Pyelonephritis and urosepsis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Acute pyelonephritis is bacterial infection of the renal pelvis and parenchyma, usually caused by ascending enteric organisms. It is distinguished from cystitis by fever, loin pain, systemic illness or renal tenderness.

Urosepsis is sepsis arising from the urinary tract. Obstruction by stone, stricture, tumour, enlarged prostate or a blocked device sustains pressure and bacterial burden and makes drainage time critical.

Treatment depends on severity, oral absorption, pregnancy, renal function, resistance risk and culture. Nitrofurantoin and oral fosfomycin do not provide adequate renal-tissue concentrations.

Resuscitation and diagnostic work proceed together: collect useful samples, start treatment promptly and define the anatomical source and latest acceptable time for drainage.

Key points

Pyelonephritis causes fever, flank or loin pain, systemic upset and urinary symptoms, although lower urinary symptoms may be absent.
Send a midstream urine culture before antibiotics in every suspected acute pyelonephritis case when this does not delay treatment.
Assess for sepsis and obstruction at presentation; an infected blocked system needs drainage as well as antimicrobial therapy.
Eligible stable non-pregnant adults may receive an oral regimen; vomiting, severe illness, pregnancy or high complication risk supports hospital referral.
NICE oral options include cefalexin 500 mg twice or three times daily for seven to ten days, adjusted within guidance for severe infection.
Use co-amoxiclav or trimethoprim only when culture confirms susceptibility; reserve ciprofloxacin for when other recommended agents are inappropriate.
Intravenous options are selected from local policy, prior microbiology and renal function; ceftriaxone 1 to 2 g once daily is one NICE-listed option.
Review intravenous therapy by 48 hours and step down to the narrowest effective oral agent when physiology, intake and susceptibility permit.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Ascending enteric infection

Uropathogenic Escherichia coli and other Enterobacterales ascend from bladder through ureters into renal pelvis and parenchyma, causing most community disease.

Obstruction and instrumentation

Stones, strictures, tumour, prostatic obstruction, reflux, catheters and urological procedures impair drainage and introduce resistant or healthcare-associated organisms.

Haematogenous seeding

Staphylococcus aureus and Candida can reach kidneys through the bloodstream, particularly with endovascular infection, injection exposure or profound immune compromise.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Renal parenchymal inflammation
Bacterial invasion recruits neutrophils into renal pelvis and interstitium, producing oedema, pain, pyuria and impaired concentrating function.
2
Pressure and bacterial burden
Obstruction raises collecting-system pressure, reduces renal perfusion and prevents clearance, allowing rapid bacterial multiplication and bloodstream invasion.
3
Systemic sepsis response
Inflammatory vasodilatation, endothelial leak and myocardial dysfunction produce tissue hypoperfusion, acute kidney injury, encephalopathy and shock.
4
Suppuration and necrosis
Delayed or ineffective treatment can create renal or perinephric abscess, papillary necrosis or gas-forming emphysematous infection.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Renal infection syndromeRed flag

Fever, rigors, loin or flank pain, costovertebral-angle tenderness, nausea and vomiting support pyelonephritis, with or without dysuria and frequency.

Systemic organ dysfunctionRed flag

Altered consciousness, low blood pressure, tachypnoea, hypoxaemia, oliguria, mottling or raised lactate indicates sepsis requiring immediate escalation.

Obstruction cluesRed flag

Colicky pain, haematuria, anuria, known stones, hydronephrosis, pelvic malignancy, neurogenic bladder or solitary kidney increases urgency for imaging and drainage.

Renal or perinephric abscessRed flag

Persistent fever, focal tenderness or bacteraemia despite active therapy suggests an abscess, infected cyst or other undrained focus.

High-risk hostRed flag

Pregnancy, diabetes, transplantation, immune suppression, male sex, renal impairment and recent instrumentation lower the threshold for admission and imaging.

Red flags requiring action

Hypotension, tachypnoea, confusion, mottling, rising lactate or oliguria indicates urinary sepsis.
Flank pain with anuria, hydronephrosis, stone history or solitary kidney suggests obstructed infection.
Pregnancy with fever or flank pain requires urgent obstetric-aware assessment and usually hospital care.
Persistent vomiting, severe dehydration or inability to take oral treatment requires intravenous therapy and reassessment.
Failure to improve within 48 hours raises concern for resistance, abscess, obstruction or an alternative diagnosis.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Midstream urine culture and susceptibilityFirst step
Why
Confirm the urinary organism and allow directed antimicrobial treatment.
Interpretation and limitations
Collect before antibiotics where possible. A negative result after prior treatment does not exclude infection; mixed growth may reflect poor collection.
02
Blood cultures
Why
Identify bacteraemia in sepsis, severe illness or diagnostically uncertain infection.
Interpretation and limitations
Take two appropriately filled sets before antibiotics when this creates no delay. Concordant urine and blood isolates strengthen source attribution.
03
Full blood count, renal profile, CRP and glucose
Why
Assess inflammatory response, renal injury, dosing safety and diabetic decompensation.
Interpretation and limitations
Creatinine guides antimicrobial and contrast decisions; normal leucocytes or CRP does not exclude early severe infection.
04
Lactate and blood gas
Why
Evaluate perfusion and metabolic disturbance when sepsis is suspected.
Interpretation and limitations
Trend lactate with clinical perfusion, urine output and response to resuscitation rather than using a single value as a diagnostic test.
05
Renal ultrasound and targeted CT
Why
Detect hydronephrosis, stone, abscess, gas-forming infection or another abdominal source.
Interpretation and limitations
Ultrasound avoids radiation and is useful in pregnancy; CT better defines stone and complications when severe illness, obstruction or poor response persists.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Lower urinary infection

Dysuria and frequency without fever, flank pain or systemic features supports cystitis rather than renal parenchymal infection.

Ureteric colic

Severe colicky flank pain and haematuria may occur without infection, but fever or sepsis converts obstruction into an emergency.

Renal infarction

Abrupt flank pain, haematuria, high lactate dehydrogenase and embolic risk can mimic infection despite negative urine culture.

Abdominal or pelvic disease

Appendicitis, cholecystitis, pancreatitis, ectopic pregnancy and pelvic inflammatory disease can produce fever and regional pain overlapping pyelonephritis.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01SEPSISResuscitate and treat immediatelyFirst stepPyelonephritis is accompanied by organ dysfunction, shock, severe vomiting or inability to take oral treatment.

1Use ABCDE, measure glucose and lactate, establish access, monitor urine output and give oxygen and intravenous crystalloid according to physiology.
2Obtain urine and blood cultures promptly and start a locally recommended intravenous regimen adjusted for allergy, renal function and previous resistant isolates.
3Image urgently when obstruction, abscess, emphysematous infection or another source is possible and involve urology before deterioration.
4Review antimicrobial route within 48 hours, but continue inpatient monitoring until sepsis and oral intake are reliably improving.

02OUTPATIENTUse oral treatment selectivelyA non-pregnant adult is stable, can take fluids and medicine and has no immediate complication concern.

1Obtain urine culture and assess pregnancy possibility, renal function, allergy, recent antibiotics and previous isolates before treatment.
2Choose a NICE-listed oral regimen using susceptibility and resistance risk; cefalexin is an option, while co-amoxiclav and trimethoprim require susceptibility.
3Use ciprofloxacin only when other commonly recommended antibiotics are inappropriate and explain serious fluoroquinolone adverse effects.
4Review if symptoms worsen or fail to begin improving within 48 hours and change therapy according to culture and clinical response.

03DRAINDecompress infected obstructionImaging or clinical findings indicate hydronephrosis, an obstructing stone, anuria or infected collecting-system pressure.

1Contact urology immediately and communicate physiology, renal function, anticoagulation, anatomy and the time of the last antimicrobial dose.
2Arrange emergency ureteric stent or percutaneous nephrostomy according to anatomy, stability and local expertise; do not wait for antibiotics to fail.
3Send urine from above the obstruction for culture during drainage when feasible and reconcile it with blood and bladder isolates.
4DefinitiveDefer definitive stone clearance until sepsis is controlled while maintaining drainage, targeted therapy and renal-function surveillance.

04REASSESSReview response and sourceSymptoms persist or expected improvement has not occurred within the planned review interval.

1Repeat observations and examination and look actively for obstruction, abscess, resistant infection or another abdominal diagnosis.
2Review cultures, antimicrobial exposure, absorption, renal function and adverse effects and narrow or change treatment with a documented reason.
3EscalationEscalate persistent fever, pain, bacteraemia or renal deterioration to urology, microbiology and critical care as clinically indicated.
4Give explicit return advice for confusion, vomiting, reduced urine output, increasing pain or new circulatory symptoms.

Key medicines and prescribing safety5 treatments · regimens, roles and cautions

NICE first-choice oral beta-lactam treatment for eligible non-pregnant adults with acute pyelonephritis.

Cefalexin oral regimen

Give 500 mg orally twice or three times daily for seven to ten days, using higher severe-infection dosing only within current guidance.

Clarify beta-lactam allergy, adjust for renal impairment, review culture susceptibility and escalate rather than merely increasing dose when vomiting, sepsis or obstruction is present.

Provides an oral option for susceptible pyelonephritis when the organism and patient factors support its use.

Co-amoxiclav oral regimen

Give 625 mg orally three times daily for seven to ten days only when urine culture confirms susceptibility.

Do not use empirically when resistance risk is significant; check penicillin allergy, renal function, previous hepatic reaction and Clostridioides difficile risk.

Provides high oral bioavailability and renal tissue activity for susceptible organisms when safer recommended options cannot be used.

Ciprofloxacin oral regimen

Give 500 mg orally twice daily for seven days only when other commonly recommended antibiotics are inappropriate.

Follow MHRA restrictions; assess tendon, neurological, psychiatric, vascular, cardiac and glycaemic risk, renal function, interactions and pregnancy, and stop for serious adverse effects.

Provides once-daily broad parenteral coverage while culture and source-control information are obtained.

Ceftriaxone intravenous regimen

Give 1 to 2 g intravenously once daily when selected by local guidance for adults requiring parenteral pyelonephritis treatment.

Clarify severe beta-lactam allergy, review biliary disease and Clostridioides difficile risk, follow local resistance policy and narrow promptly when susceptibility allows.

Provides rapid Gram-negative activity in severe urinary infection or where resistance risk affects empirical treatment.

Gentamicin initial regimen

Give 5 to 7 mg/kg intravenously as an initial dose when locally indicated, then use weight, renal function and serum-level guided dosing.

Use the local dosing weight and nomogram, check pregnancy, renal and auditory risk, obtain levels before repeat dosing and avoid unplanned prolonged exposure.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Septic shock

Bloodstream spread causes vasoplegia, tissue hypoperfusion and multiorgan failure, especially when urinary obstruction remains undrained during treatment.

Renal and perinephric abscess

Focal suppuration produces persistent fever or pain despite therapy and may require image-guided or operative drainage.

Acute kidney injury

Sepsis, dehydration, bilateral obstruction and nephrotoxic treatment can combine to reduce renal filtration and significantly disturb electrolytes.

Emphysematous infection

Gas-forming necrotising renal infection occurs particularly with diabetes or obstruction and needs urgent multidisciplinary source control.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Repeat observations, mental state, perfusion and urine output frequently until systemic illness has clearly resolved.
Review creatinine and electrolytes daily during severe infection, aminoglycoside use, obstruction or active fluid resuscitation.
Check urine and blood culture results daily and narrow, change or stop therapy with a documented duration.
Confirm improvement within 48 hours; persistent fever or pain requires imaging review and reconsideration of abscess or obstruction.
After drainage, document device patency, definitive stone or obstruction plan and urology follow-up before discharge.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Obstruction changes everything

An infected blocked kidney is a source-control emergency; apparently active antibiotics cannot reliably overcome infected high-pressure urine.

Bladder drugs are insufficient

Nitrofurantoin and oral fosfomycin achieve urinary but not dependable renal parenchymal concentrations and should not treat pyelonephritis.

Oral does not mean weak

A suitable oral agent can treat stable disease when absorption, susceptibility and follow-up are reliable; route follows physiology and pharmacology.

Culture is routine here

Unlike straightforward cystitis, suspected pyelonephritis warrants urine culture because resistance and treatment consequences are greater.

Pregnancy lowers admission threshold

Maternal sepsis and obstetric complications can evolve quickly, so pregnant patients need prompt culture, treatment assessment and obstetric involvement.

11Common pitfallsFrequent interpretation and management errors.

01
Do not use nitrofurantoin or single-dose oral fosfomycin for renal parenchymal infection.
02
Do not postpone urological drainage of infected obstruction while waiting to see whether another antibiotic dose works.
03
Do not prescribe ciprofloxacin routinely without considering recommended alternatives and current MHRA restrictions.
04
Do not interpret persistent fever after 48 hours as expected without reassessing susceptibility, abscess and obstruction.
05
Do not discharge a vomiting or septic patient merely because blood pressure transiently improves after fluid.