What's the next step in managing a 42-year-old diabetic female patient with pyelonephritis of the right kidney and a Double J (DJ) stent in place, who has been treated with piperacillin/tazobactam (Inj pipzo 4.5) for 5 days, meropenem (Inj meropenem) for 5 days, and ceftazidime/avibactam (Inj ceftazidime plus avibactam 2.5 Gm) for 5 days, and presents with leukocytosis (raised WBC count of 24,000) without fever, but occasional fever spikes, and is symptomatically better?

Next Steps in Management of Persistent Leukocytosis and Fever Spikes Despite Broad-Spectrum Antibiotics

Immediately obtain repeat blood and urine cultures, and perform urgent imaging (CT scan with contrast) to evaluate for complications such as renal abscess, perinephric abscess, or persistent obstruction, as failure to improve within 48-72 hours of appropriate therapy mandates investigation for these complications. 1, 2

Immediate Diagnostic Evaluation

Your patient has received 15 days of escalating broad-spectrum antibiotics (piperacillin-tazobactam, meropenem, and ceftazidime-avibactam) yet maintains persistent leukocytosis (WBC 24,000) with occasional fever spikes despite symptomatic improvement. This clinical picture suggests either:

• Inadequate source control - The DJ stent may be obstructed, malpositioned, or serving as a nidus for biofilm-related infection 3
• Complicated pyelonephritis - Abscess formation, emphysematous pyelonephritis (particularly in diabetics), or perinephric extension 1, 2
• Resistant organism - Despite broad coverage, an unidentified resistant pathogen may be present 1

Critical Imaging and Cultures

• Obtain CT scan of abdomen/pelvis with IV contrast immediately to evaluate for renal or perinephric abscess, emphysematous changes, or obstruction - diabetic patients have up to 50% risk of atypical presentations and complications 1
• Repeat blood cultures (2 sets from separate sites) and urine culture before any antibiotic changes to identify persistent or new pathogens 1, 2
• Review all prior culture data and sensitivities to ensure current coverage is appropriate 1

Source Control Assessment

The DJ stent must be evaluated as a potential source of persistent infection, as intravascular devices and urinary catheters infected with gram-negative bacilli often require removal for cure, particularly with biofilm-producing organisms. 3

• Consider DJ stent exchange or removal if imaging shows no drainable collection - the stent may harbor biofilm-producing organisms (Pseudomonas, Acinetobacter, Stenotrophomonas) that are notoriously difficult to eradicate with antibiotics alone 3
• If obstruction is identified on imaging, urgent decompression within hours is required as obstructive pyelonephritis with sepsis has high mortality without drainage 2
• If abscess is identified (>3 cm), percutaneous or surgical drainage is indicated in addition to continued antibiotics 1, 2

Antibiotic Management Considerations

Given the extensive antibiotic exposure and persistent inflammation despite symptomatic improvement, several scenarios must be considered:

If Cultures Remain Negative

• Continue current ceftazidime-avibactam as it provides excellent coverage for ESBL-producing Enterobacteriaceae and Pseudomonas, which are common in complicated UTI with instrumentation 4, 5
• Total duration should be 10-14 days for complicated pyelonephritis - you are currently at day 15 total, so consider completing 14 days from when fever resolves if source control is achieved 3, 1
• Do not add additional antibiotics empirically without culture data, as this increases toxicity without proven benefit 3

If New Resistant Organism Identified

• For carbapenem-resistant Enterobacteriaceae (CRE), continue ceftazidime-avibactam as it has 73% cure rate for complicated UTI with CRE 6, 5
• For MDR Pseudomonas, ceftazidime-avibactam or addition of an aminoglycoside may be considered based on susceptibilities 5
• Combination therapy with two active agents should be continued for the full treatment duration if XDR/PDR organisms are identified 3

Monitoring and Response Assessment

• Most patients with appropriate therapy become afebrile within 48-72 hours - your patient's occasional fever spikes at day 15 are concerning 1, 2
• Persistent leukocytosis without clinical deterioration may represent slow resolution in diabetic patients, but imaging is still mandatory to exclude complications 1, 7
• Monitor renal function closely - adjust antibiotic doses if creatinine clearance declines, typically reducing by 30-50% with significant eGFR reduction 1, 2

Diabetes-Specific Considerations

Diabetic patients with pyelonephritis have significantly higher rates of complications (renal abscess, emphysematous pyelonephritis) and lower cure rates compared to non-diabetic patients. 1, 7

• Maintain tight glucose control with target <180 mg/dL using insulin infusion if needed, as hyperglycemia impairs immune function and promotes bacterial growth 2
• Diabetic patients had 75.4% cure rates versus 86.1% in non-diabetics in large trials, reflecting increased comorbidities and complications 7
• Up to 50% of diabetic patients lack typical flank tenderness, so absence of classic symptoms does not exclude serious complications 1

Critical Pitfalls to Avoid

• Never delay imaging in a patient who fails to improve within 72 hours - mortality increases significantly with delayed diagnosis of abscess or obstruction 1, 2
• Do not assume symptomatic improvement equals cure - persistent leukocytosis and fever spikes mandate investigation regardless of subjective improvement 1, 2
• Avoid removing the DJ stent without imaging first - if obstruction or abscess is present, stent removal without drainage could worsen sepsis 2
• Do not continue escalating antibiotics indefinitely without source control - if a drainable collection or obstructed stent is present, antibiotics alone will fail 3, 2

Recommended Algorithm

1. Order CT abdomen/pelvis with IV contrast today 1, 2
2. Obtain repeat blood and urine cultures before any antibiotic changes 1, 2
3. Continue ceftazidime-avibactam at current dose pending imaging and culture results 4
4. If imaging shows abscess >3 cm or obstruction: arrange urgent drainage/intervention 1, 2
5. If imaging negative and cultures negative: consider DJ stent exchange as potential biofilm source 3
6. If cultures grow resistant organism: adjust antibiotics based on susceptibilities and continue for 10-14 days total 1, 5
7. Optimize glucose control to target <180 mg/dL 2