Background
The genus Providencia is composed of several species of gram negative bacilli that produce urease. [1] Organisms belonging to the genus Providencia are closely related to the genera Morganella and Proteus. With advances in genomics and sequencing, the taxonomy has undergone many changes. To date, five species (Providencia rettgeri [P rettgeri], P stuartii, P alcalifaciens, P rustigianii, and P heimbachae) have been identified in humans. [2] Of these, three species (P rettgeri, P stuartii, and P alcalifaciens) are capable of causing disease in humans. Two novel species have been identified in fruit flies but are not notable human pathogens. [3]
Providencia is a ubiquitous organism that can be found both in the environment and as a commensal organism of the human microbiome, primarily in the gastrointestinal tract. [4] As such, the isolation of Providencia from a clinical specimen does not always indicate clinical infection, and patients should be screened for an appropriate clinical syndrome. The most common clinical syndrome attributable to Providencia is urinary tract infections (UTIs) in patients with long-term indwelling urinary catheters (most commonly due to P stuartii and P rettgeri). [1, 2, 5] Other clinical syndromes include gastroenteritis in returning travelers (primarily P alcalifaciens), pneumonia (including hospital and ventilator associated), bacteremia, and wound infections. [1, 4, 6]
Pathophysiology
As discussed previously, Providencia spp are ubiquitous in the environment and can be isolated from water, soil, and sewage. Several species are known commensal organisms of the human gastrointestinal tract. [6, 7]
In humans, P stuartii and P rettgeri primarily have been implicated in catheter associated urinary tract infections (CAUTI). [1, 2, 5] Providencia’s predilection for colonizing long-term indwelling urinary catheters is felt to be mediated by an adhesin: mannose-resistant/Klebsiella-like (MR/K) hemagglutinin. [8] It is important to note that chronic indwelling urinary catheters often are colonized with bacteria, and growth of Providencia from the urine of a patient with a catheter not always indicates infection in the absence of symptoms suggesting an appropriate clinical syndrome. Other virulence factors include the production of urease, which can be associated with the formation of nephrolithiasis and then can place patients at risk for urinary tract obstruction and subsequent infections including pyelonephritis. Urease as a virulence factor is supported further by an increase in nephrolithiasis and bacteremia in patients with P stuartii and Proteus mirabilis co-infection. [9] Providencia species are also recognized as an etiology of “Purple Urine Bag Syndrome (PUBS)”, a syndrome characterized by purple appearing urine due to the metabolism of tryptophan to indole by colonizing/infecting bacteria in chronic indwelling catheters. If PUBS is observed, it is important to assess for signs and symptoms of urinary tract infection, while again noting that PUBS can occur in the setting of colonization and is not necessarily a sign of CAUTI. [10]
Providencia species have been isolated in the blood. Blood stream infections (BSI) due to Providencia most commonly are secondary to a urinary source. Manipulation of the urinary tract is a risk factor for Providencia BSI. Pulmonary source (pneumonia) and primary bacteremia have been documented but are less common. Interestingly, BSI with Providencia often are polymicrobial. [11, 12, 13]
Providencia alcalifaciens has been identified as a possible cause of traveler’s diarrhea/foodborne gastroenteritis, but the true scope is difficult to determine as the most commonly used diagnostic assays for TD/GE do not test for Providencia. [6, 7, 14, 15]
Pneumonia, especially ventilator associated pneumonia, has been reported. [16, 17] There have been few case reports documenting less common clinical syndromes secondary to Providencia infection including one case of infective endocarditis [18] and several cases of ocular infections (keratitis, conjunctivitis, and endophthalmitis). [19] Providencia has been isolated from wound infections, especially burns, but almost always as part of a polymicrobial infection with more virulent pathogens (ie, MRSA or Pseudomonas). [4, 20] Given Providencia’s pervasive presence in the nosocomial setting, any culture, especially a polymicrobial culture, with the growth of Providencia should be interpreted with caution.
Epidemiology
Providencia is distributed worldwide. The epidemiology of Providencia is difficult to describe for several reasons including difficulty in distinguishing colonization from infection in the most at-risk patients and lack of inclusion of Providencia on molecular diagnostic panels (Gastrointestinal Pathogen Panel, Blood Culture Identification Panel).
Providencia infections previously were considered to be an uncommon pathogen; [21] however, the prevalence has been increasing. It is important to note that the prevalence of multi-drug resistant Providencia, especially extended spectrum beta-lactamase (ESBL) and carbapenemase producing isolates, also is increasing. [2, 16, 22, 23, 24, 25]
In terms of gastroenteritis, several countries, including Nigeria, India, and Bangladesh have published studies on the isolation of Providencia alcalifaciens from symptomatic patients with diarrhea. [7] Several other countries have reported foodborne outbreaks including Japan, Turkey, and Kenya. [26]
Race
All races appear to be equally susceptible to Providencia infection.
Sex
Sex does not appear to be a risk factor for Providencia infection. It is interesting to note that one study found a significant difference in Providencia bacteruria between men and women with long-term urinary catheters (more frequently isolated from women). This may be due to the higher frequency of condom catheter use in males. [8]
Age
Because older patients are more likely to have both chronic indwelling urinary catheters and frequent contact with the nosocomial environment, they are at increased risk for Providencia colonization and infection.
Prognosis
Reported mortality rates for Providencia infections range from 6-33%. One study from India reported a 20% mortality rate for Providencia CAUTI; however, the majority of these patients were critically ill, and it is not evident whether mortality in these cases was completely attributable to Providencia. [21]
Another review reported a mortality rate of 6-33% for Providencia BSI with the highest risk of mortality in polymicrobial BSI. [27]
Polymicrobial co-infections and relative antimicrobial resistance are likely major contributors to mortality in Providencia BSI.
