The mode of action (MOA) of penicillin G interferes with the final stage of bacterial cell wall synthesis causing disruption of the osmotic pressure gradient with ensuing lysis and cell death, whereas the MOA of streptomycin sulfate modifies the permeability of the cell wall, interferes with prokaryote protein synthesis and cellular respiration by irreversibly binding to the 30S ribosome subunit to cause a misreading/miscoding of the mRNA. In essence, this activity freezes the 30S initiation complex (i.e.,30S-mRNA-tRNA) and interrupts any further progress in the initiation phase to chain-elongating ribosome. Both antibiotics, penicillin when combined with streptomycin synergistically enhance their range of activities and increase their effectiveness as opposed to when utilized on an individual basis.
The efficacy of the penicillin-streptomycin synergistic combination is accomplished when two individual drugs (i.e., both are bactericidal) interfere with different constituents in the bacterial cellular or metabolic pathways. The result is an effect greater than could be attributed to their additive action. In theory, a drug affecting the permeability of the cell membrane (i.e., streptomycin), plus a drug affecting the cell wall (i.e., penicillin), when used in combination, may be more effective than either drug used alone.
Important note: In some cases, some antibiotics when used in combination often exert atypical cytotoxic effects at lower concentrations than when utilized on an individual basis. Please consult other comprehensive pharmacology references regarding antibiotic properties, characteristics, interactions and possible incompatibilities.

Penicillin-Streptomycin is a combination solution of an aminoglycoside (streptomycin) and β-lactam antibiotic (penicillin). It accords a broad-spectrum bacteriocidal activity against both gram-positive and gram-negative bacteria.

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