[Infectious myositis]. / Myosites infectieuses.

Infectious myositis is a rare condition that can be caused by bacteria, viruses, parasites or fungi. Muscle pain or weakness are symptoms shared by all type of myositis. Diagnosis is made on clinical presentation: fever and poor general state is found in bacterial myositis, diffuse muscle pain with flu-like symptoms in viral causes, eosinophilia and a tropical travel history can be related to parasitic etiology, and immunocompromising condition suggests fungal infection. Rhabdomyolysis, leukocytosis and elevated C-reactive protein are common. Imaging (computed tomography or magnetic resonance imaging) can be useful to detect which muscle is affected. The causative organism can be identified on blood cultures, skeletal muscle biopsy, serology or any other pathogen specific test. Treatment depends on the causative organism. Open surgical or imaging-guided drainage is usually necessary in bacterial myositis.

Evaluation of quantitative PCR for early diagnosis of Pseudomonas aeruginosa infection in cystic fibrosis: a prospective cohort study.

OBJECTIVES: Early detection of Pseudomonas aeruginosa lung positivity is a key element in cystic fibrosis (CF) management. PCR has increased the accuracy of detection of many microorganisms. Clinical relevance of P. aeruginosa quantitative PCR (qPCR) in this context is unclear. Our aim was to determine P. aeruginosa qPCR sensitivity and specificity, and to assess the possible time saved by qPCR in comparison with standard practice (culture). METHODS: A multicentre cohort study was conducted over a 3-year period in 96 patients with CF without chronic P. aeruginosa colonization. Sputum samples were collected at each visit. Conventional culture and two-step qPCR (oprL qPCR and gyrB/ecfX qPCR) were performed for 707 samples. The positivity criteria were based on the qPCR results, defined in a previous study as follow: oprL qPCR positivity alone if bacterial density was <730 CFU/mL or oprL qPCR combined with gyrB/ecfX qPCR if bacterial density was ≥730 CFU/mL. RESULTS: During follow up, 36 of the 96 patients with CF were diagnosed on culture as colonized with P. aeruginosa. This two-step qPCR displayed a sensitivity of 94.3% (95% CI 79.7%-98.6%), and a specificity of 86.3% (95% CI 83.4%-88.7%). It enabled P. aeruginosa acquisition to be diagnosed earlier in 20 patients, providing a median detection time gain of 8 months (interquartile range 3.7-17.6) for them. CONCLUSIONS: Implementing oprL and gyrB/ecfX qPCR in the management of patients with CF allowed earlier detection of first P. aeruginosa lung positivity than culture alone.

Probiotics: a new way to fight bacterial pulmonary infections?

Antibiotics, of which Fleming has identified the first representative, penicillin, in 1928, allowed dramatical improvement of the treatment of patients presenting with infectious diseases. However, once an antibiotic is used, resistance may develop more or less rapidly in some bacteria. It is thus necessary to develop therapeutic alternatives, such as the use of probiotics, defined by the World Health Organization (WHO) as "micro-organisms which, administered live and in adequate amounts, confer a benefit to the health of the host". The scope of these micro-organisms is broad, concerning many areas including that of infectious diseases, especially respiratory infections. We describe the rational use of probiotics in respiratory tract infections and detail the results of various clinical studies describing the use of probiotics in the management of respiratory infections such as nosocomial or community acquired pneumonia, or on specific grounds such as cystic fibrosis. The results are sometimes contradictory, but the therapeutic potential of probiotics seems promising. Implementing research to understand their mechanisms of action is critical to conduct therapeutic tests based on a specific rational for the strains to be used, the dose, as well as the chosen mode and rhythm of administration.

[Kinetics of Pseudomonas aeruginosa virulence gene expression during chronic lung infection in the murine model]. / Cinétique d'expression des gènes de virulence de Pseudomonas aeruginosa au cours d'une infection pulmonaire chronique dans le modèle murin.

UNLABELLED: Pseudomonas aeruginosa is a Gram-negative bacillus frequently encountered in human diseases. P. aeruginosa produces a large number of secreted and cell associated virulence factors. Their production is coordinated by various systems of gene regulation. The correlation and sequential intervention of regulation systems during a pulmonary infection have not been determined yet. OBJECTIVE: The aim of this study was to analyze the expression of three P. aeruginosa virulence genes (exoS, lasI, and algD) during the first seven days of chronic lung infection. To do so, mice were infected intratracheally with agarose beads containing P. aeruginosa. RESULTS: The results were a progressive decrease of exoS transcription and an increase of algD, and lasI transcription during infection. This dynamic evolution was consistent with the clinical observation, which demonstrated a progressive loss of type III secretion system function and an increase in the mucoid phenotype development in P. aeruginosa strains from cystic fibrosis patients. CONCLUSION: The development of a P. aeruginosa pulmonary chronic infection associates a decrease of gene expression related to a type III secretion system and an increase of alginate production.

Quorum-sensing activity and related virulence factor expression in clinically pathogenic isolates of Pseudomonas aeruginosa.

Respiratory isolates of Pseudomonas aeruginosa were collected from 58 critically-ill patients with ventilator-associated pneumonia. Expression of elastase and pyocyanin was assessed semi-quantitatively, while quorum-sensing activity was assessed by quantifying the levels of the autoinducers N-3-oxododecanoyl-L-homoserine lactone (C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL). Correlations were sought between quorum-sensing activity and the expression of these two virulence factors, and all results were compared to those obtained with the laboratory reference strains PA103, a strain defective in quorum-sensing, and PAO1, a functional quorum-sensing strain. More than two-thirds of clinically pathogenic isolates had increased levels of elastase and/or pyocyanin, and high quorum-sensing activity, as assessed by autoinducer levels. However, a strong correlation between quorum-sensing activity and virulence factor production was revealed only for elastase and not for pyocyanin (C12-HSL/elastase, r = 0.7, p 2 x 10(-9); C4-HSL/elastase, r = 0.7, p 2 x 10(-9)). These data suggest that the pathogenicity of P. aeruginosa isolates from critically-ill patients with ventilator-associated pneumonia is caused, at least in part, by an increase in elastase production regulated by quorum-sensing, while increased pyocyanin production in these isolates may be regulated predominantly by mechanisms other than quorum-sensing.

Keratinocyte growth factor improves alterations of lung permeability and bronchial epithelium in allergic rats.

Chronic allergic asthma is associated with marked inflammatory reaction, microvascular leakage and epithelium injury. As previously shown in a rat model of chronic asthma, these alterations increase lung permeability and distal airway fluid clearance. Keratinocyte growth factor (KGF) has been shown to induce epithelial cell proliferation and to protect from acute lung injuries. Therefore, the current authors evaluated the potential role of KGF treatment on lung permeability and airway inflammation in rats with chronic asthma. KGF (1 mg x kg(-1)) was administered intravenously before the last ovalbumin (OVA) challenge in sensitised rats. Permeability was assessed by the leak of radiolabelled albumin from the alveolar and systemic compartments. Histopathological analysis was also performed. Treatment with KGF decreased the leak of both markers and decreased the level of extravascular lung water in sensitised rats challenged with OVA. KGF treatment also reduced the inflammatory cell number in bronchoalveolar lavage fluid but not in bronchial mucosa. KGF markedly limited the allergen-induced alterations in epithelium integrity and the expression of the intercellular junction proteins beta-catenin and zonula occludens protein-1. In conclusion, keratinocyte growth factor administration markedly limits lung permeability and airway inflammation, an effect associated with a decrease in epithelium alterations during chronic allergic asthma. These data open new prospects in the therapeutic strategy of asthma.

[Pneumonia with septicemia caused by Pasteurella multocida in an immunocompetent patient]. / Pneumonie à Pasteurella multocida compliquée de choc septique chez un patient non immunodéprimé

Pneumonia with septicemia caused by Pasteurella multocida was diagnosed in an immunocompetent patient exposed to a dog. This case is remarkable by two aspects: first the absence of visible cutaneous lesion, and second the localization and severity of the infection caused by P. multocida even though the patient was immunocompetent. P. multocida can cause respiratory and systemic infection, and it is a possible diagnosis in case of exposure to animals, even without history of bite or scratch. Furthermore, severe infections caused by this pathogen can occur in immunocompetent patients, so that the implication of specific host factors in the severity of the disease can be suspected. Genetic features could be one of these.

Fulminant Epstein-Barr virus (EBV) hepatitis in a young immunocompetent subject.

We report a case of fulminant hepatitis related to a primary Epstein-Barr virus (EBV) infection in an immunocompetent 15-year-old male patient. The main causes of fulminant hepatitis are viral infections, drugs, and autoimmune diseases. Primary Epstein-Barr virus infection is usually a benign, self-limited disease in pediatrics but can exceptionally be fatal.

[Acute exacerbation of chronic obstructive pulmonary disease and antibiotics: analysis of comparative trials]. / Antibiothérapie des exacerbations de bronchopneumopathie chronique obstructive: analyse critique des essais cliniques.

OBJECTIVE: The authors had for aim to assess the role of antibiotics in acute exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: Comparative antibiotic trials were collected through systematic search on Medline data base--well-designed studies were selected. RESULTS: Eight equivalence studies were selected. No clear difference between antibiotics was demonstrated. The shortest treatment was as effective as the longest. CONCLUSION: No antibiotic has demonstrated its superiority. A new generation of antibiotic comparative trials for exacerbation of COPD is clearly needed.

[Quorum sensing: a new clinical target for Pseudomonas aeruginosa?]. / Quorum sensing: une nouvelle cible thérapeutique pour Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic bacteria causing a wide variety of infections. The bacterial virulence depends on a large panel of cell-associated and extracellular factors. Quorum sensing (QS) allows cell-to-cell communication: sensing the environment, this system coordinates the expression of various genes within the bacterial population. QS is based on an interaction between a small diffusible molecule, an acylhomoserine lactone (AHL), and a transcriptionnal activator. Two QS systems, the las and rhl systems, have been identified in P. aeruginosa. The las system associates the transcriptionnal activator protein LasR and LasI responsible for the synthesis of a specific AHL: C12-HSL. This system was shown to activate the expression of a large number of virulence factors. Similarly, the rhl system associates the transcriptionnal activator protein RhlR with RhlI, which is responsible for the synthesis of another AHL: C4-HSL. Synthesis and secretion of a number of virulence factors are controlled by QS. Utilization of different animals models showed the crucial role of QS in the pathogenesis of P. aeruginosa infections. The discovery of QS has given a new opportunity to treat bacterial infection by another means than growth inhibition. New drugs inhibiting QS were recently discovered: furanone compounds can repress a large number of QS-regulated genes, including numerous P. aeruginosa virulence factor genes. Furanone administration to mice infected with P. aeruginosa significantly reduced lung bacterial load compared with the control group.

Alveolar response to Pseudomonas aeruginosa: role of the type III secretion system.

The type III secretion system (TTSS) is a specialized cytotoxin-translocating apparatus of gram-negative bacteria which is involved in lung injury, septic shock, and a poor patient outcome. Recent studies have attributed these effects mainly to the ExoU effector protein. However, few studies have focused on the ExoU-independent pathogenicity of the TTSS. For the present study, we compared the pathogenicities of two strains of Pseudomonas aeruginosa in a murine model of acute lung injury. We compared the CHA strain, which has a functional TTSS producing ExoS and ExoT but not ExoU, to an isogenic mutant with an inactivated exsA gene, CHA-D1, which does not express the TTSS at all. Rats challenged with CHA had significantly increased lung injury, as assessed by the wet/dry weight ratio for the lungs and the protein level in bronchoalveolar lavage fluid (BALF) at 12 h, compared to those challenged with CHA-D1. Consistent with these findings, the CHA strain was associated with increased in vitro cytotoxicity on A549 cells, as assessed by the release of lactate dehydrogenase. CHA was also associated at 12 h with a major decrease in polymorphonuclear neutrophils in BALF, with a proinflammatory response, as assessed by the amounts of tumor necrosis factor alpha and interleukin-1beta, and with decreased bacterial clearance from the lungs, ultimately leading to an increased mortality rate. These results demonstrate that the TTSS has a major role in P. aeruginosa pathogenicity independent of the role of ExoU. This report underscores the crucial roles of ExoS and ExoT or other TTSS-related virulence factors in addition to ExoU.

[Bacteremia and pneumonia due to Yersinia enterocolitica serotype O:3 in an immunocompetent patient]. / Bactériémie et pneumopathie à Yersinia enterocolitica sérotype O:3 chez un immunocompétent.

The authors report a rare case of Yersinia enterocolitica O:3 pneumonia in an immunocompetent 70-year old man. There was no evidence of acute gastrointestinal disease. Diagnosis was confirmed by blood cultures. He responded with resolution of the infection after 21 days of therapy with a third-generation cephalosporin then by cotrimoxazole. Only 15 cases have been reported so far. Most of the patients were immunocompromised. This is the first case in France.

Invasive pulmonary aspergillosis in chronic obstructive pulmonary disease: an emerging fungal pathogen.

Acute invasive pulmonary aspergillosis occurs predominantly in immunocompromised hosts, with increasing numbers of cases of invasive aspergillosis among patients with chronic obstructive pulmonary disease (COPD) being reported. Among 13 cases of invasive aspergillosis diagnosed in COPD patients admitted to the intensive care unit with acute respiratory distress, the only risk factor for invasive fungal infection was corticosteroid treatment. Invasive aspergillosis should be suspected in COPD patients receiving steroid treatment who have extensive pulmonary infiltrates. Survival depends on rapid diagnosis and early appropriate treatment. A decrease or interruption of steroid treatment should be considered as part of the overall therapeutic strategy.

The WHO Onchocerciasis Control Programme: retrospect and prospects.

The history of onchocerciasis control in Africa and the genesis of the WHO Onchocerciasis Control Programme in West Africa (OCP) are briefly reviewed. The importance of experience gained in anti-locust campaigns in helping to plan the OCP is stressed. Members of the Simulium damnosum species complex are the vectors of onchocerciasis, which OCP is controlling with insecticide treatments on the stretches of rivers where the Simulium breed. Migrations of flies have been responsible for reinfestations of controlled areas and the spread of insecticide resistance. The management of these problems and related research are described, but it is emphasized that despite setbacks OCP is achieving its aims. A strategy for the future is outlined: vector control supplemented by chemotherapy is expected to continue until the year 2004.