Common Antibacterial Agents

Aminoglycosides
Among aerobic bacteria, aminoglycoside resistance is commonly due to modifiying enzymes that are coded by genes on plasmids or the chromosomes (Opal et al.,2000).
Cephalosporins
The first generation agents were active against Methicillin-susceptible S. aureus, Penicillin-susceptible S. penumoniae and other common Gram positive bacteria as well as many community acquired Gram negative bacilli (Reese et al., 2000).
The second generation agents cephamandole and later cefuroxime were developed because of their activity against ampicillin-susceptible and resistant H. influenzae and many S. pneumoniae (Reese et al., 2000).
The third generation agents were active against hospital acquired pathogens and P. aeruginosa. In addition, the once daily ceftriaxone agent has significant Gram positive activity (Reese et al., 2000).
Cefepime has sometimes been called a fourth generation agent, but it may be better summarized as a hybrid of cefotaxime and ceftazidime (Marshall and Blair, 1999).
The main cause of resistnace to cephalosporins are the production of -lactamases that inactivates these antibiotics by splitting the amide bond of the -lactam ring. Resistance to -lactam antimicrobial agents, especially extended-spectrum cephalosporins and other antimicrobial agents among clinical isolates of Gram-negative bacteria, is on the rise worldwide (Pfaller, 1999).
Numerous -Lactamases exist, encodied either by chromosomal genrs or by transferable genes located on plasmids or transposons (Medeiros, 1984).

Fluoroquinolones
Resistance to quinolones and fluoroquinolones among the causative bacteria has become increasingly problematic due to these drugs have paramount importance in the treatment of several other infectious diseases(Karaca et al., 2005). Their appropriate spectrum and good tolerability have also led to increased empirical adoption in uncomplicated infections, although their usage for these conditions in outpatients is still under debate(Piatti et al.,2008).
Fluoroquinolones, some of the most frequently prescribed antimicrobial agents worldwide, target the bacterial type II topoisomerases gyrase and topoisomerase IV.

Glycopeptides
Vancomycin and other glycopeptides antibiotics such as teicoplanin bind to D-alanine-D-alanine, which is present at the termini of peptidoglycan precursors. The large glycopeptides molecules prevent the incoportaiton of the precursors into the cell wall. (Dultka et al., 1990).
Carbapenem
Imipenem is a carbapenem released in 1985, has a very broad spectrum of activity. It is combined with cilastratin, a potent enzyme inhibitor, which prevents the inactivation of imipenem in the kidney (Reese and Betts, 1996b).
Chloramphenicol
Resistance to chloramphenicol in Gram-positive and Gram-negative organisms is primarily mediated by the inactivating enzyme chloramphanicol acetyltransferase. This is an intracellular enzyme that inactivates the drug by 3-acetylation and is encoded by plasmid-borne or chromosomal genes (Davies, 1979).
Lincosamides:
Clindamycin is bactericidal for some organisms but generally is bacteriostatic, depending on the bacterial speciecs inoculum of bacteria, and concentration of antibiotic available (Steigobigel, 2000).
Marcolides:
The commonly used macrolides are erythromycin and the semi synthetic derivatives of erythromycin, clarithromycin and azithromycin, which have structural modifications to improve tissue penetration and broaden their spectrum of activity (Gold and Moellering, 1999).
Erythromycin esterases have been isolated from E. coli that hydrolyze the lactone ring of the antibiotic and thus result in its inactivation (Barthelemy et al., 1984).
Monobactams:
Aztreonam is the first clinically useful monobactam. It is active against most of the Gram negative aerobes without the nephrotoxicity of aminoglycosides. It interferes with the biosynthesis of bacterial cell walls by binding to penicillin binding proteins (Hellinger and Brewer, 1999).
Penicillins:
When it was introduced in 1944, benzyl penicillin was active against about 95% of S. aureus isolates but the remainder had -lactamase and were resistant. Within 5 years, the proportion of enzyme producers had grown to 50%, reflecting gene transfer and strain selection; subsequently this proportion has risen to around 90% (Lacey, 1984).
Rifamycin:
Rifampin is a very potent bactericidal anti-staphylococcal agent. It blocks protein synthesis by inhibiting RNA polymerase. It penetrates well into tissues and abscesses, which are poorly penetrated by most other anti-staphylococcal agents. High-level resistance occurs if rifampin is used alone due to point mutation in the -subunit RNA polymerase target. Accordingly, rifampin should be used only in combination with another anti-staphylococcal agent to which the isolate is susceptible (Cahmbers, 1997a).
Tetracyclines:
There are two mechanisms of tetracycline resistance in Staphylococci, both of which have been found in CoNS. The first mechanism involves a membrane protein that mediates active efflux of the drug. The major gene in Staphylococci encoding the efflux protein (tet K) is usually plasmid encoded and mediated resistance to tetracycline and doxycycline but not minocycline (Levy, 1984). The second mechanism for resistance involves a cytoplasmic protein that reduces the sensitivity of the ribosome to the drug. The gene encoding the ribosomal protection protein (Tet M) is carried on the chromosome and mediates resistance to minocycline, tetracycline,and doxycycline. Most clinical CoNS isolates seem to bear the (tet K) determinant (Bismuth et al., 1990).