BACTERIAL INFECTIONS Unimpaired skin protects the underlying tissue and is an excellent frontline defense against invasion of pathogenous

s microorganisms thanks also to the presence of skin microbiota Staphylococcus epidermidis Few hundred per cm2 Prevalent bacterium found on the dry surfaces Forearm and back Propionibacteria 10,000 per cm2 On damp areas Armpits and groin Can observe also corynebacterium and negative coagulase staphylococci Skin microbiota is made of microorganisms belonging to a very limited number of species and that the bacterial load of the healthy skin is kept constant

SKIN Barrier between the body and the environment Site of frequent infections Integrity of this barrier is influenced by the degree of scaling but also several factors whose alterations upset the environmental balance of resident flora and predispose the subject to infection Displays a microbicidal activity even when its physical integrity is impaired Contains bioactive molecules Antimicrobicidal peptides: Defensins Cathelicidins Two different microorganisms can be found in the in the skin microbiota Permanent resident flora Always present If removed reforms within 24 72 hrs Made up of aerobic or microaerophilic Temporary or transient flora Settle only on temporarily on the skin from the external environment or from the adjacent mucosal areas Bacterial species present are numerous , since most organisms can at least temporarily reside on the skin They cannot multiply and colonize the skin S. epidermidis main bacterium resident on free skin Propionibacterium ances, granulosum and avidum in the area of the follicular ostium with reduced oxygen supply Peptostreptococcus Anaerobic staphylococci Present in 20% of humans Esp in forehead and elbow crease Corynebacterium Gram (+) lipophil bacteria Settle in sebum rich areas Brevibacterium Present particularly in humid areas Gram (-) bacteria are not normal components of the skin flora Staphylococcus aureus Present in the nose and perianal area Can spread to other areas of the skin Gram (-) bacteria can also be isolated particularly Enterobacteriaciae Part of the normal intestinal flora Pseudomonaciae Found in the environment Most readily in damp areas Possible colonization and invasion by other pathogenous microorganisms is counteracted by both the host defenses and by the resident flora, which contrast colonization by other microorganisms competing for

nutrients or producing peptides with antimicrobial activity Most skin infections are self limited in healthy individuals Primary infections Infections arising from healthy skin Caused by a single microbial species Entry point of the germ is often unknown although slight trauma is probably implicated Secondary infections Develop from preexisting lesions which facilitate the entry of the microorganisms Most common examples are: Atopic dermatitis Psoriatic lesions Other eczematous disorders Also prone to this complication is Surgical or injury wounds Burns Insect bites or stings Ulcers Areas of maceration Usually polymicrobial Generally caused by microorganisms that themselves have little pathogenic power When humoral or cell mediated immune defense is low, secondary infections arise more readily and develop more rapidly Once the skin barrier has been penetrated, microorganisms belonging to the resident flora, mainly coagulase negative anaerobic staphylococci can cause infections esp skin abscesses Also responsible for skin infections are microorganisms that, acquired from the environment, are temporarily part of the skin flora, for example S. aureus and Streptococcus pyogenes

In general, a skin infection can follow three different events 1. 2. 3. A lesion of the skin that favors infection from the outside Skin manifestations of systemic infections, which can spread through the blood from the site of infection to the skin or by direct invasion/penetration Skin damage caused by toxins

Bacterial infections can be classified on the basis of the site involved Folliculitis - Infections with bacterial etiology associated with inflammatory process limited to the hair follicle they are characterized by the presence of abscesses and the formation of pustules or papules Impetigo infection limited to the epidermis and characterized by a bullous rash that evolves in crusts or pustules Erysipelas acute erythematous infection that spreads rapidly and is usually associated with systemic infections Cellulitis lesion located in the subcutaneous fat and mainly involves the derma Both involves an intense inflammatory process Necrotizing infections infections characterized by rapidly progressive cellulitis that causes extensive damage to the tissue below the derma, in particular to the muscular tissue and impairs blood flow, subsequent to which necrotizing fasciitis and gas gangrene (infections not considered of dermatological competence) arise

GRAM POSITIVE COCCI Responsible for most skin infections Often the same microorganism can cause different infections according to the different layers of the skin that it is able to colonize

STAPHYLOCOCCI

Aerobic Gram positive cocci Catalase positive Irregular, grapelike clusters Although, MC are the single and paired cells Dominant species of staphylococcus on the skin is Staph Epidermidis (face and chest) S. hominis has a lesser but still substantial role Because of the normal colonization of the skin by coagulase negative staph, it is difficult to be sure that the small, localized lesion such as folliculitis is really caused by these organisms S. epidermidis, S. hominis and coagulase negative staph are now well established pathogens in certain areas of the skin S. AUREUS

Toxin implicated in this syndrome is known as exfoliating toxin or scalded skin toxin Initially skin lesions may be mild, but the toxin causes the destruction of the desmosomes and the detachment of the superficial layer of the epidermis Regarded as a sporadic disease with most cases in children aged 0.5 to 2 years. Few adults are reported, chiefly in the immunosuppressed, although cases in immunocompetent adults are known

IMPETIGO Characterized by golden, stuck on crusts or blisters (bullae) The blisters are most probably caused by small amounts of epidermolytic toxin or by the toxin in an otherwise resistant host of cases are in patients < 20 y/o, with about 35% in those younger than 10 In Europe, it is chiefly a staph disease, though 1/3 of the lesions have both S aureus and S pyogenes In AIDS patients an extensive atypical intertriginous form of bullous impetigo has been reported as part of the AIDS-related pruritus Besides infection such as boils or impetigo, S aureus also colonizes and aggravates the lesions such as those of atopic dermatitis When the density of the S aureus exceeds a certain level, such as 106/cm2, an exudative or impetiginized form of lesion occurs The reason for the overgrowth of S aureus in atopic dermatitis and not in diseases such as psoriasis is not known Protein A elicits a much less vigorous response in atopics than in normal skin or psoriatics, but this may be the result rather than the cause of colonization There is some evidence that fatty acids which may control staph colonization are deficient in atopics

species of coagulase positive staph remains a potent pathogen able to exhibit new antibiotic resistance patterns and to contribute to infect both immunocompetent and incompetent host permanently colonizes the moist squamous epithelium of the anterior nostrils of 20% population and is transiently associated with another 60% organism can cause superficial skin infections primary staph infections of the skin are chiefly boils, furuncles, and other localized pustular lesions and impetigo plus its more severe manifestation, scalded skin syndrome expresses a wide range of secreted and cell surface associated virulence factors, including surface proteins that promote adhesion to damaged tissue and to surface of the host cells, which bind proteins in the blood to help evade immune responses and promote iron uptake most strains express a polysaccharide capsule S aurues has been regarded as a non invasive pathogen but is now evident that the bacterium can invade many types of host cells by a mechanism involving the formation of fibronectin bridge between the bacterial fibronectin-binding proteins and host a5b1 integrin molecules which triggers internallization The microorganism can secrete a range of extracellular enzymes such as Proteases Hyaluronidase Lipase Nuclease that facilitate tissue destruction and the spread of membrane damaging toxins which causes cytolytic effects on the host cells and tissue damage and superantigens, which contribute to the symptoms of septic shock

Management

Therapy of choice for staph infections is Penicillase resistant penicillin the administration of erythromycin is frequent, although an increase in the frequency of erythromycin resistant strains has been reported methicillin resistant S aureus (MRSA) is a problem particularly for hospitals Vancomycin is the only drug available but strains to it are also emerging (vancomycin reistant intensive Staph aureus - VISA)

STREPTOCOCCI Gram positive, spherical aerobic and facultatively anaerobic bacteria Arranged in chains or pairs Non sporing Catalase negative Oxidase negative Mainly nonmotile Hemolysis in blood agar culture provides useful division of strep into those that are Beta hemolytic zone of complete hemolysis Alpha hemolytic (viridian strep) zone of incomplete hemolysis

TOXIC SHOCK SYNDROME characterized by fever and confusion, with an erythematous rash resembling scarlet fever and desquamation in the later stages symptoms accompanied by diarrhea, vomiting, and hypotensive shock TSS is caused by exotoxins MC of which is TSST-1 produced mainly by strains of phage group 1 S. aureus The toxin acts as superantigen, stimulating the production of T cells and the release of cytokines

Non hemolytic no effect on RBC Hemolytic strep are further divided according to the carriage of polysaccharide of teichoic acid or lancefield group antigens Direct strep infection may take on a number of forms
Group A hemolytic strep Major strep pathogen

SCALDED SKIN SYNDROME (RITTER DISEASE) Caused by a strain of toxigenous S aureus

S PYOGENES

But non group A strep also play a part and have become more commonly recognized with the widespread use of modern, rapid laboratory test kits Etiological agent of strep impetigo and erysipelas, skin pathologies also caused by S aureus Infection generally arises from contact with infected skin lesions in other individuals Once S pyogenes colonized the skin, it invades the epithelium through small wounds, with consequent development of the lesion A complex interaction of bacterial host defense factors underlies the initiation, devt and clinical manifestations of strep infection M protein molecule Major virulence factor of strep Double stranded coiled-coil structure projecting from the cell surface

Which act on the BV of the skin and causes diffuse rash arising in association with strep pharyngitis accompanied by scarlet fever

Clinical manifestations of similar to staph toxic shock syndrome are often supported by strep toxins, particularly the pyrogenous exotoxin A, generally produced by M1, M3 or M5 phagotypes of the S pyogenes strains

Streptococcal toxic shock syndrome (STTS) varies somewhat from staphylococcus or classic forms Primary site of infection is the skin, often surgical wounds STTS follows chickenpox or can infect immunodepressed patients These clinical pictures often contrast with those seen in patients with staphylococcal toxic shock syndrome, in whom the primary infection is often subclinical

The functional properties of M protein include binding of fibrinogen, fibronectin, and B2 microglobulin; adherence to the host cells; interference with complement deposition; and the conferring of resistance to phagocytosis The quantitiy of M protein expressed on the cell surface appears to be an important factor in the pathogenesis Freshly isolated strains of group A,C and G strep, particularly those from invasive infections are often rich in this substance and serotypes of S pyogenes such as M1, which expresses large quantities, are commonly associated with an invasive disease Enhancement of M protein expression may be a factor underlying the increased virulence observed when strep are rapidly passed from host to host

Necrotizing Fasciitis Acute or subacute infection that spreads above the fascial planes causing thrombosis of the vessels and necrosis of the dermis and subcutaneous fat Caused by hemolytic or anaerobic strep or staph aureus May follow a trivial or unapparent injury to the skin and presents initially with cellulitis, which quickly develops a dusky discoloration, hemorrhagic bullae and underlying areas of necrosis There is risk of septicemia and rapid death Commonly seen in elderly patients, often in association with serious preexisting medical disorders The rationale for antimicrobial therapy for strep infections of the skin is to hasten the resolution of the lesion to reduce the risks of suppurative and non suppurative complications to reduce the chances of transmission of infection to others

The binding of fibrinogen and fibronectin by strep structures may play an important part in the attachment of microorganisms to wounds an clots in the first stages of colonization and infection F protein Another projecting cell surface molecule with similarities to M protein Inactivates complement C5a, a major signal substance for the chemotactic attraction of leukocytes and binding to the Fc portion of immunoglobulin (Ig) G and IgA antibodies

Teichoic acid Also contribute to the virulence of S pyogenes by helping the microorganism bind to the epithelial cells A strep infection develops 24-48 hrs from the penetration of the skin and stimulates a marked inflammatory response

S pyogenes elaborates a series of toxic products and enzymes like hyaluronidase that helps the microorganism to spread in the tissues Lymphatic system involvement is common, which causes lymhadenitis and lymphanigitis Skin infection by S pyogenes may be complicated by non suppurative sequelae such as nephritis and scarlet fever Conversely, streptococcal infection, at other sites in the body may lead to skin manifestations, such as rheumatic fever and acute guttate psoriasis Many strep infections are toxin mediated. Lysogenic strains of S pyogenes produce one or more types of pyrogenous exotoxins (previously called erythrogenic) like SPE A causes scarlet fever

streptococci are still remarkably sensitive to PCN other alternative drugs are available including erythromycin, tetracycline, and cephalosporin

Coryneform bacteria another gram positive bacteria belonging to the skin microbiota responsible for skin odor and can be associated with pathologies of the skin

SPE - B SPE C

this heterogenous group of microorganisms includes both aerobic and anaerobic pleomorphic bacteria that do not form spores because of their similarity to the diphtheria bacillus, these microorganisms were formerly referred to as diphtheroids in cutaneous infections, Coryneform bacteria are clearly involved both as primary pathogen and secondary superinfection of the other cutaneous infections such as syphilis and streptococcal and pyoderma several cutaneous lesions from which Coryneforms can be recovered and in which they are seen as playing an important pathophysiological roles these include: trichomycosis axillaris erythrasma interdigital toe-web-space infections

Its pathogenic properties depends on the ability to produce toxins Only the strains infected by the pro-phage b have toxb gene and produce the exotoxin C diphtheria are more common in tropical and subtropical areas but epidemics have been described in temperate climates like North America MC clinical findings: Erosive ulcerative lesions with thick crusts Key therapy is the administration of the antitoxin which should be administered early on Antibiotic therapy can be performed with PCN G or erythromycin

Anaerobic coryneforms Genus Propionobacterium and P acnes is the most numerous species This bacterium plays an important role in acne but is not considered the cause P acnes proliferates and generates inflammation provoking substances, resulting in disruption of the follicular epithelium and progressive inflammation as the contents of the follicle are injected into the dermis P acnes is also a frequent opportunistic pathogen Some authors report the isolation of P acnes from an infected wound and in osteomyelitis and endocarditis There are several reports of meningitis and botryomycosis due to P acnes The antibiotics used to treat acne include TCN and erythromycin

acne pitted keratolysis

about 20% of the popn is colonized by Corynebacterium minutissimum which causes erythrasma only in some cases

Erythramsa superficial cutaneous infection ranging from low grade scaling to thicky macereated areas of the skin preferred sites are the skin folds predisposing factors are obesity, diabetes, hyperhidrosis most infections show a typical reddish fluorescence with Woods light the fluorescence a result of a production of porphyrins, which fluoresce under long wave UV light

Gram negative bacterial skin infections Much less frequent than gram positive infections but have considerable clinical importance Pseudomonas aeroginosa Is the cause of some superficial infections with particular characteristics The microorganisms readily colonizes damp environmental pockets and as such some areas of the body Increase in cases of folliculitis from P aeruginosa in people attending saunas, Jacuzzis, and swimming pools The skin rash is itchy papules or pustules characteristically distributed in the areas rich in apocrine and eccrine sweat glands There may be associated symptoms of the infection in other areas eg. Mastodynia and ear ache

Corynebacterium diphtheria NOT an inhabitant of normal skin Although it may be recovered from intact skin under epidemic conditions This microorganism is more commonly found on mucous membranes Skin may be the primary port of entry Can be auto or hetero inoculated in an otherwise insignificant wound High frequency of asymptomatic carriers Strains of C. dihptheriae have been divided into gravis, intermedius, mitis types

These disorders tend to have a spontaneous recovery but the use of quinolones may be useful Genus Pseudomonas is frequently isolated from surgical wounds, varicose ulcers bed sores and burns particularly during and after antibiotic therapy The presence alone of Pseudomonas in these sites is a sign of infection but the real danger is that the germ may multiply in depth and cause bacteremia Other gram negative organisms can cause folliculitis during antibiotic treatment of acne, usually with TCN When in young people receiving therapy for acne there is an increase in the pustular lesions, a gram negative superinfection of the follicles should be suspected, in particular by Proteus or Pseudomonas After surgeries or traumas associated with contamination of the wound, serious skin infections by mixed aerobic of anaerobic flora can occur These are generally cellulitis with diffuse necrosis of the skin and subcutaneous layers at times extending to the muscles The therapy for these syndromes is surgery with intense antibiotic support Broad spectrum therapy is indicated such as aminoglycosides plus clindamycin, piperacillin, cefocxitin are useful against anaerobes and imipenem, ceftazidime, Ciprofloxacin, and combinations containing beta lactamase inhibitors and the association of piperacillin and tazobactam are effective against anaerobes and facultative bacteria