Safety and Efficacy of a 5-Minute Infusion versus the Standard 30-minute Infusion for Antibiotics in an Outpatient Setting

Highlights•

We studied the rapid infusion of ceftriaxone, ertapenem, meropenem and daptomycin.

There were no rapid infusion-related adverse reactions for any patients.

The rapid infusion of these four antibiotics is safe and well tolerated.

AbstractObjective

: In the outpatient setting, antibiotics such as ceftriaxone, ertapenem, daptomycin and meropenem (for patients with end-stage kidney disease) are generally, administered via once-daily infusions. It is common practice to administer these antibiotics over 30-minutes even though the manufacturers’ product summaries, recommend use of rapid infusions. In February 2017, we switched to rapid infusion as part of a continuous quality improvement effort to improve our outpatient services.

Method

: We conducted a prospective observational study of the safety and efficacy of rapid infusions of ceftriaxone, ertapenem, daptomycin and meropenem between February 2017 and June 2018 at the Outpatient Parenteral Antibiotic Therapy centre, National University Hospital, Singapore . Data collected included patient, demographics, antibiotic indications, treatment duration, treatment outcomes, vascular access and infusion-related adverse events.

Results

: A total of 4326 doses were administered via rapid infusion to 184 patients: ceftriaxone (doses=2616, n=105), ertapenem (doses=1584, n=76), meropenem (doses= 84, n=2) and daptomycin (doses=42, n=1). There were no rapid infusion-related adverse reactions for any patients during the entire treatment duration.

Conclusion

: The rapid administration of intravenous ceftriaxone, ertapenem, meropenem and daptomycin in an outpatient setting is clinically safe and well tolerated.

KeywordsThe National University Hospital Outpatient Parenteral Antibiotic Therapy (OPAT) centre was established in 2004 and now provides for over 350 patients yearly. OPAT refers to the administration of intravenous (IV) antibiotics for management of infections in the outpatient setting without requiring hospital admission or as a transition following hospitalisation. It is a cost-effective and safe alternative to inpatient care. Depending on the pharmacokinetic profile, antibiotics are generally administered either via 24-hour infusion devices or once-daily infusions (Fisher D Michaels J Hase R Zhang J Kataria S Sim B Tsang JK Pollard J Chan M Swaminathan S. Outpatient parenteral antibiotic therapy (OPAT) in Asia: missing an opportunity.).Ceftriaxone, ertapenem, daptomycin and meropenem (for patients with end-stage kidney disease) fall in this latter category. It is common practice within the hospital setting to administer these antibiotics over 30-minutes even though the manufacturers’ product summaries recommend use of rapid infusions with no increase in adverse reactions nor compromise in treatment efficacy: ceftriaxone (4 minutes), daptomycin (2 minutes) and meropenem (5 minutes) (). For ertapenem, there is currently no manufacturer recommendation for rapid infusions. However, one study conducted on 12 healthy volunteers found rapid infusion of ertapenem over 5 minutes to be well-tolerated and bioequivalent to a 30-minute infusion with no compromise in level of pharmacodynamic attainment (Wiskirchen DE Housman ST Quintiliani R Nicolau DP Kuti JL. Comparative pharmacokinetics, pharmacodynamics, and tolerability of ertapenem 1 gram/day administered as a rapid 5-minute infusion versus the standard 30-minute infusion in healthy adult volunteers.).Within the inpatient setting, our hospital uses a point-of-care activated system for IV infusion of antibiotics, usually over 30-minutes, due to benefits such as savings in terms of nursing time, cost and safety (Woon CM Tan TE Hooi PY Teoh SN Wu TS. Point-of-care activated system versus conventional intravenous admixture system at an academic medical centre in Singapore.). In the outpatient setting, IV rapid infusion of antibiotics is more useful, as the speed of medication infusion can impact the number of patients treated, patient wait times, duration patients are connected to infusors as well as nursing workload (Patel S Green H Gray J Rutter M Bevan A Hand K Jones CE Faust SN. Evaluating Ceftriaxone 80 mg/kg Administration by Rapid Intravenous Infusion—A Clinical Service Evaluation.). A reduction of antibiotic infusion time by approximately 25 minutes equates to many hours saved over the total treatment course. Additionally, rapid infusions are administered using minimal fluid volume. This benefits patients who are fluid-restricted and saves costs on diluents ().Based on the recommendations above, we switched to rapid infusion of the four antibiotics as part of a continuous quality improvement effort to improve our OPAT services in February 2017. A prospective observational study of the safety and efficacy of rapid infusions of these antibiotics was conducted between February 2017 and June 2018. The data collected included patient demographics, antibiotic indications, treatment duration, treatment outcomes, vascular access and infusion-related adverse events. A total of 4326 doses were administered via rapid infusion to 184 patients: ceftriaxone (doses=2616, n=105), ertapenem (doses=1584, n=76), meropenem (doses= 84, n=2) and daptomycin (doses=42, n=1). Of these, 61% were male (n= 113), 68% were below the age of 65 (n=125) and 94% (n=173) had antibiotics administered via peripherally inserted central lines (PICC). The median duration of treatment was 21 days (range 2 to 82 days). Genito-urinary tract infections (n=30, 40%) and liver abscesses (n=36, 34%) were the commonest indications for ertapenem (Zhou J Sulaiman Z Llorin RM Hee KH Lee LS Lye DC Fisher DA Tam VH. Pharmacokinetics of ertapenem in outpatients with complicated urinary tract infections.) and ceftriaxone respectively (Table 1).

Table 1Summary of patient demographics, treatment indications, treatment, duration, treatment outcomes, line access and adverse events

There were no rapid infusion-related adverse reactions for any patients during the entire treatment duration. In particular, 45% (n=34) of patients who received ertapenem were aged > 65 years old and all completed treatment with no significant central nervous system adverse events. These events (e.g. seizures) were observed in previous studies when high peak concentrations were achieved during rapid infusion of beta-lactams, especially in patients with impaired renal function or underlying brain lesions (Wiskirchen DE Housman ST Quintiliani R Nicolau DP Kuti JL. Comparative pharmacokinetics, pharmacodynamics, and tolerability of ertapenem 1 gram/day administered as a rapid 5-minute infusion versus the standard 30-minute infusion in healthy adult volunteers.). Majority of the patients completed their treatment successfully in OPAT (ertapenem=87%, ceftriaxone=84%). Re-admission to hospital was due to worsening of their underlying co-morbidities or for elective surgical procedures. Six patients had treatment ceased early, these were based on clinical responses to treatment and is similar to the rate reported in previous OPAT studies (Fisher D Michaels J Hase R Zhang J Kataria S Sim B Tsang JK Pollard J Chan M Swaminathan S. Outpatient parenteral antibiotic therapy (OPAT) in Asia: missing an opportunity.).In conclusion, the rapid administration of intravenous ceftriaxone, ertapenem, meropenem and daptomycin in an outpatient setting is clinically safe and well tolerated. Clinicians in both inpatient and outpatient settings should consider changing current infusion guidelines for these antibiotics appropriate to their clinical practice. Changes are unlikely to save on manpower needs of the service, but the time saved could enable staff to treat more people or undertake additional tasks. Patient recruitment to OPAT may be enhanced by the shorter attendance time required. Furthermore, such additions to the efficiency of administration may enable more hospitals to develop formal centralized OPAT programmes with the inherent advantages previously published (Fisher D Michaels J Hase R Zhang J Kataria S Sim B Tsang JK Pollard J Chan M Swaminathan S. Outpatient parenteral antibiotic therapy (OPAT) in Asia: missing an opportunity.).Funding source

None.

Ethics Approval Statement

Ethics approval was obtained from the National Healthcare Group Domain Specific Review Board (NHG DSRB) 2018/00869.

Uncited References:, Trad MA Zhong LH Llorin RM Tan SY Chan M Archuleta S Sulaiman Z Tam VH Lye DC Fisher DA. Ertapenem in outpatient parenteral antimicrobial therapy for complicated urinary tract infections.Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

ReferencesButterfield-Cowper JM Burgner K.

Effects of iv push administration on β-lactam pharmacodynamics.

American Journal of Health-System Pharmacy. 74 (): e170-e175Fisher D Michaels J Hase R Zhang J Kataria S Sim B Tsang JK Pollard J Chan M Swaminathan S.

Outpatient parenteral antibiotic therapy (OPAT) in Asia: missing an opportunity.

Journal of Antimicrobial Chemotherapy. 72: 1221-1226

MIMS Singapore. https://www.mims.com/singapore /[accessed 5 May 2021 ].

Patel S Green H Gray J Rutter M Bevan A Hand K Jones CE Faust SN.

Evaluating Ceftriaxone 80 mg/kg Administration by Rapid Intravenous Infusion—A Clinical Service Evaluation.

The Pediatric infectious disease journal. 40: 128-129Spencer S Ipema H Hartke P Krueger C Rodriguez R Gross AE Gabay M. Intravenous push administration of antibiotics: literature and considerations. 53. Hospital pharmacy, : 157-169 ()Trad MA Zhong LH Llorin RM Tan SY Chan M Archuleta S Sulaiman Z Tam VH Lye DC Fisher DA.

Ertapenem in outpatient parenteral antimicrobial therapy for complicated urinary tract infections.

Journal of Chemotherapy. 29 (): 25-29Wiskirchen DE Housman ST Quintiliani R Nicolau DP Kuti JL.

Comparative pharmacokinetics, pharmacodynamics, and tolerability of ertapenem 1 gram/day administered as a rapid 5-minute infusion versus the standard 30-minute infusion in healthy adult volunteers.

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 33 (): 266-274Woon CM Tan TE Hooi PY Teoh SN Wu TS.

Point-of-care activated system versus conventional intravenous admixture system at an academic medical centre in Singapore.

Journal of Pharmacy Practice and Research. 48 (): 80-84Zhou J Sulaiman Z Llorin RM Hee KH Lee LS Lye DC Fisher DA Tam VH.

Pharmacokinetics of ertapenem in outpatients with complicated urinary tract infections.

Journal of Antimicrobial Chemotherapy. 69: 2517-2521Article InfoPublication History

Accepted: July 6, 2021

Received: June 18, 2021

Publication stageIn Press Journal Pre-ProofIdentification

DOI: https://doi.org/10.1016/j.ijid.2021.07.018

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© 2021 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

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