Table 6.

Antibiotic and extract potentiating effects in two-component combinations. Reported interactions of Combretum species with antimicrobials and with extracts of other plants.

Species, Extracts and Antibiotics Combinations	Screening Method and Antibiotic Potentiating Effect; FICI, Reduction of MIC	Reference
Combretum edwardsii Hexane, dichloromethane, and ethyl acetate fractions of Combretum edwardsii leaves + cefotaxime, ampicillin, chloramphenicol, penicillin and amoxicillin	Checkerboard method: Drug-resistant E. coli: Synergistic effect of a hexane fraction and cefotaxime. FICI value of 0.07. Multidrug resistant Klebsiella pneumoniae: Synergistic effects of hexane, dichloromethane, and ethyl acetate fractions with cefotaxime. FICI values between 0.03 and 0.12. A combination of the ethyl acetate extract and cefotaxime provided the strongest synergistic effects with an FICI value of 0.03. Penicillin-resistant Staphylococcus aureus: Synergistic effects of hexane, dichloromethane, and ethyl acetate fractions in combination with ampicillin, chlorampenicol, penicillin, and amoxicillin. FICI values between 0.05 and 0.37. The most effective combination was that of a hexane extract and amoxicillin, showing an FICI value of 0.05.	[30]
Combretum kraussii Hexane, dichloromethane, ethyl acetate, and water fractions of Combretum kraussii leaves + cefotaxime, ampicillin, chloramphenicol, penicillin and amoxicillin	Checkerboard method: Drug-resistant E. coli: Synergistic effects of dichloromethane and ethyl acetate extracts in combination with cefotaxime. FICI values of 0.07 and 0.064, respectively. The most effective combination was that of an ethyl acetate extract and cefotaxime. Multidrug resistant Klebsiella pneumoniae: Synergistic effects of hexane, dichloromethane, ethyl acetate, and water fractions in combination with cefotaxime. FICI values of 0.062–0.38. The most effective combination was that of a hexane extract and cefotaxime. Penicillin resistant Staphylococcus aureus: Synergistic effects of hexane, dichloromethane, ethyl acetate, and water extracts in combination with ampicillin, amoxicillin, chloramhenicol, and penicillin. FICI values between 0.04–0.38. The most effective combination was a water extract and penicillin.	[30]
Combretum hereroense, Citrus lemon, and Apodytes dimidiata Hexane, dichloromethane, acetone, and methanol extracts of the leaves in two-species extract combinations	Serial microdilution method: The MICs of the crude extracts against Mycobacterium smegmatis ranged between 0.1 mg/mL (dichloromethane extract of Apodytes dimidiata) and 3 mg/mL (hexane extract of Citrus lemon). The MICs of the C. hereroense crude extracts ranged between 0.6 and 1.6 mg/mL, with the acetone and dichloromethane extracts being the most growth inhibitory. The best combinations; Combretum hereroense with Apodytes dimidiata, hexane and acetone, and dichloromethane and methanol; resulted in MIC values of 0.04 mg/mL and showed synergistic effects.	[31]
Combretum erythrophyllum, Combretum molle, Harpephyllum caffrum, Quercus acutissima, and Solanum mauritianum Water, ethyl acetate, and acetone extracts of the leaves in two-species extract combinations	Microplate dilution assay and FIC-index calculation: MIC values of 0.04– > 2.5 mg/mL of the crude extracts of C. erythrophyllum against the tested Fusarium spp., with the strongest effects shown by the acetone and ethyl acetate extracts (MIC values of 0.04–0.08 mg/mL). Strong synergistic effects of the acetone extract of C. erythrophyllum in combination with acetone extracts of Harpephyllum caffrum, Quercus acutissima, and Solanum mauritianum against Fusarium proliferatum and F. verticillioides (MIC valuess of 0.002–0.001 mg/mL). MIC 0.04– > 2.5 mg/mL of the crude extracts of C. molle against the Fusarium spp. All tested extracts, including the water extracts, showed strong inhibition against F. proliferatium and F. solani (an MIC of 0.04 mg/mL). The ethyl acetate extract of C. molle demonstrated a strong synergistic effect in combination with an ethyl acetate extract of Nicotiana glauca against Fusarium proliferatum (an MIC of 0.001 mg/mL). Strong synergistic effects of the water extract of C. molle with a water extract of Withania somnifera against Fusarium proliferatum (an MIC of 0.002 mg/mL). Synergistic effects of acetone extracts of C. molle with acetone extracts of Quercus acutissima (an MIC of 0.001 mg/mL) against F. proliferatum.	[19]
Combretum molle Methanol extract of the leaves + kanamycin and streptomycin	Antibiotic modulation assay using a microdilution method: At subinhibitory concentrations (MIC/2 and MIC/4) the leaf–methanol extract of C. molle resulted in a two- to sixty-four-fold increase of the antibacterial effects of kanamycin and streptomycin against Gram-negative bacteria (e.g., E. coli, Enterobacter aerogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Providencia stuartii), including multidrug-resistant clinical strains. No FIC index values were calculated.	[205]

Abbreviations: FICI—fractional inhibitory concentration index that indicates the quality of the interaction (synergistic, additive, intermediate, or antagonistic); and MIC—minimum inhibitory concentration.