Effect of loracarbef on the normal oropharyngeal and intestinal microflora.

20 healthy volunteers received loracarbef capsules 200 mg b.i.d. for 7 days. Saliva and stool specimens were taken before loracarbef administration and on the 2nd, 5th, and 7th day during the administration period, and again 2, 5 and 9 days after withdrawal of the antibiotic to study the effect of loracarbef on the normal microflora. The concentrations of loracarbef in serum, saliva and faeces were determined by an agar diffusion method. The mean serum peak concentration attained after 1 h was 6.8 mg/l and the saliva concentrations were in the range 0-0.9 mg/l. The loracarbef concentrations in faeces ranged from 0 to 0.9 mg/kg. The changes in the the oropharyngeal microflora were minor and only bacteroides rods were affected. In the intestinal aerobic microflora, the number of enterococci and streptococci slightly increased while staphylococci, micrococci, corynebacteria, bacillus and enterobacteria were not affected. The number of bifidobacteria and eubacteria in the anaerobic microflora decreased while no other bacterial groups were affected. One week after withdrawal of loracarbef, both the oropharyngeal and intestinal microflora had returned to normal. No new colonizing loracarbef resistant microorganisms were observed during the investigation period.     

Impact of cefaclor on the normal human oropharyngeal and intestinal microflora

Cefaclor was given orally in doses of 250 mg every 8 h for 7 days to 10 volunteers. Saliva and faecal specimens were taken up to 16 days for cultivation of aerobic and anaerobic microorganisms and for assay of cefaclor. Cefaclor was not detected in saliva or faeces. In the oropharynx only minor changes in the anaerobic part of the microflora were observed. The microflora was normalized within 1 week after the administration of cefaclor had stopped. The aerobic intestinal microflora was unchanged during and after cefaclor administration while a minor impact on the anaerobic intestinal microflora was observed. The anaerobic intestinal flora returned to its normal state within 1 week. No new colonization with cefaclor resistant microorganisms were observed and no side effects were registered during the investigation period.     

Comparative effects of cefadroxil and phenoxymethylpenicillin on the normal oropharyngeal and intestinal microflora

Summary The ecological effects on the commensal microflora in saliva and stool samples were studied during administration of two commonly used antibiotics: cefadroxil 500 mg b.i.d. for 10 days and phenoxymethylpenicillin 1 g b.i.d. for 10 days. Twenty healthy volunteers participated in the study. In the oropharyngeal microflora the aerobic microflora was significantly suppressed during administration of cefadroxil while no significant changes were noticed in the anaerobic microflora. Administration of phenoxymethylpenicillin caused a strong decrease in the number of viridans streptococci and an overgrowth ofNeisseria cocci. The total numbers of anaerobic oropharyngeal microorganisms were suppressed during phenoxymethylpenicillin administration. In the intestinal microflora the variation in numbers of aerobic and anaerobic microorganisms was minor in both groups. The microflora became normalised 2 weeks after withdrawal of the drugs. It was concluded that peroral administration of cefadroxil to healthy volunteers resulted in minor ecological disturbances in the oropharyngeal and intestinal microflora, which were in the same range as for phenoxymethylpenicillin.     

Impact of cefixime on the normal intestinal microflora

The ecological effects on the normal intestinal microflora after cefixime tablets in doses of 200 mg twice daily for 7 days were studied in 10 healthy volunteers. Stool specimens were collected before and 2, 4, 7, 14 and 21 days after start of treatment. Plasma samples were collected during 12 h after the first dose on day 1 and 1 sample was taken on day 7 for bioassay of cefixime concentration. Peak plasma concentration of cefixime occurred after about 4 h with a mean of 3.0 mg/l. The mean AUC0----oc after a single dose was estimated at 21.9 mg x h/l and the mean elimination half-life was 3.9 h. The mean plasma concentration of cefixime 3 h after the morning dose on day 7 was 2.0 mg/l. The concentrations of cefixime in faeces increased during treatment. One subject had detectable concentrations in faeces on day 2, three subjects on day 4 and 8 subjects on day 7 in the order of 237-912 mg/kg faeces. There was a marked decrease in the numbers of streptococci and Escherichia coli and an increase in the numbers of enterococci during the administration of cefixime. In the anaerobic microflora, the numbers of cocci, clostridia and bacteroides were suppressed while there were minor changes in the numbers of bifidobacteria. Clostridium difficile was isolated in 5 subjects on day 7 but cytotoxin was only detected in one subject. The intestinal microflora was normalized within 2 weeks after treatment had stopped. Slightly soft stools were reported by 7 subjects. One subject had abdominal pain and diarrhoea 1 week after treatment followed by anal irritation and itching.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of clindamycin on the intestinal flora in patients with enteric hyperoxaluria

Enteric hyperoxaluria is due to increased absorption of oxalate, especially in the colon. However, this mechanism is not fully understood. Little is also known about the composition of the intestinal flora in these patients. Eleven patients with hyperoxaluria (greater than 0.45 mmol/24 h) after jejunoileal bypass were therefore studied under surgical ward conditions for 5 days. The patients were maintained on a constant diet. During days 3, 4, and 5 clindamycin (Dalacina), 1.8 g/24 h, was given parenterally in three divided doses. All patients had hyperoxaluria, with a mean oxalate absorption of 0.94 +/- 0.09 mmol/24 h (+/- SEM). No significant disturbances in the colonic microflora were found. The degree of hyperoxaluria did not change during clindamycin administration, in spite of a significant decrease in the number of anaerobic bacteria. Our patients with enteric hyperoxaluria seem to have a normal colonic microflora. The degree of hyperoxaluria did not seem to be related to changes in the intestinal anaerobic flora.     

Single- and multiple-dose pharmacokinetics of oral moxifloxacin and clarithromycin,and concentrations in serum,saliva and faeces

Moxifloxacin and clarithromycin are important antibacterial drugs in the treatment of community-acquired respiratory tract infections. In a double-blind, randomized, 2-period cross-over study the pharmacokinetics of moxifloxacin versus clarithromycin were determined after single and multiple doses in 12 healthy male volunteers. The concentrations of the antibiotics in serum, saliva and faeces were measured by validated high-performance liquid chromatographic methods. In serum, moxifloxacin exhibited a mean peak concentration of 3.1 +/- 0.6 mg/l after a time to peak concentration of 1.67 +/- 0.96 h on day 1, with a significant increase to 3.98 +/- 1.10 mg/l on day 7 (p < 0.05). The area under the curve-12 revealed a highly significant increase from 28.2 + 4.1 mg*h/l on day 1 to 39.5 +/- 6.6 mg*h/l on day 7 (p < 0.01). There were also significant differences in terminal half-life between day 1 and day 7 [10.6 h (range 9.0-12.8) vs 14.9 h (range 12.6-28.1); p < 0.01] and in mean residence time (15.1 +/- 1.9 vs 18.2 +/- 2.4 h; p < 0.01). The concentrations of moxifloxacin in saliva were well equilibrated with serum at a relatively constant saliva-serum ratio of about 0.8. Pharmacokinetic parameters of clarithromycin and its metabolite, 14-hydroxy-clarithromycin, were similar to previously published data. Accumulation was found. No serious adverse events were observed with either study drug.     

Urine bactericidal activity of pefloxacin versus norfloxacin in healthy female volunteers after a single 800-mg oral dose

Summary In an open randomised crossover study the antibacterial activity of pefloxacin and norfloxacin was assessed in the urine after a single 800-mg oral dose in 14 healthy female volunteers. Pefloxacin demonstrated lower peak concentrations in the urine than norfloxacin (mean, 217.2 mg/l versus 492.9 mg/l as determined by the microbiological assay) but pefloxacin was present over a longer period of time in sufficient concentrations than norfloxacin. Mean urine levels of at least 2 mg/l were present for 7 days after pefloxacin administration and 2 days after norfloxacin administration as determined by the microbiological assay. Overall, the urinary recovery of pefloxacin and norfloxacin amounted to 49.3% and 25.1%, respectively, of the total administered dose. The average urine bactericidal activity against the five test organisms was as follows: against reference strainEscherichia coli ATCC 25922 susceptible to nalidixic acid (Nal-S) for 5 days with pefloxacin and 2 days with norfloxacin; against three clinical isolates, one strain each ofE. coli resistant to nalidixic acid (Nal-R),Klebsiella pneumoniae Nal-R, andStaphylococcus saprophyticus, for 3 days with pefloxacin and 24 h with norfloxacin; and against a clinical isolate ofEnterococcus faecalis for 2 days with pefloxacin and 12 h with norfloxacin. In conclusion, pefloxacin as a single dose proved to have sufficiently high and long-lasting urine bactericidal activity against urinary pathogens. These findings support the results of a meta-analysis of seven clinical trials in patients with uncomplicated lower UTI, demonstrating a single oral dose of 800 mg pefloxacin to be as effective as a conventional treatment with comparative drugs [21].     

Effect of erythromycin acistrate and erythromycin stearate on human colonic microflora

The effects of erythromycin acistrate (2'-acetyl erythromycin stearate), a new erythromycin derivative, and erythromycin stearate on the faecal microflora were compared in a randomized cross-over study. 12 healthy volunteers were given either drug 500 mg t.i.d. for 1 week. Their faeces were studied before, immediately after, and 1 week after the drug administration period. After a wash-out period of 4 weeks, the drugs were interchanged. Both erythromycin acistrate and erythromycin stearate induced changes in the normal colonic microflora to about the same extent. The most marked effect was the suppression of gram-negative anaerobic and aerobic rods. Clostridium difficile appeared in 1 subject on both drugs. Also the counts of aerobic gram-positive cocci were altered; enterococci increased in number. An increased resistance to erythromycin was noted among staphylococci and enterococci after both drugs.     

Serum and saliva concentrations of sulfamethoxazole and trimethoprim in adults and children: relation between saliva concentrations and in vitro activity against nasopharyngeal pathogens

The combination sulfamethoxazole/trimethoprim (SMX/TMP) was given orally to 4 healthy adult volunteers in mean daily doses of 23.0/4.6 mg/kg body weight for 6 days. The serum and saliva concentrations of the drugs were assayed on days 1, 3 and 6. On the first day (0-12 h) there was no measurable concentration of SMX in the saliva. On days 3 and 6 the mean peak levels of SMX in saliva were 7.8 and 9.8 micrograms/ml, i.e. 8-9% of the corresponding mean peak serum levels. In contrast, the concentrations of TMP in saliva were more than twice as high as those in serum. The mean SMX/TMP ratios in saliva days 3 and 6 were 1.3 and 1.4, respectively, i.e. approximately one-twentieth of the mean SMX/TMP ratios in serum. SMX/TMP was also administered to children with serous otitis media. The drug concentrations in saliva were assayed 2-3 h after administration on days 6 and 9 of a 10-day course, with a mean daily dose of 34.5/6.9 mg/kg body weight. The mean saliva concentration of SMX in the children was slightly higher than in adults and the mean TMP concentration about half of that in adults. The mean SMX/TMP ratio in the children's saliva was 4.2. The in vitro activity of SMX/TMP 20:1 and 4:1 was determined against H. influenzae, D. pneumoniae, B. catarrhalis and group A streptococci. H. influenzae, D. pneumoniae and group A streptococci were found more susceptible to TMP than to SMX, while the reverse was true for B. catarrhalis. In the 3 former, the potentiation of SMX by TMP was more pronounced than was the potentiation of TMP by SMX, while the opposite was recorded for B. catarrhalis. The most beneficial effect of the SMX/TMP combination against nasopharyngeal pathogens was recorded for B. catarrhalis and the weakest effect for H. influenzae and group A streptococci. With the exception of B. catarrhalis, the administration of TMP alone to adults may be just as effective against nasopharyngeal pathogens as is the SMX/TMP combination in children.     

A review on the impact of 4-quinolones on the normal oropharyngeal and intestinal human microflora

Summary During the last few years the impact of the newer 4-quinolones, ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin, on the human microflora has been studied by several investigators. This review article summarizes the published data concerning these studies. The results show that the oropharyngeal flora is affected only slightly or not at all by the 4-quinolones. All the newer 4-quinolones have a similar effect on the normal intestinal flora. The gram-negative aerobic flora is strongly suppressed during administration of 4-quinolones, while the gram-positive flora is only slightly affected. The anaerobic microflora is hardly affected at all. The emergence of resistant bacterial strains is uncommon, although one study shows increased MIC-values for anaerobes during ciprofloxacin administration. Replacement by yeasts or other inherently resistant microorganisms does not often seem to be a problem. High concentrations of the 4-quinolones are reached in faeces, values between 100–2,200 mg/kg being reported. Since the 4-quinolones do not cause marked ecological disturbances in the intestinal microflora, they may be suitable for selective decontamination in immunocompromised patients, for prophylaxis of urinary tract infections and for treatment of bacterial intestinal infections.

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Einfluß der 4-Chinolone auf die normale oropharyngeale und intestinale Flora des Menschen. Übersicht

Zusammenfassung In den vergangenen Jahren wurden mehrere Untersuchungen zur Beeinflussung der menschlichen Mikroflora durch die neuen 4-Chinolone Ciprofloxacin, Enoxacin, Norfloxacin, Ofloxacin und Pefloxacin durchgeführt. Die vorliegende Übersichtsarbeit faßt die aus diesen Studien publizierten Daten zusammen. Die Ergebnisse zeigen, daß 4-Chinolone die oropharyngeale Flora und auch die normale Darmflora kaum oder überhaupt nicht verändern. Unter der Therapie mit 4-Chinolonen ist die aerobe gramnegative Flora stark supprimiert, die grampositive Flora dagegen kaum beeinträchtigt. Die anaerobe Mikroflora wird kaum verändert. Nur selten treten resistente Bakterienstämme auf. In einer Studie wurden allerdings unter Behandlung mit Ciprofloxacin erhöhte MHK-Werte für Anaerobier festgestellt. Zu einer Verdrängung der normalen Flora zugunsten von Hefen oder anderen Mikroorganismen mit inhärenter Resistenz kommt es offensichtlich nur selten. 4-Chinolone werden in hoher Konzentration in den Faeces gefunden, die publizierten Konzentrationen liegen zwischen 100 und 2200 mg/kg. Da die 4-Chinolone die Ökologie der Mikroflora des Darmes nicht wesentlich beeinträchtigen, eignen sie sich möglicherweise für die selektive Dekontamination bei abwehrgeschwächten Patienten, die Prophylaxe von Harnwegsinfektionen und Behandlung intestinaler bakterieller Infektionen.

     

Influence of ciprofloxacin on the colonic microflora in young and elderly volunteers: no impact of the altered drug absorption

The colonic microflora was studied before, on the fifth day of dosing, and 2 weeks after a 5-day oral course of ciprofloxacin 500 mg BID given to 7 young and 7 elderly, healthy volunteers. Considerable changes in the aerobic microflora were found, while the effects on the anaerobic bacteria were less pronounced. Despite larger absolute bioavailability of the first dose in the elderly (77 vs. 63%; p less than 0.05), the effect of ciprofloxacin on the microflora was similar in the two groups of volunteers. A higher number of clostridia were detected in faeces from elderly subjects before, during, and after the ciprofloxacin regimen.     

Effect of piperacillin/tazobactam therapy on intestinal microflora.

The effect of piperacillin/tazobactam treatment upon the intestinal microflora was studied in 20 patients with intraabdominal infections. The patients received piperacillin 4 g combined with tazobactam 500 mg q 8 h by intravenous injection for 4-8 days. Stool specimens were collected before, during and after therapy for cultivation of aerobic and anaerobic microorganisms. Six patients had measurable concentrations of piperacillin (1.2-276 mg/kg/faeces) and 4 patients tazobactam concentrations (0.8-22.2 mg/kg/faeces) in the faecal specimens during therapy. The number of enterobacteria and enterococci slightly decreased while there were no changes in the number of staphylococci and bacilli. The anaerobic microflora was also slightly affected. There was a minor decrease in the number of bifidobacteria, eubacteria, lactobacilli, clostridia and veillonella but the numbers of anaerobic Gram-positive cocci and bacteroides were not influenced by the treatment. After therapy, the aerobic and anaerobic microflora returned to normal levels in all patients. None of the patients had Clostridium difficile or cytotoxin in the stools or developed diarrhoea.     

Saliva and serum testosterone following oral testosterone undecanoate administration in normal and hypogonadal men

Since saliva testosterone reflects the testosterone fraction available to target tissues the therapeutic effectiveness of orally administered testosterone undecanoate was assessed by measuring testosterone in serum and saliva. Matched saliva and serum samples were obtained from 12 normal men and 8 hypogonadal men before and at hourly intervals after the oral administration of 120 mg testosterone undecanoate. The test was repeated in 3 men after they had taken 40 mg testosterone undecanoate twice daily for 4 to 5 weeks. Following testosterone undecanoate administration serum and saliva testosterone always showed parallel increases. However, the absorption curves showed a high interindividual variability in the time when maximum concentrations were reached, as well as in the maximum levels themselves. The increases in serum and saliva testosterone were similar in normal and hypogonadal men. In normal men basal levels were reached 4 h after the maximum had occurred, while in hypogonadal men testosterone levels were not different from basal levels 2 h after the maximum. The study shows that testosterone undecanoate is well absorbed from the gut and releases significantly elevated amounts of testosterone which is available to target tissues. As the absorption pattern was always parallel in both fluids, hydrolysis of the circulating testosterone ester by the tissue itself seems to effect no additional increase of testosterone in the tissue.     

Ecological effects of linezolid versus amoxicillin/clavulanic acid on the normal intestinal microflora

Twelve healthy subjects (6 females, 6 males; age range 18-40 y) participated in this trial. Linezolid was given as 600 mg tablets b.i.d. for 7 d and amoxicillin/clavulanic acid as 1000 mg tablets o.d. for 7 d. The washout period between the administration of the 2 antibacterial agents was 4 weeks. Faecal samples were collected prior to administration (Days -2 and -1), during administration (Days 4 and 8) and after administration (Days 14, 21 and 35) for microbiological analyses. The samples were diluted in pre-reduced media and inoculated aerobically and anaerobically on non-selective and selective media. Different colony types were identified to genus level by morphological, biochemical and molecular analyses. During the administration of linezolid, enterococci in the intestinal aerobic microflora were markedly suppressed while Klebsiella organisms increased in number. In the anaerobic microflora, the numbers of bifidobacteria, lactobacilli, clostridia and Bacteroides decreased markedly while no impact on the other anaerobic bacteria was observed. The microflora was normalized in all volunteers after 35 d. Amoxicillin/clavulanic acid administration caused increased numbers of enterococci and Escherichia coli in the aerobic intestinal microflora while numbers of bifidobacteria, lactobacilli and clostridia decreased significantly. Clostridium difficile strains were recovered from 3 of the volunteers. At the last visit, the intestinal microflora of the volunteers had returned to normal levels. The administration of linezolid mainly had an impact on the gram-positive bacteria and linezolid thus had an ecological profile different from that of amoxicillin/clavulanic acid.     

Pleural penetration of ciprofloxacin in patients with empyema thoracis

We evaluated the pharmacokinetics of a single 200-mg dose of ciprofloxacin, administered as a 30-minute infusion, into pleural exudate in five elderly patients with empyema thoracis. Ciprofloxacin was measured by HPLC and the pharmacokinetic parameters were determined by noncompartmental methods. Mean peak serum levels 30 minutes after administration were 1.98 +/- 0.07 mg/L. Terminal serum half-lives ranged from 3.9 to 5.1 h. Mean concentrations of ciprofloxacin in pleural exudate were 1.44 +/- 0.42 mg/L at a mean time of 4.5 +/- 2.5 h. After this time, the pleural exudate level exceeded the corresponding serum twofold to tenfold. The mean percentage penetration into the inflammatory compartment was approximately 210 percent. Our data suggested that ciprofloxacin penetrates well into the pleural fluid of patients with empyema thoracis. The concentrations achieved were well above the MIC90 of most pathogens normally found in patients with empyema thoracis for a period of approximately 12 h.     

脊椎结核患者寒性脓肿及血液中三种抗结核药物浓度的比较

目的对脊椎结核患者血液和寒性脓肿中的异烟肼、利福平和氧氟沙星进行药代动力学分析，为临床选择治疗方案提供参考。方法８例脊椎结核患者于用药后０．５、０．７５、１．０、１．５、２．０、４．０、６．０、９．０、１２．０、１６．０和２４．０小时同时抽取静脉血和寒性脓肿作为标本，用高效液相色谱法检测上述药物浓度，其数据用３Ｐ８７程序进行处理。结果异烟肼、利福平和氧氟沙星的血中峰浓度分别为１０．８７±７．０９μｇ／ｍｌ、９．９８±３．５３μｇ／ｍｌ和５．２９±０．７２μｇ／ｍｌ；与此同时寒性脓肿中上述三药的峰浓度分别为２．８４±１．６３μｇ／ｍｌ、０．５７±０．２６μｇ／ｍｌ和３．１９±１．２９μｇ／ｍｌ。结论患者服用异烟肼和氧氟沙星后，在寒性脓肿中药物浓度均超过其有效的抑菌浓度，药物浓度上升和消除较血清慢。而利福平不易渗入寒性脓肿中，峰浓度仅达到其最低抑菌浓度     

Acetylcysteine protects against acute renal damage in patients with abnormal renal function undergoing a coronary procedure

OBJECTIVES: We sought to evaluate the efficacy of the antioxidant acetylcysteine in limiting the nephrotoxicity after coronary procedures. BACKGROUND: The increasingly frequent use of contrast-enhanced imaging for diagnosis or intervention in patients with coronary artery disease has generated concern about the avoidance of contrast-induced nephrotoxicity (CIN). Reactive oxygen species have been shown to cause CIN. METHODS: We prospectively studied 121 patients with chronic renal insufficiency (mean [+/-SD] serum creatinine concentration 2.8 +/- 0.8 mg/dl) who underwent a coronary procedure. Patients were randomly assigned to receive either acetylcysteine (400 mg orally twice daily) and 0.45% saline intravenously, before and after injection of the contrast agent, or placebo and 0.45% saline. Serum creatinine and blood urea nitrogen were measured before, 48 h and 7 days after the coronary procedure. RESULTS: Seventeen (14%) of the 121 patients had an increase in their serum creatinine concentration of at least 0.5 mg/dl at 48 h after administration of the contrast agent: 2 (3.3%) of the 60 patients in the acetylcysteine group and 15 (24.6%) of the 61 patients in the control group (p < 0.001). In the acetylcysteine group, the mean serum creatinine concentration decreased significantly from 2.8 +/- 0.8 to 2.5 +/- 1.0 mg/dl (p < 0.01) at 48 h after injection of the contrast medium, whereas in the control group, the mean serum creatinine concentration increased significantly from 2.8 +/- 0.8 to 3.1 +/- 1.0 mg/dl (p < 0.01). CONCLUSIONS: Prophylactic oral administration of the antioxidant acetylcysteine, along with hydration, reduces the acute renal damage induced by a contrast agent in patients with chronic renal insufficiency undergoing a coronary procedure.     

Galacto-oligosaccharides Stimulate the Growth of Bifidobacteria but Fail to Attenuate Inflammation in Experimental Colitis in Rats

Background: Galacto-oligosaccharides potentially attenuate colonic inflammation by two mechanisms: through beneficial effects on intestinal microflora and by increasing the colonic short-chain fatty acid concentration. The purpose of this study was to investigate the effects of galacto-oligosaccharides on the development of inflammation and on the growth of bifidobacteria in trinitrobenzene sulphonic acid (TNBS)-induced colitis, a model that has been shown to benefit from short-chain fatty acid administration and to be associated with alterations in the colonic microflora. Methods: Rats were given daily either whey-derived or lactose-derived galacto-oligosaccharides (4 g kg -1 day -1 , p.o.), starting 10 days before colitis induction, or dexamethasone (2 mg kg -1 day -1 , s.c., a positive control), starting at colitis induction. Colon wet weight, macroscopic damage and myeloperoxidase activity were assessed 72 h after the induction of colitis. Faecal bifidobacteria were counted at the beginning of the study, and immediately before and 72 h after colitis induction. Results: Galacto-oligosaccharides increased the colonic levels of bifidobacteria but also the levels of other bacterial species. Neither whey-derived nor lactose-derived galacto-oligosaccharides reduced the severity of inflammation. Conclusions: Galacto-oligosaccharides are able to modify gut microflora in severe TNBS-induced colitis, but unable to attenuate the inflammation.     

Galacto-oligosaccharides stimulate the growth of bifidobacteria but fail to attenuate inflammation in experimental colitis in rats

BACKGROUND: Galacto-oligosaccharides potentially attenuate colonic inflammation by two mechanisms: through beneficial effects on intestinal microflora and by increasing the colonic short-chain fatty acid concentration. The purpose of this study was to investigate the effects of galacto-oligosaccharides on the development of inflammation and on the growth of bifidobacteria in trinitrobenzene sulphonic acid (TNBS)-induced colitis, a model that has been shown to benefit from short-chain fatty acid administration and to be associated with alterations in the colonic microflora. Methods: Rats were given daily either whey-derived or lactose-derived galacto-oligosaccharides (4 g kg(-1) day(-1), p.o.); starting 10 days before colitis induction, or dexamethasone (2 mg kg(-1) day(-1), s.c., a positive control), starting at colitis induction. Colon wet weight, macroscopic damage and myeloperoxidase activity were assessed 72 h after the induction of colitis. Faecal bifidobacteria were counted at the beginning of the study, and immediately before and 72 h after colitis induction. Results: Galacto-oligosaccharides increased the colonic levels of bifidobacteria but also the levels of other bacterial species. Neither whey-derived nor lactose-derived galacto-oligosaccharides reduced the severity of inflammation. Conclusions: Galacto-oligosaccharides are able to modify gut microflora in severe TNBS-induced colitis, but unable to attenuate the inflammation.     

Effect of antimicrobial agents on the ecological balance of human microflora

The normal microflora acts as a barrier against colonisation of potentially pathogenic microorganisms and against overgrowth of already present opportunistic microorganisms. Control of growth of opportunistic microorganisms is termed colonisation resistance. Administration of antimicrobial agents, therapeutically or as prophylaxis, causes disturbances in the ecological balance between the host and the normal microflora. Most studies on the impact of antimicrobial agents on normal microflora have been carried out on the intestinal flora. Less is known on the effects on oropharyngeal, skin, and vaginal microflora. Disturbances in the microflora depend on the properties of the agents as well as of the absorption, route of elimination, and possible enzymatic inactivation and/or binding to faecal material of the agents. The clinically most common disturbances in the intestinal microflora are diarrhoea and fungal infections that usually cease after the end of treatment. A well-balanced microflora prevents establishment of resistant microbial strains. By using antimicrobial agents that do not disturb colonisation resistance, the risk of emergence and spread of resistant strains between patients and dissemination of resistant determinants between microorganisms is reduced. In this article, the potential ecological effects of administration of antimicrobial agents on the intestinal, oropharyngeal, and vaginal microflora are summarised. The review is based on clinical studies published during the past 10 years.