Temocillin (6 g daily) given by continuous infusion allows a larger proportion of critically ill patients to have free drug serum concentrations covering infections caused by Enterobacteriaceae with an MIC of 16 mg/L compared with administration three times daily. Clinical efficacy compared with carbapenems in documented severe infections needs to be further studied.
Clinical and microbiological efficacies of temocillin are unaffected by ESBL/dAmpC production, confirming its potential application as a carbapenem-sparing agent. Both CCR and MCR are optimized by a regimen of 2 g twice daily ORAE in ESBL/dAmpC-positive infection.
Background. Listeria monocytogenes tends to survive in phagocytes. Granulocyte macrophage colony-stimulating factor (GM-CSF) protects mice against L. monocytogenes infection, and mice knocked out for the GM-CSF gene are more susceptible to these infections.Methods. THP-1 cells were used to characterize the GM-CSF receptor (binding isotherms; STAT5 phosphorylation), measure the intracellular growth of L. monocytogenes (5 h after phagocytosis), examine the influence of a 24-h incubation with GM-CSF before infection, measure the production of tumor necrosis factor (TNF)-a and the expression of nitric oxide synthase (iNOS), and evaluate the influence of anti-GM-CSF receptor (GMCSFRa) and anti-TNF-a antibodies and the addition of N q -nitro-L-arginine methyl ester (L-NAME) and catalase.Results. THP-1 cells display functional GM-CSFRa. GM-CSF impairs the intracellular growth of L. monocytogenes to ∼65% of its value in unstimulated cells. This effect is abolished by anti-GM-CSFRa, anti-TNF-a antibodies, and catalase (and, to a lesser extent, by L-NAME). GM-CSF stimulates the release of TNF-a and the expression of iNOS. TNF-a added to unstimulated cells (even in large amounts) does not fully reproduce the impairment in the growth of L. monocytogenes caused by GM-CSF.Conclusions. GM-CSF impairs the intracellular growth of L. monocytogenes by a synergistic action of the GM-CSF-triggered release of autocrine TNF-a and hydrogen peroxide and the production of NO (associated with the stimulation of the expression of iNOS).
The pathogenicity of Listeria monocytogenes is related to its ability of invading and multiplying in eukaryotic cells. Its main virulence factors are now well characterized, but limited proteomic data is available concerning its adaptation to the intracellular environment. In this study, L. monocytogenes EGD (serotype 1/2a) grown in human THP-1 monocytes (24 h) were successfully separated from host organelles and cytosolic proteins by differential and isopycnic centrifugation. For control, we used cell homogenates spiked with bacteria grown in broth. Proteomes from both forms of bacteria were compared using a 2-D-DIGE approach followed by MALDI-TOF analysis to identify proteins. From 1684 distinct spots, 448 were identified corresponding to 245 distinct proteins with no apparent contamination of host proteins. Amongst them, 61 show underexpression (stress defense; transport systems, carbon metabolism, pyrimidines synthesis, D-Ala-D-Ala ligase) and 22 an overexpression (enzymes involved in the synthesis of cell envelope lipids, glyceraldehyde-3-phosphate, pyruvate and fatty acids). Our proteomic analysis of intracellular L. monocytogenes (i) suggests that bacteria thrive in a more favorable environment than extracellularly, (ii) supports the concept of metabolic adaptation of bacteria to intracellular environment and (iii) may be at the basis of improved anti-Listeria therapy.
A formulary decision was made at a large provider of acute hospital services in Surrey to replace piperacillin/tazobactam with amoxicillin+temocillin for the empiric treatment of severe hospital-acquired pneumonia. This decision was made because the use of broad-spectrum-β-lactam antibiotics is a known risk factor for Clostridium difficile infection (CDI) and for the selection of resistance. After the antibiotic formulary was changed, a retrospective audit was conducted to assess the effect of this change. Data from patients hospitalised between January 2011 and July 2012 for severe hospital-acquired pneumonia and treated empirically with piperacillin/tazobactam or amoxicillin+temocillin were reviewed retrospectively. Clinical characteristics of patients, data related to the episode of pneumonia, clinical success and incidence of significant diarrhoea and CDI were analysed. One hundred ninety-two episodes of severe hospital-acquired pneumonia in 188 patients were identified from hospital records. Ninety-eight patients received piperacillin/tazobactam and 94 amoxicillin+temocillin. At baseline, the two treatment groups were comparable, except that more patients with renal insufficiency were treated with piperacillin/tazobactam. Clinical success was comparable (80 versus 82 %; P = 0.86), but differences were observed between piperacillin/tazobactam and amoxicillin+temocillin for the rates of significant diarrhoea (34 versus 4 %, respectively; P < 0.0001) and for CDI (7 versus 0 %, respectively; P < 0.0028). This preliminary study suggests that the combination amoxicillin+temocillin is a viable alternative to piperacillin/tazobactam for the treatment of severe hospital-acquired pneumonia. This combination appears to be associated with fewer gastrointestinal adverse events. Further studies are needed to evaluate the place of amoxicillin+temocillin as empiric treatment of severe hospital-acquired pneumonia.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.