[Show abstract][Hide abstract] ABSTRACT: 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 ≥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)).
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.
[Show abstract][Hide abstract] ABSTRACT: The incidence of acute pancreatitis varies from 5 to 80 per 100,000 throughout the world. The most common cause of death in these patients is infection of pancreatic necrosis by enteric bacteria, spurring the discussion of whether or not prophylactic antibiotic administration could be a beneficial approach. In order to provide evidence of the effect of antibiotic prophylaxis in severe acute pancreatitis (SAP) we performed an updated systematic review and meta-analysis on this topic.
The review of randomized controlled trials was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. We conducted a search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. For assessment of the treatment effects we calculated the risk ratios (RRs) for dichotomous data of included studies.
Fourteen trials were included with a total of 841 patients. The use of antibiotic prophylaxis was not associated with a statistically significant reduction in mortality (RR 0.74 [95% CI 0.50-1.07]), in the incidence of infected pancreatic necrosis (RR 0.78 [95% CI 0.60-1.02]), in the incidence of non-pancreatic infections (RR 0.70 [95% CI 0.46-1.06]), and in surgical interventions (RR 0.93 [95% CI 0.72-1.20]).
In summary, to date there is no evidence that supports the routine use of antibiotic prophylaxis in patients with SAP.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: The incidence of acute pancreatitis varies from 5 to 80 per 100,000 inhabitants throughout the world. The most common cause of death in these patients is infection of pancreatic necrosis by enteric bacteria, spurring the discussion of whether or not prophylactic antibiotic administration could be a beneficial approach. We therefore analyzed randomized clinical trials, which form the basis of guidelines and recommendations on this topic.
One trial demonstrated that antibiotic prophylaxis reduces mortality, but the statistical design of this trial was questionable. Another important trial, showing an effect of antibiotic prophylaxis on the incidence of pancreatic sepsis, used the wrong statistical test to analyze their data. An analysis with the correct test could not confirm this effect. Three randomized clinical trials demonstrated that antibiotic prophylaxis in severe acute pancreatitis could reduce the incidence of extrapancreatic infections. Two trials showed a significant reduction of the overall infection rate; while in one of them peripancreatic and extrapancreatic infections alone were not significantly different. Two double blinded studies could not demonstrate a significant effect of antibiotic prophylaxis on pancreatic/peripancreatic infection, extrapancreatic infection or mortality.
Our analysis shows that some of the reported significant effects of prophylactic antibiotic treatment are either questionable or less clinically relevant. With regards to reduction in mortality and the incidence of infected pancreatic necrosis, no convincing evidence exists which supports the routine administration of prophylactic antibiotics in severe acute pancreatitis.
[Show abstract][Hide abstract] ABSTRACT: Benign pancreatic tumors should undergo surgical resection when they are symptomatic or – in the case of incidental discovery – bear malignant potential. This is the case for the majority of benign pancreatic tumors, especially for intraductal papillary mucinous neoplasms or mucinous cystic adenomas. In addition, resection is indicated for all tumors where preoperative diagnostic fails to provide an exact classification.
Several different operative techniques are available. The treatment of choice depends on the localization of the tumor, its size and on whether there is evidence of malignant transformation. Partial duodenopancreatectomy is the oncological treatment of choice for tumors of the pancreatic head whereas for tumors of the pancreatic tail a left-sided pancreatectomy is appropriate. Middle pancreatectomy or duodenum-preserving resection of the pancreatic head is not a radical oncologic procedure. They should only be performed in cases of tumors without malignant potential.
Der Radiologe 08/2008; 48(8):732-739. DOI:10.1007/s00117-008-1669-y · 0.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Benign pancreatic tumors should undergo surgical resection when they are symptomatic or--in the case of incidental discovery--bear malignant potential. This is the case for the majority of benign pancreatic tumors, especially for intraductal papillary mucinous neoplasms or mucinous cystic adenomas. In addition, resection is indicated for all tumors where preoperative diagnostic fails to provide an exact classification.Several different operative techniques are available. The treatment of choice depends on the localization of the tumor, its size and on whether there is evidence of malignant transformation. Partial duodenopancreatectomy is the oncological treatment of choice for tumors of the pancreatic head whereas for tumors of the pancreatic tail a left-sided pancreatectomy is appropriate. Middle pancreatectomy or duodenum-preserving resection of the pancreatic head is not a radical oncologic procedure. They should only be performed in cases of tumors without malignant potential.
Der Radiologe 07/2008; 48(8):732; 734-9. · 0.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The clinical course in acute necrotizing pancreatitis is mainly determined by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic regimens for early and late treatment was investigated in the taurocholate model of necrotizing pancreatitis in the rat.
Seventy male Wistar rats were divided into five pancreatitis groups (12 animals each) and a sham-operated group (10 animals). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals received two different antibiotic regimes (20 mg/kg imipenem or 20 mg/kg ciprofloxacin plus 20 mg/kg metronidazole) early at 2, 12, 20, and 28 h after induction of pancreatitis or late at 16 and 24 h after induction of pancreatitis or no antibiotics (control). Animals were examined after 30 h for pancreatic and extrapancreatic infection.
Early and late antibiotic treatment with both regimes could significantly reduce pancreatic infection from 58 to 8-25%. However, extrapancreatic infection was only reduced by early antibiotic therapy. While quinolones also reduced bacterial counts in small and large bowel, imipenem did not.
In our animal model of necrotizing pancreatitis, early and late treatment with ciprofloxacin/metronidazole and imipenem reduce bacterial infection of the pancreas. Extrapancreatic infection, however, is reduced significantly only by early antibiotic treatment. The effectivity of early antibiotic treatment in the clinical setting should be subject to further investigation with improved study design and sufficient patient numbers.
Langenbeck s Archives of Surgery 06/2007; 392(3):365-70. DOI:10.1007/s00423-007-0166-5 · 2.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
These pharmacokinetic results support the assumption that ertapenem is suitable for the treatment of intraabdominal infections.
[Show abstract][Hide abstract] ABSTRACT: Infectious complications are the leading cause of death in patients with severe acute pancreatitis. Currently, there is controversy concerning the therapeutic possibilities to reduce the incidence of bacterial infection in this disease. Numerous studies are available which apparently support the prophylactic use of antibiotics in patients with necrotizing pancreatitis. The results, however, are contradicting and interpretation is difficult as these studies have used various antibiotic drugs with different application schemes and heterogeneous study end points. This article gives a critical overview of the background of antibiotic treatment in severe acute pancreatitis, the published data on antibiotic treatment and an outlook on the topics that need to be addressed by future research.
[Show abstract][Hide abstract] ABSTRACT: Severe acute pancreatitis is considered to be a subgroup of acute pancreatitis with the development of local and/or systemic complications. A significant correlation exists between the development of pancreatic necrosis, the frequency of bacterial contamination of necrosis and the evolution of systemic complications. Bacterial infection and the extent of necrosis are determinants for the outcome of severe acute pancreatitis. The late course of necrotizing pancreatitis is determined by bacterial infection of pancreatic and peripancreatic necroses. Mortality increases from 5-25% in patients with sterile necrosis to 15-28% when infection has occurred. The use of prophylactic antibiotics has been recommended in patients with necrotizing pancreatitis. Several controlled clinical trials demonstrated a significant reduction in pancreatic infections or a significant reduction of hospital mortality. However, the results of these clinical trials are controversial and not convincing. Recently, the largest randomized placebo-controlled, double-blind trial has been able to demonstrate that antibiotic prophylaxis with ciprofloxacin and metronidazole has no beneficial effects with regard to the reduction of pancreatic infection and the decrease of hospital mortality. The clinical data from this placebo-controlled trial do not support antibiotic prophylaxis in all patients with necrotizing pancreatitis, but in specific subgroups of patients with pancreatic necrosis and a complicated course.
[Show abstract][Hide abstract] ABSTRACT: Antibiotic prophylaxis in necrotizing pancreatitis remains controversial. Until now, there have been no double-blind studies dealing with this topic.
A total sample size of 200 patients was calculated to demonstrate with a power of 90% that antibiotic prophylaxis reduces the proportion of patients with infected pancreatic necrosis from 40% placebo (PLA) to 20% ciprofloxacin/metronidazole (CIP/MET). One hundred fourteen patients with acute pancreatitis in combination with a serum C-reactive protein exceeding 150 mg/L and/or necrosis on contrast-enhanced CT scan were enrolled and received either intravenous CIP (2 x 400 mg/day) + MET (2 x 500 mg/day) or PLA. Study medication was discontinued and switched to open antibiotic treatment when infectious complications, multiple organ failure sepsis, or systemic inflammatory response syndrome (SIRS) occurred. After half of the planned sample size was recruited, an adaptive interim analysis was performed, and recruitment was stopped.
Fifty-eight patients received CIP/MET and 56 patients PLA. Twenty-eight percent in the CIP/MET group required open antibiotic treatment vs. 46% with PLA. Twelve percent of the CIP/MET group developed infected pancreatic necrosis compared with 9% of the PLA group (P = 0.585). Mortality was 5% in the CIP/MET and 7% in the PLA group. In 76 patients with pancreatic necrosis on contrast-enhanced CT scan, no differences in the rate of infected pancreatic necrosis, systemic complications, or mortality were observed.
This study detected no benefit of antibiotic prophylaxis with respect to the risk of developing infected pancreatic necrosis.
[Show abstract][Hide abstract] ABSTRACT: An efficient Operating Room (OR) management might increase the cost-effectiveness of an OR. For this purpose, we have evaluated the coordination and the times of the solitary processes that are involved in the patient turnover. The mean time between skin suture of the preceding patient and incision of the following patient (SI-time) was, depending on the type of operation, between 44 and 78 minutes. Mean empty-room time (ERT) was 7 minutes. SI-times depended on various factors, including the times necessary to discharge the preceding patient from the OR and the times necessary for induction of anesthesia or for preparation of the OR. Altogether, our data provide evidence for the fact, that optimisation of the patients turnover can decrease SI-times between 10-15 minutes. Although this period appears too short to reliably allow an additional scheduled operation during regular working hours, an improved coordination may result in reduced overtimes of the OR-staff and thus should increase staff satisfaction.
Zentralblatt für Chirurgie 02/2004; 129(1):4-9. DOI:10.1055/s-2004-44875 · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The change in hospital funding with diagnosis related groups (DRG), medical advances as well as demographic changes will call for new quantitative and qualitative standards imposed on German hospitals. Increasing costs and competition in the health care sector requires new and innovative strategies for resource management. Today's policy is mainly defined by rationing and intensified workload. The introduction of DRGs will presumably further constrict management perspectives on pure financial aspects. However, to ensure future development, compassionate services and continued existence of hospitals, a balance of seemingly conflicting perspectives, such as finance, customer, process, learning and growth are of utmost importance. Herein doctors and nurses in leading positions should play a key role in changing management practice. For several years the balanced scorecard has been successfully used as a strategic management concept in non-profit organizations, even in the health care sector. This concept complies with the multidimensional purposes of hospitals and focuses on policy deployment. Finally it gives the opportunity to involve all employees in the original development, communication and execution of a balanced scorecard approach.
Der Anaesthesist 11/2003; 52(10):947-56. DOI:10.1007/s00101-003-0574-z · 0.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There has been a steady rise in the incidence of pancreatic fungal infections. Even though fungal infections of the pancreas are not very common, they are often nosocomial.
To review pancreatic fungal infections and to compare their clinical characteristics with those of bacterial pancreatic infections, along with the causes and approaches to diagnosis and treatment.
Because of the lack of randomized, prospective trials, standardized recommendations for use of antifungal prophylaxis would be premature. The most important aspect of prophylaxis against pancreatic fungal infection is minimizing the factors that predispose the pancreas to fungal infections.
Isolation of fungal elements from necrotic pancreatic tissue and treatment of local infection are vital. Treatment of local candidal infection should be initiated with surgical necrosectomy. Systemic antifungal therapy should be started early in the course of the disease, but whether antifungal agents should be added to the prophylactic antibiotic regimens for patients with necrotizing pancreatitis remains questionable.
[Show abstract][Hide abstract] ABSTRACT: Shock and pancreatitis are closely associated. Shock can be a sequel of severe pancreatitis and systemic shock may induce pancreatitis. This chapter discusses both features with regard to their clinical and pathophysiological characteristics.
Baillière' s Best Practice and Research in Clinical Gastroenterology 07/2003; 17(3):345-55. · 3.48 Impact Factor