Does cefuroxime (a second-generation cephalosporin) cover drug-resistant Streptococcus pneumoniae (pneumococcus)?

Cefuroxime Does NOT Adequately Cover Drug-Resistant Pneumococcus

Cefuroxime should not be relied upon for empiric treatment of drug-resistant Streptococcus pneumoniae, as it demonstrates poor activity against penicillin-resistant strains and cannot be predicted by susceptibility testing of other cephalosporins. 1

Key Evidence Against Cefuroxime for Drug-Resistant Pneumococcus

In Vitro Susceptibility Data

The IDSA guidelines provide clear susceptibility data stratified by penicillin resistance 1:

• Penicillin-susceptible strains (MIC <0.1 mg/mL): Cefuroxime covers >90% (111 rating)
• Intermediate resistance (MIC 0.1-1.0 mg/mL): Cefuroxime covers only >50% (1 rating)
• High-level resistance (MIC >2 mg/mL): Cefuroxime covers <40% (2 rating)

This represents a dramatic loss of coverage as resistance increases, making cefuroxime unreliable for drug-resistant strains. 1

Critical Guideline Statements

The IDSA explicitly states: "Cefuroxime is less active against S. pneumoniae, and the activity of this or other cephalosporins cannot be predicted by results of in vitro susceptibility tests with cefotaxime or ceftriaxone." 1

This means even if third-generation cephalosporins show susceptibility, cefuroxime may still fail. 1

Comparative Activity

A greater proportion of pneumococci exhibit resistance to second-generation cephalosporins (like cefuroxime) compared to third-generation agents (cefotaxime, ceftriaxone). 1

Among penicillin-resistant strains, up to one-half also have reduced susceptibility to third-generation cephalosporins, with even higher rates for second-generation agents. 1

Geographic Resistance Patterns

In Spain, where drug-resistant pneumococcus is highly prevalent, surveillance data showed 46% resistance to cefuroxime among 1,113 S. pneumoniae isolates, compared to only 13% for cefotaxime and 8% for ceftriaxone. 2

Higher percentages of resistance to cefuroxime were observed among both penicillin-intermediate and penicillin-resistant strains. 2

Clinical Context: When Cefuroxime May Still Be Used

Limited Exception for Intermediate Resistance

One retrospective study found that patients with pneumococcal bacteremia caused by intermediately resistant (not fully resistant) pneumococci could be treated with cefuroxime without increased mortality. 3

However, this study specifically noted:

• No cases of fully resistant pneumococci were isolated 3
• All isolates were only intermediately resistant to penicillin 3
• The authors concluded this approach "may be appropriate" only "in regions where fully resistant pneumococci are rare" 3

Important Caveat About Mortality Data

One study linked cefuroxime use in bacteremic pneumococcal pneumonia caused by penicillin non-susceptible strains to increased mortality. 1

Preferred Alternatives for Drug-Resistant Pneumococcus

For confirmed or suspected drug-resistant pneumococcus, use: 1

1. High-dose amoxicillin (3 g/day for adults; 90 mg/kg/day in children) - overcomes intermediate resistance 1
2. Third-generation cephalosporins: Cefotaxime or ceftriaxone (NOT cefuroxime) 1
3. Respiratory fluoroquinolones: Levofloxacin, moxifloxacin, gemifloxacin 1
4. Vancomycin or linezolid: For high-level resistance (MIC ≥4 mg/mL) 1

Clinical Algorithm

When considering antibiotics for pneumococcal pneumonia:

• If penicillin-susceptible: Penicillin, amoxicillin, or cefuroxime acceptable 1
• If intermediate resistance suspected: Use high-dose amoxicillin or third-generation cephalosporin 1
• If high-level resistance suspected (MIC ≥4 mg/mL): Use respiratory fluoroquinolone, vancomycin, or linezolid 1
• Never rely on cefuroxime for empiric coverage when drug resistance is a concern 1

Common Pitfall to Avoid

Do not assume that susceptibility to cefotaxime or ceftriaxone predicts susceptibility to cefuroxime - this is explicitly stated as unreliable in guidelines. 1