Penetration of Meropenem and Cefepim into Pancreatic Tissue During the Course of Experimental Acute Pancreatitis

Sağlamkaya, Uğur; Mas, Mehmet Refik; Yaşar, Mehmet; Şimşek, İsmail; Mas, Nüket; Kocabalkan, Fikri

doi:10.1097/00006676-200204000-00009

Cited by 27 publications

(22 citation statements)

References 27 publications

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“…Another potential advantage of meropenem over imipenem/cilastatin is that it can be given intravenously at a high rate without an increased risk of nausea or vomiting [29]. We currently provide evidence in a controlled experimental setting that meropenem can penetrate to pancreatic tissue in sufficient therapeutic concentrations, both in the early and late phases of ANP in rats [30], but the effectiveness of meropenem for prevention of secondary pancreatic infections in experimental AP is unknown. We have shown in this study that meropenem is effective for prevention of secondary pancreatic infections in experimental AP, both initiated early and late.…”

Section: Discussionmentioning

confidence: 99%

Is late antibiotic prophylaxis effective in the prevention of secondary pancreatic infection?

et al. 2003

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Section: Discussionmentioning

confidence: 99%

Is late antibiotic prophylaxis effective in the prevention of secondary pancreatic infection?

et al. 2003

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“…The result for piperacillin agrees with the finding of no change in penetration into diseased tissue as reported previously (19). However, the current result for meropenem is in conflict with the work of Saglamkaya et al (17). They investigated animals both 6 h (disease characterized by edema) and 48 h (more necrotic tissue) following treatment with combined glycodexoxycholic acid infusion and intravenous cereulein to induce SAP.…”

mentioning

confidence: 72%

“…Perhaps this penetration would continue to decrease with time as the diseased tissue becomes less edematous. Several studies have shown that penetration differences (both increased and decreased) into diseased versus control tissue are more marked in the earlier and/or more edematous forms of acute pancreatitis (9,10,17), with evidence suggesting that this is on May 9, 2018 by guest http://aac.asm.org/ related to capillary pancreatic blood flow (9). The presence of more severe necrosis in Saglamkaya's work than in the present model may also have contributed to the higher penetration ratio at the 48-h time point.…”

mentioning

confidence: 99%

Changes in Antibiotic Distribution Due to Pancreatitis

Fanning¹,

Robertson²,

Prins³

et al. 2011

Antimicrob Agents Chemother

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This work sought to define how pancreatitis affected antibiotic distribution in a perfused rat pancreas model. The distribution kinetics of four antibiotics were examined in control animals and animals with pancreatitis. Meropenem and piperacillin distributed into the extracellular space, and their distribution kinetics were unaffected by pancreatitis. In contrast, in pancreatic cells from animals with pancreatitis, ciprofloxacin showed a reduced uptake and clindamycin showed a reduced distribution.Although the use of antibiotics in treating pancreatitis still remains controversial (3,4,15), bacterial infection is the leading cause of morbidity and mortality in patients with severe acute pancreatitis (SAP) (14). Studies have investigated penetration into diseased human tissue (1, 2, 5, 13), as well as a variety of animal models (6, 9, 10, 16).However, there appear to be few studies examining the rate of antibiotic uptake into pancreatic tissue. To our knowledge, this is one of the few studies investigating the rate of uptake of antibiotics in normal and diseased pancreas and most likely the first in the isolated perfused pancreas. Such a model enables the precise rate of uptake and efflux for antibiotics in the pancreas to be defined, as well as the nature of their distribution in the normal and diseased pancreas.All procedures involving animals were carried out with adherence to the University of Queensland Animal Care Committee guidelines (Animal Ethics Committee [AEC] project PAH/588/06/NHMRC). Pancreatitis was induced by giving male Wistar rats a single injection of 6 mg of dibutyltin dichloride (DBTC) per kg of body weight, via the tail vein, according to a previously described method (16). Rats were not allowed to eat from 104 h postinjection, and following the final blood sample at 120 h postinjection, they were anesthetized as previously described (8). The pancreas perfusions were carried out similarly to the method described previously (8) with a series of 5 individual 20-l bolus injections (7): piperacillin (2 mg/ml), meropenem (1 mg/ml), ciprofloxacin (200 g/ml), clindamycin (1 mg/ml), and [14 C]sucrose with 3 H-labeled water (each drug bolus contained 125 I-labeled albumin). The perfusate and outflow profiles were analyzed as described previously to obtain the unbound fraction in perfusate (fu), volume of distribution of albumin or albumin space (V alb ), volume of distribution of sucrose or sucrose space (V suc ), volume of distribution of water or water space (V water ), drug distribution volume (V), fraction unbound in tissues (fu T ), permeation rate constant k in (permeability rate constant from the vascular space to the extravascular space), efflux rate constant k out (permeability rate constant from the extravascular space to the vascular space), and permeability surface area product (PS) (7, 8). Fibrosis was quantified using a method that has been previously utilized for the liver (11).Histological examination of the diseased pancreas showed pathologies, including the formation of ductal comp...

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“…This is despite the fact that scientists have, for many decades, infused three forms of DCA into experimental animals to induce reproducible pancreatic injury. The three forms include the bile salt sodium deoxycholate, 7 – 9 the taurine conjugated bile salt (taurodeoxycholate), 10 and the glycine conjugated bile acid (glycodeoxycholic acid) 11 – 13 …”

Section: Discussionmentioning

confidence: 99%

Elevated Deoxycholic Acid and Idiopathic Recurrent Acute Pancreatitis: A Case Report with 48 Months of Follow-up

Plotnikoff

2014

Glob Adv Health Med

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Recurrent pancreatitis is a potentially life-threatening condition with a well-established differential diagnosis. In a significant number of cases, no explanation exists. This case report documents one patient with a clear pattern of recurrent acute pancreatitis and no identifiable cause despite great effort. After 7 years of recurrent symptoms, she was found to have marked elevation of fecal deoxycholic acid (DCA), a secondary bile acid used to precipitate pancreatitis in animal models. This report documents cessation of symptoms/hospitalizations with normalization of her fecal DCA levels. This secondary bile acid is easily measured in stool. Needed now is an observational study of fecal DCA levels in patients with recurrent acute pancreatitis.

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Penetration of Meropenem and Cefepim into Pancreatic Tissue During the Course of Experimental Acute Pancreatitis

Cited by 27 publications

References 27 publications

Is late antibiotic prophylaxis effective in the prevention of secondary pancreatic infection?

Is late antibiotic prophylaxis effective in the prevention of secondary pancreatic infection?

Changes in Antibiotic Distribution Due to Pancreatitis

Elevated Deoxycholic Acid and Idiopathic Recurrent Acute Pancreatitis: A Case Report with 48 Months of Follow-up

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