Attributable Cost and Length of Stay Associated with Nosocomial Gram-Negative Bacterial Cultures.

Few studies have estimated the excess inpatient costs due to nosocomial cultures of Gram-negative bacteria (GNB), and those that do are often subject to time-dependent bias. Our objective was to generate estimates of the attributable costs of the underlying infections associated with nosocomial cultures by using a unique inpatient cost data set from the U.S. Department of Veterans Affairs that allowed us to reduce time-dependent bias. Our study included data from inpatient admissions between 1 October 2007 and 30 November 2010. Nosocomial GNB-positive cultures were defined as clinical cultures positive for Acinetobacter, Pseudomonas, or Enterobacteriaceae between 48 h after admission and discharge. Positive cultures were further classified by site and level of resistance. We conducted analyses using both a conventional approach and an approach aimed at reducing the impact of time-dependent bias. In both instances, we used multivariable generalized linear models to compare the inpatient costs and length of stay for patients with and without a nosocomial GNB culture. Of the 404,652 patients included in the conventional analysis, 12,356 had a nosocomial GNB-positive culture. The excess costs of nosocomial GNB-positive cultures were significant, regardless of specific pathogen, site, or resistance level. Estimates generated using the conventional analysis approach were 32.0% to 131.2% greater than those generated using the approach to reduce time-dependent bias. These results are important because they underscore the large financial burden attributable to these infections and provide a baseline that can be used to assess the impact of improvements in infection control.

In-hospital costs of community-acquired colonization with multidrug-resistant organisms at a German teaching hospital.

BACKGROUND: Antibiotic resistance is a challenge in the management of infectious diseases and can cause substantial cost. Even without the onset of infection, measures must be taken, as patients colonized with multi-drug resistant (MDR) pathogens may transmit the pathogen. We aim to quantify the cost of community-acquired MDR colonizations using routine data from a German teaching hospital. METHODS: All 2006 cases of documented MDR colonization at hospital admission recorded from 2011 to 2014 are matched to 7917 unexposed controls with the same primary diagnosis. Cases with an onset MDR infection are excluded from the analysis. Routine data on costs per case is analysed for three groups of MDR bacteria: Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), and multidrug-resistant gram-negative bacteria (MDR-GN). Multivariate analyses are conducted to adjust for potential confounders. RESULTS: After controlling for main diagnosis group, age, sex, and Charlson Comorbidity Index, MDR colonization is associated with substantial additional costs from the healthcare perspective (€1480.9, 95%CI €1286.4-€1675.5). Heterogeneity between pathogens remains. Colonization with MDR-GN leads to the largest cost increase (€1966.0, 95%CI €1634.6-€2297.4), followed by MRSA with €1651.3 (95%CI €1279.1-€2023.6), and VRE with €879.2 (95%CI €604.1-€1154.2). At the same time, MDR-GN is associated with additional reimbursements of €887.8 (95%CI €722.1-€1053.6), i.e. costs associated with MDR-colonization exceed reimbursement. CONCLUSIONS: Even without the onset of invasive infection, documented MDR-colonization at hospital admission is associated with increased hospital costs, which are not fully covered within the German DRG-based hospital payment system.

Increased Costs Associated with Bloodstream Infections Caused by Multidrug-Resistant Gram-Negative Bacteria Are Due Primarily to Patients with Hospital-Acquired Infections.

The clinical and economic impacts of bloodstream infections (BSI) due to multidrug-resistant (MDR) Gram-negative bacteria are incompletely understood. From 2009 to 2015, all adult inpatients with Gram-negative BSI at our institution were prospectively enrolled. MDR status was defined as resistance to ≥3 antibiotic classes. Clinical outcomes and inpatient costs associated with the MDR phenotype were identified. Among 891 unique patients with Gram-negative BSI, 292 (33%) were infected with MDR bacteria. In an adjusted analysis, only history of Gram-negative infection was associated with MDR BSI versus non-MDR BSI (odds ratio, 1.60; 95% confidence interval [CI], 1.19 to 2.16; P = 0.002). Patients with MDR BSI had increased BSI recurrence (1.7% [5/292] versus 0.2% [1/599]; P = 0.02) and longer hospital stay (median, 10.0 versus 8.0 days; P = 0.0005). Unadjusted rates of in-hospital mortality did not significantly differ between MDR (26.4% [77/292]) and non-MDR (21.7% [130/599]) groups (P = 0.12). Unadjusted mean costs were 1.62 times higher in MDR than in non-MDR BSI ($59,266 versus $36,452; P = 0.003). This finding persisted after adjustment for patient factors and appropriate empirical antibiotic therapy (means ratio, 1.18; 95% CI, 1.03 to 1.36; P = 0.01). Adjusted analysis of patient subpopulations revealed that the increased cost of MDR BSI occurred primarily among patients with hospital-acquired infections (MDR means ratio, 1.41; 95% CI, 1.10 to 1.82; P = 0.008). MDR Gram-negative BSI are associated with recurrent BSI, longer hospital stays, and increased mean inpatient costs. MDR BSI in patients with hospital-acquired infections primarily account for the increased cost.

Combating blood stream infections during induction chemotherapy in children with acute myeloid leukemia: Single center results in India.

Optimal management of infectious complication is the biggest challenge in children receiving chemotherapy for acute myeloid leukemia (AML). We have analyzed the data of children undergoing AML induction chemotherapy at our center from 2002 to 2016 and found that Gram-negative infections are more predominant when compared to the published literature. There also has been a surge in multidrug-resistant (MDR) infections over the last 4 years, which has increased the need for supportive care and escalated the cost of care. We have introduced certain novel methods to combat MDR sepsis and decrease mortality rates.

Evaluation of the efficiency of hospital antibiotic policy applied Dr Jan Biziel University Hospital No 2 in Bydgoszcz in 2009-2013.

UNLABELLED: The Hospital Infection Control Team (HICT) of Dr Jan Biziel University Hospital No 2 in Bydgoszcz developed and implemented the principles of a rational antibiotic therapy in 2008. A behavior algorithm has worked since 01.10.2008. Implementation of the principles of a rational antibiotic therapy was part of the hospital antibiotic policy. THE AIM OF THE STUDY: is to evaluate either introductory principles of the rational antibiotic therapy, after five-year experience lived up to expectations in the range specified by the authors. MATERIAL AND METHODS: Hospital microbiological maps, comparisons of antibiotic cost, specification of microbiological tests made before and after introduction of the principles of a rational antibiotic therapy have been analyzed. Annual antibiotic consumption has been counted according to the defined daily dose (DDD) index created by the WHO. RESULTS: After 6 years of implementation of the rational antibiotic therapy principles, the decrease in number of isolated strains which are resistant to Klebsiella pneumoniae ESBL and Acinetobacter baumanii (resistant to carbapenems) has been indicated. The number of the Pseudomonas aeruginosa isolates has increased approximately three times, and the number of resistant isolates to carbapenem has grown six times. The cost of antibiotics has been gradually decreased in 2012 in order to represent 9,66% of all drug budget (without drug programs). Detailed analysis of antibiotic consumption has showed that after the implementation of rational antibiotic therapy principles the consumption of meropenem has increased twice in comparison to the all drugs. The number of microbiological tests grew from 0,20 to 0,29 per one patient, which means material to microbiological tests has been taken from every third patient. Annual DDD index calculated on 100 person-days has been reduced from 59,552 in 2007 to 39,90 in 2009, and it is 47,88 in 2013. The principles of rational antibiotic therapy in comparison with the other elements of antibiotic policy in hospital have caused positive changes in antibiotic ordinance. CONCLUSIONS: 1. It is required to adhere to the principles of a rational antibiotic therapy by medical staff mainly on the administrative restriction of access to antibiotics. 2. Monitoring changes in drug resistance of hospital flora is an essential element of the principles of a rational antibiotic therapy modification.

Prevention and control of blood stream infection using the balanced scorecard approach.

AIM: to obtain formulation of an effective and efficient strategy to overcome blood stream infection (BSI). METHODS: operational research design with qualitative and quantitative approach. The study was divided into two stages. Stage I was an operational research with problem solving approach using qualitative and quantitative method. Stage II was performed using quantitative method, a form of an interventional study on strategy implementation, which was previously established in stage I. The effective and efficient strategy for the prevention and control of infection in neonatal unit Cipto Mangunkusumo (CM) Hospital was established using Balanced Scorecard (BSC) approach, which involved several related processes. RESULTS: the BSC strategy was proven to be effective and efficient in substantially reducing BSI from 52.31°/oo to 1.36°/oo in neonates with birth weight (BW) 1000-1499 g (p=0.025), and from 29.96°/oo to 1.66°/oo in BW 1500-1999 g (p=0.05). Gram-negative bacteria still predominated as the main cause of BSI in CMH Neonatal Unit. So far, the sources of the microorganisms were thought to be from the environment of treatment unit (tap water filter and humidifying water in the incubator). Significant reduction was also found in neonatal mortality rate weighing 1000-1499 g at birth, length of stay, hospitalization costs, and improved customer satisfaction. CONCLUSION: effective and efficient infection prevention and control using BSC approach could significantly reduce the rate of BSI. This approach may be applied for adult patients in intensive care unit with a wide range of adjustment.

Cost-effectiveness analysis of polymyxin B versus colistin for treating patients with carbapenem-resistant gram-negative bacterial infections.

The prevalence of carbapenem-resistant gram-negative bacterial (CRGNB) infection is continuously increasing, and polymyxin B and colistin are considered last-resort drugs. This study compared the cost-effectiveness of polymyxin B with that of colistin for the treatment of intensive care unit patients with CRGNB infection from the Chinese healthcare perspective. A decision-analytic Markov model was constructed to assess the cost-effectiveness of polymyxin B compared with colistin over a period of 5 years using evidence from phase trials and other publicly available studies. The model was developed in Treeage Pro 2022 and comprises a decision tree depicting initial hospitalization and a Markov model with four states projecting long-term health and economic impacts following discharge. Uncertainty was tested with one-way sensitivity analyses and probabilistic sensitivity analyses. The quality-adjusted life years (QALYs), direct medical costs, and incremental cost-effectiveness ratio (ICER) were estimated at willingness-to-pay (WTP) thresholds of $12,674 to $38,024 per QALY. According to the base analyses, the cost incurred by patients receiving colistin treatment was $12,244.77, leading to a gain of 1.35 QALYs. In contrast, patients treated with polymyxin B had a lower cost of $7,306.71 but yielded 1.07 QALYs. The ICRE of colistin was $18032.25/QALY. At a $12,674/QALY threshold, the results were sensitive to several variables, including the probability of cure with polymyxin B, the cost of drugs, the utility of discharge to home, the utility of discharge to long-term care, and the cost of nephrotoxicity with renal replacement therapy. After all model inputs varied across a wide range of reasonable values, only the probability of being cured with polymyxin B resulted in an ICER above the $38,024/QALY threshold. According to the probabilistic sensitivity analyses, colistin was the optimal strategy in 38.2% and 62.8% of the simulations, at $12,674/QALY and $38,024/QALY, respectively. Our study findings suggest that, when considering the Chinese healthcare perspective, colistin is likely to be more cost-effective than polymyxin B for patients with CRGNB infection, especially when the WTP threshold is set at one-time the per capita GDP. However, as the WTP threshold increases from one to three times the per capita GDP, the cost-effectiveness acceptability of colistin improves, increasing from 38.2 to 62.8%.

An institutional perspective on the impact of recent antibiotic exposure on length of stay and hospital costs for patients with gram-negative sepsis.

BACKGROUND: Prior antibiotic exposure has been associated with the emergence of antibiotic resistance in subsequent bacterial infections, whose outcomes are typically worse than similar infections with more antibiotic susceptible infections. The influence of prior antibiotic exposure on hospital length of stay (LOS) and costs in patients with severe sepsis or septic shock attributed to Gram-negative bacteremia has not been previously examined. METHODS: A retrospective cohort study of hospitalized patients (January 2002-December 2007) was performed at Barnes-Jewish Hospital, a 1200-bed urban teaching hospital. Patients with Gram-negative bacteremia complicated by severe sepsis or septic shock had data abstraction from computerized medical records. We examined a consecutive cohort of 754 subjects (mean age 59.3 ± 16.3 yrs, mean APACHE II 23.7 ± 6.7). RESULTS: Escherichia coli (30.8%), Klebsiella pneumoniae (23.2%), and Pseudomonas aeruginosa (17.6%) were the most common organisms isolated from blood cultures. 310 patients (41.1%) had exposure to antimicrobial agents in the previous 90 days. Patients with recent antibiotic exposure had greater inappropriate initial antimicrobial therapy (45.4% v. 21.2%; p < 0.001) and hospital mortality (51.3% v. 34.0%; p < 0.001) compared to patients without recent antibiotic exposure. The unadjusted median LOS (25th percentile, 75th percentile) following sepsis onset in patients with prior antimicrobial exposure was 13.0 days (5.0 days, 24.0 days) compared to 8.0 days (5.0 days, 14.0 days) in those without prior antimicrobial exposure (p < 0.001). In a Cox model controlling for multiple confounders, prior antibiotic exposure independently correlated with remaining hospitalized (Adjusted hazard ratio: 1.473, 95% CI: 1.297-1.672, p < 0.001). Adjusting for potential confounders indicated that prior antibiotic exposure independently increased median attributable LOS by 5.0 days. Similarly, total hospital costs following sepsis onset was significantly greater among patients with prior antimicrobial exposure (median values: $94,737 v. $21,329; p < 0.001). CONCLUSIONS: Recent antibiotic exposure is associated with increased LOS and hospital costs in Gram-negative bacteremia complicated by severe sepsis or septic shock. Clinicians and hospital administrators should consider the potential impact of recent antibiotic exposure when formulating empiric treatment decisions for patients with serious infections attributed to Gram-negative bacteria.

The cost and management of different types of clinical mastitis in dairy cows estimated by dynamic programming.

The objective of this study was to estimate the cost of 3 different types of clinical mastitis (CM) (caused by gram-positive bacteria, gram-negative bacteria, and other organisms) at the individual cow level and thereby identify the economically optimal management decision for each type of mastitis. We made modifications to an existing dynamic optimization and simulation model, studying the effects of various factors (incidence of CM, milk loss, pregnancy rate, and treatment cost) on the cost of different types of CM. The average costs per case (US$) of gram-positive, gram-negative, and other CM were $133.73, $211.03, and $95.31, respectively. This model provided a more informed decision-making process in CM management for optimal economic profitability and determined that 93.1% of gram-positive CM cases, 93.1% of gram-negative CM cases, and 94.6% of other CM cases should be treated. The main contributor to the total cost per case was treatment cost for gram-positive CM (51.5% of the total cost per case), milk loss for gram-negative CM (72.4%), and treatment cost for other CM (49.2%). The model affords versatility as it allows for parameters such as production costs, economic values, and disease frequencies to be altered. Therefore, cost estimates are the direct outcome of the farm-specific parameters entered into the model. Thus, this model can provide farmers economically optimal guidelines specific to their individual cows suffering from different types of CM.

Healthcare resource use in hospitalized patients with carbapenem-resistant Gram-negative infections.

OBJECTIVES: Antimicrobial resistance (AMR) is a threat to global public health. Infections with resistant organisms are more challenging to treat, often delay patient recovery and can increase morbidity and mortality. Healthcare costs associated with treating patients with AMR organisms are poorly described. In particular, data for specific organisms, such as those harbouring carbapenem resistance, are lacking. METHODS: This was a retrospective, matched (1:1), single-centre, cohort study at a Central London hospital, comparing costs and resource use of 442 adult inpatients infected with either carbapenem-sensitive (CSO) or carbapenem-resistant organisms (CRO) over a two-year period. Resource use and micro-costing data were obtained from the hospital Patient, Education and Research Costing System (PERCS), and included both direct and indirect costs. RESULTS: Overall, the median healthcare-related cost of treating a patient with a CRO was more than double (£49,537 vs £19,299) that of treating a patient with a CSO. There were statistically significant increases in expenditure across 21 of 44 measured parameters including critical care costs, which accounted for the greatest proportion of overall costs in both groups. Infections were predominantly of the respiratory tract (41%) and caused by Pseudomonas aeruginosa (76%). CONCLUSIONS: Infection with CROs increases healthcare expenditure significantly. Many of the costs, including patient support, portering and catering, have been underappreciated in previous work. We additionally note that patients infected with CROs have longer hospital stays, and increased theatre operating times compared with patients infected with CSOs.

Attributable hospital cost and length of stay associated with health care-associated infections caused by antibiotic-resistant gram-negative bacteria.

Determination of the attributable hospital cost and length of stay (LOS) are of critical importance for patients, providers, and payers who must make rational and informed decisions about patient care and the allocation of resources. The objective of the present study was to determine the additional total hospital cost and LOS attributable to health care-associated infections (HAIs) caused by antibiotic-resistant, gram-negative (GN) pathogens. A single-center, retrospective, observational comparative cohort study was performed. The study involved 662 patients admitted from 2000 to 2008 who developed HAIs caused by one of following pathogens: Acinetobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., or Pseudomonas spp. The attributable total hospital cost and LOS for HAIs caused by antibiotic-resistant GN pathogens were determined by comparison with the hospital costs and LOS for a control group with HAIs due to antibiotic-susceptible GN pathogens. Statistical analyses were conducted by using univariate and multivariate analyses. Twenty-nine percent of the HAIs were caused by resistant GN pathogens, and almost 16% involved a multidrug-resistant GN pathogen. The additional total hospital cost and LOS attributable to antibiotic-resistant HAIs caused by GN pathogens were 29.3% (P < 0.0001; 95% confidence interval, 16.23 to 42.35) and 23.8% (P = 0.0003; 95% confidence interval, 11.01 to 36.56) higher than those attributable to HAIs caused by antibiotic-susceptible GN pathogens, respectively. Significant covariates in the multivariate analysis were age >or=12 years, pneumonia, intensive care unit stay, and neutropenia. HAIs caused by antibiotic-resistant GN pathogens were associated with significantly higher total hospital costs and increased LOSs compared to those caused by their susceptible counterparts. This information should be used to assess the potential cost-efficacy of interventions aimed at the prevention of such infections.

Ertapenem administered as outpatient parenteral antibiotic therapy for urinary tract infections caused by extended-spectrum-beta-lactamase-producing Gram-negative organisms.

OBJECTIVES: Infections with extended-spectrum-beta-lactamase-producing organisms are an increasing public health concern. We reviewed the use of an outpatient parenteral antibiotic therapy (OPAT) programme to facilitate the early discharge from hospital of patients with ESBL-associated urinary tract infections. METHODS: A retrospective review of patients treated for urinary tract infections caused by ESBL-producing organisms through the OPAT programme at the Royal Hallamshire Hospital, Sheffield, UK over a 4 year period to January 2010 was conducted. Data on patient demographics, clinical presentation and laboratory results were collected. RESULTS: Twenty-four OPAT episodes involving 11 patients were identified. Six patients (54.5%) had an underlying urological abnormality on presentation to OPAT. All patients were treated with parenteral ertapenem. Two patients had multiple infections treated by OPAT. The mean duration of the OPAT episodes was 9.9 days (range 3-42). A total of 238 inpatient bed days were avoided, with resultant cost savings. CONCLUSIONS: Ertapenem administration through OPAT may help to decrease the costs associated with ESBL infections by reducing the number of inpatient bed days required for their successful treatment.

Attributable burden in patients with carbapenem-nonsusceptible gram-negative respiratory infections.

OBJECTIVE: We aimed to describe the clinical and economic burden attributable to carbapenem-nonsusceptible (C-NS) respiratory infections. METHODS: This retrospective matched cohort study assessed clinical and economic outcomes of adult patients (aged ≥18 years) who were admitted to one of 78 acute care hospitals in the United States with nonduplicate C-NS and carbapenem-susceptible (C-S) isolates from a respiratory source. A subset analysis of patients with principal diagnosis codes denoting bacterial pneumonia or other diagnoses was also conducted. Isolates were classified as community- or hospital-onset based on collection time. A generalized linear mixed model method was used to estimate the attributable burden for mortality, 30-day readmission, length of stay (LOS), cost, and net gain/loss (payment minus cost) using propensity score-matched C-NS versus C-S cohorts. RESULTS: For C-NS cases, mortality (25.7%), LOS (29.4 days), and costs ($81,574) were highest in the other principal diagnosis, hospital-onset subgroup; readmissions (19.4%) and net loss (-$9522) were greatest in the bacterial pneumonia, hospital-onset subgroup. Mortality and readmissions were not significantly higher for C-NS cases in any propensity score-matched subgroup. Significant C-NS-attributable burden was found for both other principal diagnosis subgroups for LOS (hospital-onset: 3.7 days, P = 0.006; community-onset: 1.5 days, P<0.001) and cost (hospital-onset: $12,777, P<0.01; community-onset: $2681, P<0.001). CONCLUSIONS: Increased LOS and cost burden were observed in propensity score-matched patients with C-NS compared with C-S respiratory infections; the C-NS-attributable burden was significant only for patients with other principal diagnoses.

Effects of repeated gram-positive and gram-negative clinical mastitis episodes on milk yield loss in Holstein dairy cows.

The objective of this study was to estimate the effects of recurrent episodes of gram-positive and gram-negative cases of clinical mastitis (CM) on milk production in Holstein dairy cows. We were interested in the severity of repeated cases in general, but also in the severity of the host response as judged by milk production loss when a previous case was caused by a similar or different microorganism. The results were based on data from 7,721 primiparous lactations and 13,566 multiparous lactations in 7 large dairy herds in New York State. The distribution of organisms in the CM cases showed 28.5% gram-positive cases, 31.8% gram-negative cases, 15.0% others, and 24.8% with no organism identified. Mixed models, with a random herd effect and an autoregressive covariance structure to account for repeated measurements, were used to quantify the effect of repeated CM and several other control variables (parity, week of lactation, other diseases) on milk yield. Our data indicated that repeated CM cases showed a very similar milk loss compared with the first case. No reduction of severity was present with increasing count of the CM case. Gram-negative cases had more severe milk loss compared with gram-positive and other cases irrespective of the count of the case in lactation. Milk loss in multipara (primipara) due to gram-negative CM was approximately 304 kg (228 kg) in the 50 d following CM. This loss was approximately 128 kg (133 kg) for gram-positive cases and 92 kg (112 kg) for other cases. The severity of a second case of gram-negative CM was not reduced by previous cases of gram-negative CM in multipara and only slightly less severe in a similar scenario in primipara cows. Similarly, a previous gram-positive case did not reduce severity of a second or third gram-positive case. Hence, our data do not support that immunological memory of previous exposure to an organism in the same generic class provides protection for a next case of CM with an organism in the same class.

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.

A Novel Algorithm to Analyze Epidemiology and Outcomes of Carbapenem Resistance Among Patients With Hospital-Acquired and Ventilator-Associated Pneumonia: A Retrospective Cohort Study.

BACKGROUND: Carbapenem resistance is a growing concern. Applying a novel algorithm, we examined epidemiology and outcomes of carbapenem resistance among gram-negative pathogens in hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). METHODS: In a retrospective cohort design within the Premier Research database (2009-2016), all hospitalized adult patients with a gram-negative organism in a respiratory or blood culture specimen who fit criteria for HAP/VAP based on International Classification of Diseases, Ninth Revision, Clinical Modification, codes were included in the study. RESULTS: Among 8,969 patients with HAP/VAP, 1,059 isolates (11.8%) were carbapenem-resistant (CR) organisms. Patients with CR organisms were more likely female (41.4% vs 33.2%; P < .001) and medical admissions (33.8% vs 27.4%, P < .001) than those with carbapenem-susceptible (CS) organisms. Patients with carbapenem resistance had higher comorbidity burden than those with carbapenem susceptibility (median [interquartile range] Charlson Comorbidity Index score, 3 [1-4] vs 2 [1-4]; P < .001). Pseudomonas aeruginosa was the most common gram-negative pathogen overall (24.9%) and among CS organisms (23.5%), and was second to Stenotrophomonas maltophilia (44.0%) among CR organisms (35.3%). Acinetobacter baumannii accounted for 11.8% of CR organisms and 2.5% of CS organisms (P < .001). Patients with carbapenem resistance were more likely than those with carbapenem susceptibility to receive inappropriate empiric therapy (25.8% vs 10.0%; P < .001). Carbapenem resistance did not affect adjusted mortality (22.9% CR vs 21.6% CS) or postinfection length of stay (except among survivors of VAP), but it was associated with excess costs ($8,921; 95% CI, 3,864-13,977). CONCLUSIONS: Using administrative data, our novel algorithm identified patients with pneumonia at high risk for death, consistent with HAP/VAP. Among them, carbapenem resistance occurred in 12% of all cases and was associated with substantial excess in hospital costs.

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.

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.

Gram-negative antibiotic resistance: there is a price to pay.

Resistance rates are increasing among several problematic Gram-negative pathogens that are often responsible for serious nosocomial infections, including Acinetobacter spp., Pseudomonas aeruginosa, and (because of their production of extended-spectrum beta-lactamase) Enterobacteriaceae. The presence of multiresistant strains of these organisms has been associated with prolonged hospital stays, higher health care costs, and increased mortality, particularly when initial antibiotic therapy does not provide coverage of the causative pathogen. Conversely, with high rates of appropriate initial antibiotic therapy, infections caused by multiresistant Gram-negative pathogens do not negatively influence patient outcomes or costs. Taken together, these observations underscore the importance of a 'hit hard and hit fast' approach to treating serious nosocomial infections, particularly when it is suspected that multiresistant pathogens are responsible. They also point to the need for a multidisciplinary effort to combat resistance, which should include improved antimicrobial stewardship, increased resources for infection control, and development of new antimicrobial agents with activity against multiresistant Gram-negative pathogens.

Impact of aminoglycoside cycling in six tertiary intensive care units: prospective longitudinal interventional study.

AIM: To determine the effect of aminoglycoside cycling in six tertiary intensive care units (ICU) on the rates of sepsis, aminoglycoside resistance patterns, antibiotic consumption, and costs. METHODS: This was a prospective longitudinal interventional study that measured the effect of change from first-line gentamicin usage (February 2002-February 2003) to amikacin usage (February 2003-February 2004) on the aminoglycoside resistance patterns, number of patients with gram-negative bacteremia, consumption of antibiotics, and the cost of antimicrobial drugs in 6 tertiary care ICUs in Zagreb, Croatia. RESULTS: The change from first-line gentamicin to amikacin usage led to a decrease in the overall gentamicin resistance of gram-negative bacteria (GNB) from 42% to 26% (P<0.001; z-test of proportions) and netilmicin resistance from 33% to 20% (P<0.001), but amikacin resistance did not change significantly (P=0.462), except for Acinetobacter baumanni (P=0.014). Sepsis rate in ICUs was reduced from 3.6% to 2.2% (P<0.001; chi(2) test), with a decline in the number of nosocomial bloodstream infections from 55/100 patient-days to 26/100 patient-days (P=0.001, chi(2) test). Furthermore, amikacin use led to a 16% decrease in the overall antibiotic consumption and 0.1 euro/patient/d cost reduction. CONCLUSION: Exclusive use of amikacin significantly reduced the resistance of GNB isolates to gentamicin and netilmicin, the number of GNB nosocomial bacteremias, and the cost of total antibiotic usage in ICUs.