ABSTRACT
Staphylococcus aureus is the most common pathogen that causes implant-associated osteomyelitis, a clinically incurable disease. Immune evasion of S. aureus relies on various mechanisms to survive within the bone niche, including the secretion of leukotoxins such as Panton-Valentine leukocidin (PVL). PVL is a pore-forming toxin exhibiting selective human tropism for C5a receptors (C5aR1 and C5aR2) and CD45 on neutrophils, monocytes, and macrophages. PVL is an important virulence determinant in lung, skin and soft tissue infections. The involvement of PVL in S. aureus pathogenesis during bone infections has not been studied extensively yet. To investigate this, humanized BALB/c Rag2-/-Il2rg-/-SirpaNODFlk2-/- (huBRGSF) mice were subjected to transtibial implant-associated osteomyelitis with community-acquired methicillin-resistant S. aureus (CA-MRSA) USA300 wild type strain (WT), an isogenic mutant lacking lukF/S-PV (Δpvl), or complemented mutant (Δpvl+pvl). Three days post-surgery, Δpvl-infected huBRGSF mice had a less severe infection compared to WT-infected animals as characterized by 1) improved clinical outcomes, 2) lower ex vivo bacterial bone burden, 3) absence of staphylococcal abscess communities (SACs) in their bone marrow, and 4) compromised MRSA dissemination to internal organs (liver, kidney, spleen, heart). Interestingly, Δpvl-infected huBRGSF mice had fewer human myeloid cells, neutrophils, and HLA-DR+ monocytes in the bone niche compared to WT-infected animals. Expectedly, a smaller fraction of human myeloid cells were apoptotic in the Δpvl-infected huBRGSF animals. Taken together, our study highlights the pivotal role of PVL during acute implant-associated osteomyelitis in humanized mice.
ABSTRACT
Nail puncture wounds through rubber-soled shoes, when presenting acutely, have a deceivingly benign appearance. High index of suspicion for a retained rubber piece should be maintained by the physician. This study investigates whether preoperative ultrasound examination can rule out a foreign body and reduce the need for surgery. It is a retrospective cohort of 125 patients with deep nail puncture wounds through a rubber-soled shoe, who underwent surgical exploration between 2008 and 2018. All patients had a preoperative ultrasound examination for detection of a rubber foreign body. The patients' median age was 29, and 112 (89.6%) were males. Median time of presentation was 1 day, but there were patients who presented up to 90 days after injury (mean 5.1 ± 15.6 days). Foreign bodies, ranging 1 to 4 mm in diameter, were surgically removed in 37 (29.6%) patients. Only 16 of these patients had a positive preoperative ultrasound examination, corresponding to sensitivity of 43.2%. Specificity of the ultrasound examination was 95%. Ultrasound examination has low sensitivity for detection of foreign bodies following a puncture wound of the foot. This is attributable to the small size of the foreign bodies in this scenario and to the complexity of sonography in this location. We conclude that ultrasound cannot be used to rule out foreign body in the foot, and should not be relied on when deciding to avoid surgery. Nevertheless, it can be a helpful adjunct preoperatively, as an assessment of the foreign body size and location.
