title: The potential of antimicrobials to induce thrombocytopenia in critically ill patients: data from a randomized controlled trial.
abstract: BACKGROUND
  Antimicrobial-induced thrombocytopenia is frequently described in the literature among critically ill patients. Several antimicrobials have been implicated, although experimental evidence to demonstrate causality is limited. We report, using a randomized trial, the potential of antimicrobials to induce thrombocytopenia.
  
  
  METHODS
  Randomized trial allocated patients to antimicrobial treatment according to standard- of-care (SOC group) or drug-escalation in case of procalcitonin increases (high-exposure group). Patients were followed until death or day 28. Thrombocytopenia defined as absolute (platelet count ≤ 100 x 109/L) or relative (≥ 20% decrease in platelet count). Analyses were performed in the two randomized groups and as a merged cohort.
  
  
  RESULTS
  Of the 1147 patients with platelet data available, 18% had absolute thrombocytopenia within the first 24 hours after admission to intensive care unit and additional 17% developed this complication during follow-up; 57% developed relative thrombocytopenia during follow-up. Absolute and relative thrombocytopenia day 1-4 was associated with increased mortality (HR: 1.67 [95% CI: 1.30 to 2.14]; 1.71 [95% CI: 1.30 to 2.30], P<0.0001, respectively). Patients in the high-exposure group received more antimicrobials including piperacillin/tazobactam, meropenem and ciprofloxacin compared with the SOC group, whereas cefuroxime was used more frequently in the SOC group (p<0.05). Risk of absolute and relative thrombocytopenia (RR: 0.9 [0.7-1.3], p=0.7439; 1.2 [1.0-1.4], p=0.06; respectively), as well as absolute platelet count (daily difference, high-exposure vs. SOC -1.7 [-3.8-0.5], p=0.14) was comparable between groups. In observational analyses, use of ciprofloxacin and piperacillin/tazobactam predicted risk of relative thrombocytopenia (vs. cefuroxime, RR: 2.08 [1.48-2.92]; 1.44 [1.10-1.89], respectively), however only ciprofloxacin were associated with a reduction in absolute platelet count (p=0.0005).
  
  
  CONCLUSIONS
  High exposure to broad-spectrum antimicrobials does not result in a reduction in thrombocytopenia in critically ill patients. However, single use of ciprofloxacin, and less so piperacillin/tazobactam, may contribute to a lower platelet count.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00271752 http://clinicaltrials.gov/ct2/show/NCT00271752.
authors: Copenhagen HIV Programme at Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Maria Egede
authors: ME
authors: Johansen
authors: Jens-Ulrik
authors: JU
authors: Jensen
authors: Morten Heiberg
authors: MH
authors: Bestle
authors: Lars
authors: L
authors: Hein
authors: Anne Øberg
authors: AØ
authors: Lauritsen
authors: Hamid
authors: H
authors: Tousi
authors: Kim Michael
authors: KM
authors: Larsen
authors: Jesper
authors: J
authors: Løken
authors: Thomas
authors: T
authors: Mohr
authors: Katrin
authors: K
authors: Thormar
authors: Pär I
authors: PI
authors: Johansson
authors: Alessandro
authors: A
authors: Cozzi-Lepri
authors: Jens D
authors: JD
authors: Lundgren
mesh_terms: D000368:Aged; D000890:Anti-Infective Agents / Q000009:adverse effects*; D016638:Critical Illness; D005260:Female; D006760:Hospitalization; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011379:Prognosis; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis
chemical_list: D000890:Anti-Infective Agents