Biliary Excretion of Cefaclor

Jm, Brogard; Pinget, M.; Comte, F; Adloff, M; Lavillaureix, J

doi:10.1159/000238075

Cited by 4 publications

(2 citation statements)

References 10 publications

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“…1973 71 92.1 [G]500 mg every 6 h (×4)imRam et al . 1973 71 Cefaclor0.62550–600.057.6 ± 2.4 [T]1000 mgoralBrogard et al 1982 72 Cefprozil1.454076—————Cefuroxime axetil1.333–5090—————Cefuroxime1.335950.510.3 ± 2.4 [T]500 mgivBrogard et al . 1981 73 5.4 [G]/42.8 [BD]1500 mgivThomas et al .…”

Section: Are All Cephalosporins the Same With Regard To CDI Risk?mentioning

confidence: 99%

Role of cephalosporins in the era ofClostridium difficileinfection

Wilcox

Chalmers

Nord

et al. 2016

J. Antimicrob. Chemother.

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The incidence of Clostridium difficile infection (CDI) in Europe has increased markedly since 2000. Previous meta-analyses have suggested a strong association between cephalosporin use and CDI, and many national programmes on CDI control have focused on reducing cephalosporin usage. Despite reductions in cephalosporin use, however, rates of CDI have continued to rise. This review examines the potential association of CDI with cephalosporins, and considers other factors that influence CDI risk. EUCLID (the EUropean, multicentre, prospective biannual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhoea) reported an increase in the annual incidence of CDI from 6.6 to 7.3 cases per 10 000 patient bed-days from 2011–12 to 2012–13, respectively. While CDI incidence and cephalosporin usage varied widely across countries studied, there was no clear association between overall cephalosporin prescribing (or the use of any particular cephalosporin) and CDI incidence. Moreover, variations in the pharmacokinetic and pharmacodynamic properties of cephalosporins of the same generation make categorization by generation insufficient for predicting impact on gut microbiota. A multitude of additional factors can affect the risk of CDI. Antibiotic choice is an important consideration; however, CDI risk is associated with a range of antibiotic classes. Prescription of multiple antibiotics and a long duration of treatment are key risk factors for CDI, and risk also differs across patient populations. We propose that all of these are factors that should be taken into account when selecting an antibiotic, rather than focusing on the exclusion of individual drug classes.

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Section: Are All Cephalosporins the Same With Regard To CDI Risk?mentioning

confidence: 99%

Role of cephalosporins in the era ofClostridium difficileinfection

Wilcox

Chalmers

Nord

et al. 2016

J. Antimicrob. Chemother.

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“…Research grade antibiotics were obtained from the following sources: augmentin (5:1 amoxicillin sodium salt to potassium clavulanate; Research Products International); azithromycin dihydrate (Thermo Scientific Chemicals); cefaclor (Thermo Scientific Chemicals); ceftriaxone sodium salt hemiheptahydrate (Thermo Scientific Chemicals); clindamycin phosphate (TCI America); and fidaxomicin (Apexbio Technology, LLC). Antibiotic concentrations used for twice daily dosing were estimated based upon previously published measurements in human feces and/or bile (50)(51)(52)(53)(54)(55)(56), although fidaxomicin dosing was limited by its maximal solubility. Clindamycin concentrations used in media were previously described (40).…”

Section: Methodsmentioning

confidence: 99%

Clostridioides difficilecolonization is not mediated by bile salts and utilizes Stickland fermentation of proline in anin vitromodel

Huang,

Johnson,

Brehm

et al. 2024

Preprint

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Treatment with antibiotics is a major risk factor forClostridioides difficileinfection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limitC. difficilecolonization include conversion of conjugated primary bile salts into secondary bile salts toxic toC. difficilegrowth, and competition between the microbiota andC. difficilefor limiting nutrients. Using a continuous flow model of the distal colon, we investigated how treatment with six clinically-used antibiotics influenced susceptibility toC. difficileinfection in 12 different microbial communities cultivated from healthy individuals. Antibiotic treatment reduced microbial richness; disruption varied by antibiotic class and microbiota composition, but did not correlate withC. difficilesusceptibility. Antibiotic treatment also disrupted microbial bile salt metabolism, increasing levels of the primary bile salt, cholate, and decreasing levels of the secondary bile salt, deoxycholate. However, decreased levels of deoxycholate did not correlate with increasedC. difficilesusceptibility. Further, bile salts were not required to inhibitC. difficilecolonization. We tested whether amino acid fermentation contributed to persistence ofC. difficilein antibiotic-treated communities.C. difficilemutants unable to use proline as an electron acceptor in Stickland fermentation due to disruption of proline reductase (ΔprdB) had significantly lower levels of colonization than wild-type strains in four of six antibiotic-treated communities tested. This data provides further support for the importance of bile salt-independent mechanisms in regulating colonization ofC. difficile.IMPORTANCEC. difficileis one of the leading causes of hospital-acquired infections and antibiotic-associated diarrhea. Several potential mechanisms through which the microbiota can limitC. difficileinfection have been identified and are potential targets for new therapeutics. However, it is unclear which mechanisms ofC. difficileinhibition represent the best targets for development of new therapeutics. These studies demonstrate that in a complexin vitromodel ofC. difficileinfection, colonization resistance is independent of microbial bile salt metabolism. Instead, the ability ofC. difficileto colonize is dependent upon its ability to metabolize proline, although proline-dependent colonization is context-dependent and is not observed in all disrupted communities. Altogether, these studies support the need for further work to understand how bile-independent mechanisms regulateC. difficilecolonization.

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Antibiotics in the Biliary Tract: A Review of the Pharmacokinetics and Clinical Outcomes of Antibiotics Penetrating the Bile and Gallbladder Wall

Thabit

2020

Pharmacotherapy

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Biliary tract infections (BTIs), including cholangitis and cholecystitis, are common causes of bacteremia. Bacteremic BTIs are associated with a mortality rate of 9–12%. The extent to which antibiotics are excreted in the bile and the ratio of their exposure to the minimum inhibitory concentration of the infecting organism are among the important factors for the treatment of BTIs. This review updates health care professionals on the distribution of antibiotics in the common bile duct, gallbladder, and gallbladder wall. Antibiotic efficacy in treating BTIs based on the latest available clinical studies is also discussed. The efficacy and pharmacokinetics of 50 antibiotics are discussed. Overall, most antibiotic classes exhibit biliary penetration that translates into clinical efficacy. Only seven antibiotics (amoxicillin, cefadroxil, cefoxitin, ertapenem, gentamicin, amikacin, and trimethoprim/sulfamethoxazole) had poor biliary penetration profiles. Three antibiotics (ceftibuten, ceftolozane/tazobactam, and doripenem) had positive clinical outcomes despite the lack of pharmacokinetic studies on their penetration into the biliary tract. Conflicting efficacy data were reported for ampicillin despite adequate biliary penetration, whereas conflicting pharmacokinetic data were reported with cefaclor and moxifloxacin. Even in the absence of supportive clinical studies, antibiotics with good biliary penetration profiles may have a place in the treatment of BTIs.

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Biliary Excretion of Cefaclor

Cited by 4 publications

References 10 publications

Role of cephalosporins in the era ofClostridium difficileinfection

Role of cephalosporins in the era ofClostridium difficileinfection

Clostridioides difficilecolonization is not mediated by bile salts and utilizes Stickland fermentation of proline in anin vitromodel

Antibiotics in the Biliary Tract: A Review of the Pharmacokinetics and Clinical Outcomes of Antibiotics Penetrating the Bile and Gallbladder Wall

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