and should not be used to treat patients with pyelonephritis, such as the patient in this case, or urosepsis.
5. In adults, 90% of uncomplicated UTIs occur in women. It is one of the most common reasons why adolescent and adult women seek health care, resulting in ~10 million physician visits annually in the United States. The simplistic view of why women have more UTIs than do men is that the shorter urethra in women results in a greater likelihood that organisms will ascend the urethra and enter the bladder. Sexual activity is thought to play a significant role in the introduction of uropathogens into the urethra. In addition, the use of spermicides, with both diaphragms and coated condoms, has been shown to predispose women to UTIs. However, other factors that may play a role in this gender difference have been identified. It has been observed that prostatic fluid inhibits the growth of common urinary tract pathogens in urine, providing a unique defense mechanism for men. It has also been observed that specific uropathogens bind to vaginal and periurethral epithelial cells. Binding in the periurethral region by these organisms is often seen in women prior to the development of UTI, as well as in women who have recurrent UTIs. Binding of uropathogens to the periurethral epithelium is highest when estrogen levels reach their peak during the menstrual cycle. These observations may further explain why a preponderance of UTIs are seen in women.
6. The clinical presentation in this patient is consistent with acute pyelonephritis. Pyelonephritis is an infection of the kidney, whereas cystitis is an infection of the bladder. The findings of fever, chills, and left flank pain, with corresponding costovertebral angle tenderness, are all consistent with pyelonephritis. If white blood cell casts were seen in the patient’s urinalysis, that finding would further support the diagnosis of pyelonephritis. Culture results would not be useful in differentiating between the two types of infections. Radiographic or cystoscopic studies would be necessary to make a definitive diagnosis of pyelonephritis, but clinical judgment is usually sufficient. The reason it is important to distinguish between pyelonephritis and cystitis is that antimicrobial treatment strategies differ. Cystitis therapy is usually brief, typically a 3-day course of trimethoprim-sulfamethoxazole unless there is a high rate of resistance to this agent in the community, while pyelonephritis therapy may be more prolonged, typically lasting 7 days to 2 weeks. The outcome of antimicrobial therapy is dependent in great part on the susceptibility of the E. coli strain. If patients are treated empirically with an antimicrobial agent to which their isolate is resistant, their outcome will be less likely to be favorable than in those patients who receive an antimicrobial agent to which their isolate is susceptible.
7. “Pathogenicity islands” are an exciting recent concept for understanding the evolution of human microbial pathogens. They are relatively large segments of DNA that encode virulence factors that have been inserted by recombination into chromosomal regions that appear to more readily allow “foreign” DNA. What that means practically is that organisms such as E. coli can quickly evolve from harmless gastrointestinal tract commensals to agents capable of causing UTI by incorporating DNA that encodes virulence factors. Acquisition of virulence factors by gene transfer is a common theme in E. coli pathogenicity, not only in strains causing UTI but also in strains that cause diarrheal disease. Two virulence factors known to be important in the pathogenesis of E. coli pyelonephritis, P fimbriae and hemolysin, have been found on pathogenicity islands. Pathogenicity islands are found much more frequently in E. coli strains that cause cystitis and pyelonephritis than in fecal isolates.
The fimbriae are the major means of adhesion of uropathogenic E. coli, allowing them to bind to the various types of epithelial cells that line the urinary tract. Two different fimbriae found on the surface of uropathogenic E. coli, types P and 1, have been well studied. The P fimbriae are so designated because they agglutinate red blood cells possessing the P blood group antigen. They bind to uroepithelial cells and are resistant to phagocytosis. More than 80% of E. coli isolates causing pyelonephritis have pathogenicity islands that encode these fimbriae. Type 1 fimbriae are distinct from the P fimbriae. Both agglutination of red blood cells and binding to uroepithelial cells by E. coli possessing type 1 fimbriae can be blocked by preincubating the organism with mannose, while binding of type P-fimbriated E. coli is not blocked by mannose. Type 1-fimbriated E. coli strains are thus said to be mannose sensitive, while type P strains are said to be mannose insensitive. Type 1 fimbriae are found more frequently in patients with cystitis and less frequently in patients with pyelonephritis. Our patient likely had a P-fimbriated E. coli strain because she had pyelonephritis.
Another important virulence factor of uropathogenic E. coli is hemolysin. Hemolysin production is detected in ~55% of E. coli recovered from patients with pyelonephritis. Studies with renal tubular cells in primary culture have shown them to be quite sensitive to the cytotoxic activity of this virulence factor.
Aerobactin is a third virulence factor, found in ~75% of E. coli strains causing pyelonephritis. Aerobactin is a siderophore. Siderophores are molecules produced by bacteria and scavenge iron, an essential nutrient for bacteria, from the host. Strains of E. coli that produce aerobactins have been shown to grow faster in urine than nonproducing strains, although how important this is in the pathogenesis of UTI is unclear.
REFERENCES
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CASE 2
The patient was a 15-year-old male who was brought to the emergency room by his sister. He gave a 24-hour history of dysuria and noted some “pus-like” drainage in his underwear and on the tip of his penis. Urine appeared clear, and urine culture was negative although urinalysis was positive for leukocyte esterase and multiple white cells were seen on microscopic examination of urine. He gave a history of being sexually active with five or six partners in the past 6 months. He claimed that he and his partners had not had any sexually transmitted infections. His physical exam was significant for a yellow urethral discharge and tenderness at the tip
