Aerobic Faecal Flora Research Articles

Bacteriological and clinical evaluations of imipenem/cilastatin sodium in neonates and premature infants

The antimicrobial activity of imipenem against group B streptococci was investigated. The clinical efficacy of imipenem/cilastatin sodium (IPM/CS) was determined in neonates and premature infants. The results are summarized below. 1. The distribution of MIC values of IPM against 55 clinical isolates of group B streptococci isolated from the vagina of pregnant women peaked at 0.024 micrograms/ml. MIC values of IPM against all clinical isolates tested were 0.05 microgram/ml or less. 2. IPM/CS was used for treatment of bacterial infections in 9 neonates and premature infants. Among these patients, clinical responses were excellent in 5 patients and good in 4 patients. No adverse reaction was observed. Abnormal laboratory test values were observed in 4 patients, eosinophilia in 2 patients and increased platelets in 2. 3. In 7 neonates and premature infants, quantitative cultures for aerobic and anaerobic fecal flora were performed. Fecal flora change was not significantly different than those observed during treatment with latamoxef or cefmenoxime. 4. Ten neonates and premature infants were investigated for effects of IPM/CS on the blood coagulation system. Prolongations of prothrombin time (PT) and activated partial thromboplastin time (APTT) were observed in 1 patient. Abnormal prothrombin (PIVKA II) was detected in the same patient. There was no tendency for inhibition of platelet function.

Changes in the aerobic faecal flora of patients treated with antibiotics for acute intra-abdominal infection

An open observational study was performed to investigate changes in the rectal flora and antibiotic susceptibility among faecal bacteria in patients treated with antibiotics for acute intra-abdominal infection. One hundred and forty patients with acute intra-abdominal infection requiring antibiotic treatment and hospitalization were included. Eight surgical units from the southern part of Sweden participated, between January 2006 and November 2007. Antibiotic treatments were according to local guidelines. Rectal swabs were obtained on admission (sample 1) and 2-14 days after the end of antibiotic treatment (sample 2). Aerobic bacteria and yeasts were analysed. The material was divided into 2 groups: 1 group with Enterobacteriaceae and 1 group with non-fermentative Gram-negative bacteria. The susceptibility to antibiotics in each group was compared between samples 1 and 2. The main finding of this study on patients with severe intra-abdominal infections was a shift in the aerobic faecal flora following antibiotic treatment, from Escherichia coli to other more resistant Enterobacteriaceae, Enterococcus faecium, and yeasts. The susceptibility to cephalosporins and piperacillin-tazobactam decreased in Enterobacteriaceae. Following antibiotic treatment, a shift in the aerobic rectal flora to species with intrinsic antibiotic resistance was observed. This indicates that the emergence of resistance is not due to new mutations, but rather to selection of more resistant species. This should be taken into account when designing treatments for secondary intra-abdominal infections.

Rifaximin—a novel antimicrobial for enteric infections

Rifaximin is a poorly absorbed rifamycin antimicrobial drug with in vitro activity against Gram-positive, Gram-negative and anaerobic bacteria. The minimal concentration that inhibits 90% of strains of bacterial pathogens (MIC 90) ranges between 32 and 64 μg/ml. Less than 1% of the drug is absorbed after oral administration. After three days of therapy, the average fecal level of this drug is 8000 μg/g of stool. Selection of resistant mutants, a problem with the related rifampin, appears to be unusual with rifaximin. Rifaximin shortens the duration of travelers' diarrhea and non-dysenteric diarrheal illness due to enterotoxigenic, enteroaggregative E. coli and Shigella sonnei without major alteration of aerobic fecal flora and without important side effects. The drug has been successfully used in preliminary studies of small bowel bacterial overgrowth syndrome and hepatic encephalopathy. To explain the beneficial effect of the drug on bacterial diarrhea without change in colonic flora or high rates of pathogen eradication, rifaximin may be more active against pathogens in the small bowel rather than the colon and/or the drug may alter the virulence of enteric pathogens in addition to organism inhibition.

Enumeration of aerobic faecal flora in healthy and diseased individuals

Studies on aerobic bacterial flora of faecal samples from healthy and diarrhoeal patients of different age groups were carried out. Giardia cysts were observed in the faecal sample of both the diarrhoeal patients. Organisms were cultivated on non-specific as well as specific enrichment media. Based on morphological, physiological and biochemical characteristics, organisms were identified to genus level. Irrespective of the age, a sharp decrease in the population of Lactobacilli, Proteus, Aeromonas, Yersinia, Micrococci and Escherichia coli with concomitant increase in the population of Klebsiella were observed in the diseased individuals when compared with the healthy ones. Significant differences were observed in the population of spore-forming Bacillus and Staphylococcus when both the diseased individuals were compared. Absence of Enterococcus and Providencia both in the child and adult diseased individuals were quite significant. Association of Candida, Pseudomonas and other aerobic spore formers only with the adult individuals confirmed some of the earlier observations. The presence of Gram-positive Diplococci and unidentified Gram-negative cocci in the healthy child were quite significant. It was therefore, evident that the alteration of resident flora was associated with the disease.

Role of endogenous and exogenous nitric oxide on intestinal mucosa and microflora in the rat.

In the present study the effects of exogenous and endogenous nitric oxide (NO) on intestinal bacteria and on the intestinal tissue integrity have been investigated in healthy rats and in rats receiving bacterial endotoxin (LPS). A segment of jejunum was taken in order to evaluate tissue damage and hematoxylin-eosin staining; microbiological studies were carried out collecting stool samples. Administration of LPS (5 mg kg-1 i.v.) induced a moderate jejunal damage, which was completely prevented by NG-nitro-L-arginine methyl ester (L-NAME), 5 mg kg-1 s.c.), thus suggesting a damage of endogenous NO on the intestinal mucosa; sodium nitroprusside (SNP, 10 mg kg-1 os) reduced significantly jejunal damage induced by LPS. Endogenous NO produced by the administration of LPS resulted to be cytotoxic for all examined aerobic and anaerobic bacteria, while exogenous NO, released from SNP, showed an inhibitory effect only on Entero. faecalis and E. coli growth. From our data, it seems reasonable to conclude that high local levels of NO are required in order to observe jejunal damage and cytotoxic effects on aerobic and anaerobic faecal flora.

Beta-lactam resistance in aerobic faecal flora from general practice patients in the UK

One hundred faecal specimens submitted to a diagnostic laboratory in Edinburgh and found to be negative for gastrointestinal pathogens were examined for the presence of antibiotic-resistant bacteria. The results were compared with findings in the healthy population in the same area. The highest incidence of resistance was observed to cefuroxime (65%) and ampicillin (60%). Of the ampicillin-resistant isolates, 62% could transfer their resistance determinants to a standard Escherichia coli host strain. In 100% of these transconjugants ampicillin resistance was shown to result from the presence of the TEM-1 beta-lactamase which was identified in a heterogeneity of plasmid profiles. These plasmids commonly mediated resistance to streptomycin and tetracycline in addition to ampicillin.

Effects of Imipenem, Cefotaxime and Cotrimoxazole on Aerobic Microbial Colonization of the Digestive Tract

Superinfections originating from a digestive tract colonized by abnormally high concentrations of aerobic microorganisms as a result of impaired resistance to colonization (CR) may complicate antibiotic therapy. In this study, patients with a moderate to severe systemic infection were randomized to receive either cefotaxime (CTX, n = 10) or cotrimoxazole (CTR, n = 10), 2 antibiotic regimens presumed to spare CR; or imipenem/cilastine (I/C, n = 19). The effect on CR was measured indirectly by comparing the aerobic faecal flora before antibiotic treatment with that on day 8 of treatment. An increase in aerobic faecal flora denotes a disturbed CR, whereas a decrease means that the organism is sensitive to the effective faecal concentration of the antibiotic. Imipenem/cilastine-treated patients showed a significant increase in enterococci and Candida spp., while the number of aerobic Gram-negative rods remained constant. Cefotaxime-treated patients had evidence of an increase in enterococci, but not of Candida spp., and Escherichia coli numbers decreased significantly. In these patients the concentration of other Gram-negative aerobic rods showed a slight increase in 6 patients with a resistant Pseudomonas strain. Cotrimoxazole-treated patients showed a significant decrease in aerobic Gram-negative rods, a significant increase in Candida spp. and no change in enterococci. It is concluded that all 3 antimicrobial agents impair colonization resistance. Whether or not this is followed by overgrowth with resistant micro-organisms depends on the active faecal concentration of the antimicrobial agent and the MIC of the aerobic micro-organisms. The risk of overgrowth of the bowel with resistant Gram-negative bacilli appears to be smaller following cotrimoxazole than following cefotaxime or imipenem/cilastine.

Effect of ampicillin versus cefuroxime on the emergence of β-lactam resistance in faecal Enterobacter cloacae isolates from neonates

Enterobacter cloacae strains dominated the aerobic faecal flora of 8.3% of 953 infants discharged from 32 Swedish neonatal intensive care units and the susceptibility of these strains to seven beta-lactam antibiotics was determined. Isolates from infants treated with cefuroxime showed slightly increased MICs only to ampicillin, cephalexin and cephalothin as compared to isolates from untreated infants matched for ward and time of sampling (P = 0.02). In contrast, E. cloacae isolates from ampicillin treated infants showed markedly elevated MICs of all agents tested including piperacillin, cefuroxime, cefotaxime and ceftazidime as compared to those from control neonates (P values between 0.001 for ampicillin and 0.017 for cefotaxime). Thus, E. cloacae with cefotaxime MICs as high as 512 mg/L were isolated only after ampicillin therapy. The resistant strains were negative in a colony DNA hybridization assay using gene probes for the plasmid beta-lactamases TEM-1, OXA-1 and SHV-1. The resistant strains also showed only one beta-lactamase band when crude cell sonicates were analysed by isoelectric focusing, and were not found in other infants in the same ward. The results indicate that the selection of chromosomal E. cloacae mutants, presumably with stably derepressed beta-lactamase production, in the faecal flora of neonates is rare during treatment with cefuroxime and more common during ampicillin therapy.

Comparison of the effects of cefuroxime axetil and cefaclor on the fecal flora in pediatric patients

An open, randomized clinical trial was performed to evaluate the effects of cefuroxime axetil, compared with those of cefaclor, on the fecal flora of children with acute infectious diseases. Thirty-two children were randomized to receive either cefuroxime axetil or cefaclor. Fecal samples were collected 24 hours before treatment, 3 and 6 to 7 days after the start of treatment, and 7 days after the completion of treatment. Cefuroxime axetil induced few changes in aerobic fecal flora, causing only a slight increase in Aerococcus viridans and a slight decrease in Enterobacter cloacae ( P < 0.05), and no changes in anaerobic flora. Cefaclor induced more marked changes in bacterial flora; it decreased the aerobes lactobacilli ( P < 0.05) and Escherichia coli ( P < 0.001) and increased Citrobacter freundii ( P < 0.001) and Proteus mirabilis ( P < 0.01), while its effects on anaerobic microorganisms produced a reduction in Fusobacterium varium and Bacteroides ureolyticus ( P < 0.05). Clostridium difficile, absent during cefuroxime treatment, was observed in three children during or soon after cefaclor therapy. We conclude that cefuroxime axetil does not induce any clinically significant changes in the intestinal microflora.

The incidence of antibiotic resistance in aerobic faecal flora in Sooth India

During a field study in South India in 1989, faecal specimens were collected from residents in villages and the town of Vellore in South India. Examination of the faecal specimens revealed that virtually the whole population carried commensal bacteria resistant to trimethoprim, ampicillin and chloramphenicol. Most specimens contained more than one type of bacterium resistant to each antibiotic. There was less resistance to nalidixic acid, with a higher proportion in the town (33%) than in the villages (13%). Although there was little cross-resistance of the ampicillin-resistant strains to later generation cephalosporins, 50% were resistant to the combination of amoxycillin and clavulanic acid. There was no significant cross-resistance of the nalidixic acid-resistant strains to fluorinated 4-quinolones, despite the free availability of ciprofloxacin and norfloxacin in the area. The probable reason for the high incidence of resistance to first generation antimicrobials is the extensive use of these agents, coupled with continuous exposure to large numbers of faecal micro-organisms.

EMERGENCE OF HIGHLY TRIMETHOPRIM-SULFAMETHOXAZOLERESISTANT SHIGELLA IN A NATIVE AMERICAN POPULATION: AN EPIDEMIOLOGIC STUDY

Resistance to trimethoprim-sulfamethoxazole (TMP-SMX) emerged among Shigella isolates from the Navajo Reservation in the southwestern United States in 1985, years after this antimicrobial agent came into common use. In the study area, TMP-SMX resistance increased dramatically from 3 per cent in 1983 to 21 per cent in 1985. Resistance was polyclonal and occurred in both S. sonnei and S. flexneri. No single plasmid was common to all resistant strains. However, all 28 TMP-SMX resistant isolates examined were resistant to ampicillin and streptomycin and had minimum inhibitory concentrations to sulfamethoxazole of greater than or equal to 4,096 micrograms/ml and to trimethoprim of greater than or equal to 1,024 micrograms/ml. The authors found that 28 of 101 Navajo children with gastrointestinal symptoms who were not taking antimicrobials had TMP-SMX-resistant aerobic fecal flora. To determine risk factors for acquiring resistant strains, they compared 40 case-patients with TMP-SMX-resistant Shigella to 66 controls with TMP-SMX-sensitive Shigella. Case-patients were more likely than controls to have used antimicrobials recently (p = 0.004) and to be hospitalized for shigellosis (p = 0.05). These findings suggest that polyclonal highly TMP-SMX-resistant Shigella emerged by transfer of trimethoprim resistance genes from aerobic bowel flora to endemic Shigella strains, that use of antimicrobials can lead to symptomatic shigellosis and thus the persistence of trimethoprim-resistant Shigella, and that appropriate therapy of shigellosis on the reservation is now a major challenge.

Influence of age on faecal carriage of P-fimbriated Escherichia coli and other gram-negative bacteria in hospitalized neonates.

The aerobic faecal flora of 953 infants aged over 5 days was studied on discharge from 22 neonatal wards in Swedish hospitals. Klebsiella/enterobacter was isolated from 74% of infants and dominated the aerobic gram-negative flora in 19 wards. Escherichia coli was carried by 42% and showed a slight dominance in two wards. Initially klebsiella/enterobacter dominated the flora but became increasingly mixed with and taken over by E. coli, carriage increasing from 21% in infants discharged after 5-7 days to 57% after 3 weeks or later. Among infants with E. coli, P-fimbriated strains were demonstrated in 23% (range 0-67) and were independent of age. Occasional clustering of such strains was observed in 3/22 wards during the study period. It is postulated that the general and local colonization patterns observed reflect differences between individual strains of E. coli and klebsiella in both their capacity for transmission and their persistence in the newborn gut. The role of P-fimbriae in intestinal colonization of neonates by E. coli was, however, not supported.

Influence of antibiotic therapy on faecal carriage of P-fimbriated Escherichia coli and other gram-negative bacteria in neonates.

The influence of previous antibiotic therapy on the aerobic faecal flora, including P-fimbriated Escherichia coli, was studied in 953 neonates at discharge from 22 neonatal wards in Sweden. Antibiotics, mainly ampicillin (with or without gentamicin) or cefuroxime, had been received by 37% of the infants. Treatment with ampicillin (with or without gentamicin) increased Klebsiella/Enterobacter and reduced Esch. coli colonization. Cephalosporin therapy (71% cefuroxime) reduced the frequency of colonization with both Esch. coli and Klebsiella/Enterobacter spp. but doubled the isolation rate of other Gram-negative bacteria (Citrobacter, Pseudomonas, Proteus and Acinetobacter spp.) and tripled the incidence of specimens yielding no aerobic Gram-negative growth. Gentamicin showed no significant ecological impact. The selection of Klebsiella/Enterobacter and P-negative Esch. coli strains by ampicillin was correlated with their resistance to this agent, while the association between P-fimbriated Esch. coli and cefuroxime therapy was not related to cefuroxime resistance.

The effect of selective decontamination of the digestive tract with the addition of systemic cefotaxime on the aerobic faecal flora of mice.

The administration per-orally to mice of the non-absorbable antibiotics polymyxin E, tobramycin and amphotericin B resulted in the elimination of detectable aerobic gram-negative rods from the faecal flora without affecting the total viable aerobic count. The addition of parental cefotaxime to the regime caused a fall in the number of aerobic lactobacilli and an increase in the number of enterococci. The rise was associated with the translocation of viable enterococci to the mesenteric lymph nodes and the spleen. The changes induced by cefotaxime were reversed when the antibiotic was withdrawn. Following withdrawal of all antibiotics the total aerobic faecal flora increased to above normal levels, but there was no associated diarrhoea. Attempts to implant exogenous enterobacteria into the digestive tract resulted in only low level colonization both in treated mice and in control mice. These results may have implications for the use of this antibiotic regime for selective decontamination of the digestive tract in humans, particularly those who are immunocompromised.

Epidemiological aspects of fecal colonization with P-fimbriated Escherichia coli in neonates

Fecal colonization with P-fimbriated Escherichia coli has caused epidemic outbreaks of extraintestinal E. coli infections in the neonatal unit of Danderyd Hospital. The aerobic fecal flora was therefore studied in 1,955 newborn children born at Danderyd Hospital during a period of 2.5 years. E. coli was found in 58% of the maternity ward children and in 57% of the neonatal unit children. A P-fimbriated strain was found in 12% and 17% of the children, respectively (p less than 0.01). There was a significant increase in the frequency of children colonized with E. coli, and especially P-fimbriated E. coli, with length of stay in the neonatal unit. There was a statistical correlation between bed occupancy and colonization with P-fimbriated E. coli (r = 0.46, p less than 0.01) during this study period. We found an incidence of P-fimbriated E. coli of 10 to 20% among the E. coli strains isolated from the fecal specimens which we regard as the baseline incidence.

The effect of imipenem/cilastatin on the aerobic faecal flora of children.

In 18 children treated with imipenem iv, quantitative cultures for aerobic faecal flora were performed on selective media (before, when possible, during and after treatment). In ten children who had not received previous antibiotic therapy, susceptible enterobacteria could be detected at a normal level throughout treatment. Eight children had received other antibiotics beforehand; during the first week of imipenem therapy, enterobacteria were undetectable in two and at low levels in three patients. In one patient previously treated with aztreonam, a strain of Pseudomonas aeruginosa became resistant to imipenem and increased in numbers. No dramatic change could be detected in group D streptococci, staphylococci or candida. The surprisingly small effect of imipenem on faecal Enterobacteriaceae could be explained by its inconstant presence in stools at the dose administered.

Efficacy of bicozamycin in preventing traveler's diarrhea

Bicozamycin was compared with a placebo in a prospective, randomized, double-blind study of the prevention of acute diarrhea among 30 American travelers newly arrived in Guadalajara, Mexico. None of the 11 subjects given bicozamycin orally for 3 wk at a dosage of 500 mg four times a day developed diarrhea as compared with an incidence of 53% diarrhea (10 of 19 subjects) in the placebo group (p = 0.003). Bicozamycin was well tolerated. Studies of changes in predominant aerobic fecal flora among the 11 subjects treated with bicozamycin showed the appearance of only one highly resistant Citrobacter freundii at the end of 1 wk of therapy and only a total of six resistant isolates at the end of 3 wk. All resistant isolates failed to transfer this resistance to a recipient Escherichia coli. Bicozamycin seems to be well suited and safe as a prophylactic agent against traveler's diarrhea.

The influence of third-generation cephalosporins on the aerobic intestinal flora.

The influence of three third-generation cephalosporins with varying degrees of biliary excretion on the aerobic flora was investigated. The faecal flora prior to therapy with one of these substances consisted mainly of anaerobic bacilli. Escherichia coli was present in concentrations of 10(9) organisms/g stool. Candida albicans and enterococci were observed in concentrations of 10(5) - 10(6) organisms/g stool. Within 24 hours after the administration of ceftriaxone and cefoperazone, the gram-negative aerobic flora was completely eradicated. C. albicans and enterococci increased to 10(9) organisms/g stool. Between the third and tenth days (mean 6.7 days) of therapy Pseudomonas aeruginosa, Enterobacter and Citrobacter in this order of frequency reappeared in the faecal flora with complete resistance to all betalactam antibiotics. C. albicans and enterococci decreased to 10(7) organisms/g stool. The anaerobic flora was largely unaltered. In contrast, cefotaxime had only a moderate influence on the aerobic faecal flora. Concentrations of gram-negative organisms decreased to 5 X 10(7) organisms/g stool during the first five days of therapy; the concomitant increase in C. albicans and enterococci was approximately 1 log 10. No alterations in the susceptibility pattern were observed. We would like to emphasize that substantial alterations of the faecal flora and the susceptibility pattern of antibiotics may accompany the use of antimicrobial agents, particularly those with a high degree of biliary elimination.

Influence of third-generation cephalosporins on aerobic intestinal flora.

Excretion of an antibiotic in bile may result in high intra-intestinal concentrations and thus alteration in the faecal flora. We investigated the effects of cefoperazone (75% biliary excretion), ceftriaxone (45%) and cefotaxime (5%) on the aerobic faecal flora. Cefoperazone reduced numbers of normal Gram-negative bacilli and selected resistant Pseudomonas, Serratia and Klebsiella-Enterobacter. Ceftriaxone was similar. However, cefotaxime had little effect on the normal Gram-negative flora, and did not promote the emergence of resistant organisms.

Rotavirus and hemolytic enteropathogenic Escherichia coli in weanling diarrhea of pigs.

Since the turn of the century, Escherichia coli has been implicated in the etiology of weanling diarrhea (colibacillosis). However, rotavirus--a virus that destroys enterocytes--has been shown recently to be causally associated with weanling diarrhea of pigs. The role of both rotavirus and hemolytic enteropathogenic E. coli in weanling diarrhea was assessed in this study. Pigs from a closed herd were farrowed and weaned by two markedly different systems: an "intensive care sanitary" system and a "conventional unsanitary" system. Pigs weaned at 3 weeks of age in the sanitary system usually experienced a rotaviral diarrhea about 16 days postweaning. No hemolytic E. coli were detected in feces from these pigs. Peers weaned at the same time by the unsanitary system commenced diarrhea 3 days postweaning. Rotavirus and nonhemolytic E. coli were detected in the feces at the onset of diarrhea and for a few days thereafter. Then, the aerobic fecal flora shifted to nearly pure hemolytic enteropathogenic E. coli. About 10 days later, the diarrhea waned, and the fecal flora shifted back to nonhemolytic E. coli. This hemolytic E. coli shedding pattern could not be duplicated in artificially inoculated sanitary pigs unless they were inoculated with the hemolytic E. coli during a rotaviral-associated diarrhea. Otherwise, the shedding of hemolytic E. coli was fleeting, and the diarrhea, if present, was mild. Pigs developed humoral antibodies to the rotavirus but not to the hemolytic E. coli. We conclude that rotavirus damages the epithelium of the small intestines, which changes the luminal environment to one that favors colonization by enteropathogenic E. coli.