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Meropenem serves as a clinically important, broad-spectrum antibiotic. While meropenem is commonly used in obese patients, its pharmacokinetics in this patient group is not well known. Our aim was to characterize the population pharmacokinetics and target attainment in plasma, subcutaneous tissue, and peritoneal fluid for meropenem in morbidly obese patients. Four doses of 1g meropenem were given as 15-min infusions every 8 h to five morbidly obese patients (body mass index [BMI], 47.6 to 62.3 kg/m 2 ). After the fourth dose, serial meropenem concentrations were determined in plasma and, via microdialysis, in subcutaneous tissue and peritoneal fluid. All concentrations were analyzed simultaneously via population modeling, and target attainment probabilities predicted via Monte Carlo simulations using the target of unbound meropenem concentrations above the MIC for at least 40% of the dosing interval. For patients with 53 kg fat-free mass, total clearance was 18.7 liters/h and volume of distribution at steady state was 27.6 liters. The concentrations in subcutaneous tissue and peritoneal fluid largely paralleled those in plasma (equilibration half-life, 90% after 1 g meropenem every 8 h as a 15-min infusion for MICs of up to 2 mg/liter in plasma and peritoneal fluid and 0.5 mg/liter in subcutaneous tissue. Meropenem pharmacokinetics in plasma and peritoneal fluid of obese patients was predictable, but subcutaneous tissue penetration varied greatly. (This study has been registered at ClinicalTrials.gov under registration no. NCT01407965.)

Ertapenem provides broad-spectrum activity against many pathogens, and its use is relevant for the prophylaxis and treatment of infections in morbidly obese patients undergoing surgery. However, its pharmacokinetics and tissue penetration in these patients are not well defined. We assessed the population pharmacokinetics and target attainment for ertapenem in the plasma, subcutaneous tissue, and peritoneal fluid of morbidly obese patients. Six female patients (body mass index, 43.7 to 55.9 kg/m 2 ) received 1,000 mg ertapenem as 15-min infusions at 0 and 26 h. On day 2, the unbound ertapenem concentrations in plasma, subcutaneous tissue, and peritoneal fluid were measured by microdialysis; total plasma concentrations were additionally quantified. The probability of attaining a target of an unbound ertapenem concentration above the MIC for at least 40% of the dosing interval was predicted via Monte Carlo simulations. The population pharmacokinetic model contained two disposition compartments and simultaneously described all concentrations. For unbound ertapenem, total clearance was 12.3 liters/h (coefficient of variation, 21.6% for between-patient variability) and the volume of distribution at steady state was 57.8 liters in patients with a 53-kg fat-free mass. The area under the concentration-time curve (AUC) for ertapenem was 49% lower in subcutaneous tissue and 25% lower in peritoneal fluid than the unbound AUC in plasma. Tissue penetration was rapid (equilibration half-life, 90%) target attainment probabilities for MICs of up to 1 mg/liter in plasma, 0.25 to 0.5 mg/liter in subcutaneous tissue, and 0.5 mg/liter in peritoneal fluid. Ertapenem presents an attractive choice for many pathogens relevant to morbidly obese patients undergoing surgery. (This study has been registered at ClinicalTrials.gov under identifier NCT01407965.)

Benign cystic teratoma of the pancreas often appears to be potentially malignant in preoperative staging. The final diagnosis is generally obtained after surgical removal. Reliable prediction is mandatory for differential treatment.A Medline query was performed for the terms cystic teratoma, dermoid cyst and pancreas. Data were analyzed for patient characteristics, clinical appearance, diagnostic findings, therapy and follow-up.Including our own, 26 cases of pancreatic cystic teratoma were identified. The majority of patients were symptomatic by unspecific gastrointestinal complaints. Up to date, imaging techniques fail at a distinct preoperative diagnosis. Surgical treatment evolved from various drainage and excision procedures into radical resection.Despite the strictly benign nature of cystic teratoma, oncologic resection is mostly inevitable due to difficult preoperative diagnosis. No reliable predictive marker was found to allow for organ- or parenchyma-preserving procedures. Therefore, surgery remains the treatment of choice to exclude malignancy.

Background: There are only limited data on tissue kinetics of ertapenem in colorectal tissue more than 3 h after administration of the drug. The purpose of this study was to assess the pharmacokinetics (PK) of ertapenem in colorectal tissue via population PK modeling. Patients and Methods: Patients ���18 years requiring surgical intervention at the colon and/or rectum were eligible (ClinicalTrials.gov identifier: NCT 00535652). Tissue and blood samples were taken during surgery after a single dose of 1 g ertapenem. Ertapenem concentration was determined by high-performance liquid chromatography/mass spectrometry. Population PK modeling was performed in S-ADAPT. Results: Twenty-three patients were enrolled. The highest tissue concentration was 6.4 �� 2.3 mg/kg, the highest total plasma concentration 51.34 �� 9.4 mg/l, the highest unbound plasma concentration 7.05 �� 1.1 mg/l, and the unbound fraction in plasma was 14���15% for total ertapenem concentrations below approximately 22 mg/l, 19% at 100 mg/l, and 25% at 250 mg/l. The estimated geometric mean terminal half-life was 2.5 h for plasma and tissue. In the Monte Carlo simulation, a single dose of 1,000 mg ertapenem achieved robust (���90%) probabilities of target attainment up to a minimum inhibitory concentration (MIC) of approximately 2 mg/l for the bacteriostasis target (free time above MIC, fT>MIC = 20%) and up to 0.25���0.5 mg/l for the near-maximal killing target (40% fT>MIC). Conclusion: Our data indicate an adequate penetration of ertapenem into uninfected colorectal tissue up to 8.5 h (35% of the dosing interval) after administration of 1 g intravenously. �� In Copyright http://rightsstatements.org/vocab/InC/1.0/, publishedVersion

The incidence of acute pancreatitis varies from 5 to 80 per 100,000 inhabitants throughout the world. Recognizing the natural course of severe acute pancreatitis a multidisciplinary approach had become the standard. The strategy of postponing surgical intervention was implemented in the treatment algorithm several years ago.A retrospective analysis of patient data from two five-year periods. The first period was from 01/1992 to 12/1997 (group 1), the second period from 10/2001 to 12/2006 (group 2).In this study, we retrospectively analyzed the impact of this approach on the outcome of our patients with necrotizing pancreatitis. The time interval between onset of disease and first necrosectomy was in the mean 19.5 days in patients of group 1 and 30 days in group 2 (p = 0.015). In group 1, 45/78 patients (57%) were operated on during the first 14 days compared to 8/32 patients (25%; p = 0.002) in group 2. The mortality was 41% in group 1 and 18% in group 2 (p = 0.026). There was also a statistically significant decrease in mortality when first necrosectomy was postponed after day 29 (p = 0.015).Our results are in line with several other analyses suggesting that the strategy of postponing surgery in patients with necrotizing pancreatitis is associated with a decreased mortality.

Objectives: Ertapenem, a class I carbapenem, is approved for the treatment of mild to severe intraabdominal infections, but its in vivo concentrations in intraabdominal tissues are unknown. The purpose of this study was to determine the concentration of ertapenem in intraabdominal tissue. Patients and methods: After informed consent 48 patients, 23 female and 25 male with a median age of 58 years (34–81), requiring surgical intervention at intraabdominal organs were enrolled. Patients received 1 g of ertapenem intravenously for perioperative prophylaxis. Tissue samples were taken after resection of parts of the organs. Plasma samples were taken when tissue samples were taken. Drug concentrations were determined by liquid chromatography/mass spectrometry. An ANCOVA test (analysis of covariance) was performed to assess organ-specific differences in ertapenem concentration and penetration ratios. Results: Mean – SD ertapenem tissue concentration (mg/kg) was 16.0 – 8.8 in the gall bladder, 12.1 – 5.3 in the colon, 7.0 – 5.7 in the small bowel, 4.5 – 2.3 in the liver and 3.4 – 2.9 in the pancreas. The mean tissue/plasma ratio was 0.19 (colon), 0.17 (small bowel), 0.17 (gall bladder), 0.088 (liver) and 0.095 (pancreas). The ANCOVA test revealed statistically significant organ-specific differences in ertapenem tissue concentration in the gall bladder versus liver/pancreas and in tissue penetration for the colon versus liver/pancreas. Conclusions: These pharmacokinetic results support the assumption that ertapenem is suitable for the treatment of intraabdominal infections.