Table 4 Description of a randomized clinical trial that should be performed to investigate CI vs. IB beta-lactam antibiotics

Population

Should only include patients with sepsis or severe sepsis

Intervention

Antibiotic dosing regimen should be similar between CI and IB group

a. A loading dose should be given to continuous infusion group to ensure rapid attainment of target antibiotic concentration

b. An equal daily antibiotic dose should be given to continuous and bolus administration group

c. Antibiotic doses should be specified according to the patient’s body weight

d. Concomitant administration of other non-beta-lactam antibiotics should be allowed

PK/PD analysis

Concurrent PK/PD analysis should be performed to support any findings

a, Measurements of antibiotic concentrations should be performed as long as contributing sites have necessary infrastructure to ensure apt sampling

b. PK/PD analysis should evaluate the relative ability of IB to achieve a C_min greater than 4 x MIC of the offending pathogen for 40-70% of the dosing interval while for CI, a C_ss greater than 4 x MIC

Methods

Design

Preferably multicenter in nature and recruits participants from different regions to improve generalizability of results

Patients

Define eligibility criteria for participants to be included into trial

a. Definition of sepsis and severe sepsis should be described in detail

b. Inclusion and exclusion criteria used should be explained

Randomization

Detailed explanation on allocation sequence generation development

Detailed allocation concealment mechanism

Blinding/masking

Outcome evaluators for the trial should be blinded to participants management

Endpoints

a. Endpoints selection should include primary (clinical outcome) and secondary (PK/PD; adverse event) endpoints

b. Data collection on the observed bacterial resistance in the two treatment arms should occur