We observed that there is an important relationship between CYP450 and cisplatin, involving increased toxicity. However, the possible mechanisms described for the involvement of CYP450 enzymes in nephrotoxicity and hepatotoxicity induced by cisplatin need to be confirmed by further studies. Therefore, there is a need for a deeper investigation focusing on cisplatin toxicity mediated by CYP450 enzymes, which would undoubtedly contribute to a better understanding of the mechanisms that have been implicated so far.
Summary
What is known and objective
Polymyxins, especially polymyxin B, has become the last line of therapy against Gram‐negative pathogens’ carbapenemase producers. However, given increasing use of polymyxin B in clinical settings its therapeutic value has been evaluated worldwide due to its toxic effects. The aim of this study was to assess the efficacy and safety of antimicrobial therapy with polymyxin B in patients with multidrug‐resistant bacteria in Brazil.
Methods
This was a prospective cohort study in a 403‐bed academic tertiary care centre, located in the countryside of Brazil. Patients receiving polymyxin B intravenous treatment for at least 72 hours were eligible for the study. Antimicrobial susceptibility, adverse reactions and clinical outcomes were submitted for descriptive analysis. Main outcomes measure the following: Patients' conditions following treatment (Treatment Success, Mortality, Treatment Failure, Inadequate Empiric Treatment or Indeterminate Response) and toxicities induced by polymyxin B (nephrotoxicity and skin hyperpigmentation).
Results and discussion
Among 247 patients, treatment success was achieved in 25.1%, while mortality was observed in 32.8%. Empirical therapy was prescribed for 26.3% of the patients. Nephrotoxicity was reported in 40.5%. The carbapenemase producer, Klebsiella pneumonia, was the bacterium most associated with mortality (22.2%).
Conclusions
Even though polymyxin B is currently the main therapy against carbapenemase producers, its use demands robust criteria to lead to positive clinical outcomes.
BackgroundCisplatin is a high-potency anticancer agent; however, it causes significant adverse drug reactions (ADRs). Potential pharmacokinetic markers must be studied to predict or prevent cisplatin-induced ADRs and achieve better prognosis. This study was designed to investigate the relationship between ADRs and kinetics of cisplatin excretion in the urine of patients undergoing high-dose cisplatin chemotherapy and radiotherapy for head and neck cancer.MethodsOutpatients with head and neck cancer received a first cycle of high-dose cisplatin chemotherapy (80–100 mg/m2) concurrent to radiotherapy. ADRs (haematological, renal, and gastrointestinal reactions) were classified based on severity by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 4, grade 0–4). The kinetics of cisplatin excretion in urine was evaluated by high-performance liquid chromatography over three time periods: 0–12, 12–24, and 24–48 h after the administration of cisplatin. Spearman Correlation test and regression analysis were performed to assess the relationship between ADRs and cisplatin excretion in the urine.ResultsIn total, 59 patients with a mean age of 55.6 ± 9.4 years were analysed; most patients were male (86.4%), white (79.7%), and with pharyngeal tumours in advanced stages (66.1%). The most frequently observed ADRs were anaemia (81.4%), lymphopenia (78%), and nausea (64.4%); mostly grades 1 and 2 of toxicity. The mean cisplatin excretion was 70.3 ± 64.4, 7.3 ± 6.3, and 5 ± 4 μg/mg creatinine at 0–12, 12–24, and 24–48 h, respectively. Statistical analysis showed that the amount of cisplatin excreted did not influence the severity of ADRs.ConclusionsThe most frequent ADRs were anaemia, lymphopenia, and nausea. Grades 1 and 2 were the severities for most ADRs. The period over which the highest cisplatin excretion observed was 0–12 h after chemotherapy, and cisplatin excretion could not predict toxicity.Graphical abstract
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