A strategy for producing high-level hematopoietic chimerism after non-myeloablative conditioning has been established in the rhesus macaque. This strategy relies on hematopoietic stem cell transplantation after induction with a non-myeloablative dose of busulfan and blockade of the IL2-receptor in the setting of mTOR inhibition with sirolimus and combined CD28/CD154 costimulation blockade. Hematopoietic stem cells derived from bone marrow and leukopheresis products both were found to be successful in inducing highlevel chimerism. Mean peripheral blood peak donor chimerism was 81% with a median chimerism duration of 145 days. Additional immune modulation strategies, such as pre-transplant CD8 depletion, donor-specific transfusion, recipient thymectomy or peritransplant deoxyspergualin treatment did not improve the level or durability of chimerism. Recipient immunologic assessment suggested that chimerism occurred amidst donor-specific down-regulation of alloreactive T cells, and the reappearance of vigorous T-mediated alloreactivity accompanied rejection of the transplants. Furthermore, viral reactivation constituted a significant transplant-related toxicity and may have negatively impacted the ability to achieve indefinite survival of transplanted stem cells. Nevertheless, this chimerisminduction regimen induced amongst the longest-lived stem cell chimerism reported to date for non-human primates and thus represents a platform upon which to evaluate emerging tolerance-induction strategies.

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Florfenicol is an important antibiotic in veterinary medicine that is used extensively in aquaculture, including salmon farming in Chile. We analysed a set of 119 florfenicol-resistant Gram-negative bacilli from seven freshwater Chilean salmon farms for the molecular determinants involved in the florfenicol resistance. Ninety-seven of these strains were glucose non-fermenting bacilli, mainly belonging to the Pseudomonas genus, whereas 22 strains were glucose-fermenters. The floR gene was detected in 26 strains (21.8%) that had been isolated from three of the seven salmon farms. Most of the floR-carrying strains were glucose fermenters (21 strains), and most of the floR-carrying strains were also resistant to streptomycin, chloramphenicol and oxytetracycline. The minimum inhibitory concentrations against florfenicol were assessed in the presence and absence of the efflux pump inhibitor Phe-Arg-beta-naphthylamide (MC-207,110). There was evidence that in the majority of non-fermenting bacteria (82 strains), florfenicol resistance was at least partially mediated by non-specific efflux pump systems. Given the diversity of antibiotic resistance patterns observed in this study in the floR-positive isolates, a single antibiotic has the potential to co-select for a diversity of resistances. For this reason, human health as well as animal health can potentially be impacted by the use of antibiotics in aquaculture. To assess this potential risk, future studies should focus on the ability of different antibiotics used in aquatic environments to co-select for multiple resistances, the molecular basis of this diversity of resistance, and whether the genes conferring resistance can be transferred to other bacteria, including those of human health concern.

Acinetobacter baumannii is an opportunistic pathogen that is frequently involved in outbreaks of infection, occurring mostly in intensive care units. The increasing incidence of carbapenem resistance in A. baumannii worldwide is a concern since it limits drastically the range of therapeutic alternatives. The most important mechanism of carbapenem resistance is the enzymatic hydrolysis mediated by carbapenemases. In A. baumannii these enzymes are usually OXA-type carbapenemases, and belong to class D according to the classification of Ambler. The OXA-type carbapenemases are divided into five subgroups, four of which correspond to acquired carbapenemases, which accounts for the distribution of genes blaOXA in different geographic areas. In this work we review the different types of OXA-type carbapenemases present in A. baumannii, emphasizing the current situation in South America with special mention to the findings in Chile.

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