b-lactamase inhibitors clavulanic acid
TRANSCRIPT
-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
Oxazolidine ring
-Lactam
9
2
53
4
176
HCO2H
O
N
O H
OH
H
-Lactamase Inhibitors-Lactamase Inhibitors
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
-Lactamase Inhibitors-Lactamase Inhibitors
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 PenicillinsClass 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
ON
HNC
CH
CO2R
S Me
Me
CO2H
O
Problem 3 - Range of ActivityProblem 3 - Range of Activity
Examples of Broad Spectrum PenicillinsExamples of Broad Spectrum PenicillinsClass 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
Problem 3 - Range of ActivityProblem 3 - Range of Activity
Examples of Broad Spectrum PenicillinsExamples of Broad Spectrum PenicillinsClass 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
HN N
O
N N
OMeO2S
N N
OO
Et
Gram-positive bacteria
Streptococcus pyogenes, Viridans streptococci, Some Streptococcus pneumoniae, Some enterococci
Gram-negative bacteria
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)
Gram-positive bacteria
Some Staphylococcus aureus, Streptocosoccus pyogenes, Viridans streptococci, Some Streptococcus pneumoniae, Some enterococci Listeria monocytogenes
Gram-negative bacteria
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
CO2HO
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
NO
HHHN S
CO2H
OAcOS7
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
NO
HHHN S
CO2H
OAcOS7
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
NO
HHHN S
CO2
NOS7
3
8. First Generation 8. First Generation CephalosporinsCephalosporins
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
MeO
H2N H
7
3
8. First Generation 8. First Generation CephalosporinsCephalosporins
First Generation Cephalosporins
CefazolinCefadroxil
Cefalexin
Gram-positive bacteria
Streptococcus pyogenes, Some virdans streptococci, Some Staphylococcus aureus, Some Streptococcus pneumoniae
Gram-negative bacteria
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
OOC
NH2
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
NO
HOMeHN S
CO2H
OOC
NH2
O
S7
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
NO
HHHN S
CO2H
O
C
OC
NH2
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)
Gram-positive bacteria
True cephalosporins have activity equivalent to first-generation agents. Cefoxitin and cefotetan have little activity
Gram-negative bacteria
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
NO
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
NO
HHHN S
CO2
N
C
OS
N
NO
H2N
Me CO2HMe
CeftazidimeCeftazidime
Gram-positive bacteria
Streptococcus pyogenes, Viridans streptococci, Many Streptococcus pneumoniae, Modest activity against Staphylococcus aureus
Gram-negative bacteria
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
NO
HHHN S
CO2H
R
C
O
N
S
NO
Me
H2N
NCH2
MeCefipime
CefpiromeNCH2
RR
Gram-positive bacteria
Streptococcus pyogenes, Viridans streptococci, Many Streptocossus pneumoniae. Modest activity against Staphylococcus aureus
Gram-negative bacteria
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
Newer Newer -Lactam Antibiotics-Lactam Antibiotics ThienamycinThienamycin analogues used in the clinicanalogues used in the clinic
NO
H
S
HN
CO2
OH
MeH
NH
NO
H
S
CO2
OH
MeH
HN C
N
O
Me
Me
H
NO
H
S
CO2
OH
MeH
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
Gram-positive bacteria
Streptococcus pyogenes, Viridans group streptococci, Streptococcus pneumoniae, Modest activity against Staphylococcus aureus, Some enterococci, Listeria monocytogenes
Gram-negative bacteria
Haemophilus influenzae, Neisseria spp., Enterobacteriaceae, Pseudomonas aeruginosa
Anaerobic bacteria
Bacteroides fragilis, Most other anaerobes.
The Carbapenems include Imipenem/cilstatin, Meropenem, and Ertapenem (all parenteral)
Newer Newer -Lactam Antibiotics-Lactam Antibiotics 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
Gram-positive bacteria
Gram-negative bacteria
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.
• http://student.ccbcmd.edu/courses/bio141/lecguide/unit2/control/vanres.html
• LINK
Gram-positive bacteria
Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes. Viridans group streptococci, Streptococcus pneumoniae, Some enterococci.
Gram-negative bacteria
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.
Gram-positive bacteria
Streptococcus pyogenes, Viridans group streptococci, Streptococcus pneumoniae, Staphylococci, Enterococci.
Gram-negative bacteria
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.
Gram-positive bacteria
Staphylococci
Gram-negative bacteria
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.
Gram-positive bacteria
Used synergistically against some: Staphylococci, Streptococci, Enterococci, and Listeria monocytogenes
Gram-negative bacteria
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.
Gram-positive bacteria
Some Streptococcus pyogenes. Some viridans streptococci, Some Streptococcus pneumoniae. Some Staphylococcus aureus.
Gram-negative bacteria
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).
Gram-positive bacteria
Streptococcus pyogenes, Streptococcus pneumoniae, Some Staphylococcus aureus
Gram-negative bacteria
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
Gram-positive bacteria
Some Streptococcus pneumoniae
Gram-negative bacteria
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
Gram-positive bacteria
Streptococcus pyogenes. Viridans group streptococci, Streptococcus pneumoniae, Staphylococci, Enterococci, Listeria monocytogenes
Gram-negative bacteria
Haemophilus influenzae, Neisseria spp. Enterobacteriaceae
Anaerobic bacteria
Bacteroides fragilis, Many other anaerobes
Atypical bacteria Mycoplasma spp.
The antimicrobial activity of Tigecycline (parenteral)
Chloramphenicol
Gram-positive bacteria
Streptococcus pyogenes, Viridans group streptococci. Some Streptococcus pneumoniae
Gram-negative bacteria
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
Gram-positive bacteria
Some Streptococcus pyogenes, Some viridans group streptococci. Some Streptococcus pneumoniae, Some Staphylococcus aureus
Gram-negative bacteria
Anaerobic bacteria
Some Bacteroides fragilis, Some Clostridium spp. Most other anaerobes.
Atypical bacteria
The Antimicrobial Activity of Clindamycin (both oral and parenteral)
Streptogramins
Gram-positive bacteria
Streptococcus pyogenes, Viridans group streptococci, Streptococcus pneumoniae, Staphylococcus aureus, Some enterococci.
Gram-negative bacteria
Anaerobic bacteria
Atypical bacteria
The Antimicrobial Activity of Quinupristin/Dalfopristin (parenteral)
The Oxazolidinones
The structure of Linezolide
Gram-positive bacteria
Streptococcus pyogenes. Viridans group streptococci, Streptococcus pneumoniae, Staphylococci, Enterococci.
Gram-negative bacteria
Anaerobic bacteria
Atypical bacteria
The Antimicrobial Activity of Linezolid (both oral and parenteral)