GOT Care!) provides a comprehensive assessment for high-risk older adults, identifies and documents these risks, and shares recommendations and rationale with the primary care provider toward risk reduction and improvement of outcomes.

Use of feedback to improve mental number line representations in primary care clinics.

BACKGROUND: As patients become more engaged in decisions regarding their medical care, they must weigh the potential benefits and harms of different treatments. Patients who are low in numeracy may be at a disadvantage when making these decisions, as low numeracy is correlated with less precise representations of numerical magnitude. The current study looks at the feasibility of improving number representations. The aim of this study was to evaluate whether providing a small amount of feedback to adult subjects could improve performance on a number line placement task and to determine characteristics of those individuals who respond best to this feedback. METHODS: Subjects from two outpatient clinic waiting rooms participated in a three phase number line task. Participants were asked to place numbers on a computerized number line ranging from 0 to 1000 in pre-test, feedback, and post-test phases. Generalized estimating equations were used to model log-transformed scores and to test whether 1) performance improved after feedback, and 2) the degree of improvement was associated with age, education level or subjective numeracy. RESULTS: There was an overall improvement in task performance following the feedback. The average percent absolute error was 7.32% (SD: 6.00) for the pre-test and 5.63% (SD: 3.71) for the post-test. There was a significant interaction between college education and post-test improvement. Only subjects without some college education improved with feedback. CONCLUSIONS: Adults who do not have higher levels of education improve significantly on a number line task when given feedback.

Thrombolysis for Massive Pulmonary Embolism in Pregnancy.

Pregnant women are at high risk for venous thromboembolism, including pulmonary embolism (PE), given expected changes in coagulation, fibrinolysis, and venous blood flow. In fact, PE is the leading cause of maternal death in the United States. Nonpregnant patients who develop PE with hypotension or show signs of deterioration after anticoagulation receive thrombolytics as a standard of care. Pregnant women, however, have been excluded from clinical trials with thrombolytics, and all data available in this population are published as case reports or case series. We reviewed all reports of thrombolytics, systemic or catheter directed, used in pregnant patients with massive PE. This article summarizes the risks for thromboembolism in pregnancy, compares and contrasts thrombolytic agents in this setting, and provides a recommendation for management of massive PE in this special population. Overall, reports suggest that the use of these agents is associated with beneficial outcomes and a relatively low risk of complications. The quality of this evidence is low, and clinical judgment is required to assess individual patients for risks versus benefits of thrombolysis.

Utilization of Continuous "Spinners" to Communicate Risk.

BACKGROUND: As patients become more involved in their medical care, they must consider the specific probabilities of both positive and negative outcomes associated with different treatments. Patients who are low in numeracy may be at a disadvantage when making these decisions. This study examined the use of a "spinner" to present probabilistic information compared to a numerical format and icon array. DESIGN: Subjects ( n = 151) were asked to imagine they suffered from chronic back pain. Two equally effective medications, each with a different incidence of rare and common side effects, were described. Subjects were randomized to 1 of 3 risk presentation formats: numeric only, numeric with icon arrays, or numeric with spinners, and answered questions regarding their risk knowledge, medication preference, and how much they liked the presentation format. RESULTS: Compared with the numeric only format, both the spinner and icon array increased risk knowledge and were rated more likeable by subjects. Subjects viewing the spinner format were also more likely to prefer the pill with the lowest side-effect burden. LIMITATIONS: The relatively small size, convenience sample, and hypothetical scenario were limitations of this study. CONCLUSIONS: The use of continuous spinners presents a new approach for communicating risk to patients that may aid in their decision making.

Association of Oseltamivir Activation with Gender and Carboxylesterase 1 Genetic Polymorphisms.

Oseltamivir, an inactive anti-influenza virus prodrug, is activated (hydrolysed) in vivo by carboxylesterase 1 (CES1) to its active metabolite oseltamivir carboxylate. CES1 functions are significantly associated with certain CES1 genetic variants and some non-genetic factors. The purpose of this study was to investigate the effect of gender and several CES1 genetic polymorphisms on oseltamivir activation using a large set of individual human liver samples. CES1-mediated oseltamivir hydrolysis and CES1 genotypes, including the G143E (rs71647871), rs2244613, rs8192935, the -816A>C (rs3785161) and the CES1P1/CES1P1VAR, were determined in 104 individual human livers. The results showed that hepatic CES1 protein expression in females was 17.3% higher than that in males (p = 0.039), while oseltamivir activation rate in the livers from female donors was 27.8% higher than that from males (p = 0.076). As for CES1 genetic polymorphisms, neither CES1 protein expression nor CES1 activity on oseltamivir activation was significantly associated with the rs2244613, rs8192935, -816A>C or CES1P1/CES1P1VAR genotypes. However, oseltamivir hydrolysis in the livers with the genotype 143G/E was approximately 40% of that with the 143G/G genotype (0.7 ± 0.2 versus 1.8 ± 1.1 nmole/mg protein/min, p = 0.005). In summary, the results suggest that hepatic oseltamivir activation appears to be more efficient in females than that in males, and the activation can be impaired by functional CES1 variants, such as the G143E. However, clinical implication of CES1 gender differences and pharmacogenetics in oseltamivir pharmacotherapy warrants further investigations.

We Give Aminoglycoside Antibiotics at the End of Hemodialysis.

We often administer dialyzable medications after dialysis to ensure that adequate concentrations are maintained in the body until the next session. In the case of aminoglycosides, we may have the opportunity to dose more aggressively predialysis, and then use the clearance of the drug by dialysis to limit toxicities. Predialysis aminoglycoside dosing is intriguing, although studies evaluating the safety and efficacy of this approach are necessary before it can be used routinely.

Motivational Interviewing to Increase Postdischarge Antibiotic Adherence in Older Adults with Pneumonia.

OBJECTIVE: To evaluate the impact of a pharmacist-led, motivational interviewing on antibiotic adherence following discharge in older adults with pneumonia. SETTING: Inpatient medical wards in a large tertiary academic medical center. PRACTICE DESCRIPTION: Older adults diagnosed with pneumonia were enrolled from December 1, 2013, to August 1, 2014, at Yale-New Haven Hospital. PRACTICE INNOVATION: Motivational interviewing-a patient-centered method of communication-has gained recognition as a tool that can aid pharmacists in addressing negative health behaviors (e.g., medication adherence, health screenings, substance abuse during counseling sessions). However, the potential role of motivational interviewing in older adults to improve medication adherence during transitions of care is not clear. In this study, in addition to standard discharge care, older adults hospitalized with pneumonia who were randomized to the intervention group received enhanced care: pharmacist-led motivational interviewing. MAIN OUTCOME MEASUREMENTS: Evaluation of adherence to prescribed antibiotic regimens and patient satisfaction with the motivational interviewing, enhanced-care session. RESULTS: Ultimately, 87% of patients in the intervention group (n = 16) compared with 64% of patients in the control group (n = 14) were adherent to their antibiotic regimens. Patient satisfaction with the motivational interviewing intervention was high. CONCLUSION: Pharmacist-led motivational interviewing sessions have the potential to positively influence antibiotic adherence rates and patient satisfaction.

Use of arsenic trioxide in a hemodialysis-dependent patient with relapsed acute promyelocytic leukemia.

Arsenic trioxide has been established for use in both relapsed and front-line treatment of acute promyelocytic leukemia. Dose adjustments are recommended to be considered in severe renal impairment although dosage reduction guidelines are not provided. In addition, toxicities of arsenic are significant. The use of arsenic trioxide has not been well studied in dialysis patients and there is a paucity of data in the literature to support the use in such a situation. We describe an 81-year-old relapsed acute promyelocytic leukemia hemodialysis-dependent patient with a pre-existing cardiac condition who was treated with 10 mg arsenic trioxide three times weekly after dialysis. These findings provide support along with the marginal amount of currently published data for an arsenic trioxide dosing regimen in hemodialysis patients.

Psychotherapeutic Agents in End-Stage Renal Disease.

Patients with end-stage renal disease (ESRD) are often affected by many comorbid conditions, including mental health disorders. Psychiatric illness among patients with ESRD has been associated with increased risks for nonadherence, hospitalizations, suicide, and all-cause mortality. We reviewed the pharmacokinetic data available with psychotherapeutic agents, focusing on physiologic data rather than specific dosing recommendations. Unfortunately data regarding the pharmacokinetics, efficacy, and safety of psychotherapeutic agents in ESRD remain rather limited. Of the agents available, it appears that the most data in this patient group were found with selective serotonin reuptake inhibitors and benzodiazepines. Given the small number of patients enrolled in many of the studies and the wide inter-individual variability, it was difficult to interpret the significance of results in many instances. A number of agents, such as tricyclic antidepressants, were associated with adverse effects that would be imperative to avoid in patients with ESRD. Psychotherapeutic medications should be started at low doses and titrated carefully, while monitoring the efficacy and safety of each agent.

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.

Pharmacokinetics of ertapenem in critically ill patients receiving continuous venovenous hemodialysis or hemodiafiltration.

This study characterizes the pharmacokinetics of ertapenem, a carbapenem antibiotic, in critically ill adult subjects receiving continuous renal replacement therapy (CRRT). Eight critically ill patients with suspected/known Gram-negative infections receiving continuous venovenous hemodialysis (CVVHD) or continuous venovenous hemodiafiltration (CVVHDF) and ertapenem were enrolled. One gram of ertapenem was infused over 30 min. Predialyzer blood samples were drawn with the first dose of ertapenem from the hemodialysis tubing at time zero, 30 min, and 1, 2, 4, 8, 12, 18, and 24 h after the start of the ertapenem infusion. Effluent was collected at the same time points. Ertapenem total serum, unbound serum, and effluent concentrations from all eight subjects were used simultaneously to perform a population compartmental pharmacokinetic modeling procedure using NONMEM. Monte Carlo simulations were performed to evaluate the ability of several ertapenem dosing regimens (500 mg once daily, 750 mg once daily, 500 mg twice daily, and 1,000 mg once daily) to obtain effective unbound serum concentrations above 0.5, 1, and 2 µg/ml. For our simulated patients, all regimens produced unbound ertapenem concentrations above 2 µg/ml for 40% of the dosing interval for at least 96% of simulated patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00877370.).

In vitro glucose kinetics during continuous renal replacement therapy: implications for caloric balance in critically ill patients.

PURPOSE: To examine the impact of continuous renal replacement therapy (CRRT) on glucose kinetics and therefore caloric balance. METHODS: In vitro experiments were conducted to characterize glucose kinetics in a variety of CRRT modalities and prescriptions. Additional experiments evaluated the impact of citrate anticoagulation using anti-coagulant dextrose solution A (ACD-A) on CRRT glucose movement. A formula was developed to predict the glucose delivery to/from the patient per day of CRRT, and this data was extrapolated to determine the net caloric impact of CRRT.
 RESULTS: A total of 104 experiments were conducted with an overall glucose extraction coefficient of 1.04 (95% CI 1.03-1.05). CRRT-related glucose removal was directly related to effluent (dialysate and/or hemofiltration) rate and pre-filter blood glucose concentration, and inversely related to dialysis solution glucose concentration. In all modalities tested, CRRT resulted in a net negative glucose balance, with estimated caloric losses ranging between 20 kcal and 550 kcal depending on the conditions tested. The addition of ACD-A resulted in net glucose delivery in some conditions and a positive caloric balance of up to 470 kcal per day. CONCLUSIONS: CRRT can have a significant effect on glucose balance and result in either significant daily caloric gains or losses, and this effect can be predicted based on CRRT prescription and patient characteristics. Clinicians should be aware of this potential impact when prescribing nutritional therapy to patients undergoing CRRT, as an imbalance in caloric feeding can adversely affect outcomes in critically ill patients.

Pharmacokinetics of oseltamivir and oseltamivir carboxylate in critically ill patients receiving continuous venovenous hemodialysis and/or extracorporeal membrane oxygenation.

STUDY OBJECTIVE: To investigate oseltamivir and oseltamivir carboxylate pharmacokinetics in critically ill patients who were receiving continuous venovenous hemodialysis (CVVHD) and/or extracorporeal membrane oxygenation (ECMO). DESIGN: Prospective, open-label, pharmacokinetic study. SETTING: Intensive care units of an academic medical center. PATIENTS: Thirteen critically ill patients aged 13 years or older with suspected or confirmed H1N1 influenza who had a prescription for oseltamivir and were concurrently receiving CVVHD and/or ECMO between October 2009 and January 2010. INTERVENTION: Oseltamivir 150 mg was administered nasogastrically or nasoenterically every 12 hours. Blood samples were collected at baseline and at 1, 2, 4, 6, 8, 10, and 12 hours after administration of the fourth oseltamivir dose or subsequent doses. In patients receiving CVVHD, effluent also was collected at the same time points. Urine was collected throughout the 12-hour dosing interval. MEASUREMENTS AND MAIN RESULTS: Eight patients received CVVHD only, four patients received both CVVHD and ECMO, and one patient received ECMO only. Pharmacokinetic parameters for the patient who received only ECMO were not reported. The median maximum plasma concentration and area under the plasma concentration-time curve for the 12-hour dosing interval (AUC(0-12) ) for the remaining 12 patients were 83.4 ng/ml and 216 ng•hour/ml, respectively, for oseltamivir and 2000 ng/ml and 21,500 ng•hour/ml, respectively, for oseltamivir carboxylate. Mean clearance due to CVVHD was 33.8 ml/minute for oseltamivir and 50.2 ml/minute for oseltamivir carboxylate. For patients who received ECMO, no substantial differences between pre- and post-ECMO oxygenator plasma concentrations were found for oseltamivir or oseltamivir carboxylate. CONCLUSION: Although the optimal pharmacokinetic-pharmacodynamic targets for oseltamivir carboxylate remain unclear, in the patients receiving CVVHD with or without ECMO, a regimen of oseltamivir 150 mg every 12 hours yielded a median oseltamivir carboxylate AUC(0-12) considerably higher than would be expected in non-critically ill patients receiving the same dosage regimen.

The pharmacokinetics of oseltamivir and oseltamivir carboxylate in a critically ill pediatric patient receiving extracorporeal membrane oxygenation and continuous venovenous hemodialysis.

This report details the pharmacokinetics of oseltamivir and oseltamivir carboxylate following administration of high-dose oseltamivir in a critically ill child receiving extracorporeal membrane oxygenation (ECMO) and continuous venovenous hemodialysis (CVVHD). A 6-year-old critically ill male patient suffering from a presumed viral illness was transferred to our institution's pediatric intensive care unit from an outside hospital after developing respiratory failure and cardiomegaly. ECMO and oseltamivir therapy were initiated upon admission, and CVVHD was started on hospital day 3. Pharmacokinetic sampling occurred at an oseltamivir dose of approximately 4 mg/kg on hospital day 6. The patient's oseltamivir and oseltamivir carboxylate area under the plasma concentration time curves for the 12-hour dosing interval (AUC(0-12)) were 30.5 and 905 ng/mLhr, respectively. Drug clearance by CVVHD was 31.6 mL/min for oseltamivir and 26.9 mL/min for oseltamivir carboxylate. Pre- and postoxygenator oseltamivir and oseltamivir carboxylate plasma concentrations did not differ substantially. The patient's oseltamivir carboxylate plasma concentrations remained well above the reported mean 50% inhibitory concentration for 2009 pandemic H1N1 virus. However, despite receiving twice the standard dose of oseltamivir, the oseltamivir carboxylate AUC(0-12) in our patient was less than that reported in noncritically ill pediatric subjects. The reduced oseltamivir carboxylate AUC(0-12) found in our patient was most likely due to decreased drug absorption.

Antibiotic dosing in critically ill patients with acute kidney injury.

A common cause of acute kidney injury (AKI) is sepsis, which makes appropriate dosing of antibiotics in these patients essential. Drug dosing in critically ill patients with AKI, however, can be complicated. Critical illness and AKI can both substantially alter pharmacokinetic parameters as compared with healthy individuals or patients with end-stage renal disease. Furthermore, drug pharmacokinetic parameters are highly variable within the critically ill population. The volume of distribution of hydrophilic agents can increase as a result of fluid overload and decreased binding of the drug to serum proteins, and antibiotic loading doses must be adjusted upwards to account for these changes. Although renal elimination of drugs is decreased in patients with AKI, residual renal function in conjunction with renal replacement therapies (RRTs) result in enhanced drug clearance, and maintenance doses must reflect this situation. Antibiotic dosing decisions should be individualized to take into account patient-related, RRT-related, and drug-related factors. Efforts must also be made to optimize the attainment of antibiotic pharmacodynamic goals in this population.

Antibiotic pharmacokinetic and pharmacodynamic considerations in patients with kidney disease.

Although pharmacokinetic changes occurring in kidney disease are well described, pharmacodynamics in kidney disease is rarely considered. Knowledge of pharmacodynamic principles can allow a clinician to maximize an antibiotic's effectiveness while minimizing adverse effects and antibacterial resistance. An antibiotic's pharmacokinetic and pharmacodynamic profiles should drive dose adjustment decisions in patients with kidney disease. For example, although the half-lives of beta-lactams and aminoglycosides are both prolonged in these patients, beta-lactams exhibit time-dependent antibacterial activity; consequently, maintenance doses should be smaller but given at the same interval. In contrast, aminoglycosides are concentration-dependent antibiotics; hence prolongation of the dosing interval while using larger doses may be advantageous. The timing of drug administration in relation to hemodialysis may be used to achieve specific pharmacodynamic goals. Aminoglycosides given before hemodialysis generate high peaks, whereas subsequent dialytic drug removal minimizes the area under the serum concentration-time curve, potentially decreasing the risk of developing toxicity. Furthermore, new dialysis prescribing patterns (eg, automated peritoneal dialysis, nocturnal dialysis) affect pharmacokinetic and pharmacodynamic parameters in ways not appreciated by clinicians. Studies quantifying the often considerable drug removal with these therapies, as well as efforts to identify pharmacodynamic targets in patients with kidney disease are essential. This paper reviews pharmacodynamic as well as pharmacokinetic issues that should be considered when prescribing antibiotics to treat infections in this population.

Vancomycin use during left ventricular assist device support.

We reviewed the frequency and duration of vancomycin use during 93 left ventricular assist device placements. Vancomycin prophylaxis was administered for a mean duration (+/- standard deviation) of 10.5 +/- 11 days. Empirical vancomycin use was frequent, with a mean duration (+/- standard deviation) of therapy of 9.8 +/- 9 days (median, 8 days) given during 81 (87%) of the implantations. The most common indications for empirical vancomycin treatment were isolated leukocytosis or driveline drainage. Strategies to improve vancomycin use during left ventricular assist device support should be considered.