Medical MicrobiologyMedical Microbiology

Lecture 6Lecture 6Dr. Saleh M Y OTHDr. Saleh M Y OTH

PhDPhDMedical Molecular Biotechnology and Infectious DiseasesMedical Molecular Biotechnology and Infectious Diseases

11/10/201011/10/2010IMS - MSUIMS - MSU

Systemic bactreiology

Streptococci and its DiseasesStreptococci and its Diseases

Systemic bactreiology

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Staphylococci- Coagulase-negative staphylococcus; frequently

involved in nosocomial and opportunistic infections

- S. epidermidis – lives on skin and mucous membranes; endocarditis, bacteremia, UTI

- S. saprophyticus – infrequently lives on skin, intestine, vagina; UTI

Staphylococci are gram positive cocci arranged in grape like clusters.

The genus Staphylococcus includes 3 species of medical importance;

Staph. aureus,

Staph. epidermidis and

Staph. saprophyticus.

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General Characteristics of the Staphylococci

- Common inhabitant of the skin and mucous membranesCommon inhabitant of the skin and mucous membranes

- Spherical cells arranged in irregular clustersSpherical cells arranged in irregular clusters

- Gram-positive Gram-positive

- Lack spores and flagellaLack spores and flagella

- May have capsuleMay have capsule

Staphylococcus aureus morphology

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S. aureus

- Grows in large, round, opaque colonies

- Optimum temperature of 37oC

- Facultative anaerobe

- Withstands high salt, extremes in pH, and high temperatures

- Produces many virulence factors

S. aureus

Major human pathogenMajor human pathogen

Habitat - part of normal flora in some humans Habitat - part of normal flora in some humans and animalsand animals

Source of organism - can be infected human Source of organism - can be infected human host, carrier, fomite or environmenthost, carrier, fomite or environment

Natural history of disease

- Many neonates, children, adults -intermittently colonised by S. aureus

- Usual sites; skin, nasopharynx, perineum

- Breach in mucosal barriers; can enter underlying tissue

- Characteristic abscesses; Disease due to toxin production

Grouping for Clinical Purposes

1. Coagulase positive Staphylococci- Staphylococcus aureus

2. Coagulase negative Staphylococci- Staphylococcus epidermidis

- Staphylococcus saprophyticus

Diseases- Due to direct effect of organism

- Local lesions of skin

- Deep abscesses

- Systemic infections

- Toxin mediated

- Food poisoning

- toxic shock syndrome

- Scalded skin syndrome

Factors predisposing to S. aureus infections

Host factors

- Breach in skin- Chemotaxis defects

- Opsonisation defects

- Neutrophil functional defects

- Diabetes mellitus

- Presence of foreign bodies

Pathogen Factors- Catalase (counteracts

host defences)

- Coagulase

- Hyaluronidase

- Lipases (Imp. in disseminating infection)

- B lactasamase(ass. With antibiotic resistance)

Skin Lesions

- Boils وخراج تقرح

- Styes دمامل

- Furuncles (infection of hair follicle)

- Carbancles (infection of several hair follicles)

- Wound infections (progressive appearance of swelling and pain in a surgical wound after about 2 days from the surgery)

- Impetigo (skin lesion with blisters that break and become covered with crusting exudate)

Deep abscessses

- Can be single or multiple

- Breast abscess can occur in 1-3% of nursing mothers in puerperiem

- Can produce mild to severe disease

- Other sites - kidney, brain from septic foci in blood

Systemic Infections

1. With obvious focus متقرحة بؤرة

- Osteomyelitis, septic arthritis

2. No obvious focus- heart (infective endocarditis)

- Brain (brain abscesses)

3. Ass. With predisposing factors - multiple abscesses, septicaemia(IV drug users)

- Staphylococcal pneumonia (Post viral)

Toxin Mediated Diseases

1. Staphylococcal food poisoning- Due to production of entero toxins

- heat stable entero toxin acts on gut

- produces severe vomiting following a very short incubation period

- Resolves on its own within about 24 hours

Toxic shock syndrome

- High fever, diarrhoea, shock and erythematous skin rash which desquamate

- Mediated via ‘toxic shock syndrome toxin’

- 10% mortality rate

- Described in two groups of patients- Ass. With young women using tampones

during menstruation

- Described in young children and men

Scalded skin syndrome

- Disease of young children- Mediated through minor Staphylococcal

infection by ‘epidermolytic toxin’ producing strains

- Mild erythema and blistering of skin followed by shedding of sheets of epidermis

- Children are otherwise healthy and most eventually recover

Virulence factors of S. aureus

Enzymes:

- Coagulase; coagulates plasma and blood; produced by 97% of human isolates; diagnostic

- Hyaluronidase; digests connective tissue

- Staphylokinase; digests blood clots

- DNase; digests DNA

- Lipases; digest oils; enhances colonization on skin

- Penicillinase; inactivates penicillin21

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Virulence factors of S. aureus

Toxins:- Hemolysins (α, β, γ, δ); lyse red blood cells

- Leukocidin; lyses neutrophils and macrophages

- Enterotoxin; induce gastrointestinal distress

- Exfoliative toxin; separates the epidermis from the dermis

- Toxic shock syndrome toxin (TSST); induces fever, vomiting, shock, systemic organ damage

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Epidemiology and Pathogenesis

- Present in most environments frequented by humans

- Readily isolated from fomites

- Carriage rate for healthy adults is 20-60%

- Carriage is mostly in anterior nares, skin, nasopharynx, intestine

- Predisposition to infection include: poor hygiene and nutrition, tissue injury, pre-existing primary infection, diabetes, immunodeficiency

- Increase in community acquired methicillin resistance - MRSA

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Staphylococcal DiseaseRange from localized to systemic

Localized cutaneous infections; invade skin through wounds, follicles, or glands- Folliculitis; superficial inflammation of hair follicle;

usually resolved with no complications but can progress- Furuncle; boil; inflammation of hair follicle or sebaceous

gland progresses into abscess or pustule بثرة

- Carbuncle; larger and deeper lesion created by aggregation and interconnection of a cluster of furuncles

- Impetigo; bubble-like swellings that can break and peel away; most common in newborns

Bullous impetigo

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Cutaneous lesions of S. aureus

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Systemic infections

- Osteomyelitis; infection is established in

the metaphysis; abscess forms

- Bacteremia; primary origin is bacteria from another infected site or medical devices; endocarditis possible

Staphylococcal osteomyelitis in a long bone

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Staphylococcal Disease

Toxigenic disease - Food intoxication – ingestion of heat stable

enterotoxins; gastrointestinal distress

- Staphylococcal scalded skin syndrome – toxin induces bright red flush, blisters, then desquamation of the epidermis

- Toxic shock syndrome – toxemia leading to shock and organ failure

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Effects of staphylococcal toxins on skin

Toxic Shock Syndrome Toxin

- Superantigen- Superantigen

- Non-specific - Non-specific binding of toxin to binding of toxin to receptors triggers receptors triggers excessive excessive immune responseimmune response

TSS Symptoms

- 8-12 h post infection

- Fever

- Susceptibility to Endotoxins

- Hypotension

- Diarrhea

- Multiple Organ System Failure

- Erythroderma (rash)

TSS Treatment

- Clean any obvious wounds and remove any - Clean any obvious wounds and remove any foreign bodiesforeign bodies

- Prescription of appropriate antibiotics to eliminate - Prescription of appropriate antibiotics to eliminate bacteriabacteria

- Monitor and manage all other symptoms, e.g. - Monitor and manage all other symptoms, e.g. administer IV fluids administer IV fluids

- For severe cases, administer methylprednisone, - For severe cases, administer methylprednisone, a corticosteriod inhibitor of TNF-a synthesisa corticosteriod inhibitor of TNF-a synthesis

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Identification of Staphylococcus in Samples

- Frequently isolated from pus, tissue Frequently isolated from pus, tissue exudates, sputum, urine, and bloodexudates, sputum, urine, and blood

- Cultivation, catalase, biochemical testing, - Cultivation, catalase, biochemical testing, coagulasecoagulase

Catalase test

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Clinical Concerns and Treatment

- 95% have penicillinase and are resistant to penicillin and ampicillin

- MRSA – methicillin-resistant S. aureus; carry multiple resistance- Some strains have resistance to all major drug groups

except vancomycin

- Abscesses have to be surgically perforated

- Systemic infections require intensive lengthy therapy

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Prevention of Staphylococcal Infections

- Universal precautions by healthcare providers to prevent nosocomial infections

- Hygiene and cleansing

Antibiotic sensitivity pattern

- Very variable and not predictable- Very important In Patient Management- Mechanisms

1. B lactamase production - plasmid mediated- Has made S. aureus resistant to penicillin group of antibiotics -

90% of S. aureus (Gp A)- β-lactamase stable penicillins (cloxacillin, oxacillin, methicillin)

used

2. Alteration of penicillin binding proteins- (Chromosomal mediated)- Has made S. aureus resistant to β-lactamase stable penicillins- 10-20% S. aureus Gp (B) GH Colombo/THP resistant to all

Penicillins and Cephalasporins)

- Vancomycin is the drug of choice

DIAGNOSIS

1. In all pus forming lesions - Gram stain and culture of pus

2. In all systemic infections- Blood culture

3. In infections of other tissues- Culture of relevant tissue or exudate

S. epidermidis

- Skin commensal

- Has predilection for plastic material

- Ass. With infection of IV lines, prosthetic heart valves, shunts

- Causes urinary tract infection in cathetarised patients

- Treatment should be aided with ABST

S. saprophyticus

- Skin commensal

- Imp. cause of UTI in sexually active young women.

- Usually sensitive to wide range of antibiotics