eMedicine Specialties > Infectious Diseases > Bacterial Infections

Proteus Infections

Author: Kelley Struble, DO, Resident Physician, Department of Internal Medicine, University of Oklahoma College of Medicine
Coauthor(s): Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Rhett L Jackson, MD, Associate Professor and Vice Chair for Education, Department of Medicine, Associate Director, Internal Medicine Residency Program, University of Oklahoma College of Medicine; Assistant Chief, Medicine Service, Oklahoma City Veterans Affairs Hospital; Gus Gonzalez, MD, Medical Oncologist, The Center for Cancer and Blood Disorders
Contributor Information and Disclosures

Updated: Jul 31, 2009

Introduction

Background

Proteus species are part of the Enterobacteriaceae family of gram-negative bacilli. Proteus organisms are implicated as serious causes of infections in humans, along with Escherichia, Klebsiella, Enterobacter, and Serratia species.

Proteus species are most commonly found in the human intestinal tract as part of normal human intestinal flora, along with Escherichia coli and Klebsiella species, of which E coli is the predominant resident. Proteus is also found in multiple environmental habitats, including long-term care facilities and hospitals. In hospital settings, it is not unusual for gram-negative bacilli to colonize both the skin and oral mucosa of both patients and hospital personnel. Infection primarily occurs from these reservoirs. However, Proteus species are not the most common cause of nosocomial infections.

Proteus mirabilis causes 90% of Proteus infections and can be considered a community-acquired infection. Proteus vulgaris and Proteus penneri are easily isolated from individuals in long-term care facilities and hospitals and from patients with underlying diseases or compromised immune systems.

Patients with recurrent infections, those with structural abnormalities of the urinary tract, those who have had urethral instrumentation, and those whose infections were acquired in the hospital have an increased frequency of infection caused by Proteus and other organisms (eg, Klebsiella, Enterobacter, Pseudomonas, enterococci, staphylococci).

Pathophysiology

Proteus species possess an extracytoplasmic outer membrane, a feature shared with other gram-negative bacteria. In addition, the outer membrane contains a lipid bilayer, lipoproteins, polysaccharides, and lipopolysaccharides.

Infection depends on the interaction between the infecting organism and the host defense mechanisms. Various components of the membrane interplay with the host to determine virulence. Inoculum size is important and has a positive correlation with the risk of infection.

Certain virulence factors have been identified in bacteria. The first step in the infectious process is adherence of the microbe to host tissue. Fimbriae facilitate adherence and thus enhance the capacity of the organism to produce disease. E coli, P mirabilis, and other gram-negative bacteria contain fimbriae (ie, pili), which are tiny projections on the surface of the bacterium. Specific chemicals located on the tips of pili enable organisms to attach to selected host tissue sites (eg, urinary tract endothelium). The presence of these fimbriae has been demonstrated to be important for the attachment of P mirabilis to host tissue.

The attachment of Proteus species to uroepithelial cells initiates several events in the mucosal endothelial cells, including secretion of interleukin 6 and interleukin 8. Proteus organisms also induce apoptosis and epithelial cell desquamation. Bacterial production of urease has also been shown to increase the risk of pyelonephritis in experimental animals. Urease production, together with the presence of bacterial motility and fimbriae, may favor the production of upper urinary tract infections (UTIs) by organisms such as Proteus.

Enterobacteriaceae (of which Proteus is a member) and Pseudomonas species are the microorganisms most commonly responsible for gram-negative bacteremia. When these organisms invade the bloodstream, endotoxin, a component of gram-negative bacterial cell walls, apparently triggers a cascade of host inflammatory responses and leads to major detrimental effects. Because Proteus and Pseudomonas organisms are gram-negative bacilli, they can cause gram-negative endotoxin-induced sepsis, resulting in systemic inflammatory response syndrome (SIRS), which carries a mortality rate of 20%-50%.

Although other organisms can trigger a similar response, it is useful to consider gram-negative bacteremia as a distinct entity because of its characteristic epidemiology, pathogenesis, pathophysiology, and treatment. The presence of the sepsis syndrome associated with a UTI should raise the possibility of urinary tract obstruction. This is especially true of patients who reside in long-term care facilities, who have long-term indwelling urethral catheters, or who have a known history of urethral anatomic abnormalities.

The ability of Proteus organisms to produce urease and to alkalinize the urine by hydrolyzing urea to ammonia makes it effective in producing an environment in which it can survive. This leads to precipitation of organic and inorganic compounds, which leads to struvite stone formation. Struvite stones are composed of a combination of magnesium ammonium phosphate (struvite) and calcium carbonate-apatite.

Struvite stone formation can be sustained only when ammonia production is increased and the urine pH is elevated to decrease the solubility of phosphate. Both of these requirements can occur only when urine is infected with a urease-producing organism such as Proteus. Urease metabolizes urea into ammonia and carbon dioxide: Urea → 2NH₃ + CO₂. The ammonia/ammonium buffer pair has a pK of 9.0, resulting in the combination of highly alkaline urine rich in ammonia.

Symptoms attributable to struvite stones are uncommon. More often, women present with UTI, flank pain, or hematuria and are found to have a persistently alkaline urine pH (>7.0).

Frequency

United States

The genitourinary tract is the site of disease responsible for gram-negative bacteremia in approximately 35% of patients. In previously healthy outpatients, E coli is by far the most often implicated cause of UTIs. In contrast, individuals with multiple prior episodes of UTI, multiple antibiotic treatments, urinary tract obstruction, or infection developing after instrumentation frequently become infected with Proteus bacteria or other bacteria such as Enterobacter, Klebsiella, Serratia, and Acinetobacter.

Bacteriuria occurs in 10%-15% of hospitalized patients with indwelling catheters. The risk of infection is 3%-5% per day of catheterization.

Mortality/Morbidity

Among long-term care residents, UTIs are the second most common infection responsible for hospital admission, second only to pneumonia. UTIs can result in sepsis if not recognized and treated rapidly. Failure to treat or a delay in treatment can result in SIRS, which carries a mortality rate of 20%-50%.

Sex

Other factors that increase infection rates include female sex, duration of catheterization, underlying illness, faulty catheter care, and lack of systemic antibiotic therapy. Infection occurs either by migration of bacteria up the catheter along the mucosal sheath or by migration up the catheter lumen from infected urine.

• UTIs are the most common clinical manifestation of Proteus infections. Proteus infection accounts for 1%-2% of UTIs in healthy women and 5% of hospital-acquired UTIs. Complicated UTIs (ie, those associated with catheterization) have a prevalence of 20%-45%.
• UTIs are more common in males then females in the neonatal population. This is a result of congenital abnormalities seen more often in males.
• After age 50 years, the ratio between men and women begins to decline because of the increasing incidence of prostate disease. UTIs in men younger than 50 years are usually caused by urologic abnormalities.

Age

UTIs are more common in persons aged 20-50 years.

Clinical

History

Approximately 95% of UTIs occur when bacteria ascend through the urethra and the bladder.

• Complicated UTIs occur with instrumentation (including Foley catheters), obstruction, calculi, or neurogenic bladder. These carry a higher risk for complications such as hospitalization and sepsis.
• Sexually active women are at greater risk for UTIs. The same is true for men, although to a lesser degree.
• Other predisposing factors for UTIs are men who have unprotected anal intercourse, an uncircumcised penis, unprotected vaginal intercourse, and/or CD4 count less than 200/µL.
• Although infrequent, chronic prostatitis should be considered in males with a history of recurrent UTIs. Obstructive symptoms are transient but may progress to infect the bladder because of poor bladder emptying.
• Frequent and unexplained incidents of renal calculi may be indicative of a chronic Proteus infection. Multiple magnesium ammonium phosphate crystals are present in the urine sediment along with radio dense renal calculus. (This calculus is less radio dense than calcium oxalate.) This results in formation and precipitation of struvite crystals, a predominant component of urinary calculi and encrustations on urinary catheters.

Physical

Patients may present with urethritis, cystitis, prostatitis, or pyelonephritis. Chronic, recurring stones may be an indication of chronic infection.

• Symptoms of urethritis are usually mild and may be dismissed by the patient.
  • Women present with dysuria, pyuria, and increased frequency of urination.
  • Presenting symptoms in males are usually mild and may include urethral discharge.
• Signs and symptoms of cystitis tend to be more prominent compared to those of urethritis.
  • In both men and women, symptoms are of sudden onset.
  • They include dysuria, increased frequency, urgency, suprapubic pain, back pain, small volumes, concentrated appearance, and hematuria. If the patient is febrile, this could be a sign of bacteremia and impending sepsis. These symptoms may not be present if the patient has an indwelling catheter.
• Prostatitis is obviously limited to men and occurs more acutely than cystitis. This becomes more common as men age.
  • In addition to symptoms of cystitis, patients with prostatitis may present with fever and chills.
  • Perianal pain and various symptoms of urinary tract obstruction may be present. The prostate may be tender and diffusely swollen.
• Pyelonephritis can be considered a progression of disease, and symptoms are therefore more profound. Sepsis can develop quickly, especially in elderly patients or those with a compromised immune system.
  • Symptoms of urethritis and cystitis may or may not be present.
  • Defining symptoms of pyelonephritis include flank pain, nausea and vomiting, costovertebral angle tenderness, fever, and, rarely, a palpable and tender kidney. Hematuria and pyuria are frequently encountered.

Causes

• Hospital-acquired infections are usually caused by interruption of the closed sterile system by hospital personnel.
• Proteus species also cause sepsis neonatorum and bacteremia with fever and neutropenia.
• Proteus species are also involved in synergistic nonclostridial anaerobic myonecrosis, which may involve subcutaneous tissue, fascia, and muscle. This condition is caused by combinations of other aerobic gram-negative bacilli (E coli or Klebsiella or Enterobacter species) and anaerobes. Surgical evaluation and intervention is critical to successful treatment.

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