- Email: [email protected]
ISS1.1 Role of carbapenem in treating serious bacterial infections
$56
Speakers' Abstracts/International Journal of Antimicrobial Agents 26S (2005) S1 $63
Learning Objectives: At the conclusion of this activity, participants should be able to: Discuss the concept of antimicrobials as contributors to the resistance epidemic; Identify the appropriate carbapenem for treating bacterial infections according to the suspected pathogen and patient type; and Examine data for empiric use of antifungal agents in the immunocompromised patient, as well as data for antifungals in documented infection in these critically ill patients.
ISSI,1
Role of Carbapenem in Treating Serious Bacterial Infections Yehuda CARMELI. Beth Israel Deaconess Medical Cente~ Harvard Medical School, Boston, Massachusetts, USA ami Tel Aviv Medical Center, Israel The ability to cure an infection relies on the patient's underlying condition, the virulence of the organism, and the promptness of adminiatering an effective antibiotic. When a patient presents with a serious infection, the physician can influence the course of the disease by starting an effective agent as early as possible. Indeed, the delay in administering initial appropriate therapy for various serious infections has been shown to iesult in serious consequences; increased patient mortality and morbidity, and increased cost to the health-care syatem. Antibiotic resistance has been recognized as a major clinical and public health problem for over haft a centuc¢. During the 80's new classes of drags effective against Gram negative pathogens were introduced: third generation cephalosporins, beta lactam/heta lactamase inhibitor combina tions, fluoroquinolones, and carbapenems. However, during the past decade iesistance to many of these classes has emei~ged and has spread among various Graso-negative pathogens. Magi-drug iesistant (MDR) Gram-negative bacilli such as Pseudomonas aeruginosa, Acinetobacter baumanii, and members of the Entcrobactcriaceac family, including Klebsiella spp., E. eoli, and Enterobaeter spp., have become common pathogens in many hospitals. Antibiotic resistance may render treatment in effective and delay the adminiatration of initial appropriate therapy. Knowledge of the local epidemiology is required to best choose an empirical antibiotic agent. Judicious use of antibiotics accounts for patients' outcomes mid the effect on the hospital ecology. Stratifying patients into risk groups and choosing empiric therapy based on patient characteristics will optimize antibiotic use. The use of group I carbapenems (ertapenem) to treat infections suspected to be caused by MDR Entcrobactcriaceac, and group II ca~eapenems (imipenem, meropenem) to treat infections caused by iesistant non-fermenter, such as/~ aeruginosa, may allow improving patients' out comes and minimize the risk of ~esistance. Strategies of balancing between the need to provide early effective therapy for serious infections and the need to limit antibiotic pressure and disease management costs will be shown.
ISSl2
Antifungal Treatment without Compromise George KARAM. Louisiana State University Sckwol of Medicine, New Orleans, Louisiana, USA A challenge in clinical medicine is to achieve an optimal degree of efficacy without compromising safety or cost effectiveness. This mandate transcends the management of bacterial infections and also applies to fungal infections. In hospitalized patients, two invasivc fungal pathogens are the most noteworthy: Camiida and Aspergillus. The classic patients in whom invasive aspeigillosis develops are those who are immunocompromised on the basis of either neutropenia or depressed cell mediated immunity. The overall clinical response rates of treating aspergillosis in these patient populations have ranged from 32% to 57%. Once patients fail initial therapy and require salvage treatment, response rates are generally 30% or less. The eclfinocandin class of
antifungal drugs represents the newest antifungal agents to be clinically available for invasivc fungal infections, and easpofungin is the first available agent in this class. In clinical trials as well as in a compassionate use program for the treatment of patients who had either failed or were intolerant of amphotericin, caspofungin had overall response rates of about 45%, which was at bast coropaz-able to the published medical literature for clinical response in patients receiving initial therapy for aspergiUosis, and better than previous reports of salvage therapy. As Candida infections have evolved in clinical practice, patient populations infected with this pathogen include not only those immuno compromised on the basis of defects in neutropliil function or cell-mediated immunity but also non-immunocompromised patients with risk factors for invasive candidal infections, including candidemia. The noteworthy trend in eandidal infections is the increasing trend toward infection caused by non albicans species of Catwlida. Like amphotcfiein B but in contrast to the presently available azoles, caspofungin is fungicidal against Catwlida isolates and is piedictably active against the non-albicans species, including those that are azole ~esistant. These properties assist the clinician in understanding the findings of the clinical trial that compared caspofungin to amphotericin B in the treatment of patients with invasive eandidiasis (in which the majority of those evaluated had candidemia) and demonstrated similar efficacy. A major observation of this trial was that caspofungin was in a statistically significant way less likely to cause adverse clinical events, laboratmy abnm'malities, nephrotoxicity, or withdrawal due to adverse effects. Analyses published in peer-ieviewed journals have noted that preventing nephrotoxicity and piecluding the attendant costs associated with the treatment of this complication may make using caspofungin a more cost effective treatment choice than amphotcfiein B in certain patient populations. Since neutropenic patients are at risk of infection with Camiida and Aspergillus, a challenge over the years has been to treat both pathogens with a single agent in febiile, neutropenic patients who do not respond to amibactgrial therapy. In the largest trial to date of empiric therapy in patients with persistent fever and neutropenia, easpofungin was compared to liposomal amphotericin B (J~ AmB). Overall, easpofungin was as effective as L A m B as empiric therapy of suspected fungal infection in this patient population. In patients who had baseline fungal infection (defined as infections present on or befme day 2 of the study), caspofungin in a statistically significant manner was superior to L-AraB both in clinical efficacy and in survival. Caspofungin was better tolerated than LAmB, with significantly lower rates of nephrotoxieity, infusion related events, drug related adverse effects, and discontinuation of therapy due to drug-ielated adverse effects. Because invasive fungal infections are common in immunocompromised patients who may be on multiple medications, including those that prevent transplant rejection, drug interactions are important to consider in the selection of antifungal therapy. In contrast to certain antifungal agents that inhibit the cytoehrome P450 enzyme system and therefore potentially lead to drug-drug interactions, caspofungin is not an inhibitor of any enzymes in the cytocl~'ome P450 system and may not substantially interact with antliejection drugs, other antifungal agents, or dfampin. Elimination of such interactions is an important consideration in a patient population already at risk of problems based on underlying disease and the multiple drugs required for their management. Because of the potentially life-threatening infections that are caused by Camiida and Aspergillus, it is important for the cliniciml to have efficacious therapy that minimizes adverse effects, piecludes significant drug-drug interactions, and offers cost effectiveness. The published literature and clinical experience support the role of caspofungin as such an agent.
Speakers' Abstracts/International Journal of Antimicrobial Agents 26S (2005) S1 $63
Learning Objectives: At the conclusion of this activity, participants should be able to: Discuss the concept of antimicrobials as contributors to the resistance epidemic; Identify the appropriate carbapenem for treating bacterial infections according to the suspected pathogen and patient type; and Examine data for empiric use of antifungal agents in the immunocompromised patient, as well as data for antifungals in documented infection in these critically ill patients.
ISSI,1
Role of Carbapenem in Treating Serious Bacterial Infections Yehuda CARMELI. Beth Israel Deaconess Medical Cente~ Harvard Medical School, Boston, Massachusetts, USA ami Tel Aviv Medical Center, Israel The ability to cure an infection relies on the patient's underlying condition, the virulence of the organism, and the promptness of adminiatering an effective antibiotic. When a patient presents with a serious infection, the physician can influence the course of the disease by starting an effective agent as early as possible. Indeed, the delay in administering initial appropriate therapy for various serious infections has been shown to iesult in serious consequences; increased patient mortality and morbidity, and increased cost to the health-care syatem. Antibiotic resistance has been recognized as a major clinical and public health problem for over haft a centuc¢. During the 80's new classes of drags effective against Gram negative pathogens were introduced: third generation cephalosporins, beta lactam/heta lactamase inhibitor combina tions, fluoroquinolones, and carbapenems. However, during the past decade iesistance to many of these classes has emei~ged and has spread among various Graso-negative pathogens. Magi-drug iesistant (MDR) Gram-negative bacilli such as Pseudomonas aeruginosa, Acinetobacter baumanii, and members of the Entcrobactcriaceac family, including Klebsiella spp., E. eoli, and Enterobaeter spp., have become common pathogens in many hospitals. Antibiotic resistance may render treatment in effective and delay the adminiatration of initial appropriate therapy. Knowledge of the local epidemiology is required to best choose an empirical antibiotic agent. Judicious use of antibiotics accounts for patients' outcomes mid the effect on the hospital ecology. Stratifying patients into risk groups and choosing empiric therapy based on patient characteristics will optimize antibiotic use. The use of group I carbapenems (ertapenem) to treat infections suspected to be caused by MDR Entcrobactcriaceac, and group II ca~eapenems (imipenem, meropenem) to treat infections caused by iesistant non-fermenter, such as/~ aeruginosa, may allow improving patients' out comes and minimize the risk of ~esistance. Strategies of balancing between the need to provide early effective therapy for serious infections and the need to limit antibiotic pressure and disease management costs will be shown.
ISSl2
Antifungal Treatment without Compromise George KARAM. Louisiana State University Sckwol of Medicine, New Orleans, Louisiana, USA A challenge in clinical medicine is to achieve an optimal degree of efficacy without compromising safety or cost effectiveness. This mandate transcends the management of bacterial infections and also applies to fungal infections. In hospitalized patients, two invasivc fungal pathogens are the most noteworthy: Camiida and Aspergillus. The classic patients in whom invasive aspeigillosis develops are those who are immunocompromised on the basis of either neutropenia or depressed cell mediated immunity. The overall clinical response rates of treating aspergillosis in these patient populations have ranged from 32% to 57%. Once patients fail initial therapy and require salvage treatment, response rates are generally 30% or less. The eclfinocandin class of
antifungal drugs represents the newest antifungal agents to be clinically available for invasivc fungal infections, and easpofungin is the first available agent in this class. In clinical trials as well as in a compassionate use program for the treatment of patients who had either failed or were intolerant of amphotericin, caspofungin had overall response rates of about 45%, which was at bast coropaz-able to the published medical literature for clinical response in patients receiving initial therapy for aspergiUosis, and better than previous reports of salvage therapy. As Candida infections have evolved in clinical practice, patient populations infected with this pathogen include not only those immuno compromised on the basis of defects in neutropliil function or cell-mediated immunity but also non-immunocompromised patients with risk factors for invasive candidal infections, including candidemia. The noteworthy trend in eandidal infections is the increasing trend toward infection caused by non albicans species of Catwlida. Like amphotcfiein B but in contrast to the presently available azoles, caspofungin is fungicidal against Catwlida isolates and is piedictably active against the non-albicans species, including those that are azole ~esistant. These properties assist the clinician in understanding the findings of the clinical trial that compared caspofungin to amphotericin B in the treatment of patients with invasive eandidiasis (in which the majority of those evaluated had candidemia) and demonstrated similar efficacy. A major observation of this trial was that caspofungin was in a statistically significant way less likely to cause adverse clinical events, laboratmy abnm'malities, nephrotoxicity, or withdrawal due to adverse effects. Analyses published in peer-ieviewed journals have noted that preventing nephrotoxicity and piecluding the attendant costs associated with the treatment of this complication may make using caspofungin a more cost effective treatment choice than amphotcfiein B in certain patient populations. Since neutropenic patients are at risk of infection with Camiida and Aspergillus, a challenge over the years has been to treat both pathogens with a single agent in febiile, neutropenic patients who do not respond to amibactgrial therapy. In the largest trial to date of empiric therapy in patients with persistent fever and neutropenia, easpofungin was compared to liposomal amphotericin B (J~ AmB). Overall, easpofungin was as effective as L A m B as empiric therapy of suspected fungal infection in this patient population. In patients who had baseline fungal infection (defined as infections present on or befme day 2 of the study), caspofungin in a statistically significant manner was superior to L-AraB both in clinical efficacy and in survival. Caspofungin was better tolerated than LAmB, with significantly lower rates of nephrotoxieity, infusion related events, drug related adverse effects, and discontinuation of therapy due to drug-ielated adverse effects. Because invasive fungal infections are common in immunocompromised patients who may be on multiple medications, including those that prevent transplant rejection, drug interactions are important to consider in the selection of antifungal therapy. In contrast to certain antifungal agents that inhibit the cytoehrome P450 enzyme system and therefore potentially lead to drug-drug interactions, caspofungin is not an inhibitor of any enzymes in the cytocl~'ome P450 system and may not substantially interact with antliejection drugs, other antifungal agents, or dfampin. Elimination of such interactions is an important consideration in a patient population already at risk of problems based on underlying disease and the multiple drugs required for their management. Because of the potentially life-threatening infections that are caused by Camiida and Aspergillus, it is important for the cliniciml to have efficacious therapy that minimizes adverse effects, piecludes significant drug-drug interactions, and offers cost effectiveness. The published literature and clinical experience support the role of caspofungin as such an agent.