Presence of tobramycin in blood and urine during selective decontamination of the digestive tract in critically ill patients, a prospective cohort study

Abstract

IntroductionTobramycin is one of the components used for selective decontamination of the digestive tract (SDD), applied to prevent colonization and subsequent infections in critically ill patients. Tobramycin is administered in the oropharynx and gastrointestinal tract and is normally not absorbed. However, critical illness may convey gut barrier failure. The aim of the study was to assess the prevalence and amount of tobramycin leakage from the gut into the blood, to quantify tobramycin excretion in urine, and to determine the association of tobramycin leakage with markers of circulation, kidney function and other organ failure.MethodsThis was a prospective observational cohort study. The setting was the 20-bed closed format-mixed ICU of a teaching hospital. The study population was critically ill patients with an expected stay of more than two days, receiving SDD with tobramycin, polymyxin-E and amphotericin-B four times daily in the oropharynx and stomach. Tobramycin concentration was measured in serum (sensitive high performance liquid chromatography - mass spectrometry/mass spectrometry (HLPC-MS/MS) assay) and 24-hour urine (conventional immunoassay), in 34 patients, 24 hours after ICU admission, and in 71 patients, once daily for 7 days. Tobramycin leakage was defined as tobramycin detected in serum at least once (> 0.05 mg/L). Ototoxicity was not monitored.ResultsOf the 100 patients with available blood samples, 83 had tobramycin leakage. Median highest serum concentration for each patient was 0.12 mg/L; 99% of the patients had at least one positive urinary sample (> 0.5 mg/L), 49% had a urinary concentration ≥ 1 mg/L. The highest tobramycin serum concentration was significantly associated with vasopressor support, renal and hepatic dysfunction, and C-reactive protein. At binary logistic regression analysis, high dopamine dose and low urinary output on Day 1 were the significant predictors of tobramycin leakage. Nephrotoxicity could not be shown.ConclusionsThe majority of acute critically ill patients treated with enteral tobramycin as a component of SDD had traces of tobramycin in the blood, especially those with severe shock, inflammation and subsequent acute kidney injury, suggesting loss of gut barrier and decreased renal removal. Unexpectedly, urinary tobramycin was above the therapeutic trough level in half of the patients. Nephrotoxicity could not be demonstrated.

Enhanced oral bioavailability of vancomycin in rats treated with long-term parenteral nutrition

“…Selective decontamination of the digestive tract (SDD) prophylaxis of BT, which prevents the overgrowth of pathogens by enteral co-administration of non-absorbable antibiotics, such as colistin, tobramycin, amphotericin B, and vancomycin (VCM) (Benus et al 2010 ; Cerdá et al 2007 ; Roos et al 2011 ) has been previously reported. It has been shown that any absorption of the non-absorbable antibiotic in the SDD regimen can be considered negligible under “normal conditions”; however, significant absorption of tobramycin was reported in critically ill patients (Oudemans-van Straaten et al 2011 ), as was VCM in patients with chemotherapy-associated and/or Clostridium difficile colitis (Aradhyula et al 2006 ; Bergeron and Boucher 1994 ). In addition, we previously reported the enhanced intestinal permeability of a hydrophilic dye, phenolsulfonphthalein, in PN-induced intestinal atrophy (Fukushima et al 2015 ).…”

Analyses of acute kidney injury biomarkers by ultra‐high performance liquid chromatography with mass spectrometry

“…Oudemans‐van Straaten et al. used HPLC–MS/MS assay for the determination of tobramycin concentration in serum and urine. The experimental conditions for the analyses of some AKI biomarkers in plasma and urine of human beings and rats are summarized in Tables and , respectively.…”

Management of Intra-abdominal Infections due to Carbapenemase-Producing Organisms

“…If the gut barrier is intact, the antibiotics exert their effect in the digestive tract and are not absorbed. However, conditions such as sepsis, shock, and major surgery can lead to gut barrier failure [54] and may result in the antibiotics leaking from the gut into the blood.…”