Mixed methods evaluation of handshake antimicrobial stewardship on adult inpatient medicine floors.

Objective: To evaluate the effects of handshake antimicrobial stewardship on medicine floors at a large tertiary care hospital. Design: Retrospective observational study. Setting: 1,278-bed academic hospital. Patients: Adults admitted to non-ICU medicine services. Interventions: A handshake stewardship team consisting of an infectious diseases (ID) physician and pharmacist reviewed charts of patients receiving antimicrobials on medicine floors without a formal ID consult. Recommendations were communicated in-person to providers and acceptance rates were examined with descriptive statistics. Additional data regarding program perception among providers were obtained via surveys. Antibiotic usage trends were extracted from National Healthcare Safety Network Antimicrobial Use option data and evaluated using an interrupted time-series analysis pre- and post-intervention. Results: The overall acceptance rate of interventions was 80%, the majority being recommendations either to discontinue (37%) or de-escalate therapy (28%). Medical residents and hospitalists rated the intervention favorably with 90% reporting recommendations were helpful all or most of the time. There was a statistically significant decrease in vancomycin (78 vs 70 DOT/1,000 d present (DP), p = 0.002) and meropenem (24 vs 17 DOT/1,000 DP, p = 0.007) usage and a statistically significant increase in amoxicillin-clavulanate usage (11 vs 15 DOT/1,000 DP, p < 0.001). Overall antibiotic usage remained unchanged by the intervention, though pre-intervention there was a nonsignificant overall increasing trend while post-intervention there was a nonsignificant decreasing trend in overall usage. There was no change in in-hospital mortality. Conclusion: The addition of handshake stewardship with adult medicine services was favorably viewed by participants and led to shifts in antibiotic usage.

Spectrum scores: Toward a better definition of de-escalation.

Spectrum scores measure antimicrobial utilization while also quantifying the spectrum of activity. Accordingly, changes in spectrum score can be used to identify antimicrobial de-escalation. We show that spectrum-score-based de-escalation has a 95.7% positive percentage agreement and 81.6% negative percentage agreement versus de-escalation defined as stopping either antistaphylococcal or antipseudomonal agents.

The Implementation and Effect of Weekend Pharmacy-Driven Antimicrobial Stewardship Services at a Large Academic Medical Center.

BACKGROUND: In September 2018, pharmacy antimicrobial stewardship (AMS) services were expanded to include weekends at this academic medical center. Activities performed by AMS pharmacists on the weekends include blood culture rapid diagnostic (RDT) review, antiretroviral therapy (ART) review, prospective audit and feedback (PAF) utilizing clinical decision support, vancomycin dosing, and operational support. The purpose of this study was to assess the operational and clinical impact of these expanded AMS services. METHODS: This single-center, quasi-experimental study included data from weekends before (9/2017-11/2017) and after (9/2018-11/2018) implementation. The descriptive primary outcome was the number of activities completed for each AMS activity type in the post-implementation group only. Secondary outcomes were time to AMS opportunity resolution, time to escalation or de-escalation following PAF or RDT alert, time to resolution of miscellaneous AMS related opportunities, length of stay (LOS), and antimicrobial use outcomes. RESULTS: During the post-implementation period 1258 activities were completed, averaging 97/weekend. Inclusion criteria for time to resolution outcomes were met by 72 patients pre-implementation and 59 patients post. The median (IQR) time to AMS opportunity resolution decreased from 18.5 hours pre-intervention (7.7-35.7) to 8.5 hours post-intervention (IQR 1.8-14.0), p < 0.01. Time to escalation was 11.6 hours compared to 1.7 hours (p = 0.1), de-escalation 16.7 hours compared to 10.8 hours (p = 0.03), and miscellaneous opportunity 40.8 hours compared to 13.2 hours (p = 0.01). No differences were observed in LOS or antimicrobial use outcomes. CONCLUSION: Presence of pharmacist-driven weekend AMS services significantly reduced time to resolution of AMS opportunities. These data support the value of weekend AMS services.

Assessment of Antibiotic De-escalation by Spectrum Score in Patients With Nosocomial Pneumonia: A Single-Center, Retrospective Cohort Study.

BACKGROUND: Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) cause significant mortality. Guidelines recommend empiric broad-spectrum antibiotics followed by de-escalation (DE). This study sought to assess the impact of DE on treatment failure. METHODS: This single-center retrospective cohort study screened all adult patients with a discharge diagnosis code for pneumonia from 2016 to 2019. Patients were enrolled if they met predefined criteria for HAP/VAP ≥48 hours after admission. Date of pneumonia diagnosis was defined as day 0. Spectrum scores were calculated, and DE was defined as a score reduction on day 3 versus day 1. Patients with DE were compared to patients with no de-escalation (NDE). The primary outcome was composite treatment failure, defined as all-cause mortality or readmission for pneumonia within 30 days of diagnosis. RESULTS: Of 11860 admissions screened, 1812 unique patient-admissions were included (1102 HAP, 710 VAP). Fewer patients received DE (876 DE vs 1026 NDE). Groups were well matched at baseline, although more patients receiving DE had respiratory cultures ordered (56.6% vs 50.6%, P = .011). There was no difference in composite treatment failure (35.0% DE vs 33.8% NDE, P = .604). De-escalation was not associated with treatment failure on multivariable Cox regression analysis (hazard ratio, 1.13; 95% confidence interval, 0.96-1.33). Patients receiving DE had fewer antibiotic days (median 9 vs 11, P < .0001), episodes of Clostridioides difficile infection (2.2% vs 3.8%, P = .046), and hospital days (median 20 vs 22 days, P = .006). CONCLUSIONS: De-escalation and NDE resulted in similar rates of 30-day treatment failure; however, DE was associated with fewer antibiotic days, episodes of C difficile infection, and days of hospitalization.

Evaluation of a hybrid antimicrobial restriction process at a large academic medical center.

We conducted a retrospective review of a hybrid antimicrobial restriction process demonstrating adherence to appropriate use criteria in 72% of provisional-only orders, in 100% of provisional orders followed by ID orders, and in 97% of ID-initiated orders. Therapy interruptions occurred in 24% of provisional orders followed by ID orders.

Antimicrobial Stewardship Practice in the Ambulatory Setting From a National Cohort.

BACKGROUND: The majority of antimicrobial use occurs in the ambulatory setting. Antimicrobial stewardship programs (ASPs) are effective in improving appropriate prescribing and are now required by accreditation bodies. METHODS: This was a cross-sectional, multicenter survey describing the current state of ambulatory ASPs in a national cohort of Vizient member hospitals with ambulatory healthcare settings and serves as a benchmark for stewardship strategies related to program effectiveness. RESULTS: One hundred twenty-nine survey responses from a variety of institution types across 44 states were received. Survey respondents reported a fully functioning ASP in 7% (9 of 129) of ambulatory practices compared with 88% (114 of 129) of inpatient institutions. Effectiveness in at least 1 antibiotic use-related outcome (ie, utilization, resistance, Clostridioides difficile infection, or cost) in the past 2 years was reported in 18% (18 of 100) of ambulatory and 84% (103 of 123) of inpatient ASPs. Characteristics of ambulatory ASPs demonstrating effectiveness were institution guidelines (89%, 16 of 18), rapid diagnostic testing for respiratory viruses or group A Streptococcus (89% 16 of 18), outpatient antibiograms (78% 14 of 18), and dedicated pharmacist support (72%, 13 of 18). Ambulatory ASP effectiveness was shown to increase as programs met more of the Centers for Disease Control and Prevention (CDC) Core Elements of Outpatient Antimicrobial Stewardship (P < .001). CONCLUSIONS: Antimicrobial stewardship programs are needed in the ambulatory setting, but they are not common. Currently, few ambulatory ASPs in this survey self-identify as fully functioning. The CDC Core Elements of antimicrobial stewardship should remain foundational for ASP development and expansion.

A Retrospective Multisite Case-Control Series of Concomitant Use of Daptomycin and Statins and the Effect on Creatine Phosphokinase.

OBJECTIVE: Daptomycin has been associated with increased creatine phosphokinase (CPK) due to muscle injury leading to myalgias and muscle weakness. Statins have been proven to cause the same effects and it is recommended to discontinue the use of statins while on daptomycin. Evidence regarding this drug interaction is mixed. This study evaluated the risk of CPK elevation in concomitant use of daptomycin and statins compared to daptomycin alone. METHOD: This is a multisite retrospective case-control study of patients who received daptomycin therapy with monitoring of CPK. Rates of CPK elevations were compared in patients receiving daptomycin with a statin versus daptomycin alone. To estimate the association between CPK elevation and daptomycin therapy controlling for other risk factors, logistic regression was used to analyze data. Statistical significance was determined at ɑ of 0.05. RESULTS: A total of 3658 patients were included in the study, with 2787 on daptomycin therapy alone and 871 with concurrent statin use. The incidence of CPK elevation was 90 events (3.2%) in the daptomycin group and 26 events (3.0%) in the concurrent statin group. Patients who received daptomycin therapy in addition to statins had no statistically significant difference from patients on daptomycin alone (hazard ratio, 1.05; P = .85; 95% confidence interval, 0.61-1.84). After adjusting for potential risk factors, the hazards ratio remained almost the same. CONCLUSIONS: Concomitant use of daptomycin and statin did not show an increase risk of CPK elevation. Clinicians may consider concomitant use of daptomycin and statin therapy with weekly CPK monitoring.

Implementation of a Stewardship Initiative on Respiratory Viral PCR-based Antibiotic Deescalation.

OBJECTIVE: Respiratory viral polymerase chain reaction (RV PCR) tests assist in rapidly identifying viral pathogens and differentiating viral versus bacterial causes of pneumonia. Studies evaluating the use of RV PCR tests on antibiotic use in adults have demonstrated mixed results. We implemented an antimicrobial stewardship (ASP) intervention for patients with a positive RV PCR test result who were receiving broad-spectrum antibiotics and aimed to assess the impact on antibiotic usage. METHODS: Retrospective quasi-experimental study of adult hospitalized patients comparing time to antibiotic deescalation, duration of antibiotic therapy, and antiviral use preintervention (January-March 2016) and postintervention (January-March 2017). RESULTS: Of 172 ASP alerts reviewed, 55 (32%) were considered actionable. Of these, 47% of interventions were accepted. No significant difference was observed in median time to antibiotic deescalation (pre: 2.7 days vs post: 2.3 days, p=0.88). Time to discontinuation of antimicrobial therapy pre- and postintervention was reduced from 4 to 1.9 days (p=0.057) for piperacillin-tazobactam, from 2.7 to 1.8 days (p=0.75) for ceftriaxone, and from 3.6 to 2 days (p=0.4) for levofloxacin, respectively. Time to initiation of oseltamivir for influenza was significantly shorter in the postintervention group (pre: 11.3 hrs vs post: 3.6 hrs, p=0.02). CONCLUSION: A third of patients receiving broad-spectrum antibiotics with a positive RV PCR had an opportunity for antimicrobial optimization, although this did not translate into a significant impact on the time to antibiotic deescalation or overall antibiotic use. Combination of RV PCR results with biomarkers to rule out bacterial coinfections and chest radiographic findings may help enhance the likelihood of accepted antibiotic deescalation recommendations and represents an area of future research.

Evaluation of an electronic antimicrobial time-out on antimicrobial utilization at a large health system.

We evaluated the impact of an electronic health record based 72-hour antimicrobial time-out (ATO) on antimicrobial utilization. We observed that 6 hours after the ATO, 21% of empiric antimicrobials were discontinued or de-escalated. There was a significant reduction in the duration of antimicrobial therapy but no impact on overall antimicrobial usage metrics.

Meropenem-Vaborbactam as Salvage Therapy for Ceftazidime-Avibactam-Resistant Klebsiella pneumoniae Bacteremia and Abscess in a Liver Transplant Recipient.

We report a case of a 24-year-old liver transplant recipient who developed hepatic artery thrombosis and graft failure, which was complicated by subphrenic abscess and persistent Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bacteremia. Ceftazidime-avibactam treatment led to emergence of resistance, and alternative combination therapy failed due to persistent infection and toxicity. The infection resolved after initiation of meropenem-vaborbactam, which created a bridge to retransplantation. Treatment-emergent ceftazidime-avibactam resistance is increasingly recognized, suggesting a role for meropenem-vaborbactam.

Cost-effectiveness of three different strategies for the treatment of first recurrent Clostridium difficile infection diagnosed in a community setting.

OBJECTIVE: A significant portion of patients with Clostridium difficile infections (CDI) experience recurrence, and there is little consensus on its treatment. With the availability of newer agents for CDI and the added burdens of recurrent disease, a cost-effectiveness analysis may provide insight on the most efficient use of resources. DESIGN: A decision-tree analysis was created to compare the cost-effectiveness of 3 possible treatments for patients with first CDI recurrence: oral vancomycin, fidaxomicin, or bezlotoxumab plus vancomycin. The model was performed from a payer's perspective with direct cost inputs and a timeline of 1 year. A systematic review of literature was performed to identify clinical, utility, and cost data. Quality-adjusted life years (QALY) and incremental cost-effectiveness ratios were calculated. The willingness-to-pay (WTP) threshold was set at $100,000 per QALY gained. The robustness of the model was tested using one-way sensitivity analyses and probabilistic sensitivity analysis. RESULTS: Vancomycin had the lowest cost ($15,692) and was associated with a QALY gain of 0.8019 years. Bezlotoxumab plus vancomycin was a dominated strategy. Fidaxomicin led to a higher QALY compared to vancomycin, at an incremental cost of $500,975 per QALY gained. Based on our WTP threshold, vancomycin alone was the most cost-effective regimen for treating the first recurrence of CDI. Sensitivity analyses demonstrated the model's robustness. CONCLUSIONS: Vancomycin alone appears to be the most cost-effective regimen for the treatment of first recurrence of CDI. Fidaxomicin alone led to the highest QALY gained, but at a cost beyond what is considered cost-effective.

Evaluation of Prophylactic Antibiotic Use for Delayed Sternal Closure After Cardiothoracic Operation.

BACKGROUND: Clinical practice guidelines provide recommendations for surgical prophylaxis in patients undergoing cardiothoracic procedures. However, currently no recommendations guide the management of antibiotic prophylaxis in patients who require delayed sternal closure after cardiothoracic operation. METHODS: This is a single-center, retrospective analysis. Data were extracted from The Society of Thoracic Surgery database and electronic medical record from July 2011 through January 2016. Patients included are adults (≥18 years old) after cardiothoracic operation with delayed sternal closure. RESULTS: A total of 167 patients were included for analysis. The majority of patients (131, 78.4%) were continued on routine antibiotics and 36 patients (21.6%) were switched to broad-spectrum antibiotics for prophylaxis. Of patients on routine antibiotic prophylaxis, 6 (4.6%) experienced a sternal surgical site infection, whereas 3 patients (8.3%) switched to broad-spectrum agents before chest closure experienced a sternal surgical site infection (p = 0.407). Eleven patients (6.6%) received an abbreviated duration of antibiotics, 52 patients (31.1%) were continued on antibiotics until the time of sternal closure, and 104 patients (62.3%) were continued on antibiotics past the time of sternal closure. The incidence of infection based on duration of prophylactic antibiotic was 0, 1 (1.9%), and 8 (7.7%), respectively (p = 0.352). CONCLUSIONS: Substantial variation was found in the duration and selection of antibiotic prophylaxis for patients with delayed sternal closure after cardiothoracic operation. Broad-spectrum antimicrobial agents and extended durations of antibiotic prophylaxis were not associated with benefits in the incidence of sternal wound infection and may increase the risk of adverse effects.

Evaluation of Antimicrobial Stewardship-Related Alerts Using a Clinical Decision Support System.

Background: Information technology, including clinical decision support systems (CDSS), have an increasingly important and growing role in identifying opportunities for antimicrobial stewardship-related interventions. Objective: The aim of this study was to describe and compare types and outcomes of CDSS-built antimicrobial stewardship alerts. Methods: Fifteen alerts were evaluated in the initial antimicrobial stewardship program (ASP) review. Preimplementation, alerts were reviewed retrospectively. Postimplementation, alerts were reviewed in real-time. Data collection included total number of actionable alerts, recommendation acceptance rates, and time spent on each alert. Time to de-escalation to narrower spectrum agents was collected. Results: In total, 749 alerts were evaluated. Overall, 306 (41%) alerts were actionable (173 preimplementation, 133 postimplementation). Rates of actionable alerts were similar for custom-built and prebuilt alert types (39% [53 of 135] vs 41% [253 of 614], P = .68]. In the postimplementation group, an intervention was attempted in 97% of actionable alerts and 70% of interventions were accepted. The median time spent per alert was 7 minutes (interquartile range [IQR], 5-13 minutes; 15 [12-17] minutes for actionable alerts vs 6 [5-7] minutes for nonactionable alerts, P < .001). In cases where the antimicrobial was eventually de-escalated, the median time to de-escalation was 28.8 hours (95% confidence interval [CI], 10.0-69.1 hours) preimplementation vs 4.7 hours (95% CI, 2.4-22.1 hours) postimplementation, P < .001. Conclusions: CDSS have played an important role in ASPs to help identify opportunities to optimize antimicrobial use through prebuilt and custom-built alerts. As ASP roles continue to expand, focusing time on customizing institution specific alerts will be of vital importance to help redistribute time needed to manage other ASP tasks and opportunities.

Compliance with Procalcitonin Algorithm Antibiotic Recommendations for Patients in Medical Intensive Care Unit.

STUDY OBJECTIVES: To describe compliance with antibiotic recommendations based on a previously published procalcitonin (PCT)-guided algorithm in clinical practice, to compare PCT algorithm compliance rates between PCT assays ordered in the antibiotic initiation setting (PCT concentration measured less than 24 hours after antibiotic initiation or before antibiotic initiation) with those in the antibiotic continuation setting (PCT concentration measured 24 hours or more after antibiotic initiation), and to evaluate patient- and PCT-related factors independently associated with algorithm compliance in patients in the medical intensive care unit (MICU). DESIGN: Single-center retrospective cohort study. SETTING: Large MICU in a tertiary care academic medical center. PATIENTS: A total of 527 adults admitted to the MICU unit over a 2-year period (November 1, 2011-October 31, 2013) who had a total of 957 PCT assays performed. PCT assays whose results were determined in the MICU were allocated retrospectively to either the initiation setting cohort or the continuation setting cohort based on timing of the PCT assay. MEASUREMENTS AND MAIN RESULTS: Each PCT assay was treated as a separate episode. Antibiotic regimens were compared between the 24-hour periods before and after the results of each PCT assay and evaluated against an algorithm to determine compliance. Clinical, laboratory, PCT-related, and microbiologic variables were assessed during the 24-hour period after the PCT assay results to determine their influence on PCT algorithm compliance. A larger proportion of PCT episodes occurred in the initiation setting (540 [56.4%]) than in the continuation setting (417 [43.5%]). Overall, compliance with PCT algorithm recommendations was low (48.5%) and not significantly different between the initiation setting and the continuation setting (49.1% vs 47.7%, p=0.678). No patient-related or PCT-related factors were independently associated with PCT algorithm compliance on multivariable logistic regression. CONCLUSION: Compliance with PCT algorithm antibiotic recommendations in both the initiation and continuation settings was lower than that reported in published randomized studies. No factors were independently associated with PCT algorithm compliance. Institutions using PCT assays to guide antibiotic use should assess compliance with algorithm antibiotic recommendations. Inclusion of a formalized antimicrobial stewardship program along with a PCT-guided algorithm is highly recommended.

Pharmacodynamic and pharmacokinetic considerations in the treatment of critically Ill patients infected with carbapenem-resistant Enterobacteriaceae.

Carbapenem-Resistant Enterobacteriaceae (CRE) are an emerging healthcare crisis. Infections due to CRE are associated with high morbidity and mortality, especially in critically ill patients. Due to the multi-drug resistant nature of these infections only limited treatment options are available. Antimicrobials that have been described for the treatment of CRE infections include carbapenems, polymyxins, fosfomycin, tigecycline, aminoglycosides, and ceftazidime-avibactam. Given the limited treatment options it is imperative the pharmacokinetic and pharmacodynamics (PK-PD) characteristics of these agents are considered to optimize treatment regimens. This review will focus on the PK-PD challenges of the current treatment options for CRE infections.

A Multifaceted Approach to Reduction of Catheter-Associated Urinary Tract Infections in the Intensive Care Unit With an Emphasis on "Stewardship of Culturing".

BACKGROUND Catheter-associated urinary tract infections (CAUTIs) are among the most common hospital-acquired infections (HAIs). Reducing CAUTI rates has become a major focus of attention due to increasing public health concerns and reimbursement implications. OBJECTIVE To implement and describe a multifaceted intervention to decrease CAUTIs in our ICUs with an emphasis on indications for obtaining a urine culture. METHODS A project team composed of all critical care disciplines was assembled to address an institutional goal of decreasing CAUTIs. Interventions implemented between year 1 and year 2 included protocols recommended by the Centers for Disease Control and Prevention for placement, maintenance, and removal of catheters. Leaders from all critical care disciplines agreed to align routine culturing practice with American College of Critical Care Medicine (ACCCM) and Infectious Disease Society of America (IDSA) guidelines for evaluating a fever in a critically ill patient. Surveillance data for CAUTI and hospital-acquired bloodstream infection (HABSI) were recorded prospectively according to National Healthcare Safety Network (NHSN) protocols. Device utilization ratios (DURs), rates of CAUTI, HABSI, and urine cultures were calculated and compared. RESULTS The CAUTI rate decreased from 3.0 per 1,000 catheter days in 2013 to 1.9 in 2014. The DUR was 0.7 in 2013 and 0.68 in 2014. The HABSI rates per 1,000 patient days decreased from 2.8 in 2013 to 2.4 in 2014. CONCLUSIONS Effectively reducing ICU CAUTI rates requires a multifaceted and collaborative approach; stewardship of culturing was a key and safe component of our successful reduction efforts. Infect Control Hosp Epidemiol 2017;38:186-188.

Experience With Rapid Microarray-Based Diagnostic Technology and Antimicrobial Stewardship for Patients With Gram-Positive Bacteremia.

OBJECTIVE To describe the impact of rapid diagnostic microarray technology and antimicrobial stewardship for patients with Gram-positive blood cultures. DESIGN Retrospective pre-intervention/post-intervention study. SETTING A 1,200-bed academic medical center. PATIENTS Inpatients with blood cultures positive for Staphylococcus aureus, Enterococcus faecalis, E. faecium, Streptococcus pneumoniae, S. pyogenes, S. agalactiae, S. anginosus, Streptococcus spp., and Listeria monocytogenes during the 6 months before and after implementation of Verigene Gram-positive blood culture microarray (BC-GP) with an antimicrobial stewardship intervention. METHODS Before the intervention, no rapid diagnostic technology was used or antimicrobial stewardship intervention was undertaken, except for the use of peptide nucleic acid fluorescent in situ hybridization and MRSA agar to identify staphylococcal isolates. After the intervention, all Gram-positive blood cultures underwent BC-GP microarray and the antimicrobial stewardship intervention consisting of real-time notification and pharmacist review. RESULTS In total, 513 patients with bacteremia were included in this study: 280 patients with S. aureus, 150 patients with enterococci, 82 patients with stretococci, and 1 patient with L. monocytogenes. The number of antimicrobial switches was similar in the pre-BC-GP (52%; 155 of 300) and post-BC-GP (50%; 107 of 213) periods. The time to antimicrobial switch was significantly shorter in the post-BC-GP group than in the pre-BC-GP group: 48±41 hours versus 75±46 hours, respectively (P<.001). The most common antimicrobial switch was de-escalation and time to de-escalation, was significantly shorter in the post-BC-GP group than in the pre-BC-GP group: 53±41 hours versus 82±48 hours, respectively (P<.001). There was no difference in mortality or hospital length of stay as a result of the intervention. CONCLUSIONS The combination of a rapid microarray diagnostic test with an antimicrobial stewardship intervention improved time to antimicrobial switch, especially time to de-escalation to optimal therapy, in patients with Gram-positive blood cultures. Infect Control Hosp Epidemiol 2016;1-6.

Influence of Colistin Dose on Global Cure in Patients with Bacteremia Due to Carbapenem-Resistant Gram-Negative Bacilli.

The increasing prevalence of multidrug-resistant (MDR) nosocomial infections accounts for increased morbidity and mortality of such infections. Infections with MDR Gram-negative isolates are frequently treated with colistin. Based on recent pharmacokinetic studies, current colistin dosing regimens may result in a prolonged time to therapeutic concentrations, leading to suboptimal and delayed effective treatment. In addition, studies have demonstrated an association between an increased colistin dose and improved clinical outcomes. However, the specific dose at which these outcomes are observed is unknown and warrants further investigation. This retrospective study utilized classification and regression tree (CART) analysis to determine the dose of colistin most predictive of global cure at day 7 of therapy. Patients were assigned to high- and low-dose cohorts based on the CART-established breakpoint. The secondary outcomes included microbiologic outcomes, clinical cure, global cure, lengths of intensive care unit (ICU) and hospital stays, and 7- and 28-day mortalities. Additionally, safety outcomes focused on the incidence of nephrotoxicity associated with high-dose colistin therapy. The CART-established breakpoint for high-dose colistin was determined to be >4.4 mg/kg of body weight/day, based on ideal body weight. This study evaluated 127 patients; 45 (35%) received high-dose colistin, and 82 (65%) received low-dose colistin. High-dose colistin was associated with day 7 global cure (40% versus 19.5%; P = 0.013) in bivariate and multivariate analyses (odds ratio [OR] = 3.40; 95% confidence interval [CI], 1.37 to 8.45; P = 0.008). High-dose colistin therapy was also associated with day 7 clinical cure, microbiologic success, and mortality but not with the development of acute kidney injury. We concluded that high-dose colistin (>4.4 mg/kg/day) is independently associated with day 7 global cure.