A 42 year-old male patient with an open diaphyseal tibia and fibula fracture of the left leg (Gustilo 3b, AO 42A2,4F2B), resulting from a car accident, initially received treatment at a peripheral hospital with a damage control external fixator. His previous medical history was not relevant, except for a prior left sciatic nerve deficit due to chronic radiculopathy. Subsequently, he was transferred to our institution (Umberto I University Hospital, Rome) after 12 days, presenting with severe soft tissue necrosis. Soon after his arrival, he underwent radical debridement and the placement of negative pressure wound therapy (NPWT) (Fig.1). Empirical antibiotic treatment with meropenem (MEM) and vancomycin (VAN) was initiated (Fig. 2).

Skin condition with the first external fixator placed, before and after the debridement

Main in-hospital events and antibiotics timeline. COL colistin, MEM meropenem, VAN vancomycin, TEC teicoplanin, NPWT negative pressure wound therapy, EF external fixator, CRAB carbapenem-resistant Acinetobacter baumannii, MRSA methicillin-resistant Staphylococcus aureus, MRSE methicillin-resistant Staphylococcus epidermidis, PDR-AB pandrug-resistant Acinetobacter baumannii, LZD linezolid, DAP daptomycin, TG tigecycline, FDC cefiderocol. *Only treatments lasting more than 72 h will be shown

In the month following the initial surgery, the patient underwent serial debridement and NPWT renewal. Almost one month after trauma, a new fracture debridement and reduction with external fixation revision were performed, transitioning from a damage control construct to a monoplanar definitive one (Procallus—Orthofix).

Two months after trauma, the plastic surgery team conducted reconstructive surgery for soft tissue loss using a latissimus dorsi free flap. Intraoperative samples collected were positive for methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis (susceptible to ampicillin), and carbapenem-resistant Acinetobacter baumannii (CRAB), susceptible only to colistin (MIC = 0.5 mcg/mL). Given the antibiotic options available at our hospital at that time, therapy with MEM, teicoplanin (TEC), and colistin (COL) was initiated. After four weeks of antibiotics, with observed improvement, the patient was discharged.

During the outpatient follow-up four months after the trauma, the patient exhibited flap swelling, decubitus on the fixator body, and modest leakage of proximal pins. Consequently, the external fixator was elevated, and empiric therapy with levofloxacin (LVX) and minocycline (MIN) was prescribed. However, after two days, the patient was readmitted to the peripheral hospital in a confused and febrile state, with severe dyspnea, and diagnosed with septic thrombo-embolism.

The patient initiated antimicrobial therapy with daptomycin (DAP), linezolid (LZD), and COL, as the blood cultures were positive for MRSA, and the skin swabs collected were positive for methicillin-resistant Staphylococcus epidermidis (MRSE) and CRAB. One week after admission, he was transferred to the Department of Infectious and Tropical Diseases of our hospital. Physical examination revealed edema in the left lower limb, purulent discharge from the proximal pins, and positive thermotactile response over the entire knee and leg region (Fig. 3).

Left leg presentation after septic thrombus embolism episode

Magnetic resonance imaging revealed corpuscular fluid collections at the anterolateral compartment of the left leg. Subsequently, source control surgery was performed, involving debridement, drainage of the collections, NPWT placement, and progressive skin closure using a “shoelace technique”. Simultaneously, MRSA and CRAB were isolated from biopsy. Two weeks after source control surgery, following the isolation of an Ab strain resistant to colistin (MIC > 4 mcg/mL) from biopsies during NPWT renewal, LZD and DAP were discontinued, and therapy continued with COL, MEM, and tigecycline (TG).

The patient’s soft tissue condition progressively improved until five weeks after source control surgery when NPWT was removed, and a dermal substitute was placed until the final combined ortho-plastic surgery eight weeks after source control surgery (approximately seven months after the initial trauma). During this surgery, a partial-thickness epidermal graft was placed, and the external fixator was stabilized by converting it to a multiplanar system (Galaxy System—Orthofix) (Fig. 4). No antibiotic delivery systems were employed, in line with our hospital’s policy, which suggests their utilization in the presence of internal fixation devices [4] or in cases involving substantial joint or endosteal collections.

Last combined ortho-plastic surgery with multiplanar external fixator

On the same day, since the susceptibility of the isolated strain to cefiderocol (FDC) was determined in the meantime, the patient discontinued the previous antibiotic therapy and initiated FDC on a compassionate basis as rescue therapy. He received 2 g every 8 h via a 3 h infusion for six weeks without experiencing side effects.

After six weeks, he was discharged from the Department of Infectious and Tropical Diseases, continuing his treatment course with clinical and radiographic follow-ups at our bone infection outpatient clinic at Umberto I University Hospital on a monthly basis. Serial X-ray examinations showed very slow progressive bone callus formation. Finally, two years after the initial trauma, the external fixator was removed (Fig. 5). Concurrently, the skin condition continued to improve, leading to flap debulking surgery three years after the flap surgery.

Radiographs post external fixator removal with evident bone consolidation

At the last available checkup conducted three years after patient discharge, the patient reported having returned to his daily activities, walking independently without the need for aids, pain-free, and with a healing skin condition.