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

Assigned ESKAPE Pathogen: Pseudomonas aeruginosa

Why is this ESKAPE Pathogen of interest
Pseudomonas aeruginosa is a common opportunistic pathogen that can cause disease not only in plants and animals but also in humans. This ESKAPE Pathogen is of utmost importance because it is a multidrug-resistant pathogen, with very advanced antibiotic resistance mechanism, that can survive under various environmental conditions. According to the Centers for Disease Control and Prevention (CDC), it is the most common disease-causing species. P. aeruginosa affects different sites within the body, including urinary tract, skin (burn or surgical wounds), and the respiratory tract and causes severe acute and chronic infections in immunocompromised patients with cancer and patients suffering from severe burns and cystic fibrosis. It is often associated with hospital-acquired infections because there is a higher risk for infection if you have surgical wounds or burns or if you are being treated with a mechanical ventilator and other medical devices such as urinary or intravenous catheters.

General Cellular and Morphological Characteristics of the Organism 
Pseudomonas aeruginosa is a Gram-negative, rod-shaped, asporogenous, and monoflagellated bacterium (Wu, 2014). Its size is about 0.5 to 0.8 µm, and it belongs to the bacterial family Pseudomonadaceae (Putty, 2007).

Pseudomonas aeruginosa is often identified by its pearlescent appearance and grape-like or tortilla-like odor (Putty, 2007). P. aeruginosa strains can produce one or more pigments: pyocyanin (blue-green), pyoverdine (yellow-green and fluorescent), and pyorubin (red-brown) (Wu, 2014).

Pseudomonas aeruginosa has simple nutritional requirements as it is often observed to grow in “distilled water” (Putty, 2007). It grows well at 25°C to 37°C, but it is its ability to grow at 42°C that help us differentiate it from many other Pseudomonas species (Wu, 2014).

Like most environmental bacteria, P. aerugionosa lives predominantly in slime-enclosed biofilms adherent to available surface from which it periodically releases (Putty, 2007). It is present in soil and aquatic environments. However, as mentioned before, it is tolerant of a variety of environmental conditions. It is also capable of growing in diesel and jet fuel, where it is known as a hydrocarbon utilizing microorganism (or “HUM bug”), causing microbial corrosion (Putty, 2007). Furthermore, it is resistant to high concentrations of salts and dyes, weak antiseptics, and many antibiotics (Putty, 2007).

Clinical Importance and Prevalence
The most difficult challenge when facing P. aeruginosa is its ability to rapidly develop resistance to multiple classes of antibiotics during treating an infection, ability to survive on minimal nutritional requirements and ability to tolerate a variety of physical conditions. These contribute to the organism’s capacity of persisting in hospital settings.

Data collected by the CDC National Nosocomial Infections Surveillance System from 1986 to 1998 reveals that P. aeruginosa was the fifth most frequently isolated nosocomial pathogen, accounting for 9% of all hospital-acquired infections in the United States; the second leading cause of nosocomial pneumonia (14 to 16%); third most common cause of urinary tract infections (7 to 11%); fourth most frequently isolated pathogen in surgical site infections (8%), and seventh leading contributor to bloodstream infections (2 to 6%) (Lister et al., 2009). In addition, more recent studies continue to show it is the leading cause among pediatric patients in the intensive care unit (Lister et al., 2009).

Infection
In hospital settings, infections by P. aeruginosa can be transmitted in hospitals by nursing staff, medical equipment, sinks, disinfectants, and food (Lister et al., 2009). Transmission occurs from improper hygiene, by patient contact with a contaminated reservoir or by ingestion of contaminated materials.

As described before, P. aeruginosa affects different sites within the body, including urinary tract, skin (burn or surgical wounds), and the respiratory tract and causes severe acute and chronic infections in immunocompromised patients with cancer and patients suffering from severe burns and cystic fibrosis (Wu, 2014).

Furthermore, exposure to contaminated water can also cause mild P. aeruginosa infections. For example, inadequately chlorinated hot tubs and swimming pools can cause ear infections and skin rashes. P. aeruginosa can also cause eye infections in users of contact lenses (Bennington-Castro, 2015).

Pathology
Bloodstream infections can cause:
• Fever and chills
• Body aches
• Light-headedness
• Rapid pulse and breathing
• Nausea and vomiting
• Diarrhea
• Decreased urination

Pneumonia can cause:
• Fever and chills
• Difficulty breathing
• Cough, sometimes with yellow, green, or bloody mucus

Urinary tract infections can cause:
• Strong urge to urinate frequently
• Painful urination
• Unpleasant odor in urine
• Cloudy or bloody urine

Wound infections can cause:
• Inflamed wound site
• Fluid leakage from wound

Ear infections can cause:
• Ear pain
• Hearing loss
• Dizziness and disorientation
(Bennington-Castro, 2015)

Ineffective Antibiotics
P. aeruginosa currently shows resistance to the following antibiotics: penicillin G; aminopenicillin, including those combined with beta-lactamase inhibitors; first and second generation cephalosporins; piperacillin; piperacillin and tazobactam; cefepime; ceftazidime; aminoglycosides; the quinolones; the carbapenems; colistin and fosfomycin (Hancock, 2000).

Effective Antibiotics
P. aeruginosa is most susceptible to the following antibiotics: cefepime, amikacin, ceftazidime, tobramycin, the combination of piperacillin and tazobactam, meropenem, imipenem, piperacillin, ciprofloxacin, gentamicin, and fosfomycin (Yayan et al., 2015).

Corresponding Safe Relative
The corresponding relative safe to P. aeruginosa is Pseudomonas putida. P. putida is a rod-shaped, flagellated, gram-negative bacterium that is found in most soil and water habitats where there is oxygen. It grows optimally at 25-30°C and can be easily isolated. Unlike P. aeruginosa, P. putida has a nonpathogenic nature; therefore, researchers find P. putida beneficial to research as it also happens to be very versatile and easy to handle (Marcus, 2003). For example, as P. putida assists in promoting plant development, researchers use it in bioengineering research to develop biopesticides and to the improve plant health (Espinosa-Urgel, 2000).

Works Cited
Bennington-Castro, Joseph. “What Is Pseudomonas Aeruginosa?” Stroke Center, Everyday Health, 7 Aug. 2015.
Espinosa-Urgel, Manuel, and Amparo SalidoJuan-Luis Ramos. “Genetic Analysis of Functions Involved in Adhesion of Pseudomonas Putida to Seeds.” Journal of Bacteriology, American Society for Microbiology Journals, 1 May 2000.
Hancock, R E, and D P Speert. “Antibiotic Resistance in Pseudomonas Aeruginosa: Mechanisms and Impact on Treatment.” Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, Aug. 2000.
Lister, Philip D., et al. “Antibacterial-Resistant Pseudomonas Aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms.” Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, Oct. 2009.
Marcus, Adam. “Versatile Soil-Dwelling Microbe Is Mapped.” GNN – Genome News Network, 10 Jan. 2003.
Putty, Murali. “Pseudomonas Aeruginosa.” EMLab P&K, Mar. 2007.
Wu, Weihui, et al. “Pseudomonas Aeruginosa.” Molecular Medical Microbiology, Academic Press, 29 Sept. 2014.
Yayan, Josef, et al. “Antibiotic Resistance of Pseudomonas Aeruginosa in Pneumonia at a Single University Hospital Center in Germany over a 10-Year Period.” PLOS ONE, Public Library of Science, 2 Oct. 2015.

Assigned ESKAPE Pathogen: Klebsiella pneumoniae

Why is this ESKAPE Pathogen of interest (in brief)
Klebsiella pneumoniae is a common nosocomial (originating in a hospital) pathogen that accounts for about 10% of all infections acquired within a hospital setting (1). It is also a common pathogen responsible for community-acquired infections, as well as a number of other diseases such as meningitis, septicemia, purulent abscesses, and pneumonia (1). Additionally, as some strains are nitrogen-fixing, K. pneumoniae is of agricultural interest because it has been observed to increase crop yields in certain agricultural conditions.

General Cellular and Morphological Characteristics of the Organism (taxonomic classification, nutrition, cell shape, habitat)
K. pneumoniae is a Gram negative, non-motile, lactose-fermenting, facultative anaerobic, rod-shaped bacterium. It is a part of the Enterobacteriacae family (6). K. pneumoniae is commonly found in the normal flora of the mouth, skin, and intestines, but can become destructive and cause damage if inhaled, specifically to the alveoli. K. pneumoniae occurs naturally in the soil and about one third of strains are nitrogen-fixing in anaerobic conditions.

https://chrislima90.weebly.com/blog/top-advice-on-klebsiella-pneumoniae

http://faculty.ccbcmd.edu/courses/bio141/labmanua/lab12/Mac_kpneumoniae.html
(Grows very well on MacConkey agar)

Clinical Importance and Prevalence
K. pneumoniae originated in a hospital setting and is now globally prevalent in hospital and community settings (6). Infections are more common in the young, the old, and the immunocompromised (6). Enterobacteriacae are becoming more and more difficult to treat because of their increasing resistance to antibiotics through the production of different enzymes such as extended-spectrum beta-lactamases and carabapenemases (6).

Infection (How does the infection occur and where is it localized?)
K pneumoniae infections are typically seen in individuals with a compromised immune system, and most infections are seen in middle-aged or older men who already have debilitating diseases. Healthy people typically do not get Klebisella pneumonia infections (3). Humans serve as the primary reservoir for this pathogen, and the pathogen is typical transmitted between individuals through fecal matter and nasal secretions. K. pneumoniae is rarely carried on the skin (2). Carrier rates of the pathogen increase significantly in hospital patients (2). Klebisella pneumonia is spread through contact, either person-to-person contact (i.e. touching the hands of an infected individual) or environmental contact (i.e. touching a contaminated surface). The bacteria cannot be spread through the air (3). Certain medical tools such as ventilators and catheters may cause an individual to be exposed as well (3). K pneumoniae are capable of infection because of fimbrial adhesins and a thick capsule that is comprised of two layers of polysaccharide fibers (6).

Pathology (What disease is caused? What are the symptoms?)
The most common disease caused by Klebisella pneumoniae is pneumonia. This occurs when Klebisella bacteria enter the respiratory tract and setting in the air sacs of the lungs, causing infection and inflammation (3). The most common symptoms of pneumonia are fever, cough, chest pain, difficulty breathing, and abnormal mucus production (4). Without treatment, pneumonia can become a very serious infection, especially in the elderly and those who are immunocompromised (4). Other diseases that can be caused by Klebisella pneumonia are septicemia, meningitis, endocarditis, and cellulitis (4).

Ineffective Antibiotics (Antibiotics to which the organism has acquired resistance)
Some K. pneumonia have become very resistant to a class of antibiotics called carbapenems (3). Resistant bacteria produce an enzyme called carbapenemase which renders carbapenems ineffective (3). These resistant bacteria are also known as KPC-producing organisms and are very difficult to treat (3).

Effective Antibiotics (Antibiotics known to inhibit the organism)
There are many effective antibiotics to treat K. pneumoniae (5). Beta-lactams, aminoglycosides, and quinolones are effective antibiotics against Klebsiella infections (5). Cephalosporins have also been used alone and in conjunction with aminoglycosides but should not be used if ESBL strains are present (5).

Corresponding Safe Relative
The corresponding safe relative is Escherichia coli (6). Most E. coli are commensal and make up about 0.1% of the of the normal intestinal flora, however some are pathogenic and has shown marked resistance to multiple antibiotics in the past decade (6).

Sources:
1. Guo, S., J. Xu, Y. Wei, Y. Li, and R. Xue. 2016. Clinical and molecular characteristics of Klebsiella pneumoniae venitllaor-associated pneumonia in mainland China. BMC Infec Dis. 16: 608
2. Yu, W.L., Y.C. Chuang. UpToDate. Clinical features, diagnosis, and treatment of Klebsiella pneumoniae infection. 2018. https://www.uptodate.com/contents/clinical-features-diagnosis-and-treatment-of-klebsiella-pneumoniae-infection
3. Centers for Disease Control and Prevention. Klebsiella pneumoniae in Healthcare Settings. 2012. https://www.cdc.gov/hai/organisms/klebsiella/klebsiella.html
4. WebMD. What is Klebsiella Pneumoniae Infection?. 2018. https://www.webmd.com/a-to-z-guides/klebsiella-pneumoniae-infection#1
5. S. Qureshi. Medscape. Klebsiella Infections Medication. 2017. https://emedicine.medscape.com/article/219907-medication#showall
6. Pendleton, J. N., Gorman, S. P., & B. F. Gilmore. Medscape. Clinical Relevance of the ESKAPE Pathogens. 2013.

About 30% of people have staph bacteria, usually living commensally on the skin and in the nostrils. Occasionally, staph can break the skin and cause infections ranging in seriousness from small boils to sepsis and pneumonia.

Staphylococcus bacteria are named so because they are round, or coccus shaped, and they are arranged in grape shaped clusters (the Greek word for grapes is transliterated to staphule). On plates, S. aureus usually create yellow or golden colonies. They grow readily between 18 and 40 degrees Celsius, and are faculitative anaerobes, meaning they will use oxygen if available but can live without it.

Staphylococcus aureus is believed to be living peacefully on the skin or in the nose of 1/3 of the world’s population. In 2006, it was found that for every 10,000 visits to the hospital, 410 of those visits were for a staph skin infection such as abscesses and cellulitis; the number of skin infections in general might be much higher due to the relative lack of seriousness of some skin problems like impetigo and boils. Staph bacteremia, or presence of staph bacteria in the blood, is the cause of an estimated 23% of all cases of sepsis, and can lead to infection of the heart and infection of the bones. Staph is also a common complication of pneumonia, and S. aureus is implicated in more than 40% of healthcare acquired pneumonias. As you can see, staph infections can occur from a variety of ways; the best prevention is simply commonsense risk mitigation, such as cleaning open wounds and having good hygiene.

The antibiotic-resistant form of staph that everyone is afraid of is MRSA (methicillin-resistant Staphylococcus aureus). MRSA infections are commonly acquired in health care settings, but up to 12% of MRSA infections now are from the broader community. Oddly, MRSA refers to staph resistant against other antibiotics, though most antibiotics it is commonly resistant to is in the beta-lactam class, which includes methicillin and penicillin. Resistance happens when staph creates the enzyme beta-lactamase to cleave an important bond in the antibiotic. It recently became resistant to vancomycin, the antibiotic doctors usually go for when they treat MRSA. The antibiotics Bactrim, clindamycin, minocycline, and doxycycline are still effective and are still widely prescribed to patients.

Instead of playing with Stapholococcus aureus in the lab, we are using Staphylococcus epidermidis.

https://www.ncbi.nlm.nih.gov/books/NBK441868/

https://www.cdc.gov/mrsa/community/index.html

https://cmr.asm.org/content/10/3/505.long

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451395/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367609/

https://en.oxforddictionaries.com/definition/staphylococcus

https://en.oxforddictionaries.com/definition/aureus

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372331/

https://www.the-hospitalist.org/hospitalist/article/125986/what-best-treatment-adult-patient-staphylococcus-aureus-bacteremia

https://academic.oup.com/femsre/article/41/3/430/3608758

https://www.uptodate.com/contents/methicillin-resistant-staphylococcus-aureus-mrsa-beyond-the-basics

Acinetobacter baumannii  is a multi-drug resistant, pathogenic bacteria that is commonly found in hospital settings.  Being that is an emerging source of nosocomial infection, and is becoming more prevalent, Acinetobacter baumannii is of interest to the medical and scientific communities (1).

A. baumannii is gram negative, aerobic, and coccobacillus in shape (Figure 1) (3).  The genus Acinectobacter was first discovered in 1911, when a Dutch scientist isolated microorganisms from soil. Originally “Acinectobacter” was used to designate non-motile bacteria. However, today it is currently the genus for “gram-negative, strictly aerobic, nonfermenting, nonfastidious, nonmotile, catalase-positive, oxidase-negative bacteria with a DNA G+C content of 39% to 47%” (2).  Differences in the carbapenemase and gyrB genes of A. Baumannii distinguish it from its close relatives. A. baumannii’s “safe” relative is A. baylyi (2). A. baumannii, Acinetobacter genomic species 3, and Acinetobacter genomic species 13TU are extremely similar, and cannot be distinguished from one another using commercial methods.  Therefore, the 3 species are often lumped together as a complex, and treated as one (2).  Acinectobacters are commonly found in soil and water in nature, and some are part of the flora of human skin. However, virtually no individuals have tested positively for A. baumannii outside of hospital settings and combat zones, so the natural habitat of A. Baumannii is currently unknown (2). Very few individuals in China and tropical Australia have been tested positively for A. baumannii (5).  In the laboratory setting, A. Baumannii  grows well on Luria-Bertani broth (LB) (1).

As mentioned prior, A. baumannii is rarely found outside of the hospital setting.  One notable exception to this is the prevalence of A. baumannii in skin infections among soldiers and other military personnel (1).   Additionally, A. baumannii is well documented in burn units and ICUs.  Immunocompromised individuals, as well as individuals with prolonged hospital stays are at the greatest risk for infection of A. baumannii (1). Hospital-acquired pneumonia and bloodstream infections, as well as post-neurosurgical meningitis, are the diseases commonly associated with A. baumannii. In 2003 the CDC reported that 7% of ICU-acquired pneumonias were caused by A. baumannii, and between 5 and 10% of cases of ICU-acquired pneumonia were due to A. baumannii (2).  It is hypothesized that soldiers returning from Afghanistan and Iraq brought this pathogen into U.S. hospitals.  A. baumannii has thrived in this setting due to its antibiotic and antiseptic resistance (2).  Infections typically begin when an external device, such as a ventilator, is used in the treatment of a patient.  The external device provides an entry site for A. baumannii, where it can then colonize (and can form biofilms)—for this example, in the lungs (1). Figure 2 below shows how A. baumannii spreads in the hospital setting, and Figure 3 shows how it affects the human body (6). Symptoms of an infection caused by A. baumannii are hard to distinguish among already ill individuals, however, they typically include fever, chills, and cough (5).

A. baumannii is known to be resistant to cephalosporins (can degrade beta-lactam), aminoglycosides, quinolones and, lately, carbapenems (3).  When A. baumannii was first treated in the 1990’s, carbapenems were effective antibiotics, but are becoming less effective over time (3). Modified efflux pumps, porins, and lactamases enable A. baumannii to be resistant to several classes of drugs (4). The World Health Organization reports that A. baumannii is susceptible to polymyxins, but academic research has focused on new developments to combat gram-negative bacteria. Outer membrane proteins of gram-negative bacteria are being targeted experimentally as potential antibiotics (3). Additionally, bacteriophages are also being investigated as potential antibiotics, due to their ability to selectively target bacteria (1).

ESKAPE Pathogen Fig 1-27hgnn4

ESKAPE Pathogen Fig 2-18eokb8

ESKAPE Pathogen Fig 3-1t4ue2e

References:

(1)   Howard, Aoife, et al. “Acinetobacter Baumannii.” Virulence, vol. 3, no. 3, 2012, pp. 243–250., doi:10.4161/viru.19700.

(2)   Peleg, A. Y., et al. “Acinetobacter Baumannii: Emergence of a Successful Pathogen.” Clinical Microbiology Reviews, vol. 21, no. 3, 2008, pp. 538–582., doi:10.1128/cmr.00058-07.

(3)   Soojhawon, Iswarduth, et al. “Discovery of Novel Inhibitors of Multidrug-Resistant Acinetobacter Baumannii.” Bioorganic & Medicinal Chemistry, vol. 25, no. 20, 2017, pp. 5477–5482., doi:10.1016/j.bmc.2017.08.014.

(4)   Vila, Jordi, et al. “Porins, Efflux Pumps and Multidrug Resistance in Acinetobacter Baumannii.” Journal of Antimicrobial Chemotherapy, vol. 59, no. 6, 2007, pp. 1210–1215., doi:10.1093/jac/dkl509

(5)   “WPRO | Multidrug-Resistant Acinetobacter Baumannii (MDRAB).” World Health Organization, World Health Organization, 7 July 2017, www.wpro.who.int/mediacentre/factsheets/fs_20101102/en/.

(6)  Dijkshoorn, Lenie, et al., “An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii”, Nature Reviews Microbiology, vol. 5, 2007, pp. 939-951

https://doi.org/10.1038/nrmicro1789

Assigned ESKAPE Pathogen: Enterococcus faecium

Why is this ESKAPE Pathogen of interest:

Enterococcus faeciumis normally found in human and other mammal gastrointestinal tracts as part of the gut microbiota. However, when located elsewhere, it can cause infections. This has become a large problem in hospitals, causing about 3% of sepsis cases in NICUs_­⁴. The emergence of VRE, or vancomycin resistant enterococci, in the early 2000s made this infection a larger issue, further compounding the growing problem of antibiotic resistance worldwide⁴.

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

This is a gram-positive aerobic bacterium that grows best on Columbia blood agar at thirty-seven degrees Celsius for twenty-four to forty-eight hours¹. It typically grow as diplococci, meaning they grow in pairs of round colonies, or as short chains of round colonies and will exhibit hemolysis on some blood medias⁸.

As previously mentioned, they typically live in the intestines. The Enterococcus genus used to be classified as group D of the Streptococcus genus; however, genetic analysis proved too large a difference between Streptococci and Enterococci to classify them in the same genus⁸.

Clinical Importance and Prevalence:

Nosocomial infections are a growing problem given both antibiotic resistance and the aging of the Baby Boomer population causing an influx of ill, elderly patients in hospitals. This organism is usually resistant to penicillin (about 90% of cases in one Australian hospital) and resistance to vancomycin has hit about 50% worldwide³. Over twenty-eight percent of people with these infections in the same hospital died within 30 days³. Some research has shown that fluoroquinolone use against these infections should be reduced, as it may play a role in the development of linezolid resistance⁶.

Infection:

E. faecium, along with its close relative Enterococcus faecalis, cause endocarditis, urinary tract infections, prostatitis, intra-abdominal infection, and cellulitis⁵. These infections typically occur from lack of correct hygiene methods in hospitals, such as handwashing⁴.

Pathology:

Symptoms vary based on the location of the infection:

• Endocarditis: fever, chills, fatigue
• UTI: pain during urination, foul smelling and/or dark/cloudy urine, polyuria
• Prostatitis: pain during urination, excessive night urination, urinary retention
• Intra-abdominal infection: fever, chills, fatigue
• Cellulitis: red skin, swelling, tenderness to the touch

Ineffective Antibiotics:

Strains isolated from humans have been shown to be resistant to vancomycin and linezolid (see above referenced sources). There is also evidence of strains resistant to chloramphenicol, tetracycline, ciprofloxacin, and erythromycin isolated from pigs in Malaysia⁵.

Effective Antibiotics:

The current recommendations include streptogramins, oxazolidinones, and Daptomycin^5,6.

Corresponding Safe Relative:

The safe relative for E. faeciumis Enterococcus raffinosus. This organism has also been found to be vancomycin resistant and can cause endocarditis². However, these infections are rare and the human immune system is normally able to withstand infection. Since the safe relative is in the same genus, it behaves similarly, but is less commonly the cause of infection in humans and less commonly resistant to antibiotics.

Sources:

1. Culture Collections. Public Health England. Accessed October 5 2018.
2. Dalal, Aman MD,Urban, Carl PhD, Rubin, David MD, Ahluwalia, Maneesha MD. Vancomycin-Resistant Enterococcus raffinosus Endocarditis: A Case Report and Review of Literature. Infectious Diseases in Clinical Practice. May 2008.
3. Kelvin W. C. Leong, Louise A. Cooley, Tara L. Anderson, Sanjay S. Gautam, BelindaMcEwan, Anne Wells, Fiona Wilson, Lucy Hughson, & Ronan F. O’Toole. Emergence of Vancomycin-Resistant Enterococcus faeciumat an Australian Hospital: A Whole Genome Sequencing Analysis.Scientific Reportsvolume 8, Article number: 6274 (2018).
4. Lakshmi Srinivasan, Jacquelyn R. Evans, in Avery’s Diseases of the Newborn (Tenth Edition), 2018
5. Larry M. Bush, MD, Charles E. Schmidt, and Maria T. Perez, MD. Enterococcal Infections. Merck Manual. Accessed Oct 5 2018.
6. Shiang ChietTan, Chun Wie Chong, Cindy Shuan Ju Teh, Peck Toung Ooi, Kwai Lin Occurrence of virulent multidrug-resistant Enterococcus faecalisand Enterococcus faecium in the pigs, farmers and farm environments in Malaysia. PubMed. August 2018.
7. Thomas E. Dobbs, Mukesh Patel, Ken B. Waites, Stephen A. Moser, Alan M. Stamm, Craig J. Hoesley. Nosocomial Spread of Enterococcus faeciumResistant to Vancomycin and Linezolid in a Tertiary Care Medical Center. Journal of Clinical Microbiology. June 2018.
8. Enterococcus. Accessed Oct 5 2018.

Assigned ESKAPE Pathogen

#6 Enterobacter Species

Why is this ESKAPE Pathogen of interest (in brief)

The Enterobacter species is of interest due to the high rates of hospital-acquired infection that it causes. A study from the National Nosocomial Infections Surveillance System showed that the Enterobacter species is the third most common cause of pneumonia in ICUs. It is of increasing interest because the species has extremely high rates of antibiotic resistance. This is of concern due to the prevalence of infection and the mortality rates associated with the infections it causes. Crude mortality rates range from 15-87%. This is an extremely wide range, making the infections caused by the Enterobacter species highly unpredictable.

https://www.britannica.com/science/Enterobacter

https://emedicine.medscape.com/article/216845-overview

https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540201/all/Enterobacter_species

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

The Enterobacter species is a rod-shaped bacteria that is gram negative. The size of each colony is 0.6-1.0 micrometers by 1.2-3.0 micrometers. The species is not capable of forming spores. It is motile due to flagella. The taxonomic classification is Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacteriales; Enterobacteriaceae. The species are facultative anaerobes; meaning the presence of oxygen is not required. They are capable of fermenting glucose and lactose. Through this fermentation, gases are produced. They are commonly found in intestinal tracts and in soil, water, and sewage. They are not harmful when found in the gut. Less commonly, they are found in urine, pus, and bodily fluids.

https://microbewiki.kenyon.edu/index.php/Enterobacter

https://www.britannica.com/science/Enterobacter

Clinical Importance and Prevalence

This Eskape pathogen is known to cause nosocomial infections. A nosocomial infection is caused due to a bacterium’s prevalence in certain locations. A nosocomial infection can also be called a hospital-acquired infection. The Enterobacter species is prevalent in ICUs and also commonly survives in equipment with water. This is because the species is able to live for a long time on surfaces. In wet environments, it is able to replicate rapidly. The most common source of spreading the bacteria is a lack of cleanliness, i.e. a lack of handwashing. This is a major source of infection in hospitals, with about 50% of infection in the ICU caused by the Enterobacter species. The species causes infections in the respiratory tract, urinary tract, intra abdominal cavity, intravascular devices, and can lead to sepsis.

https://www.healthline.com/health/hospital-acquired-nosocomial-infections

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

The Enterobacter species cause nosocomial infections in immunocompromised patients. The most common types of Enterobacter that cause human infection are E. cloacae, E. aerogenes, E. gergoviae, and E. agglomerans. Infections occur endogenously or exogenously. Endogenous sources of infection are the most common type of nosocomial infections caused by the Enterobacter species. The endogenous sources include the skin, respiratory tract, urinary tract, and gastrointestinal tract. The endogenous source tend to be the site of localization for the species.

https://emedicine.medscape.com/article/216845-overview

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

An infection caused by the Enterobacter species include a heart rate exceeding 90 bpm, a respiration rate greater than 20, and a fever above 100.4 °F or below 96.8°F. Other symptoms include hypotension, septic shock, cyanosis, and hypoxemia. Diseases and conditions that can be caused by this species are eye and skin infections, meningitis, bacterial blood infections, pneumonia, and urinary tract infections.

https://emedicine.medscape.com/article/216845-overview

http://www.antimicrobe.org/b97.asp

https://www.britannica.com/science/Enterobacter

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

Effective Antibiotics (Antibiotics known to inhibit the organism)

This species has developed resistance to a number of different antibiotics, especially in hospital settings. Infections and diseases caused by the Enterobacter species have been treated with an aminoglycoside, a fluoroquinolone, a cephalosporin, or imipenem. Over time, however, Enterobacter species has developed resistance to most beta lactam drugs and many other different drug types. Another source suggests that “third generation” cephalosporins, penicillins, and quinolones have become ineffective antibiotics as a result of increasing resistance. However, there are some antibiotics that are still effective. “Fourth generation” cephalosporins and carbapenems remain a viable option for treatment. Aminoglycosides are noted to be viable as well, but need to be combined with another type of antibiotic to allow for successful treatment. Lastly, quinolones are able to be used against many strains of the Enterobacter species, but similar to the trend of other drugs, emerging resistance is of concern. More specifically, Polymyxin B, Levofloxacin, Doripenem, Imipenem, Meropenem, Cefepime, Ciprofloxacin, Trimethoprim-sulfamethoxazole, Ertapenem, and Tigecycline are all examples of antibiotics that seem to remain effective and are largely avoiding resistance for now.

http://www.antimicrobe.org/b97.asp

https://www.britannica.com/science/Enterobacter

https://catalog.hardydiagnostics.com/cp_prod/Content/hugo/Enterobacter.htm

Corresponding Safe Relative

The corresponding safe relatives are the Enterobacter aerogenes and the Erwinia carotovora.

(Source: Lab handout)

Images:

Enterobacter cloacae

https://jamanetwork.com/journals/jamadermatology/fullarticle/413232

https://www.researchgate.net/figure/A-localized-infection-of-Enterobacter-cloacae-developed-on-the-patients-left-forehead_fig4_258503948

Sources:

https://microbewiki.kenyon.edu/index.php/Enterobacter

http://www.antimicrobe.org/b97.asp

https://www.britannica.com/science/Enterobacter

https://emedicine.medscape.com/article/216845-overview

https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540201/all/Enterobacter_species

https://catalog.hardydiagnostics.com/cp_prod/Content/hugo/Enterobacter.htm

Davin-Regli, Anne, and Jean-Marie Pagès. “Enterobacter Aerogenes and Enterobacter Cloacae; Versatile Bacterial Pathogens Confronting Antibiotic Treatment.” Frontiers in Microbiology 6 (2015): 392. PMC

Davis, Elizabeth et al. “Antibiotic Discovery throughout the Small World Initiative: A Molecular Strategy to Identify Biosynthetic Gene Clusters Involved in Antagonistic Activity.” MicrobiologyOpen 6.3 (2017): e00435. PMC

Santajit, Sirijan, and Nitaya Indrawattana. “Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens.” BioMed Research International 2016 (2016): 2475067. PMC

1. Enterococcus faecuim

2. Staphylococcus aureus

3. Klebsiella pneumoniae

4. Acinetobacter baumannii

5. Pseudomonas aeruginosa

6. Enterobacter species