akinohanayuki ブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.



UpToDate より


Necrotizing soft tissue infections are characterized clinically by fulminant tissue destruction, systemic signs of toxicity, and high mortality rate. Conditions associated with necrotizing infection include diabetes, drug use, obesity, immunosuppression, recent surgery, and traumatic wounds. 
There are two bacteriologic categories of necrotizing soft tissue infections: type I (polymicrobial infection) and type II (group A or other beta-hemolytic streptococcal infection). In type I infection, at least one anaerobic species is isolated in combination with one or more facultative anaerobic streptococci (other than group A) and members of the Enterobacteriaceae. In type II infection, group A streptococci or other beta-hemolytic streptococci are isolated alone or in combination with other species, most commonly S. aureus. 
Necrotizing cellulitis presents with thin, dark wound drainage and gas formation in the skin (but sparing of the fascia and deep muscles). The onset is gradual, but subsequently the process may spread rapidly. Pain, swelling, and systemic toxicity are not prominent features; absence of these findings helps distinguish the process from true gas gangrene. Surgical exploration and debridement are required to distinguish between anaerobic cellulitis and fasciitis or myonecrosis. 
Necrotizing fasciitis is a deep infection of the subcutaneous tissue that results in progressive destruction of fascia and fat. The affected area is usually erythematous (without sharp margins), swollen, warm, shiny, and exquisitely tender. The process progresses rapidly over several days, with changes in skin color from red-purple to patches of blue-gray. Skin breakdown with bullae (containing thick pink or purple fluid) and frank cutaneous gangrene may be observed within three to five days. The development of anesthesia may precede the appearance of skin necrosis and provide a clue that the process is necrotizing fasciitis rather than cellulitis. In advanced infection, high fever and systemic toxicity are generally observed. 
Necrotizing myositis (also called spontaneous gangrenous myositis) is an aggressive infection of skeletal muscle. The clinical presentation consists of fever, exquisite pain, and swelling of the affected muscle with induration. Initially, the overlying skin may be uninvolved, but subsequently erythema, warmth, petechiae, bullae, and vesicles may develop. The infection can progress over several hours to involve contiguous muscle groups and soft tissue. Onset of hypotension may occur rapidly with development of streptococcal toxic shock syndrome. 
Surgical exploration is the only way to definitively establish the diagnosis of necrotizing fasciitis and distinguish it from other entities. In addition, prompt surgical exploration facilitates early debridement and allows material to be obtained for appropriate cultures. Radiographic imaging studies can be useful to help determine whether muscle tissue is involved but should not delay surgical intervention when there is crepitus on examination or clinical evidence of progressive soft tissue infection.
Treatment of necrotizing infection consists of early and aggressive surgical exploration and debridement of necrotic tissue, together with broad spectrum empiric antibiotic therapy and hemodynamic support. Acceptable antibiotic regimens include administration of a carbapenem or beta-lactam-beta-lactamase inhibitor, together with clindamycin (600 to 900 mg intravenously every eight hours for adults and 40 mg/kg per day divided every eight hours in children), as well as an agent with activity against methicillin-resistant S. aureus (MRSA). Antibiotic treatment should be tailored to Gram stain, culture, and sensitivity results when available. 
Intravenous immune globulin (IVIG) contains neutralizing antibodies against some streptococcal superantigens and clostridial toxins. Data on the efficacy of this agent in the setting of necrotizing infection are limited. For cases of necrotizing fasciitis due to group A Streptococcus complicated by streptococcal toxic shock syndrome, we suggest administration of IVIG (Grade 2C).
Antibiotic therapy 
 The optimal approach to empiric antibiotic therapy for necrotizing infection is uncertain; data are limited since most clinical trials exclude such patients. In general, empiric treatment of necrotizing infection should consist of broad-spectrum antimicrobial therapy, including activity against gram-positive, gram-negative, and anaerobic organisms; special consideration for group A Streptococcus (GAS) and Clostridium species should be taken.
Acceptable regimens include administration of:
  • A carbapenem or beta-lactam-beta-lactamase inhibitor, plus
  • Clindamycin (dosed at 600 to 900 mg intravenously every eight hours in adults or 40 mg/kg per day divided every eight hours in neonates and children) for its antitoxin effects against toxin-elaborating strains of streptococci and staphylococci), plus
  • An agent with activity against methicillin-resistant S. aureus (MRSA; such as vancomycin, daptomycin, or linezolid). In neonates and children, vancomycin (15 mg/kg/dose every six to eight hours) is the usual empiric antibiotic for MRSA; the six-hour dosing interval is employed for sicker children.
For patients who have particular exposures that may suggest infections with specific organisms, such as trauma in fresh water (Aeromonas) or sea water (V. vulnificus), it is appropriate to ensure that empiric therapy includes antimicrobial agents active against such organisms. 
Options for carbapenems include imipenem, meropenem, or ertapenem. Meropenem (20 mg/kg per dose every eight hours) is the appropriate carbapenem for use in neonates with a postnatal age >7 days and children. Options for beta-lactam-beta-lactamase inhibitors include piperacillin-tazobactam, ampicillin-sulbactam, or ticarcillin-clavulanate. Patients with hypersensitivity to these agents may be treated either with an aminoglycoside or a fluoroquinolone, plus metronidazole.
Antibiotic treatment should be tailored to Gram stain, culture, and sensitivity results when available. In the setting of known group A streptococcal or other beta-hemolytic streptococcal infection, treatment may be narrowed to the combination of penicillin (4 million units intravenously every four hours in adults >60 kg in weight and with normal renal function or 300,000 units/kg per day divided every six hours in children) and clindamycin (600 to 900 mg intravenously every eight hours in adults or 40 mg/kg per day divided every eight hours in neonates and children). Therapy against MRSA may be discontinued after methicillin-resistant staphylococcal infection has been excluded.
The optimal duration of antibiotic treatment has not been defined in clinical trials. Antibiotics should be continued until no further debridements are needed and the patient’s hemodynamic status has normalized; this duration must be tailored to individual patient circumstances.