What is the treatment for OXA-48 (Oxacillinase-48) resistant Klebsiella (Klebsiella pneumoniae) infections?

Treatment of OXA-48 Resistant Klebsiella Pneumoniae Infections

Ceftazidime/avibactam should be used as the first-line treatment option for infections caused by OXA-48-like producing carbapenem-resistant Klebsiella pneumoniae. 1, 2

First-Line Treatment Approach

• Ceftazidime/avibactam is recommended as the first-line treatment for OXA-48-producing carbapenem-resistant Enterobacterales (CRE) infections, including Klebsiella pneumoniae 1, 2
• The recommended dosage for adults is 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) administered every 8 hours by intravenous infusion over 2 hours 3
• For intra-abdominal infections, ceftazidime/avibactam should be combined with metronidazole 3
• Treatment duration depends on the infection site: 5-14 days for intra-abdominal infections, 7-14 days for urinary tract infections, and 7-14 days for pneumonia 3

Evidence Quality and Considerations

• The recommendation for ceftazidime/avibactam has a CONDITIONAL strength with VERY LOW certainty of evidence 1, 2
• This recommendation is based on observational studies with small sample sizes that have shown promising results 1
• One comparative study demonstrated favorable outcomes in patients with severe CRE infections where OXA-48 was the predominant carbapenemase 1
• Delay in diagnosis and initiation of appropriate antimicrobial therapy is associated with poor outcomes in OXA-48-producing Enterobacteriaceae infections 4

Alternative Treatment Options

• For patients where ceftazidime/avibactam is unavailable or contraindicated, consider the following alternatives:
  • Cefiderocol may be considered as an alternative option based on in vitro activity, though clinical evidence is limited 1, 5
  • For ESBL-negative OXA-48-producing Klebsiella pneumoniae, cephalosporins (cefepime, ceftriaxone) might be considered in selected cases 6
  • Combination therapy with fosfomycin plus carbapenems (imipenem or meropenem) or tigecycline has shown synergistic activity in vitro 7
  • In severe cases, combination therapy with double carbapenems (meropenem and imipenem), amikacin, colistin, and tigecycline has been used successfully in pediatric patients 8

Important Clinical Considerations

• Rapid identification of the specific carbapenemase is crucial for early initiation of appropriate therapy 1
• Local epidemiology and resistance patterns should guide therapy decisions 2
• OXA-48 producers that do not co-produce extended-spectrum β-lactamases (ESBLs) may retain susceptibility to certain cephalosporins, but 92.5% of isolates in one study co-produced ESBLs 4, 6
• Mortality rates for OXA-48-producing Enterobacteriaceae bloodstream infections are high (30-day mortality of 50% reported in one study), highlighting the importance of prompt appropriate treatment 4
• Avoid colistin in combination with fosfomycin as this combination has shown antagonistic effects in vitro 7

Treatment Algorithm

1. Confirm OXA-48 production through rapid diagnostic testing 1
2. Initiate ceftazidime/avibactam as first-line therapy 1, 2
3. For intra-abdominal infections, add metronidazole 3
4. If ceftazidime/avibactam is unavailable:
   • Consider cefiderocol if available 1, 5
   • For ESBL-negative isolates only: consider cephalosporins based on susceptibility testing 6
   • For severe infections: consider combination therapy with carbapenems plus other active agents (fosfomycin, aminoglycosides, tigecycline) based on susceptibility 8, 7
5. Adjust therapy based on clinical response and microbiological data 1
6. Complete appropriate duration of therapy based on infection site 3