What is the treatment for severe left lower extremity (LLE) resistant cellulitis?

From the Guidelines

Severe left lower extremity (LLE) resistant cellulitis requires aggressive treatment with broad-spectrum antibiotics and supportive care, and I recommend starting with intravenous vancomycin (15-20 mg/kg every 12 hours) plus piperacillin-tazobactam (4.5g every 6 hours) for empiric coverage of MRSA and gram-negative organisms, as suggested by the Infectious Diseases Society of America guidelines 1.

Key Considerations

• The patient's condition necessitates broad-spectrum antibiotic coverage, including MRSA and gram-negative organisms, due to the severity and resistance of the cellulitis.
• Vancomycin plus piperacillin-tazobactam is a recommended empiric regimen for severe infections, according to the guidelines 1.
• If the patient has a severe penicillin allergy, piperacillin-tazobactam can be substituted with meropenem (1g every 8 hours) to maintain broad-spectrum coverage.
• Obtaining wound cultures before starting antibiotics is crucial to guide targeted therapy and adjust the treatment plan as necessary.
• Supportive care, including elevation of the affected limb, pain control with acetaminophen and opioid analgesics if needed, and daily wound assessments, is essential for managing the condition and preventing complications.
• Identifying and treating predisposing conditions, such as edema, obesity, eczema, venous insufficiency, and toe web abnormalities, is important for preventing recurrence, as emphasized in the guidelines 1.

Treatment Approach

• The initial treatment should focus on empiric coverage with broad-spectrum antibiotics, followed by targeted therapy based on culture results.
• The recommended duration of antimicrobial therapy is 5 days, but treatment should be extended if the infection has not improved within this time period, as stated in the guidelines 1.
• After clinical improvement, typically 2-3 days of IV therapy, transition to oral antibiotics based on culture results for a total treatment duration of 10-14 days.
• Monitoring for complications, such as bacteremia, osteomyelitis, or necrotizing fasciitis, is crucial, and surgical consultation should be considered if signs of abscess, necrosis, or compartment syndrome are present.

Additional Considerations

• Resistant cellulitis may indicate an unusual pathogen, inadequate previous antibiotic therapy, or underlying conditions that should be addressed to prevent recurrence.
• Prophylactic antibiotics may be considered in patients with recurrent cellulitis, despite attempts to treat or control predisposing factors, as suggested in the guidelines 1.

From the FDA Drug Label

The types of ABSSSI included were cellulitis/erysipelas (41%), wound infection (29%), and major cutaneous abscess (30%) The primary endpoint in Trial 1 was early clinical response defined as no increase from baseline lesion area at 48-72 hours after the first dose and oral temperature of ≤37. 6°C, confirmed by a second temperature measurement within 24 hours in the ITT population. The primary endpoint in Trial 2 was early clinical response defined as at least a 20% decrease from baseline lesion area at 48-72 hours after the first dose in the ITT population

The FDA drug label does not provide information on the treatment of severe LLE resistant cellulitis. However, it does provide information on the treatment of cellulitis/erysipelas with tedizolid (PO) and daptomycin (IV) in the context of acute bacterial skin and skin structure infections (ABSSSI) and complicated skin and skin structure infections (cSSSI), respectively.

• Tedizolid (PO): The clinical trials for tedizolid (PO) included patients with cellulitis/erysipelas, but the label does not specifically address severe LLE resistant cellulitis.
• Daptomycin (IV): The clinical trials for daptomycin (IV) included patients with complicated skin and skin structure infections, including cellulitis, but the label does not specifically address severe LLE resistant cellulitis.

In the absence of direct evidence, a conservative clinical decision would be to consider alternative treatments for severe LLE resistant cellulitis. 2 3

From the Research

Severe LLE Resistant Cellulitis

• Severe lower limb cellulitis can be challenging to diagnose and treat due to its clinical presentation and potential resistance to antibiotics 4.
• The majority of non-purulent, uncomplicated cases of cellulitis are caused by β-hemolytic streptococci or methicillin-sensitive Staphylococcus aureus, and targeted coverage with oral antibiotics such as penicillin, amoxicillin, and cephalexin is sufficient 4.
• However, some patients with cellulitis may fail to respond to first-line antibiotics, which can negatively affect patient care and result in unnecessary hospital admissions 5.

Treatment Options

• A systematic review of randomized controlled trials found no significant differences in clinical response to different antibiotic types, administration routes, treatment durations, or doses for lower limb cellulitis 5.
• The combination of piperacillin and tazobactam has been shown to be effective against serious soft tissue infections, including cellulitis, but may require increased doses in cases of poor perfusion 6.
• The addition of vancomycin to piperacillin-tazobactam has been found to be synergistic against methicillin-resistant Staphylococcus aureus (MRSA) in vitro 7, 8.

Antibiotic Resistance

• MRSA is a significant concern in the treatment of cellulitis, and combination therapy with vancomycin and a β-lactam may be effective against invasive MRSA infections 8.
• However, reduced susceptibility to vancomycin can occur, and combination therapy may not be effective against unique MRSA strain types 7, 8.