Antibiotics and Synthetic

antimicrobial agents:
their properties and uses
 Antibacterial antibiotics 70
Antifungals 20
Antiviral agents 40

NOTES
Prescription of drugs vary from inpts to
outpts because of problem in administration
Outpatients maybe prescribed with
parenteral antibiotics because of ease of
administration
Antibacterial antibiotics
B-lactams Aminoglycosides
Tetracyclines Glycopeptides
Macrolides Antitubercular
Sulphonamides antibiotics
Quinolones MRSA
Other antibiotics
Beta lactam antibiotics

Penicillins
Cephalosporins
Carbapenems
Monobactams
Beta lactamase
inhibitors
Clavulanic Acid,
Sulbactam,
Tazobactam
 NOTES
- Same mechanism of action
- All possess b-lactam ring as an
integral part of structure
- Differ in characteristics
Types of Penicillins

Naturally occuring
- produced by fermentation of moulds
- Penicillum notatum, P. chrysogenum
ex. PenG(benzylpenicillin)
PenV(phenoxymethylpenicillin)
Semisynthetic
- penicillin nucleus isolation
6-aminopenicillamic acid (6-APA)
 NOTES
Synthetic phenylacetic acid +
growth of Penicillum mould
- acylation of 6-APA some
organism produce enzymes(penicillin
amylase or B-lactamase)
Penicillins
Active against g(+) bacteria;
g(-) : H.influenzae; E.coli; Salmonella;
shigella; Proteus
Psedomonas aeruginosa
B-lactamase sensitive
Penicillins
Penicillin G (benzylpenicillin), Penicillin V
(phenoxymethyl penicillin) for g(+)

Broad spectrum penicillins amovicillin, ampicillin

(bacampicillin, pivampicillin, talampicillin) for g(-)

Antipseudomonas penicillins carbenicillin, ticarcillin,

piperacillin

Beta lactamase meticillin, flucloxacillin, oxacillin,

cloxacillin
 NOTES

G(-) H.influenzae; E.coli; Salmonella;

shigella;Proteus
Psedomonas also g(-) organism not
part of broad spectrum
bacampicillin, pivampicillin,
talampicillin remedy for poor oral
absorption of ampicillin
Penicillin adverse Rx
Diarrhoea
Hypersensitivity
Loss of normal flora
Seizures if with renal dx
(Na,K accumulation)
NOTES
G(-) H.influenzae; E.coli; Salmonella; shigella;Proteus

Psedomonas also g(-) organism not part of broad

spectrum
bacampicillin, pivampicillin, talampicillin remedy for poor
oral absorption of ampicillin
Cephalosporins
1st generation
- originally as alternative for staph infections
-moderate antimicrobial activity and resistance to
staphylococcal infection
- but not g(-), B-lactamase

2nd generation
- good resistance to staph & g(-) B-lactamase
- improved potency toward H. influenzae, enterobacteria
Cephalosporins increase activity to G(-) species; and
increased resistance to B-lactamase
Cephalosporins
3rd generation
- higher activity toward g(-)
- little value on staph treatment
- used in combination w/gentamycin or aminoglycosides
for synergy

4th generation
- remedy spread of strains producing extended-
spectrum B-lactamases
- good enzyme resistance
- Pseudomonas, enterics, Staph, S. pneumoniae,
Hemophilus, Neisseria
Cephalosporins
1st generation
cefadroxil, cefazolin, cephalexin,
cephaloridine, cephalothin, cephapirin,
cephradine

2nd generation
- Cefaclor, cefamandole, cefonicid, cefuroxime,
cefprozil, loracarbef, ceforanide, cephamycins
cefoxitin, cefmetazole, cefotetan
cephalosporins
3rd generation
- Cefoperazone, cefotaxime, ceftazidime,
ceftizoxime, ceftriaxone, cefixime,
cefpodoxime proxetil, cefditoren pivoxil,
ceftibute, moxalactam
4th generation
- Cefepime, cefpirome
Other beta lactam drugs - developed
resistance to penicillin and cephalosporins
Carbapenems (confused with olivanic acid,
thienamycin as synonyms)
- penicillin and cephalosporin derivatives
- generic term for group w/c includes olivanic acids
and
thienamycins

Imipenem (N-formimidoyl derivative of thienamycin)

has broad spectrum antimicrobial activity and
good resistance to almost all B-lactamases;
- in-vitro stable
- with cilastatin renal dx
Other beta lactam drugs
Monobactams
- good resistance to B-lactamases,
active against g(-)
- inactive against S. aureus, g(+), anaerobes
- limited for hospital use; formulated as
injectable
- Tx P. aeruginosa in synergy w/
(aminoglycosides,
gentamicin, tobramycin)
B-lactamase inhibitors
Clavulanic acid isolated from
Streptomyces clavuligerus
Co-amoxiclav = amoxicillin + clavulanic
acid
- for S.aureus, E.coli, H.influenzae,
Klebsiella sp
Penicillamic acids:
- ampicillin + sulbactam
- piperacillin + tazobactam
Hypersensitivity

Skin allergies - ampicillin

Anaphylactic reactions - benzylpenicillin
Tetracyclines

Exhibit bactericidal activity in the lab,

bacteristatic activity in the body
- inhibits ribosomal function
Alternative to macrolides and
B-lactams(allergy)

Tetracyclines- increasing bacterial

resistance
Tetracyclines
Important antibiotic for:
- Clamydia infection trachoma
- rickettsia typhus
- spirochete lyme disease
- brucellosis, bubonic plague
Active against g(+) bacteria, g(-) bacteria
Tx for MRSA
Tx for acne, genital infections, H.pylori
Prophylaxis Plasmodium falciparum malaria
Tetracyclines
Oral products available in the market
Administered 4x a day coz absorption is
inhibited by food, antacids, milk
More improved 2x a day
Once a day

Dont administer w/ milk, antacids or

FeSO4
Tetracyclines
Nausea, vomitting
Not given to <12yrs or late pregnancy coz
tetracycline chelates with calcium
Accumulation of tetracyclines in kidneys
contraindication with kidney functions
- except doxycycline, micocycline
Adverse Rx: not for pregnant or child < 8 y/o,
deposition in bones, teeth, hypersensitivity,
GI, liver, renal, tissue toxicity
Tetracyclines

Tigecycline tx MRSA
Doxycycline prophylaxis for
P.falcoparum
Minocycline tetracycline resistant
S.aureus
Tetracycline
Short acting chlortetracycline,
tetracycline
Intermediate acting demeclocycline,
methacycline
Long acting doxycycline,
minocycline
Macrolides

Alternative for penicillin allergy

For respiratory, skin infection

Act by inhibiting protein synthesis in

bacteria
Extremely bitter taste
Macrolides - Erythromycin
Indication:
g(+) corynebacteria,
mycoplasma, legionella,
chlamydia, g(-) neisseria,
H.influenzae, campylobacter,
Helicobacter, ricketsias,
Mycobacterium avium(HIV)
Macrolides-Erythromycin

Poor acid stability

GI side effect

Bacteria acquire resistance easily

Macrolides

Roxithromycin

Clarithromycin

Azithromycin

telithromycin
Macrolides - Clarithromycin

Improved acid stability & oral

absorption, more expensive than
Erythromycin
Metab in liver; adjust for renal dx
Macrolides - Azithromycin
Indication: vs. Chlamydia
Antifolate drugs
Sulfonamides
Structure similar to p-aminobenzoic
acid(PABA)
MOA: reversibly blocks folic acid synthesis

Bacteriostatic: sulfonamide alone

Bactericidal: combination
Indication: g(+), g(-), nocardia, chlamydia,
rickettsia stimulated growth
Antifolate drugs - sulfonamides
Silver Sulfadiazines (burns)
Sulfadiazines (prevention of rheumatic
fever)
Dapsone Tx for leprosy (Dapsone
Diaminodiphenylsulfone)

Sulfamethoxazole
Antifolate drugs
Trimethoprim
Trimethoprim + sulphamethoxazole (co-
trimoxazole) Tx UTI, RTI
Fluoroquinolones - UTI

Co-trimoxazole Tx pneumocystis
pneumonia, toxoplasmosis, nocardiasis
Antifolate drugs
Pyrimethamine Tx toxoplasmosis,
pneumocystis pneumonia
Pyrimethamine + sulphadoxine Tx
malaria
Quinolones
Have much in common w/ cephalosporin
NA cephalothin
Both are improved(50yrs) most widely used
antibiotic
UTI Tx
All are bactericidal, inhibits bacterial enzymes
Cause tendon damage: not prescribed to
children
GI disturbance
Some quinolones lic for veterinary medicine
Quinolones
1st generation
- Absence of fluorine atom at position 6
- Designated as quinolones
- Cinoxacin, acrosoxacin, pipemidic acid

- Restricted to E.coli, Enterobacteriaceae

- 2nd, 3rd, 4th generation- termed as

fluroquinolones
Quinolones

2nd generation
- Ciprofloxacin, norfloxacin, ofloxacin,
levofloxacin

- greater affinity to E.coli, other G(-) urinary

pathogens
- wider antibacterial spectrum g(+)cocci,
P.aeruginosa
Quinolones

3rd generation
- Greater activity against S.pneumoniae
- moxifloxacin

4th generation
- Trovafloxacin
Aminoglycosides
MOA: irreversible inhibitors of protein
synthesis - binds w/ 30 S

Adverse Rx: ototoxic (auditory &

vestibular), nephrotoxic
Aminoglycosides

Streptomycin TB Tx
Neomycin topical / opthalmic
products
Aminoglycosides
Gentamicin
- used as blind therapy
-Tx bacterial endocarditis, g(-) infections

Tobramycin
- Sl. Less active than gentamicin

Amikacin synthetic derivative Kanamycin

- more stable for bacterial enzyme inactivation
Gentamycin & tobramycin naturally occuring
All three Tx P.aeruginosa Tx, cystic fibrosis pts
Glycopeptides
Vancomycin
Teicoplanin
Glycopeptide
Vancomycin
- old drug
- Tx MRSA
- restricted to: g(+), S.aureus, S.epidermidis,
streptococci, Cl.defficile, Ent.faecalis
- inhibitor of peptidoglycan synthesis

- damage to kidney, ears

- requires blood level monitoring during therapy
Large molecular size can not penetrate g(-) bacteria
Glycopeptide
Teicoplanin
- given intravenous, intramuscular
injection vs intravenous of vancomycin
- lipophilic better tissue penetration
- eliminates blood monitoring
Antitubercular antibiotics
Streptomycin TB Tx
Isoniazid(rapidly growing cells)
- combined w/ streptomycin
- combined w/ rifampicin (dormant
bacteria)
- (+) pyrizinamide(bacteria in acidic
environment) & ethambutol
TB mycobacterium; persists for a long time in
dormant state
- Tx 4-6mos, oral medication
Antitubercular antibiotics

Tx in 2 phases:
1. Initial phase 2mos
- isoniazid, rifampicin,
pyrizinamide(w/ or w/o ethambutol)
2. Continuation phase 4mos
- isoniazid, rifampicin
Antitubercular antibiotic

Second-line drugs:
- amikacin, capreomycin, cycloserine,
newer macrolides (azithromycin,
clarithromycin), moxifloxacin
Antitubercular antibiotic
Rifampicin
- antitubercular drug
- Tx nonmycobacterial infections:
staphylococci
- rifampicin + vancomycin(another
antibiotic)

Rifabutin semisynthetic refampicin

Other MRSA antibiotics and G(+)
cocci infections
MRSA methicillin resistant
staphylococcus aureus
VISA vancomycin intermediate
staphylococcus aureus
GISA glycopeptide intermediate
staphylococcus aureus
Other MRSA antibiotics and G(+)
cocci infections
1. Fixed ratio 2 streptogramin fixed
ratio combination (30:70)
dalfopristin, quinupristin
2. Linezolid
3. Daptomycin
Other MRSA antibiotics and G(+)
cocci infections
1. Fixed ratio 2 streptogramin
fixed ratio combination (30:70)
dalfopristin, quinupristin

**Tx vancomycin-resistant
Ent.faecium, multiresistant strains
staphylococci, pneumococci
Other MRSA antibiotics and G(+)
cocci infections
2. Linezolid
synthetic,
Tx MRSA, VRE & pneumococcal
infection
3. Daptomycin
destabilize bacterial cell wall
Tx skin, soft tissue G(+) infections
Tx VISA, GISA
Miscellaneous antibacerial
antibiotics
Clindamycin
- G(+) cocci(MRSA)
- oral Tx staphylococcal bone, joint
infections, acne, peritonitis, falciparum
malaria

- w/cephalosporins most firmly

associated w/pseudomembranous colitis
(Cl. Defficile)
Miscellaneous antibacerial
antibiotics
Fusidic acid
- steroid-like bactericidal antibiotic
- staphylococci
- active against penicillin-resistant strain of
S.aureus, MRSA
- combi w/ erythromycin or clindamycin

- pediatric oral suspension, cream, ointment,

tablet, injection
Miscellaneous antibacterial
antibiotics
Mupirocin
- Antibiotic against staphylociccus,
streptococcus
- Topical Tx S.aureus infection (MRSA)
from nose
- More effective than chlorhexidine or
fusidic acid
Miscellaneous antibacterial
antibiotics
Colistin
- Tx Serratia marcescens, proteus
sp., g(+) organisms
- restricted to P. aeruginosa lung
infection as intravenous injection,
nebulized
- Tx burns w/acinetobacter sp
infection
Miscellaneous antibacterial
antibiotics
Chloramphenicol
- Tx rickettsias
- restricted to H.influenzae (life
threatening)
- opthalmic infections
- Tx vet med
Miscellaneous antibiotic

Metronidazole

- vaginitis (T.vaginalis),
amoebiasis, giardiasis

Nitrofurantoin Tx cystitis
Antifungal antibiotics
Azoles
2 subgroups:
1. Imidazoles

2. triazoles

Topical products
For superficial dermatophyte infection
Pityriasis infection(flaky skin, dandruff)
C.albicans
Azoles
Imidazoles
- older group, large group
- against bacteria-metronidazole
- protozoa timidazole
- helminths mebendazole
- fungi clotrimazole, miconazole,
ketokonazole, econazole, sulconazole,
tioconazole
Miconazole oral tx for intestinal fungal
infections
 Azoles
Triazoles
-fluconazole*-Tx dermatophytes,
pityriasis,candida infection
-itraconazole* - alternative for
amphoterecin
-posaconazole for severe infections,
-voriconazole other antibiotics have failed
*Widely used
*itraconazole alternative for amphoterecin (aspergillus
infection)
- associated w/ liver toxicity
Polyenes
Amphoterecin B
Nystatin
Polyenes
Amphoterecin B
- fungal pathogens systemic mycoses
- more toxic but more effective than
itraconazole
-poorly absorbed in GIT- intravenous
injection
Polyenes
Nystatin
- orally transmitted, or by cream
- Tx C.albicans intestine, mouth
Echinocandins
Funjicidal - Aspergillus sp, Candida sp.
Pneumocystis jirovecii(P.carinii)

Caspofungin invasive aspergillosis,

candidiasis
Caspofungin unresponsive to
amphotericin B, or itraconazole
Anidulafungin & Micafungin invasive
candidiasis
Other antifungal agents
Flucytocin yeast,candida, cryptococcus, torulopsis;
- combined w/fluconazole, amphoterecin
Terbinafine Tx fungal nail infection
Griseofulvin dermatophyte: hair, skin, nail
Tolnaftate Tx, prophylaxis for tinea
Amorolfine cream or nail lacquer tinea
Antiviral agents
HIV
Antiretroviral drugs
problems:
Virus becoming resistant
Drug toxicity
Patient adherence to medication
HAART highly active antiretroviral
therapy
HIV
Tenofovir, emtricitabine, efavirenz
Abacavir, lamivudine, efavirenz
Protease inhibitor: retinovir, lopinavir
1st line Tx:
Regimens + protease inhibitor
Herpes and CMV infection
HSV-1 (cold sores face, lips)
HSV-2 (genital herpes)
Varicella zoster virus(chickenpox,
shingles)
Epstein-Barr virus(IM-glandular fever)
CMV(retinitis)
Herpes infection
Inosine pranobex
Idoxuridine
Aciclovir injection, tablet*, cream*
Valaciclovir (prodrug)*
Peniciclovir

All 4 used to Tx herpes simplex, varicella, zoster

infection
Aciclovir * - administered 4-5x a day to be effective
Valaciclovir - * administered 2-3x a day
CMV infection
Ganciclovir
Valganciclovir
Cidofovir herpesvirus, AIDS pts w/CMV
Foscarnet
Viral Hepatitis
HBV
Lamivudine
Tenofovir
Adefovirdipivoxil
Entecavir
Telbivudine

6-mos treatment or more

Viral Hepatitis
HCV
Interferon-a + ribavirin
Peginterferon a2a + ribavirin (more effective)
Ribavirin alone not effective
Influenza virus
Influenza virus A, B, C (C mild infection)

Amantadine influenza A
2 neuramidase inhibitors:
Oseltamivir oral administration
Zanamivir - inhalation
Respiratory Syncytial virus
RSV related to measles, mumps

Ribavirin
Palivizumab monoclonal antibody