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Immediately after their introduction in the beginning of the fourties of the previous century, the agents used to combat infectious diseases caused by bacteria were regarded with suspicion, but not long thereafter antibiotics had the status of miracle drugs. For decades mankind has lived under the impression that infectious diseases were no longer a threat to human health. This optimism was so high at a certain moment that antibiotics were also used against viral infections, whereas viruses are not even sensitive to antibiotics. This wrong use, or if one likes, misuse of antibiotics took also place in animal husbandry, where many tons of antibiotics were added to the feed of healthy animals, just because they grew so nicely from these additives. However, also in the use of antibiotics an ancient law in physics, "action equals reaction" turned out to be applicable. Bacteria reacted to the fact that they were attacked by changing their hereditary properties (through mutation) or by taking up parts of the hereditary properties of organisms (bacteria and fungi) able to produce certain antibiotics themselves. As a result of this reaction, already a short while after the introduction of antibiotics, the first bacteria could be isolated that had become insensitive (immune) for particular antibiotics. The bacteria in fact, had even more surprises in store. They turned out to be fanatic collectors of the pieces of hereditary properties that made them immune for antibiotics and like a stamp collector puts his stamps in an album, they also put their collection in an album (an integron). In this way, the best collectors have now become insensitive to more than ten different types of antibiotics. At the moment there are even bacteria that are not sensitive anymore to whatever type of antibiotic and for these bacteria treatment with antimicrobial agents is no longer available. Where, "work together, live together" is the current motto of the Dutch government, "work together to survive together" might be the motto of bacteria. They put this into practice by passing on their album with its integron collection from one bacterial species to the other. In this way a bacterium that used to be sensitive and could very well be treated with antibiotics can in one stroke become resistant to sometimes thirteen different antimicrobial agents, resulting in the fact that an infection with such a bacterium becomes untreatable. In this thesis research with respect to the sensitivity of the bacterium Salmonella, which can cause intestinal infections in human and animals, for antimicrobial agents is described. Since the (wrong) use of antibiotics can influence the development of resistance to antibiotics, in these studies a comparison has been made between Salmonella bacteria isolated from human, pigs, cattle and poultry in Vietnam and The Netherlands. Whereas in The Netherlands antibiotics are only available on prescription by a physician or veterinarian, antibiotics can be purchased over the counter in Vietnam. This leads to a significantly different attitude in both countries with respect to handling antibiotics. Examples are i.e. not taking a course of antibiotics of the correct dose, not taking a course of antibiotics of sufficient duration, not only taking a course of antibiotics in the case of bacterial infections and the continuing use of antibiotics as growth promoters in Vietnam. Resistance to antibiotics in Salmonella bacteria isolated in Vietnam turned out to occur frequently. In the Netherlands where the development of resistance has been monitored and registered for years the problem was hardly less. In Salmonella isolates from some animal species even resistance to antibiotics for which the use of that antibiotic is not allowed in that animal, was observed. In the current studies Salmonella bacteria have been isolated, both in Vietnam and in the Netherlands that have a collection in their integron album which is unique and has not been described before. At the end of the thesis the measures that could be taken to counteract the development of antibiotic resistance are discussed. The necessity of continuously making an inventory of the situation at local, regional, national and global level is accentuated, as is the shared responsibility that the government and civilians have with respect to the improper use of antibiotics.

Argues that current demand-side policy of the Food and Drug Administration and the Centers for Disease Control is the wrong route to address the issue of antibiotic resistance as it reduces the value to a pharmaceutical company of investing in the creation of new antibiotics. In this light, three externalities associated with antibiotic usage are discussed: public health, antibiotic resistance, and supply-side externalities. A cost-benefit analysis of FDA policies related to increased antibiotic scrutiny ensues, finding that requiring additional testing for antibiotics makes little sense with respect to patient welfare. Two harmful effects on antibiotic resistance of this FDA policy are denying the market use of an additional antibiotic, Ketek, and the loss of pharmaceutical company incentive to develop new antibiotics.

Beatriz Espinosa Franco1, Marina Altagracia Martínez2, Martha A Sánchez Rodríguez1, Albert I Wertheimer31Facultad de Estudios Superiores Zaragoza (UNAM), Mexico; 2Universidad Autónoma Metropolitana Unidad Xochimilco, Mexico; 3Temple University, Philadelphia, Pennsylvania, USABackground: The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a serious worldwide problem which is increasing and has implications for morbidity, mortality, and health care both in hospitals and in the community.Objectives: To analyze current research on the determinants of antibiotic resistance and comprehensively review the main factors in the process of resistance in order to aid our understanding and assessment of this problem.Methods: We conducted a MedLine search using the key words "determinants", "antibiotic", and "antibiotic resistance" to identify publications between 1995 and 2007 on the determinants of antibiotic resistance. Publications that did not address the determinants of antibiotic resistance were excluded.Results: The process and determinants of antibiotic resistance are described, beginning with the development of antibiotics, resistance and the mechanisms of resistance, sociocultural determinants of resistance, the consequences of antibiotic resistance, and alternative measures proposed to combat antibiotic resistance.Conclusions: Analysis of the published literature identified the main determinants of antibiotic resistance as irrational use of antibiotics in humans and animal species, insufficient patient education when antibiotics are prescribed, lack of guidelines for treatment and control of infections, lack of scientific information for physicians on the rational use of antibiotics, and lack of official government policy on the rational use of antibiotics in public and private hospitals.Keywords: antibiotic drug resistance, determinants, social-biological

The current study was carried out to detect Salmonella spp. contamination on chicken carcasses and to determine the antibiotic susceptibility profiles and serotype distribution of the isolates. A total of 200 packaged fresh raw chicken samples sold at retail in different markets in central Anatolia were analysed between April 2005 and March 2006. Salmonella spp. was detected in 34% (68/200) of samples using cultural technique and were confirmed by PCR. Ten Salmonella serovars were identified; predominant ones included Typhimurium, Infantis and Heidelberg. All of the Salmonella spp. isolates tested, exhibited resistance to one or more antimicrobial agents used. Resistance to penicillin, oxacillin, clindamycin, vancomycin, erythromycin and ampicillin were evident 100%, 97%, 97%, 92.6%, 89.7% and 85.2%, respectively. Also resistance to tetracycline (67.6%), streptomycin (61.7%), neomycin (55.8%) and cephalothin (52.9%) was observed but a small percentage of the isolates demonstrated resistance to gentamicin (14.7%), chloramphenicol (10.2%), cefotaxime (2.9%) and amikacin (2.9%). As a result, high prevalence of Salmonella spp. and the relatively high resistance among the bacteria tested could pose public health and therapeutic problems in consumers as potential vehicle of resistant Salmonella foodborne infections. To avoid Salmonella contamination, hygienic rules of slaughter and poultry meat processing must be rigorously observed and antibiotic use must be controlled by governmental agencies to prevent increased resistance of antibiotics. © 2010 Elsevier Ltd.

When they do not use formal quantitative risk assessment methods, many scientists (like other people) make mistakes and exhibit biases in reasoning about causation, if‐then relations, and evidence. Decision‐related conclusions or causal explanations are reached prematurely based on narrative plausibility rather than adequate factual evidence. Then, confirming evidence is sought and emphasized, but disconfirming evidence is ignored or discounted. This tendency has serious implications for health‐related public policy discussions and decisions. We provide examples occurring in antimicrobial health risk assessments, including a case study of a recently reported positive relation between virginiamycin (VM) use in poultry and risk of resistance to VM‐like (streptogramin) antibiotics in humans. This finding has been used to argue that poultry consumption causes increased resistance risks, that serious health impacts may result, and therefore use of VM in poultry should be restricted. However, the original study compared healthy vegetarians to hospitalized poultry consumers. Our examination of the same data using conditional independence tests for potential causality reveals that poultry consumption acted as a surrogate for hospitalization in this study. After accounting for current hospitalization status, no evidence remains supporting a causal relationship between poultry consumption and increased streptogramin resistance. This example emphasizes both the importance and the practical possibility of analyzing and presenting quantitative risk information using data analysis techniques (such as Bayesian model averaging (BMA) and conditional independence tests) that are as free as possible from potential selection, confirmation, and modeling biases.

We explored the association of antibiotic-resistant phenotypes and genotypes in Acinetobacter spp. with clinical outcomes and characteristics in 75 patients from a major military treatment facility. Amikacin resistance was associated with nosocomial acquisition of Acinetobacter baumannii, and carbapenem resistance and blaOXA-23 were associated with the need for mechanical ventilation. The presence of blaOXA-23 also correlated with longer hospital and ICU stay. Associations between blaOXA-23 and complexity, duration, and changes made to antibiotic regimens also existed.

Changes in the drug susceptibility pattern were observed in Vibrio cholerae O1 isolated in the Lao People's Democratic Republic during 1993 to 2000. In this study, 50 V. cholerae O1 strains were selected during this period for studying the presence of class I integron and SXT constin. Twenty-four streptomycin-resistant strains out of 26 isolated before 1997 contained a class I integron harboring the aadA1 gene cassette. Twenty-four strains isolated after 1997 contained an SXT constin (a large conjugative element). Twenty of the strains were resistant to chloramphenicol, tetracycline, streptomycin, and trimethoprim-sulfamethoxazole, while four strains were susceptible to the antibiotic tested. The resistance genes included in the SXT constins were floR, tetA, strAB, and sulII, which encode resistance to chloramphenicol, tetracycline, streptomycin, and sulfamethoxazole, respectively. The antibiotic resistance gene cluster was found to be deleted in the four susceptible strains. SXTLAOS did not contain dfrA1 or dfr18, which confer resistance to trimethoprim in SXTET and SXTMO10, respectively. A hot spot region of SXTLAOS was sequenced, and we identified two novel open reading frames showing homology to sO24 (exonuclease) and sO23 (helicase) of the genomic island associated with the multidrug resistance region of Salmonella enterica serovar Typhimurium DT104. Analysis of SXTLAOS showed that there is a continuous flux of genes among V. cholerae SXT constins which should be carefully monitored.

Minireview.-- Free via Open Access. ; In recent years, the explosive spread of antibiotic resistance determinants among pathogenic, commensal, and environmental bacteria has reached a global dimension. Classical measures trying to contain or slow locally the progress of antibiotic resistance in patients on the basis of better antibiotic prescribing policies have clearly become insufficient at the global level. Urgent measures are needed to directly confront the processes influencing antibiotic resistance pollution in the microbiosphere. Recent interdisciplinary research indicates that new eco-evo drugs and strategies, which take ecology and evolution into account, have a promising role in resistance prevention, decontamination, and the eventual restoration of antibiotic susceptibility. This minireview summarizes what is known and what should be further investigated to find drugs and strategies aiming to counteract the ¿four P¿s,¿ penetration, promiscuity, plasticity, and persistence of rapidly spreading bacterial clones, mobile genetic elements, or resistance genes. The term ¿drug¿ is used in this eco-evo perspective as a tool to fight resistance that is able to prevent, cure, or decrease potential damage caused by antibiotic resistance, not necessarily only at the individual level (the patient) but also at the ecological and evolutionary levels. This view offers a wealth of research opportunities for science and technology and also represents a large adaptive challenge for regulatory agencies and public health officers. Eco-evo drugs and interventions constitute a new avenue for research that might influence not only antibiotic resistance but the maintenance of a healthy interaction between humans and microbial systems in a rapidly changing biosphere. ; Work in the laboratories of F.B. and T.M.C. is funded by research grants from the European Commission (LSHM-2006-037410, LSHMCT-2008-223031, KBBE-2008-2B-227258, and PAR-241476-FPHEALTH 2009), the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (grants PS09/02381 and PI10/02588; the CIBERESP research network in Epidemiology and Public Health [CB06/02/0053]), and the Regional Government of Madrid (DeRemicrobiana Network [CAM.S-SAL-0246- 2006]). Work in the laboratory of F.D.L.C. is supported by research grants from the Spanish Ministry of Education (BFU2008-00995/ BMC), the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (REIPI network [RD06/0008/1012]) and the European Commission (LSHM-CT- 2005_019023). We are also grateful to the Spanish Network for the Study of Plasmids and Extrachromosomal Elements (REDEEX) for encouraging and funding cooperation among Spanish microbiologists working on the biology of mobile genetic elements (Spanish Ministry of Science and Innovation, reference number BFU 2008-0079-E/ BMC). ; Peer Reviewed

This article investigates the interplay of natural and human systems with reference to the growing global problem of antibiotic resistance. Among the diverse causes of antibiotic resistance, we focus broadly on three related causes: pharmaceutical practice and the liberal consumption of antibiotics, the use of antibiotic-containing products in the home, and the use of antibiotics in commercial animal husbandry and agriculture. We draw a parallel between pesticide and antibiotic resistance and examine whether lessons learned from one case may be applicable to the other. Although our main focus is a microecological analysis examining how humans are changing their environments, our conclusion addresses larger implications of this problem for global health. Through the theoretical lens of political ecology, we ask how we may address the "tragedy of the antibiotic commons" through public education and consumer activism as well as global health governance.

The wide utilization of biocides poses a concern on the impact of these compounds on natural bacterial populations. Furthermore, it has been demonstrated that biocides can select, at least in laboratory experiments, antibiotic resistant bacteria. This situation has raised concerns, not just on scientists and clinicians, but also on regulatory agencies, which are demanding studies on the impact that the utilization of biocides may have on the development on resistance and consequently on the treatment of infectious diseases and on human health. In the present article, we explored the possibility that the widely used biocide triclosan might induce antibiotic resistance using as a model the opportunistic pathogen Stenotrophomonas maltophilia. Biochemical, functional and structural studies were performed, focusing on SmeDEF, the most relevant antibiotic- and triclosan-removing multidrug efflux pump of S. maltophilia. Expression of smeDEF is regulated by the repressor SmeT. Triclosan released SmeT from its operator and induces the expression of smeDEF, thus reducing the susceptibility of S. maltophilia to antibiotics in the presence of the biocide. The structure of SmeT bound to triclosan is described. Two molecules of triclosan were found to bind to one subunit of the SmeT homodimer. The binding of the biocide stabilizes the N terminal domain of both subunits in a conformation unable to bind DNA. To our knowledge this is the first crystal structure obtained for a transcriptional regulator bound to triclosan. This work provides the molecular basis for understanding the mechanisms allowing the induction of phenotypic resistance to antibiotics by triclosan. ; This work was supported by the Spanish Ministry of Science and Innovation (grant numbers BIO2008-00090 to JLM and BFU2008-02595 and CSD2009-00088 to AR), by the European Union [grant numbers KBBE-227258 (BIOHYPO) and C-HEALTH/0601 [PAR] to JLM) and the Regional Government of Madrid (grant number PBIO-0214-2006 to AR) ; Peer reviewed