PLoS ONE (Jan 2013)

The potential of antimicrobials to induce thrombocytopenia in critically ill patients: data from a randomized controlled trial.

  • Maria Egede Johansen,
  • Jens-Ulrik Jensen,
  • Morten Heiberg Bestle,
  • Lars Hein,
  • Anne Øberg Lauritsen,
  • Hamid Tousi,
  • Kim Michael Larsen,
  • Jesper Løken,
  • Thomas Mohr,
  • Katrin Thormar,
  • Pär I Johansson,
  • Alessandro Cozzi-Lepri,
  • Jens D Lundgren

DOI
https://doi.org/10.1371/journal.pone.0081477
Journal volume & issue
Vol. 8, no. 11
p. e81477

Abstract

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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.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.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).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.ClinicalTrials.gov NCT00271752 http://clinicaltrials.gov/ct2/show/NCT00271752.