Cost evaluation of continuation of therapy with dalbavancin compared to standard-of-care antibiotics alone in hospitalized persons who inject drugs with severe gram-positive infections.

PURPOSE: Persons who inject drugs (PWID) are at risk for severe gram-positive infections and may require prolonged hospitalization and intravenous (IV) antibiotic therapy. Dalbavancin (DBV) is a long-acting lipoglycopeptide that may reduce costs and provide effective treatment in this population. METHODS: This was a retrospective review of PWID with severe gram-positive infections. Patients admitted from January 1, 2017, to November 1, 2019 (standard-of-care [SOC] group) and from November 15, 2019, to March 31, 2022 (DBV group) were included. The primary outcome was the total cost to the healthcare system. Secondary outcomes included hospital days saved and treatment failure. RESULTS: A total of 87 patients were included (37 in the DBV group and 50 in the SOC group). Patients were a median of 34 years old and were predominantly Caucasian (82%). Staphylococcus aureus (82%) was the most common organism, and bacteremia (71%) was the most common type of infection. Compared to the SOC group, the DBV group would have had a median of 14 additional days of hospitalization if they had stayed to complete their therapy (P = 0.014). The median total cost to the healthcare system was significantly lower in the DBV group than in the SOC group ($31,698.00 vs $45,093.50; P = 0.035). The rate of treatment failure was similar between the groups (32.4% in the DBV group vs 36% in the SOC group; P = 0.729). CONCLUSION: DBV is a cost-saving alternative to SOC IV antibiotics for severe gram-positive infections in PWID, with similar treatment outcomes. Larger prospective studies, including other patient populations, may demonstrate additional benefit.

Evaluating Initial Empiric Therapy for Neutropenic Fever in Vancomycin-Resistant Enterococcus-Colonized Patients.

OBJECTIVES: Vancomycin-resistant enterococcus infections impact mortality in oncology patients. Given the low rate of vancomycin-resistant enterococcus bacteremia, low virulence of vancomycin-resistant enterococcus, and advent of rapid diagnostic systems, vancomycin-resistant enterococcus-directed empiric therapy in vancomycin-resistant enterococcus-colonized patients with neutropenic fever may be unnecessary, promoting increased antimicrobial resistance, drug-related toxicity, and cost. METHODS: Vancomycin-resistant enterococcus-colonized adults admitted for hematopoietic stem cell transplantation or induction therapy for acute leukemia/myeloid sarcoma with neutropenic fever were stratified by vancomycin-resistant enterococcus bacteremia development and empiric vancomycin-resistant enterococcus-directed antimicrobial strategy for first neutropenic fever (Empiric Therapy vs. non-Empiric Therapy). Primary endpoints included vancomycin-resistant enterococcus-related, in-hospital, and 100-day mortality rates. Secondary outcomes included vancomycin-resistant enterococcus bacteremia incidence for first neutropenic fever and the entire hospitalization, length of stay, Clostridioides difficile infection rate, and duration and cost of vancomycin-resistant enterococcus-directed therapy. RESULTS: During first neutropenic fever, 3 of 70 eligible patients (4%) developed vancomycin-resistant enterococcus bacteremia. Although all 3 (100%) were non-Empiric Therapy, no mortality (0%) occurred. Of 67 patients not developing vancomycin-resistant enterococcus bacteremia, 42 (63%) received Empiric Therapy and 25 (37%) non-Empiric Therapy. Empiric Therapy had significantly greater median duration (3 days vs. 0 days; P<.001) and cost ($1604 vs. $0; P<.001) of vancomycin-resistant enterococcus-directed therapy but demonstrated no significant differences in clinical outcomes. CONCLUSION: Available data suggest Empiric Therapy may offer no clinical benefit to this population, regardless of whether vancomycin-resistant enterococcus is identified in blood culture or no pathogen is found. Such an approach may only expose the majority of patients to unnecessary vancomycin-resistant enterococcus-directed therapy and drug-related toxicities while increasing institutional drug and monitoring costs. Even in the few patients developing vancomycin-resistant enterococcus bacteremia, waiting until the organism is identified in culture to start directed therapy likely makes no difference in mortality. This lack of benefit warrants consideration to potentially omit empiric vancomycin-resistant enterococcus-directed therapy in first neutropenic fever in many of these patients.

Economic evaluation of vancomycin-resistant enterococci (VRE) control practices: a systematic review.

Preventing vancomycin-resistant enterococci (VRE) infection is a healthcare priority. However, the cost-effectiveness of VRE control interventions is unclear. The aim of this study was to synthesize evidence on economic evaluation of VRE control practices such as screening, contact precautions, patient cohorting, and others. The literature was searched from January 1985 to June 2018, and included economic evaluations of VRE control practices in hospital settings, published in English. A total of 4711 articles were screened; nine primary studies met our criteria. All studies evaluated some form of VRE screening and contact precautions, in populations ranging from single hospital wards (or select patient groups) to multiple healthcare facilities. There was significant variability in the interventions and comparisons used. Most studies (N = 7) conducted a cost-effectiveness analysis; two studies were cost-consequence studies. All economic evaluations were from the hospital perspective. Four studies found implementing enhanced VRE-specific control practices to be cost-effective/cost-saving and two studies found that discontinuing VRE-specific control practices was not cost-effective. Three studies found decreasing VRE-specific control practices to be cost-effective/cost-saving. The quality of the included studies was generally low according to the Joanna Briggs Institute (JBI) checklist for economic evaluations; major limitations included risks of bias in intervention effect estimates, and a lack of sensitivity analyses. Most studies show that some form of VRE screening and use of Contact Precautions is cost-effective. The low study quality and heterogeneity of interventions and comparators precludes definitive conclusions about the cost effectiveness of specific VRE control interventions. Additional high-quality economic evaluations are needed to strengthen the available evidence.

Dalbavancin use in an academic medical centre and associated cost savings.

Dalbavancin is a lipoglycopeptide antibiotic with unique weekly dosing active against Gram-positive organisms. This retrospective study included 37 patients receiving a mean of 2.7 weeks of dalbavancin. Nine patients (24%) were re-admitted to the hospital within 30 days. A total of 617 hospital days were saved, estimated to result in US$1 495 336 in savings and a mean cost avoidance of US$40 414 per patient. Dalbavancin provides a valuable antibiotic option that may minimise healthcare expenditure.

Economic burden of antibiotic resistance in ESKAPE organisms: a systematic review.

Background: Antibiotic resistance (ABR) is one of the biggest threats to global health. Infections by ESKAPE (Enterococcus, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and E. coli) organisms are the leading cause of healthcare-acquired infections worldwide. ABR in ESKAPE organisms is usually associated with significant higher morbidity, mortality, as well as economic burden. Directing attention towards the ESKAPE organisms can help us to better combat the wide challenge of ABR, especially multi-drug resistance (MDR). Objective: This study aims to systematically review and evaluate the evidence of the economic consequences of ABR or MDR ESKAPE organisms compared with susceptible cases or control patients without infection/colonization in order to determine the impact of ABR on economic burden. Methods: Both English-language databases and Chinese-language databases up to 16 January, 2019 were searched to identify relevant studies assessing the economic burden of ABR. Studies reported hospital costs (charges) or antibiotic cost during the entire hospitalization and during the period before/after culture among patients with ABR or MDR ESKAPE organisms were included. The costs were converted into 2015 United States Dollars. Disagreements were resolved by a third reviewer. Results: Of 13,693 studies identified, 83 eligible studies were included in our review. The most studied organism was S. aureus, followed by Enterococcus, A. baumannii, E. coli, E. coli or/and K. pneumoniae, P. aeruginosa, and K. pneumoniae. There were 71 studies on total hospital cost or charge, 12 on antibiotic cost, 11 on hospital cost or charge after culture, 4 on ICU cost, 2 on hospital cost or charge before culture, and 2 on total direct and indirect cost. In general, ABR or MDR ESKAPE organisms are significantly associated with higher economic burden than those with susceptible organisms or those without infection or colonization. Nonetheless, there were no differences in a few studies between the two groups on total hospital cost or charge (16 studies), antibiotic cost (one study), hospital cost before culture (one study), hospital cost after culture (one study). Even, one reported that costs associated with MSSA infection were higher than the costs for similar MRSA cases. Conclusions: ABR in ESKAPE organisms is not always, but usually, associated with significantly higher economic burden. The results without significant differences may lack statistical power to detect a significant association. In addition, study design which controls for severity of illness and same empirical antibiotic therapy in the two groups would be expected to bias the study towards a similar, even negative result. The review also highlights key areas where further research is needed.

Patterns of Health Care Costs Due to External Ventricular Drain Infections.

BACKGROUND: External ventricular drain (EVD) infections are a significant cause of morbidity among neurosurgical patients and have been correlated with increased length of hospital stay and longer requirements for intensive care. To date, no studies have examined the financial impact of EVD infections. METHODS: Patients who underwent EVD placement between December 2010 and January 2016 were included in the study. Clinical records were retrospectively reviewed and health care cost data were obtained from the hospital's finance department. Clinical information included patient demographics, details from the hospital course, and outcomes. Total costs, direct/indirect, and fixed/variable costs were analyzed for every patient. RESULTS: Over the 5-year study period, 246 EVDs were placed in 243 patients with an overall infection rate of 9.9% (N = 24). The median EVD duration for infected versus noninfected patients was 19 and 9 days, respectively (P < 0.0001). Median length of intensive care unit stay also was increased for patients with EVD infection (30 days vs. 13 days, P < 0.0001). Total health care costs were significantly greater for infected patients (US$ 168,692 vs. US$ 83,919, P < 0.0001). This trend was comparable for all other cost subtypes, including fixed-direct costs, fixed-indirect costs, variable direct costs, and variable-indirect costs. CONCLUSIONS: EVD infection has a substantial effect on clinical morbidity and healthcare costs. These results demonstrate the imperative need to improve EVD infection prevention, particularly in the setting of a value-based health care system.

Reconsidering Strategies for Managing Chronic Periprosthetic Joint Infection in Total Knee Arthroplasty: Using Decision Analytics to Find the Optimal Strategy Between One-Stage and Two-Stage Total Knee Revision.

BACKGROUND: Periprosthetic joint infection (PJI) following total knee arthroplasty is a growing concern, as the demand for total knee arthroplasty (TKA) expands annually. Although 2-stage revision is considered the gold standard in management, there is substantial morbidity and mortality associated with this strategy. One-stage revision is associated with lower mortality rates and better quality of life, and there has been increased interest in utilizing the 1-stage strategy. However, surgeons are faced with a difficult decision regarding which strategy to use to treat these infections, considering uncertainty with respect to eradication of infection, quality of life, and societal costs with each strategy. The purpose of the current study was to use decision analysis to determine the optimal decision for the management of PJI following TKA. METHODS: An expected-value decision tree was constructed to estimate the quality-adjusted life-years (QALYs) and costs associated with 1-stage and 2-stage revision. Two decision trees were created: Decision Tree 1 was constructed for all pathogens, and Decision Tree 2 was constructed solely for difficult-to-treat infections, including methicillin-resistant infections. Values for parameters in the decision model, such as mortality rate, reinfection rate, and need for additional surgeries, were derived from the literature. Medical costs were derived from Medicare data. Sensitivity analysis determined which parameters in the decision model had the most influence on the optimal strategy. RESULTS: In both decision trees, the 1-stage strategy produced greater health utility while also being more cost-effective. In the Monte Carlo simulation for Decision Trees 1 and 2, 1-stage was the dominant strategy in about 85% and 69% of the trials, respectively. Sensitivity analysis showed that the reinfection and 1-year mortality rates were the most sensitive parameters influencing the optimal decision. CONCLUSIONS: Despite 2-stage revision being considered the current gold standard for infection eradication in patients with PJI following TKA, the optimal decision that produced the highest quality of life was 1-stage revision. These results should be considered in shared decision-making with patients who experience PJI following TKA. LEVEL OF EVIDENCE: Economic and Decision Analysis Level IV. See Instructions for Authors for a complete description of levels of evidence.

Excess cost and inpatient stay of treating deep spinal surgical site infections.

AIM: To determine the excess cost and hospitalisation associated with surgical site infections (SSI) following spinal operations in a New Zealand setting. METHODS: We identified inpatients treated for deep SSI following primary or revision spinal surgery at a regional tertiary spinal centre between 2009 and 2016. Excess cost and excess length of stay (LOS) were calculated via a clinical costing system using procedure-matched controls. RESULTS: Twenty-eight patients were identified. Twenty-five had metalware following spinal fusion surgery, while three had non-instrumented decompression and/or discectomy. Five were diagnosed during their index hospitalisation and 23 (82%) were re-admitted. The average excess SSI cost was NZ$51,434 (range $1,398-$262,206.16) and LOS 37.1 days (range 7-275 days). Infections following metalware procedures had a greater excess cost (average $56,258.90 vs. $11,228.61) and LOS (average 40.4 days vs. 9.7 days) than procedures without metalware. CONCLUSION: The costs associated with spinal SSI are significant and comparable to a previous New Zealand study of hip and knee prosthesis SSI. More awareness of the high costs involved should encourage research and implementation of infection prevention strategies.

Pharmacokinetic drug evaluation of dalbavancin for the treatment of skin infections.

INTRODUCTION: Acute bacterial skin and skin structure infections (ABSSIs), defined as a bacterial infection of the skin with a lesion size area of at least 75 cm, are a leading cause of hospital admission and ambulatory care visits worldwide. Dalbavancin is a lipoglycopeptide antibiotic recently approved by the United States Food and Drug Administration (FDA) and by European Medicines Agency (EMA) for ABSSSIs. The authors review and provide updates of efficacy and safety by several studies on dalbavancin. Areas covered: A PubMed search was performed for relevant literature. We especially focused our attention on pharmacokinetics. Expert opinion: Dalbavancin provides an important new therapy for management of ABSSI, maintaining a spectrum of activity similar to vancomycin against gram-positive organisms. Use of dalbavancin, with its 1-week-shot treatment, consist in a reduction of the length of hospital stay or in a reduction of hospital admissions, with important cost savings.

Controlling for endogeneity in attributable costs of vancomycin-resistant enterococci from a Canadian hospital.

BACKGROUND: Decisions regarding the optimal provision of infection prevention and control resources depend on accurate estimates of the attributable costs of health care-associated infections. This is challenging given the skewed nature of health care cost data and the endogeneity of health care-associated infections. The objective of this study is to determine the hospital costs attributable to vancomycin-resistant enterococci (VRE) while accounting for endogeneity. METHODS: This study builds on an attributable cost model conducted by a retrospective cohort study including 1,292 patients admitted to an urban hospital in Vancouver, Canada. Attributable hospital costs were estimated with multivariate generalized linear models (GLMs). To account for endogeneity, a control function approach was used. RESULTS: The analysis sample included 217 patients with health care-associated VRE. In the standard GLM, the costs attributable to VRE are $17,949 (SEM, $2,993). However, accounting for endogeneity, the attributable costs were estimated to range from $14,706 (SEM, $7,612) to $42,101 (SEM, $15,533). Across all model specifications, attributable costs are 76% higher on average when controlling for endogeneity. CONCLUSIONS: VRE was independently associated with increased hospital costs, and controlling for endogeneity lead to higher attributable cost estimates.

Vancomycin-Resistant Enterococcus Colonization and Bacteremia and Hematopoietic Stem Cell Transplantation Outcomes.

The association between pre-hematopoietic stem cell transplantation (HSCT) vancomycin-resistant Enterococcus (VRE) colonization, HSCT-associated VRE bacteremia, and HSCT mortality is disputed. We studied 161 consecutive patients with acute leukemia who underwent HSCT at our hospital between 2006 and 2014, of whom 109 also received leukemia induction/consolidation on our unit. All inpatients had weekly VRE stool surveillance. Pre-HSCT colonization was not associated with increases in HSCT mortality but did identify a subgroup of HSCT recipients with a higher risk for VRE bacteremia and possibly bacteremia from other organisms. The major risk factor for pre-HSCT colonization was the number of hospital inpatient days between initial admission for leukemia and HSCT. One-third of evaluable patients colonized before HSCT were VRE-culture negative on admission for HSCT; these patients had an increased risk for subsequent VRE stool surveillance positivity but not VRE bacteremia. Molecular typing of VRE isolates obtained before and after HSCT showed that VRE strains frequently change. Postengraftment VRE bacteremia was associated with a much higher mortality than pre-engraftment VRE bacteremia. Pre-engraftment bacteremia from any organism was associated with an alternative donor and resulted in an increase in hospital length of stay and cost. Mortality was similar for pre-engraftment VRE bacteremia and pre-engraftment bacteremia due to other organisms, but mortality associated with post-engraftment VRE bacteremia was higher and largely explained by associated severe graft-versus-host disease and relapsed leukemia. These data emphasize the importance of distinguishing between VRE colonization before HSCT and at HSCT, between pre-engraftment and postengraftment VRE bacteremia, and between VRE bacteremia and bacteremia from other organisms.

Impact of a Rapid Blood Culture Assay for Gram-Positive Identification and Detection of Resistance Markers in a Pediatric Hospital.

CONTEXT: Molecular diagnostics allow for rapid identification and detection of resistance markers of bloodstream infection, with a potential for accelerated antimicrobial optimization and improved patient outcomes. Although the impact of rapid diagnosis has been reported, studies in pediatric patients are scarce. OBJECTIVE: To determine the impact of a molecular blood-culture assay that identifies a broad-spectrum of pathogens and resistance markers in pediatric patients with gram-positive bloodstream infections. DESIGN: Data on the time to antimicrobial optimization, the length of hospitalization, and the hospital cost following implementation of a rapid assay were prospectively collected and compared with corresponding preimplementation data. RESULTS: There were 440 episodes from 383 patients included, 221 preimplementation episodes and 219 postimplementation episodes. Overall time to antimicrobial optimization was shortened by 12.5 hours (P = .006), 11.9 hours (P = .005) for bloodstream infections of Staphylococcus aureus specifically. Duration of antibiotics for those with probable blood-culture contamination with coagulase-negative staphylococci was reduced by 36.9 hours (P < .001). Median length of stay for patients admitted to general pediatric units was 1.5 days shorter (P = .04), and median hospital cost was $3757 (P = .03) less after implementation. For S aureus bloodstream infections, median length of stay and hospital cost were decreased by 5.6 days (P = .01) and $13,341 (P = .03), respectively. CONCLUSIONS: Implementation of molecular assay for the detection of gram-positive pathogens and resistance markers significantly reduced time to identification and resistance detection, resulting in accelerated optimization of therapy, shorter length of stay, and decreased health care cost.

Continuous vs. intermittent vancomycin therapy for Gram-positive infections not caused by methicillin-resistant Staphylococcus aureus.

BACKGROUND: The aim of this study was to evaluate the effects of vancomycin pharmacokinetics (PKs) on effectiveness and safety in the treatment of Gram-positive infections due to pathogens other than methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Prospective study including septic patients received either continuous (N.=21) or intermittent (N.=21) infusions of vancomycin; the target drug concentration was 15-20 mg/L and target area under the curve of vancomycin concentrations over the minimum inhibitory concentration of the pathogen on day 1 (AUC24/MIC) >400. Clinical and microbiological responses, the development of acute kidney injury (AKI) and therapy costs were recorded. RESULTS: The median AUC24/MIC was 195(133-343) vs. 189(136-328) mg/L*h in the continuous and intermittent infusion groups. Target drug concentrations were achieved in 15/21 vs. 9/21 (P=0.12) patients and AUC24/MIC>400 in only 5/21 vs. 3/21 (P=0.35) patients of continuous and intermittent groups, respectively. High clinical cure (17/21 for continuous vs. 17/21 for intermittent, P=1.00) and microbiological eradication (17/21 vs. 15/21, P=0.47) were observed in both groups and not associated with drug concentrations or with AUC24/MIC. AKI was diagnosed during therapy in 5/21 patients in the continuous group and 8/21 in the intermittent group (P=0.32). The median total therapy costs were lower in the continuous than in the intermittent group (377 [304-485] vs. 552 [371-644] €, P=0.04). CONCLUSIONS: Vancomycin resulted in high clinical response during non-MRSA Gram-positive infections treatment even at drug concentrations lower than those for MRSA. A continuous infusion of vancomycin was associated with a significant reduction in therapy costs compared to intermittent infusions.

Assessing the economic value of avoiding hospital admissions by shifting the management of gram+ acute bacterial skin and skin-structure infections to an outpatient care setting.

OBJECTIVE: To estimate, from a US payer perspective, the cost offsets of treating gram positive acute bacterial skin and skin-structure infections (ABSSSI) with varied hospital length of stay (LOS) followed by outpatient care, as well as the cost implications of avoiding hospital admission. METHODS: Economic drivers of care were estimated using a literature-based economic model incorporating inpatient and outpatient components. The model incorporated equal efficacy, adverse events (AE), resource use, and costs from literature. Costs of once- and twice-daily outpatient infusions to achieve a 14-day treatment were analyzed. Sensitivity analyses were performed. Costs were adjusted to 2015 US$. RESULTS: Total non-drug medical cost for treatment of ABSSSI entirely in the outpatient setting to avoid hospital admission was the lowest among all scenarios and ranged from $4039-$4924. Total non-drug cost for ABSSSI treated in the inpatient setting ranged from $9813 (3 days LOS) to $18,014 (7 days LOS). Inpatient vs outpatient cost breakdown was: 3 days inpatient ($6657)/11 days outpatient ($3156-$3877); 7 days inpatient ($15,017)/7 days outpatient ($2495-$2997). Sensitivity analyses revealed a key outpatient cost driver to be peripherally inserted central catheter (PICC) costs (average per patient cost of $873 for placement and $205 for complications). LIMITATIONS: Drug and indirect costs were excluded and resource use was not differentiated by ABSSSI type. It was assumed that successful ABSSSI treatment takes up to 14 days per the product labels, and that once-daily and twice-daily antibiotics have equal efficacy. CONCLUSION: Shifting ABSSSI care to outpatient settings may result in medical cost savings greater than 53%. Typical outpatient scenarios represent 14-37% of total medical cost, with PICC accounting for 28-43% of the outpatient burden. The value of new ABSSSI therapies will be driven by eliminating the need for PICC line, reducing length of stay and the ability to completely avoid a hospital stay.

Frequency, risk factors, and outcomes of vancomycin-resistant Enterococcus colonization and infection in patients with newly diagnosed acute leukemia: different patterns in patients with acute myelogenous and acute lymphoblastic leukemia.

OBJECTIVE To determine the frequency, risk factors, and outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in patients with newly diagnosed acute leukemia. DESIGN Retrospective clinical study with VRE molecular strain typing. SETTING A regional referral center for acute leukemia. PATIENTS Two hundred fourteen consecutive patients with newly diagnosed acute leukemia between 2006 and 2012. METHODS All patients had a culture of first stool and weekly surveillance for VRE. Clinical data were abstracted from the Intermountain Healthcare electronic data warehouse. VRE molecular typing was performed utilizing the semi-automated DiversiLab System. RESULTS The rate of VRE colonization was directly proportional to length of stay and was higher in patients with acute lymphoblastic leukemia. Risk factors associated with colonization include administration of corticosteroids (P=0.004) and carbapenems (P=0.009). Neither a colonized prior room occupant nor an increased unit colonization pressure affected colonization risk. Colonized patients with acute myelogenous leukemia had an increased risk of VRE bloodstream infection (BSI, P=0.002). Other risk factors for VRE BSI include severe neutropenia (P=0.04) and diarrhea (P=0.008). Fifty-eight percent of BSI isolates were identical or related by molecular typing. Eighty-nine percent of bloodstream isolates were identical or related to stool isolates identified by surveillance cultures. VRE BSI was associated with increased costs (P=0.0003) and possibly mortality. CONCLUSIONS VRE colonization has important consequences for patients with acute myelogenous leukemia undergoing induction therapy. For febrile neutropenic patients with acute myelogenous leukemia, use of empirical antibiotic regimens that avoid carbapenems and include VRE coverage may be helpful in decreasing the risks associated with VRE BSI.

Antimicrobial resistance: impact on clinical and economic outcomes and the need for new antimicrobials.

INTRODUCTION: Antimicrobial resistance is a well-recognized global threat; thus, the development of strong infection control policies coupled with antimicrobial stewardship strategies and new therapies is required to reverse this process. In its 2013 report on antimicrobial resistance, the Centers for Disease Control and Prevention focused on this problem while presenting estimated annual rates of infections with antimicrobial-resistant organisms and their related mortality rates. Whereas some resistant pathogens were considered less threatening, others such as carbapenem-resistant Enterobacteriaceae were associated with higher mortality rates owing to limited treatment options. AREAS COVERED: An overview of the most common antimicrobial-resistant pathogens, focusing on risk factors for acquisition, clinical and economic outcomes, as well as current treatment options. Strategies to optimize antimicrobial therapy with currently available agents, in addition to newly developed antimicrobials are also discussed. EXPERT OPINION: The emergence of pathogens with a variety of resistance mechanisms has intensified the challenges associated with infection control and treatment strategies. Therefore, prudent use of currently available antimicrobial agents, as well as implementing measures to limit spread of resistance is paramount. Although several new antimicrobials have been recently approved or are in the pipeline showing promise in the battle against resistance, the appropriate use of these agents is required as the true benefits of these treatments are to be recognized in the clinical care setting.

Vancomycin-resistant Enterococcus colonization in the intensive care unit: clinical outcomes and attributable costs of hospitalization.

BACKGROUND: The clinical and economic impact of vancomycin-resistant Enterococcus (VRE) colonization remains unclear. Little data are available on factors affecting hospitalization length of stay (LOS) and costs. This study aimed to estimate mortality, LOS, and hospitalization costs for VRE colonized patients compared with a matched hospital population. METHODS: We performed a retrospective propensity score matched cohort study comparing the outcomes of patients with VRE colonization with those of uncolonized subjects matched at the time they were admitted to the intensive care unit (ICU). Between January 2008 and December 2010, we obtained rectal swab cultures within 24 hours of ICU admission to detect VRE colonization. RESULTS: During the study period, 567 (7.2%) of the 7,703 patients were colonized with VRE. There were 199 VRE colonized patients compared with 199 uncolonized patients using the propensity score. VRE colonized patients when compared with uncolonized patients were likely to have a higher case fatality rate (24.6% vs 17.1%; OR, 2.35). Longer total admission days were observed in the VRE colonized patients (28.7 vs 21.4 days; multiplicative effect, 1.25; P = .004). VRE colonization is found to be a significant factor associated with increased ICU cost in the multivariable regression model ($6,065 vs $5,298; multiplicative effect, 1.22; P = .029). Multivariable analysis identified the factors affecting ICU cost as follows: VRE colonization (odds ratio [OR], 1.20; P = .038), ICU length of stay (OR, 1.93; P < .001), ICU type (OR, 1.51; P = .001), valvular heart disease (OR, 2.38; P = .27), hospitalization within 12 months (OR, 1.21; P = .037), and use of invasive devices (OR, 1.28; P = .017). CONCLUSION: Compared with a matched hospital population, VRE colonization was associated with increased mortality, LOS, and costs. Strict infection control programs, including preemptive isolation for a high-risk group, should be helpful.

Impact of different antimicrobial therapies on clinical and fiscal outcomes of patients with bacteremia due to vancomycin-resistant enterococci.

Vancomycin-resistant enterococci (VRE) are a growing health problem, and uncertainties exist regarding the optimal therapy for bloodstream infection due to VRE. We conducted systematic comparative evaluations of the impact of different antimicrobial therapies on the outcomes of patients with bloodstream infections due to VRE. A retrospective study from January 2008 to October 2010 was conducted at Detroit Medical Center. Unique patients with blood cultures due to VRE were included and reviewed. Three major therapeutic classes were analyzed: daptomycin, linezolid, and ß-lactams. Three multivariate models were conducted for each outcome, matching for a propensity score predicting the likelihood of receipt of one of the therapeutic classes. A total of 225 cases of bacteremia due to VRE were included, including 86 (38.2%) cases of VR Enterococcus faecalis and 139 (61.8%) of VR Enterococcus faecium. Bacteremia due to VR E. faecalis was more frequent among subjects treated with ß-lactams than among those treated with daptomycin or linezolid. The median dose of daptomycin was 6 mg/kg of body weight (range, 6 to 12 mg/kg). After controlling for propensity score and bacteremia due to VR E. faecalis, differences in mortality were nonsignificant among the treatment groups. Therapy with daptomycin was associated with higher median variable direct cost per day than that for linezolid. This large study revealed the three therapeutic classes (daptomycin, linezolid, and ß-lactams) are similarly efficacious in the treatment of bacteremia due to susceptible strains of VRE.

Prevention of gram-positive infections in peritoneal dialysis patients in Hong Kong: a cost-effectiveness analysis.

BACKGROUND: Gram-positive bacteria are the major causative pathogens of peritonitis and exit site infection in patients undergoing peritoneal dialysis (PD). We investigated the cost-effectiveness of regular application of mupirocin at the exit site in PD recipients from the perspective of health care providers in Hong Kong. METHODS: A decision tree was designed to simulate outcomes of incident PD patients with and without regular application of mupirocin over a 1-year period. Outcome measures included total direct medical costs, quality-adjusted life-years (QALYs) gained, and gram-positive infection-related mortality rate. Model inputs were derived from the literature. Sensitivity analyses evaluated the impact of uncertainty in all model variables. RESULTS: In a base case analysis, the mupirocin group had a higher expected QALY value (0.6496 vs 0.6456), a lower infection-related mortality rate (0.18% vs 1.64%), and a lower total cost per patient (US $258 vs $1661) compared with the control group. The rate of gram-positive peritonitis without mupirocin and the risk of gram-positive peritonitis with mupirocin were influential factors. In 10,000 Monte Carlo simulations, the mupirocin group had significantly lower associated costs, higher QALYs, and a lower mortality rate 99.9% of the time. CONCLUSIONS: Topical mupirocin appears to be a cost-effective preventive measure against gram-positive infection in incident patients undergoing PD. The cost-effectiveness of mupirocin is affected by the level of infection risk reduction and subject to resistance against mupirocin.