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Stability data on β-lactam-filled elastomeric devices used in outpatient settings in subtropical and tropical climates is lacking. While extensive stability studies have been performed on β-lactam antibiotics at lower room temperatures, there is not enough evidence to assure their physicochemical stability in elastomeric devices at high temperature conditions. This study aimed to develop and validate simple precise analytical tests for stability determination, and to evaluate the in-use physicochemical stability of β-lactam-filled elastomeric devices in subtropical climates. With outpatient practices rising in popularity, validated analytical tests for stability assessment of elastomeric devices are a necessity, especially when used in warmer weathers. This study successfully developed and validated analytical tests, and stability assessments of β-lactam-filled elastomeric devices incubated under room temperature conditions of 30°C and 40°C were conducted. The results showed that the two different β-lactam-filled elastomeric devices tested remained stable after 24 h of continuous infusion at constant temperatures of 30°C and 40°C. These results suggest that flucloxacillin and cefazolin-filled elastomeric devices are stable at temperatures of 30°C and 40°C and safe to be used in subtropical climates. However, this is only a pilot study and larger scale field-based studies that contemplate multiple real-life ambient fluctuations are needed to ensure the stability of such devices.

Background: Febrile neutropaenia (FN) is a very common complication in patients with haematological malignancies and is associated with considerable morbidity and mortality. Broad-spectrum antipseudomonal βlactam antibiotics (BLA) are routinely used for the treatment of cancer patients with FN. However, the clinical efficacy of BLA may be diminished in these patients because they present with pathophysiological variations that compromise the pharmacokinetic (PK) parameters of these antibiotics. Optimised administration of BLA in prolonged infusions has demonstrated better clinical outcomes in critically ill patients. However, there is a paucity of data on the usefulness of this strategy in patients with FN. The aim of this study is to test the hypothesis that the administration of BLA would be clinically more effective by extended infusion (EI) than by intermittent infusion (II) in haematological patients with FN. Methods: A randomised, multicentre, open-label, superiority clinical trial will be performed. Patients with haematological malignancies undergoing chemotherapy or haematopoietic stem-cell transplant and who have FN and receive empirical antibiotic therapy with cefepime, piperacillin-tazobactam or meropenem will be randomised (1:1) to receive the antibiotic by EI (during half the time of the dosing interval) in the study group, or by II (30 min) in the control group. The primary endpoint will be clinical efficacy, defined as defervescence without modifying the antibiotic treatment administered within the first 5 days of therapy. The primary endpoint will be analysed in the intention-to-treat population. The secondary endpoints will be pharmacokinetic/pharmacodynamic (PK/PD) target achievement, bacteraemia clearance, decrease in C-reactive protein, overall (30-day) case-fatality rate, adverse events and development of a population PK model of the BLA studied. Discussion: Data on the usefulness of BLA administration in patients with FN are scant. Only three clinical studies addressing this issue have been published thus far, with contradictory results. Moreover, these studies had some methodological flaws that limit the interpretation of their findings. If this randomised, multicentre, phase IV, open-label, superiority clinical trial validates the hypothesis that the administration of BLA is clinically more effective by EI than by II in haematological patients with FN, then the daily routine management of these high-risk patients could be changed to improve their outcomes. Trial registration: European Clinical Trials Database: EudraCT 2018–001476-37. ClinicalTrials.gov, ID: NCT04233996.