The document discusses various classes of antimicrobial agents including their classification, mechanisms of action, spectra of activity, and examples. It covers antibiotics such as penicillin, cephalosporins, aminoglycosides, and macrolides. It also addresses antimicrobial resistance, rational antibiotic usage, and combination therapy.
Most Beautiful Call Girl in Bangalore Contact on Whatsapp
Antimicrobial agents
1. • Dr Karishma S Halageri
1st year PG
Dept of Public Health Dentistry
Antimicrobial agents
2. CONTENTS
Introduction
classification of antimicrobial agents
Selection of antimicrobial agents
Antibiotics
Classification of antibiotics
Antimicrobial resistance
Factors involved in the usage of antibiotics rationally
Ideal antibiotics
antibiotics combination
3. Contents
Disadvantage and misuse of antibiotics
Antimetabolites
Antifungal drugs
Antiviral drugs
Antiprotozoal drugs
Public health significance
Conclusion
References
4. Introduction
An antimicrobial is an agent that kills or inhibits the growth of
microorganisms without harming the cells of the host. The
antimicrobial agent may be a chemical compounds and physical
agents. These agents interfere with the growth and reproduction of
causative organisms like bacteria, fungi, parasites , virus .
5. Classification of antimicrobial agents
Drugs by susceptible organisms
Antibacterial
Antiviral
Antifungal
Antiprotozoal
Anthelmintic
6. Selection Of Antimicrobial Agents
Organisms identity
and its sensitivity to
particular organism
The site of infection
The safety of the
agent
Patient factors
The cost of the
therapy
7. • Acutely ill patient
• Selecting a drug
Empiric therapy prior to organism
identification
• Blood brain barrier ,prostate
Identification and sensitivity of the
organism
• Disk diffusion method
Laboratory methods of
identification
The effect of site of infection on
therapy
8. Status of the patient
1.Immune system
2.Renal dysfunction
3.Hepatic dysfunction
4.Poor Perfusion
5.Pregnancy
6.Lactation
7.age
Safety of the agent
Cost of therapy
9. Chemotherapeutic spectra
• Agents acting on a single or limited group of
microorganisms .
Narrow spectrum
• Active against gram+ve and significant number of
gram-ve microorganims
Extended spectrum
• Affect a wide variety of microbial species
Broad spectrum
10. Antibiotics
A substance produced by which selectively suppress
the growth of or kill other microorganisms at low
concentrations and has the capacity to inhibit the
growth of bacteria. It has a high chemotherapeutical
index to reduce the active process in bacteria . in a
diluted solution.
11.
12. Classification of antibiotics
1. Based on chemical structures
2. Based on the sources
3. Based on mechanism of action
4. Based on spectrum of action / activity
5. Based on modes of action
13. 1. Based on chemical structures
1. Groups of sulfonamides
Sulfamethoxazole, sulfadiazine
2. Groups of Penicillin
Penicillin G (Benzyl penicillin), Penicillin V,
Ampicillin, amoxicillin, nafcillin
3. Groups of cephalosporin's
cefalotin, cefazolin, cefamandole, cefuroxime,cefotaxime, ceftriaxone.
4. Groups of aminoglycosides
streptomycin,neomycin, kanamycin, gentamycin, tobramycin
5. Groups of chloramphenicol
chloramphenicol, tiamphenicol
14. 6. Groups of tetracyclines
chlortetracycline,oxytetracycline, doxycycline, minocycline
7. Groups of macrolides
erythromycin,roxithromycin, spiramycin, azithromycin
8. Groups of polyenes
amphotericin B, nystatin
9. Groups of Lincomycins
lincomycin, clindamycin
10. Groups of polymixins
Polymyxin B, Polymyxin E
15. II. Based on the sources
a. Antibiotic from microbes
A.B. from fungi - Penicillin from P. notatum
A.B. from bacteria
• A.B. from eubacteria - polymyxin from bacillus polymyxa
• A.B. from micromonosporaceae - gentamyicin from
micromonospora purpurea
b. Antibiotics from algae - Usnat Acid
c. Antibiotics from higher plants - Garlisina from Allium sativum
d. Antibiotics from animals - Eritrina from hemoglobin of cow
16. III. Based on mechanism of action
A. Inhibition of cell wall synthesis leads to the death
of the bacteria lysis (bactericidal effect)
penicillin, cycloserine, vancomycin, bacitracin
B. Disruption of cell membrane function
polymyxin (polymyxin B, polymyxin E), polyenes, nystatin
C. Inhibition of protein synthesis:
This antibiotics inhibit one of the reactions in the
process of transcription
1. Inhibition of translation process of microbes
17. • Inhibit ribosome on the 30 S subunit
-streptomycin, tetracyclines, netilmycin, kanamycin
• Inhibit ribosome on the 50 S subunit
-chloramphenicol, clindamycin, lincomycin
Inhibits the transcription process of microbes
-Rifampin, actinomycin
D. Inhibits specific metabolic reaction
Inhibits the enzymatic reactions
-sulfonamides, INH, PAS,
trimethoprim
18. IV. Based on spectrum of action
Broad spectrum: Effective to Gram +, Gram - bacteria, mycoplasmas,
chlamydiae, rickettsiae, sometimes protozoa
-chloramphenicol, tetracyclines
Narrow spectrum: Effective to Gram +ve / Gram -ve bacteria only
- penicillins, cephalosporins, erythromycins, polymyxins
19. Antimicrobial resistance – WHO (2017)
Antimicrobial resistance occurs when microorganisms such as
bacteria, viruses, fungi and parasites change in ways that render
the medications used to cure the infections they cause ineffective.
When the microorganisms become resistant to most
antimicrobials they are often referred to as “superbugs”. This is a
major concern because a resistant infection may kill, can spread
to others, and imposes huge costs to individuals and society.
20. Lack of government commitment to address these issues, poor
surveillance and a diminishing arsenal of tools to diagnose, treat and
prevent also hinder the control of antimicrobial drug resistance.
21. Some approaches to solve
resistance problems
1. Reduce the usage of prophylactic antibiotics
2. Use narrow spectrum antibiotics
3. Always follow directions for use of antibiotics
4. Prescribe antibiotics based on clinical situation
and not on patient’s will or pharmaceutical advertisements.
Rational drug: drugs given after accurate
diagnosis. It will be effective with minimal side effects .
22. 1. Accurate diagnosis
2. Accurate choices of antibiotics
3. Deliver accurate dose
4. Accurate dosing interval
5. Accurate examinations of pathophysiologic conditions
of the patient
Factors involved in the usage of AB rationally,
effectively and safely.
23. Ideal antibiotics :
Effective even in the presence of body fluids exudate,
protein or enzymes.
Ability to reach the infected tissue, enough drug
concentration during the span of a dosing interval in blood /
infected area.
Do not cause resistance
Have a minimal toxic effects for the patient
Safe for pregnancy and pediatric patients
cost effective
25. Antibiotic Combinations :
The result may be addictive , potentiative or antagonistic
Addictive response :one in which the antimicrobial effect of the
combination is equal to the sum of the effects of the two drugs
alone.
Potentiative interaction: one in which the effect of the
combination is GREATER than the sum of the effects of the
individual agents.
Antagonistic response : in certain cases the combination of two
antibiotics may be less effective than one of the agents by itself .
26. Disadvantages of antibiotic combinations
Increased risk of toxic and allergic reactions
Possible antagonism of antimicrobial agents
Increased risk of superinfection
Selection of drug resistant bacteria
Increased cost
27.
28. Penicillin
Mechanism of action: the drugs weaken the cell wall, causing
the bacterium to take up excessive amounts of water and then
rupture
Penicillinases (beta- lactamases)
enzymes that cleave the beta-lactam ring and thereby render
penicillin and other beta-lactam antibiotics
Classification :
Narrow-spectrum (penicillinase sensitive)
Narrow-spectrum that are penicillinase resistant (antistaphylococcal)
Broad spectrum penicillin's (aminopenicillins)
Extended spectrum penicillin's (antipseudomonal)
29. PENICILLIN G
ANTIMICROBIAL SPECTRUM : active against most gram +ve bacteria,
gram –ve cocci (Neisseria, meningitis) and spirochetes .
With few exceptions gram –ve bacteria are resistance .
Therapeutic uses:
• Pneumonia and meningitis caused by streptococcus pneumonia
• Pharyngitis caused by streptococcus pyogens
• Infectious endocarditis( streptococcus viridans)
• Gangrene , tetanus
• Syphilis (treponema pallidum)
Side effects and toxicities :
• Pain at the site of infection , neurotoxicity with too high
plasma levels.
Inadvertent intra-arterial injection can produce severe reactions
(gangrene,necrosis) and must be avoided .
30. PENICILLIN ALLERGY
Penicillin are the most common cause of drug allergy (1-10% of the patients
will experience an allergic response) there is no direct relationship
between size of dose and intensity of allergic response.
Cross sensitivity :5-10% of patients allergic to penicillin's are also allergic
to cephalosporin's
Types of allergic reactions:
• Immediate (occurring 2-30 min after administration)
• Accelerated (occur within 1-72 hours)
• Late reactions (days or even weeks)
• Anaphylaxis (laryngeal edema, bronchoconstriction, severe
hypotension) in 0.2% of patients ,treatment – epinephrine +
respiratory support .
31. Skin tests for penicillin allergy
Penicillin skin testing , Solensky, Franklin Adkinson Jr, Feb 2014
32. Management of patients with history of
penicillin allergy
Ask patients for previous history of allergy to penicillin
If the patient refers to a positive history of allergy AVOID
PENICILLIN entirely
If the allergy is mild a CEPHALOSPORINE is appropriate as
alternative.
If the allergy is severe avoid CEPHALOSPHORINS
For many infections VANCOMYCIN AND ERYTHROMYCIN are
effective and safe .
34. EXTENDED SPECTRUM PENICILLINS
Used to treat infections with Pseudomonas Aeruginosa (ie Ticarcillin)
Penicillins combined with beta lactamase inhibitor
ie Amoxicillin + clavulanic acid = Augmentin
a.Carboxypenicillins : Carbenicillin, ticarcillin,
b. Aminopenicillin : Amipicillin, amoxicilllin.
c. Ureidopenicillin : Mezlocillin, piperacillin.
35. CEPHALOSPORINS
Broad spectrum antibiotics with low toxicity
mechanism of action : disruption of cell wall synthesis
and consequent lysis of cell .
36. CEPHALOSPORINS
First generation-
More active
Second
generation-
Third generation Forth generation
More active
against
gram positive
organism
more selective
against gram
positive and
gram negative
organisms
Highly active
against gram
negative
organisms
similar
antibacterial
activity as that 0f
third generation
but highly
resistant to beta
lactamases
Parenteral-
Cephalothin
Cefazolin
Cephaloridine
Oral-
Cephalexin
Cephadine
Cefadroxil
Parenteral
Cefuroxime
Cefoxitin
Oral
Cefaclor
Cefuroxime acetyl
Parenteral-
Cefotaxim
Ceftizoxime
Ceftriaxone
Cefoperazone
Oral
cefexim
Parenteral-
Cefepime
Cefiperome
37. Adverse effects
Allergic reactions : rash that develops after days of treatment
severe immediate reactions are rare.
Bleeding : five cephalosporins cause bleeding tendencies
(cefamandole , cefmentazole, cefoperazone , cefotetan and
moxalactam )
2 mechanism involved :
-reduction in prothrombin levels and
- impairment of platelet aggregation .
(only with moxalactam )
Thrombophlebitis : it may develop during IV infusion (>change in infusion
site)
Pain at site of IV infusion
38. IMIPENEM
Relatively new beta-lactam antibiotic with very broad spectrum.
Antimicrobial spectrum : highly active against gram +ve and gram-ve cocci .
It is also the most effective beta-lactam antibiotic against anaerobic bacteria.
Pharmacokinetics
it is not absorbed from the GI tract .
IV or IM administration .
Adverse effects
(generally well tolerated)
• GI effects (nausea, vomiting , diarrhoea)
• Hypersensitivity reactions (rashes ,pruritus )
• Superinfections with bacteria or fungi develop in about 4%of patients .
• Rarely seizures have occurred
40. Aminoglycosides
• Action: severe infections
• MOA :Disruption of bacterial Protein Synthesis
• Antimicrobial spectrum: aerobic gram-ve bacilli(E.Coli,
klebsiella, pneumonia, proteus mirabilis, pseudomonas
aeruginosa)
the drugs are inactive against most gram+ve bacteria
the drugs are ineffective against anaerobes.
• Potential for serious AE
ototoxicity, nephrotoxicity
• Not given orally due to their poor absorption
• Low dose: bacteriostatic
• High dose: bactericidal
• Gentamicin , tobramycin, amikacin
41. Macrolides
MOA: bind to the 23S rRNA in the 50S subunit ribosome
inhibiting protein synthesis
Dose: 250-500 mg/day x 5-10 days
anti bacterial spectrum – similar to penicillin (against gram+ve bacteria
and against some gram-ve )
against penicillin resistant staphylococci.
partially destroyed by gastric juice, (enteric coated tablets)
• Various preparation- enteric coated tablets
Estolate form (most resistant by gastricacid)
• Drugs belonging to this group- erythromycin, olindomycin, Spiramycin
42. New macrolides- roxithromycin, clarithromycin
Similar spectrum of erythromycin
More resistant to acid hydrolysis.
Better tissue level are achieved
Therapeutic uses:
Legionella pneumophila pneumonia (legionnaires disease)
Whooping cough (bordetella pertussis)
Corynebacterium diptheriae (diphtheria)
Chlamydial infections
Mucoplasma pneumonia
Alternative to penicillin G in penicillin allergy
43. Adverse effects
GI effects (nausea , vomiting , diarrhoea)
liver injury (cholestatic hepatitis . Happens with erythromycin estolate
in adults with pre existing history of liver disease )
Drug interactions :
CAUTION WHEN combined with astemizole and terfenadine
(antihistamines) , theophylline , warfarin(anticoagulant), carbamazepine
(anticonvulsant)
Erythromycin antagonises the effect of chloramphenicol and
clindamycin .
44. Lincosamides
Clindamycin (Cleocin)
MOA: binds to the 50S ribosomal subunit and inhibits protein synthesis
Antimicrobial spectrum : anaerobic bacteria (gram-ve and gram +ve)
Widely distributed in tissue fluids and tissues, including bone.
Avoid in the routine odontogenic infection
An excellent alternative drug in penicillin-resistant anaerobic infections
Used in Osteomyelitis of the jaws
Dose: 100-450mg 6 h x 7-10 days
Adverse events: -GI upset, pseudomembranous colitis
(symptoms include profuse watery diarrhoea ,abdominal pain fever and
leucocytosis)
- hypersensitivity reactions (rashes)
Drug interactions: neuromuscular blocking agents
45. Tetracycline
Broad spectrum antibiotic.
MOA: Suppression of bacterial growth by inhibiting protein synthesis
Low absorption through GIT.
Rapid renal excretion
Therapeutic uses
Treatment of infectious diseases (rickettsial diseases – rocky mountain
spotty fever , typhus fever , Q fever )
Infections caused by chlamydia trachomatis , brucellosis , cholera ,
pneumonia caused by mucoplasma pneumonia , lyme disease .
46. Gastric infections with helicobacter pylori
Treatment of acne (orally and topically for severe acne vulgaris )
Peptic ulcer disease (combination of tetracycline's, metronidazole
and bismuth salicylate against helicobacter pylori )
Absorption : the drugs should not be administered together with
-calcium supplements
-milk products and iron supplements
-magnesium containing laxatives
-antacids
47. Adverse Effects Of Tetracyclines
Gastrointestinal irritation(nausea , vomiting , diarrhoea )
Effects on bones and teeth (teeth discolouration in children under 5 years
old
the drugs can also supress long –bone growth )
Superinfection (C. difficile pseudomembranous colitis ,fungus infections
usually with candida albicans
Hepatotoxicity(fatty infiltration of the liver)
Renal toxicity (the drugs may exacerbate renal dysfunction in patients
with pre-existing kidney dysfunction )
Photosensitivity
48. Doxycycline (Vibramycin)
MOA: inhibit protein synthesis by preventing aminoacyl transfer
RNA from entering the acceptor sites on the ribosome
Dose: 100mg bid x 7-14 days
High potency.
Complete absorption from intestine.
High plasma binding.
Contraindications: - Food
- pregnancy
Drug interactions: anti-epileptics
52. 4. Anti - Metabolites
•Sulfonamides
•Trimethoprim
53. Sulfonamides
MOA: suppression of bacterial growth by inhibiting synthesis of folic acid
Antimicrobial spectrum : Enterococcus –poorly expressed , S. pneumonia ,
Ps. aeruginosa
THERAPEUTIC USES : urinary tract infections .
Adverse effects :
• Hypersensitivity reactions (rashes , drug fever , photosensitivity )
• Hematologic effects (haemolytic anaemia in patients with G-6PD deficiency)
• Kernicterus
• The drugs should not be given to infants under the age of 2months,
pregnant and breast feeding mothers
54. Trimethoprim
MOI: Inhibitor of dihydrofolate reductase ( suppresses bacterial
synthesis of DNA ,RNA and proteins
Therapeutic uses :
It is approved only for the initial treatment of acute uncomplicated urinary
tract infections due to susceptible organisms
(E.coli,proteus mirabilis etc )
Adverse effects :
• Generally the drug is well tolerated
• Most common adverse effect include itching and rash
• GI reactions occur occasionally
Caution when administering the drug to patients with suspected folate
deficiency – increase danger of bone marrow suppression
55. Fluoroquinolones
Ciprofloxacin (Cipro), Garenoxacin
MOA: Inhibition of DNA gyrase
Antimicrobial spectrum: Gram-negative and Gram-positive ( Anaerobes,,
S.pneumoniae and Pseudomonas)
Dose: 250-500 mg qid x 7-10 days
Contraindications: <18 yrs old, pregnancy
Adverse events: spontaneous tendon rupture
Drug interactions: probenecid, warfarin
Ciprofloxacin, Levofloxacin, Norfloxacin, Ofloxacin
Spectrum -Staphylococci, Streptococci and Pneumococci (sporfloxacin).
More widespread tissue distribution
56. Antifungal Agents
Major antifungal drugs comes from three families
Polyenes (Amphotericin B)
Imidazole's (ketoconazole , miconazole)
Antimetabolites (flucytosine)
57. Classification of antifungal drugs
Topical Systemic
Amphotericin B Amphotericin B
Carbol-Fuchsin Dapsone
Clotrimazole Fluconazole
Econazole Flucytosine
Ketoconazole Griseofulvin
Nystatin Itraconazole
Silver Sulfadiazine Ketoconazole
Oxiconazole Miconazole
Miconazole KI (Potassium Iodide)
58. Amphotericin B
Obtained from Streptomyces nodosus
It is a member of the polyene family of antibiotics
Administered by IV infusion with 5%dextrose (0.1mg/ml) or
(0.3mg/ml)
Can be applied topically as a 3%cream ,ointments or lotion is useful in
treatment of superficial candida infections .
Adverse effects:
Local irritation
gastrointestinal disturbances
Hypotension
Renal toxicity
Delirium along with fever, nausea ,abdominal pain , anorexia
59. AZOLE DERIVATIVES
Clotrimazole (Mycelex), ketoconazole (Nizoral), fluconazole (Diflucan)
MOA: inhibit cell wall synthesis
Dose: 100mg 6.5 h; 200mg 8.5h; 300mg 9.6h
Therapeutic uses:
-blastomycosis
-histoplasmosis
-effective against chronic mucocutaneous candidiasis
-successful treatment of oral candidiasis by systemic ketoconazole
ADVERSE EFFECTS :
-anorexia
-epigastric pain
–GI upset
-hepatotoxicity
-adrenocortical suppression with high doses
Drug interactions: major p-450 enzyme inhibitor
60. TREATMENT OF ORAL CANDIDIASIS
Clotrimazole troches 10 mg ,dissolve 1 troche in mouth 5
times a day for 14 days
Nystatin oral suspension 500,000 units: Swish 5 mL in mouth
then swallow (optional), 4 times a day
for 14 days
Nystatin pastilles 100,000 units: dissolve 1 in mouth 4
times a day for 14 days
clotrimazole 1% cream
Topical agents (mild to moderate oral candidiasis)
61. Systemic agents
Fluconazole 100 mg: Dispense 15 tablets, take 2 tablets on day
1,
followed by 1 tablet a day for the remainder of the
14-day treatment period
Itraconazole oral
suspension
10 mg/10 mL: Dispense 140 mL, swish and
swallow
10 mL per day for 7 to 14 days.
Voriconazole 200 mg: Dispense 14 tablets, take 1 tablet twice
daily
for 2 weeks or at least 7 days following resolution
of symptoms
62. Antiviral Drugs
• Viruses have no cell wall and made up of nucleic acid
components
• Viruses are obligate intracellular parasite
• They do not have a metabolic machinery of their own –uses host
enzymes
• Certain viruses multiply in the cytoplasm but others do in
nucleus
• Most multiplication take place before diagnosis is made
63. Antiviral Medications
Antiviral drugs
Used to treat infections caused by viruses other than HIV
Antiretroviral drugs
Used to treat infections caused by HIV, the virus that causes
AIDS
Herpes-Simplex Viruses
- HSV-1 (oral herpes)
-HSV-2 (genital herpes)
Varicella Zoster Virus
Chickenpox
Shingles
64. Antiviral drugs : nonretroviral
Mechanism of action
Inhibit viral replication
Used to treat non-HIV viral infections
Influenza viruses
HSV (herpes simplex virus), VZV (varicella zoster virus)
CMV (cytomegalovirus)
Hepatitis A, B, C (HAV, HBV, NCV)
Adverse Effects
Vary with each drug
Healthy cells are often killed also, resulting in serious toxicities
65. Antiviral spectrum ,MOA and clinical uses of
antiviral drugs
Agent Antiviral
spectrum
Mechanism of action Clinical uses
Amantidine,rimantidine Influenza A virus Blockade of uncoating
process
Prophylaxis of influenza A infection .
Idoxuridine HSV Inhibition of DNA synthesis Treatment of herpetic keratitis
Vidarabine , trifluridine HSV Inhibition of DNA synthesis Treatment of herpetic keratitis and
keratoconjuctivitis
Penciclovir HSV Inhibition of DNA synthesis Treatment of recurrent herpetic
labialis
Acyclovir HSV and VZV Inhibition of DNA synthesis Treatment of primary and recurrent
herpetic infections , mucocutaneous
herpetic infections in
immunocompromised patients ,VZV
infections ,herpetic encephalitis
66. Agent Antiviral
spectrum
Mechanism of action Clinical uses
Foscarnet HSV, VZV, CMV Inhibition of DNA synthesis Treatment of CMV retinitis and
acyclovir resistant HSV and VZV
infections
Ribavirin RSV inhibition of DNA synthesis ,
purine metabolism
Treatment of RSV pneumonia and
bronchitis
Reverse
transcriptase
inhibitors
HIV Inhibition OF DNA synthesis Treatment of HIV infection and AIDS
Protease
inhibitor
HIV Blockade of HIV protease Treatment of HIV infection and AIDS
68. Metronidazole
Uses :
-anaerobes in intra abdominal abscess
-bone and joint infections ,septicaemia
-peptic ulcer disease
-endometritis
• In Periapical abscess , periodontal abscess , acute pericoronitis
of impacted or partially erupted teeth : often used in
conjugation with Amoxicillin .
• Primary agent used in ANUG 500mg TID for 5-7days
ADVERSE EFFECTS :
nausea ,diarrhoea ,metallic taste
infrequent adverse effects : hypersensitivity reactions,
headache ,vomiting , CNS toxicity in long term systemic use
69. Triple Antibiotic Paste
metronidazole, ciprofloxacin, and minocycline
combination would be needed -diverse flora in root canal
metronidazole -at a high concentration, it cannot kill all the bacteria, indicating the
necessity for combination of other drugs
Metronidazole (nitroimidazole) -a broad spectrum against protozoa &anaerobic
bacteria.
Minocycline (semisynthetic tetracycline) with a similar spectrum of activity.
Ciprofloxacin, a synthetic fluoroquinolone, has a bactericidal mode of action
Increase in root thickness and length, resembling normal maturation of the root. the
infected area requires a normal blood supply which is no longer in necrotic pulps.
Therefore, local application of antibiotics most effective mode for delivering the
drug. •30% reduction in bacteria -2 weeks.
successful treatment- sterilization of canals and healing of periapical pathology,
immature root development, necrotic pulps, and apical periodontitis
•drawbacks of this technique- Development of resistant bacterial strains and tooth
discoloration
J Phrm Bioallied Science Aug 2012,4(suppl2) S230-233
70. New era of antimicrobial therapeutics
There has been an urgent need for new avenues of therapeutic
treatment, and a new era of prophylytic (preventative) treatment
has begun. Here the most plausible approaches are :
-antimicrobial peptides
-bacteriophage therapy
-bacterial vaccines
-cationic peptides
-cyclic D,L-a-peptides
-Bacterial interference
71. Newer antimicrobial agents in use
Newer Antibiotics in Use
Cefepime- 4th Generation cefalosporin
Aztreonam
Linezolid
Tigecycline
Teicoplanin
Levofloxacin/Moxifloxacin
Imipenem/Meropenem
Daptomycin
Tigecycline
Dalfopristin-quinupristin
72. Newer antifungals in use
• Voriconazole, ravuconazole, and posaconazole
• Echinocandins and pneumocandins are a new class of antifungals
• Acylhydrazones
New antivirals in use
• Doravirine
• Ribavirin
• Phosphonoformate
73. Public Health Significance
Only little is known about the occurrence, fate, effects and risks
associated with the release of antibiotics and other drugs into the
environment. There is still a lack of fundamental data on the occurrence,
fate and effects of antimicrobials in the environment needed for proper
risk assessment and risk management both for humans and the
environment.
Although antibiotics are used by patients outside hospitals, in livestock
attention should also be paid to their use in hospitals.
74. Emergence of resistance to multiple antimicrobial agents in pathogenic bacteria
has become a significant public health threat as there are fewer, or even
sometimes no, effective antimicrobial agents available for infections caused by
these bacteria.
Gram‐positive and Gram‐negative bacteria are both affected by the emergence
and rise of antimicrobial resistance.
Increasing resistance to antimicrobial agents that are important in the treatment
of human diseases, such as fluoroquinolones and third-generation
cephalosporins for the treatment of Salmonella and Campylobacter infections,
has significant public health implications
77. CONCLUSION
The therapeutic benefit of antimicrobial agents should be
balanced with their unintended adverse consequences.
Inappropriate antibiotic use is associated with antibiotic
resistance and Clostridium defficile infections,
Antimicrobial drugs prescribing should be prudent,
thoughtful and rational.
78. References
Goodman & Gilman .The pharmacologic basis of therapeutics :2011:12th
edition:1365-1382
K.D.Tripathi Essentials of Medical Pharmacology:2013:7th edition:702-930
Franklin S.Weine.Endodontic Therapy:2003:6th edition:450-560
Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II,
Rolston KV, Young JA, Wingard JR. Clinical practice guideline for the use of
antimicrobial agents in neutropenic patients with cancer: 2010 update by the
Infectious Diseases Society of America. Clinical infectious diseases. 2011 Feb
15;52(4):e56-93.ntology 2000. 2002 Jan;28(1):106-76.
Cohen ML. Epidemiology of drug resistance: implications for a post—
antimicrobial era. Science. 1992 Aug 21;257(5073):1050-5.
79. References
Lorian V, editor. Antibiotics in laboratory medicine. Lippincott Williams &
Wilkins; 2005.
Taneja N, Rao P, Arora J, Dogra A. Occurrence of ESBL & Amp-C [beta]-
lactamases & susceptibility to newer antimicrobial agents in complicated UTI.
Indian Journal of Medical Research. 2008;127(1):85.
Anderson AD, Nelson JM, Rossiter S, Angulo FJ. Public health consequences of
use of antimicrobial agents in food animals in the United States. Microbial
Drug Resistance. 2003 Dec 1;9(4):373-9
Hinweis der Redaktion
We usually classify them according to the organism they are effective against or by their mechanism of action. Antibacterial drugs are classified according their spectrum of activity. Such as narrow spectrum are effective against a few types of bacteria whereas wide spectrum has a wider range of bacteria
Selection of most appropriate agents require knowledge of
Ideally antimicrobials is selected after organism has been identified and its drug sensitivity is established , in critically ill patients delay could be fatal so immediate empiric therapy is indicated .
-acutely ill pt-infections of unkown origin(neutropenic pt decrese neutrophil count ,indicating bacterial infection )therapy is initiated after specimens are send to lab but before results of culture are available .
Selecting drug-in absence of sensitivity data is influenced by site of infection or pt history (ex hospital or community acquired ,pt immunocompromised )
Bbb excludes many antibiotics(semipermeable membrane separating blood from csf constituting a barrier to passage of cells,particles, large molecules )trimethoprim for bacterial prostatitis coz it is lipid soluble
2. poor kidney function (serum creatinine levels are used as index for renal function for adjustment of drug regimens 3. antibiotics that are conc/eliminated by the liver (ex:erythromycin , tetracycline )are contraindicated in pt with liver disease4.dec circulation to an anatomic area ,ex loer limb in diabetic ,reduces amount of antibiotic reaching extremities5. pregnancy aminoglycosides avoided due to ototoxicity ,tetracyclines causes tooth dysplasia inhibition of bone growth ,streptomycin damage 8th cranial nerve with skeletal defects in fetus 6.lactation may enter nursing infant 7. in neonates chloramphenicol and sulphonamides causes toxic effects , young children tetracyclines shoyld be avoided –affect bone growth,quinolones affect cartilage growth
Narrow spec: isoniazid only against mycobacteria ,
Ext spec :ampicillin cephalosporins ,aminoglycosides
Broad spec: tetracycline ,chloramphenicol
Chemotheraupeutical Index- ratio of maximum tolerated dose of chemical agent used in chemotherapy to its minimum effective dose .
History divided into 3 phases
a)Period of empirical useof mouldy curd by Chinese on boils ,chaulmoogra oil by hindus in leprosy
b)ehrlichs phase of dyes and organometallic comp .with discovery of microbes in later half
c)Modern era of chemotherapy by Domagk in1935 by demonstrating the therapeutic effect of prontosil a sulfonnamide dye in pyogenic infection then sulfapyridine was first sulfanamide to be marketed in 1938
Ww2-1939-1945
Antimicrobals all work in different ways. In addition antibiotics may be classified as Bacteriocidal- kills bacteria or bacteriostatic inhibit bacteria, but doesn’t actually kill them. it can be reversible unless the host itself has destroyed the organism.
Sulfonomides, erythromycin and tetracyclines are examples of bacteriostatic drugs. Penicillins and the cephalosporins weaken the cell wall bybinding with certain proteins to to decrese synthesis of the cell wall. These antibiotics are also called autolytic in that they also destroy the cell wall by destroying such as with vancomycin. Inhibition of protein synthesis: there are drugs that are able to disrupt bacterial protein synthesis9ribosomes0. examples are erthromycin and clindamycin. Inhibition of nucleic acid synthesis inhibit DNa synthesis that is used for bacterial repliation such as the fluorquinolones. Inhibition of metabolic pathways(antimetabolites). Nucleic acid synthesis is dependent on folic acid for productionthere are certin drugs that prevent this process from occurringsuch as the sulfonomides. Destruc of cell membrane permeability: the antifungal drugs acta to alter the cell wall permeabilitythey act as inhibitors of enzymes involved in the synthesis of sterols which are essential components of the fungalsmembranes.
Lastly, we have inhibition of viral enzymesthese drugs inhibit essential enzymes for replication. Acyclovir is an example of this type of drug
Inh – isoniazid, pas- para aminosalisylic acid used to treat tb
Antimicrobial resistance occurs naturally but is facilitated by the inappropriate use of medicines, for example using antibiotics for viral infections such as cold or flu, or sharing antibiotics. Low-quality medicines, wrong prescriptions and poor infection prevention and control also encourage the development and spread of drug resistance
Mic –minimum inhibitory conc (to confirm resistance )
Addictive ex : combination of 2 b lactam antibiotics in painkillers (aspirin+paracetamol) (potentiative/synergisum: amphicillin+gentamycin in enterococcal carditis,
Antagonistic: (bacteriostatic +bacteriocidal )
Older patients treated w ith trimethoprim/sulfamethoxazole who are concurrently taking ACE inhibitors or ARBs have an increased risk for hospitalization due to hyperkalemia. It was associated with the quick and clinically significant rise in potassium, which then caused an unrecognized arrhythmic death.
Suprainfection “:: a new infection that appears during the course of treatment of primary infection
Fever of unknown origin FUO
Inscision and drainage after that
trimethoprim+ clindamycin
Natural penicillins penicillin g known as benzyl penicillins , v –phenoxymethyl penicillin
– Pen VK and Pen G MOA /;inhibition of enzyme responsible for cross linking of peptidoglycan polymer during last stage of bacterial cell wall synthesis
Bactericidal
Allergic reaction: rare (4 per 100,000)
Spectrum:
– Strep, staph, enterococcus, neiseria, treponema, listeria
Resistance:
– Mostly staph (>80%)
allergen is introduced into the skin -contact with cutaneous mast cells -Binding of the allergen occurs ,patient's mast cells are coated with IgE recognizing that specific allergen. -then adjacent allergen-specific IgE -cross-linked on the mast cell surface & activated ,positive skin test,
•transient "wheal-and-flare" reaction (15 to 20 min) •central area of superficial skin edema (wheal) surrounded by erythema (flare). Pruritic reaction represents the immediate phase. •cutaneous mast cells are not activated, (no edema or erythema develo& the test is
negative)
Penicillin resistant penicillins –highly effective against s aureus methicillin given parentally , nafcillin can be given orally
Acid labile: unstable ,readily undergo change in solu, molecule which changes in acidic conditions
Acid resistanc : drugs stable towards the destructive action of acids
B lactamase inhibitor ex clavulanic acid and sulbactam , tazobactam
By combination with thesethey extend range of antibacterial activity
Much less used in dentistry than penicillin, these antibiotic are synthesised from fungus cephalosporium acremonium
1st gen – cefadroxil (duracef) cephalexin(Keflex) –alt to penicillin for odontogenic infections
MOA: DISRUPT THE PEPTIDOGLYCAN LAYER FORMING TGE BACTERIAL CELL WALL
Prothrombin- factor 2 clotting
Inflamation in vein related to thrombus . Blood clot -thrombophlebitis
Imipenem trade name –piramixin 250-500mg iv
Ototoxicity – toxic to earcochlea or auditory nerve (tinittus,hearing loss,dizziness)
Ex;gentamycin,neomysin,amikasin-given frequently against tobramysin and gentamysin resistant organism all are given generic version or iv , neo fradin is given orally
Erythromycin Erythromycin is a second-choice bacteriostatic antibiotic, becoming first choice for treating dental infections in patients allergic to penicillin.
Neuromuscular blocking agents –skeletal muscle relaxation during surgery , endotracheal intubation. –quaternary ammonium salts ,succinyl choline ,mivacurium
Resistance – Enteroccocus
Rocky mountain spotty fever-characterised by rash, transmitted by bite of tick ,
(formation of chelates reduces absorption)
Photosensitivity- the drugs increase sensitivity of skin to UV radiation )
Brand name –doryx,doxyhexal,doxylin
Posology –appropriate dosage of drugs
Competitive inhibitor of enzyme- dihydropteroate synthase(dhps) enzyme involbed in folate synthesis
Kernicterus (a disorder in new born caused by deposition of bilirubin in brain).
Ex: sulfisoxazole,zonisamide
for uti combined with diuretics frusemide ,torsemide
Ex: Bactrim,septra
Trade name ; primsolproloprim 200mg
Probenecid-uricosuric agent in renal imapirment
Warfarin-anticoagulant
Fungal diseases may take the form of superficial infections involving skin and mucous membrane or systemic infections involving internal organs
Superficial mycoses managed by topical drugs ,systemic fungsl infections 2types acc to state of patients – opportunistic mycoses or immunocompromised pts and acc fungi involved
Moa: these drugs attack the ergosterol , a lipid component of fungal cell wall .since humans have cholesterol as their major cell membrane component these wont affect it. They act by inducing pores in cell wall, then they will be unable to maintain water and electrolytic homeostasis and therefore dies
It is poorly water soluble and sufficiently soluble with iv infusion in 5%dextrose . It is extremely unstable in solution particularly In normal saline .
Caution should be taken when this is taken with other nephrotoxic drugs coz it may cause hypokalemia ,it can increase digitalis toxicity .
Moa:inhibit cytochrome p450 , this decreases conversion of 14 alphamethyl sterols to ergosterol ,mp membrane component ,failure of ergosterol synthesis causes altered membrane permeability –loss os ability to maintain normal intracellular environment .
Ketaconazole in past was used as mrdical adrenectomy when surgical treatment was unavailable,contraindicated or unaffordable .
Adrenocortical suppression :serum testosterone level decreases ,no effect on estrogen or progesterone levels but might be menstrual irregularities
-Antiviral drugs are purine or pyrimidine analogs -many antiviral drugs are prodrugs ,they must be phosphorylated by viral or cellular enzymes in order to become active -antiviral agents inhibits active replication .
Trade name-flagyl metronidazole is nitromidazole class inhibit nucleic acid synthesis by disrupting dna of microbial cells
It is antibiotic and antiprotozoal
The rapid onset of resistance reduces the efficacy of most conventional antimicrobial drugs and is a general cause of concern for human well-being. Bacterial vaccines
. Bacterial genomics allows scientists to scan an entire bacterial genome for specific sequences that may be used to stimulate a protective immune response against specific bacterial strains. This approach expedites the drug discovery process and, more importantly, provides a more rational, target-based approach. The best targets are essential bacterial genes that are common to many species of bacteria, which code for proteins with the ability to gain accesses through lipid membranes, and possess no homology to human genes.
Bacterial interference refers to the antagonism between bacterial species during the process of surface colonisation and acquisition of nutrients. The clinical evidence on the potential applications of microorganisms for the prevention and/or treatment of infections in the upper respiratory, urogenital and gastrointestinal tracts
Currently, use of standard antifungal therapies can be limited because of toxicity, low efficacy rates, and drug resistance. New formulations are being prepared to improve absorption and efficacy of some of these standard therapies. Various new antifungals have demonstrated therapeutic potential. These new agents may provide additional options for the treatment of superficial fungal infections and they may help to overcome the limitations of current treatments