Proteus, Providencia, and Morganella Species

Microbiology and Epidemiology

Organisms belonging to the genera Proteus, Providencia, and Morganella are phylogenetically related members of the family Morganellaceae fam.nov , order Enterobacterales ord.nov. (former family Enterobacteriaceae) and are often referred to as the Proteeae. All members of these genera have phenylalanine deaminase activity, and most have urease activity and motility. Organisms can be isolated readily in the laboratory on enriched media, such as blood and chocolate agars, and on gram-negative selective media, such as MacConkey agar, on which they appear as colorless colonies because they do not ferment lactose. Identification of these species can be successfully achieved by the use of proteomic methods such as matrix-assisted laser desorption/ionization–time of flight (MALDI-TOF) mass spectrometric analysis.

There are many named Proteus species and several unnamed genospecies. The named species include P. mirabilis, P. vulgaris, P. penneri, P. hauseri, P. terrae, and P. cibarius. The three species of primary human clinical significance are P. mirabilis, P. penneri, and P. vulgaris. All three species produce hydrogen sulfide and swarm on noninhibitory agar medium. P. mirabilis is positive for ornithine and negative for indole production, whereas P. vulgaris is negative for ornithine but positive for indole. P. penneri is a species that accommodates indole-negative, genetically distinct variants of P. vulgaris.

There are at least five named Providencia species, including four that produce indole: P. stuartii, P. rettgeri, P. alcalifaciens, and P. rustigianii. P. alcalifaciens, P. stuartii, P. rettgeri , and newly described P. rustigianii, P. heimbachae are of clinical importance. Providencia species can be differentiated from Proteus species and M. morganii based on their ability to use citrate as the sole carbon source and to ferment d -mannitol. M. morganii and M. psychrotolerans are the only two named Morganella species. M. morganii has subspecies morganii and sibonii. M. morganii usually is positive for indole, urea, and ornithine.

Proteus, Providencia, and M. morganii are found in the natural environment in soil and water and in environmental sources in healthcare facilities. They are normal flora in the gastrointestinal tract of humans, other mammals, and birds. ^, These organisms can colonize the skin and respiratory mucosa of hospitalized patients and healthcare personnel and can be transmitted to other patients. Members of all three genera also commonly colonize reptiles and fish.

Investigations of pathogenic mechanisms of these organisms have focused on P. mirabilis as an agent of urinary tract infection (UTI). Virulence factors that appear to contribute to pathogenicity include motility, production of fimbrial proteins, and other factors that facilitate attachment to uroepithelial cells. Other studies have demonstrated the ability of Providencia spp. to attach to and invade human cells in tissue culture and implicated these organisms as agents of gastroenteritis, including travelers’ diarrhea.

P. mirabilis causes most cases of infection due to members of the Proteus, Providencia, and Morganella genera and is considered primarily a community-associated pathogen. Other members of these genera often are isolated in healthcare-associated infections (HAIs), such as UTIs, burn wounds, and bloodstream infections (BSIs). From 2015 to 2017, Proteus spp. were found to be the cause in 3.2% of adult HAIs reported by the National Health Safety network. Proteus spp. accounted for 5.8% adult catheter-associated UTI and 1.7% of pediatric catheter-associated UTI from 2015 to 2017. ^, Wound infections due to Proteus spp . have occurred after surgical procedures (e.g., spinal fusions, myocutaneous flap surgery in patients with spinal injury), animal bites, burns, and with decubitus ulcers. ^,

Clinical Manifestations

Proteus spp. is the third most frequent agent of UTI in childhood after Escherichia coli and Klebsiella spp., accounting for between 5% and 12% of pediatric UTI cases. In one series of primary UTI in males, P. mirabilis replaced E. coli as the most prevalent pathogen. Proteus spp. also frequently cause recurrent UTIs. The urease enzyme produced by P. mirabilis and related bacteria hydrolyzes urea in the urine, forming ammonium hydroxide. This reaction increases urinary pH, which is toxic to renal cells and promotes precipitation of inorganic and organic compounds, leading to the formation of struvite stones. These stones can act as foreign bodies, rendering infections difficult to eradicate and promoting reinfection. Recovery of Proteus spp. from urine should alert the physician to the possibility of urolithiasis.

Toxic encephalopathy due to a high serum concentration of ammonia has been reported as a complication of P. mirabilis and P. rettgeri UTI in children with prune belly syndrome. ^, Xanthogranulomatous pyelonephritis, most commonly due to E. coli and P. mirabilis, is a rare type of chronic pyelonephritis that can be mistaken for Wilms tumor. This diagnosis should be considered for a child with a renal mass, hematuria, anemia, and leukocytosis, and it can be associated with urinary tract obstruction and nephrolithiasis.

Proteus, Providencia, and Morganella spp . have been recovered from children with a variety of infections other than UTIs, including chronic suppurative otitis media. P. mirabilis is the third most common organism recovered from cultures of ear drainage in children with tympanostomy tubes; Pseudomonas aeruginosa and Staphylococcus aureus are recovered more commonly. Intracranial and extracranial complications due to P. mirabilis have been associated with mastoiditis and chronic otitis media. ^, Proteus spp. have been reported as a cause of folliculitis, pneumonia, BSI, sacroiliitis, and meningitis; hepatic, pulmonary, renal, and splenic abscesses; osteomyelitis in patients with sickle cell anemia; sinusitis in neurologically impaired children; soft tissue or wound infections complicating trauma, burns, surgical procedures, and skin lesions associated with Buruli ulcers, cutaneous leishmaniasis, and hidradenitis suppurativa; necrotizing fasciitis associated with omphalitis; spinal cord abscess complicating a dermal sinus; and brain abscess as a complication of neonatal meningitis and after neurosurgical procedures. Many of these infections occur in neonates and immunocompromised hosts.

In a 21-year review, P. mirabilis was the cause of gram-negative meningitis in 3 (6%) of 49 term infants and in 1 (6%) of 18 infants who were 1–3 months old. Proteus spp. also have been associated with pump pocket infections in patients receiving intrathecal baclofen for spasticity. Neonatal infections, including early- and late-onset septicemia, meningitis, and brain abscess, have been attributed to M. morganii . ^{, ,} Proteus spp. and M. morganii contamination of improperly stored fish can lead to scombroid poisoning with an anaphylactic-like syndrome after human consumption.

Providencia spp. are recovered occasionally from patients with chronic otitis media or infected burn wounds and rarely from patients with meningitis. It also can be responsible for diarrhea (especially P. alcalifaciens ). When recovered from the urinary tract, Providencia spp. typically are found in the setting of an underlying structural, physiologic, or neurologic abnormality (e.g., neurogenic bladder).

Treatment

Treatment of infections due to these organisms can be difficult because of frequent antimicrobial resistance. Proteus spp., M. morganii and