Intro
Febrile neutropenia is associated with significant morbidity and high mortality in the event of delayed or inappropriate antimicrobial treatment. In the case of bacterial infection, antibiotic treatment of febrile neutropenic patients should be given as early as possible. All patients therefore receive immediate empirical antibiotic therapy at the onset of fever: broad-spectrum beta-lactam antibiotics are the recommended first-line treatment for febrile neutropenia. Therapeutic adjustment of concentrations is a little studied aspect.
Objectives
The objectives of this thesis were firstly to estimate the rate of inappropriate blood levels of broad- spectrum beta-lactam antibiotics, despite optimal adaptations of dosage to renal function in febrile neutropenic patients, for whom inappropriate treatment could have serious, potentially lethal consequences.
Secondly, we tried to estimate the clinical impact of measuring blood antibiotic concentrations and targeted intervention with individualised dosage adjustment in febrile neutropenic patients, compared with adjustment based only on usual dosage recommendations according to renal function
Methods
Measurement of blood concentrations in the control arm had not been communicated to the treating physicians and adjustments were only empirical.
Results
Comparison of the primary composite endpoint (survival, absence of toxicity and positive therapeutic response) showed no statistically significant difference between the two arm survival curves (log-rank test: P=.8). However, analysing individually each endpoints, the result showed a significant difference in the probability of developing antibiotic-induced toxicity with a decreased 6% (log rank test: P=.02) for the TDM arm. Blood concentrations showed a significant statistical difference on day 7 and on day 14 between the two arms. On the experimental branch 85% of the blood concentration were appropriate opposed to the 72% in the control arm, showing a 13% difference in reaching an appropriate dosage for the patient (log rank test: P=.012); 16% were considered too low for the control arm (TDM 13%) and 12% too high (TDM only 2%). Finally, only 4% of the treatments were adapted until the 7th day in the control arm while having 28% unrecognized (i.e. no TDM) inappropriate blood concentrations (compared to 27% adaptation in the experimental arm with P log rank <.001).
Conclusion
This study did not show a statistically significant benefit on therapeutic success associated to antibiotics blood concentration measurements. However, it did manage to enlighten the need of better individual dosage management to avoid the risk of toxicity or underdosage that lead to more undesirable effect or longer time of treatment. It also showed the need for further pharmacokinetics’ study to achieve a more appropriate dosage for the patients treated with B-lactam antibiotics.