What is the working diagnosis for a 58‑year‑old Filipino woman with hypertension and type 2 diabetes mellitus who presents with fever, left flank pain, left costovertebral angle tenderness, oliguria, vomiting, leukocytosis, anemia, hypoalbuminemia, acute kidney injury (serum creatinine 222.9 µmol/L), and a urine culture growing Escherichia coli resistant to cefuroxime, ceftriaxone, and ciprofloxacin?

Working Diagnosis: Acute Complicated Pyelonephritis with Acute Kidney Injury

This 58-year-old Filipino woman with diabetes and hypertension presents with acute complicated pyelonephritis complicated by acute kidney injury (AKI), evidenced by fever (38°C), left flank pain, left costovertebral angle tenderness, oliguria, elevated creatinine (222.9 µmol/L), leukocytosis (13.35 × 10⁹/L with 75.2% neutrophils), and urine culture growing ESBL-producing E. coli resistant to cefuroxime, ceftriaxone, and ciprofloxacin.

Clinical Reasoning

Why This is Complicated Pyelonephritis

• Classic triad present: fever (38°C), left flank pain, and left CVA tenderness definitively indicate upper urinary tract involvement 1
• Systemic inflammatory response: leukocytosis (13.35 × 10⁹/L) with neutrophil predominance (75.2%) confirms systemic infection 1
• Oliguria and AKI: serum creatinine 222.9 µmol/L (approximately 2.5 mg/dL) represents acute kidney injury, which classifies this as complicated disease 1
• Diabetes mellitus: this patient's diabetes is a critical complicating factor—diabetic patients are at significantly higher risk for renal abscesses, emphysematous pyelonephritis, and have atypical presentations in up to 50% of cases 1
• Multidrug-resistant organism: the E. coli isolate resistant to cefuroxime, ceftriaxone, and ciprofloxacin indicates an ESBL-producing organism, which further complicates management 1, 2

Supporting Laboratory Findings

• Urinalysis: pyuria (abundant WBCs), bacteriuria (moderate gram-negative bacilli), and albuminuria (+1) confirm active infection 1
• Urine culture: 40-50 gram-negative bacilli per oil immersion field with moderate growth of E. coli susceptible only to amikacin, gentamicin, piperacillin-tazobactam, and ertapenem 1
• Hypoalbuminemia (29 g/L): suggests systemic inflammatory response and possible capillary leak 1
• Anemia (Hgb 10.8 g/dL): may reflect chronic disease or dilution from fluid resuscitation 3

Differential Considerations

Why Not Simple Cystitis?

• Fever, flank pain, CVA tenderness, and systemic symptoms (vomiting, oliguria) definitively exclude uncomplicated lower UTI 1
• The presence of AKI further confirms upper tract involvement 1

Why Not Urosepsis (Yet)?

• Blood pressure stable (130/70 mmHg) without hypotension
• No altered mental status or signs of organ dysfunction beyond the kidneys
• However, this patient is at high risk for progression to urosepsis given diabetes, AKI, and multidrug-resistant organism 1
• The qSOFA score should be calculated: respiratory rate 24/min (1 point), but BP and mental status are normal 1

Critical Red Flags in This Case

Diabetes significantly increases risk of complications 1:

• Up to 50% of diabetic patients with pyelonephritis lack typical flank tenderness, making diagnosis more challenging 1
• Higher risk of renal abscess formation and emphysematous pyelonephritis 1
• This patient fortunately has classic symptoms, but requires close monitoring

Oliguria with AKI 1:

• Creatinine 222.9 µmol/L represents significant renal impairment
• Oliguria suggests either prerenal azotemia from volume depletion or acute tubular injury from infection
• Urgent imaging is required to exclude obstruction, which would mandate immediate decompression 1

ESBL-producing organism 1, 2:

• Resistance to cefuroxime, ceftriaxone, and ciprofloxacin confirms ESBL production
• This pattern is increasingly common in community-onset UTIs, occurring in approximately 13% of febrile UTIs requiring hospitalization 2
• Empiric therapy with third-generation cephalosporins or fluoroquinolones would have been discordant in this case 2

Immediate Management Priorities

1. Imaging to Exclude Obstruction (URGENT)

Renal ultrasound should be performed immediately 1:

• Diabetes, renal dysfunction, and oliguria mandate urgent imaging to exclude obstruction 1
• If obstruction is present, urgent urological decompression is required to prevent irreversible renal damage and progression to urosepsis 1, 3
• Ultrasound is preferred initially as it avoids contrast nephrotoxicity in the setting of AKI 1

If patient remains febrile after 72 hours or deteriorates clinically, contrast-enhanced CT should be obtained 1:

• CT is superior for detecting renal abscess, emphysematous pyelonephritis, or perinephric extension 1
• In diabetic patients, a lower threshold for CT imaging is appropriate given higher complication rates 1

2. Empiric Antibiotic Therapy

Given the culture results showing susceptibility to amikacin, gentamicin, piperacillin-tazobactam, and ertapenem, immediate empiric therapy should be:

Preferred regimen 1, 4:

• Piperacillin-tazobactam 3.375 g IV every 6 hours (or 4.5 g every 8 hours if severe)
• This provides excellent coverage for ESBL-producing E. coli and achieves high urinary concentrations 1
• Adjust dose for renal function: with creatinine 222.9 µmol/L (estimated CrCl ~30-40 mL/min), extend interval to every 8 hours 4

Alternative regimen 1, 4:

• Ertapenem 1 g IV once daily is an excellent carbapenem option for ESBL organisms
• Requires dose adjustment: 500 mg IV once daily if CrCl <30 mL/min 4

Aminoglycoside considerations 1:

• While the organism is susceptible to amikacin and gentamicin, aminoglycosides should be avoided as monotherapy in the setting of AKI (creatinine 222.9 µmol/L) due to nephrotoxicity risk 1
• If used, gentamicin should be given as a single daily dose (5-7 mg/kg) with close monitoring of levels and renal function 1

Duration of therapy 1:

• Minimum 14 days for complicated pyelonephritis with AKI 1
• May consider 7 days only if patient becomes afebrile within 48 hours and shows rapid clinical improvement, but given diabetes and AKI, 14 days is safer 1

3. Supportive Care

Fluid resuscitation 1, 3:

• Oliguria with elevated creatinine suggests volume depletion
• Administer IV crystalloids (normal saline or lactated Ringer's) to restore euvolemia
• Monitor urine output, blood pressure, and repeat creatinine at 24-48 hours

Avoid nephrotoxic agents 1:

• Discontinue or adjust doses of enalapril and other nephrotoxic medications
• NSAIDs should be strictly avoided

Glycemic control 1:

• Tight glucose control is essential in diabetic patients with pyelonephritis to reduce complication risk 1
• Monitor blood glucose closely as infection and stress will increase insulin requirements

4. Monitoring for Clinical Response

Reassess at 48-72 hours 1, 3:

• If fever persists beyond 72 hours, obtain contrast-enhanced CT immediately to evaluate for abscess, emphysematous pyelonephritis, or other complications 1, 3
• If clinical deterioration occurs (hypotension, altered mental status, worsening renal function), escalate to ICU care and consider urosepsis management 1
• Repeat urine culture is not routinely needed if clinical improvement occurs 1

Common Pitfalls to Avoid

Do not delay imaging in diabetic patients with pyelonephritis 1:

• Diabetes is a major risk factor for complicated disease
• Lower threshold for CT imaging is appropriate

Do not use fluoroquinolones or third-generation cephalosporins empirically 1, 2:

• This organism is resistant to both classes
• In regions with high ESBL prevalence (>10%), empiric use of these agents results in discordant therapy in up to 63% of cases 2

Do not underestimate the severity of AKI 1:

• Creatinine 222.9 µmol/L with oliguria requires aggressive fluid resuscitation and close monitoring
• Failure to recognize and treat AKI can lead to irreversible renal damage

Do not assume clinical improvement means cure 1:

• Complete the full 14-day course of antibiotics
• Diabetic patients may have delayed response or silent complications 1

Do not treat based on urinalysis alone in future episodes 1, 5:

• This patient will likely have recurrent UTIs given diabetes
• Each episode requires urine culture to guide targeted therapy and monitor resistance patterns 1, 5

Prognosis and Follow-Up

• Most patients respond within 48-72 hours to appropriate antibiotic therapy 3
• Diabetic patients may have prolonged recovery and require extended monitoring 1
• Follow-up imaging is not routinely needed if clinical response is adequate 1
• Repeat creatinine at 1-2 weeks to ensure renal function recovery
• Consider prophylactic strategies if recurrent UTIs develop, including optimization of diabetes control and evaluation for structural abnormalities 1, 5