Bacterial infection profiles in lung cancer patients with febrile neutropenia

<p>Abstract</p> <p>Background</p> <p>The chemotherapy used to treat lung cancer causes febrile neutropenia in 10 to 40% of patients. Although most episodes are of undetermined origin, an infectious etiology can be suspected in 30% of cases. In view of the scarcity of data on lung cancer patients with febrile neutropenia, we performed a retrospective study of the microbiological characteristics of cases recorded in three medical centers in the Picardy region of northern France.</p> <p>Methods</p> <p>We analyzed the medical records of lung cancer patients with neutropenia (neutrophil count < 500/mm³) and fever (temperature > 38.3°C).</p> <p>Results</p> <p>The study included 87 lung cancer patients with febrile neutropenia (mean age: 64.2). Two thirds of the patients had metastases and half had poor performance status. Thirty-three of the 87 cases were microbiologically documented. Gram-negative bacteria (mainly enterobacteriaceae from the urinary and digestive tracts) were identified in 59% of these cases. <it>Staphylococcus </it>species (mainly <it>S. aureus</it>) accounted for a high proportion of the identified Gram-positive bacteria. Bacteremia accounted for 60% of the microbiologically documented cases of fever. 23% of the blood cultures were positive. 14% of the infections were probably hospital-acquired and 14% were caused by multidrug-resistant strains. The overall mortality rate at day 30 was 33% and the infection-related mortality rate was 16.1%. Treatment with antibiotics was successful in 82.8% of cases. In a multivariate analysis, predictive factors for treatment failure were age >60 and thrombocytopenia < 20000/mm³.</p> <p>Conclusion</p> <p>Gram-negative species were the most frequently identified bacteria in lung cancer patients with febrile neutropenia. Despite the success of antibiotic treatment and a low-risk neutropenic patient group, mortality is high in this particular population.</p

Mise au point d'un test phénotypique basé sur la restauration de la sensibilité au moxalactam par l'EDTA pour l'identification rapide des métallo-b-lactamases chez les entérobactéries

Face à l émergence des b-lactamases à spectre étendu et des céphalosporinases hyperproduites et plasmidiques, l utilisation des carbapénémes s est accentuée favorisant la sélection de souches productrices de carbapénémases. Les métallo-b-lactamases (MBL) telles que NDM-1 sont un enjeu de santé publique en raison de leur caractère transmissible fortement épidémique parmi les entérobactéries. Les recommandations actuelles conseillent de tester la sensibilité aux carbapénèmes pour le screening des souches d entérobactéries sécrétrices de MBL et la mise en œuvre de techniques complémentaires, comme le Hodge test, pour confirmer le résultat. Malheureusement, cette méthode est prise à défaut lorsque le niveau de production de l enzyme est insuffisant pour conférer une résistance aux carbapénèmes. Pour se départir du problème, nous avons développé une nouvelle technique de dépistage basée sur la détermination de la sensibilité au moxalactam. Cette céphamycine présente la particularité d être exclusivement et fortement hydrolysée par les MBL. Nous avons testé le screening des MBL par le moxalactam (MOX) puis par un test de synergie MOX/EDTA utilisant un inhibiteur spécifique des MBL. Tous les transconjuguants et les souches cliniques produisant une MBL apparaissaient résistants au moxalactam. Le test de synergie MOX/EDTA s est révélé positif pour tous les isolats. Ce test de dépistage présente une sensibilité et une spécificité de 100 % pour le dépistage des MBL. Il s agit d une méthode de détection phénotypique peu coûteuse, rapide et facile d interprétation pouvant être utilisée en routine dans tous les laboratoires y compris ceux des pays émergents.The use of carbapenem has increased over the emergence of extended spectrum b-lactamases, thus allowing the selection of carbapenemase-producing clinical isolates. Metallo-b-lactamases (MBL) such as NDM-1 are a major public health problem due to their hight epidemic potential among Enterobacteriaceae. Current recommendations advocate suceptibility testing to carbapenems to screen for MBL producing enterobacterial and to carry out additionnal tests, such as the Hodge test, to confirm the result. Unfortunately, this approach fails to detect carbapenemase production in low-producing enterobacterial isolates. To overcome this lack of sensitivity, we developed a new screening technique based on susceptibility testing to moxalactam. This cephamycin has the pediculiarity to be highly hydrolysed by MBL but classes A, C, D b-lactamases. All MBL producing transconjugants and clinical isolates that were test in our study were resistant to moxalactam, thus confirming the sensitivity of this test. The MOX/EDTA synergy test was positive for all MBL isolates whereas it was negative for all clinical isolates producing KPC, AmpC or OXA-48 b-lactamases which confirms the specificity of this confirmation method. This assay, which is performed with inexpensive reagents, is appropriate for specific MBL identification in countries with limited resources.AMIENS-BU Santé (800212102) / SudocSudocFranceF

[Bronchial carcinoma and intensive care.]

International audienceINTRODUCTION: Lung cancer is a disease with a poor prognosis. Therapeutic innovations in oncology and the optimisation of intensive care patient management have improved the prognosis of lung cancer presenting with acute life-threatening respiratory or cardiac emergencies. OBSERVATION: We reported on the case of a patient with lung cancer presenting with mildly abundant haemoptysis, who was hospitalised in intensive care. After multidisciplinary discussion, the patient was intubated following recurrent haemorrhage that resulted in respiratory failure. The outcome was favourable. Four months later, this patient was still alive and autonomous. DISCUSSION: After years of pessimism, the medical literature has revealed an improvement in lung cancer patients' survival. Respiratory failure and shock are the main reasons for admission to the intensive care unit. The mortality risk factors depend more on acute conditions than on the underlying lung cancer. The patient's admission must be made before multiorgan failure occurs, along with the implementation of non invasive therapies. The use of intensive care as a bridge to overcome an acute event is a possible means of caring for the patient. CONCLUSION: Consideration of the acute event is important when deciding whether to hospitalise a patient with lung cancer in intensive care. An early admission, if indicated, is desirable. The course in the first 72hours provides a good estimation of the patient's prognosis and helps to achieve better treatment

Osteoblastic Reaction in Non-small Cell Lung Carcinoma and its Association to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Response and Prolonged Survival

IntroductionThe aim of this study was to describe the characteristics and epidermal growth factor receptor (EGFR) mutational status of patients with non-small cell lung cancer (NSCLC) with osteoblastic reactions diagnosed before or during treatment with EGFR tyrosine kinase inhibitors (TKIs).MethodsRetrospective study including patients with 36 NSCLC with at least one site of osteoblastic reaction at the time of diagnosis or during treatment with EGFR-TKI.ResultsThe rate of patients with mutated EGFR tumors with osteoblastic reactions before or after EGFR-TKI treatment was similar. Median progression-free survival (PFS) for the entire group was more than 9 months and median survival was more than 12 months. There was no statistically significant difference in survival between patients with osteoblastic reactions before initiation of TKI and those diagnosed during TKI treatment. Patients with extraosseous metastases when treated with TKI had the lowest survival (P < 0.0001).ConclusionsIn patients with NSCLC treated with TKI, initial or development of an osteoblastic reaction seems to be related to a more favorable outcome. In patients with osteoblastic reactions, tumors present with clinical and biologic characteristics of better survival and response to TKI. The occurrence of osteoblastic reactions during treatment with TKI, while primary tumor and metastases are stable or in response, should not be considered as disease progression

Senescence Induced by UVB in Keratinocytes Impairs Amino Acids Balance

Skin is one of the most exposed organs to external stress. Namely, UV rays are the most harmful stress that could induce important damage leading to skin aging and cancers. At the cellular level, senescence is observed in several skin cell types and contributes to skin aging. However, the origin of skin senescent cells is still unclear but is probably related to exposure to stresses. In this work, we developed an in vitro model of UVB-induced premature senescence in normal human epidermal keratinocytes. UVB-induced senescent keratinocytes display a common senescent phenotype resulting in an irreversible cell cycle arrest, an increase in the proportion of senescence-associated β-galactosidase‒positive cells, unrepaired DNA damage, and a long-term DNA damage response activation. Moreover, UVB-induced senescent keratinocytes secrete senescence-associated secretory phenotype factors that influence cutaneous squamous cell carcinoma cell migration. Finally, a global transcriptomic study highlighted that senescent keratinocytes present a decrease in the expression of several amino acid transporters, which is associated with reduced intracellular levels of glycine, alanine, and leucine. Interestingly, the chemical inhibition of the glycine transporter SLC6A9/Glyt1 triggers senescence features.</p

Sensitive and Specific Phenotypic Assay for Metallo-β-Lactamase Detection in Enterobacteria by Use of a Moxalactam Disk Supplemented with EDTA ▿

Moxalactam is highly hydrolyzed by plasmid-mediated metallo-β-lactamases (MBLs), whereas it is poorly inactivated by serine-active carbapenemases. This study demonstrated that moxalactam resistance constituted an effective screen for MBL expression in enterobacteria, which could be confirmed, even in low-MBL-producing isolates, by a disk potentiation test using moxalactam and EDTA