SKIN AND SOFT TISSUE INFECTIONS

By:
Martin Rey Edrick C. Santos, RPh

A written paper submitted in partial fulfillment of the course

Disease Management 2

at the

Department of Pharmacy
Centro Escolar University - Makati

Submission Date: October 31, 2022

 SKIN AND SOFT TISSUE INFECTIONS

I. DEFINITION

Skin and soft tissue infections (SSTIs) encompasses any type of microoganism, whether it is bacterial,
viral, or fungal, that enters any break in the skin and invades the epidermis, dermis, subcutaneous tissue,
or superficial fascia. SSTIs primarily manifest with painful, warm, erythematous skin lesions and may also
lead to purulent fluid collections and necrosis of the affected tissue. SSTIs are classified into two groups,
which can either be uncomplicated infections or complicated infections. Uncomplicated SSTIs are simple
infections that are most commonly caused by gram-positive pathogens such as Staphylococcus and
Streptococcus. These infections are generally not risky and are mostly treated with outpatient care.
Examples of uncomplicated infections include folliculitis, impetigo, carbuncles, furuncles, cellulitis.
Complicated SSTIs, on the other hand, are rapidly spreading infections have a higher tendency to be
polymicrobial which means that the infection can be caused by different microorganisms. This type of
infection requires immediate medical attention because it involves deep tissues. Complicated SSTIs
include abscesses, ulcers, necrotising fasciitis, bites, and burns.

II. ETIOLOGY

The skin is the largest organ of the body which protects us from microbes and the elements, helps
regulate body temperature, and permits the sensations of touch, heat, and cold. It is the first line of
defense of the human body as it acts as our barrier to the unsterile outside environment.

The skin has many ways to protect our bodies from the outside world. It normally has an acidic pH where
many pathogens cannot survive. Together with its acidic properties, it has the ability to secrete sebaceous
substances that inhibit the reproduction of bacteria by free fatty acids. The skin also has the ability to
constantly shed off the outermost part of the epidermis as the body gets rid off the dead skin cells
contaminated with foreign pathogens. The skin also has a healthy normal skin flora which can protect us
from dermatological infections by competing with foreign microorganisms for growth. With a healthy mix of
normal skin flora, foreign pathogens cannot grow extensively and invade our bodies.

The normal flora of the skin consists of gram-positive bacteria such as Staphylococcus epidermidis,
Staphylococcus aureus, Streptococcus spp., Corynebacterium spp., Propionibacterium spp., gram-
negative bacteria such as Enterobacteriaceae, and yeast which includes Candida spp. When our skin
becomes damaged through physical contact (e.g. cuts, bruises, burns) or through chemical means by
rubbing antibacterial soaps which cause the imbalance of the normal skin flora, foreign pathogens can
now invade the insides of our bodies through the skin’s damaged barrier. Furthermore, without the right
mix of the normal skin flora, certain types of bacteria can now proliferate and cause skin infections which
may go deeper into the skin and muscle layers. In more serious cases, the infection may become
systemic.

III. EPIDEMIOLOGY

SSTIs are common and range in severity from minor, self-limiting, superficial infections to life-threatening
diseases. According to the study of Dryden, recent epidemiological trends have shown an increase not
only in healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA), but also in MRSA
acquired in the community. Many of the latter strains produce exotoxins and are epidemiologically distinct
from healthcare-acquired strains.

In the United States, SSTIs are common infections in all healthcare settings. Between 2005 and 2010, in
a large US-based, multicenter, retrospective cohort of ambulatory and inpatient encounters among nearly
50 million commercially insured individuals aged 0–64 years, Miller and colleagues reported the
frequency of SSTIs to be 2.3 million cases, which was far higher than that of either urinary tract infections
or pneumonia.

In another study, Kaye and colleagues noted the absolute volume of SSTI hospitalizations, as well as
SSTI diagnoses, increased in the United States in 2011. Similarly, Lee and colleagues assessed US

 trends in SSTIs between 2000 and 2012 and found a 40% increase (2.4 million to 3.3 million) in the
overall incidence of SSTIs during this period.

IV. PATHOPHYSIOLOGY

The epidermis of the skin does not contain blood vessels and is protected against infections by its
outermost layer called the stratum corneum. Skin and soft tissue infections occur when microbes invade
the different layers of the skin overwhelming the natural host defenses.

SSTIs can be community-acquired or nosocomial acquired. Common pathogens that can cause
community-acquired SSTIs include S. aureus, which is the most common identifiable cause of purulent
SSTIs, and beta-haemolytic streptococci. Nosocomial-acquired SSTIs which can be usually contracted
from the hospital, may be caused by the infection of S. aureus, Enterococcus spp., Pseudomonas
aeruginosa, Escherichia coli, and other Enterobacteriaceae.

V. RISK FACTORS

SSTIs are predominantly caused by aerobic gram-positive cocci, specifically the beta-hemolytic
streptococci and S. aureus. Other microorganisms also cause SSTIs but not most of the time. It depends
on the nature of the SSTI and whether it is acquired in the hospital or in the community.

• Surgery. During surgery, the cut or wound of the skin is readily exposed to the environment where
various microorganisms roam around. The exposed skin is no longer protected by stratum corneum
and is vulnerable to infections by pathogens, particularly S. aureus with variable rates of methicillin-
resistance. Surgical site infection usually occurs more than 48 hours after an incision and is
characterized by localized wound-related erythema, heat, induration and purulent discharge.
Involvement of deep structures should always be considered and management depends on the
surgical site.

• Diabetes. Patients with diabetes for a long time may have peripheral nerve damage and reduced blood
flow to their extremities. This increases the chance of having infections. The high sugar levels in the
blood and tissues allow bacteria to grow and allow infections to develop more quickly.

• Vascular insufficiency. Vascular insufficiency occurs when the leg veins do not allow blood to flow
back to the heart. This can cause dry, itchy skin that is prone to rashes, as well as infections and
wounds. Skin and underlying tissues can be inflamed due to poor blood circulation that typically
happens in the lower legs.

• Immobilization. Patients, most often the elderly, who are disabled or paralyzed are at high risk of
developing decubitus ulcers resulting from prolonged pressure, friction, and moisture on the skin.
Prolonged immobilization can also cause embolism which can block the blood flow through the arteries
and may cause vascular insufficiency.

• Poor hygiene. People with poor hygiene may have high risk of developing skin and soft tissue
infections due to bacteria and other pathogens that are accumulating on their bodies. These pathogens
may proliferate and enter the body systems to cause infections if not cleaned properly.

• Animal or human bites. The depth and site of the bite is critical. Bites on the hand are common so it is
important to take close monitoring on tendon involvement and maintenance of function. Infections are
polymicrobial, usually which came from the oral flora of the one who bit. Examples of bacteria in the
oral flora are S. aureus, aerobic and anaerobic streptococci, Clostridium spp., Fusobacteria and gram-
negative bacteria.

• Open wounds underwater. Wounds obtained under water may be at high risk of being contaminated
with harmful pathogens since the exposed wound is directly in contact with water especially if it is
contaminated with plenty of bacteria. Both fresh and saline water contain millions of microorganisms.
Vibrio vulnificus and Aeromonas hydrophilia are frequently responsible. In hospitals, some hydrophilic

 organisms such as Pseudomonas and Stenotrophomonas can also cause SSTIs, particularly in
compromised, post-operative patients. Systemic infection is unusual.

• Skin punctures. Puncturing the skin through the use of needle or injections can be dangerous
especially if not performed by trained healthcare professionals. The full range of infections, ranging
from simple injection-site abscesses to necrotising infections, can be seen in hospitals and clinics.
Developing systemic infection and venous thromboembolism can occur in SSTI patients due to risk of
translocation of skin microorganisms directly into the blood stream. Gram-positive organisms,
particularly S. aureus and betahemolytic streptococci, are usually implicated. Clostridium spp.,
particularly C. perfringens and C. novyi, can cause devastating, rapidly progressive infections
associated with marked leukocytosis and systemic inflammatory response.

• Immunosuppression. People with weak immune system may develop SSTIs, particularly caused by
S. aureus and S. pyogenes. Gram-negative organisms, including P. aeroginosa, should be considered
in the context of neutropenia and line-related SSTI. Fungal infections such as Fusarium, Aspergillus, or
Sporothrix spp. are less frequently seen, but may occur when a patient has neutropenia, organ
transplant, or taking long-term immunosuppressive drugs.

VI. SIGNS AND SYMPTOMS

SSTIs are characterized by a varying degree of erythema or redness, pain or tenderness, and warmth.
Uncomplicated SSTIs are generally mild and infect only the outermost portions of the epidermis.
Complicated SSTIs involve the deeper skin structures (eg. fascia, muscle layers) which may require
surgical intervention due to more serious and potentially life threatening systemic symptoms.

Complicated SSTIs are distinguished from uncomplicated SSTIs by the presence of the following signs:
severe constant pain, blistering and bruising, edema beyond the margin of the erythema, numbness of
the affected skin, presence of gas in the tissues, systemic inflammatory response, and multi-organ failure.

Uncomplicated SSTIs

An impetigo is a superficial, non follicular pustules which occurs prominently on exposed areas of the face
and extremities. It can be characterised as honey-crusted lesions where the pustules may rupture and
forms a thick crust. A subtype of impetigo is the bullous impetigo characterised by lesions with a central
moist crust and an outer zone of blister formation. Causative pathogens include S. aureus and beta-
hemolytic streptococci.

Folliculitis is a superficial skin infection localised at hair follicles where multiple clustered lesions are at
least 5 mm, erythematous and pruritic containing pus. Lesions may spontaneously drain and resolve.
Pathogens include various types: Streptecocci, Staphylococci, Candida, and occasionally P. aeruginosa.

A furuncle is also an infection of the hair follicle but a complication of folliculitis. It may involve small skin
abscess extending through the dermis into the subcutaneous tissue. Common pathogen causing this is S.
aureus.

A carbuncle is a contagious skin infection in the epidermis layer that often involves a group of hair
follicles. The infected portion of the skin forms a lump, called mass, occurring deep into the skin. The
infected mass is filled with fluid, pus, and dead tissue. Fluid may be simply drained out of the carbuncle,
but sometimes the mass is so deep that it cannot drain on its own. Having a carbuncle may present with
fever, mostly in diabetic patients. S. aureus commonly cause carbuncles.

Cellulitis is a noncontagious infection of the dermis, which may extend into the subcutaneous tissues. The
hallmark signs of cellulitis are erythema, warmth, swelling, and tenderness. It usually affects the lower
legs, but it can also occur on the face, arms and other areas. If left untreated, the infection can spread to
the lymph nodes and bloodstream and rapidly become life-threatening. Erysipelas is a superficial form of
cellulitis which affects the upper dermis and is raised above surrounding skin with a well demarcated
edge. Cellulitis can be obtained through different environments where there are bacteria. When a person
is exposed to fresh water, he may be infected by Aeromonas hydrophilia. If the patient is exposed to salt

water and got infected with cellulitis, it may be due to Vibrio vulnificus. If the wound is contaminated with
soil, Pseudomonas, Clostridium, or Bacillus may cause the cellulitis. Facial cellulitis may be caused by
Haemophilus influenzae and may be complicated by otitis and sinusitis.

Cellulitis and erysipelas may be accompanied by a systemic inflammatory response and localized
lymphadenopathy which may occur following a minor skin breach or an insect bite. Pathogens include S.
aureus including MRSA, Streptococci (groups A, B, C, G), and Streptococcus progenies for post-
operative wound infections. For immunocompromised patients with cellulitis, the cause is polymicrobial
including gram-positive, gram-negative, and anaerobes. Risk of infection is increased in
immunocompromised patients, following trauma or surgery, in those with Tinea pedis, diabetes mellitus,
peripheral vascular disease, or peripheral edema, and in very obese people.

Decubitus ulcers are pressure sores or bedsores are injuries to skin and underlying tissues. Bedsores
most often develop on skin that covers bony areas of the body such as heels, ankles, hips, and tailbone.
Patients with bedsores may develop tissue ischemia and neural damage that can lead to necrosis. Even
a small skin defect can cause deep necrosis of deeper tissues. Causative agents are polymicrobial
consisting of S. aureus, gram-negative bacteria such as Enterobacter, and anaerobes such as
Bacteroides. Complications of bedsores may lead to severe cellulitis, osteomyelitis, and sepsis.

Complicated SSTIs

Scalded skin syndrome is induced by epidermolytic exotoxins (exfoliatin) A and B, which are released by
S. aureus. This causes detachment of the skin within the epidermal layer.

Necrotizing fasciitis involves tissues deep into the dermis reaching up to the superficial part of the muscle.
Infection moves along the injury which started as a direct consequence of a more superficial infection.
Underlying tissues often feel wooden and may have dark discoloration of the skin. It is often associated
with high fever, sepsis, and septic shock. It can be due to a single microorganism, usually streptococci or
less commonly community-acquired MRSA, A. hydrophila, or V. vulnificus, or due to more than one
microorganism, involving a mixed aerobe–anaerobe bacterial flora. Polymicrobial causes are common in
diabetics and patients with vascular insufficiency.

Myositis involves the muscles and two forms of SSTIs can be attributed to it. First is the anaerobic
streptococcal myositis which usually occurs after surgery or open trauma, when infections reach deep
into the muscles and fascial planes. The other one is pyomyositis in which there is a pus within a muscle
group usually presenting with localized pain, muscle spasm, and fever.

Synergistic necrotising cellulitis is a necrotising soft tissue infection involving muscle groups, in addition to
superficial skin and fascia.

Fournier gangrene involves the perineum and genitalia, usually in patients with underlying disease,
particularly diabetes mellitus. Onset is usually sudden but can be insidious. An initial superficial focus of
infection becomes necrotic and spreads to deep tissues and along fascial planes. Most cases are caused
by mixed aerobic and anaerobic flora. S. aureus and Pseudomonas species are sometimes present,
usually in mixed culture. S. aureus is known to cause this infection as the sole pathogen.

Clostridial myonecrosis, or gas gangrene, can be described by severe localized pain, systemic
inflammatory response and rapidly evolving skin changes within 24 hours of trauma. It is commonly
caused by Clostridium perfringens. Affected areas become tense, fluid-filled blisters develop and gas is
visible on plain radiographs. Spontaneous gangrene can complicate malignancy and neutropenia, is
usually blood-borne from a colonic focus and occurs in the absence of trauma.

Burn wounds are tissue damage that results from heat, overexposure to the sun, or other radiation, or
chemical or electrical contact. It can be minor skin injuries or life-threatening emergencies depending on
the depth and extent of damage through the skin layers. Pathogens involved are the usual skin flora,
Staphylococci and Streptococci. Nosocomial infections may be infected by SPACE organisms (Serratia,
Pseudomonas, Acinetobacter, Citrobacter, Enterobacter).

 VII. DIAGNOSIS

If the patient has suspected SSTI, several tests are done in order to determine which microorganisms are
causing the injury as well as the depth and extent of the injury. The most basic test to diagnose SSTIs is
the observation of the physical characteristics of the infected area. The physician will be able to determine
what kind of SSTI has inflicted the patient especially if it is only superficial by knowing the physical
description of the skin infection. If the infection has reached deep into the subcutaneous layer or deeper,
other diagnostic tests can be done to the patient.

• Laboratory tests. A sample of pus or liquid draining from the infection site may be analyzed to
determine which type of microorganism is causing the infection.

• Blood tests. A blood sample will be taken from the patient to help identify which specific organism is
infecting the patient.

• Biopsy. A tissue sample is taken from the infected area to view under a microscope. This can identify
more specifically the infectious agent.

• CT scan. A CT scan combines X-ray and computer technology to produce detailed cross-sectional
images of tissue, and bone and blood vessels. This can determine the depth and extent of the infection
through the skin layers.

• Lumbar puncture. This is done to determine if there is an indication also for CNS infection.
The severity of SSTIs can be determined by several clinical factors: extent and intensity of inflammation,
distribution and depth of infection, presence of systemic inflammatory response, and significant
comorbidities. These clinical factors can help determine which kind treatments are suitable for the patient,
if it is appropriate to confine the patient in the hospital or not, and whether a parenteral route or oral
therapy is appropriate.

The patient will be required to be treated with IV therapy if he cannot tolerate oral therapy or had a failed
oral therapy in his previous treatments, and his symptoms has significant localized heat, erythema, and
induration.

To determine if the patient should be hospitalized, the following criteria should be satisfied: severe
localized pain, new onset of confusion, rapidly evolving skin lesions or skin blistering, systolic blood
pressure <100 mmHg, and sepsis syndrome which can be described as having any of two: heart rate
>100 beats/min, respiratory rate >20 breaths/min, temperature >38C or <36C, and what cell count > 12 or
<4 x 109 cells/L.

VIII. PROGNOSIS

The prognosis of SSTIs vary according to the depth and extent of the infection through the skin an muscle
layers. Uncomplicated SSTIs affect only the superficial part of the skin and they rarely cause any
systemic infections. The healing period can take only a few weeks to restore the skin’s normal condition
with proper treatment. As for complicated SSTIs, the healing period takes longer and the time to restore
healthy skin might take months or years. Sometimes, the skin can’t restore its normal physical
appearance and physiology at all, especially for necrotizing SSTIs and severe burns.

IX. NON-PHARMACOLOGICAL TREATMENTS

Abscesses are common in SSTIs due to bacterial infection. These are painful collections of pus which
may develop under the skin, or in organs, or in spaces between organs. In addition to antibiotics,
drainage of abscess is important to prevent further pain and damage to the infected area. Superficial
minor infections (eg., impetigo, folliculitis, furuncle, carbuncle), with pus may be drain on its own. With
warm compress on the infected skin, it can promote the spontaneous easy drainage of abscess. Drainage
of abscess may be done through using a needle or surgery in deeper infections (eg., cellulitis,

complicated SSTIs). The surgeon makes a small incision on the infected skin then inserts a drainage
catheter into it allowing the pus to drain out into a bag.

Patients who developed necrotizing SSTIs are required to undergo surgical procedure where in severe
cases, aggressive debridement is done. Debridement is a procedure that involves thorough cleaning of
the wound and removing all hyperkeratotic, infected, and necrotic dead tissue, foreign debris, and
residual material from dressings. This procedure avoids possible bacterial proliferation due to dead
tissues. While the patient is recovering from debridement, it is important to remove pressure points to
avoid bedsores. This can be done through frequent repositioning of the patient on the bed, providing soft
pads on beds to reduce pressure, keeping the skin clean, and ensuring that the skin is dry. When the
patient has already bedsores, application of medicated gauze or other special dressings can protect the
wound from infections.

Infection control for preventing an outbreak scenario includes laundering beddings, linens, and garments
of the infected person. Ensure to change wound dressings frequently, and practice good hygiene all the
time. Also, it is important to screen the patient for the presence of S. aureus in nasal carriage.

Rest and leg elevation is important in hastening the recovery process from lower limb SSTIs.

X. PHARMACOLOGICAL TREATMENTS

Topical antibiotics for uncomplicated SSTIs such as impetigo has shown to be efficacious. Examples of
these are mupirocin, retapamulin, fusidic acid, erythromycin, and tetracycline. Topical antibiotics decrease
bacterial colonization and infection. It also promotes faster wound healing. Oral antibiotics like co-
amoxiclav, cephalexin or cloxacillin have also shown to have high efficacy as well. Oral therapy is
recommended for patients with numerous lesions such as in patients with cellulitis or in outbreaks
affecting several people to help decrease transmission of infection. When MRSA is suspected or
confirmed, the use of sulfamethoxazole-trimethoprim is recommended. Uncomplicated SSTIs are rarely
treated with systemic antibiotics unless the patient has multiple lesions, immunosuppressed, or has signs
of systemic infection.

Ciprofloxacin, meropenem, or imipenem may be used for the treatment of cellulitis caused by A.
hydrophilia when a patient is exposed to fresh water. Doxycycline, cefotaxime, or ciprofloxacin may be
used for cellulitis caused by V. vulnificus obtained through exposure to salt water.

Empiric therapy is prescribed to the patient if the SSTI is more serious with high risk of MRSA infection as
well as significant comorbid illnesses (eg., diabetes mellitus, congestive heart failure, dialysis), and the
test results are not yet available to determine the specific causative agents. Vancomycin is the standard
treatment among IV antibiotics. Other broad spectrum antibiotics for complicated SSTIs include
carbapenems, and piperacillin-tazobactam. Linezolid can be used if the bacteria is resistant to
vancomycin. Gentamicin, daptomycin, and metronidazole can be considered as alternatives, depending
on how the patient can tolerate these drugs especially their side effects. Consultation from experts should
be sought when using these alternatives. Clindamycin may be added to inhibit toxin production.

Once the diagnostic test results have been determined, a narrower spectrum of antibiotics can be
administered to the patient depending on several factors such as anatomical site of infection, resistance
patterns, as well as MRSA risk.

For hospitalized patients requiring IV treatment, considering the patient is not allergic to penicillin, drugs
of choice are narrow-spectrum beta-lactam antibiotics such as benzylpenicillin (for beta hemolytic
streptococci) and flucloxacillin (for both beta-hemolytic streptococci and staphylococci). Either of these
choices can be prescribed as first line, however, if it is a MRSA infection or polymicrobial infection as seen
from the diagnosis, the drug of choice will be flucloxacillin. If the patient is allergic to penicillin drugs,
vancomycin or clindamycin is usually selected. A continuous infusion of either flucloxacillin (12 grams per
24 hours) or vancomycin (2 grams per 24 hours), following an initial IV dose, is administered to the
patient if the SSTI is severe enough. The purpose of this is for the antibiotic levels to be constantly above
the minimum inhibitory concentration to optimize efficacy in eradicating the causative agents. Also, severe
SSTIs should be managed with fluid resuscitation aside from broad spectrum antibiotics.

 For patients with necrotising or rapidly progressive infections, IV clindamycin at a dose of 900 mg every 8
hours is added to enhance cover against toxigenic S. pyogenes. Clindamycin reduces the production of
streptococcal toxic shock protein by its action on bacterial mitochondria. It is also active when beta-
lactams are rendered ineffective, which occurs during the static growth phase of streptococci when
penicillin binding protein production is temporarily stopped.

Patients with SSTIs involving the lower limbs should be assessed for signs of T. pedis and should be
treated with topical antifungals such as miconazole or terbinafine. For severe tinea infections, oral
terbinafine may be required.

Treatments for animal bites include co-amoxiclav, or moxifloxacin plus 8 clindamycin for 5 to 10 days.
Patients may be considered for tetanus toxoid in addition to these antibiotics.

Treatments for decubitus ulcers include piperacillin-tazobactam, carbapenems, clindamycin, or 3rd

generation cephalosporin or fluoroquinolones. If the pathogen is suspected MRSA, use vancomycin.

XI. PATIENT COUNSELING

Follow good hygienic practices, as well as contact isolation of contagious SSTI patients such as impetigo,
to prevent the spreading of SSTIs to other people. This practice must be encouraged, especially in
neonatal and pediatric intensive care units, as well as for patients with HIV infection and a rash.

The emergence of MRSA is a serious problem. It is important that the patient will follow the instructions of
a medical expert upon the administration of antibiotics especially in treating SSTIs since there are cases
where broad spectrum antibiotics are required. With proper guidance and compliance of the patient,
developing bacterial resistance can be prevented.

Patients with severe burns may have resistance patterns and the metabolism of drugs may be increased
which can affect the efficacy as well as adverse drug reactions of other drugs. It is important for the
patient to consult with a healthcare professional for appropriate antibiotic treatments and drug therapy
regimen.

REFERENCES

https://www.amboss.com/us/knowledge/Skin_and_soft_tissue_infections

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https://academic.oup.com/ofid/article/4/1/ofw255/2632203?login=true

https://pubmed.ncbi.nlm.nih.gov/19560670/

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