Acute Pyelonephritis

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

Gram-negative bacteria dominate as causative agents:

• 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.

Gram-positive bacteria are less frequent

• 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

Uncomplicated Acute Pyelonephritis

• Occurs in immunocompetent individuals with no anatomical or functional abnormalities.
• Typical pathogens such as Escherichia coli are common culprits.

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

Age

• 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.

Gender

• 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.

Pregnancy

• 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

Structural Abnormalities

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

Obstructions

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

Foreign Bodies

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

Systemic Conditions

Metabolic and Immune Disorders

• 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.

Immunosuppression

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

Recent Medical Interventions

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

Behavioral and Lifestyle Factors

• 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.

Microbiological and Antimicrobial Considerations

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

• The growing prevalence of extended-spectrum beta-lactamase (ESBL) producers and fluoroquinolone-resistant organisms complicates treatment.
• Resistance risk factors include:
  • Recent antibiotic use, especially broad-spectrum agents.
  • Recurrent urinary tract infections.
  • Hospitalisation or increased healthcare interactions.
  • Indwelling catheters and advanced age.
• Resistance is further exacerbated by inappropriate antibiotic use and global issues such as overuse in healthcare and agriculture, self-medication, and regulatory failures.

Mechanisms of Infection

Ascending Infection

• Bacteria colonise 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 colonisation and infection.
• Staghorn calculi formed by urea-splitting bacteria (e.g., Proteus mirabilis) can exacerbate infections, causing pyonephrosis or xanthogranulomatous pyelonephritis.

Bacterial Virulence Factors

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.

Siderophores

• Aid in iron acquisition, essential for bacterial growth and persistence.

Protectins

• Lipopolysaccharides (LPS) resist phagocytosis.
• Other proteins, like OmpT, cleave host defense molecules.

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.
• 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:
  • 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.
• This significantly increases 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.
• This rose 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

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.

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.

Nausea and Vomiting

• Common symptoms, though the severity varies from mild discomfort to severe emesis.

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

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.

Gastrointestinal Symptoms

• Anorexia, nausea, and vomiting are common, while diarrhea occurs infrequently.

Malaise and Weakness

• Generalised flu-like symptoms, including myalgia, chills, and fatigue, are frequent in moderate to severe infections.

Special Populations

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.

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.

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

Urinary Tract and Renal Factors

• History of recurrent UTIs, renal stones, or catheter use.
• Polycystic kidney disease or anatomical abnormalities.

Lifestyle and Behavioral Factors

• Frequent sexual activity or a new sexual partner.
• Recent spermicide use or stress incontinence.

Medical and Immune Status

• Immunosuppression (e.g., corticosteroid or immunosuppressant use, HIV).
• Diabetes mellitus or chronic kidney disease.

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

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.

Heart Rate

• Tachycardia may accompany fever, dehydration, or systemic illness.

Blood Pressure

• Usually normal, though hypotension (systolic BP <90 mm Hg) may indicate septic shock or severe dehydration.

Abdominal Examination

Suprapubic Tenderness

• Commonly mild to moderate.
• Rebound tenderness, guarding, and rigidity are typically absent unless another pathology is present.

Bowel Sounds

• Generally active and normal unless complicated by other abdominal conditions.

Flank and Costovertebral Angle (CVA) Examination

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.

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

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.

Male Examination

• Check for signs of prostatitis or other urological abnormalities.

Atypical Presentations

Children

• May lack classic findings and present with nonspecific signs like irritability, vomiting, or failure to thrive.

Elderly Patients

• Often present with altered mental status, anorexia, or generalised decline, with minimal localised findings.

Renal Transplant Recipients

• Pain localises to the lower quadrant where the transplanted kidney is palpable.

Initial Laboratory Investigations

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%).

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.

Full Blood Count (FBC)

• Leukocytosis: Reflects systemic inflammation.
• Neutrophilia: Suggests bacterial infection.

Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP)

• Both are nonspecific markers elevated in systemic infections and inflammation.

Urea, Electrolytes, and Creatinine

• Used to evaluate renal function.
• Abnormalities suggest renal impairment or acute kidney injury secondary to infection.

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

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.

Sepsis Markers

• Includes lactic acid, procalcitonin, and neutrophil-to-lymphocyte ratio (>5), which help assess systemic inflammation and sepsis.

Imaging Studies

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.

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.

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.

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

Pregnant Patients

• Begin with ultrasound; consider MRI if findings are inconclusive.
• Avoid CT due to fetal radiation exposure unless absolutely necessary.

Children

• Early imaging is recommended to detect congenital anomalies or structural abnormalities predisposing to recurrent infections.

Obstructive Pyelonephritis

• Requires urgent imaging (typically CT) to identify and address obstructing stones or abscesses.

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

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.

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.

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.

Urethritis

• Signs/Symptoms: Urethral discharge, itching, dysuria.
• Investigations: Gram stain and culture of discharge; nucleic acid amplification tests.

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

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.

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

Lower Lobe Pneumonia

• Signs/Symptoms: Cough, pleuritic chest pain, fever; examination shows reduced breath sounds, rales, or rhonchi.
• Investigations: Chest radiography confirms pneumonia.

Appendicitis

• Signs/Symptoms: Right lower quadrant pain, nausea, vomiting, fever.
• Investigations: Abdominal ultrasound or CT.

Diverticulitis

• Signs/Symptoms: Left lower quadrant pain, fever, altered bowel habits.
• Investigations: Abdominal CT shows colonic wall thickening and pericolic fat stranding.

Ectopic Pregnancy

• Signs/Symptoms: Abdominal or pelvic pain, amenorrhea, vaginal bleeding.
• Investigations: Serum β-hCG and transvaginal ultrasound.

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

• Signs/Symptoms: Severe flank pain radiating to the groin, hematuria.
• Investigations: Noncontrast CT or renal ultrasound.

Perinephric Abscess

• Signs/Symptoms: Persistent fever, flank pain despite antibiotic therapy.
• Investigations: Contrast-enhanced CT reveals fluid collection around the kidney.

Ureterolithiasis/Urolithiasis

• Signs/Symptoms: Acute flank pain, hematuria; associated with obstruction or infection.
• Investigations: Noncontrast CT or ultrasound.

Pyonephrosis (Obstructive Pyelonephritis)

• Signs/Symptoms: Fever, flank pain, and systemic toxicity.
• Investigations: CT shows dilated renal pelvis with echogenic debris or gas.

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

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 if sepsis is suspected.

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

Community Management

• Treat uncomplicated cases (non-pregnant, premenopausal women with no urological abnormalities or significant comorbidities) with oral antibiotics.

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

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).

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.

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).

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

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.

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

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.

Culture Review

• Adjust antibiotics based on urine culture and susceptibility results to use a narrow-spectrum agent where possible.

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.

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

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.

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.

Kidney Transplant Patients

• Acute pyelonephritis within three months of transplantation increases graft loss risk by over 40%.

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

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.

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.

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.

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.

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.

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

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.

Chronic Pyelonephritis

• Description: Persistent inflammation and infection leading to progressive renal damage and dysfunction.
• Management: Long-term antibiotics and addressing structural abnormalities.

Xanthogranulomatous Pyelonephritis

• Description: Rare, destructive chronic infection leading to renal enlargement and abscess formation.
• Management: Often requires nephrectomy.

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.

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

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.

Diabetic Patients

• Complications: Increased risk of emphysematous pyelonephritis, bacteremia, prolonged fever, and higher mortality.

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.

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