Gram positive infections

Notes

Introduction

Bacteria are prokaryotic (single-celled) microorganisms that are found in both human health and disease.

Bacteria range in size from approximately 0.5-5.0 micrometers in length and different in morphology. Typical shapes of bacteria include spheres (i.e. cocci) and rods (i.e. bacilli) .

The human body is colonised with trillions of bacteria in normal health. This collective is known as the human microbiota and is important for normal functioning. 

Bacteria are also the cause of many clinically relevant infections in humans. Microbiology describes the branch of medicine that deals with microorganisms, such as bacteria, which are critical in all aspect of medicine.

Bacterial structure

The general structure of a bacterium includes the cell wall, cell membrane, capsule, flagella, fimbriae, nuclear material, cytoplasm and other intracellular components. 

Cell wall

The cell wall forms the outer aspect of bacteria, which protects it against host immune defences and external osmotic pressures. The cell wall differs depending on whether the organisms is gram positive or gram negative. These are the two major groups of bacteria.

Gram positive organisms have a thick peptidoglycan layer composed of polysaccharides and charged amino acids interlaced with other major polymers like teichoic acid. Underneath the peptidoglycan layers is the cell membrane. 

Gram negative organisms have an outer cell membrane that contains lipopolysaccharides (LPS). Beneath the outer membrane is a smaller peptidoglycan layer compared to gram positive organisms and then the cell membrane.  LPS is the key feature of gram negative organisms that contains lipid A. When broken down and released into the circulation, lipid A stimulates a profound inflammatory response that can lead to septic shock.   

Some bacteria do not have a cell wall (i.e. mycoplasma). Bacteria without a cell wall replicate intracellularly within host cells. Due to the absence of a cell wall these bacteria cannot be identified on gram stain. 

Cell membrane

Similar to the plasma membrane in mammalian eukaryotic cells, the cytoplasmic membrane surrounds the cytosol and acts as a chemical barrier controlling substances pass in and out the cell

Capsule

Some bacteria contain a capsule that is external to the cell wall. Bacterial capsules are composed of high-molecular-weight polysaccharides. We can use knowledge of capsular structure to subcategorise bacteria (i.e. Streptococcus pneumoniae).

Flagella

Flagella are spiral-shaped filaments consisting of protein and flagellin. They assist in bacterial movement.

Fimbriae

Small hair-like appendages, also known as pili, most commonly seen in gram-negative bacteria. Fimriae are composed of proteins called pilins (hence pili). Fimbriae assist in adherence to cell surfaces.

Nuclear material

Nuclear material in bacteria is free within the cytoplasm. In addition, DNA is found in structures known as plasmids, which are small rings of DNA found in the cytoplasm. Bacterial plasmids usually contain genes important for virulence and may be transferred from one microorganism to another. 

Intracellular components

Bacteria contain many important intracellular components such as ribosomes. Ribosomes in bacteria are smaller (70S) than eukaryotic ribosomes (80S) and due to this difference they may be targeted by antibiotics

Gram staining

Gram staining is a technique used to identify microorganisms under a microscope and differentiate between two major groups of bacteria (gram positive and gram negative).

Gram staining colours the bacterial cell walls red/pink or violet/blue. In gram positive bacteria, the cell wall is stained violet/blue due to the thick peptidoglycan layer. This causes retention of the violet crystal used during the gram staining technique. In gram negative bacteria, the cell wall is stained red/pink due to the thin peptidoglycan layer. Here, there is less retention of the crystal.

Classification

Bacteria can be broadly divided into two main groups (gram positive or gram negative) based on gram staining of the bacterial cell well.

Gram positive bacteria are further divided based on the morphology, which can be assessed under the microscope. The two major groups are cocci (spheres) and bacilli (rods). 

Further differentiation is then based on laboratory and molecular techniques that assess the different characteristics of gram positive bacteria. 

Staphylococcus

Staphylococcal infections are extremely common. They are broadly divided into coagulase positive (i.e. S. Aureus) and coagulase negative (i.e. S. saprophyticus)

Types

There are three main types of Staph to be aware of:

  • Staphylococcus aureus (methicillin-sensitive: MSSA)
  • Staphylococcus aureus (methicillin-resistant: MRSA)
  • Coagulase negative Staphylococcus (CoNS)

CoNS consists of a group of > 40 microorganisms that are generally considered together in clinical practice. They are usually detected when there is contamination during blood sampling. This is because they are commonly found on the skin. However, they can cause significant infections in patients with iatrogenic devices (i.e. lines). 

Shape

Staphylococcal microorganisms form cocci in clusters. 

Locations

Common locations include skin, mouth, nose and throat. They live harmlessly on the skin of 1 in 3 people. 

Infections

Typical infections associated with Staphylococcus include:

  • Skin infections (i.e. cellulitis impetigo)
  • Endocarditis (typically right-sided valves in association with IVDU)
  • Septic arthritis
  • Osteomyelitis

Staphylococcus can release an exotoxin leading to specific infections including acute gastroenteritis, toxic shock syndrome and scalded skin syndrome.

  • Toxic shock syndrome (TSS)
    • TSS toxin-1
    • Diffuse erythematous rash, diarrhoea, vomiting, fever, desquamation of palms and soles with septic shock
    • Classically following infected ‘lost tampon’ used during menses
    • However, 50% cases now unrelated to menses.
  • Scalded skin syndrome (SSS)
    • Exfoliative toxin A & B
    • Classically affects neonates
    • Widespread blistering rash with exfoliation of skin
    • Fluid loss and heat loss are most common problems.

Treatment

Management depends on resistant patterns and allergy status, but options typically include flucloxacillin (MSSA) or vancomycin (CoNS, MRSA).

Streptococcus

Streptococcal microorganisms cause a wide range of clinically relevant infections.

Streptococcal classification is more complex and bacteria are broadly divided into three groups: alpha-, beta- and gamma-haemolytic.

Types

Streptococcal microorganisms are divided by their haemolytic properties. The two major groups are alpha- and beta-haemolytic. Beta-haemolytic bacteria are further divided based on Lancefield grouping.

  • Alpha-haemolytic
    • Streptococcus pneumonia
    • Streptococcus viridans 
  • Beta-haemolytic
    • Group A (S. pyogenes)
    • Group B (S. agalactiae)
    • Group C (S. dysgalactiae)
    • Group D (S. Bovis)
    • Others

Traditionally, enterococcal microorganisms were classified as beta-haemolytic group D streptococci. However, they have now been reclassified to an independent genus

Shape

Streptococcal microorganisms typically form cocci in chains. Some Streptococci, like S. Pneumoniae, form Diplococci (two bacteria together).

Locations

Streptococci are commonly found on the skin and in the throat.

Infections

Infections associated with streptococci depend on the type (i.e. alpha vs. beta-haemolytic) and include the following:

  • Group A - beta-haemolytic
    • Tonsillitis/pharyngitis
    • Cellulitis +/- Necrotising fasciitis
    • Scarlet fever
    • Rheumatic fever
  • Group B - beta-haemolytic
    • Neonatal infections (meningitis, pneumonia, sepsis)
    • Found in vaginal flora in high percentage of pregnancies
  • Alpha-haemolytic
    • Pneumonia
    • Meningitis
    • Endocarditis (usually left-sided from alpha-haemolytic microorganisms)
    • Dental infections

Enterococci (re-classified from streptococci) can form part of the normal bowel flora. They are commonly associated with UTIs, biliary infections, intra-abdominal infections and endocarditis. 

Treatment

Antibiotics used to treat streptococcal infections include beta-lactams (i.e. penicillin, ceflasporins). In severe cases, or those with high resistance, glycopeptides (i.e. vancomycin) or carbapenems (i.e meropenem) are used.

Other

There are four other major groups of gram positive bacteria that cause clinically significant infections in humans.

These four are the gram positive rods that are broadly divided into spore-forming (Bacillus, Clostridium) and non-sporing (Listeria, Corynebacterium). They are briefly discussed below.

Clostridium

Clostridium is an anaerobic gram positive rod that causes a range of clinically important infections related to toxin release. 

  • Clostridium difficile (i.e. 'C. Diff')
    • Profuse, watery diarrhoea due to secretions of two toxins (A & B)
    • Commonly associated with antibiotic use and overgrowth of 'C. diff' in the bowel
    • In severe cases causes pseudomembranous colitis and toxic mega colon
  • Clostridium botulinum
    • Causes flaccid paralysis due to secretion of neurotoxin.
    • Toxin now commercially available as Botox
  • Clostridium Tetani
    • Causes tetanus from release of tetanus toxin, vaccinations available
  • Clostridium perfringens
    • Cause of gas gangrene via alpha toxin leading to myonecrosis

Listeria

Listeria monocytogenes can cause meningitis, often in neonates, or patients who have consumed unpasturised milk. 

Bacillus

Bacillus cereus is a common cause of food poisoning (i.e. gastroenteritis). It classically occurs following consumption of re-heated rice. 

Corynebacterium

Corynebacterium diphtheria releases an exotoxin that causes the potentially fatal condition diphtheria. Widespread vaccination programme now in place. 

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