Human plasma protein levels alter the in vitro antifungal activity of caspofungin: An explanation to the effect in critically ill?

BACKGROUND: Recent studies have shown low caspofungin concentrations in critically ill patients. In some patients, the therapeutic target, area under the total plasma concentration curve in relation to the minimal inhibition concentration (AUCtot /MIC), seems not to be achieved and therapeutic drug monitoring (TDM) has been proposed. Caspofungin is highly protein-bound and the effect of reduced plasma protein levels on pharmacodynamics has not been investigated. OBJECTIVES: Fungal killing activity of caspofungin in vitro was investigated under varying levels of human plasma protein. METHODS: Time-kill studies were performed with clinically relevant caspofungin concentrations of 1-9 mg/L on four blood isolates of C. glabrata, three susceptible and one strain with reduced susceptibility, in human plasma and plasma diluted to 50% and 25% using Ringer's acetate. RESULTS: Enhanced fungal killing of the three susceptible strains was observed in plasma with lower protein content (p < .001). AUCtot /MIC required for a 1 log10 CFU/ml kill at 24 h in 50% and 25% plasma was reduced with 36 + 12 and 80 + 9%, respectively. The maximum effect was seen at total caspofungin concentrations of 4-9 × MIC. For the strain with reduced susceptibility, growth was significantly decreased at lower protein levels. CONCLUSIONS: Reduced human plasma protein levels increase the antifungal activity of caspofungin in vitro, most likely by increasing the free concentration. Low plasma protein levels in critically ill patients with candidemia might explain a better response to caspofungin than expected from generally accepted target attainment and should be taken into consideration when assessing TDM based on total plasma concentrations.

Device infections related to cardiac resynchronization therapy in clinical practice-An analysis of its prevalence, risk factors and routine surveillance at a single center university hospital.

BACKGROUND: The implantation rates of cardiac implantable electronic devices have steadily increased, accompanied by a steeper rise of device related infections (DRI). HYPOTHESIS: The prevalence of DRI for cardiac resynchronization therapy (CRT) is higher in clinical practice than reported previously, even at a university hospital, and likely higher than reported to the national device registry. METHODS: Electronic medical records of consecutive patients undergoing a CRT procedure between January 2016 and December 2017 were analyzed. Clinical history, procedure related variables and complications were reviewed by specialists in cardiology and infectious diseases. RESULTS: A total of 171 patients, mean aged 74 years, 138 males (80.7%) were included. Twelve DRI occurred in 10 patients during mean 2.5 years follow-up, giving a prevalence of 7% (incidence of 29/1000 person-years). Reoperation, pocket haematoma, ≥3 procedures, previous device infection and indwelling central venous line were the strongest predictive factors according to univariate analysis. Out of 63/171 (36.8%) major complications, 31(49.2%) were lead-related. There were 49/171 (28.7%) reoperations and 15/171 (8.8%) minor complications. The number major complications and DRI reported to the national device registry were 7/171 (4.1%) and 2/171 (0.6%), respectively, reflecting a 5-fold underreporting. CONCLUSIONS: The high rate of CRT device infections is in sharp contrast to those reported by others and to the national device registry. Although a center specific explanation cannot be excluded, the high rates highlight a major issue with registries, reinforcing the need for better surveillance and automatic reporting of device related complications.

[Rare but potentially life-threatening - Multisystem inflammatory syndrome in adults - a case description]. / Hyperinflammation hos vuxna med covid-19 ­ ovanligt men allvarligt.

Multisystem inflammatory syndrome in adults, MIS-A, is a rare but severe post-covid-19 immunologic complication. The presentation is similar to Multisystem inflammatory syndrome in children, MIS-C. Both MIS-A/C are life-threatening immunologic syndromes characterized by hypotension, skin rashes, myocardial affection, coagulopathy and GI symptoms.  Here we describe a case of MIS-A in a 35-year-old previously healthy female who, five weeks after a mild covid-19 infection, presented with a life-threatening immunological reaction. The patient made a swift recovery upon treatment with immunoglobulins, corticosteroids and an interleukin-1 receptor antagonist. We want to highlight the importance of immunological derangements following covid-19 infections in adults. We also present a treatment suggestion for MIS-A based on the management routine for MIS-C, which has been developed from international discussions and collaborations by pediatric rheumatologists in Sweden and around the world.

Comparison of species identification of endocarditis associated viridans streptococci using rnpB genotyping and 2 MALDI-TOF systems.

Streptococcus spp. are important causes of infective endocarditis but challenging in species identification. This study compared identification based on sequence determination of the rnpB gene with 2 systems of matrix-assisted laser desorption ionization-time of flight mass spectrometry, MALDI Biotyper (Bruker) and VITEK MS IVD (bioMérieux). Blood culture isolates of viridans streptococci from 63 patients with infective endocarditis were tested. The 3 methods showed full agreement for all 36 isolates identified in the Anginosus, Bovis, and Mutans groups or identified as Streptococcus cristatus, Streptococcus gordonii, or Streptococcus sanguinis. None of the methods could reliably identify the 23 isolates to the species level when designated as Streptococcus mitis, Streptococcus oralis, or Streptococcus tigurinus. In 7 isolates classified to the Mitis group, the rnpB sequences deviated strikingly from all reference sequences, and additional analysis of sodA and groEL genes indicated the occurrence of yet unidentified Streptococcus spp.