Evaluation of Meropenem Extended Versus Intermittent Infusion Dosing Protocol in Critically Ill Patients

Abstract

<jats:p> Extended infusion (EI) administration of β-lactams can improve target attainment in critically ill patients with altered pharmacokinetics/pharmacodynamics. To optimize meropenem dosing in patients with severe sepsis/septic shock, our Antimicrobial Stewardship Program implemented a EI meropenem (EIM) protocol in an 18-bed Medical Intensive Care Unit in March 2014. In this retrospective study, we compared intensive care unit (ICU) mortality and clinical response in patients who received meropenem for ≥72 hours administered per EIM protocol of 1 g over 3 hours every 8 hours versus intermittent infusion (IIM) protocol of 500 mg over 30 minutes every 6 hours. Age, weight, comorbidities, severity of illness, and vasopressor use were comparable between groups (EIM protocol n = 52, IIM protocol n = 96). The IIM protocol group had higher rates of renal dose adjustment at meropenem initiation. Among 56 identified gram-negative (GN) pathogens, 94% had meropenem minimal inhibitory concentration ≤0.25 mg/L. The ICU mortality was lower (19 vs 37%; P = .032) and clinical response was higher (83% vs 46%; P &lt; .01) in the EIM protocol versus IIM protocol group. Total vasopressor days were shorter (2 vs 3 days; P = .038), and white blood cell normalization rate was higher (87% vs 51%; P &lt; .01) in the EIM protocol versus IIM protocol group. There was no difference in days of mechanical ventilation, duration of therapy, and ICU stay. The IIM protocol was also identified as an independent risk factor associated with ICU mortality (hazard ratio: 3.653, 95% confidence interval: 1.689-7.981; P = .001) after adjusting for Sequential Organ Failure Assessment score. In this cohort of patients with severe sepsis/septic shock and highly susceptible GN pathogens, there was improved mortality and clinical response in the EIM protocol group. </jats:p>

Loading dose and efficacy of continuous or extended infusion of beta‐lactams compared with intermittent administration in patients with critical illnesses: A subgroup meta‐analysis and meta‐regression analysis

“…1). In these studies, outcomes were reported with mortality, clinical cure, microbiological eradication, length of ICU or hospital stay, duration of mechanical ventilation, the percentage of time that the free antibiotic concentration exceeds the MIC (%fT > MIC) and %fT > 4 × MIC 7‐37 . All eligible trials involved the use of beta‐lactams including piperacillin/tazobactam, ticarcillin‐clavulanate, cefepime, ceftazidime, ceftriaxone, cefoperazone, doripenem, imipenem/cilastatin or meropenem.…”

“…The %fT > MIC might decrease to zero for continuous infusion and may remain at a low‐to‐intermediate level when using prolonged or short‐term infusions. It would be interesting to see whether improved RRs in the comparison of continuous and short‐term infusions would result in lower CrCl values 8,9,17,25 …”

Therapeutic Drug Monitoring of Meropenem and Piperacillin in Critical Illness—Experience and Recommendations from One Year in Routine Clinical Practice

“…Augmented renal clearance is a well-known risk factor for target failure in antibiotic dosing [35,45], and a number of published studies have shown that prolonged infusion is a valuable treatment option with respect to target attainment, pathogen eradication, and the reduction of mortality [34,46,47]. Nevertheless, many treating physicians in Germany, where the SmPC does not support prolonged infusion, feel uncomfortable with this type of treatment.…”

Comparison of extended versus intermittent infusion of antipseudomonal beta-lactams for the treatment of critically ill patients with respiratory infections: A systematic review and meta-analysis

“…Characteristics of the studies included in the meta-analysis are described in Table 1. Among nine total studies, two were RCTs (Lyu et al, 2018;Ammar and Abdalla, 2018), three were quasi-experimental studies (Fahimi et al, 2012;Arnold et al, 2013;Bauer et al, 2013) and four were retrospective cohort studies (Lodise et al, 2007;Lee et al, 2012;Ibrahim et al, 2017;Ahmed et al, 2018). The studies spanned three continents (USA, Asia and Africa).…”

“…The conventional II period was 30-60 min and the extended infusion duration was 3-4 h. Five studies used the same total daily doses in both arms. In several studies, the β-lactam doses were adjusted for renal insufficiency (Lodise et al, 2007;Lee et al, 2012;Arnold et al, 2013;Bauer et al, 2013;Ibrahim et al, 2017;Ahmed et al, 2018). None of the studies were funded by pharmaceutical companies.…”