Effect of new antimicrobial agents on the ecological balance of human microflora

Rashid, Mamun Ur; Weintraub, Andrej; Nord, Carl Erik

doi:10.1016/j.anaerobe.2011.11.005

Cited by 62 publications

(64 citation statements)

References 60 publications

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“…The effects of antibiotics on the microbiota and its potential alterations have impacts on pathogen colonization and nosocomial infections. Antibiotic use may facilitate resistance gene transfer across the intestinal tract (6,22). Further clinical studies with the avibactam combination are needed to know the pharmacokinetics and its clinical significance.…”

Section: Discussionmentioning

confidence: 99%

“…Knowledge about the interaction between antimicrobial agents and the normal microbiota gives the clinician the possibility to choose agents associated with lesser degrees of ecological disturbances (5,6). Consequently, the risk of the development of resistant strains and the transfer of resistance elements between microorganisms is reduced (5,6).…”

mentioning

confidence: 99%

“…Consequently, the risk of the development of resistant strains and the transfer of resistance elements between microorganisms is reduced (5,6). Consideration of the ecological consequences is also an important step to prevent distribution of resistant strains between persons (5, 6).…”

mentioning

confidence: 99%

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Ecological Effect of Ceftaroline-Avibactam on the Normal Human Intestinal Microbiota

Rashid

Rosenborg

Panagiotidis

et al. 2015

Antimicrob Agents Chemother

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Ceftaroline-avibactam is a new combination of the antibiotic ceftaroline with a novel non-␤-lactam ␤-lactamase inhibitor, avibactam. The purpose of the present study was to investigate the effect of ceftaroline-avibactam on the human intestinal microbiota. Fourteen healthy volunteers received ceftaroline-avibactam (600 mg ceftaroline fosamil and 600 mg avibactam) intravenously over 2 h every 8 h on days 1 to 6 and as a single dose on day 7. Fecal samples were collected on day ؊1 (within 24 h of the first infusion on day 1) and on days 2, 5, 7, 9, 14, and 21. Escherichia coli numbers decreased during the study and normalized on day 21. An increased number of Klebsiella bacteria appeared on day 14 and normalized on day 21. The number of other enterobacteria decreased during the study, and the number of enterococci decreased from days 2 to 7 and normalized on day 9. Candida numbers increased from days 5 to 9 and normalized after day 14. The number of lactobacilli decreased during the study and recovered on day 14. The number of bifidobacteria decreased on day 2 and normalized on day 21. The number of Bacteroides bacteria was unchanged. Clostridium difficile numbers decreased on days 7 and 9 and increased on days 14 and 21. A toxigenic C. difficile strain was detected in one volunteer on day 21 with no reported adverse events. Plasma samples were collected on days

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Ecological Effect of Ceftaroline-Avibactam on the Normal Human Intestinal Microbiota

Rashid

Rosenborg

Panagiotidis

et al. 2015

Antimicrob Agents Chemother

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“…Therefore, the question is whether the PD effect of the agent on certain "indicator species" of the resident microflora is identical to or different from its PD effect on pathogens. Most frequently, the following species are examined when measuring the ecological impact of antibacterials: coagulase-negative staphylococci (CoNS) and Propionibacterium acnes as indicators of the nasal and skin flora; Streptococcus salivarius, S. mitis, Neisseria species, and micrococci as indicators of the aerobic oropharyngeal flora; anaerobic cocci and Lactobacillus, Fusobacterium, and Bacteroides species as indicators of the anaerobic oropharyngeal flora; E. coli, other members of the family Enterobacteriaceae, enterococci, and Candida species as indicators of the intestinal aerobic flora; and Bacteroides, Bifidobacterium, and Clostridium species and lactobacilli as indicators of the intestinal anaerobic flora (71,72).…”

Section: Pd Effects On the Human Resident Microflora As A Model Of A mentioning

confidence: 99%

“…The ecological effects of investigational agents on the nasal, oropharyngeal, skin, and intestinal flora are routinely analyzed by the evaluation of quantitative (i.e., shifts in viable counts of commensals during and after exposure) and qualitative (i.e., changes in susceptibility, overgrowth by or replacement with other species) parameters (71,72). In principle, any reduction of viable bacterial counts during the drug administration period compared to the baseline value can be considered a quantitative drug exposurerelated PD effect, representing a PK-PD parameter in connection with the drug's PKs.…”

Section: Pd Effects On the Human Resident Microflora As A Model Of A mentioning

confidence: 99%

Alternative Strategies for Proof-of-Principle Studies of Antibacterial Agents

Dalhoff¹,

Weintraub²,

Nord³

2014

Antimicrob Agents Chemother

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The proof that a new antibacterial agent is not only active in vitro but also effective in vivo under clinically relevant conditions is currently provided (i) by using appropriate nonclinical models of infection and pharmacokinetic-pharmacodynamic (PK-PD) analysis providing evidence of the likelihood of clinical efficacy and (ii) by examining the study drug in exploratory clinical trials, as well as dose and schedule finding during phase II of clinical development. This approach is both time-consuming and costly. Furthermore, PK-PD targets for any novel antibacterial agent cannot be derived from studies with experimental animals. Therefore, alternative strategies have to be identified to prove the principle that a novel antibacterial agent is active under clinically relevant conditions. This review summarizes evidence that the quantitative analysis of shifts in the viable counts of pathogens in infected patients or the evaluation of the PD effect of an investigational agent on indicator organisms of the human resident microflora or colonizers of healthy volunteers, if paralleled with PK monitoring of serum and the target site, provides an alternative to a classical proof-of-principle study in the course of a phase II study program.

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Nutraceuticals in Poultry Health and Disease

Filazı

Yurdakök-Dikmen

2019

Nutraceuticals in Veterinary Medicine

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Effect of new antimicrobial agents on the ecological balance of human microflora

Cited by 62 publications

References 60 publications

Ecological Effect of Ceftaroline-Avibactam on the Normal Human Intestinal Microbiota

Ecological Effect of Ceftaroline-Avibactam on the Normal Human Intestinal Microbiota

Alternative Strategies for Proof-of-Principle Studies of Antibacterial Agents

Nutraceuticals in Poultry Health and Disease

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