Question

What is the classification and history of Providencia?

What is the significance of it? How does it relate to science, environment, or health?

Is it pathogenic? If so, what does it cause and what is the treatment? Who does it affect? What part of the world is it found in?

Is there anything about Providencia that makes it unique and interesting?

Answer 1

Kingdom:             Bacteria

Phylum:               Proteobacteria

Class:     Gammaproteobacteria

Order:   Enterobacteriales

Family: Enterobacteriaceae

Genus: Providencia

Species

P. stuartii

P. sneebia

P. rettgeri

P. rustigianii

P. heimbachae

P. burhodogranariea

P. alcalifaciens

The first species of the genus now known as Providencia was isolated by Rettger in 1904. The bacterium was initially seen in chickens in what was believed to be an epidemic of fowl cholera. The bacterium was not further characterized until 1918, when it was named Bacterium rettgerii by Hadley et al. Organisms belonging to the genus Providencia have undergone many taxonomic changes since their first description, with frequent confusion and overlap between organisms of the closely related genera Providencia,Proteus, and Morganella.

Kauffmann first proposed the genus name Providencia in 1951, referring to a group of organisms studied by Stuart and colleagues at Brown University in Providence, Rhode Island. By 1983, the 4 species in the Providencia genus at that time were fully differentiated with DNA hybridization and urea hydrolyzation. In 1986, Providencia heimbachae was the fifth species discovered.

The 5 species currently in the genus Providencia, in descending order of prevalence, include Providencia stuartii, Providencia rettgeri, Providencia alcalifaciens, Providencia rustigianii, and P heimbachae.

Providencia species are found in multiple animal reservoirs, including flies, birds, cats, dogs, cattle, sheep, guinea pigs, and penguins, and are resident oral flora in reptiles such as pythons, vipers, and boas. Providencia species are also found commonly in soil, water, and sewage. Examples of Providencia infections in animals include neonatal diarrhea due to P stuartii infection in dairy cows and enteritis caused by P alcalifaciens infection in dogs. P rettgeri has been isolated in crocodiles with meningitis/septicemia and in chickens with enteritis. P heimbachae has been isolated in penguin feces and an aborted bovine fetus.

In humans, Providencia species have been isolated from urine (most common), stool, and blood, as well as from sputum, skin, and wound cultures. P stuartiisepticemia is primarily of urinary origin. One case study has described P stuartii as the etiology of infective endocarditis. Another case report found P rettgeri to be a cause of ocular infections, including keratitis, conjunctivitis, and endophthalmitis.

P stuartii is frequently isolated in patients with indwelling urinary catheters and is known to persist in the urinary tract after bladder access is attained. In one study, the mean duration of bacterial colonization was 6.4 months. The persistence of bacteria in the urinary tract is thought to be due to an adhesin, mannose-resistant/Klebsiella -like (MR/K) hemagglutinin, which allows bacteria to adhere to urinary catheters (mediated by 3 fimbriae). In a 1994 study by Rahav et al, persistence patterns in males and females were found to differ, with P stuartiishowing more persistence in females. Reasons theorized include different receptor characteristics in male and female urinary tracts and a bacterial predilection for Foley catheters over condom catheters, which are used more commonly in males.

ESBL-positive P stuartii is an increasing problem in hospitalized patients. In one study, 52% of 223 P stuartii isolates were found to be positive for ESBL in a hospital population that included ICU, medical, and surgical wards over a 4-year span.

P alcalifaciens, P rettgeri, and P stuartii have been implicated in gastroenteritis. In one study, P rettgeri and P stuartii were found to be highly invasive using in vivo testing with Caco-2, a human colon carcinoma cell line. However, a common virulence plasmid was not identified in Providencia species. Providenciaspecies, most commonly P agalactiae, have been demonstrated in the stool of symptomatic patients, although testing protocols used to identify diarrheagenic bacterial pathogens do not generally include Providencia.

Providencia species are found worldwide. A study that examined ESBL-producing Enterobacteriaceae distribution worldwide (including Providencia species) found that the prevalence of ESBL-positive bacteria varied across geographical boundaries. The highest percentage of ESBL-positive isolates as found in Latin America (44%) and the lowest in Netherlands and Germany (2% and 2.6%, respectively). Another multidrug-resistant outbreak of Providencia stuartii was reported in Greece in 2012.

Mortality/Morbidity

The mortality rate in patients with Providencia bloodstream infection ranges from 6-33%. The rate is greater in polymicrobial infection.

Providencia species are readily isolated from urine and blood using standard laboratory media. Most commercially available identification systems used in clinical laboratories accurately identify P. stuartii, P. alcalifaciens, and P. rettgeri (61). P. alcalifaciens appears as lactose-negative colonies on MacConkey agar . Urease activity is variable but common in Providencia spp., particularly those isolated from urinary tract infections . Transfer of large conjugative plasmids from one Providencia species to another can add phenotypic traits that alter the species as identified by commercially available systems . These traits include ability to ferment lactose and sucrose.

Pathogenesis

P. stuartii can directly adhere to urinary catheters , and adherence is associated with the presence of the mannose-resistant/Klebsiella-like hemagglutinatin, also known as MR/K fimbriae . P. stuartii isolates are also capable of adhering to uroepithelial cells through a process that also appears to involve fimbriae . P. stuartii pathogenesis can be investigated using a mouse model of ascending urinary tract infection . In this model, infection with P. stuartii results in robust colonization of the bladder and kidneys, and bacteremia in a small percentage of mice.

P. alcalifaciens is an invasive enteric pathogen. Strains of P. alcalifaciens, isolated from patients with diarrhea, show invasion of Hep-2 and HeLa cells in vitro. Janda et al. reported that some P. alcalifaciens strains, as well as strains of P. stuartii and P. rettgeri, can invade HEp-2 monolayers . Injection of an outbreak strain into a rabbit ileal loop caused fluid accumulation, along with evidence of mucosal inflammation on histologic examination

ANTIMICROBIAL THERAPY

Drug of Choice

Based on emerging patterns of antimicrobial resistance, definitive therapy for infection due to P. stuartii or P. rettgeri requires appropriate antimicrobial susceptibility testing. Because of widespread resistance to multiple antimicrobials and emerging resistance to fluoroquinolones, third generation cephalosporins (cefotaxime, ceftriaxone, and cefepime should be considered first line therapy for infections due to these species. Although there is very little information upon which to base treatment recommendations for infections due to P. alcalifaciens, ampicillin or a 2nd generation cephalosporin would be a reasonable choice based upon in vitro susceptibility testing.

Specific Infections

Urinary Tract Infection: Infections due to P. stuartii or P. rettgeri may be treated with third-generation cephalosporins. Seriously ill patients, or those unable to take oral medications, should receive parenteral therapy. Appropriate regimens include ceftriaxone 1 gm daily, cefotaxime 1 gm every 6-8 hours, and cefepime 0.5 – 1 gm every 12 hours. Stable patients able to take oral medications may receive an oral expanded-spectrum cephalosporin such as cefixime 500 mg daily or cefpodoxime 200 mg every 12 hours. Oral cephalosporin therapy may be particularly appropriate for treatment of urinary tract infections in nursing home patients, in whom parenteral therapy may be impractical. Because urinary tract infections due to these organisms is nearly always complicated by catheterization or other anatomic or functional abnormality of the urinary tract, treatment duration should be 10-14 days.

Bacteremia: Bacteremic infection due to P. stuartii or P. rettgeri most frequently arises from the urinary tract, although bacteremia may occur secondary to pneumonia or burn wound infection. Patients should receive treatment with a third-generation cephalosporin as outlined above. As ESBL production by P. stuartii and P. rettgeri is on the rise, it would be reasonable to test blood isolates for ESBL production since it may not be detected by routine clinical laboratory susceptibility tests.

Enteritis: Enteritis due to P. alcalifaciens appears to be of mild-to-moderate severity in healthy adults and children. It is likely that the majority of infections resolve spontaneously without treatment; there are no published studies of therapy. It would be reasonable to treat patients with severe or prolonged diarrhea with ampicillin or amoxicillin, 500 mg four times daily.

Alternative Therapy

Infections Due to P. stuartii or P. rettgeri: Aztreonam is an appropriate alternative to cephalosporins in patients with cephalosporin allergy. Aminoglycosides are another alternative if the infecting isolate is susceptible, but resistance to multiple aminoglycosides is common. If the isolate produces an ESBL, imipenem or meropenem would be appropriate. Parenteral or oral quinolones could be considered based on susceptibility. However, frequent use of quinolones in a facility tends to foster widespread quinolone resistance among multiple different strains of Providencia. Thus routine quinolone use is not recommended.

Enteritis Due to P. alcalifaciens: Reasonable alternatives to ampicillin or a cephalosporin include certain aminoglycosides, aztreonam or tetracycline, based on the results of susceptibility testing.

ADJUNCTIVE THERAPY

Urinary catheters of patients with urinary tract infections should be removed or changed; this is particularly important for infections due to P. stuartii, since the continuing presence of adherent organisms on the catheter may provide a nidus for recurrent infection. Fluid and electrolyte replacement are essential in the treatment of P. alcalifaciens enteritis.

ENDPOINTS FOR MONITORING THERAPY

In patients with urinary tract infection and bacteremia, defervescence and clearing of the organism from the urine or blood are appropriate endpoints.

VACCINES

There are no available vaccines.

There are currently 8 recognized species within the genus: P. alcalifaciens, P. burhodogranaeriae, P. heimbachae, P. rettgeri, P. rustigianii, P. sneebia, P. stuartii,and P. vermicola . Like other members of the tribe Proteeae, Providencia species produce the enzyme phenylalanine deaminase, which catalyzes the conversion of phenylalanine to phenylpyruvate.

P. stuartii is the most frequently encountered human pathogen within the genus. The most frequent site of isolation is the urinary tract of chronically catheterized patients in hospitals and long-term care facilities. Among this patient population, P. stuartii is recognized as a persistent colonizer. It is common for multiple strains to be present simultaneously in a particular institution. The urine of chronically catheterized patients is the usual reservoir of the organism. Nosocomially acquired P. stuartii are typically resistant to multiple antimicrobials . P. rettgeri is also primarily a cause of nosocomial urinary tract infection. Neither organism is likely to cause urinary tract infection in ambulatory persons.

Reservoirs of P. alclifaciens include water, wastewater and soil. It appears to be an agent of gastrointestinal infections in humans and has been reported to cause hemorrhagic pneumonia in piglets . Settings in which this agent has been implicated include foodborne enteritis and traveler's diarrhea. A large food-borne outbreak of P. alcalifaciens-associated diarrhea occurred in Japan . An outbreak of enteritis caused by P. alcalifaciens occurred among Czech Army Field Hospital personnel during their stay in Turkey.

Human isolates of P. rustigianii and P. heimbachae are rare; their role, if any, in human disease is uncertain . P. vermicola was first isolated from a nematode and later from a diseased rohu fish , but this species has not been implicated in human infection. P. sneebia and P.burhodogranaeriae were isolated from fruit flies and have not been reported to cause human infection.