Amoxicillin and coumadin

Check for undiagnosed allergies leading to chronic rhinorrhea. In 1929, Alexander Fleming isolated

penicillin

By 1941, benzylpenicillin could be produced in sufficient quantity to treat several infected patients.

Clinical trials with the agent, conducted by Florey and colleagues, were successful and during World War II, benzylpenicillin was used to treat patients with streptococcal, gonococcal, and treponemal infections. Shortages of the agent continued until the late 1940s when production of large amounts of drug became possible by a deep-fermentation procedure (85). Since then, many synthetic penicillins have been developed, but resistance to the agents has increased.

Despite the emergence of resistance to penicillins and the development of other classes of anti-infective agents, the penicillins remain one of the most important anti-infective classes of drugs well into the nineties. In fact, penicillin G is still the drug of choice for many types of infections, including syphilis and certain types of endocarditis. Chemical Structure (Figure 1) The basic chemical structure of all penicillins consists of a beta-lactam ring, a thiazolidine ring, and a side chain (6-aminopenicillanic acid).

The antibacterial activity of the penicillins lies within the beta-lactam ring. Any alteration in this ring structure forms penicilloic acid and the antibacterial activity of the compound is lost.

The side chain varies with each penicillin compound and generally determines the spectrum of activity, as well as the pharmacokinetic properties of the compound.

There are several natural penicillins (penicillin dihydro F, X, and K), of which benzylpenicillin (penicillin G) is the most active and is the only natural penicillin used clinically (164). Manipulations of the side chain have produced compounds that are stable against certain bacteria, such asВ Staphylococcus aureus , which produce beta-lactamase enzymes (penicillinase).

The side chain sterically inhibits the beta-lactamase hydrolysis of the beta-lactam ring. Other penicillin compounds have side chains, which are stable against beta-lactamases produced by gram-negative rods.

Side chain changes can also increase the bacterial permeability of the compound and can result in increased oral absorption from the intestinal tract by rendering oral agents more stable to gastric acid breakdown (167,В 186). Classification of Penicillins and Spectrum of Activity.

The penicillin compounds can be divided into categories based upon their spectrum of activity (Table 1).

Minimum inhibitory concentration (MIC) data for 50% and 90% of specific organisms are located in TablesВ 2В andВ 3В (10,В 70,В 150,В 228,В 245,В 255,В 257,В 261). For gram-negative organisms and anaerobes, resistance in up to 15% of strains is possible; therefore MIC90s must be interpreted cautiously. Penicillin G is a natural penicillin that is produced directly from fermentation ofВ Penicillium crysogenum .

Penicillin V is a derivative of penicillin G and because of similarities in spectrum of activity, is considered a natural penicillin. The natural penicillins have activity against non-beta-lactamase producing gram-positive cocci, including viridans streptococci, group A streptococci,В Streptococcus pneumoniae , and anaerobic streptococcus ( Peptostreptococcus ,В Peptococcus В sp.).В Enterococcus В sp.

Other potential organisms with susceptibility include non-penicillinase producing strains ofВ Staphylococcus aureus В and coagulase-negativeВ Staphylococcus , however because of the high likelihood of resistance, it is inappropriate to use natural penicillins as empiric treatment for a suspectedВ Staphylococcal В infection unless the organism’s susceptibility is known.

The natural penicillins have activity against Clostridium sp. (excludingВ Clostridium difficile ) andВ Actinomyces В sp. Activity against gram-negative cocci is keflex amoxicillin limited and includesВ Neisseria meningitidis , non- penicillinase producingВ Neisseria gonorrheae , andВ Pasteurella multocida .

Similar toВ staphylococcal В infection, natural penicillins should not be used for treatment of gonorrhea due to the increased potential of a resistant organism and subsequent amoxicillin cipla treatment failure. The anaerobic coverage of penicillin V is less than that of penicillin G. Natural penicillins also have excellent activity against the spirochete,В Treponema pallidum , the causative organism of syphilis. The agents in this group are also known as the antistaphylococcal penicillins. The addition of an isoxazolyl side chain to the penicillin compound protects the beta-lactam ring from acid hydrolysis by penicillinases produced byВ Staphylococcus В sp. Methicillin, the first agent synthesized in this group, is rarely used currently due to a higher incidence of occurrence of interstitial nephritis and is no longer commercially available in the United States. Nafcillin and oxacillin are the agents commonly used parenterally, while dicloxacillin is available for oral use.

These agents have activity againstВ Staphylococcus В sp (including penicillinase-producing strains). Strains of methicillin-resistantВ Staphylococcus aureus (MRSA) and methicillin-resistantВ Staphylococcus В epidermidis В (MRSE) exist and can be the prevalentВ Staphylococcal В organism in certain areas, such as certain hospitals or wards within the hospital. These organisms are not sensitive to the penicillinase-resistant penicillins.

as compared to the natural penicillins, based on MIC data, use of the penicillinase-resistant penicillins is acceptable (i.e. the MICs are low enough relative to achievable serum concentrations) for use against these organisms.

Clinically, in serious, life-threatening infections where a gram-positive organism is suspected, combinations of penicillin G plus a penicillinase-resistant penicillin can be utilized to achieve maximal streptococcal andВ staphylococcal В coverage.

A notable exception to the gram-positive coverage of this class of penicillins is the Enterococci.

These organisms are not susceptible to this class of penicillins.

Anaerobic activity ranges from minimal to none and gram-negative activity is virtually nonexistent.