What are the first-line intravenous (IV) antibiotics for sepsis caused by cellulitis?

From the Guidelines

The first-line intravenous antibiotics for sepsis caused by cellulitis should include vancomycin plus either piperacillin-tazobactam, cefepime, or a carbapenem such as meropenem, as recommended by the Infectious Diseases Society of America 1. This combination provides broad-spectrum coverage against both gram-positive organisms (particularly methicillin-resistant Staphylococcus aureus) and gram-negative bacteria that may be causing the infection. The dosing for vancomycin is typically 15-20 mg/kg every 8-12 hours, with appropriate monitoring and adjustment based on levels, while piperacillin-tazobactam is given at 4.5g every 6-8 hours, cefepime at 2g every 8 hours, or meropenem at 1g every 8 hours. Some key points to consider when selecting antibiotics for sepsis caused by cellulitis include:

• Coverage for MRSA and streptococci is crucial, especially in patients with systemic signs of infection or risk factors for MRSA 1.
• The total duration of therapy is typically 7-14 days depending on clinical response, with consideration for transition to oral antibiotics once the patient shows clinical improvement, is hemodynamically stable, and can tolerate oral medications.
• Cultures of blood or cutaneous aspirates, biopsies, or swabs should be considered in patients with severe infections or those who are immunocompromised 1.
• Adjustments to the antibiotic regimen should be made based on culture results and susceptibility data, as well as the patient's clinical response to treatment. It's also important to note that the Infectious Diseases Society of America recommends vancomycin plus either piperacillin-tazobactam or imipenem/meropenem as a reasonable empiric regimen for severe infections 1. In general, the choice of antibiotics should be guided by the severity of the infection, the patient's underlying health status, and the likelihood of specific pathogens being involved. For example, if Pseudomonas is suspected, ensure the gram-negative coverage includes anti-pseudomonal activity. Overall, the goal of antibiotic therapy in sepsis caused by cellulitis is to provide effective coverage against the likely pathogens while minimizing the risk of adverse effects and promoting optimal patient outcomes.

From the FDA Drug Label

1. CLINICAL STUDIES 14. 1 Acute Bacterial Skin and Skin Structure Infections (ABSSSI) Adult Patients A total of 1396 adults with clinically documented complicated skin and skin structure infection were enrolled in two identical randomized, multi-center, multinational, double-blind, non-inferiority trials (Trials 1 and 2) comparing Teflaro (600 mg administered IV over 1 hour every 12 hours) to vancomycin plus aztreonam (1 g vancomycin administered IV over 1 hour followed by 1 g aztreonam administered IV over 1 hour every 12 hours). This analysis evaluated responder rates based on achieving both cessation of lesion spread and absence of fever on Study Day 3 in the following subgroup of patients: Patients with lesion size ≥ 75 cm2 and having one of the following infection types: Major abscess with ≥ 5 cm of surrounding erythema Wound infection Deep/extensive cellulitis

The first-line intravenous (IV) antibiotics for sepsis caused by cellulitis include:

• Ceftaroline (600 mg administered IV over 1 hour every 12 hours)
• Vancomycin plus aztreonam (1 g vancomycin administered IV over 1 hour followed by 1 g aztreonam administered IV over 1 hour every 12 hours) 2

From the Research

First-Line IV Antibiotics for Sepsis Caused by Cellulitis

• The selection of appropriate antimicrobial therapy for patients with sepsis is based on the most likely source of infection, the most common pathogens at that site, knowledge of antimicrobial susceptibility patterns in the local community and institution, and host factors 3.
• For sepsis caused by cellulitis, the most common pathogens include Streptococcus and Staphylococcus species.
• Vancomycin is a useful bactericidal antibiotic for selective clinical infections, including serious staphylococcal infections, and is given intravenously in most cases, usually in a dose of 1 g every 12 hours in patients who have normal renal function 4.
• The initial dose of hydrophilic antimicrobials such as ß-lactams, aminoglycosides, and vancomycin should be given at a high dose regardless of renal function 5.
• Common empiric antimicrobial regimens for sepsis include piperacillin/tazobactam plus vancomycin and ceftriaxone plus vancomycin 6.

Antibiotic Dosing Principles

• Effective pathogen eradication occurs when the dose of antibiotic reaches or maintains optimal concentrations relative to the minimum inhibitory concentration for the pathogen 7.
• Time-dependent antibiotics, such as β-lactams, can be given as extended or continuous infusions 7.
• Concentration-dependent antibiotics such as aminoglycosides are optimized by using high, once-daily dosing strategies with serum concentration monitoring 7.
• Vancomycin and fluoroquinolones are dependent on both time and concentration above the minimum inhibitory concentration 7.

Clinical Considerations

• Prompt initiation of appropriate antimicrobial therapy is essential for achieving the best possible outcomes in patients with sepsis 3.
• Delay of antimicrobial administration in patients with severe sepsis and septic shock has been associated with a decrease in survival to hospital discharge 6.
• Cultures should be drawn prior to administration of antimicrobials and repeated within 48 hours 6.
• Empiric antimicrobial regimens should be appropriate for the most likely pathogens for the infection site 6.