Quinolones

The ecological impact of quinolone administration on the fecal microbiota is described in Table 7.

Ciprofloxacin

The ecological consequences of ciprofloxacin have been evaluated in patients in connection with colorectal surgery (92), in patients with acute leukaemia in remission (96), in prevention of bacterial infections in cirrhosis (101,102) and in treatment of travelers' diarrhea (103). A number of studies have also been performed on healthy volunteers (93-95,97-100,104,105). Ciprofloxacin is excreted in feces in extremely high concentrations and has an activity mainly against Gram-negative aerobic rods. Marked suppression or elimination of enterobacteria has also been shown to occur, both in patients and in the healthy subjects examined. The extension of disturbances has varied depending on the doses. Minor alterations of numbers of Gram-positive aerobic cocci, mainly enterococci, have further been observed and in some studies minor alterations were detected also in the anaerobic microbiota. Ciprofloxacin-resistant species of Pseudomonas and Acinetobacter have been detected during treatment of patients with acute leukaemia (96) and in healthy volunteers who were given ciprofloxacin intravenously (98). Furthermore, 4 of 7 ciprofloxacin-treated patients with travelers' diarrhea acquired multi-resistant E. coli and in 4 subjects increased MIC values of ciprofloxacin for Bacteroides spp. were detected (103).

Enoxacin

The effect of enoxacin on the colonic microbiota in human volunteers has been examined (106). Enterobacteria were almost completely suppressed during administration of the drug whereas other aerobic and anaerobic species were not significantly affected.

Garenoxacin

The ecological effect of garenoxacin has been evaluated in healthy individuals receiving oral doses ranging between 100 and 1200 mg daily (107). Higher doses resulted in marked effects on the intestinal microbiota; the strongest effect was noticed in reduced numbers of Bacteroides species. Fecal concentrations of garenoxacin also increased with higher doses as well as the selection of resistant strains, mainly enterococci and enterobacteria. In comparison, the Bacteroides species strains were less susceptible to the quinolone agent.

Gatifloxacin

Gatifloxacin has been given to healthy subjects in order to study the impact on the normal intestinal microbiota (108). Gatifloxacin possesses a broad spectrum of antimicrobial activity and the administration resulted in not only elimination or strong suppression of E. coli strains but also in decreased numbers of enterococci and increased numbers of staphylococci. The numbers of clostridia and fusobacteria decreased significantly in the anaerobic microbiota.

Gemifloxacin

Gemifloxacin is another agent with a broad spectrum of antimicrobial activity. It is active both against Gram-positive and Gram-negative bacteria. The ecological impact of the agent has been investigated in a placebo-controlled study in healthy volunteers (109) and in a randomized cross-over study where the effect of a single dose was investigated in healthy subjects (110). In the first mentioned study, the effect of gemifloxacin was shown to be selective with reduced numbers mainly of enterococci, streptococci and enterobacteria. The single dose caused a pronounced reduction in the numbers of E. coli and to a lesser extent also of enterococci and Bacteroides species. New quinolone-resistant isolates of Gram-negative aerobes appeared in some subjects.

Levofloxacin

Levofloxacin has been shown to cause a selective reduction in the normal microbiota of healthy subjects, mainly directed towards Gram-negative aerobic rods (111,112). The numbers of enterococci were reduced to a lesser extent. Increased MIC values against strains of Bacteroides was detected in one study (111).

Lomefloxacin

Almost a complete eradication of Gram-negative aerobic rods have been shown to occur in the intestinal microbiota of volunteers during administration of lomefloxacin (113). Aerobic Gram-positive and anaerobic microorganisms were virtually unaffected.

Moxifloxacin

The ecological impact of moxifloxacin has been evaluated in healthy subjects (72). The administration caused significant decreases of enterococci and enterobacteria while no other major changes were observed.

Norfloxacin

A number of studies have investigated the ecological effects of norfloxacin on the normal intestinal microbiota (86,114-119). All studies have been performed in healthy subjects and the results have been consistent. Elimination or strong suppression of enterobacteria has been observed and slight reductions of enterococci have been detected in connection with the highest dosing regimens. Only minor fluctuations of other species have been seen.

Ofloxacin

The potential of ofloxacin to disturb the intestinal microbiota has been studied in healthy volunteers (112,120) as well as in patients undergoing gastric surgery (121). In both volunteers and in patients the numbers of enterobacteria were strongly suppressed or eliminated and the numbers of enterococci were significantly reduced. In patients the numbers of lactobacilli, bifidobacteria, eubacteria and species of Veillonella and Bacteroides were also affected.

Pefloxacin

The influence of pefloxacin on the gastrointestinal microbiota with regard to colonization resistance has been evaluated in two studies on healthy volunteers (104,122). Gramnegative aerobic rods were eliminated during treatment while the numbers of enterococci were slightly suppressed. In one of the studies a significant increase of yeasts was detected in half of the subjects (122).

Rufloxacin

The impact of rufloxacin on intestinal microbiota has been studied in healthy male volunteers after a single dose (119) and in connection with prophylactic treatment of patients with cancer (123). The single dose significantly reduced the numbers of Enterobacteriaceae. This was also observed in patients but the number of Bacteroides species was affected as well, however to a lesser extent. The MIC values of rufloxacin for enterococci increased significantly during the second week of treatment.

Sitafloxacin

Sitafloxacin has been shown to markedly suppress both the aerobic and anaerobic intestinal microbiota in healthy persons (124). Most anaerobic microorganisms as well as the aerobic Gram-negative rods were eliminated on the third day of administration until one day after the discontinuation of the drug.

Sparfloxacin

Administration of sparfloxacin to male volunteers has been shown to have a strong impact on E. coli and to moderately reduce the numbers of enterococci (125).

Trovafloxacin

The ecological impact of trovafloxacin has been evaluated in connection with multiple (126) and single doses (110) administered to healthy males. The numbers of Enterobacteriaceae were suppressed in both studies, after long-term use below the detection limit. A single dose also resulted in decreased counts of B. fragilis group species in some subjects.

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