What is the diagnosis for Pyelonephritis (inflammation of the kidney) with normal Urine Routine Microscopy (RM)?

From the Guidelines

Pyelonephritis should be treated empirically with antibiotics even if the urine analysis is normal, as clinical suspicion and presentation are crucial for diagnosis and treatment. According to the European Association of Urology guidelines on urological infections, published in 2024 1, fluoroquinolones and cephalosporins are the recommended antimicrobial agents for oral empiric treatment of uncomplicated pyelonephritis.

Some key points to consider in the management of pyelonephritis with normal urine analysis include:

• Clinical presentation, such as fever, chills, flank pain, nausea, vomiting, or tenderness at the costovertebral angle, is essential for diagnosis 1.
• Urine culture and antimicrobial susceptibility testing should be performed in all cases of pyelonephritis, despite normal urinalysis results 1.
• Evaluation of the upper urinary tract via ultrasound should be performed to rule out urinary tract obstruction or renal stone disease, especially in patients with a history of urolithiasis, renal function disturbances, or a high urine pH 1.
• Additional investigations, such as a contrast-enhanced computed tomography scan, or excretory urography, should be considered if the patient remains febrile after 72 h of treatment, or immediately if there is a deterioration in clinical status 1.

In terms of treatment, fluoroquinolones, such as ciprofloxacin or levofloxacin, and cephalosporins are the preferred options for oral empiric treatment. The choice of antibiotic should be based on local resistance patterns and optimized, with carbapenems and novel broad-spectrum antimicrobial agents reserved for patients with multidrug-resistant organisms 1.

It is essential to note that normal urinalysis in pyelonephritis may occur due to various factors, such as early infection, prior antibiotic use, dehydration limiting bacterial excretion, or urinary tract obstruction preventing infected urine from reaching the bladder. Despite normal urinalysis, patients with flank pain, fever, and costovertebral angle tenderness should be treated for presumed pyelonephritis if clinical suspicion is high, as prompt treatment is crucial to prevent complications and improve outcomes 1.

From the Research

Pyelonephritis with Normal Urine RM

• Pyelonephritis is a bacterial infection of the kidney and renal pelvis, and it should be suspected in patients with flank pain and laboratory evidence of urinary tract infection 2.
• The combination of the leukocyte esterase test and the nitrite test has a sensitivity of 75 to 84 percent and a specificity of 82 to 98 percent for urinary tract infection 3.
• Urine cultures are positive in 90 percent of patients with acute pyelonephritis, and cultures should be obtained before antibiotic therapy is initiated 3.
• The use of blood cultures should be reserved for patients with an uncertain diagnosis, those who are immunocompromised, and those who are suspected of having hematogenous infections 3.

Diagnosis and Management

• Urine culture with antimicrobial susceptibility testing should be performed in all patients and used to direct therapy 2.
• Imaging, blood cultures, and measurement of serum inflammatory markers should not be performed in uncomplicated cases 2.
• Outpatient management is appropriate in patients who have uncomplicated disease and can tolerate oral therapy 2.
• Fluoroquinolones and trimethoprim/sulfamethoxazole are effective oral antibiotics in most cases, but increasing resistance makes empiric use problematic 2, 4, 5.

Treatment Options

• Levofloxacin is a fluoroquinolone antibacterial that has become one of the cornerstones of antibiotic therapy of complicated UTIs and pyelonephritis 5.
• Oral antibiotics including amoxicillin, amoxicillin-clavulanic acid, and cephalexin have potential to be effective for a proportion of patients with pyelonephritis 6.
• Ciprofloxacin may be effective at lower doses than currently prescribed 6.
• A pharmacokinetic-pharmacodynamic assessment of oral antibiotics for pyelonephritis suggests that there is a pharmacological basis to consider alternative treatments/novel dosing regimens for the oral treatment of pyelonephritis 6.