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Antibiotic-resistant fecal Escherichia coli in healthy children. Induced by the use of antibiotics?

OBJECTIVE: To determine the rate of antibiotic resistance of fecal E. coli from healthy children and to infer if it is acquired environmentally or induced by antibiotic use. MATERIAL AND METHODS: Cross sectional study in children from schools and day care centers in Leon, Mexico. Prior antibiotic use (60 days) was questioned to the parents. A single fecal sample was cultured and an isolated colony suggestive of E. coli was submitted to biochemical identification and testing of disk susceptibility to 12 antibiotics. RESULTS: Four hundred fifty-six isolates were studied from children of 10 institutions, with ages ranging from 3 to 72 months (mean, 42.41). Use of antibiotics was referred in 242 children (53.07%). The antibiotics more commonly used were trimethoprim/sulfa, ampicillin, and penicillin (34, 20.5, and 18%). The highest rate of resistance was found for tetracycline, ampicillin, and trimethoprim/sulfa (64.4, 52.63, and 46.05%). The resistance to ciprofloxacin, amikacin, gentamicin, and ceftriaxone was less than 5%. Resistance to five or more antimicrobials was found in 93 isolates (20.39%); this rate was higher in isolates from children who received antibiotics (59/242, 24.38% vs. 34/214, 15.89%) (p = .025; OR 1.71, IC 95% 1.04-2.81). CONCLUSIONS: The study suggests that saprophyte bacteria acquires resistance through both, use of antibiotics and from the environment. These results support the concept that antimicrobial resistance must be considered as a public health problem

Rational antibiotic use and academic staff.

This study was devised to determine the knowledge, attitude and behaviour of an educated group of people towards antibiotic use and self-medication with antibiotics. Of 1380 members of academic staff (excluding those from the Faculty of Medicine) of Ege University, 602 were chosen by systematic sampling methods. Two groups were formed. Group A included academic staff from the Faculties of Dentistry and Pharmacy and Group B, members of all other faculties. The mean age was 37.4+/-11.0 and 47.0% were females. The mean antibiotic knowledge score was 7.16+/-3.32. Self-medication with antibiotics was admitted by 45.8% of the total samle and 15.6% of the respondents used antibiotics until their symptoms disappeared regardless of the period of prescription. In Group A 48.8% and in Group B 80.7% of the respondents believed that antibiotics could be used for common cold. It is concluded that priority should be given to knowledge-based behaviour education programmes for the more highly educated community; there must also be restriction on the sale of antibiotics without prescription

Antibiotic glycosyltransferases.

In the biosynthesis of several classes of antibiotics, sugars are attached to aglycone scaffolds by antibiotic-specific glycosyltransferases in the latter stages of the pathways. Two glycosylation pathways will be examined: the glycopeptide antibiotics of the vancomycin class and the aminocoumarin antibiotics of the novobiocin class. An oxidatively cross-linked heptapeptide scaffold is sequentially glucosylated and vancosaminylated by GtfE and GtfD, respectively, in vancomycin maturation, while in chloroeremomycin assembly the same heptapeptide is glucosylated by GtfB, then epivancosaminylated at two distinct sites by GtfA and GtfC. The specificity and mechanism of these glycosyltransferases will be discussed. In novobiocin biosynthesis, three enzymes (NovM, NovP and NovN) are thought to act sequentially to transfer an L-noviose moiety to the novobiocic acid aglycone (NovM), followed by 4'-hydroxyl methylation (NovP) and 3'-hydroxyl carbamoylation to produce the mature antibiotic structure, targeting the GyrB subunit of DNA gyrase. Initial characterization of NovM and NovP will be discussed

Influence of intestinal flora on the development of fibrosis and cirrhosis in a rat model.

BACKGROUND AND AIMS: The gut flora play a significant role in the disposition of many foreign substances, as well as producing nutrients and toxins that may be absorbed and reach the liver. This study examines the influence of antibiotic-induced alterations in gut flora on the development of hepatic fibrosis in a rat model. METHODS: Thirty-six male Porton rats were fed alcohol (3.9 g/kg per day) in the drinking water and exposed to carbon tetrachloride (CCl4) vapor (80 p.p.m.) for 6 h each night, five nights per week. Half were also given neomycin (330 mg/kg per day) and polymyxin B (105 mg/kg per day) in the drinking water. Fecal cultures were carried out at 0, 3, 8 and 13 weeks; rats were killed at 14 weeks. Coded liver section were assessed for fibrosis using a graded scale (0, no abnormal fibrosis to 4, early or established cirrhosis). RESULTS: Rats that received antibiotics had significantly higher fibrosis scores than those that did not (mean score 2.4 vs 1.4, P < 0.01, ordinal logistic regression). Three rats, all of which were in the antibiotic group, were cirrhotic. Rats that had received antibiotics fell into three groups. Four had overgrowth of Proteus mirabilis; in these the fibrosis scores (mean 1.5) were similar to those in the rats that did not receive antibiotic. In six, no organisms could be cultured; fibrosis scores of these (mean 2.3) were slightly elevated (P = 0.03), but this was mainly because of a single rat in this subgroup being cirrhotic. The remaining eight had overgrowth of Morganella morganii; these had significantly (P < 0.001) elevated fibrosis scores. Furthermore, in this subgroup, fibrosis scores were significantly correlated (Spearman's r = 0.82, P = 0.01) with the number of weeks of Morganella colonization. CONCLUSIONS: Antibiotic treatment exacerbated fibrosis in the alcohol/CCl4 rat model; this effect appeared to be related to the type of gut flora and may be endotoxin-mediated

Pharmacokinetics and pharmacodynamics of oral beta-lactam antibiotics as a two-dimensional approach to their efficacy.

Pharmacokinetic and pharmacodynamic parameters are increasingly recognized as important determinants of the therapeutic efficacy of an antibiotic. For beta-lactam antibiotics, the most important determinant of the antimicrobial efficacy, and hence predictor of therapeutic efficacy, is the length of time that serum concentrations exceed the MIC. Dosing schedules for beta-lactam antibiotics should maintain serum concentrations above the MIC for the bacterial pathogen for at least 50% of the dosing interval to achieve therapeutic efficacy and prevent the development of resistance. This is a basic criterion for the clinical efficacy of beta-lactams. A combination of microbiological activity and pharmacokinetic characteristics was applied to calculate the time that serum antibiotic concentrations exceed the MIC for the major respiratory tract pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Klebsiella pneumoniae. In contrast with some other oral beta-lactam antibiotics, cefpodoxime 200 mg bd maintains serum concentrations above the MIC for each organism for at least 50% of the dosing interval and may therefore be an attractive choice for empirical therapy of community-acquired lower respiratory tract infections

Optimizing antibiotic therapy-the Aberdeen experience.

OBJECTIVE: To study the quality and continuity of treatment in the Acute Medicines Assessment Unit (AMAU) with regard to empirical prescription of antibiotics, mode of administration, adherence to ward antibiotic policy, as well as collection, awareness and utilization of microbiological investigations. METHODS: A prospective study over a 3-month period at the AMAU, Aberdeen Royal Infirmary (ARI), a teaching hospital in north-eastern Scotland, was performed. The study included all patients started on empirical antibiotics on admission to the AMAU and followed up until their discharge. RESULTS: Of 1303 patients admitted, 221 (17%) were started on empirical antibiotics. This was in accordance with hospital antibiotic policy in 52% of cases. Appropriate specimens were taken from 77% of patients. Culture results showed that 29% (n = 65) of the patients had clinically significant growth of organisms. Of the 65 patients with clinically significant culture results, 49% (n = 32) were on an inappropriate empirical regimen. In 55%, the medication was not changed to a more appropriate antibiotic. In 72% of the patients with a negative culture, the culture report had no obvious effect on the duration or type of antibiotic being administered. Intravenous antibiotics were used in 60% of patients. CONCLUSION: This study demonstrates a significant overuse of antibiotics, especially intravenous forms, despite a paucity of positive sepsis parameters and chest X-ray findings in these patients The duration of treatment could be shortened and an early switch policy introduced if culture results and sepsis profiles were taken into consideration, as there was a large number of unproven infections. Suggestions are made about how these improvements in prescribing could be made within the current administrative set-up of AMAUs

STRAMA questionnaire on general practitioners' knowledge concerning antibiotics and resistance. Lack of time impedes exchange of information

The Uppsala county regional group of the Swedish Strategic Programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance (STRAMA) sent a questionnaire to all the general practitioners in the county concerning their knowledge of antibiotics and bacterial resistance. The questionnaire also asked which sources were used for information on these topics, and inquired as to their views concerning the services provided by the local clinical microbiological laboratory. A third part of the questionnaire contained descriptions of three patients with infectious diseases, and each general practitioner was asked to indicate appropriate diagnostic tests and/or antibiotic treatment. The questionnaire was completed by 70% (100/145). The general awareness of which antibiotics to use for empirical treatment of urinary tract infection was good. Awareness of antibiotic resistance in S. pyogenes, H. influenzae, S. pneumoniae and MRSA was moderately good (59-80%). About 60% thought it was difficult to find information concerning resistance and use of antibiotics. Lack of time was the main reason for not being able to seek such information actively. The regional STRAMA-group believes that this kind of survey followed by reporting back of results with informative comments on the topics concerned is a useful model for education.

Behavior of pythium Torulosum zoospores during their interaction with tobacco roots and Bacillus cereus.

Bacillus cereus UW85 suppresses seedling damping-off diseases caused by Oomycetes and produces antibiotics that inhibit development of Oomycetes in culture. The goal of this study was to determine how UW85 and its antibiotics affected the behavior of an Oomycete, Pythium torulosum, in its interaction with plant roots. We studied tobacco seedlings inoculated with zoospores of P. torulosum and UW85 culture, culture filtrate, washed cells, antibiotics (zwittermicin A or kanosamine), purified from cultures of UW85, and UW030, a mutant of UW85 that does not suppress disease and does not produce the antibiotics. Microscopic observation revealed that all of the treatments inhibited zoospore activity around roots and encystment on roots. Treatment with UW85 culture, culture filtrate, zwittermicin A, or kanosamine delayed cyst germination and the elongation rate of germ tubes, whereas treatment with UW030 or washed UW85 cells did not. In an in vitro seedling bioassay of disease suppression, the antibiotics, zwittermicin A and kanosamine, suppressed disease singly or together, although UW85 culture suppressed disease more effectively than did the antibiotics. The results show that B. cereus cultures affect zoospore behavior in the presence of roots, and B. cereus-produced antibiotics, zwittermicin A and kanosamine, contribute to disease suppression and inhibition of germ tube elongation in the presence of the plant root

Microbiological aspects and antibiotic therapy of diabetic foot infections

q IMMUNOLOGICAL AND MICROBIOLOGICAL ASPECTS OF DIABETIC FOOT INFECTIONS: Diabetic patients are at increased risk of severe skin and bone infections. Immunological disturbances are reasonable and due to altered specific and unspecific cellular immune responses. Analysis of epidemiology and microbial pathogenicity shows that staphylococci seem to be predestined to induce such infections. Staphylococcus aureus and coagulase-negative staphylococci are able to adhere to the wound ground by a sequela of mechanisms. Initial bacterial adherence is due to hydrophobicity, ion exchanges, and specific binding of bacterial adhesion molecules to cellular receptors. Moreover, staphylococci secrete polysaccharides which form a biofilm together with multilayer cell clusters. The highly structured communities within a biofilm are resistant to distinct immunoeffectors and have a decreased susceptibiliy to antibiotics in vivo.q ASPECTS OF ANTIBIOTIC THERAPY: Assessing the severity of an infection is essential to selecting an antibiotic regimen, the mode of drug administration, and the duration of therapy. Regimens for severe and chronic infections are broader spectrum and often intravenously to obtain high drug concentrations immediately. Infections of the bone often require an antibiotic therapy for > 4 weeks, while a 1- to 2-week therapy for mild to moderate infections has been found to be effective.q CONCLUSIONS: Because of the tremendous progress in diagnostics and therapy of diabetic foot infections, infectious complications can be successfully treated by appropriate wound care, metabolic control, and early surgical and antibiotic intervention. Bacterial biofilms involved into chronic infections are new aspects currently not visualized by clinical therapy. Besides the classic antimicrobial therapy, new concepts of an enzymatic therapy or the inhibition of bacterial "communication" (quorum sensing) are in progress and the hope for the future.

Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease?

BACKGROUND: One of the mechanisms evoked to explain the increasing prevalences of asthma and allergy, in particular among children, is the 'Western lifestyle' or 'hygiene' hypothesis. As early childhood infections are assumed to hold a protective effect on the development of asthma and allergies, the use of antibiotics at that sensitive age may lead to an increased risk of asthma and allergy. OBJECTIVE: The aim of this study is to investigate the association between the use of antibiotics in the first year of life and the subsequent development of asthma and allergic disorders. METHODS: In a population-based sample of 7-and-8-year-old children questionnaire and skin prick test data were collected from 1206 and 675 subjects, respectively. Prevalence rates of asthma, allergic disorders and skin test positivity were compared between children with and without early life use of antibiotics, taking into account other possible risk factors including early respiratory infections. The effect of genetic predisposition was investigated by stratified analyses of children with and without parental hay fever. RESULTS: The use of antibiotics during the first year of life was significantly associated with asthma (OR = 1.7, 95% CI 1.0-3.1), hay fever (OR = 2.3, 95% CI 1.3-3.8) and eczema (OR = 1.3, 95% CI 1.0-1.8). No significant relationship was found with skin test positivity (OR = 1.1, 95% CI 0.7-1.7). After stratification for the presence of parental hay fever, children without parental hay fever did not show any significant associations between antibiotics use and asthma or allergy, whereas in children with parental hay fever the use of antibiotics was significantly related with asthma (OR = 2.3, 95% CI 1.1-5.1), hay fever (OR = 2.8, 95% CI 1.5-5.1) and eczema (OR = 1.6, 95% CI 1.0-2.6), and of borderline statistical significance with skin test positivity (OR = 1.6, 95% CI 0.9-3.0). CONCLUSION: Early childhood use of antibiotics is associated with an increased risk of developing asthma and allergic disorders in children who are predisposed to atopic immune responses. These findings support recent immunological understanding of the maturation of the immune system