==== Front Ann Intensive Care Ann Intensive Care Annals of Intensive Care 2110-5820 Springer International Publishing Cham 33275170 781 10.1186/s13613-020-00781-6 Letter to the Editor Response to: 500 mg as bolus followed by an extended infusion of 1500 mg of meropenem every 8 h failed to achieve in one-third of the patients an optimal PK/PD against nonresistant strains of these organisms: is CRRT responsible for this situation? Kothekar Amol 1 http://orcid.org/0000-0001-7384-4886Divatia Jigeeshu Vasishtha jdivatia@yahoo.com 1 Myatra Sheila Nainan 1 Gota Vikram 2 1 grid.410871.b0000 0004 1769 5793Department of Anesthesiology, Critical Care and Pain, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India 2 grid.410869.20000 0004 1766 7522Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Homi Bhabha National Institute, Kharghar, Navi Mumbai, India 4 12 2020 4 12 2020 2020 10 16412 10 2020 21 11 2020 © The Author(s) 2020Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.issue-copyright-statement© The Author(s) 2020 ==== Body We thank Prof. Honore and colleagues for their interest in our article [1] and their thought-provoking comments [2]. They are indeed correct in observing that in our study pertaining to the patients with severe sepsis or septic shock, 3 h extended infusions (EI) of 1000 mg of meropenem, administered every 8 h failed to achieve a fraction of time (fT) > 4 μg/mL > 40 in more than one-third of patients. We were, therefore, intrigued by their title “500 mg as bolus followed by an extended infusion of 1500 mg of meropenem every 8 h failed to achieve in one-third of the patients an optimal PK/PD against nonresistant strains of these organisms”. We believe that their title needs to be corrected as the results of our modelling clearly showed that 500 mg as bolus followed by an extended infusion of 1500 mg of meropenem every 8 h would achieve fT > 4 μg/mL > 40 effective against non-resistant strains of these organisms in all patients. They also raise an important question regarding the proportion of patients in the study who received continuous renal replacement therapies (CRRT), as meropenem is known to have significant elimination by CRRT [3]. None of our patients during the study period of 72 h required or were subjected to any form of renal replacement therapy including CRRT. Therefore, it follows that the lower exposure observed in eight out of 24 (33%) patients in our study was due to an inherent alteration in the disposition of meropenem in our cohort of patients and not due to extraneous factors such as CRRT. We would like to note that the observations made by Isla et al. may not apply in our case due to inherent difference in study population [1, 3]. Patients in the study by Isla et al. had higher APACHE II scores (19.4 ± 6.8 vs 15.4 ± 8.09) and SOFA scores (13.1 ± 4.0 vs 7.35 ± 3.62) compared to our study population. Moreover, their patients had lower calculated creatinine clearance (CLCR) (37.4 ± 42.3 mL/min vs 73.8 ± 26.6 mL/min) and frequent need of CRRT (50% of patients). We excluded patients with baseline calculated creatinine clearance (CLCR) < 50 mL/min and those not expected to survive for 72 h. To conclude, lower exposure of conventional 3 h of extended infusions of meropenem in adult patients with severe sepsis and septic shock in our study indicates altered natural disposition of meropenem rather than elimination of meropenem by CRRT. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Acknowledgements None. Authors’ contributions JVD, AK and VG were involved in writing of the manuscript. JVD, SNM, AK and VG substantively revised the manuscript. JVD took the overall responsibility of the project. All authors have approved the submitted version and have agreed both be personally accountable for the author’s own contributions and would ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, will be appropriately investigated, resolved, and the resolution documented in the literature. All authors read and approved the final manuscript. Funding None. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate Not applicable (manuscript does not report on or involve the use of any animal or human data or tissue). Consent for publication Not applicable. (Individual details, images or videos are not included). Competing interests All the authors declare no conflict of interest. ==== Refs References 1. Kothekar AT Divatia JV Myatra SN Patil A Nookala Krishnamurthy M Maheshwarappa HM Siddiqui SS Gurjar M Biswas S Gota V Clinical pharmacokinetics of 3-h extended infusion of meropenem in adult patients with severe sepsis and septic shock: implications for empirical therapy against Gram-negative bacteria Ann Intensive Care. 2020 10 10 4 10.1186/s13613-019-0622-8 31925610 2. Honore et al. 500 mg as bolus followed by an extended infusion of 1500 mg of meropenem every 8 hours failed to achieve in one third of the patients an optimal PK/PD against nonresistant strains of these organisms: Is CRRT responsible for this situation? Ann Intensive Care. 2020. 3. Isla A Rodríguez-Gascón A Trocóniz IF Bueno L Solinís MA Maynar J Sánchez-Izquierdo JA Pedraz JL Population pharmacokinetics of meropenem in critically ill patients undergoing continuous renal replacement therapy Clin Pharmacokinet 2008 47 173 180 10.2165/00003088-200847030-00003 18307371