The major causative pathogens of acute pyelonephritis are gram-negative bacteria. Escherichia coli causes approximately 60% to 80% of uncomplicated infections.  Attention has recently focused on uropathogenic E coli as being responsible for a significant proportion of treatment-resistant infections.    Other gram-negative pathogens include Proteus mirabilis (responsible for about 15% of infections) as well as Klebsiella (approximately 20%), Enterobacter, and Pseudomonas species.  Less commonly, gram-positive bacteria such as Enterococcus faecalis, Staphylococcus saprophyticus, and S aureus may be seen.
Complicated acute pyelonephritis is more common in older people, in people with diabetes, and in the immunosuppressed. Organisms differ in these cases and include a broad range of pathogens, many of which are resistant to multiple antibiotic agents and are more likely associated with complicated disease. In older hospitalized patients, because of increased usage of catheters (portals to infection), gram-negative organisms such as P mirabilis, Klebsiella, Serratia, and Pseudomonas are more common etiologies, and only 60% of cases are due to E coli.   In people with diabetes, infections are predominantly a result of Klebsiella, Enterobacter, Clostridium, or Candida. Those with immunosuppression (e.g., HIV, malignancy, transplantation) are especially prone to silent infections as a result of nonenteric, aerobic, gram-negative rods and Candida.
Acute uncomplicated pyelonephritis most often develops as a result of an ascending UTI. In these cases, symptoms of cystitis often precede acute pyelonephritis, particularly in patients with uncomplicated infections. Alternatively, pathogenesis may involve hematogenous seeding of the kidneys in patients with bacteremia. Typically, in women who develop acute pyelonephritis, pathogens first colonize the distal urethra and vaginal introitus and then ascend via the bladder and ureters to the kidney. Women with cystitis-like symptoms (e.g., burning on urinating, urgency) commonly (30%) have asymptomatic pyelonephritis, rarely causing kidney damage.
Men are more prone to prostatitis and BPH, which cause a urethral obstruction leading to bacteriuria and consequently often pyelonephritis. Dilation and obstruction of the ureter cause inflammation of the kidney parenchyma, which is seen on histopathologic examination as purulent exudates in the renal tubules. Image 1 Image 2 Image 3 Image 4 Additionally, obstruction as a result of any cause (e.g., calculi, tumor, foreign body, BPH, or neurogenic bladder) often leads to treatment failure and eventual renal abscess, as continued blockage may lead to reinfection. Chronically ill patients and those receiving immunosuppressive therapy are at highest risk.  Seeding in the kidney from bone or skin may occur from metastatic staphylococcal or fungal infections as well.
Uropathogenic E coli are a common cause of infection in patients with normal urinary tract anatomy.  The enhanced virulence potential of uropathogenic E coli is thought to derive mainly from factors that enhance the ability of these strains to adhere to and colonize the urinary tract. These factors include flagella, which increase motility, hemolysins that break down RBCs, and iron-scavenging molecules that pick up the iron released from red cell lysis to use for cell growth and adhesions on the bacterial fimbriae that help the organisms stick to the uroepithelial surface. The proteins requied for P-fimbrial biogenesis, a mannose-resistant adhesin of uropathogenic Escherchia coli, are encoded by the pap gene cluster codons. P fimbriae appear to play some role in mediating adherence to uroepithelial cells in vivo and establishing an inflammatory response during renal colonization, thus contributing to kidney damage during acute pyelonephritis.  Other properties assist the bacteria in avoiding or subverting host defenses, injuring or invading host cells and tissues, and stimulating a noxious inflammatory response.  Virulence of uropathogenic E coli has been linked to the presence of pathogenicity islands, unstable large regions of the bacterial genome encoding for these virulence factors, which are present in approximately 80% of E coli strains identified in the blood and urine of patients with acute pyelonephritis.  More than 30 bacterial species carrying pathogenicity islands have been described.