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Published on: August 30, 2018
The potential of antimicrobials to induce thrombocytopenia in critically ill patients: data from a randomized
Maria Egede Johansen1, Jens-Ulrik Jensen, Morten Heiberg Bestle
1Copenhagen HIV Programme at Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
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).
Conclusion:
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.
Trial Registration:
ClinicalTrials.gov NCT00271752 http://clinicaltrials.gov/ct2/show/NCT00271752.
Insights
High antimicrobial exposure in critically ill patients did not increase thrombocytopenia risk. However, specific antibiotics like ciprofloxacin may lower platelet counts, warranting further investigation into antimicrobial-induced thrombocytopenia.
Area of Science:
- Critical Care Medicine
- Pharmacology
- Hematology
Background:
- Antimicrobial-induced thrombocytopenia is a known complication in critically ill patients.
- Limited experimental evidence exists to establish causality between antimicrobials and thrombocytopenia.
- This study investigated the potential of antimicrobials to induce thrombocytopenia in a critically ill population.
Purpose of the Study:
- To determine if high exposure to broad-spectrum antimicrobials increases the risk of thrombocytopenia in critically ill patients.
- To explore the association between specific antimicrobial agents and the development of thrombocytopenia.
- To evaluate the impact of antimicrobial treatment strategies on platelet counts.
Main Methods:
- A randomized trial comparing standard-of-care (SOC) antimicrobial treatment with a high-exposure strategy based on procalcitonin levels.
- Patients were monitored for absolute (platelet count ≤ 100 x 10^9/L) and relative (≥ 20% decrease) thrombocytopenia until day 28 or death.
- Statistical analyses included comparisons between randomized groups and observational analyses of specific antimicrobial use.
Main Results:
- Thrombocytopenia was common, with 18% experiencing absolute and 57% relative thrombocytopenia during follow-up.
- Absolute and relative thrombocytopenia were associated with increased mortality.
- No significant difference in thrombocytopenia risk was observed between the high-exposure and SOC groups, but observational analyses linked ciprofloxacin and piperacillin/tazobactam to increased relative thrombocytopenia risk.
Conclusions:
- High antimicrobial exposure does not appear to increase thrombocytopenia risk in critically ill patients.
- Individual antibiotics, particularly ciprofloxacin, may be associated with reduced platelet counts.
- Further research is needed to elucidate the mechanisms of antimicrobial-induced thrombocytopenia.
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