Dermatology Infectious Diseases+Pharmacology

Empiric Therapy Considerations

1. what are the likely sites of infxn

2. that are the most likely pathogens

3. what animicrobials are most likley to be active against the pathogens
   -pathogen susceptibility to abx
   -community vs nosocomial pathogens
   -achievable concentration at site of action
   -bactericidal vs bacteriostatic

Gram+ vs Gram- Bacteria

gram+

• strep agalactiae

• strep pyogenes

• staph aureus

gram -

• pseudomonas

• e coli

• kleibsiella

• enterobacter

Pharmacologic Agent Considerations

absorption

• are there any barriers to PO absorption

distribution

• does the mx get to the site of action

metabolism

• are there any drug-drug interactions that result in subtherapeutic or supratherapeutic concentrations of your mx

excretion

• do we need to dose adjust our antifungals due to decreased renal fxn/excretion

SSTIs (General)

fxn

• epithelium→1st line of defense

acute care+ambulatory care presentations

variable in severity of illness

general considerations

• status of host defenses

• associated manifestations:
  -severity of illness
  -toxicity

predisposing conditions

• excessive skin moisture

• decreased skin perfusion

• damage to layer of skin

Impetigo

E: 2-5 y/o
beta hemolytic streptococci
s aureus

CM:
blisters:

• numeruous

• well-localized

• erythematous

• pruitic

• face

• extremities

C: cellulitis

Impetigo Tx Goals

prevent spread of infxn/contagion+complications

relief of sx

improve cosmetic appearance

Impetigo Tx

NP

MX:

1st line

• PO dicloxacillin

• PO cephalexin

alternatives

• PO clindamycin

• topical mupirocin

Folliculitis

E:
S aureus
candida

CM:
small papules
hair follicle involvement

Folliculitis/Furuncles/Carbuncles Tx Goals

resolution of infxn with minimal/no scarring

avoiding complications

Folliculitis Tx

topical mupirocin

antifungal shampoo

Furuncles

E:
staphylococci
young men

CM:
boils
SQ skin involvement

Furuncles Tx

systemic dicloxacillin x 5-10 days

systemic cephalexin x 5-10 days

Carbuncles

E: staphylococci
consider→CA-MRSA
DM pts

CM:
several larger follicles→into SQ fat
-back of neck

painful

Carbuncles Tx

NP

• incision+drainage

MX

• systemic dicloxacillin x 5-10 days

• systemic cephalexin x 5-10 days

• systemic bactrim x 5-10 days

• systemic doxycycline x 5-10 days

• systemic clindamycin x 5-10 days

Cellulitis

PP: break in skin→infxn of dermis+SQ tissue
-complicated vs uncomplicated

E:
S aureus
-purulent/exudative→MRSA
beta-hemolytic strep
polymycrobial
DM
vascular insufficiency
IVDA

90%→leg

• trauma

• surgery

• burns

• skin dxs

CM:
red+infected area:

• lesions not raised

• poorly-defined margins

• painful

• tender

DX:
±leukocytosis
abscess→blood cultures+img studies
culture+sensitivity

Erysipelas vs Cellulitis

erysipelas

• low grade fever

• flu-like sxs

• angry red

• burning pain

• spider-like

• raised above surrounding skin

• defined borders

cellulitis

• lesions not raised

• poorly defined margins

Cellulitis Tx

NP

• 1st line tx→incision+drainage

• elevate+immobilize limb

• open purulent lesions→sterile saline dressing

MX

localized→PO
systemic signs+sxs+comorbid conditions→IV
tx length→x 5-7 days

MSSA/GAS:

• dicloxacillin

• cephalexin

CA-MRSA:

• clindamycin

• doxycycline

• bactrim

• resistance→vancomycin or linezolid

Cellulitis Special Considerations

comorbid conditions
-immunocompromised
-DM
-vascular insufficiency

• increased risk of gram- bacilli
  -e coli
  -p aeruginosa
  -±anaerobes

IVDA

• site of infxn→ante-cubital region of the arm

• abscess formation

• consider→PO bx

tx selection based on

• empiric→local antibiogram/guidelines

MRSA Risk Factors

CA-MRSA

• skin trauma

• close contact sports

• shave/wax
  -armpits
  -groin

• tattoos

• body piercings

• prisoner

• physical contact
  -draining cut
  -MRSA carrier

• share dirty personal items/equippment

HA-MRSA

• surgical wound

• intravenous (IV) line

• prolonged hospitalization

• recent abx use

• weak immune system

• close MRSA contact
  -family members
  -pts
  -healthcare workers

• hemodialysis

Erysipelas E+Tx

E:
s pyogenes
other beta hemolytic strep spp

TX:
inpt→IV
outpt→PO

• beta-lactam

• allergy→clindamycin

Cutaneous Abscesses (Furuncle/Carbuncle) E+Tx

E:
s aureus

TX:
incision+drainage
recurrent→mupirocin

Non-Purulent Cellulitis E+Tx

E:
s pyogenes
other beta-hemolytic strep spp
MSSA
CA-MRSA

TX:
beta lactam
clindamycin
linezolid
beta lactam+bactrim
beta lactam+doxycyline
beta lactam+minocycline

Purulent/Trauma-Related Cellulitis E+Tx

E: s aureus
MRSA

TX:
clindamycin
bactrim
doxycycline
minocycline
linezolid

Necrotizing Fasciitis (NF)

PP: necrosis of SQ tissue+fascia
-rapidly progressing
-life-threatening

E:
monomicrobial (30%)
-invasive group a strep
-clostridium perfringens
-CA-MRSA
-toxin production→toxic shock

polymicrobial (70%)
-anaerobes
-enterobacteriaceae
-facutative anaerobes
-p aeurginosa

surgery/trauma:
-bowel
-decubitus ulcer
-perianal involvement

CM:
early→severe pain around infxd area
-erythematous+edematous+warm
-ischemia→present

late→area becomes numb
-progressively gangrenous
-fever
-sepsis

DX:
WBC→elevated
ESR→elevated
CRP→elevated

gas/fluid collection→MRI+CT
-may delay tx

C:
mortality rate→high (50%)
-DM
-immunocompromised
-obese

untxd→invade muscles+circulation→amputation (50%)

Necrotizing Fasciitis (NF) Tx

NP: 1st line→surgery
fluids
nutrition status

MX:

adjunct to surgery

• zosyn or meropenem
  +

• vancomycin/daptomycin/linezolid

strep/clostridium infxn→add clindamycin

group a strep/c perfringens→IV penicillin G+IV clindamycin

Viral Skin Infections (General)

herpex simplex virus (HSV)

HSV 1→PO

HSV 2→genitals

DX:
HSV 1+recurrent infxns→laboratory confirmation

HSV 2→clinical

tissue culture

Genital HSV Infection (HSV 2)

RF:
multiple sexual partners
increasing age
female
low socioeconomic status
HIV

E: sexual contact→HSV 2
22% in US

CM:
primary

1. incubation period→2-12 days
   -mean→4 days

2. prodrome
   -itching
   -burning
   -erythema

3. multiple transient+painful vesicles on genitals

4. systemic sxs:
   -fever
   -headache
   -malaise
   -abdominal pain
   -myalgia

recurrent infxn

• similar sxs

• less severe+shorter duration

C: pregnancy→increased transmission rate (50%)

Genital HSV Infection (HSV 2) Tx

initial→antiviral therapy
recurrent→supressive therapy

topical acyclovir→less effective

primary

• PO acyclovir TID x 7-10 days

• PO valacyclovir BID x 7-10 days

• PO famiciclovir TID x 7-10 days

recurrent (6+ outbreaks/yr)

• PO acyclovir TID x 5 days

• PO valacyclovir daily x 5 days

• PO famiciclovir BID x 5 days

suppressive therapy

• PO acyclovir BID

• PO famicyclovir BID

• PO valacyclovir daily/BID

pregnancy:

• PO acyclovir TID x at 36 weeks gestation

• PO valacyclovir BID x at 36 weeks gestation

Orolabial HSV Infection

PP: m/c form of mucocuteanous herpes infxn

RF: female
hx→STDs+multiple sexual partner/s
white (35-60%)

E: HSV-1
primary→u5 y/o
recurrence→UV radiation

CM:
primary (u5 y/o)

• painful vesicles

• ulcerative erosions
  -tongue
  -palate
  -gingiva
  -buccal mucosa
  -lips

• fever

• malaise

• myalgia

reucurrences→shorter+less severe

P:
recurrences→2-3 times/yr

Orolabial HSV Infection Tx

no topical tx→not effective

start x within 72 hrs

initial

• PO acyclovir 5ID x 7-10 days

recurrent

• high-dose antiviral mx

• start early→decreases size+duration of lesions

recurrent+immunocompromised

• PO acyclovir 5ID x 5 days

• PO valacyclovir q12h x 1 day

• PO famiciclovir single dose

long-term recurrent+immunocompromised

• reduces recurrences

• prolongs initial recurrence time

• PO acyclovir BID

• PO valacyclovir daily

Tinea Infections (General)

PP: dermatophyte infxn

E: fungus→dermatophytes

• corporis→body (ringworm)

• cruris→groin (jock itch)
  -teens
  -young adults
  -male

• unguium (onychomycosis)→nails

• pedis→foot (athlete’s foot)

CM:

corporis (ringworm)

• red+annular+scaly pruitic patch

• central clearing

• active border

cruris (jock itch)

• upper thigh

• opposite the scrotum

tinea pedis (athlete’s foot)

• skin between toes→spreads

spreading surfaces:

• sole

• sides

• dorsum

Tinea Infections Tx

1st line

• topical terbinafine

• topical butenafine

PO antifungal agents

• extensive tx

• topical tx fail

• immunocompromised

• severe moccasin-type tinea pedis

Tinea Infections CIs

DO NOT USE

• nystatin→resistant

• griseofulvin (for onychomycosis)→terbinafine better

• combo products→aggravate fungal infxns
  -bethamethasone+clotrimazole

• topical clotrimazole/micronazole→topical butenafine/terbinafine better

Tinea Unguium (Onychomycosis) (General)

dermatophyte fungal infxn of toenails

teens/adults+dystrophic toenails

m/c→big toe
-little toe→chronic trauma

mimics

• chronic trauma

• psoriasis

Tinea Unguium (Onychomycosis) Tx

tx duration→long (x 3-6 months)

recurrences→common (up to 50%)

no topical tx→ineffective

1st line→PO terbinafine
2nd line→PO fluconazole

PO tx fail→ciclopirox nail lacquer (penlac)+pt edu about low cure rate

assessment of cure/follow-up→9-12 months

Candidiasis Tx

based upon

• anatomic location

• underlying dxs

• immune status

• infxn RFs

• specific candida species

• candida sensitivity to specific antifungal txs

tx

• echinocandins caspofungin

• micafungin

• anidulafungin

• fluconazole

• lipid formulations of amphotericin B

Azoles (General)

MX+I→immunocompomised pts prophx:
aspergillus

• posaconazole

• voriconazole

• itraconazole

esophageal candidiasis

• fluconazole

MOA:
differs among agents

ROA:

• multiple CIs→check specific mx labeling

• narrow tx window→dose adjustment
  -transplant mx
  -adjust before+after tx

AE:
hepatoxicity
rash
QTc prolongation
-exception isavuconazole→shortens QTc

CI:
CYP450 inhibitors
p-glycoprotein (P-gp) inhibitors
organic cation transporter 2 (OCT2)

Fluconazole

MX: azoles

MOA:
good

• most candida spp

• cryptococcus neoformans

• cocciodiodes immitis

moderate

• c glabrata

• can be “susceptible-dose dependent”

poor

• molds

• c krusei

I: candidiasis
candidiasis prophx
cryptococcal meningitis step-down tx
some dimorphic fungi

ROA: highly bioavailable (IV=PO dosage)
only azole that gets into urine→renal dose adjustment

Echinocandins

MX: anidulafungin
micafungin
caspofungin

MOA: inhibits synthesis of beta-1 3-D-glucan→breaks down fungal cell wall
-distributes widely

exceptions:
-eye
-CNS
-urine

I: invasive candidiasis
-candida spp→fungicidal

ROA: no PO formulation

AE: mild infusion rxn→slows infusion rate
hepatoxicity (uncommon)

CI: molds→neither cidal nor static
not CYP450 metabolized→fewer mx interactions than azoles
not renally eliminated→can’t use for urinary tract

Terbinafine

MOA: inhibits squalene oxidase of fungi→decreased ergosterol synthesis
-bioavailability→only 40%
-hepatic metabolism
-renal excretion

I: trichophyton spp
candida (not used clinically)
-onychomycosis
-tinea capitis
-athlete’s foot
-jock itch
-ringworm

ROA: PO
topical

distribution:
-nails
-fat
-skin

half life→200-400 hrs

AE: headache
GI sxs
hepatotoxicity
derm infxns
toxic epidermal necrolysis (TEN)
neutropenia

Butenafine

MOA: fungicidal activity against tinea-causing dermatophytes

I: dermatophytes

ROA: topical
superior to clotrimazole+miconazole