We heard it before. Continuous administration of antibiotics might be associated with better outcomes. However, results from smaller randomized controlled trials of beta-lactam showed inconsistent conclusions. Therefore, a large RCT was conducted

Settings: 31 ICUs in Croatia, Italy, Kazakhstan, Russia between June 2018 – August 2022.

Randomized, double-blind control trial.

Participants:

• Patients with sepsis or septic shock who were given meropenem by their clinicians. 
• A total of 607 patients were enrolled: 303 continuous meropenem vs. 304 intermittent administration of meropenem.

Outcome measurement: 

• Primary outcome: all cause mortality at day 28.
• Secondary outcome: emergency of pan-drug resistant bacteria at day 28.

Study Results:

• 369 (61%) had septic shock, while 33% had low respiratory tract infection. There were 442 (73%) had invasive mechanical ventilation. 
• Median SOFA score was 9 [6-11]; the median daily meropenem dose was 0.04 g/kg/day (total of 3 g/day).
• The all cause mortality at 28 days was 91 (30%) for continuous group vs. 99 (33%) (P = 0.50) for intermittent group.
• The rate of emergence of pandrug resistant bacteria was 68/288 (24%) vs. 70/280 (25%) (P= 0.70)

Discussion:

• The current study involved more high risk patients, as the median SOFA was high at 9
• There was no therapeutic monitoring in this study, so the minimal inhibitory concentration was not known.
• Continuous meropenem might be less labor-intensive than intermittent meropenem, which required administration every 8 hours.

Conclusion: 

In critically ill patients with sepsis, continuous administration of meropenem did not improve mortality nor reduce the emergence of pandrug resistant bacteria.

References

Monti G, Bradic N, Marzaroli M, Konkayev A, Fominskiy E, Kotani Y, Likhvantsev VV, Momesso E, Nogtev P, Lobreglio R, Redkin I, Toffoletto F, Bruni A, Baiardo Redaelli M, D'Andrea N, Paternoster G, Scandroglio AM, Gallicchio F, Ballestra M, Calabrò MG, Cotoia A, Perone R, Cuffaro R, Montrucchio G, Pota V, Ananiadou S, Lembo R, Musu M, Rauch S, Galbiati C, Pinelli F, Pasin L, Guarracino F, Santarpino G, Agrò FE, Bove T, Corradi F, Forfori F, Longhini F, Cecconi M, Landoni G, Bellomo R, Zangrillo A; MERCY Investigators. Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial. JAMA. 2023 Jul 11;330(2):141-151. doi: 10.1001/jama.2023.10598. PMID: 37326473; PMCID: PMC10276329.