Coagulase negative staphylococci (Student Notes)

The coagulase-negative staphylococci are not as pathogenic as staphylococcus aureus.

Many of them belong to the normal bacterial flora of the skin and mucosal layers and are only facultative or opportunistic pathogens. Which means that they only cause infections under certain conditions.

There are many different species that belong to this group, but the major ones are:

• Staphylococcus Epidermidis
• Staphylococcus haemolyticus
• Staphylococcus Hominis
• Staphylococcus saprophyticus.

Staphylococcus epidermidis

Staphylococcus epidermidis is an integral member of the bacterial flora of the skin. While not very pathogenic it is a facultative pathogenic bacteria that can cause infections after gaining entry into the body on medical devices.

Laboratory features

Staphylococcus Epidermidis is predominantly found on the skin (hence its name). Like all other staphylococci, it is a gram-positive coccus that forms blue/purple stained grape-like clusters when viewed under the microscope with gram staining. 

They are easily cultivated on regular agar and blood agar plates. Here they appear as small colonies with a white/gray pigment, which is easily recognized on blood agar.

This makes it easy to distinguish from Staphylococcus aureus which has yellow pigments that give their colonies a yellow color.

Staphylococcus epidermidis does not possess any hemolytic enzymes and does not show any hemolysis on blood agar.

They do, Like all staphylococcus species, express catalase enzymes making them catalase positive. But, unlike staphylococcus aureus, they do not express coagulase enzymes and are coagulase-negative. 

Virulence factors

As mentioned, Staphylococcus epidermidis belongs to the skin flora and are facultative pathogenic bacteria.

This means that it can become pathogenic and cause disease under certain conditions. This includes if it allowed entry, e.g. through skin lesions or on medical catheters. 

Under these conditions, the infection is aided by some virulence factors.

One of the most prominent is its ability to adhere to plastic or metal medical instruments, on which they form biofilms. These instruments include IV catheters as well as metal joint prosthesis, which can lead to infections once introduced to the patients

Its ability to form biofilms is its production of an extracellular polysaccharide material called polysaccharide intercellular adhesin.

This creates a slimy layer that facilitates attachment to these devices and also acts as a barrier to antimicrobial agents.

In order to prevent infections in patients, catheters should be changed routinely, and other long-lasting or permanent medical devices should be kept sterile before being introduced to the body.

Diseases/infections

Infections with Staphylococcus Epidermidis are not as frequent and severe as infections caused by staphylococcus aureus.

Most infections are associated with the use of medical devices such as IV catheters and metal prostheses.

Patients with a congenital heart valve deformity known as bicuspid aortic valve are prone to develop endocarditis due to Staphylococcus Epidermidis introduced to the body through IV catheters. It can also affect IV drug users.

Due to its ability to adhere to metal prostheses, Staphylococcus Epidermidis infections can also be seen as hip replacement surgery.

Treatment

Most Staphylococcus Epidermidis infections are effectively treated with antibiotics. However, the most important means of treatment is that the source of the infection is removed. This includes metal prostheses, which have to be replaced. 

The antibiotic of choice should be based on antibiogram tests, however, most strains tend to be sensitive to vancomycin, especially together with either rifampin and an aminoglycoside such as gentamicin.

Some strains of Staphylococcus Epidermidis have developed resistance to β-lactam AB’s, through the same mechanism as Staphylococcus Aureus, and are termed methicillin-resistant staphylococcus epidermidis (MRSE). In addition, vancomycin-resistant Staphylococcus Epidermidis strains have also been identified (VRSE)

Staphylococcus saprophyticus

Staphylococcus saprophyticus is also a part of the normal skin flora, especially in the genital region.

While not very pathogenic, it is one of the most common causes of urinary tract infections as its displacement into the urinary tract in women can cause urinary tract infections.

Laboratory features and cultivation

This staphylococcus species is a gram-positive cocci which shows the characteristic grape-like clusters when viewed under the microscope after staining.

They are easily cultivated on agar and blood agar plates, where they appear as white/gray colonies.

They are catalase-positive, but coagulase-negative, and have no hemolytic enzymes an therefore no hemolysis is observed with cultivation on blood agars.

Staphylococcus saprophyticus is naturally resistant to the Antibiotic novobiocin. This trait is useful as it enables us to separate between Staphylococcus epidermidis and Staphylococcus saprophyticus in the lab. 

Their colonies appear similar but colonies of Staphylococcus Epidermidis will be novobiocin sensitive, while colonies of Staphylococcus Saprophyticus will not.

Virulence factors and diseases/infections

Staphylococcus Saprophyticus belongs to the normal skin flora, predominantly in the genital and perineal area. When displaced from this area to the urinary tract, it can cause urinary tract infections. 

Sexual activity is often the cause of such displacement, as it can displace the bacteria from the female genital tract and allow entry into the urinary tract.

Once in the urinary tract, it adheres to the urinary epithelium (urothelium) with the help of surface-associated proteins. In addition, Staphylococcus Saprophyticus possess urease enzymes which contribute to its ability to cause UTI’s. 

The urease can catalyze the hydrolysis of urea into Co2 and ammonia (NH3), which irritates the urinary epithelium, resulting in inflammation associated with cystitis/UTI’s.

UTI’s brought upon by Staphylococcus Saprophyticus infections is the second most common cause of UTI’s in women between 17-27 years old. Because sexual activity often is the contributing factor and due to its occurance, it has been given the name honeymoon cystitis.

While most cases of Staphylococcus Saprophyticus cystitis is mild and self-limiting, some infections can progress causing pyelonephritis and septicemia.

Treatment

While Staphylococcus Saprophyticus UTIæs can be self-limiting, they can also be treated with trimethoprim-sulfamethoxazole or nitrofurantoin.

In the case of systemic infections such as pyelonephritis and septicemia, the bacteria are usually sensitive towards ampicillin.

Staphylococcus haemolyticus and hominis:

Like most of the coagulase negative staphylococci, haemolyticus and hominis are also found in the bacterial flora of the skin. Both can cause infections if allowed entry into the body, usually after attaching to medical devices.

Laboratory characteristics and cultivation

Like the other members of the staphylococcus genus, they are G+ cocci, showing the characteristic grape-like clustering when viewed under the microscope.

Both species are easily cultivated on agar and blood agar plates, where they form white colonies with weak or no hemolysis. 

Unlike Staphylococcus Saprophyticus, but similar to Staphylococcus Epidermidis, both are novobiocin sensitive.

Virulence factors and disease/infections

Both species belong to the normal flora of the skin and are usually found in regions rich in Apocrine glands, such as the axilla and pubic region

While Staphylococcus haemolyticus is considered the most pathogenic of the two, they share their most important virulence factor which is their ability to create biofilms.

This protects them both from the immune systems and circulating antibiotics once they have gained access to the body.

Both are considered nosocomial pathogens which can adhere to catheters and other medical devices, enabling them access to the body where they can cause orthopedic prosthesis infections, bacteremia and sepsis.

Staphylococcus Haemolyticus infections are known to cause endocarditis, peritonitis, UTI’s, osteomyelitis and septic arthritis in some cases.

Treatment

Both special tend to form biofilms, and if the infection is associated with implantation of any medical device, the best treatment is to remove it if possible.

If not, Staphylococcus hominis is the easiest to treat of the two. Most, if not all, strains are susceptible to penicillin, erythromycin, and novobiocin.

Staphylococcus haemolyticus is very difficult to treat. It has the highest level of antibiotic resistance among coagulase-negative staphylococci.

multidrug resistance is common and various strains are resistant to one or more of these antibiotics:

• Penicillins
• Cephalosporins
• Macrolides
• Quinolones
• Tetracyclines
• Aminoglycosides
• Glycopeptides
• Fosfomycin

If removal of the associated medical device is not possible, or if there is no device, vancomycin is the antibiotic of choice, however, vancomycin-resistant strains have begun to emerge.