Acute Kidney Injury Associated with Area under the Curve versus Trough Monitoring of Vancomycin in Obese Patients.

Vancomycin is a first-line agent used in the treatment of methicillin-resistant Staphylococcus aureus; however, vancomycin is associated with acute kidney injury (AKI). Previous literature demonstrates decreased incidence of AKI using 24-h area under the concentration-time curve (AUC24) monitoring, but its safety is unknown in obese populations. Patients ≥18 years, with body mass indices (BMI) ≥30 kg/m2, admitted between August 2015 and July 2017 or October 2017 and September 2019, who received vancomycin for ≥72 h and had level(s) drawn within 96 h of initiation were included. The primary outcome was incidence of AKI. Secondary outcomes included inpatient mortality rate, median inpatient length of stay, median vancomycin trough concentration, and median vancomycin AUC24. AKI was identified using the highest serum creatinine value compared with the value immediately prior to vancomycin initiation based on Kidney Disease Improving Global Outcomes (KDIGO) criteria. Overall, 1,024 patients met inclusion criteria, with 142 out of 626 patients in the trough group and 65 out of 398 patients in the AUC24 group meeting criteria for AKI (22.7% versus 16.3%, P = 0.008). Logistic regression of the data to account for confounding factors maintained significance for the reduction in incidence of AKI with AUC24 monitoring compared to trough monitoring (P = 0.010). Monitoring of vancomycin with AUC24 was associated with a decreased risk of AKI when compared with trough monitoring in obese patients.

Focusing the Lens on the CAMERA Concepts: Early Combination ß-Lactam and Vancomycin Therapy in Methicillin-Resistant Staphylococcus aureus Bacteremia.

Methicillin-resistant Staphylococcus aureus (MRSA) has grown to become a major burden on health care systems. The cumulation of limited therapeutic options and worsened patient outcomes with persistent MRSA bacteremia has driven research in optimizing its initial management. The guidelines published by the Infectious Diseases Society of America currently recommend combination therapy for refractory MRSA bacteremia, but the utility of combining antibiotics from the start of therapy is under investigation. The alternative strategy of early use of ß-lactam antibiotics in combination with vancomycin upon initial MRSA bacteremia detection has shown promise. While this concept has gained international attention, providers should give this strategy serious consideration prior to implementation. The objective of this review is to examine retrospective and prospective evidence for early combination with vancomycin and ß-lactam antibiotics, as well as explore potential consequences of combination therapy.

Incidence of Acute Kidney Injury among Patients Treated with Piperacillin-Tazobactam or Meropenem in Combination with Vancomycin.

Acute kidney injury (AKI) increases during empirical antimicrobial therapy with the combination of piperacillin-tazobactam (TZP) and vancomycin (VAN) compared to the number of incidences with monotherapy or the combination of cefepime and VAN. Limited data regarding the impact of meropenem (MEM) combined with VAN exist. This study examined the AKI incidence among patients treated with MEM plus VAN (MEM+VAN) or TZP+VAN. Data were collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust from September 2007 through October 2015. Adults without previous renal disease who received MEM+VAN or TZP+VAN for at least 2 days were included. AKI was assessed using risk, injury, failure, loss, and end-stage (RIFLE) criteria. Inverse probability of treatment weighting was utilized to control for differences between groups. In total, 10,236 patients met inclusion criteria, with 9,898 receiving TZP+VAN and 338 receiving MEM+VAN. AKI occurred in 15.4% of MEM+VAN patients and in 27.4% of TZP+VAN patients (P < 0.001). TZP+VAN was associated with increased AKI compared to the level with MEM+VAN (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.82 to 3.52), after controlling for confounders. Use of MEM+VAN should be considered an appropriate alternative therapy to TZP+VAN if nephrotoxicity is a major concern. The results of this study demonstrate that judicial use of TZP+VAN for empirical coverage of infection is needed.

Influence of ß-Lactam Infusion Strategy on Acute Kidney Injury.

Limited literature is available assessing nephrotoxicity with prolonged ß-lactam infusions. This study compared the incidence of acute kidney injury (AKI) associated with a prolonged ß-lactam infusion or an intermittent infusion. This was a retrospective, matched-cohort study at an academic medical center from July 2006 to September 2015. Adult patients who received piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) for at least 48 h were evaluated. Patients were excluded for preexisting renal dysfunction or pregnancy. The primary outcome was difference in incidence of AKI evaluated using the RIFLE (risk, injury, failure, loss, and end-stage) criteria. Patients in the intermittent group were matched 3:1 to patients in the prolonged-infusion group based on the following: ß-lactam agent, age, gender, Charlson comorbidity index, baseline creatinine clearance, hypotension, receipt of vancomycin, and treatment in an intensive care unit. A total of 2,390 patients were included in the matched analysis, with 1,700 receiving intermittent infusions and 690 receiving prolonged infusion. The incidence of AKI was similar in the prolonged-infusion group to that in the intermittent-infusion group (21.6% versus 18.6%; P = 0.1). After multivariate regression, prolonged infusion was not associated with increased odds of AKI (odds ratio [OR], 1.07; 95% confidence interval [95% CI], 0.83 to 1.39). Independent predictors of AKI included TZP therapy, concomitant nephrotoxins, hypotension, and heart failure. Although AKIs were numerically more common in patients receiving prolonged ß-lactam infusions than those receiving intermittent infusions, prolonged infusion was not an independent risk factor for AKI.

Nephrotoxicity in Patients with or without Cystic Fibrosis Treated with Polymyxin B Compared to Colistin.

Nephrotoxicity is the primary adverse effect of the polymyxins. The relative rates of toxicity of polymyxin B and colistin have not been fully elucidated, especially in patients with cystic fibrosis (CF). A retrospective cohort study of adults treated with polymyxin B or colistin for at least 48 h was conducted. The primary endpoint was the incidence of kidney injury assessed by RIFLE (i.e., risk, injury, failure, loss, end-stage renal disease) criteria. Risk factors for kidney injury were evaluated using multivariate Cox regression. A total of 414 patients were evaluated, 220 of whom had CF. In patients without CF, there was no difference in kidney injury with polymyxin B and colistin (42.9% versus 50.3%, P = 0.46). Loop diuretic exposure was a risk factor for kidney injury (adjusted hazard ratio [aHR], 1.82; 95% confidence interval [CI], 1.16 to 2.83) in this population. In patients with CF, polymyxin B and colistin were associated with similar rates of kidney injury (34.5% versus 29.8%, P = 0.77). Diabetes (aHR, 2.68; 95% CI, 1.01 to 7.11), loop diuretics (aHR, 3.02; 95% CI, 1.36 to 6.73), and progressive care unit admission (aHR, 8.21; 95% CI, 2.55 to 26.46) were risk factors for kidney injury, while higher baseline serum creatinine levels (per 1 mg/dl) were protective (aHR, 0.08; 95% CI, 0.01 to 0.48). Total unadjusted kidney injury in polymyxin-treated patients was less frequent in those who had CF (30.5% versus 48.5%, P < 0.001). Polymyxin B and colistin are associated with a high incidence of kidney injury; cystic fibrosis may be protective against polymyxin nephrotoxicity, but further investigation is needed to confirm this conjecture.

Nephrotoxicity during Vancomycin Therapy in Combination with Piperacillin-Tazobactam or Cefepime.

Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in the incidence of acute kidney injury (AKI) when it is combined with antipseudomonal beta-lactams. This study compared the incidence of AKI associated with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). This was a retrospective, matched cohort study that was conducted at an academic medical center between September 2010 and September 2014 and that included adult patients without severe chronic or structural kidney disease, dialysis, pregnancy, cystic fibrosis, or a hospital transfer receiving TZP-VAN or FEP-VAN for at least 48 h. The primary outcome was the difference in the AKI incidence between the TZP-VAN and FEP-VAN groups, evaluated using the risk, injury, failure, loss of kidney function, and end-stage kidney disease (RIFLE) criteria. Patients in the two groups were matched on the basis of age, sex, severity of illness, baseline creatinine clearance, hypotension, number of nephrotoxicity risk factors, and intravenous contrast exposure. In total, 4,193 patients met all inclusion criteria (3,605 received TZP-VAN and 588 received FEP-VAN). The unadjusted AKI incidence was 21.4% in patients receiving TZP-VAN, whereas it was 12.6% in patients receiving FEP-VAN (P < 0.001). After the patients were matched, 1,633 patients receiving TZP-VAN and 578 patients receiving FEP-VAN were evaluated. The AKI incidence remained higher in patients receiving TZP-VAN than in those receiving FEP-VAN (21.4% versus 12.5%, P < 0.0001). This trend remained true for all classifications of the RIFLE criteria. After controlling for remaining confounders, TZP-VAN therapy was associated with 2.18 times the odds of AKI than FEP-VAN therapy (95% confidence interval, 1.64 to 2.94 times) in logistic regression. AKI was significantly more common in patients receiving vancomycin in combination with piperacillin-tazobactam than in those receiving vancomycin in combination with cefepime. This finding reinforces the need for the judicious use of combination empirical antimicrobial therapy.

Daptomycin Dose Optimization in Pediatric Staphylococcus aureus Bacteremia: A Pharmacokinetic/Pharmacodynamic Investigation.

Daptomycin is an antibiotic with Gram-positive activity, including methicillin-resistant Staphylococcus aureus, for which optimal pediatric dosing is unknown. This study aimed to evaluate daptomycin exposures achieved with package label dosing and to identify dosing regimens necessary to enhance efficacy and minimize toxicity in children with S. aureus bacteremia. Monte Carlo simulations were performed to determine probability of target attainment (PTA) for six pediatric age cohorts. Area under the curve to minimum inhibitory concentration ratio (AUC0-24:MIC) ≥666 was used to determine the PTA for efficacy (PTAE). Minimum concentration (Cmin) ≥24.3 mg/L determined the PTA for toxicity (PTAT). Acceptable dosing regimens were those which achieved the combined target of ≥90% PTAE and ≤5% PTAT. Package label dosing of daptomycin yielded insufficient efficacy with only 26.3% PTAE in children 13-24 months, 39.5% PTAE in children 2-6 years, 30.1% PTAE in children 7-11 years, and 50.1% PTAE in adolescents ≥12 years. To achieve the combined efficacy and safety target, doses of 18-24 mg/kg in children 3-12 months, 20-24 mg/kg in children 13-24 months, 19-24 mg/kg in children 2-6 years, 17-19 mg/kg in children 7-11 years, and 10-14 mg/kg in adolescents ≥12 years are necessary. Package label dosing resulted in suboptimal exposure for the majority of pediatric patients in all age groups evaluated. If targeting validated efficacy and safety endpoints, daily daptomycin doses of at least 20 mg/kg in children ≤6 years, 17 mg/kg in children 7-11 years, and 10 mg/kg in adolescents ≥12 years are necessary. Clinical studies evaluating these higher doses are needed.

Vancomycin AUC0-24 estimation using first-order pharmacokinetic methods in pediatric patients.

INTRODUCTION: The optimal dosing and monitoring of vancomycin in pediatrics is still unknown but has evolved to emphasize area under the curve over 24 h (AUC0-24) over minimum concentration (Cmin) monitoring. Real-world data supporting the feasibility of two-concentration kinetics with first-order equations for the estimation of vancomycin AUC0-24 in pediatric patients are lacking. OBJECTIVES: To describe the interplay of vancomycin dose, AUC0-24, and Cmin using first-order equations within four pediatric age groups. METHODS: This is a single-center, retrospective cohort study analyzing pediatric patients (<18 years) receiving intravenous vancomycin between 2020 and 2022. Included patients received at least 24 h of intravenous vancomycin with two concentrations obtained within 96 h of therapy initiation. Patients with baseline renal dysfunction were excluded. Patients were divided into four age categories: neonates (≤28 days), infants (29 days to <1 year), children (1-12 years), and adolescents (13-17 years). First-order equations were utilized to estimate pharmacokinetic parameters and AUC0-24. RESULTS: Overall, 219 patients (median age of 6 years [IQR 1-12]) met inclusion criteria. The median vancomycin daily dose was 30 mg/kg in neonates, 70 mg/kg in infants and children, and 52 mg/kg in adolescents. Median Cmin and AUC0-24 values among all age groups were 8.68 mg/L and 505 mg * h/L, respectively. For AUC0-24 values outside of the therapeutic range (400-600 mg * h/L), more values were SUPRAtherapeutic (>600 mg * h/L) than SUBtherapeutic (<400 mg * h/L). The overall trend within our data showed suboptimal correlation between Cmin and AUC0-24. However, 71% of patients with Cmin values of 5-10 mg/L had an AUC0-24 within the therapeutic range of 400-600 mg * h/L, whereas 23 patients (92%) with a SUPRAtherapeutic AUC0-24 had a Cmin value ≥15 mg/L. Approximately 10% of patients experienced acute kidney injury. CONCLUSIONS: Our data describe the relationship between vancomycin dose, Cmin, and AUC0-24 in pediatric patients. We demonstrated the feasibility of using first-order equations to estimate AUC0-24, using two concentrations obtained at steady state to monitor efficacy and safety in pediatric patients receiving intravenous vancomycin. Our data showed suboptimal correlation between AUC0-24 and Cmin, which indicates that Cmin should not be used as a surrogate marker for a therapeutic AUC0-24 in pediatric patients. In alignment with the 2020 vancomycin consensus guidelines, we suggest utilizing AUC0-24 for efficacy and safety monitoring.

Performance of ePlex® blood culture identification panels in clinical isolates and characterization of antimicrobial stewardship opportunities.

We assessed the performance of GenMark's ePlex® Blood Culture Identification (BCID) Panels for overall agreement of organism identification and resistance mechanism detection with standard microbiologic methods. This study included patients with a positive blood culture from May 2020 to January 2021. The primary outcomes were to assess concordance of ePlex® organism identification with standard identification methods and concordance of ePlex® genotypic resistance mechanism detection with standard phenotypic susceptibility testing. Secondary outcomes included panel specific performance and characterization of antimicrobial stewardship opportunities. The overall identification concordance rate in 1276 positive blood cultures was 98.1%. The overall concordance for the presence of resistance markers was 98.2% and concordance for the absence of resistance markers was 100%. A majority of ePlex® results (69.5%) represented opportunities for potential antimicrobial stewardship intervention. High concordance rates between the ePlex® BCID panels and standard identification and susceptibility methods enable utilization of results to guide rapid antimicrobial optimization.

Clinical epidemiology of carbapenem-resistant enterobacteriaceae in community hospitals: a case-case-control study.

BACKGROUND: The occurrence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing at an alarming rate worldwide. Despite that increase, there are limited data identifying risk factors. OBJECTIVE: To evaluate risk factors associated with the acquisition of CRE among hospitalized patients. METHODS: We performed a retrospective case-case-control study in 4 community hospitals from June 2007 through June 2012. Case group 1 (CG1) consisted of patients with CRE. Case group 2 (CG2) consisted of patients with carbapenem susceptible Enterobacteriaceae (CSE). CG2 patients were matched to CG1 patients by site of infection and species of Enterobacteriaceae. Hospitalized controls were matched 2:1 by date of admission and hospital location to patients in CG1. Two sets of analyses were conducted comparing demographics, comorbidities, and antibiotic exposures of CG1 and CG2 to controls and then contrasted to identify unique risk factors associated with CRE. RESULTS: Overall, 104 patients (CG1, 25 patients; CG2, 29 patients, control, 50 patients) were evaluated. CRE and CSE consisted mostly of Klebsiella spp. (63%) from a urinary source (28%). In multivariable analyses, intensive care unit (ICU) stay (OR 12.48; 95% CI 1.14-136.62; p = 0.04) and cumulative number of antibiotic days (OR 1.47; 95% CI 1.02-2.16; p = 0.04) were distinct independent predictors of CRE isolation; whereas, cumulative health care exposures (OR 2.03; 95% CI 1.20-3.41; p < 0.01) and vancomycin exposure (OR 6.70; 95% CI 1.15- 38.91; p = 0.03) were predictors for CSE. CONCLUSIONS: CRE should be considered in patients requiring ICU admission, particularly those who have received multiple antibiotics. Antibiotic stewardship efforts should be directed at reducing all antibiotic exposures as opposed to any specific antibiotic class to reduce the risk of CRE.

Association of vancomycin-induced acute kidney injury with trough versus AUC monitoring in patients receiving extended durations of therapy.

Objective: Vancomycin therapy is associated with an increased risk of acute kidney injury (AKI). Previous studies suggest that area under the curve (AUC) monitoring reduces the risk of AKI, but literature is lacking to support this in patients receiving longer durations of vancomycin therapy. Design: Retrospective cohort study. Method: Patients ≥18 years old, admitted between August 2015 and July 2017 or October 2017 and September 2019, and received at least 14 days of intravenous (IV) vancomycin therapy were included in the study. Our primary outcome was the incidence of AKI between trough monitoring and AUC monitoring groups using Kidney Disease Improving Global Outcomes criteria. Secondary outcomes included inpatient mortality, median inpatient length of stay, and median intensive care unit length of stay. Results: Overall, 582 patients were included in the study, with 318 patients included in the trough monitoring group and 264 included in the AUC monitoring group. The median duration of vancomycin therapy was 23 days (interquartile range, 16-39). Patients within the trough monitoring group had a higher incidence of AKI compared to the AUC monitoring group (45.6% vs 28.4%, p < 0.001). Furthermore, logistic regression analysis showed that AUC monitoring was associated with a 54% lower incidence of AKI (OR 0.46, 95% CI [0.31-0.69]). All-cause inpatient mortality was numerically higher in the trough monitoring group (12.9% vs 8.3%, p = 0.078). Conclusions: In patients who received at least 14 days of IV vancomycin therapy, AUC monitoring was associated with a lower incidence of AKI.

Treatment of Klebsiella pneumoniae carbapenemase (KPC) infections: a review of published case series and case reports.

The emergence of Klebsiella pneumoniae carbapenemases (KPCs) producing bacteria has become a significant global public health challenge while the optimal treatment remains undefined. We performed a systematic review of published studies and reports of treatment outcomes of KPC infections using MEDLINE (2001-2011). Articles or cases were excluded if one of the following was fulfilled: no individual patient data provided, no treatment regimen specified, no treatment outcome specified, report of colonization, or greater than three antibiotics were used to treat the KPC infection. Data extracted included patient demographics, site of infection, organism, KPC subtype, antimicrobial therapy directed at KPC-infection, and treatment outcome. Statistical analysis was performed in an exploratory manner. A total of 38 articles comprising 105 cases were included in the analysis. The majority of infections were due to K. pneumoniae (89%). The most common site of infection was blood (52%), followed by respiratory (30%), and urine (10%). Forty-nine (47%) cases received monotherapy and 56 (53%) cases received combination therapy directed at the KPC-infection. Significantly more treatment failures were seen in cases that received monotherapy compared to cases who received combination therapy (49% vs 25%; p= 0.01). Respiratory infections were associated with higher rates of treatment failure with monotherapy compared to combination therapy (67% vs 29% p= 0.03). Polymyxin monotherapy was associated with higher treatment failure rates compared to polymyxin-based combination therapy (73% vs 29%; p= 0.02); similarly, higher treatment failure rates were seen with carbapenem monotherapy compared to carbapenem-based combination therapy (60% vs 26%; p= 0.03). Overall treatment failure rates were not significantly different in the three most common antibiotic-class combinations: polymyxin plus carbapenem, polymyxin plus tigecycline, polymyxin plus aminoglycoside (30%, 29%, and 25% respectively; p=0.6). In conclusion, combination therapy is recommended for the treatment of KPC infections; however, which combination of antimicrobial agents needs to be established in future prospective clinical trials.

Time Above All Else: Pharmacodynamic Analysis of ß-Lactams in Critically Ill Patients.

ß-Lactams are the most commonly used antibiotics in intensive care units (ICUs). As critically ill patients often experience pharmacokinetic aberrations, and rates of antimicrobial resistance vary between hospital settings, reliance on tertiary sources or package labeling to guide empiric dosing often results in suboptimal ß-lactam exposure. The primary objective was to identify ß-lactam regimens capable of achieving ≥90% cumulative fraction of response (CFR) against 7 Gram-negative pathogens within 4 ICUs at our institution. Unit-specific minimal inhibitory concentration (MIC) distribution data was used in combination with published pharmacokinetic parameters in critically ill patients to perform Monte Carlo simulations. The percentage of time for which the unbound concentration of antibiotic remained above the MIC (%ƒT > MIC) was used as the pharmacodynamic target: 70%ƒT >MIC for cefepime, 40%ƒT > MIC for meropenem, and 50%ƒT > MIC for piperacillin/tazobactam. Regimens were modeled to determine the likelihood of achieving ≥90% CFR. Overall, intermittently dosed cefepime, meropenem, and piperacillin/tazobactam failed to achieve ≥90% CFR for every organism. Cefepime 2 g intermittent bolus every 8 hours failed to achieve ≥90% CFR for Klebsiella pneumoniae or Enterobacter cloacae despite susceptibility rates exceeding 90%. Piperacillin/tazobactam 4.5 g prolonged infusion (PI) every 6 hours achieved <85% CFR for Pseudomonas aeruginosa and <50% CFR for Acinetobacter baumannii in every ICU. Meropenem 2 g PI every 8 hours and meropenem 2 g PI every 6 hours were the only regimens capable of achieving ≥90% CFR for P aeruginosa in all units. Use of Monte Carlo simulations, with incorporation of local MIC distribution data, provides a mechanism to effectively predict optimal agent and dose selection within specific hospital systems, thereby enhancing pharmacokinetic/pharmacodynamic optimization and improving clinical efficacy.

Changing times: The impact of gram-negative breakpoint changes over the previous decade.

We assessed breakpoint changes of 13,101 Enterobacterales and Pseudomonas aeruginosa isolates from the past decade. All ß-lactams and fluoroquinolones demonstrated decreased susceptibilities following breakpoint changes. Enterobacter cloacae experienced the largest average decrease in susceptibility amongst the Enterobacterales at 5.3% and P. aeruginosa experienced an average decrease in susceptibility of 9.3%.

Comparison of Bayesian-derived and first-order analytic equations for calculation of vancomycin area under the curve.

INTRODUCTION: Consensus guidelines recommend targeting a vancomycin area under the curve to minimum inhibitory concentration (AUC24 :MIC) ratio of 400-600 to improve therapeutic success and reduce nephrotoxicity. Although guidelines specify either Bayesian software or first-order equations may be used to estimate AUC24 , there are currently no large studies directly comparing these methods. OBJECTIVE: To compare calculated vancomycin AUC24 using first-order equations with two-drug concentrations at steady state to Bayesian two- and one-concentration estimations. METHODS: This was a single-center, retrospective cohort study of 978 adult hospitalized patients receiving intravenous vancomycin between 2017 and 2019. Patients were included if they received at least 72 h of vancomycin and had two-serum drug concentrations obtained. AUC24 was calculated using first-order analytic (linear), Bayesian two-concentration, and Bayesian one-concentration methods for each patient. The InsightRx™ software platform was used to calculate Bayesian AUC24 . Pearson's correlation and clinical agreement (based on AUC24  classified as subtherapeutic, therapeutic, or supratherapeutic) were used to assess agreement between methods. Bland-Altman plots were used to assess mean difference (MD) and 95% limits of agreement (LOA). RESULTS: Excellent agreement was observed between linear and Bayesian two-concentration methods (r = 0.963, clinical agreement = 87.4%) and Bayesian two-concentration and one-concentration methods (r = 0.931, clinical agreement = 88.5%); however, a degree of variability was noted with 95% LOA -99 to 76 (MD = -11.5 mg*h/L) and -92 to 113 (MD = -10.4 mg*h/L), for the respective comparisons. The agreement between linear and Bayesian one-concentration approaches was less than prior comparisons (r = 0.823, clinical agreement = 76.8%) and demonstrated the greatest amount of variability with 95% LOA -197 to 153 (MD = -21.9 mg*h/L). CONCLUSIONS: Linear and Bayesian two-concentration methods demonstrated high-level agreement with acceptable variability and may be considered comparable to estimate vancomycin AUC24 . As linear and Bayesian one-concentration methods demonstrated significant variability and suboptimal agreement, concerns exist surrounding the interchangeability of these methods in clinical practice, particularly at higher extremes of AUC24 .

Appropriateness of antibiotic use in patients with and without altered mental status diagnosed with a urinary tract infection.

Objective: The objective of this study was to determine antibiotic appropriateness based on Loeb minimum criteria (LMC) in patients with and without altered mental status (AMS). Design: Retrospective, quasi-experimental study assessing pooled data from 3 periods pertaining to the implementation of a UTI management guideline. Setting: Academic medical center in Lexington, Kentucky. Patients: Adult patients aged ≥18 years with a collected urinalysis receiving antimicrobial therapy for a UTI indication. Methods: Appropriateness of UTI management was assessed in patients prior to an institutional UTI guideline, after guideline introduction and education, and after implementation of a prospective audit-and-feedback stewardship intervention from September to November 2017-2019. Patient data were pooled and compared between patients noted to have AMS versus those with classic UTI symptoms. Loeb minimum criteria were used to determine whether UTI diagnosis and treatment was warranted. Results: In total, 600 patients were included in the study. AMS was one of the most common indications for testing across the 3 periods (19%-30.5%). Among those with AMS, 25 patients (16.7%) met LMC, significantly less than the 151 points (33.6%) without AMS (P < .001). Conclusions: Patients with AMS are prescribed antibiotic therapy without symptoms indicative of UTI at a higher rate than those without AMS, according to LMC. Further antimicrobial stewardship efforts should focus on prescriber education and development of clearly defined criteria for patients with and without AMS.

Efficacy and safety of vancomycin loading doses in critically ill patients with methicillin-resistant Staphylococcus aureus infection.

BACKGROUND: While vancomycin loading doses may facilitate earlier pharmacokinetic-pharmacodynamic target attainment, the impact of loading doses on clinical outcomes remains understudied. Critically ill patients are at highest risk of morbidity and mortality from methicillin resistant Staphylococcus aureus (MRSA) infection and hypothesized to most likely benefit from a loading dose. We sought to determine the association between receipt of a vancomycin loading dose and clinical outcomes in a cohort of critically ill adults. METHODS: Four hundred and forty-nine critically ill patients with MRSA cultures isolated from blood or respiratory specimens were eligible for the study. Cohorts were established by receipt of a loading dose (⩾20 mg/kg actual body weight) or not. The primary outcome was clinical failure, a composite outcome of death within 30 days of first MRSA culture, blood cultures positive ⩾7 days, white blood cell count up to 5 days from vancomycin initiation, temperature up to 5 days from vancomycin initiation, or substitution (or addition) of another MRSA agent. RESULTS: There was no difference in the percentage of patients experiencing clinical failure between the loading dose and no loading dose groups (74.8% versus 72.8%; p = 0.698). Secondary outcomes were also similar between groups, including mortality and acute kidney injury, as was subgroup analysis based on site of infection. Exploratory analyses, including assessment of loading dose based on quartiles and a multivariable logistic regression model showed no differences. CONCLUSION: Use of vancomycin loading doses was not associated with improved clinical outcomes in critically ill patients with MRSA infection.

Pharmacist Survey: Pharmacist Perception of Vancomycin Area Under the Curve Therapeutic Drug Monitoring.

BACKGROUND: Evidence suggests the standard vancomycin trough goal of 15 to 20 mg/L for serious Staphylococcus aureus infections is associated with acute kidney injury, whereas appropriate monitoring of 24-hour area under the curve (AUC) may decrease nephrotoxicity. As a result, institutions have transitioned to AUC monitoring, the predictive pharmacokinetic/pharmacodynamic parameter of vancomycin to improve safety outcomes. However, this method may require increased pharmacist time and effort. Pharmacist perception of the practice change is largely unknown and warrants investigation. METHODS: An electronic survey was disseminated via e-mail to pharmacists 5 months post-AUC implementation. Items of interest were focused on pharmacist perception, including quantity of patients monitored using AUC, justification of the practice change, differences in efficacy and safety, and changes in monitoring time requirements. RESULTS: The pharmacist survey was distributed to 196 pharmacists and 84 responded (43% response rate). Eighty-one pharmacists had monitored patients using AUC methods. Sixty-nine percent of these respondents perceived the change to result in increased or slightly increased patient safety, 27% described no difference, and 4% stated safety was decreased or slightly decreased. Forty-two percent perceived the transition to result in increased or slightly increased efficacy, while 48% noted no difference and 10% responded that efficacy was decreased or slightly decreased. Pharmacists stated the creation of an institutional calculator decreased the time required to calculate AUC. CONCLUSION: After the change to AUC monitoring, pharmacists perceived improvements in safety outcomes while efficacy was at least similar if not increased.