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.

Antibiotic expected effectiveness and cost under real life microbiology: evaluation of ertapenem and ceftriaxone in the treatment of community-acquired pneumonia for elderly patients in Spain.

BACKGROUND: Clinical efficacy of antibiotics may be affected by changes in the susceptibility of microorganisms to antimicrobial agents. The purpose of this study is to assess how these changes could affect the initial efficacy of ertapenem and ceftriaxone in the treatment of community-acquired pneumonia (CAP) in elderly patients and the potential consequences this may have in health care costs. METHODS: Initial efficacy in elderly was obtained from a combined analysis of two multicenter, randomized studies. An alternative scenario was carried out using initial efficacy data according to the pneumonia severity index (PSI). Country-specific pathogens distribution was obtained from a national epidemiological study, and microbiological susceptibilities to first- and second-line therapies were obtained from Spanish or European surveillance studies. A decision analytic model was used to compare ertapenem versus ceftriaxone for CAP inpatient treatment. Inputs of the model were the expected effectiveness previously estimated and resource use considering a Spanish national health system perspective. Outcomes include difference in proportion of successfully treated patients and difference in total costs between ertapenem and ceftriaxone. The model performed one-way and probabilistic sensitivity analyses. RESULTS: First-line treatment of CAP with ertapenem led to a higher proportion of successfully treated patients compared with ceftriaxone in Spain. One-way sensitivity analysis showed that length of stay was the key parameter of the model. Probabilistic sensitivity analysis showed that ertapenem can be a cost-saving strategy compared with ceftriaxone, with a 59% probability of being dominant (lower costs with additional health benefits) for both, elderly patients (>65 years) and patients with PSI >3. CONCLUSION: The incorporation of the current antimicrobial susceptibility into the initial clinical efficacy has a significant impact in outcomes and costs in CAP treatment. The treatment with ertapenem compared with ceftriaxone resulted in better clinical outcomes and lower treatment costs for two segments of the Spanish population: elderly patients and patients with severe pneumonia (PSI >3).

Antimicrobial susceptibility of Gram-negative organisms from intraabdominal infections and evolution of isolates with extended spectrum ß-lactamases in the SMART study in Spain (2002-2010).

INTRODUCTION: The SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study records the antimicrobial susceptibility of Gram-negative bacilli obtain from intraabdominal infections with special focus in isolates with extended spectrum ß-lactamases (ESBLs). MATERIAL AND METHODS: The antimicrobial susceptibility of 8,869 isolates was analyzed by microdilution during the SMART study performed in Spain from 2002 to 2010. Isolates were recovered in 16 centres. RESULTS: Escherichia coli was the most prevalent pathogen (60.9% from intraabdominal infections acquired in the community and 49.9% in those from nosocomial origin) followed by Klebsiella pneumoniae (8.9% vs 9.2%). Pseudomonas aeruginosa was more common in intraabdominal infections from nosocomial origin (5.6% community and 8.6% nosocomial). Frequency of ESBL-producing isolates was: E. coli, 8.7%; K. pneumoniae, 8.4%; Klebsiella oxytoca, 1.4%; and Proteus mirabilis, 1.6%. Overall, ESBL-producing isolates were more frequently isolated from elderly patients (6.8% >60 years). Ertapenem and meropenem were the most active antimicrobials (susceptibility range with EUCAST criteria, 89.0-100%) when considering all Enterobacteriaceae isolates and also against ESBL producers (95.5-100%). Susceptibility of amoxicillin/clavulanic acid and piperacillin/tazobactam was lower, particularly among ESBL-producing isolates. Nevertheless, ertapenem maintained a good activity (susceptibility >95%) in ESBL-producers that were resistant to amoxicillin/clavulanic acid, piperacillin/tazobactam or fluoroquinolones. CONCLUSIONS: Antimicrobial susceptibility data from the SMART-Spain study reinforce current therapeutic guidelines of intraabdominal infections that include ertapenem as the empirical choice for treatment. This is also supported by the high frequency of ESBL-producers in our geographic area.

Antimicrobial susceptibility of Gram-negative organisms from intra abdominal infections and evolution of isolates with extended spectrum Beta-lactamases in the SMART study in Spain (2002-2010)

Introducción. El estudio SMART (Study for Monitoring Antimicrobial Resistance Trends) tiene como objetivo monitorizar la sensibilidad a los antimicrobianos de los microorganismos gramnegativos aislados en la infección intraabdominal, con especial seguimiento de los que producen Beta-lactamasas de espectro extendido (BLEE). Material y métodos. Se han analizado por microdulución los datos de sensibilidad de 8.869 aislados recogidos en el estudio SMART en España entre 2002 y 2010 en el que han participado 16 centros. Resultados. Escherichia coli fue el patógeno más frecuente (60,9% en la infección intraabdominal adquirida en la comunidad y 49,9% en la nosocomial) seguido de Klebsiella pneumoniae (8,9% vs 9,2%). Pseudomonas aeruginosa fue más habitual en la infección nosocomial (5,6% comunitaria y 8,6% nosocomial). La frecuencia de aislados con BLEE fue: E. coli 8,7%, K. pneumoniae 8,4%, Klebsiella oxytoca 1,4% y Proteus mirabilis 1,6%. En los pacientes de mayor edad aumentó la proporción global de aislados con BLEE (6,8% en pacientes >60 años). Ertapenem y meropenem fueron los antimicrobianos más activos en el conjunto de las enterobacterias (rango de sensibilidad con criterios EUCAST, 89- 100%) y también entre los aislados con BLEE (95,5-100%). La actividad de amoxicilina/ácido clavulánico y piperacilina/tazobactam fue considerablemente inferior, en particular en los aislados con BLEE. Ertapenem mantuvo una buena actividad (sensibilidad >95%) en los productores de BLEE resistentes a amoxicilina/ácido clavulánico, piperacilina/tazobactam o fluoroquinolonas. Conclusiones. Los datos de sensibilidad del estudio SMART en España avalan las guías terapéuticas actuales de infecciónintraabdominal que sitúan al ertapenem como tratamiento empírico de elección, teniendo en cuenta sobre todo la elevada frecuencia de aislados con BLEE en nuestro medio(AU)

Introduction. The SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study records the antimicrobial susceptibility of Gram-negative bacilli obtain from intraabdominal infections with special focus in isolates with extended spectrum Beta-lactamases (ESBLs). Material and Methods. The antimicrobial susceptibility of 8,869 isolates was analyzed by microdilution during the SMART study performed in Spain from 2002 to 2010. Isolates were recovered in 16 centres. Results. Escherichia coli was the most prevalent pathogen (60.9% from intraabdominal infections acquired in the community and 49.9% in those from nosocomial origin) followed by Klebsiella pneumoniae (8.9% vs 9.2%). Pseudomonas aeruginosa was more common in intraabdominal infections from nosocomial origin (5.6% community and 8.6% nosocomial). Frequency of ESBL-producing isolates was: E. coli, 8.7%; K. pneumoniae, 8.4%; Klebsiella oxytoca, 1.4%; and Proteus mirabilis, 1.6%. Overall, ESBL-producing isolates were more frequently isolated from elderly patients (6.8% >60 years). Ertapenem and meropenem were the most active antimicrobials (susceptibility range with EUCAST criteria, 89.0-100%) when considering all Enterobacteriaceae isolates and also against ESBL producers (95.5-100%). Susceptibility of amoxicillin/clavulanic acid and piperacillin/tazobactam was lower, particularly among ESBL-producing isolates. Nevertheless, ertapenem maintained a good activity (susceptibility >95%) in ESBL-producers that were resistant to amoxicillin/clavulanic acid, piperacillin/tazobactam or fluoroquinolones. Conclusions. Antimicrobial susceptibility data from the SMART-Spain study reinforce current therapeutic guidelines of intraabdominal infections that include ertapenem as the empirical choice for treatment. This is also supported by the high frequency of ESBL-producers in our geographic area(AU)