akinohanayuki ブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.

Antimicrobial stewardship program ちょこっとまとめ

Antimicrobial stewardship program (ASP) は戦略です。

戦略とは、長期的計画です。
長期的とは、5年位を考えます。
よって、ASPが本当に有効であったか、5年くらいの検討が必要です。
 
ASPの新規性は失われてきましたが、
自施設に落とし込む作業が進められ、着実な成果が今後報告されることを期待してます。
 
なお、ASPの難しさは、科学性の基本である再現性が難しいことです。
 
よって、予後アウトカムは
EGDTなどアルゴリズムの方が再現性あるのではないでしょうか。
ASP論文に多い前後比較研究において、予後アウトカム解釈は、医療技術進歩や重症度を慎重に踏まえる必要があり難しいです。
 
それでは
 
有名論文や薬剤師が関与したいくつかのASP論文をざっくり振り返り。
 
 
Am J Health Syst Pharm 2015 Mar 15; 72(6):466-8.
 
Pharmacist-driven antimicrobial stewardship program in an institution without infectious diseases physician support.
 
length of stay for community-acquired pneumonia (mean ± S.D., 2.69 ± 0.10 days versus 3.40 ± 0.23 days; p = 0.03). 
Two years after ASP implementation, annual cost savings attributed to the program were estimated at $355,000.
 
 
Hosp Pharm 2015 Jun; 50(6):477-83.
 
Antimicrobial Stewardship Programs: Comparison of a Program with Infectious Diseases Pharmacist Support to a Program with a Geographic Pharmacist Staffing Model.
 
At the hospital staffed by a dedicated ID pharmacist, 96.8% of patients received initial antimicrobial therapy that adhered to local treatment guidelines compared to 87% of patients at the hospital that assigned antimicrobial stewardship duties to ward pharmacists (P < .002). Therapy was modified within 24 hours of availability of laboratory data in 86.7% of cases at the Dedicated ID Pharmacist Hospital versus 72.6% of cases at the Geographic Model Hospital (P < .03). When a patient's illness was determined not to be caused by a bacterial infection, antibiotics were discontinued in 78.0% of cases at the Dedicated ID Pharmacist Hospital and in 33.3% of cases at the Geographic Model Hospital (P < .0002).
 
 
Lancet Infect Dis 2015 Dec; 15(12):1438-49.
 
Effects of national antibiotic stewardship and infection control strategies on hospital-associated and community-associated meticillin-resistant Staphylococcus aureus infections across a region of Scotland: a non-linear time-series study.
 
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During antibiotic stewardship, use of 4C and macrolide antibiotics fell by 47% (mean decrease 224 defined daily doses [DDDs] per 1000 OBDs, 95% CI 154-305, p=0·008) in hospitals and 27% (mean decrease 2·52 DDDs per 1000 IDs, 0·65-4·55, p=0·031) in the community. Hospital prevalence densities of MRSA were inversely related to intensified infection prevention and control, but positively associated with MRSA rates in neighbouring hospitals, importation pressures, bed occupancy, and use of fluoroquinolones, co-amoxiclav, and third-generation cephalosporins, or macrolide antibiotics that exceeded hospital-specific thresholds. Community prevalence density was predicted by hospital MRSA rates and above-threshold use of macrolides, fluoroquinolones, and clindamycin. MRSA prevalence density decreased during antibiotic stewardship by 54% (mean reduction 0·60 per 1000 OBDs, 0·01-1·18, p=0·049) in hospital and 37% (mean reduction 0·017 per 10 000 IDs, 0·004-0·029, p=0·012) in the community. Combined with infection prevention and control measures, MRSA prevalence density was reduced by 50% (absolute difference 0·94 cases per 1000 OBDs, 0·27-1·62, p=0·006) in hospitals and 47% (absolute difference 0·033 cases per 10 000 IDs, 0·018-0·048, p<0·0001) in the community.
 
 
JAMA Intern Med 2015 Jul; 175(7):1120-7.
 
Effectiveness of an Antimicrobial Stewardship Approach for Urinary Catheter-Associated Asymptomatic Bacteriuria.
 
Study surveillance included 289,754 total bed-days. The overall rate of urine culture ordering decreased significantly during the intervention period (from 41.2 to 23.3 per 1000 bed-days; incidence rate ration [IRR], 0.57; 95% CI, 0.53-0.61) and further during the maintenance period (to 12.0 per 1000 bed-days; IRR, 0.29; 95% CI, 0.26-0.32) (P < .001 for both). At the comparison site, urine cultures ordered did not change significantly across all 3 periods. There was a significant difference in the number of urine cultures ordered per month over time when comparing the 2 sites using longitudinal linear regression (P < .001). Overtreatment of ASB at the intervention site fell significantly during the intervention period (from 1.6 to 0.6 per 1000 bed-days; IRR, 0.35; 95% CI, 0.22-0.55), and these reductions persisted during the maintenance period (to 0.4 per 1000 bed-days; IRR, 0.24; 95% CI, 0.13-0.42) (P < .001 for both). Overtreatment of ASB at the comparison site was similar across all periods (odds ratio, 1.32; 95% CI, 0.69-2.52). When analyzed by type of ward, the decrease in ASB overtreatment was significant in long-term care.
 
 
Infect Dis Ther 2015 Sep; 4(Suppl 1):5-14.
 
Antimicrobial Stewardship with Pharmacist Intervention Improves Timeliness of Antimicrobials Across Thirty-three Hospitals in South Africa.
 
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A total of 32,985 patients who received intravenous antibiotics were assessed for hang-time compliance with first doses of new antibiotic orders. Over the 60-week period, 21,069 patients received antibiotics within an hour following prescription and were assessed as hang-time compliant. The change in improvement of hang-time compliance following implementation of a pharmacist-driven hang-time process improvement protocol was 41.2% pre-intervention week 1 (164/398) to 78.4% post-intervention week 60 (480/612; P < 0.0001). Pharmacists reviewed and evaluated twice as many patients during the final 4 weeks (1680) compared to the first 4 weeks (834; P < 0.0001).
 
 
Am J Infect Control 2015 Jun
Published Online: June 19, 2015
 
Design and analysis of a pharmacist-enhanced antimicrobial stewardship program in Thailand.
 
There were 150 patients in the SoC group, 104 in the IDCP group, and 320 in the IDCP plus IDC group. Most antibiotic prescriptions were for empirical therapy (n = 373, 65%), and the top-ranked indications were infections of the respiratory tract (n = 287, 50%) and urinary tract (n = 165, 29%). By multivariate analysis, compared with SoC, the 2 other groups were less likely to be prescribed inappropriate antibiotic use (P < .001), had de-escalation of antibiotics (P < .001), received antibiotics <7 days (P < .001), and had subjects with shorter hospital LOSs (P < .001). There were no group differences in mortality.
 
 
Am J Health Syst Pharm 2014:227-30.
 
Incorporating pharmacy student activities into an antimicrobial stewardship program in a long-term acute care hospital.
 
The rate of patient discharge to skilled nursing facilities was significantly higher during the intervention period versus the baseline period (p = 0.016); no other significant comparisons were found. The mean ± S.D. antimicrobial costs per patient day were $75.37 ± $11.85 in the baseline period and $64.13 ± $13.78 in the intervention period (p = 0.022). This difference represents a cost savings of $261,630 during the two-year intervention period.
 
 
Clin. Infect. Dis. 2014 Oct 15.:S108-11.
 
Outcomes and metrics for antimicrobial stewardship: survey of physicians and pharmacists.
 
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We conducted a survey to compare antimicrobial stewardship outcomes considered to be most important with those used in practice as metrics. Respondent opinion of important outcomes compared with those collected as metrics were antimicrobial use (15% vs 73%), antimicrobial cost (10% vs 73%), appropriateness of antimicrobial use (56% vs 51%), infection-related mortality rate (34% vs 7%), and antibiotic-associated length of stay (22% vs 12%). Patient outcomes are important to many practitioners but are rarely used as metrics.
 
 
Am J Health Syst Pharm 2014 Jun 15; 71(12):1019-28.
 
Evaluation of dedicated infectious diseases pharmacists on antimicrobial stewardship teams.
In the year after ASP implementation, aggregate direct antimicrobial acquisition costs at the two study sites decreased 17.3% from prior-year levels and increased by 9.1% at the three comparator sites. Significant decreases in the consumption of targeted antimicrobial classes (antipseudomonals, quinolones, and agents active against methicillin-resistant Staphylococcus aureus) were observed at the ASP sites. Among the 2446 ASP interventions recorded, 72% involved discontinuing or narrowing the use of broad-spectrum antimicrobials. Although rates of health care-associated Clostridium difficile infection were little changed at both study sites after ASP implementation, HSMR data indicated substantial gains in combating sepsis and C. difficile and respiratory infections.
 
 
JAMA 2013 Jun 12; 309(22):2345-52.
 
Effect of an outpatient antimicrobial stewardship intervention on broad-spectrum antibiotic prescribing by primary care pediatricians: a randomized trial.
 
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Broad-spectrum antibiotic prescribing decreased from 26.8% to 14.3% (absolute difference, 12.5%) among intervention practices vs from 28.4% to 22.6% (absolute difference, 5.8%) in controls (difference of differences [DOD], 6.7%; P = .01 for differences in trajectories). Off-guideline prescribing for children with pneumonia decreased from 15.7% to 4.2% among intervention practices compared with 17.1% to 16.3% in controls (DOD, 10.7%; P < .001) and for acute sinusitis from 38.9% to 18.8% in intervention practices and from 40.0% to 33.9% in controls (DOD, 14.0%; P = .12). Off-guideline prescribing was uncommon at baseline and changed little for streptococcal pharyngitis (intervention, from 4.4% to 3.4%; control, from 5.6% to 3.5%; DOD, -1.1%; P = .82) and for viral infections (intervention, from 7.9% to 7.7%; control, from 6.4% to 4.5%; DOD, -1.7%; P = .93).
 
 
Ann Pharmacother 2012 Nov; 46(11):1484-90.
 
Antimicrobial stewardship pharmacist interventions for coagulase-negative staphylococci positive blood cultures using rapid polymerase chain reaction.
 
In the postintervention group, antistaphylococcal antibiotics were discontinued 32.0 hours sooner from time of rPCR result (median 57.7 vs 25.7 hours; p = 0.005), total antibiotic exposure decreased 43.5 hours (97.6 vs 54.1 hours; p = 0.011), infection-related LOS decreased 4.5 days (10 vs 5.5 days; p = 0.018), and infection-related costs decreased $8338 ($28,973 vs $20,635; p = 0.144). The pharmacist initiated vancomycin in 7 (21.9%) patients with CoNS bloodstream infections.
 
 
Int J Clin Pharm 2012 Apr; 34(2):290-4.
 
Impact of the pharmacist on a multidisciplinary team in an antimicrobial stewardship program: a quasi-experimental study.
 
After the start of ASP there was a significant reduction of consumption of all antimicrobials. The pharmacist contributed to the significant reduction in consumption of fluoroquinolones, clindamycin and ampicillin/sulbactam and in increase in total cephalosporins use in stage 3. Adherence rate to the ASP team recommendations was 64.1%. There was a significant reduction of 69% in hospital antibiotics costs.
 
 
J Pharm Pract 2012 Apr; 25(2):190-4.
 
Pharmacist-managed antimicrobial stewardship program for patients discharged from the emergency department.
 
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Positive cultures were identified in 177 patients, 104 and 73 in pre- and post-implementation groups, respectively. Median time to culture review in the pre-implementation group was 3 days (range 1-15) and 2 days (range 0-4) in the post-implementation group (P = .0001). There were 74 (71.2%) and 36 (49.3%) positive cultures that required notification in the pre- and post-implementation groups, respectively, and the median time to patient or PCP notification was 3 days (range 1-9) and 2 days (range 0-4) in the 2 groups (P = .01). No difference was seen in the appropriateness of therapy. 
 
 
Am J Health Syst Pharm 2010 May 1; 67(9):746-9.
 
Implementation of a care bundle for antimicrobial stewardship.
 
A total of 160 patients and 442 antibiotic orders were evaluated. During the intervention phase, 168 interventions were made, with an acceptance rate of 91%. The rate of appropriate deescalation rose from 72% to 90% (p = 0.01). Compliance with all quality indicators rose from 16% to 43% (p < 0.001).
 
Pharmacotherapy 2009 May; 29(5):593-607.
 
Insights from the Society of Infectious Diseases Pharmacists on antimicrobial stewardship guidelines from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America.
 
In 2007, the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America published a document that addressed the major considerations for the justification, description, and conduct of antimicrobial stewardship programs. Our document is intended to continue the dialogue of these formalized programmatic strategies. We briefly review the guidelines, including the two primary strategies (prospective auditing with feedback, and preauthorization), and the supplemental strategies (education, information technology, transitional therapy, de-escalation or streamlining, and dose optimization). Discussions are introduced or furthered in the areas of program goals, barriers and solutions, and outcome measures. Definition and training of infectious diseases pharmacists are presented in detail. We offer keys to future success, which include continued collaboration and expanded use of information technology.
 
 
J. Hosp. Infect. 2007 Jun.:73-81.
 
The role of microbiology and pharmacy departments in the stewardship of antibiotic prescribing in European hospitals.
 
A total of 124 hospitals provided both datasets. 121 (71%) of Clinical Microbiology departments and 66 (41%) of Pharmacy departments provided out of hours clinical advice. 70 (41%) of microbiology/infectious disease specialists and 28 (16%) of pharmacists visited wards on a daily basis. The majority of laboratories provided monitoring of blood cultures more than once per day and summary data of antibiotic susceptibility testing (AST) for empiric prescribing (86% and 73% respectively). Most of the key laboratory and pharmacy-led initiatives examined did not vary significantly by geographical location. Hospitals from the North and West of Europe were more likely to examine blood cultures more than once daily compared with other regions (p < 0.01). Hospitals in the North were least likely routinely to report susceptibility results for restricted antibiotics compared to those in the South-East and Central/Eastern Europe (p < 0.01). Hospital wards in the North were more likely to hold antibiotic stocks (100%) compared with hospitals in the South-East which were least likely (39%) (p < 0.001). Conversely, hospital pharmacies in the North were least likely to dispense antibiotics on an individual patient basis (16%) compared with hospital pharmacies from Southern Europe (60%) (p = 0.01). Hospitals that routinely reported susceptibility results for restricted antibiotics had significantly lower median total antibiotic use in 2001 (p < 0.01). Hospitals that provided prescribing advice outside normal working hours had significantly higher antibiotic use compared with institutions that did not provide this service (p = 0.01). 
 
 
Pharmacotherapy 2004 Jul; 24(7):896-908.
 
Antimicrobial stewardship programs as a means to optimize antimicrobial use. Insights from the Society of Infectious Diseases Pharmacists.
 
Each year, approximately 2 million people in the United States contract an infection during a hospital stay. An increasing percentage of these institutionally acquired infections are attributed to antimicrobial-resistant organisms. At the same time, studies and surveys suggest that as much as half of all antimicrobial use is inappropriate. Recommendations for preventing and reducing antimicrobial resistance in hospitals stress the importance of improving antimicrobial use, referred to as antimicrobial stewardship, at the institutional level. Antimicrobial stewardship programs have served as wake-up calls to both clinicians and health care administrators. We review the more recent literature concerning the impact of antimicrobial stewardship programs on costs, outcomes, and resistance and summarize important considerations for implementation of these programs.
 
 
日本からのASP論文
 
J Clin Pharm Ther 2015 Dec 18.
Article first published online: 18 DEC 2015
 
Early optimization of antimicrobial therapy improves clinical outcomes of patients administered agents targeting methicillin-resistant Staphylococcus aureus.
 
The time to administer effective antimicrobials was significantly (median number of days, 3 before vs. 0 after, P < 0·001) shortened, and the rate of de-escalation was significantly elevated (47·1% vs. 96·2%, P < 0·001) after implementation of daily review. The 60-day clinical failure associated with Gram-positive bacterial infection was significantly reduced (33·3% vs. 17·6%, P = 0·007) after intervention.
 
 
J. Infect. Chemother. 2016 Feb; 22(2):90-5.
 
Effect of interventions by an antimicrobial stewardship team on clinical course and economic outcome in patients with bloodstream infection.
 
We identified a total of 308 cases of BSI from January to December, 2012 (pre-intervention group) and 324 cases of BSI from April, 2013 to March, 2014 (post-intervention group). No significant differences in the in-hospital mortality or 30-day mortality rates were observed between both the groups. Inappropriate therapy was initiated in a significantly lower proportion of patients in the post-intervention group (18.5% vs. 11.4%; P = 0.012). Multivariate analysis confirmed that inappropriate therapy was significantly associated with in-hospital mortality (odds ratio, 2.62; 95% confidence interval, 1.42-4.82; P = 0.002).
 
 
J Pharm Policy Pract 2014; 7(1):10.
 
Contribution of antimicrobial stewardship programs to reduction of antimicrobial therapy costs in community hospital with 429 Beds --before-after comparative two-year trial in Japan.
 
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In the study, recommendations were made for 465 cases out of 1,427 cases subject to the core strategy, and recommendations for 251 cases (54.0%) were accepted. After ASP, the antimicrobial therapy costs decreased by 25.8% (P = 0.005) from those before ASP. Among the secondary outcomes, significant changes were observed in the amount of aminoglycosides used, which decreased by 80.0% (P < 0.001) and the detection rate of MRSA, which decreased by 48.3% (P < 0.001).
 
 
Int. J. Clin. Pract. 2012 Oct; 66(10):999-1008.
 
Outcome measurement of extensive implementation of antimicrobial stewardship in patients receiving intravenous antibiotics in a Japanese university hospital.
 
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Prolonged use of antibiotics over 2 weeks was significantly reduced after active implementation of antimicrobial stewardship (2.9% vs. 5.2%, p < 0.001). Significant reduction in the antimicrobial consumption was observed in the second-generation cephalosporins (p = 0.03), carbapenems (p = 0.003), aminoglycosides (p < 0.001), leading to a reduction in the cost of antibiotics by 11.7%. The appearance of methicillin-resistant Staphylococcus aureus and the proportion of Serratia marcescens to Gram-negative bacteria decreased significantly from 47.6% to 39.5% (p = 0.026) and from 3.7% to 2.0% (p = 0.026), respectively. Moreover, the mean hospital stay was shortened by 2.9 days after active implementation of antimicrobial stewardship.
 
 
Yakugaku Zasshi 2010 Aug; 130(8):1105-11.
 
Impact of antimicrobial stewardship by infection control team in a Japanese teaching hospital.
 
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Although the number of inpatient admissions and operations increased 1.53- and 1.39-fold, respectively, in the seven years from 2001 to 2007, the expenditure on specific antimicrobials decreased markedly with AUD of specific antimicrobials decreasing from 39.6 to 29.2. The percentage of inpatients receiving specific antimicrobials decreased from 19.8% to 9.8%, and the ratio of the number of inpatients administered a specific antimicrobial within seven days to the number of inpatients administered each specific antimicrobial increased to over 60%. This led to reduction in the total expenditure of antimicrobials by about 100 million yen annually. The incidence of hospital-associated MRSA (HA-MRSA) infection decreased from 0.93% (2003) to 0.68% (2007).