Acute Pyelonephritis

Overview 

• Terminology: Derived from the Greek words pyelo- (pelvis), nephros (kidney), and -itis (inflammation), it refers to inflammatory infections of the kidney and upper urinary tract structures.
• Pathogens:
  • Primary: Escherichia coli (most common, especially in uncomplicated cases, accounting for 60%-80%).
  • Others: Proteus mirabilis, Klebsiella spp., Enterobacter spp., Pseudomonas spp.. Gram-positive organisms like Enterococcus faecalis and Staphylococcus aureus are less common.
• Categories:
  • Uncomplicated: Infections in healthy individuals with normal urinary anatomy.
  • Complicated: Linked to anatomical or functional abnormalities (e.g., vesicoureteral reflux, stones) or conditions such as diabetes or immunosuppression.
    
    

Pathogens and Their Prevalence

• Escherichia coli: Responsible for 70%-95% of uncomplicated cases and 21%-54% of complicated cases.
• Proteus mirabilis: Found in 1%-10% of cases, more common in complicated infections.
• Klebsiella spp.: Accounts for 1%-17% of cases.
• Pseudomonas aeruginosa: Rarely seen in uncomplicated infections but present in up to 19% of complicated cases.
• Enterobacter spp. and Citrobacter spp.: More prevalent in complicated infections.

• Enterococcus faecalis and Staphylococcus aureus: Seen more often in complicated cases (up to 23%).
• Coagulase-negative staphylococci: Found in 5%-10% of uncomplicated cases and 1%-4% of complicated cases.
• Uncommon pathogens include mycobacteria, fungi such as Candida spp., and opportunistic organisms like Corynebacterium urealyticum. These are typically encountered in immunocompromised patients or those with long-term catheterization.
  
  

General Classification

1. Uncomplicated Acute Pyelonephritis
   • Occurs in immunocompetent individuals with no anatomical or functional abnormalities. Typical pathogens such as Escherichia coli are common culprits.
2. Complicated Acute Pyelonephritis
   • Occurs in individuals with predisposing factors such as structural or functional abnormalities, immunosuppression, or underlying medical conditions that impair normal urinary tract defenses.
     
     

Patient-Specific Factors

• Infants and children: Congenital abnormalities, such as vesicoureteral reflux, increase susceptibility.
• Young adults: Women are at higher risk due to a shorter urethra and increased UTI prevalence.
• Older adults (>60 years): Age-related anatomical changes, comorbidities, and reduced immunity contribute to higher risks.
  
  

• Women: Hormonal changes, shorter urethras, and proximity to the anus predispose to ascending infections.
• Men: Conditions like prostatitis, benign prostatic hyperplasia, or anatomical abnormalities lead to increased risk.
  
  

• Hormonal and mechanical changes during pregnancy, such as progesterone-induced ureteral dilation and bladder displacement by the growing uterus, cause urinary stasis.
• Increased risk of vesicoureteral reflux and asymptomatic bacteriuria progressing to pyelonephritis.
  
  

Anatomical and Functional Abnormalities

• Vesicoureteral reflux.
• Polycystic kidney disease.
• Horseshoe kidney.
• Double ureter.
• Ureterocele.

• Benign prostatic hyperplasia.
• Renal stones or staghorn calculi.
• Bladder neck obstruction.
• Posterior ureteral valve.
• Neurogenic bladder.
  
  

• Indwelling urinary catheters or ureteric stents.
• Nephrostomy tubes or urethral strictures.
  
  

Systemic Conditions

• Diabetes mellitus: Glucosuria, impaired immunity, and recurrent instrumentation increase susceptibility.
• Sickle cell disease: Vascular abnormalities and ischemia contribute to infections.
• Chronic kidney disease: Reduced renal function diminishes local immune defenses.
  
  

• Organ transplantation and associated immunosuppressive therapy.
• Chemotherapy, radiotherapy, or corticosteroid use.
• Alcohol dependence.
• HIV infection or other causes of immunodeficiency.
  
  

• Recent urinary tract instrumentation, such as cystoscopy.
• Hospitalisations and healthcare-associated exposures.
  
  

• Frequent sexual activity, especially in young women, increases mechanical trauma and bacterial migration.
• Use of spermicides, such as nonoxynol-9, disrupts protective vaginal flora.
• Postmenopausal changes, including vaginal atrophy and reduced lactobacilli, increase risk.

• Antimicrobial Resistance: Prior use of broad-spectrum antibiotics predisposes to multidrug-resistant infections.
• Recurrent UTIs: Persistent infections can increase the likelihood of complications.
• Healthcare Interactions: Increased exposure to multidrug-resistant organisms in hospital settings.

Antimicrobial Resistance

• Recent antibiotic use, especially broad-spectrum agents.
• Recurrent urinary tract infections.
• Hospitalisation or increased healthcare interactions.
• Indwelling catheters and advanced age.
  
  

Mechanisms of Infection

Ascending Infection

• Bacteria colonize the periurethral area and ascend through the urethra to the bladder, eventually reaching the kidneys via the ureters.
• Host factors like female anatomy (shorter urethra), hormonal changes, and urinary stasis increase susceptibility.
• The majority of infections are caused by uropathogenic Escherichia coli (UPEC), which utilises adhesive mechanisms to attach to uroepithelial cells and evade host defenses.
  
  

Hematogenous Spread

• This less common route occurs when bacteria access the kidney through the bloodstream, usually in cases of bacteremia or sepsis.
• Gram-positive organisms like Staphylococcus aureus are associated with intravenous drug use and infective endocarditis.
• Hematogenous spread of gram-negative organisms is rare and typically occurs with underlying urinary obstruction.
  
  

Obstruction and Urinary Stasis

• Conditions such as urinary stones, tumors, or prostatic hyperplasia can obstruct urine flow, promoting bacterial colonization and infection.
• Staghorn calculi formed by urea-splitting bacteria (e.g., Proteus mirabilis) can exacerbate infections, causing pyonephrosis or xanthogranulomatous pyelonephritis.
  
  

Bacterial Virulence Factors

1. Adhesins:
   • Type 1 fimbriae mediate initial colonization but are mannose-sensitive and facilitate bacterial clearance by immune cells.
   • P fimbriae, mannose-resistant, enhance adhesion to epithelial cells and are highly associated with pyelonephritis and urosepsis.
2. Siderophores:
   • Aid in iron acquisition, essential for bacterial growth and persistence.
3. Protectins:
   • Lipopolysaccharides (LPS) resist phagocytosis.
   • Other proteins, like OmpT, cleave host defense molecules.
4. Toxins:
   • Alpha-hemolysin and cytotoxic necrotizing factor-1 disrupt host cellular functions and enhance inflammation.
     
     

Host Response and Inflammatory Mechanisms

• UPEC adhesion triggers an inflammatory cascade via receptors such as Toll-like receptor 4 (TLR4) and glycosphingolipid (GSL).
• Chemokines like interleukin-8 (IL-8) recruit neutrophils, which mediate bacterial clearance but can also exacerbate tissue damage.
• Inflammatory cytokines and reactive oxygen species contribute to renal scarring, with collagen deposition replacing functional renal tissue in severe cases.
  
  

Incidence and Prevalence

• In the United States, the annual incidence is 15-17 cases per 10,000 females and 3-4 cases per 10,000 males, amounting to approximately 250,000 cases annually. Treatment costs are estimated at $2.14 billion per year.
• In England, over one-third of women report experiencing a urinary tract infection (UTI) in their lifetime, while in Scotland, UTIs are the most common healthcare-associated infection among hospitalised adults.
  
  

Age and Gender Distribution

• Women are disproportionately affected, especially those aged 18-49 years, with an incidence of 28 cases per 10,000 women.
  • Pyelonephritis incidence exhibits a trimodal distribution:
    • Peak ages: 0-4 years, 15-35 years, and a gradual increase post-50, peaking at 80 years.
• Men show a bimodal distribution:
  • Peaks at ages 0-4 years and post-35 years, with the highest rates at 85 years.
• Seasonal variation has been noted, with peaks during summer months (July-August) in women and August-September in men.
  
  

High-Risk Groups

• Pregnant Women:
  • Pyelonephritis occurs in 20-30% of pregnant women with untreated asymptomatic bacteriuria, most commonly in the late second or early third trimester. The overall incidence of asymptomatic bacteriuria ranges from 2-9.5%.
  • Complications include maternal morbidity, preterm delivery, and low birth weight.
  • Recent evidence questions the benefit of treating asymptomatic bacteriuria, citing low rates of pyelonephritis in both treated and untreated groups.
• Infants and Children:
  • Up to 25% of children with UTIs may have upper urinary tract involvement without overt symptoms.
• Older Adults:
  • The gender disparity in incidence narrows significantly with advancing age.
• Renal Transplant Patients:
  • Pyelonephritis affects 30-50% of renal transplant recipients within the first two months post-surgery, significantly increasing the risk of graft loss and mortality.
• Men:
  • Higher mortality rates compared to women, potentially due to associated conditions like diabetes, nephrolithiasis, and kidney disease.

Other Epidemiological Observations

• Geographical Data:
  • Limited large-scale epidemiological data are available globally, though some regional studies in Sweden and the United States have provided insights.
• Progression from UTI to Pyelonephritis:
  • In Sweden, a large cohort study revealed that 0.47% of UTIs treated with antibiotics progressed to pyelonephritis, rising to 1.43% when antibiotic prescriptions were not filled within five days.
• Seasonal Trends:
  • The incidence of pyelonephritis exhibits seasonal peaks, with the highest rates recorded during warmer months.
    
    

Classic Symptoms

1. Fever
   • Fever often exceeds 103°F (39.4°C) and may be accompanied by rigors and chills.
   • Fever may be absent in early stages, mild cases, or older patients.
2. Flank Pain
   • Almost universally present and described as dull, aching pain in the lower back, under the ribs, or in the flank region.
   • Pain may radiate to the groin, suggesting ureteral involvement or obstruction.
3. Nausea and Vomiting
   • Common symptoms, though the severity varies from mild discomfort to severe emesis.
4. Costovertebral Angle Tenderness (CVA Tenderness)
   • A hallmark finding on examination; palpation elicits pain and helps differentiate pyelonephritis from other causes of flank pain, such as renal or ureteral stones.
     
     

Associated Symptoms

1. Lower Urinary Tract Symptoms (LUTS)
   • Symptoms of cystitis, such as urinary frequency, urgency, dysuria, and hematuria, may be present.
   • Hemorrhagic cystitis with gross hematuria occurs in 30%-40% of females but is rare in males, prompting consideration of alternative diagnoses.
2. Gastrointestinal Symptoms
   • Anorexia, nausea, and vomiting are common, while diarrhea occurs infrequently.
3. Malaise and Weakness
   • Generalised flu-like symptoms, including myalgia, chills, and fatigue, are frequent in moderate to severe infections.
     
     

Special Populations

1. Children
   • Classic symptoms are often absent. Common presentations include:
     • Fever, vomiting, and feeding difficulties in neonates and infants.
     • Failure to thrive in children under 2 years.
2. Elderly Patients
   • May present atypically with:
     • Altered mental status or sudden dementia.
     • Generalised deterioration or decompensation in other organ systems.
     • Fever and loss of appetite.
3. Renal Transplant Patients
   • Pain may localise to the lower quadrant of the abdomen where the transplanted kidney is palpable.
     
     

Indicators of Complicated Pyelonephritis

• Structural abnormalities (e.g., vesicoureteral reflux, ureterocele, polycystic kidney disease).
• Functional abnormalities (e.g., neurogenic bladder, urinary stasis).
• Metabolic conditions (e.g., diabetes mellitus).
• Recent urinary tract instrumentation or antibiotic use.
• Male sex, advanced age, pregnancy, or symptoms persisting beyond 7 days.
  
  

Risk Factors to Elicit in History

1. Urinary Tract and Renal Factors
   • History of recurrent UTIs, renal stones, or catheter use.
   • Polycystic kidney disease or anatomical abnormalities.
2. Lifestyle and Behavioral Factors
   • Frequent sexual activity or a new sexual partner.
   • Recent spermicide use or stress incontinence.
3. Medical and Immune Status
   • Immunosuppression (e.g., corticosteroid or immunosuppressant use, HIV).
   • Diabetes mellitus or chronic kidney disease.
4. Pregnancy
   • UTIs and untreated asymptomatic bacteriuria in pregnancy increase the risk of pyelonephritis, premature delivery, and fetal mortality.
     
     

General Appearance

• Most patients appear uncomfortable or mildly ill.
• A toxic appearance suggests complications such as sepsis, perinephric abscess, or significant dehydration.

Vital Signs

1. Temperature
   • Fever (>39.4°C or 103°F) is common but may be absent in early stages, mild cases, or elderly patients.
   • Hypothermia (<36°C) in older adults may indicate sepsis.
2. Heart Rate
   • Tachycardia may accompany fever, dehydration, or systemic illness.
3. Blood Pressure
   • Usually normal, though hypotension (systolic BP <90 mm Hg) may indicate septic shock or severe dehydration.

Abdominal Examination

1. Suprapubic Tenderness
   • Commonly mild to moderate.
   • Rebound tenderness, guarding, and rigidity are typically absent unless another pathology is present.
2. Bowel Sounds
   • Generally active and normal unless complicated by other abdominal conditions.

Flank and Costovertebral Angle (CVA) Examination

1. Flank Pain
   • A hallmark finding, often described as dull or aching and typically unilateral.
   • In cases involving both kidneys, bilateral CVA tenderness may be noted.
2. CVA Tenderness
   • Elicited with mild to moderate palpation or percussion over the affected kidney.
   • Helps distinguish pyelonephritis from other causes of flank pain, such as ureteral stones.

Additional Diagnostic Considerations

1. Pelvic Examination (for Women)
   • Cervical, uterine, or adnexal tenderness is absent in pyelonephritis.
   • Positive findings suggest alternative diagnoses, such as pelvic inflammatory disease or urethritis.
2. Male Examination
   • Check for signs of prostatitis or other urological abnormalities.

Atypical Presentations

1. Children
   • May lack classic findings and present with nonspecific signs like irritability, vomiting, or failure to thrive.
2. Elderly Patients
   • Often present with altered mental status, anorexia, or generalised decline, with minimal localised findings.
3. Renal Transplant Recipients
   • Pain localises to the lower quadrant where the transplanted kidney is palpable.
     
     

Initial Laboratory Investigations

1. Urinalysis
   • Pyuria: Defined as >5-10 white blood cells (WBCs) per high-power field (hpf) on centrifuged urine; significant pyuria (>20 WBCs/hpf) is observed in nearly all cases.
   • Nitrites: Indicate nitrate-reducing bacteria such as E. coli, but sensitivity is low (~25%); a negative result does not exclude infection.
   • Proteinuria: Up to 2 g/day is common; levels exceeding 3 g/day may suggest glomerulonephritis.
   • Bacteriuria: Presence of bacteria under oil-immersion microscopy (≥100,000 colony-forming units/mL) confirms infection.
   • Hematuria: Microscopic hematuria is common in uncomplicated cases, while gross hematuria is more prevalent in women (~40%).
2. Urine Culture and Sensitivity
   • Gold standard for confirming bacterial etiology and identifying antibiotic resistance patterns.
   • Collection should be done before initiating antibiotics for optimal results.
3. Full Blood Count (FBC)
   • Leukocytosis: Reflects systemic inflammation.
   • Neutrophilia: Suggests bacterial infection.
4. Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP)
   • Both are nonspecific markers elevated in systemic infections and inflammation.
5. Urea, Electrolytes, and Creatinine
   • Used to evaluate renal function.
   • Abnormalities suggest renal impairment or acute kidney injury secondary to infection.
6. Blood Culture
   • Indicated for hospitalised patients or those with systemic symptoms like sepsis.
   • Positive in 15%-30% of cases, particularly in bacteremic patients. Blood samples should be collected before antibiotic administration.
     
     

Advanced and Optional Laboratory Tests

1. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL)
   • A novel biomarker with high sensitivity (>90%) for diagnosing acute pyelonephritis in children.
   • Threshold value: 29.4 ng/mL.
2. Sepsis Markers
   • Includes lactic acid, procalcitonin, and neutrophil-to-lymphocyte ratio (>5), which help assess systemic inflammation and sepsis.
     
     

Imaging Studies

1. Renal Ultrasound
   • Preferred initial imaging for pregnant patients to avoid radiation.
   • Identifies hydronephrosis, renal stones, or abscesses.
   • Limitations: Low sensitivity for small abscesses or nonobstructive pyelonephritis.
2. Contrast-Enhanced CT (CECT)
   • Gold standard for diagnosing complicated pyelonephritis.
   • Typical findings include wedge-shaped hypodense defects, fat stranding, diminished renal enhancement, and abscess formation.
   • Noncontrast CT is preferred for suspected urolithiasis.
3. MRI
   • Used when CT is contraindicated (e.g., in pregnancy or contrast allergies).
   • Identifies nephritis, abscesses, and vascular involvement without radiation exposure.
   • Cost and limited availability are concerns.
4. CT Urography and MR Urography
   • Advanced techniques for detailed urinary tract imaging.
   • Useful in evaluating hematuria or structural abnormalities.

Indications for Imaging

• Persistent fever >48 hours despite antibiotics.
• Recurrent or complicated pyelonephritis.
• Anatomical abnormalities or renal transplant.
• Suspicion of obstructive pyelonephritis or sepsis.
• High-risk groups (e.g., poorly controlled diabetes, immunosuppressed patients).
  
  

Special Considerations

1. Pregnant Patients
   • Begin with ultrasound; consider MRI if findings are inconclusive.
   • Avoid CT due to fetal radiation exposure unless absolutely necessary.
2. Children
   • Early imaging is recommended to detect congenital anomalies or structural abnormalities predisposing to recurrent infections.
3. Obstructive Pyelonephritis
   • Requires urgent imaging (typically CT) to identify and address obstructing stones or abscesses.
4. Acute Lobar Nephronia
   • Rare intermediate stage between pyelonephritis and renal abscess.
   • Best diagnosed with contrast-enhanced CT, showing mass-like renal defects
     
     

Urinary Tract Conditions

1. Lower Urinary Tract Infection (UTI)
   • Signs/Symptoms: Dysuria, urinary urgency, and frequency; lacks systemic symptoms such as fever, chills, or back pain.
   • Investigations: Urinalysis and urine culture confirm infection but exclude systemic involvement.
2. Cystitis
   • Signs/Symptoms: Similar to a UTI with dysuria, frequency, and urgency; no systemic signs like fever or nausea.
   • Investigations: Clinical presentation is key; no specific differentiating tests.
3. Acute Prostatitis (in men)
   • Signs/Symptoms: Fever, suprapubic or rectal pain, dysuria, urinary frequency, or retention; may follow anal intercourse.
   • Investigations: Digital rectal examination reveals a tender, enlarged prostate. Urine collected after prostate massage shows WBCs.
4. Urethritis
   • Signs/Symptoms: Urethral discharge, itching, dysuria.
   • Investigations: Gram stain and culture of discharge; nucleic acid amplification tests.
5. Chronic Pyelonephritis
   • Signs/Symptoms: History of recurrent UTIs, structural abnormalities (e.g., stones), or metabolic disorders like diabetes; may lead to permanent renal scarring.
   • Investigations: Imaging studies (e.g., ultrasound or CT) show small, irregular, scarred kidneys.
     
     

Reproductive and Pelvic Conditions

1. Pelvic Inflammatory Disease (PID)
   • Signs/Symptoms: Lower abdominal or pelvic pain, fever, abnormal vaginal discharge, and cervical tenderness; history of sexual activity.
   • Investigations: Cervical swabs for Neisseria gonorrhoeae or Chlamydia trachomatis; microscopic examination of vaginal discharge.
2. Chronic Pelvic Pain Syndrome
   • Signs/Symptoms: Dysuria, pelvic pain, pain during intercourse, and frequent voiding; symptoms recur with negative cultures.
   • Investigations: Diagnosis is clinical; no specific tests available.
     
     

Abdominal and Thoracic Conditions

1. Lower Lobe Pneumonia
   • Signs/Symptoms: Cough, pleuritic chest pain, fever; examination shows reduced breath sounds, rales, or rhonchi.
   • Investigations: Chest radiography confirms pneumonia.
2. Appendicitis
   • Signs/Symptoms: Right lower quadrant pain, nausea, vomiting, fever.
   • Investigations: Abdominal ultrasound or CT.
3. Diverticulitis
   • Signs/Symptoms: Left lower quadrant pain, fever, altered bowel habits.
   • Investigations: Abdominal CT shows colonic wall thickening and pericolic fat stranding.
4. Ectopic Pregnancy
   • Signs/Symptoms: Abdominal or pelvic pain, amenorrhea, vaginal bleeding.
   • Investigations: Serum β-hCG and transvaginal ultrasound.
5. Cholecystitis
   • Signs/Symptoms: Right upper quadrant pain, fever, nausea, Murphy's sign positive.
   • Investigations: Abdominal ultrasound reveals gallbladder wall thickening and pericholecystic fluid.
     
     

Renal and Urological Conditions

1. Nephrolithiasis (Kidney Stones)
   • Signs/Symptoms: Severe flank pain radiating to the groin, hematuria.
   • Investigations: Noncontrast CT or renal ultrasound.
2. Perinephric Abscess
   • Signs/Symptoms: Persistent fever, flank pain despite antibiotic therapy.
   • Investigations: Contrast-enhanced CT reveals fluid collection around the kidney.
3. Ureterolithiasis/Urolithiasis
   • Signs/Symptoms: Acute flank pain, hematuria; associated with obstruction or infection.
   • Investigations: Noncontrast CT or ultrasound.
4. Pyonephrosis (Obstructive Pyelonephritis)
   • Signs/Symptoms: Fever, flank pain, and systemic toxicity.
   • Investigations: CT shows dilated renal pelvis with echogenic debris or gas.
5. Xanthogranulomatous Pyelonephritis
   • Signs/Symptoms: Severe flank pain, fever, weight loss; associated with staghorn calculi.
   • Investigations: CT reveals large nonfunctioning kidneys with renal calculi and perinephric fibrosis.
     
     

Urgent Management

1. Sepsis Evaluation
   • Always assess for possible sepsis using a systematic approach, such as the National Early Warning Score 2 (NEWS2).
   • Refer patients with suspected sepsis for emergency care. In the community, use blue-light ambulance services for urgent hospital transfer.
   • In hospital settings, escalate care to senior clinicians (e.g., ST4-level doctor in the UK) if sepsis is suspected.
2. Empirical Antibiotic Therapy
   • Collect urine samples for culture before administering antibiotics.
   • Initiate empirical antibiotic therapy immediately based on local resistance patterns, clinical severity, and patient risk factors.

Treatment Settings

1. Community Management
   • Treat uncomplicated cases (non-pregnant, premenopausal women with no urological abnormalities or significant comorbidities) with oral antibiotics.
2. Hospitalisation
   • Admit patients with severe symptoms or complications such as:
     • High fever (>39.4°C).
     • Significant dehydration or inability to tolerate oral fluids.
     • Comorbidities (e.g., diabetes, kidney dysfunction, immunosuppression).
     • Suspected urinary obstruction or abscess.
     • Pregnancy with severe symptoms.
       
       

Antibiotic Therapy

1. Uncomplicated Pyelonephritis
   • First-line oral antibiotics:
     • Cefalexin: 500 mg twice or thrice daily for 7–10 days.
     • Amoxicillin/clavulanate: 500/125 mg three times daily for 7–10 days (if culture confirms susceptibility).
     • Trimethoprim: 200 mg twice daily for 14 days (if susceptibility confirmed).
     • Ciprofloxacin: 500 mg twice daily for 7 days (use only if other options unsuitable).
2. Complicated Pyelonephritis
   • First-line intravenous antibiotics:
     • Cefuroxime: 750 mg to 1.5 g three or four times daily.
     • Gentamicin: Initial 5–7 mg/kg/day, adjusted based on renal function.
     • Ciprofloxacin: 400 mg twice daily (if oral options unsuitable).
   • Review IV antibiotics within 48 hours and switch to oral antibiotics where possible, based on clinical response and culture results.
3. Antibiotic Duration
   • Uncomplicated cases: Typically 5–7 days for fluoroquinolones or 7–10 days for beta-lactams.
   • Complicated cases: Minimum 14 days, especially for men (due to frequent prostatic involvement).
4. Special Considerations
   • Avoid antibiotics with inadequate renal penetration (e.g., nitrofurantoin, fosfomycin).
   • Monitor renal function and perform therapeutic drug monitoring for agents like gentamicin or amikacin.
     
     

Specific Populations

1. Pregnant Women
   • Use cefalexin (500 mg twice or thrice daily for 7–10 days) as first-line oral therapy.
   • For severe cases requiring hospitalisation, use cefuroxime IV as the first-line agent.
   • Avoid fluoroquinolones and trimethoprim due to safety concerns.
   • Monitor closely for maternal and fetal complications, such as preterm labor.
2. Men
   • Treat all UTIs in men as complicated due to the risk of prostatic involvement.
   • Consider a minimum antibiotic course of 14 days with fluoroquinolones (if appropriate).
     
     

Supportive Care

• Encourage fluid intake to prevent dehydration.
• For pain relief, recommend paracetamol as first-line analgesia. Add a weak opioid like codeine if necessary but avoid NSAIDs due to the risk of acute kidney injury.

Monitoring and Follow-Up

1. Reassessment
   • Reevaluate if symptoms worsen or fail to improve within 48 hours of antibiotic initiation.
   • Rule out alternative diagnoses or complications such as abscess formation, sepsis, or resistant organisms.
2. Culture Review
   • Adjust antibiotics based on urine culture and susceptibility results to use a narrow-spectrum agent where possible.
3. Routine Post-Treatment Cultures
   • Not recommended in asymptomatic patients unless they are pregnant or have recurrent infections.
     
     

Uncomplicated Pyelonephritis

• General Outlook:
  • In healthy, nonpregnant women, prognosis is excellent with complete recovery and minimal long-term kidney damage.
  • For healthy men without complicating conditions, the prognosis is also favorable, but urologic evaluation is recommended to exclude underlying abnormalities.
• Resolution Time:
  • Symptoms typically resolve within days to weeks with appropriate antibiotics.
  • Recurrence is rare if therapy is completed as prescribed.
• Mortality Risk:
  • Uncomplicated pyelonephritis is rarely fatal in the antibiotic era unless complications such as sepsis or abscess formation occur.
    
    

Complicated Pyelonephritis

• Older Patients and Comorbidities:
  • Prognosis is less favorable for elderly patients or those with conditions such as diabetes, chronic kidney disease, or immunosuppression.
  • Mortality rates are significantly higher in this group, ranging from 10% to 20% in severe cases.
• Complications:
  • Sepsis: Accounts for up to 16.1% of genitourinary-related severe sepsis cases, with mortality reaching 25%-42% in older adults.
  • Emphysematous Pyelonephritis: Mortality rates can exceed 60% with localised gas in the renal parenchyma and 80% if gas spreads to the perinephric space.
  • Perinephric Abscess and Pyonephrosis: Associated with 20%-50% mortality in untreated cases.
• Pregnancy-Related Pyelonephritis:
  • High risk of premature labor, acute kidney injury, acute respiratory distress syndrome, and fetal complications such as restricted growth or death.
  • Recurrence before delivery occurs in 18%-20% of cases.
    
    

Long-Term Effects and Special Populations

1. Kidney Scarring
   • In children, scarring occurs in 6%-15% of cases following febrile UTIs, often linked to vesicoureteral reflux (VUR).
   • In adults, single episodes of acute pyelonephritis result in kidney scarring in up to 46% of cases, with recurrent infections posing a lower additional risk.
   • Scarring is four times more likely after pyelonephritis in pregnant women compared to nonpregnant women.
2. Acute Kidney Injury (AKI)
   • Rarely occurs but is more common in elderly patients, those with bilateral disease, or cases involving septic shock.
   • Risk factors include preexisting renal impairment, age >65, and delayed treatment.
3. Kidney Transplant Patients
   • Acute pyelonephritis within three months of transplantation increases graft loss risk by over 40%.
4. Patients with Diabetes
   • Higher incidence of bacteremia (30.7% vs. 11% in nondiabetics), prolonged fever, and increased mortality (12.5% vs. 2.5%).

Mortality and Morbidity

• Mortality Rates:
  • Overall mortality ranges from 7.4% to 20% in severe cases.
  • Male patients, bedridden individuals, and those with recent antibiotic use are at higher risk.
• Morbidity:
  • Hospitalisation rates are higher in men, older adults, and patients with comorbidities.
  • Longer hospital stays are linked to diabetes, catheter use, and changes in initial therapy.
    
    

Short-Term Complications

1. Sepsis and Urosepsis
   • Description: Systemic inflammatory response to infection, often life-threatening.
   • Risk Factors: Delayed diagnosis, multidrug-resistant pathogens, immunosuppression.
   • Management:
     • ICU care with hemodynamic support.
     • Remove precipitating factors (e.g., infected catheters).
     • Broad-spectrum antibiotics, later tailored to culture results.
2. Acute Kidney Injury (AKI)
   • Description: Temporary decline in renal function caused by severe infection, obstruction, or nephrotoxic drugs.
   • Management:
     • Avoid nephrotoxic medications.
     • Adjust dosages of necessary drugs based on renal function.
     • Supportive care, including fluid management.
3. Antibiotic Failure
   • Description: Resistance to empirical therapy, recurrent infections, or failure to clear the infection due to biofilm-forming pathogens or internal foreign bodies (e.g., stones, catheters).
   • Management:
     • Perform repeat cultures to guide therapy.
     • Remove or replace indwelling devices.
     • Consider surgical intervention for abscess drainage or infected stones.
4. Renal Abscess and Perinephric Abscess
   • Description: Collection of pus within or around the kidney.
   • Diagnosis: Ultrasound or CT.
   • Management:
     • Antibiotics.
     • Percutaneous or surgical drainage for larger abscesses.
5. Emphysematous Pyelonephritis
   • Description: Severe, necrotising infection with gas formation in renal tissues.
   • Risk Factors: Diabetes mellitus, female sex.
   • Diagnosis: Confirmed with CT.
   • Management:
     • Immediate antibiotics.
     • Surgical intervention, including nephrectomy if required.
   • Mortality Rate: Up to 38%, but outcomes improve with combined medical and surgical treatment.
6. Papillary Necrosis
   • Description: Ischemic necrosis of renal papillae, commonly associated with diabetes, obstruction, or analgesic nephropathy.
   • Management: Treat underlying infection and provide supportive care.

Long-Term Complications

1. Renal Scarring and Atrophy
   • Description: Permanent damage to the renal parenchyma due to unresolved infection or delayed treatment.
   • Risk Factors: Recurrent infections, vesicoureteral reflux, or unrecognised obstructive causes.
   • Management:
     • Prevent recurrence with prophylactic antibiotics if necessary.
     • Monitor renal function regularly.
2. Chronic Pyelonephritis
   • Description: Persistent inflammation and infection leading to progressive renal damage and dysfunction.
   • Management: Long-term antibiotics and addressing structural abnormalities.
3. Xanthogranulomatous Pyelonephritis
   • Description: Rare, destructive chronic infection leading to renal enlargement and abscess formation.
   • Management: Often requires nephrectomy.
4. Recurrent UTIs
   • Description: Repeated infections caused by colonisation with resistant organisms or incomplete eradication of prior infections.
   • Management:
     • Repeat urine cultures for targeted therapy.
     • Address risk factors such as catheter use or anatomical abnormalities.
5. Renal Vein Thrombosis
   • Description: Rare complication resulting in clot formation within the renal vein.
   • Management: Anticoagulation and treatment of the underlying infection.
     
     

Complications in Specific Populations

1. Pregnant Women
   • Complications: Preterm labor, low birth weight, acute kidney injury, acute respiratory distress syndrome, and fetal death.
   • Management: Hospital admission for close monitoring, antibiotics safe in pregnancy (e.g., cefalexin), and supportive care.
2. Diabetic Patients
   • Complications: Increased risk of emphysematous pyelonephritis, bacteremia, prolonged fever, and higher mortality.
3. Kidney Transplant Patients
   • Complications: Acute pyelonephritis can cause graft loss in over 40% of cases within three months of transplantation.
   • Management: Early intervention with antibiotics and strict monitoring.
     
     

1. American College of Physicians. Short-course antibiotic treatment in pyelonephritis. ACP Journal Club. 2024.
2. American College of Radiology. Imaging in pyelonephritis. Radiology Guidelines. 2023.
3. Bergeron MG. Treatment of pyelonephritis in adults. Med Clin North Am. 1995;79(3):619-49.
4. Chuang Y-W, Liu H-Y, et al. Mortality of severe sepsis with acute pyelonephritis. J Microbiol Immunol Infect. 2013;46(4):310-316.
5. European Association of Urology. Guidelines on urological infections. European Association of Urology. 2023.
6. Hodson EM, Willis NS, Craig JC. Antibiotics for acute pyelonephritis in children. Cochrane Database Syst Rev. 2007;(4):CD003772.
7. Kofteridis DP, Papadimitraki E, Mantadakis E, et al. Effect of diabetes mellitus on the clinical and microbiological features of bacteremia. Int J Infect Dis. 2009;13(1):e2-e7.
8. Kuo CY, Lin WR, Chen WC, et al. Risk factors for emphysematous pyelonephritis. J Clin Med. 2020;9(7):2143.
9. National Institute for Health and Care Excellence (NICE). Pyelonephritis (acute): antimicrobial prescribing. NICE. 2018.
10. Public Health England. Diagnosis of urinary tract infections: quick reference tool for primary care for consultation and local adaptation. Public Health England. 2020.