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.

De-escalation ちょこっと復習

De-escalationは、薬剤師参画として重要です。
 
耐性菌予防やコストはもちろんですが、
副作用予防など守りに徹する薬剤師が責めの提案議論できる場面の一つです。
 
我々の施設において、De-escalation提案は
ディフェンダーフリーキック能力と呼んでいますw
 
重症度判断とフォローが難しいのですが、
勇気出して、主治医に相談して欲しいです。
 
ただし、欠点は定義がふわふわ。
 
なお
Antimicrobial stewardships 論文は、どのくらいDe-escalation推奨したか確認すると、薬剤師の本気度が感じられると思います。
是非、確認してみて下さい。
 
De-escalationエビデンスは、まだまだ少ないのですが、有名論文の結果部分を切り取って振り返り。
 
REVIEW
 
Clin Infect Dis. (2015) 
First published online: December 23, 2015
 
A systematic review of the definitions, determinants and clinical outcomes of antimicrobial de-escalation in the intensive care unit.
 
free 今のところ?
 
De-escalation (DE) is a strategy to reduce the spectrum of antimicrobials and aims to prevent the emergence of bacterial resistance. We present a systematic review describing the definitions, determinants and outcomes associated with DE. We included 2 RCTs and 12 cohort studies. There was considerable variability in the definition of DE. It was more frequently performed in patients with broad-spectrum and/or appropriate antimicrobial therapy (p=0.05 to 0.002), when more agents were used (p=0.002), in the absence of MDR pathogens (p<0.05). Where investigated, lower or improving severity scores were consistently associated with DE (p=0.04 to <0.001). The pooled effect of DE on mortality is protective (RR 0.68, 95% CI 0.52-0.88). As the determinants of DE are markers of clinical improvement and/or of lower risk of treatment failure this effect on mortality cannot be retained as evidence. None of the studies were designed to investigate the effect of DE on antimicrobial resistance.
 
 mortality rate

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13 : Empiric broad-spectrum antibiotic therapy of nosocomial pneumonia in the intensive care unit: a prospective observational study. Critical care (London, England) 2006; 10(3): R78
15 : De-escalation therapy rates are significantly higher by bronchoalveolar lavage than by tracheal aspirate. Intensive care medicine 2007; 33(9): 1533-40. 
17 : Does de-escalation of antibiotic therapy for ventilator-associated pneumonia affect the likelihood of recurrent pneumonia or mortality in critically ill surgical patients? The Journal of trauma 2009; 66(5): 1343-8
24 : De-escalation after empirical meropenem treatment in the intensive care unit: Fiction or reality? Journal of Critical Care 2010; 25(4): 641-6
22 : De-escalation as part of a global strategy of empiric antibiotherapy management. A retrospective study in a medicosurgical intensive care unit. Critical Care 2010; 14(6). 
18 :  Impact of de-escalation therapy on clinical outcomes for intensive care unit-acquired pneumonia. Critical Care 2011; 15(2). 
20 : Antibiotic strategies in severe nosocomial sepsis: Why do we not de-escalate more often? Critical Care Medicine 2012; 40(5): 1404-9. 
11 : Early use of imipenem/cilastatin and vancomycin followed by de-escalation versus conventional antimicrobials without de-escalation for patients with hospital-acquired pneumonia in a medical ICU: A randomized clinical trial. Critical Care 2012: R28
21 : Factors influencing the implementation of antibiotic de-escalation and impact of this strategy in critically ill patients. Critical Care 2013; 17(4). 
19 : Does antibiotic de-escalation for nosocomial pneumonia impact intensive care unit length of stay? Infectious Diseases in Clinical Practice 2013; 21(3): 172- 6.
16 : De-escalation of antimicrobial treatment in neutropenic patients with severe sepsis: results from an observational study. Intensive care medicine 2014; 40(1): 41-9.
14 :  Deescalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive care medicine 2014; 40(1): 32- 40.
12 :  De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial. Intensive care medicine 2014. 
23 : Antimicrobial de-escalation in septic cancer patients: is it safe to back down? Intensive care medicine 2015.
 
 
RCT
 
Intensive Care Med 2014 Oct; 40(10):1399-408.
 

De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial.

 
The median duration of ICU stay was 9 [interquartile range (IQR) 5-22] days in the de-escalation group and 8 [IQR 4-15] days in the continuation group, respectively (P = 0.71). The mean difference was 3.4 (95 % CI -1.7 to 8.5). A superinfection occurred in 16 (27 %) patients in the de-escalation group and six (11 %) patients in the continuation group (P = 0.03). The numbers of antibiotic days were 9 [7-15] and 7.5 [6-13] in the de-escalation group and continuation group, respectively (P = 0.03). Mortality was similar in both groups.
 
 
Critical Care 2012, 16:R28
 
Early use of imipenem/cilastatin and vancomycin followed by de-escalation versus conventional antimicrobials without de-escalation for patients with hospital-acquired pneumonia in a medical ICU: a randomized clinical trial.
 
free
 
Between November 2004 and October 2006, 109 MICU patients with HAP were enrolled. Initial antimicrobial adequacy was significantly higher in the DE than in the NDE group for Gram-positive organisms (100% versus 14.3%; P<0.001), but not for Gram-negative organisms (64.3% versus 85.7%; P=0.190). Mean intensive care unit (ICU) stay, and 14-day, 28-day, and overall mortality rates did not differ in the two groups. Among culture-positive patients, mortality from methicillin-resistant Staphylococcus aureus (MRSA) pneumonia was higher in the DE group, even after early administration of vancomycin. Multidrug-resistant organisms, especially MRSA, were more likely to emerge in the DE group (adjusted hazard ratio for emergence of MRSA, 3.84; 95% confidence interval, 1.06 to 13.91).
 

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Journal Article
 
Surg Infect (Larchmt) 2016 Jan; 17(1):48-52.
 
De-Escalation of Antibiotics Does Not Increase Mortality in Critically Ill Surgical Patients.
 
A total of 2,658 infections were identified. De-escalation was identified for 995 infections and non-deescalation occurred in 1,663. Patients were similar in age (de-escalated 55 ± 16 y vs. 56 ± 16, p = 0.1) and gender (de-escalated 60% males vs. 58%, p = 0.4). There were substantially greater APACHE II scores in non-deescalated patients (15 ± 8 vs. 14 ± 8, p = 0.03). A greater mortality rate among patients with infections treated without de-escalation was observed compared with those treated with de-escalation (9% vs. 6%, p = 0.002). Total antibiotic duration was substantially longer in the de-escalated group (15 ± 13 d vs. 13 ± 13, p = 0.0001). Multivariable analysis found that de-escalation decreased mortality rates (OR = 0.69; 95%CI, 0.49-0.97; p = 0.04) and high APACHE II score independently increased mortality rates (OR = 1.2; 95%CI, 1.1-1.2; p = 0.0001). Other parameters included were age and infection site.
 
 
J. Antimicrob. Chemother. 2016 Feb; 71(2):539-46.
 
Antimicrobial de-escalation of treatment for healthcare-associated pneumonia within the Veterans Healthcare Administration.
 
Among 9319 patients, the de-escalation proportion was 28.3% (95% CI 27.4-29.2), which varied 6-fold across facilities [median (IQR) facility-level de-escalation proportion 29.1% (95% CI 21.7-35.6)]. Variables associated with de-escalation included initial broad-spectrum therapy (OR 1.5, 95% CI 1.4-1.5 for each 10% increase in spectrum), collection of respiratory tract cultures (OR 1.1, 95% CI 1.0-1.2) and care in higher complexity facilities (OR 1.3, 95% CI 1.1-1.6). Respiratory tract cultures were collected from 35.3% (95% CI 32.7-37.7) of patients.
 
 
Intensive Care Med 2015 Nov; 41(11):1931-40.
 
Antifungal de-escalation was not associated with adverse outcome in critically ill patients treated for invasive candidiasis: post hoc analyses of the AmarCAND2 study data.
 
Among the 647 included patients, early de-escalation at day 5 after antifungal initiation occurred in 142 patients (22%), including 48 (34%) patients whose SAT was stopped before day 6. After adjustment for the baseline confounders, early SAT de-escalation was the solely factor not associated with increased 28-day mortality (RR 1.12, 95% CI 0.76-1.66).
 
 
Intensive Care Med 2015 Nov; 41(11):2022-3.
 
Antimicrobial de-escalation in septic cancer patients: is it safe to back down?
 
de-escalating antimicrobial therapy in septic cancer patients admitted to the ICU from the UCC was associated with shorter ICU and hospital LOS. No adverse effect of de-escalation on mortality was found. Future sepsis studies should focus on investigating whether de-escalation can definitively improve patient outcomes and/or slow emerging antimicrobial resistance.
 
 
Clin. Microbiol. Infect. 2015 Oct; 21(10):936.e11-8.
 
De-escalation therapy among bacteraemic patients with community-acquired pneumonia.
 
de-escalation therapy (DET)  was not associated with an increased risk of 30-day mortality
 
 
J. Antimicrob. Chemother. 2015 Apr; 70(4):1219-25.
 
Safety and clinical outcomes of carbapenem de-escalation as part of an antimicrobial stewardship programme in an ESBL-endemic setting.
 
The de-escalation recommendations for 300 patients were evaluated; 204 (68.0%) were accepted. The patient demographics and disease severity were similar. The clinical success rates were similar [de-escalated versus not de-escalated, 183/204 (89.7%) versus 85/96 (88.5%), P=0.84], as was the survival at hospital discharge [173/204 (84.8%) versus 79/96 (82.3%), P=0.58]. In the de-escalated group, the duration of carbapenem therapy was shorter (6 versus 8 days, P<0.001), the rate of adverse drug reactions was lower [11/204 (5.4%) versus 12/96 (12.5%), P=0.037], there was less diarrhoea [9/204 (4.4%) versus 12/96 (12.5%), P=0.015], there was a lower incidence of carbapenem-resistant Acinetobacter baumannii acquisition [4/204 (2.0%) versus 7/96 (7.3%), P=0.042] and there was a lower incidence of CDAD [2/204 (1.0%) versus 4/96 (4.2%), P=0.081].
 
 
Infect Control Hosp Epidemiol 2013 Dec; 34(12):1310-3.
 
Carbapenem de-escalation therapy in a resource-limited setting.
 
Pulmonary infection (P=.01) and an infectious diseases consultation (P=.04) were associated with carbapenem de-escalation; pulmonary infection and septic shock were associated with unsuccessful de-escalation. Successful de-escalation was associated with lower mortality (0% vs 23%; P<.001) and shorter duration of carbapenem use (4 vs 10 days; P ≤ .001).
 
 
Intensive Care Med 2014 Jan; 40(1):32-40.
 
De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock.
 
A total of 712 patients with severe sepsis or septic shock at ICU admission were treated empirically with broad-spectrum antibiotics. Of these, 628 were evaluated (84 died before cultures were available). De-escalation was applied in 219 patients (34.9%). By multivariate analysis, factors independently associated with in-hospital mortality were septic shock, SOFA score the day of culture results, and inadequate empirical antimicrobial therapy, whereas de-escalation therapy was a protective factor [Odds-Ratio (OR) 0.58; 95% confidence interval (CI) 0.36-0.93). Analysis of the 403 patients with adequate empirical therapy revealed that the factor associated with mortality was SOFA score on the day of culture results, whereas de-escalation therapy was a protective factor (OR 0.54; 95% CI 0.33-0.89). The PS-adjusted logistic regression models confirmed that de-escalation therapy was a protective factor in both analyses. De-escalation therapy was also a protective factor for 90-day mortality.
 
 
Infect Control Hosp Epidemiol 2013 Dec; 34(12):1259-65.
 
The use of best practice alerts with the development of an antimicrobial stewardship navigator to promote antibiotic de-escalation in the electronic medical record.
 
Antibiotic use and response data were collected 1 day before stewardship recommendation via the best practice alert (BPA) tool and 1 day after the BPA tool response. A total of 1,285 stewardship BPAs were created. Two hundred and forty-four (18.9%) of the BPAs were created and acted upon within 72 hours for the purpose of de-escalation: 169 (69%) were accepted, 30 (12%) were accepted with modification, and 45 (18%) were rejected. Statistically significant decreases in total antibiotic use as well as in use of broad-spectrum (anti-methicillin-resistant Staphylococcus aureus and anti-pseudomonal) agents occurred when accepted recommendations were compared with rejected recommendations.
 
 
Infection 2013 Feb; 41(1):203-10.
 
De-escalation of antimicrobial therapy for bacteraemia due to difficult-to-treat Gram-negative bacilli.
 
The treatment was initially appropriate in 79 of 133 patients (59 %), of whom 49 (62 %) were candidates for and 28 (57 %) underwent treatment de-escalation. No treatment failure was observed among these 28 patients, while 2 of 11 patients (18 %) whose treatment was not de-escalated died (p = 0.13). The median cost of antimicrobials was <euro>250/patient lower in the de-escalated than in the non-de-escalated group (p < 0.001).
 
 
Infection 2013 Feb; 41(1):211-4.
 
Why is antimicrobial de-escalation under-prescribed for urinary tract infections?
 
Eighty patients were included. De-escalation was prescribed for 32 of 69 patients for whom it was possible from both a bacteriological and clinical point of view (46 %, 95 % CI, 34-59 %). Initial treatment was switched to amoxicillin (n = 21), co-amoxiclav (n = 2), or cotrimoxazole (n = 8). Thirteen conditions justifying not de-escalating antibacterial therapy were detected in 11 of 48 patients who were not de-escalated (23 %, 95 % CI, 12-37 %): shock, n = 5; renal abscess, n = 1; obstructive uropathy, n = 4; bacterial resistance or clinical contraindication to both cotrimoxazole and β-lactams, n = 3.
 
 
Crit Care 2011; 15(2):R79.
 
Impact of de-escalation therapy on clinical outcomes for intensive care unit-acquired pneumonia.
 
The 137 patients comprised 44 (32.1%) who received de-escalation therapy and 93 in the non-de-escalation group. The de-escalation group showed a lower pneumonia-related mortality rate than the non-de-escalation group by day 14 (2.3% vs. 10.8%, respectively; P = 0.08) and by day 30 (2.3% vs. 14%, respectively; P = 0.03) after the diagnosis of pneumonia. The variables independently associated with ICU-acquired pneumonia-related mortality included the Acute Physiology and Chronic Health Evaluation II (APACHE II) score and the modified Clinical Pulmonary Infection Score (CPIS) after 5 days with pneumonia. The non-de-escalation group had significantly higher APACHE II score and modified CPIS after 5 days with ICU-acquired pneumonia compared to the de-escalation group. Among all patients, 20.4% (28 of 137) had negative cultures for pathogens, and 42.9% (12 of 28) received de-escalation therapy. The latter 12 patients received de-escalation therapy and survived 30 days after the diagnosis of pneumonia.
 
 
Crit Care 2010; 14(6):R225.
 
De-escalation as part of a global strategy of empiric antibiotherapy management. A retrospective study in a medico-surgical intensive care unit.
 
A total of 116 patients were studied corresponding to 133 infections. Antibiotic therapy was de-escalated in 60 cases (45%). De-escalation, primarily accomplished by a reduction in the number of antibiotics used, was observed in 52% of severe sepsis or septic shock patients. Adequate empiric antibiotic and use of aminoglycoside were independently linked with de-escalation. De-escalation therapy was associated with a significant reduction of recurrent infection (19% vs 5% P = 0.01). Mortality was not changed by de-escalation.
 
 
J Trauma 2009 May; 66(5):1343-8.
 
Does de-escalation of antibiotic therapy for ventilator-associated pneumonia affect the likelihood of recurrent pneumonia or mortality in critically ill surgical patients?
 
One hundred thirty-eight of 1,596 SICU patients developed VAP during the study period (8.7%). For VAP patients, the mean Acute Physiologic and Chronic Health Evaluation III score was 82.7 points with a mean age of 63.8 years. The RP rate was 30% and did not differ between patients receiving DT (27.3%) and those who did not receive DT (35.1%). Overall mortality was 37% (55% predicted by A3 norms) and did not differ between those receiving DT (33.8%) or not (42.1%). The most common pathogens for primary VAP were methicillin-resistant Staphylococcus aureus (14%), Escherichia coli (11%), and Pseudomonas aeruginosa (9%) whereas P. aeruginosa was the most common pathogen in RP. The AIT for all VAP was 93%. De-escalation of therapy occurred in 55% of patients with AIT whereas 8% of VAP patients required escalation of antibiotic therapy. The most commonly used initial antibiotic choice was vancomycin/piperacillin-tazobactam (16%) and the final choice was piperacillin-tazobactam (20%). Logistic regression demonstrated no specific parameter correlated with development of RP. Higher A3 (Odds ratio, 1.03; 95% confidence interval, 1.01-1.05) was associated with mortality whereas lack of RP (odds ratio, 0.31; 95% confidence interval, 0.12-0.80), and AIT reduced mortality (odds ratio, 0.024; 95% confidence interval, 0.007-0.221). Age, gender, individual pathogen, individual antibiotic regimen, and the use of DT had no effect on mortality.
 
 
Crit Care Med. 2004 Nov;32(11):2183-90.
 
De-escalation therapy in ventilator-associated pneumonia.
 
One hundred and twenty-one episodes of ventilator-associated pneumonia were diagnosed. Change of therapy was documented in 56.2%, including de-escalation (the most frequent cause) in 31.4% (increasing to 38% if isolates were sensitive). Overall intensive care unit mortality rate was 32.2%. Inappropriate antibiotic therapy was identified in 9% of cases and was associated with 14.4% excess intensive care unit mortality. Quantitative tracheal aspirates and bronchoscopic samples (58 protected specimen brush and three bronchoalveolar lavage) were associated with 32.7% and 29.5% intensive care unit mortality and 29.3% and 34.4% de-escalation rate. De-escalation was lower (p < .05) in the presence of nonfermenting Gram-negative bacillus (2.7% vs. 49.3%) and in the presence of late-onset pneumonia (12.5% vs. 40.7%). When the pathogen remained unknown, half of the patients died and de-escalation was not performed.