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A. Cellulitis [1]navigator

  1. Infection of the hypodermis and dermis
  2. Most commonly on limbs after skin abrasion or other break
  3. Common Forms of "Simple" Cellulitis
    1. Periorbital cellulitis
    2. Buccal cellulitis - usually due to Haemophilus influenzae
    3. Complication of body piercing - increasing incidence
    4. Following lumpectomy or mastectomy
    5. Liposuction - group A strep, peptostreptococcus
    6. Post-operative early wound infection mainly group A strep (see below)
    7. Perianal cellulitis - group A strep
    8. Catheter related infections (see below)
    9. Erythema migrans - Lyme disease (extremities, trunk; site of tick bite)
  4. Differential Diagnosis of Cellulitis [5]
    1. Deep vein thrombosis
    2. Superficial thrombophlebitis
    3. Contact dermatitis
    4. Insect stings
    5. Spider bite - may appear as vasculitis, deep infection [32]
    6. Drug reactions
    7. Eosinophilic cellulitis (Wells Syndrome)
    8. Gouty arthritis
    9. Foreign body reactions
    10. Uncommon: carcinoma erysipelatoides, FMF, urticaria, lymphedema, lupus, sarcoid
    11. Uncommon: lymphoma, leukemia, Paget disease, panniculitis
  5. Treatment of Simple Cellulitis [11]
    1. Common organisms inhabit skin flora
    2. Susceptibility testing is required in all cases, as antibiotic resistance is emerging
    3. Oral agents may be used in otherwise healthy persons without systemic symptoms
    4. Streptococcus: penicillin very good; second line vancomycin or cefazolin or oxacillin
    5. Staphylococcus aureus: oxacillin (nafcillin), vancomycin, cefazolin, Unasyn®
    6. Methicillin resistant Staph aureus increasingly common (see below)
    7. Consider prevalence of vancomycin resistant staph aureau (VRSA) when treating
    8. Exposure to salt water at site of skin break - Vibrio vulnificus, Mycobacterium marinum
    9. In immunocompromised patients, particularly those with liver disease, Vibrio vulnificus can severe cellulitis with bullae and ulcers, progressing to full septic picture
    10. Exposure to fresh water at site of skin break - Aeromonas species, Myco. marinum
  6. Methicillin Resistant Staph aureus (MRSA) [2,11,12]
    1. Increasing incidence of cellulitis caused by community acquired MRSA (CA-MRSA)
    2. MRSA now the most common cause of skin and soft-tissue infections in some emergency rooms in USA [6,12]
    3. CA-MRSA usually sensitive to doxycycline (minocycline), clindamycin, trimethoprim + sulfamethoxazole (TMP/SMX)
    4. However, TMP/SMX (1-2 double strengths tablets bid) may not provide adequate coverage for Streptococcus pyogenes (GAS)
    5. Linezolid, 600mg op q12 hours po, is expensive but has excellent efficacy (typically reserve for second line)
    6. Rifampin 600mg qd may be added to TMP/SMX or doxycycline; should not be used alone
    7. Intravenous agents for more severe infections: vancomycin, daptomycin, linezolid, tigecycline, Synercid® [11,12]
    8. Fluoroquinolones should not be used to treat MRSA as resistance levels are high
  7. Periorbital Cellulitis
    1. Should be treated aggressively to prevent eye involvement
    2. Broad-spectrum agents such as ampicillin-sulbactam (Unasyn®) ± MRSA coverage
  8. Complex Cellulitis
    1. Dirty wounds (see below)
    2. Injection drug abuse (IVDA) - usually S. aureus, group A strep, enterococcus, anaerobes [4]
    3. Consider mixed infection with underlying chronic disease, particularly diabetes
    4. In deep infections, particularly in diabetics, consider abscess and osteomyelitis
    5. Anaerobic cellulitis (see below)
    6. Necrotizing fasciitis (see below)
    7. Abscess
    8. Human or animal bites
  9. Diabetic Foot Infections
    1. Usually associated with significant peripheral neuropathy
    2. Trauma to lower limb often not noticed by patient
    3. Foot infections will often progress to serious nature
    4. Includes gram positive, gram negative, and anaerobic organisms
    5. Neutrophil dysfunction and other immune insufficiency contributes
    6. G-CSF (filgrastim) has been tested for diabetic foot infections
    7. G-CSF significantly reduced hospital stay and IV antibiotic use
    8. Treatment with broad spectrum antibiotics such as ticarcillin-clavulonate (Timentin®)
  10. Anaerobic Cellulitis and Gangrene
    1. Meleney's Synergistic gangrene - Staph aureus, anaerobic streptococci, post-surgical
    2. Clostridial cellulitis - C. perfringes, usually after local trauma or surgery
    3. Non-clostridial anaerobic cellulitis - mixed infections, usually in diabetics
    4. Gas Gangrene - C. perfringes, C. histolyticum, C. septicum, usually severe trauma
  11. Abscess
    1. Concerning for gas producing organisms
    2. Needs irrigation and drainage (closed space infection with poor blood supply)
    3. May involve soft tissues, fascia, muscle (pyomyositis), bone, or all layers
    4. Concern for development of osteomyelitis

B. Superficial Skin Infections navigator

  1. Impetigo (Pyoderma)
    1. Superficial skin infection usually in children
    2. Usually caused by Group A ß-hemolytic streptococci (GAS), usually S. pyogenes
    3. Staphylococcus aureus increasingly involved (usually bullous impetigo)
    4. Superficial skin infection usually in children
    5. Macules or papules progressing rapidly to vesicles, pustules, exudative crusts
    6. Often associated with insect bites, rhinorrhea, or minor abrasions
    7. Risk for development of glomerulonephritis but not rheumatic fever
    8. Penicillin im x 1 or erythromycin is given unless S. aureus is suspected
    9. Topical potent therapy with mupirocin (Bactroban®, apply tid) is very effective [17]
    10. Combination topical therapy with bacitracin+polymyxin+neomycin also effective [11]
    11. Retapamulin (Altabax®) 1% ointment (pleuromutilin antibiotic) is FDA approved for treatment of bullous and and non-bullous impetigo and also covers S. aureus [34]
  2. Erysipelas
    1. Superficial skin infection, bright red, indurated skin, usually in young adults
    2. Warmth, erythema, pain, leukocytosis, fever, lymphadenitis are most common
    3. Usually caused by ß-hemolytic GAS
    4. Some cases caused by Streptococci Groups B (newborns), C or G
    5. Organism can rarely be aspirated from advancing edge
    6. Penicillin iv or po, clindamycin, or first generation cephalosporin
    7. First generation cephalosporins such as cefalexin, cephadroxil, may also be used
  3. Folliculitis
    1. Infections involving hair follicles (includes carbuncles and furunculosis)
    2. Usually occur in areas of perspiration and/or friction
    3. Includes neck, face, axillae, buttocks
    4. S. aureus is most common cause
    5. Pseudomonas aeruginosa implicated from swimming pools, whirlpools
    6. Candida infrequently found
    7. Dicloxacillin, first generation cephalosporin, erythromycin po for moderate cases
    8. Mild cases usually heal spontaneously or with topical therapy
  4. Group G Streptococci [25]
    1. Increasing incidence of bacteremia due to these organisms
    2. Typically occurs in older men
    3. Skin or soft tissue infection implicated in most cases
  5. Diaper Dermatitis

C. Surgical Wound Infectionnavigator

  1. Usually caused by S. aureus [1]
  2. Prophylaxis prior to surgery with cephalosporins
    1. Ineffective prophylaxis in ~ 0.5% of patients
    2. Apparently due to production of ß-lactamases
    3. Topical mupirocin (Bactroban®) is very effective at reducing infection rates [17]
    4. Ertapenem, a long acting carbapenem, is more effective than cefotetan for prevention of surgical-site infection in patients undergoing elective colorectal surgery [8]
  3. MRSA - treat with vancomycin or newer agent since acquired in hospital
  4. Gram negative rods occasionally found
  5. Maintaining normothermia perioperatively reduces wound infections substantially
  6. Supplemental Perioperative Oxygen
    1. Giving 80% oxygen perioperatively reduced surgical wound infections ~50% [21]
    2. Surgical wound infection rates with 80% perioperative oxygen were 14.9% versus 24.4% with 30% oxygen [33]
    3. Strongly recommend supplemental perioperative oxygen to prevent surgical infections
  7. Intranasal Mupirocin (Bactroban® Nasal) [26]
    1. Reduces rate of nosocomial Staphylococcus aureus in S. aureus carriers by ~50%
    2. No effect of intranasal mupirocin on rate of S. aureus surgical wound infection
  8. Infections in surgical implants usually require debridement and/or removal, systemic antibiotics for 2-6 weeks, and replacement [30]

D. Dirty Woundsnavigator

  1. Good Debridement and irrigation
    1. Primary closure with sutures or novel tissue adhesives (octylcyanoacrylate)
    2. Tissue adhesives may have reduced secondary infections
  2. Coverage for G+ and anaerobes (such as Clostridium perfringens) may be required
  3. Oxacillin (nafcillin) ± Metronidazole
  4. Need to insure that patient is vaccinated for tetanus
    1. Give toxoid to patients whose last tetanus immunization was >4 years prior to admission
    2. Tetanus immunoglobulin recommended to ensure resistance to organism
    3. Consider patient's underlying immune status
    4. Particularly important in patients with IVDA
    5. Magnesium sulfate of now benefit in severe tetanus infection [10]
  5. Concern for development of osteomyelitis

E. Necrotizing Fasciitis [19] navigator

  1. Increasing indicence due to invasive Group A streptococci
    1. Patients with underlying chronic diseases at highest risk
    2. Older patients at increased risk
    3. Persons with contact >4 hours with carrier of organism at increased risk
    4. Nearly 50% of patients had toxic shock syndrome with fasciitis
    5. Groups B and G streptococci can also cause this syndrome [24]
  2. Gangrenous or crepitant cellulitis
    1. Usual focus is a local superficial wound with spreading
    2. Pain - often excruciating
    3. Erythema
    4. Edema and/or Crepitance is usually marked
    5. Muscle damage may occur and manifest as serum increased creatinine kinase (CPK)
  3. Death of muscle (myonecrosis) may occur [3]
    1. Especially with compartment syndrome
    2. Bacterial Myositis (septic myositis) also called pyomyositis
    3. Incidence of pyomyositis increasing in USA, mainly in immunocompromised persons
    4. HIV infection, diabetes mellitus, malignancy, rheumatologic conditions usually underlying
    5. Multifocal involvement with reduced symptoms more common in immunocompromise
    6. S. aureus (~70%), Salmolella (~5%), Bartonella (~7%), Gram Negative (~8%), others
    7. Pyomyositis is a surgical emergency and requires rapid debridement
    8. Rapidly progressive, often fatal if not treated aggressively
  4. Types of Necrotizing Fasciitis
    1. Necrotizing Fasciitis Type 1 - mixed anaerobes, Gram negative bacilli
    2. Necrotizing Fasciitis Type 2 - Group A streptococcus, penetrating injuries, surgery, burn
    3. Invasive group A streptococci are most common overall
    4. Toxic-shock syndrome toxin producing strains are commonly found
  5. Systemic symptoms out of proportion to local reaction
    1. Hypotension
    2. Rhabdomyolysis with renal failure
    3. Left Ventricular failure
    4. Toxic-Shock like syndrome
    5. Bacteremia
  6. Treatment
    1. Gram Positive Antibiotic coverage with clindamycin ± penicillin
    2. Consider vancomycin, oxacillin, cefazolin instead of penicillin
    3. Single dose of aminoglycoside only (high risk for renal failure)
    4. Consider additional gram negative coverage with ceftazidime, aztreonam, or a penam
    5. In patients at risk, strong anaerobic coverage with metronidazole should be added
    6. Blood cultures, wound culture and Gram stain should aid antibiotic selection
    7. Intravenous Fluids (consider added bicarbonate for severe acidosis)
    8. Prompt surgical exploration and debridgement is essential for recovery
    9. Pulmonary artery catheter may be helpful in assessing cardiovascular status
  7. Poor Prognostic Features in Streptococcal Disease
    1. Increased age
    2. Hypotension
    3. Bacteremia
    4. No correlation with serotype or exotoxin genes
  8. Overall mortality is 20-50% despite current intensive care

F. Differential Diagnosis [19]navigator

  1. Cutaneous anthrax - gelatinous edema surrounding eschar of anthrax lesion
  2. Vaccinia vaccination - erythema and induration around vaccination site at 10-12 days
  3. Insect bite - hypersensitivity reaction
  4. Acute gout
  5. Deep vein thrombosis (with thrombophlebitis)
  6. Fixed drug reaction
  7. Pyoderma gangrenosum - lesions become nodular or bullous and ulcerate
  8. Neutrophilic dermatosis - Sweet's syndrome, with fever, plaques and vesicles
  9. Kawasaki disease - fever, conjunctivitis, lymphadenopathy, oropharyngeal erythema
  10. Wells' syndrome - urticaria like lesions with central clearing, eosophilia
  11. Familial Mediterranean fever associated cellulitis-like erythema
  12. Carcinoma erysipeloides - metastatic carcinoma with lymphatic involvement, no fever

G. Hand Infections [19]navigator

  1. Singifcant morbidity can occur without prompt identification and treatment
  2. Host factors contributing to morbidity
    1. Diabetes mellitus
    2. Immunocompromised state (HIV, immunosuppression)
    3. Intravenous drug abuse
    4. Tropical fish acquarium exposure
    5. Sexually transmitted diseases
  3. Common Hand Infections (Table 2, Ref [19])
    1. Paronychia
    2. Felon
    3. Herpetic Whitlow
    4. Pyogenic flexor tenosynovitis
    5. Clenched fist injury or human bite
  4. Paronychia
    1. Infection of the nail bed
    2. Hand infection usually with bacteria, foot infection usually due to fungus
    3. Paronychia of the hand usually due to gram positive cocci
    4. In diabetics or other immunocompromise, gram negatives and mixed infections
    5. Incision and drainage must be performed if infection is established or host at high risk
    6. Staphylococci or streptococci usually treated with first generation cephalosporin
    7. Mixed infections treated with amoxicillin-clavulanate (Augmentin®)
    8. Intravenous antibiotics may be required for severe infections
  5. Felon
    1. Abscess at the distal pulp or phanx pad of fingertip
    2. Usually caused by inoculation of bacteria into fingertrip through penetrating trauma
    3. Thumb or index finger usually affected
    4. Associated with splinters, blisters, glass, abrasions, minor puncture wounds
    5. Severe throbbing pain and swelling, tense area with poor joint motility
    6. If fluctuance is present, then incision and drainage should be done
    7. Treatment with first generation caphlosporin or antistaphylococcal penicillin
  6. Herpetic Whitlow
    1. Due to herpes simplex virus (HSV) 1 or 2
    2. Rare condition due to autoinoculation of virus through broken skin
    3. May occur as acomplication of primary oral or genital HSV lesions
    4. Abrupt onset of edema, erythema, localized tenderness
    5. Pain out of proportion to physical findings
    6. Fever, lymphadenitis, epitrochlear and axillary lymphadenopathy may occur
    7. Small, clear vesicles are present early on
    8. May mimic felon or paronychia
    9. Usually self limited but anti-HSV agents may be given within first 48 hours
    10. Recurrence in 30-50% of cases
  7. Pyogenic Flexor Tenosynovitis
    1. Flexor tendons in hand are enclosed in synovial sheaths
    2. Following inoculation, infections of the tendons progress rapidly within the sheath
    3. Area is also poorly vascularized
    4. Four signs: uniform symmetric digit swelling, digit held in partial flexion at rest, excessive tenderness along entire course of flexor tendon sheath, pain with passive extension
    5. Susually due to gram positive skin organisms; anaerobes may complicate
    6. Neisseria gonorrhea or Candida albicans suspected with sexually active or immunocomprise
    7. Treatment appropriate for most likely organisms
    8. Incision and drainage with cather irrigation of sheath if not improved in 12-24 hours
  8. Clenched Fist / Human Bite
    1. Usually due to direct bite or to "fight bite" (clenched fist injury)
    2. Clenched fist injury usually with 3-5 mm laceration on dorsum of hand or overlying MCP joint
    3. Radiographs should obtained to evaluate for fracture
    4. Thorough examination of area for possible extension of infections
    5. Mainly normal oral flora and skin flora
    6. Staph aureus, streptococci common
    7. Eikenella corrodens
    8. Gram negative bacilli
    9. Prophylactic oral antibiotics if outpatient therapy (Augmentin® preferred)
    10. In penicillin allergy, clindamycin with fluoroquinolone or TMP/SMX (Bactrim®, Septra®)
    11. Wounds need to be explored, copiously irrigated and debrided
    12. Hospitalization with broad spectrum antibiotics often indicated
    13. Tetanus booster given if previous one >5 years

H. Catheter Related Infections [7,15,27] navigator

  1. Epidemiology [9]
    1. Annually, ~49,000 catheter related infections in intensive care units (ICU)
    2. 24,300 deaths among patients with catheter related infections in ICU
    3. This is ~5 per 1000 catheter-days
    4. Patients with hemodialysis catheters have 1.6-6.6 catheter-related bloodstream infections for every 1000 catheter-days
    5. About 15% of infected patients will have disseminated intravascular coagulation, shock,or renal failure (sepsis syndromes)
    6. ~17,000 deaths in ICU directly related to catheter associated infections
    7. Femoral venous catheterization has 4.8X increased infection risk versus subclavian [23]
    8. Tunneled femoral catheters have ~50% infection risk compared with non-tunneled [18]
    9. In patients requiring renal replacement therapy, femoral and jugular access had similar levels of nosocomial complications including infection risk [36]
  2. Skin Organisms
    1. Staph epidermidis
    2. Staph aureus
    3. Bacillus species
    4. Corynebacterium species
  3. Iatrogenic Organisms
    1. Commonly carried by medical personnel
    2. Pseudomonas aeruginosa
    3. Acinetobacter
    4. Stenotrophomonas (Xanthomonas) maltophilia
    5. Enterococci
    6. Candida albicans
    7. Candida parapsilosis
  4. Physical Prevention of Catheter Related Infections [14,22]
    1. Hand washing
    2. Full barrier precautions when inserting central venous catheter
    3. Subcutaneous tunneling for short term catheters in jugular or femoral vein
    4. Cleaning skin with chlorhexidine gluconate
    5. Avoiding femoral site whenever possible (see increased risk above)
    6. Catheters should only be changed when clinically indicated, not routinely
    7. Implementation of these guidelines lead to >40% reduction in cathter related infections
  5. Other Physical Prevention Measures [14,22]
    1. Contamination shields for pulmonary artery catheters
    2. Skin preparation with alcoholic chlorhexidine is more efficacious than aqueous providone-iodine in preventing blood culture contamination [14,20]
    3. Antiseptic chamber filled or sponge filled hub on central venous catheters
  6. Pharmacologic Prevention of Catheter Related Infections [14,22,27,35]
    1. Both topical and intraluminal antibiotics reduced rates of bacteremia and need for catheter removal due to infection by >65-80% [35]
    2. Antiseptic impregnated catheters also effective
    3. Chlorhexidine + silver sulfadiazine impregnated catheters have 60% reduction in colonization rates, >40% reduction in blood stream infections versus placebo [15]
    4. Central catheters with chlorhexidine+silver sulfadiazine lead to 55% reduction in colony counts and possible reduction in blood stream infections [13]
    5. Minocycline+rifampin impregnated catheters have 70% reduction in colonization rates and 8% bactermias compared to those with silver sulfadiazine+chlorhexidine [16]
    6. Consider antibiotic impregnated catheters in all debilitated patients [27,35]
  7. Diagnosis [29]
    1. Catheter related bacteremia can be diagnosed rapidly with special staining
    2. Gram stain - acridine orange leukocyte cytospin (AOLC) test requires 30 minutes
    3. As little as ~100µL of catheter drawn blood required
    4. Catheter need not be removed
    5. Cytospin and staining is carried out on the sample
    6. Sensitivity 96% and specificity 92% (compares well with direct culture)
    7. Strongly recommended for use
  8. Treatment
    1. Catheter removal following blood culture draw is essential
    2. Catheter tip and tunneled portion should be cultured as well
    3. Coverage for gram positive organisms initially is focus
    4. Consider gram negative bacteria and/or fungal coverage in debilitated patients
    5. Methicillin resistant straphylococci are increasingly common
    6. Vancomycin resistance is also increasing
    7. Antibiotic (rifampin+minocycline) coated hemodialysis catheters associated with reduced risk of infection [28]

I. Infection in Joint Prosthesis [30,31]navigator

  1. Diagnosis requires at least one of the following:
    1. Growth of same microorganism at least 2 cultures of synovial fluid or periprosthetic tissue
    2. Purulence of synovial fluid or at the implant site
    3. Acute inflammation of periprosthetic tissue on histopathology
    4. Presence of sinus tract communicating with the prosthesis
  2. Microorganisms Causing Infection
    1. Coagulase negative staphylococci (S. epidermidus and others) ~35%
    2. Staphylococcus aureus ~17%
    3. Mixed flora ~10%
    4. Streptococci ~10%
    5. Gram negative bacilli ~5%
    6. Enterococi ~5%
    7. Anaerobes ~3%
    8. No infectious agent in ~10%
  3. Microorganisms can form biofilms when present in large numbers
    1. Cell-to-cell signalling molecules activate genes involved in biofilm formation
    2. Biofilms protect microorganisms from antibiotics and host immune responses
    3. Microorganisms in biofilms are highly resistant to killing
  4. Foreign bodies are devoid of microcirculation which also makes host defense difficult
  5. Infection occurs either by direct inoculation or through hematogenous seeding
  6. Infections are classified as early, Delayed, or Late
    1. Early infections - develop <3 months after surgery; mainly due to high level inoculation
    2. Delayed - 3-24 months after surgery; mainly due to low level direct inoculation
    3. Late - develop >24 months after surgery; mainly from hematogenous seeding
  7. Four possible surgical approaches
    1. Debridement + retention of prosthesis
    2. Removal of infected implant without replacement
    3. One stage replacement
    4. Two stage replacement
  8. In mechanically stable prosthesis, aggressive systemic medical therapy may be adequate
    1. In general, 3-6 months of systemic antibiotics are required
    2. Specific agents have been recommended depending on the organism involved [31]

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