Review
Copyright ©The Author(s) 2015.
World J Crit Care Med. Feb 4, 2015; 4(1): 13-28
Published online Feb 4, 2015. doi: 10.5492/wjccm.v4.i1.13
Table 1 Non-protocolised antibiotic stewardship programmes
Kollef et al[18]19979351601Prospective cohort study Follow-up 6 moIncidence of VAP Incidence of bloodstream infection and sepsis Duration of mechanical ventilation LOS Mortality680Non-protocolised Components Rotating antibiotic schedule1 Positive study 2 ↓ in resistant Gram negative organisms 3 ↓ in VAP incidence 4 No change to mortality 5 No change to LOS1 No information on antibiotic usage 2 6 mo follow-up period only
Evans et al[91]19989435330Prospective observational study Follow-up 1 yrAntibiotic use Antibiotic cost Cost of hospitalisation Number of adverse events caused by anti-infective agents No. of days of excessive antibiotic dosage LOS Mortality1681Non-protocolised Components Computerised decision support tool1 Positive study 2 ↓ in total antibiotics cost 3 No change in DDD 4 ↓ in susceptibility-mismatch 5 ↓ in allergy-mismatch 6 ↓ of mortality 7 ↓ of LOS from 4.9 d to 2.7 d (4.9 to 8.3 d if overridden)1 Less patients in post-intervention group 2 Young patients (mean age < 50 yr)
Price et al[84]199910548192Retrospective observational study Follow-up 1 moAntibiotic cost Antibiotic resistance LOS321Non-protocolised Components Antibiotic guideline1 Positive study 2 77% ↓ in antibiotic cost 3 No change to LOS 4 No change to mortality1 Surgical ICU only 2 1 mo FU follow-up 3 High compliance rate with guideline (95.6%) 4 High baseline APACHEII score (38.0-39.1)
Roger et al[64]200011089498Retrospective observational study Follow-up 2 moAntibiotic use Antibiotic cost61Non-protocolised Components ID specialist input1 Positive study 2 ↓ in duration of treatment from mean 23 d to 13 d 3 ↓ in total antibiotic days from 596 d to 455 d 4 19% ↓ in total antibiotic cost 5 No change to mortality 6 No change to LOS1 2 mo follow-up period
Fox et al[63]200111712090Retrospective observational study Follow-up 1 yrAntibiotic use LOS Days on mechanical ventilation Days with fever No. of cultures performed Antibiotic resistance Antibiotic cost295Non-protocolised Components ID specialist input1 Negative study 2 No change to antibiotic usage 3 57% ↓ in antibiotics cost 4 ↑ infection rate 5 No change in LOS1 Trauma ICU only 2 Young patients (age < 35 yr)
Mullett et al[90]200111581483Retrospective observational study Follow-up 6 moAntibiotic cost Rate of anti-infective sub-therapeutic and excessive-dose days1758Non-protocolised Components Computerised decision support tool1 Negative study 2 No change to total cost of antibiotics 3 ↓ of excessive dose days and sub-therapeutic days (i.e., dose optimisation)1 Paediatric ICU only 2 Significantly younger patients in post-intervention group
Dos Santos et al[61]200314552737Retrospective observational study Follow-up 1 yrAntibiotic use Antibiotic cost1473Non-protocolised Components ID specialist input1 Positive study 2 ↓ in cephalosporin, carbapenems and vancomycin usage 3 ↑ in penicillin usage 4 ↓ of cost by 37%1 Limited patient characteristics 2 No information on antibiotic resistance 3 No information on LOS and mortality
Du et al[62]200312682477Prospective observational study Follow-up 1 yrAntibiotic use Antibiotic resistance LOS1205Non-protocolised Components Antibiotic restriction Senior clinician input1 Positive study 2 ↓ in 3rd generation cephalosporin usage 3 ↑ in cefepime usage 4 No change to resistance pattern 5 ↓ in LOS from 13.1 d to 9.3 d1 Significant reduction in APACHEII scores and organ failure % in post-intervention group 2 High baseline Pseudomonas and Acinetobacter rate 3 No information on mortality
Geissler et al[82]200312528022Retrospective observational study Follow-up 4 yrAntibiotic use Antibiotic resistance Antibiotic cost1704Non-protocolised Components Antibiotic guideline1 Positive study 2 35% ↓ in antibiotic days 3 37% ↓ in antibiotics cost 4 Significant ↓ in total number of resistant isolates1 High baseline mortality 2 No data on LOS
Micek et al[81]200415136392RCT Follow-up 14 moAntibiotic use Incidence of VAP LOS Mortality290Non-protocolised Components Antibiotic discontinuation policy1 Positive study 2 ↓ of antibiotic treatment duration 3 No change to LOS 4 No change to mortality1 Medical ICU only 2 Limited microbiology data
Aubert et al[80]200515620440Retrospective observational study Follow-up 1 yrAntibiotic use Microbiological profile and antibiotic resistance781Non-protocolised Components Antibiotic restriction1 Positive study 2 ↓ in fluoroquinolone usage by 75.8% 3 ↓ in usage of aminoglycosides and macrolides 4 ↓ of antibiotic resistance in Pseudomonas 5 No change to mortality 6 No change to LOS1 No information on antibiotic usage
Sintchenko et al[89]200515802478Prospective observational study Follow-up 6 moAntibiotic use LOS Mortality5176 patient-daysNon-protocolised Components Computerised decision support tool1 Positive study 2 Significant ↓ in total DDD from 1925 to 1606, particularly vancomycin and beta-lactam resistant penicillins 3 ↓ of mean LOS from 7.15 to 6.22 d 4 No change to mortality1 6 mo follow-up period 2 No information on antibiotic resistance
Bochicchio et al[88]200616500251Randomised pilot study Follow-up 6 moAntibiotic decision accuracy125Non-protocolised Components Computerised decision support tool1 Positive study 2 ↑ in decision accuracy (verified by ID specialists)1 No information on antibiotic usage 2 No information on antibiotic resistance
Brahmi et al[78]2006a16944257Retrospective observational study Follow-up 2 yrAntibiotic use727Non-protocolised Components Antibiotic restriction1 Positive study 2 Significant ↓ in ceftazidime usage 3 ↓ in tazocin and imipenem resistance 4 ↑ resistance to penicillins1 High baseline rate of VAP patients (63%-70%) 2 High baseline resistance rate among Pseudomonas (59% to tazocin, 58% to ciprofloxacin, 58% to imipenem, 47% to ceftazidime) 3 No info on mortality and LOS
Thursky et al[87]200616415039Prospective observational study Follow-up 6 moAntibiotic use Antibiotic susceptibility-mismatches Mortality1060Non-protocolised Components Computerised decision support tool1 Positive study 2 ↓ of total DDD from 1670 to 1490 3 ↓ in usage of ceftriaxone, vancomycin and carbapenems 4 ↓ of susceptibility-mismatch 5 No change to mortality1 6 mo follow-up period 2 High baseline mortality (19%) 3 Fewer isolates in intervention group 4 No information on LOS
Brahmi et al[79]2006b17027213Prospective cohort study Follow-up 2 yrAntibiotic use Antibiotic resistance318Non-protocolised Components Antibiotic guideline1 Positive study 2 ↓ in duration of treatment from 14.1 to 11.9 d 3 ↓ in antibiotics cost 4 ↓ in LOS from 20.4 to 16.9 d 5 No change to mortality
de Araujo et al[69]200717625777Retrospective observational study Follow-up 1 yrLOS Days of parenteral nutrition Requirement for mechanical ventilation Antibiotic use995Non-protocolised Components Rotating antibiotic schedule1 Positive study 2 ↓ in cefepime usage 3 ↑ in tazocin usage 4 No change to LOS
1 Neonatal ICU only 2 High baseline rates of Pseudomonas and Klebsiella 3 No information on mortality
Ntagiopoulos et al[77]200717629680Retrospective observational study Follow-up 6 moAntibiotic use Antibiotic resistance147Non-protocolised Components Antibiotic restriction1 Positive study 2 ↓ of overall antibiotic usage by 55% 3 ↓ in resistance in Pseudomonas 4 ↑ in resistant strains of Klebsiella and Acinetobacter 5 No change to mortality 6 No change to LOS1 Male predominance 2 High baseline mortality 3 6 mo follow-up period 4 High baseline ceftazidime and fluoroquinolone resistance 5 90% policy compliance among clinicians
Ding et al[76]200818493864Retrospective observational study Follow-up 2 yrAntibiotic use Rate of bacterial resistance900Non-protocolised Components Antibiotic guideline Staff education1 Positive study 2 ↓ in usage of 3rd generation cephalosporin 3 ↑ in usage of beta-lactams 4 ↓ in antibiotics cost 5 No change to LOS1 Paediatric ICU only 2 High baseline antibiotic utilisation (98.7% patients were on antibiotics) 3 High baseline resistance rate (> 60% to cefepime, for E coli and Klebsiella; > 20% to cefepime and imipenem, for Pseudomonas) 4 No information on mortality
Peto et al[60]200819011742Retrospective observational study Follow-up 2 yrAntibiotic use Incidence of sepsis LOS Mortality3403Non-protocolised Components Senior clinician input1 Positive study 2 ↓ of mean DDD from 162.9 to 101.3. 3 No change to LOS 4 No change to mortality1 Surgical ICU only with > 60% neurological patients 2 Low baseline resistance rate 3 Increased patient turnover since intervention
Marra et al[59]200918986735Retrospective observational study Follow-up 10 moAntibiotic resistance360Non-protocolised Components ID specialist input1 Positive study 2 ↓ of total DDD by 12.1% 3 ↓ of resistant strains of Pseudomonas, Klebsiella and Acinetobacter1 High baseline resistance rate 2 Limited patient characteristics 3 Unknown sample size 4 No information on mortality and LOS
Meyer et al[74]201019904488Retrospective observational study Follow-up 3 yrMortality Antibiotic use11887Non-protocolised Components Antibiotic prophylaxis1 Positive study 2 15% ↓ in total antibiotic usage primarily cefuroxime and co-trimoxazole 3 Sustained ↓ to antibiotic usage 4 No change to LOS 5 No change to mortality1 Surgical ICU only 2 Limited resistance data
Yong et al[86]201020215130Retrospective observational study Follow-up 4.5 yrAntibiotic susceptibilities of Pseudomonas, Klebsiella, Acinetobacter and Enterobacteriaceae13295Non-protocolised Components Computerised decision support tool1 Positive study 2 No change to Abx usage 3 ↑ susceptibility to imipenem for Pseudomonas, Acinetobacter and Enterobacter 4 ↑ susceptibility to gentamicin for Pseudomonas and Enterobacter 5 No change to LOS1 Limited patient characteristics 2 No information on mortality
Sharma et al[75]201021206622Retrospective observational study Follow-up 4 moAntibiotic use Antibiotic resistance177Non-protocolised Components Antibiotic restriction1 Negative study 2 ↓ of carbapenem usage 3 ↑ in beta-lactam usage1 Medical ICU only 2 No information on overall antibiotic usage 3 4 mo follow-up period 4 No pre-intervention arm 5 Male predominance 6 High baseline Acinetobacter isolates 7 High baseline resistance rate
Raymond et al[68]201111395583Prospective cohort study Follow-up 1 yrMortality Duration of treatment Antibiotic cost LOS1456Non-protocolised Components Rotating antibiotic schedule1 Positive study 2 ↓ in infection rate by 25% 3 ↓ in infections caused by resistant organisms 4 ↓ in usage of aminoglycosides, vancomycin and antifungals 5 ↑ in usage of clindamycin 6 ↓ in mortality from 38.1% to 15.5% 7 No change to LOS1 No information on overall antibiotic usage 2 High baseline mortality rate
Dortch et al[67]201121091186Retrospective observational study Follow-up 8 yrIncidence of infection caused by MDR organisms Antibiotic use20846Non-protocolised Components Antibiotic guidelines Antibiotic prophylaxis Rotating antibiotic schedules1 Positive study 2 Significant ↓ of total broad spectrum antibiotic usage 3 ↓ in total infection rate 4 ↓ in MDR Pseudomonas, Acinetobacter and Enterobacter isolates1 Surgical ICU only 2 High baseline respiratory infection rate 3 High baseline Enterobacter infection rate 4 Concomitant infection control policy
Slain et al[57]201121687626Retrospective observational study Follow-up 7 yrAntibiotic use Antibiotic resistanceN/ANon-protocolised Components Prospective audits Antibiotic restriction Staff education Antibiotic guidelines Rotating antibiotic schedules1 Positive study 2. Overall ↓ of DDD 3 Fluctuations due to resistance and change in protocols 4 ↑ in resistance to ciprofloxacin, tazocin, cefepime1 Pseudomonas infections only 2 Limited patient characteristics 3 No information on mortality or LOS
Chiu et al[73]201121085051Prospective observational study Follow-up 1 yrAntibiotic use190Non-protocolised Components Antibiotic guideline1 Negative study 2 No change to overall antibiotic usage 3 ↓of vancomycin usage1 Neonatal ICU only 2 Limited patient characteristics 3 Limited resistance data 4 No information on mortality and LOS
Sarraf-Yazdi et al[66]201222445457Retrospective observational study Follow-up 9 yrAntibiotic use Antibiotic resistance321Non-protocolised Components Rotating antibiotic schedules1 Positive study 2 No change in total antibiotic usage 3 ↓ in prescribed dosage of target antibiotics 4 ↓ in resistance against ceftazidime and tazocin1 No LOS or mortality data 2 Limited patient characteristics
Sistanizad et al[72]201324250656Prospective cohort study Follow-up 9 moAntibiotic use Susceptibility of P. aeruginosa, A. baumanni, K. pneumonia and E. coliN/ANon-protocolised Components Antibiotic restriction1 Positive study 2. 60% ↓ in imipenem use 3 ↑ in carbapenem sensitivity for Klebsiella and Pseudomonas1 No mortality and LOS data 2 Limited patient characteristic data
Rimavi et al[58]201323873275Prospective cohort study Follow-up 3 moAntimicrobial use Treatment duration APACHEII score LOS Mechanical ventilation days Mortality rate246Non-protocolised Components ID specialist input1 Positive study 2 Significant ↓ in overall antibiotic usage 3 ↓ of LOS 4 No change to mortality1 Medical ICU only 2 Follow-up period of only 3 mo 3 Limited resistance data
Bauer et al[71]201323571547Retrospective cohort study Follow-up N/ADuration of mechanical ventilation LOS Mortality1433Non-protocolised Components Intermittent vs extended dosing regimen of cefipime1 Positive study 2. ↓ of mortality from 20% to 3% 3 ↓ of LOS 4 ↓ of antibiotic cost per patient by $23183 in extended dosing group1 Pseudomonas infection only 2 No information on antibiotic resistance 3 No follow-up
Ramsamy et al[65]201323725954Retrospective observational study Follow-up 1 yrAntibiotic use Antibiotic resistance227Non-protocolised Components Antibiotic restriction1 Negative study 2 6.5% inappropriate broad- spectrum antibiotic usage1 Trauma ICU 2 No pre-intervention arm 3 Limited patient characteristics 4 No information on mortality and LOS
Apisarnthanarak et al[98]201424485368Retrospective observational study Follow-up 1 yrRate of XDR Acinetobacter baumanni acquisition rate per 1000 patient days Rate of Acinetobacter baumanni infection or colonisation1365Not specified1 Positive study 2 Significant ↓ in XDR Acinetobacter baumanni infection or colonisation rates1 Type of ASP not specified 2 No information on antibiotic usage 3 Concomitant infection control policy (Use of disinfectant-detergent; Enhanced isolation; Active surveillance cultures for all ICU patients)