Personalized ß-lactam dosing in patients with coronavirus disease 2019 (COVID-19) and pneumonia: A retrospective analysis on pharmacokinetics and pharmacokinetic target attainment.

ABSTRACT: Pathophysiological changes are important risk factors for critically ill patients with pneumonia manifesting sub-therapeutic antibiotic exposures during empirical treatment. The effect of coronavirus disease 2019 (COVID-19) on antibiotic dosing requirements is uncertain. We aimed to determine the effect of COVID-19 on ß-lactam pharmacokinetics (PK) and PK target attainment in critically ill patients with a personalized dosing strategy.Retrospective, single-center analysis of COVID-19 ± critically ill patients with pneumonia (community-acquired pneumonia or hospital-acquired pneumonia) who received continuous infusion of a ß-lactam antibiotic with dosing personalized through dosing software and therapeutic drug monitoring. A therapeutic exposure was defined as serum concentration between (css) 4 to 8 times the EUCAST non-species related breakpoint).Data from 58 patients with pneumonia was analyzed. Nineteen patients were tested COVID-19-positive before the start of the antibiotic therapy for community-acquired pneumonia or hospital-acquired pneumonia. Therapeutic exposure was achieved in 71% of COVID-19 patients (68% considering all patients). All patients demonstrated css above the non-species-related breakpoint. Twenty percent exceeded css above the target range (24% of all patients). The median ß-lactam clearance was 49% compared to ß-lactam clearance in a standard patient without a significant difference regarding antibiotic, time of sampling or present COVID-19 infection. Median daily doses were 50% lower compared to standard bolus dosing.COVID-19 did not significantly affect ß-lactam pharmacokinetics in critically ill patients. Personalized ß-lactam dosing strategies were safe in critically ill patients and lead to high PK target attainment with less resources.

Discontinuing ß-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial.

BACKGROUND: Shortening the duration of antibiotic therapy for patients admitted to hospital with community-acquired pneumonia should help reduce antibiotic consumption and thus bacterial resistance, adverse events, and related costs. We aimed to assess the need for an additional 5-day course of ß-lactam therapy among patients with community-acquired pneumonia who were stable after 3 days of treatment. METHODS: We did this double-blind, randomised, placebo-controlled, non-inferiority trial (the Pneumonia Short Treatment [PTC]) in 16 centres in France. Adult patients (aged ≥18 years) admitted to hospital with moderately severe community-acquired pneumonia (defined as patients admitted to a non-critical care unit) and who met prespecified clinical stability criteria after 3 days of treatment with ß-lactam therapy were randomly assigned (1:1) to receive ß-lactam therapy (oral amoxicillin 1 g plus clavulanate 125 mg three times a day) or matched placebo for 5 extra days. Randomisation was done using a web-based system with permuted blocks with random sizes and stratified by randomisation site and Pneumonia Severity Index score. Participants, clinicians, and study staff were masked to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, defined by apyrexia (temperature ≤37·8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause. A non-inferiority margin of 10 percentage points was chosen. The primary outcome was assessed in all patients who were randomly assigned and received any treatment (intention-to-treat [ITT] population) and in all patients who received their assigned treatment (per-protocol population). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT01963442, and is now complete. FINDINGS: Between Dec 19, 2013, and Feb 1, 2018, 706 patients were assessed for eligibility, and after 3 days of ß-lactam treatment, 310 eligible patients were randomly assigned to receive either placebo (n=157) or ß-lactam treatment (n=153). Seven patients withdrew consent before taking any study drug, five in the placebo group and two in the ß-lactam group. In the ITT population, median age was 73·0 years (IQR 57·0-84·0) and 123 (41%) of 303 participants were female. In the ITT analysis, cure at day 15 occurred in 117 (77%) of 152 participants in the placebo group and 102 (68%) of 151 participants in the ß-lactam group (between-group difference of 9·42%, 95% CI -0·38 to 20·04), indicating non-inferiority. In the per-protocol analysis, 113 (78%) of 145 participants in the placebo treatment group and 100 (68%) of 146 participants in the ß-lactam treatment group were cured at day 15 (difference of 9·44% [95% CI -0·15 to 20·34]), indicating non-inferiority. Incidence of adverse events was similar between the treatment groups (22 [14%] of 152 in the placebo group and 29 [19%] of 151 in the ß-lactam group). The most common adverse events were digestive disorders, reported in 17 (11%) of 152 patients in the placebo group and 28 (19%) of 151 patients in the ß-lactam group. By day 30, three (2%) patients had died in the placebo group (one due to bacteraemia due to Staphylococcus aureus, one due to cardiogenic shock after acute pulmonary oedema, and one due to heart failure associated with acute renal failure) and two (1%) in the ß-lactam group (due to pneumonia recurrence and possible acute pulmonary oedema). INTERPRETATION: Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing ß-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow substantial reduction of antibiotic consumption. FUNDING: French Ministry of Health.

A Comprehensive Prospective Study of the Costs Associated With Evaluation of beta-Lactam Allergy

BACKGROUND: Being labeled as allergic to penicillin (unverified beta-lactam allergy) can result in patients receiving broader-spectrum antibiotics than necessary that may be more toxic, less effective, and/or more expensive than alternative options. OBJECTIVE: We aimed to evaluate the real costs of evaluating beta-lactam allergy. METHODS: We performed a prospective real-life observational study designed to evaluate all adult patients who consulted for suspected beta-lactam allergy over a 1-year period. Direct and indirect costs were systematically recorded. Direct health costs were calculated based on the number of visits and all additional and diagnostic tests performed, direct nonhealth costs based on the number of visits and the distance from their homes to the Allergy Department, and indirect costs based on absenteeism. RESULTS: A total of 296 patients with suspected allergy to beta-lactams were evaluated in our outpatient clinic from June 1, 2017 to May 31, 2018. Total direct health care costs were (Euro)28 176.70, with a mean (SD) cost of (Euro)95.19 (37.20). Direct nonhealth costs reached (Euro)6551.73, that is, (Euro)22.13 (40.44) per patient. Indirect health costs reached (Euro)20 769.20, with a mean of (Euro)70.17 (127.40). In summary, the total cost was (Euro)55 497.63, that is, a cost per patient of (Euro)187.49 (148.14). CONCLUSIONS: When all possible costs are taken into account, the evaluation of beta-lactam allergy is not expensive and can reduce future expense arising from unnecessary use of more expensive and less effective antibiotics

INTRODUCCIÓN: Un diagnóstico no verificado de alergia a la penicilina o a los betalactámicos (BL) conlleva que los pacientes reciban antibióticos de amplio espectro, que pueden ser más tóxicos, menos efectivos, y/o de mayor coste. OBJETIVO: Evaluar los costes reales de un estudio de alergia a los betalactámicos. MÉTODOS: Se diseñó un estudio observacional prospectivo en condiciones de práctica clínica habitual en el que se evaluaron todos los pacientes adultos que consultaron por sospecha de alergia a BL durante un año. Los costes directos e indirectos se recogieron sistemáticamente. Los costes directos sanitarios se calcularon teniendo en cuenta el número de visitas y todas las pruebas diagnósticas realizadas; en los costes directos no sanitarios se consideraron el número de visitas y los kilómetros desde el domicilio hasta el Servicio de Alergología; en los costes indirectos se evaluó el absentismo. RESULTADOS: Se evaluaron 296 pacientes remitidos desde el 1 de junio de 2017 hasta el 31 de mayo de 2018. Los costes directos totales sanitarios fueron 28.176,70 (Euro): coste medio (desviación estándar, DS) de 95,19 (Euro) (37,20). Los costes directos no sanitarios alcanzaron, 6.551,73: coste medio 22,13 (40,44). Los costes indirectos fueron 20.769,20 (Euro): coste medio (DS) 70,17 (127,40). En resumen, la cantidad total fue de 55.497,63 (Euro), lo que supone un coste medio de 187,49 (Euro) (148,14). CONCLUSIONES: Considerando todos los costes posibles, la evaluación de la alergia a betalactámicos no es cara y puede ahorrar gastos futuros debido a una utilización innecesaria de antibióticos más caros y menos efectivos

Fight Against Antimicrobial Resistance: We Always Need New Antibacterials but for Right Bacteria.

Antimicrobial resistance in bacteria is frightening, especially resistance in Gram-negative Bacteria (GNB). In 2017, the World Health Organization (WHO) published a list of 12 bacteria that represent a threat to human health, and among these, a majority of GNB. Antibiotic resistance is a complex and relatively old phenomenon that is the consequence of several factors. The first factor is the vertiginous drop in research and development of new antibacterials. In fact, many companies simply stop this R&D activity. The finding is simple: there are enough antibiotics to treat the different types of infection that clinicians face. The second factor is the appearance and spread of resistant or even multidrug-resistant bacteria. For a long time, this situation remained rather confidential, almost anecdotal. It was not until the end of the 1980s that awareness emerged. It was the time of Vancomycin-Resistance Enterococci (VRE), and the threat of Vancomycin-Resistant MRSA (Methicillin-Resistant Staphylococcus aureus). After this, there has been renewed interest but only in anti-Gram positive antibacterials. Today, the threat is GNB, and we have no new molecules with innovative mechanism of action to fight effectively against these bugs. However, the war against antimicrobial resistance is not lost. We must continue the fight, which requires a better knowledge of the mechanisms of action of anti-infectious agents and concomitantly the mechanisms of resistance of infectious agents.

Clinical cure rate and cost-effectiveness of carbapenem-sparing beta-lactams vs. meropenem for Gram-negative infections: A systematic review, meta-analysis, and cost-effectiveness analysis.

The increasing incidence of infections caused by extended-spectrum beta-lactamase (ESBL)/AmpC-producing bacteria leads to increasing use of carbapenems and risk of carbapenem resistance. Treatment success of carbapenem-sparing beta-lactams (CSBs) for ESBL infections is unclear. The aim of this study was to appraise the clinical cure rate and estimate the cost-effectiveness of meropenem vs. CSBs (piperacillin-tazobactam, temocillin, ceftazidime-avibactam, and ceftolozane-tazobactam) for urinary tract infections (UTIs) or intra-abdominal infections (IAIs) due to ESBL/AmpC-producing bacteria. A systematic literature search of the Cochrane library, EMBASE, PubMed, and Web of Science was conducted to identify studies assessing the clinical cure rate of the antibiotics. To assess the cost-effectiveness of CSBs vs. meropenem, a combined decision analytic and Markov model was probabilistically analysed over a 5-year period. The main outcome was presented as the incremental cost-effectiveness ratio and evaluated with a threshold of €20 000 per life year gained (LYG). From 656 identified articles, 17 and 14 studies were included in the qualitative synthesis and quantitative synthesis, respectively. A clinical cure of ceftazidime-avibactam and ceftolozane-tazobactam was comparable to meropenem in patients with complicated IAIs (cIAIs) due to ESBL (Risk ratio [RR]=1·04, 95% confidence interval [CI]=0·95-1·13). Both temocillin and ceftolozane-tazobactam were deemed cost-effective compared to meropenem with €157·58 and €13 398·34 per LYG, respectively, in patients with UTIs due to ESBL. However, only ceftazidime-avibactam (plus metronidazole) was cost-effective for the treatment of IAIs, with €16 916·77 per LYG. These results show that several CSBs can be considered as viable candidates for the treatment of UTIs and IAIs caused by ESBL.

Cost of Nosocomial Outbreak Caused by NDM-1-Containing Klebsiella pneumoniae in the Netherlands, October 2015-January 2016.

During October-December 2015, 29 patients in a hospital in the Netherlands acquired nosocomial infection with a multidrug-resistant, New Delhi-metallo-ß-lactamase-positive Klebsiella pneumoniae strain. Extensive infection control measures were needed to stop this outbreak. The estimated economic impact of the outbreak was $804,263; highest costs were associated with hospital bed closures.

Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial.

BACKGROUND: An increasing amount of evidence supports antibiotic therapy for treating uncomplicated acute appendicitis. The objective of this study was to compare the costs of antibiotics alone versus appendicectomy in treating uncomplicated acute appendicitis within the randomized controlled APPAC (APPendicitis ACuta) trial. METHODS: The APPAC multicentre, non-inferiority RCT was conducted on patients with CT-confirmed uncomplicated acute appendicitis. Patients were assigned randomly to appendicectomy or antibiotic treatment. All costs were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis during the 1-year follow-up. The cost estimates were based on cost levels for the year 2012. RESULTS: Some 273 patients were assigned to the appendicectomy group and 257 to antibiotic treatment. Most patients randomized to antibiotic treatment did not require appendicectomy during the 1-year follow-up. In the operative group, overall societal costs (€5989·2, 95 per cent c.i. 5787·3 to 6191·1) were 1·6 times higher (€2244·8, 1940·5 to 2549·1) than those in the antibiotic group (€3744·4, 3514·6 to 3974·2). In both groups, productivity losses represented a slightly higher proportion of overall societal costs than all treatment costs together, with diagnostics and medicines having a minor role. Those in the operative group were prescribed significantly more sick leave than those in the antibiotic group (mean(s.d.) 17·0(8·3) (95 per cent c.i. 16·0 to 18·0) versus 9·2(6·9) (8·3 to 10·0) days respectively; P < 0·001). When the age and sex of the patient as well as the hospital were controlled for simultaneously, the operative treatment generated significantly more costs in all models. CONCLUSION: Patients receiving antibiotic therapy for uncomplicated appendicitis incurred lower costs than those who had surgery.

Cost-effectiveness of antibiotic treatment strategies for community-acquired pneumonia: results from a cluster randomized cross-over trial.

BACKGROUND: To determine the cost-effectiveness of strategies of preferred antibiotic treatment with beta-lactam/macrolide combination or fluoroquinolone monotherapy compared to beta-lactam monotherapy. METHODS: Costs and effects were estimated using data from a cluster-randomized cross-over trial of antibiotic treatment strategies, primarily from the reduced third payer perspective (i.e. hospital admission costs). Cost-minimization analysis (CMA) and cost-effectiveness analysis (CEA) were performed using linear mixed models. CMA results were expressed as difference in costs per patient. CEA results were expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per prevented death. RESULTS: A total of 2,283 patients were included. Crude average costs within 90 days from the reduced third payer perspective were €4,294, €4,392, and €4,002 per patient for the beta-lactam monotherapy, beta-lactam/macrolide combination, and fluoroquinolone monotherapy strategy, respectively. CMA results were €106 (95% CI €-697 to €754) for the beta-lactam/macrolide combination strategy and €-278 (95%CI €-991 to €396) for the fluoroquinolone monotherapy strategy, both compared to the beta-lactam monotherapy strategy. The ICER was not statistically significantly different between the strategies. Other perspectives yielded similar results. CONCLUSIONS: There were no significant differences in cost-effectiveness of strategies of preferred antibiotic treatment of CAP on non-ICU wards with either beta-lactam monotherapy, beta-lactam/macrolide combination therapy, or fluoroquinolone monotherapy. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov, number NCT01660204 , on May 2nd, 2012.

Once-Daily Ceftriaxone Plus Metronidazole Versus Ertapenem and/or Cefoxitin for Pediatric Appendicitis.

BACKGROUND: Appendicitis is a common surgical emergency in pediatric patients, and broad-spectrum antibiotic therapy is warranted in their care. A simplified once-daily regimen of ceftriaxone and metronidazole (CTX plus MTZ) is cost effective in perforated patients. The goal of this evaluation is to compare a historic regimen of cefoxitin (CFX) in nonperforated cases and ertapenem (ERT) in perforated and abscessed cases with CTX plus MTZ for all cases in terms of efficacy and cost. METHODS: A retrospective review compared outcomes of nonperforated, perforated, and abscessed cases who received the historic regimen or CTX plus MTZ. Length of stay, time to afebrile, time to full feeds, postoperative abscess, and wound infection rates, inpatient readmissions, and antibiotic costs were evaluated. RESULTS: There were a total of 841 cases reviewed (494 nonperforated, 247 perforated, and 100 abscessed). Overall, the CTX plus MTZ group had a shorter time to afebrile (P < .001). Treatment groups did not differ in length of stay. Postoperative abscess rates were similar between groups (4.1% vs 3.3%, not significant). Other postoperative complications were similar between groups. Total antibiotic cost savings were over $110 000 during the study period (from November 2010 to June 2013). CONCLUSIONS: Both CFX and/or ERT and CTX plus MTZ result in low abscess and complication rates, suggesting both are effective strategies. Treatment with CTX plus MTZ results in a shorter time to afebrile, while also providing significant antibiotic cost savings. Ceftriaxone plus MTZ is a streamlined, cost-effective regimen in the treatment of nonperforated, perforated, and abscessed appendicitis.

Are new antibiotics better than beta-lactams for non-critical inpatients with community-acquired pneumonia? / ¿Son los nuevos antibióticos superiores a los betalactámicos para los pacientes hospitalizados, no críticos, con neumonía adquirida en la comunidad?

Treatment for community-acquired pneumonia in immunocompetent adults is mainly empirical. Beta-lactam antibiotics have been traditionally considered first-line therapy. New antibiotics could be more effective but the evidence is not clear until now, and its use could entail greater costs, an increase in bacterial resistance and other adverse effects. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 36 randomized trials addressing this question. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded new antibiotics are not better than beta-lactam antibiotics for the treatment of non-critical inpatients with community-acquired pneumonia in relation to clinical failure or adverse effects.

El tratamiento de la neumonía adquirida en la comunidad en el adulto inmunocompetente es empírico, siendo tradicionalmente los antibióticos betalactámicos la terapia de primera línea. Se ha postulado que nuevos antibióticos podrían ser más efectivos, pero hasta el momento este planteamiento no ha sido corroborado por la evidencia disponible y su uso podría asociarse a mayor costo, aumento de la resistencia bacteriana y otros efectos adversos. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas realizadas en 30 bases de datos, identificamos seis revisiones sistemáticas que en conjunto incluyen 36 estudios aleatorizados pertinentes a la pregunta. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que los nuevos antibióticos no son mejores que los antibióticos betalactámicos en pacientes adultos hospitalizados con neumonía no severa en cuanto a riesgo de fracaso clínico o efectos adversos.

Impact of an antimicrobial stewardship initiative to evaluate ß-lactam allergy in patients ordered aztreonam.

PURPOSE: An evaluation of the clinical and economic impact of an antimicrobial stewardship quality initiative (ASQI) focusing on allergy assessment in patients with a documented ß-lactam allergy prescribed aztreonam was conducted. METHODS: This retrospective study was executed at a hospital with an interdisciplinary antimicrobial stewardship program (ASP). A total of 186 patients with self-reported ß-lactam allergies who were prescribed aztreonam while admitted during a 36-month time period surrounding the ASQI implementation were included. The primary study outcome was median time in hours to aztreonam discontinuation among nonanaphylactic patients. RESULTS: After implementation of the ASQI, the percentage of patients continued on aztreonam for the duration of therapy was nearly cut in half, and a greater percentage of patients were switched to ß-lactam antibiotics. No adverse effects associated with ß-lactam therapy were observed in any study patient. Antimicrobial cost savings was not associated with any difference in clinical outcomes. Overall, hospitalwide aztreonam prescribing and aztreonam use declined. Institutional aztreonam orders per 1000 patient-days decreased from 1.5 to 1 after implementation of the ASQI. Additionally, hospitalwide aztreonam days of therapy per 1000 patient-days was reduced from 3.6 in the pre-ASQI period to 1.8 in the post-ASQI period. CONCLUSION: An ASQI that included critical evaluation of patient-reported ß-lactam allergies led to decreased aztreonam use, reduced antimicrobial expenditure, and similar clinical outcomes to those observed before implementation.

Comparison of the effectiveness and antibiotic cost among ceftriaxone, ertapenem, and levofloxacin in treatment of community-acquired complicated urinary tract infections.

PURPOSE: To study characteristics of patients with community-acquired complicated urinary tract infections (cUTIs) and to compare effectiveness and antibiotic cost of treatment with ceftriaxone (CRO), levofloxacin (LVX), and ertapenem (ETP). METHODS: This retrospective study enrolled patients who had community-acquired cUTIs admitted to Division of Infectious Diseases in a single medical center from January 2011 to March 2013. Effectiveness, antibiotic cost, and clinical characteristics were compared among patients treated with CRO, LVX, and ETP. RESULTS: There were 358 eligible cases, including 139 who received CRO, 128 treated with ETP, and 91 with LVX. The most common pathogen was Escherichia coli. The susceptibilities of these three agents were higher and more superior than first-line antibiotics. Treatment with ETP was associated with a significantly shorter time to defervescence since admission (CRO: 39 hours, ETP: 30 hours, and LVX: 38 h; p = 0.031) and shorter hospitalization stay (CRO: 4 days, ETP: 3 days, and LVX: 4 days; p < 0.001). However, the average antibiotic costs in the CRO group were significantly lower than that in the other two groups [CRO: 62.4 United States dollars (USD), ETP: 185.33 USD, and LVX: 204.85 USD; p < 0.001]. CONCLUSION: The resistance of cUTIs isolates to first-line antibiotic is high. Using ETP, CRO, and LVX in the treatment of cUTIs for good clinical response should be suggested. Among the three agents, ETP had better susceptibility than CRO and LVX, reached defervescence sooner, and was associated with shorter hospital stays. However, using CRO in cUTIs was less expensive than the other two agents.

Comparative Effectiveness of Beta-lactam Versus Macrolide Monotherapy in Children with Pneumonia Diagnosed in the Outpatient Setting.

BACKGROUND: Most children diagnosed with community-acquired pneumonia (CAP) are treated in the outpatient setting. The objective of this study was to determine the comparative clinical effectiveness of beta-lactam monotherapy and macrolide monotherapy in this population. STUDY DESIGN: Children, 1-18 years old, with a clinical diagnosis of CAP at an outpatient practice affiliated (n = 71) with Geisinger Health System during January 1, 2008 to January 31, 2010 were eligible. The primary exposure was receipt of beta-lactam or macrolide monotherapy. The primary outcome was treatment failure defined as change in antibiotic prescription within 14 days of the initial pneumonia diagnosis. Propensity scores were used to determine the likelihood of receiving macrolide monotherapy. Treatment groups were matched 1:1, based on propensity score, age group and asthma status. Multivariable conditional logistic regression models estimated the association between macrolide monotherapy and treatment failures. RESULTS: Of 1999 children with CAP, 1164 were matched. In the matched cohorts, 24% of children had asthma. Patients who received macrolide monotherapy had no statistical difference in treatment failure regardless of age when compared with patients who received beta-lactam monotherapy. CONCLUSION: Our findings suggest that children diagnosed with CAP in the outpatient setting and treated with beta-lactam or macrolide monotherapy have the same likelihood to fail treatment regardless of age.

Impact of a Dynamic Microbiological Environment on the Clinical Efficacy of Ertapenem and Piperacillin/Tazobactam in the Treatment of Complicated Community-Acquired Intra-Abdominal Infection in Spain: A Cost-Consequence Analysis.

BACKGROUND AND OBJECTIVE: The microbial susceptibility of many antibiotics has been affected by prescribing patterns and their extensive use. The purpose of this evaluation was to assess how these changes could affect the initial efficacy of ertapenem and piperacillin/tazobactam in the treatment of complicated intra-abdominal infections (IAIs) acquired in the community and the potential consequences this may have in healthcare costs in Spain. METHODS: The Initial efficacy of ertapenem and piperacillin/tazobactam for patients with APACHE (Acute Physiology and Chronic Health Evaluation) II scores <10 was extracted from a multicenter randomized study and were combined with the current microbial susceptibilities obtained from the SMART study, a multinational surveillance program. Country-specific pathogens distribution was extracted from a national study in patients with community-acquired IAI. The estimated effectiveness was used in a decision-analytic model to compare total costs between ertapenem and piperacillin/tazobactam in the treatment of complicated IAI. The model performs extensive one-way and probabilistic sensitivity analyses. RESULTS: The model suggested a savings of €209 (year 2012 values) per patient when complicated IAIs acquired in the community (APACHE II <10) were treated with ertapenem instead of piperacillin/tazobactam. One-way sensitivity analyses showed length of stay as the key driver parameter. Further analysis of this parameter and probabilistic sensitivity analysis confirmed the robustness of our evaluation, with a 58% likelihood of ertapenem being dominant. CONCLUSIONS: Ertapenem appears to be a cost-saving strategy over piperacillin/tazobactam for the treatment of patients with complicated IAIs acquired in the community in Spain.

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.

A prospective randomized controlled multicenter trial comparing antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis (APPAC trial).

BACKGROUND: Although the standard treatment of acute appendicitis (AA) consists of an early appendectomy, there has recently been both an interest and an increase in the use of antibiotic therapy as the primary treatment for uncomplicated AA. However, the use of antibiotic therapy in the treatment of uncomplicated AA is still controversial. METHODS/DESIGN: The APPAC trial is a randomized prospective controlled, open label, non-inferiority multicenter trial designed to compare antibiotic therapy (ertapenem) with emergency appendectomy in the treatment of uncomplicated AA. The primary endpoint of the study is the success of the randomized treatment. In the antibiotic treatment arm successful treatment is defined as being discharged from the hospital without the need for surgical intervention and no recurrent appendicitis during a minimum follow-up of one-year (treatment efficacy). Treatment efficacy in the operative treatment arm is defined as successful appendectomy evaluated to be 100%. Secondary endpoints are post-intervention complications, overall morbidity and mortality, the length of hospital stay and sick leave, treatment costs and pain scores (VAS, visual analoque scale). A maximum of 610 adult patients (aged 18-60 years) with a CT scan confirmed uncomplicated AA will be enrolled from six hospitals and randomized by a closed envelope method in a 1:1 ratio either to undergo emergency appendectomy or to receive ertapenem (1 g per day) for three days continued by oral levofloxacin (500 mg per day) plus metronidazole (1.5 g per day) for seven days. Follow-up by a telephone interview will be at 1 week, 2 months and 1, 3, 5 and 10 years; the primary and secondary endpoints of the trial will be evaluated at each time point. DISCUSSION: The APPAC trial aims to provide level I evidence to support the hypothesis that approximately 75-85% of patients with uncomplicated AA can be treated with effective antibiotic therapy avoiding unnecessary appendectomies and the related operative morbidity, also resulting in major cost savings.

[Antibiotic consumption and its costs of purchase in Polish neonatology networks units]. / Zuzycie antybiotyków i koszty ich zakupu w oddzialach Polskiej sieci neonatologicznej.

AIM: The study presents the results of the analysis of antibiotic consumption and its direct costs in selected neonatal units. MATERIAL AND METHODS: Data were collected retrospectively (the year 2007) in five hospitals, during the pilot phase of the Polish Neonatal Network . Antibiotic consumption was assessed using the Defined Daily Dose (DDD). The costs were assessed as the costs of purchase of one DDD. RESULTS: The study included 11 922 children hospitalized in the period from 1.01 to 31.12.2007. In this group, 731 infants have birth weight < 1500 grams (from 2.2% to 64.2% in individual units, median--7.3%). The mean consumption of antibacterial drugs was 48.52 DDD/1 000 person-days (P-D) of stay among the entire study population (median--42,52), and varied from 23.13 to 85.82 DDD/1,000 P-D. However, this difference has not been statistically significant. The most commonly used group of antibiotics were beta-lactams--in four out of five units the percentage of its usage ranged from 48.71% to 74.67%. Next group were aminoglicosides--in one unit its usage reached 56.97% and in other ranged from 5.01% to 22.53%. Glycopeptides and macrolides were also used in every unit of the studied group. The usage of glycopeptides ranged from 1.7% to 10.81% and of macrolides from 1.32% to 15.71%. Different kinds of antibiotics were used occasionally. The differences of costs of purchase of one DDD between hospitals were greater and varied from 17,64 PLN/ DDD to 84,58 PLN/ DDD (average costs). A considerable range of costs index values was also noted for different groups of antibiotics. The costs of purchase of one DDD of beta-lactams varied from 19.54 PLN/ DDD to 68.35 PLN/ DDD; for aminoglicosides the cost varied from 4.61 PLN/ DDD to 122.9 PLN/ DDD, for glycopeptides--from 31.40 PLN/ DDD to 283.13 PLN/ DDD and in case of macrolides: from 12.05 PLN/ DDD to 90.77 PLN/ DDD. This differentiation of the cost of purchasing a single defined daily dose, taking into account the specific groups of antibiotics, did not have the characteristics of statistical significance. CONCLUSIONS: As expected, the antibiotic regimens in the studied wards were similar. This is due to a homogeneous population of hospitalized patients. However, the differences of costs of purchase of antibiotics observed in the study, indicate the considerable variety of the treatment patterns in Polish neonatology units and the need to develop and implement recommendations of effective pharmacotherapy for patients in intensive neonatal care units and the implementation of a unified model of infections surveillance.

National survey on continuous and extended infusions of antibiotics.

PURPOSE: A national survey was conducted to evaluate the use of continuous and extended infusions for administering ß-lactams and vancomycin. METHODS: The survey was sent to a random sample of 1000 acute care hospital pharmacists in the United States to evaluate the use of continuous and extended infusions of antibiotics. In addition, the same survey was sent to members of the Society of Infectious Diseases Pharmacists (SIDP) to assess the adoption of these infusion strategies. RESULTS: In the random-sample survey, 29 (11.2%) and 15 (5.8%) hospitals reported using continuous and extended infusions, respectively. Common rationales for adopting continuous and extended infusions were greater efficacy, equal or less toxicity, and cost savings. The SIDP survey revealed that 30 (50%) and 21 (35%) of responding pharmacists have initiated continuous and extended infusions, respectively. Common rationales for adopting continuous and extended infusions were greater efficacy, equal or less toxicity, and cost savings. Both surveys found that penicillins were the antibiotics most frequently administered as continuous and extended infusions. CONCLUSION: The results of a survey sent to a random sample of hospital pharmacists and to SIDP members indicated that the majority did not use either continuous or extended infusions of antibiotics. SIDP survey respondents more frequently reported the use of both continuous and extended infusions than the respondents of the random-sample survey, and the percentage of time above the minimum inhibitory concentration was the most frequently assessed pharmacokinetic-pharmacodynamic parameter for both groups.

Ertapenem compared to combination drug therapy for the treatment of postpartum endometritis after cesarean delivery.

OBJECTIVE: Ertapenem is a broad spectrum carbapenem approved for the treatment of postpartum endometritis. Data regarding clinical outcomes after treatment with ertapenem for endometritis after cesarean delivery are limited. Our objectives were to compare clinical outcomes and cost of ertapenem versus a multi-drug regimen for treatment of endometritis after cesarean delivery. METHODS: Retrospectively, patients with endometritis after cesarean delivery who were treated with ertapenem (group A) were compared to those treated with a combination regimen (group B). Mann-Whitney U and Fisher's Exact were used for statistical analysis with p value <0.05 considered statistically significant. RESULTS: Sixty-three patients were included: 31 in group A and 32 in group B. Demographics and intrapartum characteristics did not differ. Number of administered doses (A: 3, B: 11.5 p < 0.0001), cost (A: $156.63, B: $54.48 p < 0.0001) and nursing time in minutes (A: 6.6, B: 25.3 p < 0.0001) were different between both groups. Wound complications were higher in group A, occurring in 7 patients compared to 1 patient in group B (p = 0.024). CONCLUSION: Although time and number of administered doses were less in group A, given the high wound complication rate in patients treated with ertapenem, this drug may not be appropriate for all patients with endometritis after CD.