van Zanten 2007.

Methods	Prospective, open‐label, randomised trial.
Participants	93 hospitalised patients (mean age range 65 to 69 years; 69% male) who required antibiotic treatment for moderate to severe acute exacerbations of COPD (GOLD class 2 to 4). Exclusion: suspected or proven resistance to cefotaxime, administration of antibiotics in the preceding 48 h, allergy to beta‐lactam antibiotics, bilirubin concentrations > 20 umol/L, serum creatinine > 120 umol/L, and whole blood count < 3.0 x 10^9/L.
Interventions	Cefotaxime 1 g i.v. given over 30 minutes, followed by 2 g i.v. continuous infusion q24h vs cefotaxime 1 g i.v. given over 30 minutes q8h; mean treatment duration 9 to 10 days.
Outcomes	Clinical assessment (successful treatment, treatment failure, non‐evaluable). Pharmacokinetic variables (t1/2, AUC, CL, Vss). Pharmacodynamic variables (MIC, numbers of patients with serum drug concentrations below MIC, numbers of patients with serum drug concentrations below 5 x MIC, average time concentrations below 5 x MIC).
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Patients randomly assigned, but method of randomisation not stated.
Allocation concealment (selection bias)	Unclear risk	Not stated.
Blinding (performance bias and detection bias) All outcomes	High risk	Not blind.
Incomplete outcome data (attrition bias) All outcomes	High risk	Not all deaths were counted. "Of the 93 patients initially enrolled, 10 were excluded for the following reasons (after randomisation): death due to cardiac failure (n = 5); antibiotic treatment in the 48‐h period before initiation of cefotaxime therapy (n = 2); final diagnosis of squamous cell carcinoma instead of infection (n = 1); and protocol violations (n = 2)" (pg. 103). Pharmacokinetic evaluation "was not measured in six patients, because three patients in group 1 died before blood samples could be drawn, and technical errors, such as lost blood samples, occurred in three patients in group 2." Pharmacodynamic evaluation had the same denominator as pharmacokinetic evaluation.
Selective reporting (reporting bias)	Unclear risk	Only mention adverse events that were drug related, not total adverse events. However, did not state a priori that they were going to report on any adverse events.
Other bias	Unclear risk	Hoechst Marion Roussel provided a restricted research grant for analysing serum cefotaxime concentrations and for assessing MIC values.