Antibiotics 2003 Ver

8/8/2019 Antibiotics 2003 Ver

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Antibiotics



Classification of antibiotics



Definition

Antibiotics are compounds produced by

various species of microorganisms and

havethe capability to kill or inhibit the growth of

other microorganisms



Classification of Antibiotics

Although antibiotics can be classified into

various ways, but the most commonly

antibiotics can be classified according to their

1.Mode of action

2.Mechanism of action



According to mode of action

Bacteriostatic

Bactericidal



Bacteriostatic

³These inhibit the growth of

microorganisms temporarily. the

therapeutic success of these agentsdepends upon the participation of defense

mechanism of the host´

The effect may be reversible when the

drug is stopped.

Infection can reoccur in immuno

compromised patient.



Examples of bacteriostatic

drugs Tetracycline

Sulfonamides

Clindamycin Chloramphenicol



Bactericidals

³This term is applied to describe those

agents which kill the microbes´

The treatment with bactericidal drugsbecome mandatory in case of those

infections that cannot be eradicated by

host defence mechanism.



Examples of bactericidal

drugs Penicillins

Cephalosporins

Aminoglycosides Monobactams



However the term bacteriostatic and

bactericidal are relative and not absolute.

As sometimes the prolonged treatment

with or higher doses of bacteriostaticagent can cause death of microbial

population. E.g.,

Chramphenicol and meningiococci

While bactericidal agents may fail to kill

microbes. E.g.,

Penicillin G and enterococci



According to Mechanism of

Action



Inhibitors of Cell Wall

Synthesis

Inhibitors of Protein

Synthesis

Inhibitors of Nucleic Acid

Synthesis and Functions

Inhibitors of

Metabolism



Inhibitors of cell wall synthesis

Amoxicillin

Ampicillin

Cloxacillin

Dicloxacillin

MethicillinOxacillin

Penicillin G

Penicillin V

Piperacillin

Ticarcillin

Penicillins Cephalosporins Carbapenems Monobactams

2nd generation1st generation 4th generation3rd generation

Inhibitors of cell wall

synthesis

Other antibiotics-lactam antibiotics

Cefadroxil

Cephalexin

Cephradine

Cephalothin

Cephaprin

Cefazolin

Cefaclor

Cefamandole

Cefonicid

Ceforanide

Cefoxitin

Cefprozil

Cefotaxime

Ceftazidime

Ceftriaxone

Cefixime

Cefepime

Meropenam

Ertapenam

Imipenam

Aztreonam

-lactamase

inhibitorsClavulanic acid

Sulbactam

Tazobactam



-lactam antibiotics



Penicillins



Antimicrobial Spectrum of

Penicillins

Penicillins and its congeners

e.g., penicillin G and penicillin V

These show higher activity against sensitive strains of Gr am +ve

Ineffective against Gram ±ve bacilli

Penicillinase r esistant penicilline.g., methicillin, naficillin, cloxacillin, dicloxacillin, f lucloxacillin

Are less potant against penicillin G sensitive MOs but are effective against penicillinase

producing staphylococcus aur eus and S.epiderimdis

They are inactive against Gram ±ve MOs

Broad spectrum penicillins

e.g., ampicillin, amoxicillin, becampicillin

Have r elatively high anti microbial activity against both Gr am +ve and Gr am +ve inc.

H.inf luenzae, E.coli, Proteus mir abilis bacteria but are readily destroyed by -lactamases



Extended spectrum penicillins:

e.g., car ebenicillin, ticarcillin

Their antimicrobial activity is extended to include Pseudomonas, Enterobacter and

Proteus spp.

Other extended spectrum penicillins:

e.g., Mezlocillin, Piper acillin

Against Pseudomonas, Klebsiella & other Gr am ±ve bacteria

Reversed spectrum:

e.g., Mecillinam, PromicillinamMore Potent against Gr am ±ve enteric bacteria than against Gram +ve

Hydrolyzed by -lactamase

-lactamase inhibitors:

e.g., clavulanic acid, Sulbactam, Tazobactam

Most active against plasmid encoded -lactamases (including the enzymes that

hydrolyze ceftizidime & cefotaxime)but are inactive at clinical achievable conc. against Type1 chromosomal -lactamases included in Gram ±ve bacilli e.g., Enterobacter,

Acinectobacter & Citrobacter by treatment with 2nd generation & 3rd generation

cephalosporins



Cephalosporins



Antimicrobial spectrum of

Cephalosporins1st gener ation:

Good activity against Gr am +ve bacteria & relatively modest activity against Gr am ±ve

microbes. Also active against Proteus mirabilis, E.coli, and Klebsiella pneumoniae (all Gram -ve) Alternatively 1st generation cephalosporins are described as drugs which act as penicillin G

substitute that are resistant to Staphylococcal penicillinase & also posses acivity against

P.mirabolis, E.coli, K.Pneumoniae

2nd gener ation:

Show modest activity against Gram +ve bacteria (less active against gr am +ve bacteria of 1st

generationdrugs) and show gr eater activity against three additional Gr am ±ve microbesnamed Haemophilus inf luenzae, some Enterobacter aerogenes and some Neisseria spp

(i.e., in comparison to 1stgeneration they have some what increased activity against ±ve

bacteria)

3rd gener ation:

Less active against Gr am +ve cocci as compared to 1st generation drugs but exhibit much

mor e activity against Gr am ±ve bacilli including those mentioned above plus most other

enteric organisms and -lactamase producing strains.

The drugs of this group have superiority over the other two generations in having access to

CNS

4th gener ation:

Have extended spectrum of activity as compared to 3rd generation and have increased

stability from hydrolysis by plasmid and chromosomally mediated -lactamases. Aerobic gr am

±ve bacilli r esistant to 3rd gener ation agents can be successfully tr eated with these.



Other -lactam

Antibiotics




Carbapen

ems

They are broadest-spectrum -lactam antibiotics currently available.

Imipenam resists hydrolysis by most -lactamases, but not the metallo--lactamases.

The drug plays an important role in emperic ther apy, bcz it is active against

penicillinase producing Gr am +ve & Gr am ±ve organisms, anaerobes, and

Pseudomonas aeroginosa (although other pseudomonas strains are resistant, and

resistant strains P.aeroginosa have been reported to arise during therapy)

Meropenam has antibacterial activity similar to that of Imipenam.




Monobactams

Aztr eonam is primarily active against Enterobacteriaceae but it also acts against

aerobic Gr am ±ve rods, including P.aeroginosa.It lacks activity against Gr am +ve organisms and anaerobes.

It is resistant to action of -lactamasaes.



Antimicrobial spectrum of -

lactamase inhibitors

These contain a -lactam ring but by themselves, do not have significant antibacterial

activity.

Instead, they bind to and inactivate -lactamases thereby protecting the antibioticsthat are normally substrates for for these enzymes.



Other inhibitors of cell

wall synthesis



Vancomycin

Teicoplanin

Fosfomycin

Bacitracin

Cycloserine




VancomycinIt is bactericidal for Gr am +ve bacteria in concentr ations of

0.5-10 g/ml. Most pathogenic Staphylococci, including those

producing -lactamase and those r esistant to naficillin and

methicillin ar e killed by 4 g/ml or less.

Vancomycin killsS

taphylococci relatively slowly and only if cellsare actively dividing; the rate is less than that of the penicillins

both in vitro and in vivo.

Vancomycin is synergistic with gentamycin and

str eptomycin against E.f aecium and E,f aecalis strains that

do not exhbit high levels of aminoglycoside resistance.



Inhibitors of Protein synthesis

Protein synthesis

inhibitors

Tetracyclines

Linezolid

Quinupristin

Aminoglycosides Macrolides

Chloramphenicol

Clindamycin

Demeclocycline

Doxycycline

Minocycline

Tetracycline

Amikacin

Gentamycin

Neomycin

Netilmycin

Streptomycin

Tobramycin

Azithromycin

Clarithromycin

Erythromycin

Telithromycin



Tetr acyclines




Tetr acyclines

Broad spectrum, bacteriostatic antibiotics

These are effective against Gram +ve and Gram ±ve bacteria as well as other Mos

than bacteria.

It is effective against Chlamydia spp, M.pneumoniae, Borrella burdorferi (a spirochete

that causes lyme disease).

Also effective against Rickettsia rickettsii that causes rocky mountain spotted fever.

Against Vibrio cholerae, Yersinia pestis, Brucella spp.

Against Clostridium perfringens and Clostridium tetani



Aminoglycosides




AminoglycosidesBactericidal

Aminoglycosides are effective in empirical treatment of

infections suspected of being due to aerobic Gram ±ve

bacilli, including Pseudomonas aeroginosa.

To achieve an additive effect, these are combined with

a -lactam antibiotic, or vancomycin, or a drug active

against anaerobic bacteria.

Aminoglycosides are only effective against aerobic

organisms, bc strict anaerobes lack oxygen-requiring

transport system.these are effective against:

Brucella spp(gentamycin+doxycycline)

Streptococcus agalactiae (gentamycin+penicillin G)

Enterococcus spp (gentamycin+penicillin G)

Klebsiella spp (gentamycin+an antipseudomonial

penicillin)

Pseudomonas aeroginosa

(tobramycin+antipseudomonial penicillin)

Yersinia pestis (streptomycin+doxycycline)



Macrolides




Macrolides

Effective against

Chlamydial spp. (azithromycin, erythromycin)

Mycoplasma pneumoniae, Ureaplasma urealyticum (erythromycin,tetracycline)

Treponema pallidum (erythromycin)

Bordetella pertussis, Campylobacter jejuni, Haemophilus inflenzae, Legionella

pneumophila (azithromycin)

Corynebacterium diphtheriae (erythromycin)

Staphylococcus aureus

Streptococcus pyogenes

Streptococcus pneumoniae



Chlor amphenicol




Chlor amphenicol

It is a broad spectrum antibiotic.

It is active not only against bacteria but alsoagainst other microbes, such as

Rickettsiae

Anaerobes (excellent activity)

It is not effective against Pseudomonas

aeroginosa and Chlamydiae

The drug is bacteriostatic (more commonly)or bactericidal, depending upon the organism.



Clindamycin




Clindamycin

Anaerobic bacteria such as Bacteroides fr agilis

Enterococcal Gr am +ve cocciClostridium difficile is always r esistant to Clindamycin.



Inhibitors of nucleic acid

function or synthesis

Inhibitors of nucleic acid

function or synthesis

DN A-gyraseinhibitors

RifampinFluoroquinolones

RN A-polymeraseinhibitors

1st generation 2nd generation 4th generation3rd generation

Nalidixic acid Ciprofloxacillin

Norfloxacillin

Ofloxacin

Gatifloxacin

Levofloxacin

Moxifloxacin

Sparfloxacin

Trovafloxacin



Fluoroquinolones




f luoroquinolonesEffective against:

E scherichia coli

Shigella dysenteriae

Shigella sonnei

Salmonella typhi

Klebsiella pneumoniae

E nterobacter cloaceae

Serratia mercescence

Proteus mirabilis

Yersinia pestis

Haemophilus influenza

Legionella pneumophilia

Pseudomonas aeroginosa

Chlamydia trachomatis

C.psittaci

C.pneumoniae

Mycoplasma pneumonia

Brucella melitensis

Brucella abortusBrucella swis

Mycobacterium tuberculosis

Mycobacterium kansasii

Mycobacterium fortuitum

Mycobacterium avim

Staphylococci

Campylobacter sppNeisseria gonorrhoeae



Inhibitors of metabolism

Inhibitors of

metabolism

Inhibitors of folate

synthesis (Sulfonamides)

Combination of inhibitors

of folate synthesis and

reduction

Inhibitors of folate

reduction

Mafenide

Silver sulfadiazine

SuccinylsulfacetamideSulfadiazine

Sulfamethoxazole

Sulfasalazine

Sulfisoxazole

Pyrimethamine

Trimethoprim

Co-trimoxazole



Sulfonamides



Antimicrobial activity of

SulfonamidesSulfonamides inhibit growth of:

Gram +ve and Gram ±ve bacteria

Nocardia

Chlamydia trachomatis Some protozoa

Some enteric bacteria as E .coli, Klebsiella,

Salmonella, Shigella, and E nterobacter

Interestingly, rickettsiae are not inhibited by

sulfonamides but are actually stimulated in their

growth.



Trimethoprim




Trimethoprim

Antimicrobial spectrum of trimethoprim

is similar to that of sulfamethoxazole.

However, trimethoprim is twenty to fifty

folds more potent than sulfonamide.

T

rimethoprim may be used alone in thetreatment of:

Acute UTIs

Bacterial prostitis (although

fluoroquinolones are preferred)

Vaginitis



Co-trimoxazole



Antimicrobial spectrum of Co-

trimoxazole Active against

Pneumocystis carinii

Haemophilus influenzae

Legionella pneumoniae E ccherichia coli

Proteus mirabilis

Salmonella typhi

Shigella

Listeria monocytogenes



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Antibiotics 2003 Ver