Acute Pyelonephritis

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Diagnosis and reasoning

This woman has presented with fever and acute right-sided flank pain; acute pyelonephritis (APN) is a key differential here, and should always be ruled out first. Other potential etiologies to keep in mind include renal infarction, as well as referred pain from cholecystitis, pancreatitis, or mesenteric ischemia. Note also that while APN is often accompanied by lower urinary tract symptoms (LUTS) such as frequency, urgency, or dysuria, their absence does not exclude this diagnosis. Subsequently, examination reveals right-sided costovertebral angle tenderness; in the current clinical context, this favors APN, although it is not pathognomonic for the condition. Urinalysis and urine cultures are an essential next step; the former reveals marked pyuria, minimal hematuria, leukocyte casts and a positive leukocyte esterase test. Considered as a whole, these further suggest at an infection of the upper urinary tract, although positive cultures are necessary for confirmation. Note that most current guidelines do not recommend routine imaging studies in otherwise healthy women with APN. However, they may be considered down the line if her symptoms persist or worsen. APN is a medical emergency; traditionally, these patients have been hospitalized and treated with intravenous (IV) broad-spectrum antibiotics (for example, fluoroquinolones). However, patients with uncomplicated APN are now increasingly treated on an outpatient basis, with oral antibiotic therapy; this proves successful in the overwhelming majority of cases. Note that there is no particular justification for a urology referral right now. Neither is there any particular clinical value in prescribing ACE inhibitors.


Discussion

Acute pyelonephritis (APN) is an infection of the renal parenchyma and renal pelvis; it is usually the result of bacterial ascent from the bladder to the kidneys via the ureters, but may occur via hematogenous spread in the chronically ill and individuals on immunosuppressants. Women between 15 to 29 years of age are at the greatest risk, followed by infants and the elderly; the high incidence of APN in young women is thought to be due to sexual intercourse, contraceptive use, and pregnancy. The condition also occurs in approximately 1 to 2% of pregnant women. In men, prostatitis and prostatic hypertrophy causing urinary stasis contribute to bacteriuria, which can cause APN; this is more common in older males. E.coli accounts for over 80% of all cases. Other key uropathogens include Enterobacteriaceae, P. aeruginosa, Enterococci, group B Streptococci, and other aerobic gram-negative bacteria. The diagnosis is usually made clinically. Typical symptoms include fever, nausea, vomiting, and flank pain accompanied by lower urinary tract symptoms (frequency, urgency, and dysuria). These may be mild, or severe and treatment-recalcitrant, especially if an obstruction is present. Flank pain is found in almost all cases and is very specific; its absence can usually safely direct the physician's attention to other conditions. Tenderness can be elicited by palpating the costovertebral angle. Fever is also characteristic, especially when higher than 38.0°C (100.4°F). However, it may be absent in elderly, the immunocompromised, or in early presentations. The diagnosis is confirmed by urinalysis and urine culture, with midstream clean-catch technique being the most frequently used method to retrieve the specimen. The leukocyte esterase and nitrite tests should be performed to detect pyuria, which is present in nearly all patients; it is also important to observe for the presence of white cell casts. Note that the Infectious Diseases Society of America (IDSA) defines pyelonephritis as a urine culture showing at least 10,000 colony-forming units (CFU) per milliliter, with corresponding clinical symptoms; this is sufficient to establish the diagnosis. However, in specific groups (such as men and pregnant women) counts between 1,000 to 9,999 CFU per milliliter may be diagnostic, assuming that a compatible clinical presentation is also present. Blood cultures are not routinely recommended, as they do not change the outcome or management. They are only indicated in the presence of diagnostic uncertainty, immunosuppression, or a suspected hematogenous source of infection. Imaging is usually not essential, except in a few selected cases; these include a poor response after three days of therapy, recurrent infection, diagnostic uncertainty, or a high probability of calculi, obstruction, abscesses, or congenital anomalies. Persons who are immunosuppressed or immunocompromised should also receive imaging, as they are at a higher risk of developing complications. CT with contrast is considered the first choice for non-pregnant women; magnetic resonance imaging (MRI) can also be used, but appears to hold no diagnostic advantage except for the avoidance of contrast in patients at risk of contrast nephropathy. Traditionally, patients with APN have been hospitalized and administered IV antibiotics. Recently though, there has been a shift to using oral therapy in outpatient settings; this has proven to be successful in more than 90% of uncomplicated cases. Note that not all patients can be treated on an outpatient basis; those with more severe presentations, or who do not respond to therapy should be admitted. Frailty, inadequate access to follow-up, and poor social support are considered relative indications for hospitalization. The IDSA recommends oral fluoroquinolones as the first line of therapy for uncomplicated APN, as the resistance of uropathogens against this class of antimicrobials is low. Pregnant women, however, should be treated with parenteral second- or third-generation cephalosporins instead. Other effective agents include oral amoxicillin-clavulanate, cephalosporins, and trimethoprim-sulfamethoxazole (Co-trimoxazole). Should the patient be hospitalized, IV antimicrobials are recommended as the initial line of management. Oral administration may be commenced once the patient's condition has improved. Clinical improvement should be apparent within the first 48 to 72 hours of starting treatment, in the absence of which additional testing is indicated. The two most common causes of treatment failure are resistant organisms and nephrolithiasis. If antibiotic therapy is administered appropriately, the prognosis of APN is good, especially in immunocompetent women with no underlying illnesses. Key complications of the condition include intrarenal and perinephric abscess formation, as well as urinary obstruction, bacteremia, and chronic renal scarring, which can impair renal function.


Take home messages

  1. Over 80% of all cases of APN are secondary to infection with E. coli.
  2. Women are five times more likely to develop APN, and five times more likely to be hospitalized, as compared to men.
  3. Imaging studies are not routinely indicated in APN.
  4. Many patients with uncomplicated APN can be treated with oral antibiotics on an outpatient basis.

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