Stability of Ampicillin plus Ceftriaxone Combined in Elastomeric Infusion Devices for Outpatient Parenteral Antimicrobial Therapy

Ampicillin; Infective endocarditis; Outpatient parenteral antimicrobial therapyAmpicil·lina; Endocarditis infecciosa; Teràpia antimicrobiana parenteral ambulatòriaAmpicilina; Endocarditis infecciosa; Terapia antimicrobiana parenteral ambulatoriaCurrently, ampicillin plus ceftriaxone (AC) is one of the preferred treatments for Enterococcus faecalis infective endocarditis. However, there is a lack of stability data for the combination of both drugs in elastomeric devices, so the inclusion of AC in Outpatient Parenteral Antimicrobial Therapy (OPAT) programs is challenging. The objective of the study was to determine the stability of AC in elastomeric pumps when stored at 8 ± 2 °C, 25 ± 2 °C, 30 ± 2 °C and 37 ± 2 °C using LC-MS/MS. The combination was diluted in 0.9% sodium chloride and the final concentrations were ampicillin 24 g/L plus ceftriaxone 8 g/L. Physical and chemical stability were evaluated at 12, 20, 24, 36 and 48 h after preparation. Stability was met at each time point if the percentage of intact drug was ≥90% of its respective baseline concentration and color and clearness remained unchanged. The drug combination was stable for 48 h when it was kept at 8 ± 2 °C. At 25 ± 2 °C and 30 ± 2 °C, they were stable for 24 h of storage. At 37 ± 2 °C, the stability criterion was not met at any time point. These results prove that AC could be included in OPAT programs using elastomeric infusion devices for the treatment of E. faecalis infections.This work was supported by the Sociedad Española de Farmacia Hospitalaria and the AFinf Working Group for the project “Stability study of antimicrobials under conditions analogous to the outpatient parenteral antibiotic therapy program (OPAT)”. A.G.-V. was supported by the Instituto de Salud Carlos III, co-financed by the European Development Regional Fund (“A way to achieve Europe”), Subprograma Miguel Servet (grant CP19/00159). L.H.-H. was supported by the Instituto de Salud Carlos III, co-financed by the European Development Regional Fund (“A way to achieve Europe”), Subprograma Juan Rodés (grant JR22/00049)

Stability of temocillin in outpatient parenteral antimicrobial therapy: is it a real option?

[Background] Temocillin is an interesting alternative to carbapenems for susceptible Enterobacteriaceae. Although its use in outpatient parenteral antimicrobial therapy (OPAT) programmes has generated interest, this has been hampered by the lack of stability data.[Objectives] The purpose of the present study was to evaluate the physical and chemical stability of temocillin at the recommended dose for its use in OPAT programmes, contained in polypropylene infusion bags or polyisoprene elastomeric devices at different temperatures, and to describe a novel LC-MS/MS developed for the quantification of temocillin.[Methods] Temocillin daily dose (6 g) was diluted in 500 mL of 0.9% sodium chloride to obtain a final concentration of 12 g/L. This solution was stored at 4°C, 25°C, 32°C and 37°C for 72 h, both in polypropylene infusion bags and in polyisoprene elastomeric pumps. Physical and chemical stability were evaluated during 72 h after manufacturing. Solutions were considered stable if colour, clearness and pH remained unchanged and if the percentage of intact drug was ≥90%.[Results] Temocillin attained the chemical stability criterion of ≥90% of the original concentration for the whole experiment in both devices at 4°C, 25°C and 32°C. At 37°C, temocillin was stable for 24 h but its concentration dropped below 90% from that timepoint. No precipitation occurred and minor colour changes were observed.[Conclusions] Temocillin is stable under OPAT conditions and it would be an appropriate candidate for the treatment of patients who can be discharged to complete therapy in an OPAT programme. For this study, an LC-MS/MS method was developed.This work was supported by the Sociedad Española de Farmacia Hospitalaria and the AFinf Working Group for the project ‘Stability study of antimicrobials under conditions analogous to the outpatient parenteral antibiotic therapy program (OPAT)’. A.G.-V. and L.H.-H. were supported by the Instituto de Salud Carlos III, co-financed by the European Development Regional Fund (‘A way to 251 achieve Europe’). A.G.-V. received financial support from the Subprograma Miguel Servet (CP19/00159). L.H.-H. received financial support from the Subprograma Juan Rodés (JR22/00049).Peer reviewe

International survey of antibiotic dosing and monitoring in adult intensive care units

AVAILABILITY OF DATA AND MATERIALS : All data generated or analyzed during this study are included in this published article [and its supplementary information files].SUPPLEMENTARY INFORMATION : TABLE S1. Definition of infusion types and duration; TABLE S2. Online survey questions; TABLE S3. Exclusions; TABLE S4. Respondents as per Region and Economy; TABLE S5. Results according to Region and Economy; Table S6. TDM utilization and beta-lactam prolonged infusion administration according to hospital type.BACKGROUND : In recent years, numerous dosing studies have been conducted to optimize therapeutic antibiotic exposures in patients with serious infections. These studies have led to the inclusion of dose optimization recommendations in international clinical practice guidelines. The last international survey describing dosing, administration and monitoring of commonly prescribed antibiotics for critically ill patients was published in 2015 (ADMIN-ICU 2015). This study aimed to describe the evolution of practice since this time. METHODS : A cross-sectional international survey distributed through professional societies and networks was used to obtain information on practices used in the dosing, administration and monitoring of vancomycin, piperacillin/tazobactam, meropenem and aminoglycosides. RESULTS : A total of 538 respondents (71% physicians and 29% pharmacists) from 409 hospitals in 45 countries completed the survey. Vancomycin was mostly administered as an intermittent infusion, and loading doses were used by 74% of respondents with 25 mg/kg and 20 mg/kg the most favoured doses for intermittent and continuous infusions, respectively. Piperacillin/tazobactam and meropenem were most frequently administered as an extended infusion (42% and 51%, respectively). Therapeutic drug monitoring was undertaken by 90%, 82%, 43%, and 39% of respondents for vancomycin, aminoglycosides, piperacillin/tazobactam, and meropenem, respectively, and was more frequently performed in high-income countries. Respondents rarely used dosing software to guide therapy in clinical practice and was most frequently used with vancomycin (11%). CONCLUSION : We observed numerous changes in practice since the ADMIN-ICU 2015 survey was conducted. Betalactams are more commonly administered as extended infusions, and therapeutic drug monitoring use has increased, which align with emerging evidence.Clinician Researcher Fellowship funding from Sunshine Coast Hospital, Health Service Study Education Research Trust Fund (SERTF), Wishlist, the Australian National Health and Medical Research Council, an Investigator Grant and an Advancing Queensland Clinical Fellowship.https://ccforum.biomedcentral.comam2024PharmacologySDG-03:Good heatlh and well-bein

Risk factors for bloodstream infections caused by extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae

The objective of this study was to identify risk factors for bacteremia by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae. Retrospective case-control study performed in a 450-bed acute care academic tertiary hospital in Barcelona, Spain. Cases included 53 patients with ESBL-producing E. coli or K. pneumoniae bacteremia, and 159 controls with non-ESBL-producing E. coli or K. pneumoniae bacteremia. Controls were matched in a 3:1 ratio to case patients according to species of infecting organism, age, and severity of illness in the 24-48h before blood sample collection for culture calculated by the Simplified Acute Physiology Score (SAPS II) system. Previous antimicrobials were more frequently administered to cases than to controls (56.5% vs 17%, p 2) of different families of antimicrobials received within 90 days before bloodstream infection was the only predictor of ESBL-producing E. coli or K. pneumoniae in blood culture (OR = 2.29, 95% CI 1.35-3.88, p = 0.002). Conclusion: Previous use of different families of antimicrobials (more than two) in patients with bloodstream infection caused by E. coli or K. pneumoniae increased the risk for ESBL-producing strains

Stability of Antimicrobials in Elastomeric Pumps: A Systematic Review.

Outpatient parenteral antimicrobial therapy (OPAThttp) programs have become an important healthcare tool around the world. Portable elastomeric infusion pumps are functional devices for ambulatory delivery of antimicrobial drugs, and their stability is an essential point to guarantee an appropriate infusion administration. We conducted a systematic review to provide a synthesis and a critical evaluation of the current evidence regarding antimicrobial stability in elastomeric pumps. Data sources were PubMed, EMBASE, and Web of Sciences. The review protocol was registered on the Center for Open Science, and it was carried out following the PRISMA guidelines. Studies were eligible if the aim was the evaluation of the physicochemical stability of an antimicrobial agent stored in an elastomeric device. Of the 613 papers identified, 33 met the inclusion criteria. The most studied group of antimicrobials was penicillins, followed by cephalosporins and carbapenems. In general, the stability results of the antimicrobials that have been studied in more than one article agree with each other, with the exception of ampicillin, flucloxacillin, and ceftazidime. The antibiotics that displayed a longer stability were glycopeptides and clindamycin. Regarding the stability of antifungals and antivirals, only caspofungin, voriconazole, and ganciclovir have been investigated. The information provided in this article should be considered in patient treatments within the OPAT setting. Further stability studies are needed to confirm the appropriate use of the antimicrobials included in this program to ensure optimal patient outcomes