Single Intravenous Dose Dalbavancin Pathway for the Treatment of Acute Bacterial Skin and Skin Structure Infections: Considerations for Emergency Department Implementation and Cost Savings.

BACKGROUND: A pathway for the treatment of acute bacterial skin and skin structure infections (ABSSSI) with a single intravenous (IV) dose of dalbavancin was previously shown to reduce hospital admissions and shorten inpatient length of stay (LOS). OBJECTIVES: To describe pathway implementation at the emergency department (ED) and evaluate cost-effectiveness of a single-dose dalbavancin administered to ED patients who would otherwise be hospitalized to receive usual care with multidose IV antibiotics. METHODS: The dalbavancin pathway was previously implemented at 11 U.S. EDs (doi:10.1111/acem.14258). Patients with ABSSSI, without an unstable comorbidity or infection complication requiring complex management, were treated with a single dose of dalbavancin. At the emergency physicians' discretion, patients were either discharged and received outpatient follow-up or were hospitalized for continued management. A decision analytic cost-effectiveness model was developed from the U.S. healthcare's perspective to evaluate costs associated with the dalbavancin pathway compared with inpatient usual care. Costs (2021 USD) were modeled over a 14-day horizon and included ED visits, drug costs, inpatient stay, and physician visits. One-way and probabilistic sensitivity analyses examined input parameter uncertainty. RESULTS: Driven largely by the per diem inpatient cost and LOS for usual care, the dalbavancin pathway was associated with savings of $5133.20 per patient and $1211.57 per hospitalization day avoided, compared with inpatient usual care. The results remained robust in sensitivity and scenario analyses. CONCLUSION: The new single-dose dalbavancin ED pathway for ABSSSI treatment, which was previously implemented at 11 U.S. EDs, offers robust cost savings compared to inpatient usual care.

Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infection in Patients With Obesity or Diabetes: A Subgroup Analysis of Pooled Phase 3 Clinical Trials.

Background: We assessed the efficacy and safety of dalbavancin, a long-acting lipoglycopeptide with activity against Gram-positive pathogens, for treatment of acute bacterial skin and skin structure infections (ABSSSI) in patients with high body mass index (BMI) and/or diabetes. Methods: Data from two phase 3 trials of dalbavancin (1000 mg intravenous [IV], day 1; 500 mg IV, day 8) versus comparator and one phase 3b trial of single-dose (1500 mg IV, day 1) versus 2-dose (1000 mg IV, day 1; 500 mg IV, day 8) dalbavancin in adults with ABSSSI were pooled and summarized separately by baseline BMI and diabetes status. Clinical success at 48 to 72 hours (≥20% reduction in lesion size), end of treatment ([EOT] day 14), and day 28 was evaluated in the intent-to-treat (ITT) and microbiological ITT (microITT) populations. Safety data were reported in patients who received ≥1 dose of study drug. Results: In the dalbavancin ITT population (BMI, n = 2001; diabetes, n = 2010), at 48 to 72 hours (and EOT) clinical success was achieved in 89.3% (EOT, 90.9%) of patients with normal BMI and 78.9% to 87.6% (EOT, 91.0% to 95.2%) of patients with elevated BMI. Clinical success after dalbavancin treatment was achieved in 82.4% (EOT, 90.8%) of patients with diabetes and 86.0% (EOT, 91.6%) of patients without diabetes. Similar trends were observed for infections due to methicillin-resistant Staphylococcus aureus or methicillin-susceptible S aureus (microITT population). Conclusions: Dalbavancin is effective, with sustained clinical success rates in patients with obesity or diabetes, with a similar safety profile across patient groups.

Regional Epidemiology of Methicillin-Resistant Staphylococcus aureus Among Adult Intensive Care Unit Patients Following State-Mandated Active Surveillance.

Background: In 2007, Illinois became the first state in the United States to mandate active surveillance of methicillin-resistant Staphylococcus aureus (MRSA). The Illinois law applies to intensive care unit (ICU) patients; contact precautions are required for patients found to be MRSA colonized. However, the effectiveness of a legislated "search and isolate" approach to reduce MRSA burden among critically ill patients is uncertain. We evaluated whether the prevalence of MRSA colonization declined in the 5 years after the start of mandatory active surveillance. Methods: All hospitals with an ICU having ≥10 beds in Chicago, Illinois, were eligible to participate in single-day serial point prevalence surveys. We assessed MRSA colonization among adult ICU patients present at time of survey using nasal and inguinal swab cultures. The primary outcome was region-wide MRSA colonization prevalence over time. Results: All 25 eligible hospitals (51 ICUs) participated in serial point prevalence surveys over 8 survey periods (2008-2013). A total of 3909 adult ICU patients participated in the point prevalence surveys, with 432 (11.1%) found to be colonized with MRSA (95% confidence interval [CI], 10.1%-12.0%). The MRSA colonization prevalence among patients was unchanged during the study period; year-over-year relative risk for MRSA colonization was 0.97 (95% CI, .89-1.05; P = .48). Conclusions: MRSA colonization prevalence among critically ill adult patients did not decline during the time period following legislatively mandated MRSA active surveillance. Our findings highlight the limits of legislated MRSA active surveillance as a strategy to reduce MRSA colonization burden among ICU patients.

Computer-Assisted Antimicrobial Recommendations for Optimal Therapy: Analysis of Prescribing Errors in an Antimicrobial Stewardship Trial.

Clinician education and prospective audit and feedback interventions, deployed separately and concurrently, did not reduce antimicrobial use errors or rates compared to a control group of general medicine inpatients at our public hospital. Additional research is needed to define the optimal scope and intensity of hospital antimicrobial stewardship interventions. Infect Control Hosp Epidemiol 2017;38:857-859.

Modifiable Risk Factors for the Spread of Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae Among Long-Term Acute-Care Hospital Patients.

OBJECTIVE To identify modifiable risk factors for acquisition of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (KPC) colonization among long-term acute-care hospital (LTACH) patients. DESIGN Multicenter, matched case-control study. SETTING Four LTACHs in Chicago, Illinois. PARTICIPANTS Each case patient included in this study had a KPC-negative rectal surveillance culture on admission followed by a KPC-positive surveillance culture later in the hospital stay. Each matched control patient had a KPC-negative rectal surveillance culture on admission and no KPC isolated during the hospital stay. RESULTS From June 2012 to June 2013, 2,575 patients were admitted to 4 LTACHs; 217 of 2,144 KPC-negative patients (10.1%) acquired KPC. In total, 100 of these patients were selected at random and matched to 100 controls by LTACH facility, admission date, and censored length of stay. Acquisitions occurred a median of 16.5 days after admission. On multivariate analysis, we found that exposure to higher colonization pressure (OR, 1.02; 95% CI, 1.01-1.04; P=.002), exposure to a carbapenem (OR, 2.25; 95% CI, 1.06-4.77; P=.04), and higher Charlson comorbidity index (OR, 1.14; 95% CI, 1.01-1.29; P=.04) were independent risk factors for KPC acquisition; the odds of KPC acquisition increased by 2% for each 1% increase in colonization pressure. CONCLUSIONS Higher colonization pressure, exposure to carbapenems, and a higher Charlson comorbidity index independently increased the odds of KPC acquisition among LTACH patients. Reducing colonization pressure (through separation of KPC-positive patients from KPC-negative patients using strict cohorts or private rooms) and reducing carbapenem exposure may prevent KPC cross transmission in this high-risk patient population. Infect Control Hosp Epidemiol 2017;38:670-677.

Regional Epidemiology of Methicillin-Resistant Staphylococcus aureus Among Critically Ill Children in a State With Mandated Active Surveillance.

BACKGROUND: In theory, active surveillance of methicillin-resistant Staphylococcus aureus (MRSA) reduces MRSA spread by identifying all MRSA-colonized patients and placing them under contact precautions. In October 2007, Illinois mandated active MRSA surveillance in all intensive care units, including neonatal intensive care units (NICUs) and pediatric intensive care units (PICUs). We evaluated MRSA trends in a large metropolitan region in the wake of this law. METHODS: Chicago hospitals with a NICU or PICU were recruited for 8 single-day point prevalence surveys that occurred twice-yearly between June 2008 and July 2011 and then yearly in 2012 to 2013. Samples from all patients were cultured for MRSA (nose and umbilicus for neonates, nose and groin for pediatric patients). Hospital-reported admission MRSA-screening results also were obtained. Point prevalence cultures were screened for MRSA by using broth enrichment, chromogenic agar, and standard confirmatory methods. RESULTS: All eligible hospitals (N = 10) participated (10 NICUs, 6 PICUs). Hospital-reported adherence to state-mandated MRSA screening at admission was high (95% for NICUs, 94% for PICUs). From serial point prevalence surveys, overall MRSA prevalences in the NICUs and PICUs were 4.2% (89 of 2101) and 5.7% (36 of 632), respectively. MRSA colonization prevalences were unchanged in the NICUs (year-over-year risk ratio [RR], 0.93 [95% confidence interval (CI), 0.78-1.12]; P = .45) and trended toward an increase in the PICUs (RR, 1.25 [95% CI, 0.72-2.12]; P = .053). We estimated that 81% and 40% of MRSA-positive patients in the NICUs and PICUs, respectively, had newly acquired MRSA. CONCLUSIONS: In a region with mandated active MRSA surveillance, we found ongoing unchanged rates of MRSA colonization and acquisition among NICU and PICU patients.

Modeling spread of KPC-producing bacteria in long-term acute care hospitals in the Chicago region, USA.

OBJECTIVE: Prevalence of bla KPC-encoding Enterobacteriaceae (KPC) in Chicago long-term acute care hospitals (LTACHs) rose rapidly after the first recognition in 2007. We studied the epidemiology and transmission capacity of KPC in LTACHs and the effect of patient cohorting. METHODS: Data were available from 4 Chicago LTACHs from June 2012 to June 2013 during a period of bundled interventions. These consisted of screening for KPC rectal carriage, daily chlorhexidine bathing, medical staff education, and 3 cohort strategies: a pure cohort (all KPC-positive patients on 1 floor), single rooms for KPC-positive patients, and a mixed cohort (all KPC-positive patients on 1 floor, supplemented with KPC-negative patients). A data-augmented Markov chain Monte Carlo (MCMC) method was used to model the transmission process. RESULTS: Average prevalence of KPC colonization was 29.3%. On admission, 18% of patients were colonized; the sensitivity of the screening process was 81%. The per admission reproduction number was 0.40. The number of acquisitions per 1,000 patient days was lowest in LTACHs with a pure cohort ward or single rooms for colonized patients compared with mixed-cohort wards, but 95% credible intervals overlapped. CONCLUSIONS: Prevalence of KPC in LTACHs is high, primarily due to high admission prevalence and the resultant impact of high colonization pressure on cross transmission. In this setting, with an intervention in place, patient-to-patient transmission is insufficient to maintain endemicity. Inclusion of a pure cohort or single rooms for KPC-positive patients in an intervention bundle seemed to limit transmission compared to use of a mixed cohort.

Understanding staff perceptions about Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae control efforts in Chicago long-term acute care hospitals.

OBJECTIVE: To identify differences in organizational culture and better understand motivators to implementation of a bundle intervention to control Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (KPC). DESIGN: Mixed-methods study. SETTING: Four long-term acute care hospitals (LTACHs) in Chicago. PARTICIPANTS: LTACH staff across 3 strata of employees (administration, midlevel management, and frontline clinical workers). METHODS: Qualitative interviews or focus groups and completion of a quantitative questionnaire. RESULTS: Eighty employees (frontline, 72.5%; midlevel, 17.5%; administration, 10%) completed surveys and participated in qualitative discussions in August 2012. Although 82.3% of respondents felt that quality improvement was a priority at their LTACH, there were statistically significant differences in organizational culture between staff strata, with administrative-level having higher organizational culture scores (ie, more favorable responses) than midlevel or frontline staff. When asked to rank the success of the KPC control program, mean response was 8.0 (95% confidence interval, 7.6-8.5), indicating a high level of agreement with the perception that the program was a success. Patient safety and personal safety were reported most often as personal motivators for intervention adherence. The most convergent theme related to prevention across groups was that proper hand hygiene is vital to prevention of KPC transmission. CONCLUSIONS: Despite differences in organizational culture across 3 strata of LTACH employees, the high degree of convergence in motivation, understanding, and beliefs related to implementation of a KPC control bundle suggests that all levels of staff may be able to align perspectives when faced with a key infection control problem and quality improvement initiative.

The effectiveness of routine daily chlorhexidine gluconate bathing in reducing Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae skin burden among long-term acute care hospital patients.

We evaluated the effectiveness of daily chlorhexidine gluconate (CHG) bathing in decreasing skin carriage of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (KPC) among long-term acute care hospital patients. CHG bathing reduced KPC skin colonization, particularly when CHG skin concentrations greater than or equal to 128 µg/mL were achieved.

Electronic algorithmic prediction of central vascular catheter use.

OBJECTIVE: To develop prediction algorithms for the presence of a central vascular catheter in hospitalized patients with use of data present in an electronic health record. Such algorithms could be used for measurement of device utilization rates and for clinical decision support rules. DESIGN: Criterion standard. SETTING: John H. Stroger, Jr, Hospital of Cook County, a 464-bed public hospital in Chicago, Illinois. PARTICIPANTS: Patients admitted to the medical intensive care unit from May 31, 2005 through June 26, 2006 (derivation data set, May 31, 2005-September 28, 2005; validation data set, September 29, 2005-June 28, 2006). METHODS: Covariates were collected from the electronic medical record for each patient; the outcome variable was presence of a central vascular device. Multivariate models were developed using the derivation set and the generalized estimating equation. Three models, each with increasing database requirements, were validated using the validation set. Device utilization ratios and performance characteristics were calculated. RESULTS: Although Charlson score and duration of intensive care unit stay were significant predictors in all models, factors that indicated use or presence of a central line were also important. Device utilization rates derived from the algorithmic models were as accurate as those obtained using manual sampling. CONCLUSIONS: Automated calculation of central vascular catheter use is both feasible and accurate, providing estimates statistically similar to those obtained using manual surveillance. Prediction modeling of central vascular catheter use may enable automated surveillance of bloodstream infections and enhance important prevention interventions, such as timely removal of unnecessary central lines.

Lost in translation? Reliability of assessing inpatient antimicrobial appropriateness with use of computerized case vignettes.

OBJECTIVE: To describe and measure reliability of a computer-assisted method of case vignette assembly and expert review to assess the appropriateness of antimicrobial therapy for hospitalized adults. DESIGN: Feasibility and reliability analysis of computer-assisted tool used to compare the effects of antimicrobial stewardship interventions. SETTING: Public teaching hospital. PATIENTS: Randomly selected adult antimicrobial recipients admitted to inpatient medicine services. METHODS: Clinical data abstracted from 504 paper medical records were merged with computerized laboratory and pharmacy data to assemble case vignettes that underwent expert review for appropriateness. We performed 3 validations, as follows: data for 35 vignettes abstracted independently by 2 research assistants were assessed for interrater agreement, expert review of 24 vignettes was compared with review of the corresponding paper medical records, and interrater reliability of antimicrobial appropriateness assessments by 2 experts was determined for 70 case vignettes. RESULTS: Vignette assembly and expert review each required 10-12 minutes per case. Potentially important discrepancies occurred in 0%-32% of clinical findings abstracted independently by 2 research assistants. Expert review of 24 vignettes and the corresponding full paper medical records yielded fair agreement (kappa, 0.30). The 2 experts identified inappropriate initial antimicrobial therapy in 67% and 61% of case vignettes reviewed independently; interrater agreement was improved after sequential case discussion and stringent application of appropriateness criteria (kappa, 0.72). CONCLUSIONS: Our case vignette assembly and expert review method is efficient, but improvements in both technical and human performance are needed to be able to yield valid estimates of the prevalence of inappropriate antimicrobial use. Assessments of antimicrobial appropriateness require validation.

Effectiveness of chlorhexidine bathing to reduce catheter-associated bloodstream infections in medical intensive care unit patients.

OBJECTIVE: To determine whether patients bathed daily with chlorhexidine gluconate (CHG) have a lower incidence of primary bloodstream infections (BSIs) compared with patients bathed with soap and water. METHODS: The study design was a 52-week, 2-arm, crossover (ie, concurrent control group) clinical trial with intention-to-treat analysis. The study setting was the 22-bed medical intensive care unit (MICU), which comprises 2 geographically separate, similar 11-bed units, of the John H. Stroger Jr (Cook County) Hospital, a 464-bed public teaching hospital in Chicago, Illinois. The study population comprised 836 MICU patients. During the first of 2 study periods (28 weeks), 1 hospital unit was randomly selected to serve as the intervention unit in which patients were bathed daily with 2% CHG-impregnated washcloths (Sage 2% CHG cloths; Sage Products Inc, Cary, Illinois); patients in the concurrent control unit were bathed daily with soap and water. After a 2-week wash-out period at the end of the first period, cleansing methods were crossed over for 24 more weeks. Main outcome measures included incidences of primary BSIs and clinical (culture-negative) sepsis (primary outcomes) and incidences of other infections (secondary outcomes). RESULTS: Patients in the CHG intervention arm were significantly less likely to acquire a primary BSI (4.1 vs 10.4 infections per 1000 patient days; incidence difference, 6.3 [95% confidence interval, 1.2-11.0). The incidences of other infections, including clinical sepsis, were similar between the units. Protection against primary BSI by CHG cleansing was apparent after 5 or more days in the MICU. CONCLUSION: Daily cleansing of MICU patients with CHG-impregnated cloths is a simple, effective strategy to decrease the rate of primary BSIs.