2. Antibiotics - chemical substances originally produced
by various species of micro-organisms (bacteria, fungi,
actinomycetes) that in high dilution suppress the
growth or cause death of other microorganisms
Objective of Rx- For curative - eradication by lethal
effect,inhibit growth & multiplication,phagocytosis
For preventive
4. Bacteriostatic
• inhibiting the growth or multiplication of bacteria
Bactericidal
• lethal effect on mature bacteria /kill the bacteria
Antibacterial spectrum
• list of bacteria which are normally susceptible to
antibacterial action of a particular agent (group or
particular organisms)
8. Classification
based on their Mechanism of Actions
1. Drugs that inhibit the synthesis of
bacterial cell walls
eg.Penicillins, Cephalosporins, Vancomycin
Clotrimazole
2. Agents that act directly on the cell
membrane
eg‘.Nystatin, Amphotericin
Antimicrobial agents 8
9. Cont-
3. Drugs inhibiting microbial protein synthesis by their
effect on bacterial ribosomes
(A) disrupt the function of 30S or 50S ribosomal subunits to reversibly inhibit
protein synthesis (mainly bacteriostatic)
eg – Chloramphenicol, Tetracyclines, Macrolides,
Clindamycin, Lincomycins
(B) agents that bind irreversibly to 30s ribosomal subunit (mainly
bactericidal)
– Aminoglycosides eg. Gentamicin
Antimicrobial agents 9
10. 4. Drugs that affect nucleic acid metabolism
eg.Rifampicin,Fluoroquinolones,Griseofulvin
Metronidazole
5. The antimetabolites - Drugs affecting the intermediary
metabolism which are essential to micro-organisms
Sulfonamides Competitive
antagonist of
Para-aminosalicylic acid PABA
(PAS)
Trimethoprim
inhibit DHFA-reductase enzyme
Pyrimethamine
11. • MOA
-inhibit the bact:cell wall syn by binding to protein,inhibit
crosslinking enz ∆ autolysis
12. Classification of Penicillins
1. Penicillin G - Benzyl penicillins
(a) Penicillin G- Crystalline I.V (Aqueous Pen G as K+ salt and Na+ salt)
(2,50000 to 10,00000 units IM, IV)
(b) Penicillin G -Procaine suspension
(3,00000 to 6,00000 units IM)
(c) Penicillin G -Benzathine suspension
(0.6 to 1.2 mega units IM)
2. Penicillins V (oral) Phenoxymethyl penicillin(250-500mg)
3. Penicillinase-resistant penicillins (Anti-staph)
Cloxacillin – orally,IM, IV
Flucloxacillin
Dicloxacillin, Oxacillin
Antimicrobial agents 12
13. • Methicillin - use as a laboratory tool for identification of
methicillin - resistant - Staphylococcus aureus (MRSA)
(MRSA = resistance to all the penicillinase-resistant penicillins and
cephalosporins) (Vancomycin is a drug of choice in MRSA)
4. Broad spectrum penicillins
Ampicillin
Amoxicillin
5. Antipseudomonal penicillins
Carboxypenicillins - Carbenicillin Indanyl (oral), Ticarcillin
Ureidopenicillins - Piperacillin
6. Penicillin β-lactamase inhibitor combination
Co-amoxiclav (Amoxicillin + clavulanic acid)
15. Organisms Usage Dosage/Route
gram (+) bacilli – Diphtheria C/pen 30-50mg/kg 6H
C. diphtheriae, Infection due to
B. anthracis, Bacillus anthracis
Clostridium, Clostridium species
Actinomyces -Actinomyces* and other
gram-positive rods
spirochetes Treponema pallidum C/pen “
(syphilis) and many other
spirochetes
Prophylatic Tx
16. Pen V
Organisms Usage Dosage/Route
•gram (+)ve cocci o minor infections oral
(except penicillinase (streptococcal pha- 15 mg/kg 6H (125-
producing ryngitis) 250mg)
staphylococci)
* narrow antibacterial o prophylaxis of 12.5 mg/kg 12 H
spectrum streptococcal infection
following rheumatic
fever and
pneumococcal
infection (following
splenectomy)
fusospirochetel
infection
(gingivostomatitis)
17. Pen resistent pen
Org Usage Dosage
more effective against staphylococcal Cloxacillin – orally,IM, IV
penicillinase producing infections-skin,LRIT 15 mg/kg 6H 12H,4-6H,
25- 50mg/kg
- staphylococci
Flucloxacillin
12.5-25 mg/kg 6H
25-50 mg/kg 8H,6H
less effective than pen. G
and pen. V against Gram
positive bacteria
Some strains of Gram H. influenzae, E. coli,
negative bacteria gonococci, Klebsiella
18. Aminopenicillins (Ampicillin, Amoxicillin)
Org Usage Dosage
gram (-)ve, (+)ve bacteria URTI (sinusitis, otitis Oral/I.M/I.V
(H. influenza, E.coli and Proteus media, acute 10-25 mg/kg 6H /8H
mirabilis)
exacerbations of severe -50mg/kg
chronic bronchitis &
epiglottitis)
Lower RTI,
UTI, Biliary tract
‴
Listeria monocytogen Meningitis,
Salmonella infection
(Enteric fever)
H. pylori
sensitive against Penicillin - β-lactamase
β-lactamase producing inhibitor combination
strains of G (+)ve & G (–)ve
bacteria*.Staph,Gono, (Clavulanic acid or
H. influenzae, E coli, Klebsiella, Sulbactam)
Proteus, 20-25 mg/kg IM,IV 6H
Bacteroides fragalis, Moraxella
catarrhalis
21. Mechanism of Action
• similar to penicillin , bactericidal, inhibit bacterial cell
wall synthesis
Classification of Cephalosporins
I. The first generation cephalosporins
Cefalexin
Cefadroxil
Cefazolin
II. The secondgeneration cephalosporins
Cefuroxime axetil ,Cefaclor (Oral)
Cefuroxime
Cefoxitin IV,IM
• Cefotetan
22. III. Third generation
Cefixime(oral)
Cefotaxime
Ceftriaxone IV,IM
Ceftazidime
IV. Fourth generation
Cefepime (I.V)
23. The First Gen:Cephalo
Drug Theraputic advantage Dosage
Gram- positive cocci upper and lower RTI Cefalexin- 7.5mg/kg 6h
(except MRSA) Cefadroxil 15-25mg/kg
12h
Cefazolin
Gram-negative bacteria urinary tract infection
Ecoli,Kleb,Proteus surgical prophylaxis
Oral cavity anaerobic
cocci
some β lactamase skin and soft tissue
producing strains infections owing to
(e.g, Staphylococcus) S. aureus and
S. pyogens
24. The second gen:cephalo
Gram + ve RTI (oral) Cefuroxime axetil 10-
15 mg/kg bd
Cefaclor 15mg/kg 8h
anaerobes (Bacteroids anaerobic infection Cefuroxime iv
fragilis) -pelvic inflammatory 25-50 mg/kg 8,12,6 hr
disease,
-Intra-abdominal inf,
- diabetic foot
Gram-ve bacteria G (-)ve bacterial
(< 3rdG)
(Neisseria,H.influenzae,
Enterobacter Proteus,
E.coli, Klebsiella)
25. The third gen:cephalo
less active against G + ve DOC for serious Cefotaxime iv
infn 25-50mg/kg-12 h
(Septicaemia,Pneu 8 h/6 h
monia,Meningitis) Ceftriaxone -iv,im
25-50mg/kg 12h,8h
Oral-Cefixime 5mg/kg od
Cefpodoxime ″ bd
more active against G -ve Enteric fever
Severe Lyme’s d/s
Gonococcal
much more active
enterobacteriaceae &
β-lactamase producing
strains
s/a (H. influenzae &
Neisseria)
some - active against P.aerug Ceftaxidime iv,im
15-25mg/kg 8h
30. Mycobacterium Mycobacterial infection Azithromycin
15mg/kg D1
7.5mg/kg D2-5
more potent than Eradication of H.pylori Chlarithromycin
erythromycin in peptic ulcer
strept, staph,Chlamydia
Mycoplsma and
H.pylori
31. Untoward Effects
- not common
• cholestatic hepatitis is common with erythromycin
estolate (esp. in pregnancy)
• allergy, GI disturbances, arrhythmia*
• reversible hearing loss
Contraindication
• liver disease, pregnancy
Drug Interaction
Erythromycin and clarithromycin inhibit CYP3A4
potentiate the effects of digoxin, theophylline & valproate
32. LINCOSAMINES
(Lincomycin and Clindamycin)
Antibacterial Activity Therapeutic Uses Dosage
Anaerobic bacteria peritonitis, Lincomycin
(Bacteroides species, pelvic inflammation 10mg/kg 8h oral
Clostridium) IM or IV (over 1h)
10 -20mg/kg (over 2h)6h
Gram +ve bacteria – Bony infections Clindamycin
more effective - osteomyelitis, 6mg/kg 6h oral
(Staph. aureus) sinusitis, periosteitis, IV over 30min,IM 12h
periodontitis 10 -20mg/kg 8h
Aspiration pneumonia,
Lung abscess
Gram - ve bacteria
Less effective
33. Untoward Effects of Lincosamines
• Diarrhoea (superinfection)
• Pseudomembranous colitis due to Clostridium difficile
which produces enterotoxin(Tx –metronidazole)
• Hypersensitivity (rare);
• Granulocytopenia, thrombocytopenia,
• Stevens -Johnson Syndrome
(can occur, but not common)
34. Antibact Rx Dose& Route
a wide range of G(+)& (-) IV 1g every 6 hours for 4
Salmonella Enteric fever weeks in enteric fever
Shigella, Bacterial meningitis Chloramphenicol sodium
V . cholerae H.influenza, succinate (1g vial) I.M, I.V
H.influenza N.meningitidis
Bordetella pertussis Strep. Pneumoniae
Brucella, Rickettsia, Anaerobic infections Orally - Chloramphenicol
anaerobic bacteria Rickettsial infection 25mg/kg/D
(typhus fever, Q fever (250 - 500 mg) 6 - 8 hourly
Brucellosis
less effect on
Staphylococcus
Ophthalmic infection Eye drop- 2-6 H
Ear Ear drop- 6H
35. Untoward Effects
less selective toxicity; may inhibit protein synthesis of
mammalian tissues
1. Haematological toxicity - bone marrow depression
(a) true toxic reaction - dose related, common with prolong therapy
or large dose
- anaemia, leucopenia, thrombocytopenia
(b) Idiosyncratic manifestation - not dose related (occurs in
genetically susceptible patients)
- aplastic anaemia --- can be fatal
36. 2. Grey (gray) syndrome (Gray baby Syndrome)
• in premature and newborn infants
• due to ineffective conjugation & poor renal excretion
with dose above 50 mg/kg/day
• dose should be limited to 50 mg/kg/day in full term
infants and 25 mg/kg/day in premature infants
3. Superinfection (oral or vaginal candidiasis) due to
alteration of normal microbial flora
4. Haemolysis in G6PD deficient patients (dose-related)
37. Antimicrobial spectrum Theraputic advantage Dosage
Mainly active against Genta IV,IM
Gram - ve bacteria UTI 7-8 mg/kg/D1,then
(Pseudomonas, Shigella, G -ve bacillary infect: 5mg/kg 12H
E.coli, Proteus, H.influ, Gonorrhoea Neonate5-7.5mg/kg/d
Brucella, Klebsiella) Bowel sterilization 24H
active against some Topical – Streptomycin IM 20-
Gram +ve wounds,burns,dermatitis 30mg/kg (max:1G)OD
Intestinal amoebiasis Amikacin IV,IM
Mycobacteria TB Prem -15mg/kg/D
(Streptomycin, Amikacin, D17.5mg/kg OD
Netilmicin, Kanamycin) Term-15mg/kg/D OD
Anaerobic bacteria are 1 wk to 10yr -15 mg/kg
resistant to Netilmicin IV,IM
aminoglycosides 1wk-10yr= 8mg/kg/D1
then 6mg/kgOD ,>10yr =
7 in D1 then 5mg/kg
Neonate5 mg/kg/D
OD
38. Unwanted effects
1. Ototoxicity
• irreversible results from progressive destruction of vestibular or
cochlear sensory cells
(a) Vestibular dysfunction
(Gentamicin, Streptomycin, Netilmicin)
(b) Auditory dysfunction – Kanamycin , Amikacin
(potent diuretics potentiate ototoxicity)
2. Nephrotoxicity
• due to accumulation of aminoglycosides in the proximal tubular
cells
3. Neuromuscular blockade (reversible)due to inhibition of prejunctional release
of ACh(Aminoglycosides potentiate d-tubocurarine)
4. Others
• rare - hypersensitive reactions
• vague feelings of paraesthesia of the lips or circumoral region
• prolong use -- superinfection, diarrhoea, malabsorption
can occur with neomycin
39. I. First Generation Quinolones
• Nalidixic acid
II. Second Generation Quinolones
• Norfloxacin
• Ciprofloxacin
III. New fluoroquinolones
• Gatifloxacin
• Moxifloxacin
40. • MOA
• Bactericidal
• Block bact synthesis by inhibiting bact DNA gyrase and
topoisomerase
• Antibact spectrum--
E.coli,Salmonella,Shigella,Enterobacter,Campylo-
bacter,Neisseria
Pseudomonas(Ciprofloxacin)
Staph( not MRSA)
Strep,Chlamydia,Mycoplasma,Legionella,Mycobact
42. • Dosage
Ciprofloxacin- oral= 5-10 mg/kg 12H
IV = 4-7 mg/kg 12 H
Norflox = 10 mg/kg 12H
Prophylaxis
15 mg/kg oral single
43. Side effects
Generally well tolerated
• nausea, abdominal discomfort, diarrhoea, headache,
dizziness, allergy, photosensitivity
• cartilaginous erosion in foetus and children (arthropathy)
and tendonitis --- limited used in children age <14 years and
pregnancy
• Increse BUSE
• Transient ↑ in Liver enzymes,Bilirubin
• Disturbance in vision,taste and smell
• Risk of haemolysis in G6PD def;
44. • Drug interaction
- Cipro,Ofloxa ,Peflox inhibit the metabolism of Theophylline
45. • Bacteriostatic
• Competitive inhibitor of dihydropteroate
synthase which is responsible for the
incorporation of PABA (para-aminobenzoic
acid) which is essential for the formation of
folic acid (pteroylglutamic acid)
47. Untoward Effects
1. Renal toxicity
• a local reaction with short-acting sulfonamides
(high doses)
• may precipitate in the urine(obstruction,haematuria)
2. Haemopoietic reactions
Anaemia-haemolytic/aplastic,granulocytopenia
H’lysis in G6PD def:
Neonatal jaundice in new-born babies(especially in last
trimester—Haemolytic jaundice)
antimicrobial agents III 47
48. Untoward Effects
3. Allergic reactions --- skin rashes, exfoliative
dermatitis, photosensitivity --- more severe with long
acting sulfonamides
• Stevens-Johnson Syndrome
- mucosal, dermal, genital and occular lesions; joint pain,
high fever, oedema, ulcerations of the lips and tongue
- erythema multiforme on skin of hands and thighs
- severe urethritis and balanitis in males
antimicrobial agents III 48
50. MOA of Cotrimoxazole
• Sulfonamides are the competitive antagonist of PABA. They
inhibit the incorporation of paraaminobenzoic acid(PABA) to
folic acid.
• Trimethoprim is a dihydrofolic acid reductase inhibitor. It
prevents the reduction of dihydrofolate to tetrahydrofolate.
• Inhibition of two consequent steps in the synthesis of DNA
and RNA of bacteria when a sulfonamide and trimethoprim
are used together.(Sequential Blockade)
• Two bacteriostatic compounds act synergistically and become
bactericidal
52. Antibacterial spectrum Rx uses Dosage
Streptococci, (1)Urinary tract TMP 1.5-3mg/kg 12H
Staphylococci, infections IV ,Oral
Neisseria (2) Respiratory tract PCP Tx 250mg/m2 stat
E. coli, infections 150mg/m 2 8H
(3) Gonococcal Prophylaxis
Salmonella, Shigella, infections for UTI- 5 mg/kg oral
Enterobacter Proteus, (4) Enteric fever PCP- 5mg/kg 3days/wk
Klebsiella, Brucella, (5) Malaria
Chlamydia (CQ resistant falciparum
except Pseudomonas malaria)
aeruginosa (6) Brucellosis
Pneumocystis carinii (7) Pneumocystis carinii
infection in AIDS Patient
Untoward effects
-Same as S’.Megaloblastic A with prolonged Rx
53. Cont - Synergists of S’
2. Pyrimethamine
also an inhibitor of DHFA reductase enzyme of malarial parasites and
toxoplasma
Pyrexine (or)
Fansidar = Sulfadoxine 500 mg + Pyrimethamine 25 mg
Therapeutic Uses --- Malaria, Toxoplasmosis
54. 3. Tetracycline
• in combination with sulfonamides produce
synergistic effects because both are
bacteriostatic drugs
4. Penicillin:
• although bactericidal, it produces a
synergistic effect when used in combination
with sulfonamides.
55. Drug Interactions with Sulfonamides
• warfarin, sulphonylureas,diphenylhydantoin
(1) potentiation of action of other drugs due to
competition at plasma protein binding site
(drug displacement interaction)
(2) inhibition of metabolism
antimicrobial agents III 55
71. Antiviral drugs
1.Nucleoside Acyclovir* HSV1,2 Herpes-oral,genital
Analogues* 20mg/kg iv VZV HS-Encephalitis
(synthesis of DNA 100mgodx 5 d CMV Varicella(immu ↓)
&RNA) Ginclovir EB CMV retinitis,
Cidofovir HHV6 Pneumonitis
Hepa C
2.Amantadine 100mg OD Influenza A,B Influenza A-H1N1
Rimantadine 200mg OD H1N1,H1N2,
(penetration of cell) H1N3
3.Foscanet CMV,VZV CMV retinitis in HIV p/t
(DNA &RNAsyn:) HSV(Aciclovir
20mg/kg iv over 30’ resist)
72. 4.Immunomodulator Hepatitis B &C Chronic hepatitis B
Interferon α HPV &C
(inhibit the transcription) CGD
Plavizumab RSV RSV Bronchiolitis
5.Ribavarin RSV RSV Bronchiolitis
(aerosol-20mg/ml 12- Pn’ia
18hrly)
(oral5-50mg)
6.Neuraminidase Influenza A & B Influenza A & B
Inhibitors
(release of virus)
Zanamivir/Oseltamivir
73. 7.Antiretroviral HIV Side effects
NRTI-competative inhibit:
activated i/c by A,neutropenia,myopathy
phosphorylation
Zidovudine(2mg/kg) Pancreatitis,Periph neuro,D
Didanosine(ddI ) Peri neuro,pancreatitis,rash
Dideoxycytidine(ddC) Peri neuro,A,Lipoatrophy
Stavudine(d4T) Headche,N,abdo pain
Lamivudine(3TC) Hepa B
Adefovir
NNRTI-inhibit viral HIV
replication by direct binding
to RT
Nevaripine Rash,Steven syn,Hepatitis
120mg/m2 daily oral
74. Protease Inhibitors
-Interfere with post-
translational
processing of HIV Asymptomatic hyper bili-
precursor proteins rubinemia,GI disturbance
Eg.Ritonavir Skin,hair changes
Indinavir
Dose-500mg/m2 8H
oral
81. Management in babies born to infected
mothers
Scenarios Therapy
- HIV mother on HAART Zidovudine
- HIV mother started on zidovudine at 14-28 2mg/kg/dose QIDx 6wks
weeks gestation OR
4mg/kg/does BDx6 wks
-HIV mother at delivery with inadequate Single dose
prophylaxis (<4 weeks) Nevirapine
+
-Infant born to HIV mother without prophylxis
Zidovudine
2mg/kg/dose QID
6 weeks
OR
4mg/kg/does BD 6 weeks
82. Antifungal agents
based on route of administration
1.Systemic
For deep fungal infection Amphotericin B (I.V)
(oral/parenteral) Flucytosine (oral)
Imidazoles and Triazoles
-Ketoconazole, Itraconazole
-Fluconazole
For superficial fungal infections Griseofulvin (Oral)
2.Topical antifungal agents Clotrimazole (CANESTEN)
- Miconazole
-Econazole
-Ketoconazole
-Nystatin (MYCOSTATIN)
Miscellaneous MYCODERM
83. Drug Dose & Rx Side effects
Preparation
Ampho.B IV 1.5 mg/kg/d Local &systemic- Hypersensitivity
(fungistatic/fungicid Intrathecal Meningitis,Endocardit Nephrotoxic
al) Oral 100mg 6h is due to Liver impairment
Cream,ointment Cryptococcus Anaemia,Hypo-k
Local installation Coccidioides
Histoplasma
Candida,
Blastomyces
Aspergillus
Griseofulvin 5-7mg/kg oral Broad spectrum Photosensitivity
(fungiststic) Topical Microsporum,Epider Porphyria
mophyton,
Trichophyton Headache
(Dermatophytosis) Hepatitis
Superficial
ringworm
infestation
(Tineacaptis,Tinea
corporis,Tinea pedis)
85. Summary
• Ampho B –drug of choice except candida
• Griseofulvin –drug of choice for dermatophytes except
aspergillus
• Fluconazole ,Miconazole _ for candida/dermatophytes
• Nystatin _ for candida
87. Blood schizontocides Alleviate symptoms-a/c attack Photosensitivity,n,v,reti-
CQ Oral 10mg/kg x 3d nal damage
Quinine Oral 8.3mg/kg x7-10 d Tinnitus,Hglycemia
Iv 20mg/kgx4h,8.3mg/kg 8H Hypotension
Mefloquine 15mg/kg stat,10mg/kg a/f 6-8hr (cinchonism)
(Prophylaxis- 5mg/kg wkly) Postural Hypotension
Cardiac conduct defect
Artesunate Oral 5mg/kg D1,2.5mg/kg D2- Relatively safe
D3
IV,IM 2mg/kg then 1 mg/kg 6H
Artemether IM 3.2mg/kg stat 1.6 mg/kg
daily
Sporontocides
Pyrimethamine
Prophylaxis
Primaguine
Proguanil
88. Tissue schizointocides To prevent parasites
becoming established in the
Liver
Pyrimethamine 25mg tab*
0.3mg/kg daily X14 d CI –Pregnancy
Primaquine
3.5mg/kg oral H’lysis in G6PDdef,BM˅,
Proguanil
alopecia
Hypnozoiticides To prevent relaspe
Primaquine
Gametocides
Primaquine
0.7mg/kg od
89. Mgt of Pl.falciparum(Paed:protocol)
• Uncomplicated • Complicated
1st line- 1st line
Artesunate odx3D IV Artesunate bdod
Mefloquine od 2nd line
Alternate: IV Quinine oral
Artemether/lumefantrine Doxycycline/Clindamycin
2nd line
Qunine
Clindamycin
90. Antihelminthics
Drugs Rx advantage Mode of Action Adverse Effects
Mebendazole Trichuriasis Broad spectrum, inhibit Worm migration
50-100mg BDx Enterobiasis microtubules, glucose (rare)
3D Ascariasis absorption
immobilization death
Albendazole Trichuriasis
200-400mg single Enterebiasis
Ascariasis
Hookworm
Pyrantel pamoate Trichuriasis Depolarization of the Mild abdominal pain
10-11mg/kg OD Ascariasis neuromuscular
Repeat in D14 Enterobiasis (Neuromuscular blocking
agent)
Levamizole Ascariasis Immunostimulants Abdominal pain
3mg/kg Enterobiasis Paralysis of the muscle of
the worm – expelled by
Repeat in 1 wk Hookworm peristalsis
Ivermectin Hookworm, filariasis, Membrane Abdominal
0.15-0.4mg/kg strongyloides hyperpolarization ; distension ,
paralysis wheeze, TOC
Thiabendazole Hookworm
200-400mg OD
91. • References:
- Paed:Protocol (2nd edition)
- Nelson Text Book (19th edition)
- Basic and Clinical Pharmacology(11th edition)
- Basic Medical Science(Easterbrook-3rd edition)
Hinweis der Redaktion
All cocci are G+ve except Neisseria,All bacilli are G-ve except B,C,C,L.All are anaerobes except Clostridia &BacteroidsRicket and Chlamy are obligate i/c parasites.chlamy- not seen under light microscope and can’t produce ATP
(increasing permeability leading to leakage of intracellular compounds)