Kevin Nechodom

Propofol is associated with favorable outcomes compared with benzodiazepines in ventilated intensive care unit patients.

RATIONALE Mechanically ventilated intensive care unit (ICU) patients are frequently managed using a continuous-infusion sedative. Although recent guidelines suggest avoiding benzodiazepines for sedation, this class of drugs is still widely used. There are limited data comparing sedative agents in terms of clinical outcomes in an ICU setting. OBJECTIVES Comparison of propofol to midazolam and lorazepam in adult ICU patients. METHODS Data were obtained from a multicenter ICU database (2003-2009). Patient selection criteria included age greater than or equal to 18 years, single ICU admission with single ventilation event (>48 h), and treatment with continuously infused sedation (propofol, midazolam, or lorazepam). Propensity score analysis (1:1) was used and mortality measured. Cumulative incidence and competing risk methodology were used to examine time to ICU discharge and ventilator removal. MEASUREMENTS AND MAIN RESULTS There were 2,250 propofol-midazolam and 1,054 propofol-lorazepam matched patients. Hospital mortality was statistically lower in propofol-treated patients as compared with midazolam- or lorazepam-treated patients (risk ratio, 0.76; 95% confidence interval [CI], 0.69-0.82 and risk ratio, 0.78; 95% CI, 0.68-0.89, respectively). Competing risk analysis for 28-day ICU time period showed that propofol-treated patients had a statistically higher probability for ICU discharge (78.9% vs. 69.5%; 79.2% vs. 71.9%; P < 0.001) and earlier removal from the ventilator (84.4% vs. 75.1%; 84.3% vs. 78.8%; P < 0.001) when compared with midazolam- and lorazepam-treated patients, respectively. CONCLUSIONS In this large, propensity-matched ICU population, patients treated with propofol had a reduced risk of mortality and had both an increased likelihood of earlier ICU discharge and earlier discontinuation of mechanical ventilation.

Importation, Antibiotics, and Clostridium difficile Infection in Veteran Long-Term Care: A Multilevel Case–Control Study

Context Variation in Clostridium difficile incidence among long-term care facilities is not well-understood. Contribution This study compared regional Veterans Health Administration long-term care facilities. There was wide variation in C difficile incidence that was largely explained by differences in overall use of antibiotics and the importation of C difficile from acute care settings, rather than individual patient factors, such as age, number of comorbidities, and antibiotic use. Implication Approaches that focus on infection control and institutional antibiotic stewardship may be most beneficial for reducing C difficile incidence in long-term care facilities. Clostridium difficile infection is a diarrheal disease that is associated with antibiotic and health care exposures. It has the highest prevalence, morbidity, and mortality of any health careassociated infection (1, 2). Risk factors have been extensively studied and include age, comorbidity burden, abdominal surgery, feeding tube use, and exposure to antibiotics and antacids (3). Almost all antibiotic classes are believed to increase risk; however, the risk is greatest for antibiotics with activity against gut flora but none against C difficile, including cephalosporins, fluoroquinolones, and clindamycin (4, 5). Antacids, especially proton-pump inhibitors, are believed to increase risk by reducing stomach acidity, thereby allowing increased numbers of viable C difficile to reach the gut. Although clinical risk factors have been extensively studied, the environmental and facility-level exposures that may drive C difficile transmission have not. What is known is that C difficile is transmitted by the fecaloral route, and patients with symptomatic disease or asymptomatic colonization have high bacterial loads in their stool and shed infectious spores into their environs for extended periods (6, 7). Exposure of patients to ward-level disease pressure, measured as the daily number of infectious patients with recent C difficile present in the same ward, predicts increased risk for infection (8). In addition to disease pressure, antibiotic use in wards has been shown to increase the risk for infection together with individual-level antibiotic exposure (9). This independent effect of ward antibiotic use may be due to the higher likelihood of asymptomatic C difficile colonization and shedding among patients with recent antibiotic exposure (7), which creates a greater environmental C difficile burden. Long-term care facilities provide services to residents requiring assistance with activities of daily living in a residential setting, skilled nursing, spinal cord injury care, and rehabilitation. In long-term care, antimicrobial use is generally high, with the point prevalence around 8%; of this, 25% to 75% may be inappropriate (10). To our knowledge, the effect of antimicrobial use on C difficile incidence in long-term care has never been explored. Further, long-term care residents have frequent contact with acute care facilities; therefore, importation of hospital-onset C difficile infection may be an important risk factor for infection in long-term care facilities (11). Models incorporating both individual- and facility-level risk factors can be used to distinguish risk factors that affect individual susceptibility to disease from those that that may be associated with the degree of environmental contamination and that may proxy spore ingestion (12). The objective of this study was to obtain a comprehensive picture of the individual and regional factors that drive C difficile infection risk across Veterans Health Administration (VHA) long-term care facilities, with an interest in the role of importation of persons with acute careonset C difficile infection and regional rates of antibiotic use. Methods Ethics Statement Study approval was obtained from the Research Ethics Board of the Veterans Affairs Salt Lake City Health Care System. The Board waived the need for consent because there was no contact with residents, and anonymity was assured. Study Design We conducted a retrospective study of VHA long-term care residents across 111 health care regions from 1 January 2006 through 31 December 2012. In the VHA, health care regions act as local health care systems and usually provide both acute and long-term care services. In most of these regions, long-term care services were delivered at a single facility (n= 89), although care was distributed across 2 or more locations (n= 22) in some regions. All long-term care facilities provide 24-hour nursing care, and some also provide psychiatric, spinal cord injury, or hospice care. This retrospective study used a multilevel, longitudinal, nested casecontrol design. To accurately estimate resident risk, a multilevel model that incorporated both resident-level risk factors (characteristics of specific at-risk persons) and regional risk factors (measures of the prevalence of residents who were likely to shed C difficile spores) was used. To allow short-term pharmaceutical exposures to be measured in an appropriate retrospective window, the analysis data set was broken down into a longitudinal resident-day format. Because the resultant data set was extensive, a nested casecontrol design was used. Population Residents were considered at risk for onset of C difficile infection in a long-term care facility if they resided in an inpatient VHA long-term care facility for 3 or more of the previous 28 days and did not have a positive C difficile test result in the prior 8 weeks. Health care regions, and eligible residents within them, were included in the risk set if there were at least 6 years of data in which long-term and acute care censuses were greater than an average of 10 eligible, at-risk persons per day for each month of the given year. Regions without acute care facilities were excluded because imported cases of C difficile infection from non-VHA acute care facilities were not captured and would have led to an underestimate of C difficile importation in those regions. Definition of Cases and Controls Residents were considered cases on the date of a positive C difficile toxin test result 3 days or more after long-term care admission and at least 8 weeks from a previous positive result (13). Positive results were identified from VHA microbiology data using natural language processing (14). Eligible controls were resident-days that did not meet the case definition and could include resident-days from persons who later became cases. A 1%, unmatched, simple random sample of eligible controls was selected for analysis. Resident Risk Factors The 7 resident risk factors assessed were age, sex, number of days of acute care hospitalization within the previous 4 weeks, number of comorbid conditions, and 3 pharmaceutical exposures. The value of each time-varying parameter was assessed for each day. For comorbidities, acute and long-term care facility discharge diagnosis codes (International Classification of Diseases, Ninth Revision, Clinical Modification) were used to assess the presence of 14 comorbid conditions in the preceding year as per the Charlson comorbidity index (15, 16). For a given resident, the total number of comorbid conditions was summed. The following 3 pharmaceutical exposure variables were assessed, each in a 4-week retrospective window: proton-pump inhibitors; any antibiotic except C difficile treatment agents (metronidazole, oral vancomycin, and fidaxomicin); and an antibiotic risk index with 4 mutually exclusive risk levels consisting of high (receipt of cephalosporins, fluoroquinolones, or clindamycin), medium (receipt of penicillins, macrolides, or sulfonamides but no high-risk agents), low (receipt of tetracyclines), or no antibiotic receipt or receipt of C difficile treatment agents only. This antibiotic risk index was based on a similar index developed in an independent cohort study (17). Pharmaceutical exposure information was drawn from administration data of the VHA electronic medical record and included all courses given during inpatient care in VHA acute or long-term care facilities. Community exposures were not considered. In addition to the 7 resident risk factors, a control variable for the duration of follow-up time, defined as the total number of days a given resident stayed in a VHA acute or long-term care facility within the past 28 days, was measured and categorized into deciles. Health Care Regional Risk Factors The 5 regional risk factors measured were average resident age, average resident comorbidities, proton-pump inhibitor use, antibiotic use, and importation of cases of acute care C difficile infection. These factors were measured from the full resident population of the regions because residents who were not at risk (that is, those recently admitted with a recent positive C difficile test result) were just as likely if not more likely to transmit C difficile. Proton-pump inhibitor use and antibiotic use (excluding the C difficile treatment agents previously mentioned) were measured as days with therapy per 1000 resident-days. Exposure on a given day contributed 1 unit to the numerator, regardless of the number of specific agents, dosage, or number of doses administered on that day. Importation of cases of acute care C difficile infection was measured as the prevalence of residents in the region who were infected with C difficile at an acute care facility in the previous 8 weeks per 10000 resident-days. Acute careonset C difficile infection was defined as a patient with a positive C difficile toxin test result 3 or more days after admission to an acute care facility. Statistical Analysis The incidence of C difficile across the VHA, and within each region, was measured using the weighted mean. In all statistical analyses, sampling weights of 1 for cases and 100 for controls corresponded to the inverse of the probability of selection, allowing analyses to produce unbiased estimates of

Taking an Antibiotic Time-out: Utilization and Usability of a Self-Stewardship Time-out Program for Renewal of Vancomycin and Piperacillin-Tazobactam

Background Antibiotic time-outs can promote critical thinking and greater attention to reviewing indications for continuation. Objective We pilot tested an antibiotic time-out program at a tertiary care teaching hospital where vancomycin and piperacillin-tazobactam continuation past day 3 had previously required infectious diseases service approval. Methods The time-out program consisted of 3 components: (1) an electronic antimicrobial dashboard that aggregated infection-relevant clinical data; (2) a templated note in the electronic medical record that included a structured review of antibiotic indications and that provided automatic approval of continuation of therapy when indicated; and (3) an educational and social marketing campaign. Results In the first 6 months of program implementation, vancomycin was discontinued by day 5 in 93/145 (64%) courses where a time-out was performed on day 4 versus in 96/199 (48%) 1 year prior (P = .04). Seven vancomycin continuations via template (5% of time-outs) were guideline-discordant by retrospective chart review versus none 1 year prior (P = .002). Piperacillin-tazobactam was discontinued by day 5 in 70/105 (67%) courses versus 58/93 (62%) 1 year prior (P = .55); 9 continuations (9% of time-outs) were guideline-discordant versus two 1 year prior (P = .06). A usability survey completed by 32 physicians demonstrated modest satisfaction with the overall program, antimicrobial dashboard, and renewal templates. Conclusions By providing practitioners with clinical informatics support and guidance, the intervention increased provider confidence in making decisions to de-escalate antimicrobial therapy in ambiguous circumstances wherein they previously sought authorization for continuation from an antimicrobial steward.

The Drivers of Acute and Long-term Care Clostridium difficile Infection Rates: A Retrospective Multilevel Cohort Study of 251 Facilities

Background Drivers of differences in Clostridium difficile incidence across acute and long-term care facilities are poorly understood. We sought to obtain a comprehensive picture of C. difficile incidence and risk factors in acute and long-term care. Methods We conducted a case-cohort study of persons spending at least 3 days in one of 131 acute care or 120 long-term care facilities managed by the United States Veterans Health Administration between 2006 and 2012. Patient (n = 8) and facility factors (n = 5) were included in analyses. The outcome was the incidence of facility-onset laboratory-identified C. difficile infection (CDI), defined as a person with a positive C. difficile test without a positive test in the prior 8 weeks. Results CDI incidence in acute care was 5 times that observed in long-term care (median, 15.6 vs 3.2 per 10000 person-days). History of antibiotic use was greater in acute care compared to long-term care (median, 739 vs 513 per 1000 person-days) and explained 72% of the variation in C. difficile rates. Importation of C. difficile cases (acute care: patients with recent long-term care attributable infection; long-term care: residents with recent acute care attributable infection) was 3 times higher in long-term care as compared to acute care (median, 52.3 vs 16.2 per 10000 person-days). Conclusions Facility-level antibiotic use was the main factor driving differences in CDI incidence between acute and long-term care. Importation of acute care C. difficile cases was a greater concern for long-term care as compared to importation of long-term care cases for acute care.

Epidemiology of nontuberculous mycobacterial infections in the U.S. Veterans Health Administration

Objective We identified patients with non-tuberculous mycobacterial (NTM) disease in the US Veterans Health Administration (VHA), examined the distribution of diseases by NTM species, and explored the association between NTM disease and the frequency of clinic visits and mortality. Methods We combined mycobacterial isolate (from natural language processing) with ICD-9-CM diagnoses from VHA data between 2008 and 2012 and then applied modified ATS/IDSA guidelines for NTM diagnosis. We performed validation against a reference standard of chart review. Incidence rates were calculated. Two nested case-control studies (matched by age and location) were used to measure the association between NTM disease and each of 1) the frequency of outpatient clinic visits and 2) mortality, both adjusted by chronic obstructive pulmonary disease (COPD), other structural lung diseases, and immunomodulatory factors. Results NTM cases were identified with a sensitivity of 94%, a specificity of >99%. The incidence of NTM was 12.6/100k patient-years. COPD was present in 68% of pulmonary NTM. NTM incidence was highest in the southeastern US. Extra-pulmonary NTM rates increased during the study period. The incidence rate ratio of clinic visits in the first year after diagnosis was 1.3 [95%CI 1.34–1.35]. NTM patients had a hazard ratio of mortality of 1.4 [95%CI 1.1–1.9] in the 6 months after NTM identification compared to controls and 1.99 [95%CI 1.8–2.3] thereafter. Conclusions In VHA, pulmonary NTM disease is commonly associated with COPD, with the highest rates in the southeastern US. After adjustment, NTM patients had more clinic visits and greater mortality compared to matched patients.

The determinants of C. difficile infection in long-term care facilities: a portrait of patient- and facility-level factors across 90 care regions in the veterans affairs health care system

Clostridium difficile infection (CDI) is an infectious diarrheal disease that is associated with antibiotic and healthcare exposures. Although individual-level risk factors have been extensively studied, the facility-level factors that drive CDI have not.