Sanjay Merchant

Cost-effectiveness of ceftolozane/tazobactam plus metronidazole compared with piperacillin/tazobactam as empiric therapy for the treatment of complicated intra-abdominal infections based on the in-vitro surveillance of bacterial isolates in the UK.

Abstract Aims: An increase in the prevalence of antimicrobial resistance among gram-negative pathogens has been noted recently. A challenge in empiric treatment of complicated intra-abdominal infection (cIAI) is identifying initial appropriate antibiotic therapy, which is associated with reduced length of stay and mortality compared with inappropriate therapy. The objective of this study was to assess the cost-effectiveness of ceftolozane/tazobactam + metronidazole compared with piperacillin/tazobactam (commonly used in this indication) in the treatment of patients with cIAI in UK hospitals. Methods: A decision-analytic Monte Carlo simulation model was used to compare costs (antibiotic and hospitalization costs) and quality-adjusted life years (QALYs) of patients infected with gram-negative cIAI and treated empirically with either ceftolozane/tazobactam + metronidazole or piperacillin/tazobactam. Bacterial isolates were randomly drawn from the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) database, a surveillance database of non-duplicate bacterial isolates collected from patients in the UK infected with gram-negative pathogens. Susceptibility to initial empiric therapy was based on the measured susceptibilities reported in the PACTS database. Results: Ceftolozane/tazobactam + metronidazole was cost-effective when compared with piperacillin/tazobactam, with an incremental cost-effectiveness ratio (ICER) of £4,350/QALY and 0.36 hospitalization days/patient saved. Costs in the ceftolozane/tazobactam + metronidazole arm were £2,576/patient, compared with £2,168/patient in the piperacillin/tazobactam arm. The ceftolozane/tazobactam + metronidazole arm experienced a greater number of QALYs than the piperacillin/tazobactam arm (14.31/patient vs 14.21/patient, respectively). Ceftolozane/tazobactam + metronidazole remained cost-effective in one-way sensitivity and probabilistic sensitivity analyses. Conclusions: Economic models can help to identify the appropriate choice of empiric therapy for the treatment of cIAI. Results indicated that empiric use of ceftolozane/tazobactam + metronidazole is cost-effective vs piperacillin/tazobactam in UK patients with cIAI at risk of resistant infection. This will be valuable to commissioners and clinicians to aid decision-making on the targeting of resources for appropriate antibiotic therapy under the premise of antimicrobial stewardship.

Risk factors for Pseudomonas aeruginosa infections in Asia-Pacific and consequences of inappropriate initial antimicrobial therapy: A systematic literature review and meta-analysis

OBJECTIVES Treating infections of Gram-negative pathogens, in particular Pseudomonas aeruginosa, is a challenge for clinicians in the Asia-Pacific region owing to inherent and acquired antimicrobial resistance. This systematic review and meta-analysis provides updated information on risk factors for P. aeruginosa infection in Asia-Pacific as well as the consequences (e.g. mortality, costs) of initial inappropriate antimicrobial therapy (IIAT). METHODS Embase and MEDLINE databases were searched for Asia-Pacific studies reporting the consequences of IIAT versus initial appropriate antimicrobial therapy (IAAT) in Gram-negative bacterial infections as well as risk factors for serious P. aeruginosa infection. A meta-analysis of unadjusted mortality was performed using a random-effects model. RESULTS A total of 22 studies reporting mortality and 13 reporting risk factors were identified. The meta-analysis demonstrated that mortality was significantly lower in patients receiving IAAT versus IIAT, with a 67% reduction observed for 28- or 30-day all-cause mortality (odds ratio=0.33, 95% confidence interval 0.20-0.55; P<0.001). Risk factors for serious P. aeruginosa infection include previous exposure to antimicrobials, mechanical ventilation and previous hospitalisation. CONCLUSION High rates of antimicrobial resistance in Asia-Pacific as well as the increased mortality associated with IIAT and the presence of risk factors for serious infection highlight the importance of access to newer and appropriate antimicrobials.

455: BURDEN OF MULTIDRUG-RESISTANT P AERUGINOSA INFECTIONS BY TYPE OF ICU AND SOURCE OF INFECTION

Critical Care Medicine • Volume 46 • Number 1 (Supplement) www.ccmjournal.org Learning Objectives: Fibromyalgia (FM) is a common condition of unclear etiology, affecting predominantly women. Although FM is a symptom-based diagnosis, affected patients have broadly dysregulated stress response and high comorbidity burden. It can be postulated that among critically ill patients, a diagnosis of FM would either have no impact or an adverse effect on shortterm outcomes. Methods: We used the Texas Inpatient Public Use Data File to identify ICU admissions of women aged 18–64 years in 2014. FM was identified by ICD-9-CM code 729.1. The association of FM with short-term mortality (defined as hospital death or discharge to hospice [MH]) was modeled using: 1) multivariate logistic regression and 2) propensity score-matched analysis. Models were adjusted for socio-demographic characteristics, comorbidities and (for logistic models) organ failure (OF), life support interventions, and APR-DRG severity of illness (SOI) and risk of death (ROD) categories. Results: There were 151,422 ICU admissions, including a diagnosis of FM in 4,274 (2.8%). When compared to non-FM, FM admissions were older (p < 0.0001), with higher number of comorbidities (p < 0.0001) and higher SOI (p = 0.0315), although with similar occurrence of OF (p = 0.1890) and ROD (p = 0.9957). Crude MH rate among FM vs non-FM ICU admissions was 2.8% vs 4.7%, respectively (p < 0.0001). On multivariate logistic regression, those with FM had MH aOR (95% CI) 0.6693 (0.4988– 0.8902); p = 0.0060. Propensity-score matching was successful in 3,616 ICU admissions with FM, who had MH aOR (95% CI) 0.4695 (0.3323–0.6633); p < 0.0001. Conclusions: In a population-based cohort of ICU-managed nonelderly women, FM had unexpectedly lower adjusted odds of MH. While FM is generally not considered consequential among ICUmanaged patients, our findings, coupled with a well-documented multidomain dysfunction of stress response in FM patients, suggest that further insights into their response to critical illness may inform preventive and interventional efforts in the critically ill in the general population. Additional studies are warranted to corroborate these results.

Antimicrobial Resistance and Attributable Burden of Pseudomonas aeruginosa in Hospitalized Patients

Abstract Background Pseudomonas aeruginosa (PA) is a leading cause of nosocomial infections. Multi-drug-resistant (MDR) PA is an increasing problem. The study objectives were to estimate PA prevalence in hospitalizations, rates of MDR PA and carbapenem-resistant (CR) PA, incremental hospital length of stay (LOS), and hospital cost attributable to MDR PA and CR PA. Methods This retrospective cohort study identified hospitalizations for MDR and CR PA with available diagnosis, laboratory, and medication data from October 1, 2013 to September 30, 2015 using the Cerner Health Facts® database. Hospitalizations with LOS <24 hours or >3x the SD of the cohort mean were excluded. MDR was defined as intermediate or resistant to at least one drug in 3 of 5 classes: aminoglycosides, extended spectrum cephalosporins, fluoroquinolones, carbapenems, and piperacillin or piperacillin-tazobactam. CR was defined as intermediate or resistant to meropenem or imipenem. Hospitalizations for MDR and non-MDR PA and for CR and non-CR PAwere matched 1:1 by propensity score. Mean (SD) and median LOS (days) and total hospital cost (US

Epidemiology, Microbiology and Outcomes of Catheter-Associated Urinary Tract Infection and Complicated Urinary Tract Infection in the USA

) were reported. Results A total of 1,045,038 hospitalizations were identified. The average patient age was 50 (SD = 27) and 57.5% were female. PA prevalence was 10.8/1,000 hospitalizations. Among hospitalizations for PA, the MDR rate was 12.3% and the CR rate was 14.5%. MDR and CR rates were higher in ICU (19.0% and 20.1%) than non-ICU hospitalizations (11.6% and 13.9%). Hospital LOS and total cost were significantly higher for the MDR PA group than the non-MDR PAgroup. Similarly higher LOS and total cost were observed in the CR group. Conclusion Our findings highlight the high rates of PA, particularly in the ICU, and the substantial economic burden associated with MDR and CR PA. Decision-makers must evaluate optimal treatment strategies and antimicrobial stewardship measures to minimize the economic impact of these infections and improve clinical outcomes in hospitalized patients.Table 1. LOS and Hospital Cost Mean (SD) Median P-value Hospital LOS (days) MDR PA 21 (19) 14 <0.0001 Non-MDR PA 17 (16) 12 CR PA 22 (20) 14 <0.0001 Non-CR PA 17 (16) 12 Hospital Costs (US

Real World Analysis of Prescribing Patterns and Susceptibility of Ceftolozane/Tazobactam (C/T) Treatment using an Electronic Medical Record (EMR) Database in the United States

) MDR PA 91,178 (106,913) 51,845 0.0007 Non-MDR PA 69,116 (74,389) 39,973 CR PA 85,819 (101,457) 49,135 0.0007 Non-CR PA 61,434 (62,717) 39,632 Disclosures D. Zhang, Merck: Employee, Salary. J. Hawkshead III, Merck: Employee, Salary. S. Merchant, 1Merck & Co., Inc.: Employee and Shareholder, Salary

Pseudomonas aeruginosa Non-susceptibility to Common Antibiotics by Source in USA Hospitals in 2015: A Multicenter Study

Abstract Background An estimated 93,300 cases of healthcare-associated urinary tract infection (UTI) were recorded in US acute care hospitals in 2011. Many are classified as catheter-associated UTI (CAUTI) or complicated UTI (cUTI). Although CAUTI and cUTI share some commonalities, strategies differ for their prevention and treatment. We examined the epidemiology, microbiology and outcome of patients with CAUTI and cUTI in a large multicenter US database. Methods This was a retrospective cohort study using the 2013–2015 Premier Healthcare Database. ICD-9-CM codes were used to identify hospitalized adults (≥18 years) with CAUTI or cUTI. The demographics, clinical characteristics, microbiology, and hospital outcomes of all identified patients were compared. Differences between groups were examined using χ2 test for categorical variables and Student’s t-test for continuous variables. Statistical significance was set at
P ≤ 0.05. Results Of 120,332 identified patients, 50,034 (41.6%) had CAUTI (87.0% present on admission [POA]) and the remainder had cUTI [95.3% POA]. Patients with CAUTI were older (71.3 ± 16.1 vs. 56.3 ± 19.5 years) and more likely to be male (62.5% vs. 30.6%) and white (71.6% vs. 66.7%) (all P < 0.001). They also had greater comorbidity burden (Charlson Comorbidity Index of 2.8 ± 2.4 vs. 1.7 ± 2.2) and a higher ICU care rate (23.2% vs. 17.8%) than cUTI patients (all P < 0.001). Although Escherichia coli was the most common pathogen in both (69.8% cUTI vs. 39.5% CAUTI), Pseudomonas aeruginosa accounted for one quarter of all CAUTIs and only 5.0% of cUTIs. Compared with cUTI, CAUTI carried a >2-fold increase in unadjusted mortality (3.6% vs. 1.6%) and a higher rate of 30-day readmission (3.9% vs. 2.5%) (all P < 0.001). Additionally, CAUTI was associated with a greater unadjusted ICU length of stay (LOS, 6.0 ± 8.8 vs. 5.5 ± 5.5 days), hospital LOS (8.4 ± 12.9 vs. 5.5 ± 6.4 days) and cost (

47: INCREMENTAL CLINICAL AND ECONOMIC BURDEN OF MULTIDRUG-RESISTANT P AERUGINOSA RESPIRATORY INFECTION

16,871+

651: EVALUATING A COMBINATION ANTIBIOGRAM FOR P AERUGINOSA RESPIRATORY ISOLATES FROM ICUS ACROSS THE U.S.

29,513 vs.

Cost Effectiveness of Letermovir as Cytomegalovirus Prophylaxis in in Allogeneic Hematopoietic Stem Cell Transplant Recipients

11,915 ±