Staphylococcus, Streptococcus and other Bacteria

• Staphylococcus and Streptococcus are types of bacteria.

Introduction to Cocci

• Bacteria can be categorized by shape into three classes: Spirochetes (spiral), Cocci (spherical), and Bacillus (rod-shaped).
• Cocci bacteria generally have a spherical, round, or ovoid shape.

Classification of Bacteria

• Bacteria are classified as either Gram-positive or Gram-negative, and as either aerobic or anaerobic.
• Aerobic Gram-negative bacilli include E. coli, Haemophillus, Klebsiella, Proteus, Acinectobacter, Pseudomonas, Yersinia, Salmonela, Campylobacter, Enterobacter, and Morganella.
• Aerobic Gram-negative cocci include Moraxella and Neisseria.
• Anaerobic Gram-negative bacilli include Bacteroides.
• Aerobic Gram-positive bacilli include Bacillus.
• Aerobic Gram-positive cocci include Staphylococcus, Streptococcus, and Enterococcus. S. aureus is coagulase-positive.
• Anaerobic Gram-positive bacilli include Actinomyces, Clostridium, and Lactobacillus.
• Anaerobic Gram-positive cocci include Strep Viridans.

Introduction to Staphylococci

• Staphylococci are commonly found in hospitals, the nasopharynx, and on the skin of 50% of people.
• While sometimes harmless, staphylococci can become pathogenic.
• The three major pathogenic species are Staphylococcus epidermidis, Staphylococcus aureus, and Staphylococcus saprophyticus.
• All staphylococci possess the enzyme catalase, which breaks down hydrogen peroxide, but lack it in streptococci.

Classification of Staphylococci

• Domain: Bacteria
• Kingdom: Eubacteria
• Phylum: Firmicutes
• Class: Bacilli
• Order: Bacillales
• Family: Staphylococcaceae
• Genus: Staphylococcus
• Examples of species: S. aureus, S. epidermidis, S. saprophyticus

Properties of Staphylococci

• Staphylococci are gram-positive, spherical, and form grape-like clusters.
• Some strains produce a capsule.
• Staphylococci are non-fastidious and capable of both aerobic and anaerobic respiration.
• They can ferment carbohydrates and produce lactic acid, but not gas.
• Staphylococci are resistant to drying and can withstand heat up to 50°C for 30 minutes.
• Some staphylococci are part of the normal flora of the skin and mucous membranes.

Clinically Important Staphylococcal Species

• The main species of clinical importance are Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus saprophyticus.
• S. aureus is coagulase-positive, which means it converts fibrinogen to fibrin, forming clots.
• Coagulase enzyme activates prothrombin, leading to blood clotting.
• Being coagulase-positive differentiates S. aureus from other staphylococcus species.

S. epidermidis

• A normal body flora found widely on human body
• Coagulase negative
• Causes infection in compromised patients with implanted appliances/devices, especially in the very young and very old
• Migrates from skin through appliances, adhering to heart valves, vascular catheters, shunts, and prosthetic joints
• Tissue destruction is mediated by degradative enzymes from S. epidermidis
• Found in infected indwelling prosthetic devices and contains a polysaccharide capsule for adherence.

S. Saprophyticus

• A common cause of urinary tract infections in sexually active young women, second to E. coli.
• Commonly acquired by females (95%) in the community and coagulase-negative.

Staphylococcus Aureus

• A Gram-positive coccus that divides in multiple planes, forming clusters.
• Some strains produce capsules and are non-fastidious.
• Capable of aerobic and anaerobic respiration.
• Produces Toxic Shock Syndrome toxin (TSST-1), which causes toxic shock syndrome.
• Produces proteins allowing bacteria to tunnel through tissues.
• Produces a diffusible exotoxin leading to Scalded Skin Syndrome.

Staphylococcus Aureus cont.

• Generally causes a broad range of human diseases, infecting almost any organ system, separated in two categories: disease caused by exotoxin release and disease due to direct organ invasion by bacteria
• Disease caused by exotoxin release includes:
  • Gastroenteritis (food poisoning)
  • Toxic shock syndrome
  • Scalded skin syndrome
• Disease due to direct organ invasion by bacteria includes:
  • Pneumonia
  • Meningitis
  • Osteomyelitis
  • UTI
  • Acute bacteria endocarditis
  • Septic arthritis
  • Skin infection
  • Bacteremia/sepsis

Diagnosis and Laboratory Identification of Staphylococci

• Grow white or golden colonies on blood agar.
• Catalase-positive and coagulase-positive.
• Most strains ferment mannitol anaerobically.

Diseases Caused by Staphylococci

• Boils, skin sepsis
• Postoperative wound infection
• Scalded skin syndrome
• Catheter-associated infection
• Foodborne infection
• Septicemia
• Endocarditis
• Toxic shock syndrome
• Osteomycetis pneumonia

Two Types of S. Aureus Diseases

• Pyogenic Infections: Abscess, boils, carbuncles, endocarditis, osteomyelitis, pneumonia, wound infections
• Toxic Mediated Infections: Food poisoning, toxic shock syndrome, scalded skin syndrome

Epidemiology and Sources of Staphylococcal Infection

• Infected lesions: Large number of staphylococcus are disseminated from large infected wounds, burns, secondary infected lesions and in sputum coughed from the lung of patients with bronchopneumonia
• Direct contact: Small discharge lesions on the hands of doctors and nurses are special danger to their patients
  • Airborne dissemination may also occur
  • Cross infection is important method of spread staphylococcal disease particularly in hospital
  • Scrupulous and hand washing is essential in preventing spread
• Food handlers: May introduce enterotoxin-producing food poisoning strains into food
• Health carriers: Staphylococcus aureus grows harmlessly on the nostrils in many health persons also commonly colonizes the perineum.
  • Organisms spread from these sites into the environment by the hands, handkerchiefs, clothing and dust consisting of skin squames and cloth fibres
• During the first day or two of life colonization also occurs in the nose and skin when babies acquire staphylococcus from their mother, nurse or environment
  • Nasal carriage in babies and older persons is usually long lasting with transmission from babies to nursing mothers causing mastitis
• Animals can disseminate S. aureus which cause infection to humans e.g. milk from diary cow with mastitis cause staphylococci food poisoning

Mode of Infection

• Acquisition can be exogenous (external source), endogenous (internal source), or from a minor lesion elsewhere on the patient's body.
• Staphylococcus does not typically grow outside the body, except in moist environments such as meat, milk, and dirty water.
• The body surfaces of humans and animals are the main reservoirs.
• Although not spore-forming, staphylococci can survive in a dormant state for months when dried in pus, sputum, bedclothes, or dust.
• Staphylococci are killed by moist heat at 65°C for 30 minutes, exposure to light, and commonly used disinfectants.

Pathogenesis of Staphylococcal Infections

• Staphylococci cause diseases by producing toxins and multiplying in tissue, leading to inflammation.
• The typical lesion is an abscess, a localized region with pus surrounded by inflamed tissue.
• Abscesses undergo central necrosis and usually drain externally, but the organism may also disseminate via the bloodstream.

Toxins and Enzymes Produced by Staphylococcus Aureus

• Enterotoxin: Causes food poisoning characterized by prominent vomiting and non-bloody diarrhea
  • Acts as a super antigen in the gastrointestinal tract, stimulating the release of interleukin 1 (IL-1) and IL-2 from macrophages and helper T cells
  • Vomiting is caused by cytokines released from lymphoid tissues
• Toxic Shock Syndrome Toxin (TSST): Causes toxic shock, especially TSST, stimulating the release of IL-1, IL-2, and tumor necrosis factor (TNF).
• Exfoliation: causes scalded skin syndrome in young children
• Several toxins can kill leukocytes and cause necrosis of tissue in vivo.
• Enzymes: coagulase, fibrinolysin, hyaluronidase, protease, nucleases, and lipase
• Coagulase: Clots plasma, walling off the infected site and retarding neutrophil migration.
• Staphylokinase: A fibrinolysis that can lyse thrombin.

S. aureus (Pyogenic Diseases)

• Skin infections are common.
• Septicemia from localized lesions, especially wound infections.
• Endocarditis.
• Osteomycetis and arthritis, especially in children.
• Post-surgical wound infections.
• Pneumonia can occur in postoperative patients.
• Abscesses.

S. aureus (Mediated Diseases)

• Food poisoning: Vomiting and diarrhea.
• Toxic shock syndrome: Fever, hypotension, a diffuse, macular, sunburn-like rash.
• Scalded skin syndrome: Fever, large bullae.

Disease Caused by Exotoxin Release

• Gastroenteritis (food poisoning)
• Staphylococcus can grow in food and produce an exotoxin. -The exotoxin stimulates peristalsis of the intestine following ingestion
• It leads to nausea, vomiting, diarrhea, abdominal pain, and occasional fever.
• Normally, the incubation period is 1-8 hours.

Toxic Shock Syndrome

• Involves sudden onset of high fever, nausea, vomiting, and watery diarrhea (enterotoxin-like).
• Followed in a few days by a diffuse erythematous (red) rash, myalgias, and hypotension with cardiac and renal failure in severe cases.
• Beta hemolysis (β-hemolysis) refers to the complete lysis of red cells in the media around and under the colonies.
• Associated with septic shock, with patients experiencing severe organ system damage which includes acute respiratory syndrome and or acute renal failure
• TSST-1 exotoxin may be released for example from infected sutures or child birth,
• Tampons left for a long time can stimulate Staphylococcus aureus to release TSST-1 exotoxin, which penetrates the vaginal mucosa

Treatment of Toxic Shock Syndrome

-Includes removing the tampon or drainage of an infected wound along with supportive care Antibiotics may help by killing bacteria and preventing exotoxin production; however it is not curative since the exotoxin, not the bacteria, causes the clinical manifestation

Staphylococcal Scalded Skin Syndrome

• Similar in pathogenesis to toxic shock syndrome.
• S. aureus strains produce exfoliatin toxin
• This exfoliatin toxin establishes a localized infection and releases a diffusible toxin that exerts distant effects.
• Typically affects neonates with local umbilical infections or older children with skin infections.
• Toxic epidermal necrolysis (Ritter's disease) occurs, characterized by large areas of denuded skin and generalized large blisters filled with clear fluid (bullae).
• Infants and young children develop toxic epidermal necrolysis (i.e, Ritter's disease), and because of the moist red areas of denuded skin, the syndrome is referred to as the scalded baby syndrome
• Lyell’s disease is when older children and adults develop localized bullae appearing red and moist.
• Healing occurs without scarring if no secondary bacterial infection occurs.
• Older children and adults can develop a scarlatina-like rash where the syndrome mimics streptococcal scarlet fever, but the tongue and palate are not involved.
• Drug allergies should be ruled out since this can present similarly and be fatal if the offending drug is not halted

Diseases Resulting from Direct Organ Invasion by Bacteria

Pneumonia

• S. aureus is a rare but severe cause of community-acquired bacterial pneumonia.
• More common in hospitalized patients, usually following a viral influenza (flu) upper respiratory illness.
• Presents with abrupt onset of fever, chills, and lobar consolidation of the lung with rapid destruction of the lung parenchyma.
• Results in cavitations (holes in the lungs).
• Destruction pneumonia causes effusions and empyema (pus in the pleural space).

Meningitis, Cerebritis, Brain Abscess

• Patients presents with high fever, stiff neck, headache, coma, and focal neurological signs

Osteomyelitis

• Bone infection which usually occurs in boys under 12 years of age, spread hematogenously and presents locally with warm swollen tissue over the bone and with systemic fever and shakes

Endocarditis

• Acute bacteria endocarditis caused by S. aureus. Characterized by a relatively short time course of less than 6 weeks.
• The infected heart valve is coated with vegetation of plateletes, bacteria and amorphous debris. Perforation of the heart is the result of extracellular enzymes and products of S. aureus
• Pieces of vegetation, known as infective emboli may dislodge, establishing a focus of infection in any organ system and is usually is necessary, emergency surgical replacement of the heart valve, to prevent death from cardiac insufficiency.
• Antimicrobial therapy is of minimal value because the agents are unable to penetrate the vegetation
• Subacute endocarditis is caused by S. epidermidis with more than 6 weeks of vegetation, is typically follows thoracic surgery and not prominent, with intravenous antimicrobial therapy to generally eliminate the infection

Other Diseases Caused by Staphylococcus

• Septic arthritis
• Skin infections
• Bacteremia/sepsis
• Urinary tract infection

Diagnostic Laboratory Tests

• Specimens:
  • Pus from abscesses, wounds, burns
  • Sputum from pneumonia cases, and faeces or vomitus from food poisoning.
• Blood:
  • From patients with suspected bacteraemia such as by septic shock, osteomyelitis or endocarditis
• Mid-stream urine:
  • From patients with suspected cystitis or pyelonephritis
• Anterior nasal and perineal swabs (moistened in saline or sterile water): -From suspected carriers

B. Smears

• Typical Staphylococci are seen in stained smears of pus or sputum.

C. Culture

• Specimens planted on blood agar plates give rise to colonies in 18 hours at 37º - haemolysis and pigment production may not occur until several days
• S. aureus – only ferment mannitol in staphylococci
• Specimens contaminated with other flora can be cultured on media containing 7.5% NaCl to inhibit the growth of the other normal flora, except that of S. aureus
• Mannitol salt agar is used to screen for nasal carriers of S.aureus

D. Catalase Test

• Positive if, upon using a drop of hydrogen peroxide on a bacterial growth, bubbles are formed to release oxygen,
• The test can also be used if pouring hydrogen peroxide over a heavy growth of bacteria on an agar slant and observing for appearance of bubbles

E. Coagulase Test

• Method includes using citrated rabbit or human plasma diluted 1:5 mixed with an equal volume of broth culture or growth from colonies, incubated at 37°C for one-four hours, with a sterile broth used as sterile broth
• The test is positive Coagulase should be completed when staphylococcus are considered pathogenic for humans

F. Susceptibility Test

• Should be done routinely on staphylococcal isolates from clinically significant infections
• Resistance to penicillin G can be predicted by a positive test for beta lactamase detection, of its gene with polymerase chain reaction(PCR)

G. Serologic and Typing Tests

• Have little practical value,
• Molecular typing technique have been used to spread of epidemic disease producing clones of S.aureus

Management/Treatment

• Most persons harbor staphylococcus on their skin and nose or throat
• Re-infection is possible if the skin is cleared of staphylococcus
• Pathogenic organisms commonly spread from one lesion to other areas with is controlled by local antisepsis of fingers and clothing

-Tetracycline are used for long-term treatment while multiple skin infections (acne, furunculosis) occurs most often in adolescents with the similar skin infection occur in patients receiving prolonged corticosteroids.

• It is difficult to eradicate pathogenic staphylococcal due to increased resistance, as well drug in central necrotic part of a suppurative lesion.

• It is also difficult to eradicating a S. aureus carrier state, but Acute haematogenous osteomyelitis is well responds to antimicrobial drugs with surgical draining and dead bone removal being chronic

• Vancomycin is often reserved with a B-lactimase for treatment of bacteremia, endocarditis and penicilin resistant staphylococci. Penicillin G should be the drug if the infection is B lactamase producing.

• Methicillin-resistant Staphylococcus aureus (MRSA) strains are resistant to B lactam -strains and a therapeutic challenge, and a hospital pathogen in intesive care units, although is increasingly common in long-stay institutions

• Systemic infection should be treated with glycopeptides (vancomycin or teicoplanin)

Prevention

• No effective immunization with toxoids or bacterial vaccine
• Cleanliness, frequent hand washing, aseptic management of lesion control spread of S. aureus
• Cefazolin is used operatively to prevent infection

Streptococcus

• Gram-positive cocci spherical bacteria that belong to the family Streptococcae, in the order Lactobaccillales and the phylum Bacillota.
• Tends to exhibit form pairs or bent (twisted) chains with one word formed in 2 greek derived prefix Streptopliant and with latin derived suffix coccus
• Some members are human pathogens whereas others are indigenous flora of the oropharynx and gastrointestinal tract.
• Scientific classification
• Domain: Bacteria
• Phylum: Bacillota
• Class: Bacilli
• Order: Lactobacillales
• Family: Streptococcaceae
• Genus: Streptococcus
• Species: (more than 100spp)

Properties of Streptococcus

• Gram positive spherical cocci arranged in pairs or chains that are typically catalase-negative
• Most important species pathogens for humans include
  • Streptococcus pyogenes
  • Streptococcal agalactiae
  • streptococcal faecalis
  • the viridans streptococcus
  • Streptococcus pneumonia

Hemolysis

• Type of hemolysis the most important characteristic for identification.
• Alfa hemolytic streptococci: form green zone around colonies due to incomplete/partially lysis of blood cells in the blood agar
• Beta hemolytic streptococci from green zones due to incomplete/partially lysis of blood cells
• Gamma hemolytic streptococci are unable to hemolyze the RBCs and are therefore known as non- hemolytic

Alpha Hemolysis

• Alpha hemolytic streptococci create a green zone around their colonies for incomplete/partially lysis blood cells in the blood agar

Beta Hemolysis

• Beta hemolytic streptococci create a clear zone around their colonies with complete lysis occurs

Gamma Hemolysis

• Gamma hemolytic streptococci are unable to hemolyze RBCs

• Historically the Lancefield antigens classification have been used as a major way of differentiating streptococci due to their number of types. Combination of tests now used such as hemolysis, antigenic combinations, biochemical reactions, growth characteristics.

Beta hemolytic Streptococci (Streptrococci pyogenes-GAS)

• Arranged into groups of A- U (known as Lancefield groups) as the determination is established precipitation tests with antisera or by immunofluorescence
• Group A (Streptococcus pyogenes)
  • The most important human pathogens are with many strain with hyaluronic acid capsule that is ant phagocytic and causes pharyngitis, and common in skin infection

Group B (S. agalactiae)

• Some cause neonatal meningitis and sepsis colonize the genital tract and hydrolyzes breakdown, inhibits glucose utilization and they are usually bacitracin -resistant.
• Group D enterococcus eg: Enterococcus faecalis and Enterococcus faccium that are member of the normal flora of the colon causing urinary and cardiovascular infection that are very hard organism not killed by Penicillin G
• Group D (enterococcus eg: Enterococcus faecalis and Enterococcus faccium and no enterococcus (S bovis)
• Non-enterococcus group D streptococci such as S. bovis can cause above infection but are less hardy organism as they are inhibited by 6.5%NaCl and killed by penicillin G
• Groups C,E,F,G,H, and K-U Streptococci infrequently cause human diseases

Transmission of Streptococcus

• Most are part of the normal flora of human throat, skin, and intestines; diseases occur when entry to the tissue with viridian and spneumonia chiefily in the oropharynx

• S.pyogenes: found to the skin of in small number with S.agalactiae found in the genital tract,

• Anareobic streptococci are found in lower intestinal tract

Pathogenesis of Streptococcus

• Group A-caused with 3 mechanisms
• inflammation caused locally
  • Exotoxins can production of the symptoms
  • The immune reactions cause inflammation of rheumatic fever

Pathogensis of Streptoccoci A

• Hyaluronidase

• Degrades hyaluronic

• Promotes spreading

• Streptokinase

• Activates plasmogen

• Digests clots

• Lyse

• Breakes thrombi, coronary heart attacks

Toxin

• Dnase (streptornase) depolymerizes DNAin exudates or necrotic tissue Other toxin and hemolysis produced by group A streptococci includes the erythrogenic/pyrogenic B toxins and the streptolysin

Virulence Factors - GAS

• Capsule: anti-phagocytosis & specific attachment to specific tissues
• M - protein in cell wall: anti-phagocytosis & specific attachment to specific tissues
• Streptolysin 0 and S: leukocidins vs neutrophils & macrophages
• Streptococcal pyrogenic exotoxins (SPE): "superantigens" directly stimulate T-cells (-1000X more than a normal immune response) and cause them release high levels of the cytokines that are responsible for fever and shock
• Pyrogenic exotoxin (SPE) and is also responsible for various tissue destruction, including skin lesions and perhapes scarlet fever, as well
• Hyaluronidase: Dissvolves the acid, basement membeanes together is a spreading faxtor

Clinical Findings

• ❖S. pyogenes (Group A Streptococcus) is the most common bacterial cause of sore throat
• ❖Pharyngitis is characterized by inflammation exudate, fever, leucocytosis and tender cervical lymph nodes

Complications

• If untreated spontaneous recovery occurs in 10 days with exrension may extend tooisitis, sinusitis and meningitis,
• The infecting streptococci may produce erythrogenic toxin and the host lacks antitoxin , which can result in scarlet fever
• Rheumatic fever may occur following pharyngitis Complications cont..
• GAS can enter skin defects to produce cellulitis, erysipelas, lymphangitis or bacteremia
• They can enter the uterus after delivery to produce endometritis and sepsis( puerperal fever)
• Streptococcal pyoderma (impertigo) is a superficial infection of abraded skin that forms pus or crusts
• It is communicable among children especially in hot humid climates Glomerulonephritis may occur following skin infections

Streptococcus

• ❖Infective endocarditis caused by viridians occurs the presence of Virulence streptococci in the blood, heart murmur, fever and embolic events

Post Streptococci Diseases

• Disorders in which a local infection with group A streptococci is followed weeks later by inflammation occurs in an orgon isnot infected

Acute Glomerulonephritis

• Occurs 2-3 weeks after skin infection by certain Group A streptococcal spp. occurs in children with features of edema with smokyurine and in children, resolves but if does occurs, use penicillin
• Can be stopped in administration within administration, prior to onset

Rheumatic Fever

• Rheumatic fever is occurs weeks after any type of Group A strep or pharyngitis with poly cardiac and auto
• Within 8 days onset, infection is prevented of infection, and is followed by long term medication

Lab diagnosis of Strep infections

• Diagnostic smear and culture may give indications with ASO

TREATMENT AND PREVENTION

• Suscept to penicillin with a strong need and can be prevented through with medication

Streptococcus Pneumonia can caused

• Pneumonia
• Bactermia
• Meningtis
• And infextions

Properties of Streptococcus Pneumonia

• are spherical that
• is connected though transmissible to with a higher presence of predisposeing factors
• with predisoposing factors- alcoholism and chronic congestion

Pathogenesis of Streptococcus Pneumonia

• A with congestion will result with tissue and fluid

Findings of Streptococcus. Pneumonia

• May induce Pleuris pain with red sputum is not treated right

Lab Diagnosis -Treat to avoid resistance

What to be aware of

• What patients are at risk

Group B streptococcal disease

• Is commonly caused with agents for neonatal menin

GROUP D STREPTOCOCCUS

• Infections in blilated and suppressed

Viridans streptococci

• dental
• endocarditis. BLOOD ARGAR