Community-Acquired MRSA Shows the Key Coverage Difference
The correct answer is A: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), as doxycycline provides reliable coverage while azithromycin does not.
Pathogen-by-Pathogen Coverage Analysis
Community-Acquired MRSA (Option A) - THE DIFFERENCE
- Doxycycline provides effective coverage against CA-MRSA and is specifically recommended in guidelines for skin and soft tissue infections where MRSA is suspected 1
- Azithromycin lacks reliable MRSA coverage and is not recommended as monotherapy when MRSA is a concern 1
- This represents a clinically significant difference in antimicrobial spectrum between these two agents
Streptococcus pneumoniae (Option B) - NO DIFFERENCE
- Both agents provide adequate coverage for S. pneumoniae in community-acquired pneumonia 1
- Guidelines list both azithromycin and doxycycline as acceptable alternatives for atypical pathogen coverage when combined with beta-lactams 1
- The 2007 IDSA/ATS guidelines specifically state that "doxycycline can be used as an alternative to a macrolide" for pneumococcal coverage 1
- However, emerging macrolide resistance is a concern in some regions, though this affects clinical decision-making rather than representing a fundamental coverage difference 1
Escherichia coli (Option C) - NO DIFFERENCE
- Both agents have limited and variable coverage against E. coli 2
- Doxycycline FDA labeling indicates E. coli coverage "when bacteriologic testing indicates appropriate susceptibility" due to widespread resistance 2
- Neither agent is considered first-line for E. coli infections, representing similar limitations rather than a coverage difference
Mycoplasma pneumoniae (Option D) - NO DIFFERENCE
- Both azithromycin and doxycycline provide excellent coverage for M. pneumoniae 1, 2, 3
- Guidelines consistently list both as appropriate choices for atypical pathogen coverage including Mycoplasma 1
- Recent evidence from 2025 comparing these agents in CAP showed both were effective, though azithromycin demonstrated lower mortality when combined with beta-lactams 4
- For M. genitalium (a related organism), both agents show efficacy, with doxycycline commonly used as initial therapy before resistance-guided treatment 5, 6
Clinical Context for MRSA Coverage
- Skin and soft tissue infections are where this coverage difference becomes most clinically relevant 1
- When CA-MRSA is suspected, doxycycline is an appropriate empiric choice, while azithromycin would require combination with other agents 1
- The 2024 WHO guidelines on essential medicines recognize doxycycline's broader gram-positive coverage compared to azithromycin 1