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Table 2 Characteristics of studies comparing outcomes for continuous versus intermittent infusions of piperacillin-tazobactam

From: Comparing clinical outcomes of piperacillin-tazobactam administration and dosage strategies in critically ill adult patients: a systematic review and meta-analysis

StudyStudy Design/Patient PopulationAge (avg)GenderDosageClinical Cure n/N (%)Mortality n/N (%)Outcome/Suggestions
Grants et al. 2002 [13]
USA
Prospective cohort study
98 ICU patients
CI - 66
II – 65
F - 37
M - 61
CI (n = 47) – 2.25 g LD + 9 g DD over 24 h CI
II (n = 51) – 3.375 g every 6 h over 30 min II
CI- 44/47 (94%)
II- 42/51 (82%)
CI- 1/47 (2.1%)
II- 5/51 (9.8%)
CI provided equivalent clinical and microbiologic to II. CI is a cost-effective alternative to II. CI is well tolerated resulting in CC.
Lau et al.
2006 [14]
USA
Randomised control trial
167 patients with gram +/− bacteria
CI – NR
II – NR
F - NR
M - NR
CI (n = 81) – 13.5 g over 24 h CI
II (n = 86) - 3.375 g every 6 h over 30 min II
CI- 70/81 (86%)
II- 76/86 (88%)
CI- 1/130 (0.8%)
II- 3/132 (2.3%)
CI are a same and reasonable alternate mode of administration. No differences in bacteriological response by pathogen was noted between CI and II.
Rafati et al.
2006 [15]
Iran
Randomised control trial
40 Septic, critically ill patients
CI - 50.1
II – 48
F - 13
M - 27
CI (n = 20) – 2.25 g LD + 9 g DD over 24 h CI
II (n = 20) – 3.375 g every 6 h over 30 min II
CI- 15/20 (75%)
II- 16/20 (70%)
CI- 5/20 (25%)
II- 6/20 (30%)
Clinical efficacy as a CI is superior to that with II. CI significantly reduces severity of illness resulting in clinical cure.
Lodise et al. 2007 [16]
USA
Retrospective cohort Study
194 ICU patients with Pa
PI - 63.2
II – 63.2
F - 75
M - 119
PI (n = 102) – 3.375 g every 8 h over 4 h PI
II (n = 92) - 3.375 g every 4-6 h over 30 min II
PI- NR
II- NR
PI- 5/41 (12.2%)
II-12/92 (13%)
No difference in baseline clinical characteristics were noted between the two dosing regimens, however, mortality rates were significantly lower with PI.
Roberts et al. 2009 [17]
Austrailia
(*) Randomised control trial
16 Critically ill adult patients
CI - 30
II – 41
F - 5
M - 11
CI (n = 8) – 4.5 g LD + 9 g DD over 24 h CI
II (n = 8) – 4 g every 6-8 h over 20 min II
CI- 8/8 (100%)
II- 8/8 (100%)
CI- 0/8 (0%)
II- 0/8 (0%)
Administration by CI with initial loading dose achieves superior PD target and CC when compared with conventional II
Lorente et al. 2009 [18]
Spain
(*) Retrospective cohort study
83 ICU patients suffering VAP
CI - 63.2
II – 61.8
F - 18
M - 65
CI (n = 37) – 4.5 g LD + 18 g DD over 24 h CI
II (n = 46) – 4 g every 6 h over 30 min II
CI- 33/37 (89.2%)
II- 26/46 (56.2%)
CI- 8/37 (21%)
II- 14/46 (30.4%)
Higher clinical efficacy achieved by continuous infusion. Higher DD reached target concentration for pathogens with higher MIC’s
Li et al.
2010 [19]
China
Randomised control trial
66 patients with severe pneumonia
PI – NR
II – NR
F - NR
M - NR
CI (n = 28) - 4.5 g every 8 h over 8 h CI
II (n = 31)- 4.5 g every 8 h over 30 min II
CI- 24/32 (75%)
II- 17/34 (50%)
CI- NR
II- NR
Results obtained from the study suggest clinical advantages of CI compared with II administration in patients suffering with severe pneumonia.
Rose et al.
2011 [35]
USA
Retrospective cohort study
90 ICU patients
PI - 58.4
II – 60.4
F - 13
M - 77
PI (n = 54) – 3.375 g every 8–12 h over 4 h PI
II (n = 36) - 3.375 g every 8–12 h over 30 min II
PI- NR
II- NR
CI- NR
II- NR
PI reduced: (1) days of therapy in ICU, (2) time spent on ventilator, (3) length of ICU and hospital stay and, (4) mortality.
Ye et al.
2011 [20]
China
Randomised control trial
66 ICU patients, gram (−) bacteria
PI – NR
II – NR
F - NR
M - NR
PI (n = 35) - 4.5 g every 8 h over a 3 h PI
II (n = 31) – 4.5 g every 8 h over 30 min II
PI- 24/35 (68.6%)
II- 13/31 (41.9%)
PI- 8/35 (22.9%)
II- 8/31 (25.8%)
Prolonged infusion is superior to traditional regimens and should be recommended as empirical therapy for gram (−) bacteria
Yost et al.
2011 [21]
USA
Retrospective cohort study
270 ICU patients with Pa
PI - 65
II – 62
F - 19
M - 141
PI (n = 186) - 3.375 g every 8 h over 4 h PI
II (n = 84) - dose not recorded, 30 min II
PI- 171/186 (90.3%)
II- 67/84 (79.8%)
PI- 18/186 (9.7%)
II- 17/84 (20.2%)
Pharmacodynamic dosing via PI’s of piperacillin-tazobactam demonstrated positive outcome compared with II. PRT need to further verify findings.
Fahmi et al. 2012 [22]Quasi experimental study
61 ICU patients with VAP
PI – NR
II – NR
F - NR
M - NR
PI (n = 31) – 3.375 g every 8 h over a 4 h PI
II (n = 30) - 3.375 g every 6 h over 30 min II
PI- NR
II- NR
PI- NR
II- NR
No significant difference in clinical outcome of PI and II. Suggest administration by PI or II according to MIC of organism.
Pereira et al. 2012 [23]
Portugal
Retrospective cohort study
346 ICU patients
CI – NR
II – NR
F - NR
M - NR
CI (n = 173) – Majority 18 g DD, every 8 h
II (n = 173) – Majority 18 g DD, 30 min II
CI- 124/173 (71.7%)
II- 124/173 (71.7%)
CI- 49/173 (28.3%)
II- 49/173 (28.3%)
Clinical efficacy of piperacillin-tazobactam dosing was independent of the mode of administration. CI is not associated with a decrease in mortality.
Lee et al.
2012 [24]
USA
Retrospective cohort study
148 ICU patients
PI – 64
II – 69.6
F - 64
M - 84
PI (n = 68) – 3.375 g every 8 h over 4 h PI
II (n = 80)- 2.25 g every 6 h over 30 min II
PI- 55/68 (81%)
II- 50/80 (62%)
PI- 13/68 (19.1%)
II- 30/80 (37.5%)
Results suggest improved 30-day mortality in ICU patients treated via PI vs CI. Clinical benefits of PI at lower MIC’s are less substantial compared with more RO.
Waxier et al. 2012 [25]
-
Retrospective cohort study
400 ICU patients
PI – NR
II – NR
F - NR
M - NR
PI (n = 200) - dose not recorded, over 4 h PI
II (n = 200) - dose not recorded, over 30 min II
PI- NR
II- NR
PI- NR
II- NR
PI patients received fewer doses and demonstrated decreased morbidity and mortality; results however are not SS so larger prospective studies are needed.
Lu et al.
2013 [26]
China
Randomized control trial
50 patients with HAP
PI – NR
II – NR
F - NR
M - NR
PI (n = 25) - 4.5 g every 6 h over a 3 h PI
II (n = 25) - 4.5 g every 6 h over 30 min II
PI- 22/25 (88%)
II- 20/25 (80%)
PI- NR
II- NR
PI’s of piperacillin-tazobactam for gram negative bacteria with high MIC values, like HAP, provide stable plasma concentration and curative clinical effect.
Cutro et al.
2014 [27]
USA
Retrospective cohort study
843 patients suffering from sepsis
PI – NR
II – NR
F - NR
M - NR
PI (n = 662) – 2.25-3.375 g every 6-12 h over 4 h PI
II (n = 181) – 2.25-4.5 g every 8-12 h over 30 min II
PI- 540/662 (81.6%)
II- 145/181 (80.1%)
PI- 72/662 (10.9%)
II- 25/181 (13.8%)
No significant difference between the two dosing regimens was observed in terms of mortality or clinical cure however PI resulted in shorter duration of therapy.
Jamal et al.
2015 [28]
Malaysia
(*) Randomised control trial
16 ICU patients
CI - 44
II – 62.5
F - 4
M - 12
CI (n = 8) - 2.25 g LD + 9 g DD over 24 h CI
II (n = 8) – 2.25 g every 6 h over 30 min II
CI- 6/8 (75%)
II- 6/8 (75%)
CI- 0/8 (0%)
II- 0/8 (0%)
CI is advantageous in the presence of more resistant pathogens as it allows achievement of rapid and consistent piperacillin-tazobactam concentrations.
Abdul et al.
2016 [33]
Malaysia
(*) Randomised control trial
85 ICU patients
CI - 54
II – 56
F - 27
M - 58
CI (n = 38) – dose not recorded
II (n = 47) – dose not recorded
CI- 22/38 (58%)
II- 15/47 (32%)
CI- 7/38 (18.4%)
II- 20/47 (42.6)
Results showed that CI piperacillin-tazobactam demonstrated higher clinical cure rates and better PK/PD target attainment compared to II.
Schmees et al. 2016 [31]
USA
Retrospective cohort study
113 ICU patients
PI - 68
II – 59.4
F - 47
M - 66
PI (n = 61) – 3.375-4.5 g every 8-12 h
II (n = 52) – dose not recorded
PI-31/61 (50.8%)
II-22/52 (42.3%)
PI-9/61 (14.8%)
II-11/52 (21.1%)
Mortality rates and length of hospital stay were significantly lower in PI patients. PI improves patient outcomes while maintaining patient safety.
Cortina et al. 2016 [29]
Spain
Randomised control trial
78 Patients with suspected Pa
CI - 64.3
II – 63.8
F - 32
M - 46
CI (n = 40) – 2.25 g LD + 8 g DD over 24 h CI
II (n = 38) – 4.5 g every 8 h over 30 min II
CI- 20/40 (50%)
II- 18/38 (47.4%)
CI- 0/40 (0%)
II- 1/38 (2.6%)
No SS difference in efficacy between CI & II. Data indicates better performance of II than CI. II cure rates almost doubled CI.
Winstead et al. 2016 [30]
USA
Retrospective cohort study
181 patients, gram (−) bacteria
PI - 65.1
II – 68.2
F - 99
M - 82
PI (n = 86) – 4.5 g LD + 3.375 g every 6 h over 3 h PI
II (n = 95) - 4.5 g every 8 h over 30 min II
PI- NR
II- NR
PI- 7/86 (8.1%)
II- 6/95 (6.3%)
No SS difference in the primary outcome of mortality and length of hospital stay, however, 30-day hospital re-admission was significantly reduced in PI patients.
Bao et al
2017 [32]
China
Randomised control trial
50 patients with HAP
PI - 69.75
II – 67.04
F - 21
M - 29
PI (n = 25) – 4.5 g every 6 h over a 3 h PI
II (n = 25) – 4.5 g every 6 h over 30 min II
PI- 22/25 (88%)
II- 20/25 (80%)
PI- 0/25 (0%)
II- 0/25 (0%)
Dosing regimen had no impact on adequacy of treatment and that PI is as effective as II. PI is potentially a more cost-effective alternative to II.
Fan et al
2017 [34]
China
Prospective cohort study
367 ICU patients
PI - 69
II – 70
F - 120
M - 247
PI (n = 182) - 4.5 g every 8-12 h over 4 h PI
II (n = 185) - 4.5 g every 8-12 h over 30 min II
PI- NR
II- NR
ssssssssPI- 21/182 (11.5%)
II- 29/185 (15.6%)
No significant difference between the two dosing regimens in terms of mortality rate and length of hospital stay
  1. ICU Intensive care unit, CI Continuous infusion, II Intermittent infusion, PI Prolonged infusion, F Female, M Male, MIC Minimal inhibition concentration, LD Loading dose, DD Daily dose, VAP Ventilator-associated pneumonia, PD Pharmacodynamic, CC Clinical cure, Pa Pseudomonas aeruginosa, SS Statistically significant, PRT Prospective randomised trials, RO Resistant organisms, HAP Hospital acquired pneumonia, NR Not recorded; (*) = studies that reported SOFA score