Kidney Week

Abstract: SA-PO629

Meropenem Renal Kinetics in Human Kidney Biopsies

Session Information

• Pharmacology
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

• 1700 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

• Sepúlveda, Rodrigo, Pontificia Universidad Católica de Chile, Santiago, Chile

Rodrigo Sepúlveda,

• Downey, Patricio, Pontificia Universidad Católica de Chile, Santiago, Chile

Patricio Downey,

• Huidobro, Juan Pablo, Pontificia Universidad Católica de Chile, Santiago, Chile

Juan Pablo Huidobro,

• Soto, Dagoberto, Pontificia Universidad Católica de Chile, Santiago, Chile

Dagoberto Soto,

• Andresen, Max, Pontificia Universidad Católica de Chile, Santiago, Chile

Max Andresen,

Background

Urinary tract infection is the most common bacterial infection. Usually it has good prognosis even though some cases can have serious complications. Last decades multi-resistant bacterial strains are arising but development of antibiotics has declined. Meropenem is a broad-spectrum antibiotic with activity against many bacteria including multi-resistant strains; however, its renal tissue kinetics is unknown.

Methods

We conducted a descriptive study in humans with indication of kidney biopsy. Meropenem was infused over 30 minutes one hour before biopsy performed and was evaluated the plasmatic concentration after meropenem infusion (T1), 60 minutes (T2) and 120 minutes (T3). Also meropenem concentration in the kidney sample was measured. It was used a fluorescent biosensor for B-Lactams antibiotics to measure levels of meropenem.

Results

In 14 patients, 64% women, body mass index was 26.3 ±2.9, eGFR was 57.5 ±44.1 ml/min/1.73m² and plasma albumin 3.8 ±0.9 g/dL.
Kidney biopsy was done at 68.9 ±20.3 minutes after meropenem infusion; the second plasma sample was obtained at 82.1 ±21.2 minutes and the third at 149.6 ±31.5 minutes. Meropenem concentrations at T1, T2 and T3 were 45.9 ±10, 20.7 ±13, 16.6 ±13 µg/mL respectively. Mean kidney sample weight was 5.9 ±3.0 mg and meropenem concentration was 3.1 ±1.9 µg/mL. For each patient a decay curve was constructed and meropenem plasma concentration was estimated at the biopsy time. The ratio of meropenem concentration between plasma and renal tissue (mP/mK) was 14 ±10% with a range of 3.8% – 34.8%.
Meropenem excretion occurs predominantly by glomerular filtration, thus plasma concentration and glomerular filtration rate determine the filtered load, modifying the urinary concentration and keeping the (mP/mK) ratio constant over time. The absence of linear correlation between (mP/mK) ratio and eGFR supports this idea. With the standard meropenem doses and normal renal function, we estimate that is possible treating with bactericide effect to bacteria with MIC90 <0.76 µg/mL.

Conclusion

With standard meropenem doses is possible achieve adequate concentration in renal parenchyma to treat, with bactericide effect, most frequent uropathogens. Nevertheless, for resistant bacteria is necessary increase the dose or consider another antibiotic. Renal failure does not avoid achieving adequate meropenem renal tissue concentrations.

Funding

• Private Foundation Support