Joseph J. Carreno

Vancomycin-Associated Renal Dysfunction: Where Are We Now?

Vancomycin has been in clinical use for over 60 years, during which time renal toxicity has been well documented. Multiple risk factors and outcomes are associated with vancomycin‐related nephrotoxicity. Risk factors include vancomycin exposure (trough levels 15 mg/L or higher, larger area under the curve, duration of therapy), host susceptibility to vancomycin (increased body weight, preexisting renal dysfunction, critical illness), and concurrent nephrotoxin therapy. Nephrotoxicity is associated with prolonged hospital stays, mortality, and the need for renal replacement therapy. To what degree vancomycin‐associated nephrotoxicity exacerbates these adverse clinical outcomes remains unclear. This article reviews the current evidence on vancomycin‐associated nephrotoxicity and explores future research directions with potential implications for improved patient safety.

Evaluation of pharmacy generalists performing antimicrobial stewardship services

PURPOSE Improvements in medication use achieved by pharmacy generalists using a care bundle approach to antimicrobial stewardship are reported. METHODS A six-month prospective, repeated-treatment, quasi-experimental study involving three month-long intervention periods and three month-long control periods was conducted in the setting of an existing antimicrobial stewardship program at a large hospital. The intervention involved prospective audit and feedback conducted by pharmacy generalists who were trained in an antimicrobial stewardship care bundle approach. During control months, a pharmacy generalist who was not trained in antimicrobial stewardship rounded with the multidisciplinary team and provided standard-of-care pharmacy services. The primary endpoint was compliance with a care bundle of four antimicrobial stewardship metrics: documentation of indication for therapy in the medical record, selection of empirical therapy according to institutional guidelines, documented performance of indicated culture testing, and deescalation of therapy when indicated. RESULTS Two-hundred eighty-six patients were enrolled in the study: 124 in the intervention group and 162 in the control group. The cumulative rate of full compliance with all care bundle components during the six-month study was significantly greater during intervention months than during control months (68.5% versus 45.7%, p < 0.001). After adjusting for infection type, antimicrobial stewardship provided by an intervention-group pharmacist was associated with improved care bundle compliance (adjusted odds ratio, 2.70; p < 0.001). No significant differences in patient outcomes during intervention and control months were detected. CONCLUSION Pharmacy generalists trained to comply with a systematic care bundle approach enhanced the quality of antimicrobial management.

Randomized Controlled Trial to Determine the Efficacy of Early Switch From Vancomycin to Vancomycin Alternatives as a Strategy to Prevent Nephrotoxicity in Patients With Multiple Risk Factors for Adverse Renal Outcomes (STOP-NT)

Background: Use of alternative antimicrobials to vancomycin is a potential strategy to reduce acute kidney injury (AKI) in high-risk patients, but current data do not support widespread adoption of this practice. Objective: To determine the efficacy of early switch to a nonnephrotoxic alternative for prevention of AKI in high-risk patients who receive vancomycin. Methods: This was an IRB-approved, prospective randomized controlled trial in a single, tertiary care academic medical center. Patients initially prescribed vancomycin between October 2011 to April 2013 with at least 2 risk factors for AKI were included. Treatment randomization was stratified by indication for therapy. Patients were randomized to continuation of dose-optimized vancomycin or early switch to an alternative antimicrobial agent. The primary end point was nephrotoxicity by consensus guideline definition adjudicated by blinded review; the secondary end point was AKI network–defined AKI. Results: A total of 103 patients were randomized; 100 were included in the modified intent-to-treat population, 51 in the vancomycin group and 49 in the alternative group. The incidence of nephrotoxicity was 6.1% in the alternative therapy arm and 9.8% in the vancomycin group (P = 0.72). The incidence of AKI was 32.7% in the alternative therapy group and 31.4% in the vancomycin group (P = 0.89). Conclusions: No significant difference in nephrotoxicity or AKI was detected among patients treated with alternative antimicrobials compared with vancomycin. The use of alternative antimicrobial therapy instead of vancomycin solely for the purpose of preventing AKI in high-risk patients does not appear to be warranted.

Ceftaroline Fosamil for the Treatment of Community-Acquired Pneumonia: from FOCUS to CAPTURE

Ceftaroline fosamil (ceftaroline hereafter) is the latest addition to the armamentarium for the treatment of patients with community-acquired pneumonia (CAP). It is currently approved by the Food and Drug Administration (FDA) for community-acquired bacterial pneumonia (CABP), which is a recent FDA indication that centers on individuals with documented bacterial pneumonias that arise in the community setting. The purpose of this review is to summarize and discuss the major findings from the Phase III CAP clinical trials as well as the clinical experience with ceftaroline among patients with CAP in the “Ceftaroline Assessment Program and Teflaro® Utilization Registry” (CAPTURE). In its two Phase III CAP trials, ceftaroline was compared to ceftriaxone among adults with radiographically confirmed CAP requiring hospitalization who were classified as Pneumonia Outcomes Research Team (PORT) risk class III or IV. Among patients with CAP, clinical success at test of cure was 84.3% vs 77.7% (difference 6.6%, 95% confidence interval [CI]: 1.6–11.8%) in those treated with ceftaroline and ceftriaxone, respectively, across the two Phase III clinical trials. Among patients with a culture-confirmed CABP, day 4 response rates were numerically higher, albeit non-significant, among patients that received ceftaroline vs. ceftriaxone (69.5% for ceftaroline vs. 59.4% for ceftriaxone, difference 10.1%, 95% CI, −0.6% to 20.6%). The efficacy of ceftaroline is supported by real-world observational data from CAPTURE for patients with both CAP and CABP. In addition, the CAPTURE program afforded an opportunity to assess the outcomes of patients who were excluded or limited in the original Phase III trials in a non-comparative fashion. These underrepresented patient populations with CAP included: patients that received prior antibiotics, patients in the ICU, patients with severe renal dysfunction, and those with methicillin-resistant Staphylococcus aureus (MRSA) isolated from respiratory or blood culture. As CAPTURE is a retrospective, non-comparator convenience sample registry, all the findings need to be interpreted with caution.

Assessment of Time to Clinical Response in Patients with Sepsis Treated Before and After Implementation of a Matrix-Assisted Laser Desorption Ionization Time-of-Flight Blood Culture Identification Algorithm

OBJECTIVE To evaluate time to clinical response before and after implementation of rapid blood culture identification technologies. DESIGN Before-and-after trial. SETTING Large, tertiary, urban, academic health-sciences center. PATIENTS Patients >18 years old with sepsis and concurrent bacteremia or fungemia were included in the study; patients who were pregnant, had polymicrobial septicemia, or were transferred from an outside hospital were excluded. INTERVENTION Prior to the intervention, polymerase chain reaction was used to identify Staphylococcus species from positive blood cultures, and traditional laboratory techniques were used to identify non-staphylococcal species. After the intervention, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) assay and FilmArray were also used to identify additional species. During both periods, the antimicrobial stewardship team provided prospective audit and feedback for all patients on antibiotics. RESULTS A total of 219 patients were enrolled in the study: 115 patients prior to the intervention and 104 after the intervention. The median time to clinical response was statistically significantly shorter in the postintervention group than in the preintervention group (2 days vs 4 days, respectively; P=.002). By Cox regression, the implementation of MALDI-TOF and FilmArray was associated with shorter time to clinical response (hazard ratio [HR], 1.360; 95% confidence interval [CI], 1.018-1.816). After controlling for potential confounders, the study group was not independently associated with clinical response (adjusted HR, 1.279; 95% CI, 0.955-1.713). Mortality was numerically, but not statistically significantly, lower in the postintervention group than in the preintervention group (7.6% vs 11.4%; P=.342). CONCLUSIONS In the setting of an existing antimicrobial stewardship program, implementation of MALDI-TOF and FilmArray was associated with improved time to clinical response. Further research is needed to fully describe the effect of antimicrobial stewardship programs on time to clinical response. Infect Control Hosp Epidemiol 2016;37:916-923.

Pilot Study of a Bayesian Approach To Estimate Vancomycin Exposure in Obese Patients with Limited Pharmacokinetic Sampling

ABSTRACT This study evaluated the predictive performance of a Bayesian PK estimation method (ADAPT V) to estimate the 24-h vancomycin area under the curve (AUC) with limited pharmacokinetic (PK) sampling in adult obese patients receiving vancomycin for suspected or confirmed Gram-positive infections. This was an Albany Medical Center Institutional Review Board-approved prospective evaluation of 12 patients. Patients had a median (95% confidence interval) age of 61 years (39 to 71 years), a median creatinine clearance of 86 ml/min (75 to 120 ml/min), and a median body mass index of 45 kg/m2 (40 to 52 kg/m2). For each patient, five PK concentrations were measured, and four different vancomycin population PK models were used as Bayesian priors to estimate the vancomycin AUC (AUCFULL). Using each PK model as a prior, data-depleted PK subsets were used to estimate the 24-h AUC (i.e., peak and trough data [AUCPT], midpoint and trough data [AUCMT], and trough-only data [AUCT]). The 24-h AUC derived from the full data set (AUCFULL) was compared to the AUC derived from data-depleted subsets (AUCPT, AUCMT, and AUCT) for each model. For the four sets of analyses, AUCFULL estimates ranged from 437 to 489 mg·h/liter. The AUCPT provided the best approximation of the AUCFULL; AUCMT and AUCT tended to overestimate AUCFULL. Further prospective studies are needed to evaluate the impact of AUC monitoring in clinical practice, but the findings from this study suggest that the vancomycin AUC can be estimated with good precision and accuracy with limited PK sampling using Bayesian PK estimation software.

Comparative incidence and excess risk of acute kidney injury in hospitalised patients receiving vancomycin and piperacillin/tazobactam in combination or as monotherapy

Combination therapy with vancomycin and piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) compared with monotherapy with either agent. This retrospective, matched cohort study was conducted to assess the comparative incidence of AKI due to combination therapy in patients receiving vancomycin and TZP in combination or as monotherapy. Patients aged ≥18 years admitted to Albany Medical Center (Albany, NY) between September 2013 and August 2014 who had received therapy for at least two consecutive days were included. Patients who were pregnant, neutropenic, had AKI on admission or with cystic fibrosis were excluded. Patients were matched on baseline risk of AKI. The main outcome of interest was AKI, defined as an increase in serum creatinine of ≥0.3 mg/L or ≥50% within 48 h. Secondary outcomes evaluated were length of hospital and ICU stay and inpatient mortality associated with AKI. The risk of AKI was 7.0%, 8.5% and 26.8% in the vancomycin monotherapy, TZP monotherapy and combination groups, respectively (P < 0.001). In the multivariate analysis, combination therapy was independently associated with an increased odds of AKI (adjusted odds ratio = 4.406, 95% confidence interval 1.472-13.188) compared with vancomycin monotherapy. The excess risk of combination therapy was 11.3%. In this matched cohort study, there was an increased incidence of AKI in patients receiving vancomycin and TZP combination therapy. Further research is needed to determine the individual strategies to best prevent inpatient AKI in patients receiving this combination therapy.

Multicenter evaluation of IV acyclovir use prior to, during, and after a national shortage*

Multicenter evaluation of IV acyclovir use prior to, during, and after a national shortage* Milena M. McLaughlin, Joseph J. Carreno, Spencer E. Harpe, Ashley O. Jensen, Ben Lomaestro & John S. Esterly To cite this article: Milena M. McLaughlin, Joseph J. Carreno, Spencer E. Harpe, Ashley O. Jensen, Ben Lomaestro & John S. Esterly (2017): Multicenter evaluation of IV acyclovir use prior to, during, and after a national shortage*, Infectious Diseases, DOI: 10.1080/23744235.2017.1325002 To link to this article: http://dx.doi.org/10.1080/23744235.2017.1325002