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Antimicrobial drugs General considerations

  1. Antimicrobial Drugs Dr. Karun Kumar Senior Lecturer Dept. of Pharmacology
  2. Chemotherapy • Treatment of • Systemic infections with • Specific drugs that • Selectively suppress the • Infecting microorganism • Without significantly affecting the host
  3. Antibiotics • Substances produced by microorganisms which • Selectively suppress the growth of or • Kill other microorganisms at • Very low concentrations
  4. • This definition excludes 1. Other natural substances which also inhibit microorganisms but are produced by higher forms (e.g. antibodies) 2. Produced by microbes but are needed in high concentrations (ethanol, lactic acid, H2O2)
  5. Antimicrobial agents • Synthetic • as well as • Naturally obtained drugs that • Attenuate microorganisms
  6. Classification based on MOA 1. Inhibit cell wall synthesis 1. Penicillins 2. Cephalosporins 3. Cycloserine 4. Vancomycin 5. Bacitracin
  7. 2. Cause leakage from cell membranes: 1. Polypeptides- 1. Polymyxins 2. Colistin 3. Bacitracin 2. Polyenes 1. Amphotericin B 2. Nystatin 3. Hamycin
  8. 3. Inhibit protein synthesis 1. Tetracyclines 2. Chloramphenicol 3. Erythromycin 4. Clindamycin 5. Linezolid
  9. 4. Cause misreading of m-RNA code and affect permeability  Aminoglycosides 5. Inhibit DNA gyrase  Fluoroquinolones 6. Interfere with DNA function  Rifampicin 7. Interfere with DNA synthesis  Acyclovir Zidovudine
  10. 8.Interfere with intermediary metabolism 1. Sulfonamides 2. Sulfones 3. Para-amino Salicylic Acid 4. Trimethoprim 5. Pyrimethamine 6. Metronidazole.
  11. Type of organisms against which primarily active 1. Antibacterial  Penicillins, Aminoglycosides, Erythromycin, Fluoroquinolones, etc. 2. Antifungal  Griseofulvin, Amphotericin B, Ketoconazole, etc.
  12. 3. Antiviral  Acyclovir, Amantadine, Zidovudine, etc. 4. Antiprotozoal  Chloroquine, Pyrimethamine, Metronidazole, Diloxanide, etc. 5. Antihelmintic  Mebendazole, Pyrantel, Niclosamide, Diethyl carbamazine, etc.
  13. Spectrum of activity 1. Narrow spectrum 1. Penicillin G 2. Streptomycin 3. Erythromycin 2. Broad spectrum 1. Tetracyclines 2. Chloramphenicol
  14. Type of action 1. Bacteriostatic (CECT Scan) 1. Chloramphenicol 2. Erythromycin 3. Ethambutol 4. Clindamycin 5. Tetracyclines 6. Sulfonamides
  15. Bactericidal (Know your ABCs and TBs) 1. Aminoglycosides 2. Beta-lactam antibiotics (PC) 3. Cotrimoxazole 4. Isoniazid 5. Rifampicin 6. Pyrazinamide
  16. Important note • Some primarily static drugs may become cidal at higher concentrations (as attained in the urinary tract), e.g. erythromycin, nitrofurantoin. • Some cidal drugs, e.g. Cotrimoxazole, Streptomycin may only be static under certain circumstances.
  17. Problems arising with AMAs 1. Toxicity 2. Hypersensitivity reactions 3. Drug resistance 4. Superinfection (Suprainfection) 5. Nutritional deficiencies 6. Masking of an infection
  18. 1. Local irritancy  Exerted at the site of administration. 1. Gastric irritation 2. Pain 3. Abscess formation at the site of i.m. injection 4. Thrombophlebitis of the injected vein 2. Systemic toxicity 1. Toxicity
  19. Thrombophlebitis
  20. • Practically all AMAs, especially 1. Erythromycin 2. Tetracyclines 3. Certain cephalosporins 4. Chloramphenicol • are irritants
  21. Therapeutic Index • The gap between the therapeutic effect DRC and the adverse effect DRC defines the safety margin or the therapeutic index of a drug
  22. • Median effective dose (ED50)  Dose which produces the specified effect in 50% individuals • Median lethal dose (LD50)  Dose which kills 50% of the recipients. • Therapeutic window  Bounded by the dose which produces minimal therapeutic effect and the dose which produces maximal acceptable adverse effect
  23. Systemic toxicity 1. High therapeutic index  Doses up to 100-fold range may be given without apparent damage to host cells. 1. Penicillins 2. Some cephalosporins 3. Erythromycin
  24. Lower therapeutic index • Doses have to be individualized and toxicity watched for. 1. Aminoglycosides  8th cranial nerve and kidney toxicity 2. Tetracyclines  Liver and kidney damage, antianabolic effect 3. Chloramphenicol  Bone marrow depression
  25. Very low therapeutic index • Use is highly restricted to conditions where no suitable alternative is available 1. Polymyxin B  Neurological and renal toxicity 2. Vancomycin  Hearing loss, kidney damage. 3. Amphotericin B  Kidney, bone marrow and neurological toxicity
  26. 2. Hypersensitivity reactions • All AMAs are capable of causing hypersensitivity reactions • Unpredictable and unrelated to dose. • Range from rashes to anaphylactic shock • Commonly involved (CPFS)  Cephalosporins Penicillins, Fluoroquinolones, Sulfonamides
  27. 3. Drug resistance • It refers to unresponsiveness of a microorganism to an AMA, and is akin to the phenomenon of tolerance seen in higher organisms. • Types 1. Natural 2. Acquired
  28. Natural resistance • Some microbes have always been resistant to certain AMAs. • They lack the metabolic process or the target site which is affected by the particular drug. • This is generally a group or species characteristic • Does not pose a significant clinical problem.
  29. Examples 1. Gram-negative bacilli are normally unaffected by penicillin G 2. Aerobic organisms are not affected by metronidazole 3. Anaerobic bacteria are not inhibited by aminoglycoside antibiotics 4. M. tuberculosis is insensitive to tetracyclines.
  30. Acquired resistance • It is the development of resistance by an organism (which was sensitive before) due to the use of an AMA over a period of time. • Can happen with any microbe • Major clinical problem • However, development of resistance is dependent on the microorganism as well as on the drug.
  31. • Some bacteria are notorious for rapid acquisition of resistance, e.g. staphylococci, coliforms, tubercle bacilli. • Others like Strep. pyogenes and spirochetes have not developed significant resistance to penicillin despite its widespread use for > 50 years.
  32. • Gonococci quickly developed resistance to sulfonamides, but only slowly and low-grade resistance to penicillin. • However, in the past 40 years, highly penicillin resistant gonococci producing penicillinase have appeared. • Resistance may be developed by mutation or gene transfer.
  33. Mutation • It is a stable and heritable genetic change that occurs spontaneously and randomly among microorganisms. • It is not induced by the AMA • Any sensitive population of a microbe contains a few mutant cells which require higher concentration of the AMA for inhibition.
  34. • These are selectively preserved and get a chance to proliferate when the sensitive cells are eliminated by the AMA. • Over time, a sensitive strain gets replaced by a resistant one, e.g. when a single antitubercular drug is used.
  35. Gene transfer • The resistance causing gene is passed from one organism to the other • Rapid spread of resistance can occur by this mechanism and high level resistance to several antibiotics (multidrug resistance) can be acquired concurrently
  36. • Resistance once acquired by any of the above mechanisms becomes prevalent due to the selection pressure of a widely used AMA, i.e. presence of the AMA provides opportunity for the resistant subpopulation to thrive in preference to the sensitive population • Resistant organisms can be drug tolerant or drug destroying or drug impermeable
  37. Drug tolerant • Loss of affinity of the target biomolecule of the microorganism for a particular AMA 1. Resistant Staph. aureus and E. coli develop a RNA polymerase that does not bind rifampin 2. Certain penicillin-resistant pneumococcal strains have altered penicillin binding proteins
  38. 3. Trimethoprim-resistance results from plasmid- mediated synthesis of a dihydrofolate reductase that has low affinity for trimethoprim. • Mutational target site modification is an important mechanism of fluoroquinolone and macrolide resistance.
  39. • Another mechanism is acquisition of an alternative metabolic pathway, e.g. certain sulfonamide resistant bacteria switch over to utilizing preformed folic acid in place of synthesizing it from PABA taken up from the medium.
  40. Drug destroying • The resistant microbe elaborates an enzyme which inactivates the drug 1. β-lactamases are produced by staphylococci, Haemophilus, gonococci, etc. which inactivate penicillin G.
  41. • The β-lactamases may be present in low quantity but strategically located periplasmically (as in gram- negative bacteria) so that the drug is inactivated soon after entry, or may be elaborated in large quantities (by gram positive bacteria) to diffuse into the medium and destroy the drug before entry.
  42. 2. Chloramphenicol acetyl transferase is acquired by resistant E. coli, H. influenzae and S. typhi 3. Many of the aminoglycoside-resistant coliforms have been found to produce enzymes which adenylate/acetylate/phosphorylate specific aminoglycoside antibiotics.
  43. Drug impermeable • Many hydrophilic antibiotics gain access into the bacterial cell through specific channels formed by proteins called ‘porins’, or need specific transport mechanisms.
  44. • These may be lost by the resistant strains, e.g. concentration of some aminoglycosides and tetracyclines in the resistant gram negative bacterial strains has been found to be much lower than that in their sensitive counterparts when both were exposed to equal concentrations of the drugs.
  45. • Similarly, the low degree penicillin-resistant gonococci are less permeable to penicillin G • Chloroquine-resistant P. falciparum accumulates less chloroquine. • The bacteria may also acquire plasmid directed inducible energy dependent efflux proteins in their cell membrane which pump out tetracyclines
  46. • Active efflux-based resistance has been detected for erythromycin and fluoroquinolones as well. • Cross resistance  Acquisition of resistance to one AMA conferring resistance to another AMA, to which the organism has not been exposed, is called cross resistance.
  47. • This is more commonly seen between chemically or mechanistically related drugs 1. Resistance to one sulfonamide means resistance to all others 2. Resistance to one tetracycline means insensitivity to all others. • Such cross resistance is often complete.
  48. • However, resistance to one aminoglycoside ay not extend to another e.g. Gentamicin- resistant strains may respond to Amikacin. • Sometimes unrelated drugs show partial cross resistance, e.g. between tetracyclines and chloramphenicol, between erythromycin and lincomycin
  49. • Cross resistance may be 1. 2-way (Between erythromycin and clindamycin and vice versa) 2. 1-way (Development of Neomycin resistance by Enterobacteriaceae makes them insensitive to streptomycin but many streptomycin-resistant organisms remain susceptible to neomycin)
  50. Prevention of drug resistance 1. No indiscriminate and inadequate or unduly prolonged use of AMAs should be made. • This would minimize the selection pressure and resistant strains will get less chance to preferentially propagate. • For acute localized infections in otherwise healthy patients, symptom-determined shorter courses of AMAs are advocated.
  51. 2. Prefer rapidly acting and selective (narrow spectrum) AMAs whenever possible; broad-spectrum drugs should be used only when a specific one cannot be determined or is not suitable. 3. Use combination of AMAs whenever prolonged therapy is undertaken, e.g. tuberculosis, SABE, HIV- AIDS. 4. Infection by organisms notorious for developing resistance, e.g. Staph. aureus, E. coli, M. tuberculosis, Proteus, etc. must be treated intensively.
  52. 4. Superinfection (Suprainfection) • Appearance of a new infection as a result of antimicrobial therapy. • Use of most AMAs causes some alteration in the normal microbial flora of the body. • The normal flora contributes to host defence by elaborating substances called bacteriocins which inhibit pathogenic organisms.
  53. • Further, the pathogen has to compete with the normal flora for nutrients, etc. to establish itself. • Lack of competition may allow even a normally nonpathogenic component of the flora, which is not inhibited by the drug (e.g. Candida), to predominate and invade. • More complete the suppression of body flora, greater are the chances of developing superinfection.
  54. • Thus, it is commonly associated with the use of broad/extended-spectrum antibiotics, such as tetracyclines, chloramphenicol, ampicillin, newer cephalosporins; especially when combinations of these are employed
  55. • Tetracyclines are more liable than Chloramphenicol and Ampicillin is more liable than Amoxicillin to cause superinfection diarrhoeas because of incomplete absorption—higher amounts reach the lower bowel and cause greater suppression of colonic bacteria. • Superinfections are more common when host defence is compromised
  56. • Sites involved in superinfection are those that normally harbour commensals, i.e. Oropharynx; intestinal, respiratory and genitourinary tracts; occasionally skin.
  57. • Superinfections are generally more difficult to treat. • The organisms frequently involved, the manifestations and drugs for treating superinfections are: 1. Candida albicans  Monilial diarrhoea, thrush, vulvovaginitis; treat with nystatin or clotrimazole 2. Resistant staphylococci  Enteritis; treat with cloxacillin or vancomycin/linezolid. 3. Proteus  Urinary tract infection, enteritis; treat with a cephalosporin or Gentamicin
  58. 4. Clostridium difficile  Pseudomembranous enterocolitis associated with the use of clindamycin, tetracyclines, aminoglycosides, ampicillin, etc. • It is more common after colorectal surgery. • The organism produces an enterotoxin which damages gut mucosa forming plaques • Metronidazole and Vancomycin are the drugs of choice. 5. Pseudomonas  Urinary tract infection, enteritis; treat with Carbenicillin, Piperacillin, Ceftazidime, Cefoperazone or Gentamicin.
  59. To minimize superinfections 1. Use specific (narrow-spectrum) AMA whenever possible. 2. Do not use antimicrobials to treat trivial, self- limiting or untreatable (viral) infections. 3. Do not unnecessarily prolong antimicrobial therapy
  60. 5. Nutritional deficiencies • Some of the B complex group of vitamins and vit K synthesized by the intestinal flora is utilized by man. • Prolonged use of antimicrobials which alter this flora may result in vitamin deficiencies. • Neomycin causes morphological abnormalities in the intestinal mucosa—steatorrhoea and malabsorption syndrome can occur.
  61. 6. Masking of an infection • A short course of an AMA may be sufficient to treat one infection but only briefly suppress another one contacted concurrently. • The other infection will be masked initially, only to manifest later in a severe form • Tuberculosis masked by a short course of Streptomycin given for trivial respiratory infection.
  62. Choice of an AMA 1. Patient factors 1. Age 2. Renal and hepatic function 3. Local factors 4. Drug Allergy 5. Impaired host defence 6. Pregnancy 7. Genetic factors
  63. 2. Organism related considerations (Oro-dental infections) 3. Drug factors 1. Spectrum of activity 2. Type of activity 3. Sensitivity of the organism 4. Relative toxicity 5. Pharmacokinetic profile 6. Route of administration 7. Evidence of clinical efficacy 8. Cost
  64. Patient factors 1. Age 1. The t½ of aminoglycosides is prolonged in the elderly and they are more prone to develop VIII nerve toxicity. 2. Tetracyclines deposit in the developing teeth and bone—discolour and weaken them—are contraindicated below the age of 6 years
  65. 2. Renal and hepatic function
  66. 3. Local factors 1. Presence of pus and secretions decrease the efficacy of most AMAs, especially sulfonamides and aminoglycosides. • Drainage of the abscess reduces the population of the causative bacteria, suppresses anaerobes by exposure to oxygen, and improves diffusion of the antibiotic into the abscess.
  67. 2. Presence of necrotic material or foreign body including catheters, implants and prosthesis makes eradication of infection practically impossible. • Bacteria adhering to foreign surfaces create a biofilm around them and grow very slowly, rendering them difficult to reach and less vulnerable to the antibiotic. 3. Haematomas foster bacterial growth; Tetracyclines, Penicillins and Cephalosporins get bound to the degraded haemoglobin in the haematoma.
  68. 4. Lowering of pH at the site of infection reduces activity of macrolide and aminoglycoside antibiotics. 5. Anaerobic environment in the centre of an abscess impairs bacterial transport processes which concentrate aminoglycosides in the bacterial cell, rendering them less susceptible 6. Penetration barriers at certain sites may hamper the access of the AMA to the site, such as in subacute bacterial endocarditis (SABE), endophthalmitis, root canal of teeth
  69. 4. Drug allergy • History of previous exposure to an AMA should be obtained. • If an AMA has caused allergic reaction—it has to be avoided in that patient, e.g. drug of choice for syphilis in a patient allergic to penicillin is tetracycline. • β-lactams, Sulfonamides and Fluoroquinolones frequently cause allergy.
  70. 5. Impaired host defence • Integrity of host defence plays a crucial role in overcoming an infection. • Pyogenic infections occur readily in neutropenic patients • If cell-mediated immunity is impaired (e.g. AIDS), infections by low grade pathogens and intracellular organisms abound.
  71. • In an individual with normal host defence, a bacteriostatic AMA may achieve cure; while intensive therapy with cidal drugs is imperative in those with impaired host defence or when the organisms are protected by a barrier—as in SABE. • Even then complete eradication of the organism may not occur.
  72. 6. Pregnancy • All AMAs should be avoided in the pregnant woman because of risk to the foetus. • Penicillins, many Cephalosporins and Erythromycin are safe, while safety data on most others is not available. • Tetracyclines are clearly contraindicated (Risk of acute yellow atrophy of liver, pancreatitis and kidney damage in the mother, as well as cause teeth and bone deformities in the offspring).
  73. • Aminoglycosides can cause foetal ear damage. • Animal studies indicate increased risk to the foetus, especially with Fluoroquinolones, Cotrimoxazole, Chloramphenicol, Sulfonamides and Nitrofurantoin. • Though Metronidazole has not been found teratogenic, its mutagenic potential warrants caution in its use during pregnancy
  74. 7. Genetic factors • Primaquine, nitrofurantoin, sulfonamides, chloramphenicol and fluoroquinolones carry the risk of producing haemolysis in G-6-PD deficient patient
  75. Oro-dental infections • The causative organisms of common orodental infections like alveolar abscesses, periodontal abscesses, dental pulp infections, chronic periodontitis, acute necrotizing ulcerative gingivitis (ANUG),etc. are usually Bacteroides and other anaerobes, aerobic gram positive cocci chiefly viridans group Streptococci and spirochetes. • The anaerobes predominate in abscesses rather than in cellulitis
  76. • Orodental infections are often mixed bacterial infections • Drugs mostly selected are from Penicillin/Amoxicillin (with or without Clavulanic acid) / some cephalosporins like Cefuroxime or cefaclor which are active on anaerobes, Erythromycin, Azithromycin, Clindamycin, Vancomycin, Doxycycline, Ofloxacin and Metronidazole/Tinidazole.
  77. • Most dentists initiate empirical therapy with Amoxicillin and Metronidazole • If possible (esp. in serious infections), specimen for bacteriological examination should be collected before initiating empirical therapy • In a few situations like ANUG and oral thrush the clinical diagnosis itself indicates the infecting organism and directs the choice of drug (Penicillin / Doxycycline + Metronidazole for ANUG; Nystatin or Clotrimazole for thrush)
  78. Drug factors 1. Spectrum of activity: For definitive therapy, a narrow-spectrum drug which selectively affects the concerned organism is preferred, because it is generally more effective than a broad spectrum AMA, and is less likely to disturb the normal microbial flora. • However, for empirical therapy, often a broad- spectrum drug has to be used to cover all likely pathogens.
  79. 2. Type of activity • A bactericidal antibiotic may be preferred over bacteriostatic because it directly reduces the number of bacteria at the site of infection, while the static drug only prevents increase in their number. • This is important in while treating patients with impaired host defence, life-threatening infections, infections at less accessible sites (endodontic infections, SABE) or when carrier state is possible (typhoid).
  80. 3. Sensitivity of the organism • Consideration of Postantibiotic effect (PAE) • PAE  After a brief exposure if the organism is placed in antibiotic-free medium, it starts multiplying again, but after a lag period which depends on the antibiotic as well as the organism. This lag period in growth resumption is known as ‘postantibiotic effect’ • A long PAE has been noted with Fluoroquinolones, Aminoglycosides and Rifampin
  81. 4. Relative toxicity • A less toxic antibiotic is preferred, e.g. a β-lactam over an Aminoglycoside or Erythromycin over Clindamycin.
  82. 5. Pharmacokinetic profile • For optimum action the antibiotic has to be present at the site of infection in sufficient concentration for an adequate length of time. • For many organisms, Aminoglycosides, FQs and Metronidazole produce ‘concentration-dependent inhibition’, i.e. Killing effect of drug is high when ratio of peak conc. to MIC is more. • The same daily dose of gentamicin produces better action when given as a single dose than if it is divided into 2–3 portions.
  83. • On the other hand, β-lactams, Vancomycin and Macrolides produce ‘time dependent inhibition’, i.e. antimicrobial action depends on the length of time the concentration remains above the MIC; division of daily dose improves the effect. • Penetration to the site of infection also depends on the pharmacokinetic properties of the drug. • A drug which penetrates better and attains higher concentration at the site of infection is likely to be more effective.
  84. • Penetration of AMAs into bone is generally poor, but Clindamycin penetrates very well and is a good choice for purulent osteitis and certain other tooth infections • The fluoroquinolones have excellent tissue penetration—attain high concentrations in soft tissues, lungs, prostate, joints, etc. • Ciprofloxacin and Rifampin have very good intracellular penetration. • Cefuroxime, Ceftriaxone, Chloramphenicol, Ciprofloxacin attain high CSF concentration. • Ampicillin, Cephalosporins and Erythromycin attain high biliary concentration.
  85. 6. Route of administration • Many AMAs can be given orally as well as parenterally, but Aminoglycosides, Penicillin G, Carbenicillin, many cephalosporins, vancomycin, etc. have to be given by injection only. • For less severe infections, an oral antibiotic is preferable; but for serious infections, e.g. meningitis, spreading cellulitis, septicaemias, a parenteral antibiotic would be more reliable
  86. 7. Evidence of clinical efficacy • Relative value of different AMAs in treating an infection is decided on the basis of comparative clinical trials. • Optimum dosage regimens and duration of treatment are also determined on the basis of such trials. • Reliable clinical trial data, if available, is the final guide for choice of the antibiotic. 8. Cost  Less expensive drugs are to be preferred
  87. Combined use of antimicrobials 1. To achieve synergism 2. To prevent emergence of resistance  TB, leprosy, HIV, H. pylori, malaria 3. To broaden the spectrum of antimicrobial action
  88. 1. To achieve synergism 1. 2 bacteriostatic agents are often additive, rarely synergistic, i.e. combination of tetracyclines, chloramphenicol, erythromycin, etc. • Special case  Sulfonamide used with trimethoprim • β-lactamase inhibitor Clavulanic acid or Sulbactam with amoxicillin or ampicillin for β-lactamase producing H. influenzae, N. gonorrhoeae and other organisms.
  89. 2. 2 bactericidal drugs are frequently additive and sometime synergistic if the organism is sensitive to both 1. Penicillin/ampicillin + streptomycin/gentamicin or vancomycin + gentamicin for enterococcal SABE. Penicillins by acting on the cell wall may enhance the penetration of the aminoglycoside into the bacterium.
  90. 2. Carbenicillin/ticarcillin + gentamicin for Pseudomonas infection, especially in neutropenic patients. 3. Ceftazidime + ciprofloxacin for Pseudomonas infected orthopedic prosthesis. 4. Rifampin + isoniazid in tuberculosis. • Complete eradication of the pathogen.
  91. 3. Combination of a bactericidal with a bacteriostatic drug may be synergistic or antagonistic depending on the organism. • Pneumococcal meningitis treated with penicillin + tetracycline had higher mortality than those treated with penicillin alone
  92. • Synergism may be seen in 1. Penicillin + sulfonamide for actinomycosis 2. Streptomycin + tetracycline for brucellosis 3. Streptomycin + chloramphenicol for K. pneumoniae infection 4. Rifampin + dapsone in leprosy
  93. 3. To broaden the spectrum of antimicrobial action 1. Treatment of mixed infection  Many orodental infections are mixed infections. Clindamycin or metronidazole are generally included (anaerobes) 2. Initial treatment of severe infections  Penicillin + streptomycin; cephalosporin or erythromycin + an aminoglycoside ± metronidazole or clindamycin 3. Topically  Bacitracin, Neomycin, polymyxin B
  94. Disadvantages of antimicrobial combinations 1. They foster a casual rather than rational outlook in the diagnosis of infections and choice of AMA. 2. Increased incidence and variety of adverse effects. Toxicity of one agent may be enhanced by another, e.g. vancomycin + tobramycin and gentamicin + cephalothin produce exaggerated kidney damage. 3. Increased chances of superinfections. 4. If inadequate doses of nonsynergistic drugs are used—emergence of resistance may be promoted. 5. Higher cost of therapy
  95. Prophylactic use of antimicrobials • Use of AMAs for preventing the setting in of an infection or suppressing contacted infection before it clinically manifests • Highly successful when directed against specific organisms 1. Rheumatic fever  Benzathine Penicillin is the drug of choice for preventing infection by group A streptococci 2. INH ± Rifampicin to prevent TB
  96. Antimicrobial prophylaxis in dentistry 1. Prevention of local wound infection 2. Prevention of distant infection (bact. Endocarditis) in predisposed pts. following dental procedures • Antiseptic rinse with chlorhexidine (0.2%) held in the mouth for 1 minute just before dental t/t (↓ severity of bacteraemia following dental extraction)
  97. Failure of antimicrobial therapy 1. Improper selection of drug, dose, route or duration of treatment. 2. Treatment begun too late. 3. Failure to take necessary adjuvant measures, e.g. drainage of abscesses, empyema, etc.; removal of renal stones, other foreign bodies; cavity closure; control of diabetes, etc.
  98. 4. Poor host defence—as in leukaemias, neutropenia and other causes, especially if a bacteriostatic AMA is used. 5. Infecting organism present behind barriers, such as vegetation on heart valves (SABE), inside the eyeball, blood brain-barrier.
  99. Disadvantages of antimicrobial combinations 1. They foster a casual rather than rational outlook in the diagnosis of infections and choice of AMA. 2. Increased incidence and variety of adverse effects. Toxicity of one agent may be enhanced by another, e.g. vancomycin + tobramycin and gentamicin + cephalothin produce exaggerated kidney failure.
  100. 3. Increased chances of superinfections. 4. If inadequate doses of nonsynergistic drugs are used—emergence of resistance may be promoted. 5. Higher cost of therapy

Editor's Notes

  1. DNA gyrase is an essential bacterial enzyme that catalyzes the ATP-dependent negative super-coiling of double-stranded closed-circular DNA.
  2. Thrombophlebitis is a phlebitis (inflammation of a vein) related to a thrombus (blood clot).
  3. Thrombophlebitis is a phlebitis (inflammation of a vein) related to a thrombus (blood clot).
  4. antianabolic. [-an′əbol′ik] pertaining to drugs or other agents that inhibit or retard anabolic processes, such as cell division and the creation of new tissue by protein synthesis.
  5. Coughing; wheezing; and pain, itching, or tightness in your chest Fainting, dizziness, confusion, or weakness Hives; a rash; and itchy, swollen, or red skin Runny or stuffy nose and sneezing Shortness of breath or trouble breathing and rapid heartbeat Swollen or itchy lips or tongue Swollen or itchy throat, hoarse voice, trouble swallowing, tightness in your throat Vomiting, diarrhea, or cramps Weak pulse, paleness Some people also remember feeling a "sense of doom” right before the attack. phylaxis in British. (faɪˈlæksɪs) medicine. medical term for protection against infection.
  6. A genetic form of angioedema. (Angioedema is also referred to as Quinke's disease.) Persons with it are born lacking an inhibitor protein (called C1 esterase inhibitor) that normally prevents activation of a cascade of proteins leading to the swelling of angioedema. Angioedema is an area of swelling of the lower layer of skin and tissue just under the skin or mucous membranes.
  7. a microorganism, especially a bacterium causing disease or fermentation.
  8. SS/MS
  9. C/T/T
  10. a mutagen is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level
  11. G6PD helps red blood cells work. It also protects them from substances in the blood that could harm them. Glucose 6-Phosphate Dehydrogenase Plays a Key Role in Protection Against Reactive Oxygen Species. glucose 6-phosphate dehydrogenase deficiency protects against falciparum malaria. The parasites causing this disease require reduced glutathione and the products of the pentose phosphate pathway for optimal growth. Thus, glucose 6-phosphate dehydrogenase deficiency is a mechanism of protection against malaria, which accounts for its high frequency in malaria-infested regions of the world.
  12. Cellulitis (sel-u-LIE-tis) is a common, potentially serious bacterial skin infection. The affected skin appears swollen and red and is typically painful and warm to the touch. Cellulitis usually affects the skin on the lower legs, but it can occur in the face, arms and other areas
  13. based on, concerned with, or verifiable by observation or experience rather than theory or pure logic.
  14. oral candidiasis
  15. AGs
  16. Empyema is defined as a collection of pus in the pleural cavity, gram-positive, or culture from the pleural fluid.