Treatment Approach for Recurrent Klebsiella Infection with Possible Occult Enterococcus
For this patient with recurrent Klebsiella infection and history of Enterococcus co-infection, I recommend ceftazidime-avibactam (2.5g IV every 8 hours) combined with ampicillin (2g IV every 6 hours) for 4-6 weeks, followed by long-term suppressive therapy if source control cannot be achieved. 1, 2
Critical Context: The NGS Test Timing Issue
The latest NGS showing only Klebsiella was performed just 3 days post-antibiotics, which creates significant diagnostic uncertainty:
- Enterococcus may still be present but suppressed by recent augmentin exposure 3
- The pattern of full relapse after each treatment course strongly suggests either inadequate source control or persistent polymicrobial infection 1
- Both organisms have repeatedly cultured together, indicating a biofilm or deep-seated focus 1
Primary Treatment Regimen
Dual Coverage Strategy
Ceftazidime-avibactam for Klebsiella:
- Dose: 2.5g (ceftazidime 2g + avibactam 0.5g) IV every 8 hours 2
- This agent specifically targets carbapenem-resistant and ESBL-producing Klebsiella, including KPC-producing strains 2, 4
- Clinical cure rates of 81-92% for complicated intra-abdominal infections with resistant Klebsiella 2
Ampicillin for presumed occult Enterococcus:
- Dose: 2g IV every 6 hours 1
- Enterococci are intrinsically resistant to cephalosporins, and ceftazidime-avibactam alone will not cover Enterococcus 3
- Given the recurrent pattern and previous positive cultures, empiric Enterococcal coverage is essential 1
Treatment Duration
- Minimum 4 weeks, preferably 6 weeks of IV combination therapy 1
- Extended duration justified by: multiple relapses, healthcare-associated infection, and likely biofilm-associated infection 1
Alternative Regimens if First-Line Fails
For Carbapenem-Susceptible Klebsiella (if susceptibilities allow):
Meropenem 1g IV every 8 hours + Ampicillin 2g IV every 6 hours 1
- This combination provides robust coverage for both organisms
- Meropenem has excellent tissue penetration for deep-seated infections 1
For Multidrug-Resistant Scenarios:
If Klebsiella shows additional resistance:
- Consider adding fosfomycin 8g IV every 8 hours to the ceftazidime-avibactam regimen 5
- Combination of fosfomycin with other agents shows synergy and reduces resistance emergence 5
If VRE (vancomycin-resistant Enterococcus) is suspected:
- Replace ampicillin with daptomycin 6-8 mg/kg IV every 24 hours 1
- Alternative: linezolid 600mg IV every 12 hours, though toxicity limits long-term use 1
Critical Management Considerations
Source Control Assessment
This patient requires urgent evaluation for:
- Undrained abscess or fluid collection 1
- Foreign body (catheter, surgical hardware, mesh) 1
- Fistula formation 1
- The recurrent pattern after 3 separate treatment courses strongly suggests inadequate source control 1
Resistance Monitoring
- Repeat cultures after 48-72 hours of therapy to document clearance 1
- If bacteremia persists beyond 72 hours, strongly consider endovascular infection or metastatic seeding 1
- Monitor for emergence of ceftazidime-avibactam resistance, which can develop during therapy 6
Long-Term Suppressive Therapy
If source cannot be eliminated or patient refuses further surgery:
For Klebsiella suppression (choose based on susceptibilities):
- Oral fluoroquinolone (ciprofloxacin 500-750mg twice daily) if susceptible 1
- Oral fosfomycin 3g every 48-72 hours 7
- Trimethoprim-sulfamethoxazole 1-2 DS tablets twice daily if susceptible 7
Must add Enterococcal coverage:
- Amoxicillin 500mg three times daily 1
- If VRE: linezolid 600mg twice daily (monitor for toxicity) or pristinamycin if available 1
Duration of Suppression
- Continue indefinitely while foreign body/source remains 1
- Monitor for toxicity, particularly with linezolid (bone marrow suppression, neuropathy) 1
Common Pitfalls to Avoid
Do not use ceftazidime-avibactam alone - this will not cover Enterococcus and guarantees treatment failure 3
Do not assume negative NGS 3 days post-antibiotics excludes Enterococcus - the organism may be suppressed but not eradicated 1
Do not use shorter treatment courses - this patient has already failed three separate 3-week courses 1
Do not delay imaging - recurrent infection after adequate antibiotics mandates evaluation for undrained collections or structural abnormalities 1
Avoid carbapenem monotherapy for polymicrobial infections - combination therapy shows superior outcomes for healthcare-associated infections with resistant organisms 1, 8