The Potential of Antimicrobials to Induce Thrombocytopenia in Critically Ill Patients: Data from a Randomized Controlled Trial

Abstract

BackgroundAntimicrobial-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.MethodsRandomized 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 ≤100x109/L) or relative (≥20% decrease in platelet count). Analyses were performed in the two randomized groups and as a merged cohort. ResultsOf 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). ConclusionHigh 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

Meropenem‐induced immune thrombocytopenia and the diagnostic process of laboratory testing

“…Although antimicrobial‐induced thrombocytopenia has been extensively described in the literature, to the best of our knowledge, this is the first confirmed case of meropenem‐induced immune thrombocytopenia. Upon additional literature review, however, we found several case reports and series documenting instances in which meropenem or other carbapenems caused severe thrombocytopenia . However, in these cases, there was no further testing of the patients' blood for drug‐induced antibodies, so we cannot definitively know whether these cases were actually DITP.…”

“…After discontinuing the offending drug, bleeding most often stops within 2 days, and the PLT count returns to normal in 4 to 7 days. 11 Although antimicrobial-induced thrombocytopenia has been extensively described in the literature, 12,13 to the best of our knowledge, this is the first confirmed case of meropenem-induced immune thrombocytopenia. Upon additional literature review, however, we found several case reports and series documenting instances in which meropenem or other carbapenems caused severe thrombocytopenia.…”

“…Upon additional literature review, however, we found several case reports and series documenting instances in which meropenem or other carbapenems caused severe thrombocytopenia. 12,14 However, in these cases, there was no further testing of the patients' blood for drug-induced antibodies, so we cannot definitively know whether these cases were actually DITP.…”

Novel Perspectives Regarding the Pathology, Inflammation, and Biomarkers of Acute Respiratory Distress Syndrome

“…The explanation for this result may be that there is a “neutralising” effect, involving harm from antibiotics counteracting any benefits from better timing of their administration. Notably, several harmful effects were reported from the “high-intensive” antibiotic strategy in the PCT-guided arm of the trial: an increase in the risk of renal failure that was attributed to piperacillin [ 100 ], a ciprofloxacin-associated increase in the risk of invasive fungal infection [ 101 ] and haematological side effects [ 102 ]. Most of the patients who had been classified as high risk (i.e., those with severe sepsis or septic shock) were already being given broad-spectrum antibiotics.…”

Fluorochinolony. Bezpieczeństwo terapii

“…Do fl uorochinolonów rekomendowanych w szpitalnym receptariuszu należą: ciprofl oksacyna, lewofl oksacyna, moksyfl oksacyna oraz norfl oksacyna. Wskazania do stosowania w poszczególnych sytuacjach klinicznych przedstawia tabela 1: Tabela [3,7,8,9,10,11]. Zastosowanie tej grupy antybiotyków u dzieci zostało ograniczone, gdyż w badaniach wykazano, że u młodych zwierząt uszkadzają one chrząstkę wzrostową, powodując -na ogół nieodwracalną -artropatię.…”