CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.

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Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.

The detection of lines in emission in planetary atmospheres provides direct evidence of temperature inversion. We confirm the trend of ultra-hot Jupiters orbiting A-type stars that show temperature inversions on their daysides by detecting metals emission lines in the dayside of KELT-20b. We first detected the planetary emission by using the G2 stellar mask of the HARPS-N pipeline, which is mainly composed of neutral iron lines, as a template. Using neutral iron templates, we performed a retrieval of the atmospheric temperature-pressure profile of the planet, confirming a thermal inversion. Then we created models of planetary emission of different species using the retrieved inverted temperature-pressure profile. By using the cross-correlation technique, we detected Fe I, Fe II, and Cr I at signal-to-noise ratio levels of 7.1, 3.9, and 3.6, respectively. The latter was detected in emission in the atmosphere of an exoplanet for the first time. Contrary to Fe I, Fe II and Cr I were detected only after the occultation and not before, hinting at different atmospheric properties in view during the pre- and post-occultation orbital phases. A further retrieval of the temperature-pressure profile performed independently during the pre- and post-occultation phases, while not highly significant, points to a steeper thermal inversion in the post-occultation.

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The renewed interest in testing synergistic interactions of antimicrobial agents is mainly related to the challenge of antimicrobial resistance. Whereas time-kill curves and checkerboard methods represent the reference tests for screening synergy, the E-test with strips in a cross formation might be an interesting alternative, but requires that minimum inhibitory concentrations (MICs) of antibiotics have been previously determined [1]. However, agreement between the different tests seems to be quite variable [1]. To be clinically useful, a synergy test should be rapid and easily interpretable.We evaluated the synergistic activity of colistin (COL) plus rifampin (RIF) against 10 clinical isolates of COL-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) comparing the checkerboard method with the E-test on Mueller-Hinton agar, alone or supplemented with RIF. The 10 tested strains resulted in KPC3 production by polymerase chain reaction and Sequence Type (ST) 512 by multilocus sequence typing (MLST) analysis (http://www.pasteur.fr/recherche/ genopole/PF8/mlst/Kpneumoniae.html). COL MICs for the checkerboard method were determined with broth microdilution in Mueller-Hinton broth alone and supplemented with RIF at the final concentration of 2, 4, 8, 16 and 32 mg/L in 96-well microtiter plates. COL MICs also were determined with the E-test method on Mueller-Hinton agar alone or supplemented with RIF at the final concentration of 2, 4, 8, 16 and 32 mg/L in Petri dishes (Fig. 1).According to the 2014 EUCAST Clinical Breakpoints, COL resistance was defined by MIC > 2 mg/L. With the checkerboard method, COL MICs for the 10 strains were 64 mg/L (5 strains) and 32 mg/L (5 strains). COL MICs decreased below the susceptibility breakpoint for 8 of 10 strains in the presence of RIF concentrations of 16 (1 strain), 8 (6 strains) and 2 mg/L (1 strain). With the E-test method, COL MICs for the 10 strains were 12 mg/L (1 strain), 8 mg/L (2 strains), 6 mg/L (4 strains) and 4 mg/L (3 strains). COL MICs for 10 of 10 strains decreased below the susceptibility breakpoint in the presence of any concentration of RIF. These results are summarized in Table 1. RIF MICs results were higher than 32 mg/L with both methods for all strains. Both methods showed similar results and were able to show that RIF decreased MICs of COL below the susceptibility breakpoint in the majority of COL-resistant KPC-Kp tested strains.The mechanism of the synergistic activity between COL and RIF might be related to the perturbation of the outer cellular membrane produced by COL that favours the penetration of RIF at intracellular concentrations able to inhibit protein synthesis [2]. The higher COL MICs values observed in our experiment with the microdilution method with respect to the E-test already have been reported and seem to be related to the adsorption of colistin to the microplate plastic wells [3,4]. Although higher COL MICs were observed with the microdilution method, the effect of adding RIF was always evident also with t...

Dog bites may result in serious bacterial infections because of various microorganisms, including gram-negative rod Capnocytophaga canimorsus, whose disease can be complicated by acute development of sepsis and/or meningitis. In this review, we report a case of C. canimorsus meningitis in a patient with major risk factors and subsequently analyze 48 other cases described in literature. Approximately a little less than 50% of reported cases had a major predisposing condition such as splenectomy, alcoholism, or immunosuppressive treatment. In almost all of the cases, recent animal exposure was reported. Sensorineural hearing loss, which has been described as a permanent complication of C. canimorsus meningitis, was present in a minority of cases (18%), and a possible association with alcoholism was observed. In conclusion, C. canimorsus should be considered as a possible cause of sporadic meningitis in adults, particularly if presenting with a subacute course or deafness and in concomitance of major predisposing conditions, such as alcoholism.