Skin and Soft Tissue Infections PDF

Skin and Soft Tissue Infections PHAR 5337 - October 24, 2023 Anne Gonzales-Luna, PharmD, BCIDP Research Assistant Professor University of Houston College of Pharmacy [email protected] 1 Learning objectives 1 2 3 Identify likely microbiologic etiology and clinical signs/symptoms associate...

Skin and Soft Tissue Infections PHAR 5337 - October 24, 2023 Anne Gonzales-Luna, PharmD, BCIDP Research Assistant Professor University of Houston College of Pharmacy [email protected] 1 Learning objectives 1 2 3 Identify likely microbiologic etiology and clinical signs/symptoms associated with skin and soft tissue infections (SSTIs) and diabetic foot infections (DFIs) Distinguish important differences in antimicrobial treatment options Select an appropriate treatment regimen given a patient’s past medical history, clinical presentation, and laboratory values 2 Helpful references • IDSA SSTI Guidelines: 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(2): e10-52. • IDSA DFI Guidelines: Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Disease Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012; 54(12): 132-173. 3 4 SSTI background • Skin and soft tissue infections (SSTIs) refer to those involving any or all layers of the skin • VERY common infections • 3.4 million emergency department (ED) visits • 13.9% of visits resulting in hospitalization • May spread from initial site of infection and lead to more severe complications • Treatment may necessitate both medical & surgical management 5 SSTI bugs MSSA, MRSA • Nearly half (46%) of all culturepositive SSTIs are caused by MRSA Beta-hemolytic streptococci Propionibacterium acnes  Cutibacterium acnes 6 7 SSTI pathophysiology Disruption of the normal host defense Primary infection: healthy skin is infected Commonly caused by a single pathogen Secondary infection: preexisting damaged skin infected Commonly polymicrobial Invasion of pathogenic microorganisms triggers inflammatory response Warmth Edema Erythema Pain Infection occurs Purulent: Have a focal point and filled with pus Non-purulent: No focal point and continue to spread Types of SSTIs Purulent https://www.cdc.gov/mrsa/pdf/MRSA_ProviderBrochureF.pdf Non-purulent http://unmhospitalist.pbworks.com/w/file/fetch/109795702/jrv160015.pdf https://www.nps.org.au/australian-prescriber/articles/bacterial-skin-and-soft-tissue-infections 8 SSTI categories Mild • Local symptoms only • Pain and/or inflammation • Swelling • Tenderness • Erythema • Pus Moderate Severe • Systemic signs of infection • Temperature >38°C or <36°C • HR >90 beats/min • RR >20 breaths/min • WBC count >12,000 • Those who have failed I&D + oral antibiotics • Immunocompromised patients Complicated Infections: involve deeper skin structures (fascia, muscle), require surgical intervention, and/or occur in immunocompromised patients 9 SSTI - goals of therapy • Relieve symptoms • Prevent formation of new lesions or spreading of existing lesions • Prevent complications • Abscess formation • Bacteremia • Amputation • Prevent recurrences • Limit cost and adverse effects of treatment 10 General treatment framework Local signs/symptoms, noncomplicated infection Systemic signs/symptoms and/or complicated infection Likely outpatient treatment Likely inpatient treatment Often empiric = definitive therapy: Often empiric  definitive: -may or may not be culture-guided -guided by antibiogram or prior patient cultures -oral -de-escalated IV, broad-spectrum therapy, or following C&S -may be IV or oral 11 General empiric treatment approaches Purulent Nonpurulent Gram stain and culture? Recommended (sample of pus) Not routinely recommended Surgical debridement? Incision and drainage (I&D) – Gold standard Surgical debridement only in severe cases Antibiotics warranted? +/-, I&D alone may resolve up to 80% of infections Yes Antibiotic activity • MSSA, MRSA • MRSA responsible for most abscesses • Mild (no systemic signs)  βhemolytic Streptococcus (alone) • Moderate (systemic signs)  βhemolytic Streptococcus + MSSA • + MRSA coverage if risk factors present MRSA risk factors: penetrating trauma, MRSA infection elsewhere, MRSA nasal colonization, or injection drug use 12 MRSA drug review: IV, PO, or both? vancomycin tigecycline daptomycin ceftaroline clindamycin doxycycline minocycline delafloxacin oritavancin dalbavancin eravacycline linezolid omadacycline Remember – tetracyclines not recommended in children <8 years old! trimethoprim/ sulfamethoxazole Topic outline Purulent Infections Nonpurulent infections Folliculitis Erysipelas Furuncle Carbuncle Diabetic foot infections Cellulitis Impetigo 14 https://aadermatology.com/hairconditions/folliculitis/ Types of purulent SSTIs https://www.merckmanuals.com/profes sional/dermatologic-disorders/bacterialskin-infections/furuncles-and-carbuncles • Folliculitis – clustering, pruritic papules (<5 mm) localized to hair follicles • Involves epidermis • Furuncle (“boil”) – walled-off mass of purulent material arising from a hair follicle https://www.nhs.uk/conditions/boils/ • Involves subcutaneous tissue • Lesions caused by MRSA often have necrotic centers (“spider bite”) • Carbuncle – adjacent furuncles coalesce to form a single inflamed area • Commonly associated with systemic signs (fever, chills, malaise) 15 General empiric treatment approaches Purulent Nonpurulent Gram stain and culture? Recommended (sample of pus) Not routinely recommended Surgical debridement? Incision and drainage (I&D) – Gold standard Surgical debridement only in severe cases Antibiotics warranted? +/-, I&D alone may resolve up to 80% of infections Yes Antibiotic activity • MSSA, MRSA • MRSA responsible for most abscesses • Mild (no systemic signs)  βhemolytic Streptococcus (alone) • Moderate (systemic signs)  βhemolytic Streptococcus + S. aureus • + MRSA coverage if risk factors present 16 Purulent SSTI treatment • • • Folliculitis or mild furuncle: warm/moist compresses Moderate furuncle or carbuncles: I&D • + oral antibiotics if patient has systemic symptoms Severe infections: I&D + culture + empiric MRSA-active antibiotics (may need inpatient treatment/IV antibiotics) Antibiotic Dose - Adults Doxycycline, minocycline 100 mg BID x5-10 days SMX-TMP Ceftaroline Vancomycin Linezolid Daptomycin 1-2 DS tablets BID x5-10 days 600 mg BID x5 days 30 mg/kg/day in 2 divided doses x5 days 600 mg BID x5 days 4-6 mg/kg/day 17 Active learning question #1 SD is a 34 yo M personal trainer who presents to the ED complaining of a small “spider bite” on his back near his armpit that feels tender. Despite the tenderness, he feels well otherwise. He states that he has never had this type of ailment before, and he has never been hospitalized. The last time he remembers taking antibiotics was when he was 20 for a sinus infection. The ED physician asks you as the ED pharmacist for therapy recommendations. What would you recommend? A. Warm, moist compress B. SMX-TMP 2 DS tablets BID x 7 days C. Cephalexin 500 mg QID x 5 days 18 Active learning question #2 Suppose SD’s “spider bite” is large and he has been experiencing fever and chills for approximately 12 hours. What do you recommend? A. Warm, moist compress B. SMX-TMP 2 DS tablets BID x 7 days C. Cephalexin 500 mg QID x 5 days 19 Impetigo presentation • Most commonly presents in children and on the face • Highly communicable spreads through close contact • Siblings, children in daycare centers and schools • Cultures should be obtained • Nonbullous (70% of cases) – caused by β-hemolytic streptococci, S. aureus, or a combination • Bullous (30% of cases) – caused by toxin-producing S. aureus Bullous impetigo (usually MSSA) • Signs/symptoms: • • • • Characteristic golden yellow (“honey-colored”) crusts Pruritis Leukocytosis Bullous form – weakness & fever 20 https://www.nps.org.au/australian-prescriber/articles/bacterial-skin-and-soft-tissue-infections Nonbullous impetigo Impetigo treatment • Topical or oral antibiotics both shown to be effective • Oral therapy recommended for patients with numerous/large lesions or in outbreaks to help decrease transmission of infection • S. aureus is usually MSSA  only use MRSA-active antibiotics for confirmed MRSA Drug Dose x duration (adults) Mupirocin (topical) TID x5 days Amoxicillin/clavulanate 875/125 mg BIB x7 days Dicloxacillin 250-500 mg QID x7 days Cephalexin 250 mg QID x7 days Clindamycin* 300-400 mg TID x7 days Doxycycline, minocycline* 100 mg BID x7 days SMX-TMP* 1-2 DS tablets BID x7 days *Only use if confirmed MRSA! 21 Nonpurulent SSTI presentation • Erysipelas: • • • • Involves superficial layers of the skin + cutaneous lymphatics Lesion has raised and sharply demarcated borders Intense red color and burning pain (“St. Anthony’s fire” ) Leukocytosis and elevated C-reactive protein (CRP) common • Cellulitis: • • • • • Involves epidermis + dermis but may spread to superficial fascia Lesions are not elevated and have poorly defined borders Purulent exudate + abscess formation possible (IV drug users) Leukocytosis, fever, hypotension, altered mental status common Bacteremia may be present (~30% of cases) 22 General empiric treatment approaches Purulent Nonpurulent Gram stain and culture? Recommended (sample of pus) Not routinely recommended Surgical debridement? Incision and drainage (I&D) – Gold standard Surgical debridement only in severe cases Antibiotics warranted? +/-, I&D alone may resolve up to 80% of infections Yes Antibiotic activity • MSSA, MRSA • MRSA responsible for most abscesses • Mild (no systemic signs)  βhemolytic Streptococcus (alone) • Moderate (systemic signs)  βhemolytic Streptococcus + S. aureus • + MRSA coverage if risk factors present 23 Nonpurulent SSTI treatment • • Mild: oral antibiotics Moderate/severe: IV antibiotics (duration may be increased up to 10-14 days) β-hemolytic streptococci MSSA MRSA Antibiotic Dose x duration* (adults) Penicillin VK 500 mg QID x5 days Dicloxacillin 500 mg QID x5 days Cephalexin 500 mg QID x5 days Cefazolin 1-2 g TID x5 days Ceftriaxone 1g daily x5 days Clindamycin 300-450 mg TID x5 days Ceftaroline 600 mg BID x5 days Vancomycin 30 mg/kg/day in 2 divided doses x5 days Linezolid 600 mg BID x5 days Daptomycin 4-6 mg/kg/day 24 MRSA decolonization for recurrent SSTIs • Consider decolonization if continued recurrence despite proper wound care and hygiene • Recurrent SSTIs: ≥2 SSTI episodes at different sites during a 6-month period • Decolonization strategies may include: • Nasal mupirocin twice daily x 5-10 days • Nasal mupirocin twice daily x 5-10 days + topical body decolonization with chlorhexidine for 5-14 days • Nasal mupirocin twice daily x 5-10 days + dilute bleach baths for 15 min twice weekly x 3 months 25 SSTI - The Future Antibiotic Oritavancin (Orbactiv®) Dalbavancin (Dalvance®) Tedizolid (Sivextro®) Delafloxacin (Baxdela®) Omadacycline (Nuzyra®) Eravacycline (Xerava®) Delafloxacin (Baxdela®) FDA Approval 2014 2014 2014 2017 2018 2018 2019 Key In Vitro Activity MRSA, streptococci MRSA, streptococci MRSA, streptococci MRSA, P. aeruginosa MRSA, streptococci MRSA, streptococci MRSA, P. aeruginosa 26 http://www.antimicrobe.org/e26.asp https://www.researchgate.net/figure/Diabetic-foot-infection-for-insensitive-repetitive-trauma-The-wound-is-close-to-deep_fig7_221920844 Diabetic Foot Infection (DFI) • 70% of all nontraumatic amputations in the United States are due to a DFI • 20% of patients with diabetes will undergo additional surgery or amputation of a 2nd limb within 12 months of the initial amputation • Osteomyelitis is one of the most serious complications of DFI • May occur in 30% to 40% of infections 27 DFI pathophysiology Risk factors: • • • • • Wound extending to the bone Foot ulcer present >30 days History of recurrent foot ulcers Traumatic wound etiology Peripheral vascular disease (PVD) in affected limb • Previous lower extremity amputation • Renal insufficiency • History of walking barefoot 28 DFI etiology • Staphylococci and streptococci are the most common pathogens, but gramnegative bacilli and/or anaerobes occur in up to 50% of cases • Chronic nature of DFI  wounds often heavily colonized by organisms not playing a role in the infection • Bone cultures > soft tissue specimens (surface swabs) Gram-positive aerobes Staphylococcus aureus Streptococcus spp. Coagulase-negative staphylococci Enterococcus spp. Gram-negative aerobes Escherichia coli Klebsiella spp. Anaerobes Peptostreptococcus spp. Bacteroides fragilis group Enterobacter spp. Other Bacteroides spp. Proteus spp. Clostridium spp. --- Pseudomonas aeruginosa --29 Organism-specific risk factors MRSA Pseudomonas aeruginosa Previous MRSA infection or colonization within the past year High-local prevalence of MRSA among S. aureus isolates High-local prevalence of Pseudomonas infection Severe infection Warm climate Frequent exposure of the foot to water 30 DFI classification Clinical Manifestation of Infection PEDIS Grade IDSA Severity No signs or symptoms of infection 1 Uninfected Local infection is present if ≥2 of the following are present: • Local swelling or induration • Erythema • Local tenderness or pain • Local warmth • Purulent discharge Infection involves only the skin and subcutaneous tissue. If erythema, must be >0.5 cm to ≤2 cm around the ulcer. 2 Mild Local infection with erythema >2 cm or involving structures deeper than skin and subcutaneous tissue. 3 Moderate Local infection with the signs of SIRS, with ≥2 of the following: • Temperature >38°C or <36°C • Heart rate >90 beats/min • Respiratory rate >20 breaths/min or PaCO2 <32 mmHg • WBC count >12,000 or <4,000 cells/μL or ≥10% bands 4 Severe 31 DFI treatment Mild • For suspected MSSA or Streptococcus: • Amoxicillin/clavulanate • Cephalexin • Dicloxacillin • Clindamycin • Levofloxacin • For suspected MRSA: • TMP/SMX • Doxycycline Moderate • Empiric therapy against MSSA, Streptococcus, Enterobacterales, and obligate anaerobes • Ampicillin/sulbactam • Cefoxitin • Ceftriaxone • Ertapenem • Meropenem • Levofloxacin or ciprofloxacin PLUS clindamycin • Moxifloxacin • Tigecycline • If MRSA is suspected, add: • Vancomycin • Daptomycin • Linezolid • If P. aeruginosa is suspected: • Piperacillin/tazobactam Severe • Empiric therapy against MRSA, Pseudomonas, Enterobacterales, and obligate anaerobes • Piperacillin/tazobactam • Meropenem • Ceftazidime • Cefepime • Aztreonam • PLUS • Vancomycin • Daptomycin • Linezolid Glycemic control must be maximized to ensure optimal wound healing!!! 32 DFI route & duration of therapy • Continue antibiotic therapy until signs of infection resolve, but not through complete healing of the wound Mild PO x 1-2 weeks Moderate Severe PO or IV, switch to PO IV, switch to PO when when patient clinically patient clinically improves x 1-3 weeks improves x 2-4 weeks • Continue antibiotics for 2-5 days following radical resection (amputation) that leaves no remaining infected tissue • Continue antibiotics ≥4 weeks when there is persistent infected or necrotic bone 33 Active learning question #3 FO is a 60 yo M with a PMH significant for uncontrolled T2DM (A1c = 12%) who presents to the ED with pain, swelling, and purulent discharge coming from the top of his foot near his toes. FO has an extensive history of foot infections and recently completed a 4-week course of vancomycin for a MRSA infection. Vitals obtained in the ED were WNL although his WBC count was 16,000 cells/μL. The ED physician classifies this wound as PEDIS grade 3 and asks you as the ED pharmacist for empiric therapy recommendations. What do you recommend? A. B. C. D. Vancomycin and piperacillin/tazobactam Vancomycin Nafcillin and metronidazole Vancomycin, ceftriaxone, and metronidazole 34 Active learning question #4 Upon reading a MRI of the infected foot, the podiatrist, ID physician, and vascular surgeon agree that the best course of action would be to perform a transmetatarsal amputation on FO. Tissue and bone cultures were obtained during surgery, and bone was sent for histology. The podiatrist that performed the surgery stated in his note that all infected tissue was removed during the debridement/amputation. Forty-eight hours following surgery the bone culture reveals MRSA, pan-sensitive K. pneumoniae, and pan-sensitive B. fragilis. You are rounding with the ID team today, and the resident asks you for therapy recommendations. What do you recommend? A. B. C. D. Vancomycin x 4 weeks Vancomycin and piperacillin/tazobactam x 5 days Vancomycin, ceftriaxone, and metronidazole x 4 weeks Vancomycin and ampicillin/sulbactam x 5 days 35 Questions? Purulent Infections Nonpurulent infections Folliculitis Erysipelas Diabetic foot infections Furuncle Carbuncle Cellulitis Impetigo 36 Skin and Soft Tissue Infections PHAR 5337 - October 24, 2023 Anne Gonzales-Luna, PharmD, BCIDP Research Assistant Professor University of Houston College of Pharmacy [email protected] 37