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

Advancing Pediatric Antibacterial Drug Development: A Critical Need to Reinvent our Approach.

The Clinical Trials Transformation Initiative convened with several groups in the pediatric antibacterial drug development community with the goal of identifying challenges and recommending ways to improve current practice. Attention to 5 major areas hold the promise of making new antibiotics available for use in children as soon as possible after they are approved for use in adults

Prevalence of carbapenem-resistant Acinetobacter baumannii from 2005 to 2016 in Switzerland

Background : We describe the prevalence of invasive carbapenem-resistant Acinetobacter spp. isolated from 2005 to 2016 in different regions of Switzerland.Methods: Using the Swiss Antibiotic Resistance Centre (anresis) database that includes data from 70% of all hospitalized patients and one third of all ambulatory practitioners in Switzerland, we analysed the number of carbapenem- susceptible and resistant Acinetobacter spp. isolated from blood or cerebrospinal fluid, and further described their temporal and regional fluctuations.Results: From 2005 to 2016, 58 cases of resistant or intermediate strains to carbapenem were observed among 632 cases of invasive Acinetobacter. Multivariable analyses indicated that the number of carbapenem-resistant isolates (mean 4.8 ± sd 2.12) and carbapenem resistance rates per region per annum (8.4% ± 13.9%) were low and stable over the studied period. Large fluctuations were observed at the regional level, with e.g. the North East region displaying resistance rates twice as high as that found in other regions.Conclusion: Despite a relatively stable number of carbapenem-resistant Acinetobacter isolates in Switzerland, our results suggest the existence of a diverse pool of A. baumannii species in hospital settings, and confirm the implication of carbapenem-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (ACB) complex in the vast majority of clinical infections and nosocomial outbreaks with notable regional fluctuations

Antimicrobial susceptibility profile of selected bacteraemic pathogens from private institutions in South Africa

Objectives. The National Antimicrobial Surveillance Forum is a continuous  surveillance organisation comprising all academic/ public and private   sector  laboratories in South Africa.Methods. The antibiotic susceptibility of blood culture isolates of  Escherichia  coli, Klebsiella pneumoniae, Enterobacter species,   Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus  aureus from patients in private hospitals in five major centres were  investigated. Antimicrobial susceptibility tests were performed by 12  participating laboratories  according to the Clinical and Laboratory Standards Institute (CLSI)  guidelines. Extended-spectrum 13-lactamase (ESBL)  production was  determined in selected species of Enterobacteriaceae  irrespective of source.Results. The overall prevalence of ampicillin resistance in blood culture isolates of E. coli (N = 471) was 84%, and 20% were resistant to the  fluoroquinolones. Considerable geographical differences were noted   between the centres with regard to the K. pneumoniae (N = 636) resistance rates for ceftriaxone and/ or cefotaxime (39- 87%). The most active   agents in the Enterobacter spp. (N = 244) were imipenem/meropenem, ertapenem, ciprofloxacin, levofloxacin and cefepime, with 100%,94%, 88%, 87% and 80% susceptibility, respectively. Carbapenem resistance in P. aeruginosa (N = 382) varied between 42% and 45%, and in the case of A. baumannii (N= 190) resistance varied between 32% and 33% for   meropenem and imipenem respectively. The nationwide incidence of  oxacillin resistance in S. aureus (N = 629) was 36%. Overall, the  prevalence of ESBL production among all isolates of K. pneumoniae was 26% (N = 7 514), while in Enterobacter spp. it was 12% (N = 4 031) and in E. coli 5% (N = 28 412).Conclusions. The data highlight the widespread problem of antibiotic  resistance among important bacteraemic pathogens in private institutions in South Africa. Continued surveillance is vital to guide appropriate  empirical therapy for invasive infections

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