From the Guidelines
Ceftazidime/avibactam and meropenem/vaborbactam are the recommended first-line treatment options for colistin-resistant Klebsiella pneumoniae infections, due to their strong efficacy and safety profiles, as evidenced by recent studies 1. When considering treatment options for colistin-resistant Klebsiella pneumoniae infections, it is essential to prioritize novel β-lactam agents that have shown promising results in recent studies.
Key Considerations
- Ceftazidime/avibactam has been shown to have a higher clinical cure rate and lower risk of nephrotoxicity compared to colistin 1.
- Meropenem/vaborbactam has also demonstrated a higher clinical cure rate, decreased mortality, and reduced nephrotoxicity compared to the best available therapy, which often includes colistin 1.
- The choice between ceftazidime/avibactam and meropenem/vaborbactam may depend on the site of infection, with meropenem/vaborbactam potentially being preferred for pneumonia due to its high epithelial lining fluid concentrations 1.
Alternative Options
- Imipenem/relebactam and cefiderocol may also be considered as potential alternatives for the treatment of colistin-resistant Klebsiella pneumoniae infections, although clinical studies on their efficacy are limited 1.
Treatment Approach
- Treatment duration typically ranges from 10-14 days, with longer courses for complicated infections.
- Source control through drainage of abscesses or removal of infected devices is crucial for successful treatment.
- Antimicrobial susceptibility testing is essential to guide therapy, as resistance patterns vary significantly.
- Consultation with infectious disease specialists is strongly recommended due to the complexity of managing these highly resistant infections.
From the FDA Drug Label
Among Gram-negative uropathogens from both arms of Trial 2, genotypic testing identified certain ESBL groups (e.g., TEM-1, SHV-12, CTX-M-15, CTX-M-27, KPC-2, KPC-3, OXA-48) and AmpC beta-lactamases expected to be inhibited by avibactam in isolates from 273/281 (97. 2%) patients in the mMITT population. The microbiological response rates at the follow-up visit by baseline CAZ-NS uropathogen in the mMITT population are presented in Table 21. Klebsiella pneumoniae42/55 (76.4)39/65 (60.0)
The treatment options for colistin-resistant Klebsiella pneumoniae infections include:
- Avibactam in combination with ceftazidime, which has shown a microbiological response rate of 76.4% in patients with Klebsiella pneumoniae infections 2.
- Carbapenem antibacterial drugs, such as meropenem, imipenem, and doripenem, which were used as the best available therapy (BAT) in the trial 2. Note that colistin resistance is often associated with efflux pumps, but the provided drug label does not directly address the treatment of colistin-resistant Klebsiella pneumoniae infections.
From the Research
Colistin Resistance in Klebsiella pneumoniae
- Colistin resistance in Klebsiella pneumoniae is a growing concern globally, including in India, with studies indicating a rise in resistance rates 3, 4, 5, 6, 7.
- The mechanisms of colistin resistance in Klebsiella pneumoniae are multifactorial, involving chromosomal genes or plasmids, with the emergence of transmissible, plasmid-mediated colistin resistance being a significant concern 4, 5.
- Efflux pumps have been identified as a mechanism of colistin resistance in diverse clones of Klebsiella pneumoniae, including those from aquatic environments in India 6.
Treatment Options for Colistin-Resistant Klebsiella pneumoniae Infections
- Combination therapy with colistin and other antibiotics, such as aminoglycosides, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin, has shown synergistic effects against colistin-resistant Klebsiella pneumoniae isolates 3.
- Combinations of colistin with amikacin, fosfomycin, or levofloxacin have been found to be effective against colistin-resistant isolates 3.
- However, the emergence of resistance to reserve drugs, including colistin, highlights the need for judicious use of antibiotics and the development of new therapeutic options 4, 5, 7.
Global and Indian Context
- Colistin resistance in Klebsiella pneumoniae has been reported globally, with increasing rates of resistance in several countries, including India 4, 5, 7.
- In India, carbapenem resistance in Klebsiella pneumoniae is high, with colistin being used as a reserve drug, leading to the emergence of colistin resistance 5.
- The need for enhanced surveillance, compliance with infection prevention procedures, and antimicrobial stewardship programs is emphasized to limit the spread of colistin-resistant Klebsiella pneumoniae in India and globally 4.