Transmission of antimicrobial resistance from pigs to humans: trues and lies

Through the years, use of antimicrobials in livestock has been the subject of an endless debate about the appropriateness of using these important medicines in the veterinary sector. This is a highly controversial topic involving ethical issues on animal welfare and human health, as well as economic interests by the pharmaceutical industry, the food industry and various professional categories, including farmers, veterinarians, pharmacists and researchers. As a consequence of all these factors, the debate has been often vigorous but not always scientifically unbiased. The aim of this lecture is to review the state-of-the-art on transmission of antimicrobial resistance (AMR) from pigs to humans with particular emphasis on specific risks that were overestimated by the scientific community in the past

Cephem Potentiation by Inactivation of Nonessential Genes Involved in Cell Wall Biogenesis of ß-Lactamase-Producing Escherichia coli

Reversal of antimicrobial resistance is an appealing and largely unexplored strategy in drug discovery. The objective of this study was to identify potential targets for “helper” drugs reversing cephem resistance in Escherichia coli strains producing β-lactamases. A CMY-2-encoding plasmid was transferred by conjugation to seven isogenic deletion mutants exhibiting cephem hypersusceptibility. The effect of each mutation was evaluated by comparing the MICs in the wild type and the mutant harboring the same plasmid. Mutation of two genes encoding proteins involved in cell wall biosynthesis, dapF and mrcB, restored susceptibility to cefoxitin (FOX) and reduced the MICs of cefotaxime and ceftazidime, respectively, from the resistant to the intermediate category according to clinical breakpoints. The same mutants harboring a CTX-M-1-encoding plasmid fell into the intermediate or susceptible category for all three drugs. Individual deletion of dapF and mrcB in a clinical isolate of CTX-M-15-producing E. coli sequence type 131 (ST131) resulted in partial reversal of ceftazidime and cefepime resistance but did not reduce MICs below susceptibility breakpoints. Growth curve analysis indicated no fitness cost in a ΔmrcB mutant, whereas a ΔdapF mutant had a 3-fold longer lag phase than the wild type, suggesting that drugs targeting DapF may display antimicrobial activity, in addition to synergizing with selected cephems. DapF appeared to be a potential FOX helper drug target candidate, since dapF inactivation resulted in synergistic potentiation of FOX in the genetic backgrounds tested. The study showed that individual inactivation of two nonessential genes involved in cell wall biogenesis potentiates cephem activity according to drug- and strain-specific patterns

Systematic Review on Global Epidemiology of Methicillin-Resistant Staphylococcus pseudintermedius: Inference of Population Structure from Multilocus Sequence Typing Data

Background and rationale: Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is a major cause of infections in dogs, also posing a zoonotic risk to humans. This systematic review aimed to determine the global epidemiology of MRSP and provide new insights into the population structure of this important veterinary pathogen.Methodology: Web of Science was searched systematically for articles reporting data on multilocus sequence typing (MLST) of S. pseudintermedius isolates from dogs or other animal or human patients and carriers. Data from the eligible studies were then integrated with data from the MLST database for this species. Analysis of MLST data was performed with eBURST and ClonalFrame, and the proportion of MRSP isolates resistant to selected antimicrobial drugs was determined for the most predominant clonal complexes.Results: Fifty-eight studies published over the last 10 years were included in the review. MRSP represented 76% of the 1428 isolates characterized by the current MLST scheme. The population of S. pseudintermedius was highly diverse and included five major MRSP clonal complexes (CCs). CC71, previously described as the epidemic European clone, is now widespread worldwide. In Europe, CC258, which is more frequently susceptible to enrofloxacin and aminoglycosides, and more frequently resistant to sulphonamides/trimethoprim than CC71, is increasingly reported in various countries. CC68, previously described as the epidemic North American clone, is frequently reported in this region but also in Europe, while CC45 (associated with chloramphenicol resistance) and CC112 are prevalent in Asia. It was estimated that clonal diversification in this species is primarily driven by homologous recombination (r/m=7.52).Conclusion: This study provides evidence that S. pseudintermedius has an epidemic population structure, in which five successful MRSP clones with specific traits regarding antimicrobial resistance, genetic diversity and geographical distribution have emerged upon a weakly clonal background through acquisition of SCCmec and other mobile genetic elements

Comparative host specificity of human- and pig- associated Staphylococcus aureus clonal lineages.

Bacterial adhesion is a crucial step in colonization of the skin. In this study, we investigated the differential adherence to human and pig corneocytes of six Staphylococcus aureus strains belonging to three human-associated [ST8 (CC8), ST22 (CC22) and ST36(CC30)] and two pig-associated [ST398 (CC398) and ST433(CC30)] clonal lineages, and their colonization potential in the pig host was assessed by in vivo competition experiments. Corneocytes were collected from 11 humans and 21 pigs using D-squame® adhesive discs, and bacterial adherence to corneocytes was quantified by a standardized light microscopy assay. A previously described porcine colonization model was used to assess the potential of the six strains to colonize the pig host. Three pregnant, S. aureus-free sows were inoculated intravaginally shortly before farrowing with different strain mixes [mix 1) human and porcine ST398; mix 2) human ST36 and porcine ST433; and mix 3) human ST8, ST22, ST36 and porcine ST398] and the ability of individual strains to colonize the nasal cavity of newborn piglets was evaluated for 28 days after birth by strain-specific antibiotic selective culture. In the corneocyte assay, the pig-associated ST433 strain and the human-associated ST22 and ST36 strains showed significantly greater adhesion to porcine and human corneocytes, respectively (p<0.0001). In contrast, ST8 and ST398 did not display preferential host binding patterns. In the in vivo competition experiment, ST8 was a better colonizer compared to ST22, ST36, and ST433 prevailed over ST36 in colonizing the newborn piglets. These results are partly in agreement with previous genetic and epidemiological studies indicating the host specificity of ST22, ST36 and ST433 and the broad-host range of ST398. However, our in vitro and in vivo experiments revealed an unexpected ability of ST8 to adhere to porcine corneocytes and persist in the nasal cavity of pigs

Susceptibility in vitro of canine methicillin-resistant and -susceptible staphylococcal isolates to fusidic acid, chlorhexidine and miconazole: opportunities for topical therapy of canine superficial pyoderma

OBJECTIVES: Increasing multidrug resistance amongst canine pathogenic staphylococci has renewed interest in topical antibacterial therapy for skin infections in the context of responsible veterinary prescribing. We therefore determined the activity in vitro of three clinically relevant topical agents and synergism between two of them against Staphylococcus pseudintermedius and Staphylococcus aureus. METHODS: The MICs of fusidic acid (n = 199), chlorhexidine (n = 198), miconazole (n = 198) and a 1:1 combination of miconazole/chlorhexidine (n = 198) were determined for canine isolates [50 MRSA and 49 methicillin-resistant S. pseudintermedius (MRSP), 50 MSSA and 50 methicillin-susceptible S. pseudintermedius (MSSP)] collected from the UK and Germany using an agar dilution method (CLSI VET01-A4). Fractional inhibitory concentration (FIC) indices were calculated to assess the interaction of miconazole with chlorhexidine. RESULTS: MICs of each drug/combination were significantly (P < 0.0005) higher for S. aureus when compared with S. pseudintermedius. Most strains (n = 172) had an MIC of fusidic acid of ≤0.03 mg/L (MIC ≥64 mg/L, n = 5 MRSA). All strains had MICs of chlorhexidine of 0.5–4 mg/L, except for one MRSA (MIC = 8 mg/L). All but four strains had MICs of miconazole of 1–4 mg/L (MIC = 16 mg/L, n = 3; MIC = 256 mg/L, n = 1). Miconazole/chlorhexidine (1:1 ratio) had a synergistic effect against 49/50 MRSA, 31/50 MSSA, 12/49 MRSP and 23/49 MSSP. CONCLUSIONS: Since the majority of these staphylococci, including methicillin-resistant isolates, had MICs that should be readily exceeded by topical skin application of these agents, their therapeutic efficacy for canine superficial pyoderma should be assessed. The synergistic interaction shown in vitro supports further clinical evaluation of miconazole/chlorhexidine combination therapy for staphylococcal infection

Evaluating interventions with victims of intimate partner violence: a community psychology approach

Purpose. Intimate Partner Violence (IPV) is one of the most common forms of domestic violence, with profound implication for women's physical and psychological health. In this text we adopted the Empowerment Process Model (EPM) by Cattaneo and Goodman (2015) to analyse interventions provided to victims of IPV by a Support Centre for Women (SCW) in Italy, and understand its contribution to women’s empowerment. Method. We conducted semi-structured interviews with ten women who had been enrolled in a program for IPV survivors at a SCW in the past three years. The interviews focused on the programs’ aims, actions undertaken to reach them, and the impact on the women’s lives, and were analysed using an interpretative phenomenological approach. Results. Results showed that the interventions provided by the SWC were adapted according to women's needs. In the early phases, women’s primary aim was ending violence, and the intervention by the SCW was deemed as helpful to the extent it provided psychological support, protection and safe housing. Women’s aims subsequently moved to self-actualisation and economic and personal independence which required professional training, internships, and social support. Although satisfying the majority of the women’s expectations, other important needs (e.g., economic support or legal services) were poorly addressed, and cooperation with other services (e.g., police or social services) was sometimes deemed as critical. Conclusions. By evaluating a program offered by a SCW to IPV survivors through the lens of the EPM model, we found that women deemed the program as effective when both individual resources and empowerment processes were promoted. Strengths, limitations and implications are discussed