Comparative Genomics and Antimicrobial Resistance Profiling of Elizabethkingia Isolates Reveal Nosocomial Transmission and In Vitro Susceptibility to Fluoroquinolones, Tetracyclines, and Trimethoprim-Sulfamethoxazole.

The Elizabethkingia genus has gained global attention in recent years as containing sporadic, worldwide, nosocomial pathogens. Elizabethkingia spp. are intrinsically multidrug resistant, primarily infect immunocompromised individuals, and are associated with high mortality (∼20 to 40%). As yet, gaps remain in our understanding of transmission, global strain relatedness, antimicrobial resistance, and effective therapy. Over a 16-year period, 22 clinical and 6 hospital environmental isolates were collected from Queensland, Australia. Identification using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (Vitek MS) and whole-genome sequencing was compared with a global strain data set. Phylogenomic reconstruction robustly identified 22 Elizabethkingia anophelis, 3 Elizabethkingia miricola, 2 Elizabethkingia meningoseptica, and 1 Elizabethkingia bruuniana isolates, most of which branched as unique lineages. Global analysis revealed that some Australian E. anophelis isolates are genetically closely related to strains from the United States, England, and Asia. Comparative genomics of clinical and environmental strains identified evidence of nosocomial transmission in patients, indicating probable infection from a hospital reservoir. Furthermore, broth microdilution against 39 antimicrobials revealed almost ubiquitous resistance to aminoglycosides, carbapenems, cephalosporins, and penicillins. Like other international strains, our isolates expressed susceptibility to minocycline and levofloxacin and the less common trimethoprim-sulfamethoxazole. Our study demonstrates important new insights into the genetic diversity, environmental persistence, and transmission of and potential effective therapy for Australian Elizabethkingia species.

Vaccination with chemically attenuated Plasmodium falciparum asexual blood-stage parasites induces parasite-specific cellular immune responses in malaria-naïve volunteers: a pilot study.

BACKGROUND: The continuing morbidity and mortality associated with infection with malaria parasites highlights the urgent need for a vaccine. The efficacy of sub-unit vaccines tested in clinical trials in malaria-endemic areas has thus far been disappointing, sparking renewed interest in the whole parasite vaccine approach. We previously showed that a chemically attenuated whole parasite asexual blood-stage vaccine induced CD4+ T cell-dependent protection against challenge with homologous and heterologous parasites in rodent models of malaria. METHODS: In this current study, we evaluated the immunogenicity and safety of chemically attenuated asexual blood-stage Plasmodium falciparum (Pf) parasites in eight malaria-naïve human volunteers. Study participants received a single dose of 3 × 107 Pf pRBC that had been treated in vitro with the cyclopropylpyrolloindole analogue, tafuramycin-A. RESULTS: We demonstrate that Pf asexual blood-stage parasites that are completely attenuated are immunogenic, safe and well tolerated in malaria-naïve volunteers. Following vaccination with a single dose, species and strain transcending Plasmodium-specific T cell responses were induced in recipients. This included induction of Plasmodium-specific lymphoproliferative responses, T cells secreting the parasiticidal cytokines, IFN-γ and TNF, and CD3+CD45RO+ memory T cells. Pf-specific IgG was not detected. CONCLUSIONS: This is the first clinical study evaluating a whole parasite blood-stage malaria vaccine. Following administration of a single dose of completely attenuated Pf asexual blood-stage parasites, Plasmodium-specific T cell responses were induced while Pf-specific antibodies were not detected. These results support further evaluation of this chemically attenuated vaccine in humans. TRIAL REGISTRATION: Trial registration: ACTRN12614000228684 . Registered 4 March 2014.

Ureaplasma urealyticum necrotizing soft tissue infection.

Ureaplasma urealyticum is a urogenital commensal and often associated with localised infection. With the advent of monoclonal immunosuppressive therapy and improved diagnostic methods, reports of non-urogenital infections are accumulating. We report a rare case of U. urealyticum necrotizing soft tissue infection and left hip septic arthritis in a hypogammaglobulinaemic patient. Consideration of this organism as an etiological agent, and potential early use of nucleic-acid diagnostic investigation with empiric therapy including activity against Ureaplasma in this patient population may be warranted.