Antimicrobial Drugs General Considerations
Question 1. Write Briefly On Bacterial Resistance To Antimicrobial Agents.
Or
Describe Briefly Drug Resistance.
Or
Explain The Mechanism Of Development Of Bacterial Resistance To Antimicrobial Agents.
Answer:
Drug resistance refers to the tolerance of microorganisms to the inhibitory action of antimicrobials.
Types Of Drug Resistance
There are two types of drug resistance, i.e.
- Natural resistance: Various microbes are resistant to certain antibiotics. These bacteria lack metabolic process or the target site which get affected by a particular drug, For Example. Gram-negative bacilli are not affected by penicillin.
- Acquired resistance: This is the resistance that is developed by an organism because of the use of an antimicrobial agent for a long period of time. This type of resistance is a major clinical problem if happens, For Example. Gonococci develop resistant to sulphonamides.
5 Mechanisms Of Antibiotic Resistance
Read And Learn More: Pharmacology Question And Answers
Occurrence Of Drug Resistance
Drug resistance occurs due to mutation or gene transfer.
- Mutation: It’s a genetic change that occurs spontaneously and is not caused by any drug. Any of the sensitive populations of microbes consists of a few mutant cells which require a high concentration of drug for inhibition. These cells are selectively preserved and get the chance to proliferate when sensitive cells are eliminated by the drug. So with time, a sensitive strain is replaced by a resistant strain. Mutation can be a single step or multistep.
- Gene transfer: It is the infection transmitted from one organism to another by conjugation or transduction or transformation.
- Conjugation: It is the sexual contact via the formation of a bridge or sex pilus which is common in Gram-negative bacilli of the same or other species. The gene-carrying resistance or R factor is transferred only if another resistance transfer factor is present.
- Transduction: It is the transfer of gene-carrying resistance via the bacteriophage. R factor is taken up by the phage and delivered to another bacterium that it infects.
- Transformation: A resistant bacterium can release the resistant carrying DNA in a medium and this can be imbibed by another sensitive organism that gets unresponsive to the particular drug.
Following are the mechanisms by which a microorganism can develop resistance to an antimicrobial agent.
5 Mechanisms Of Antibiotic Resistance
- Secretion of inactivating enzyme: Microorganisms such as staphylococci, gonococci, etc. secrete β lactamases which destroy penicillin.
- Effl pump mechanism: This prevents the accumulation of drugs in microorganisms, For Example. is the resistance of Gram-positive and Gram-negative bacteria to tetracyclines.
- There is reduced entry of antimicrobial agents in a microorganism because of alteration in the channel which is required for its entry into the microorganism.
- Alteration inside the binding site: Change in penicillin-binding proteins in various pneumococci with a decrease in the affinity for penicillin.
- Absence of metabolic pathway: Bacterias which resist the sulphonamides utilize and perform folic acid without any need for metabolic steps.
Question 2. Write Short Note On Antibiotic Prophylaxis In Dental Procedures.
Answer:
Antimicrobial prophylaxis is done for two distinct purposes viz.
Antibiotic Prophylaxis In Dental Procedures
- Prevention of dental wound infection, and
- Prevention of distant infection (Example. Bacterial endocarditis) in predisposed patients following dental procedures.
Prophylaxis Of Dental Wound Infection
Prophylaxis In Dental
- Wound infection occurs due to microbial contamination of the surgical site. It is important for the dental surgeon to see that the wound left after tooth extraction, etc. does not get infected.
- Use of sterile instruments, cross-infection control measures (antiseptic/disinfectant, etc.), and good surgical technique to minimize tissue damage, hematoma, and devascularization are the primary, and often the only measures needed. In addition, systemic antimicrobial prophylaxis is advocated in selected situations.
- Prophylaxis should be employed only when there is a clear risk of wound infection that outweighs the possible drawbacks of antibiotic use. In general, antibiotic prophylaxis is not required for routine dental surgery, except in patients at special risk.
- Simple extractions and minor periodontal procedures in otherwise healthy subjects are associated with a very low risk of wound infection.
- The incidence of postoperative infection is quite low even after difficult surgery such as removal of the impacted third molar, and antimicrobial prophylaxis is not required. However, it may be given when surgery involves extensive instrumentation, bone cutting is prolonged.
- Prophylaxis should also be given for procedures in which a prosthesis is inserted into the bone or soft tissue, such as dental implants.
- Extensive reconstructive surgery of the upper or lower jaw also warrants antibiotic prophylaxis.
- All orodental procedures which disturb/damage mucosa including extractions, scaling, etc. need to be covered by prophylaxis in diabetics, corticosteroid recipients, and other immunocompromised subjects.
- When the surgery has been performed in the presence of local infection, a continuation of the prophylactic antimicrobials beyond 4 hours after the dental procedure may be justified.
- In case of prolonged dental surgery, the antibiotic may be repeated IV during the procedure.
- Amoxycillin is the first choice of drug for prophylaxis.
Prevention Of Distant Infection or Prevention Of Infectious Disease
- Injury to a mucosa that is laden with bacteria introduces some of the bacteria into the bloodstream.
- Transient bacteremia occurs regularly during dental extraction, scaling, intraligamentary local anesthetic injection, root canal treatment, placement of a dental implant, or any other procedure in which the gingival margin is manipulated. The blood-borne bacteria can cause life—threatening endocarditis in subjects with posttraumatic or congenital endocardial abnormalities such as mitral stenosis and other valvular defects, artificial heart valves, or previous history of bacterial endocarditis. It is imperative that in above mentioned oriental procedures antibiotic prophylaxis is necessary in susceptible individuals.
- Antiseptic rinse with chlorhexidine (0.2%) held in the mouth for l minute just before dental treatment has been advocated as an adjuvant measure because it has been shown to reduce the severity of bacteremia following dental extraction.
Question 3. Write A Short Note On Antimicrobial Prophylaxis.
Answer:
Antimicrobial prophylaxis refers to the use of antimicrobials for preventing the setting of infection or suppressing the contracted infection before it becomes clinically manifested.
- Prophylaxis is often against all organisms capable of causing infection.
Various prophylactic uses may be categorized as:
1. Prophylaxis Against Specific Organisms:
- Rheumatic fever: Long-acting penicillin G
- Tuberculosis: Isoniazide alone or with rifampicin
- Meningococcal meningitis: Rifampicin
- Gonorrhea/Syphilis: Procaine and penicillin
- Malaria and endemic diseases: Chloroquine/Mefloquine
2. Prevention Of Infection In High-Risk Situations:
- Dental extraction, tonsillectomy, and endoscopies cause damage to mucosa harboring bacteria-bacteremia to occur.
- Appropriate prophylaxis with a suitable penicillin/cephalosporin
- Chronic obstructive lung disease: Ampicillin/tetracycline
- Surgical prophylaxis: Extensive, prolonged, and often combined use of AMAs is made for prophylaxis of infection after all surgical procedures.
- Many drugs like penicillin + streptomycin are injected as a single dose at the beginning of surgery to effectively reduce the incidence of wound infection.
- For dirty contaminated wounds (roadside accidents) ceftizoxime + gentamicin + metronidazole may be used.
Antimicrobial Prophylaxis In Surgery
3. Prevention Of Infection In General
- Neonates: Especially after prolonged or instrumental delivery.
- To prevent postpartum infections in mothers.
- Viral upper respiratory tract infections
- To prevent secondary bacterial invasion.
Question 4. Classify Antimicrobial Agents Based On Their Mechanism Of Action.
Answer:
Classification Of Antimicrobial Agents Based On Mechanism Of Action
- Inhibit cell wall synthesis: Penicillins, cephalosporins, cycloserine, vancomycin, and bacitracin.
- Cause leakage from cell membranes: Polypeptidespolymyxins, colistin, bacitracin polyene amphotericin B, nystatin, hamycin.
- Inhibit protein synthesis: Tetracyclines, chloramphenicol, erythromycin, clindamycin, linezolid.
- Cause misreading of mRNA code and affect permeability: Aminoglycosides-Streptomycin, Gentamycin, etc.
- Inhibit DNA gyrase: Fluoroquinolones-Ciproflxacin and others.
- Interfere with DNA function: Rifampin, Metronidazole.
- Interfere with DNA synthesis: Acyclovir, Zidovudine.
- Interfere with intermediary metabolism: Sulfo amides, sulfones, para-aminosalicylic acid (PAS), trimethoprim, pyrimethamine, ethambutol.
Question 5. Write An Account Of Drug Induced Superinfections And Its Management.
Answer:
- Superinfection refers to the appearance of a new infection as a result of antimicrobial therapy for another infection.
- The etiologic organism of superinfection is different from that of the primary disease.
- Most of the antimicrobial drugs mainly broad-spectrum antibiotics, ampicillin, etc. cause alteration of normal bacterial flora due to which host defense mechanism becomes impaired. Now the pathogenic microorganism invades the host, multiplies, and leads to superinfection.
Following Are The Drug-Induced Super Infections And Their Management:
- Candida albicans leads to oral thrush, monilial diarrhea, and vulvovaginitis which is treated with nystatin or clotrimazole.
- Resistant staphylococci lead to enteritis which is treated by cloxacillin, vancomycin, and linezolid.
- Clostridium difficile leads to pseudomembranous enterocolitis associated with the use of clindamycin, tetracycline, aminoglycosides, ampicillin, cotrimoxazole for treating this metronidazole and vancomycin are the drugs of choice.
- Proteus leads to UTI and enteritis which is treated with cephalosporin or gentamicin.
- Pseudomonas leads to UTI and enteritis which is treated with carbenicillin, piperacillin, and gentamycin.
Question 6. Enumerate Drugs Effective In Staphylococcal Infection.
Answer:
The following are the drugs effective in staphylococcal infection:
- Cephalosporins
- Nafcillin or related antibiotics
- Sulfa drugs
- Vancomycin.
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