Antimircobials Part II

In this, we will try and go through some common antimicrobials which are still used in most of the clinics, and we will conclude by giving an insight into the futuristic antimicrobials that may come.

Antimicrobials agents that can interfere with folate synthesis or action

In the 1930s a landmark discovery was made before the penicillin was discovered. A dye which was metabolized could convert into an active substance called sulfanilamide and be able to suppress the growth of microorganisms. Resistance has decreased its use, but some like Co-Trimoxazole is still being used. In fact, co-trimoxazole is still used in children.

“The person who discovered the sulfa drug was Domagk, he thought that the staining property of the dye is responsible for killing the germs, his daughter was cured of the infection, but she was left with a permanent red skin”.

Mechanism of Action

This section is interesting, the sulfonamide action is bacteriostatic, it prevents the growth of bacteria by competing with PABA (para amino benzoic acid ) for the enzyme, dihydropteroate synthetase. This effect can be overcome if an excess of PABA is present.

Procaine is an anesthetic agent that is PABA esters, so it can antagonize the effects of sulfonamide.

Route of dosing is oral, and it gets metabolized in the liver, the major product is an acetylated derivative that doesn’t have any antibacterial action.

Adverse effects

Like most drugs, these come with some unwanted effects too, it is hard on the renal system, because of the acetylated metabolites which gets precipitated in the urine. It can cause Steven Johnson Syndrome and toxic epidermal necrolysis, fever and anaphylactoid reactions.

Trimethoprim

A relative of the antimalarial drug Pyrimethamine, since both are folate antagonists. Its also bacteriostatic and it is widely used for pulmonary, urinary and variety of infections. It is often used for Pneumocystis Carini, toxoplasmosis which is a protozoan infection, or nocardiosis (a bacterial infection). Trimethoprim action can be potentiated by the use of sulphonamides, due to the same mechanism of action.

Its concentration is fairly high in the lungs, kidneys and cerebrospinal fluid. It is well absorbed orally and gets widely distributed in tissues and fluids. Its a weak base so when the ph of the urine drops, elimination by kidney increases.

Adverse effects

Megaloblastic anemia, which is due to folate deficiency can be seen due to long term administration.

Beta Lactam Antibiotics

Penicillins

1941 was the year Penicillins were proved as a remarkable drug. It was extracted from the culture of Penicillium Notatum, and the first dose was given to a policeman for septicemia, with multiple abscesses. Prior to 1941 topical penicillin was also used by Paine, a graduate of St. Mary’s who had acquired the penicillin mold from Fleming.

Mechanism of action

All beta-lactams interfere with the synthesis of bacterial cell wall peptidoglycan. The penicillin-binding proteins are present on the cell wall, they can inhibit the transpeptidation enzyme that crosslinks the peptide chains attached to the backbone of the peptidoglycan.

Clinical uses are wide and spread out. They can be given by mouth or in severe infections, intravenously, and often in combination with other antibiotics.

Individual sensitivity testing is required depending on local conditions.

Some common conditions and the drugs used are

Benzylpenicillin– bacterial meningitis

Flucloxacillin– bone and joint infection e.g – staphylococcus infection

Phenoxymethylpenicillin– pharyngitis

Amoxicillin– otitis media ( organisms commonly included are S.pyrogenes, Haemophilus influenzae)

Ticarcillin, Piperacillin– Psuedomonas aeruginosa

The above list is not complete, and the treatment with penicillins is sometimes given empirically if the causative organism is likely to be susceptible to penicillin.

Types of Penicillins and their antimicrobial activity

Penicillin G and Penicillin V were the two first naturally occurring penicillins. Semisynthetic penicillins include B-lactamase resistant penicillins ( eg- meticillin, flucloxacillin, temocillin).

Some broad-spectrum penicillins are – ampicillin, amoxicillin, and extended spectrum antibiotics are – ticarcillin, piperacillin.

Pivmecillinam is a prodrug of mecillinam which also has a wide spectrum of action.

Absorption of penicillins can depend on their stability in the acid, and if the patient has taken food or he/she is an empty stomach. Slow-release injections are also available like benzathine benzylpenicillin, is also useful in treating conditions like syphilis. This is because organisms like Treponema pallidum are very slow growing.

Intrathecal administration is not in use any longer due to convulsions observed in patients.

Penicillins are lipid soluble so they can cross the blood-brain barrier only if meninges are inflamed, but this way they can reach therapeutic concentrations in the cerebrospinal fluid.

Route of elimination for most penicillins is renal and it mostly happens rapidly.

Adverse effects

Penicillins are relatively free of unwanted effects, hypersensitivity is a huge challenge, so patients are often asked if they have any previous experience to it. Acute anaphylactic shocks are rare but they can be fatal. Skin rashes and fever are common, a delayed type of serum sickness occurs infrequently.