What investigations should be done for neutropenic sepsis with thrombocytopenia and eosinophilia suspected to be caused by Amoxicillin-clavulanic acid (Amoxicillin-clavulanate)?

Investigations for Neutropenic Sepsis with Thrombocytopenia and Eosinophilia Secondary to Amoxicillin-Clavulanic Acid

Immediately obtain two sets of blood cultures (one from peripheral vein and one from any indwelling catheter if present), complete blood count with differential, comprehensive metabolic panel including renal and liver function, coagulation studies, C-reactive protein, urinalysis with culture, chest radiograph, and discontinue amoxicillin-clavulanic acid while initiating broad-spectrum antibiotics that do not include beta-lactams. 1

Essential Immediate Investigations

Microbiological Studies

• Two sets of blood cultures from peripheral vein and any indwelling venous catheters before starting alternative antibiotic therapy 1
• Urine microscopy and culture 1
• Sputum microscopy and culture if respiratory symptoms present 1
• Stool microscopy and culture if gastrointestinal symptoms present 1
• Skin lesion aspirate/biopsy/swab if skin manifestations present 1

Hematologic and Biochemical Studies

• Urgent complete blood count to confirm neutrophil count, platelet count, and document eosinophil levels 1
• Bone marrow examination should be considered given the severe cytopenias, as drug-induced immune mechanisms can cause bone marrow hypoplasia 2
• Coagulation screen (PT, PTT, fibrinogen) to assess for disseminated intravascular coagulation risk, particularly important given thrombocytopenia 1
• Comprehensive metabolic panel including renal function (creatinine, BUN) and liver function tests (transaminases, bilirubin, alkaline phosphatase) 1
• C-reactive protein as inflammatory marker 1
• Lactate level for assessment of tissue perfusion and sepsis severity 1

Imaging Studies

• Chest radiograph as baseline imaging 1
• High-resolution chest CT if fever persists despite 72 hours of appropriate antibiotics or if respiratory symptoms develop, as neutropenic patients are at high risk for fungal infections 1

Drug-Specific Investigations

Given the suspected amoxicillin-clavulanic acid-induced cytopenias, additional testing is warranted:

• Direct antiglobulin test (Coombs test) and drug-dependent antibody testing using fluorescent antiglobulin technique, as penicillin-induced immune cytopenias are mediated by complement-fixing IgG antibodies 2
• Peripheral blood smear to evaluate cell morphology and rule out other causes of cytopenias 3
• Viral serologies (EBV, CMV, HHV-6) if DRESS syndrome is suspected given the eosinophilia, as viral reactivation commonly accompanies DRESS 4

Critical Management Considerations

The eosinophil count of 5 cells is actually eosinopenia (not eosinophilia), which is common in acute bacterial sepsis and represents consumption during the acute inflammatory response. However, if the question implies eosinophilia developed later or was misreported, consider DRESS syndrome evaluation with RegiSCAR scoring 4.

Antibiotic Selection

Do not restart amoxicillin-clavulanic acid. For empirical therapy in neutropenic sepsis, initiate:

• Monotherapy with meropenem, imipenem/cilastatin, piperacillin/tazobactam, or ceftazidime 1
• Add aminoglycoside if severe sepsis with hemodynamic instability, though this increases nephrotoxicity risk 1
• Avoid vancomycin unless specific indications exist: suspected catheter-related infection, known colonization with resistant gram-positive organisms, or positive blood cultures for gram-positive bacteria before identification 1

Monitoring Parameters

• Serial complete blood counts every 24-48 hours to monitor neutrophil and platelet recovery 3, 5
• Daily renal function if aminoglycosides used 1
• Hemodynamic monitoring (central venous pressure, mean arterial pressure, urine output, central venous oxygen saturation) if hypotension present, targeting MAP ≥65 mmHg 1

Common Pitfalls to Avoid

• Do not delay blood cultures waiting for fever spike; obtain immediately before starting alternative antibiotics 1
• Do not use aminoglycosides as sole empirical therapy due to nephrotoxicity concerns in neutropenic patients 1
• Do not assume eosinophilia without confirming absolute eosinophil count, as "5 cells" likely represents severe eosinopenia in sepsis context
• Do not overlook bone marrow evaluation in severe drug-induced cytopenias, as immune-mediated suppression of precursor cells can occur 2
• Do not restart any beta-lactam antibiotic in this patient given the severe reaction 3, 5, 4