Penetration of Imipenem into Human Pancreatic Juice following Single Intravenous Dose Administration&lt;sup&gt;1&lt;/sup&gt;

Brattström, C; Malmborg, Anna‐Stina; Tydén, G

doi:10.1159/000238652

Cited by 20 publications

(13 citation statements)

References 10 publications

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“…Imipenem and ertapenem have both been shown to penetrate pancreatic tissue and pancreatic fluid at levels exceeding the minimum inhibitory concentration (MIC 90 ) for the most commonly seen bacteria after as little as a single intravenous dose. 105,106 Similar findings were documented for moxifloxacin, with concentrations greater than the MIC 90 after a dose of 400 mg, either oral or intravenous. 107 An in vitro study of the most commonly isolated bacteria from pancreatic necrosis -E. coli, Enterobacter cloacae, Enterococcus faecalis, Bacteroides fragilis -compared the effectiveness of imipenem, ertapenem and moxifloxacin against these pathogens.…”

Section: Diagnosis and Management Of Local Complications Of Acute Pansupporting

confidence: 65%

Clinical practice guideline: management of acute pancreatitis

Greenberg¹,

Hsu²,

Bawazeer³

et al. 2016

cjs

340

352

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There has been an increase in the incidence of acute pancreatitis reported worldwide. Despite improvements in access to care, imaging and interventional techniques, acute pancreatitis continues to be associated with significant morbidity and mortality. Despite the availability of clinical practice guidelines for the management of acute pancreatitis, recent studies auditing the clinical management of the condition have shown important areas of noncompliance with evidence-based recommendations. This underscores the importance of creating understandable and implementable recommendations for the diagnosis and management of acute pancreatitis. The purpose of the present guideline is to provide evidence-based recommendations for the management of both mild and severe acute pancreatitis as well as the management of complications of acute pancreatitis and of gall stone-induced pancreatitis.Une hausse de l'incidence de pancréatite aiguë a été constatée à l'échelle mondiale. Malgré l'amélioration de l'accès aux soins et aux techniques d'imagerie et d'intervention, la pancréatite aiguë est toujours associée à une morbidité et une mortalité importantes. Bien qu'il existe des guides de pratique clinique pour la prise en charge de la pancréatite aiguë, des études récentes sur la vérification de la prise en charge clinique de cette affection révèlent des lacunes importantes dans la conformité aux recommandations fondées sur des données probantes. Ces résultats mettent en relief l'importance de formuler des recommandations compréhensibles et applicables pour le diagnostic et la prise en charge de la pancréatite aiguë. La présente ligne directrice vise à fournir des recommandations fondées sur des données probantes pour la prise en charge de la pancréatite aiguë, qu'elle soit bénigne ou grave, ainsi que de ses complications et de celles de la pancréatite causée par un calcul biliaire.A cute pancreatitis can range from a mild, self-limiting disease that requires no more than supportive measures to severe disease with lifethreatening complications. The most common causes of acute pan creatitis are gallstones and binge alcohol consumption.1 There has been an increase in the incidence of acute pancreatitis reported worldwide. Despite improvements in access to care, imaging and interventional techniques, acute pancreatitis continues to be associated with significant morbidity and mortality.A systematic review of clinical practice guidelines for the management of acute pancreatitis revealed 14 guidelines published between 2004 and 2008 alone.2 Although these guidelines have significant overlap in their recommendations for diagnosing and managing acute pancreatitis, there is disagreement in some aspects of both the timing and types of interventions that should be used for both mild and severe acute pancreatitis. The availability of new imaging modalities and noninvasive therapies has also changed clinical practice. Finally, despite the availability of guidelines, recent studies auditing clinical management of acute pancreatitis have sh...

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Section: Diagnosis and Management Of Local Complications Of Acute Pansupporting

confidence: 65%

Clinical practice guideline: management of acute pancreatitis

Greenberg¹,

Hsu²,

Bawazeer³

et al. 2016

cjs

340

352

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“…In these conditions, while the serum drug levels are generally within normal ranges (4,8,25,28,32), the physiological interindividual variability is further enhanced by the disease. This is supported by the concentration of antibiotics in necrotic pancreatic tissue compared with nonnecrotic samples.…”

Section: Discussionmentioning

confidence: 99%

“…(26,46). Mezlocillin and imipenem belong to the same class of moderately liposoluble acids and therefore present the same characteristics of penetration into pancreatic juice (8,15,38), as rapid distribution and elimination (27); for this reason, the trough concentrations (at 6 h) may be lower than MICs for 90% of susceptible bacteria commonly found in pancreatic infections. How long the concentrations of antibiotic in the infection site remain above the MIC is a decisive factor for the therapeutic efficacy of beta-lactams (16,18).…”

Section: Discussionmentioning

confidence: 99%

“…In our opinion, the pancreatic juice itself might be a useful carrier for the antibiotic in such situations: pancreatic juice leaking via the ductal lesions may presumably reach the parenchymal necrotic focus and thus the infection risk areas. This hypothesis is borne out by the findings that antibiotics with good excretion in pancreatic juice (4,8,11,28,(35)(36)(37)(38) were the same ones which presented adequate penetration into NP (7,9,10,25). The presence of antibiotics in pancreatic juice is the result of a further membrane passage and depends on blood and/or pancreatic levels, drug characteristics, pH environment, and pancreatic secretion mechanisms.…”

Section: Discussionmentioning

confidence: 99%

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Behavior of antibiotics during human necrotizing pancreatitis

Bassi

Pederzoli

Vesentini

et al. 1994

Antimicrob Agents Chemother

128

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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...

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“…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

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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.

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Penetration of Imipenem into Human Pancreatic Juice following Single Intravenous Dose Administration<sup>1</sup>

Cited by 20 publications

References 10 publications

Clinical practice guideline: management of acute pancreatitis

Clinical practice guideline: management of acute pancreatitis

Behavior of antibiotics during human necrotizing pancreatitis

Antibiotics in severe acute pancreatitis

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