Selective antimicrobial modulation of the intestinal tract by norfloxacin in human volunteers and in gnotobiotic mice associated with a human fecal flora

Pecquet, Sophie; Andremont, Antoine; Tancrède, C

doi:10.1128/aac.29.6.1047

Cited by 77 publications

(31 citation statements)

References 22 publications

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“…Concentrations of ofloxacin in feces may be as high as 400 ,ug/g (6) or even higher (28 vated drug (28,51), which would allow organisms for which the MICs are lower, such as those observed in the present study, to persist in the flora of the gastrointestinal tract. Such a phenomenon has been observed in experiments with animals (42).…”

Section: Discussionmentioning

confidence: 60%

Emergence of fluoroquinolone-resistant Escherichia coli at a cancer center

Kern¹,

Andriof²,

Oethinger³

et al. 1994

Antimicrob Agents Chemother

189

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Prophylactic treatment with fluoroquinolones of patients with profound neutropenia has been found to be useful for preventing gram-negative bacteremia and has become a standard preventive-therapy strategy in many cancer centers, but the development of bacterial resistance is a cause of concern. During the past few years, we have observed an increasing number of patients with leukemia from whom fluoroquinolone-resistant strains of Escherichia coli were isolated. The increase was significant in this patient population, and among patients with other underlying diseases, the rates of isolation of such strains per number of discharges were significantly lower and did not increase. Most of the leukemia case patients (16 of 19) had been pretreated with an oral quinolone (ofloxacin), with cumulative doses until the first isolation of a resistant E. coli strain ranging from 0 to 97.8 g (median, 14.4 g). Repeated isolation of such strains was seen in 8 of 17 patients during a follow-up period of .4 weeks and in 1 of 6 patients during a follow-up period of .16 weeks. Ten patients developed bacteremia (mortality, 1 of 10). On the basis of the number of patients with leukemia admitted to the hematology-oncology service, the incidence of bacteremia caused by fluoroquinolone-resistant E. coli increased from <0.5% in 1988-1989 and 0.8% in 1990-1991 to 4.5% in 1992-1993 (P < 0.01). MICs for nine isolates obtained from cultures of blood from different patients ranged between 8 and 16 ,ig/ml (ciprofloxacin and PD 131628), 8 and 32 ,ug/ml (ofloxacin and BAY Y 3118), and 16 and 32 ,Lg/ml (sparfloxacin) and indicated resistance to trimethoprim-sulfamethoxazole, ampicillin, doxycycline, and chloramphenicol. Of nine isolates obtained from cultures of blood from different patients and that were subjected to genomic DNA typing by pulsed-field gel electrophoresis ofXbaI digests, seven were typeable. Among these, four different genotypes were identified, suggesting both the independent development and the horizontal spread of resistant clones ofE. coli.Several controlled studies have suggested that oral fluoroquinolones, particularly ciprofloxacin and ofloxacin, may be useful prophylactic antibacterial agents in neutropenic cancer patients (4,9,10,15,22,29,30,56). Fluoroquinolone treatment in these patients was associated with a significant reduction and virtual absence of infections caused by members of the family Enterobacteriaceae, with less fever (8, 39) and a shorter duration of antimicrobial therapy (22,29,39). Such beneficial effects were observed, even though such treatment has rapidly led to the emergence of resistance in gram-positive organisms not infrequently associated with clinical failures of prophylaxis and therapy (11, 16, 23-26, 34, 38, 52, 53, 55 (14,44), and Escherichia coli (2,17,31,35,45). Since enteric bacilli appear to be the primary target organisms of fluoroquinolone prophylaxis in neutropenic patients, increasing levels of resistance to fluoroquinolones in these species, particularly E. coli, would have a maj...

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Section: Discussionmentioning

confidence: 60%

Emergence of fluoroquinolone-resistant Escherichia coli at a cancer center

Kern¹,

Andriof²,

Oethinger³

et al. 1994

Antimicrob Agents Chemother

189

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“…Elimination of fecal aerobic gramnegative bacteria and concomitant stability of the anaerobic flora have been described after ingestion of norfloxacin (5,8) or ciprofloxacin (3) by human volunteers. It is probably related to the enterohepatic circulation of fluoroquinolones (6).…”

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confidence: 99%

Effect of oral ofloxacin on fecal bacteria in human volunteers

Pecquet¹,

Andremont²,

Tancrède³

1987

Antimicrob Agents Chemother

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Intestinal members of the family Enterobacteriaceae were eliminated in five human volunteers treated with oral ofloxacin for 5 days. No emergence of resistant Enterobacteriaceae was observed. Counts of group D streptococci were significantly reduced. Colonization by Candida sp. was observed in all five volunteers during ofloxacin treatment. The anaerobic flora was fairly stable from one sample to another before treatment and was not substantially modified by ofloxacin.The prospective clinical benefits of fluoroquinolones include their uses in severe bacterial gastroenteritis and selective decontamination of the gastrointestinal tracts of neutropenic patients (6). Elimination of fecal aerobic gramnegative bacteria and concomitant stability of the anaerobic flora have been described after ingestion of norfloxacin (5,8) or ciprofloxacin (3) by human volunteers. It is probably related to the enterohepatic circulation of fluoroquinolones (6). Since another new fluoroquinolone, ofloxacin, is more active in vitro against anaerobic bacteria than are the other fluoroquinolones (9, 10, 12), we thought it of interest to study the effect on fecal bacteria of its administration to human volunteers.Five healthy, fully informed adults received oral ofloxacin twice daily for 5 days in doses of 200 mg. None had taken antimicrobial agents for at least 1 month before the study. Blood samples were drawn on the first and the last days of treatment at 1 h after drug ingestion. Freshly passed fecal samples were obtained once before treatment, daily during treatment, and daily for 1 week thereafter.Fecal anaerobes were counted on Aranki agar in an anaerobic glove box as described earlier (2). In five volunteers, a total of 814 clones which were recovered from 10-8 or 10-9 dilutions of samples obtained before and after 4 days of treatment (82 ± 7 clones per sample) were classified according to their Gram stain properties, shape and positions of spores, and growth characteristics under anaerobic and aerobic conditions, as previously described (8). Anaerobes were classified as oxygen-sensitive or -tolerant strains, based on their resistance to 1 h of exposure to atmospheric oxygen (1).Group D streptococci were counted on bile-esculin agar (Difco Laboratories, Detroit, Mich.), and staphylococci were counted on mannitol-salt agar (Bio-Merieux, Charbonnieres-les-Bains, France). Organisms of the Enterobacteriaceae family were counted on Drigalski agar (IPP, Paris, France) without antimicrobial agents or supplemented with either 4 ,ug of ofloxacin (kindly provided by Diamant Pharmaceuticals) per ml or 4 or 40 ,ug of nalidixic acid (Winthrop Laboratories, Clichy, France) per ml. These media were incubated for 48 h at 37°C. Yeast cells were counted on Sabouraud dextrose agar (Difco) incubated at room temperature for 1 week. The ofloxacin concentrations in human sera and feces were measured by agar diffusion assay (4). Mueller-Hinton agar at pH 7.3 and Klebsiella pneumoniae 1082E were used.Bacterial counts were converted into common logarithms. C...

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“…Norfloxacin dosage (400 mg/day) was blood pressure prior to HS, blood (leukocyte and polyestablished according to previous studies in gnotobiotic mice; morphonuclear leukocyte count, hematocrit, and biliruthe dosage was adjusted to the body weight of the rats. 19 bin) and AF analyses (total proteins, leukocytes, and Previously, a pilot study was performed on five rats in order to ascertain that 400 mg/day of norfloxacin was effective in polymorphonuclear leukocyte count) of rats included in eradicating gram-negative bacilli from fecal samples without the study are detailed in Table 1. Ascites appeared toxic effects.…”

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confidence: 99%

Selective intestinal decontamination with norfloxacin reduces bacterial translocation in ascitic cirrhotic rats exposed to hemorrhagic shock

et al. 1996

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Bacterial translocation (BT) can be involved in theGastrointestinal hemorrhage facilitates the developpathogenesis of severe infections due to bacteria of ment of severe bacterial infections, mainly bacteremia enteric origin that complicates bleeding cirrhotic and spontaneous bacterial peritonitis (SBP), in cirpatients. To assess the effect of hemorrhagic shock rhotic patients.1-3 These life-threatening infections, (HS) on the incidence of BT and if selective intestinal with hospital mortality rate of 20% to 40%, 4-8 are due decontamination (SID) reduces this incidence, we mainly to aerobic gram-negative bacilli of enteric oristudied six groups of Sprague-Dawley rats: ascitic gin. [4][5][6][7][8] Bacterial translocation (BT), i.e., the passage of rats, ascitic rats exposed to HS with and without pre-enteric bacteria through the intestinal barrier to mesvious norfloxacin prophylaxis, healthy rats, and enteric lymph nodes (MLNs), has been shown to be healthy shocked rats with and without previous norinvolved in the pathogenesis of SBP in ascitic cirrhotic floxacin prophylaxis. BT tended to be higher in ascitic rats with shock than without shock (69% vs. 41%, rats.9,10 Moreover, hemorrhagic shock (HS) has been P Å .15) and was significantly higher in healthy rats widely demonstrated to promote BT in otherwise with than without shock (50% vs. 0%, P Å .01). Nor-healthy animals, 11,12 as well as in rats with portal hyfloxacin significantly reduced translocation in as-pertension.13,14 Furthermore, it has been suggested recitic shocked rats in comparison with nondecontami-cently that HS could enhance BT in cirrhotic condinated ascitic shocked rats (31% vs. 69%, P Å .038). tions.15 Therefore, it is conceivable that HS due to This effect was due mainly to a reduction of gram-gastrointestinal bleeding could favor BT in cirrhotic negative BT (0% vs. 37%, P Å .008). In addition, nor-patients. floxacin prevented translocation in healthy shockedNorfloxacin, a fluoroquinolone that selectively inhibrats. Accordingly, aerobic gram-negative bacteria its aerobic gram-negative intestinal flora, is effective in disappeared from fecal flora in all rats administered norfloxacin, except for Klebsiella species in one con-reducing the incidence of SBP in hospitalized cirrhotic trol rat. Cecal severe submucosal edema, chronic in-patients with low protein content in ascitic fluid 16 (AF). flammatory infiltrate, and intestinal lymphangiec-It is also effective in preventing the recurrence of SBP tasia were significantly more frequent in ascitic produced by gram-negative organisms. 17 In addition, rats than in control rats. Intestinal mucosal injury selective intestinal decontamination (SID) with norrelated with HS, particularly subepithelial cecal floxacin has also been proven to be useful in the prophyedema, was observed only in ascitic shocked rats. In laxis of bacterial infections in bleeding cirrhotic paconclusion, HS increases the incidence of BT both in tients.2 These data raise the possibility that norfloxacin ascitic cirrhotic and hea...

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Selective antimicrobial modulation of the intestinal tract by norfloxacin in human volunteers and in gnotobiotic mice associated with a human fecal flora

Cited by 77 publications

References 22 publications

Emergence of fluoroquinolone-resistant Escherichia coli at a cancer center

Emergence of fluoroquinolone-resistant Escherichia coli at a cancer center

Effect of oral ofloxacin on fecal bacteria in human volunteers

Selective intestinal decontamination with norfloxacin reduces bacterial translocation in ascitic cirrhotic rats exposed to hemorrhagic shock

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