Ertapenem for Infections Caused by ESBL-producing Bacteria
Ertapenem for Infections Caused by ESBL-producing Bacteria
This is a case series in which data were collected from January 2005 (protocol initiation) to May 2010. The University of Massachusetts Memorial Medical Center Institutional Review Board approved this study and granted a waiver of informed consent. Patients were included if they were adults (≥18 years) who received ertapenem within this time period and had a documented infection (identified by International Classification of Diseases, 9th revision codes) with a positive culture for an ESBL-producing gram-negative organism demonstrating in vitro susceptibility to the carbapenem class. We excluded data from patients who received ertapenem for fewer than 48 hours, had received a group 2 carbapenem, had ESBL cultures documented to be nonpathogenic, or lacked concurrent antimicrobial therapy for microbes not susceptible to ertapenem. We used the following definitions for the sites of infections: urinary tract infection, urine culture greater than 100,000 colonies/mL with positive urinalysis; pneumonia, positive sputum culture accompanied by a positive chest X-ray; bacteremia, positive blood culture in any number of bottles; intraabdominal infection, positive drainage and fluid culture from an intraabdominal source; and skin and soft tissue infection, positive tissue culture and clinical documentation. Ertapenem use was identified by extracting drug usage reports from the hospital's pharmacy software. ESBL cultures were identified using the hospital's microbiology database. Detection of ESBL and determination of antibiotic susceptibility followed standards set by the Clinical and Laboratory Standards Institute. Data collected included age, sex, concomitant and previous antibiotic exposure, infection site(s), C-reactive protein, white blood cell count, comorbidities or underlying conditions, clinical parameters (ie, temperature, heart rate, blood pressure), intensive care unit (ICU) stay if applicable, length of hospital stay, and mortality.
The primary endpoint of this study was to describe clinical and microbiologic response rates achieved with ertapenem as a first-line agent. The secondary endpoint was to examine patient- or clinical-related factors associated with failure of ertapenem as a first-line agent. The following definitions were used to describe the primary outcome. Clinical response was defined as the clinical improvement or resolution as measured by either previously elevated markers of infection (ie, leukocytosis, fever, elevated C-reactive protein, and/or other specific markers dependent on the infection site), and/or discharge from the hospital. Therapeutic failure was defined as the lack of improvement in clinical parameters after receipt of ertapenem for longer than 96 hours or switching the regimen to another active antibiotic with in vitro susceptibility (eg, aminoglycosides). Microbiologic cure was defined as negative subsequent cultures from a previously positive culture site upon completion of ertapenem therapy. Eradication failure was defined as continued growth of the ESBL-producing organism(s) after receipt of ertapenem for an appropriate duration (dependent on the site of infection). Relapse was defined as a recurrent infection with the same ESBL strain after an appropriate course of treatment with ertapenem. Undeterminable outcome was assigned to patients who died prior to receipt of appropriate duration of antibiotics or who had been discharged prior to evaluation and/or documentation of the aforementioned treatment outcome. Effective antibiotics were defined as antibiotics with in vitro activity against ESBLs and potential clinical efficacy against these infections.
Methods
This is a case series in which data were collected from January 2005 (protocol initiation) to May 2010. The University of Massachusetts Memorial Medical Center Institutional Review Board approved this study and granted a waiver of informed consent. Patients were included if they were adults (≥18 years) who received ertapenem within this time period and had a documented infection (identified by International Classification of Diseases, 9th revision codes) with a positive culture for an ESBL-producing gram-negative organism demonstrating in vitro susceptibility to the carbapenem class. We excluded data from patients who received ertapenem for fewer than 48 hours, had received a group 2 carbapenem, had ESBL cultures documented to be nonpathogenic, or lacked concurrent antimicrobial therapy for microbes not susceptible to ertapenem. We used the following definitions for the sites of infections: urinary tract infection, urine culture greater than 100,000 colonies/mL with positive urinalysis; pneumonia, positive sputum culture accompanied by a positive chest X-ray; bacteremia, positive blood culture in any number of bottles; intraabdominal infection, positive drainage and fluid culture from an intraabdominal source; and skin and soft tissue infection, positive tissue culture and clinical documentation. Ertapenem use was identified by extracting drug usage reports from the hospital's pharmacy software. ESBL cultures were identified using the hospital's microbiology database. Detection of ESBL and determination of antibiotic susceptibility followed standards set by the Clinical and Laboratory Standards Institute. Data collected included age, sex, concomitant and previous antibiotic exposure, infection site(s), C-reactive protein, white blood cell count, comorbidities or underlying conditions, clinical parameters (ie, temperature, heart rate, blood pressure), intensive care unit (ICU) stay if applicable, length of hospital stay, and mortality.
The primary endpoint of this study was to describe clinical and microbiologic response rates achieved with ertapenem as a first-line agent. The secondary endpoint was to examine patient- or clinical-related factors associated with failure of ertapenem as a first-line agent. The following definitions were used to describe the primary outcome. Clinical response was defined as the clinical improvement or resolution as measured by either previously elevated markers of infection (ie, leukocytosis, fever, elevated C-reactive protein, and/or other specific markers dependent on the infection site), and/or discharge from the hospital. Therapeutic failure was defined as the lack of improvement in clinical parameters after receipt of ertapenem for longer than 96 hours or switching the regimen to another active antibiotic with in vitro susceptibility (eg, aminoglycosides). Microbiologic cure was defined as negative subsequent cultures from a previously positive culture site upon completion of ertapenem therapy. Eradication failure was defined as continued growth of the ESBL-producing organism(s) after receipt of ertapenem for an appropriate duration (dependent on the site of infection). Relapse was defined as a recurrent infection with the same ESBL strain after an appropriate course of treatment with ertapenem. Undeterminable outcome was assigned to patients who died prior to receipt of appropriate duration of antibiotics or who had been discharged prior to evaluation and/or documentation of the aforementioned treatment outcome. Effective antibiotics were defined as antibiotics with in vitro activity against ESBLs and potential clinical efficacy against these infections.
