Study of blood level of lifesaving antibiotic meropenum in serious ICU patients in relation to blood level that kills bacteria.

Completed

• Conditions: critically ill patients in ICU

• Registration Number: CTRI/2013/07/003850
• Lead Sponsor: Tata Memorial Hospital

Brief Summary

Meropenem is a broad spectrum antibiotic belonging to carbapenem group**.** Meropenem is used as empirical therapy in severe sepsis to cover gram negative bacilli. Meropenem is a time-dependent antibiotic, whose antibacterial activity is related to the ‘time for which the free concentration is maintained above the MIC during a dosing interval’ (f T >MIC).  The f T>MIC required for optimal bactericidal activity for carbapenems has been reported to be 40% . Presently in TMH ICU Meropenem is routinely given as an infusion over 3 hours. However plasma meropenem levels achieved in critically ill septic patients might be variable due to pharmacokinetic changes in sepsis.

This study is designed to determine whether  the current dosing strategy of Meropenem is achieving

·         Meropenem plasma level > MIC (2 microgram/ ml) for intermediate Enterobacteriaceae GNB’s

·         Meropenem concentration above MIC for more than 40% of times between two doses. (fT>MIC of 40%)

We will also determine whether the levels achieved with this strategy will inhibit sensitive and intermediate strains of non lactose fermenter GNB’s like acinetobacter and pseudomonas.

25 consecutive patients meeting inclusion and exclusion criteria will be enrolled. Plasma Meropenem concentration will be determined using a validated reverse phase  HPLC assay.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06-16
• Last Update Posted: 2017-12-29

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• Inclusion criteria •Adult critically ill patients •Age 18 yr to 70 yrs •Known or suspected sepsis.
• •Baseline plasma creatinine concentration within upper limit of normal •Meropenem (MEROMER®) therapy initiated in ICU and expected to be continued for at least 3 days.

Exclusion Criteria

Not provided

Study & Design

• Study Type: Observational
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
T1. Peak plasma meropenem level	time zero, 5 min, 15 min, 30 min, and 1, 1.5, 2, 3, 4, 5, 6 and 8 h after the first dose of meropenum
1. fT (Time duration for which plasma concentration is above MIC)	time zero, 5 min, 15 min, 30 min, and 1, 1.5, 2, 3, 4, 5, 6 and 8 h after the first dose of meropenum
2. Proportion of patients with fT 40% of dosing interval.	time zero, 5 min, 15 min, 30 min, and 1, 1.5, 2, 3, 4, 5, 6 and 8 h after the first dose of meropenum
3. Pharmacokinetics parameters including AUC, Cmax, Tmax, Volume of Distribution (Vd), Half-life (T1/2), Clearance (Cl) and elimination rate constant (Kel)	time zero, 5 min, 15 min, 30 min, and 1, 1.5, 2, 3, 4, 5, 6 and 8 h after the first dose of meropenum
4. Time to MIC after first dose	time zero, 5 min, 15 min, 30 min, and 1, 1.5, 2, 3, 4, 5, 6 and 8 h after the first dose of meropenum

Secondary Outcome Measures

Name	Time	Method
1. Pharmacokinetics parameters including AUC, Cmax, Tmax, Volume of Distribution (Vd), Half-life (T1/2), Clearance (Cl) and elimination rate constant (Kel)	2. Time to MIC after first dose

Trial Locations

Locations (2)

Dr. Gota Laboratory, Clinical Pharmacology, ACTREC; 🇮🇳 Raigarh, MAHARASHTRA, India

Intensive Care Unit, Tata Memorial Hospital; 🇮🇳 Mumbai, MAHARASHTRA, India

Dr. Gota Laboratory, Clinical Pharmacology, ACTREC

🇮🇳Raigarh, MAHARASHTRA, India

Dr Vikram Gota

Principal investigator

02227405130

vgota@actrec.gov.in