P1A Recombinant β-Lactamase Prevents Emergence of Antimicrobial Resistance in Gut Microflora of Healthy Subjects during Intravenous Administration of Ampicillin

Tarkkanen, A; Heinonen, Tuula; Jõgi, Rain; Mentula, Silja; Rest, M E van der; Donskey, Curtis J.; Kemppainen, Tuomas; Gurbanov, Konstantin; Nord, Carl Erik

doi:10.1128/aac.00853-08

Cited by 41 publications

(31 citation statements)

References 35 publications

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“…Oral treatment with enteric-coated beta-lactamases has been used in dogs and in humans [79,80] in an attempt to prevent the appearance of antibiotic resistance in the gut during intravenous ampicillin administration. The desired effect is destruction by the beta-lactamase of residual antibiotic in the distal gut, to prevent the acquisition of resistance without affecting systemic drug levels.…”

Section: Are There Methods To Prevent or Treat Gut Colonisation With mentioning

confidence: 99%

“…The desired effect is destruction by the beta-lactamase of residual antibiotic in the distal gut, to prevent the acquisition of resistance without affecting systemic drug levels. Both studies were encouraging, in particular the study in human patients, which included a control group [79,80]. However, the development of this compound has been stopped due to a lack of resources.…”

Section: Are There Methods To Prevent or Treat Gut Colonisation With mentioning

confidence: 99%

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The gut is the epicentre of antibiotic resistance

Carlet

2012

Antimicrob Resist Infect Control

179

141

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The gut contains very large numbers of bacteria. Changes in the composition of the gut flora, due in particular to antibiotics, can happen silently, leading to the selection of highly resistant bacteria and Candida species. These resistant organisms may remain for months in the gut of the carrier without causing any symptoms or translocate through the gut epithelium, induce healthcare-associated infections, undergo cross-transmission to other individuals, and cause limited outbreaks. Techniques are available to prevent, detect, and treat the carriage of resistant organisms in the gut. However, evidence on these techniques is scant, the only exception being selective digestive decontamination (SDD), which has been extensively studied in neutropenic and ICU patients. After the destruction of resistant colonizing bacteria, which has been successfully obtained in several studies, the gut could be re-colonized with normal faecal flora or probiotics. Studies are warranted to evaluate this concept.

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Section: Are There Methods To Prevent or Treat Gut Colonisation With mentioning

confidence: 99%

Section: Are There Methods To Prevent or Treat Gut Colonisation With mentioning

confidence: 99%

The gut is the epicentre of antibiotic resistance

Carlet

2012

Antimicrob Resist Infect Control

179

141

View full text Add to dashboard Cite

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“…This type of emergence and dissemination of resistance can be reduced not only by isolation procedure but also by reduction of exposure of intestinal flora to antibiotics. Some reports suggest that this can be achieved by administering oral beta-lactamases (47,48) or other compounds (49), as companions for antibiotic treatments, a concept recently termed "eco-evo drugs" (50).…”

Section: Discussionmentioning

confidence: 99%

Emergence of Imipenem-Resistant Gram-Negative Bacilli in Intestinal Flora of Intensive Care Patients

Armand-Lefèvre

Angebault

Barbier

et al. 2013

Antimicrob Agents Chemother

240

142

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Intestinal flora contains a reservoir of Gram-negative bacilli (GNB) resistant to cephalosporins, which are potentially pathogenic for intensive care unit (ICU) patients; this has led to increasing use of carbapenems. The emergence of carbapenem resistance is a major concern for ICUs. Therefore, in this study, we aimed to assess the intestinal carriage of imipenem-resistant GNB (IR-GNB) in intensive care patients. For 6 months, 523 consecutive ICU patients were screened for rectal IR-GNB colonization upon admission and weekly thereafter. The phenotypes and genotypes of all isolates were determined, and a case control study was performed to identify risk factors for colonization. The IR-GNB colonization rate increased regularly from 5.6% after 1 week to 58.6% after 6 weeks in the ICU. In all, 56 IR-GNB strains were collected from 50 patients: 36 Pseudomonas aeruginosa strains, 12 Stenotrophomonas maltophilia strains, 6 Enterobacteriaceae strains, and 2 Acinetobacter baumannii strains. In P. aeruginosa, imipenem resistance was due to chromosomally encoded resistance (32 strains) or carbapenemase production (4 strains). In the Enterobacteriaceae strains, resistance was due to AmpC cephalosporinase and/or extended-spectrum ␤-lactamase production with porin loss. Genomic comparison showed that the strains were highly diverse, with 8 exceptions (4 VIM-2 carbapenemaseproducing P. aeruginosa strains, 2 Klebsiella pneumoniae strains, and 2 S. maltophilia strains). The main risk factor for IR-GNB colonization was prior imipenem exposure. The odds ratio for colonization was already as high as 5.9 (95% confidence interval [95% CI], 1.5 to 25.7) after 1 to 3 days of exposure and increased to 7.8 (95% CI, 2.4 to 29.8) thereafter. In conclusion, even brief exposure to imipenem is a major risk factor for IR-GNB carriage.

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“…The protective effect of a recombinant beta-lactamase, P1A, has been evaluated in 34 human volunteers taking ampicillin (Tarkkanen et al, 2009). In the ampicillin group without P1A, a decrease of Bifidobacterium , Streptococcus , Lactobacillus , and an increase of E. coli and yeasts, were noted in the intestinal microbiota.…”

Section: Perspectives: How To Decrease the Densities Of Colonization mentioning

confidence: 99%

Causes, consequences, and perspectives in the variations of intestinal density of colonization of multidrug-resistant enterobacteria

Ruppé¹,

Andremont²

2013

Front. Microbiol.

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The intestinal microbiota is a complex environment that hosts 10 13 to 10 14 bacteria. Among these bacteria stand multidrug-resistant enterobacteria (MDRE), which intestinal densities can substantially vary, especially according to antibiotic exposure. The intestinal density of MDRE and their relative abundance (i.e., the proportion between the density of MDRE and the density of total enterobacteria) could play a major role in the infection process or patient-to-patient transmission. This review discusses the recent advances in understanding (i) what causes variations in the density or relative abundance of intestinal colonization, (ii) what are the clinical consequences of these variations, and (iii) what are the perspectives for maintaining these markers at low levels.

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P1A Recombinant β-Lactamase Prevents Emergence of Antimicrobial Resistance in Gut Microflora of Healthy Subjects during Intravenous Administration of Ampicillin

Cited by 41 publications

References 35 publications

The gut is the epicentre of antibiotic resistance

The gut is the epicentre of antibiotic resistance

Emergence of Imipenem-Resistant Gram-Negative Bacilli in Intestinal Flora of Intensive Care Patients

Causes, consequences, and perspectives in the variations of intestinal density of colonization of multidrug-resistant enterobacteria

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