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8/9/2019 Antimicrobials Overview_ Batch 31
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Overview of antimicrobial agents
Dr. Vasudha Devi
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Tips- basics
F. All protein synthesis inhibitors are staticaccept aminoglycosides
Combination of protein synthesis inhibitorsmay be cidal ( cotrimoxazole)G. If a prototype drug act only on G-ve organism,the subsequent drugs developed in that class act
on G +ve also and Vice versa…example,ciprofloxacin acts mainly on G –ve organisms,where as other drugs ( newer) act on G +ve also.
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• Drugs having low penetrability, will not act onintracellular organisms ( like beta lactams have noaction on intracellular pathogens like ligonella,chlamydia)
• Some tables and graphs are very informative and helpyou to understand this topic…Selected ones are used inthis overview and underlined words are veryimportant.
• You are not required to remember the wholespectrum. Instead, identify the common uses (infections) of a particular drug and rememberorganism causing that infection
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Clinically important bacteriaGram +ve
Cocci
StaphylococcusS. aureus
S. epidermidis
StreptococcusS. pyogenes
S. viridansS. Pneumoniae
EnterococcusE. faecalis
Bacilli
ClostridiumC. tetani
C. perfringensC.difficile
C. botulinum
Corynebacterim diphtheriae
Listeria monocytogenes
Bacillus anthracis
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Gram -veCocci
Neisseria N.gonorrheaeN.menigitidis
BacilliEnterobacteriaceae
Escherichia coliSalmonella typhiShigella
KlebsiellaProteusHelicobacter pyloriColiforms
Pseudomonas aeruginosa
Ligionella pneumophiliaCamphylobacterVibrio choleraeHaemophilus influenzaeBordetella pertussis
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others
• Spirochetes
Treponema pallidum
Leptospira• Reckettsia• Chlamydiae
(intracellular)Chlamydia trachomatis
Chlamydia pneumoniae
• Mycoplasma pneumoniae( lack cell wall)
• Pnemocystis carini
(Pneumocystis jiroveci)
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Diseases caused – S. aureus: abscess (furuncle, carbuncle),
endocarditis, pneumonia – S. epidermidis : skin flora; Biofilm formation on
plastic devices infectionEndocarditis
– S. pyogenes: Pharyngitis, sinusitis, otitis media,rheumatic fever, glomerulonephritis, septicemia
–
S. viridans: endocarditis, septicemia – S. Pneumoniae: pneumonia, meningitis, sinusitis – E. faecalis: endocarditis, UTI
•
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C. tetani: tetanus
C. perfringens: gas gangreneC.difficile: pseudomembranous colitisC. botulinum: food poisoning
All are anaerobic
Corynebacterium diphtheriae (aerobic):Diphtheria
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Escherichia coli: UTI, dysenterySalmonella typhi: typhoid, food poisoning
Shigella: gastroenteritis, dysenteryKlebsiella: UTIProteus: UTIHelicobacter pylori: peptic ulcerColiformsPseudomonas aeruginosa: UTI, pneumonia, burninfection
Vibrio cholerae: CholeraHemophilous influenzae: sinusitis, bronchitis,pneumonia, meningitis
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Treponema pallidum: syphilis
Leptospira : leptospirosisChlamydia trachomatis: sexually transmitted disease(lymphogranuloma venereum)
• Pneumocystitis carnii: pneumonia in AIDS,lung infection in immunocompromised
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Bactericidal• Penicillins• Cephalosporins• Carbapenems• Monobactams• Vancomycin• Quinolones• Aminoglycosides• Bacitracin• Colistin• Polymyxin B• Cotrimoxazole
Bacteriostatic• Tetracyclines• Sulfonamide• Trimethoprim• Macrolides• Chloramphenicol• Clinidamycin• Lincomycin• Nitrofurantoin•
Linezolid• Telithromycin
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Betalactams
Inhibition of transpeptidase↓
Accumulation of precursor cell wall units
Formation of an imperfect cell wall↓
Activation of cells autolytic enzymes↑ osmotic drive
↓ Cell lysis
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Betalactams
• Have different uses• No action on those lack cell wall (mycoplasma)•
No action on intracellular pathogens(ligonella, chlamydia): cannot cross
ll b h bl (
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Penicillins: remember this table (not routesfor all), you can write uses using this
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Narrow spectrum penicillins
• Pen V and GSpectrum: all G +ve cocci and bacilli
SpirochetesNo action on staph (produce β lactamases)No action on G –ve
• β lactamase resistant penicillinsSpectrum: Like Pen G + Staph
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Amoxicillin+ clavulanic acid:• useful in β lactamase producing organisms:
Staph, Srep pneumonia, H.influenzae,Neisseria, E.coli, proteus, Klebsiella
• But not in MRSA
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Ureidopenicillins and carboxypenicillins:Spectrum: same as aminopenicillins +
pseudomonasUse: UTI, septicemia, burn infection caused by
pseudomonas; in combination withgentamicin
Resistance to cloxacillin/nafcillin: MRSAdue to altered PBP
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Cephalosporins
• Not active on enterococcus, MRSA, G +ve bacilli• 1st generation: X BBB
Excreted in kidneySensitive to β lactamase
degradationCocci > Bacilli ( G – ve)
Cefazolin: penetrates tissues surgical prophylaxis
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2nd generation
• Cefuroxime cross BBB• Cefoxitin
G –ve cocci and bacilli (like Amoxicillin +clavulanic) > G +ve cocci+
Anaerobes (Lower abdominal and gynecologicalinfection)Not used much
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3rd generation ( V. V. Imp)
• Ceftriaxone, cefitaxime, cefixime• G –ve cocci and bacilli, anaerobes > G +ve
cocci ( less than 1 st generation)• All cross BBB• Highly resistant to β lactamase producing G –
ve bacteria
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4 th generation
• Spectrum: same as 3 rd generation for G –vecocci and bacilli; but highly activeNot on anaerobes
• Used in infection resistant to 3 rd generation hospital acquired infection
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Monobactams
• Betalactam• Spectrum: like aminoglycosides•
Used in patients with renal impairment whereAMG cannot be used• No cross sensitivity with other betalactams
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Carbapenems
• Spectrum: G-ve bacilli, G +ve and anaerobes
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Glycopeptides: vancomycin,teicoplanin
• Large molecules: do not penetrate into G –vecells used in G +ve infections
• Act at an earlier stage than beta-lactams: notused in combination
• iv: used in MRSA, patients allergic to beta-lactams, Orally: in Clostridium difficileinfection
• With AMG for enterococcal endocarditis
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Drugs used in MRSA
• Vancomycin• Teicoplanin•
Daptomycin + gentamicin• Linezolid• Quinupristin + dalfopristin
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Protein synthesis inhibitors
• All are bateriostaticACCEPT aminoglycosides
• May become cidal when used in combination:cotrimoxazole, quinupristine + dalfopristine
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• Just forunderstanding. Do notmug up.
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Aminoglycosides
• Polar: Given iv or im• Do not cross BBB• Used in mainly in serious G –ve infections• Remember general properties of this group
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• Just forunderstanding. Donot mugup.
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Tetracyclines• Are active against wide variety of bacteria, but their
use is restricted due to widespread resistance• Given orally• Absorption: complete only for doxycycline and
minocycline: other drugs remain in the intestine - problems
• Well distributed and penetrates host cells to reachintracellular organisms
• Used in infection caused by mycoplasma, chlamydiae,
rickettsiae• Avoid them in pregnancy and in children < 8 years of
age
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Macrolides
Erythromycin• Well distributed, penetrates host ells• Spectrum: like ampicillin Aerobic
microorganisms causing respiratory tractinfection, mycoplasma, chlamydia
• Relatively free of serious toxic effectsAzithromycin
Spectrum: same as erythromycin + more activityagainst H. influenza and intracellular organisms
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Streptogramins
• Combination: Quinupristin + dalfopristin• Bactericidal• In Serious infection: MRSA
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Cotrimoxazole• Sulfamethoxazole + trimethoprim• Widely distributed, reach intracellular organisms• Concentrated in prostatic fluid•
Folic acid pathway inside the cell• Drug need to reach the cytoplasm• G +ve has thick cell wall difficult to cross• Hence active on G –ve organisms: UTI, typhoid,
Diarrhea due to shigella & salmonella• Mainly used in G-ve infections, chlamydia,
pneumocystitis carinii pneumonia
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Quinolones
• Many generations available with variedactivity
• Act by inhibiting DNA replication henceneed to enter the cell
• Entry is easy with G –ve (cocci and bacilli)through porin channels ( no cell wall)
• Low PPB good penetration to tissuespenetrates intracellular organisms
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• Justforunderstanding. Donot
mugup.