b - Lactamase Inhibitors

-Lactamase Inhibitors-Lactamase Inhibitors

Clavulanic acidClavulanic acid (Beecham 1976)(from (Beecham 1976)(from Streptomyces clavuligerusStreptomyces clavuligerus))

• Weak, unimportant antibacterial activityWeak, unimportant antibacterial activity• Powerful irreversible inhibitor of Powerful irreversible inhibitor of -lactamases - suicide substrate-lactamases - suicide substrate• Used as a sentry drug for ampicillin Used as a sentry drug for ampicillin • Augmentin = amoxicillin+ clavulanic acidAugmentin = amoxicillin+ clavulanic acid• Allows less amoxicillin per dose and an increased activity spectrumAllows less amoxicillin per dose and an increased activity spectrum• Timentin = ticarcillin + clavulanic acidTimentin = ticarcillin + clavulanic acid

No acylaminoside chain

Sulphur replaced by O

-Lactam

N

O

OCOOH

OH1

2

34

56

7


Augmentin = Amoxicillin + Clavulanic Acid

Penicillanic acid sulfone derivativesPenicillanic acid sulfone derivatives

• Suicide substrates for Suicide substrates for -lactamase enzymes-lactamase enzymes• Sulbactam has a broader spectrum of activity vs Sulbactam has a broader spectrum of activity vs -lactamases than -lactamases than

clavulanic acid, but is less potentclavulanic acid, but is less potent• Unasyn = ampicillin + sulbactamUnasyn = ampicillin + sulbactam• Tazobactam has a broader spectrum of activity vs Tazobactam has a broader spectrum of activity vs -lactamases than -lactamases than

clavulanic acid, and has similar potencyclavulanic acid, and has similar potency• Tazocin or Zosyn = piperacillin + tazobactamTazocin or Zosyn = piperacillin + tazobactam


NO

S

CO2

OO

Me

Me

Na

NO

S

CO2

OO

Me

NN

N

12

3

56

7

6

3

SulbactamSulbactam TazobactamTazobactam

Gram-positive bacteria

Some Staphylococcus aureus, Streptococcus pyogenes, Viridans streptococci, Some Streptoocus pneumoniae, Some enterococci Listeria monocytogenes

Gram-negative bacteria

Neisseria spp. Haemophilus influenzae, Many Enterobacteriaceae

Anaerobic bacteria

Clostridia spp. (except C. difficile), Actinomyces israellii, Bacteroides spp.

Spirochetes Borrelia burgdorferi

The aminopenicillins + -lactamase inhibitor combinations include ampicillin-sulbactam (parenteral) and amoxicillin-clavulanate (oral)

Problem 3 - Range of ActivityProblem 3 - Range of Activity

Examples of Broad Spectrum PenicillinsExamples of Broad Spectrum Penicillins

Class 2 - COClass 2 - CO22H at the H at the -position (carboxypenicillins)-position (carboxypenicillins)

ExamplesExamples

• Carfecillin = prodrug for carbenicillinCarfecillin = prodrug for carbenicillin• Active over a wider range of Gram -ve bacteria than ampicillinActive over a wider range of Gram -ve bacteria than ampicillin• Active vs. Active vs. Pseudomonas aeruginosaPseudomonas aeruginosa• Resistant to most Resistant to most -lactamases-lactamases• Less active vs Gram + bacteria (note the hydrophilic group)Less active vs Gram + bacteria (note the hydrophilic group)• Acid sensitive and must be injectedAcid sensitive and must be injected• Stereochemistry at the Stereochemistry at the -position is important-position is important• COCO22H at the H at the -position is ionised at blood pH-position is ionised at blood pH

R = H CARBENICILLINR = H CARBENICILLINR = Ph CARFECILLINR = Ph CARFECILLINH H

O

N

HNC

CH

CO2R

S Me

Me

CO2H

O



Class 2 - COClass 2 - CO22H at H at -position (carboxypenicillins)-position (carboxypenicillins)

ExamplesExamples

• Administered by injectionAdministered by injection• Identical antibacterial spectrum to carbenicillinIdentical antibacterial spectrum to carbenicillin• Smaller doses required compared to carbenicillinSmaller doses required compared to carbenicillin• More effective against More effective against P. aeruginosaP. aeruginosa• Fewer side effectsFewer side effects• Can be administered with clavulanic acidCan be administered with clavulanic acid

TICARCILLINTICARCILLINS

N

Me

MeO

HH

CO2H

HN

O

CO2H

S



Class 3 - Urea group at the Class 3 - Urea group at the -position (ureidopenicillins)-position (ureidopenicillins)

ExamplesExamples

• Administered by injection Administered by injection • Generally more active than carboxypenicillins vs. streptococci and Generally more active than carboxypenicillins vs. streptococci and

HaemophilusHaemophilus species species• Generally have similar activity vs Gram - aerobic rodsGenerally have similar activity vs Gram - aerobic rods• Generally more active vs other Gram - bacteriaGenerally more active vs other Gram - bacteria• Azlocillin is effective vs Azlocillin is effective vs P. aeruginosaP. aeruginosa• Piperacillin can be administered alongside tazobactamPiperacillin can be administered alongside tazobactam

Azlocillin

Mezlocillin

Piperacillin

S

N

Me

MeO

HH

CO2H

HN

O

NH

O

R2N

HNN

O

NN

OMeO2S

N N

OO

Et


Streptococcus pyogenes, Viridans streptococci, Some Streptococcus pneumoniae, Some enterococci


Neisseria meningitidis, Some Haemophilus influenzae, Some Enterobacteriaceae, Pseudomonas aeruginosa

Anaerobic bacteria

Clostridia spp. (except C. difficile), Some Bacteroides spp.

The Extended Spectrum Penicillins include Piperacillin and Ticarcillin (parenteral) as well as Carbenicillin (oral)


Some Staphylococcus aureus, Streptocosoccus pyogenes, Viridans streptococci, Some Streptococcus pneumoniae, Some enterococci Listeria monocytogenes


Neisseria spp. Haemophilus influenzae, Most Enterobacteriaceae, Pseudomonas aeruginosa

Anaerobic bacteria

Clostridia spp. (except C. difficile), Bacteroides spp.

Extended-Spectrum Penicillin + -Lactamase Inhibitor Combinations include:Piperacillin-tazobactam as well as ticarcillin-clavulanate (both pairs are parenteral)

CEPHALOSPORINSCEPHALOSPORINS

N

S

OAc

CO2H

O

HN H HC

O

R

1. Introduction1. Introduction

• Antibacterial agents which inhibit bacterial cell wall synthesisAntibacterial agents which inhibit bacterial cell wall synthesis

• Discovered from a fungal colony in Sardinian sewer water Discovered from a fungal colony in Sardinian sewer water (1948) (1948)

• Cephalosporin C identified in 1961Cephalosporin C identified in 1961

Giussepe Brotzu noticed that the substance cultured from the sewer water had activity against Salmonella typhi, the active cause of typhoid feverTyphoid fever is transmitted human to human by contact with contaminated feces.

6. Mechanism of Action6. Mechanism of Action

NO

HHHNR

O

S

CO2H

OC

Me

O

7

OH

Ser Enzyme

-CH3CO2-

NO

HHHNR

O

S

CO2HO

Ser

Enzyme

• The acetoxy group acts as a good leaving group and aids the The acetoxy group acts as a good leaving group and aids the mechanismmechanism

Generation Parenteral Agents

Oral Agents

First-generation Cefazolin Cefadroxil, cephalexin

Second-generation Cefotetan, cefoxitin, cefuroxime

Cefaclor, cefprozil, cefuroxime axetil, loracarbef

Third-generation Cefotaxime, ceftazidime, ceftizoxime, ceftriaxone

Cefdinir, cefditoren, cefpodoxime proxetil, ceftibuten, cefixime

Fourth-generation Cefepime

The Cephalosporins

8. First Generation 8. First Generation CephalosporinsCephalosporins CephalothinCephalothin

N

O

HHHN S

CO2H

OAcOS

7

3

• First generation cephalosporinFirst generation cephalosporin• More active than penicillin G vs. some Gram - bacteriaMore active than penicillin G vs. some Gram - bacteria• Less likely to cause allergic reactionsLess likely to cause allergic reactions• Useful vs. penicillinase producing strains of Useful vs. penicillinase producing strains of S. aureusS. aureus• Not active vs. Not active vs. Pseudonomas aeruginosaPseudonomas aeruginosa• Poorly absorbed from GIT Poorly absorbed from GIT • Administered by injectionAdministered by injection• Metabolised to give a free 3-hydroxymethyl group Metabolised to give a free 3-hydroxymethyl group

(deacetylation)(deacetylation)• Metabolite is less activeMetabolite is less active

Cephalothin - drug metabolismCephalothin - drug metabolism

StrategyStrategy• Replace the acetoxy group with a metabolically stable leaving Replace the acetoxy group with a metabolically stable leaving

groupgroup

N

O

HHHN S

CO2H

OAcOS

7

3

MetabolismMetabolismN

O

HHHN S

CO2H

OHOS

Less activeLess activeOH is a poorer leaving groupOH is a poorer leaving group

8. First Generation 8. First Generation CephalosporinsCephalosporins

CephaloridineCephaloridine

• The pyridine ring is stable to metabolismThe pyridine ring is stable to metabolism

• The pyridine ring is a good leaving group (neutralisation of The pyridine ring is a good leaving group (neutralisation of charge)charge)

• Exists as a zwitterion and is soluble in waterExists as a zwitterion and is soluble in water

• Poorly absorbed through the gut wallPoorly absorbed through the gut wall

• Administered by injection Administered by injection

N

O

HHHN S

CO2

NOS

7

3


CefalexinCefalexin

• The methyl group at position 3 is not a good leaving group The methyl group at position 3 is not a good leaving group

• The methyl group is bad for activity but aids oral absorption - The methyl group is bad for activity but aids oral absorption - mechanism unknownmechanism unknown

• Cefalexin can be administered orallyCefalexin can be administered orally

• A hydrophilic amino group at the A hydrophilic amino group at the -carbon of the side chain -carbon of the side chain helps to compensate for the loss of activity due to the methyl helps to compensate for the loss of activity due to the methyl groupgroup

NO

HHHN S

CO2H

Me

O

H2N H

7

3


First Generation Cephalosporins

CefazolinCefadroxil

Cefalexin


Streptococcus pyogenes, Some virdans streptococci, Some Staphylococcus aureus, Some Streptococcus pneumoniae


Some Eschericia coli, Some Klebsiella pneumoniae, Some Proteus mirabilis

First Generation Cephalosporins include Cefazolin (parenteral) as well as cefadroxil and cefalexin (oral).

9.1 Cephamycins9.1 Cephamycins

9. Second Generation Cephalosporins9. Second Generation Cephalosporins

• Isolated from a culture of Isolated from a culture of Streptomyces clavuligerusStreptomyces clavuligerus

• First First -lactam to be isolated from a bacterial source-lactam to be isolated from a bacterial source

• Modifications carried out on the 7-acylamino side chainModifications carried out on the 7-acylamino side chain

NO

HOMeHN S

CO2H

OO

CNH2

O

HO2C

H2N H Cephamycin CCephamycin C

CefoxitinCefoxitin

• Broader spectrum of activity than most first generation Broader spectrum of activity than most first generation cephalosporinscephalosporins

• Greater resistance to Greater resistance to -lactamase enzymes-lactamase enzymes• The 7-methoxy group may act as a steric shieldThe 7-methoxy group may act as a steric shield• The urethane group is stable to metabolism compared to the The urethane group is stable to metabolism compared to the

esterester• Introducing a methoxy group to the equivalent position of Introducing a methoxy group to the equivalent position of

penicillins (position 6) eliminates activity.penicillins (position 6) eliminates activity.

9.1 Cephamycins9.1 Cephamycins

9. Second Generation Cephalosporins9. Second Generation Cephalosporins

N

O

HOMeHN S

CO2H

OO

CNH2

O

S

7

3

CefuroximeCefuroxime

• Much greater stability against some Much greater stability against some -lactamases-lactamases• Resistant to esterases due to the urethane groupResistant to esterases due to the urethane group• Wide spectrum of activityWide spectrum of activity• Useful against organisms that have gained resistance to Useful against organisms that have gained resistance to

penicillinpenicillin• Not active against Not active against P. aeruginosaP. aeruginosa• Used clinically against respiratory infectionsUsed clinically against respiratory infections

9. Second Generation 9. Second Generation CephalosporinsCephalosporins 9.2 Oximinocephalosporins9.2 Oximinocephalosporins

N

O

HHHN S

CO2H

O

C

O

CNH2

O

O

NO

Me

• Second generation• The second-generation cephalosporins have a

greater Gram-negative spectrum while retaining some activity against Gram-positive cocci. They are also more resistant to beta-lactamase.

• Cefaclor (Ceclor, Distaclor, Keflor, Raniclor) • Cefonicid (Monocid) • Cefprozil (cefproxil; Cefzil) • Cefuroxime (Zinnat, Zinacef, Ceftin,

Biofuroksym) • Cefuzonam

Forms of Cefuroxime (2nd generation cephalosporin)

Cefuroxime sodium(ZINACEF)

Cefuroxime axetil

(CEFTIN)

More second generation cephalosporins: Loracarbef (Lorabid)


True cephalosporins have activity equivalent to first-generation agents. Cefoxitin and cefotetan have little activity


Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Haemophilus influenzae, Neisseria spp.

Anaerobic bacteria

Cefoxitin and cefotetan have moderate anaerobic activity.

The Second-generation cephalosporins include Cefotetan, cefoxitin, and cefuroxime (all parenteral) as well as Cefaclor, cefprozil, cefuroxime axetil, and loracarbef (all oral).

• Aminothiazole ring enhances penetration of cephalosporins across the outer Aminothiazole ring enhances penetration of cephalosporins across the outer membrane of Gram - bacteriamembrane of Gram - bacteria

• May also increase affinity for the transpeptidase enzymeMay also increase affinity for the transpeptidase enzyme• Good activity against Gram - bacteriaGood activity against Gram - bacteria• Variable activity against Gram + cocciVariable activity against Gram + cocci• Variable activity vs. Variable activity vs. P. aeruginosaP. aeruginosa• Lack activity vs MRSALack activity vs MRSA• Generally reserved for troublesome infectionsGenerally reserved for troublesome infections

10. Third Generation Cephalosporins10. Third Generation Cephalosporins OximinocephalosporinsOximinocephalosporins

N

O

HHHN S

CO2H

R

C

O

N

S

NO

Me

H2N

CH2OCOMeH

CefotaximeCeftizoxime

N

NNCH2S

O

OH

Me

Ceftriaxone

RR

AminothiazoleAminothiazole ringring

Ceftriazone (Rocephin) is a popular third generation cephalosporin

It is the drug of choice for bacterial meningitis

• Injectable cephalosporinInjectable cephalosporin• Excellent activity vs. Excellent activity vs. P. aeruginosaP. aeruginosa and other Gram - bacteria and other Gram - bacteria• Can cross the blood brain barrierCan cross the blood brain barrier• Used to treat meningitisUsed to treat meningitis

10. Third Generation Cephalosporins10. Third Generation Cephalosporins OximinocephalosporinsOximinocephalosporins

N

O

HHHN S

CO2

N

C

OS

N

NO

H2N

Me CO2HMe

CeftazidimeCeftazidime


Streptococcus pyogenes, Viridans streptococci, Many Streptococcus pneumoniae, Modest activity against Staphylococcus aureus


Escherichia coli, Klebsiella pneumoniae, Proteus spp. Haemophilus influenzae, Neisseria spp. Some Enterobacteriaceae.

Anaerobic bacteria

Atypical bacteria

Spirochetes Borrelia burgorferi

The Third-generation Cephalosporins include Cefotaxime, ceftazidime, ceftizoxime, and ceftriaxone (all parenteral) as well as Cefdinir, cefditoren, cefpodoxime proxetil, ceftibuten, and cefixime (all oral).

• Zwitterionic compoundsZwitterionic compounds• Enhanced ability to cross the outer membrane of Gram negative bacteriaEnhanced ability to cross the outer membrane of Gram negative bacteria• Good affinity for the transpeptidase enzymeGood affinity for the transpeptidase enzyme• Low affinity for some Low affinity for some -lactamases-lactamases• Active vs. Gram + cocci and a broad array of Gram - bacteriaActive vs. Gram + cocci and a broad array of Gram - bacteria• Active vs. Active vs. P. aeruginosaP. aeruginosa

11. Fourth Generation 11. Fourth Generation CephalosporinsCephalosporins OximinocephalosporinsOximinocephalosporins

N

O

HHHN S

CO2H

R

C

O

N

S

NO

Me

H2N

NCH2

MeCefipime

CefpiromeNCH2

RR


Streptococcus pyogenes, Viridans streptococci, Many Streptocossus pneumoniae. Modest activity against Staphylococcus aureus


Escherichia coli, Klebsiella pneumoniae, Proteus spp. Haemophilus influenzae, Neisseria spp. Many other Enterobacteriaceae, Pseudomonas aeruginosa.

Anaerobic bacteria

Atypical bacteria

Fourth Generation Cephalosporins include cefepime (parenteral).

Newer Newer -Lactam Antibiotics-Lactam Antibiotics

ThienamycinThienamycin (Merck 1976)(from Streptomyces cattleya) (Merck 1976)(from Streptomyces cattleya)

• Potent and wide range of activity vs Gram + and Gram - bacteriaPotent and wide range of activity vs Gram + and Gram - bacteria• Active vs. Active vs. Pseudomonas aeruginosaPseudomonas aeruginosa• Low toxicityLow toxicity• High resistance to High resistance to -lactamases-lactamases• Poor stability in solution (ten times less stable than Pen G)Poor stability in solution (ten times less stable than Pen G)

Oppositestereochemistry to penicillins

Carbon

Carbapenam nucleus

Plays a rolein ß-lactamaseresistance

Acylamino sidechain absent

O

N

S

OH

H3C

CO2

H

NH3

H

Double bond leading to high ring strain and an increasein -lactam ring reactivity


ThienamycinThienamycin analogues used in the clinicanalogues used in the clinic

NO

H

S

HN

CO2

OH

Me

HNH

NO

H

S

CO2

OH

Me

H

HN C

N

O

Me

Me

H

NO

H

S

CO2

OH

Me

H

HN C

N

O

HMe

CO2

ImipenemImipenem

Ertapenem(2002)Ertapenem(2002)

MeropenemMeropenem

Primaxin = Imipenem + Cilastatin

Cilastatin is an inhibitor of a human enzyme, renal dehydropeptidase, which degrades carbapenems

Meropenem, Merrem, AstraZeneca

Ertapenem, Invanz, Merck


Streptococcus pyogenes, Viridans group streptococci, Streptococcus pneumoniae, Modest activity against Staphylococcus aureus, Some enterococci, Listeria monocytogenes


Haemophilus influenzae, Neisseria spp., Enterobacteriaceae, Pseudomonas aeruginosa

Anaerobic bacteria

Bacteroides fragilis, Most other anaerobes.

The Carbapenems include Imipenem/cilstatin, Meropenem, and Ertapenem (all parenteral)


Clinically useful monobactamClinically useful monobactam

• Administered by intravenous injectionAdministered by intravenous injection• Can be used for patients with allergies to penicillins Can be used for patients with allergies to penicillins

and cephalosporinsand cephalosporins• No activity vs. Gram + or anaerobic bacteriaNo activity vs. Gram + or anaerobic bacteria• Active vs. Gram - aerobic bacteriaActive vs. Gram - aerobic bacteria

Aztreonam



Haemophilus influenzae, Neisseria spp. Most Enterobacteriaceae, Many Pseudomonas aeruginosa.

Anaerobic bacteria

Atypical bacteria

The Monobactams include only Aztreonam, which is parenteral

Vancomycin

Mechanism of Action of Vancomycin

Vancomycin binds to the D-alanyl-D-alanine dipeptide on the peptide side chain of newly synthesized peptidoglycan subunits, preventing them from being incorporated into the cell wall by penicillin-binding proteins (PBPs). In many vancomycin-resistant strains of enterococci, the D-alanyl-D-alanine dipeptide is replaced with D-alanyl-D-lactate, which is not recognized by vancomycin. Thus, the peptidoglycan subunit is appropriately incorporated into the cell wall.

• Vancomycin Animation

http://student.ccbcmd.edu/courses/bio141/lecguide/unit2/control/vancores_fl.html


Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes. Viridans group streptococci, Streptococcus pneumoniae, Some enterococci.


Anaerobic bacteria Clostridium spp. Other Gram-positive anaerobes.

Atypical bacteria

Antimicrobial Activity of Vancomycin

Daptomycin

• Daptomycin is a lipopeptide antibiotic

• Approved for use in 2003

• Lipid portion inserts into the bacterial cytoplasmic membrane where it forms an ion-conducting channel.

Link

http://video.google.com/videosearch?hl=en&safe=off&rlz=1W1ADSA_en&q=cubicin%20show&oq=&um=1&ie=UTF-8&sa=N&tab=wv#emb=0&hl=en&q=cubicin+&view=3&qvid=cubicin+&vid=7891924496618676715


Streptococcus pyogenes, Viridans group streptococci, Streptococcus pneumoniae, Staphylococci, Enterococci.


Anaerobic bacteria

Some Clostridium spp.

Atypical

Antimicrobial Activity of Daptomycin

Rifamycins

• Rifampin is the oldest and most widely used of the rifamycins

• Rifampin is also the most potent inducer of the cytochrome P450 system

• Therefore, Rifabutin is favored over rifampin in individual who are simultaneously being treated for tuberculosis and HIV infection, since it will not result in oxidation of the antiviral drugs the patient is taking

• Rifaximin is a poorly absorbed rifamycin that is used for treatment of travelers’ diarrhea.


Staphylococci


Haemophilus influenzae, Neisseria meningitidis

Anaerobic bacteria

Mycobacteria Mycobacterium tuberculosis, Mycobacterium avium complex, Mycobacteriumleprae.

The Rifamycins include Rifampin, Rifabutin, Rifapentine, and Rifaximin, all of which can be administered orally. Rifampin can also be administered parenterally.

Aminoglycosides

The structure of the aminoglycoside amikacin. Features of aminoglycosides include amino sugars bound by glycosidic linkages to a relatively conserved six-membered ring that itself contains amino group substituents.

Bacterial resistance to aminoglycosides occurs via one of three mechanisms that prevent the normal binding of the antibiotic to its ribosomal target:

(1) Efflux pumps prevent accumulation of the aminoglycoside in the cytosol of the bacterium.

(2) Modification of the aminoglycoside prevents binding to the ribosome.

(3) Mutations within the ribosome prevent aminoglycoside binding.


Used synergistically against some: Staphylococci, Streptococci, Enterococci, and Listeria monocytogenes


Haemophilus influenzae, Enterobacteiaceae, Pseudomonas aeruginosa

Anaerobic bacteria

Atypical bacteria

Mycobacteria Mycobacterium tuberculosis, Mycobacterium avium complex.

The Aminoglycosides include Streptomycin, Gentamicin, Tobramycin, and Amikacin (all parenteral), as well as Neomycin (oral).

Macrolides and Ketolides

The structures of erythromycin and telithromycin Circled substituents and distinguish telithromycin from the macrolides. Substituent allows telithromycin to bind to a second site on the bacterial ribosome.


Some Streptococcus pyogenes. Some viridans streptococci, Some Streptococcus pneumoniae. Some Staphylococcus aureus.


Neiseria spp. Some Haemophilus influenzae. Bordetella pertussis

Anaerobic bacteria

Atypical bacteria

Chlamydia spp. Mycoplasma spp. Legionella pneumophila, Some Rickettsia spp.

Mycobacteria Mycobacterium avium complex, Mycobacterium leprae.

Spirochetes Treponema pallidum, Borrelia burgdorferi.

The macrolide group consists of Erythromycin, Clarithromycin, and Azithromycin (all oral, with erythromycin and azithromycin also being available parenterally).


Streptococcus pyogenes, Streptococcus pneumoniae, Some Staphylococcus aureus


Some Haemophilus influenzae, Bordetella pertussis

Anaerobic bacteria

Atypical bacteria Chlamydia spp. Mycoplasma spp. Legionella pneumophila

The related ketolide class consists of Telithromycin (oral).

The Tetracycline Antibiotics

The structure of tetracycline


Some Streptococcus pneumoniae


Haemophilus influenzae, Neisseria meningitidis

Anaerobic bacteria

Some Clostridia spp. Borrelia burgdorferi, Treponema pallidum

Atypical bacteria Rickettsia spp. Chlamydia spp.

The Tetracycline Class of Antibiotics consists of Doxycycline and Tigecycline (parenteral) as well as Tetracycline, Doxycycline and Minocycline (oral)

Tigecycline


Streptococcus pyogenes. Viridans group streptococci, Streptococcus pneumoniae, Staphylococci, Enterococci, Listeria monocytogenes


Haemophilus influenzae, Neisseria spp. Enterobacteriaceae

Anaerobic bacteria

Bacteroides fragilis, Many other anaerobes

Atypical bacteria Mycoplasma spp.

The antimicrobial activity of Tigecycline (parenteral)

Chloramphenicol


Streptococcus pyogenes, Viridans group streptococci. Some Streptococcus pneumoniae


Haemophilus influenzae, Neisseria spp. Salmonella spp. Shigella spp.

Anaerobic bacteria

Bacteroides fragilis. Some Clostridia spp. Other anaerobic Gram-positive and Gram negative bacteria

Atypical bacteria Rickettsia spp. Chlamydia trachomatis, Mycoplasma spp.

The Antimicrobial Activity of Chloramphenicol

Clindamycin


Some Streptococcus pyogenes, Some viridans group streptococci. Some Streptococcus pneumoniae, Some Staphylococcus aureus


Anaerobic bacteria

Some Bacteroides fragilis, Some Clostridium spp. Most other anaerobes.

Atypical bacteria

The Antimicrobial Activity of Clindamycin (both oral and parenteral)

Streptogramins


Streptococcus pyogenes, Viridans group streptococci, Streptococcus pneumoniae, Staphylococcus aureus, Some enterococci.


Anaerobic bacteria

Atypical bacteria

The Antimicrobial Activity of Quinupristin/Dalfopristin (parenteral)

The Oxazolidinones

The structure of Linezolide


Streptococcus pyogenes. Viridans group streptococci, Streptococcus pneumoniae, Staphylococci, Enterococci.


Anaerobic bacteria

Atypical bacteria

The Antimicrobial Activity of Linezolid (both oral and parenteral)

b - Lactamase Inhibitors

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