There are antibiotics having a β-Lactam ring. The two major groups are Penicillin’s and Cephalosporin. Monobactams and Carbapenems are relatively later additions.
Penicillin was the first antibiotic to be used clinically in 1941.It is a miracle that the least toxic drug of its kind was the first to be discovered. It was originally obtained from the fungus Penicillin notatum, but the present source is a high yielding mutant of P. chrsogenum.
All β-Lactam antibiotics interfere with the synthesis of bacterial cell wall.
Penicillin -G (Benzyl Penicillin)
Penicillin-G (Benzyl Penicillin – PnG) is a narrow spectrum antibiotic; activity is limited primarily to gram-positive bacteria, few gram-negative ones and anaerobes.
Penicillin G is one of the most nontoxic antibiotics; up to 20 MU has been injected in a day without any organ toxicity.
Local irritancy and direct toxicity: Pain at i.m. injection site, nausea on oral ingestion and thrombophlebitis of injected vein are dose-related expressions of irritancy.
Toxicity to the brain may be manifested as mental confusion, muscular twitching, convulsions and coma, when very large doses (> 20 MU) are injected i.v.; especially in patients with renal insufficiency.
Bleeding has also occurred with such high doses due to interference with platelet function. Intrathecal injection of PnG is no longer recommended because it has caused arachnoiditis and degenerative changes in spinal cord
Accidental i.v. injection of Procaine Penicillin produces CNS stimulation, hallucinations and convulsions due to procaine. Being insoluble, it may also cause micro embolism.
Hypersensitivity: These reactions are the major problem in the use of Penicillin. An incidence of 1-10% is reported. Individuals with an allergic diathesis are more prone to develop penicillin reactions. PnG is the most common drug implicated in drug allergy, because of which it has practically vanished from use in general practice.
Frequent manifestations of penicillin allergy are-rash, itching, urticaria and fever. Wheezing, angioneurotic edema, serum sickness and exfoliative dermatitis are less common. Anaphylaxis is rare (1 to 4 per 10,000 patients), but may be fatal.
All forms of natural and semisynthetic penicillin can cause allergy, but it is more commonly seen after parenteral than oral administration. Incidence is highest with procaine penicillin: procaine is itself allergic. The cause of penicillin hypersensitivity is unpredictable, i.e. an individual who tolerated penicillin earlier may show allergy on subsequent administration and vice versa.
Topical application of penicillin is highly sensitizing (contact dermatitis and other reactions). Therefore, all topical preparations of penicillin (including eye ointment) have been banned, except for use in eye as freshly prepared solution in case of gonococcal ophthalmia.
If a patient is allergic to penicillin, it is best to use an alternative antibiotic. Hyposensitization by the injection of increasing amounts of penicillin intradermally at hourly intervals may be tried only if there is no other choice.
Penicillin G is the drug of choice for infections caused by organisms susceptible to it, unless the patient is allergic to this antibiotic. However, use has decline very much due to fear of causing anaphylaxis.
- Streptococcal infections: Like pharyngitis,otitis media,scarlet fever,rheumatic fever respond to ordinary doses of PnG because pyogenes has not developed significant resistance. However, the risk of injecting PnG for this infection is seldom taken now. For subacute bacterial endocarditis(SABE) caused by Strep.viridans or faecalis high doses(10-20 MU i.v. daily) along with gentamicin given for 2-6 weeks is needed.
- Pneumococcal infections: PnG is not used now for empirical therapy of pneumococcal(lobar) pneumonia and meningitis because many strains have become highly penicillin resistant. However, PnG 3-6 MU i.v. every 6 hours is the drug of choice if organism is sensitive.
- Meningococcal infections: Are still mostly responsive; meningitis and other infections may be treated with intravenous injection of high doses.
- Gonorrhoea: PnG has become unreliable for treatment of gonorrhea due to spread of resistant strains.
- Syphilis: pallidum has not shown any resistance and PnG is the drug of choice. Early and latent syphilis is treated either with daily i.m. injection of 1.2 MU of procaine penicillin for 10 days or with 1-3 weekly doses of 2.4 MU benzathine penicillin. For late syphilis, benzathine penicillin 2.4 MU weekly for 4 weeks is recommended.Cardiovascular and neurosyphilis requires sod.PnG 5 MU i.m. 6 hourly for 10-14 days followed by the above regimen.
- Diptheria: Antotoxin therapy is of prime importance. Procaine penicillin 1-2 MU daily for 10 days is used to prevent carrier state.
- Tetanus and gas gangrene: Antitoxin and other measures are more important; PnG 6-12 MU/day is used to kill the causative organism and has adjuvant value.
- Penicillin G is the drug of choice for rare infections like anthrax, actinomycosis, rat bite fever and those caused by listeria monocytogenes, Pasteurella multocida.
- Prophylactic uses:
- Rheumatic fever: Low concentrations of penicillin prevent colonization by streptococci that are indirectly responsible for rheumatic fever. Benzathine penicillin 1.2 MU every 4 weeks till 18 years of age or 5 years after an attack, whichever is more.
- Bacterial endocarditis: Dental extractions, endoscopies, catheterization, etc. cause bacteremia which in patients with valvular defects can cause endocarditis. PnG can afford protection, but amoxicillin is preferred now.
- Agranulocytosis patients: Penicillin has been used alone or in combination with streptomycin to prevent respiratory and other acute infections, but cephalosporins + an aminoglycoside or fluoroquinolone are preferred now.