U3 medicine - pharmacology of dermatologic infections & diseases

gram positive bacteria

Streptococcus and Staphylococcus

S. aureus

S. pyogenes

S. agalactiae

gram negative bacteria

bacilli

E. coli

Klebsiella

Enterobacter

Pseudomonas

most common pathogens of skin infections

Staphylococcus aureus

B-hemolytic streptococci

-Strepotoccus pyogenes (GAS)

-Strepotoccus agalactiae

cellulitis

infection of the dermis and SQ tissue, 90% involving the leg

occurs after a break in skin barrier

signs

erythema, warmth, swelling, tenderness, indistinct margins

may have fever or lymphadenitis

common organisms:

B-hemolyytic streptococci (GAS) Staphylococcus aureus

cellulitis

painful and tender infected area

rapidly spreading areas of redness, edema and heat

erysipelas = low grade fever, flu-like symptoms, angry red, raised above surrounding skin, defined borders

cellulitis •

-lesions not raised and poorly defined margins

W/ or w/o leukocytosis

consider blood cultures and imaging studies (abscess)

consider Incision and Drainage (I&D)

cellulitis treatment

non pharm = I&D

Dicloxicillin or Cephalexin

Clindamycin, Doxycycline, or Bactrim

is resistance, consider Vancomycin or Linezolid

cellulitis special considerations

comorbid conditions (consider IV)

-i.e immunosuppressed, diabetes, or vascular insufficiency

-increased risk of gram-negative bacilli

IVDA (IV drug abuse)

-site of infection: ante-cubital region of the arm

-abscess formation

-consider oral bacteria

folliculitis/furuncles/carbuncles

Folliculitis

-small erythematous papules/pustules centered on hair follicles, often itchy or mildly tender

Furuncles (boils)

-deeper infection of hair follicle, painful nodules with purulent center

Carbuncles

-larger, interconnecting abscesses, often with systemic symptoms (fever, malaise)

Organism

-most commonly S. aureus

impetigo

highly contagious superficial infection, common in children aged 2-5

numerous, well-localized, erythematous and pruritic lesions

present as blisters w/ or w/o symptoms

can develop into cellulitis

Non-bullous = honey-colored crusted lesions, especially on face/extremities

Bullous = flaccid bullae that rupture easily.

organisms

S. aureus

B hemolytic streptococci (GAS)

impetigo treatment

penicillin used to be mainstay of therapy

Dicloxacillin or Cephalexin PO

alternative = Clindamycin PO

maybe topical mupirocin

folliculitis

inflammation of the hair follicles

small papules

caused by S. aureus, Candida

treatment: topical abcx or antifungal

agents

topical mupirocin

antifungal shampoo

topical mupicorin and antifungal shampoo

treatment of folliculitis

furuncles

boils; large, tender, swollen areas

caused by a Staphylococcal infection around hair follicles or sebaceous glands

treatment is abx: dicloxicillin, cephalexin

dicloxicillin, cephalexin

treatment for furuncles

carbuncles

larger and several follicles into SQ fat and back of the neck

painful , usually in patients with diabetes mellitus

caused by Staphylococci

treatment: I&D, abx

-Dicloxicillin, Cephalexin, or CA-MRSA agents (Bactrim, Doxycyline, clindamycin)

Dicloxicillin, Cephalexin

or CA-MRSA agents (Bactrim, Doxycyline, clindamycin)

treatment of carbuncles

pt has higher risk for being infected with CA-MRSA

if pt...

has skin trauma (eg, "turf burns," cuts, or sores)

is athlete of a close contact sport

shaves or wax to remove body hair, particularly of the armpits and groin

has tattoos or body piercing or prisoner

has physical contact with a person who has a draining cut or sore or is a carrier of MRSA

shares personal items or equipment that is not cleaned

pt has higher risk for being infected with HA-MRSA

if pt...

has a surgical wound and/or intravenous (IV) line

being hospitalized for a prolonged period of time

recent use of antibiotics

having a weakened immune system due to a medical condition or its treatment

being in close proximity to other patients, family members, or health care workers who are colonized with MRSA

hemodialysis

necrotizing fasciitis

uncommon, rapidly progressing, life-threatening

necrosis of the SQ tissue and fascia = "flesh eating bacteria”

high mortality (up to 50%) , especially in diabetes, immunocompromised, or obese

polymicrobial

-70% of the cases

-anaerobes, enterobacteriaceae, facultative anaerobes

-usually after surgery or trauma involving bowel, decub ulcer or perianal involvement

monomicrobial

-30% of cases (more severe than polymicrobial)

-invasive Group A Strep (GAS) or Clostridium perfringens or CA-MRSA

-toxin production --> Toxic shock

type 1 NF

polymicrobial infection with aerobic and anaerobic bacteria

70% of cases

type 2 NF

monomicrobial infection

30% of cases

necrotizing fasciitis

early on = similar to cellulitis

-severe pain after infected, warm, red area

late disease = area goes numb

-becomes gangrenous, septic, pt becomes febrile

if left untreated = myonecrosis and septic shock, hypotension and multiple organ failure

-50% require amputation of extremity

first line treatment = surgery asap

second line = abx

-piperacillin-tazobactam or meropenem + vancomycin, daptomycin, or linezolid

-additional clindamycin

-if GAS identified then penicilin G or Clindamycin G

penicillin VK

drug of choice for Group A strep

cephalexin or dicloxacillin (PO)

cefazolin, nafcillin, or oxacillin (IV)

drug of choice for MSSA skin and soft tissue infection

hsv

herpes simplex virus type 1

-gingivostomatitis, herpes labialis

hsv-2

-genital lesions

-itching, burning, redness

-multiple transiet painful vesicles

-fever, headache, malaise

oral acyclovir

treatment of genital hsv

more effective than topical acyclovir but also reduces duration of viral sheeding and length of time before lesions crust

primary infection of hsv-2

treatment

-acyclovir PO

-valacyclovir PO

-famciclovir PO

transmission in pregnancy

transmission rates of HSV to neonates during pregnancy are low in women with non-primary HSV infections, but they approach 50% in women with primary infections

C section delivery should be performed in women with primary or recurrent genital herpes at the time of labor to reduce the risk of neonatal transmission

hsv-1

painful vesicles and ulcerative erosions on the tongue, palate, gingiva, buccal mucosa and lips

affects children under 5, but affects 30-60% of population

-fever, malaise possible

-triggered by UV radiation

oral acyclovir

treatment for hsv-1

accelerates loss of crusts and can reduce the mean duration of pain by 36%

treatment for recurrent infections

-acyclovir PO

-valacyclovir PO

-famciclovir PO

fungi

yeasts

-reproduce asexually via budding

mold

-reproduce via spores

-grows in the form of "hyphae"

dimorphic

-exists as mold/yeast

-some will switch forms depending on temp

yeasts

-reproduce asexually via budding

Candida spp.

Cryptococcus

mold

-reproduce via spores

-grows in the form of "hyphae"

Aspergillus spp.

Fusarium

Scedosporium

Zygomycetes

dimorphic fungi

-exists as mold/yeast

-some will switch forms depending on temp

Histoplasma

Blastomyces

Coccidiodes

Paracoccidiodes

dermatophytosis

"ringworm" disease of the nails, hair, and/or stratum corneum of the skin caused by fungi called dermatophytes

tinea capitis

ringworm infection of the head, scalp, eyebrows, eyelashes

tinea favosa

ringworm infection of the scalp (crusty hair)

tinea corporis

ringworm infection of the body (smooth skin)

typically presents as a red, annular, scaly, pruritic patch with central clearing and an active border

worsening after empiric treatment with a topical steroid should raise the suspicion of a dermatophyte infection

cultures are usually not necessary to diagnose

tinea cruris

ringworm infection of the groin (jock itch)

most commonly affects adolescent and young adult males, and involves the portion of the upper thigh opposite the scrotum

tinea unguium

ringworm infection of the nails

aka onychomycosis

mimics include chronic trauma and psoriasis

the great toes are most often involved in onychomycosis and trauma-related dystrophy, but exclusive little toe involvement is likely related to trauma

oral terbinafine

treatment of tinea unguium

3-6 month tx course

-toenails grow/repair slowly

recurrence is common

oral flucanazole is an option

tinea barbae

ringworm infection of the beard

tinea manuum

ringworm infection of the hand

tinea pedis

ringworm infection of the foot (athlete's foot)

typically involves the skin between the toes, but can spread to the sole, sides, and dorsum of the involved foot

terbinafine (lamisil)

and

betanafine (lotrimin ultra)

treatment of tinea infections

tinea corporis, tinea cruris, and tinea pedis are generally responsive to topical creams like the following

contraindicated treatment for tinea infections

do not use nystatin

do not use griseofulvin to treat onychomycosis

do not use combo products such as bethmethasone/clotrimazole

do not use tropical clotrimazole or miconazole

candiasis

treatments used to manage Candida infections vary substantially

latest recommendations include the echinocandins caspofungin, micafungin, and anidulafungin, along with fluconazole, as well as lipid formulations of amphotericin B in various situations

presentation: beefy red rash with satellite lesions, often in warm/moist areas (skin folds, diaper area).

symptoms: itching, burning.

organism: Candida albicans.

azoles

adverse reactions

-rash

-QTc prolongation

-hepatotoxicity

drug interactions - inhibition of CYP450 enzymes and some inhibit p-glycoprotein (P-gp) and organic cation transporter 2

used for prophylaxis against fungal infections in immunocompromised hosts

azoles

posaconazole, voriconazole, itraconazole, fluconazole

fluconazole

used to treat many forms of candidiasis, prophylaxis against candidiasis, step-down therapy in cryptococcal meningitis, some dimorphic fungi

covers

most Candida spp.

Cryptococcus neoformans

Coccidioides immitis

C. glabrata

poor activity against molds, C. krusei

renally dose adjusted bc only azole that gets into the urine

highly bioavailable --> IV dose = oral dose

echinocandins

anidulafungin

micafungin

caspofungin

echinocandins

mechanism of action: inhibit the synthesis of beta-1,3-D-glucan, which is a cell wall component

fungicidal against Candida spp., activity in molds is neither cidal nor static

pharmacokinetics: no oral formulation; fewer drug interactions than azoles (not CYP450 metabolized); distributed widely except for the eye, central nervous system, and urine; not renally eliminated (can't use for urinary tract!)

adverse events: mild infusion reactions (can slow infusion rate), hepatotoxicity possible but uncommon

echinocandins

same spectra of activity for all three echinocandins

Activity

Good: Candida spp., Aspergillus spp.

Moderate: C. parapsillosis, increasing C. glabrata resistance

Poor: non-Aspergillus molds, Cryptococcus neoformans

clinically, the echinocandins are interchangeable and have similar efficacy

fungi

has ergosterol instead of cholesterol

area of target of antifungals

caspofungin (cancidas)

treats

-Invasive candidiasis

-Esophageal candidiasis

-febrile neutropenia

-salvage aspergillosis

drug interactions

-possibly added hepatotoxicity with cyclosporine

metabolism

-in liver but not by P450

micafungin (mycamine)

treats

-Invasive candidiasis

-Esophageal candidiasis

-prophylaxis in stem cell transplant pts

drug interactions

-increases AUCs of sirolimus, nifedipine

metabolism

-in liver but not by P450

anidulafungin (eraxis)

treats

-Invasive candidiasis

-Esophageal candidiasis

metabolism

-enzymatic degradation in plasma

no drug interactions

terbinafine

mechanism

-inhibits squalene epoxidase of fungi, which leads to decreased ergosterol synthesis

pharmacokinetics

-Only 40% bioavailable

-distributed to nails, fat, and skin

-hepatic metabolism, but metabolites are excreted in urine

-half life of up to 200 to 400 hours

terbinafine

treats

-onychomycosis

-tinea capitis

-athletes foot

-tinea cruris

good activity against dermatophytes such as Trichophyton spp., Candida

adverse reactions

-headache, gastrointestinal, hepatotoxicity, dermatologic infections (including serious skin reactions such as Stevens-Johnson syndrome [SJS], toxic epidermal necrolysis [TEN]), neutropenia

butenafine

a new antifungal agent with primary fungicidal activity against dermatophytes that cause tinea infections

available for topical application

superior to clotrimazole and miconazole for Tinea infections