Types of antibiotics : Antibiotics

Cell wall acting biosynthetic antibiotics. Non-cell wall active agents (Bacterial Protein Synthesis inhibitors )
 Penicillin  Aminoglycosides.
 Cephalosporin  Macrolides.
 Carbapenem  Tetracyclines
 Monobactam  Lincosamides.
 Vancomycin  Chloramphenicol.

Penicillin Cephalosporins
Consists of thiazolidine ring connected to B-lactam ring Contains B-lactam ring as penicillin
to which is attached a side chain

Chemistry

Antistaph. Extended spectrum Antipseudomonal

Natural penicillins
penicillins penicillins penicillins 1st generation 2nd generation 3rd generation 4th generation
Penicillin G Methicillin Ampicillin Carbenicillin Cephalexin O Cefotetan Cefixime O Cefepime
Penicillin V Oxacillin Amoxicillin Piperacillin Cefadroxil O Cefuroxime O Cefdinir
Nafcillin Cefazolin Cefaclor O Ceftriaxone
+ Clavulanic acid or Cefamandole Cefotaxime ÷
Sulbactam Ceftazidime +
Effective against: Effective against: Effective against: Effective against: Cefoperazone
st
For : More t1/2 than 1 Gen. For : Same spectrum to
Names Gram +/- cocci Penicillinase- Gram +ve & -ve organisms Pseudomonas Impetigo For : URTIs & Acute otitis More gram –ve bacilli 3rd Gen.
Gram + bacilli producing including gram -ve Bacilli: aeruginosae and Cellulitis media (Serratia marcescens) More resistance to
Anaerobes. staphylococci Salmonella Shigella other gram –ve Prophylaxis Less active against Cefotaxime preferred in B-lactamases
Spirochetes. H. influenza H. pylori organisms of surgical Gram +ve but more neonates while Enterobacter
E. coli wound Gram –ve Ceftriaxone not resistant to all
Susceptible to infections (↑ bilirubin). Cephalosporins
Used with
inactivation by Ceftazidime & except cefepime
aminoglycosides for
B-lactamase. BUT NOT effective against cefoperazone active
gram -ve Bacilli
Klibsiella, Proteus & against P.aeruginosae.
Pseudomonas aeruginosae
Administration Administration ‫ينفع في كل الحاالت‬
Oral  penicillin V
Ph.Kinetics
Intravenous  Pen G (potassium or sodium)
Intramuscular  Pen G Benzathine or procaine. (Extend t1/2)
 Absorption Absorption ‫يمتص كويس‬
Amoxicillin  Most completely absorbed
Pen G  Impeded by food in stomach, so not given oral. Distribution
Distribution Distributed well through body fluids
All cross placenta ‫آمن‬ Only 3rd generation well into CSF
Minimal penetration into bone and CSF (Relatively insoluble in lipid) Excretion
Excretion By kidneys
Excreted unchanged in urine by tubular secretion ( by kidneys ) Cefoperazone and ceftriaxone excreted through bile and feces
Action on bacteria : Bactericidal Action on bacteria : Bactericidal

Mechanism of action Mechanism of action

Bind to penicillin binding proteins (PBPs)  Inhibition of transpeptidase  Inhibition Inhibition of cross linkages between peptidoglycan chains  inhibition of cell wall synthesis
of cross linkages between peptidoglycan chains  inhibition of cell wall synthesis
Activate bacterial autolysins  cell wall lysis Spectrum as in "Names"
Ph. Dynamics
Spectrum as in "Names" Resistance as penicillin

Resistance
B-lactamase activity  Hydrolyzes b-lactam ring
Decreased permeability to drug
Altered penicillin binding proteins  Require greater antibiotic concentrations

Treatment of : Prophylaxis of : Meningitis (by 3rd and 4th generations)

1. Gram +ve Cocci : Pharyngitis / Boils / Lobar 1. Streptococcal infection in Osteomyelitis
pneumonia Rheumatic fever  Benzathine Skin infection
2. Gram -ve Cocci : Meningococcal meningitis / penicillin 1 .2 million U IM/ Typhoid or biliary infection
Gonorrhea month for 5 years or up to age of UTIs MOST URGENT
Uses 3. Gram +ve Bacilli : Anthrax / Diphtheria / 21 which is ever longer. RTIs
Tetanus / Gas gangrene. 2. Before dental procedures  Gonorrhea
4. Gram -ve Bacilli: SSHHE Procaine penicillin 600.000 U IM ENT infections
5. Spirochetes : Syphilis 2-3 hours iNtestinal infection
6. Pseudomonas ( + gentamicin ) 3. Bacterial endocarditis Topical infection
7. Actinomycosis 4. Gonorrheal neonatal ophthalmia
1. Allergic Reactions : Urticaria - Angioedema - Anaphylactic shock due to Penicilloic acid 1. Allergy as penicillin 10%
which acts as a hapten – Treated by : Adrenaline + Cortisol + Anti-histaminics 2. Nephrotoxic
2. Diarrhea due to superinfection - especially after oral Ampicillin: loop diuretics ‫ او‬aminoglycosides ‫خصىصا انجيم األول و خصىصا نى اديناه مع‬
Candida albicans  monilial thrush & diarrhea Treat by Nystatin. 3. Dislike = Disulfiram like action
Enterotoxins produced by Staph. or C. difficile  Pseudomembranous colitis - 4. ↓ Prothrombine = ↓ clotting factors ( 1972 ) anti vit K effects
Side effects Bleeding ‫ فيعمم‬،‫خصىصا انجيم انحانث‬
Treated by Oral vancomicin or Metronidazole.
3. Na+ or K+ over load  Dangerous in renal or cardiac patients. ( Cation toxicity )
4. CNS irritation (seizures)  If Large Dose or intra-thecal injection of penicillin.
5. Platelet dysfunction by Carbenicillin  Bleeding
6. Nephritis by Methicillin
 Carbapenems Monobactams Vancomycin
Chemistry Chemistry Chemistry
Differ from penicillin in sulfur atom of thiazolidine ring Synthetic b-lactam antibiotics Natural
Synthetic b-lactam antibiotics

Names Name Pharmacokinetics

1. Imipenem Combined with cilastatin Aztreonam Administration  IV infusion to treat systemic
2. Meropenem infections & Oral route only for C. difficile colitis.
Absorption  Poorly absorbed orally
Pharmacokinetics Pharmacokinetics Distribution  Limited penetration into the CSF
Administration  Intravenous use. (IV infusion) Administration  IV or IM ‫ ساعات‬8 ‫كم‬ except in meningitis & Pass placental barrier
Distribution  Penetrates well into CNS. Absorption  Poorly absorbed orally causing deafness of fetus.
Excretion  by kidneys. Distribution  Limited penetration into the CSF. Excretion  by kidneys.
N:B Partly broken down by dehydropeptidase in the proximal tubule to Excretion  by kidneys.
form toxic metabolite that may cause nephrotoxicity. So, given with t1/2 = about 2 hours
cilastatin (dehydropeptidase inhibitor) to prevent cleavage and toxic
metabolite formation.
t1/2 = about 1 hour Pharmacodynamics
Pharmacodynamics Action on bacteria  bactericidal
Pharmacodynamics Action on bacteria  bactericidal Mechanism of action  as penicillin
Action on bacteria  bactericidal Mechanism of action  as penicillin Spectrum  Gram +ve
Mechanism of action  as penicillin Spectrum  Gram –ve only (including pseudomonas) (including MRSA and C. difficile)
Spectrum  Gram +ve & Gram –ve (including pseudomonas) & anaerobes
Uses Uses
Uses Safe alternative for penicillin (piperacillin) and Prophylaxis for subacute bacterial
Infections require multiple antibiotics (useful in nosocomial infections) cephalosporin (ceftazidime) in allergic patients against G- endocarditis in penicillin allergic patients for
Mixed infections ve infections high-risk surgery.
Beta lactam of choice for Enterobacter Methicillin-resistant staphylococci (MRSA)
Not used alone for serious pseud. infections Safe alternative for aminoglycosides, especially in elderly Pseudomembranous colitis caused by
Not used for MRSA infections and patients with renal impairment clostridium difficile.

Side effects Side effects Side effects

Nausea – vomiting – diarrhea Phlebitis Minimal resistant bacteria, but not
Excessive levels with renal failure may lead to seizures Superinfection with staph Vancomycin resistant enterococci (VRE)
Patients who allergic to penicillins may be allergic to imipenem ↑ hepatic enzymes Ototoxicity
Skin rash Nephrotoxicity
Disadvantages of Imipenem/cilastatin VS. Meropenem Red man syndrome  rapid IV infusion leads
1. High incidence of seizures, whereas meropenem is not. to histamine release causing VD of cutaneous
2. A 1g of Imipenem/cilastatin require 200 ml saline to dissolve, whereas A 1g of blood vessels and flashing
meropenem dissolves in only 20 ml saline. Hence, meropenem can be given
either by IV bolus or IV infusion Whereas Imipenem/cilastatin should be given
only by IV infusion, So less suitable for fluid restricted patients
3. Not suitable for outpatients
 Aminoglycosides Macrolides
Isolated from Streptomyces griseus
Chemistry
6 membered rings with 2 glycosylated aminosugars
1st Generation 2nd Generation 3rd Generation 4th Generation
Streptomycin Gentamicin. Tobramycin Netilmycin 1. Erythromycin 4. Roxithromycin
Names Clanamycin Sizomycin Amikacin 2. Clarithromycin 5. Spiramycin
Neomycin 3. Azithromycin. 6. Telithromycin
Monomycin
Administration and Absorption Erythromycin Clarithromycin Azithromycin
Poorly absorbed orally  only for treatment of GIT infection and GIT sterilization Food delays Food delays absorption. Food delays absorption
IV or IM to treat systemic infection (15 to 25 mg/kg) absorption. Rapidly absorbed from GIT
Topically – Inhalation – Intrathecally Absorption Incomplete Widely distributed except
but adequate CSF
Distribution from intestine
Can't pass BBB even in meningitis Not metabolized
Pass placental barrier causing fetal deafness Excretion and actively
Excretion secreted in bile
Kinetics By kidneys. t1/2 1.5 h 4–6h 2 – 4 days
250-
500mg/BD/oral
Dose 500 mg once daily
Maximal dose =
4g/day
Lower frequency of GI Once daily dosing
intolerance No inhibition of
Advantages
Half-life is about 3 cytochrome P-450
times to erythromycin.
Action on bacteria : Bactericidal but static on TB bacilli Action on bacteria : Bacteriostatic but bactericidal acc. to their concentration

Mechanism of action Mechanism of action

Bind to 30S ribosomal subunit  Misreading of m-RNA  Inhibition of protein Bind to 50S ribosomal subunit  Inhibiting the translocation steps of protein synthesis
synthesis
Increases cell permeability through making transient hole formation in the cell Spectrum
membrane  Displace Ca and Mg & Uptake of the aminoglycoside through the Gram +ve and Gram –ve bacteria
holes. Intracellular bacteria
Dynamics
Post antibiotic effect so once daily. Calm my leg Chlamydia – Mycoplasma – legionella
BRC Borrelia – Rickettsia - Coxiella
Spectrum Spirochetes
Gram –ve bacilli : Klibsiella, Proteus & Pseudomonas aeruginosae & Shigella & E. coli
Few Gram +ve cocci
No effect on : +ve bacilli &-ve cocci & anaerobes
 1. Gram –ve bacilli ( UTIs – RTIs  pneumonias – Septicemia – No effect on meningitis 1. RTIs :
2. TB - Plague a. Upper : Pharyngitis – tonsillitis – sore throat – whooping cough
3. Brucellosis b. Lower : Pneumonia – COPD
4. Subacute bacterial endocarditis (SBE) 2. STDs : Gonorrhea – Syphilis
Uses 5. Neomycin : ( Topical – To sterile GIT – In hepatic coma ) 3. ENT infections : Sinusitis – Otitis media
4. MAC (Mycobacterium avium complex) infection in AIDS R SEMPL T
5. Peptic ulcer ( in triple therapy )
6. Lyme disease
7. Topical : Acne vulgaris
NNN 1. GI intolerance Diarrhea Anorexia Nausea
1. Nerve toxic ( Vestibular and cochlear damage ) 2. Cholestatic hepatitis
Side effects 2. Nephrotoxicity 3. Inhibits cytochrome P450 – CYP 3A
3. Neuromuscular blocking 4. Lots of drug interactions
5. QT prolongation  Ventricular arrhythmias
1. With other ototoxic drugs  furosemide, minocycline Drug interactions
2. With other nephrotoxic drugs  vancomycin, cisplatin Erythromycin and Clarithromycin ONLY– are inhibitors of cytochrome p450 system in the liver and
may increase concentrations of :
3. Pregnancy  fetal ototoxicity Theophylline
Contraindications
4. Elderly patients Digoxin
Valproic acid, Carbamazepine
5. Cautious use of muscle relaxants Phenytoin
6. Do not mix with any other drug in same syringe Cyclosporine

Tetracyclines Quinolones (accidental discovery)

Tetracycline
Doxycycline
Chlortetracycline
Oxytetracycline
Minocycline
Names

Absorption
Lipid soluble  Penetrate many cell types and tissue compartment
Topically – Inhalation – Intrathecally

Kinetics Distribution
Poorly pass BBB
 Tetracycline 0-24%
 Doxycycline 13-26 %
Excretion Unchanged by kidneys.
 Action on bacteria : Bacteriostatic ‫مهما زادت انجرعة‬ Action on bacteria : Bactericidal

Mechanism of action Mechanism of action

Bind to 30S ribosomal subunit  Inhibition of aminoacyl t-RNA from reaching Inhibit DNA gyrase (topoisomerase II ) synthesis which responsible for supercoiling of
m-RNA ribosomal complex  Inhibition of protein synthesis bacterial DNA
Resistance Inhibit DNA topoisomerase IV

Dynamics

1. 2nd line in Calm my leg ‫بعد انـمايكرونيدز‬ 1. UTIs ( esp. Prostatitis )

2. 1st line in BRC ‫( قبم انـمايكرونيدز‬Doxycycline 100mg / 12h / 14 days) 2. STDs ( Chlamydial infections / PID )
3. GIT infections ( Cholera / Typhoid / Shigellosis / Traveller diarrhea )
3. Vibrio cholera (Doxycycline 300 mg single dose) 4. RTIS ( Pneumonia / H. influenza / Pseudomonas )
4. Acne (Doxycycline + Clindamycin) topically 5. Osteomyelitis / Diabetic foot
5. SIADH ( Demeclocycline 150-300 mg ) 6. Others :
Uses a. MDR TB
b. Prophylaxis in neutropenic patients

1. Bone and joints :

1. Chelation with Ca, Mg, Al, Fe
a. Arthropathy (damage growing cartilage)
2. GI upset  Esophageal ulceration & superinfection
b. Tendonitis and tendon rupture
Side effects 3. Photosensitivity  Avoid Sun exposure
2. CVS : Prolonged QT interval
4. Shelf-Life  Nephrotoxic derivatives  Acquired Fanconi Syndrome
3. CNS : Confusion, insomnia, dizziness, anxiety, and seizures  Inhibit GABA in 1% of patients
(glycosuria– proteinuria – aminoaciduria)
4. GIT : DAN and antibiotic associated colitis
1. Children (not absolute)
2. Pregnancy.
3. Lactation.
1. Pregnancy  Hepatotoxic to the fetus 4. Epilepsy.
Contraindications
2. Youth  Deposition (Pigmentation) of bones and teeth 5. QT prolongation.
 Lincosamides Chloramphenicol
Clindamycin
Names
Lincomycin
As macrolides Action on bacteria bactericidal on :
Pneumococcus.
Meningococcus.
H. influenzaе.
on the others bacteriostatic.
Dynamics
Mechanism of action
Bind to 50S ribosomal subunit  Inhibition of peptidyl transferase  Inhibition of protein
synthesis
Spectrum
Bacteria which are stable to penicillin
1. Antibiotic for anaerobic and gram +ve cocci infections 1. Meningitis (Can cross BBB)
2. Protozoan infections : 2. Typhoid fever
Uses Toxoplasmosis (2nd line( Clindamycin + Pyrimethamine 3. Paratyphoid fever
PCP (2nd line( Clindamycin + Primaquine 4. Brucellosis
Plasmodium falciparum Clindamycin + Quinine 5. Tularemia
1. Bone marrow suppression (Hematotoxicity)  Hypochrome and aplastic anemia,
granulocytopenia, thrombocytopenia
2. Hepatotoxicity
3. Neurotoxicity
Side effects 4. Grey baby syndrome ‫جحث انسنحين‬
5. Disbacteriosis and superinfection
6. Depression of cardiovascular activity (up to collapse, heart failure)
7. Dyspepsia

Sulfonamides Trimethoprim Cotrimoxazole

Mechanism of Action of Sulpha Mechanism of Action Advantages
Inhibit microbial folic acid synthesis Inhibits dihydrofolate reductase thus Expanded number of organisms. Decreased resistance.
Competitive inhibition of the incorporation of Para-amino-benzoic interfering with folic acid synthesis and Bactericidal. Decreased toxicity
acid (PABA) into tetrahydropteroic acid hence purine synthesis
Therapeutic Uses
Spectrum of Activity Combined with the sulfonamides to UTIs RTIs : pneumonia (PCP)
Antibacterial Antiprotozoal potentiate their Activity by sequential
Gram +ve activity Plasmodium : inhibition of folic acid synthesis Adverse Effects
Gram –ve activity (Sulfadoxine + Pyrimethamine = Fansidar) Fixed drug combination with Hypersensitivity Urinary tract disturbances -formation of crystalline
Intracellular organisms Toxoplasmosis : Sulfamethoxazole (1:5 ratio) reactions: allergic rashes aggregates in urinary tract, hematuria and
Branching bacteria (Sulfadiazine + Pyrimethamine) Oral Drug  80mg Trimethoprim / 400 Photosensitivity obstruction.  Drink Adequate Fluids.
(Actinomyces / Nocardia) PCP : mg Sulfamethoxazole (Septra) Drug fever Hematological effects : Leukopenia,
(Sulfamethoxazole + Trimethoprim = SXT) IV Drug  16mg Trimethoprim + 80mg Stevens-Johnson thrombocytopenia and megaloblastosis. Most likely
Sulfamethoxazole /ml syndrome in patients with preexisting folate deficiency or in
patients taking prolonged therapy.
 Metronidazole
Pharmacokinetics
1. Action on bacteria and protozoa : -Cidal
2. Mechanism of action
a. Reduced inside bacteria and protozoa by ferrodoxin into active metabolite
b. Binds to DNA  Inhibits nueclic acid
3. Spectrum
Strict anaerobic bacteria
Clostridium – bacteroides
Trichomonas vaginalis
Some protozoa :
 E. histolytica
 Giardia
Uses & Side effects

Uses Side effects

1. Anaerobic bacteria 1. Seizures
2. C. difficile 2. Reversible neutropenia
3. Bacterial vaginosis 3. Peripheral neuropathy
4. Amoebiasis
5. Giardiasis 4. Hepatitis
6. H. pylori 5. Pancreatitis
6. Epigastric pain

7. Metallic taste
8. Steven-Jonson

Polymyxin B Mupirocin Oxazolidinones

Group of basic peptides active against Gram (-) & bactericidal Ointment for topical application. Toxic to humans, but had antibiotic properties
treatment of serious enteric infections (Pathogenic E. coli, Active against staph aureus; in. Isoleucyl tRNA synthetase. “Superbugs” led to their re-exploration
Shigella, Enterobacter, Klebsiella and Pseudomonas, not Indicated for impetigo, intranasal application for elimination of Development of less toxic derivatives
Proteus) MRSA carriage by patient or health care workers Mechanism of Action  Act on the 50 S rRNA Similar to
Poor tissue distribution. Macrolides
Attach to and disrupt bacterial cell membrane, bind and Different from Macrolides  Inhibit the initiation of bacterial
inactivate endotoxin. protein synthesis. & Prevent the formation of a functional
Toxicity includes neurological and renal effects topical initiation complex
(+Bacitracin - Neomycin)