Download Skin Infections

UPDATE SKIN AND SOFT TISSUE(SST)
INFECTIONS:
Features of Management
Thomas M File, Jr MD MSc
MACP, FIDSA, FCCP
Professor of Internal Medicine
Northeast Ohio Medical University;
Chair, Infectious Disease Division
Summa Health System
Akron, Ohio, USA
•IDSA Guidelines. Stevens D. et al. www.idsociety.org;
•MRSA Guideline. Liu et al. www.idsociety.org;
•File TM Jr. and Stevens DL. Skin and Soft-tissue Infections. 3rd Ed. Published by Handbooks in
Health Care Co. Newton, PA, 2011
BACTERIAL SKIN AND SOFT
TISSUE INFECTIONS
• Primary Pyoderma
• Impetigo, erysipelas,
folliculitis, carbuncles
• Infections secondary to pre-existing
conditions
• Surgical wounds, trauma,
bites, decubitus infections,
diabetic foot infections
• Necrotizing infections
• Polymicrobial
• Monomicrobial (Grp A Strep;
Clostridium)
Photos courtesy T File MD
BACTERIAL SST INFECTIONS
General approach to therapy
•Antimicrobial therapy
• Directed against likely pathogens
• Common organisms
• Specific pathogens based on epidemiology
• Emerging antimicrobial resistance
• Community-onset MRSA; macrolide-Resist S.
pyogenes
• Healthcare-associated pathogens
•Surgical I& D, Debridement,
Excision
Mimics of Skin and Soft Tissue Infections
• Acute allergic reaction
• Contact dermatitis
• Stasis dermatitis
• Toxin (eg chemical)
• Trauma
• Thermal reaction
• Acute gout
• Polychondritis
Stasis dermatitis (dermnet.com)
Acute gout (www.definegout.com
Recurrent polychondritis; courtesy of N Scalera MD
Common Skin Infections
(Primary Pyoderma)
Infection
Common Pathogens
Folliculitis
Staphylococcus aureus
Whirlpool folliculitis Pseudomonas aeruginosa (usually self-limited)
Abscess
Staphylococcus aureus
Impetigo
Streptococcus pyogenes, and Staphylococcus
aureus
Erysipelas
Staphylococcus aureus, and Streptococcus
pyogenes
Cellulitis
Streptococcus pyogenes, and Staphylococcus
aureus
Lymphangitis
Streptococcus pyogenes
Pyoderma-Antimicrobial therapy
•S. pyogenes
• Beta-lactams: penicillins, cephalosporins, carbapenems
• Others: macrolides (some resistance), clindamycin,
tetracycline ??
•S. aureus
• MSSA: antistaphylococcal penicillins (i.e., dicloxacillin,
nafcillin, oxacillin); cephalosporins; clindamycin;
macrolides
• MRSA
• Hosp-acquired: Vancomycin, linezolid, daptomycin,
televancin, ceftaroline, tigecycline
• Comm-assoc: above plus Trimethoprim/sulfamethoxazole;
doxcycline; clindamycin
CASE: A 45 y/o healthy male presents to the ED
with one day of fever and painful red leg. Temp
100.4F; BP 130/80; P 84; Leg area shown
According to the 2014 IDSA Skin infection
Guideline, what is most appropriate therapy?
a.
b.
c.
d.
e.
Cefepime
Photo courtesy T File MD
Penicillin G
Vancomycin
Vancomycin + piperacillin/tazobactam
Linezolid
IDSA Guidleine 2014
Nonpurulent Cellulitis:
-hemolytic strep vs. S. aureus?
•Empiric Rx for -hemolytic strep recommended
•Prospective study1, 248 hospitalized pts
•73% due to -hemolytic strep ; 27%
with no identified cause.
•Overall 96% response rate to -lactam
antibiotic.MRSA is unknown.
•Empiric Rx for MRSA if fails to respond to lactam
• Consider in patients with systemic toxicity
IDSA MRSA guideline www.idsociety.org; 1Jeng et al Medicine 2010; 89:217-26 2Elliott et al Pediatrics 2009;
123:e959-66
Cellulitis:
Duration of Antimicrobial Therapy
• In cases of uncomplicated 4 cellulitis, a 5-day course of
antimicrobial therapy is as effective as 10-days, if clinical 5
improvement has occurred by 5 days*
• In some patients, cutaneous inflammation and systemic
features worsen after initiating therapy, probably because
sudden destruction of the pathogens releases potent
enzymes that increase local inflammation.
• New FDA criteria: No extension of erythema at 72 hrs.
(FDA Guidance Aug 2010 www.fda.gov/Drugs/Guidances)
*Hepburn MJ, et al. Arch Intern Med 29 2004; 164:1669-74
• Prospective study 216 patients
cellulitis
• Cultures: blood, tissue, swabs; paired
serology-ASO
• Finding: Data on 203
• 173/203 (85%)—Beta-Strep
• 24 had S aureus; 18 also Beta Strep
(13 treated with PCN did well)
Open Forum Infect Dis. Nov 2015; DOI: 10.1093/ofid/ofv181
Pasquale TR et al. Am J Health Syst Pharm. 2014 Jul 1;71(13):1136-9.
CASE: A 60 y/o healthy female presents to
you with a ‘boil’. She is afebrile and has a 3
cm carbuncle on her neck. There is no
significant surrounding erythema
What is most appropriate therapy?
a. Incision and drainage
b. Antimicrobial therapy—
amoxicillin/clavulanate
c. Antimcrobial therapy—
trimethoprim/sulfamethoxazole
d. Antimicrobial therapy—amoxicillin +
trimethoprim/sulfamethoxazole
e. Incision and drainage + ciprofloxacin
Community-associated (CA)MRSA
• Increasing cause of Community skin infections
• Genotypically and phenotypically unique from
nosocomical MRSA
Less resistant to non-beta-lactam agents
Often susceptible to trim/sulfa, clindamycin,
tetracyclines
Panton-Valentine leukocidin-- virulence factor
• Risk factors
athletes, inmates, military recruits, men who have sex
with men, injection drug user, prior antibiotic use
• Increases need to culture
And erythromycin
File T. Cleve Clinic Med J. 2007
Treatment of focal, pustular skin
infections (furuncles, carbuncles)
• For simple abscesses or boils, incision and drainage alone is likely
to be adequate
• Antibiotic therapy is recommended for abscesses associated with
the following conditions:
• severe or extensive disease
• presence of associated cellulitis,
• signs and symptoms of systemic illness,
• associated comorbidities or immunosuppression,
• extremes of age
• abscess in an area difficult to drain (eg, face, hand, and genitalia),
lack of response to incision and drainage alone
From Inf Dis Soc Am Guidelines 2011. www.idsociety .org
•NIH study
• >1000 patients, 2009-2013
• I&D + Trim/Sulf 2 DS BD vs I&D + placebo
• Results:
• Better test of cure with T/S
• Other findings:
• Decrease new lesions within 3 weeks
• Decrease household infections
• Trend for fewer hospitalizations.
• Slightly more GI Adverse effects (42 vs 36%)
Talan era l. NEJM 2016; 374: 823-
Another NIH study:
Prelim report
•786 patients: Single Abscess < 5 cm;
CURE (ITT/Eval)
Placebo
Clindamycin Trim/Sulfa (one
DS BD)
All
68.9/80
83/93
81/93
94
93
S aureus
76
Chambers H. Am Society Micro meeting June 17, 2016
Serious Skin Infection
•36 y/o female noted
onset tender nodule of
leg 4 days earlier;
increasing pain, fever,
surrounding erythema
•T-102.50 F; BP 100/60; P
110; 10 X 7 cm
erythema with central
pustule
•WBC 18,000; creat 1.6
Photo courtesy of T. File MD
MRSA SSTI: 2014 Guidance From IDSA1
Antibiotic
Dosage, Adults
Dosage, Children
Comment
Vancomycin
30 mg/kg/d in 2
divided doses IV
40 mg/kg/d in 4 divided
doses IV
For penicillin allergic pts; parenteral
drug of choice for treatment of
infections caused by MRSA
Linezolid
600 mg Q12h
IV or 600 mg BID
PO
10 mg/kg Q12h IV or PO for
children <12 y
Bacteriostatic; limited clinical
experience; no cross-resistance with
other antibiotic classes; expensive
Clindamycin
600 mg Q8h IV or
300–450 mg QID
PO
25–40 mg/kg/d in 3 divided
doses IV or
30–40 mg/kg/d in 3 divided
doses PO
Bacteriostatic; potential of crossresistance and emergence of
resistance in erythromycin-resistant
strains; inducible resistance in
MRSA.
Important option for children.
Daptomycin
4 mg/kg Q24h IV
N/A
Bactericidal; possible myopathy
Ceftaroline
600 mg BID IV
N/A
Bactericidal
Doxycycline,
minocycline
100 mg BID PO
Not recommended for age
<8 y
Bacteriostatic; limited recent clinical
experience
Trimethoprimsulfamethoxazol
e
1–2 doublestrength tablets
BID PO
8–12 mg/kg/d (based on
trimethoprim component)
in either 4 divided doses IV
or 2 divided doses PO
Bactericidal; limited published
efficacy data
*Guidelines published before FDA approval of tedizolid, dalbavancin and oritavancin
New Therapeutic Options for Skin/Soft Tissue
Infections (focus on MRSA )
Drug
Dalbavancin IV
(Dalvance™)
Oritavancin IV
(Orbactiv™)
Tedizolid IV/po
(Sivextro™)
Class
Lipoglycopeptide/
Cidal
Lipoglycopeptide/
Cidal
Oxazolidinone/Inhi
bitory
Key Clinical Trials
Prolonged T1/2; Two-dose regimen:
1,000 mg followed by 500 mg 1 week
later as an IV infusion over 30 min; or
1.5 Gm X 1 dose. Est Cost $4200
Prolonged T1/2; 1,200-mg single dose
by IV infusion over 3 h; may interact
with coagulation tests; Est Cost $2800
200 mg once daily orally or as an IV
infusion over 1 h for 6 d; Est Cost
$260/day
Treating Skin Infections:
a New Paradigm
•Dalbavancin and Oritavancin make in possible to
treat complicated skin structure infections on
outpatient basis without compromising efficacy
and without need for indwelling IV
•“..could profoundly affect how these infections are
managed, by reducing or in some cases
eliminating costs and risks of hospitalization.”
Chambers HF NEJM 2014; 270: 2238-9
3/21/05
3/22/05
18 y/o male treated with amox/clav for ‘spider’ bite at
local urgent care center.
Photos courtesy of T. File MD
20 y/o female with recurrent sores; on
amox/clav for 4 days without improvement
Photo courtesy of T. File MD
Patient with recurrent Furunculosis
•Usually in immunocompetent patients
•R/O diabetes, other condition
•Often colonized with S. aureus
•Nasal, perineum
•Therapy
•Antibacterial soap ( chlorhexidine)
•Nasal Bactroban
•Systemic antimicrobials-? benefit
• Antistaph agent + rifampin (10 days)
• Clindamycin (best nasal secretion levels), 150 mg/d for up to 3 months
• Klempner MS, Styrt B. Prevention of recurrent staphylococcal skin
infections with low-dose oral clindamycin therapy. JAMA 1988
11;260:2682-5.
INFECTIONS ASSOCIATED WITH
UNDERLYING CONDTIONS
•Infections
•Post Op wound infections
•Lower extremity cellulitis
•Diabetic foot ulcers
•Decubitus ulcers
•Bite wound infections
•Post Trauma infections
•Perforated bowel
Photo courtesy of T. File MD
BACTERIOLOGY: SST Infections
associated with underlying conditions
•Gram positive Cocci
• S aureus
• MSSA
• MRSA (Hospital-acquired; Community-acquired)
• VIRSA,VRSA
• Streptococcal spp (including Grp B and other spp)
• Enterococci (VRE)
•Gram negative Bacilli
• Enterobacteriaciae
• Pseudomonas sp
•Anaerobes
ANTIMICROBIAL ACTIVITY
Agents
Staph**/Strep
Nafcillin/Cefazolin
+
Cefoxitin/
+
Cefotetan
Ceftaroline
+
Amp/sulb (amox/clav)
+
Pip/tazo; Ticar/C
+
Ertapenem
+
Imipenem/Mero
+
FQ + Clinda (metronid) +
GNB
0
+/-*
Anaerobes
0
+
+*
+/-*
+
+*
+
+
+
+
+
+
+
* not for Pseudomonas
** If MRSA: Vancomycin (>99%), Linezolid (>99%), Daptomycin (>99%), Ceftaroline [Others:
Trim/sulf (60-80%), Minocin (90%),
DIABETIC FOOT INFECTIONS
62 y/o postman with fever and draining foot ulcer
Photo courtesy of T. File MD
DIABETIC FOOT INFECTIONS
•Predisposing factors
• Peripheral neuropathy
• Maldistribution of weight (trohic ulsers)
• Failure to sense problems (corns, calluses)
• Vascular insufficiency
•Bacterial etiology
• Early,superficial--Staph, Strep
• Late, deep--Mixed
•Therapy-Surgery and antimicrobial agents;
Multi-disciplinary approach
Post-Op
6 Weeks later
Photos courtesy of T. File MD
Effect of Early Surgery on
Subsequent
Above Ankle Amputation
(Tan JS et al. Clin Infect Dis 1996;23:286-291)
67
70
63
Number of Patients
60
50
40
30
24
20
10
10
0
Antibiotics Alone
Antibiotics plus Initial Surgery
Subsequent Amputation
No Amputation
Other Specific Skin Infections
Epidemiology
Common Pathgen(s)
Therapy
Cat/Dog Bites
P. multocida;
Capnocytophaga
Amox/clav (Doxy; FQ
or SXT + Clinda)
Human bites
Mixed flora
Hand Surgeon; ATB
as above
Fresh water injury
Aeromonas
FQ; Broad Spectrum
Beta-lactam
Salt water injury
(warm)
Vibrio vulnificus
FQ; Ceftazidime
Meat-packing
Erysipelothrix
Penicillin
Cat scratch
Bartonella
Azithromycin
IDSA Guidelines. Stevens D. et al. Clin Infect Dis 2005; 42:1379-406
NECROTIZING SKIN INFECTIONS
Characteristics
• Often perineal or lower extremity(esp for mixed
infections)
• Abnormal inflammatory response(less “purulent”)
• Often rapidly spreading
• Putrid discharge(what organisms?)/crepitance often
present
• Often associated with: Diabetes
Vascular disease
Trauma(including bites)
Surgery
NECROTIZING SKIN INFECTIONS
Pathophysiology
•Mixed aerobic/anaerobic infection
• Synergistic infection
• Presence of faculatative organisms creates better
anaerobic environment for anaerobes
• virulence factors of one organism assists another
organsm(anti-phagocytic effect of B. fragilis capsule
• Growth factors
•Monomicrobial (e.g.,Strep; Staph; Clostridia)
• toxins
• enzymes
S. Aureus
Polymicrobial
NECROTIZING SKIN INFECTIONS
• Manifestations
• Tissue necrosis, spreading, bullae, severe pain
• Often severe intensity of illness
• REQUIRES EXPEDITIOUS SURGERY
• Several anatomical syndromes
• E.g., Necrotizing fasciitis; Gas Gangrene; others
• Cannot easily differentiate syndromes on basis of initial
clinical presentation
• Initial approach is similar: Early surgery and antibiotics
• Microbiology
• Mixed anaerobes/aerobes
• Monomicrobial
• Streptococcus pyogenes/Staphylococcus aureus (CA-MRSA)
• Clostridia sp (perfringens most common)
Diabetic woman with rapidly spreading
gangrenous infection
Photo courtesy of T. File MD
Photo courtesy of T. File MD
Infection 8 hours after amputation
Photo courtesy of T. File MD
Gas Gangrene due to C. perfringens
Photos courtesy of T. File MD
S. PYOGENES NECROTIZING
FASCIITIS
•Increasing frequency over past decade
• Result of specific toxins-Streptococcal pyrogenic
exotoxins(SPE). These cause release of
cytokines(e.g.., TNF) which can mediate fever,
shock, and tissue injury
•Most cases sporadic(occasional 2nd spread);
often in normal host
•Bacteremia in approx 50%
•Mortality-20-40%
•Therapy-Rapid surgery, antibiotics
Photo courtesy of T. File MD
CLUES SUGGESTING NECROTIZING
FASCIITIS RATHER THAN CELLULITIS
• Pain more severe than expected(followed by
anesthesia)
• Rapidly spreading swelling and inflammation
• Bullae(but can be seen with cellulitis as well)
• Necrosis
• Toxic shock syndrome
• Elevated creatine kinase level(why?)
• Risks: Varicella, NSAID
NECROTIZING FASCIITIS
Diagnosis
•CT or MRI
•Edema alone fascia
•Direct Inspection (surgical)
•Swollen, dull gray, string
•Thin exudate (not ‘pus’)
•Tissue easily dissected
•Biopsy
IDSA Guidelines. Stevens D. et al. Clin Infect Dis 2005; 42:1379-406
NECROTIZING INFECTIONS;
THERAPEUTIC APPROACH
•Surgical debridement/excision
•Antimicrobial therapy
• Directed initially against mixed aerobic/anaerobic flora
• Ampicillin/sulbactam or Piperacillin/tazobactam PLUS
Clindamycin (theoretically to inhibit protein synthesis and
suppress bacterial toxin) PLUS Ciprofoxacin;
Other Regimens: Imipenem, meropenem, ertapenem,
Clindamycin PLUS Aminoglycoside or Fluoroquinolone
•Recommendation to use intravenous
immunoglobulin cannot be made with certainty
• (Kaul et al. Clin Inf Dis, 1999; Norrby-Teglund et al. Curr Rep Inf Dis,
2001; Low et al. ICAAC 2003)
IDSA Guidelines. Stevens D. et al. Clin Infect Dis 2005; 42:1379-406
BACTERIAL SST
INFECTIONS
General approach to therapy
•Surgical I& D, Debridement, Excision
•Antimicrobial therapy
•Directed against likely pathogens
• Common organisms
• Specific pathogens based on epidemiology
• Emerging antimicrobial resistance
• Community-onset MRSA; macrolide-R S. pyogenes
• Healthcare-associated pathogens