Antimicrobials Overview_ Batch 31

8/9/2019 Antimicrobials Overview_ Batch 31

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Overview of antimicrobial agents

Dr. Vasudha Devi



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.



• 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



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



Gram -veCocci

Neisseria N.gonorrheaeN.menigitidis

BacilliEnterobacteriaceae

Escherichia coliSalmonella typhiShigella

KlebsiellaProteusHelicobacter pyloriColiforms

Pseudomonas aeruginosa

Ligionella pneumophiliaCamphylobacterVibrio choleraeHaemophilus influenzaeBordetella pertussis



others

• Spirochetes

Treponema pallidum

Leptospira• Reckettsia• Chlamydiae

(intracellular)Chlamydia trachomatis

Chlamydia pneumoniae

• Mycoplasma pneumoniae( lack cell wall)

• Pnemocystis carini

(Pneumocystis jiroveci)



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

•



C. tetani: tetanus

C. perfringens: gas gangreneC.difficile: pseudomembranous colitisC. botulinum: food poisoning

All are anaerobic

Corynebacterium diphtheriae (aerobic):Diphtheria



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



Treponema pallidum: syphilis

Leptospira : leptospirosisChlamydia trachomatis: sexually transmitted disease(lymphogranuloma venereum)

• Pneumocystitis carnii: pneumonia in AIDS,lung infection in immunocompromised



Bactericidal• Penicillins• Cephalosporins• Carbapenems• Monobactams• Vancomycin• Quinolones• Aminoglycosides• Bacitracin• Colistin• Polymyxin B• Cotrimoxazole

Bacteriostatic• Tetracyclines• Sulfonamide• Trimethoprim• Macrolides• Chloramphenicol• Clinidamycin• Lincomycin• Nitrofurantoin•

Linezolid• Telithromycin



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



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 (



Penicillins: remember this table (not routesfor all), you can write uses using this



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



Amoxicillin+ clavulanic acid:• useful in β lactamase producing organisms:

Staph, Srep pneumonia, H.influenzae,Neisseria, E.coli, proteus, Klebsiella

• But not in MRSA



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



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



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



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



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



Monobactams

• Betalactam• Spectrum: like aminoglycosides•

Used in patients with renal impairment whereAMG cannot be used• No cross sensitivity with other betalactams



Carbapenems

• Spectrum: G-ve bacilli, G +ve and anaerobes



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



Drugs used in MRSA

• Vancomycin• Teicoplanin•

Daptomycin + gentamicin• Linezolid• Quinupristin + dalfopristin



Protein synthesis inhibitors

• All are bateriostaticACCEPT aminoglycosides

• May become cidal when used in combination:cotrimoxazole, quinupristine + dalfopristine



• Just forunderstanding. Do notmug up.



Aminoglycosides

• Polar: Given iv or im• Do not cross BBB• Used in mainly in serious G –ve infections• Remember general properties of this group



• Just forunderstanding. Donot mugup.



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



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



Streptogramins

• Combination: Quinupristin + dalfopristin• Bactericidal• In Serious infection: MRSA



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



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



• Justforunderstanding. Donot

mugup.



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