Successful treatment and digestive decolonisation of a patient with osteitis caused by a carbapenemase-producing Klebsiella pneumoniae isolate harbouring both NDM-1 and OXA-48 enzymes.

OBJECTIVES: Carbapenem resistance in Klebsiella pneumoniae is an increasing problem worldwide and infections caused by this bacterium can be difficult to treat. This study reported the case of a patient from Romania, who was hospitalised in Bulgaria after an accident trauma. He then came to France for treatment of an osteitis caused by a Klebsiella pneumoniae carrying both blaNDM-1 and blaOXA-48. METHOD: The resistome of this extremely drug-resistant bacterium was analysed both with phenotypic (large antibiotic susceptibility testing) and genomic methods (genome sequencing). The genetic environment of the two carbapenemases was studied. RESULTS: Klebsiella pneumoniae ST307 carrying both a blaNDM-1 and blaOXA-48 gene was located on two different plasmids: Inc L/M and IncFII. The patient was successfully treated by a combination of intravenous colistin (9 MUI, then 4.5 MUI bd), intravenous fosfomycin (4g tds) and oral doxycycline (100mg bd) for 3 months. Faecal microbiota transplantation was successfully conducted for stool carriage. CONCLUSION: The ST307 type is becoming endemic in hospital environments and is frequently associated with carbapenem resistance. Treatment of infection caused by multidrug-resistant bacteria is a clinical challenge, and the use of old antibiotics associated with screening and decolonisation of the reservoirs can be an efficient therapeutic alternative.

Potential Role of L-Arginine and Vitamin E Against Bone Loss Induced by Nano-Zinc Oxide in Rats.

The purpose of this study was to illustrate the effects of zinc oxide nanoparticles (ZnO-NPs) administration on bone turnover and bone resorbing agents in rats and how L-arginine (L-arg) or vitamin E (vit E) co-administrations might affect them. Fasting rats were randomly divided into four groups (n = 10): G1-normal healthy animals; G2-ZnO-NPs-exposed rats (600 mg/kg-1/day-1); G3-ZnO-NPs-exposed rats co-administrated L-arg (200 mg/kg-1/day-1); G4-ZnO-NPs-exposed rats co-administrated vit E (200 mg/kg-1/day-1). The ingredients were orally administered daily. The body weight and food consumption of rats were recorded during the administration period and the experiment continued for three consecutive weeks. The results demonstrated that ZnO-NPs administration induced bone loss in rats as manifested by reduced activity of bone alkaline phosphatase (B-ALP) and increased level of C-terminal peptide type I collagen (CTx). The increase of inflammatory markers, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by ZnO-NPs suggests that deleterious effects of ZnO-NPs on bone turnover were, in part, due to inflammation. Confirming to this suggestion, both L-arg and vit E reduced TNF-α and IL-6 levels and consequently decreased bone resorption as indicated by reduced serum CTx level. This study proved that ZnO-NPs can induce bone turnover, which may be reduced by L-arg or vit.E co-administration, partly by anti-inflammatory mechanism.

Plectranthus amboinicus attenuates inflammatory bone erosion in mice with collagen-induced arthritis by downregulation of RANKL-induced NFATc1 expression.

OBJECTIVE: Plectranthus amboinicus has been known to treat inflammatory diseases or swelling symptoms. We investigated whether P. amboinicus exhibited an inhibitory effect on osteoclastogenesis in vitro and inflammatory bone erosion in collagen-induced arthritis (CIA) mice, an animal model of rheumatoid arthritis. We attempted to identify the active component of P. amboinicus involved in regulation of osteoclastogenesis. METHODS: We treated M-CSF- and RANKL-stimulated murine bone marrow-derived macrophages (BMM) and RANKL-induced RAW264.7 cells with different concentrations of P. amboinicus or rosmarinic acid, a phytopolyphenol purified from P. amboinicus, to monitor osteoclast formation by TRAP staining. The mechanism of the inhibition was studied by biochemical analysis such as RT-PCR and immunoblotting. CIA mice were administered gavages of P. amboinicus (375 mg/kg) or placebo. Then clinical, histological, and biochemical measures were assessed to determine the effects of P. amboinicus on synovial inflammation and bone erosion by H&E staining of the inflamed joints and ELISA. RESULTS: Rosmarinic acid strongly inhibited RANKL-induced NF-κB activation and nuclear factor of activated T cells c1 (NFATc1) nuclear translocation in BMM, and also inhibited RANKL-induced formation of TRAP-positive multinucleated cells. A pit formation assay and the CIA animal model showed that P. amboinicus significantly inhibited the bone-resorbing activity of mature osteoclasts. CONCLUSION: We postulated that rosmarinic acid conferred the inhibitory activity on P. amboinicus for inhibition of osteoclastogenesis via downregulation of RANKL-induced NFATc1 expression. Our results indicated the possibility of P. amboinicus as a new remedy against inflammatory bone destruction.

Clinical aspects and management of bisphosphonates-associated osteonecrosis of the jaws.

OBJECTIVE: An increasing incidence of osteonecrosis of the jaws (ONJ) in patients treated with intravenous bisphosphonates has been reported in the literature. The aim of this study was to evaluate the clinical aspects, diagnostic investigations, and management of ONJ associated with bisphosphonates in a series of 12 patients. METHOD: Our patients included 1 asymptomatic and 11 symptomatic subjects. For the symptomatic patients, the osteonecrosis was diagnosed through histological investigations of exposed bone that showed avascular and necrotic tissue with inflammatory infiltrate. The patients were complaining of swelling, fever, and bone exposure involving the jaws. The asymptomatic patient presented as an occasional finding during a routine dental examination and the necrosis was confirmed on the basis of imaging investigations. Radiographic, scintigraphic, and microbiological examinations were carried out for all patients. Treatment included antibiotics, minor surgical interventions, and hyperbaric oxygen therapy. RESULTS: The radiological investigations revealed osteolytic areas and the scintigraphy demonstrated increased bone metabolism. The microbiological analysis showed pathogenic micro-organisms in the majority of patients. Therapy was useful in obtaining short-term symptomatic relief. CONCLUSIONS: Histological, radiological, nuclear medicine, and microbiological investigations are important diagnostic tools for patients with bisphosphonates-associated osteonecrosis of the jaws. However, a long-term follow-up is necessary if we are to better understand the treatment outcome.

A comparison of tissue reactions to Ketac-Fil and amalgam.

The objective of this study was to compare the bone tissue reactions of Ketac-Fil to the most commonly used retrograde filling material, amalgam, in a rat model. Forty-eight Harlan rats were divided into three groups: amalgam, Ketac-Fil, and controls. Following anesthesia, the right lower incisor was extracted from each animal. A 3-mm long x 1-mm diameter polyethylene tube filled with amalgam or Ketac-Fil was implanted in the extraction site. The animals were killed at 14, 42, and 90 days; and the mandibles were dissected en block and processed histologically. The inflammatory reaction was assessed by the number of plasma cells, lymphocytes, polymorphonuclear neutrophils, giant cells, and osteoclasts within 100 microns of the implant. Bone formation was determined as either present or absent in the same area. There was no statistically significant bone apposition within 100 microns of the Ketac material, and there was a statistically significant increase in inflammation in the amalgam group. This study indicates that both Ketac-Fil and amalgam are relatively biocompatible, and provides support for clinical usage tests of Ketac-Fil as a retrograde filling material.

Osseous reaction to implanted ZOE retrograde filling materials in the tibia of rats.

The osseous reaction of IRM and EBA cement were studied utilizing an intraosseous implant technique in rats. Samples of IRM, EBA cement, and amalgam were placed into polyethylene tubes and subsequently introduced surgically into rat tibias. Specimens of each were evaluated histologically after 7, 14, 21, 56, and 100 days. The IRM and amalgam samples demonstrated essentially complete healing at 56 days. The EBA cement samples displayed a slightly greater inflammatory response up to the 56-day interval; however, they also showed complete healing by 100 days. A favorable osseous reaction was seen with both of these zinc oxide-eugenol materials.