There is an increased recogmnon of the importance of microbial flora as a reservoir of potential pathogens, and iatrogenic changes in intestinal microecology have been considered having clinical importance. We studied the effects on rat intestinal microflora of newer quinolones administered by different routes, and Aztreonam (AZT), a beta-lactam antibiotic with a selective activity against aerobic gram-negative bacteria. The following drugs were administered to rats (5 each group) at the usual human therapeutic doses: norfloxacin (NF, 10 mg/kg/die, os); ciprofloxacin (CP, 8 mg/kg/die, os); pefloxacin (PF, 10 mg/kg/die, os; i.p.); AZT (100 mg/kg/die, i.m.). Faecal specimens were collected after 2-4-7-11 days of treatment. Qualitative and quantitative determination of aerobic and anaerobic flora was done by standard techniques. Fluoroquinolones (FQ) reduced the counts of strains of Enterobacteriaceae ~, Proteus mirabilis) while aerobic grampositive bacteria (enterococci, staphylococci, lactobacilli) were little affected. PF induced a progressive increase in counts of enterococci. A slight decrease (l-2log) in anaerobic bacterial counts was observed at the beginning of treatments (2-4 days), but disappeared during the FQ administration of 7-11 day course. Among anaerobes Bacteroides were the most sensitive species to antimicrobial effects of NF and PF. FQ reduced the yeasts counts (-4 log). The oral and parenteral PF administration caused similar qualitative and quantitative changes. AZT induced a marked inhibition of Enterobacteriaceae only). A little reduction in counts of anaerobic species after 4 treatments was also observed. There was a progressive overgrowth of yeasts in rats given AZT. Appreciable concentrations of all drugs were detected in faeces at different times. AZT reached high concentrations on day 11 (in 4/6 rats). Faecal flora returned to its pretreatment composition by approximately 3 weeks after the last dose of drugs. We consider this method a reliable and useful experimental model to assess the impact on intestinal flora of new antimicrobial agents. These results showed that the potential of an antimicrobial agent to change the intestinal microflora is related to its antimicrobial activity, dose and pharmacokinetic properties.

Changes in rat intestinal microflora following oral and parenteral administration of antimicrobial drugs

BERTAZZONI MINELLI, Elisa;BENINI, Anna
1990

Abstract

There is an increased recogmnon of the importance of microbial flora as a reservoir of potential pathogens, and iatrogenic changes in intestinal microecology have been considered having clinical importance. We studied the effects on rat intestinal microflora of newer quinolones administered by different routes, and Aztreonam (AZT), a beta-lactam antibiotic with a selective activity against aerobic gram-negative bacteria. The following drugs were administered to rats (5 each group) at the usual human therapeutic doses: norfloxacin (NF, 10 mg/kg/die, os); ciprofloxacin (CP, 8 mg/kg/die, os); pefloxacin (PF, 10 mg/kg/die, os; i.p.); AZT (100 mg/kg/die, i.m.). Faecal specimens were collected after 2-4-7-11 days of treatment. Qualitative and quantitative determination of aerobic and anaerobic flora was done by standard techniques. Fluoroquinolones (FQ) reduced the counts of strains of Enterobacteriaceae ~, Proteus mirabilis) while aerobic grampositive bacteria (enterococci, staphylococci, lactobacilli) were little affected. PF induced a progressive increase in counts of enterococci. A slight decrease (l-2log) in anaerobic bacterial counts was observed at the beginning of treatments (2-4 days), but disappeared during the FQ administration of 7-11 day course. Among anaerobes Bacteroides were the most sensitive species to antimicrobial effects of NF and PF. FQ reduced the yeasts counts (-4 log). The oral and parenteral PF administration caused similar qualitative and quantitative changes. AZT induced a marked inhibition of Enterobacteriaceae only). A little reduction in counts of anaerobic species after 4 treatments was also observed. There was a progressive overgrowth of yeasts in rats given AZT. Appreciable concentrations of all drugs were detected in faeces at different times. AZT reached high concentrations on day 11 (in 4/6 rats). Faecal flora returned to its pretreatment composition by approximately 3 weeks after the last dose of drugs. We consider this method a reliable and useful experimental model to assess the impact on intestinal flora of new antimicrobial agents. These results showed that the potential of an antimicrobial agent to change the intestinal microflora is related to its antimicrobial activity, dose and pharmacokinetic properties.
Rat intestinal microflora; oral and parenteral administration; antibiotics
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11562/20636
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 0
  • ???jsp.display-item.citation.isi??? ND
social impact