Treatment for Acinetobacter Infections with KPC Resistance
For Acinetobacter infections with KPC (Klebsiella pneumoniae carbapenemase) resistance, ceftazidime/avibactam or meropenem/vaborbactam should be used as first-line treatment options. 1, 2
First-Line Treatment Options
- Ceftazidime/avibactam or meropenem/vaborbactam are the most effective first-line treatments for KPC-producing organisms with strong recommendation and moderate certainty of evidence 1, 2
- Meropenem/vaborbactam has demonstrated higher clinical cure rates, decreased mortality, and reduced nephrotoxicity compared to traditional therapies in clinical studies 2
- For respiratory infections such as pneumonia, meropenem/vaborbactam may be particularly effective due to better epithelial lining fluid concentrations (intrapulmonary penetration ratios of 63% for meropenem and 65% for vaborbactam) 2, 3
Alternative Treatment Options
- Imipenem/relebactam and cefiderocol may be considered as alternatives when first-line options are not available (conditional recommendation, low certainty of evidence) 1, 2
- Polymyxins (colistin) can be effective for carbapenem-resistant Acinetobacter with acceptable toxicity, with clinical cure rates of approximately 57% reported in patients with Acinetobacter VAP 1
- Ampicillin-sulbactam at optimal doses may be effective in some cases, even against some imipenem-resistant isolates 1
- Tigecycline has activity against many multidrug-resistant organisms, though resistance can develop through MDR efflux pumps in Acinetobacter 4, 5
Combination Therapy Considerations
- Combination therapy may be more effective than monotherapy for highly resistant strains 5, 6
- Fosfomycin-containing combination therapy may be considered, particularly when combined with tigecycline, polymyxin, or carbapenems 2
- Aminoglycosides may be used in combination regimens, though susceptibility is variable and tissue penetration may be limited 1
- Aerosolized antibiotic delivery (colistin or aminoglycosides) can be considered as adjunctive therapy for respiratory infections to improve local drug concentrations 1
Diagnostic Considerations
- Rapid molecular testing should be used to identify specific carbapenemase types to guide appropriate therapy 3, 7
- KPC-producing bacteria are often misidentified by routine susceptibility testing and may be incorrectly reported as sensitive to carbapenems 8
- Resistance to ertapenem is common in KPC-producing organisms and may be a better indicator of KPC presence 8
Monitoring and Follow-up
- Monitor for emergence of resistance, particularly with newer agents 2, 4
- Daily clinical assessment for treatment response is essential, with follow-up cultures to document clearance of infection 3
- For bloodstream infections, a minimum of 7-14 days of appropriate therapy is recommended 2, 3
Important Pitfalls to Avoid
- Traditional antibiotic regimens, including colistin monotherapy, have shown poor efficacy and unfavorable toxicity profiles compared to newer agents 7
- Acinetobacter species can rapidly develop resistance during treatment, particularly through MDR efflux pump mechanisms 4, 9
- Inappropriate use of carbapenems should be avoided to reduce selective pressure for resistance 7
- Third-generation cephalosporins should be avoided as monotherapy when ESBL-producing organisms are suspected or isolated 1