Christ‐Crain 2006

Methods	Randomised clinical trial, single‐centre, emergency department at the University Hospital Basel, Switzerland
Participants	Inclusion criteria: CAP with X‐ray confirmation in the emergency department Exclusion criteria: patients with cystic fibrosis or active pulmonary tuberculosis, patients with hospital‐acquired pneumonia and severely immunocompromised patients Included in this analysis: 302 out of 302 randomised patients
Interventions	Guiding antibiotic decisions in emergency department patients with CAP with repeated procalcitonin measurements Algorithm used in this study: a procalcitonin level of less than 0.1 µg/L suggested the absence of bacterial infection and the initiation or continuation of ABs was strongly discouraged. A procalcitonin level between 0.1 and 0.25 µg/L indicated that bacterial infection was unlikely and the initiation or continuation of ABs was discouraged. A procalcitonin level from 0.25 to 0.5 µg/L was considered to indicate a possible bacterial infection and the initiation or continuation of AB therapy was encouraged. A procalcitonin level greater than 0.5 µg/L strongly suggested the presence of bacterial infection and AB treatment and continuation was strongly encouraged. Re‐evaluation of the clinical status and measurement of serum procalcitonin levels was recommended after 6 to 24 h in all patients from whom ABs were withheld. Procalcitonin levels were reassessed after 4, 6 and 8 d. ABs were discontinued on the basis of the procalcitonin cut‐offs defined above. In patients with very high procalcitonin values on admission (e.g. greater than 10 µg/L), discontinuation of ABs was encouraged if levels decreased to levels less than 10% of the initial value (e.g. 1 µg/L, instead of less than 0.25 µg/L)
Outcomes	Antibiotic use Mortality ICU admission Hospital readmission Complications due to CAP Cure defined as resolution of clinical, laboratory and radiographic signs of CAP Improvement was defined as reduction of clinical signs and symptoms, improvement of laboratory findings and reduction of the number or intensity of radiographic signs of CAP Treatment success represented the sum of the rates for cure and improvement. Treatment failure included death, recurrence, relapse, or persistence of clinical, laboratory and radiologic signs of CAP and patients lost to follow‐up
Notes	Funding: funding obtained from Brahms (Hennigsdorf, Germany), Pfizer (Schweiz AG) and Mepha (Schweiz AG) was used for assay material and salaries of technical personnel involved in laboratory work and for shipping and handling of data and specimens and presentation of data at scientific meetings. Additional support, which provided more than two‐thirds of the total study costs, was granted by funds from the Departments of Internal Medicine and Emergency Medicine, the Stiftung Forschung Infektionskrankheiten (SFI) and, mainly, from the Departments of Endocrinology and Pulmonary Medicine, University Hospital Basel, Switzerland Follow‐up: fixed period of 6 weeks Registration: ISRCTN04176397
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Independent statistician created randomisation list
Allocation concealment (selection bias)	High risk	Quote: "On admission, patients were randomly assigned to one of the two groups by sealed, opaque envelopes." Envelopes were not numbered
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Open‐label trial where physicians knew in which group patients were and where procalcitonin levels were only communicated in the intervention arm
Blinding of outcome assessment (detection bias) All outcomes	High risk	Non‐blinded study members
Incomplete outcome data (attrition bias) All outcomes	Low risk	Follow‐up for mortality: 300/302 (99%)
Selective reporting (reporting bias)	Low risk	Outcomes correspond to study protocol
Other bias	Unclear risk	87% adherence to procalcitonin algorithm in procalcitonin group