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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 ?