The “Static” and “Cidal” Antibiotic Myth – Really No Difference

From “Antibiotics:  5 Myths Debunked” on Medscape – by Dr Brad Spellberg (10/20/16)

Myth 5: Cidal Antibiotics Result in Superior Clinical Outcomes and Less Risk for Emergence of Resistance Than Do Static Antibiotics

This is another widespread clinical belief that is based on no evidence. First, contrary to common belief, bacteriostatic (“static”) antibiotics do kill bacteria; they just require a higher concentration to achieve specific thresholds of bacterial reduction. The formal definition of a bactericidal (“cidal”) antibiotic is one for which the minimum bactericidal concentration (MBC) of the drug is fourfold or more above the minimum inhibitory concentration (MIC) of the drug.[9]

The MBC is the concentration of the drug that results in a 1000-fold reduction in bacterial density at 24 hours of growth. The MIC is the concentration that inhibits visible growth at 24 hours of growth. These definitions are arbitrary: Why should it be that MBC requires a 1000-fold reduction in bacterial density as opposed to a 100-, 500-, 5000-, or 10,000-fold reduction? Why 24 hours? Why must the MBC not be more than fourfold above the MIC, as opposed to twofold, or 16-fold, or 23-fold?

Finally, an antibiotic that achieves a > 1000-fold reduction in bacterial density but does so at a concentration that is eightfold above the MIC of the drug is considered static, even though it clearly kills the bacteria.

Given that these terms have been defined by accepted convention and are not based on specific scientific principles, perhaps it is not surprising that there is no clinical evidence of benefit of cidal agents over static agents. A systematic literature review identified 28 randomized controlled trials that compared the efficacy of static vs cidal antibiotics, head to head, for patients with invasive bacterial infection (Table).

Table. Randomized Controlled Trials Comparing Cidal vs Static Therapy

Disease Drugs Efficacy
Typhoid fever[10-13] Chloramphenicol (static) or azithromycin (static) vs levofloxacin (cidal) or cefixime (cidal) No significant difference
Cellulitis[14] Doxycycline (static) vs TMP/SMX (cidal) No significant difference
Chlamydia (genital)[15] Azithromycin (static) vs rifalazil (cidal) No significant difference
Meningococcal meningitis[16] Chloramphenicol (static) vs ceftriaxone (cidal) No significant difference
Febrile neutropenia[17] Linezolid (static) vs vancomycin (cidal) No significant difference
MRSA infections[18] (across infection sites) Linezolid (static) vs TMP/SMX + rifampin (cidal) No significant difference
Gram-positive infections in
children[19]
Linezolid (static) vs vancomycin (cidal) No significant difference
Skin infections[20] Linezolid (static) vs vancomycin (cidal) No significant difference
Gram-positive catheter-associated bloodstream infection and skin infections[21] Linezolid (static) vs vancomycin (cidal) No significant difference
Pediatric severe community-acquired pneumonia[22,23] Chloramphenicol (static) vs beta lactam + gentamicin (cidal) No significant difference
Community-acquired pneumonia[24-26] Doxycycline (static) vs beta lactam or fluoroquinolone (cidal) No significant difference
Aspiration pneumonia[27-29] Clindamycin (static for anaerobes) vs beta-lactam (cidal) No significant difference
Nosocomial pneumonia[30] Linezolid (static) vs vancomycin (cidal) No significant difference
Ventilator- associated pneumonia[31] Tigecycline (static) vs imipenem (cidal) No significant difference
Cellulitis[32-34] Linezolid (static) vs vancomycin (cidal) Linezolid (static) superior
Streptococcus pneumoniaecommunity pneumonia[35] Linezolid (static) vs cephalosporin (cidal) Linezolid (static) superior
MRSA nosocomial pneumonia[36] Linezolid (static) vs vancomycin (cidal) Linezolid (static) superior
Ventilator-associated pneumonia[37] Tigecycline (static) vs imipenem (cidal) Imipenem (cidal) superior
MRSA = methicillin-resistant Staphylococcus aureus; TMP/SMX = trimethoprim/sulfamethoxazole

Almost no trials found a significant difference in efficacy between static vs cidal antibiotics. The exceptions? Three studies found the static agent linezolid to be superior in efficacy to the cidal agent vancomycin for the treatment of complicated skin infections,[32-34] and one trended toward superiority of linezolid (P =.057).[20] A trial found that linezolid was superior in efficacy to vancomycin for the treatment of MRSA pneumonia,[36]and another found linezolid to be superior in efficacy to cephalosporins for pneumococcal pneumonia.[35]

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