Human polyspecific immunoglobulin attenuates group A streptococcal virulence factor activity and reduces disease severity in a murine necrotizing fasciitis model.

OBJECTIVES: Streptococcus pyogenes causes life-threatening invasive infections including necrotizing fasciitis (NF). Current treatment guidelines recommend the use of a cell-wall-active antibiotic combined with a protein synthesis inhibitor and surgical debridement in NF patients. Adjunctive therapy with intravenous immunoglobulin (IVIG) has been proposed for superantigen-associated streptococcal toxic shock syndrome. So far, benefits of IVIG treatment remain unclear and prospective clinical studies are scarce. Thus, we aimed to assess the effects of IVIG on virulence factor activity in vitro, ex vivo in patients and in vivo in a NF mouse model. METHODS: We investigated the effect of IVIG on the activity of the virulence factors streptolysin O (SLO), streptodornase 1 (Sda1), S. pyogenes cell envelope protease and streptococcal pyrogenic exotoxin B in vitro and ex vivo in patient sera. Additionally, we assessed the influence of IVIG on the clinical outcome in a murine NF model. RESULTS: In vitro, IVIG inhibited various streptococcal virulence factors. Further, IVIG treatment of group A Streptococcus-infected mice led to a reduced skin lesion size (median (interquartile range) day 3 intraperitoneal administration: 12 mm2 (9-14.5) vs. 4 mm2 (0.8-10.5), subcutaneous: 10.3 mm2 (6.9-18.6) vs. 0.5 mm2 (0.1-6.8)) and lower SLO activity. After treatment with IVIG, patient sera showed an elevated titre of specific SLO (7/9) and Sda1 (5/9) antibodies, reducing SLO and Sda1 activity. CONCLUSIONS: The clear reduction in disease severity in IVIG-treated mice and inhibition of virulence factor activity in mouse and human sera suggest that IVIG may be beneficial in invasive group A Streptococcus infections such as NF in addition to streptococcal toxic shock syndrome.

Competence for transcranial color-coded Duplex sonography is rapidly acquired.

BACKGROUND: Transcranial color-coded Duplex sonography (TCCD) is a non-invasive bedside tool with broad diagnostic potential in the intensive care setting. Implementation of TCCD requires repeated reliable measurements of flow velocities despite data acquisition by multiple operators with varying experience. Thus the learning curve of TCCD and agreement of measurements between experienced and inexperienced operators is of great interest and unstudied so far. METHODS: Six untrained ICU-residents and 2 trained operators participated and performed TCCD examinations of the mean cerebral artery (MCA) in 10 volunteers. Measurements of the residents were compared to the according measurements of the trained operators. Operators were either actively supervised during their first five examinations or performed the examinations without supervision. RESULTS: A total of 480 measurements were obtained. Mean flow velocity (MFV) did not differ significantly between trained and untrained operators in the two groups (P=0.78 in not-supervised and P=0.82 in supervised group). We found a favorable learning curve in both groups (ICC 0.8, CI 95% 0.6-0.91- in not supervised and ICC 0.81 CI 95% 0.63-0.92 in supervised group). However, supervision helped trainees to acquire skills more rapidly and to perform more accurate measurements (ICC 0.77 (95% CI 0.39-0.94) to ICC 0.91 (95% CI 0.77-0.98) and ICC 0.66 (95% CI 0.11-0.91) to ICC 0.84 (95% CI 0.58-0.96), respectively. CONCLUSION: TCCD of the MCA in volunteers is an easy to learn tool with a favorable learning curve. A short-term learning program including initial supervised measurements yields reliable results in the hands of inexperienced operators.