Cost-effectiveness of imipenem/cilastatin/relebactam for hospital-acquired and ventilator-associated bacterial pneumonia.

Aim: This study evaluates the cost-effectiveness of imipenem/cilastatin/relebactam (IMI/REL) for treating hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in an 'early adjustment prescribing scenario'. Methods: An economic model was constructed to compare two strategies: continuation of empiric piperacillin/tazobactam (PIP/TAZ) versus early adjustment to IMI/REL. A decision tree was used to depict the hospitalization period, and a Markov model used to capture long-term outcomes. Results: IMI/REL generated more quality-adjusted life years than PIP/TAZ, at an increased cost per patient. The incremental cost-effectiveness ratio of $17,529 per QALY is below the typical US willingness-to-pay threshold. Conclusion: IMI/REL may represent a cost-effective treatment for payers and a valuable option for clinicians, when considered alongside patient risk factors, local epidemiology, and susceptibility data.

Population pharmacokinetic/pharmacodynamic assessment of imipenem/cilastatin/relebactam in patients with hospital-acquired/ventilator-associated bacterial pneumonia.

In the phase III RESTORE-IMI 2 study (ClinicalTrials.gov: NCT02493764), the combination antibacterial agent imipenem/cilastatin/relebactam (IMI/REL) demonstrated noninferiority to piperacillin/tazobactam for the end points of all-cause mortality at day 28 and favorable clinical response at the early follow-up visit in adult participants with gram-negative hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP). Existing population pharmacokinetic models for imipenem (IPM) and REL were updated using data from patients with HABP/VABP from RESTORE-IMI 2. Creatinine clearance (CrCl), body weight, infection type, and ventilation status were significant covariates in the updated model. The following simulations were performed to calculate the pharmacokinetic/pharmacodynamic joint probability of target attainment among patients with HABP/VABP and varying degrees of renal function: augmented renal clearance (CrCl ≥150 ml/min), normal renal function (CrCl ≥90 to <150 ml/min), renal impairment (mild, CrCl ≥60 to <90 ml/min; moderate, CrCl ≥30 to <60 ml/min; or severe, CrCl ≥15 to <30 ml/min), and end-stage renal disease (CrCl <15 ml/min). At the recommended IMI/REL dosing regimens across renal categories, greater than 90% of patients in all renal function groups were predicted to achieve joint pharmacokinetic/pharmacodynamic targets at a minimum inhibitory concentration breakpoint of ≤2 µg/ml, regardless of ventilation status. This modeling and simulation analysis supports use of the recommended IMI/REL dosing regimens, adjusted based on renal function, in patients with HABP/VABP.

Pharmacokinetics and Monte Carlo Dosing Simulations of Imipenem in Critically Ill Patients with Life-Threatening Severe Infections During Support with Extracorporeal Membrane Oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO), a cardiopulmonary bypass device, has been found to increase the profound pathophysiological changes associated with life-threatening severe infections in patients with multiple comorbidities, which results in alterations of pharmacokinetic patterns for antibiotics. OBJECTIVES: The aims of this study were (1) to determine the pharmacokinetics of imipenem and (2) to assess the probability of target attainment (PTA) for imipenem in critically ill patients with life-threatening severe infections during support with ECMO. METHODS: The pharmacokinetic studies were carried out following administration of 0.5 g of imipenem every 6 h on the 4th dose of drug administration in 10 patients and a Monte Carlo simulation was performed to determine the PTA of achieving 40% exposure time during which the plasma drug concentrations remained above minimum inhibitory concentration (T > MIC) and 80% T > MIC. RESULTS: The median values of volume of distribution and total clearance (CL) of imipenem in these patients were 13.98 L and 9.78 L/h, respectively. A high PTA (≥ 90%) for a target of 80% with a MIC of 4 µg/mL in patients with CLCR 60-120 mL/min and flow rate of ECMO circuit 3-5.5 L/min was observed when imipenem was administered by a 4-h infusion of 1 g every 6 h. CONCLUSIONS: A high dosage regimen such as 1 g every 6 h of imipenem may be required to achieve pharmacodynamic targets against less susceptible pathogens in this patient population. CLINICALTRIAL. GOV IDENTIFIER: NCT03776305, date of registration: 11 December 2018.

Effect of a "handshake" stewardship program versus a formulary restriction policy on High-End antibiotic use, expenditure, antibiotic resistance, and patient outcome.

This study reports the effect of implementing an antibiotic stewardship program (ASP) based on the "handshake" strategy for 2 years on multiple endpoints compared with that in a preceding period when an antimicrobial restriction policy was only applied in the absence of a complete program in a tertiary-care Lebanese hospital. The studied endpoints were broad-spectrum antibiotic consumption, antibiotic expenditure, nosocomial bacteremia incidence rate, and patient outcome.An interrupted time series analysis was undertaken to assess the changes in the trend (ΔT) and level (ΔL) of the aforementioned endpoints among adult inpatients before (October 2013 to September 2015) and after the introduction of the ASP (October 2016 to September 2018).After the implementation of the "handshake" ASP, marked changes were observed in the consumption of broad-spectrum antibiotics. The mean use density levels for imipenem and meropenem decreased by 13.72% (P = 0.017), coupled with a decreasing rate of prescription (ΔT = -24.83 defined daily dose [DDD]/1,000 patient days [PD]/month; P = 0.02). Tigecycline use significantly decreased in level by 69.19% (P < 0.0001) and in trend (ΔT = -25.63 DDD/1,000 PD/month; P < 0.0001). A reduction in the use of colistin was also documented but did not reach statistical significance (ΔL = -8.71%, P = 0.56; ΔT = -5.51 DDD/1,000 PD/month = -5.5; P = 0.67). Antibiotic costs decreased by 24.6% after ASP implementation (P < 0.0001), and there was a distinct change from an increasing rate to a decreasing rate of expenditure (ΔT = -12.19 US dollars/PD/month; P = 0.002). The incidence rate of nosocomial bacteremia caused by carbapenem-resistant gram-negative bacteria (CRGNB) decreased by 34.84% (P = 0.13) coupled with a decreasing trend (ΔT = -0.23 cases/1,000 PD/month, P = 0.08). Specifically, a noticeable reduction in the incidence rate of bacteremia due to carbapenem-resistant Acinetobacter baumannii was documented (ΔL = -54.34%, P = 0.01; ΔT = -0.24 cases/1000 PD/month, P = 0.01). Regarding patient outcome, all-cause mortality rates did not increase in level or in rate (ΔL = -3.55%, P = 0.59; ΔT = -0.29 deaths/1000 PD/month, P = 0.6). The length of stay and 7-day readmission rate remained stable between the two periods.In conclusion, the "handshake" ASP succeeded in controlling the prescription rates of antibiotics and in decreasing the nosocomial bacteremia rates caused by CRGNB without compromising patient outcome in our facility. It also had an economic effect in reducing antibiotic costs compared with the previous restriction policy on antimicrobial dispensing.

Cost-effectiveness analysis of ceftazidime/avibactam compared to imipenem as empirical treatment for complicated urinary tract infections.

Ceftazidime/avibactam (CAZ-AVI) is a novel, fixed-dose combination antibiotic that has been approved in Europe and the United States for patients with complicated urinary tract infections (cUTIs) based on results of a Phase III, randomized, comparative study (RECAPTURE study). The present analysis evaluated cost-effectiveness of CAZ-AVI as an empirical treatment for hospitalized patients with cUTIs from the Italian publicly funded healthcare (third-party payer) perspective. A sequential, patient-level simulation model was developed that followed the clinical course of cUTI and generated 5000 pairs of identical patients (CAZ-AVI or imipenem as empirical treatment). The model included additional impact of resistant pathogens; patients who did not respond to empirical treatment were switched to second-line treatment of colistin+high dose carbapenem in both groups. The time horizon of the model was five years, with an annual discount rate of 3% applied to both costs and quality-adjusted life-years (QALYs). The analysis demonstrated that an intervention sequence (CAZ-AVI followed by colistin+high dose carbapenem) compared with a comparator sequence (imipenem followed by colistin+high dose carbapenem) was associated with a net incremental cost of €1015 per patient but provided better health outcomes in terms of clinical cure (97.65% vs. 91.08%; ∆ = 6.57%), shorter hospital stays (10.65 vs. 12.55 days; ∆ = 1.90 days), and QALYs gained per patient (4.190 vs. 4.063; ∆ = 0.126). The incremental cost-effectiveness ratio was €8039/QALY, which is well below the willingness-to-pay threshold of €30 000/QALY in Italy. The results showed that CAZ-AVI is expected to be a cost-effective treatment compared with imipenem for cUTI in Italy.

Melioidosis.

Burkholderia pseudomallei is a Gram-negative environmental bacterium and the aetiological agent of melioidosis, a life-threatening infection that is estimated to account for ∼89,000 deaths per year worldwide. Diabetes mellitus is a major risk factor for melioidosis, and the global diabetes pandemic could increase the number of fatalities caused by melioidosis. Melioidosis is endemic across tropical areas, especially in southeast Asia and northern Australia. Disease manifestations can range from acute septicaemia to chronic infection, as the facultative intracellular lifestyle and virulence factors of B. pseudomallei promote survival and persistence of the pathogen within a broad range of cells, and the bacteria can manipulate the host's immune responses and signalling pathways to escape surveillance. The majority of patients present with sepsis, but specific clinical presentations and their severity vary depending on the route of bacterial entry (skin penetration, inhalation or ingestion), host immune function and bacterial strain and load. Diagnosis is based on clinical and epidemiological features as well as bacterial culture. Treatment requires long-term intravenous and oral antibiotic courses. Delays in treatment due to difficulties in clinical recognition and laboratory diagnosis often lead to poor outcomes and mortality can exceed 40% in some regions. Research into B. pseudomallei is increasing, owing to the biothreat potential of this pathogen and increasing awareness of the disease and its burden; however, better diagnostic tests are needed to improve early confirmation of diagnosis, which would enable better therapeutic efficacy and survival.

Efficacy of Appropriate Antimicrobial Therapy on the Survival of Patients With Carbapenem Nonsusceptible Klebsiella Pneumoniae Infection: A Multicenter Study in Taiwan.

The impact of antimicrobial treatment on the outcome of carbapenem nonsusceptible Klebsiella pneumoniae (CnsKP) infections needs to be elucidated. This nationwide, multicenter study was conducted to evaluate the impact of appropriate antimicrobial therapy on 14-day mortality among patients with CnsKP infection in Taiwan.Patients with CnsKP infections from 11 medical centers and 4 regional hospitals in Taiwan were enrolled in 2013. Carbapenem nonsusceptibility was defined as a minimum inhibitory concentration of ≥2 mg/L for imipenem or meropenem. Predictors of 14-day mortality were determined using the Cox proportional regression model. The influence of infection severity on the impact of appropriate use of antimicrobials on 14-day mortality was determined using the Acute Physiology and Chronic Health Evaluation (APACHE) II score.Overall 14-day mortality was 31.8% (49/154). Unadjusted mortality for appropriate antimicrobial therapy was 23.1% (18/78 patients). Appropriate therapy was independently associated with reduced mortality (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.24-0.80; P = 0.007). A subgroup analysis revealed that the benefit of appropriate therapy was limited to patients with higher APACHE II scores (HR for patients with scores >15 and ≤35, 0.46; 95% CI 0.23-0.92; and for those with scores >35, 0.14; 95% CI, 0.02-0.99).In conclusion, appropriate antimicrobial therapy significantly reduces 14-day mortality for CnsKP infections. Survival benefit is more notable among more severely ill patients.

Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator-associated pneumonia and evaluation of dosage regimens.

AIMS: Significant alterations in the pharmacokinetics (PK) of antimicrobials have been reported in critically ill patients. We describe PK parameters of imipenem in intensive care unit (ICU) patients with suspected ventilator-associated pneumonia and evaluate several dosage regimens. METHODS: This French multicentre, prospective, open-label study was conducted in ICU patients with a presumptive diagnosis of ventilator-associated pneumonia caused by Gram-negative bacilli, who empirically received imipenem intravenously every 8 h. Plasma imipenem concentrations were measured during the fourth imipenem infusion using six samples (trough, 0.5, 1, 2, 5 and 8 h). Data were analysed with a population approach using the stochastic approximation expectation maximization algorithm in Monolix 4.2. A Monte Carlo simulation was performed to evaluate the following six dosage regimens: 500, 750 or 1000 mg with administration every 6 or 8 h. The pharmacodynamic target was defined as the probability of achieving a fractional time above the minimal inhibitory concentration (MIC) of >40%. RESULTS: Fifty-one patients were included in the PK analysis. Imipenem concentration data were best described by a two-compartment model with three covariates (creatinine clearance, total bodyweight and serum albumin). Estimated clearance (between-subject variability) was 13.2 l h(-1) (38%) and estimated central volume 20.4 l (31%). At an MIC of 4 µg ml(-1) , the probability of achieving 40% fractional time > MIC was 91.8% for 0.5 h infusions of 750 mg every 6 h, 86.0% for 1000 mg every 8 h and 96.9% for 1000 mg every 6 h. CONCLUSIONS: This population PK model accurately estimated imipenem concentrations in ICU patients. The simulation showed that for these patients, the best dosage regimen of imipenem is 750 mg every 6 h and not 1000 mg every 8 h.

In vivo assessment of drug efficacy against Mycobacterium abscessus using the embryonic zebrafish test system.

Mycobacterium abscessus is responsible for a wide spectrum of clinical syndromes and is one of the most intrinsically drug-resistant mycobacterial species. Recent evaluation of the in vivo therapeutic efficacy of the few potentially active antibiotics against M. abscessus was essentially performed using immunocompromised mice. Herein, we assessed the feasibility and sensitivity of fluorescence imaging for monitoring the in vivo activity of drugs against acute M. abscessus infection using zebrafish embryos. A protocol was developed where clarithromycin and imipenem were directly added to water containing fluorescent M. abscessus-infected embryos in a 96-well plate format. The status of the infection with increasing drug concentrations was visualized on a spatiotemporal level. Drug efficacy was assessed quantitatively by measuring the index of protection, the bacterial burden (CFU), and the number of abscesses through fluorescence measurements. Both drugs were active in infected embryos and were capable of significantly increasing embryo survival in a dose-dependent manner. Protection from bacterial killing correlated with restricted mycobacterial growth in the drug-treated larvae and with reduced pathophysiological symptoms, such as the number of abscesses within the brain. In conclusion, we present here a new and efficient method for testing and compare the in vivo activity of two clinically relevant drugs based on a fluorescent reporter strain in zebrafish embryos. This approach could be used for rapid determination of the in vivo drug susceptibility profile of clinical isolates and to assess the preclinical efficacy of new compounds against M. abscessus.

Continuous regional arterial infusion for acute pancreatitis: a propensity score analysis using a nationwide administrative database.

INTRODUCTION: Although continuous regional arterial infusion (CRAI) of a protease inhibitor and an antibiotic may be effective in patients with severe acute pancreatitis, CRAI has not yet been validated in large patient populations. We therefore evaluated the effectiveness of CRAI based on data from a national administrative database covering 1,032 Japanese hospitals. METHODS: In-hospital mortality, length of stay and costs were compared in the CRAI and non-CRAI groups, using propensity score analysis to adjust for treatment selection bias. RESULTS: A total of 17,415 eligible patients with acute pancreatitis were identified between 1 July and 30 September 2011, including 287 (1.6%) patients who underwent CRAI. One-to-one propensity-score matching generated 207 pairs with well-balanced baseline characteristics. In-hospital mortality rates were similar in the CRAI and non-CRAI groups (7.7% vs. 8.7%; odds ratio, 0.88; 95% confidence interval, 0.44-1.78, P = 0.720). CRAI was associated with significantly longer median hospital stay (29 vs. 18 days, P < 0.001), significantly higher median total cost (21,800 vs. 12,600 United States dollars, P < 0.001), and a higher rate of interventions for infectious complications, such as endoscopic/surgical necrosectomy or percutaneous drainage (2.9% vs. 0.5%, P = 0.061). CONCLUSIONS: CRAI was not effective in reducing in-hospital mortality rate in patients with acute pancreatitis, but was associated with longer hospital stay and higher costs. Randomized controlled trials in large numbers of patients are required to further evaluate CRAI for this indication.

Evaluating the impact of a pharmacist's absence from an antimicrobial stewardship team.

PURPOSE: Results of a study to determine the impact of a clinical pharmacist's temporary absence from a hospital's antimicrobial stewardship team are presented. METHODS: A retrospective chart review was conducted to compare the appropriateness of the use of selected antimicrobial medications with and without regular pharmacist involvement on the hospital's antimicrobial stewardship team. The charts of two samples of patients were evaluated: (1) 119 patients who had received prolonged (≥72 hours) imipenem-cilastatin, linezolid, or micafungin therapy over a three-month period during which a clinical pharmacist routinely provided interventions to help ensure the drugs were used according to institutional guidelines and (2) 111 patients treated with one of the three drugs during a three-month period when the clinical pharmacist did not serve on the stewardship team. RESULTS: Relative to the period of active pharmacist involvement in antimicrobial stewardship, rates of inappropriate use of imipenem-cilastatin, linezolid, and micafungin during the pharmacist's absence were deemed to have increased by 27, 39, and 35 percentage points, respectively, with corresponding increases in the average duration of therapy of 0.7, 4.0, and 3.2 days; in addition, the number of cases of Clostridium difficile infection increased more than threefold (from 8 to 25) during the pharmacist's absence. CONCLUSION: The temporary absence of a pharmacist from the antimicrobial stewardship team was associated with increased rates of inappropriate use of restricted antimicrobial agents and consequent increases in average durations of therapy.

Comparative assessment of antimicrobial usage measures in the Department of Veterans Affairs.

We compared 2 data sources--antimicrobial orders and bar-coded medication administration (BCMA)--for calculating the number of grams used, grams used based on defined daily dose, and days of therapy at one Veterans Affairs Medical Center for 2009-2010. The number of grams used calculated from BCMA data provided the most informative antimicrobial utilization measure.

[Assessment of efficacies of imipenem, cefoperazone-sulbactam and cefepime in rats with experimental thigh abscess model with multidrug resistant and susceptible Acinetobacter baumannii strains]. / Sefoperazon-sulbaktam, imipenem ve sefepimin antibiyoterapi etkinliklerinin çogul dirençli ve duyarli acinetobacter baumannii ile olusturulan deneysel ikili apse modelinde karsilastirilmasi.

Imipenem, cefaperazon-sulbactam and cefepime are the antibiotics of choice for the treatment of soft tissue infections due to Acinetobacter baumannii. In this study, it was aimed to determine the invivo and invitro efficacy of, these antibiotics against drug susceptible and multidrug resistant A.baumannii in an experimental abscess model. Abscess models were established in Wistar-Albino type female rats. Susceptibility tests were performed by E-test. Rats were divided randomly into four groups with eight rats in one group. Standard absorbent paper discs containing 6 log10 CFU microorganisms were used to form an abscess model. The first group was regarded as the control group and the other three groups were the study group each treated with one of the test antibiotics. Cardiac blood samples for serum antibiotic efficacy test, were obtained on the fourth day of treatment and 30 minutes after the last dose. The number of live bacteria at the area of infection was determined by colony count method. All of the three antibiotics reached sufficient concentration in sera of rats and there were no statistically important difference between the efficacies of these antibiotics (p= 0.778). In all of the antibiotic-treated groups, the weight of the abscess material were less, macroscopic views were smaller and the colony counts per gram of abscess tissue were less than the control group (p< 0.001). All antibiotics were effective against susceptible and resistant strains in vitro. No resistance was detected against imipenem, cefaperazon-sulbactam and cefepime in the course of therapy. Cefaperazone-sulbactam and cefepime were as effective as imipenem against susceptible and multi-drug resistant A.baumannii both in vivo and in vitro. Since irrational use of extended spectrum cephalosporins are frequently associated with the emergence of carbapenem resistant strains, the use of relatively narrow spectrum antibiotics should better be considered in the empirical treatment of A.baumannii infections.

Extensively drug-resistant tuberculosis: New Zealand's first case and the challenges of management in a low-prevalence country.

In 2010, an immigrant from Burma was the first person to be diagnosed in New Zealand with extensively drug-resistant tuberculosis (XDR-TB). The strain of Mycobacterium tuberculosis is the most resistant reported to date in Australasia. Key difficulties of managing this disease in a low-prevalence country were delays from drug-susceptibility testing and in acquiring appropriate medicines, and a lack of evidence-based guidelines. Solutions are needed for New Zealand and the wider region as more cases of XDR-TB are likely to be encountered in the future.

The impact of a nationwide antibiotic restriction program on antibiotic usage and resistance against nosocomial pathogens in Turkey.

PURPOSE: Antimicrobial resistance among microorganisms is a global concern. In 2003, a nationwide antibiotic restriction program (NARP) was released in Turkey. In this study we evaluated the effect of NARP on antibiotic consumption, antimicrobial resistance, and cost. MATERIALS AND METHODS: The data obtained from all of the four university hospitals, and one referral tertiary-care educational state hospital in Ankara. Antimicrobial resistance profiles of 14,233 selected microorganisms all grown in blood cultures and antibiotic consumption from 2001 to 2005 were analyzed retrospectively. RESULTS: A negative correlation was observed between the ceftriaxone consumption and the prevalence of ceftriaxone resistant E.coli and Klebsiella spp. (rho:-0.395, p:0.332 and rho:-0.627, p:0.037, respectively). The decreased usage of carbapenems was correlated with decreased carbapenems-resistant Pseudomonas spp. and Acinetobacter spp (rho:0.155, p:0.712 and rho:0.180, p:0.668, respectively for imipenem). Methicillin resistance rates of S.aureus were decreased from 44% to 41%. After two years of NARP 5,389,155.82 USD saving occurred. CONCLUSION: NARP is effective in lowering the costs and antibiotic resistance.

Medical resource utilization among patients with ventilator-associated pneumonia: pooled analysis of randomized studies of doripenem versus comparators.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is associated with increased medical resource utilization, but few randomized studies have been conducted to evaluate the effect of initial antibiotic therapy. To assess medical resource utilization in patients with VAP, we conducted a pooled analysis of two prospective, randomized, open-label, multicenter, phase III studies, which also showed that doripenem was clinically noninferior to comparators. METHODS: We assessed durations of mechanical ventilation, intensive care unit (ICU) stay, and hospitalization in patients with VAP who received at least 1 dose of doripenem or a comparator in the phase III studies. Comparators were piperacillin/tazobactam (study 1) and imipenem (study 2). We analyzed between-group differences in medical resource utilization endpoints by comparison of Kaplan-Meier curves with generalized Wilcoxon test and in microbiologic eradication rates by two-sided Fisher's exact test. RESULTS: 625 patients with VAP were evaluated and received at least 1 dose of doripenem (n = 312) or a comparator (n = 313). Median durations of mechanical ventilation (7 versus 10 days; P = 0.008) and hospitalization (22 versus 26 days; P = 0.010) were shorter for doripenem than comparators; corresponding ICU stays were 12 and 13 days (P = 0.065). All-cause, overall mortality rates were similar (51/312 [16%] versus 47/313 [15%]; P = 0.648). MIC90 values against Pseudomonas aeruginosa for doripenem versus imipenem were 4 versus 16 microg/mL in study 2. P. aeruginosa was eradicated from 16/24 (67%) doripenem recipients and 10/24 (42%) comparator recipients (P = 0.147). In patients with P. aeruginosa at baseline, median durations of mechanical ventilation (7 versus 13 days; P = 0.031) and ICU stay (13 versus 21 days; P = 0.027) were shorter for doripenem; corresponding hospital stays were 24 and 35 days (P = 0.129). CONCLUSIONS: Doripenem was associated with lower medical resource utilization than comparators. Differences in antipseudomonal activity may have contributed to these findings. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00211003 (study 1) and NCT00211016 (study 2).

Economic assessment of doripenem versus imipenem in the treatment of ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP), the most common nosocomial infection in critically ill patients, is associated with significantly longer duration of mechanical ventilation, and increased mortality, hospital days, and health-care costs. A previously published prospective, randomized study established the noninferiority of intravenous (IV) doripenem versus IV imipenem/cilastatin ('imipenem') for VAP. This study compares the economic outcomes of IV therapy with doripenem versus imipenem as first-line treatment for VAP. METHODS: A decision-analytic model of inpatient care and outcomes for VAP was used to estimate costs associated with VAP treatment. The model calculates total hospital costs, comprising costs of initial and concomitant therapy, and costs associated with mechanical ventilation, intensive care unit stays, and total days in hospital. RESULTS: Total treatment costs for doripenem were $10,630 lower than for imipenem ($71,259 vs. 81,889), driven primarily by differences in costs of mechanical ventilation ($45,224 for doripenem, $57,348 for imipenem). Probabilistic sensitivity analyses found doripenem consistently cost saving versus imipenem in 1,000 simulations. Study limitations include use of a simple model to represent a complex disease process and reliance on trial data that may not reflect real-world care and outcomes. CONCLUSIONS: Doripenem is a cost saving first-line treatment for VAP versus imipenem while providing an equivalent rate of cure.

Epidemiology and impact of imipenem resistance in Acinetobacter baumannii.

BACKGROUND: Acinetobacter baumannii is an emerging gram-negative pathogen that can cause healthcare-acquired infections among patients. Treatment is complicated for cases of healthcare-acquired infection with A. baumannii resistant to imipenem. OBJECTIVE: To elucidate the risk factors for imipenem-resistant A. baumannii (IRAB) infection or colonization and to identify the effect of resistance on clinical and economic outcomes. METHODS: We analyzed data from 2 medical centers of the University of Pennsylvania. Longitudinal trends in the prevalence of IRAB clinical isolates were characterized during the period from 1989 through 2004. For A. baumannii isolates obtained from 2001 through 2006, a case-control study was conducted to investigate the association between prior carbapenem use and IRAB infection or colonization, and a cohort study was performed to identify the effect of IRAB infection or colonization on mortality, length of stay after culture, and hospital cost after culture. RESULTS: From 1989 through 2004, the annual prevalence of IRAB isolates ranged from 0% to 21%. During the period from 2001 through 2006, there were 386 unique patients with A. baumannii isolates, and 89 (23.1%) had IRAB isolates. Prior carbapenem use was independently associated with IRAB infection or colonization (adjusted odds ratio, 3.04 [95% confidence interval, 1.07-8.65]). There was a borderline significant association between IRAB infection or colonization and mortality, although this association was limited to isolates recovered from blood samples (adjusted odds ratio, 5.30 [95% confidence interval, 0.81-34.59]). Compared with patients with imipenem-susceptible A. baumannii infection or colonization, patients with IRAB infection or colonization had a longer hospital stay after culture (median, 21 vs 16 days; P = .07) and greater hospital charges after culture (mean, $334,516 vs $276,059; P = .03). After controlling for patient location in an intensive care unit, transfer from another facility, and length of hospital stay before culture, there was no longer an independent association between IRAB infection or colonization and higher cost after culture and length of stay after positive culture result. CONCLUSIONS: Many A. baumannii isolates exhibit imipenem resistance, which is strongly associated with prior use of carbapenems. Given the high mortality rate associated with A. baumannii infection or colonization, interventions to curb further emergence of cases of IRAB infection and strategies to optimize therapy are needed.

Clinical and economic consequences of ventilator-associated pneumonia.

Increasing drug resistance rates among gram-negative pathogens that frequently cause ventilator-associated pneumonia have resulted in increased hospital mortality, longer hospital stays, and higher inpatient health care costs. There is an urgent need for effective therapies that lessen the clinical and economic consequences of this nosocomial infection. In a randomized, multicenter, prospective, phase 3 trial, medical resource use associated with doripenem was compared with that associated with imipenem for the treatment of ventilator-associated pneumonia. Analysis of medical resource use revealed that patients who received doripenem had a significantly shorter duration of hospital stay (22 vs. 27 days; P = .01)and duration of mechanical ventilation use (7 vs. 10 days; P = .03) than did patients who received imipenem. In addition, the duration of intensive care unit stay tended to be shorter for patients who received doripenem. The reduced medical resource use achieved with use of doripenem for treatment of ventilator-associated pneumonia may provide not only clinical benefits to patients but also economic benefits to hospitals and health care systems.

Management and prevention of diabetic foot ulcers and infections: a health economic review.

Diabetic foot ulcers and infections are common and incur substantial economic burden for society, patients and families. We performed a comprehensive review, on a number of databases, of health economic evaluations of a variety of different prevention, diagnostic and treatment strategies in the area of diabetic foot ulcers and infections. We included English-language, peer-reviewed, cost-effectiveness, cost-minimization, cost-utility and cost-benefit studies that evaluated a treatment modality against placebo or comparator (i.e. drug, standard of care), regardless of year. Differences were settled through consensus. The search resulted in 1885 potential citations, of which 20 studies were retained for analysis (3 cost minimization, 13 cost effectiveness and 4 cost utility). Quality scores of studies ranged from 70.8% (fair) to 87.5% (good); mean = 78.4% +/- 5.33%.In diagnosing osteomyelitis in patients with diabetic foot infection, magnetic resonance imaging (MRI) showed 82% sensitivity and 80% specificity. MRI cost less than 3-phase bone scanning + Indium (In)-111/Gallium (Ga)-67; however, when compared with prolonged antibacterials, MRI cost $US120 (year 1993 value) more without additional quality-adjusted life-expectancy. Prevention strategies improved life expectancy and QALYs and reduced foot ulcer rates and amputations.Ampicillin/sulbactam and imipenem/cilastatin were both 80% successful in treating diabetic foot infections but the latter cost $US2924 more (year 1994 value). Linezolid cure rates were higher (97.7%) than vancomycin (86.0%) and cost $US873 less (year 2004 value). Ertapenem costs were significantly lower than piperacillin/tazobactam ($US356 vs $US503, respectively; year 2005 values). Becaplermin plus good wound care may be cost effective in specific populations. Bioengineered living-skin equivalents increased ulcer-free months and ulcers healed, but costs varied between countries. Promogran produced more ulcer-free months than wound care alone (3.75 vs 3.41 months, respectively). Treatment with cadexomer iodine resulted in higher rates of healed ulcer (29% vs 11%) and lower weekly treatment costs (Swedish krona [SEK]903 vs SEK1421; year 1993 values) than standard care. Filgrastim decreased hospital stays, time to resolution and costs (36% lower) compared with usual care. Adjunctive hyperbaric oxygen produced an incremental cost per QALY at year 1 of $US27 310 and $US2255 at year 12 (year 2001 values).Overall, preventive strategies were shown to be cost effective and potentially cost saving. Various antibacterial regimens are cost effective but empiric choices should be based on local resistance patterns. MRI was cost effective compared with three-phase bone scanning + In-111/Ga-67 but not against prolonged antibacterial therapy. Other innovations (becaplermin, bioengineered living-skin equivalents, filgrastim, cadexomer iodine ointment, hyperbaric oxygen, Promogran may be cost effective in this population but more studies are needed to confirm these findings.