Thread by @Ahmed_HBabiker

1/ Yday on micro rounds we discussed Group A streptococcus (GAS). We briefly touched on the rationale behind using adjunctive clindamycin for severe forms of invasive GAS. So here is a short tweetorial on the topic. @CarlosdelRio7 @Dr_AmyKacin @colleenkraftmd

https://twitter.com/CarlosdelRio7/status/1173644134546059266

2/ GAS is an aerobic GPC. GAS invasive disease (iGAS) is defined by isolation of GAS from a normally sterile body site. The most severe of these invasive disease entities are generally thought to be necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS).

3/ Currently, the addition of clindamycin therapy to B-lactams and surgical debridement is recommended by the IDSA for Necrotizing fasciitis and used routinely in management of STSS, despite low rates of PCN resistance . What is the rationale?

doi.org/10.1093/cid/ci…

4/ iGAS pathogenicity is linked to the production of many virulence factors. Most important of all are M protein (anti-phagocytic), streptolysin O, NADase and streptococcal pyrogenic exotoxins A and B.

5/ The exotoxins act as superantingens, which trigger excessive stimulation of T lymphocytes, leading to a massive release of T cell mediators and pro-inflammatory cytokines leading to the dreaded streptococcal toxic shock syndrome

doi.org/10.1111/j.1600…

6/ While clindamycin does result in reduction of exotoxin production (protein synthesis inhibitor) and other virulence factors (even in clindamycin resistant strains, see below). Another reason for its use is due to the Eagle or inoculum phenomenon,

doi.org/10.1093/infdis…

7/ In 1952, Dr. Eagle used a mouse model of streptococcus myositis to demonstrate that penicillin had reduced efficacy with a high inoculum size. This was hypothesized due to a physiological stationary growth phase the bacteria exhibited with a large inoculum size

8/ Later in similar streptococcus myositis mouse models Steven et al compared the relative efficacies of B-lactams, clindamycin and erythromycin and found the efficacy of clindamycin was not altered by the inoculum size and was superior to penicillin at the inoculum sizes studied

9/ Analysis of penicillin binding proteins (PB) during various stages of growth revealed the binding of radiolabeled penicillin was decreased due to loss of PBs 1+4 in stationary growth phase bacteria.

10/ Leading them to conclude the inoculum effect was due to loss of PBs during the stationary growth phase. Robust clin data to confirm benefit is limited. Retrospective and population surveillance studies of iGAS (mostly STSS) do show a trend towards benefit with adj clinda

11/ I'll end with this stunning 2019 Audubon Photography Award Winner photo taken by Kevin Ebi of a bald eagle tussling with a fox over a rabbit .

#IDTwitter #FOAMed #MicroRounds