Influence of amoxycillin, erythromycin and roxithromycin on colonization resistance and on appearance of secondary colonization in healthy volunteers

Vollaard, E. J.; Clasener, H. A. L.; Griethuysen, A. J. A. van; Janssen, A. J. H. M.; Sanders-Reijmers, A. J.

doi:10.1093/jac/20.suppl_b.131

Cited by 16 publications

(4 citation statements)

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“…Knowledge of the antibiotic impact on the fecal flora is especially helpful in neutropenic and intensive care unit patients, for whom the concept of colonization resistance (12,26,40,41) has become a major issue. In addition, the detection of resistant bacterial strains in fecal flora during or after antibiotic treatment is of great importance.…”

Section: Resultsmentioning

confidence: 99%

Multiple-dose pharmacokinetics of cefprozil and its impact on intestinal flora of volunteers

Lode

Müller

Börner

et al. 1992

Antimicrob Agents Chemother

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The pharmacokinetics of cefprozil were determined with 12 volunteers (8 received cefprozil and 4 received a placebo) after oral administration of 500 mg every 12 h over an 8-day period in a randomized, double-blind, placebo-controlled design. Concentrations in serum and urine were measured by high-pressure liquid chromatography and bioassay. The pharmacokinetic parameters were calculated on the basis of an open one-compartment model. The mean maximum concentration in serum on day 1 was 11.5 ± 2.6 mg/liter, and the time to reach maximum concentration was 122.3 ± 30 min after administration. Bioavailability parameters (area under the concentration-time curve from zero to infinity, maximum concentration of the drug in serum, and urinary recovery) indicated an excellent absorption. No accumulation over the 8-day period was registered. Cefprozil had a short biological elimination half-life of 58 ± 10 min and a renal clearance of 210 ± 51 ml/min, indicating high rates of renal excretion and tubular secretion. Analysis of the fecal flora showed an ecological impact of cefprozil on the intestinal microflora, such as a moderate decrease in enterobacteria and a slight increase in enterococci, staphylococci, and bacteroides during the study. The number of all bacterial species was already normalized 4 days after the administration period. The tolerance of cefprozil proved to be excellent; only a slight and reversible increase of liver enzymes (in two volunteers), mild cephalalgia, tiredness, and soft stool were registered during the 8-day period. Cefprozil had excellent absorption, no accumulation over an 8-day period, and only a limited impact on the intestinal microflora.Cefprozil (BMY-28100) is a new oral cephalosporin antibiotic with improved antimicrobial activity and efficacy against a broad spectrum of gram-positive and gram-negative pathogens (6,8,15,20,37). The objectives of our trial were to determine the pharmacokinetic properties of cefprozil after single and multiple dosing, to determine the effect on the intestinal flora in volunteers, and to assess the tolerance of cefprozil over an 8-day application period.(Part of this paper was presented previously [28a].) MATERIALS AND METHODSStudy design. The study was based on a randomized, double-blind, placebo-controlled, multiple-dose design. The protocol was approved by the local ethics committee.Volunteers. Twelve healthy test subjects (six females and six males) participated in the study. Eight of them received cefprozil, and four (two females and two males) took placebos. Mean (+ standard deviation) age (24 ± 2 years), body weight (65 ± 9 kg), body surface (1.78 m2 + 0.18), and creatinine clearance (108 + 23 ml/min/1.73 m2) showed no differences between placebo-and antibiotic-treated volunteers. The volunteers were healthy according to medical histories, physical examinations, hematologic tests, clinical chemistries, and urinalyses. These parameters were examined several times before, during, and after the study and showed no pathological alterations. All subjec...

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Section: Resultsmentioning

confidence: 99%

Multiple-dose pharmacokinetics of cefprozil and its impact on intestinal flora of volunteers

Lode

Müller

Börner

et al. 1992

Antimicrob Agents Chemother

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“…More than 50 years ago, it was found that loss of obligate anaerobic bacterial populations from the lower gastrointestinal tract strongly correlated with susceptibility to infection, which suggests that these commensal organisms were providing colonization resistance (13). Compositional analyses of colonic microbial populations in humans after antibiotic treatment demonstrated that loss of obligate anaerobes frequently results in expansion of γ-proteobacteria and enterococci; these findings suggest that the complex, pre-antibiotic commensal microbiota suppresses the expansion of the oxygen-tolerant bacterial species (14, 15). …”

Section: Colonization Resistance Mediated By Commensal Bacteriamentioning

confidence: 96%

Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens

Pamer

2016

Science

348

233

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The intestinal microbiota, which is composed of diverse populations of commensal bacterial species, provides resistance against colonization and invasion by pathogens. Antibiotic treatment can damage the intestinal microbiota and, paradoxically, increase susceptibility to infections. Reestablishing microbiota-mediated colonization resistance after antibiotic treatment could markedly reduce infections, particularly those caused by antibiotic-resistant bacteria. Ongoing studies are identifying commensal bacterial species that can be developed into next-generation probiotics to reestablish or enhance colonization resistance. These live medicines are at various stages of discovery, testing, and production and are being subjected to existing regulatory gauntlets for eventual introduction into clinical practice. The development of next-generation probiotics to reestablish colonization resistance and eliminate potential pathogens from the gut is warranted and will reduce health care–associated infections caused by highly antibiotic-resistant bacteria.

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“…The observation that antibiotic therapy reduced colonization resistance making the host susceptible to bacterial infections was observed very early in the literature [56][57][58][59]. Gut microbial compositional analysis of an antibiotic-treated mice showed the expansion of γ-proteobacteria and enterococci, suggesting that gut microbiota somehow suppressed the expansion of oxygen-tolerant species [94,95]. A study on healthy volunteers treated for a week or less with antibiotics reported persistent effects on their bacterial flora that included a loss of biodiversity on the gut flora, insurgence of antibiotic resistance strains, and upregulation of antibiotic resistance genes [96].…”

Section: Antibiotic-associated Colitismentioning

confidence: 99%

The Therapeutic Potential of the “Yin-Yang” Garden in Our Gut

Srikumar¹,

Fanning²

2019

Role of Microbes in Human Health and Diseases

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The gut microbiota is made up of trillion microorganisms comprising bacteria, archaea, and eukaryota living in an intimate relationship with the host. This is a highly diverse microbial community and is essentially an open ecosystem despite being deeply embedded in the human body. The gut microbiome is continually exposed to allochthonous bacteria that primarily originates from food intake. Comprising more than 1000 bacterial species, the gut microbiota endows so many different functions-so many that can be considered as an endocrine organ of its own. In this book chapter, we summarize the importance of gut microbiota in the development and maintenance of a healthy human body. We first describe how the gut microbiota is formed during the birth of a human baby and how a healthy microflora is established overtime. We also discuss how important it is to maintain the microbiota in its homeostatic condition. A discussion is also given on how alterations in the microbiota are characteristic of many diseased conditions. Recent investigations report that reestablishing a healthy microbiota in a diseased individual using fecal microbial transplant can be used as a therapeutic approach in curing many diseases. We conclude this chapter with a detailed discussion on fecal microbial transplants.

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Influence of amoxycillin, erythromycin and roxithromycin on colonization resistance and on appearance of secondary colonization in healthy volunteers

Cited by 16 publications

References 0 publications

Multiple-dose pharmacokinetics of cefprozil and its impact on intestinal flora of volunteers

Multiple-dose pharmacokinetics of cefprozil and its impact on intestinal flora of volunteers

Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens

The Therapeutic Potential of the “Yin-Yang” Garden in Our Gut

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