Bowel Flora Research Articles

Influence of temocillin on human bowel flora.

The influence of temocillin on intestinal flora was investigated in 6 healthy volunteers, each of whom received intravenous temocillin 1g twice daily over a period of 6 to 7 days. Dilution series of stool samples were investigated before, during and immediately after treatment, as well as 9 to 14 days after treatment had been stopped. The basic effect of temocillin was a pronounced reduction in Enterobacteriaceae during and immediately after treatment. Nine to 14 days after conclusion of treatment, the Enterobacteriaceae had almost reattained their original numbers. No clear influence could be established for temocillin on the total numbers of aerobic bacteria, strict anaerobes, or the members of the Bacteroides fragilis group. The number of enterococci increased slightly during treatment, but antibiotic-resistant Enterobacteriaceae were not selected by treatment. It can be concluded that in these volunteers the colonisation resistance of the colon was maintained during treatment, and that temocillin exerted an influence comparable to a selective decontamination of the intestine.

Persistence of HLA-B27 cross-reactive bacteria in bowel flora of patients with ankylosing spondylitis.

Previous studies have shown that antisera raised in rabbits to certain enteric bacteria (cross-reactive bacteria) are capable of specifically lysing in a 51chromium-release lymphocytotoxicity test the lymphocytes of HLA-B27-positive (B27+) patients with ankylosing spondylitis (AS). This study investigated the clinical relevance of this finding by ascertaining whether Escherichia coli isolated from the rectal swabs of 20 B27+ AS patients (B27+ AS+) and 46 controls (35 B27- AS- and 11 B27+ AS-) were able to absorb the lymphocytotoxic activity of these antisera. All isolates from B27+ AS+ patients and one from a B27- AS- individual were capable of removing this activity. These organisms persisted in the bowel flora of five selected patients for at least 9 months. Cross-reactive bacteria were also found in a range of gram-positive organisms, including streptococcal, staphylococcal, and clostridial species. The relevance of these findings is discussed in terms of a pathogenetic concept relating the persistence of cross-reactive bacteria in the bowel flora of B27+ individuals to an early event in the development of AS.

Patients with active Crohn's disease have elevated serum antibodies to antigens of seven enteric bacterial pathogens

A variety of bacterial pathogens including Campylobacter, Yersinia, Listeria, Brucella, and Mycobacteria have been suggested as potential etiologic agents for Crohn's disease. To assess the role of these organisms we studied responses to eight antigens in sera from patients with active Crohn's disease and healthy age- and sex-matched controls. In complement-fixation assays, the sera from the Crohn's disease patients had enhanced reactivity compared with the control sera to all seven orally ingested pathogens studied; however, only the difference in distribution of liters to Yersinia pseudotuberculosis was statistically significant (p < 0.0025). There was no difference between the two groups in reactivity to arabinomannan, a common mycobacterial antigen. Seroreactivity to enteric pathogens not resident in the bowel flora probably represents a nonspecific sensitization to cross-reacting antigens. Lack of response to the mycobacterial antigen suggests that widespread mycobacterial disease with high bacillary load is not present in Crohn's disease.

Mechanisms of antibiotic resistance and their dissemination of resistance genes in the hospital environment.

The dissemination of resistance determinants among bacterial populations depends on ecological and epidemiological properties as well as additional factors: 1) the mechanism of resistance or its specificity toward a certain drug, and 2) the genetic basis in relation to the mobility of the genetic material and its survival in bacteria. From two resistance mechanisms directed toward old-fashioned drugs, namely sulfonamides (Su) and streptomycin (Sm), we can deduce that a resistance mechanism is encoded by a special sort of genetic material. Thus the linked SmSu resistance mediated by a sulfonamide-resistant dihydropteroatsynthetase II and the aminoglycoside phosphotransferase APH-(3") is always located on very small pBP1-like plasmids. Such plasmids survive without selective pressure of drugs in Enterobacteriaceae in the bowel flora of humans and animals. Both resistance determinants can be mediated by a transposon which codes for the production of a dihydropteroatsynthetase I in connection with an aminoglycoside adenylyltransferase AAD-(3"). These two mechanisms are genetically linked as well. The basic structure is a transposon designated Tn2411, which belongs to a whole family of transposons, all including the basic structure; however, their genetic exchange and substitution leads to structures coding for many different enzymatic characters: ANT-(2") (Gentamicin resistance), CAT (Chloramphenicol resistance), AAC-(6') (resistance to all modern aminoglycosides), TEM-1, OXA-1, OXA-2, or PSE (beta-lactam resistance). Resistance to the modern beta-lactamase-stable antibiotics is mediated by mutation in the regulatory genes of chromosomally-determined beta-lactamases. A spread of these resistance mechanisms can be avoided as long as the responsible genes are not located on sufficient structures like small plasmids or efficient transposons.

New toxicology: Carcinogenesis III

Summary This is the final article of a series of three. After briefly recapitulating the first two, this article will move on to consider the sources of malignant disease in the real world: diet and the bowel flora are important in this context. We will then look at some of the intermediate stages between carcinogenesis and the appearance of frank malignancy—here the topological order of DNA and oncogenes are important. Insight into natural resistance to carcinogenic influences can be gained from the study of congenital DNA repair syndromes. We will then look in more detail at the nature of these DNA repair systems and the ways in which it is possible to stimulate them. From such understanding effective therapy may evolve.

The pathogenesis of recurrent urinary tract infection: The bowel, bladder hypokalemia connection

A conceptual approach to the understanding of the pathogenesis of recurrent nonobstructive urinary tract infections is presented. Abnormal colonic function is associated with potassium wastage which alters smooth muscle function of both the bowel and bladder. Hypokalemia additionally results in the elaboration of an alkaline urine and bladder dysfunction leads to urinary stasis. Vaginal and perineal contamination from the bowel flora are etiologically important in the genesis of such infections. Thus, a linkage exists between bowel dysfunction, potassium wastage and recurrent urinary tract infection.

Increased Recovery of Klebsiella from the Gastrointestinal Tract of Reiter's Syndrome and Ankylosing Spondylitis Patients

Because of the known association between Gram-negative enteric bacteria and certain seronegative arthropathies. the bowel flora was examined in 59 Native Americans: 25 with ankylosing spondylitis. 18 with Reiter's syndrome and 16 healthy controls. Of the 43 ankylosing spondylitis and Reiter's syndrome patients, 35 (81%) were HLA-B27 positive. A significant difference in the isolation of Klebsiella from the stools of ankylosing spondylitis and Reiter's syndrome patients was noted only when the patients were divided on the basis of disease activity. Klebsiella was isolated from 14 of 26 (54%) patients with either active ankylosing spondylitis or active Reiter's syndrome, compared to two of 16 (13%) controls (p = 0.0077) and two of 17(12%)patients with inactive disease (p = 0.0055). The role of Klebsiella in the pathogenesis of HLA-B27 arthropathies is unknown, but recent literature would suggest an immunologic interaction between the antigens of Klebsiella and those of the histocompatibility complex.

Inhibition of Clostridium difficile by faecal streptococci.

The inhibitory activity of seven strains of faecal streptococci against 34 strains of Clostridium difficile was examined in vitro after growth of the streptococci for 24 and 48 h. All strains of C. difficile were inhibited at 48 h but at 24 h the inhibition was variable. Streptococcus faecium, a group D streptococcus and an ungroupable streptococcus exhibited the most striking inhibitory activity. Lowering of pH of the medium occurred at the site of inhibition, but the pH change alone did not explain the inhibition of C. difficile. This antagonism may be related in vivo to the resistance to intestinal colonisation by C. difficile exhibited by the normal bowel flora, and in vitro to failures to isolate C. difficile from faecal specimens.

Segmented filamentous bacteria in the rodent small intestine: Their colonization of growing animals and possible role in host resistance toSalmonella

The establishment and proliferation of a model population of autochthonous surface-associated microorganisms in the small bowel of growing rats (2-12 weeks of age) was studied. Segmented filamentous bacteria on the distal ileal villi were examined by scanning electron microscopy (SEM) and countedin situ by transect line analysis. In young animals, these bacteria first colonized the villous base, but occupied all areas on the villus by adult age. Their distribution on Peyer's patches was also noted.In growing animals, colonization of the ileal villi by filamentous bacteria was significantly correlated to the development of host resistance to fatal infection by orally-dosedSalmonella enteritidis. In animals givenSalmonella and examined by SEM and transmission EM (TEM), the pathogen was seen only on ileal tissue surfaces, predominantly the villous base, from which the autochthonous population was absent. Conversely, in animals with filamentous bacteria,Salmonella surface colonization was not observed. The results suggest a possible protective role for the surface flora in the small bowel.

Clostridium difficile in a pediatric outpatient population.

Clostridium difficile has been implicated as one cause of hospital-acquired diarrhea in children, yet the prevalence of this organism in outpatient children with diarrhea has not been established. Over a 1-year period, 306 outpatient children ranging in age from 2 weeks to 16 years were cultured for C. difficile and potential bacterial pathogens. C. difficile was isolated from 7.0% of patients with diarrhea (12 of 171) and 14.8% of controls with nondiarrheal illnesses (20 of 135). The 32 patients yielding C. difficile were significantly younger than the other study patients. C. difficile was isolated in conjunction with another enteric pathogen in only one case. Antibiotic exposure in the month prior to culture was no different between the 32 positive patients and the overall population. Moreover the patients yielding C. difficile were clinically indistinguishable from the other study patients. C. difficile appears to comprise part of the normal bowel flora in some children beyond the neonatal period and despite a negative history of recent antibiotic usage.

Effects of ampicillin plus sulbactam on bowel flora in patients undergoing colorectal surgery.

The influence of a combination of ampicillin and a beta-lactamase inhibitor, sulbactam, on colonic bacterial flora was studied in patients undergoing colorectal surgery. Drug concentrations were determined in serum, intestinal mucosa, and feces. The results of the drug concentrations were correlated with changes in the numbers of aerobic and anaerobic bacterial bowel flora. Ampicillin and sulbactam were given intravenously to 21 patients in 500-mg doses of each drug every 8 h for 2 days. The first dose was given when anesthesia was begun. The concentrations of ampicillin in serum were significantly higher (0.01 greater than P greater than 0.001) than those of sulbactam. In contrast, at all time intervals, the concentrations of sulbactam in intestinal mucosa were significantly higher than those of ampicillin (0.05 greater than P greater than 0.01). The serum half-life of the two drugs was the same at 2.2 h. After one dose of the antibiotics, sulbactam was detectable in the feces of four patients, and ampicillin was detectable in the feces of 11 patients. During the 2 days of ampicillin and sulbactam prophylaxis, no measurable decrease occurred in the anaerobic flora of the bowel; a mean decrease of 3 logs occurred in the anaerobic bowel flora. The results of this study show that ampicillin and sulbactam prophylaxis had a greater effect on the anaerobic bowel flora than on the aerobic bowel flora. In light of the in vitro spectrum of ampicillin and sulbactam activity, it was surprising that bowel aerobic flora was unchanged.

Spontaneous bacterial peritonitis in alcoholic cirrhosis with ascites

Aerobic enteric organisms, especially Escherichia coli, are the most common cause of spontaneous bacterial peritonitis in alcoholic cirrhosis with ascites, despite the preponderance of anaerobic bacteria in the bowel flora. The major routes of infection are transmural migration of gastrointestinal flora, lymphatic spread, and hematogenous seeding. Most patients present with fever and chills, abdominal pain, leukocytosis, and hypotension, although some may be asymptomatic. Differentiation from secondary peritonitis, which is essential in determining appropriate therapy, is difficult. Microbiologic studies of the ascitic fluid can provide valuable clues in this regard. Although most patients respond favorably to antibiotic therapy, mortality is high because of complications of the underlying disorder.

Isolation of Clostridium difficile from patients with inactive Crohn's disease

Based upon studies of patients with inflammatory bowel disease, Clostridium difficile and an associated cytotoxin have been proposed as contributory factors in relapse of disease. These studies have not included a comprehensive search for other bacterial pathogens. Fifty patients with Crohn's disease were investigated to determine if selected enteric pathogens colonize the bowel and if they play a role in the activity of the disease. Clostridium difficile was recovered from 8% of patients, all with inactive disease, and recovery of the organism did not presage relapse. Except for Salmonella species in one asymptomatic patient, no other bacterial pathogens were isolated. It was concluded that Clostridium difficile may be part of the bowel flora of patients with Crohn's disease without relationship to activity of disease.

Trimethoprim-sulfamethoxazole and trimethoprim alone in the prophylaxis of childhood urinary tract infection.

In 1975 trimethoprim-sulfamethoxazole (TMP-SMZ) was found effective in the prophylaxis of childhood urinary tract infection. The rate of recurrence in 130 children who received prophylaxis was only 0.05 infections per year. No fecal coliforms were found in 70% of rectal swabs, and only 10% of the isolates of coliform organisms were resistant to TMP. During effective, low-dose urinary prophylaxis with TMP-SMZ in 130 children for periods of two to 10 years, no effects of the drug on hematologic or renal function were observed, and somatic growth was normal. However, the frequency of resistance to TMP among fecal coliforms increased from less than 10% in 1970-1975 to 34% in 1980. This increase was not related to the duration of prophylaxis and appeared to represent a secular increase in TMP resistance among coliforms. TMP alone also was effective in urinary prophylaxis; only three of 39 children experienced a recurrence of urinary tract infection during a total of 309 months of prophylaxis in 1978-1980. The effect of TMP prophylaxis on the bowel flora was similar to that of TMP-SMZ prophylaxis. Resistance to TMP was found in 16% of isolates from rectal swabs from children receiving TMP alone.

Intravenous metronidazole for treatment of infections involving anaerobic bacteria.

Intravenous metronidazole was administered, either by continuous or intermittent infusion, to 20 patients with infections involving anaerobic bacteria; 14 of the 20 patients were changed to oral administration of metronidazole for completion of therapy. Six of eight patients with infections derived from oropharyngeal bacterial flora were cured; the addition of ampicillin was required in one patient, however, because of an incomplete response to metronidazole. Eight of eleven evaluable patients with infections derived from bowel flora were also cured by metronidazole or metronidazole plus an aminoglycoside. Of 93 anaerobic bacteria isolated before therapy, 89 were susceptible to 16 micrograms or less of metronidazole per ml. Mean plasma levels of metronidazole were 27.6 +/- 11.4 micrograms/ml in patients receiving continuous infusions of drug and 19.9 +/- 10.7 micrograms/ml (trough) in patients receiving intermittent infusions. Two patients developed peripheral neuropathy during therapy. Metronidazole is an effective agent for the treatment of anaerobic infections. Because metronidazole is not active against facultative and aerobic bacteria, the addition of a second antimicrobial agent may be required for the treatment of mixed anaerobic-aerobic infections.

Talampicillin in the Treatment and Prophylaxis of Urinary Tract Infection in Children

9 children presenting with an ampicillin-sensitive coliform urinary tract infection were treated with talampicillin using 1 week of full-dose treatment followed by low-dose prophylaxis. The bowel coliforms were ampicillin-resistant at the start in one girl and became resistant in the remaining 8 within 4 months. During a total of 44 months of talampicillin therapy, 6 girls (2 with vesico-ureteric reflux) developed a symptomatic re-infection of the urinary tract, a recurrence rate of 1 per 7.3 months, or 1.6 recurrences per annum. A further 12 girls were given prophylactic talampicillin, 9 after an initial therapeutic course of co-trimoxazole for 1 week and 3 following a period of prophylaxis with low-dose co-trimoxazole. The rectal swab from one girl showed partial ampicillin resistance but 9 of the remaining 11 showed that a predominance of ampicillin-resistance coliforms had emerged in the bowel flora within 4 months. 5 of the 12 also developed a symptomatic ampicillin-resistant urinary infection within 4 months, a recurrence rate of 1 per 7.1 months or 1.7 recurrences per annum. Talampicillin, though very effective in treating urinary infection, is not recommended for the prevention of subsequent recurrence.

The How of Breast Milk and Infection

There are some 500 million cases of diarrhea in infants and children each year in the developing countries. Although many cases can be managed successfully by oral rehydration, these are diseases that should be prevented. There is considerable evidence that breast milk has antibacterial properties, but there is no conclusive evidence that the properties measured are correlated with protection of the infant against infection. Some of the benefit conferred by breast milk could be nutrition, or it could be dependent on the effect of pH and bowel flora. Much diarrheal disease is because of virus infections, and milk contains not only rotavirus antibodies but other antiviral substances as well. The maternal cells in milk may be immunologically active and may possibly produce interferon. It is important to avoid being prematurely confident as to why "breast is best". 1 possibility that needs to be explored is that the infant inhales sufficient milk while feeding to protect its respiratory tract.

Small intestinal bacterial overgrowth syndrome

The patient serving as a focus for our discussion had many symptoms and findings characteristic of the proliferation and overgrowth of a bacterial microflora in the small intestine. This syndrome has been recognized by several descriptive terms: blind-loop syndrome (BLS), small intestinal stasis syndrome, contaminated small bowel syndrome, and stagnant loop syndrome. Each emphasizes that alterations in intestinal structure or function permit the development of an abnormal small bowel flora which is the major pathophysiologic determinant of those clinical features which distinguish the syndrome (l-4). The classic syndrome is characterized by megaloblastic anemia due to vitamin B,, deficiency, and weight loss and diarrhea due to fat malabsorption. There are many causes for the syndrome. With each, there is some disruption or normal processes which prevent small intestinal bacterial overgrowth, such as intestinal motility, mucosal antibacterial defenses, and gastric acidity (5). The syndrome may occur at all ages but is primarily recognized in later life. It also may occur in a less florid manner when associated with or superimposed on other disorders of the gastrointestinal tract.

Vulvovaginitis in Children and Adolescents

Vulvovaginitis is a common problem among both prepubertal and adolescent girls. Since the approach to the examination, the etiology of the vaginal discharge, and the treatment are quite different in the two age groups, this article is divided into two major sections: vaginal discharge in the prepubertal child and vaginal discharge in the adolescent.VAGINAL DISCHARGE IN PREPUBERTAL CHILDThe proximity of the vagina to the anus and the thin uncornified vaginal mucosa make the young child particularly susceptible to vulvovaginal infections with a mixed bacterial flora. Not only is perineal hygiene often inadequate in this age group, especially among overweight girls, but bubblebaths, harsh soaps, close-fitting pants, and nylon tights all contribute to vulvar irritation. Anal scratching associated with pinworm infestations may contaminate the vaginal area with a variety of bowel flora; rarely an adult pinworm may find its way into the vagina. A vaginal discharge may also occur with systemic infections such as measles, scarlet fever and chicken pox. Young girls frequently have redness and irritation for several days; these conditions disappear with the application of a bland ointment and warm baths.Ths history of vulvovaginitis may include complaints of itching, discharge, dysuria, or redness. It is important to elicit the quantity, color, and duration of the discharge, perineal hygiene, use of medication and soaps, symptoms of anal pruritus, and recent infections in the child or the family.

Elemental diets in treatment of acute Crohn's disease.

Twenty-seven patients with 32 acute exacerbations of Crohn's disease were treated for four weeks with an elemental diet. At the end of treatment 29 of the exacerbations had remitted both clinically and biochemically. After six months six patients had relapsed. These findings suggest that the elemental diet is effective in treating acute Crohn's disease, but the reasons are not clear. The diet may be effective because it provides nutritional support, is hypoallergenic, acts as a medical bypass from the affected area, or alters bowel flora. The patient's general wellbeing is improved by the supply of adequate energy and essential foodstuffs in a form easily available without further digestion and given in a safe, simple, non-toxic way.