Latest CLSI Guidelines for Klebsiella pneumoniae
The latest CLSI guidelines recommend that when using the new interpretive criteria for Klebsiella pneumoniae, routine testing for extended-spectrum β-lactamases (ESBL) is no longer necessary before reporting susceptibility results, though ESBL testing may still be useful for epidemiological or infection control purposes. 1
Key Interpretive Criteria Changes for K. pneumoniae
- For non-meningitis infections treated with intravenous penicillin, the new susceptibility breakpoints are ≤2 mg/L (susceptible), 4 mg/L (intermediate), and ≥8 mg/L (resistant) 1
- For oral penicillin treatment, the breakpoints remain unchanged at ≤0.06 mg/L (susceptible), 0.12–1 mg/L (intermediate), and ≥2 mg/L (resistant) 1
- Implementation of new carbapenem breakpoints can eliminate the need for screening or confirmatory testing for Klebsiella pneumoniae carbapenemases (KPC) by the modified Hodge test (MHT), except for epidemiology and infection control purposes 1
- For drugs with limited availability in many countries (moxalactam, cefonicid, cefamandole, and cefoperazone), ESBL testing should still be performed, and if positive, these drugs should be reported as resistant 1
Treatment Recommendations Based on Resistance Pattern
For Susceptible K. pneumoniae:
- Third and fourth-generation cephalosporins (ceftriaxone, cefotaxime, cefepime) are recommended as effective first-line treatments 2
- For susceptible non-meningitis pneumococcal infections, penicillin G 2 g (3.2 mU) IV Q4h is adequate for strains with a penicillin MIC of ≤8 mg/L 1
For ESBL-producing K. pneumoniae:
- Carbapenems (meropenem, imipenem-cilastatin, or ertapenem) remain the first-line treatment options 3
- The new ceftazidime (≤4 μg/mL) and unchanged cefepime (≤8 μg/mL) susceptible breakpoints fail to identify many ESBL-producing K. pneumoniae strains 1
For Carbapenem-resistant K. pneumoniae:
- Newer agents such as ceftazidime/avibactam and meropenem/vaborbactam are recommended as first-line options for carbapenem-resistant K. pneumoniae 1, 2, 3
- Imipenem/relebactam and cefiderocol may be considered as alternatives for KPC-producing strains 2, 3
- For MBL-producing strains, ceftazidime/avibactam plus aztreonam is preferred 4, 3
Diagnostic Testing Recommendations
- The modified Hodge test (MHT) is recommended for testing carbapenem-susceptible Enterobacteriaceae with elevated MICs or reduced disk diffusion zone sizes for the presence of carbapenemases 1
- MHT has demonstrated sensitivity and specificity exceeding 90% in identifying carbapenemase-producing Enterobacteriaceae 1
- Rapid molecular testing should be used to identify specific carbapenemase types to guide appropriate therapy 3
- Surveillance cultures (rectal or perirectal swabs) can help detect unrecognized CRKP colonization that may serve as reservoirs for transmission 1
Infection Control Considerations
- Early detection through targeted surveillance and strict infection control measures can help control the spread of carbapenem-resistant K. pneumoniae 1
- Contact precautions and reinforcement of hand hygiene are essential infection control measures 1
- Patients with unrecognized CRKP colonization have served as reservoirs for transmission during healthcare-associated outbreaks 1
Important Caveats and Pitfalls
- Local epidemiology and resistance patterns should be considered when selecting empiric therapy 4, 3
- Emergence of resistance to newer agents like ceftazidime/avibactam in KPC-producing isolates should be monitored 4
- For severe infections with multidrug-resistant strains, combination therapy with more than one in vitro active drug may be beneficial when limited to older agents like polymyxins, aminoglycosides, tigecycline, or fosfomycin 4
- Mortality is significantly lower with newer agents like ceftazidime/avibactam compared to older regimens 4