Penetration of mezlocillin into pancreatic Juice

Pederzoli, Paolo; Orcalli, F; Falconi, Massimo; Bozzini, L.; Martini, Nello

doi:10.1093/jac/17.3.397

Cited by 14 publications

(6 citation statements)

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“…Hypovolemia, edema, fluid sequestration, and increase in VOL. 38,1994 on April 27, 2019 by guest http://aac.asm.org/ Downloaded from enzymes are additional variability factors in the course of acute pancreatitis.…”

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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Behavior of antibiotics during human necrotizing pancreatitis

Bassi

Pederzoli

Vesentini

et al. 1994

Antimicrob Agents Chemother

128

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“…10.9%; Klebsiella 5%; Serratia 3.8%; Pseudomonas aeruginosa 16.6%; Bacteroides fragilis 15.9%). Effective treat ment of pancreatic infections with anti biotics depends essentially on the choice of the appropriate drug and on the anti biotic concentrations obtained in the pan creatic tissue; since drug concentrations in the pancreatic juice are a rough index of the drug tissue levels, the study of the penetration of antibiotics into the pan creatic juice is important in therapeutic terms, as previously pointed out by con tributions of our research unit focused on the concentrations in pancreatic juice of rifampicin [6,7], mezlocillin [8], and cef tazidime [7], Ciprofloxacin (Bayer Italia), a new compound belonging to the series of 4-quinolone carboxilic acids, has a broad antibacterial spectrum [II] with marked in vitro activity (MIC < 0.25 mg/l) against gram-negative aerobic rods (e.g. entero bacteria including Serratia spp.…”

Section: Introductionmentioning

confidence: 95%

Ciprofloxacin Penetration in Pancreatic Juice

et al. 1987

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The penetration of ciprofloxacin in pancreatic juice was investigated in 5 patients with pancreatic fistula. The drug was administered as a single oral dose of 500 mg after which serial samples of pancreatic juice and serum were collected for ciprofloxacin assay. The following pharmacokinetic parameters (means ± SD) were estimated from the serum level versus time curves: clearance 11.51 ± 2.85 (ml/min/kg); V_darea 3.08 ± 1.20 ml/kg; terminal half-life 3.10 ± 0.92 h; mean residence time 5.64 ± 1.40 h. Ciprofloxacin serum levels declined rapidly after the third hour, whereas concentrations in pancreatic juice remained elevated (above 1 mg/l) for nearly 12 h. The pancreatic juice/serum ciprofloxacin concentration ratio increased gradually fom 0.63 ± 0.45 after 0.5 h to 6.18 ± 4.59 after 12 h (means ± SD). Our data indicate that while the drug elimination half-life from the serum is short, the time-course of ciprofloxacin levels in the pancreatic juice conforms to a much slower disappearance rate. In particular, the ciprofloxacin levels achieved in pancreatic juice are constantly greater than the MICs of the bacteria generally responsible for pancreatic infections.

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“…Previous studies on the distribution of antibiotics into the human pancreatic juice have been performed in patients with pancreatic fistulas [9][10][11] or in patients subjected to endoscopic retrograde cho langiopancreatography [4,13,14]. The fluid studied in these settings may well be a mixture of pancreatic juice, serous fluid and bile.…”

Section: Introductionmentioning

confidence: 99%

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

Brattström¹,

Malmborg²,

Tydén³

1989

Chemotherapy

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The penetration of imipenem into the human pancreatic juice following a single intravenous dose of 500 mg was investigated in five patients who had undergone pancreatic transplantation. With a special technique for segmental pancreatic transplantation it was possible to collect pure pancreatic juice at regular intervals. Simultaneous blood and pancreatic juice samples were collected immediately before drug administration and then at 0.5, 1, 1.5, 2.5, 3.5 and 5.5 h thereafter. The antibiotic concentrations were determined by the agar diffusion method. The mean peak level in serum was 24.6 ± (SE)2.6 mg/l and occurred 0.5 h after administration. The mean peak concentration in pancreatic juice was not reached until 1.5 h after administration, and the level was then 1.7 ± (SE)0.3 mg/l. Thereafter the levels in serum and pancreatic juice declined in parallel, and the concentration in pancreatic juice was then about 13% of that in serum. Although imipenem penetrates into the pancreatic juice at a very low degree, the concentrations exceeded the MIC values for many bacteria associated with pancreatic infections. Imipenem could therefore be an alternative as monotherapy in the treatment of pancreatic infections.

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Penetration of mezlocillin into pancreatic Juice

Cited by 14 publications

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Behavior of antibiotics during human necrotizing pancreatitis

Behavior of antibiotics during human necrotizing pancreatitis

Ciprofloxacin Penetration in Pancreatic Juice

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

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