clinically important gram + bacteria

coagulase test

slide coagulase test: agglutination reacts

staphytect test: agglutination reacts

tube coagulase test: fibrin clot = coagulase positive

staphylococci

gram positive cocci in clusters

opportunistic bacteria

low intrinsic virulence - usually don’t cause infections in normal patients

may cause serious infections in certain circumstances - immunocompromise. foreign body e.g. staph. epidermidis

virulent bacteria

colonization

infections e.g. S. aureus

normal flora

staphlycocci

staphylococcus aureus

found in moist skin folds, mucosal surfaces, nasopharynx. increased in diabetes mellitus, intravenous drug users and foreign body is present

lots of virulence factors - even though it colonizes healthy adults

infection occurs when there is a break in the skin or there is entry through the mucous membranes allowing access to adjoining tissues

MSRA: methicillin resistance

pathogenesis

• gets in - portal of entry

• attaches to cells

• defeats/evades the immune system

• causes damage to host cells

• gets out and spreads further

portal of entry

• ingestions

• inhalation

• penetration/inoculation

• sexual

• transplacental (vertical transmission)

attaches to cells/surfaces

microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) - surface proteins that facilitate initial attachment to hose tissue

1. fibrin/fibrinogen binding protein (clumping factor) - attachment of blood clots and traumatized tissue

2. fibronectin, fibrinogen and collagen binding proteins - e.g. collagen binding protein promoted collagen attachment and is found in strains that cause osteomyelitis/septic arthritis

capsule - adherence to foreign bodies e.g. intravascular )IV) catheter

immune evasion

inhibition of phagocytosis (capsule)

survival within phagocytes

production of extracellular substances that promote invasion

• invasins

• enzymes

virulence factor - coagulase

enzyme - converts fibrinogen into fibrin clot. coats bacterial cells in self protein

virulence factor - protein A

surface protein - binds IgG(heavy chain Fc region) hindering opsonization and phagocytosis

virulence factor - alpha toxin

hemolysin - causes lysis of blood components, particularly monocytes and platelets

virulence factors - staphylokinase

enzyme - dissolves fibrin clots to facilitate spread

virulence factors - hyaluronidase

enzyme - breaks down hyaluronic acid in connective tissue, aiding in tissue spread

virulence factor - toxic shock syndrome toxin 1

superantigen (exotoxin) - stimulates T-cells to over produce IL-1, IL-2 and TNF-alpha

virulence factor - enterotoxin

six types (A, B, C, D, E and G) - cause vomiting and diarrhea when ingested

virulence factors - exfoliative toxins (A and B)

esterase and protease activity - target proteins that maintain epidermal integrity

virulence factors - Panton-valentine leucocidin (PVL)

cytotoxin - causes pores in leukocytes resulting lysis

virulence factor - biofilm

community of bacterial cells attached to a surface - extracellular matrix of polysaccharide or protein protects bacteria from phagocytosis. resistant to antibiotics

transmission of S. Aureus infections

direct contact: person to person spread is common via carraige on the skin (especially the hands)

can also be picked up from contact with the environment - hospital environments are known reservoirs

classification of staphylococcal infections

1. skin and soft tissue

2. systemic - invasive

3. systemic - toxin mediated

skin and soft tissue infections

boils are superficial infections where you get a collection of pus - can be spontaneously draining or be encouraged by a warm moist compress. recurrent may need antibiotic treatment

folliculitis is a superficial skin infection involving hair follicles - treatment not always needed

furuncles and carbuncles are deeper infections usually preceded by folliculitis - common on hairy skin. spontaneous or surgical draining needed. patients can be systemically unwell with carbuncles

S. aureus s the most likely pathogen

systemic staphylococcus aureus infections

1. bloodstream infection (BSI) or bacteremia/septicemia

2. pyelonephritis and renal abscess

3. deep abscesses e.g. brain, liver

endocarditis

usually secondary to BSI

high fever, heart murmur, emboli, non specific features (pain, weight loss), Osler’s nodes

clinicians must investigate for primary focus e.g. IV line site

treatment requires prolonged IV vancomycin and gentamycin

pneumonia

hematogenous - septic emboli/R side endocarditis/IV device

risk factors: viral respiratory infection (influenza or measles), cystic fibrosis, healthcare contact, aspiration

osteomyelitis

hematogenous spread or secondary to local trauma

vertebrae the most common site for hematogenous spread - long bone metaphysis in childeren

diagnosis is made by direct needle aspiration or bone scan

can be acute or chronic

pain, high fever, rigors and high WCC

treatment: IV Flucloxacillin pending C and S

septic arthritis

hot, swollen joint

knee, hip, elbow and shoulder are most common joints affected by metastatic spread i.e. from BSI± endocarditis

treatment usually with IV flucloxacillin (14 days)

toxin mediated conditions

food poisoning/gastroenteritis - short incubation period, self limiting

scaled skin syndrome - cleaves middles layers of skin. often occurs in outbreaks

toxic shock syndrome - multi system disease. high fever, hypotension, sunburn rash on soles and palms. vomiting diarrhea, confusion/headache. IV vancomycin plus gentamicin

antibiotics

treatment generally not required for mild soft tissue infections e.g. boil/carbuncle

flucoxacillin if susceptible and significant skin/soft tissue infection for 7-10days

longer duration if systemic infection i.e. 2 weeks for BSI if source/focus removed, 4-6 weeks for endocarditis

exam for signs of metastatic infection. ECHO, scans and repeat blood cultures after 72 hours

coagulase negative staphylococci

staphylococcus epidermis

• less virulent than S. aureus i.e. less toxins

• opportunistic pathogen

• prolific biofilm producer

• mainly associated with device related infections e.g. prosthetic joints, intravascular lines etc.

• can be highly resistant to beta lactam antibiotics

staphylococcus saprophyticus

• frequent cause of urinary tract infection in women of reproductive years

• UTI requires empiric treatment with nitrofurantoin, trimethoprim or amoxicillin in this instance

clostridia

gram positive bacilli

clostridium spp.

all form endospores and produce powerful exotoxins

mostly strict anaerobes

ubiquitous organisms i.e. present in soil, water, sewage

C. tetani

tetanus: life threatening illness caused by a neurotoxin (tetanospasmin) resulting in tetanic paralysis

decreasing incidence sue to vaccine

treatment involve use of antibiotics (benzyl penicillin or metronidazole)

neutralization of toxin with tetanus immunoglobulin

C. botulinum

botulism: associates with contaminated food products, usually pork and canned foods with spores or from wound

Botox (toxin) results in flaccid paralysis

serious illness requiring intensive care, toxin neutralization, antibiotics and wound debridement

C. perfrinigens

causes gas gangrene

extremely serious, rapidly progressive infection

imminent risk to both limb and life

rapid destruction of muscle and severe systemic toxicity

prompt debridement of all nonviable tissue is essential

acute onset of heaviness in the area followed by severe pain, devitalization of limb, mottled skin, fluid or gas-filled blisters on the skin

clostridium difficile

bacterium that normally lives in the large intestine - common in the bowel of babies and infants but rarely causes problems

antibiotics = main risk factor for infection

disruption of normal colonic flora

at least 2 types of toxin A and B

C. difficile infection symptoms

variable (depends on the patient)

asymptomatic to potentially fatal

• diarrhea, stomach cramps, nausea, fever, loss of appetite, acute abdomen colitis

plaques of yellow fibrin and inflammatory debris adherent to reddened mucosa

types of C. difficile infection (CDI)

new

• first episode of CDI

recurrent

• common 8-50% cases

• CDI that occurs within 8 weeks. following the onset of a previous episode

• risk of recurrence increases with each recurrence - if a patient has 2+ episodes of CDI, the risk of additional recurrences increases to 50-65%

CDI treatment

isolation and contact precautions

antibiotics should be reviewed and stopped if possible. If not possible to stop, switch to agent with a lower propensity to induce C. difficile

supportive therapy (fluids etc.)

is this severe or non-severe infection?

is this new or recurrent infection?

CDI prevention and control

1. antibiotic stewardship

2. infection prevention and control

Corynebacterium diphtheriae

the organism has a worldwide distribution, humans are the only known reservoir

prior to vaccination, significant cause of nursery deaths

at risk: childeren/unvaccinated/overcrowding

reservoir: cases and asymptomatic carriers

spread is by droplet

nasal carriers may shed for weeks

reduced incidence with immunization programs - covered in diphtheria, tetanus and pertussis vaccine

Corynebacterium diphtheriae clinical features

incubation period 2-6 days

may involve any mucus membrane or skin

low grade fever

classified based on site of infection: anterior nasal, tonsillar and pharyngeal, cutaneous, ocular

treatment with benzylpenicillin or erythromycin plus antitoxin

infected person may develop bull neck

rules for antibiotic treatment of infections caused by gram positives

most commonly use cell wall active agents

penicillin

• nearly all beta hemolytic streptococci susceptible

• high levels of resistance in S. aureus and CoNS

cephalosporins

• for penicillin resistant pneumococci

• used for treatment of meningitis

• used if allergy to penicillin

• resistance common is listeria monocytogenes

vancomycin

• if beta lactam anaphylaxis

• if resistance to beta lactans suspected