Providencia Infections 

The genus Providencia includes urease-producing gram-negative bacilli that are responsible for a wide range of human infections. Although most Providencia infections involve the urinary tract, they are also associated with gastroenteritis and bacteremia. Providencia infections are uncommon and are usually nosocomial. They represent an emerging problem because of the increasing prevalence of antibiotic resistance secondary to extended-spectrum beta-lactamase (ESBL).

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.^[1]

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.^[2] P heimbachae has been isolated in penguin feces and an aborted bovine fetus.^[3]

In humans, Providencia species have been isolated from urine (most common), stool, and blood, as well as from sputum, skin, and wound cultures. P stuartii septicemia is primarily of urinary origin. One case study has described P stuartii as the etiology of infective endocarditis.^[4] Another case report found P rettgeri to be a cause of ocular infections, including keratitis, conjunctivitis, and endophthalmitis.^[5]

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.^[6] 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).^{[6, 7]} In a 1994 study by Rahav et al, persistence patterns in males and females were found to differ, with P stuartii showing 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.^[6]

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.^[8]

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.^{[9, 10]} Providencia species, 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.

Frequency

United States

P stuartii and, to a lesser extent, P rettgeri are the most common Providencia species that cause human infection. While uncommon in most clinical settings, these organisms tend to cause cystitis in patients with bladder catheters and are primarily associated with complicated urinary tract infections. In a Canadian study in 2001, Providencia species were isolated in 18% of complicated urinary tract infections.^[11] In contrast, Providencia bacteriuria in acute hospital settings is rare (0.3-1%).^[6]

The prevalence of Providencia infections are generally low, although it is increasing. More significantly, Providencia infections with antimicrobial resistance patterns are increasing. In 2003, a study at an Italian university hospital with medical, surgical, and intensive care units found that the prevalence of ESBL-producing P stuartii in the general patient population increased from 31% in 1999 to 62% in 2002. Over a 4-year span, P stuartii was isolated in 0.08% of patients. Of these isolates, 87% were found in urine, 10% in blood, and 3% in respiratory tract secretions.^[8]

P stuartii is most often found in complicated urinary tract infections in patients with chronic indwelling urinary catheters or condom catheters. Providencia species are rarely a cause of uncomplicated urinary tract infections. In a study of patients with urinary catheters living in a retirement home, P stuartii was the most commonly isolated bacteria, found in 59% of urine specimens. (The next most common was Escherichia coli, at 32%.)^[6]

Providencia species, specifically P alcalifaciens and P rettgeri, have also been shown to be an infrequent cause of foodborne gastroenteritis. In 1996, a large outbreak of foodborne P alcalifaciens infections occurred in Japan at multiple schools, affecting student and teacher populations.^[12] This was the first reported outbreak of foodborne P alcalifaciens gastroenteritis. Providencia species, especially P rettgeri, have also been implicated as cause of traveler’s diarrhea. In a Japanese study, 130 patients with diarrhea were evaluated at the Kansai Airport quarantine station, and Providencia species were isolated in 15.4% of stool samples. Most travelers who reported diarrhea had traveled to Southeast Asia.^[9]

International

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).^[13]

Mortality/Morbidity

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

Race

All races appear to be equally susceptible to Providencia infection.

Sex

Males and females appear to be equally susceptible to Providencia infection. In one study, however, a significant difference was seen in the persistence pattern of bacteriuria in women versus men among nursing-home patients with long-term urinary catheterization (88.25% vs 50.5%).^[6]

Age

• Elderly persons are at much greater risk of P stuartii or P rettgeri infection, most likely because these infections are associated with the use of indwelling urinary catheters, which are more common used in elderly populations.
• P alcalifaciens gastroenteritis has been documented in children and adults. In a 2005 study, a large outbreak of gastroenteritis was found to be attributable to P alcalifaciens infection. The outbreak involved students and teachers of two kindergartens and one high school. The prevalence of infection was higher in children (53% of kindergartners affected vs 36% of adult teachers).^[12] Another study demonstrated that P rettgeri infection is a potential cause of traveler's diarrhea in adults.^[9]