Is cefuroxime (Cefuroxime) effective for treating Klebsiella infections?

Cefuroxime Effectiveness for Klebsiella Infections

Cefuroxime has documented activity against susceptible Klebsiella species and is FDA-approved for treating Klebsiella infections, but its clinical utility is severely limited by high rates of resistance, particularly from ESBL-producing strains, making it an unreliable choice in contemporary practice. 1

FDA-Approved Indications

• Cefuroxime is officially indicated for treatment of infections caused by susceptible Klebsiella species, including lower respiratory tract infections, urinary tract infections, skin and skin-structure infections, and septicemia 1
• The FDA label specifically lists Klebsiella spp. as a susceptible organism for multiple infection types 1

Critical Limitations in Modern Clinical Practice

Resistance Patterns

• ESBL production is a major concern: Cefuroxime can select for extended-spectrum β-lactamase (ESBL)-producing Klebsiella strains, with prevalence of cefuroxime resistance reaching 8.3% in some surveillance data 2
• ESBL-producing strains may show susceptibility to cefuroxime on testing but still demonstrate elevated MICs that predict clinical failure 2
• The CLSI guidelines specifically note that interpretive criteria for cefuroxime (parenteral) were not revised in 2010 updates, meaning ESBL testing remains relevant for guiding therapy 3

Pharmacokinetic/Pharmacodynamic Concerns

• Recent PK/PD modeling demonstrates that even with aggressive dosing (1500 mg q6h), cefuroxime achieves probability of target attainment (PTA) <90% for E. coli and K. pneumoniae in healthy young volunteers 4
• The target of time above MIC (T>MIC) >50% cannot be reliably achieved for Klebsiella species even with maximal dosing 4
• This contrasts sharply with its adequate PTA for Streptococcus pneumoniae, highlighting organism-specific limitations 4

Historical vs. Contemporary Context

When Cefuroxime Was Effective

• Early studies (1976-1983) showed cefuroxime had "excellent in vitro activity" against Enterobacteriaceae including Klebsiella, with particular utility against cephalosporin-resistant strains 5, 6, 7
• It demonstrated beta-lactamase stability against many gram-negative producers at that time 6

Current Reality

• The emergence of ESBLs has fundamentally changed the landscape, with cefuroxime potentially selecting for resistant strains through selective pressure 2
• Cefuroxime-resistant Klebsiella often show cross-resistance to ciprofloxacin (10-fold MIC elevation) 2

Recommended Alternatives for Klebsiella Infections

For Carbapenem-Resistant Strains

• First-line: Ceftazidime/avibactam or meropenem/vaborbactam for KPC-producing strains 8
• For OXA-48 producers: Ceftazidime/avibactam 8
• For MBL producers: Ceftazidime/avibactam plus aztreonam 8

For Susceptible Strains

• Carbapenems remain the treatment of choice for carbapenem-susceptible, ESBL-producing Klebsiella 8
• Third-generation cephalosporins (ceftriaxone, ceftazidime) are preferred over cefuroxime when susceptibility is confirmed 3

Clinical Pitfalls to Avoid

• Do not rely on cefuroxime for empiric therapy of suspected Klebsiella infections in hospital settings where ESBL prevalence is significant 2
• Do not assume susceptibility based on older literature; local antibiograms and individual susceptibility testing are essential 3
• Avoid prolonged cefuroxime use as it creates selective pressure for ESBL emergence 8, 2
• Do not use cefuroxime for serious infections (septicemia, pneumonia) caused by Klebsiella without confirmed susceptibility and consideration of PK/PD limitations 4

When Cefuroxime Might Still Be Considered

• Community-acquired urinary tract infections with documented susceptibility and no ESBL production 1
• Skin and soft tissue infections with confirmed susceptibility 1
• Only after culture-directed therapy confirms MIC values predict adequate T>MIC achievement 4