Impaired Target Site Penetration of Vancomycin in Diabetic Patients following Cardiac Surgery

Soft tissue infections constitute a serious complication following surgery in diabetic patients and frequently require the administration of vancomycin. However, despite antibiotic treatment, mortality of patients with postoperative infections remains high and might be related to an impaired penetration of anti-infective agents to target tissues. Therefore, the present study was designed to measure vancomycin tissue concentrations in six diabetic and six nondiabetic patients after cardiac surgery. Vancomycin was administered as a continuous intravenous infusion at an infusion rate of 80 to 120 mg/h. Vancomycin concentrations in soft tissues and plasma were measured in all patients during steady state as “therapeutic window” concentrations in plasma by microdialysis on day 8 ± 4 after initiation of vancomycin treatment. Vancomycin tissue concentrations in diabetic patients were significantly lower than in nondiabetics (3.7 mg/liter versus 11.9 mg/liter; P = 0.002). The median vancomycin(tissue)/vancomycin(plasma) concentration ratio was 0.1 in diabetic patients and 0.3 in nondiabetics (P = 0.002). Our study demonstrated that vancomycin penetration into target tissues is substantially impaired in diabetic patients versus nondiabetics. Insufficient tissue concentrations could therefore possibly contribute to failure of antibiotic treatment and the development of antimicrobial resistance in diabetic patients

The Impact of Nonconvulsive Status Epilepticus after Cardiac Surgery on Outcome

Neurological complications after heart surgery are associated with tremendous morbidity and mortality. Nonconvulsive status epilepticus (NCSE), which can only be verified by EEG, may cause secondary brain damage. Its frequency and its impact on outcomes after cardiac surgery is still unclear. We collected the neurological files and clinical data of all our patients after heart surgery who, in the course of their ICU stay, had been seen by a neurologist who ordered an EEG. Within 18 months, 1457 patients had cardiac surgery on cardiopulmonary bypass. EEG was requested for 89 patients. Seizures were detected in 39 patients and NCSE was detected in 11 patients. Open heart surgery was performed in all 11 NSCE patients, of whom eight showed concomitant brain insults. None had a history of epilepsy. Despite the inhibition of seizure activity with antiseizure medication, clinical improvement was only noted in seven NCSE patients, three of whom were in cerebral performance category 2 and four in category 3 at hospital discharge. The four patients without neurological benefit subsequently died in the ICU. The occurrence of NCSE after open cardiac surgery is significant and frequently associated with brain injury. It seems prudent to perform EEG studies early to interrupt seizure activity and mitigate secondary cerebral injury

In Vivo Measurement of Levofloxacin Penetration into Lung Tissue after Cardiac Surgery

Nosocomial pneumonia is a severe complication after cardiac surgery (CS). Levofloxacin, a fluoroquinolone, qualifies for the therapy of postoperative pneumonia. However, penetration properties of levofloxacin into the lung tissue could be substantially affected by CS: atelectasis, low cardiac output after CS, high volume loads, and inflammatory capillary leak potentially influence drug distribution. The aim of our study was to gain information on interstitial antibiotic concentrations in lung tissue in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. Therefore, six patients undergoing elective CS participated in this prospective study. A dose of 500 mg of levofloxacin was administered intravenously in addition to standard antibiotic prophylaxis immediately after the end of surgery. Time versus concentration profiles of levofloxacin in the interstitial lung tissue and plasma were determined. A microdialysis technique was used for lung interstitial concentration measurements. The microdialysis procedure was well tolerated in all patients and no adverse events were observed. The median area under the concentration curve (AUC) of levofloxacin in interstitial lung fluid was 18.6 μg · h/ml (range, 10.1 to 33.6). The median AUC for tissue (AUC(tissue)) of unbound levofloxacin/AUC(total) in plasma was 0.6 (range, 0.4 to 0.9). The median unbound AUC(tissue)/MIC was 2.4 (range, 1.3 to 4.2) for Pseudomonas aeruginosa. Our study demonstrated the feasibility and safety of microdialysis in human lung tissue in vivo after CS. The unbound AUC/MIC ratio revealed that levofloxacin used in the described manner was borderline sufficient for the treatment of nosocomial pneumonia caused by Klebsiella pneumoniae and insufficient for the treatment of pneumonia caused by Pseudomonas aeruginosa, because the breakpoint of 30 to 40 for AUC/MIC could not be reached by the conventionally used dosage schema in our post-CS setting. Penetration was lower than in previous reports