Assessment of the validity of peer scores and peer feedback in an online peer assessment platform (Kritik).

BACKGROUND AND PURPOSE: Online peer assessment platforms aim to improve the accuracy of peer scores (numerical scores based on a rubric) and hold students accountable for peer feedback (written comments). We evaluated the validity of peer scores and peer feedback using the online platform, Kritik. EDUCATIONAL ACTIVITY AND SETTING: The course was a two-credit hour online infectious diseases pharmacotherapy elective consisting of twelve third-year students enrolled in a four-year doctor of pharmacy program. Students analyzed patient cases and created video presentations of their therapeutic care plan weekly. Each student scored three peers' presentations using a rubric and provided peer feedback in Kritik. The instructor independently scored the presentations. The students' presentation scores, which was the weighted average of three peers' scores, was compared to the instructor's score. Students also rated the peer feedback they received using two Likert-type scales (feedback-on-feedback [FoF] ratings). Two faculty rated 97 randomly selected peer feedback (written comments) and recorded their FoF ratings separately. Students completed an anonymous course evaluation and exit survey. FINDINGS: The Pearson correlation coefficient between weighted peer scores and instructor scores for 91 presentations was r = 0.880. There was fair agreement in FoF ratings between students and faculty based on weighted kappa. All students would recommend the course and had a positive experience with peer assessment and the platform. SUMMARY: Weighted peer scores strongly correlated with instructor scores, and students held each other accountable for peer feedback in Kritik. Our findings should be confirmed in different contexts and settings.

Optimal ceftazidime/avibactam dosing exposure against KPC-producing Klebsiella pneumoniae.

OBJECTIVES: Infections due to carbapenem-resistant Enterobacterales are considered urgent public health threats and often treated with a ß-lactam/ß-lactamase inhibitor combination. However, clinical treatment failure and resistance emergence have been attributed to inadequate dosing. We used a novel framework to provide insights of optimal dosing exposure of ceftazidime/avibactam. METHODS: Seven clinical isolates of Klebsiella pneumoniae producing different KPC variants were examined. Ceftazidime susceptibility (MIC) was determined by broth dilution using escalating concentrations of avibactam. The observed MICs were characterized as response to avibactam concentrations using an inhibitory sigmoid Emax model. Using the best-fit parameter values, %fT>MICi was estimated for various dosing regimens of ceftazidime/avibactam. A hollow-fibre infection model (HFIM) was subsequently used to ascertain the effectiveness of selected regimens over 120 h. The drug exposure threshold associated with bacterial suppression was identified by recursive partitioning. RESULTS: In all scenarios, ceftazidime MIC reductions were well characterized with increasing avibactam concentrations. In HFIM, bacterial regrowth over time correlated with emergence of resistance. Overall, suppression of bacterial regrowth was associated with %fT>MICi ≥ 76.1% (100% versus 18.2%; P < 0.001). Using our framework, the optimal drug exposure could be achieved with ceftazidime/avibactam 2.5 g every 12 h in 5 out of 7 isolates. Furthermore, ceftazidime/avibactam 2.5 g every 8 h can suppress an isolate deemed resistant based on conventional susceptibility testing method. CONCLUSIONS: An optimal drug exposure to suppress KPC-producing bacteria was identified. The novel framework is informative and may be used to guide optimal dosing of other ß-lactam/ß-lactamase inhibitor combinations. Further in vivo investigations are warranted.

Optimizing pharmacokinetics/pharmacodynamics of ß-lactam/ß-lactamase inhibitor combinations against high inocula of ESBL-producing bacteria.

OBJECTIVES: Reduced in vitro ß-lactam activity against a dense bacterial population is well recognized. It is commonly attributed to the presence of ß-lactamase(s) and it is unknown whether the inoculum effect could be diminished by a ß-lactamase inhibitor. We evaluated different ß-lactam/ß-lactamase inhibitor combinations in suppressing a high inoculum of ESBL-producing bacteria. METHODS: Three clinical isolates expressing representative ESBLs (CTX-M-15 and SHV-12) were examined. The impact of escalating ß-lactamase inhibitor (tazobactam or avibactam) concentrations on ß-lactam (piperacillin or ceftazidime) MIC reduction was characterized by an inhibitory sigmoid Emax model. The effect of various dosing regimens of ß-lactam/ß-lactamase inhibitor combinations was predicted using %T>MICi and selected exposures were experimentally validated in a hollow-fibre infection model over 120 h. The threshold exposure to suppress bacterial regrowth was identified using recursive partitioning. RESULTS: A concentration-dependent reduction in ß-lactam MIC was observed (r2 ≥0.93). Regrowth could be suppressed in all six experiments using %T>MICi ≥73.6%, but only one out of six experiments below the threshold (P = 0.015). The exposures to suppress regrowth might be attained using the clinical dose of avibactam, but a much higher dose than the standard dose would be needed for tazobactam. CONCLUSIONS: A dense population of ESBL-producing bacteria could be suppressed by an optimized dosing regimen of selected ß-lactam/ß-lactamase inhibitor combinations. The reversibility of enzyme inhibition could play an important role in diminishing the inoculum effect. In vivo investigations to validate these findings are warranted.

MIC profiling of ceftazidime/avibactam against two carbapenemase-producing Klebsiella pneumoniae isolates.

OBJECTIVES: The aim of this study was to correlate the results of a modified susceptibility testing method with outcomes of ceftazidime/avibactam (CAZ/AVI) therapy. METHODS: Two bloodstream K. pneumoniae isolates (CAZ/AVI-susceptible) from an abdominal source were recovered from two unrelated patients. Both patients were treated with CAZ/AVI but had discordant outcomes: KP118 (eradication within 24 h) and KP286 (persistent bacteraemia for over 30 days). Carbapenemase production in the two isolates was confirmed by Carba NP test. The CAZ minimum inhibitory concentration (MIC) was determined with escalating AVI concentrations (0-16 mg/L). The concentration-response was characterised by the sigmoid inhibitory maximum effect model. The best-fit parameter values were used to predict %T > MICi associated with CAZ/AVI exposures expected in peritoneal fluid after standard dosing (2.5 g every 8 h). These CAZ/AVI exposures were simulated in a hollow-fibre infection model (HFIM), and the bacterial responses were correlated with observed clinical outcomes. RESULTS: The AVI-dependent reduction in CAZ MIC was well characterised in both bacterial isolates (r2 ≥ 0.98). In the HFIM, sustained suppression of KP118 (T > MICi = 100%) was observed over 5 days, but not with KP286 (T > MICi < 100%). These observations are consistent with the clinical course of the patients. CONCLUSIONS: The discordant patient outcomes could be potentially explained by MIC profiling of CAZ/AVI. This method appears to be more robust than conventional susceptibility testing in predicting positive clinical outcome of CAZ/AVI therapy, and the clinical utility of this approach should be further investigated.

Using the Theory of Planned Behavior to Evaluate Factors That Influence PharmD Students' Intention to Attend Lectures.

Objective. To use the theory of planned behavior (TPB) to evaluate the contribution of attitude, subjective norm, and perceived behavioral control in predicting students' intention to attend class lectures in a Doctor of Pharmacy (PharmD) curriculum in which lecture recordings were available. Methods. A survey instrument based on the TPB was developed from focus groups with PharmD students. The survey was then distributed to first through third year students at the conclusion of the 2017-2018 academic school year. Respondents were asked to evaluate their beliefs regarding lecture attendance and their intention to attend lectures during the upcoming fall semester. Predictors of intention were evaluated using descriptive statistics and multiple logistic regression analyses. Results. Responses from 198 of 383 students contained usable data (52% effective response rate). The TPB constructs of attitude and subjective norm were predictors of high intention to attend lectures. Students with a positive attitude towards lecture attendance (eg, believed that purposeful active learning is desirable and occurs during class) were nearly 30% more likely to have high intention to attend lectures. Students with a positive subjective norm (ie, perceived social pressure from professors and classmates to attend lectures) were 66% more likely to have high intention to attend lectures. Perceived behavioral control was not associated with high intention to attend lectures. Conclusion. Interventions aimed at improving students' attitudes and subjective norm may be beneficial in improving students' intention to attend class lectures.

Molecular epidemiology of toxigenic Clostridioides difficile isolates from hospitalized patients and the hospital environment in Dhaka, Bangladesh.

Epidemiology of Clostridioides difficile (syn. Clostridium difficile) infection (CDI) in Bangladesh is poorly understood. This study assessed the epidemiology of CDI in hospitalized patients and hospital environmental contamination of toxigenic C. difficile at two large urban Bangladesh hospitals. This 12-month prospective observational cohort study collected stool samples from adults with diarrhea and recent antimicrobial exposure during 2017. Environmental samples were collected by swabbing surfaces of hospital common areas. Samples underwent toxigenic culture. C. difficile isolates were tested for toxins A and B and PCR-ribotyped. Of 208 stool samples, 18 (8.7%) were positive for toxigenic C. difficile. Of 400 environmental samples, 45 (11%) were positive for toxigenic C. difficile. Ribotypes present in ≥10% of stool isolates were 017 (38%), 053-163 (13%), and a novel ribotype (FP435 [13%]). Common ribotypes in environmental isolates were 017 (22%), 053-163 (11%), 106 (24%). This is the first report describing current epidemiology of CDI in at risk hospitalized adult patients in Bangladesh.

Learning Experiences Within Infectious Diseases Pharmacy Residency Programs in the United States: A Cross-Sectional Survey.

BACKGROUND: Pharmacists with residency training in infectious diseases (ID) optimize antimicrobial therapy outcomes in patients and support antimicrobial stewardship (AS) programs. Although most ID residencies are accredited and assessed by certain standards, the degree to which these programs are similar is not known. METHODS: A 19-item, cross-sectional, multicentered, electronic survey was distributed via e-mail to pharmacy residency program directors (RPDs) of all 101 second-year postgraduate (PGY-2) ID residency programs in the United States. RESULTS: Survey responses were collected from 71 RPDs (70.3%); 64.8% were associated with an academic medical center and 97.2% focused primarily in adult ID. Rotations in the microbiology laboratory, adult AS, and adult ID consult were required in 98.6% of residency programs. Only 28.2% of responding programs required pediatric AS and pediatric ID consult rotations. Programs at academic medical centers were more likely to offer immunocompromised host ID consult (P = .003), pediatric ID consult (P = .006), and hospital epidemiology (P = .047) rotations but less frequently offered outpatient AS (P = .003), viral hepatitis clinics (P = .001), and travel medicine clinics (P = .007) rotations compared to programs at nonacademic medical centers. Residents were frequently involved in AS committees (97.2%), pharmacokinetic dosing of antimicrobials (83.1%), precepting pharmacy trainees (80.3%), and performing research projects (91.5%). CONCLUSIONS: The PGY-2 ID pharmacy residency programs demonstrated consistency in required adult ID consult, antimicrobial management activities, committee service, and teaching and research opportunities. Pediatric experiences were less common. The PGY-2 ID residency programs prepare pharmacists to become antimicrobial stewards for adult patients.

Significant Publications on Infectious Diseases Pharmacotherapy in 2017.

PURPOSE: The most significant peer-reviewed articles pertaining to infectious diseases (ID) pharmacotherapy, as selected by panels of ID pharmacists, are summarized. SUMMARY: Members of the Houston Infectious Diseases Network (HIDN) were asked to nominate peer-reviewed articles that they believed most contributed to the practice of ID pharmacotherapy in 2017, including the areas of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). A list of 33 articles related to general ID pharmacotherapy and 4 articles related to HIV/AIDS was compiled. A survey was distributed to members of the Society of Infectious Diseases Pharmacists (SIDP) for the purpose of selecting 10 articles believed to have made the most significant impact on general ID pharmacotherapy and the single significant publication related to HIV/AIDS. Of 524 SIDP members who responded, 221 (42%) and 95 (18%) members voted for general pharmacotherapy- and HIV/AIDS-related articles, respectively. The highest ranked articles are summarized below. CONCLUSION: Remaining informed on the most significant ID-related publications is a challenge when considering the large number of ID-related articles published annually. This review of significant publications in 2017 may aid in that effort.

Outcomes associated with Clostridium difficile infection in patients with chronic liver disease.

Patients with chronic liver disease (CLD) have frequent exposure to Clostridium difficile infection (CDI) risk factors but the incidence and aetiology of CDI on this population is poorly understood. The aim of this study was to assess the incidence, disease presentation and outcomes of CDI in patients with underlying CLD. The Health Care and Utilization Project National Inpatient Sample (HCUP-NIS) 2009 dataset was used to identify patients with CLD who developed CDI along with matched non-CLD patients with CDI. Using the NIS dataset, the incidence rate of CDI was 189.4/10 000 discharges in CLD patients vs. 83.7/10 000 discharges in the non-CLD matched cohort (P < 0.001). Compared with non-CLD, comorbidity-matched controls with CDI, CLD patients with CDI had higher likelihood of in-hospital mortality (8.8% vs. 18.6%, P < 0.001), increased length of stay by 1.19 days (P < 0.001) and increased total costs by $8632 (P < 0.001). In separate analyses using a tertiary case database of hospitalised patients in Houston, Texas (2006-2016) with CLD and CDI (n = 41) compared with patients with CDI but not CLD (n = 111), CLD patients had significantly higher Charlson comorbidity index (P < 0.0001) but similar risk factors for CDI and CDI-related disease presentation compared with non-CLD patients. In conclusion, CDI-related risk factors were almost universally present in the CLD population. CDI resulted in worse outcomes in this population.

Prevalence and predictors of spontaneous bacterial peritonitis due to ceftriaxone-resistant organisms at a large tertiary centre in the USA.

OBJECTIVES: The epidemiology of spontaneous bacterial peritonitis (SBP) due to ceftriaxone-resistant organisms has not been well studied in the USA. The primary objective of this study was to assess the prevalence and predictors of ceftriaxone-resistant SBP at a large US tertiary-care centre. METHODS: This 1:1:4 case-case-control study included 141 adults with liver cirrhosis admitted from November 2011 to March 2016. Case group 1 were patients with SBP with a ceftriaxone-resistant organism (n=21). Case group 2 were patients with SBP with a ceftriaxone-susceptible organism (n=26). The control group were patients without SBP (n=94). Multiple logistic regression analysis was used to identify predictors of ceftriaxone-resistant SBP. RESULTS: Fifty isolates were identified from 47 patients with culture-positive SBP (case groups 1 and 2). Of these 50 isolates, 32 (64%) were Gram-negatives [mostly Enterobacteriaceae (91%)], 15 (30%) were Gram-positives and 3 (6%) were Candida spp. The prevalence of ceftriaxone resistance in patients with culture-positive SBP was 45% (21/47). The most common ceftriaxone-resistant organisms were ESBL-producing Enterobacteriaceae (45%). Independent predictors of ceftriaxone-resistant SBP included duration of ß-lactam therapy in the past 90days (aOR=1.07, 95% CI 1.01-1.13) and recent invasive gastrointestinal procedure (aOR=12.47, 95% CI 2.74-56.67). CONCLUSIONS: The prevalence of ceftriaxone-resistant SBP was significant at a US tertiary centre. Local epidemiological data and identification of risk factors associated with ceftriaxone-resistant SBP, e.g. increased usage of previous ß-lactam therapy and invasive gastrointestinal procedure, may help clinicians identify patients requiring alternative empirical antibiotics.

Accelerate PhenoTestTM BC Kit Versus Conventional Methods for Identification and Antimicrobial Susceptibility Testing of Gram-Positive Bloodstream Isolates: Potential Implications for Antimicrobial Stewardship.

BACKGROUND: The Accelerate PhenoTestTM BC kit (AXDX) provides rapid organism identification (ID) and antimicrobial susceptibility testing (AST) results. Its potential role for antimicrobial stewardship is unknown. OBJECTIVE: To compare the diagnostic accuracy of AXDX with conventional methods (CMs) and assess AXDX's potential role for antimicrobial stewardship in patients with Gram-positive bloodstream infections (BSIs). METHODS: This retrospective cohort study included adults with Staphylococcus aureus or Enterococcus spp BSIs from July 2014 to January 2016 at a tertiary care medical center. Available isolates were tested on AXDX, and ID and AST results from AXDX were compared with those from CMs (VITEK 2 or ETEST). The following antibiotics were assessed for categorical agreement (CA) and essential agreement (EA) between the methods: ampicillin and daptomycin ( Enterococcus spp only), erythromycin and cefoxitin ( S aureus only), linezolid, and vancomycin. Potential role of AXDX for stewardship was assessed via a retrospective audit by infectious diseases clinicians. RESULTS: We included 231 patients with S aureus (n = 112) or Enterococcus spp (n = 119) BSIs, and 106 unique isolates were available for ID and AST performance analyses. Sensitivity and specificity of AXDX for ID were 98.0% and 99.5%, respectively. CA and EA for the tested antibiotics were >97%. In Monte Carlo simulations, AXDX coupled with stewardship personnel (either 24/7 or Monday to Friday) would have allowed unnecessary therapy to be stopped and active/targeted therapy to be started ≥24 hours sooner in >50% of patients. CONCLUSIONS: Compared with CMs, AXDX had similar diagnostic accuracy and can potentially optimize therapy sooner in patients with Gram-positive BSIs.

Rezafungin (CD101), a next-generation echinocandin: A systematic literature review and assessment of possible place in therapy.

OBJECTIVES: Rezafungin (CD101) is a novel echinocandin currently under development. The purpose of this study was to perform a systematic literature review of published evidence on rezafungin and an antimicrobial stewardship audit of real-world use of echinocandins to determine areas of unmet medical needs and potential places in therapy for rezafungin. METHODS: The systematic literature review identified 8 peer-reviewed manuscripts and 19 separate abstracts. A stewardship audit was performed on hospitalised patients receiving echinocandins to better understand potential future areas of use for rezafungin. RESULTS: Rezafungin is a cyclic hexapeptide with a lipophilic tail derived from anidulafungin, with a choline moiety at the C5 ornithine position resulting in increased in vitro and in vivo stability compared with other echinocandins. Microbiological data showed similar susceptibility and resistance development between rezafungin and other echinocandins. Rezafungin has a long half-life (80h) and a favourable safety profile that allows for high doses (up to 400mg) given once weekly. A phase 2 study is ongoing. The antimicrobial stewardship audit of echinocandin identified several areas of possible use for rezafungin, including patients receiving daily echinocandins for >7 days, patients who remained in the hospital to complete a full course of daily echinocandin therapy, and patients who required an echinocandin scheduled via an infusion clinic after discharge. CONCLUSION: Rezafungin is a novel echinocandin currently in phase 2 studies, differentiated by a long half-life that allows once-weekly dosing and a safety profile that allows higher doses. Several potential areas of use for rezafungin were identified.

Significant Publications on Infectious Diseases Pharmacotherapy in 2016.

PURPOSE: This is a summary of the most important articles on infectious diseases (ID) pharmacotherapy published in peer-reviewed literature in 2016 as selected by clinical pharmacists with ID expertise. SUMMARY: The Houston Infectious Diseases Network (HIDN) was asked to identify articles published in peer-reviewed literature in 2016 that were believed to contribute significantly to ID pharmacotherapy, including human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). A list of 46 articles on general ID pharmacotherapy and 8 articles on HIV/AIDS were nominated. Members of the Society of Infectious Diseases Pharmacists (SIDP) were surveyed to select 10 general ID articles believed to have made a significant impact on general ID pharmacotherapy and 1 article most significant to HIV/AIDS pharmacotherapy. Of 445 SIDP members surveyed, 212 (47.6%) and 95 (21.3%) members voted for general ID pharmacotherapy- and HIV/AIDS-related articles, respectively. The 11 highest-ranked papers (10 general ID-related articles and 1 HIV/AIDS-related article) are summarized here. CONCLUSION: With the large number of ID-related articles published each year, it can be challenging to stay current with the most relevant ID publications. This review of significant publications in 2016 may provide a starting point for that process.

Prevalence of extended-spectrum beta-lactamase and carbapenemase-producing bloodstream isolates of Klebsiella pneumoniae in a tertiary care hospital.

To improve prescribing of empiric therapy, the local molecular epidemiology of extended-spectrum beta-lactamases (ESBLs) and Klebsiella pneumoniae carbapenemases (KPCs) in bloodstream isolates of K. pneumoniae were evaluated. Isolates resistant to third generation cephalosporins were screened phenotypically for ESBLs and carbapenemases, and subsequently confirmed by PCR for the presence of ESBL (blaTEM, blaSHV and blaCTX-M) and carbapenemase (blaKPC, blaVIM, blaNDM and blaOXA-48) genes. Hydrolytic activity (functional gene expression) was quantified using a nitrocefin degradation assay and correlated to ceftazidime or meropenem MIC. Clonality was assessed by repetitive element-based PCR. Beta-lactamases were functionally expressed in 13 isolates (15.5%); 7 (53.8%) harboured blaCTX-M-15 and 6 (46.2%) carried the blaKPC-2 gene. Correlation of hydrolytic activity to MIC yielded a coefficient of 98% for isolates expressing ESBLs alone and 56% for carbapenemase producers. Four unique ESBL-expressing clones and five carbapenem-resistant clones were identified. All 13 resistant isolates were susceptible to ceftazidime/avibactam (MIC ≤ 8/4 mg/L).

Bacteremia in Patients With Liver Cirrhosis: Prevalence and Predictors of Multidrug Resistant Organisms.

GOALS: The objective of this study was to assess the prevalence and predictors of multidrug resistant organisms (MDRO) in cirrhotic patients with bacteremia at a large tertiary center in the United States. BACKGROUND: The epidemiology of bacteremia in patients with liver cirrhosis has not been well studied in the United States. STUDY: This case-case control study included 180 adults with liver cirrhosis hospitalized from 2011 to 2015. Case group 1 were patients with bacteremia due to a MDRO (n=30). Case group 2 were patients with bacteremia due to a non-MDRO (n=60). Control group comprised patients without bacteremia (n=90). MDRO was defined as bacteria that was nonsusceptible to ≥1 agent in ≥3 antimicrobial categories. RESULTS: Of the 90 bacteremia episodes, 44% were because of gram-positive bacteria, 50% were because of gram-negative bacteria, and 6% were polymicrobial. MDROs caused 30 of 90 (33%) bacteremia episodes, including methicillin-resistant Staphylococcus species [12% (11/90)], fluoroquinolone-resistant Enterobacteriaceae [10% (9/90)], and Enterococcus faecium [3% (3/90)]. Eight percent of Enterobacteriaceae produced extended-spectrum ß-lactamases. Four independent predictors of MDROs were identified: nonwhite race [adjusted odds ratio (aOR), 3.35; 95% confidence interval (CI), 1.19-9.38], biliary cirrhosis (aOR, 11.75; 95% CI, 2.08-66.32), blood cultures obtained >48 hours after hospital admission (aOR, 6.02; 95% CI, 1.70-21.40), and recent health care exposure (aOR, 9.81; 95% CI, 2.15-44.88). CONCLUSIONS: A significant proportion of bacteremia in cirrhotic patients was due to MDROs at a large US tertiary care center. Local epidemiology data and identification of risk factors associated with MDROs may help with optimal empiric antibiotic selection.

Significant publications on infectious diseases pharmacotherapy in 2015.

PURPOSE: The most important articles on infectious diseases (ID) pharmacotherapy published in the peer-reviewed literature in 2015, as nominated and selected by panels of pharmacists and others with ID expertise, are summarized. SUMMARY: Members of the Houston Infectious Diseases Network were asked to nominate articles published in prominent peer-reviewed journals in 2015 that were thought to have a major impact in the field of ID pharmacotherapy. A list of 55 nominated articles on general ID-related topics and 10 articles specifically related to human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) was compiled. In a national online survey, members of the Society of Infectious Diseases Pharmacists (SIDP) were asked to select from the list 10 general ID articles believed to have made a significant contribution to the field of ID pharmacotherapy and 1 article contributing to HIV/AIDS pharmacotherapy. Of the 361 SIDP members surveyed, 153 (42%) and 76 (21%) participated in the selection of general ID-related articles and HIV/AIDS-related articles, respectively. The 11 highest-ranked publications (10 general ID-related articles and 1 HIV/AIDS-related article) are summarized here. CONCLUSION: With the growing number of significant ID-related publications each year, it can be challenging to stay current with the literature. This review of important ID pharmacotherapy publications in 2015 may be helpful in identifying key articles and lessening this burden.

Evaluation of Enoxaparin Dosing as a Risk Factor for Bleeding in Lung Transplant Recipients.

BACKGROUND: Lung transplant recipients commonly develop complications that lead to anticoagulation. Standard FDA-approved enoxaparin dosing in this population results in a high incidence of above-goal anti-Xa levels, but its association with bleeding remains unclear. OBJECTIVE: To evaluate the association between enoxaparin dosing and bleeding in lung transplant recipients and assess the relationship between dosing and anti-Xa levels. METHODS: We conducted a single-center retrospective cohort study of adult lung transplant recipients who received therapeutic enoxaparin between 2000 and 2012 at a tertiary academic center. We dichotomized enoxaparin dosing regimens into standard dose (FDA-approved doses with a 10% rounding margin) and reduced dose. Clinicians ordered anti-Xa levels as deemed clinically appropriate. The primary outcome was major bleeding or clinically relevant nonmajor bleeding. RESULTS: Of 222 patients treated with enoxaparin, 33 (14.9%) had bleeding events, of which half (17/33) were major. Bleeding occurred in 25/146 (17.1%) patients who received standard-dose enoxaparin versus 8/76 (10.5%) patients who received reduced-dose enoxaparin (P = 0.190). Multiple logistic regression demonstrated an independent association between standard-dose enoxaparin and bleeding, after adjusting for confounders (adjusted odds ratio = 3.04; 95% CI = 1.14-8.10). The median enoxaparin dose in patients with above-goal versus at-goal anti-Xa levels was 0.89 versus 0.76 mg/kg every 12 hours; P = 0.006. However, doses yielding at-goal anti-Xa levels had an interquartile range of 0.67 to 0.90 mg/kg, which overlapped with doses yielding above- and below-goal anti-Xa levels. CONCLUSIONS: Enoxaparin dose reduction and anti-Xa level monitoring can improve drug safety and facilitate individualized dose optimization in lung transplant recipients.