Continuous infusion, therapeutic drug monitoring and outpatient parenteral antimicrobial therapy with ceftazidime/avibactam: a retrospective cohort study.
[en] [en] OBJECTIVES: Based on recent pharmacokinetic/pharmacodynamic (PK/PD) evidence, continuous-infusion (CI) β-lactam administration is increasingly recommended for serious infections. Since 2016, the combination ceftazidime/avibactam (CAZ/AVI) is administered as per the manufacturer's instructions as an intermittent infusion of 2.5 g every 8 h. Thus, CI has not yet been evaluated in clinical trials.
METHODS: We aimed to evaluate the use of CI of CAZ/AVI in a retrospective case series from December 2016 to October 2019. All isolates displayed in vitro susceptibility to CAZ/AVI according to EUCAST definitions. Patients were initially given CAZ/AVI as CI of 5 g every 12 h, and dosages were adjusted according to therapeutic drug monitoring of ceftazidime with a therapeutic goal of ≥4-5 × MIC in plasma and/or at the site of infection.
RESULTS: CAZ/AVI was administered by CI in 10 patients with infections mainly caused by multidrug-resistant Pseudomonas aeruginosa (54.5%) and Klebsiella pneumoniae (36.4%). Bacteraemia occurred in 30% of cases. Sepsis or septic shock was present in 20% of cases. CAZ/AVI was used as monotherapy in 60% of cases. Clinical cure and microbiological eradication were achieved in 80% and 90% of cases, respectively. The 30-day mortality after CAZ/AVI treatment onset was 10%. The therapeutic goals of ≥4-5 × MIC in plasma and/or at the site of infection were achieved in 100% and 87.5% of cases, respectively, without adverse events.
CONCLUSION: Despite a limited number of patients, CI of CAZ/AVI provided promising results after optimisation of PK/PD parameters both in plasma and at the site of infection.
Disciplines :
Immunology & infectious disease
Author, co-author :
GONCETTE, Véronique ; Centre Hospitalier Universitaire de Liège - CHU > > Service officine et gaz médicaux
Layios, Nathalie ; Centre Hospitalier Universitaire de Liège - CHU > > Service des soins intensifs
DESCY, Julie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de microbiologie clinique
FRIPPIAT, Frédéric ; Centre Hospitalier Universitaire de Liège - CHU > > Service des maladies infectieuses - médecine interne
Language :
English
Title :
Continuous infusion, therapeutic drug monitoring and outpatient parenteral antimicrobial therapy with ceftazidime/avibactam: a retrospective cohort study.
Shirley, M., Ceftazidime–avibactam: a review in the treatment of serious Gram-negative bacterial infections. Drugs 78 (2018), 675–692, 10.1007/s40265-018-0902-x.
World Health Organization (WHO). Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis. 2017, WHO, Geneva, Switzerland https://www.who.int/medicines/areas/rational_use/PPLreport_2017_09_19.pdf?ua=1 [accessed 14 December 2020].
Lal, A., Jaoude, P., El-Solh, A.A., Prolonged versus intermittent infusion of β-lactams for the treatment of nosocomial pneumonia: a meta-analysis. Infect Chemother 48 (2016), 81–90, 10.3947/ic.2016.48.2.81.
Vardakas, K.Z., Voulgaris, G.L., Maliaros, A., Samonis, G., Falagas, M.E., Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials. Lancet Infect Dis 18 (2018), 108–120, 10.1016/S1473-3099(17)30615-1.
Onorato, L., Di Caprio, G., Signoriello, S., Coppola, N., Efficacy of ceftazidime/avibactam in monotherapy or combination therapy against carbapenem-resistant Gram-negative bacteria: a meta-analysis. Int J Antimicrob Agents 54 (2019), 735–740, 10.1016/j.ijantimicag.2019.08.025.
European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters. Version 9.0. 2019 https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_9.0_Breakpoint_Tables.pdf [accessed 14 December 2020].
Roberts, J.A., Paul, S.K., Akova, M., Bassetti, M., De Waele, J.J., Dimopoulos, G., et al. DALI: defining antibiotic levels in intensive care unit patients: are current β-lactam antibiotic doses sufficient for critically ill patients?. Clin Infect Dis 58 (2014), 1072–1083, 10.1093/cid/ciu027.
Guilhaumou, R., Benaboud, S., Bennis, Y., Dahyot-Fizelier, C., Dailly, E., Gandia, P., et al. Optimization of the treatment with β-lactam antibiotics in critically ill patients—guidelines from the French Society of Pharmacology and Therapeutics (Société Française de Pharmacologie et Thérapeutique–SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d'Anesthésie et Réanimation–SFAR). Crit Care, 23, 2019, 104, 10.1186/s13054-019-2378-9.
AllerganUSA, Inc. AVYCAZ full prescribing information. 2019, Allergan USA, Inc., Madison, NJ https://media.allergan.com/actavis/actavis/media/allergan-pdf-documents/product-prescribing/Avycaz_Final_PI_CBE-0_10_2019.pdf [accessed 14 December 2020].
Holmgren, K., Cars, O., Danielson, B.G., Fellström, B., Wikström, B., Ceftazidime as prophylactic treatment in renal stone surgery: clinical evaluation and pharmacokinetics in renal tissue. Scand J Urol Nephrol 21 (1987), 315–321, 10.3109/00365598709180790.
Buijk, S.L.C.E., Gyssens, I.C., Mouton, J.W., Van Vliet, A., Verbrugh, H.A., Bruining, H.A., Pharmacokinetics of ceftazidime in serum and peritoneal exudate during continuous versus intermittent administration to patients with severe intra-abdominal infections. J Antimicrob Chemother 49 (2002), 121–128, 10.1093/jac/49.1.121.
Dimelow, R., Wright, J.G., MacPherson, M., Newell, P., Das, S., Population pharmacokinetic modelling of ceftazidime and avibactam in the plasma and epithelial lining fluid of healthy volunteers. Drugs R D 18 (2018), 221–230, 10.1007/s40268-018-0241-0.
Heffernan, A.J., Sime, F.B., Lipman, J., Dhanani, J., Andrews, K., Ellwood, D., et al. Intrapulmonary pharmacokinetics of antibiotics used to treat nosocomial pneumonia caused by Gram-negative bacilli: a systematic review. Int J Antimicrob Agents 53 (2019), 234–245, 10.1016/j.ijantimicag.2018.11.011.
Abbas, A.M.A., Taylor, M.C., Da Silva, A.J.J.M., Francis, R.A., Bennet, C., Penetration of ceftazidime into the human prostate gland following intravenous injection. J Antimicrob Chemother 15 (1985), 119–121, 10.1093/jac/15.1.119.
Wittmann, D.H., Schassan, H.H., Kohler, F., Seibert, W., Pharmacokinetic studies of ceftazidime in serum, bone, bile, tissue fluid and peritoneal fluid. J Antimicrob Chemother 8 (1981), 293–297, 10.1093/jac/8.suppl_b.293-a.
Carmeli, Y., Armstrong, J., Laud, P.J., Newell, P., Stone, G., Wardman, A., et al. Ceftazidime–avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study. Lancet Infect Dis 16 (2016), 661–673, 10.1016/S1473-3099(16)30004-4.
Torres, A., Zhong, N., Pachl, J., Timsit, J.F., Kollef, M., Chen, Z., et al. Ceftazidime–avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect Dis 18 (2018), 285–295, 10.1016/S1473-3099(17)30747-8.
Denooz, R., Charlier, C., Simultaneous determination of five β-lactam antibiotics (cefepim, ceftazidim, cefuroxim, meropenem and piperacillin) in human plasma by high-performance liquid chromatography with ultraviolet detection. J Chromatogr B Anal Technol Biomed Life Sci 864 (2008), 161–167, 10.1016/j.jchromb.2008.01.037.
Lee, Y.R., Miller, P.D., Alzghari, S.K., Blanco, D.D., Hager, J.D., Kuntz, K.S., Continuous infusion versus intermittent bolus of β-lactams in critically ill patients with respiratory infections: a systematic review and meta-analysis. Eur J Drug Metab Pharmacokinet 43 (2018), 155–170, 10.1007/s13318-017-0439-5.
Jager, N.G.L., van Hest, R.M., Lipman, J., Roberts, J.A., Cotta, M.O., Antibiotic exposure at the site of infection: principles and assessment of tissue penetration. Expert Rev Clin Pharmacol 12 (2019), 623–634, 10.1080/17512433.2019.1621161.
Abdul‑Aziz, M.H., Alffenaar, J.W.C., Bassetti, M., Bracht, H., Dimopoulos, G., Marriott, D., et al. Antimicrobial therapeutic drug monitoring in critically ill adult patients: a position paper. Intensive Care Med 46 (2020), 1127–1153, 10.1007/s00134-020-06050-1.
Tumbarello, M., Trecarichi, E.M., Corona, A., De Rosa, F.G., Bassetti, M., Mussini, C., et al. Efficacy of ceftazidime–avibactam salvage therapy in patients with infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Clin Infect Dis 68 (2019), 355–364, 10.1093/cid/ciy492.
Temkin, E., Torre-Cisneros, J., Beovic, B., Benito, N., Giannella, M., Gilarranz, R., et al. Ceftazidime–avibactam as salvage therapy for infections caused by carbapenem-resistant organisms. Antimicrob Agents Chemother, 61, 2017, 10.1128/AAC.01964-16 e01964-19.
