Impact of Lactobacillus acidophilus on the normal intestinal microflora after administration of two antimicrobial agents

Summary Twenty healthy volunteers participated in a comparative study concerning the influence ofLactobacillus acidophilus supplements on the normal intestinal microflora after the administration of two antimicrobial agents, enoxacin and clindamycin, respectively.L. acidophilus NCFB 1748 was given as a fermented milk product containing 5 × 10⁸–2 × 10⁹ CFU/ml to ten of the volunteers immediately after the administration of the antimicrobial agents. On the seventh day of enoxacin administration enterobacteria were eliminated in nine of ten subjects. Enterococci disappeared or decreased significantly in five subjects. During theL. acidophilus supplementation, there was a significant increase in the number ofEscherichia coli in one subject, while enterococci returned to the same level as before enoxacin administration in all subjects. In the clindamycin group, the anaerobic microflora was strongly suppressed in all volunteers. Lactobacilli disappeared in two subjects and decreased in five. Administration ofL. acidophilus resulted in a significant increase in the number of lactobacilli in all subjects, while most other anaerobic bacteria returned to the same levels as before clindamycin administration one week later. In two subjects, Bacteroides increased to earlier high levels on days 14 to 16 in theLactobacillus group, while there was no similar increase in the clindamycin group. Though there was a partial restoration of the intestinal microflora due to the reestablishment of lactobacilli and enterococci,L. acidophilus administration could not accelerate the normalization of most other strongly suppressed microorganisms in the intestine.

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Einfluß von Lactobacillus acidophilus auf die physiologische Flora des Darmes nach Applikation von zwei antimikrobiellen Substanzen

Zusammenfassung Bei 20 gesunden freiwilligen Probanden wurde der Einfluß vonLactobacillus acidophilus auf die physiologische Mikroflora des Darmes nach Gabe von zwei antimikrobiellen Substanzen, Enoxacin bzw. Clindamycin, im Rahmen einer Vergleichsstudie untersucht.L. acidophilus NCFB 1748 wurde in einer Konzentration von 5 ×10⁸ – 2 × 10⁹ KBE/ml als fermentiertes Milchprodukt unmittelbar nach Gabe der Antibiotika an zehn der Probanden verabreicht. Bei neun der zehn Probanden waren am siebten Tag nach Gabe von Enoxacin Enterobakterien eliminiert. Bei fünf Personen verschwanden Enterokokken oder waren signifikant vermindert. WennL. acidophilus zugegeben wurde, kam es bei einer Person zu einer signifikanten Zunahme derEscherichia coli-Zahlen und in allen Fällen zu einem Anstieg der Enterokokkenzahlen auf Werte wie vor der Applikation von Enoxacin. Bei allen Probanden der Clindamycin-Gruppe war die anaerobe Mikroflora erheblich vermindert. Bei zwei Personen verschwanden Laktobazillen und gingen in fünf Fällen zurück. Bei allen Testpersonen führte die Gabe vonL. acidophilus zu einem signifikanten Anstieg der Laktobazillen, die meisten anderen anaeroben Bakterien waren nach einer Woche wieder in derselben Zahl vorhanden wie vor Gabe von Clindamycin. Bei zwei Personen derLactobacillus-Gruppe stieg die Zahl der Bacteroides-Keime an den Tagen 14–16 auf Werte wie vor Antibiotikagabe an, während in der Clindamycin-Gruppe kein vergleichbarer Anstieg zu verzeichnen war. Obwohl es durch Regeneration der Laktobazillen und Enterokokken zu einer teilweisen Wiederherstellung der intestinalen Mikroflora kam, konnte durch Gabe vonL. acidophilus die Normalisierung der meisten übrigen, stark supprimierten Mikroorganismen im Darm nicht beschleunigt werden.

     

Effect of antipyretic agents on uptake,transport, and release of antimicrobial agents by human polymorphonuclear leukocytes

Polymorphonuclear leukocytes (PMNL) concentrate, transport, and release certain antimicrobial agents as they move in a chemotactic gradient. Antipyretic agents are frequently used in febrile patients receiving antimicrobial agents. Thus, the influence of ibuprofen, acetaminophen, and acetylsalicylic acid on uptake, transport, and release of azithromycin and moxifloxacin was studied. Uptake of the antimicrobial agents by human PMNL and the effect of the antipyretics were quantitated by bioassay of released antimicrobial agent. Transport and release were determined in chemotactic plates overlaid with sentinel bacteria that could detect transported and released antimicrobial agent. None of the antipyretics altered PMNL directed or non-directed movement. Uptake of azithromycin was significantly inhibited by acetylsalicylic acid but not by the other antipyretics. All of the antipyretic agents studied at therapeutic levels inhibited transport and release of both azithromycin and moxifloxacin. Administration of any of these antipyretic agents with antimicrobial agents that are transported and released by PMNL could compromise the efficacy of therapy.     

Bifidobacterium strains from resident infant human gastrointestinal microflora exert antimicrobial activity

BACKGROUND AND AIMS: The gastrointestinal microflora exerts a barrier effect against enteropathogens. The aim of this study was to examine if bifidobacteria, a major species of the human colonic microflora, participates in the barrier effect by developing antimicrobial activity against enterovirulent bacteria. METHODS: Antibacterial activity was examined in vitro against a wide range of Gram negative and Gram positive pathogens. Inhibition of Salmonella typhimurium SL1334 cell association and cell invasion was investigated in vitro using Caco-2 cells. Colonisation of the gastrointestinal tract in vivo by bifidobacteria was examined in axenic C3/He/Oujco mice. Antimicrobial activity was examined in vivo in axenic C3/He/Oujco mice infected by the lethal S typhimurium C5 strain. RESULTS: Fourteen human bifidobacterium strains isolated from infant stools were examined for antimicrobial activity. Two strains (CA1 and F9) expressed antagonistic activity against pathogens in vitro, inhibited cell entry, and killed intracellular S typhimurium SL1344 in Caco-2 cells. An antibacterial component(s) produced by CA1 and F9 was found to be a lipophilic molecule(s) with a molecular weight of less than 3500. In the axenic C3/He/Oujco mice, CA1 and F9 strains colonised the intestinal tract and protected mice against S typhimurium C5 lethal infection. CONCLUSION: Several bifidobacterium strains from resident infant human gastrointestinal microflora exert antimicrobial activity, suggesting that they could participate in the "barrier effect" produced by the indigenous microflora.     

Significance of antimicrobial activities testing of antimicrobial agents in human urine]

In order to clarify the in vivo effect of the new quinolones in the urinary tract, we investigated the antimicrobial activities against Escherichia coli in the human urine. Human urine was prepared from a normal volunteer. After cations were removed by chelating resin, human urine was supplemented with 50, 100, or 500 micrograms of Mg2+ per ml using MgCl2 or 10, 50, or 150 micrograms of Ca2+ per ml using CaCl2. The pH of human urine was adjusted to 5.5, 7.0, or 8.0 with HCl or NaOH. Four clinical isolates of E. coli and E. coli NIHJ JC-2 were used. And antimicrobial activities of the new quinolones (norfloxacin, enoxacin, ofloxacin and ciprofloxacin) against these strains were measured using various urines as mediums. Antimicrobial activities of the new quinolones were reduced in the presence of high concentration of magnesium or low pH of urine. However, there was no influence of calcium concentration of urine on antimicrobial activities of the new quinolones. From these results, the component of the urine should be checked in the treatment of the patients with urinary tract infection.     

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.     

Hepatotoxicity of antimicrobial agents

Antimicrobial agents are a common and important cause of hepatotoxicity. As a class, the antimicrobials contain many and varied structures, leading to a wide clinical spectrum of hepatotoxicity. Minor liver injury, manifest only as liver enzyme elevations, is common with some antimicrobials. Clinically significant injury is unusual but can adopt almost any form. Classical acute hepatocellular, cholestatic, or mixed reactions are most often seen. Other forms of hepatotoxicity including granulomatous reactions, steatosis, chronic hepatitis, and cirrhosis have also been described. Generally, antimicrobial-associated hepatotoxicity is mild and self-limited; most cases resolve after withdrawal of the offending medication. Occasionally, however, liver injury presents as a fulminant life-threatening condition or may develop into a chronic illness with significant morbidity. This article presents a summary of reported hepatotoxicity associated with the major classes of antimicrobials and, where possible, identifies potential risk factors and management strategies to assist clinical practice.     

Effect of lactic acid producing bacteria on the human intestinal microflora during ampicillin treatment

20 healthy volunteers participated in a double blind study concerning the effect of lactic acid producing bacteria on the intestinal microflora during ampicillin treatment. 10 volunteers received 500 mg ampicillin tablets t.i.d. together with capsules containing lactic acid producing bacteria (Lactobacillus acidophilus and Bifidobacterium bifidum) for 7 days, and the other 10 volunteers were given 500 mg ampicillin tablets together with placebo capsules t.i.d. for 7 days. Both groups of volunteers continued the intake of the capsules t.i.d. for another 14 days after the ampicillin administration had been completed. The number of enterococci, streptococci and corynebacteria decreased during ampicillin administration but returned to normal levels after 14 days. Yeasts increased during the antibiotic treatment but returned to the same levels as before treatment within 14 days. Escherichia coli strains were suppressed in most volunteers during ampicillin administration. The numbers of anaerobic gram-positive cocci and rods decreased in most subjects during ampicillin treatment but were normalized within 2 weeks. Bacteroides strains were recovered in higher numbers in the lactic acid producing bacteria group compared to the placebo group. The volunteers receiving lactic acid producing bacteria were recolonized slightly faster than those having placebo. There were adverse effects observed in 3 subjects receiving ampicillin plus placebo. In the lactic acid producing bacteria group, one subject had diarrhoea on day 3 to on day 3 to day 7.     

慢性腹泻与肠道菌群失调

肠道固有菌以共生的形式定居于人体肠道 ,形成一个天然防御屏障 ,抵抗外来致病菌的侵袭 ,如机体内外环境的变化使肠正常菌群的生理组合遭到破坏 ,产生病理性组合 ,称肠道菌群失调。肠道菌群失调所致慢性腹泻是临床常见的症状 ,此往往易被忽视。1　肠道菌群的组成及功能人类消化道中含 10 14 个细菌 ,为体细胞的 10倍 ,粪便湿重的 4 0 %以上是细菌。消化道内所含细菌因部位而异 ,成人胃至回肠上部细菌很少 ,肠道上段至下段则细菌逐渐增多。胃内存在的菌群主要有乳酸杆菌、链球菌、双歧杆菌、梭菌、韦荣球菌、大肠埃希菌类及酵菌等。人类肠…     

Effect of norfloxacin on human oropharyngeal and colonic microflora and multiple-dose pharmacokinetics

10 healthy volunteers received 200 mg norfloxacin orally every 12 h for 7 days. Saliva, throat and faecal specimens were collected days 0, 3, 5, 7, 14 and 21 to study the effect of norfloxacin on the normal microflora. The concentrations of norfloxacin in serum, urine, saliva and faeces were determined by a microbiological method and all samples except faeces were also assayed by high-pressure liquid chromatography (HPLC). The pharmacokinetics of norfloxacin were studied on day 3. The mean peak serum concentration (+/- SD) attained after 0.75-1.0 h was 0.75 +/- 0.15 mg/l measured by HPLC, and the mean terminal serum half-life was 4.2 +/- 0.6 h. The mean cumulative urinary elimination was 29% during 12 h after dosing. There was no significant difference between values obtained by microbiological assay and by HPLC. The saliva concentration was approximately 30% of the serum levels 1.0-1.5 h after administration. No accumulation in faeces was found during the administration period, and mean concentrations were 940 mg/kg. The changes in the oropharyngeal flora were minor and only branhamella were affected. In the colonic flora, the number of enterobacteria was strongly depressed while the anaerobic microflora was only slightly affected. Two weeks after the administration period, both the oropharyngeal and colonic microflora had returned to normal.     

Effect of ceftibuten on the normal intestinal microflora

Summary 14 healthy volunteers were given 400 mg ceftibuten orally once daily for ten days. Stool specimens were collected before, during and after ceftibuten administration. Ceftibuten was well absorbed; on average 123 mg was excreted in urine 0–6 h after dosing, while only two volunteers had detectable concentrations of ceftibuten in faeces (3.2 mg/kg). There was an overgrowth of enterococci during the administration period, while the numbers ofEscherichia coli and anaerobic cocci were reduced. Six volunteers were colonized byClostridium difficile during the days 4 to 17. Beta-lactamase activity was detected in faecal samples from eight volunteers and increased significantly during the administration period.

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Einfluß von Ceftibuten auf die normale intestinale Mikroflora

Zusammenfassung 14 gesunde freiwillige Probanden nahmen 14 Tage lang täglich 400 mg Ceftibuten oral. Stuhlproben wurden vor, während und nach Gabe von Ceftibuten gewonnen. Ceftibuten wurde gut resorbiert. Im Durchschnitt wurden 0–6 Stunden nach Einnahme 123 mg mit dem Urin ausgeschieden. Im Stuhl konnte Ceftibuten nur bei zwei Probanden nachgewiesen werden (3,2 mg/kg). Während der Einnahme des Antibiotikums hatten Enterokokken überwuchert, die Zahlen vonEscherichia coli und anaeroben Kokken waren vermindert. Sechs Probanden zeigten während der Tage 4–17 eine Kolonisation mitClostridium difficile. Bei acht Probanden wurde -Laktamase-Aktivität in Stuhlproben nachgewiesen; sie nahm während der Applikationsphase signifikant zu.

     

Pharmacokinetics of antimicrobial agents in the elderly

The elderly can be easily infected by certain organisms due to underlying diseases and complications. The pharmacokinetics of cefotiam, ceftriaxone, ceftizoxime, cefpodoxime proxetil, carumonam, clarithromycin, amikacin, ofloxacin and lomefloxacin in the elderly should be considered when choosing antibiotics for elderly patient with regard to infected site, causative organisms, pharmacokinetics and side effects. Pharmacokinetics in the elderly reflect potential renal dysfunction, so that t1/2 was elongated and AUC increased with age. Intravenous administration in the elderly, especially in the subjects with low body weight, the administered dose and intervals must be considered. With oral administration there was no constant tendency of the intestinal absorption.     

Use of antimicrobial agents in animal feeds: implications for human health

The inclusion of subtherapeutic doses of antimicrobial agents in animal feed is credited for having contributed to lower costs of meat, milk, and eggs. The practice often is associated with the acquisition of resistant enteric flora by the involved animals, a phenomenon that in turn may contribute to the human reservoir of coliforms and salmonellae resistant to antimicrobial agents. Farm workers may transiently acquire resistant intestinal flora and on rare occasions develop salmonellosis. Although irrefutable evidence of the growth-promoting properties of antibiotics in animal feed was provided 30-40 years ago, additional studies--with a focus on mechanisms of the effect--are presently needed. It may be possible to identify factors effective in promoting growth without deleterious effects on the intestinal flora. A national program of surveillance of antimicrobial administration (in both subtherapeutic and therapeutic doses) to food-producing animals should be established. Molecular epidemiologic research efforts must be undertaken to determine whether genetic information of animal origin contributes significantly to the human environmental pool of antimicrobial resistance. In the meantime, it does not appear that the banning of drugs as feed additives, with concomitant unrestricted use of these agents for the treatment of both animals and people, would favorably influence the problems of antimicrobial resistance and salmonellosis in human populations.     

Interactions of cyclosporine with antimicrobial agents

A number of antimicrobial agents may have untoward interactions with cyclosporine. Concurrent use of ketoconazole or erythromycin results in increased serum cyclosporine levels, with associated potential nephrotoxicity or neurotoxicity. Rifampin and perhaps nafcillin induce cytochrome P-450-dependent isoenzyme metabolism of cyclosporine. The resultant decreased bioavailability of cyclosporine may precipitate graft rejection. The aminoglycosides, trimethoprim-sulfamethoxazole, and amphotericin B have been associated with increased nephrotoxicity, independent of the levels of cyclosporine or antibiotic present. Anticipation of potential antibiotic interactions and appropriate monitoring of levels of cyclosporine and antibiotics and of renal function are critical to the avoidance of reversible causes of graft failure or organ toxicity.     

In vitro testing of antimicrobial agents

Antimicrobial susceptibility tests provide information that may be helpful in the initial selection of antimicrobials to be used in therapy, may prompt a change in an existing regimen to one including a more active antimicrobial agent, or may allow substitution of one antimicrobial agent with another equally effective but less expensive antimicrobial agent. The clinical value of bactericidal testing is less clear-cut due, at least in part, to methodologic variations and biological and technical variables. Standardization of methods provides both intralaboratory and interlaboratory reproducibility, as well as interpretability of results.     

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.     

Guideline for use of topical antimicrobial agents

This Guideline is based on published data available at the time of writing. The ideal means for comparing performance of various antimicrobial agents is through the conduct of carefully designed, large-scale clinical trials. Recommendations contained in this Guideline are subject to modification as additional data become available. It particularly should be noted that the implementation of universal precautions or body substance isolation has resulted in marked increase in the use of gloves for direct patient contact. Whether there is an additional cost-benefit rationale for handwashing with an antimicrobial agent remains to be studied.