Model Systems of Human Intestinal Flora, to Set Acceptable Daily Intakes of Antimicrobial Residues

The veterinary use of antimicrobial drugs in food producing animals may result in residues in food, that might modify the consumer gut flora. This review compares three model systems that maintain a complex flora of human origin: (i) human flora associated (HFA) continuous flow cultures in chemostats, (ii) HFA mice, and (iii) human volunteers. The "No Microbial Effect Level" of an antibiotic on human flora, measured in one of these models, is used to set the accept¬able daily intake (ADI) for human consumers. Human volunteers trials are most relevant to set microbio¬log¬ical ADI, and may be considered as the "gold standard". However, human trials are very expensive and unethical. HFA chemostats are controlled systems, but tetracycline ADI calculated from a chemostat study is far above result of a human study. HFA mice studies are less expensive and better controlled than human trials. The tetracycline ADI derived from HFA mice studies is close to the ADI directly obtained in human volunteers

Detection of Multi-drug Resistant \u3cem\u3eEscherichia coli\u3c/em\u3e in the Urban Waterways of Milwaukee, WI

Urban waterways represent a natural reservoir of antibiotic resistance which may provide a source of transferable genetic elements to human commensal bacteria and pathogens. The objective of this study was to evaluate antibiotic resistance of Escherichia coli isolated from the urban waterways of Milwaukee, WI compared to those from Milwaukee sewage and a clinical setting in Milwaukee. Antibiotics covering 10 different families were utilized to determine the phenotypic antibiotic resistance for all 259 E. coli isolates. All obtained isolates were determined to be multi-drug resistant. The E. coli isolates were also screened for the presence of the genetic determinants of resistance including ermB (macrolide resistance), tet(M) (tetracycline resistance), and β-lactamases (blaOXA, blaSHV, and blaPSE). E. coli from urban waterways showed a greater incidence of antibiotic resistance to 8 of 17 antibiotics tested compared to human derived sources. These E. coli isolates also demonstrated a greater incidence of resistance to higher numbers of antibiotics compared to the human derived isolates. The urban waterways demonstrated a greater abundance of isolates with co-occurrence of antibiotic resistance than human derived sources. When screened for five different antibiotic resistance genes conferring macrolide, tetracycline, and β-lactam resistance, clinical E. coli isolates were more likely to harbor ermB and blaOXA than isolates from urban waterway. These results indicate that Milwaukee’s urban waterways may select or allow for a greater incidence of multiple antibiotic resistance organisms and likely harbor a different antibiotic resistance gene pool than clinical sources. The implications of this study are significant to understanding the presence of resistance in urban freshwater environments by supporting the idea that sediment from urban waterways serves as a reservoir of antibiotic resistance

Carbapenemase-producing Enterobacteriaceae isolates collected in Portuguese hospitals

Objectives: In Portugal, little is known on carbapenemase (CARB)-producing Enterobacteriaceae. The aim of this study was to identify the resistance mechanisms of Enterobacteriaceae isolates, identified at hospital laboratories as carbapenem (CA) non-susceptible. Methods: This study included 61 Enterobacteriaceae isolates (26 Klebsiella spp, 15 Escherichia coli, 9 Enterobacter spp, 6 Morganella morgannii, 4 Proteus mirabilis, 1 Serratia marcescens), collected between 04/2006 and 09/2011 and sent to the NIH-Lisbon for CA susceptibility confirmation. Antimicrobial susceptibility of clinical isolates was performed by disk diffusion method (CA-SFM). Clinical isolates showing synergism between CA and boronic acid (BOR) (and/or clavulanic acid, CLAV) or with EDTA were considered presumptively CARB-producers from class A or Class B, respectively. PCR and sequencing were applied to detect and identify CARB-encoding genes; the respective genetic environment was revealed by sequencing using PCR mapping. Direct transfer of the CA resistance phenotype was attempted by mating-out assays. Antibiotics susceptibility (MIC) of transconjugants and respective isolates were tested by microdilution. Results: The majority of isolates were collected from the urine (57.4%) of elderly (≥65 years old) male patients (54.1%), admitted at the emergency room/ambulatory (24.6%) and at internal medicine (18.0%) wards. Among all isolates, 50.8% were nonsusceptible to at least one CA, being 67.2% multidrug-resistant; 16 isolates showed synergy between CA and BOR (and/or CLAV). Among those, 5 were KPC-3-producers (4 Klebsiella pneumoniae and 1 Enterobacter clocae), collected in 2010 (2) and 2011 (3). The blaKPC-3 genes were confirmed to be carried by plasmids. Genetic environment of blaKPC-3 gene revealed the presence of a Tn4401 transposon in all but one isolate (E. cloacae), suggesting that this last gene was included in other Tn4401-like isoform. We also detected a VIM-2-producing Klebsiella oxytoca, collected in 2009, among the 7 isolates that showed synergy between imipinem and EDTA. No blaGES, blaNDM or blaIMP were detected. Conclusion: In conclusion, this study provides new data regarding the molecular epidemiology of CARB-producing Enterobacteriaceae in Portugal. Overall, our results emphasize the need of a concerted action to manage CA use. This is supported by EARS-Net, which reported an increase in CA nonsusceptibility of K. pneumoniae isolates from 0.72% in 2008 to 1.58% in 2010

Review article: the global emergence of Helicobacter pylori antibiotic resistance.

BackgroundHelicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma.AimTo review recent trends in H. pylori antibiotic resistance rates, and to discuss diagnostics and treatment paradigms.MethodsA PubMed literature search using the following keywords: Helicobacter pylori, antibiotic resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing.ResultsThe prevalence of bacterial antibiotic resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other antibiotics show similar trends, although less pronounced.ConclusionsSince the choice of empiric therapies should be predicated on accurate information regarding antibiotic resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric antibiotic therapy but also inform the development of better methods to identify H. pylori antibiotic resistance at diagnosis. Patient-specific tailoring of effective antibiotic treatment strategies may lead to reduced treatment failures and less antibiotic resistance

Antimicrobial Resistance: An Update from the Canadian Committee on Antibiotic Resistance

The present article is one of a series prepared by the Canadian Committee on Antibiotic Resistance (CCAR). These articles are designed to update readers on current activities intended to limit the development and transmission of antibiotic resistance in Canada. Headquartered in Vancouver, British Columbia, the CCAR provides outreach to public and professional communities through activities focused on infection prevention and control, resistance surveillance and optimal antibiotic use

The effect of combined sewer overflows on the abundance of antibiotic resistance genes and bacteria in the James River

Antibiotic resistance is a major threat to human health. Clinical situations are the main focus for antibiotic resistance research, but understanding the spread of resistance in the environment is also vital. A major contributor to this spread is wastewater from combined sewer overflow (CSO) events. The effect of CSO events on antibiotic resistance in the James River near Richmond, Virginia was studied using genomic and microbiological approaches. The abundance of genes associated with resistance to quinolones (qnrA) and tetracycline (tetW) was strongly correlated with the presence of fecal indicator bacteria (E. coli abundance) as well as total nitrogen and phosphorus loads, which suggests an anthropogenic source of these genes. Abundance of the blaTEM gene, which confers resistance to β-lactam antibiotics, was elevated during CSO events and increased with precipitation and river discharge. Bacteria isolated during a CSO event were resistant to more antibiotics and had higher multi-drug resistance when compared to isolates from a non-event. This study demonstrated that CSO events are contributing to the spread of antibiotic resistance