Human pancreatic tissue concentration of bactericidal antibiotics

Büchler, Markus W.; Malfertheiner, Peter; Frieβ, Helmut; Isenmann, Rainer; Vanek, E.; Grimm, H.; Schlegel, Paul G.; Friess, Thomas; Beger, H. G.

doi:10.1016/0016-5085(92)91450-i

Cited by 269 publications

(157 citation statements)

References 62 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…The choice of antibiotics in preventing infected necrosis during necrotizing pancreatitis should be based on their antimicrobial activity, penetration rate, persistence, and therapeutic concentrations in the necrotic pancreatic area. These requisites are provided by pefloxacin and metronidazole and to a variable extent by imipenem and mezlocillin.Superinfection of necrotic tissue in the course of acute necrotizing pancreatitis is a decisive prognostic factor with regard to morbidity and mortality (2,3,5,7,20,25,33,34,40).This has prompted attempts to identify the patients at septic risk (3,5,20), the microorganisms responsible for the superinfection (1), the times of infection in the natural history of the disease (3,20), the therapeutic measures to be adopted (1-3, 5, 20, 34), and possible effective prophylaxis (7,9,10,19,23,25,33).The ideal antibiotic for therapy and/or prophylaxis should be targeted at the microorganisms responsible for the septic complications and should reach the infection site in therapeutic concentrations.To date, several studies have been conducted to evaluate the penetration of various different antibiotics into healthy pancreatic tissue and juice (4, 7-11, 28, 35-38). None of these studies has been conducted with humans in the course of disease, and to the best of our knowledge, the effective ability of antibiotics to penetrate the infection risk areas has never been assessed.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Behavior of antibiotics during human necrotizing pancreatitis

Bassi

Pederzoli

Vesentini

et al. 1994

Antimicrob Agents Chemother

128

View full text Add to dashboard Cite

The aim of the study was to verify whether antibiotics excreted by the normal pancreas are also excreted in human necrotizing pancreatitis, reaching the tissue sites of the infection. Twelve patients suffering from acute necrotizing pancreatitis were treated with imipenem-cilastatin (0.5 g), mezlocillin (2 g), gentamicin (0.08 g), amikacin (0.5 g), pefloxacin (0.4 g), and metronidazole (0.5 g). Serum and necrotic samples were collected simultaneously at diferent time intervals after parenteral drug administration by computed tomographyguided needle aspiration, intraoperatively, and from surgical drainages placed during surgery. Drug concentrations were determined by microbiological and high-performance liquid chromatography assays. All antibiotics reached the necrotic tissues, but with varying degrees of penetration, this being low for aminoglycosides (13%) and high in the case of pefloxacin (89%o) and metronidazole (990%). The concentrations of pefloxacin (13.0 to 23 ,Lg/g) and metronidazole (8.4 ,ug/g) in the necrotic samples were distinctly higher than the MICs for the organisms most commonly isolated in this disease; the concentrations in tissue of imipenem (3.35 ,ug/g) and mezlocillin (8.0 and 15.0 ,ug/g) did not always exceed the MICs for 90% of strains tested, whereas the aminoglycoside concentrations in necrotic tissue (0.5 p.g/g) were inadequate. Repeated administration of drugs (for 3, 7, 17, and 20 days) seems to enhance penetration of pefloxacin, imipenem, and metronidazole into necrotic pancreatic tissue. The choice of antibiotics in preventing infected necrosis during necrotizing pancreatitis should be based on their antimicrobial activity, penetration rate, persistence, and therapeutic concentrations in the necrotic pancreatic area. These requisites are provided by pefloxacin and metronidazole and to a variable extent by imipenem and mezlocillin.Superinfection of necrotic tissue in the course of acute necrotizing pancreatitis is a decisive prognostic factor with regard to morbidity and mortality (2,3,5,7,20,25,33,34,40).This has prompted attempts to identify the patients at septic risk (3,5,20), the microorganisms responsible for the superinfection (1), the times of infection in the natural history of the disease (3,20), the therapeutic measures to be adopted (1-3, 5, 20, 34), and possible effective prophylaxis (7,9,10,19,23,25,33).The ideal antibiotic for therapy and/or prophylaxis should be targeted at the microorganisms responsible for the septic complications and should reach the infection site in therapeutic concentrations.To date, several studies have been conducted to evaluate the penetration of various different antibiotics into healthy pancreatic tissue and juice (4, 7-11, 28, 35-38). None of these studies has been conducted with humans in the course of disease, and to the best of our knowledge, the effective ability of antibiotics to penetrate the infection risk areas has never been assessed. Such areas of the retroperitoneum are characterized by the presence of necrotic fragments of pa...

show abstract

mentioning

confidence: 99%

“…This has prompted attempts to identify the patients at septic risk (3,5,20), the microorganisms responsible for the superinfection (1), the times of infection in the natural history of the disease (3,20), the therapeutic measures to be adopted (1-3, 5, 20, 34), and possible effective prophylaxis (7,9,10,19,23,25,33).…”

mentioning

confidence: 99%

Behavior of antibiotics during human necrotizing pancreatitis

Bassi

Pederzoli

Vesentini

et al. 1994

Antimicrob Agents Chemother

128

View full text Add to dashboard Cite

show abstract

“…In addition, on the basis of changes in plasma concentrations in healthy adults in a Phase I study 14 , it has been suggested that as the number of doses of DRPM increases, the time above the MIC of DRPM increases. In the present study, the incidence of WON in the DRPM group tended to be lower than in the non-DRPM group, indicating the clinical ef cacy of CRAI with DRPM and NM.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of Continuous Regional Arterial Infusion with Doripenem and Protease Inhibitors for Severe Acute Pancreatitis

Yamamiya

Kitamura

Ishii

et al. 2015

Showa Univ J Med Sci

View full text Add to dashboard Cite

: Doripenem DRPM is a relatively new drug belonging to the carbapenem antibiotic group. We hypothesized that the pharmacological characteristics of DRPM could make it useful in the treatment of severe acute pancreatitis SAP . We investigated the usefulness of continuous regional arterial infusion CRAI with DRPM and protease inhibitors for SAP. Two hundred and forty-two patients with SAP were admitted to Showa University Hospital between November 2002 and June 2013. Of these, 53 patients were treated with CRAI with carbapenem antibiotics and nafamostat mesilate NM , a serine protease inhibitor, via the celiac and superior mesenteric arteries. Clinical outcomes were evaluated retrospectively in 34 patients treated with DRPM and 19 patients undergoing non-DRPM therapy meropenem n 11, imipenem n 6 ; biapenem n 2 . The median time to commencement of oral intake was significantly shorter in the DRPM than non-DRPM group 9 vs 14 hospital days, respectively ; P 0.01 . In addition, the rate of walled-off necrosis in the DRPM group tended to be lower than in the non-DRPM group 37.5 vs 64.7 , respectively, P 0.069 . The results of the present study suggest that CRAI with DRPM and NM for SAP could have equivalent therapeutic effects to CRAI with other carbapenem antibiotics and NM.

show abstract

“…The frequency of fungi may be increased by the use of broad-spectrum antibiotics [31]. The more frequent infectious agents are shown in Table 4 [32]. Monobacterial infection occurs in 55-60% of cases of infected necrosis, the rest being multibacterial.…”

Section: Antibiotic Prophylaxismentioning

confidence: 99%

“…All patients with these features received treatment with antibiotics. Other multicentric, double blind, randomized trial comparing meronem and placebo showed no statistically significant difference between the treatment groups for pancreatic or peripancreatic infection, mortality or requirement for surgical intervention, and did not support early prophylactic antimicrobial use in patients with severe acute necrotizing pancreatitis [37] (Table 5) [4,18,32,[38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56].…”

Section: Antibiotic Prophylaxismentioning

confidence: 99%

Antibiotics in severe acute pancreatitis

Serrablo

Tejedor²,

Martínez

2014

Open Medicine

View full text Add to dashboard Cite

AbstractAcute pancreatitis (AP) is a local inflammatory response with systemic effects and an adverse evolution in 20% of cases. Its mortality rate is 5–10% in sterile and 15–40% in infected pancreatic necrosis. Infection is widely accepted as the main reason of death in AP. The evidence to enable a recommendation about antibiotic prophylaxis against infection of pancreatic necrosis is conflicting and difficult to interpret. Up to date, there is no evidence that supports the routine use of antibiotic prophylaxis in patients with severe AP. Treatment on demand seems to be the better option, avoiding excessive treatment and selection of bacterial. In infected acute pancreatitis, antibiotics of choice are imipenem, meronem or tigecycline in patients allergic to beta-lactams. Also fluconazole must be given in determinate clinical situations.

show abstract

Human pancreatic tissue concentration of bactericidal antibiotics

Cited by 269 publications

References 62 publications

Behavior of antibiotics during human necrotizing pancreatitis

Behavior of antibiotics during human necrotizing pancreatitis

Usefulness of Continuous Regional Arterial Infusion with Doripenem and Protease Inhibitors for Severe Acute Pancreatitis

Antibiotics in severe acute pancreatitis

Contact Info

Product

Resources

About