Antibiotics in Necrotizing Soft Tissue Infections

Abstract

Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections characterized by an extensive necrosis of skin and subcutaneous tissues. Initial urgent management of NSTIs relies on broad-spectrum antibiotic therapy, rapid surgical debridement of all infected tissues and, when present, treatment of associated organ failures in the intensive care unit. Antibiotic therapy for NSTI patients faces several challenges and should (1) carry broad-spectrum activity against gram-positive and gram-negative pathogens because of frequent polymicrobial infections, considering extended coverage for multidrug resistance in selected cases. In practice, a broad-spectrum beta-lactam antibiotic (e.g., piperacillin-tazobactam) is the mainstay of empirical therapy; (2) decrease toxin production, typically using a clindamycin combination, mainly in proven or suspected group A streptococcus infections; and (3) achieve the best possible tissue diffusion with regards to impaired regional perfusion, tissue necrosis, and pharmacokinetic and pharmacodynamic alterations. The best duration of antibiotic treatment has not been well established and is generally comprised between 7 and 15 days. This article reviews the currently available knowledge regarding antibiotic use in NSTIs.

Keywords: anti-toxinic; antibiotic; beta-lactam; clindamycin; necrotizing soft tissue infections; pharmacodynamics; pharmacokinetics; piperacillin-tazobactam; tissue diffusion.

Figure 2

Suggested antibiotic treatment for necrotizing soft tissue infection (NSTI) and future perspectives. The mainstem of empiric treatment is a broad-spectrum beta-lactam (e.g., piperacillin-tazobactam) with additional aminoglycosides in case of septic shock. Clindamycin should be added in case of documented or suspected group A streptococcus (GAS) infection (limb infection, features of streptococcal toxic shock, absence of comorbidities, blunt trauma, absence of chronic skin lesions, homelessness, injectable drug use, non-steroidal anti-inflammatory drug use). Coverage of resistant gram-negative bacilli by carbapenems should be used according to local ecology and individual risk factors (hospital acquired infection, beta-lactam, or quinolone exposure in the previous 3 months, history of extended spectrum beta-lactamase (ESBL) carrying, germ colonization/infection or travel to high ESBL endemicity aeras in the previous 3 months). Similarly, use of anti-methicillin resistant Staphylococcus aureus (MRSA) drugs such as vancomycin, linezolid, or daptomycin should be considered in case of local endemicity, residence in a long-stay care facility, chronic dialysis, permanent transcutaneous medical devices or prior MRSA infection/colonization. Pharmacokinetics (PK) and Pharmacodynamics (PD) should be optimized by use of high-loading doses and prolonged infusions for molecules with time-dependent bactericidal activity such as beta-lactams, and therapeutic drug monitoring should be used when available.

Figure 1

Pharmacokinetic (PK) and pharmacodynamic (PD) alterations in patients with necrotizing soft tissue infection (NSTI). Features of septic shock from any cause (increased distribution volume, altered renal clearance, hypoalbuminemia, and reduced tissue perfusion) abound for optimizing delivery of hydrophilic and time-dependent drugs such as beta-lactams by using high-loading doses and prolonged infusion with therapeutic drug monitoring. Specificities of NSTI with tissue necrosis and local ischemia resulting in hindered tissular diffusion are consistent with the need for urgent and aggressive surgical debridement of necrotic tissues. Molecules with higher tissue diffusion, such as lipophilic molecules (e.g., clindamycin, linezolid and daptomycin), might be of interest in this setting.