Methicillin-resistant Staphylococcus aureus Pyomyositis inducing Guillain-Barré Syndrome - A rare and unexpected clinical presentation

Tropical pyomyositis is characterized by deep suppurative skeletal muscle infection most commonly by Staphylococcal Aureus (S. aureus) with increasing incidence of infection by community acquired methicillin resistant S. aureus(CA-MRSA). The initial clinical presentation is generally non-specific and requires a high index of suspicion. We report the clinical course of a child from subtropical area of North India who developed multiple deep pyogenous collections, complicated with CA-MRSA septicaemia and followed by unusual complications consistent with Guillain-Barré Syndrome.

The Urtica Dioica Agglutinin Prevents Rabies Virus Infection in a Muscle Explant Model

Infection with the rabies virus (RABV) causes fatal encephalitis and paralysis in humans and animals. Post-exposure prophylaxis (PEP) consists of vaccination and the injection of anti-rabies immunoglobulins (RIGs) around the (bite) wound. This is 100% effective in preventing disease if administered in a timely manner. However, the costs, the required cold chain for storage and transport and the limited availability of RIGs makes the treatment challenging. Cheaper and easier to produce alternatives are urgently needed. To aid in the discovery and development of such alternative therapeutics, we developed a physiological relevant infection model. Strips of freshly dissected swine skeletal muscle were placed under tension in culture medium and infected with RABV. Viral antigens were produced in the muscle explants and the virus production increased significantly over time, indicating that RABV infects and replicates in the muscle explants. Subsequently, in a search for inhibitors of RABV entry in muscle cells, we first screened a panel of 34 different lectins in a RABV / BHK-21J cell assay. The Urtica Dioica (stinging nettle) Agglutinin (UDA; a N-acetyl-D-glucosamine specific agglutinin) was found to be able to completely inhibit infection of cells with the RABV (EC50 8.2 μg/mL) by preventing binding of the virus to the host cell. When the infection of the muscle strips was carried out in the presence of UDA, infection of the tissue was completely prevented. We thus developed a physiological relevant RABV muscle infection model and identified an easy to produce component that (i) may serve as a reference for further studies and (ii) holds promise as an alternative for RIGs in PEP.

In Vitro and In Vivo Antibacterial Activities of DC-159a, a New Fluoroquinolone

ABSTRACT DC-159a is a new 8-methoxy fluoroquinolone that possesses a broad spectrum of antibacterial activity, with extended activity against gram-positive pathogens, especially streptococci and staphylococci from patients with community-acquired infections. DC-159a showed activity against Streptococcus spp. (MIC90, 0.12 μg/ml) and inhibited the growth of 90% of levofloxacin-intermediate and -resistant strains at 1 μg/ml. The MIC90s of DC-159a against Staphylococcus spp. were 0.5 μg/ml or less. Against quinolone- and methicillin-resistant Staphylococcus aureus strains, however, the MIC90 of DC-159a was 8 μg/ml. DC-159a was the most active against Enterococcus spp. (MIC90, 4 to 8 μg/ml) and was more active than the marketed fluoroquinolones, such as levofloxacin, ciprofloxacin, and moxifloxacin. The MIC90s of DC-159a against Haemophilus influenzae, Moraxella catarrhalis, and Klebsiella pneumoniae were 0.015, 0.06, and 0.25 μg/ml, respectively. The activity of DC-159a against Mycoplasma pneumoniae was eightfold more potent than that of levofloxacin. The MICs of DC-159a against Chlamydophila pneumoniae were comparable to those of moxifloxacin, and DC-159a was more potent than levofloxacin. The MIC90s of DC-159a against Peptostreptococcus spp., Clostridium difficile, and Bacteroides fragilis were 0.5, 4, and 2 μg/ml, respectively; and among the quinolones tested it showed the highest level of activity against anaerobic organisms. DC-159a demonstrated rapid bactericidal activity against quinolone-resistant Streptococcus pneumoniae strains both in vitro and in vivo. In vitro, DC-159a showed faster killing than moxifloxacin and garenoxacin. The bactericidal activity of DC-159a in a murine muscle infection model was revealed to be superior to that of moxifloxacin. These activities carried over to the in vivo efficacy in the murine pneumonia model, in which treatment with DC-159a led to bactericidal activity superior to those of the other agents tested.

The role of copepods (Cyclopsspp.) in eliminating the actinospore stages of fish-parasitic myxozoans

The actinospore consumption of copepods (Cyclopsspp.)was demonstrated by laboratory observations. It was observed that in experimental dishes the number of actinospores floating in the water decreased, or such actinospores were completely eliminated, in the presence of copepods. The ingestion of actinospores by copepods and their further fate were monitored by fluorescent staining and by conventional histological techniques. The actinospores were observed to have got caught on the filters of Cyclopsspp. Two and a half hours after the copepods had been placed into water containing actinospores, their digestive tract was found to contain spores that had extruded their filaments from the polar capsules. After copepods having ingested the actinospores of the species Myxobolus pseudodisparhad been fed to roaches, no muscle infection developed in the fish host. It is likely that Cyclopsspp. can filter out actinospores floating in the water also from natural waters, thus decreasing the chance of development of myxosporean infections.

Interleukin-10 Limits Local and Body Cavity Inflammation during Infection with Muscle-Stage Trichinella spiralis

ABSTRACT The aim of this study was to characterize cellular responses to muscle-stage Trichinella spiralis. From its intracellular habitat in muscle, T. spiralis secretes potent glycoprotein antigens that elicit a strong systemic host immune response. Despite the magnitude and prolonged nature of this response, nurse cells are rarely destroyed by infiltrating cells. We tested the hypothesis that the anti-inflammatory cytokine interleukin-10 (IL-10) moderates cellular responses to muscle-stage parasites. Trichinella larvae colonize the diaphragm in large numbers, prompting us to evaluate regional responses in body cavities in addition to local responses in muscle. Mice deficient in IL-10 demonstrated an exaggerated inflammatory response around nurse cells and in the pleural cavity. The effect of IL-10 was most evident 20 days following muscle infection. The increased intensity of the response in IL-10-deficient mice did not affect parasite establishment or survival. Between 20 and 50 days postinfection, the inflammatory response was diminished in both wild-type and IL-10-deficient mice. Muscle infection also elicited an antibody response, characterized initially by mixed isotypes directed at somatic larval antigens and changing to an immunoglobulin G1-dominated response directed at tyvelose-bearing excreted or secreted antigens. We conclude that IL-10 limits local and regional inflammation during the early stages of muscle infection but that chronic inflammation is controlled by an IL-10-independent mechanism that is coincident with a Th2 response.

In Vivo Efficacy of the New Ketolide Telithromycin (HMR 3647) in Murine Infection Models

ABSTRACT We compared the oral antibacterial activities of telithromycin (HMR 3647), a new ketolide drug, in different infections induced in mice byStaphylococcus aureus, Streptococcus pneumoniae, streptococci, enterococci, and Haemophilus influenzae with those of various macrolides and pristinamycin. Unlike all other comparators, telithromycin displayed a high therapeutic activity, particularly in septicemia induced by erythromycin A-resistant pathogens, where the ketolide was the only active compound, displaying effective doses between 3 and 26 mg/kg of body weight. Against H. influenzae, telithromycin was the most effective compound. Telithromycin displayed bacteriostatic behavior against S. pneumoniae and H. influenzae. The ketolide was also active against thigh muscle infection induced by S. aureus. The pharmacokinetic properties of telithromycin accounted for its outstanding well-balanced oral in vivo efficacy against both gram-positive cocci, whatever their phenotype of resistance, andH. influenzae.