Clindamycin Affects Group AStreptococcusVirulence Factors and Improves Clinical Outcome

Abstract

Group A Streptococcus (GAS) has acquired an arsenal of virulence factors, promoting life-threatening invasive infections such as necrotizing fasciitis. Current therapeutic regimens for necrotizing fasciitis include surgical debridement and treatment with cell wall-active antibiotics. Addition of clindamycin (CLI) is recommended, although clinical evidence is lacking. Reflecting the current clinical dilemma, an observational study showed that only 63% of the patients with severe invasive GAS infection received CLI. This work thus aimed to address whether CLI improves necrotizing fasciitis outcome by modulating virulence factors of CLI-susceptible and CLI-resistant GAS in vitro and in vivo. Treatment with CLI reduced extracellular DNase Sda1 and streptolysin O (SLO) activity in vivo, whereas subinhibitory CLI concentrations induced expression and activity of SLO, DNase, and Streptococcus pyogenes cell envelope protease in vitro. Our in vivo results suggest that CLI should be administered as soon as possible to patients with necrotizing fasciitis, while our in vitro studies emphasize that a high dosage of CLI is essential.

Etiology and Clinical Characteristics of Acute Suppurative Osteomyelitis in Children a Single Center Study in China

“…The drug has good tissue penetration and good effects against bacterial toxins and is recommended as an empirical treatment for bone and joint infections in regions where the drug resistance rate is lower than 10-15% [3,16] . The drug is also recommended in combination with other sensitive drugs to enhance the e cacy and improve the prognosis [17] . Chinese strains are highly resistant to clindamycin and macrolides [10] .…”

Human Streptococcal Necrotizing Fasciitis Histopathology Mirrored in a Murine Model

“…2 The GAS serotype M1 is most often isolated from patients with NF 14e16 as was the case in one-third of our patients. To test for potential differences between M1 clinical isolates, the histology of murine NF caused by three distinct GAS isolates, M1T1 5448, 12 CI416, and CI529, 5 was analyzed and compared. Thereby, reflecting clinics where no relevant differences in clinical presentation of the various GAS strains are observed, also histology revealed no isolate-specific differences.…”

“…7,8 Microvascular thrombosis and secondary inflammatory changes in neighboring vessels are common, and tissue hemorrhage is sometimes observed. The presence of intracellular GAS inside neutrophils and macrophages 5,10 as well as the presence of GAS biofilm-like structures 11 in NF tissue was recently described in a clinical observational study.…”

“…The clinical GAS isolates M1T1 5448, 12 CI416, and CI529 5 were mixed 1:1 with sterile cytotex beads (Sigma-Aldrich, Buchs, Switzerland) and 3 Â 10 7 colony forming units in 100 mL were injected subcutaneously into the flanks of 7-to 9-weekeold female C57Bl/6 wild-type mice (Janvier Labs, Le Genest-Saint-Isle, France). 5 Mice were sacrificed 6 or 8 hours after infection (five mice in total), as well as 24 hours (six mice) and 72 hours after infection (16 mice), and skin samples were collected for histology. This work, conducted under the protocol ZH251/14, was approved by the Institutional Animal Care and Use Committee of the University of Zurich.…”

“…3 Current treatment regimens are based on observational clinical studies 4 and some experimental work in murine NF models. 5,6 However, GAS is not a murine pathogen, and no detailed comparison and validation of the histologic presentation of human and murine NF have been performed so far. Although human NF histopathology has been extensively described, 1,7e9 this has been lacking for murine models.…”