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

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