Assigned ESKAPE Pathogen

Enterococcus faecium

Why is this ESKAPE Pathogen of interest (in brief)

Enterococcus faecium can exist commensally within human or animal gastrointestinal tracts but can also be pathogenic in that it can cause neonatal meningitis and endocarditis (1). There have been strains of Enterococcus faecium identified as resistant to vancomycin – coined Vancomycin-Resistant E. faecium (VRE). Enterococcus faecium has also show tolerance to handwash alcohols in hospitals (2). Since alcohol-based disinfectants are used to control hospital infections worldwide, it is frightening that the multidrug-resistant Enterococcus faecium displays tolerance to commonly used hand rub alcohol solutions. VRE can survive on inanimate surfaces for weeks – including medical equipment – which explains how most VRE infections are acquired nosocomially (3).

General Cellular and Morphological Characteristics of the Organism (taxonomic classification, nutrition, cell shape, habitat)

Enterococcus faecium belongs to Domain: Bacteria, Class: Bacilli, Order: Lactobacillales, Family: Enterococcaceae, Genus: Enterococcus and Species: faecium. This ESKAPE pathogen are Gram positive cocci (spherical in shape) that form short to medium length chains. They can also exist in pairs or single cells. E. faecium are also Facultative anaerobes that are ovoid in shape (1). They do not have cytochrome enzymes and are catalase negative (1). Enterococci are found in the feces of most healthy adults – where there are more faecalis than faecium although both are present. Lower percentages were found in oral cavities in healthy students (1). These bacilli tend to live in the gastrointestinal tract of humans and animals and live in feces and sewage. They are able to withstand harsh environmental conditions including high temperatures, periods of drying, and some antiseptics (1).

Clinical Importance and Prevalence

E. faecium’s high level of inherent and acquired resistance (especially VRE’s) along with the pathogen’s ability to survive on surfaces in hospitals makes it an important bacterium to study clinically. VRE constitute about 43% of all Enterococci isolates (4) making it a severe threat across the world, especially in hospitals that rely upon vancomycin or related antibiotics to combat infection. The bacterium has shown tolerance to hand-rub alcohols, making it a greater threat in hospitals (2). Additionally, this pathogen affects largely older adults with comorbidity, leading to heightened mortality rates (3). Furthermore, Enterococci harbor transferable genetic elements, meaning that resistant genes can be passed to both Gram positive and negative bacteria by conjugation systems with plasmids and transposons (4). This potential of E. faecium to pass on its multidrug resistance to other bacteria in a horizontal fashion is particularly frightening.

Infection (How does the infection occur and where is it localized?), Pathology (What disease is caused? What are the symptoms?)

E. faecium is known to cause urinary tract infections, intraabdominal, pelvic and wound infections, superinfections, and bacteremias (often with other organisms) (5). Lower urinary tract infections including cystitis, prostatitis, and epididymitis are seen in older men (5). Enterococci can also cause infection in the abdominal lining in conjunction with liver cirrhosis or in patients with chronic peritoneal dialysis (5). This ESKAPE pathogen is the third most common organism seen in nosocomial infections (3). Another notable infection of E. faecium is endocarditis. Bacteremia and endocarditis are common infections of Enterococci. The mortality associated with these infections is likely partly due to the demographic of patients who present: older adults with multiple underlying diseases such as diabetes. Synergistic, bactericidal attack is required for treatment of endocarditis (5). Multidrug resistant Enterococci are arising, including Vancomycin Resistant Enterococcus (VRE). Enterococcal surface proteins are virulence factors that contribute to infection in humans (5).

Ineffective Antibiotics (Antibiotics to which the organism has acquired resistance)

E. faecium has shown greater antibiotic-resistance than E. faecalis (3). More than half of its pathogenic isolates express resistance to vancomycin, ampicillin, and high levels of aminoglycosides (3). Additionally, the pathogen has shown resistance to some handwash alcohols (2). Enterococci also exhibit inherent and acquired resistance to cephalosporins, clindamycin, tetracycline, and penicillins. A mutation in the domain V of the 23 S rRNA of E. faecium appears responsible for linezolid resistance (5). Additionally, resistance to quinupristin-dalfopristin may be due to enzyme modification, and drug efflux (5).

Effective Antibiotics (Antibiotics known to inhibit the organism)

VRE can be successfully treated with sultamicillin (5). For most Enterococcal infections, single-drug therapies with penicillin, ampicillin, or vancomycin is adequate although resistance against these antibiotics has been observed (3). Currently, linezolid, daptomycin, tigecycline and the streptogramins (quinupristin/dalfopristin) have shown activity against VRE’s (3).

Corresponding Safe Relative

Enterococcus faecium’s safe relative is Enterococcus raffinosus (6). This non-faecialis and non-faecium enterococcus has rarely been connected to human infections (6). One of the first and only reported cases of E. raffinosus infection was endocarditis in an 85 year old man described in 2009 by Antonio Mastroianni in Le Infezioni in Medicina (6).

References

(1) Murray BE. (1990). The life and times of the Enterococcus. Clinical Microbiology Review. 3(1):46-65.

(2) Pidot SJ., Gao W., Buultjens A.H., Monk IR., Guerillot R., Carter GP., Lee JY., Lam, M., Grayson L., Ballard SA., Mahony AA., Grabsch EA., Kotsanas D., Korman TM., Coombs GW., Robinson JO., Silva A., Seemann T., Howden BP., Johnson PD., Stinear TP. (2018). Increasing tolerance of hospital Enterococcus faecium to handwash alcohols. Science Translational Medicine. 10(452).

(3) Dobbs TE., Patel M., Waites KB., Moser SA., Stamm AM., Hoesley CJ. (2006). Nosocomial Spread of Enterococcus faecium Resistant to Vancomycin and Linezolid in a Tertiary Care Medical Center. Journal of Clinical Microbiology.

(4) Olawale KO., Fadiora SO., Taiwo SS. (2011). Prevalence of Hospital-Acquired Enterococci Infections in Two Primary-Care Hospitals in Osogbo, Southwestern Nigeria. African Journal of Infectious Diseases. 5(2):40-46.

(5) Higuita NA. and Huycke MM. (2014). Enterococcal Disease, Epidemiology, and Implications for Treatment. Print.

(6) Mastroianni A. (2009). Enterococcus raffinosus endocarditis. First case and literature review. Le Infezioni in Medicina. 1:14-20.

Assigned ESKAPE Pathogen

My assigned ESKAPE Pathogen was Pseudomonas Aeruginosa

Why is this ESKAPE Pathogen of interest (in brief)

Pseudomonas Aeruginosa is of interest, because it is a common infection in hospitals after surgery, burn victims, and in individuals with weakened immune systems.

General Cellular and Morphological Characteristics of the Organism (taxonomic classification, nutrition, cell shape, habitat)

Pseudomonas Aeruginosa is a gammaproteobacteria.  This means that it is a gram negative bacteria.  It is rod-shaped and does not produce spores, but it does have a flagellum that allows it to move efficiently. It thrives in temperatures between 25ºC and 37ºC, but it can also survive in temperatures up to 42ºC making them more deadly in hospitals and clinical environments. They produce pigments that are typically a greenish color, and it can grow aerobically or anaerobically under minimal nutrition – it has even been known to grow in distilled water!

Clinical Importance and Prevalence

Pseudomonas Aeruginosa is able to grow in a wide range of environments under minimal nutrition, so it becomes dangerous in hospitals as it can easily infect someone who is immunocompromised.  Typical patients who become infected are cancer patients and burn victims,

Infection (How does the infection occur and where is it localized?)

Pseudomonas Aeruginosa can occur in most areas in the body where there is some sort of a body cavity or mucus membrane.  It can also occur on the skin of burn victims, and most places excluding in the blood.

Pathology (What disease is caused? What are the symptoms?)

Bacterial infection is caused, and can lead to colony growth, tissue invasion, and eventually the spread of the bacteria into other parts of the body.  Pneumonia can also occur from the infection of Pseudomonas Aeruginosa.

Ineffective Antibiotics (Antibiotics to which the organism has acquired resistance)

The organism has acquired resistance to all antibiotics except fluoroquinolones, gentamicin, and imipenem.

Effective Antibiotics (Antibiotics known to inhibit the organism)

Same as above.

Corresponding Safe Relative

Pseudomonas Putida

Putty, Murali. “Pseudomonas Aeruginosa.” Testing Lab Analysis: Mold, Legionella, Asbestos, Environmental Microbiology, USP 797, Radon, Lead, March, 2007.

Prince, Alice S. “Pseudomonas Aeruginosa.” NeuroImage, Academic Press, 2012

1. Assigned ESKAPE Pathogen

Staphylococcus Aureus

2. Why is this ESKAPE Pathogen of interest (in brief)

Staphylococcus Aureus(S. aureus)is a fairly common bacteria, anywhere from 30 to 50 percent of humans have this bacteria growing on them (1, 2). Typically, S. aureus is found on human skin and mucous membranes, and is not of any concern until it crosses into the bloodstream or internal tissues (2). Infections typically are spread in clinical and hospital settings, but can also occur in non-clinical environments (2).  The major concern regarding S. aureusis a particular strain, methicillin-resistantS. aureus, or MRSA, which is a highly difficult form of S. aureus to treat due to resistance and has a very high morbidity rate (3).

3. General Cellular and Morphological Characteristics of the Organism (taxonomic classification, nutrition, cell shape, habitat)

Staphylococcus aureusis a Gram⁺bacteria with a cocci shape (round, spherical shape) and is a member of the Staphylococcaceae family (2). Interestingly, they form clusters of about 1µm in diameter, which can look like grapes when stained (2). However, unstained, S. aureus present as golden colonies (2).

The optimal growing temperature for S. aureusis 37C, while it will grow between 7 and 48C and can survive in temperatures of below -20C (4). Unlike many other bacterium, S. aureus is resistant to high salt content(4). Additionally, S. aureus has the ability to grow under aerobic and anaerobic conditions, although aerobic conditions are preferred(4). Typical medias for colony growth include, blood agar. Tryptic soy agar, and heart infusion agar (5).

As mentioned earlier, S. aureus is typically found in the mucous membranes and on the skin of humans, and are found particularly in the nasal passage (5). However, S. aureuscan also be found in food, and due to its ability to survive in harsh conditions S. aureus is a source of food poisoning (4).

4. Clinical Importance and Prevalence

S. aureus infections have stabilized in numbers since the 1990s, with about 10-30 cases per 100,000 people per year (1). However, the number of MRSA diagnosis has been rapidly increasing over the same time period (1). Both community and health care related epidemics have contributed to the increasing number of MRSA outbreaks (1). Newer more intense infection control procedures have helped to reduce the number of outbreaks in recent years (1).

5. Infection (How does the infection occur and where is it localized?)

Infection is most common in people at the “extremes of life,” i.e. infants and the older populations (1). Additionally, humans working in the health professions, hospitalized people, and individuals that are immunocompromised are at a greater risk of contracting the infection (2). S. aureusis transmitted via direct contact or fomites (objects that have the bacteria on them such as clothing, tools, furniture) from person to person (2). Infections can occur in virtually every part of the body, however are most common in skin and soft tissues.

6. Pathology (What disease is caused? What are the symptoms?)

Many different diseases can be the result of  S. aureus. These include, endocarditis, osteomyelitis, septic arthritis, gastroenteritis, meningitis, toxic shock syndrome, urinary tract infections, pneumonia, but the most common being skin and soft tissue infections (2). Depending on the strain and location of the infection as well as the resulting disease, symptoms vary greatly. However, for ease of answering the question, the symptoms for some of the diseases are as follows:

Skin infections (abscess and cellulitis)  / MRSA :  Swollen, painful bumps that are warm and full of pus, and associated with a fever. Untreated, these lead to deeper more painful infections and can burrow into the skin (6).

Osteomyelitis: fever/chills, swelling of the infected limb with redness, and eventually stiffness and inability to maneuver infected limb. Diagnosis involves blood tests, and potentially a bone scan (7).

Pneumonia: Difficulty breathing, fever, chills, cough. This is diagnosed via chest x-ray and usually involves treatment with antibiotics and hospitalization (8). (Ironic because S. aureus pneumonia is usually transmitted in hospital settings)

7. Ineffective Antibiotics (Antibiotics to which the organism has acquired resistance)

Depending on the strain, S. aureus is resistant to a variety of antibiotics (9). The emergence of antibiotic strains began in the 1950s with penicillin resistance (9). Then, in the 1960s, the first strains of methicillin resistant S. aureusemerged (9). And more recently, vancomycin resistant strains emerged (9). Thus, S. aureuscan be resistant to the majority of antibiotics, and discovery of new treatments is ever so important.

8. Effective Antibiotics (Antibiotics known to inhibit the organism)

Treatment of S. aureusis usually done with penicillinase-resistant beta-lactams (5). Penicillin is the typical antibiotic of choice for sensitive strains (2). However, due to the many different strains ofS. aureus, characterization of the bacteria may be necessary before treatment. For example, the MRSA strains are resistant to beta lactams and are typically treated with vancomycin. Additionally, other treatments may coincide with the antibiotics such as fluid replacement.

9. Corresponding Safe Relative

Staphylococcus epidermidis

Reference:

1. Tong, S. Y. C., Davis, J. S., Eichenberger, E., Holland, T. L., & Fowler, V. G. (2015). Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management.Clinical Microbiology Reviews, 28(3), 603–661. http://doi.org/10.1128/CMR.00134-14
2. Taylor TA, Unakal CG. Staphylococcus Aureus. [Updated 2017 Oct 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-.Available from: https://www.ncbi.nlm.nih.gov/books/NBK441868/
3. Green, B. N., Johnson, C. D., Egan, J. T., Rosenthal, M., Griffith, E. A., & Evans, M. W. (2012). Methicillin-resistantStaphylococcus aureus: an overview for manual therapists. Journal of Chiropractic Medicine, 11(1), 64–76. http://doi.org/10.1016/j.jcm.2011.12.001
4. https://www.foodstandards.gov.au/publications/Documents/Staphylococcus%20aureus.pdf
5. https://www.ncbi.nlm.nih.gov/books/NBK8448/
6. Chambers, H. F., & DeLeo, F. R. (2009). Waves of Resistance:Staphylococcus aureus in the Antibiotic Era. Nature Reviews. Microbiology, 7(9), 629–641. http://doi.org/10.1038/nrmicro2200
7. https://www.mayoclinic.org/diseases-conditions/mrsa/symptoms-causes/syc-20375336
8. https://www.healthline.com/health/osteomyelitis
9. http://www.health.state.mn.us/divs/idepc/diseases/staph/basics.html