Elexacaftor-Tezacaftor-Ivacaftor corrects monocyte microbicidal deficiency in cystic fibrosis

Question. Cystic Fibrosis (CF), which is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), is characterized by chronic bacterial lung infection and inflammation. In CF, monocytes and monocyte-derived macrophages have been shown to display defective phagocytosis and antimicrobial activity against relevant lung pathogens, including Pseudomonas aeruginosa. Thus, we addressed the effect of the CFTR triple modulator therapy, Elexacaftor/Tezacaftor/Ivacaftor (ETI), on the activity of CF monocytes against P. aeruginosa. Materials/patients and Methods Monocytes from people with CF (PWCF) before and after 1 and 6 months of ETI therapy were isolated from blood and infected with P. aeruginosa to assess phagocytic activity and intracellular bacterial killing. The oxidative burst and IL-6 secretion were also determined. Monocytes from healthy controls were also included. Results and answer to the question Longitudinal analysis of the clinical parameters confirmed an improvement of lung function and lung microbiology by ETI. Both the phagocytic and microbicidal deficiencies of the CF monocytes also improved significantly, although not completely. Furthermore, we measured an exuberant oxidative burst in CF monocytes before therapy, which was reduced considerably by ETI. This led to an improvement of the ROS-dependent bactericidal activity. Inflammatory response to bacterial stimuli was also lowered compared to pre-therapy. PWCF on ETI therapy, in a real-life setting, in addition to clinical recovery, showed significant improvement in monocyte activity against P. aeruginosa, which may have contributed to the overall effect of ETI on pulmonary disease. This also suggests that CF monocyte dysfunctions may be specifically targeted to ameliorate lung function in CF

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Changes in susceptibilities to teicoplanin, vancomycin and other antibiotics among Staphylococcus aureus isolates in a tertiary-care University hospital.

Changes in antibiotics susceptibilities were evaluated among 374 nosocomial clinical isolates of Staphylococcus aureus collected from 1986 to 1994 in a tertiary-care University hospital where methicillin-resistant S. aureus (MRSA) is an increasing cause of infection. Significant increases in resistance to ciprofloxacin, clindamycin and rifampicin were observed among MRSA isolates in recent years. No resistance to glycopeptides was observed. However, during the last 2 years a significant trend towards a decreasing susceptibility to teicoplanin was observed among MRSA isolates

In vitro activity of fosfomycin in combination with vancomycin or teicoplanin against Staphylococcus aureus isolated from device-associated infections unresponsive to glycopeptide therapy

Fosfomycin is a molecule that inhibits the early stage of peptidoglycan synthesis and shows a broad-spectrum bactericidal activity against Gram-positive and Gram-negative bacteria. Using the Killing-curve method, we tested the in vitro bactericidal activity of fosfomycin alone or in combination with vancomycin or teicoplanin at a concentration of 8 microg/mL, that is easily achievable in serum at standard dosing regimens, against seven methicillin-resistant Staphylococcus aureus strains, isolated from patients with well documented device-associated infections unresponsive to or relapsing after glycopeptide therapy. MICs of vancomycin ranged from 1 to 4 microg/mL, MICs of teicoplanin from 2 to 8 microg/mL; MICs of fosfomycin were 8 microg/mL for two strains and >128 microg/mL for the remaining strains. The seven strains proved tolerant when tested for vancomycin and teicoplanin used alone at 2x MIC concentration. Fosfomycin was bactericidal (reduction of 2 log of the inoculum) only against the two susceptible strains. In all cases both vancomycin and teicoplanin in combination with fosfomycin developed bactericidal synergism already at a concentration of 1x MIC. If these results are confirmed by in vivo experiments, the combination of fosfomycin with glycopeptides might be useful for treating device-associated infections, and in preventing the phenomenon of increasing MICs for glycopeptides

In vitro activity of fosfomycin in combination with vancomycin or teicoplanin against Staphylococcus aureus isolated from device-associated infections unresponsive to glycopeptide therapy

Fosfomycin is a molecule that inhibits the early stage of peptidoglycan synthesis and shows a broad-spectrum bactericidal activity against Gram-positive and Gram-negative bacteria. Using the Killing-curve method, we tested the in vitro bactericidal activity of fosfomycin alone or in combination with vancomycin or teicoplanin at a concentration of 8 microg/mL, that is easily achievable in serum at standard dosing regimens, against seven methicillin-resistant Staphylococcus aureus strains, isolated from patients with well documented device-associated infections unresponsive to or relapsing after glycopeptide therapy. MICs of vancomycin ranged from 1 to 4 microg/mL, MICs of teicoplanin from 2 to 8 microg/mL; MICs of fosfomycin were 8 microg/mL for two strains and >128 microg/mL for the remaining strains. The seven strains proved tolerant when tested for vancomycin and teicoplanin used alone at 2x MIC concentration. Fosfomycin was bactericidal (reduction of 2 log of the inoculum) only against the two susceptible strains. In all cases both vancomycin and teicoplanin in combination with fosfomycin developed bactericidal synergism already at a concentration of 1x MIC. If these results are confirmed by in vivo experiments, the combination of fosfomycin with glycopeptides might be useful for treating device-associated infections, and in preventing the phenomenon of increasing MICs for glycopeptides

Ethylene oxide sterilization of autologous bone flaps following decompressive craniectomy.

In patients undergoing decompressive craniectomy, the bone flap is temporarily preserved either in the subcutaneous tissue of the patient or frozen. However, there are some drawbacks related to these methods. In 16 patients in whom the bone flap was removed for decompressive craniectomy, the bone was firstly washed in hydrogen peroxide and then placed in hermetically-sealed bags and sterilized using ethylene oxide. The bone was repositioned after an average period of 4.3 months. One patient sustained an infection of the surgical wound which required permanent exclusion of the bone flap. In all the others, esthetic and functional results were good after an average follow-up of 20 months. Control CT-scan of the bone flap demonstrated preservation of its structural features with fusion of the bone margins and revitalization of the flap. On MRI a subdural space was again visible. Sterilization of the bone flap with ethylene oxide in patients undergoing decompressive craniectomy avoids some of the drawbacks related to the techniques currently used. The easiness, low cost, good aesthetic and functional results of this procedure make it a valid alternative to other techniques for preservation of autologous bone in decompressive craniectomies