Adherence to National Consensus Guidelines and Association with Clinical Outcomes in Patients with Candidemia.

BACKGROUND: National consensus guidelines outline recommendations for best practices in treating patients with candidemia. This study evaluated the impact of receiving care adherent to the best practice recommendations on clinical outcomes in patients with candidemia. METHODS: This retrospective, multicenter study included patients with candidemia from 2010 to 2015 at 9 hospitals. The primary outcome was the composite of 30-day in-hospital mortality and 90-day candidemia recurrence. Outcomes were compared between those receiving and not receiving care adherent to the guideline recommendations. Inverse probability weights with regression adjustment were utilized to determine the average treatment effect of adherent care on the composite outcome. RESULTS: 295 patients were included with 14.2% meeting criteria for the composite outcome (11.9% mortality and 2.4% recurrence). The average treatment effect of adherent care was not significant (P = .75). However, receiving appropriate initial antifungal treatment and central venous catheter removal were both associated with the composite (average treatment effect of -17.5%, P = .011 and -8.8%, P = .013, respectively). In patients with a source of infection other than the central line, central venous catheter removal was not associated with the composite (P = .95). The most common reason for failure to receive appropriate initial antifungal treatment was omission of the loading dose. CONCLUSIONS: Central venous catheter removal and appropriate initial antifungal treatment were associated with a lower incidence of the composite of mortality and recurrence. Additional studies are needed to determine the optimal duration of therapy following candidemia clearance.

Clinical outcomes of Stenotrophomonas maltophilia infection treated with trimethoprim/sulfamethoxazole, minocycline, or fluoroquinolone monotherapy.

OBJECTIVES: The historical treatment of choice for Stenotrophomonas maltophilia infection is trimethoprim/sulfamethoxazole and this is primarily based on preclinical studies. The objective of this study was to examine the clinical outcomes of patients receiving monotherapy with different agents. METHODS: This was a retrospective study of adult patients receiving monotherapy for S. maltophilia infection with trimethoprim/sulfamethoxazole (TMP/SMX), a fluoroquinolone, or minocycline from 2010 to 2016. The primary outcome was clinical failure, a composite of recurrence, alteration of therapy due to adverse reaction or concern for clinical failure, or 30-day in-hospital mortality. The secondary outcome was 30-day in-hospital mortality. To account for treatment selection bias, multivariate regression and propensity score weighting were conducted. RESULTS: 284 patients were included (217 received TMP/SMX, 28 received a fluoroquinolone, and 39 received minocycline). The TMP/SMX and minocycline groups appeared to include similar patients whereas the fluoroquinolone group appeared to represent a slightly less severely ill population. Clinical failure was similar between groups (36%, 29%, and 31% in the TMP/SMX, fluoroquinolone, and minocycline groups, respectively, P=0.69) as was 30-day mortality (15%, 7%, and 5% in the TMP/SMX, fluoroquinolone, and minocycline groups, respectively, P=0.16). After controlling for confounding factors, receipt of minocycline (adjusted odds ratio [OR]=0.2 [0.1-0.7]) but not a fluoroquinolone (adjusted OR=0.3 [0.1 to 2.1]) was associated with lower mortality compared with TMP/SMX. This association persisted after propensity score weighting. CONCLUSIONS: Outcomes were similar or better with alternatives to TMP/SMX monotherapy, which indicates this may not be the treatment of choice for infections caused by S. maltophilia.

Financial Sustainability of an Oregon Rural Health, Primary Care, and Pharmacist-Run Comprehensive Medication Management Program Through Direct Medical Billing.

BACKGROUND: Although several states recognize pharmacists as providers and allow credentialing, this practice is not recognized nationwide. Following adoption of Oregon House Bill 2028, pharmacists are recognized as providers, allowing "health insurers to provide payment or reimbursement for their services to patients." Before this law, and in several instances currently, pharmacist-run programs were financially justified through soft dollars saved by improving patient outcomes, reducing emergency department use, and decreasing readmission rates. OBJECTIVE: To determine if direct billing of third-party payers covers the direct cost of a comprehensive medication management (CMM) program in an ambulatory rural health adult population with uncontrolled diabetes or hypertension. METHODS: This study of a population derived from 2 Oregon rural health primary care clinics was a retrospective chart review of adults (aged ≥18 years) with a primary diagnosis of diabetes mellitus or hypertension who completed a CMM visit with a clinical pharmacist from March 2017 to June 2018. In determining the financial sustainability of a pharmacist-run CMM program, the following primary outcomes were evaluated: (a) percentage of visits completed per insurance type; (b) median reimbursement rate (dollars per visit) per insurance type; and (c) the estimated number of visits per day to cover 100% of the total CMM cost annually. The secondary outcome was the percentage of the major third-party payers that allowed credentialing of pharmacists. All outcomes were evaluated using descriptive statistics. RESULTS: 664 CMM visits were included. Visits per insurance type comprised Medicare Advantage (34%), traditional Medicare (25%), Oregon State Medicaid (20.9%), commercial (17.8%), and self-pay (cash; 1.4%). Median reimbursement rate (dollars per visit) was highest from Oregon Medicaid, followed by Medicare Advantage, and lowest among commercial, self-pay (cash), and traditional Medicare. Total reimbursement received throughout the duration of this pilot project covered 14.1% of the total CMM program cost. It was estimated that approximately 17 visits per day are needed to cover 100% of the total CMM cost annually per pharmacist relying solely on direct revenue within these clinics. Currently, of the 18 contracted insurance companies, only 50% recognize and allow credentialing of pharmacists as providers. CONCLUSIONS: Pharmacist-run services within the 2 rural health primary care clinics were not financially justifiable via direct billing of third-party payers alone. The lack of credentialing, recognition of pharmacists as providers, and reimbursement is inadequate for program expansion and sustainability without relying on additional revenue streams or benefits from improved patient outcomes. Currently, federal insurance significantly contributes to this lack of funding. DISCLOSURES: No outside funding provided support for this research; however, funding from Willamette Valley Community Health was given in the form of a grant to partially fund the comprehensive medication management pilot program. Pharmacists were paid from this grant, while Sublimity Pharmacy compensated pharmacists in the form of benefits. The authors have nothing to disclose. This work was presented in part as a poster at the ASHP Midyear Clinical Meeting; December 4, 2018; Anaheim, CA, and as a peer-reviewed podium presentation at the Northwestern States Residency Conference; May 4, 2019; Portland, OR.

Ceftaroline-Associated Neutropenia: Case Series and Literature Review of Incidence, Risk Factors, and Outcomes.

Ceftaroline is increasingly prescribed for "off-label" indications involving longer durations and higher doses. There have been postmarketing case reports of neutropenia among patients who have received extended durations of ceftaroline, but limited published data currently exist on its incidence and risk factors. We review a total of 37 published cases of ceftaroline-associated neutropenia including cases (n = 4) identified in our health care system. The median time from ceftaroline initiation to development of neutropenia (range) was 25 (8-125) days, with a median duration of neutropenia (range) of 4 (1-16) days. Agranulocytosis (absolute neutrophil count [ANC] nadir < 100 cells/mm3) developed in 49% of cases (n = 18), and there was an ANC nadir of 0 in 27% (n = 10). The overall incidence of neutropenia among cases receiving ceftaroline for ≥7-14 days (range) was 12% (7%-18% per individual study), higher than for comparator antibiotics in the literature. Risk factors for ceftaroline-associated neutropenia varied among studies and remain poorly defined.

Review and Validation of Bayesian Dose-Optimizing Software and Equations for Calculation of the Vancomycin Area Under the Curve in Critically Ill Patients.

BACKGROUND: Vancomycin area under the concentration-time curve (AUC) has been linked to efficacy and safety. An accurate method of calculating the AUC is needed. METHODS: Bayesian dose-optimizing software programs available for clinician use and first-order pharmacokinetic equations were evaluated for their ability to estimate vancomycin AUC. A previously published rich pharmacokinetic data set of 19 critically ill patients was used for validation of the AUC estimation. The AUC estimated using subsets of the full data set by Bayesian software and equations was compared with the reference AUC. Accuracy (ratio of estimated AUC to the reference AUC) and bias (percentage difference of estimated AUC to reference AUC) were calculated. RESULTS: Five Bayesian dose-optimizing software programs (Adult and Pediatric Kinetics [APK], BestDose, DoseMe, InsightRx, and Precise PK) and two first-order pharmacokinetic equations were included. Of the Bayesian programs, InsightRx was the most adaptable, visually appealing, easiest to use, and had the most company support. Utilizing only the trough, accuracy (range 0.79-1.03) and bias (range 5.1-21.2%) of the Bayesian dose-optimizing software were variable. Precise PK and BestDose had the most accurate estimates with the accuracy values of BestDose exhibiting the most variability of all the programs; however, both programs were more difficult to use. Precise PK was the least biased (median 5.1%). Using a single nontrough value produced similar results to that of the trough for most programs. The addition of a second level to the trough improved the accuracy and bias for DoseMe and InsightRx but not Precise PK and BestDose. APK did not reliably estimate the AUC with input of two levels. Using two levels, the pharmacokinetic equations produced similar or better accuracy and bias as compared with Bayesian software. CONCLUSION: Bayesian dose-optimizing software using one or more vancomycin levels and pharmacokinetic equations utilizing two vancomycin levels produce similar estimates of the AUC.

Prospective evaluation of vancomycin pharmacokinetics in a heterogeneous critically ill population.

Rich pharmacokinetic data on vancomycin in critically ill patients are lacking. The purpose of this study was to evaluate the pharmacokinetics of vancomycin in this population using rich pharmacokinetic sampling. Nineteen critically ill patients received individualized vancomycin doses by intermittent infusion to achieve target trough concentrations (15-20 mg/L). Blood samples were collected following the third or later dose of vancomycin. Serial blood samples were collected at 30 min following initiation of the vancomycin infusion; at the end of the infusion; serially at 60, 120, 300, and 480 min after the infusion finished; and immediately prior to the next dose. Vancomycin concentration-time profiles at steady state were fit to a noncompartmental model to determine the pharmacokinetic parameters. Vancomycin trough concentration was correlated to AUC0-24 (r = 0.83, P < 0.001). Total body weight was a predictor of volume of distribution (r = 0.43, P = 0.03). Age, serum creatinine, and creatinine clearance (CrCl) were found to be predictors for vancomycin clearance (r = -0.67, -0.52, and, 0.72, respectively). CrCl was the best predictor of vancomycin systemic clearance, and addition of other variables to a multivariate model failed to improve model fit. Vancomycin trough concentration may not be an adequate surrogate of AUC0-24. Additional research is needed to determine dosing strategies to optimize AUC0-24 while limiting toxicity.

Ceftaroline for the treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus: a case series.

Despite limited clinical data, ceftaroline is commonly used for treatment of complicated, invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). A retrospective chart review was conducted of adult patients receiving ceftaroline for MRSA osteomyelitis admitted between April 2011 and March 2016 at a five-hospital system. Twelve patients met the inclusion criteria. All patients received prior antimicrobial therapy with a median time to switch to ceftaroline of 45.5 days. Five of the 12 patients (41.7%) met criteria for ceftaroline failure. Patients with vertebral osteomyelitis (58%) had a longer length of stay, longer ceftaroline treatment, but similar success rates to those with non-vertebral osteomyelitis (57% vs. 60%). Ceftaroline is a viable alternative for a challenging patient population that has failed or are unable to receive other therapies.

Comparative analysis of neutropenia in patients receiving prolonged treatment with ceftaroline.

Objectives: Ceftaroline is often used in durations greater than that studied in clinical trials. Several retrospective, non-comparative studies have suggested a higher than anticipated incidence of neutropenia in patients receiving prolonged treatment with ceftaroline. We sought to determine if ceftaroline was associated with neutropenia by comparing the incidence with ceftaroline treatment with treatment with several comparative antibiotics. Methods: Patients receiving 14 or more consecutive days of treatment with ceftaroline were compared with patients receiving cefazolin, daptomycin, linezolid, nafcillin or vancomycin (control group). The primary outcome was the development of neutropenia. Multivariate logistic regression and propensity score weighting using inverse probability weights with regression adjustment were used to control for confounding variables. Results: A total of 753 patients were included (53 that received ceftaroline and 700 that received a comparative antibiotic). Ceftaroline was associated with a greater incidence of neutropenia as compared with the control group (17.0% versus 3.9%, P < 0.001). Several covariates were also associated with neutropenia and included younger age, lower baseline absolute neutrophil count, liver disease and bone and joint infections. After controlling for these confounders, receipt of ceftaroline continued to be associated with the development of neutropenia (adjusted OR 3.97, P = 0.003). Analysis after propensity score weighting confirmed this finding. Conclusions: The results of this study suggest that prolonged treatment with ceftaroline is associated with a greater incidence of neutropenia as compared with other antibiotics that are often used for treatment of staphylococcal infections. Careful monitoring of absolute neutrophil count is recommended in patients receiving >14 days of ceftaroline.

Forecasting academic success through implementation of an online prerequisite review tutorials program for first year pharmacy students.

OBJECTIVE: Online prerequisite review (OPR) tutorials were designed and implemented to reinforce foundational scientific material in order to protect in-class time, foster self-directed learning, and ensure all students have similar baseline knowledge. METHODS: Twenty-one tutorials covering undergraduate prerequisite material were developed by faculty and organized into six core modules, comprising basic biology, chemistry, and physiology topics. A quiz on this material was given on the first day of each course. This score was correlated with the final exam score at course completion. Additional student and faculty feedback was collected through surveys. RESULTS: 2372 quiz-exam pairings were collected over three consecutive fall semesters. A one point increase in the quiz score was associated with a 3.6 point (95% confidence interval 3.1-4.0) higher exam score, as well as a greater probability of passing the exam (P<0.0001). Furthermore, simple linear regression revealed a positive correlation between quiz and exam scores (P<0.0001). Three full years of student survey data revealed an overwhelmingly positive perception of the OPR tutorials, and surveyed faculty reported better use of class time and improved student competency and participation. CONCLUSIONS: Implementation of OPR tutorials may give faculty more efficient use of class time, and their associated quizzes serve as an early indicator for students at-risk of not passing who are candidates for early interventions. Furthermore, the OPR tutorial design gives it great transferability to biomedical post-graduate programs.

Impact of an Antimicrobial Stewardship Program on Antibiotic Use at a Nonfreestanding Children's Hospital.

BACKGROUND: Pediatric stewardship programs have been successful at reducing unnecessary antibiotic use. Data from nonfreestanding children's hospitals are currently limited. This study is an analysis of antibiotic use after implementation of an antimicrobial stewardship program at a community nonfreestanding children's hospital. METHODS: In April 2013, an antimicrobial stewardship program that consisted of physician-group engagement and pharmacist prospective auditing and feedback was initiated. We compared antibiotic use in the preintervention period (April 2012 to March 2013) with that in the postintervention period (April 2013 to March 2015) in all units except the neonatal intensive care unit and the emergency department. In addition, drug-acquisition costs, antibiotic-specific use, death, length of stay, and case-mix index were examined. RESULTS: Antibiotic use decreased by 16.8% (95% confidence interval, 18.0% to -9.2%; P < .001) in the postintervention period. Vancomycin use decreased by 38% (P = .001), whereas antipseudomonal ß-lactam use was unaltered. Drug-acquisition cost savings were estimated to be $67 000/year over the 2-year postintervention period. Lengths of stay and mortality rates were unchanged in the postintervention period after adjusting for case-mix index. CONCLUSIONS: Implementation of a simple stewardship initiative with limited resources at a community nonfreestanding children's hospital effectively reduced antibiotic use without an overt negative impact on overall clinical outcomes. The results of this study suggest that nonfreestanding children's hospitals can achieve substantial reductions in antibiotic use despite limited resources.

Impact of rapid identification of Staphylococcus aureus bloodstream infection without antimicrobial stewardship intervention on antibiotic optimization and clinical outcomes.

Few studies have evaluated the clinical impact of polymerase chain reaction (PCR) for Staphylococcus aureus bloodstream infections in resource-limited settings that lack direct antimicrobial stewardship intervention. This retrospective cohort study compared patients with standard microbiological identification (n=343) to those with additional identification by (PCR) (n=130). Time to initiation of optimal therapy was similar between groups but substantially shorter in the PCR group for those infected with methicillin susceptible S. aureus (median 40.0h vs. 28.3h, P=0.001). After controlling for confounding factors including infectious diseases consultation, the PCR group had a shorter time to initiation of optimal therapy by 9.7h (95% CI 4.3-15.0h). Clinical outcomes were similar in the non-PCR and PCR groups. While time to initiation of optimal therapy was shorter in the PCR group, greater reductions may be realized through additional education, direct antimicrobial stewardship intervention, or additional clinician notification.

Outpatient antibiotic stewardship: Interventions and opportunities.

Improving the use of antibiotics across the continuum of care is a national priority. Data outlining the misuse of antibiotics in the outpatient setting justify the expansion of antibiotic stewardship programs (ASPs) into this health care setting; however, best practices for outpatient antibiotic stewardship (AS) are not yet defined. In a companion article, we focused on recommendations to overcome challenges related to the implementation of an outpatient ASP (e.g., building the AS team and defining program metrics). In this document, we outline AS interventions that have demonstrated success and highlight opportunities to enhance AS in the outpatient arena. This article summarizes examples of point-of-care testing, policies and interventions, and education strategies to improve antibiotic use that can be used in the outpatient setting.

A call to action for outpatient antibiotic stewardship.

OBJECTIVES: To address the public health threat of antibiotic resistance, there has been an enhanced call for antibiotic stewardship programs throughout the health care continuum. SUMMARY: While antibiotic stewardship programs have been well described in the inpatient setting, data on effectiveness and guidance on implementing outpatient programs is scarce. Establishing stewardship practices in the outpatient setting is necessary because more than 60% of human antibiotic use occurs in this setting. CONCLUSION: In this article, we highlight the importance and need for stewardship in the outpatient setting, discuss strategies for the development of stewardship teams, and discuss potential metrics that can be used to assess effectiveness of antibiotic stewardship interventions.

Effects of Lemon and Seville Orange Juices on the Pharmacokinetic Properties of Sildenafil in Healthy Subjects.

PURPOSE: Several severe drug interactions have been reported when sildenafil, a potent drug for the treatment of erectile dysfunction, is co-administered with drugs or herbal remedies that inhibit cytochrome P450 (CYP) 3A4. This study evaluates the effects of two citrus fruit juices, lemon and Seville orange, on the pharmacokinetics of sildenafil in male healthy subjects following a single oral dose. METHODS: We conducted an open-label, three-way crossover study in nine healthy male volunteers. Participants received a single oral dose of sildenafil (50 mg) after pretreatment with 250 mL of either water (control), undiluted lemon juice, or Seville orange juice for 3 consecutive days. All subjects were monitored for adverse effects during the study period. Plasma samples were collected for 12 h after dosing and analyzed for sildenafil concentration. RESULTS: Compared with pretreatment with water, Seville orange juice significantly increased the area under the plasma concentration-time curve from time zero to infinity and the peak plasma concentration of sildenafil by 44 % (90 % confidence interval [CI] 30-60) and 18 % (90 % CI 108-129), respectively, without affecting the time to reach peak plasma concentration. Additionally, Seville orange juice significantly reduced the apparent oral clearance of sildenafil by 30 % (90 % CI 63-75) without affecting its elimination half-life. In contrast, lemon juice did not cause any significant alterations in the pharmacokinetics of sildenafil. There was no significant treatment-related adverse effects reported during the study. CONCLUSIONS: Although it is considered as a moderate CYP3A4 inhibitor, Seville orange only caused a mild increase in exposure to sildenafil after a single oral dose, without manifestation of any adverse effects. The enhanced bioavailability of sildenafil by Seville orange may be attributed to inhibition of its intestinal first-pass effect (CYP3A4 and or p-glycoprotein). Lemon juice, in contrast, had no effects on the pharmacokinetics of sildenafil.

Impact of Infectious Diseases Consultation on Clinical Outcomes of Patients with Staphylococcus aureus Bacteremia in a Community Health System.

Staphylococcus aureus bacteremia (SAB) causes high rates of morbidity and death. Several studies in academic health settings have demonstrated that consultations from infectious diseases specialists improve the quality of care and clinical outcomes for SAB. Few data that describe the impact in resource-limited settings such as community hospitals are available. This retrospective cohort study evaluated the adherence to quality-of-care indicators and the clinical outcomes for SAB in a five-hospital community health system (range of 95 to 272 available beds per hospital), for patients with versus without infectious diseases consultation (IDC). IDC was provided if requested by the attending physician. The primary outcome was the incidence of treatment failure, defined as 30-day in-hospital death or 90-day SAB recurrence. Other outcomes included adherence to quality-of-care indicators. A total of 473 adult patients with SAB were included, with 369 (78%) receiving IDC. We identified substantial differences in baseline characteristics between the IDC group and the no-IDC group, including greater incidences of complicated bacteremia and intravenous drug users in the IDC group, with similar rates of severe illness (measured by Pitt bacteremia scores). Adherence to quality-of-care indicators was greater for patients with IDC (P < 0.001). After adjustment for other predicting variables, IDC was associated with a lower rate of treatment failure (adjusted odds ratio, 0.42 [95% confidence interval, 0.20 to 0.86]; P = 0.018). IDC provided better quality of care and better clinical outcomes for patients with SAB who were treated at small, resource-limited, community hospitals.

Impact of standardization of antimicrobial prophylaxis duration in pediatric cardiac surgery.

OBJECTIVES: The optimal duration of antimicrobial prophylaxis following pediatric cardiac surgery is still debated. Adult studies suggest that shorter durations are adequate, but there is a paucity of data on pediatric patients. METHODS: This quasi-experimental study reviewed the charts of patients 18 years and younger who underwent cardiac surgery from April 2011 to November 2014 at a single institution. Starting in April 2013, a protocol was implemented to limit antimicrobial prophylaxis to 48 hours following sternal closure. Two analyses were performed: (1) identification of risk factors for surgical site infections from the entire cohort, and (2) comparison of surgical site infection incidence in the pre- and postprotocol groups. RESULTS: In the entire cohort, delayed sternal closure (adjusted odds ratio [OR], 5.7; 95% confidence interval [CI], 1.8-17.9) and younger age (adjusted OR, 2.1; 95% CI, 1.1-3.8) were associated with incidence of surgical site infection. Following the protocol change, duration of antimicrobial prophylaxis decreased from 4.2 ± 2.7 to 1.9 ± 1.3 days (P < .0001). After adjusting for age and delayed sternal closure, the postprotocol group had an adjusted OR of 0.98 (95% CI, 0.32-3.00) for occurrence of surgical site infection. Other outcomes were not altered following the protocol change. CONCLUSIONS: Restricting antimicrobial prophylaxis to 48 hours following pediatric cardiac surgery did not increase the incidence of surgical site infection at our institution. Further study is needed to validate this finding and to identify practices that reduce surgical site infections in those with delayed sternal closure.

Prospective, Controlled Study of Acyclovir Pharmacokinetics in Obese Patients.

The current recommendations for intravenous (i.v.) acyclovir dosing in obese patients suggest using ideal body weight (IBW) rather than total body weight (TBW). To our knowledge, no pharmacokinetic analysis has validated this recommendation. This single-dose pharmacokinetic study was conducted in an inpatient oncology population. Enrollment was conducted by 1:1 matching of obese patients (>190% of IBW) to normal-weight patients (80 to 120% of IBW). All patients received a single dose of i.v. acyclovir, 5 mg/kg, infused over 60 min. Consistent with current recommendations, IBW was used for obese patients and TBW for normal-weight patients. Serial plasma concentrations were obtained and compared. Seven obese and seven normal-weight patients were enrolled, with mean body mass indexes of 45.0 and 22.5 kg/m(2), respectively. Systemic clearance was substantially higher in the obese than normal-weight patients (mean, 19.4 ± 5.3 versus 14.3 ± 5.4 liters/h; P = 0.047). Area under the concentration-time curve was lower in the obese patients (15.2 ± 2.9 versus 24.0 ± 9.4 mg · h/liter; P = 0.011), as was maximum concentration (5.8 ± 0.9 versus 8.2 ± 1.3 mg/liter; P = 0.031). Utilization of IBW for dose calculation of i.v. acyclovir in obese patients leads to lower systemic exposure than dosing by TBW in normal-weight patients. While not directly evaluated in this study, utilization of an adjusted body weight for dose determination appears to more closely approximate the exposure seen in normal-weight patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01714180.).

Worsening renal function in patients with baseline renal impairment treated with intravenous voriconazole: A systematic review.

The objective of this paper was to review the risk of worsening renal function in patients with pre-existing renal impairment receiving intravenous voriconazole (IVV). Controversy exists regarding the cause and risk of renal dysfunction in patients treated with IVV. Whilst some studies implicate renally excreted cyclodextrin, a pharmaceutical formulation stabiliser, as the cause of renal dysfunction following voriconazole administration, others provide contradicting evidence. Here we analyse the available literature to gain an insight into the significance of renal toxicity in patients treated with IVV. PubMed was searched for relevant studies to December 2014. To account for publication bias, abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy, the Infectious Diseases Society of America/ID Week, and the European Congress of Clinical Microbiology and Infectious Diseases from 2008-2014 were reviewed. Bibliographies of all identified articles were reviewed and cross-referenced for additional sources. Seven retrospective studies were identified for inclusion in the review; no prospective studies were identified. Based on the available evidence, we conclude that there is no strong evidence suggesting an increased incidence of worsening renal function with IVV use. No study thus far has provided direct conclusive evidence for cellular and physiological renal toxicity due to IVV at clinically prevalent doses.