Classification of antibioticsby

Dr.Bassem alaa el-din

(CWI)B-lactam

Same MOA: Inhibit cell wall synthesis Bactericidal (except against Enterococcus

sp.) Short elimination half-life Primarily renally eliminated (except nafcillin,

oxacillin, ceftriaxone, cefoperazone) Cross-allergenicity - except aztreonam

B-lactam Adverse effects

• Hypersensitivity – Higher incidence with parenteral

administration or procaine formulation Mild to severe allergic reactions – rash to

anaphylaxis and death Antibodies produced against metabolic by-

products or penicillin itselfCross-reactivity exists among all penicillins

and even other -lactamsDesensitization is possible

B-lactam Adverse effects

• Neurologic – especially with penicillins and carbapenems (imipenem and meropenem) Especially in patients receiving high doses in the

presence of renal insufficiency Irritability, confusion, seizures

• HematologicLeukopenia, neutropenia, thrombocytopenia –

in prolonged therapy (> 2 weeks)

B-lactam Adverse effects

• Gastrointestinal Increased LFTs, nausea, vomiting, diarrhea,

pseudomembranous colitis (C. difficile diarrhea)

• Interstitial Nephritis Cellular infiltration in renal tubules (Type IV

hypersensitivity reaction – characterized by abrupt increase in serum creatinine; can lead to renal failure

Especially with methicillin or nafcillin

(CWI)B-lactam Penicillins• Natural Penicillins:• Aqueous penicillin G• Penicillin G• Pencillin VK• Beta lacatamse resistant Penicillins• Methicillin• Nafcillin• Oxacillin• Cloxacillin• Dicloxacillin• Aminopenicillins• These are extended spectrum antibiotics.• Ampicillin• Amoxicillin• Carboxypenicillins• These are also extended spectrum antibiotics.• Carcenicillin• Ticarcillin• Ureidopenicillins• These are extended spectrum antibiotics.• Mezlocillin• Piperacillin

(CWI)B-lactam Penicillins

• Penicillins/inhibitor combination• Ampicillin/sulbactam• Ticarcillin/clavulanate• Piperacillin/tazobactam• Amoxicillin/clavulanate

(CWI)B-lactam Penicillins

(CWI)Cephalosporins

• Divided into 4 major groups called “Generations”

• Are divided into Generations based on antimicrobial activity resistance to beta-lactamase

(CWI)Cephalosporins

(CWI)Cephalosporins

• First Generation:• The optimum activity of all first generation

cephalosporin drugs is against gram-positive bacteria such as staphylococci and streptococci. They also have little gram-negative spectrum.

(CWI)Cephalosporins

• Second Generation:• The drugs that come under second generation

have more spectra against gram-negative bacteria (Haemophilus influenzae, Enterobacter aerogenes) in comparison to the first generation. Their gram positive spectrum is less than the first generation.

(CWI)Cephalosporins

• Third Generation:• Third generation cephalosporin drugs

are broad spectrum and the effective against both gram positive and gram negative bacteria. However their optimum activity is against gram negative bacteria.

3rd G Cephalosporin Cefotaxime

3rd G Cephalosporin Cefotaxime

(CWI)Cephalosporins

• Fourth Generation:• These are extended spectrum antibiotics. They

are resistant to beta lactamases.

(CWI)Carbapenems

• Imipenem• Meropenem• Ertapenem• Most broad spectrum of activity of all antimicrobials• Have activity against gram-positive and gram-negative

aerobes and anaerobes• Bacteria not covered by carbapenems include MRSA,

VRE, coagulase-negative staph, C. difficile, Nocardia• Additional ertapenem exceptions:

• Pseudomonas and Enterococcus

(CWI)Carbapenems(Meropenem)

Ertapenem

(CWI)Monobactams

Aztreonam bind preferentially to PBP 3 of gram-negative aerobes; has little to no activity against gram-positives or anaerobesGram-negativeE. coli, K. pneumoniae, P. mirabilis, S. marcescensH. influenzae, M. catarrhalisEnterobacter, Citrobacter, Providencia, MorganellaSalmonella, ShigellaPseudomonas aeruginosa

(NAS)Flouroquinolones

• Novel group of synthetic antibiotics developed in response to growing resistance

• The fluorinated quinolones (FQs) represent a major therapeutic advance: Broad spectrum of activity Improved PK properties – excellent bioavailability,

tissue penetration, prolonged half-lives Overall safety

• Disadvantages: resistance, expensive

(NAS)Flouroquinolones

Gram-positive – newer FQs with enhanced potency

• Methicillin-susceptible Staphylococcus aureus• Streptococcus pneumoniae (including PRSP)• Group A/B/C/G and viridans streptococci –

limited activity• Enterococcus sp. – limited activity

(NAS)Flouroquinolones

Gram-Negative – all FQs have excellent activity (cipro=levo>gati>moxi)• Enterobacteriaceae – including E. coli, Klebsiella

sp, Enterobacter sp, Proteus sp, Salmonella, Shigella, Serratia marcescens, etc.

• H. influenzae, M. catarrhalis, Neisseria sp.• Pseudomonas aeruginosa – significant resistance

has emerged; ciprofloxacin and levofloxacin with best activity

(NAS)Flouroquinolones

Atypical Bacteria – all FQs have excellent activity against atypical bacteria including:

• Legionella pneumophila - DOC• Chlamydia sp.• Mycoplasma sp.• Ureaplasma urealyticum

Other Bacteria – Mycobacterium tuberculosis, Bacillus anthracis

(NAS)Flouroquinolones(Levofloxacin)85 L.E

(NAS)Flouroquinolones

(NAS)Flouroquinolones Adverse effects

• Articular Damage Arthopathy including articular cartilage damage,

arthralgias, and joint swelling Observed in toxicology studies in immature dogs Led to contraindication in pediatric patients

and pregnant or breastfeeding women Risk versus benefit

• Other adverse reactions: tendon rupture, dysglycemias, hypersensitivity

(PSI)Macrolides

• Erythromycin is a naturally-occurring macrolide derived from Streptomyces erythreus – problems with acid lability, narrow spectrum, poor GI intolerance, short elimination half-life

• Structural derivatives include clarithromycin and azithromycin: Broader spectrum of activity Improved PK properties – better bioavailability, better

tissue penetration, prolonged half-lives Improved tolerability

(PSI)Macrolides

Macrolides typically display bacteriostatic activity, but may be bactericidal when present at high concentrations against very susceptible organisms

Time-dependent activity

(PSI)Macrolides

Gram-Positive Aerobes – erythromycin and clarithromycin display the best activity

(Clarithro>Erythro>Azithro)• Methicillin-susceptible Staphylococcus aureus• Streptococcus pneumoniae (only PSSP) – resistance is

developing• Group A/B/C/G and viridans streptococci• Bacillus sp., Corynebacterium sp.

(PSI)Macrolides

Gram-Negative Aerobes – newer macrolides with enhanced activity

(Azithro>Clarithro>Erythro)

• H. influenzae (not erythro), M. catarrhalis, Neisseria sp., Campylobacter jejuni, Bordetella pertussis

• Do NOT have activity against any Enterobacteriaceae or Pseudomonas

(PSI)Macrolides

Atypical Bacteria – all macrolides have excellent activity against atypical bacteria including:

• Legionella pneumophila - DOC• Chlamydia sp.• Mycoplasma sp.• Ureaplasma urealyticum

(PSI)Aminoglycosides

• Are bactericidalGram-Positive Aerobes most S. aureus and coagulase-negative staph (but not DOC)viridans streptococci (in combination with a cell-wall agent)Enterococcus sp. (only in combination with a cell-wall agent)

Gram-Negative Aerobes (not streptomycin)E. coli, K. pneumoniae, Proteus sp.Acinetobacter, Citrobacter, Enterobacter sp.Morganella, Providencia, Serratia, Salmonella, ShigellaPseudomonas aeruginosa (amik>tobra>gent)

Mycobacteria– tuberculosis - streptomycin– atypical - streptomycin or amikacin

(PSI)Aminoglycosides

• Adverse effects• Nephrotoxicity and ototoxicity

(CWI)Vancomycin

Gram-positive bacteria– Methicillin-Susceptible AND Methicillin-Resistant S.

aureus and coagulase-negative staphylococci– Streptococcus pneumoniae (including PRSP), viridans

streptococcus, Group A/B/C/G streptococcus– Enterococcus sp.– Corynebacterium, Bacillus. Listeria, Actinomyces– Clostridium sp. (including C. difficile), Peptococcus,

Peptostreptococcus

No activity against gram-negative aerobes or anaerobes

(CWI)VancomycinClinical uses

• Infections due to methicillin-resistant staph including bacteremia, empyema, endocarditis, peritonitis, pneumonia, skin and soft tissue infections, osteomyelitis

• Serious gram-positive infections in -lactam allergic patients

• Infections caused by multidrug resistant bacteria• Endocarditis or surgical prophylaxis in select cases• Oral vancomycin for refractory C. difficile colitis

(CWI)VancomycinAdverse effects

Red-Man Syndrome – flushing, pruritus, erythematous rash on face and

upper torso– related to RATE of intravenous infusion; should be

slowly infused over at least 60 minutes– resolves spontaneously after discontinuation– may lengthen infusion (over 2 to 3 hours) or pre-

treat with antihistamines in some cases

(CWI)Vancomycin

(PSI) Oxazolidinones

• Linezolid (Zyvox®) is the first available agent which received FDA approval in April 2000; available PO and IV

• Developed in response to need for agents with activity against resistant gram-positives (MRSA, VRE) vancomycin-resistant Enterococcus

(PSI) Oxazolidinones

• Bacteriostatic: (cidal against some bacteria) Gram-Positive Bacteria

– Methicillin-Susceptible, Methicillin-Resistant AND Vancomycin-Resistant Staph aureus and coagulase-negative staphylococci

– Streptococcus pneumoniae (including PRSP), viridans streptococcus, Group streptococcus

– Enterococcus faecium AND faecalis (including VRE)– Bacillus. Listeria, Clostridium sp. (except C. difficile),

Peptostreptococcus, P. acnes

Gram-Negative Aerobes – relatively inactiveAtypical Bacteria

– Mycoplasma, Chlamydia, Legionella

(PSI) Oxazolidinones Pharmacology

• Concentration-independent bactericidal activity

• Absorption – 100% bioavailable• Distribution – readily distributes into well-

perfused tissue; CSF penetration 70%

(PSI) Oxazolidinones Adverse effects

• Thrombocytopenia – 2 to 4%– Most often with treatment durations of > 2 weeks– Therapy should be discontinued – platelet counts

will return to normal

(PSI) Oxazolidinones

Linezolid is a reversible, nonselective inhibitor of monoamine oxidase MAOI.

• Tyramine rich foods, adrenergic drugs and serotonergic drugs should be avoided due to the potential drug-food and drug-drug interactions.

• A significant pressor response has been observed in normal adult subjects receiving linezolid and tyramine doses of more than 100 mg.

• Therefore, patients receiving linezolid need to avoid consuming large amounts of foods or beverages with high tyramine content.

(PSI) Lincosamides

• Clindamycin typically displays bacteriostatic activity, but may be bactericidal when present at high concentrations against very susceptible organisms

(PSI) Lincosamides

Gram-Positive Aerobes • Methicillin-susceptible Staphylococcus

aureus (MSSA)• Methicillin-resistant Staphylococcus aureus

(MRSA) – some isolates• Streptococcus pneumoniae (only PSSP) –

resistance is developing• Group and viridans streptococci

(PSI) Lincosamides

Anaerobes – activity against Above the Diaphragm Anaerobes (ADA)

Peptostreptococcus some Bacteroides spActinomyces Prevotella sp.Propionibacterium FusobacteriumClostridium sp. (not C. difficile)

Other Bacteria – Toxoplasmosis gondii, Malaria

(PSI) Lincosamides Adverse effects

• Gastrointestinal – 3 to 4 % Nausea, vomiting, diarrhea, dyspepsia

• C. difficile colitis – one of worst offenders Mild to severe diarrhea Requires treatment with metronidazole

• Hepatotoxicity - rare Elevated transaminases

• Allergy - rare

• Thank you any question ?