The Five Killers


There are some bacteria that are so infamous that they are put into a group called "The Five Killers". The symptoms of infection with these bacteria must be identified quickly by physicians in order to prevent serious illness, but spreading awareness to the public is also important to know what symptoms to look for.



Terms and layout


The five killers are named so because they:

1. Often cause sepsis and septic shock.

2. Have a quick clinical course (ie patiens get very sick very fast)

3. Are very lethal unless treatment is given.


Bacteremia- bacterial presence in blood. Typical symptoms include shivering and high fever.


Septic shock- septic shock arises from a systemic inflammatory reaction the body initiates to combat bacteremia. This is lethal unless treated. The widespread inflammation causes a drop in blood pressure due to vasodilation, which starves tissues of oxygen. Symptoms include tachycardia, tachypnea, altered level of conciousness, vomiting and high fever.


I will exemplify each pathogen with some fictive cases that illustrate a typical presentation with an acute infection with these organisms.


Pathogen 1

A 56 year old man seeks the emergency department. He tells the attending doctor that he is a fisherman and cut his thumb on his fishing hook after reeling in a big cod 3 days ago. The thumb has since become very swollen and painful and he is feeling "very unwell". Upon inspection, the man has developed a fever, and the doctor takes his blood pressure to see it is 90/60 mmHg, which is low. When listening to the man's heart he has a distinct tachycardia (a pulse above 100). The doctor quickly orders blood cultures and blood tests to be taken before, with the agreement of her colleagues, they start empiric broad-spectrum antibiotic treatment and intravenous fluids. The patient's thumb is drained from pus from a large abscess that was formed from the wound, and the surrounding tissue around the wound is cultured as well. He is put into a hospital bed a starts to improve with treatment.


The cultures all come back positive for the same pathogen. Staphylococcus Aureus.

Microscopic image of Staphylococcus Aureus with the typical grape-cluster morphology as well as blue tint due to the Gram staining, indicating they are Gram-positive bacteria. The red haze seen is likely blood.


Yellow Staphylococci, or Staph Aureus, is perhaps the most infamous bacteria on this list. The strain called MRSA- Methicillin resistant Staphylococcus Aureus, is becoming a global health concern as the strain has acquired immunity to several types of B-lactam antibiotics, like Penicillin G.

S. Aureus has a range of toxins and virulence factors it utilizes to cause disease, but perhaps the most dangerous toxin is the Toxic-Shock syndrome toxin that this bacterium produces, which causes a severe shock syndrome and has a high mortality. It has a large arsenal of enzymes to escape host defense and to invade tissues.



Pathogen 2.

A mother and her 5-year old son seeks their primary care physician. The boy looks tired and pale. The mother tells the doctor her son has stopped eating and drinking since a few days and she is barely able to make him eat. His voice has also become hoarse.


Upon investigation the boy has a fever, and is shown to have massively swollen tonsills covered with white stripes. The physician takes a throat swab and sends the specimen to be cultured, but due to the doctor's expertice, they know exactly what pathogen is responsible and prescribes Penicillin to the boy.


The cultures come back three days later positive for Streptococcus Pyogenes.

Streptococcus pyogenes and their characteristic chain-morphology as well as blue tint from the Gram staining, indicating they are Gram-positive bacteria.


Although the case described above seems innocuous, the bacteria S. Pyogenes has been called "flesh-eating bacteria" by the media. This bacteria is notorious for causing a wide range of unpleasant conditions:

- Rheumatic fever

- Streptococcal pharyngitis (Strep throat)

- Wound infection/skin infections, like Scarlet Fever.

- Necrotizing fasciitis (graphic).

- Post Streptococcal Glomerulonephritis, an acute inflammation of the kidneys following resolution of the bacterial infection.

S.Pyogenes has a virulence factor called the M-protein, which has a range of abilities.

- The M protein can cause molecular mimicry, where antibodies against this protein cross-reacts with host tissues. This is the cause behind rheumatic fever, where antibodies attack proteins on the heart valves, often causing a condition called Mitral valve stenosis.

- M protein stops activation of the complement system and delays Macrophage activation

- Is a superantigen, causing an excessive inflammatory response from T-cells in the body.



Pathogen 3.

A 30-year old woman comes to the emergency department with shortness of breath, fever and a phlegm-rich cough. She tells the doctor in the ER that she just came home from a trip from Spain and developed symptoms shortly after coming home. The doctors take a quick-test for inflammatory markers, which is severely elevated. The woman's oxygen saturation is 88%, which is borderline hypoxic. The woman is rushed to X-ray her chest. The X-ray shows several infiltrates on both her lower lobes in her lungs. Some of the phlegm the patient is able to cough up is taken to be cultured, together with blood cultures, afterwards she is given a Penicillin with broader spectrum, oxygen therapy and is put up for monitoring. Her vitals start to improve.


The cultures all come back positive for Streptococcus Pneumoniae.

A rich specimen of Streptoccus pneumoniae, with a diplococcus morphology (each bacteria is a pair of two spheres). A blue tint can be seen from Gram staining, indicating that the bacteria is Gram-positive.


Pneumococci are gram-positive, spherical, diplococci that frequently infects the lungs and causes bacterial pneumonia, described above. Pneumonia is a serious condition associated with significant mortality in elderly, and even young and healthy individuals can become very sick from the infection, leaving impaired lung function for weeks after.


Southern parts of Europe has , due to misuse of antibiotics unfortunatley, selected forth an antibiotic resistant strain of Pneumococcus, hence why taking patient history is important.


Pneumococcus are dangerous because they invade the alveolus deep down in the lungs, which distrupts the gas exchange by causing the alveoli to fill with fluid due to inflammation. Although they have no specific toxins or virulence factors, the fact that they invade the sterile environment in the lungs is what makes it so dangerous.



Pathogen 4.

A 20-year old male college student comes to the emergency department with a severe headache, vomiting, neck stiffness and a high fever. He is found to have a lowered blood pressure pressure, 108/72 mmHg, and an increased heart rate of 101 beats per minute, a clinical tachycardia. A spinal tap is performed, when fluid from around the spinal cord is drained from the patient. The cerebrospinal fluid from the patient is shown to be full of inflammatory cells and a bacteria that stains red with Gram's test. Urgently, the patient is given corticosteroids before being infused with saline solution and intravenous antibiotics.

The patient is asked who else he has been in contact with. The patient says he lives in a dorm and went to first period classes at college before feeling very ill and coming to the hospital. The hospital urgently calls the college to make contact with all students the patient was close to. The patient himself calls his dorm-mates to come to the hospital. Everyone in contact with the patient is to be given antibiotics as a precaution.

The clinical presentation and the culture match up with what was behind these findings, namely, Neisseria Meningitidis.

A rich specimen of Neisseria Meningitidis, having a diplococcus morphology as well as a red tint, indicating the bacteria is Gram-negative.


Meningococci are highly lethal, highly contagious, Gram-negative bacteria that is particularly insidious and utilizes a loophole in the immune system to cause bacterial meningitis, an inflammation of the coverings of the brain. They are spread through respiratory droplets and saliva, and one infected person can easily infect several others. Meningitis typically presents with neck stiffness, fever and severe headache, and the symptoms have developed quickly.


Meningitis is associated with individuals who have a genetic defect in the complement system, a part of the innate immune system. This creates a loop-hole which buys the bacteria time and gives it and opportunity to infect the nervous system.


Although the bacteria has no specific toxins or virulence factors aside from its capsule which gives adhesion-properties, the fact that the bacteria invades tissue that is supposed to be sterile is what makes it so dangerous, just like with Pneumococcus.

The patient was given immunosuppressive medication (Cortiosteroids) before being given antibiotics. The reason for this is that Gram-negative bacteria have an endotoxin, Lipopolysaccharide, thats becomes active once the bacteria dies. Therefore, to prevent a severe immune reaction to the bacterial toxin, the patient's immune system was suppressed before he was given antibiotics.



Pathogen 5.

A 22-year old woman seeks the emergency department with vomiting, right-sided flank pain, chills and a fever. She tells her doctor the symptoms started a week ago with frequent and painful urination and has now progressed to a fever and severe flank pain. The doctor gently taps the patient's right side and she cries out in pain. Urgently, blood cultures and blood tests are ordered, along with a urine sample from the patient. A urine-strip test reveals the presence of blood, white blood cells, and is nitrite positive, indicating that there is nitrogen metabolizing bacteria in the urine. The urine is quickly sent to be cultured as well.


The patient is started on multiple antibiotics and intravenous fluids, as the chills indicate that the infection has likely begun to become systemic. She rapidly improves with treatment and the pain becomes less severe.


The next day, results come back positive for Uropathogenic Escherichia Coli.


Escherichia Coli with their characteristic rod-shaped appearance as well as red tint, indicating the bacteria is Gram-negative.

E.coli is perhaps the most well studied bacterium in the world. It is an inhabitant of the large intestine in most humans and a common pathogen behind Urinary tract infections (cystitis, pyelonephritis), described above. It also causes gastroenteritis (food poisoning/diarrhea) and sepsis, often through a primary urinary tract infection.

E.coli has several subtypes and overall has several virulence factors. Most infamous though, must be EHEC (Enterohemorraghic E.coli), which can cause inflammation of the large bowel, as well as kidney damage with their Shiga-Toxin, leading to a condition known as Hemolytic Uremic Syndrome.



Sources:

Cases are partially taken from/ inspired by:

Lectures by Per- Erik Lindgren, Professor of Medicinal Microbiology, Linköping University

and Åsa Nilsdotter, PhD, Cheif Physician, Clinic for infectious disease, Vrinnevisjukhuset, Norrköping.

Murray's Medical Microbiology, 8th Edition.



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