- Email: [email protected]
SP32-3 OPAT in Japan: the journey and lessons
S36
Keynote sessions and Symposia / International Journal of Antimicrobial Agents 42S2 (2013) S1–S40
OPAT can offer a wide variety of antimicrobial treatments especially if these are stable for adequate time periods once constituted. Regimens include, once daily at the infusion centre however with good vascular access and increasingly developed infusion technologies more options are available including 24 and 48 hour continuous infusors and also 1 hour infusors for intermittent dosing at home. Antibiotic provision at hospital-based infusion centres is preferred in 76% of cases with the remainder receiving home based therapy either via self, a caregiver or by visiting nurses. Increasing acceptance among clinicians and patients has paralleled published evidence of improvements to patients’ quality of life, safety, cost savings to hospitals (bed days saved) as well as cost savings to patients/insurers. Clinical outcomes in OPAT services worldwide consistently compare well with inpatient care. Healthcare costs have been shown in Singapore, European and North American OPATs to be < 20% of that observed in inpatient care. Our median treatment course is 16 days (range 1–205). The median age of patients we treat is 56 years (range 7–94). The most common diagnoses treated in our settings are osteomyelitis (15.1%), primary bacteraemia (10.0%) and liver abscess (9.8%). The most frequently prescribed antibiotics are ceftriaxone (21.6%) and ertapenem (18.2%). OPAT has been shown to be safe, cost effective and preferred by many patients and their caregivers. Internationally it is now accepted as a core service in most hospitals.
gave us more antimicrobial choices and enabled us to continue the most appropriate antibiotics in outpatient settings. Nine patients have been treated in our OPAT program and no major complication has been experienced so far. We believe OPAT is beneficial for better quality of life of patients, prevention of nosocomial infection, efficient hospital-bed management and medical cost saving. The benefit of OPAT is expected to be significant in Japan since Japan has a large elderly population who often require prolonged hospitalization for parenteral antibiotic therapy. However, there are many barriers for expanding OPAT: insufficient knowledge of healthcare workers about OPAT, limitation of home care services, and lack of insurance coverage. It is necessary that we spend more effort to make it a standard practice for patients who need parenteral antibiotics therapy.
SP32-2 Re-admission from OPAT: Risk factors and outcome
The PK/PD paradigm offers a rational approach to antibiotics therapeutic use. There are also some relationships between PK/PD features of antibiotics and the adverse reactions. An important aspect in antibiotic therapy is to balance the antibiotic concentrations in order to achieve optimal antibacterial action and minimal adverse reactions. Adverse reactions to antibiotics can be divided into PK/PD dependent and PK/PD non-dependent reactions. Allergic reactions, phototoxicity and other side effects are not dependent on the PK/PD characteristics of antibiotics. The three most important PK/PD parameters for evaluating an antibacterial’s activity (the Cmax/MIC ratio, the T> MIC, and the 24 h-AUC/MIC ratio) are also important for some adverse reactions induction. The aminoglycosides and fluoroquinolones, substances for which the antibacterial efficacy depends on the Cmax/MIC and AUC/MIC, induce the highest incidence of adverse reactions. The nephrotoxicity of aminoglycosides and colistin, hepatotoxicity, neurological and metabolic effects of a lot of antibacterial drugs are dependent on Cmax. The ototoxicity of aminoglycosides is also still dose and Cmax dependent. The antibiotic-induced alterations in the intestinal microbiota depends on some PK (intestinal secretion and absorption and others) and PD features of the antibiotic. Central Nervous System adverse effects of quinolones may be related to chemical structures of individual drugs but also to Cmax. A relationship exists between the pattern of exposure to antibiotics and emergence of resistance. The development of bacterial resistance to antibiotics is dependent on AUC24/mutant prevention concentration (MPC) and MPC/MIC ratio. The carbapenems’ MPC/MIC ratios were mostly 8–16 against Pseudomonas aeruginosa . The beta-lactams, which are largely dose-independent drugs and for which the antibacterial effect depends on the T> MIC, have fewer side effects compared to other groups of antibacterials. No data exist on correlations between the incidence of adverse reactions and post antibiotic effect. It is not very clear if macrolides, fluoroquinolones, and ansamycins which are active against intracellular bacteria have also a higher incidence of side effects compared to antimicrobials which have a poor penetrabilitity in human cells. Quinolones’ high intracellular concentrations in both infected and non-infected cells, can influence the activity of various subcellular compartments and by this way produce adverse reactions. The specific cellular pharmacokinetic properties of antibiotics could modulate not only antibacterial activity but also partially the side effects of antibiotics.
D.C. Lye *. Communicable Disease Centre, Institite of Infectious Disease and Epidemiology, Tan Tock Seng Hospital; Yong Loo Lin School of Medicine, National University of Singapore, Singapore E-mail address : [email protected] Outpatient parenteral antibiotic therapy (OPAT) has been successfully practised in North America, Europe, Australasia, and selected countries in Asia. Supported by a strong evidence base of cohort studies, OPAT is generally safe in a wide variety of acute and chronic infections being treated by almost all available intravenous antibiotics. Readmission to hospital can occur in 10–15% as a result of worsening of infection being treated, underlying co-morbidity or complication of OPAT. In the last category, this can involve vascular access or side effects of antibiotics. In a large prospective study of 2229 patients in Singapore, 84.1% completed treatment while 9% experienced clinical deterioration. The remainder was re-admitted for elective procedures, side effects of antibiotics and complications of vascular access. Independent risk factors for clinical deterioration were home OPAT, age > 70 years and non-private patients. Concerns on safety of OPAT will be discussed with reference to infections (e.g. endocarditis, osteomyelitis), antibiotics (e.g. vancomycin, aminoglycosides), mode of delivery of OPAT (e.g. caregiver OPAT), and special patient cohorts (e.g. elderly, injecting drug users, febrile neutropenia). Knowing risk for complications in OPAT allows optimal implementation of OPAT in reducing prolonged hospital stay, overall cost of care and nosocomial complications, while measures can be implemented to mitigate risk in OPAT. SP32-3 OPAT in Japan: the journey and lessons R. Hase *. Department of Infectious Diseases, Kameda Medical Center, Japan E-mail address : [email protected] Well-organized OPAT (outpatient parenteral antimicrobial therapy) practice does not exist in Japan, thus the phrase OPAT is not commonly used. Although once-daily drugs, mainly ceftriaxone, are often prescribed at outpatient clinics, other antibiotics are rarely used. Ceftriaxone tends to be overused due to its convenience, and those treatments are usually done without support of Infectious Diseases specialists. We started our OPAT project at Kameda Medical Center in 2012. The aim of our project is to offer a treatment option at home, to use appropriate parenteral antibiotics at clinics, and to shorten the duration of hospitalization in the ward. Continuous infusion therapy
Symposium 33. Collateral effects of antiinfectives – from theory to practice SP33-1 The importance of PK/PD relationships for the adverse effects of antiinfectives M. Nechifor *. Department of Pharmacology, “Gr. T. Popa” University of Medicine and Pharmacy, Iasi, Romania E-mail address : [email protected]
Keynote sessions and Symposia / International Journal of Antimicrobial Agents 42S2 (2013) S1–S40
OPAT can offer a wide variety of antimicrobial treatments especially if these are stable for adequate time periods once constituted. Regimens include, once daily at the infusion centre however with good vascular access and increasingly developed infusion technologies more options are available including 24 and 48 hour continuous infusors and also 1 hour infusors for intermittent dosing at home. Antibiotic provision at hospital-based infusion centres is preferred in 76% of cases with the remainder receiving home based therapy either via self, a caregiver or by visiting nurses. Increasing acceptance among clinicians and patients has paralleled published evidence of improvements to patients’ quality of life, safety, cost savings to hospitals (bed days saved) as well as cost savings to patients/insurers. Clinical outcomes in OPAT services worldwide consistently compare well with inpatient care. Healthcare costs have been shown in Singapore, European and North American OPATs to be < 20% of that observed in inpatient care. Our median treatment course is 16 days (range 1–205). The median age of patients we treat is 56 years (range 7–94). The most common diagnoses treated in our settings are osteomyelitis (15.1%), primary bacteraemia (10.0%) and liver abscess (9.8%). The most frequently prescribed antibiotics are ceftriaxone (21.6%) and ertapenem (18.2%). OPAT has been shown to be safe, cost effective and preferred by many patients and their caregivers. Internationally it is now accepted as a core service in most hospitals.
gave us more antimicrobial choices and enabled us to continue the most appropriate antibiotics in outpatient settings. Nine patients have been treated in our OPAT program and no major complication has been experienced so far. We believe OPAT is beneficial for better quality of life of patients, prevention of nosocomial infection, efficient hospital-bed management and medical cost saving. The benefit of OPAT is expected to be significant in Japan since Japan has a large elderly population who often require prolonged hospitalization for parenteral antibiotic therapy. However, there are many barriers for expanding OPAT: insufficient knowledge of healthcare workers about OPAT, limitation of home care services, and lack of insurance coverage. It is necessary that we spend more effort to make it a standard practice for patients who need parenteral antibiotics therapy.
SP32-2 Re-admission from OPAT: Risk factors and outcome
The PK/PD paradigm offers a rational approach to antibiotics therapeutic use. There are also some relationships between PK/PD features of antibiotics and the adverse reactions. An important aspect in antibiotic therapy is to balance the antibiotic concentrations in order to achieve optimal antibacterial action and minimal adverse reactions. Adverse reactions to antibiotics can be divided into PK/PD dependent and PK/PD non-dependent reactions. Allergic reactions, phototoxicity and other side effects are not dependent on the PK/PD characteristics of antibiotics. The three most important PK/PD parameters for evaluating an antibacterial’s activity (the Cmax/MIC ratio, the T> MIC, and the 24 h-AUC/MIC ratio) are also important for some adverse reactions induction. The aminoglycosides and fluoroquinolones, substances for which the antibacterial efficacy depends on the Cmax/MIC and AUC/MIC, induce the highest incidence of adverse reactions. The nephrotoxicity of aminoglycosides and colistin, hepatotoxicity, neurological and metabolic effects of a lot of antibacterial drugs are dependent on Cmax. The ototoxicity of aminoglycosides is also still dose and Cmax dependent. The antibiotic-induced alterations in the intestinal microbiota depends on some PK (intestinal secretion and absorption and others) and PD features of the antibiotic. Central Nervous System adverse effects of quinolones may be related to chemical structures of individual drugs but also to Cmax. A relationship exists between the pattern of exposure to antibiotics and emergence of resistance. The development of bacterial resistance to antibiotics is dependent on AUC24/mutant prevention concentration (MPC) and MPC/MIC ratio. The carbapenems’ MPC/MIC ratios were mostly 8–16 against Pseudomonas aeruginosa . The beta-lactams, which are largely dose-independent drugs and for which the antibacterial effect depends on the T> MIC, have fewer side effects compared to other groups of antibacterials. No data exist on correlations between the incidence of adverse reactions and post antibiotic effect. It is not very clear if macrolides, fluoroquinolones, and ansamycins which are active against intracellular bacteria have also a higher incidence of side effects compared to antimicrobials which have a poor penetrabilitity in human cells. Quinolones’ high intracellular concentrations in both infected and non-infected cells, can influence the activity of various subcellular compartments and by this way produce adverse reactions. The specific cellular pharmacokinetic properties of antibiotics could modulate not only antibacterial activity but also partially the side effects of antibiotics.
D.C. Lye *. Communicable Disease Centre, Institite of Infectious Disease and Epidemiology, Tan Tock Seng Hospital; Yong Loo Lin School of Medicine, National University of Singapore, Singapore E-mail address : [email protected] Outpatient parenteral antibiotic therapy (OPAT) has been successfully practised in North America, Europe, Australasia, and selected countries in Asia. Supported by a strong evidence base of cohort studies, OPAT is generally safe in a wide variety of acute and chronic infections being treated by almost all available intravenous antibiotics. Readmission to hospital can occur in 10–15% as a result of worsening of infection being treated, underlying co-morbidity or complication of OPAT. In the last category, this can involve vascular access or side effects of antibiotics. In a large prospective study of 2229 patients in Singapore, 84.1% completed treatment while 9% experienced clinical deterioration. The remainder was re-admitted for elective procedures, side effects of antibiotics and complications of vascular access. Independent risk factors for clinical deterioration were home OPAT, age > 70 years and non-private patients. Concerns on safety of OPAT will be discussed with reference to infections (e.g. endocarditis, osteomyelitis), antibiotics (e.g. vancomycin, aminoglycosides), mode of delivery of OPAT (e.g. caregiver OPAT), and special patient cohorts (e.g. elderly, injecting drug users, febrile neutropenia). Knowing risk for complications in OPAT allows optimal implementation of OPAT in reducing prolonged hospital stay, overall cost of care and nosocomial complications, while measures can be implemented to mitigate risk in OPAT. SP32-3 OPAT in Japan: the journey and lessons R. Hase *. Department of Infectious Diseases, Kameda Medical Center, Japan E-mail address : [email protected] Well-organized OPAT (outpatient parenteral antimicrobial therapy) practice does not exist in Japan, thus the phrase OPAT is not commonly used. Although once-daily drugs, mainly ceftriaxone, are often prescribed at outpatient clinics, other antibiotics are rarely used. Ceftriaxone tends to be overused due to its convenience, and those treatments are usually done without support of Infectious Diseases specialists. We started our OPAT project at Kameda Medical Center in 2012. The aim of our project is to offer a treatment option at home, to use appropriate parenteral antibiotics at clinics, and to shorten the duration of hospitalization in the ward. Continuous infusion therapy
Symposium 33. Collateral effects of antiinfectives – from theory to practice SP33-1 The importance of PK/PD relationships for the adverse effects of antiinfectives M. Nechifor *. Department of Pharmacology, “Gr. T. Popa” University of Medicine and Pharmacy, Iasi, Romania E-mail address : [email protected]