TNF Blockers Get Boxed Warning on 2 Bacterial InfectionsTNF Blockers Get Boxed Warning on 2 Bacterial Infections

A recent FDA review of the drug class, prescribed for various forms of arthritis and other disorders, uncovered serious and sometimes fatal infections by Legionella and Listeria. Medscape Medical News (Source: Medscape Today Headlines)

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Bacterial and fungal microflora in surgically removed lung cancer samples

Conclusions:A diversity of pathogens could be identified in surgically extracted tissue samples of patients with lung cancer, with mycoplasma strains being present in all samples. These results point to an etiologic role for chronic infection in lung carcinogenesis. Confirmation of these observations and additional studies are needed to further characterize the etiologic role of inflammation in lung carcinogenesis. (Source: Journal of Cardiothoracic Surgery)

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In Vitro and In Vivo Profile of ACH-702, an Isothiazoloquinolone, against Bacterial Pathogens.

Authors: Pucci MJ, Podos SD, Thanassi JA, Leggio MJ, Bradbury BJ, Deshpande M ACH-702, a novel isothiazoloquinolone, was assessed for antibacterial activity against a panel of gram-positive and gram-negative clinical isolates and found to possess broad-spectrum activity, especially against antibiotic-resistant gram-positive strains including methicillin-resistant Staphylococcus aureus (MRSA). For gram-negative bacteria, ACH-702 showed exceptional potency against Haemophilus influenzae, Moraxella catarrhalis, and Neisseria sp., but was less active against members of the Enterobacteriaceae. Good antibacterial activity was also evident against several anaerobes as well as Legionella pneumophila and Mycoplasma pneumoniae. Excellent bactericidal activity was observed for ACH-702 against sev...

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Profile of bacterial pneumonia during Hajj.

This study was aimed to determine the most common causes of bacterial pneumonia during the 2005 Hajj season and to relate the findings with clinical conditions. Methods : A total of 141 patients with suspected pneumonia from the three main tertiary care hospitals in Makkah, Saudi Arabia, were investigated during Hajj season, 2005. Sputum and serum samples were collected and investigated for the possible presence of typical or atypical causative agents. Results : Of the 141 clinically suspected pneumonia cases, 76 (53.9%) were confirmed positive by microbiological tests. More than 94 per cent of the confirmed cases were in the age group >50 yr, and 56.6 per cent of the cases were men. The most frequent isolates were Candida albicans (28.7%) and Pseudomonas aeruginosa (21.8%), followed by...

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Anchoring of bacterial effectors to host membranes through host-mediated lipidation by prenylation: a common paradigm.

Authors: Al-Quadan T, Price CT, London N, Schueler-Furman O, Abukwaik Y Abstract Post-translational lipidation by prenylation of the CaaX-box C-terminal motif in eukaryotic proteins facilitates anchoring of hydrophilic proteins, such as Ras and Rab, to membranes. A large cadre of bacterial effectors injected into host cells is anchored to host membranes by unknown mechanisms. As already documented for Legionella and Salmonella, we propose a common paradigm of microbial exploitation of the host prenylation machinery for anchoring of injected effectors to host membranes. This is supported by numerous potential microbial CaaX-box-containing proteins identified using refined bioinformatic tools. We also propose utilization of the CaaX motif as a membrane-targeting tag for proteins expr...

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In Vitro and In Vivo Profile of ACH-702, an Isothiazoloquinolone, against Bacterial Pathogens.

Achillion Pharmaceuticals, New Haven, CT 06511.

ACH-702, a novel isothiazoloquinolone, was assessed for antibacterial activity against a panel of gram-positive and gram-negative clinical isolates and found to possess broad-spectrum activity, especially against antibiotic-resistant gram-positive strains including methicillin-resistant Staphylococcus aureus (MRSA). For gram-negative bacteria, ACH-702 showed exceptional potency against Haemophilus influenzae, Moraxella catarrhalis, and Neisseria sp., but was less active against members of the Enterobacteriaceae. Good antibacterial activity was also evident against several anaerobes as well as Legionella pneumophila and Mycoplasma pneumoniae. Excellent bactericidal activity was observed for ACH-702 against several bacterial pathogens in time-kill assays and postantibiotic effects (PAEs) >1 h were evident in both laboratory and clinical strains of staphylococci at 10x MIC, similar in most cases to those observed for moxifloxacin at the same MIC multiple. In vivo efficacy was demonstrated against S. aureus in murine sepsis and thigh infection models with decreases in CFU/thigh equal to or greater than those observed after vancomycin treatment. Macromolecular synthesis assays showed specific dose-dependent inhibition of DNA replication in staphylococci and biochemical analyses indicated potent dual inhibition of two essential DNA replication enzymes: DNA gyrase and topoisomerase IV. Additional biological data in support of an effective dual targeting mechanism-of-action include: low MIC values (=0.25 µg/ml) against staphylococcal strains with single mutations in both gyrA and grlA (parC), retention of good antibacterial activity (MICs =0.5 µg/ml) against staphylococcal strains with two mutations in both gyrA and grlA, and low frequencies for selection of higher-level resistance (<10(-10)). These promising initial data support further study of isothiazoloquinolones as potential clinical candidates.

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