What is the spectrum of activity for cephalosporins (CEPH), carbapenems (CARB), monobactams (MONO), beta-lactams (β-lactams), beta-lactam inhibitors (BLI), linezolid (LINEZOLID), vancomycin (VANCO), and clindamycin (CLINDA)?

Spectrum of Activity for Major Antibiotic Classes

Beta-Lactams (β-lactams)

Beta-lactams inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), resulting in bactericidal activity that is time-dependent rather than concentration-dependent. 1, 2

Penicillins

• Natural penicillins (penicillin G, penicillin V): Primarily active against Gram-positive cocci including Streptococcus pneumoniae and Streptococcus pyogenes; remain the treatment of choice for streptococcal infections 3, 2
• Penicillinase-resistant penicillins (dicloxacillin, nafcillin, flucloxacillin): Target methicillin-susceptible Staphylococcus aureus (MSSA) specifically 3
• Aminopenicillins (amoxicillin, ampicillin): Amoxicillin is the most active oral β-lactam against pneumococci due to excellent bioavailability; covers streptococci and some Gram-negative organisms like Escherichia coli and Proteus mirabilis 3, 2
• Extended-spectrum penicillins (piperacillin): Provide broader Gram-negative coverage including Pseudomonas aeruginosa 4

Cephalosporins

Cephalosporins are inherently less active than penicillin/amoxicillin against S. pneumoniae, with baseline MICs typically fourfold higher than amoxicillin. 3

• First-generation (cefazolin, cephalexin): Most active against MSSA and streptococci; cover Klebsiella, E. coli, and P. mirabilis 3, 5
• Second-generation (cefuroxime, cefoxitin): Substantial activity against Haemophilus influenzae; cefoxitin adds anaerobic coverage 3, 5
• Third-generation (ceftriaxone, ceftazidime, cefotaxime): Pronounced activity against Enterobacteriaceae; ceftazidime specifically targets P. aeruginosa; once-daily dosing available with ceftriaxone 3, 5
• Fourth-generation (cefepime): Broad spectrum covering both Gram-positive cocci and Gram-negative bacilli including P. aeruginosa; highly resistant to chromosomally-encoded beta-lactamases 1, 6

Important caveat: No cephalosporin covers enterococci or methicillin-resistant staphylococci (MRSA) 1

Beta-Lactamase Inhibitors (BLI)

Beta-lactamase inhibitors restore the activity of companion penicillins when resistance is mediated by beta-lactamase production. 2, 7

• Amoxicillin-clavulanate: Covers MSSA, streptococci, H. influenzae, Moraxella catarrhalis, and anaerobes; first-choice oral agent for skin/soft tissue infections per IDSA 3, 8
• Ampicillin-sulbactam: Similar spectrum to amoxicillin-clavulanate for parenteral use 3
• Piperacillin-tazobactam: Very broad spectrum including P. aeruginosa, Enterobacteriaceae, MSSA, streptococci, and anaerobes; first-choice for febrile neutropenia 3
• Ticarcillin-clavulanate: Antipseudomonal activity with anaerobic coverage 3

High-dose amoxicillin-clavulanate (4g amoxicillin/250mg clavulanate daily for adults; 90mg/kg amoxicillin with 6.4mg/kg clavulanate for children) overcomes penicillin-resistant S. pneumoniae. 3

Carbapenems

Carbapenems provide the broadest antimicrobial spectrum of all beta-lactams, covering essentially all pathogenic organisms except MRSA and vancomycin-resistant enterococci. 5, 2

• Imipenem-cilastatin: Active against MSSA, streptococci, Enterobacteriaceae, P. aeruginosa, and anaerobes; higher rates of pseudomembranous colitis compared to other beta-lactams 3
• Meropenem: Similar spectrum to imipenem with improved safety profile; preferred carbapenem for most indications 3, 6
• Ertapenem: Broad spectrum including MSSA, streptococci, Enterobacteriaceae, and anaerobes; does NOT cover P. aeruginosa; once-daily dosing 3, 4
• Doripenem: Similar to meropenem in spectrum 3

Critical warning: Overuse of carbapenems has promoted emergence of carbapenem-resistant Enterobacteriaceae (CRE), requiring treatment with tigecycline, colistin, or high-dose tigecycline plus carbapenem combinations 3

Monobactams

Aztreonam is active exclusively against aerobic Gram-negative bacilli, including P. aeruginosa, making it useful for penicillin-allergic patients with Gram-negative infections. 5, 6

• Covers Enterobacteriaceae and P. aeruginosa 5
• No activity against Gram-positive organisms or anaerobes 5
• Safe alternative in patients with severe penicillin allergy 6

Linezolid

Linezolid is an oxazolidinone that inhibits bacterial protein synthesis by binding to the 23S ribosomal RNA of the 50S subunit; it is bacteriostatic against staphylococci and enterococci but bactericidal against most streptococci. 9

Spectrum

• Gram-positive only: MRSA, vancomycin-resistant Enterococcus faecium (VRE), methicillin-susceptible S. aureus, S. pneumoniae (including multi-drug resistant strains), S. pyogenes, and S. agalactiae 3, 9
• No Gram-negative or anaerobic activity 9

Clinical Efficacy

• Superior to vancomycin for skin/soft tissue infections (OR 1.40,95% CI 1.01-1.95) and MRSA infections (OR 1.41,95% CI 1.03-1.95) 3
• No difference in efficacy for bacteremia or pneumonia compared to vancomycin 3

Toxicities

• Significantly more thrombocytopenia (RR 13.06,95% CI 1.72-99.22) and nausea (RR 2.45,95% CI 1.52-3.94) than vancomycin 3
• Reversible, nonselective monoamine oxidase inhibitor—patients must avoid tyramine-rich foods and sympathomimetic agents 9

Resistance concern: Point mutations in 23S rRNA can develop during therapy, particularly in VRE with unremoved prosthetic devices or undrained abscesses 9

Vancomycin

Vancomycin is a glycopeptide antibiotic active exclusively against Gram-positive organisms, serving as the traditional standard for MRSA and serious staphylococcal infections. 3

Spectrum

• MRSA, methicillin-susceptible S. aureus, coagulase-negative staphylococci, streptococci, and Clostridium species 3
• No activity against vancomycin-resistant enterococci (VRE), Gram-negative bacteria, or most anaerobes 3

Clinical Use

• First-line for necrotizing fasciitis (combined with piperacillin-tazobactam or carbapenem) 3
• Recommended for diabetic foot infections when MRSA suspected 3
• Requires serial monitoring of serum levels to avoid nephrotoxicity 3

Important trend: Vancomycin MICs for MRSA are gradually increasing, potentially reducing efficacy 3

Clindamycin

Clindamycin is a lincosamide that inhibits bacterial protein synthesis by binding to the 23S RNA of the 50S ribosomal subunit; it is bacteriostatic. 10

Spectrum

• Gram-positive: MSSA (not MRSA), S. pneumoniae (penicillin-susceptible), S. pyogenes, S. agalactiae, S. epidermidis (methicillin-susceptible) 3, 10
• Anaerobes: Clostridium perfringens, Fusobacterium species, Peptostreptococcus anaerobius, Prevotella melaninogenica, Cutibacterium acnes 10
• No Gram-negative activity 10

Clinical Applications

• Recommended for impetigo, purulent skin/soft tissue infections, and non-purulent cellulitis 3
• Useful for necrotizing fasciitis caused by Streptococcus or Clostridium (combined with penicillin) 3
• Inhibits bacterial toxin production, making it valuable for toxin-mediated infections 3

Critical caveat: Macrolide-resistant staphylococci and beta-hemolytic streptococci should be screened for inducible clindamycin resistance using the D-zone test before use 10

Practical Considerations

• Available in both oral and parenteral formulations 3
• Limited evidence supporting use for severe S. aureus infections 3
• Cross-resistance with macrolides and streptogramin B due to overlapping ribosomal binding sites 10