Pharmacotherapy of infectious disease:

5. Skin and Skin Structure Infections

Mengist Awoke (MSc, Assistant Professor)

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Lesson objectives
1. Discuss skin structure and function responsible for preventing infection.

2. Describe the epidemiology, etiology, pathogenesis, and clinical

manifestations associated with acute bacterial skin and skin structure
infections (ABSSSIs).

3. Identify goals of therapy associated with clinical response in patients

with ABSSSI.

4. Recommend effective Non-pharmacological, and empiric and definitive

antimicrobial regimens

5. Monitor chosen antimicrobial therapy for safety and efficacy.

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Introduction

 The largest organ of the body  Barrier against toxins,

 It has three layers pathogens and dehydration

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Introduction….
Intact skin generally is resistant to infection.
 Mechanical barrier,
 Its relative dryness,
 Slightly acidic pH,
 Colonizing bacteria,
 Frequent desquamation, and
 Production of various antimicrobial defense chemicals,
including sweat(which contains IgG and IgA), prevent
invasion by various microorganisms.
 SSTIs involving any or all layers of the skin (epidermis, dermis,
subcutaneous fat), fascia, and muscle.
 most common infections seen in community and hospital settings.

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Introduction….
Normal flora of the skin
 Staphylococcus epidermidis
 Staphylococcus aureus (can be
pathogen)
 Streptococcus sp.
 Micrococcus species
 Peptostreptococcus species
 Neisseriae species
 Propionibacterium species
 Diphtheroids
 Candida species (can be
pathogenic)
 Acinetobacter species (can be
pathogenic)
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Risk factors of SSI

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 Pathophysiology of SSTIs
Any risk factors,
 Skin puncture, abrasion,
 underlying diseases (eg,
diabetes), PAD, SAM,
 Recent antibiotic Rx, and
young/old age
(a) high concentrations of bacteria (more
than 105 microorganisms),
(b) excessive moisture of the skin,
(c) inadequate blood supply,
(d) availability of bacterial nutrients, and
(e) damage to the corneal layer allowing
for bacterial penetration

Impairs skin protection

against microbes

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Common SSTIs

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Common SSTIs…
Primary Infections
 Caused by a single pathogen, usually affect normal skin.
 Impetigo, folliculitis, and boils are common types.
 The most common primary skin pathogens are S aureus, B-
hemolytic streptococci, and coryneform bacteria.
 Organisms usually enter through a break in the skin.
Secondary Infections
 Secondary infections occur in skin that is already diseased.
 Because of the underlying disease, the clinical picture and
course of these infections vary.

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Common SSTIs…

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1. Impetigo
It’s a common skin infection that can occur in any age-group
but most frequently affects children between 2 and 5 years.
Starts as a red, itchy sore.
As it heals, a crusty, yellow or “honey-colored” scab forms over the sore

Pathogens
β-Hemolytic streptococci (Streptococcus pyogenes or Group A Streptococcus
[GAS]) and S. aureus
Transmitted easily within the body and to other persons

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Treatment
Goals :
Preventing infection spread within the patient and
to others,
Symptom relief (eg, itching)
Infection resolution
Preventing recurrence
Improving cosmetic appearance
Prevention of the rare but serious complications

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 Non-pharmacological Rx
Increased hygiene along with soaking and cleansing lesions
with soap and water.
Use skin emollients to dry skin areas….reduce spread and
urge to scratch itchy lesions.
Natural remedies ? tea tree oil and Manuka honey may
provide some anecdotal benefit

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Pharmacological Rx
Antibiotic therapy is recommended to prevent spread of
infection and complications.

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Pharmacological Rx…

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Pharmacological Rx…
The following steps outline the proper administration topical
preparations:
1. Applicants wash hands thoroughly with warm water and
antibacterial soap.
2. Using a clean washcloth soaked in warm soapy water,
gently rub the crusty lesions to loosen the debris, thus
allowing for adequate antibiotic penetration.
 In order to prevent further infection…take care to avoid scrubbing the
lesions.
3. Apply a thin layer of the prescribed ointment to each sore,
including the surrounding area.
4. When finished, wash hands well and, if necessary, apply a
piece of gauze to the infected area.

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Complications and preventions
 A rare complication of impetigo is poststreptococcal
glomerulonephritis (PSGN)…2 weeks after infection
Prevention ?
Proper hygiene
Washing hands vigorously with antibacterial soap and water
and taking regular baths
Instructed to use clean washcloths and towels every time
Avoid sharing any personal care products such as clothing
and towels
Not attend school or playgroups until 48 hours after
starting treatment or until the sores have blistered and
dried up.
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2. Folliculitis, Furuncles, and Carbuncles

 Folliculitis is inflammation of the hair follicle and is caused by

physical injury, chemical irritation, or infection.
 Infection occurring at the base of the eyelid is referred to as
a stye.

 While folliculitis is a superficial infection with pus present only

in the epidermis,
 furuncles and carbuncles occur when a follicular infection extends from
around the hair shaft to involve deeper areas (subcutaneous tissue) of
the skin
 The lesions are called carbuncles when adjacent furuncles coalesce to
form a single inflamed area

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Folliculitis, Furuncles, and Carbuncles

S. aureus and CA-MRSA

Klebsiella, Enterobacter, and Proteus species.. facial skin, nasal mucous membranes,
and neighbouring areas

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Folliculitis, Furuncles, and Carbuncles…Clinical
Presentation

Folliculitis
 Clustering, pruritic papules localized to hair follicles.
 Generally develop in areas subject to friction and perspiration.
 Papules are generally 5 mm or less in diameter and erythematous.
 Papules evolve into pustules that generally spontaneously rupture in
several days.
 Systemic signs (fever, malaise) are uncommon.

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Folliculitis, Furuncles, and Carbuncles…Clinical
Presentation

Furuncles
 Inflammatory, draining nodule involving a hair follicle.
 Generally develop in areas subject to friction and perspiration.
 Lesions are discrete, whether occurring as singular or multiple nodules.
 Lesion starts as a firm, tender, red nodule that becomes painful and
fluctuant.
 Lesions often drain spontaneously.
 Lesions caused by CA-MRSA often have necrotic centers
 Systemic signs are uncommon.

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Folliculitis, Furuncles, and Carbuncles…Clinical
Presentation

Carbuncles
Formed when adjacent furuncles coalesce to form a single inflamed
area.
Form broad, swollen, erythematous, deep, and painful follicular
masses.
Commonly develop on the back of the neck
Commonly associated with systemic signs (fever, chills, malaise).
Bacteremia with secondary spread to other tissues is common.

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Rx of Folliculitis, Furuncles, and Carbuncles
Desired Outcomes
 Relieving discomfort,
 Preventing further spread of the infection, and
 Preventing recurrence
 Non-pharmacological Rx
 Local application of moist heat (38°C to 40°C applied for 15 to 20
minutes),
 Daily chlorhexidine washes and daily washing of personal items such
as towels, bedding, and clothes
 Drainage of the lesion,
 Phototherapy,

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Pharmacological Rx
Topical antibiotics….number of lesions is limited
 Fusidic acid 2% cream twice daily
 Clindamycin 2% gel twice daily
 Mupirocin 2% ointment applied two to three times daily
 Applied for 7 days.
• S/E dermatitis, dryness, or pruritus over the applied area
 Topical antiseptic agents alone or in combination with
antibiotics…. especially in recurrent furunculosis
 Benzoyl peroxide 2% to 10% twice daily gel, cream, soap, or Solution
 Hypochlorite 3% to 5% solution
 Systemic antibiotics…systemic symptoms such as fever,
lymphadenitis, or cellulitis appear

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Pharmacological Rx..
 First‐line oral antibiotics
 Dicloxacillin (250 mg four times daily) and
 Cephalosporins (such as cefadroxil 500 mg twice daily)
 Antibiotic‐resistant S.Aureus
 Clindamycin, tetracyclines, trimethoprim‐sulphamethoxazole, linezolid,
or glycopeptide (vancomycin) may be used
 For gram‐negative folliculitis (antipseudomonal activity)
• Oral or parenteral ciprofloxacin 400 to 500 mg twice daily
 Duration of Rx varied across the etiologies
• 5 to 10 days…gram +ve bacteria
• 7 to 14 days…. gram –ve bacteria and MRSA

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 Pharmacological Rx..
Drug Regimen

Cefadroxil Adult: 1 g orally daily in a single dose or in divided doses twice a day
Pediatric: 30 mg/kg orally once daily or in equally divided doses every 12 hours
Ciprofloxacin Adult: 500 mg orally every 12 hours for 7 to 14 days; 400 mg IV every 12 hours for 7
to 14 days
Clindamycin Adult: 150 to 300 mg orally every 6 hours, 600 to 1200 mg/d IV or IM divided every 6
to 12 hours
Pediatric: 8 to 16 mg/kg/d ORALLY divided every 6 to 8 hours; 15 to 20 mg/kg/d IV or
IM divided every 6 to 8 hours
Tetracyclines Adult: 500 mg orally twice daily or 250 mg orally 4 times per day
Pediatric: (older than 8 years) 25 to 50 mg/kg orally in 4 equally divided doses
Trimethoprim‐sulphamethoxazo Adult: sulfamethoxazole 800 mg/trimethoprim 160 mg to sulfamethoxazole 1600
le mg/trimethoprim 320 mg orally twice daily
Pediatric: (older than 1 month) based on trimethoprim component: 8 to 12 mg/kg/d
orally in 2 divided doses
Linezolid Adult: 400 to 600 mg ORALLY every 12 hours for 10 to 14 days
Pediatric: (birth through 11 years) 10 mg/kg IV or ORALLY every 12 hours
vancomycin) Adult: 30 mg/kg/d IV in 2 divided doses or 40 mg/kg/d IV in 4 divided doses
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Evaluation of Therapeutic Outcomes
 Many follicular infections resolve spontaneously without
medical or surgical intervention.
 Lesions should be incised if they do not respond to a few days
of moist heat and nonprescription topical agents.
 Following drainage, most lesions begin to heal within several days
without antimicrobial therapy.
 Any patient who is unresponsive to several days of systemic
antibiotic therapy or suffers recurrent infection should have a
culture and sensitivity test performed to guide continued
antibiotic selection.

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3. Erysipelas
 It’s distinct form of cellulitis involving the more superficial
layers of the skin and cutaneous lymphatics
 It is characterized by an area of erythema that is well
demarcated, raised, and burning pain
 Often affects the lower extremities, with the face being the
second most commonly affected site.

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3. Erysipelas…Risk factor/Etiology
Risk Factors
 Excising the saphenous vein for bypass
 Lymphatic edema (major risk factor)
 Lymphatic obstruction
 Arteriovenous fistula
 Status post-surgery (eg mastectomy)
 Nephrotic syndrome
 Immunocompromised state
 Insect bites, stasis ulceration, surgical incisions, and venous insufficiency
 obesity, lymphedema, athlete’s foot, leg ulcers, eczema, intravenous drug
abuse, poorly controlled diabetes, and liver disease
 Almost always caused by β-hemolytic streptococci
 Group A streptococci (S.pyogenes)
 Occurs in areas of preexisting lymphatic obstruction or edema

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3. Erysipelas…Treatment
 Goals
 Rapid eradication of the infection,
 Providing relief of symptoms (pain, tenderness, fever)
 Preventing recurrent infection
 Mild-to-moderate cases
 IM procaine penicillin G or penicillin VK for 7 to 10 days
 Penicillin-allergic patients
 treated with clindamycin

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3. Erysipelas…Treatment
Inpatient vs outpatient Rx
 Children younger than 3 months,
 Critically ill appearing patient
 Local complications,
 Debilitated patient (chronic conditions, the elderly) or
 If there is a risk of non-compliance with or failure of outpatient
treatment.
 Treat other patients as outpatients.

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3. Erysipelas…Treatment
Outpatient Rx (7 to 10 days)
Cefalexin
PO for Children 1 month to under 12 years: 25 mg/kg 2 times daily
Children 12 years and over and adults: 1 g 2 times daily or
Amoxicillin/clavulanic acid (co-amoxiclav) in the ratio of 8:1
or 7:1
Children < 40 kg: 25 mg/kg 2 times daily
Children ≥ 40 kg and adults2 times daily
For penicillin-allergic patients, clindamycin
Children: 10 mg/kg 3 times daily;
Adults: 600 mg 3 times daily.
In the event of worsening clinical signs after 48 hours of
antibiotic treatment, consider IV route.
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3. Erysipelas…Treatment
Inpatient Rx
First line therapy]
 Cloxacillin IV infusion over 60 minutes
 Children 1 month to under 12 years: 12.5 to 25 mg/kg every 6 hours
 Children 12 years and over and adults: 1 g every 6 hours or
 Amoxicillin/clavulanic acid (co-amoxiclav) by slow IV injection (3
minutes) or IV infusion (30 minutes).
 Children under 3 months: 30 mg/kg every 12 hours
 Children 3 months and over: 20 to 30 mg/kg every 8 hours (max. 3 g
daily)
 Adults: 1 g every 8 hours
 If pencillin allergy: clindamycin IV infusion over 30 minutes
 If there is clinical improvement after 48 hours switch PO at the
doses indicated above to complete 7 to 10 days of treatment.

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3. Erysipelas…Treatment
 If there is no clinical improvement after 48 hours, consider
MRSA:
 Clindamycin IV infusion over 30 minutes (If resistance rate is
low (e.g., <10%).
 Children 1 month and over: 10 mg/kg every 8 hours
 Adults: 600 mg every 8 hours
 After 48 hours, change to clindamycin PO at the doses
indicated above to complete 7 to 10 days of treatment.
 If resistance is High, Rx?

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4. Cellulitis

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4. Cellulitis
 It is an infection of epidermis, dermis and may spread
subsequently within the superficial fascia.
 It’s a common and potentially serious infection caused by
bacteria.
 It usually affects the arms and legs

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4. Cellulitis
 Injection drug users….. S. aureus, including MRSA and
Clostridium species
 Diabetics……mixed aerobic and anaerobic pathogens
 Complications of cellulitis
oLocal abscess,
oMyositis,
oOsteomyelitis,
oSeptic arthritis,
oBacteremia,
oEndocarditis, and
oSepsis.

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4. Cellulitis….Clinical presentation
 Signs and symptoms
 fever, chills, or malaise and complain that the affected area feels hot
and painful.
 Erythema and edema of the skin.
 Lesions are nonelevated and have poorly defined margins.
 Affected areas generally are warm to touch
 Purulent drainage, exudates, and/or abscesses
 Tender lymphadenopathy associated with lymphatic involvement
 Systemic findings such as hypotension, dehydration, and
altered mental status are common.
 Lab Tests: Cultures, Gram stain, CBC

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4. Cellulitis…Treatment
Goals
 Rapid eradication of the infection
 Prevention of further complications
 Avoidance of unnecessary antimicrobials that contribute to increased
resistance, and
 Minimizing toxicities and cost of therapy
 Non-pharmacological Rx
 Elevation and immobilization of the involved area to decrease swelling
 Cool sterile saline dressings may decrease pain and can be followed
later with moist heat to aid in localization of the cellulitis
 Surgical intervention (incision and drainage)

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4. Cellulitis…Treatment

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Evaluation of Therapeutic Outcomes
 If treated promptly with appropriate antibiotics, the majority
of patients with cellulitis are cured rapidly.
 Culture and sensitivity results should be evaluated carefully
for both the adequacy of culture material and the presence
of resistant organisms.
 Additional high-quality samples for culture may be needed
for microbiologic analysis.
 Failure to respond to therapy also may be indicative of an
underlying local or systemic problem or a misdiagnosis.

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5. Necrotizing Soft-tissue Infections

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5. Necrotizing Soft-tissue Infections

NF is a rapidly progressive, life-threatening infection causing necrosis of

subcutaneous tissue and fascia.
Due to GAS infection, its associated mortality rate approaches 25%
Most frequently involve the abdomen, perineum, and lower extremities.
NF can affect any age-group.
The major clinical entities of necrotizing infections are necrotizing fasciitis
and clostridial myonecrosis (gas gangrene)

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5. Necrotizing Soft-tissue Infections

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5. Necrotizing Soft-tissue Infections…RFs
 Diabetes
 Chronic disease
 Immunosuppressive drugs (eg, prednisolone)
 Malnutrition
 Age > 60 years
 Intravenous drug misuse
 Peripheral vascular disease
 Renal failure
 Underlying malignancy
 Obesity
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5. Necrotizing Soft-tissue
Infections…etiology and classification
 Caused by aerobic and/or anaerobic bacteria and
 Results in progressive destruction of the superficial fascia and
subcutaneous fat

80%

flesh-eating bacteria Eg. S. pyogenes

5% Gas production and muscle necrosis…gas

gangrene

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5. Necrotizing Soft-tissue
Infections…etiology and classification

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5. Necrotizing Soft-Tissue Infections…Clinical
presentation

• Rapid diagnosis is critical due to the aggressive nature and

high associated mortality (20%-50%).
Symptoms
• Fever, chills, and leukocytosis and
• Shock and organ failure…type II infections.
• Pain in the affected area and systemic toxicity are
characteristically more pronounced than with cellulitis.

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5. Necrotizing Soft-Tissue
Infections…Clinical presentation
Signs
 Affected area…hot, swollen, and erythematous without sharply
demarcated margins.
 Affected area… shiny, exquisitely tender, and very painful.
 Diffuse swelling of the area is followed by the appearance of bullae
filled with clear fluid.
 Rapidly progressive infection with the frequent development of a
maroon or violaceous color of the skin after several days.
 Infection may rapidly evolve into a cutaneous gangrene, sometimes
with myonecrosis.
 Investigations: Tissue samples (culture and susceptibility
testing), MRI/CT, CBC, chemistry, C-reactive protein…..

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5. Necrotizing Soft-Tissue
Infections…Treatment
Goals
Rapid eradication of the infection,
Prevention of further complications, and
Reduction in mortality
Avoidance of unnecessary antimicrobials that contribute to increased
resistance, and
Minimizing toxicities and cost of therapy
Non-pharmacological Rx
 Immediate and aggressive surgical debridement of all necrotic tissues
 Hyperbaric oxygen therapy
 Occlusive conventional dressings using humid or vaseline gauze
dressings

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 5. Necrotizing Soft-Tissue
Infections…pharmacological Rx

The mean
11/17/2023 duration of antibiotic therapy for NF
BY MAis 4–6 weeks. 51
Evaluation of Therapeutic Outcomes
 Vital signs and laboratory tests should be monitored carefully
for signs of resolution of the infection.
 Change in antimicrobial therapy or additional surgical
debridement may be needed in patients who do not show
signs of improvement.

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6. Diabetic Foot Infections

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6. Diabetic Foot Infections….Introduction
Diabetic foot infections range in severity from superficial
paronychia to deep infection involving bone.
Major types of foot infections are seen in diabetic patients:
deep abscesses, cellulitis of the dorsum, and mal perforans
ulcers
The lifetime risk of developing at least one foot ulcer in
persons with diabetes is estimated at 30%.
DFIs are the main risk factor for limb amputation, and in
addition to significant morbidity and impact on quality of life,
the healthcare costs
71,000 lower-extremity amputations/year
20% of them will undergo additional surgery or amputation of a second
limb within 12 months of the initial amputation

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DFI…RFs/Etiology
Risk factors Etiology of DFIs

30%

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 Pathophysiology
1. Neuropathy
 Affect the motor nerve supply of small intrinsic muscles of the foot, resulting in
muscular imbalance, abnormal stresses on tissues and bone, and repetitive injuries
 Diminished sensory perception
 Absence of pain and unawareness of minor injuries and ulceration
2. Sympathetic nerve supply may be damaged,
 Resulting in an absence of sweating that may lead to dry cracked skin and secondary
infection
3. Atherosclerosis (micro/macro angiopathy)
 Ischemia and PAD, ultimately leading to skin breakdown, infection, and impaired
wound healing.
4. Impaired phagocytosis and intracellular microbicidal function
 Defects in cell-mediated immunity make patients with diabetes more susceptible to certain types of
infection and impair the patients’ ability to heal wounds adequately

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DFI...Clinical presentation and Dx

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DFI...Clinical presentation and Dx

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DFI...Clinical presentation and Dx
DFI are classified into four categories based on clinical
presentation using the PEDIS scale (perfusion, extent/ size,
depth/tissue loss, infection, sensation)

PEDIS 1

PEDIS 2

PEDIS 3

PEDIS 4

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Treatment
Goals
 Successfully treat infected wounds by using effective nondrug
and antibiotic therapy;
 Prevent additional infectious complications;
 Preserve as much normal limb function as possible;
 Avoid unnecessary use of antimicrobials that contribute to
increased resistance; and
 Minimize toxicities and cost while increasing patient quality of
life.

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Non-pharmacological Rx
 Debridement of necrotic or nonviable tissue,
 Wound dressings,
 Vascular or orthopedic surgery, and
 Off-loading pressure from the wound
 Prevention
Periodic foot examinations with monofilament testing and patient
education regarding proper foot care,
Optimal glycemic control, and
Smoking cessation are key preventative strategies

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Pharmacological Rx
Selection of empiric antimicrobial therapy guided by
 Severity of a patient’s infection and Based on the PEDIS scale,

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Pharmacological Rx

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Evaluation of Therapeutic Outcomes

 Therapy should be reevaluated carefully after 48 to 72 hours

to assess favorable response.
 Change in therapy (or route of administration, if oral) should
be considered if clinical improvement is not observed at this
time.
 For optimal results, drug therapy should be appropriately
modified according to information's from deep-tissue culture
and the clinical condition of the patient.
 Infections in diabetic patients often require extended courses
of therapy because of impaired host immunity and poor
wound healing.

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