22. Principles for combined antibacterial drug prescribing.
Covers when combining antibacterial drugs is justified, set out as a table of indications with examples such as mixed aerobe and anaerobe infections, empirical cover for septic shock, synergy, tuberculosis and resistant organisms, and atypical cover in pneumonia. It then explains interaction types (synergy, additive effect, antagonism) in a second table, notes the disadvantages of combinations including toxicity and flora disruption, and closes with principles on choosing drugs and de-escalating once the pathogen is known.
Topic 22 of 30 in the MU Sofia syllabus for Clinical Pharmacology (Medicine, Year 5). The free AceMed note covers it in 5 sections, about 140 words (2 min of reading), with 15 flashcards.
In this note
Introduction
Indications for combination therapy
Interactions between antibiotics
Disadvantages of combinations
Principles
Introduction
Most infections are treated with a single antibiotic. Combinations add cost, adverse reactions and interactions, so they need a clear reason.
Interactions between antibiotics
Classic rule (Jawetz): bactericidal + bactericidal is often synergistic; bacteriostatic + bacteriostatic is additive; bactericidal + bacteriostatic may be antagonistic.
Disadvantages of combinations
More adverse reactions and additive toxicity (e.g. aminoglycoside + vancomycin or loop diuretic: nephro- and ototoxicity).
Greater disruption of normal flora: Clostridioides difficile, candidiasis, selection of resistant organisms.
Higher cost; false reassurance that can delay finding the cause.
Principles
Use a combination only for one of the indications above.
Choose drugs with different mechanisms and no antagonism or overlapping toxicity.
Review at 48–72 h and de-escalate to a single targeted agent once the pathogen is known.
Combine antibiotics only for mixed infections, empirical cover of life-threatening sepsis, synergy, or to prevent resistance (TB), and de-escalate as soon as cultures allow.
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