Involvement of T cells in enhanced resistance to Klebsiella pneumoniae septicemia in mice treated with liposome-encapsulated muramyl tripeptide phosphatidylethanolamine or gamma interferon

We have previously shown that prophylactic administration of the liposome-encapsulated immunomodulating agents muramyl tripeptide phosphatidylethanolamine (MTPPE) and gamma interferon (IFN-gamma) results in strongly increased survival of mice from a normally lethal septicemia with Klebsiella pneumoniae. It was anticipated that the treatment acts on macrophages and nonspecifically augments host resistance to various infections. In the present study, we provide evidence for a key role for T cells in host defense potentiation by the liposomal immunomodulators toward K. pneumoniae septicemia. It is shown that both CD4 and CD8 cells are important in immunomodulation, most likely due to production of IFN-gamma. Depletion of circulating IFN-gamma resulted in strong reduction of the antimicrobial host defense activation. Administration of interleukin-10 resulted in decreased antimicrobial host defense activation by liposomal immunomodulators. Moreover, administration of liposomal immunomodulators was shown to induce predominantly T-helper type 1 (Th1) cell populations in the spleen. These findings indicate that immunomodulation with liposomal MTPPE and IFN-gamma favors Th1 and NK cell activation

Sterically stabilized amphotericin B-liposomes: Toxicity and biodistribution in mice

In this study it was investigated whether long-circulating amphotericin B (AMB) containing liposomes could be prepared by incorporation of polyethylene glycol (1900) derivatized distearoylphosphatidylethanolamine (PEG-DSPE), and whether the incorporation of PEG-DSPE affected toxicity and biodistribution of the preparation in mice. Toxicity of two formulations of liposomes containing both PEG-DSPE and AMB (PEG-AMB-LIP, types 1 and 2) was compared with that of AMB-liposomes without PEG-DSPE (AMB-LIP) as well as that of MB-deoxycholate (AMB-DOC). The maximum tolerated dosage (MTD) of AMB-DOC, expressed in terms of death during treatment for 5 consecutive days or significant increases in the parameters used to monitor renal and hepatic functions, was 0.8 mg/kg per day. AMB-LIP were the least toxic, the MTD being 11 mg/kg per day. The formulation with AMB complexed to DSPG (PEG-AMB-LIP type 1) was as toxic as AMB-DOC. This PEG-AMB-LIP formulation was omitted from further studies on biodistribution. With AMB complexed to PEG-DSPE (PEG-AMB-LIP type 2) toxicity was substantially reduced, resulting in a MTD of 9 mg/kg per day. Biodistribution of radiolabeled PEG-AMB-LIP type 2 was compared with that of AMB-LIP. Blood residence time of PEG-AMB-LIP type 2 was prolonged as compared to AMB-LIP; For PEG-AMB-LIP type 2 at 24 h after administration 30% of the injected dosage of AMB in intact liposomes was circulating versus 6% for AMB-LIP

An outbreak of ST307 extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae in a rehabilitation center: An unusual source and route of transmission

Objective: Nosocomial outbreaks due to multidrug-resistant microorganisms in rehabilitation centers have rarely been reported. We report an outbreak of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (ESBL-K. pneumoniae) on a single ward in a rehabilitation center in Rotterdam, The Netherlands.Design: Outbreak description.Setting: A 40-bed ward of a rehabilitation center in the Netherlands.Methods: In October 2016, 2 patients were found to be colonized by genetically indistinguishable ESBL-K. pneumoniae isolates. Therefore, an outbreak management team was installed, by whom a contact tracing plan was made. In addition to general outbreak measures, specific measures were formulated to allow continuation of the rehabilitation process. Also, environmental cultures were taken. Multiple-locus variable-number tandem-repeat analysis and amplification fragment-length polymorphism were used to determine strain relatedness. Selected isolates were subjected to whole-genome multilocus sequence typing.Results: The outbreak lasted 8 weeks. In total, 14 patients were colonized with an ESBL-K. pneumoniae, of whom 11 patients had an isolate belonging to