Table 2.

The factors determining whether prolonged or continuous infusion has a benefit over standard infusion

Factors	Descriptions on whether prolonged or continuous infusion has a benefit over standard infusion
MIC of bacterial pathogens	Meropenem: The PTA (ie, 40% T>MIC) with short (0.5-hour) infusion of 1 g meropenem every 8 hours was higher than those with prolonged (3-hour) infusion regimens for CPKP isolates with MIC 4–8 mg/L rather than MIC ≥16 mg/L or ≤2 mg/L (MIC 4 mg/L: 98%–99% vs 61%–83%; MIC 8 mg/L: 55%–79% vs 23%–33%).14
	Piperacillin/tazobactam: The benefits of prolonged infusion were selective and most likely observed in patients with less susceptible pathogens, ie, prolonged infusion had no advantages over standard infusion against isolates with susceptible MICs of 8 or 16 mg/L, whereas it produced more than twice the final bacterial kill against less susceptible isolates with an intermediate MIC of 32 mg/L.39
	Piperacillin/tazobactam: For pathogens with MICs of ≤8 mg/L, extended infusion did not substantially improve PTA, and standard infusion was likely sufficient. However, piperacillin/tazobactam 100/12.5 mg/kg given as an extended infusion every 6–8 hours may be optimal for empirical or directed therapy in critically ill pediatric patients with infections caused by less susceptible pathogens.40
Diagnosis and disease severity	Piperacillin/tazobactam: Patients with severe disease (SOFA score≥ 9), rather than those with mild disease (SOFA score<9), benefited from prolonged infusion (eg, shorter days of antibiotics use and ventilator time, longer survival, better clinical efficacy, and lower 28-day mortality rate).41
	Piperacillin/tazobactam: ICU patients exhibited no significant differences in outcomes following two dosing methods (extended infusion over 4 hours vs regular infusion over 30 minutes), whereas patients with urinary or intra-abdominal infections had lower mortality and clinical failure rates following extended infusion treatment.42
	Piperacillin/tazobactam: There was a lower mortality rate in the extended-infusion group who had infectious organisms identified (9.3% vs 22.4%, P=0.01) or were diagnosed with respiratory tract infections (8.9% vs 18.7%, P=0.02).43
	Meropenem: ICU patients exhibited the lowest target attainment rates, whereas internal medicine patients achieved the highest target attainment rates following short (0.5-hour) and prolonged (3-hour) infusion regimens of 1 g meropenem every 8 hours.14
Bacterial density	Piperacillin/tazobactam: for the lower initial bacterial density, trough total plasma piperacillin concentration/MIC ratios of 3.4 and 10.4 following bolus and extended-infusion regimens, respectively, were able to suppress the emergence of piperacillin resistance. For the higher initial bacterial density, both infusion regimens were associated with progressive growth of a resistant subpopulation, and thus combination therapy may be required to maximize bacterial killing and prevent antimicrobial resistance.44
Total daily dose	Imipenem/cilastatin: In critically ill patients with nosocomial pneumonia, concentrations of imipenem were above the target concentration (4×MIC of 2 mg/L) for ≥40% of the dosing interval in every patient in the bolus group (1 g imipenem/1 g cilastatin over 30 minutes every 8 hours), whereas in the extended group (0.5 g of imipenem by a 3-hour infusion every 6 hours) this PK/PD index (40% fT>4×MIC) was achieved in only 20% of patients. Moreover, 70% of the patients in the extended group did not reach the desired drug concentrations at all.22
Renal clearance	Meropenem: In adult patients with septic shock and possible increased renal clearance, meropenem doses should be increased and/or administration by prolonged or continuous infusion should be considered to increase the likelihood of obtaining therapeutic drug concentrations. In patients with normal renal function, however, standard intermittent dosing (30 minutes) seems to be sufficient.15

Abbreviations: CPKP, carbapenemase-producing Klebsiella pneumoniae; ICU, intensive care unit; MIC, minimum inhibition concentration; PK/PD, pharmacokinetic/pharmacodynamic; PTA, probability of target attainment; SOFA, sequential organ failure assessment; T>MIC, time for which drug concentrations exceed the MIC.