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Table 3 Antibiotic dosage and outcome data of previously published for CI vs. IB of beta-lactam antibiotics

From: Continuous beta-lactam infusion in critically ill patients: the clinical evidence

Study Types of infection Number of patients (APACHE score a) Antibiotic dosage regimen Concurrent PK/PD analysis Clinical outcome measures CI IB p value
CI IB CI IB
Angus et al. [87] Melioidosis 10 (15) 11 (21) 12 mg/kg LD, then 4 mg/kg every 1 hr 40 mg/kg every 8 hr Yes Mortality 20% 36.4% 0.89
Bodey et al. [89] Pneumonia, UTI, septicemia and neutropenic fever 167 (ND) 162 (ND) 3 g LD, then 12 g/24 hr 3 g every 6 hr No Clinical cure 64.8% 56.5% ND
Buck et al. [81] Pneumonia, cholangitis and FUO 12 (ND) 12 (ND) 2 g LD then 8 g/24 hrb 4 g every 8 hrb Yes Clinical response 67% 67% ND
Buijk et al. [52] Intra-abdominal infections 12 (16) 6 (14) 1 g LD then 4.5 g/24 hr 1.5 g every 8 hr Yes Mortality 25% 33% 1.0
Georges et al. [80] Pneumonia and septicemia 24 (45c) 23 (44c) 2 g/12 hrs twice daily 2 g every 12 hr Yes Mortality 12% 13% NDd
Clinical cure 85% 67% NDd
Duration of MV 24 ± 13 25.3 ± 10 NDd
LOS ICU 34 ± 17 40 ± 15 NDd
Hanes et al. [86] Pneumonia 17 (13) 14 (11) 2 g LD then 60 mg/kg every 24 hr 2 g every 8 hr Yes Duration of MV 22.9 ± 19.9 13.3 ± 6.1 0.16
LOS ICU 26.8 ± 20.1 15.5 ± 5.9 0.11
LOS Hospital 41.7 ± 30.5 28.7 ± 15.9 0.37
Duration of leukocytosis 7.8 ± 7.3 11.3 ± 4.7 0.35
Duration of pyrexia 7.9 ± 4.4 4.3 ± 2.5 0.06
Kojika et al. [82] Abdominal abscess 5 (ND) 5 (ND) 0.5 g every 8 hr (over 3 hr) 0.5 g every 8 hr (over 30 min) No Mortality 20% 0%  
Lagast et al. [88] Septicemia 20 (ND) 25 (ND) Day 1: 1 g LD then 3 g/24 hr Day 2 +: 4 g/24 hr 2 g every 12 hr No Mortality 25% 16% ND
Clinical cure 70% 80% ND
Lau et al. [79] Abdominal infections 81 (8) 86 (8) 2 g LD then 12 g/24 hre 3 g every 6 hre No Mortality 0.76% 2.6%  
Clinical cure 86.4% 88.4% 0.817
Adverse events 89.2% 87.1%  
Lubasch et al. [83] Chronic bronchitis 41 (ND) 40 (ND) 2 g LD then 2 g/7 hr twice daily 2 g every 8 hr Yes Clinical cure 90.2% 90% NDd
Bacteriological cure 90.2% 87.5% NDd
Nicolau et al. [84] Pneumonia 17 (14) 18 (16) 1 g LD then 3 g/24 hrf 2 g every 8 hrf No Clinical cure 41% 33% 0.592
Duration of MV 7.9 ± 4.0 8.3 ± 4.3 0.97
LOS ICU 8.5 ± 3.4 9.3 ± 4.0 0.691
Time to defervescence 3.1 ± 2.1 5.2 ± 2.3 0.015
WBC normalization 7.3 ± 3.0g 5.5 ± 4.2g 0.259
Pedeboscq et al. [85] Gastrointestinal-related infections 3 (ND) 4 (ND) 12 g/24 hr 4 g every 8 hr Yes Mortality 0% 0% ND
Rafati et al. [78] Pneumonia, UTI, abdominal infections, SSI and septicemia 20 (16) 20 (14) 2 g LD then 8 g/24 hr 3 g every 6 hr Yes Mortality 30% 25% 0.72
Decrease in illness severity    CI > ITh
Duration of pyrexia 2.4 ± 1.5 1.7 ± 0.7 0.08
WBC normalization 75% 83% ND
Roberts et al. [75] Septicemia 29 (19) 28 (16) 0.5 g LD then 2 g/24 hr Day 1: 2.5 g/24 hr Day 2: 2 g/24 hr No Mortality 10% 0% 0.25
Clinical curei 52% 20% 0.04
Duration of MV 4.3 ± 4.5 3.4 ± 4.1 0.33
LOS ICU 10.8 ± 23.2 5.6 ± 6.0 0.29
LOS hospital 42 ± 6.9 24 ± 2.1 0.34
Sakka et al. [77] Pneumonia 10 (26) 10 (28) 1 g LD then 2 g/24 hr 1 g every 8 hr Yes Mortality 10% 20% ND
Van Zanten et al. [76] COPD exacerbations 40 (ND) 43 (ND) 1 g LD then 2 g/24 hr 1 g every 8 hr Yes Clinical cure 93% 93% 0.93
  1. APACHE, Acute Physiology and Chronic Health Evaluation score; CI, continuous infusion; IB, intermittent bolus; PK/PD, pharmacokinetic/pharmacodynamic; UTI, urinary tract infection; FUO, fever of unknown origin; SSI, surgical site infection; COPD, chronic obstructive pulmonary disease; ND, not described; LD, loading dose; MV, mechanical ventilation; LOS, length of stay; ICU, intensive care unit; WBC, white blood cells.
  2. aValues are reported as mean.
  3. bDose reduction in renal dysfunction-if creatinine clearance 25–60 mL/min (CI group 6.75 g/24 hr; IT group 4.5 g q12hr); if creatinine clearance <25 mL/min (CI group 4.5 g/24 hr; IB group 4.5 g every 24 hr).
  4. cValues are SAPS II score.
  5. d P values for nonsignificance were not reported.
  6. eDose reduction in renal dysfunction-if creatinine clearance 20–40 mL/min (CI group 8 g-1 g/24 hr; IB group 2 g −0.25 g every 6 hr).
  7. fDose reduction in renal dysfunction-if creatinine clearance 31–50 mL/min (CI group 2.5 g/24 hr; IB group 2 g every 12 hr); if creatinine clearance 21–30 mL/min (CI group 2 g/24 hr; IB group 2 g every 24 hr).
  8. gx 109/L.
  9. hSignificant difference in APACHE II scores on days 2, 3, and 4.
  10. i A priori analysis.