Mandibular osteomyelitis due to Raoultella species.

INTRODUCTION: Raoultella is a genus of aerobic Gram-negative bacilli belonging to the family Enterobacteriaceae that are commonly found in water, soil and aquatic environments. With improved bacterial identification techniques, Raoultella species (namely R. planticola and R. ornithinolytica) have been an increasingly reported cause of infections in humans. CASE PRESENTATION: An 85-year-old man presented to hospital with a several-week history of left jaw pain and trismus. His medical history was significant for left mandibular osteomyelitis treated 1 year previously with amoxicillin-clavulanate. On admission, a computed tomography scan demonstrated a 2.6×1.7×1.6 cm peripherally enhancing collection surrounding the left posterior mandibular body. Two aspirates of the abscess grew a bacterium belonging to the genus Raoultella, with discordant species identification (R. ornithinolytica versus R. planticola) using two different techniques. A potential source of infection included a left lower molar tooth which was extracted months preceding the original diagnosis of osteomyelitis. CONCLUSION: This is the first case of mandibular osteomyelitis caused by Raoultella species reported in the literature. In contrast to other forms of osteomyelitis, the pathogenesis of mandibular osteomyelitis involves contiguous spread from an odontogenic focus. Risk factors for mandibular osteomyelitis include a history of fracture, irradiation, diabetes and steroid therapy. This report adds to the growing literature of infections caused by this genus of bacteria, and raises the possibility of this organism's role in odontogenic infections.

Combination Therapy with Tenofovir Disoproxil Fumarate/Emtricitabine/Elvitegravir/Cobicistat Plus Darunavir Once Daily in Antiretroviral-Naive and Treatment-Experienced Patients: A Retrospective Review.

BACKGROUND: Patients with drug-resistant HIV often require complex antiretroviral regimens. However, combining fixed-dose combination tablets such as tenofovir-disoproxil-fumarate, emtricitabine, and cobicistat-boosted elvitegravir (TDF/FTC/EVG/cobi) with darunavir (DRV) can provide a simple, once-daily (QD), 2-tablet regimen for patients with drug-resistant HIV. Primary objective was to determine the percentage of patients with HIV-1 RNA <40 copies/mL at 48 weeks. METHODS: We performed a retrospective chart review of patients initiated on TDF/FTC/EVG/cobi plus DRV. RESULTS: Among the 21 included patients, prior resistance showed a median of 2 nucleoside reverse transcriptase inhibitor mutations, 1 nonnucleoside reverse transcriptase mutation, and 1 protease inhibitor mutation. At week 48, 14 (67%) patients achieved HIV-1 RNA <40 copies/mL, 1 patient experienced viral rebound, and 6 (29%) had missing data or discontinued therapy. No patient discontinued for adverse events. CONCLUSION: According to this observational study, QD TDF/FTC/EVG/cobi plus DRV is considered safe, well tolerated, and generally effective in suppressing HIV drug-resistant virus.

New perspectives of infections in cardiovascular disease.

Infections have been recognized as significant causes of cardiac diseases for many decades. Various microorganisms have been implicated in the etiology of these diseases involving all classes of microbial agents. All components of the heart structure can be affected by infectious agents, i.e. pericardium, myocardium, endocardium, valves, autonomic nervous system, and some evidence of coronary arteries. A new breed of infections have evolved over the past three decades involving cardiac implants and this group of cardiac infectious complications will likely continue to increase in the future, as more mechanical devices are implanted in the growing ageing population. This article will review the progress made in the past decade on understanding the pathobiology of these infectious complications of the heart, through advances in genomics and proteomics, as well as potential novel approach for therapy.An up-to-date, state-of-the-art review and controversies will be outlined for the following conditions: (i) perimyocarditis; (ii) infective endocarditis; (iii) cardiac device infections; (iv) coronary artery disease and potential role of infections.

Disseminated fungal infection in a renal transplant recipient involving Macrophomina phaseolina and Scytalidium dimidiatum: case report and review of taxonomic changes among medically important members of the Botryosphaeriaceae.

We report the first case of human infection with the fungal plant pathogen Macrophomina phaseolina in a Sri Lankan-born Canadian man following a renal transplant in India. The patient subsequently succumbed to invasive infection with Scytalidium dimidiatum. Molecular sequence analysis confirmed the identification of both fungi and revealed that they are related species within the ascomycete family Botryosphaeriaceae. We review the rationale for the recent reclassification of S. dimidiatum as Neoscytalidium dimidiatum and of Nattrassia mangiferae (formerly considered a synanamorph of S. dimidiatum) as Neofusicoccum mangiferae. This and other recent cases illustrate the potential for plant pathogenic fungi to cause invasive human diseases which are refractory to antifungal therapy.

An outbreak of foodborne botulism in Ontario.

Botulism is a rare paralytic illness resulting from a potent neurotoxin produced by Clostridium botulinum. Botulism in Canada is predominately due to C botulinum type E and affects mainly the First Nations and Inuit populations. The most recent outbreak of botulism in Ontario was in Ottawa in 1991 and was caused by C botulinum type A. We report an outbreak of foodborne type B botulism in Ontario, which implicated home-canned tomatoes. The outbreak was characterized by mild symptoms in two cases and moderately severe illness in one case. The investigation shows the importance of considering the diagnosis of botulism in patients presenting with cranial nerve and autonomic dysfunction, especially when combined with gastrointestinal complaints; it also highlights the importance of proper home canning technique.

Successful discontinuation of therapy for disseminated Mycobacterium avium complex infection after effective antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) is associated with improvement or resolution of several HIV-associated opportunistic infections. Although prophylaxis against disseminated Mycobacterium avium complex infection may be successfully discontinued after a favorable response to HAART, the 1999 guidelines from the U.S. Public Health Service/Infectious Diseases Society of America recommend continuing therapy for disseminated M. avium complex infection, regardless of the response to HAART. OBJECTIVE: To examine the outcome among patients with disseminated M. avium complex infection whose antimycobacterial therapy was discontinued after a favorable response to HAART. DESIGN: Retrospective chart review between May 2000 and May 2001. SETTING: 13 Canadian HIV clinics. PATIENTS: 52 HIV-infected adults (43 men; mean age, 37.3 years) in whom successful antimycobacterial therapy for disseminated M. avium complex infection was discontinued after a favorable virologic response to HAART. MEASUREMENTS: Survival, survival free of disseminated M. avium complex infection, and CD4(+) cell count responses. RESULTS: At the time of diagnosis of disseminated M. avium complex infection, the median CD4(+) cell count was 0.016 x 10(9) cells/L, and the median plasma HIV RNA level was 90 000 copies/mL (plasma HIV RNA levels were available for only 21 patients). The patients received a median of 32 months of antimycobacterial therapy that included ethambutol plus either clarithromycin or azithromycin. When antimycobacterial therapy was discontinued, the median CD4(+) cell count was 0.23 x 10(9) cells/L and the median plasma HIV RNA level was less than 50 copies/mL. A median of 20 months after discontinuation of antimycobacterial therapy, only 1 patient had developed recurrent M. avium complex disease (37 months after stopping antimycobacterial therapy). This patient had stopped HAART 2 months earlier because of uncontrolled HIV viremia. Twenty months after stopping antimycobacterial therapy, the other 51 patients had a median CD4(+) cell count of 0.288 x 10(9) cells/L; 34 (67%) had undetectable plasma HIV RNA levels, and 8 (15%) had plasma HIV RNA levels of 50 to 1000 copies/mL. CONCLUSIONS: Discontinuation of successful disseminated M. avium complex therapy after a successful response to HAART is safe and reduces patients' pill burdens, potential drug adverse effects, drug interactions, and costs of therapy.

Chlamydial heat-shock protein-60 antibody and correlation with Chlamydia pneumoniae in atherosclerotic plaques.

A study was performed to determine whether serum antibody to Chlamydial heat-shock protein-60 (CHSP-60) and C-reactive protein (CRP) were associated with the presence of Chlamydia pneumoniae in atheromatous plaques in 75 patients. The mean (+/-SD) ELISA optical density (OD) of anti-CHSP-60 was 0.19+/-0.15 in 54 patients with detectable C. pneumoniae antigen, versus an OD of 0.11+/-0.08 in 21 patients without detectable C. pneumoniae I antigen (P=.008). Higher anti-CHSP-60 at an OD > or =0.12 was present in 38 (70.4%) of patients with detectable C. pneumoniae in atheromas, compared with 5 (23.8%) of patients without C. pneumoniae antigen (P<.001; 2-tailed test). The mean CRP concentration was 7.4+/-10.3 mg/L in patients with detectable C. pneumoniae antigen, versus 5.7+/-6.1 mg/L in those without (P=.556). Immune response to CHSP-60 may play a role in atherogenesis, but CRP serum levels does not appear to be related to C. pneumoniae infection.

Influence of clarithromycin on early atherosclerotic lesions after Chlamydia pneumoniae infection in a rabbit model.

Chlamydia pneumoniae may play a role in atherogenesis and vascular diseases, and antibiotics may prove useful in these conditions. Three groups of New Zealand White rabbits (24 per group) were infected via the nasopharynx with C. pneumoniae on three separate occasions (2 weeks apart). Group I was untreated and sacrificed at 12 weeks; group II received clarithromycin at 20 mg/kg/day for 8 days, beginning 5 days after each inoculation (early treatment); and group III received a similar dose of clarithromycin starting 2 weeks after the third inoculation and continued for 6 weeks thereafter (delayed treatment). To test for a possible anti-inflammatory effect of clarithromycin, two other groups of uninfected rabbits (12 animals in each) were fed 0.5% cholesterol-enriched chow, and one of these groups was treated with clarithromycin at 30 mg/kg/day for 6 weeks. Of 23 untreated infected rabbits, 8 developed early lesions of atherosclerosis, whereas 2 of the 24 early-treated group II had similar changes (P = 0.036 [75% efficacy]). However, in the delayed-treatment group, group III, 3 of 24 rabbits developed early lesions of atherosclerosis, thus demonstrating 62.5% reduction compared to the untreated controls (P = 0.07 [trend to statistical significance]). C. pneumoniae antigen was detected in 8 of 23 group I (untreated) rabbits versus 1 of 24 of the early-treated (group II) rabbits and 4 of 24 animals in the delayed group III (P = 0.009 and 0.138, respectively). All of the untreated, cholesterol-fed rabbits had moderate to advanced atherosclerosis (grade III or IV); clarithromycin had no effect on reducing the prevalence of but did reduce the extent of atherosclerosis in the cholesterol-fed rabbits by 17% compared to untreated controls. Thus, clarithromycin administration modified C. pneumoniae-induced atherosclerotic lesions and reduced the ability to detect organism in tissue. Early treatment was more effective than delayed treatment.

Infections and their role in atherosclerotic vascular disease.

BACKGROUND: Complications of atherosclerosis are the leading cause of mortality in developed countries, and infections may play a role in the pathogenesis. Numerous studies have addressed this issue in the past decade. TYPES OF STUDIES REVIEWED: The author examined peer-reviewed studies and reviews on the role of microbes or infections in atherosclerosis, cardiovascular disease and cerebrovascular disease. He included selected articles on epidemiology, pathology, in vitro experiments, animal models and clinical studies. RESULTS: Cross-sectional and retrospective studies have shown an association between Chlamydia pneumoniae antibodies and cardiovascular disease, but prospective studies have not been as convincing. Studies on the association between cardiovascular disease and periodontal disease or loss of teeth have produced conflicting results. Cytomegalovirus infection is associated mainly with accelerated arteriosclerosis after cardiac transplantation. Infectious agents can induce biological mechanisms important for atherogenesis. Mice and rabbit studies have indicated that C. pneumoniae is capable of initiating or accelerating the progression of atherosclerosis. Limited studies on cytomegalovirus also suggest the ability to induce early changes of atherosclerosis in a rodent model. Preliminary clinical trials of treatment for C. pneumoniae infection suggest a possible short-term benefit, but larger randomized trials for longer periods are in progress. CONCLUSION AND CLINICAL IMPLICATIONS: Infectious agents may play an important role in atherogenesis, but currently the jury is not in. Further management of cardiovascular disease could change radically if this concept were proven.

Chlamydia pneumoniae infection of endothelial cells induces transcriptional activation of platelet-derived growth factor-B: a potential link to intimal thickening in a rabbit model of atherosclerosis.

Smooth muscle cell (SMC) proliferation and intimal thickening are hallmark features of atherosclerotic disease, and Chlamydia pneumoniae may contribute to atherogenesis by imparting biological effects on SMCs. An in vitro endothelial cell model and a normocholesterolemic rabbit model were used to test the hypothesis that infection with C. pneumoniae induces SMC growth factor production, SMC proliferation, and aortic intimal thickening. Using reverse-transcriptase polymerase chain reaction, it was demonstrated that C. pneumoniae infection of endothelial cells induced platelet-derived growth factor (PDGF)-B messenger RNA expression. In C. pneumoniae-infected rabbits, maximum intimal thickness (MIT) was significantly greater than that in uninfected animals (P< .0001). MIT correlated with the presence of C. pneumoniae antigen (P= .043) and PDGF-B (P= .002) in aortic tissues, and C. pneumoniae antigen was independently correlated with the presence of PDGF-B in aortic tissues (P= .009). These results suggest that C. pneumoniae-induced SMC proliferation and intimal thickening may be mediated through PDGF-B and may be a molecular mechanism by which C. pneumoniae infection could contribute to atherogenesis.