Combination therapy is becoming a theme of infectious diseases and is increasingly being accepted as a reducer of microbial resistance.

Synergistic effects manifest in different ways: improving bioavailability decreasing metabolism, and excretion of the active component reversal of resistance and modulation of adverse effects (Wagner and Ulrich-Merzenich, 2009 Rasoanaivo et al., 2011).

( 2011), “synergy” or “potentiation” means that the effect of the combination is greater than the sum of the individual effects. The rationale is to enhance the activity by achievement of a synergistic effect. Combination therapy has over the years become one of the most effective strategies in combating bacterial infections caused by drug resistant pathogens. coli is due to the production of TEM-1 (Cooksey et al., 1990) while the most common class A beta-lactamases found in Klebsiella are the chromosomal and plasmid-borne SHV enzymes and the plasmid-mediated TEM enzymes (Bush, 2001). TEM-1 (class A) is the most commonly encountered beta-lactamase in Gram-negative bacteria. Members of the family Enterobacteriaceae commonly express plasmid-encoded beta-lactamases (TEM and SHV) which confer resistance to penicillins but not to expanded-spectrum cephalosporins. Beta-lactamases are the most significant and prevalent mechanism of resistance to beta-lactams. Class A, C, and D beta-lactamases use a serine as a nucleophile to hydrolyze the beta-lactam bond while class B beta-lactamases (carbapenemases) use Zn 2+ to deactivate beta-lactams. Beta-lactamases are classified into four different classes (A, B, C, and D) based on structural comparisons or four groups (1–4) based on hydrolytic and inhibitor profiles (Ambler et al., 1991 Bush and Jacoby, 2010). One of such resistance mechanisms is the hydrolysis of the active site, beta lactam ring, of beta-lactam antibiotics by beta-lactamases, and thereby rendering the antibiotic ineffective. Some of the commonly used antibiotics, especially beta-lactam antibiotics are rendered infective through some resistance mechanisms employed by drug-resistant bacteria. Due to this resistance, the clinical efficacy of current antimicrobial agents is decreasing against many pathogens. The emergence and spread of drug-resistant bacteria remains a major challenge to public health in the treatment of bacterial infections.

krausii could be potential sources of broad spectrum antibiotic resistance modifying compounds. The few synergistic interactions observed in the present study suggest that the crude extracts of the leaves of M. pneumoniae and 80% of the combinations against S. Synergistic interactions were detected in 13% of the combinations against E. edwardsii was the most active against Escherichia coli. krausii was the most active against Klebsiella pneumoniae and ethyl acetate leaf extract of C. nemorosa was the most active (MIC = 37 μg/ml) against S. Generally, Staphylococcus aureus was the most susceptible of the three strains of bacteria while the other two beta-lactamase producing Gram-negative bacteria were the most resistant. The plant fractions tested in the present study displayed varying levels of antibacterial activity depending on the bacterial strains. The MICs of the plant extracts and antibiotics were in the range of 0.037–6.25 and 0.001–2.5 mg/ml, respectively. The interactions of plant extracts and antibiotics were studied using a checkerboard method. Using the rapid p-iodonitrotetrazolium chloride colorimetric assay, minimum inhibitory concentration values of plant extracts and antibiotics were determined. edwardsii, Combretum krausii, and Maytenus nemorosa as well as their interactions with selected antibiotics against drug resistant bacterial strains. The study investigated the antibacterial activity of crude extracts of C.

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