Enterococcus Faecalis is a gram-positive bacterium that can cause a variety of nosocomial infections, and urinary tract infections are the most common. These infections can be exceptionally difficult to treat, because of drug resistance. Despite their troublesome nature, little is known about the host or bacterial factors necessary for E. faecalis to cause disease in the urinary tract.
Enterococcus faecalis is a tenacious species of bacteria that is
growing increasingly resistant to antibiotics. The bacterium is capable
of forming "microbial communities," in which it attaches to other
microbial cells to form what's known as a biofilm. These biofilms are
especially resistant to antibiotic therapy.2
The ability of Enterococcus Faecalis to cause disease in the kidney is well established by its tropism. The diagnosis of upper versus lower urinary tract infection caused by enterococci, as with gram-negative bacilli, is generally based on signs and symptoms. Thus the presence of fever and flank pain, with or without lower tract symptoms of dysuria, frequency, and urgency suggest upper tract infection.
Histologic examination of bladder and kidney tissues demonstrated that E. faecalis induced an inflammatory response in the kidney but not in the bladder.
E. faecalis-mediated urinary tract infection appears to occur via a strikingly different mechanism than E. coli-mediated urinary tract infection. In a typical E. coli
urinary tract infection, the bacteria invade the superficial umbrella
cells and replicate to high levels, forming intracellular biofilms, a
process that induces a TLR4-mediated cytokine response that recruits
neutrophils to the site of infection. In enterococcal urinary tract infection, there is little to no inflammation in the bladder
Furthermore, neutrophils represented only a minority of the inflammatory
cells targeted to the site of infection, which typically is in the
kidney. We found that TLR2, which is hypothesized to play a similar role
in the innate response to gram-positives as TLR4 does for gram-negative
pathogens, does not play a substantial role in the innate response to E. faecalis in the urinary tract
Since facultative anaerobes are able to grow in both the presence and absence of oxygen, they can survive in many different environments, adapt easily to changing conditions, and have a selective advantage over other bacteria. As a result most life-threatening pathogens are facultative anaerobes.
The ability of facultative anaerobic pathogens to survive without oxygen is important, since their infection is shown to reduce oxygen levels in their host's gut tissue. Moreover the ability of facultative anaerobes to limit oxygen levels at infection sites is beneficial to them and other bacteria, as dioxygen can form reactive oxygen species (ROS). These species are toxic to bacteria and can damage their DNA among other constituents.
Actinomycosis is an infrequent invasive bacterial disease, that has been recognized for over a century. Actinomyces spp. are filamentous Gram-positive bacilli mainly belonging to the human commensal flora of the oropharynx, gastrointestinal tract, and urogenital tract. To date multiple different clinical features of actinomycosis have been described as various anatomical sites, such as face, bone and joint, respiratory tract, genitourinary tract, digestive tract, central nervous system, skin, and soft tissue structures.
Actinomyces are often isolated with other normal commensals such as Aggregatibacter Actinomycetemcomitans, Eikenella Corrodens, Capnocytophaga, Fusobacteria, Bacteroides, Staphylococci, Streptococci, or Enterobacteriaceae depending on the site of infection.
It is difficult to discriminate colonization of mucosa-contaminating samples and infection due to Actinomyces, except when the culture is pure and associated with the presence of polynuclear neutrophils.
Actinomyces infections could be polymicrobial and associated with other bacteria named “companion microbes,” which contribute to initiation and development of infection by inhibiting host defenses or reducing oxygen tension.
The multimicrobial nature of infection is well described in animal models and in human cervicofacial actinomycosis.
Isolation and identification of these causative bacteria occur in only a minority of cases; the failure rate of culture is high because of previous antibiotic therapy, inhibition of Actinomyces growth by concomitant and/or contaminant microorganisms, inadequate culture conditions, or inadequate short-term incubation.
Because of the microaerophilic or strict anaerobic character of Actinomyces, strict anaerobic processing (rapid transport to the laboratory and/or transport in an anaerobic transport medium) and anaerobic growth conditions should be used for primary isolation.
The most appropriate clinical specimens are tissue from surgical biopsy or pus; swabs must be avoided.
The identification of Actinomyces in mucosa, where these bacteria are normal inhabitants, is of little significance in the absence of sulfur granules.
A Gram stain of the specimen is usually more sensitive than culture, especially if the patient had received antibiotics. Actinomyces are non-spore-forming Gram-positive rods. Except for A. meyeri, which is small and non-branching, all the other species are branching filamentous rods.
Growth of Actinomyces is slow; it appears within at least 5 days and may take up to 15–20 days. Thus incubation of at least 10 days is required before conclusion of a negative culture. Most Actinomyces spp. are facultative anaerobes, but some relevant species (such as A. meyeri) are strictly anaerobic. Cultures must be incubated in an anaerobic atmosphere.
Penicillin G or amoxicillin are considered drugs of choice for the treatment of actinomycosis. Third-generation cephalosporins are less frequently used even if they are considered to be active on A. israelii; It is important to note that some species are resistant to ceftriaxone (Actinomyces europaeus and Actinomyces graevenitzii). Piperacillin–tazobactam, imipenem, and meropenem are considered to be active, but the use of these broad-spectrum antibiotics should be limited to avoid acquisition of resistant flora. Oxacillin, cloxacillin, and cephalexin, a first-generation cephalosporin, are not considered to be active. Metronidazole and aminoglycosides have no in vitro activity against Actinomyces. Fluoroquinolones (Ciprofloxacin and Moxifloxacin) are usually considered to be inactive, but data is limited and controversial. Doxycycline is considered to have a poor activity on Actinomyces spp., but clinical successes have been reported with this drug. Macrolides and Clindamycin have been used successfully as alternatives. As Actinomyces spp. do not produce beta-lactamases, it is not useful to combine amoxicillin with beta-lactam inhibitors such as clavulanic acid, except if co-pathogens such as Enterobacteriaceae are involved in the disease
Enterococcus faecalis formerly classified as part of the group D Streptococcus system, is a Gram-positive commensal bacterium inhabiting the gastrointestinal tracts of humans]. Like other species in the genus Enterococcus, E. faecalis is found in healthy humans and can be used as a probiotic. As an opportunistic pathogen E. faecalis can cause life-threatening infections especially in the nosocomial (hospital) environment, where naturally high levels of antibiotic resistance found in E. faecalis contribute to its pathogenicity. E. faecalis has been frequently found in reinfected root canal-treated teeth in prevalence values ranging from 30% to 90% of cases Re-infected root canal-treated teeth are nine times more likely to harbor E. faecalis than cases of primary infections.
Physiopathological pathways of cervicofacial actinomycosis explain that predisposing conditions include poor oral hygiene and oral mucosa trauma by dental extraction, Other predisposing factors include male sex, immunosuppression, alcoholism, and malnutrition.
Although cervicofacial actinomycosis is the most frequent form of actinomycosis with bone involvement, Actinomyces spp. could also be involved in extra-facial bone and joint infection. Various clinical forms of extra-facial bone and joint actinomycosis have been described: hematogenous spread of localized actinomycosis; contiguous spread of pulmonary actinomycosis to the spine; and polymicrobial bone and joint infection following bone exposition.
Concerning hematogenous spread of localized actinomycosis, Brown reported a case of hematogenous infection of total hip arthroplasty 9 months after a noninvasive dental procedure with Actinomyces spp. in intraoperative specimen cultures. Zaman reported a case of chronic hematogenous infection due to Actinomyces spp. of prosthetic joint in an intravenous drug user. Concerning the contiguous spread of pulmonary actinomycosis to the spine, case 2 had contiguous spread to the spine with thoracic spondylitis of the T3 vertebral body associated with anterior paravertebral abscess).
Genitourinary tract actinomycosis is the second most frequent clinical form of actinomycosis. The main clinical feature of genitourinary tract actinomycosis is pelvic actinomycosis in women using an intrauterine device (IUD). Other clinical presentations have been described, such as primary bladder actinomycosis and testicular actinomycosis.
Primary bladder actinomycosis can mimic bladder carcinoma, with macroscopic hematuria associated with thickening of the bladder wall.
Symptoms are unspecific, and patients frequently experience focal weakness, sensory losses, and seizures.
Primary skin and soft-tissue actinomycosis is poorly described. Skin disruption may facilitate invasion of Actinomyces spp.
A granuloma is a focal aggregate of immune cells which forms in response
to a persistent inflammatory stimulus. It characteristically
demonstrates the compact organization of mature macrophages which may
or may not be associated with other inflammatory cell types. Granulomas
are evolutionarily ancient structures found throughout both vertebrate
and invertebrate species and are likely to have evolved as a protective
mechanism to destroy or encapsulate foreign material. They were
first identified and described as "tubercules" in the lungs of
tuberculosis sufferers as early as 1679.
Granuloma formation begins with an inflammatory trigger, such as an
infectious pathogen or a foreign body. Macrophages are recruited to the
site of inflammation and activated as part of the innate immune
response. If the recruited and activated macrophage is unable to remove
the inflammatory stimulus efficiently, a further immune response may be
triggered, orchestrated by dendritic cells and major histocompatibility
complex II. Additional macrophages are recruited to the site, and a
chronic inflammatory reaction develops. The macrophages form a tight
aggregate around the inflammatory stimulus and may become surrounded by a
peripheral cuff of lymphocytes. This inflammatory focus is known as a
granuloma.
