Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial.
BACKGROUND
In previous smaller trials, a procalcitonin (PCT) algorithm reduced antibiotic use in patients with lower respiratory tract infections (LRTIs).


OBJECTIVE
To examine whether a PCT algorithm can reduce antibiotic exposure without increasing the risk for serious adverse outcomes.


METHODS
A multicenter, noninferiority, randomized controlled trial in emergency departments of 6 tertiary care hospitals in Switzerland with an open intervention of 1359 patients with mostly severe LRTIs randomized between October 2006 and March 2008.


METHODS
Patients were randomized to administration of antibiotics based on a PCT algorithm with predefined cutoff ranges for initiating or stopping antibiotics (PCT group) or according to standard guidelines (control group). Serum PCT was measured locally in each hospital and instructions were Web-based.


METHODS
Noninferiority of the composite adverse outcomes of death, intensive care unit admission, disease-specific complications, or recurrent infection requiring antibiotic treatment within 30 days, with a predefined noninferiority boundary of 7.5%; and antibiotic exposure and adverse effects from antibiotics.


RESULTS
The rate of overall adverse outcomes was similar in the PCT and control groups (15.4% [n = 103] vs 18.9% [n = 130]; difference, -3.5%; 95% CI, -7.6% to 0.4%). The mean duration of antibiotics exposure in the PCT vs control groups was lower in all patients (5.7 vs 8.7 days; relative change, -34.8%; 95% CI, -40.3% to -28.7%) and in the subgroups of patients with community-acquired pneumonia (n = 925, 7.2 vs 10.7 days; -32.4%; 95% CI, -37.6% to -26.9%), exacerbation of chronic obstructive pulmonary disease (n = 228, 2.5 vs 5.1 days; -50.4%; 95% CI, -64.0% to -34.0%), and acute bronchitis (n = 151, 1.0 vs 2.8 days; -65.0%; 95% CI, -84.7% to -37.5%). Antibiotic-associated adverse effects were less frequent in the PCT group (19.8% [n = 133] vs 28.1% [n = 193]; difference, -8.2%; 95% CI, -12.7% to -3.7%).


CONCLUSIONS
In patients with LRTIs, a strategy of PCT guidance compared with standard guidelines resulted in similar rates of adverse outcomes, as well as lower rates of antibiotic exposure and antibiotic-associated adverse effects.


BACKGROUND
isrctn.org Identifier: ISRCTN95122877.
Schuetz
Philipp
P
Department of Internal Medicine, Kantonsspital Aarau, Tellstrasse, CH-5001 Aarau, Switzerland.
Christ-Crain
Mirjam
M
Thomann
Robert
R
Falconnier
Claudine
C
Wolbers
Marcel
M
Widmer
Isabelle
I
Neidert
Stefanie
S
Fricker
Thomas
T
Blum
Claudine
C
Schild
Ursula
U
Regez
Katharina
K
Schoenenberger
Ronald
R
Henzen
Christoph
C
Bregenzer
Thomas
T
Hoess
Claus
C
Krause
Martin
M
Bucher
Heiner C
HC
Zimmerli
Werner
W
Mueller
Beat
B
D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D003661:Decision Support Techniques; D004363:Drug Utilization; D004636:Emergency Service, Hospital; D005260:Female; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D011498:Protein Precursors / Q000097:blood*; D012141:Respiratory Tract Infections / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide