Bacterial Infections 07/02/2011

BY: MOHAMMED ALSAIDAN

Normal skin flora NORMAL SKIN FLORA

Class Organisms Location on body

Aerobic cocci Staphylococcus aureus*, S. saprophyticus, S. epidermidis† , Micrococcus luteus, M. roseus, M. varians

All body sites, especially intertriginous areas

Aerobic coryneform Corynebacterium minutissimum, C. lipophilicus, C. xerosis, C. jeikeium, Brevibacterium epidermidis

Intertriginous areas (e.g. axillae, groin, toe webs)

Anaerobic coryneform bacteria

Propionibacterium acnes, P. granulosum, P. avidum

Sebaceous glands and follicles

Gram-negative bacteria Acinetobacter spp. Axillae, perineum, antecubital fossa

Yeast Malassezia furfur Skin rich in sebaceous glands (e.g. scalp)

Impetigo • It is the most common bacterial infection in children

• highly contagious, spreading rapidly via direct person-to-person contact

• The primary pathogen is S.aureus and, less commonly, Streptococcus pyogenes

• Non Bullous : usually at site of trauma

• Bullous: (considered a localized form of SSSS) elaborates several exfoliative toxins (A–D), targeting desmoglein 1 acantholysis in granular layer mimicking P.folaceus

Impetigo

• Predisposing factors include • warm temperature, high humidity,• poor hygiene• atopic diathesis • skin trauma (chickenpox, insect bite, abrasion, laceration, burn)• S. aureus colonization

Impetigo work up?

• Diagnosis is usually made clinically

• Exudate from beneath the crust and fluid from intact bullae can be sent for culture and sensitivity

• Leukocytosis in 50%

Treatment

• local wound care• Cleansing• removal of crusts• wet dressings

• For healthy patients with a few, isolated superficial lesions and no systemic symptoms:• mupirocin 2% ointment or fusidic acid equally effective to oral

antibiotics

Folliculitis

• Folliculitis: infection localized to the hair follicle• Furuncle: entire follicle and surrounding tissue are involved • carbuncle : multiple furuncles grouped together

• S. aureus is the most common infectious cause of folliculitis

• Gram-ve folliculitis A.V. treated with long courses of oral antibiotics

• Pseudomonas folliculitis use of hot tubs

Folliculitis

• Factors predisposing • occlusion• maceration and hyperhydration with hot and humid weather, • shaving, plucking or waxing hair• topical corticosteroids• diabetes mellitus • atopic dermatitis.• Obesity • Immunodeficiency• Poor hygiene

Folliculitis

• Site: face, chest, back, axillae or buttocks

• superficial folliculitis (Bockhart's impetigo) are small, 1–4 mm pustules or crusted papules on an erythematous base

• Gram stain and bacterial cultures in recurrent or treatment-resistant cases

Folliculitis treatment

• Localized:• antibacterial washes • bacitracin or mupirocin 2% may also be used for 7-10 days

• Widespread or recurrent:• appropriate β-lactam antibiotics, macrolides or clindamycin

• Chronic S. aureus carriage • mupirocin 2% ointment applied twice daily to the nares,

axillae/groin and/or submammary area for 5 days.

Furuncles, Carbuncles

• S. aureus is the most common causative organism

• Furuncles usually begin as a hard, tender, red nodule that enlarges and becomes painful and fluctuant; rupture results in decreased pain, Systemic symptoms are usually absent

Furuncles, Carbuncles

• Carbuncles are collections of furuncles that extend deep into the subcutaneous tissue.

• The surface usually displays multiple draining sinus tracts and occasionally ulcerates.

• They usually occur in areas with thicker skin (e.g. nape of neck, back, thigh)

• Systemic symptoms are usually present.

• Carbuncles are slow to heal scar formation

Treatment • simple furuncles: • warm compresses may promote maturation, drainage and

resolution of symptoms

• Fluctuant lesions • incision and drainage

• Systemic antibiotics should be used in four instances: • (1) furuncles around the nose, within the nares or in the external

auditory canal• (2) large and recurrent lesions• (3) lesions with surrounding cellulitis• (4) lesions not responding to local care

MRSA

• Furunculosis is the most frequently reported manifestation of community acquired MRSA

• MRSA can manifest as :• abscesses or frank cellulitis• impetigo, bullous impetigo, scalded skin syndrome, nodules or

pustules• bacteremia, septic shock and a toxic shock-like syndrome

• The major cause of methicillin resistance is the production of an altered (i.e. reduced affinity) penicillin-βinding protein (PBP) called PBP2a

Treatment

• Emperical treatment with Vancomycin is indicated in :• patients with severe, life-threatening infection • in patients with a history of MRSA colonization• in intravenous drug users

Blistering Distal Dactylitis • children aged 2-16 years

• Presents as a localized infection of the volar fat pad of a finger or a toe

• Blister formation and involvement of the nail fold or more proximal portion of the digit

• Darkening of the surrounding skin before blister formation

Blistering Distal Dactylitis • Group A β-hemolytic Streptococcus, S. aureus and, rarely, S.

epiermidis are the responsible organisms

DDx:• herpetic whitlow • thermal or chemical burn• acute paronychia• bullous impetigo (vesicles more superficial)• frictional bullae

Blistering Distal Dactylitis Treatment • Incision and drainage plus • a 10-day course of an oral antistaphylococcal antibiotic (e.g.

cephalexin) can prevent development of new sites of infection as well as local extension.

Ecthyma

• Considered as : ulcerated form of non-bullous impetigo like lesion

• due to either a primary infection with Str. pyogenes or streptococcal superinfection of a pre-existing ulceration

Staphylococcal Scalded Skin Syndrome

• Staphylococcal toxin-mediated infections includes:• ssss• bullous impetigo• toxic shock syndrome

• Exfoliative toxins (ETs) ETA and ETB are serine proteases with a very high specificity for human desmoglein 1 (DG-1)

Staphylococcal Scalded Skin Syndrome

• Increased frequency of staphylococcal scalded skin syndrome in children younger than 5 years due to :

• Absence of antibodies specific for exotoxins• Immature renal function in this age group may impair clearance• The relative quantity of DG-1 in the skin differs with age

SSSS clinical features

Clinical features:• Prodrome • Severe tenderness of the skin• Erythema• Flaccid bullae within the superficial epidermis. • In 1-2 days, the bullae are sloughed moist skin and areas of

thin, varnish-like crust.

SSSS clinical features

• The flexural areas are the first to exfoliate.

• Scaling and desquamation continue for 3-5 days

• Re-epithelialization in 10-14 days, without scarring

• The Nikolsky sign is positive.

• The mortality rate is 3% for children, over 50% in adults, and almost 100% in adults with underlying disease

SSSS work up

• Cultures taken from intact bullae are negative

• Blood cultures are almost always negative in children, but may be positive in adults

• The leukocyte count may be elevated or normal

• Electrolytes and renal function should be followed closely in severe cases

• PCR serum test for the toxin is available.

SSSS work up

• Biopsy: separation of the epidermis at the granular layer. An inflammatory cell infiltrate is typically not present

• Negative IF

• In (TEN), inflammatory (lymphocytic) infiltrate is present, and the plane of separation is deeper, at the level of the basement membrane.

DDx

• sunburn• drug reaction• Kawasaki disease• extensive bullous impetigo• viral exanthem, toxic shock syndrome, GVHD, TEN and

pemphigus foliaceus.

SSSS treatment

• Localized disease :• Oral treatment with a β-lactamase-resistant antibiotic

e.g.dicloxacillin, cloxacillin, for a minimum of 1 week • Emollient• Isolation • treatment of S. aureus carriers

• Extensive, generalized forms of SSSS • hospitalization and parental antibiotics.

Toxic Shock Syndrome

• It is a multisystem disease caused by an exotoxin produced by S. aureus toxic shock syndrome toxin-1 (TSST-1). In the absence of antibodies against TSST-1. TSST-1

• Dermatologic manifestations are more extensive and predictable in staphylococcal TSS than in streptococcal TSS.

Toxic Shock Syndrome

• Sudden onset of high fever with myalgias, vomiting, diarrhea, headache and pharyngitis

• Diffuse macular erythroderma > scarlatiniform eruption with flexural accentuation

• Erythema and edema, then Delayed desquamation of palms and soles

• Hyperemia of conjunctiva and mucous membranes

• Strawberry tongue

• After recovery, Beau's lines, telogen effluvium may occur

DDx:• SSSS• scarlet fever • early TEN• Kawasaki disease• Rocky Mountain spotted fever

Treatment

• Remove Foreign bodies and any source of infection • Beta-lactamase-resistant antibiotics or antibiotics that

suppress toxin production, such as clindamycin, rifampin or fluoroquinolones.

• In severe cases of shock unresponsive to antibiotics, low-dose corticosteroids

Severe cases of TSS :• intensive supportive therapy (intravenous fluids and

vasopressor agents).

Streptococcal Toxic Shock Syndrome

• Rapidly progressive, often fatal illness

• Toxins act as superantigens and can cause stimulation of T cells By binding to the class II MHC of APC

• Most common initial symptom is severe local pain in an extremity

• Mortality 30 to 60%

• Severe complications of streptococcal TSS include renal failure, DIC , and adult RDS

Streptococcal Toxic Shock Syndrome

• Most cases require intensive supportive therapy with aggressive intravenous fluid and vasopressors.

• Clindamycin inhibit the production of bacterial toxins (the cause of shock) and is the first-line treatment.

• Early surgical intervention e.g. debridement or fasciotomy can be life-saving

Scarlet Fever

• Between 1 and 10 years of age

• >10 years antibodies prevent rash but not the sore throat

• Caused by toxins types A, B and C by group A streptococci

• Lead to a delayed-type hypersensitivity reaction

Clinical features • Prodrome

• Rash appears 12–48 hours after the fever.

• The rash starts as erythema of the neck, chest and axillae, and behind the ears.

• After 4-6 hours, the remainder of the body is involved

• spares the face , but cheeks may have flushing (although some circumoral pallor is characteristic).

Clinical features

• Pastia lines (where the rash runs together in the armpits and groin) appear and can persist after the rash is gone

• The rash: tiny papules on an erythematous background–blanches with pressure

• It resembles a ‘sunburn with goose pimples’ and feels like sandpaper

Extracutaneous manifestation

• The throat is red and edematous and develops an exudate after 3-4 days

• There is tender cervical adenopathy and palatal petechiae.

• The tongue is initially white with bright red papillae, but later becomes beefy red (‘red strawberry tongue’).

• After 7-10 days, desquamation affecting the hands and feet

Clinical features

• Complications of scarlet fever include • Otitis• Mastoiditis• Sinusitis• Pneumonia• Myocarditis• Meningitis• Arthritis• Hepatitis• Acute glomerulonephritis• Rheumatic fever

Scarlet fever work up

• CBC: elevated leukocyte count with a left shift, mild hemolytic anemia with reticulocytosis can occur.

• Nose and throat cultures will grow group A streptococci.

• Detection of antistreptolysin O (ASO), antihyaluronidase, antifibrinolysin and anti-DNase B antibodies are useful in detecting the streptococcal infection.

• Early in the disease, a mild albuminuria and hematuria can be seen.

Scarlet fever work up

• The differential diagnosis of scarlet fever includes• hypersensitivity reaction to drugs• Measles• Rubella• toxic shock syndrome• SSSS• Kawasaki disease and toxin-mediated erythema.

Treatment

• penicillin is the drug of choice (10-14-day course)

• Antibiotic treatment as long as 10 days after the onset of symptoms will prevent the development of rheumatic fever.

• Erythromycin can be used in penicillin-allergic patients.

Erysipelas

• It is an infection of the dermis with significant lymphatic involvement

• Caused by infection with:• group A streptococci and less often by • S. aureus, • Pneumococcus species, • Klebsiella pneumoniae, • Yersinia enterocolitica, • Haemophilus influenzae type

Clinical features Erysipelas

• Abrupt onset of prodrom (clearly demarcated erythematous plaque) hot, tense, tender and indurated with non-pitting edema

• The lower extremity is the most common location

• LAP , with or without lymphatic streaking.

• Pustules, vesicles, bullae and small areas of hemorrhagic necrosis may also form.

• When the infection resolves, desquamation and postinflammatory pigmentary changes may occur

Work up Erysipelas

• Elevated leukocyte count with a left shift.

• Blood cultures are positive in only about 5% of cases.

• Swabs from local ports of entry, pustules or bullae, the throat, and the nares may be helpful.

• Anti-DNase B and ASO titers are good indicators of streptococcal infections.

Treatment Erysipelas

• The treatment of choice is 10-14-day course of penicillin

• Erythromycin in penicillin-allergic patients

• Hospital admission and I.V or I.M. antibiotics for children and debilitated patients.

• prophylaxis with daily penicillin for Recurrent erysipelas

Streptococcal Intertrigo

• Sharply demarcated, erythematous patches or thin plaques are observed in an intertriginous zone

• Distinct, foul smell is suggestive.

• Infants are particularly vulnerable due to irritation and frictional forces in moist deep skin folds of the neck, axillae, antecubital and popliteal fossae, and inguinal region.

• Discrete psoriasiform lesions may also be seen.

• group A streptococci >>> S. aureus and Proteus mirabilis.

Streptococcal Intertrigo

• The differential diagnosis includes• cutaneous candidiasis• seborrheic dermatitis• irritant contact dermatitis.

• Simple intertrigo responds to measures that reduce friction and minimize moisture

• A 10-day course of oral penicillin is effective in most instances, with failure of conservative methods

Streptococcal Perianal Disease

• Due to Str. pyogenes

• Sharply demarcated, bright, perianal erythema extending 2–3 cm around the anal verge

• Patients may complain of painful defecation, blood-streaked stools, prolonged perianal irritation or pruritus soiling of undergarments.

• Systemic symptoms are absent.

• The infection may be preceded by a pharyngitis and should always be considered in patients with guttate psoriasis

Streptococcal Perianal Disease

DDX • candidiasis, seborrheic dermatitis, pinworm infection,

inflammatory bowel disease, child abuse, and the early phase of Kawasaki disease.

Rx:• 10-14-day course of penicillin or erythromycin. • After treatment, the area should be recultured to exclude

recurrence

Cellulitis

• Cellulitis is an infection of the deep dermis and subcutaneous tissue

• most commonly Str. pyogenes and S. aureus• In childhood S. aureus >>>> H. influenzae • Diabetic ulcers and decubitus ulcers ( Gram+ve cocci and

Gram-ve and anaerobes)

• immunocompetent via break in the skin barrier• immunocompromised bloodborne route is most common

Cellulitis clinical features

• Systemic symptoms: fever, chills and malaise.

• 4 cardinal signs of inflammation: rubor (erythema), calor (warmth), dolor (pain), and tumor (swelling).

• The lesion usually has ill-defined, non-palpable borders. In severe infections, vesicles, bullae

• Pustules ,necrotic tissue, ascending lymphangitis and regional lymph node involvement may occur.

Cellulitis clinical features

• Children head and neck region• Adults extremities• I.V. drug abusers the upper extremities

• Complications include • acute glomerulonephritis (streptococci)• Lymphadenitis• subacute bacterial endocarditis. • Damage to lymphatic recurrent cellulitis

CellulitisLABs: • WBC is usually normal or only slightly elevated. • Blood cultures are almost always negative except H. influenzae• In children and immunocompromised patients, needle

aspiration and skin biopsy may be appropriate for atypical organisms

DDx :• DVT, stasis dermatitis, superficial thrombophlebitis,

panniculitis (especially lipodermatosclerosis)• pseudocellulitis

Cellulitis treatment • Immobilization and elevation, application of wet dressings to

areas with exudate.

• Mild cases 10-day course of an oral antibiotic that cover . Str. pyogenes and S. aureus

• Seriously ill or facial cellulitis Hospitalization and I.V antibiotics

• Diabetic or decubitus ulcers broad-spectrum coverage (e.g. piperacillin/tazobactam or metronidazole plus ciprofloxacin)

• Antibiotics adjusted according to cultures and sensitivities results

• NO NSAIDs

Pyomyositis• A primary bacterial infection of the skeletal muscles, most

commonly by S. aureus , untreated disease can progress to septicemia and septic shock

• Associated with HIV infection, I.V. drug abuse, immunosuppression and DM

Clinically :• Myalgias and low-grade fever, progressive over 1-2 weeks

‘woody’ induration on palpation

• Muscle abscess formation in the second stage of disease, and frank septicemia may follow.

Pyomyositis

Work up • MRI as soon as pyomyositis is suspected. • some cases can be confirmed by ultrasound-guided aspiration. DDx• Cellulitis, hematoma, dermatomyositis/polymyositis, HIV-

associated myopathies, DVT, osteomyelitis, septic arthritis, and necrotizing fasciitis

Rx• Surgical incision and drainage, I.V. antibiotics until clinical

improvement followed by oral antibiotics for a total of 3 weeks

Botryomycosis• Chronic, purulent and granulomatous bacterial infection, most

commonly caused by S. aureus.

• Cutaneous botryomycosis presents as cutaneous and subcutaneous nodular masses, abscesses, ulcers or verrucous plaques. +/– multiple sinuses and fistulae

• Most patients have localized disease on the extremities and it may be preceded by trauma

Botryomycosis• The lesions can involve the underlying muscle or bone

• Systemic symptoms are infrequent

• The lungs are the most common extracutaneous site of involvement, but any organ can be affected

Botryomycosis biopsies • Biopsy reveal a chronic non-specific inflammatory reaction

with fibrosis. Foreign body type giant cells are commonly seen.

• 1–3 mm granular bodies which have basophilic centers representing bacteria, cells and debris.

• The periphery has a homogeneous, eosinophilic, hyaline appearance secondary to a host immunoglobulin response (Splendore–Hoeppli phenomenon).

• The granules stain easily with PAS, Gram and Giemsa stains.

At high power, the center of the concretion consists of basophilic granular material. A brightly eosinophilic band encases the

bacteria .

Botryomycosis work up • Microscopic examination (fresh mount or 20% KOH) will show

coarse granules with club-like projections.

• Gram staining of crushed granules will usually display masses of staphylococci.

• Bacterial and fungal cultures should be performed.

• DDx: mycetoma, actinomycosis,, abscesses, dimorphic fungal infections, orf, tuberculosis and atypical mycobacterial infections

Treatment • Excision and debridement.

• Antibiotics usually do not penetrate the lesion adequately.

• The CO2 laser used successfully.

Necrotising Fasciitis

• is essentially a ‘severe inflammation of the muscle sheath that leads to necrosis of the subcutaneous tissue and adjacent fascia, that is difficult to diagnose early and difficult to manage effectively.

Types

Risk factors for NF• >50 years of age• Diabetes mellitus• Peripheral vascular disease• Intravenous drug use• Alcoholism• Immunosuppression• Obesity

GASNF and GAS toxic shock syndrome (STSS)

• 50% of type II NF cases are associated with STSS.• STSS is an exotoxin-driven disease that significantly increases

the mortality of streptococcal NF alone from <40% to 67% with up to half of patients needing amputation

Clinical diagnosis of NF• Hx:• minor trauma• insect or human bites• recent surgery• skin infection or ulcers • injection sites and • illicit intravenous drug usage

• Many cases, however, remain idiopathic

Clinical diagnosis of NF• Hx:• foreign travel >>> resistant or unusual organisms• trauma involving soil contamination >>> fungal • Raw seafood ingestion or wound exposure to seawater >>> Vibrio

spp. • tonsillitis, impetigo, or recent non-steroidal anti-inflammatory

agent (NSAID) >>> streptococcal infection

Clinical diagnosis of NF

• Severe pain precedes skin changes by 24 to 48 h in >97.8% of patients

• Mild erythema, cellulitis or swelling overlying the affected area.

• tender area >> smooth, swollen area of skin with distinct margins progressing to dusky blue/purple, ‘bruising’ violaceous plaques, and finally full thickness necrosis with haemorrhagic bullae

Radiology

• US findings correlate reasonably well with histological fat changes in NF

• T2-weighted images on MRI are probably the best radiological adjunctive investigation, but are more sensitive than specific

Labs• Blood cultures are positive in 11 to 60% of patients with

GASNF

• Haemoglobinuria is common in GASNF

• Blister fluid is often sterile.

• Tissue biopsy is the investigation of choice for stain and C/S

• Disseminated intravascular coagulation and thrombocytopenia are common

Labs

• ARF

• CRP levels of >16 mg/dL, with a sensitivity of 89% and specificity of 90%, have been reported

• Raised serum creatinine kinase (CK) indicates myositis or myonecrosis

Labs

• CK levels of 600 U/L gave a sensitivity of 58% and a specificity of 95% for cases of NF.

• 30% hypocalcaemic

• Hypoalbuminaemia and hyponatraemia

• high serum lactate with severe metabolic acidosis

The LRINEC (Laboratory Risk Indicator for Necrotising Fasciitis)

The LRINEC (Laboratory Risk Indicator for Necrotising Fasciitis)

• A score of 6 >> raises the suspicion

• A score 8 >> ‘strongly predictive’ of NF

• Predict mortality

Histopathology • Deep incisional biopsies are more useful than punch biopsies

• Biopsy should include the advancing edge and central necrotic areas

• Histological examination reveals underlying thrombi, necrosis, polymorphonuclear infiltrate, microorganisms, and vasculitis.

• Gram staining is important, since a paucity of leucocytes in the presence of Grampositive cocci may be seen in GASNF or CA-MRSA due to leucocidin mediated destruction of WBCs.

Management

Surgical • Prompt diagnosis

• Aggressive surgery removes the source of infection and toxins

• (VAC) dressing with a continuous pressure of 40 to100 mmHg is useful for wound coverage and encourages granulation

• the tissue oxygen tension can be measured with a probe using transcutaneous soft tissue oximetry. lower in NF than cellulitis

Role of hyperbaric oxygen (HBO)

• HBO switches off a-toxin production from Clostridium spp

• increase the bactericidal action of neutrophils

• Decrease mortality to 12%

Antibiotics

• Broad-spectrum empirical therapy covering most types of NF

• Then >> based on culture data.

• Clindamycin: switching off exotoxin production even in stationary phase organisms

Empirical protocol

• I.V. clindamycin 1.2 to 1.8 g six-hourly with I.V. imipenem 0.5 to 1 g six-hourly.

• IF MRSA : I.V. linezolid 600 mg BID or daptomycin 6 mg/kg may be added in preference to vancomycin

• For Vibrio spp. >> doxycycline 100 mg twice daily plus intravenous ceftazidime 2 g eight-hourly is recommended

I.V.I.G• IVIG may • promote clearance of GAS by the immune system• neutralise streptococcal superantigens• act as an immunomodulatory agent

• contraindication • selective IgA deficiency • history of anaphylaxis with immunoglobulins.

• 2 g/kg, with the option of a second dose if necessary after 24 h. rate of 20 mL/h, increasing incrementally after 10 min to a maximum of 160 mL/h.

prognosis

• Bad prognostic factors: Not type 1 myonecrosis or myositis STSS High serum lactate combined with low sodium Late operation % BSA Acidosis Peripheral vascular disease Advanced age Other comorbidities

Antimicrobial prophylaxis for contacts of GASNF• 27% of household contacts may be GAS carriers (200 times

more likely to occur)

• CDC, do not recommend routine testing for GAS colonisation or administration of chemoprophylaxis to household contacts.

• UK Health Protection Agency in 2004, recommend prophylaxis to mothers and babies if either was infected during the neonatal period

• Household contacts should be informed about the clinical manifestations of pharyngeal and GAS infection