Suggested options for empiric treatment of cellulitis in neonates*

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1 Suggested options for empiric treatment of cellulitis in neonates* Infants 0 to 4 weeks of age Infants <1 week of age Infants 1 week of age BW <1200 g BW 1200 to 2000 g BW >2000 g BW 1200 to 2000 g BW >2000 g Empiric parenteral therapy options Vancomycin PLUS 15 mg/kg IV every to 15 mg/kg IV every 10 to 15 mg/kg IV every 10 to 15 mg/kg IV every 10 to 15 mg/kg IV every either: hours 12 or 18 hours 8 or 12 hours 8 or 12 hours 6 or 8 hours Cefotaxime 50 mg/kg IV every mg/kg IV every mg/kg IV every 8 or 50 mg/kg IV every 8 50 mg/kg IV every 6 or hours hours 12 hours hours 8 hours OR Gentamicin 2.5 mg/kg IV every 18 to 2.5 mg/kg IV every mg/kg IV every mg/kg IV every 8 or 2.5 mg/kg IV every 8 24 hours hours hours 12 hours hours Oral therapy options (for completion of therapy when pathogen unknown) Clindamycin Δ 5 mg/kg orally every 12 5 mg/kg orally every 12 5 mg/kg orally every 8 5 mg/kg orally every 8 5 to 7.5 mg/kg orally hours hours hours hours every 6 hours Linezolid 10 mg/kg orally every 8 10 mg/kg orally every 8 10 mg/kg orally every 8 10 mg/kg orally every 8 10 mg/kg orally every 8 or 12 hours or 12 hours or 12 hours hours hours BW: birth weight; IV: intravenously. * Treatment of cellulitis in neonates usually requires hospitalization and parenteral therapy. Empiric therapy must include coverage for group BStreptococcus in addition to methicillin-resistant Staphylococcus aureus and other beta-hemolytic streptococci. Optimal dose should be based on determination of serum concentrations. Δ If isolate is susceptible. Dosing every 12 hours is recommended for infants <34 weeks' gestation and <1 week of age. Data from: American Academy of Pediatrics. Antibacterial drugs for newborn infants: Dose and frequency of administration. In: Red Book: 2009 Report of the Committee on Infectious Diseases, 28th ed, Pickering LK (Ed), American Academy of Pediatrics, Elk Grove Village, IL p.745. Graphic Version 3.0

2 Options for oral treatment of methicillin-resistant Staphylococcus aureus (MRSA) Treatment Adult dose Pediatric dose (children >28 days)* Clindamycin 300 to 450 mg orally three times daily 40 mg/kg per day orally divided in three or four doses Trimethoprim-sulfamethoxazole 1 to 2 DS tablets orally twice daily 8 to 12 mg trimethoprim component/kg per day orally divided in two doses Doxycycline 100 mg orally twice daily 45 kg: 4 mg/kg per day orally divided in two doses >45 kg: 100 mg orally twice daily Minocycline 200 mg orally once, then 100 mg orally twice daily 4 mg/kg orally once, then 4 mg/kg per day divided in two doses Linezolid 600 mg orally twice daily <12 years: 30 mg/kg per day orally divided in three doses 12 years: 600 mg orally twice daily Tedizolid 200 mg orally once daily Insufficient data The doses recommended above are intended for patients with normal renal function; the doses of some of these agents must be adjusted in patients with renal insufficiency. DS: Double strength (ie, 160 mg trimethoprim with 800 mg sulfamethoxazole per tablet) * The weight-based pediatric dose should not exceed the usual adult dose. Dosing for neonates is provided separately; refer to the separate UpToDate table "Treatment of cellulitis in neonates". Not recommended for children <8 years of age. Data adapted from: Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014;59:e10; and Liu C, Bayer A, Cosgrove SE, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children. Clin Infect Dis 2011; 52:e18. Graphic Version 12.0

3 Parenteral antimicrobial therapy for infections due to methicillin-resistant Staphylococcus aureus (MRSA) in adults Drug Adult dose Vancomycin 15 to 20 mg/kg/dose every 8 to 12 hours, not to exceed 2 g per dose Daptomycin Skin and soft tissue infection 4 mg/kg IV once daily Bacteremia 6 mg/kg IV once daily* Linezolid Ceftaroline 600 mg IV (or orally) twice daily 600 mg IV every 12 hours Dalbavancin (for skin and soft tissue infection) 1 g IV on day 1, followed by 500 mg IV on day 8 Tedizolid (for skin and soft tissue infection) Telavancin 200 mg IV (or orally) once daily 10 mg/kg once daily IV: intravenously. * Because daptomycin exhibits concentration-dependent killing, some experts recommend doses of up to 8 to 10 mg/kg IV once daily, which appear safe, though additiona l studies are needed [1,2]. Dose adjustment for renal impairment is indicated. References: 1. Figueroa DA, Mangini E, Amodio-Groton M, et al. Safety of high-dose intravenous daptomycin treatment: three-year cumulative experience in a clinical program. Clin Infect Dis 2009; 49: Benvenuto M, Benziger DP, Yankelev S, Vigliani G. Pharmacokinetics and tolerability of daptomycin at doses up to 12 milligrams per kilogram of body weight once daily in healthy volunteers. Antimicrob Ther Chemother 2006; 50:3245. Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52:285. Graphic Version 16.0

4 Empiric antimicrobial therapy for nonpurulent cellulitis (including beta-hemolytic streptococci and MSSA but not MRSA) Adults Children age >28 days Oral therapy Dicloxacillin 500 mg orally every six hours 25 to 50 mg/kg per day orally in four doses Cephalexin* 500 mg orally every six hours 25 to 50 mg/kg per day orally in three or four doses Clindamycin 300 to 450 mg orally every six to eight hours 20 to 30 mg/kg per day orally in four doses Intravenous therapy Cefazolin* 1 to 2 grams intravenously every eight hours 100 mg/kg per day intravenously in three or four doses Oxacillin 2 grams intravenously every four hours 150 to 200 mg/kg per day intravenously in four or six doses Nafcillin 2 grams intravenously every four hours 150 to 200 mg/kg per day intravenously in four or six doses Clindamycin 600 to 900 mg intravenously every eight hours 25 to 40 mg/kg per day intravenously in three or four doses Table shows antibiotic selections for initial empirical treatment of infections not involving the face. Selection and/or dosing should be modified based on the results of culture and sensitivity testing. Pediatric dose should not exceed usual adult dose. If risk of MRSA, refer to UpToDate topic on treatment of skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus in adults for empirical treatment recommendations. MSSA: methicillin-susceptible S. aureus; MRSA: methicillin-resistant S. areus. * Dose alteration for renal insufficiency may be needed. Alternate therapy for patients at risk of severe hypersensitivity reaction to penicillins and cephalosporins. Graphic Version 12.0

5 Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) colonization Recent hospitalization Residence in a long-term care facility Recent antibiotic therapy HIV infection Men who have sex with men Injection drug use Hemodialysis Incarceration Military service Sharing needles, razors, or other sharp objects Sharing sports equipment Diabetes Graphic Version 7.0 Prolonged hospital stay

6 Options for empiric oral therapy for treatment of both methicillin-resistant Staphylococcus aureus (MRSA) and beta-hemolytic streptococci Antibiotic agent Adult dose Pediatric dose (children >28 days)* Clindamycin 300 to 450 mg orally three times daily 40 mg/kg per day orally divided in three or four doses Amoxicillin PLUS 500 mg orally three times daily 25 to 50 mg/kg per day orally divided in three doses Trimethoprim-sulfamethoxazole 1 double-strength tablet orally twice daily 8 to 12 mg trimethoprim component/kg per day orally divided in two doses Amoxicillin PLUS 500 mg orally three times daily 25 to 50 mg/kg per day orally divided in three doses Doxycycline 100 mg orally twice daily 45 kg: 4 mg/kg per day orally divided in two doses >45 kg: 100 mg orally twice daily Amoxicillin PLUS 500 mg orally three times daily 25 to 50 mg/kg per day orally divided in three doses Minocycline 200 mg once, then 100 mg orally twice daily 4 mg/kg orally once, then 4 mg/kg per day divided in two doses Linezolid 600 mg orally twice daily <12 years: 30 mg/kg per day orally divided in three doses 12 years: 600 mg orally twice daily Tedizolid 200 mg orally once daily NOTE: Pediatric doses should not exceed the usual adult doses shown. * Dosing for neonates provided separately. (Refer to the UpToDate table on treatment of cellulitis in neonates.) Not recommended for children <8 years of age. Selected data from: Liu C, Bayer A, Cosgrove SE, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children. Clin Infect Dis 2011; 52:e18. Graphic Version 9.0

7 Antimicrobial therapy for erysipelas For adults For children age >28 days* Oral therapy Penicillin 500 mg orally every six hours 25 to 50 mg/kg per day orally in three or four doses Amoxicillin 500 mg orally every eight hours 25 to 50 mg/kg per day orally in three doses Erythromycin 250 mg orally every six hours 30 to 50 mg/kg per day orally in two to four doses Parenteral therapy Ceftriaxone 1 g intravenously every 24 hours 50 to 75 mg/kg per day intravenously in one or two doses Cefazolin 1 to 2 g intravenously every eight hours 100 mg/kg per day intravenously in three doses * Maximum single dose should not exceed dose for adults. May not be adequate therapy in areas with relatively high resistance rates among beta-hemolytic streptococci. Graphic Version 5.0

8 GRAPHICS Differential diagnosis of necrotizing myositis and fasciitis Clinical finding Type I* Type II* Gas gangrene Pyomyositis Myositis viral/parasitic Fever Diffuse pain Local pain Δ Systemic toxicity Gas in tissue Obvious portal of entry ++++ ± Diabetes mellitus ++++ ± * Type I and type II refer to the forms of necrotizing fasciitis; spontaneous gangrenous myositis is type II. Pain with influenza consists of diffuse myalgia; pleurodynia may be associated with severe, localized pain (eg, devil's gri p); pain with trichinosis may be severe and localized. Δ Severe pain is as sociated with necrotizing fasciitis due to group A streptococcal infection; the pain may not be severe in type I necrotizing fasciitis because it is commonly associated with diabetes with neuropathy. 50 percent of patients with necrotizing fasciitis due to group A streptococcal infection do not have an obvious portal of entry. Gas gangrene associated with trauma may be caused by Clostridium perfringens, C. septicum, or C. histolyticum, which always have an obvious portal of entry; in comparison, spontaneous gas gangrene caused by C. septicum usually does not have an obvious portal of entry (organisms lodge in tissue as a result of bacteremia originating from a bowel por tal of entry). Graphic Version 3.0

9 Differential diagnosis of crepitant soft tissue wounds* Factor Clostridial cellulitis Nonclostridial anaerobic cellulitis Clostridial myonecrosis (gas gangrene) Anaerobic streptococcal myositis Necrotizing fasciitis (type I) Infected vascular gangrene Synergistic necrotizing cellulitis Δ Noninfectious causes of gas in tissues Predisposing Local trauma Diabetes Local trauma or Local trauma Diabetes mellitus, abdominal Peripheral Diabetes mellitus, Mechanical effects of penetrating trauma, injuries involving the use of conditions or surgery mellitus, surgery surgery, perineal infection arterial cardiorenal disease, obesity, compressed air, entrapment of air under loosely sutured wounds or under preexisting insufficiency perirectal infection ulcers, irrigation of wounds with hydrogen peroxide, IV catheter placement, localized dissection of air from tracheostomy or spontaneous mediastinal emphysema infection Incubation period Usually >3 Several days 1-2 days 3-4 days 1-4 days >5 days 3-14 days Less than 1 hour days Onset Gradual Gradual or Acute Not as rapid as gas Acute Gradual Acute Usually present immediately after trauma or manipulation; may not be rapid gangrene recognized until examination several hours later Pain Mild Mild Marked Occurs late, Moderate or severe Variable Severe Mild marked

10 Swelling Moderate Moderate Marked Moderate Marked Moderate or marked Moderate or marked Slight or absent Skin appearance Minimal Minimal Yellow-bronze, Erythema Erythematous cellulitis, areas of skin Discolored or Scattered areas of skin Only those resulting from initiating trauma discoloration discoloration dark bullae, green- necrosis black necrosis black patches of necrosis Exudate Thin, dark Dark pus Serosanguineous Abundant, Seropurulent None "Dishwater" pus None seropurulent Gas ± Variable but present; does not extend Odor Sometimes Foul Variable, slightly Slight, "sour" Foul Foul Foul None foul foul or peculiarly sweet Systemic toxicity Minimal Moderate Marked Only late in course Moderate or marked Minimal Marked None

11 Muscle None None None Dead ++ None involvement ±: rarely present; ++: present to mild extent; +++: present to moderate extent; ++++: extensive. Intravenous: IV. * In addition to the causes of crepitant infections listed in this table, Aeromonas hydrophila myositis may be associated with gas in soft tissues. The term "necrotizing fasciitis" is used here to designate forms of this syndrome other than streptococcal gangrene. Δ Syngergistic necrotizing cellulitis is essentially the same process as type I necrotizing fasciitis. Because the former occasionally tends to involve muscle, it is given a separate designation here; however, the two processes are clinically indistinguishable in most cases. Reproduced from: Pasternack MS, Swartz MN. Cellulitis, necrotizing fasciitis, and subcutaneous tissue infections. In: Principles and Practice of Infectious Diseases, 7th ed, Mandell GL, Bennett JE, Dolin R (Eds), Elsevier, Philadelphia Table used with the permission of Elsevier Inc. All rights reserved. Graphic Version 1.0 Fournier's gangrene in a patient with diabetes

12 Necrotizing fasciitis of the perineum (Fournier's gangrene) can involve the scrotum. The infection can begin abruptly with severe pain and may spread rapidly. Spontaneous gangrenous myositis Muscle biopsy from a patient with spontaneous gangrenous myositis due tostreptococcus pyogenes (group A Streptococcus). Left panel: Necrotic muscle fibers with numerous infiltrating leukocytes. Right panel: Gram stain shows Gram positive bacteria in an area of muscle necrosis. Necrotizing fasciitis on CT

13 An axial CT scan through the lower pelvis (A) in a patient with Crohn's disease and a right hip replacement (arrowhead) shows a fistulous tract (arrow) from the rectum to the soft tissues of the right hip. Image B shows bubbles of gas in the swollen hamstring muscles (arrows) and circumferential edema of the thigh (asterisks) compared with the normal-sized left thigh. Image C is a coronal reconstruction of the thighs and exemplifies the difference in size caused by inflammatory edema (asterisk). Image D is a sagittal reconstruction and shows gas bubbles throughout the hamstring musculature (arrows). CT: computed tomography.

14 Parenteral antimicrobial therapy for infections due to methicillin-resistant Staphylococcus aureus (MRSA) in adults IV: intravenously.* Because daptomycin exhibits concentration-dependent killing, some experts recommend doses of up to 8 to 10 mg/kg IV once daily, which appear safe, though additional studies are needed [1,2]. Dose adjustment for renal impairment is indicated. rug Adult dose Vancomycin 15 to 20 mg/kg/dose every 8 to 12 hours, not to exceed 2 g per dose Daptomycin Skin and soft tissue infection 4 mg/kg IV once daily Bacteremia 6 mg/kg IV once daily* Linezolid Ceftaroline 600 mg IV (or orally) twice daily 600 mg IV every 12 hours Dalbavancin (for skin and soft tissue infection) 1 g IV on day 1, followed by 500 mg IV on day 8 Tedizolid (for skin and soft tissue infection) Telavancin 200 mg IV (or orally) once daily 10 mg/kg once daily

15 Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities Clinical classification of a diabetic foot infection Infection severity Uninfected Mild Clinical manifestations of infection Wound lacking purulence or any manifestations of inflammation. Presence of 2 manifestations of inflammation (purulence, or erythema, pain, tenderness, warmth, or induration), but any cellulitis/erythema extends 2 cm around the ulcer, and infection is limited to the skin or superficial subcutaneous tissues; no other local complications or systemic illness. Moderate Infection (as above) in a patient who is systemically well and metabolically stable but which has 1 of the following characteristics: cellulitis extending >2 cm, lymphangitic streaking, spread beneath the superficial fascia, deep-tissue abscess, gangrene, and involvement of muscle, tendon, joint or bone. Severe Infection in a patient with systemic toxicity or metabolic instability (eg, fever, chills, tachycardia, hypotension, confusion, vomiting, leukocytosis, acidosis, severe hyperglycemia, or azotemia). Foot ischemia may increase the severity of any infection, and the presence of critical ischemia often makes the infection severe. Reproduced with permission from: Lipsky, BA, Berendt, AR, Deery, HG, et al. Diagnosis and Treatment of Diabetic Foot Infections. Clin Infect Dis 2004; 39:885. Copyright 2004 The University of Chicago Press.

16 Oral agents for empiric treatment of mild to moderate diabetic foot infections SINGLE-drug regimens with activity against streptococci and staphylococci (MSSA) Cephalexin or Dicloxacillin or Amoxicillin-clavulanate or clindamycin TWO-drug regimens with activity against streptococci and MRSA Clindamycin* or Linezolid or Penicillin or cephalexin or dicloxacillin PLUS Trimethoprim-sulfamethoxazole or doxycycline TWO-drug regimens with activity against streptococci, MRSA, aerobic gram-negative bacilli and anaerobes Trimethoprim-sulfamethoxazole PLUS Amoxicillin-clavulanate -OR- Clindamycin PLUS Ciprofloxacin or levofloxacin or moxifloxacin Antibiotic dosing for adults Cephalexin 500 mg every 6 hours Dicloxacillin 500 mg every 6 hours Clindamycin 300 to 450 mg every 6 to 8 hours

17 Linezolid 600 mg every 12 hours Penicillin V potassium 500 mg every 6 hours Trimethoprim-sulfamethoxazole (cotrimoxazole) 2 double-strength tablets (trimethoprim 160 mg and sulfamethoxazole 800 mg per tablet) every 12 hours Doxycycline 100 mg orally every 12 hours Amoxicillin-clavulanate 875/125 mg every 12 hours Ciprofloxacin 750 mg every 12 hours Levofloxacin 750 mg every 24 hours Moxifloxacin 400 mg every 24 hours MSSA: methicillin-susecptible staphylococcus aureus; MRSA: methicillin-resistant staphylococcus aureus. * Check susceptibility testing. Many of these agents require adjustment of the dose in the setting of renal dysfunction. Data courtesy of authors with additional data from: Lipsky BA, et al Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2012; 54:e132.

18 Parenteral agents for empiric treatment of moderate to severe diabetic foot infections Dosing (adult)* Activity against Pseudomonas Beta-lactam/beta-lactamase inhibitors Ampicillin-sulbactam 3 g every 6 hours No Piperacillin-tazobactam 4.5 g every 6 to 8 hours Yes, when dosed every 6 hours Carbapenems Imipenem-cilastatin 500 mg every 6 hours Yes Meropenem 1 g every 8 hours Yes Ertapenem 1 g every 24 hours No Fluoroquinolones Moxifloxacin 400 mg IV every 24 hours Yes Δ Other regimens Metronidazole PLUS one of the following: 500 mg IV every 8 hours No Ceftriaxone 1 to 2 g every 24 hours No Ceftazidime 2 g every 8 to 12 hours Yes Cefepime 2 g every 12 hours Yes Ciprofloxacin 400 mg IV every 8 to 12 hours Yes Δ Levofloxacin 750 mg IV every 24 hours Yes Δ Aztreonam 2 g every 6 to 8 hours Yes PLUS one of the following if MRSA coverage is warranted

19 Vancomycin Linezolid Daptomycin 15 to 20 mg/kg every 8 to 12 hours 600 mg IV every 12 hours 4 to 6 mg/kg every 24 hours * Many of these agents require adjustment of the dose in the setting of renal dysfunction. Empiric coverage for Pseudomonas aeruginosa may not be necessary except in severe cases or when the patient has particular ri sk for involvement with this organism, such as a macerated wound or one with significant water exposure. Δ Variable activity against Pseudomonas. Consult local susceptibility data before use. These agents should be used in combination with an agent that has good gram-positive coverage, such as Vancomycin, Linezolid, or Daptomycin. Maximum 2 grams per dose. Adjust dose to maintain vancomycin serum concentrations of 15 to 20 mg/dl. Total daily doses abov e 4 g per day have been associated with increased risk of nephrotoxicity. Because of the toxicity associated with long-term Linezolid use, we do not recommend this agent for treatment of osteomyelitis. Data courtesy of authors with additional data from: Lipsky BA, et al Infectious Diseases Society of America clinical pr actice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2012; 54:e132.

20 Staphylococcal toxic shock syndrome. Clinical criteria for staphylococcal toxic shock syndrome (issued by the Centers for Disease Control and Prevention) Fever T >38.9 C (102.0 F) Hypotension Systolic blood pressure 90 mmhg for adults or less than fifth percentile by age for children <16 years of age; orthostatic drop in diastolic blood pressure 15 mmhg Orthostatic syncope or dizziness Rash Diffuse macular erythroderma Desquamation 1 to 2 weeks after onset of illness, particularly involving palms and soles Multisystem involvement (3 or more of the following organ systems) Gastrointestinal: Vomiting or diarrhea at onset of illness Muscular: Severe myalgia or creatine phosphokinase elevation >2 times the normal upper limit Mucous membranes: Vaginal, oropharyngeal, or conjunctival hyperemia Renal: Blood urea nitrogen or serum creatinine >2 times the normal upper limit, or pyuria (>5 white blood count/hpf) Hepatic: Bilirubin or transaminases >2 times the normal upper limit Hematologic: Platelets <100,000/microL Central nervous system: Disorientation or alterations in consciousness without focal neurologic signs in the absence of fever and hypotension Negative results on the following tests, if obtained Blood, throat, or cerebrospinal fluid cultures for another pathogen (blood cultures may be positive for Staphylococcus aureus) Serologic tests for Rocky Mountain spotted fever, leptospirosis, or measles

21 *Criteria for a confirmed case include a patient with fever >38.9 C, hypotension, diffuse erythroderm, desquamation (unless the patient dies before desquamation can occur), and involvement of at least three organ systems. A probable case is a patient who is missing one of the characteristics of the confirmed case definition. Data from CDC: Case definitions for public health surveillance MMWR Morb Mortal Wkly Rep 1990; 39(RR-13):1. CDC: Case definitions for infectious conditions under public health surveillance. MMWR Morb Mortal Wkly Rep 1997; 46(RR-10):39. Rash in Staphylococcal toxic shock syndrome Erythematous maculopapular eruption on the abdomen in a patient with staphylococcal toxic shock syndrome (TSS). The erythroderm of TSS can be subtle and resemble a sunburn. Courtesy of Charles V Sanders. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

22 Toxic shock syndrome Macular erythema in toxic shock syndrome. Conjunctival suffusion in staphylococcal toxic shock syndrome Conjunctival suffusion in a patient with staphylococcal toxic shock syndrome (TSS).

23 Desquamation

24 Epidemiology, clinical manifestations, and diagnosis of streptococcal toxic shock syndrome Clinical criteria for staphylococcal toxic shock syndrome (issued by the Centers for Disease Control and Prevention) Fever T >38.9 C (102.0 F) Hypotension Systolic blood pressure 90 mmhg for adults or less than fifth percentile by age for children <16 years of age; orthostatic drop in diastolic blood pressure 15 mmhg Orthostatic syncope or dizziness Rash Diffuse macular erythroderma Desquamation 1 to 2 weeks after onset of illness, particularly involving palms and soles Multisystem involvement (3 or more of the following organ systems) Gastrointestinal: Vomiting or diarrhea at onset of illness Muscular: Severe myalgia or creatine phosphokinase elevation >2 times the normal upper limit Mucous membranes: Vaginal, oropharyngeal, or conjunctival hyperemia Renal: Blood urea nitrogen or serum creatinine >2 times the normal upper limit, or pyuria (>5 white blood count/hpf) Hepatic: Bilirubin or transaminases >2 times the normal upper limit Hematologic: Platelets <100,000/microL Central nervous system: Disorientation or alterations in consciousness without focal neurologic signs in the absence of fever and hypotension Negative results on the following tests, if obtained

25 Blood, throat, or cerebrospinal fluid cultures for another pathogen (blood cultures may be positive for Staphylococcus aureus) Serologic tests for Rocky Mountain spotted fever, leptospirosis, or measles Criteria for a confirmed case include a patient with fever >38.9 C, hypotension, diffuse erythroderm, desquamation (unless th e patient dies before desquamation can occur), and involvement of at least three organ systems. A probable case is a patient who is missing one of the characteristics of the confirmed case definition. Data from CDC: Case definitions for public health surveillance MMWR Morb Mortal Wkly Rep 1990; 39(RR-13):1. CDC: Case definitions for infectious conditions under public health surveillance. MMWR Morb Mortal Rep 1997; 46(RR-10):39.

26 Treatment of streptococcal toxic shock syndrome Rapid empiric management of streptococcal toxic shock syndrome in adults Diagnosis Isolation of GAS from a normally sterile site (eg, blood cerebrospinal, pleural, or peritoneal fluid, tissue biopsy, or surgical wound) and hypotension plus evidence of failure of two of more organ systems: Renal failure Coagulopathy Liver involvement Adult respiratory distress syndrome Erythematous macular rash Soft tissue necrosis Management Hemodynamic support Massive amounts of intravenous fluids Vasopressors (eg, dopamine and/or norepinephrine) Surgical therapy Prompt and aggressive exploration and debridement of suspected sites of infection Consider surgical intervention in patients who have fever and excruciating pain, particularly with soft tissue swelling or formation of violaceous vesicles or bullae Empiric antibiotics Immediately begin empiric antibiotics, following culture of blood and suspected site of infection, with broad-spectrum antibiotics

27 including: Clindamycin (900 mg IV every eight hours) plus one of the following: A carbapenem (eg, imipenem 500 mg every six hours or meropenem 1 g every eight hours) or A combination drug containing a penicillin plus beta-lactamase inhibitor 1 g every eight hours) (eg, ticarcillin-clavulanate 3.1 g every four hours or piperacillin-tazobactam 4.5 g every six hours) Tailored antibiotics (eg, once diagnosis of toxic shock syndrome due to GAS is established) Clindamycin (900 mg IV every eight hours) plus Penicillin G (4 million units IV every four hours) Intravenous immune globulin Treatment with intravenous immune globulin (1 g/kg day one, followed by 0.5 g/kg days two and three) GAS: group A Streptococcus; IV: intravenous.

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