ANTIBIOTICS AND SYNTHETIC ANTIMICROBIAL a.

Penicillins
AGENTS: THEIR PROPERTIES AND USES  Active against g(+) bacteria
 G(-): H. influenza, E.coli, Salmonella,
Antibacterial antibiotics – 70 Shigella, Proteus
Antifungals – 20  Pseudomonas Aeruginosa – also g(-)
Antiviral agents – 40 organism not part of broad spectrum
 B-lactamase sensitive
o Prescription of drugs vary from
inpatients to outpatients because of Types:
problem in administration 1. Naturally occurring
o Outpatients maybe prescribed with - Produced by fermentation of
parenteral antibiotics because of ease moulds
of administration - Penicillum notatum, P.
chyrsogenum
Antibacterial Antibiotics Ex. PenG (benzylpenicillin), PenV
1) B-lactams (phenoxymethylpenicillin)
2) Tetracyclines
3) Macrolides 2. Semisynthetic
4) Sulphonamides - Penicillin nucleus isolation
5) Quinolones - 6-aminopenicillamic acid (6-
6) Aminoglycosides APA)
7) Glycopeptides
8) Antitubercular antibiotics 3. Synthetic
9) MRSA - Phenylacetic acid + growth of
10) Other antibiotics Penicillum mould
- Acylation of 6-APA
-- - Some organism produce
enzymes (penicillin amylase or
1) Beta-lactams B-lactamase)
 Same mechanism of action
 All possess B-lactam ring as an integral  Penicillin G (benzylpenicillin), Penicillin
part of structure V (phenoxymethyl penicillin) – for g(+)
 Differ in characteristics  Broad spectrum penicillins – amovicillin,
ampicillin – for g(-)
a. Penicillins  Bacampicillin, pivampicillin, talampicillin
b. Cephalosporins – for poor oral absorption of ampicillin
c. Carbapenems  Antipseudomonas penicillins –
d. Monobactams carbenicillin, ticarcillin, piperacillin
e. Beta lactamase inhibitors  Beta lactamase – meticillin,
- Clavulanic acid flucloxacillin, oxacillin, cloxacillin
- Sulbactam
- Tazobactam Adverse Rx:
 Diarrhea
 Hypersensitivity
 Loss of normal flora – higher dose of
penicillin remain in the colon
 Seizures – if with renal diagnosis
o Accumulation of Na, K may arise with
high dose injections of patients with
poor kidney function

b. Cephalosporins
 Increase activity to g(-) species
 Increased resistance to B-
lactamase

 1st generation
~~
 - originally as alternative for staph f. Monobactam
infections  good resistance to B-lactamases,
- moderate antimicrobial activity and active against g(-)
resistance to staphylococcal infection  inactive against S. aureus, g(+),
- but not g(-), B-lactamase anaerobes
 limited for hospital use; formulated as
Ex: cefadroxil, cefazolin, cephalexin, injectable
cephaloridine, cephalothin, cephapirin,  Tx P. aeruginosa in synergy w/
cephradine (aminoglycosides, gentamicin,
tobramycin)
 2nd generation
- good resistance to staph & g(-) B- B-lactamase inhibitors
lactamase a. Co-amoxiclav
- improved potency toward H. - amoxicillin + clavulanic acid
influenzae, enterobacteria - for S.aureus, E.coli,
H.influenzae, Klebsiella sp
Ex: Cefaclor, cefamandole, cefonicid, b. Penicillamic acids
cefuroxime, cefprozil, loracarbef, ceforanide, - ampicillin + sulbactam
cephamycins – cefoxitin, cefmetazole, - piperacillin + tazobactam
cefotetan
 Clavulanic acid – isolated from
 3rd generation Streptomyces clavuligerus
- higher activity toward g(-)
- little value on staph treatment Hypersensitivity
- used in combination w/gentamycin or  Skin allergies – amipicillin
aminoglycosides for synergy  Anaphylactic rxns – benzylpenicillin

Ex: Cefoperazone, cefotaxime, ceftazidime, --

ceftizoxime, ceftriaxone, cefixime,
cefpodoxime proxetil, cefditoren pivoxil, 2) Tetracyclines
ceftibute, moxalactam  Exhibit bactericidal activity in the
lab, bacteriostatic activity in the
 4th generation body
- remedy spread of strains producing  Inhibits ribosomal function
extended-spectrum B-lactamases  Alternative to macrolides and b-
- good enzyme resistance lactams (allergy)
- Pseudomonas, enterics, Staph, S.  Increases bacterial resistance
pneumoniae, Hemophilus, Neisseria  Important antibiotic for:
- Clamydia infection – trachoma
Ex: Cefepime, cefpirome - rickettsia – typhus
c. Carbapenems - spirochete – lyme disease
 Penicillin and Cephalosporin derivatives - brucellosis, bubonic plague
 Generic term for group w/c includes  Active against g(+) bacteria, g(-)
olivanic acids and thienamycins bacteria
 Confused with olivanic acids,  Tx for MRSA
thienamycin as synonyms  Tx for acne, genital infections,
H.pylori
d. Imipenem  Prophylaxis Plasmodium falciparum
 Has broad spectrum antimicrobial malaria
activity and good resistance to almost  Oral products available in the
all B-lactamases market
 In-vitro stable  Administered 4x a day – coz
 With cilastatin – renal diagnosis absorption is inhibited by food,
 N-formimdidoyl derivative of antacids, milk
thienamycin  More improved – 2x a day
 Once a day
e. Meropenem  Don’t administer w/ milk, antacids,
 w/o cilastatin for renal diagnosis or FeSO4
  Nausea, vomitting - Improved acid stability & oral
 Not given to <12yrs or late absorption, more expensive
pregnancy – coz tetracycline than Erythromycin
chelates with calcium - Metabolism in liver; adjust for
 Accumulation of tetracyclines in renal dx
kidneys – contraindication with
kidney functions (except c. Azithromycin
doxycycline, micocycline) - Indication: vs. Chlamydia
Adverse Rx:
 Not for pregnant or child < 8 y/o --
 Deposition in bones, teeth,
hypersensitivity, GI, liver, renal [Antifolate drugs]
 Tissue toxicity 3) Sulfonamides
 Structure similar to p-aminobenzoic
 Tigecycline – tx MRSA acid (PABA)
 Doxycycline – prophylaxis for o P-aminobenzoic acid (PABA) –
P.falcoparum basis of antibacterial activity of
 Minocycline – tetracycline resistant sulfonamide
S.aureus  MOA: reversibly blocks folic acid
synthesis
o Short acting – chlortetracycline,  Bacteriostatic: sulfonamide alone
tetracycline  Bactericidal: combination
o Intermediate acting – demeclocycline,  Indication: g(+), g(-), nocardia,
methacycline chlamydia, rickettsia
o Long acting – doxycycline, minocycline
 Silver Sulfadiazines (burns)
--  Sulfadiazines (prevention of rheumatic
fever)
3) Macrolides  Dapsone – Tx for lepros
 Alternative for penicillin allergy (Diaminodiphenylsulfone)
 For respiratory, skin infection  Sulfamethoxazole
 Act by inhibiting protein synthesis in
bacteria ~ Trimethoprim
 Extremely bitter taste  Trimethoprim + sulphamethoxazole (co-
trimoxazole) – Tx UTI, RTI
a. Erythromycin  Co-trimoxazole – Tx pneumocystis
b. Roxithromycin pneumonia, toxoplasmosis, nocardiasis
c. Clarithromycin  UTI – fluoroquinolones
d. Azithromycin
e. Telithromycin ~ Pyrimethamine
 Tx toxoplasmosis, pnyemocystis
~~ pneumonia

a. Erythromycin ~ Pyrimethamine + sulphadoxine

- Indication: g(+) corynebacteria,  Tx malaria
mycoplasma, legionella,
chlamydia --
- g(-) neisseria, H.influenzae,
campylobacter, Helicobacter, 4) Quinolones
ricketsias, Mycobacterium  Have much in common w/
avium (HIV) cephalosporin
- Poor acid stability  Both are improved(50yrs) most widely
- GI side effect used antibiotic
- Bacteria acquire resistance  UTI Tx
easily  All are bactericidal, inhibits bacterial
enzymes
b. Clarithromycin  Cause tendon damage: not prescribed
to children
 GI disturbance o All three – tx P.aeruginosa,
 Some quinolones – lic for veterinary cyctis fibrosis
medicine
--
 st
1 generation
- Absence of fluorine atom 6) Glycopeptides
- Designated as “quinolones” a. Vancomycin
- Cinoxacin, acrosoxacin, - old drug
pipemidic acid - Tx MRSA
- Nalidixic acid , cephalothin - restricted to: g(+), S.aureus,
- Restricted to E.coli, S.epidermidis, streptococci,
Enterobacteriacae Cl.defficile, Ent.faecalis
- inhibitor of peptidoglycan
 2nd generation synthesis
- Fluoroquinolones - damage to kidney, ears
- Ciprofloxacin, norfloxacin, - requires blood level monitoring
ofloxacin, levofloxacin during therapy
- greater affinity to E.coli, other - Large molecular size – cannot
G(-) urinary pathogens penetrate g(-) bacteria
- wider antibacterial spectrum
g(+)cocci, P.aeruginosa b. Teicoplanin
- given intravenous,
 3rd generation intramuscular injection vs
- Fluoroquinolones intravenous of vancomycin
- Greater activity against - lipophilic – better tissue
S.pneumoniae penetration
- Moxifloxacin - eliminates blood monitoring

 4th generation --
- Fluoroquinolones
- Trovafloxacin 7) Antituberular antibiotics
a. Streptomycin
~~ - TB tx
b. Isoniazid
5) Aminoglycosides - Combined w/ streotomycin
 MOA: irreversible inhibitors of - Combined w/ rifampicin
protein synthesis - binds w/ 30 (dormant bacteria)
S c. Pyrizinamide
 Adverse Rx: ototoxic (auditory & - Bacteria in acidic environment
vestibular), nephrotoxic & ethambutol
 Damage to kidneys, 8th cranial
nerve (ear)  Tuberculosis
 Streptomycin – TB Tx - Mycobacterium
 Neomycin – topical / opthalmic - Persists for a long time in
products dormant state
- Tx 4-6 mos, oral medication
 Gentamicin
- naturally occurring Tx in 2 phases:
- used as “blind therapy” 1. Initial phase
-Tx bacterial endocarditis, g(-) infections - 2 months
 Tobramycin - RIPE (w/ or w/o ethambutol)
- Natural occurring 2. Continuation phase
- Sl. less active than gentamicin - 4 months
 Amikacin - RI
- synthetic derivative of
Kanamycin Second-line drugs
- more stable for bacterial 1. Amikacin
enzyme inactivation 2. Capreomycin
 3. Cycloserine - steroid-like bactericidal
4. Newer macrolides (azithromycin, antibiotic
clarithromycin) - staphylococci
5. Moxifloxacin - active against penicillin-
resistant strain of S.aureus,
a. Rifampicin MRSA
- Antitubercular drug - combi w/ erythromycin or
- Tx nonmycobacterial infections: clindamycin
staphylococci - pediatric oral suspension,
- Rifampicin + vancomycin cream, ointment, tablet,
(another antibiotic) injection
b. Rifabutin
- Semisynthetic rifampicin 3. Mupirocin
- Prophylaxis – M. avium - Antibiotic against
staphylociccus, streptococcus
-- - Topical Tx S.aureus infection
(MRSA) from nose
8) Other MRSA antibiotics and G(+) cocci - More effective than
infection chlorhexidine or fusidic acid

a. MRSA – methicillin resistant 4. Colistin

staphylococcus aureus - Tx Serratia marcescens, proteus
b. VISA – vancomycin intermediate sp., g(+) organisms
staphylococcus aureus - restricted to P. aeruginosa lung
c. GISA – glycopeptide intermediate infection as intravenous
staphylococcus aureus injection, nebulized
- Tx burns w/acinetobacter sp
1. Fixed ratio 2 streptogramin – fixed ratio infection
combination (30:70)
dalfopristin, quinupristin 5. Chloramphenicol
- Tx vancomycin-resistant Ent. - Tx rickettsias
Faceium, multiresistant strains - restricted to H.influenzae (life
staphylococci, pneumococci threatening)
2. Linezolid - opthalmic infections
- Synthetic - Tx vet med
- Tx MRSA, VRE, pneumococcal
infection 6. Metronidazole
3. Daptomycin - Vaginitis (T. vaginalis),
- Destabilize bacterial cell wall amoebiasis, giardiasis
- Tx skin, soft tissue G(+)
infections 7. Nitrofurantoin
- Tx VISA, GISA - Tx cystitis

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Miscellaneous antibacterial antibiotics Antifungal antibiotics

1. Clindamycin 1. Azoles
- G(+) cocci(MRSA)  Topical products
- oral Tx staphylococcal bone,  For superficial dermatophyte
joint infections, acne, infection
peritonitis, falciparum malaria  Pityriasis infection(flaky skin,
- w/cephalosporins – most firmly dandruff)
associated  C.albicans
w/pseudomembranous colitis
(Cl. Deficile) 2 subgroups:
a. Imidazoles
2. Fusidic acid  older group, large group
  against bacteria-
metronidazole Other antifungal agents
 protozoa – timidazole 1. Flucytocin – yeast,candida,
 helminths – cryptococcus, torulopsis; combined
mebendazole w/fluconazole, amphoterecin
 fungi – clotrimazole, 2. Terbinafine – Tx fungal nail infection
miconazole, 3. Griseofulvin – dermatophyte: hair, skin,
ketokonazole, nail
econazole, sulconazole, 4. Tolnaftate – Tx, prophylaxis for tinea
tioconazole 5. Amorolfine – cream or nail lacquer tinea
 Miconazole – oral tx
for intestinal fungal --
infections
Antiviral agents
b. Triazoles 1. HIV
 fluconazole*-Tx dermatophytes, - Antiretroviral drugs
pityriasis,candida infection - problems:
 itraconazole* - alternative for o Virus becoming
amphotericin (aspergillus resistant
infection), associated w/ liver o Drug toxicity
toxicity o Patient adherence to
 posaconazole – for severe medication
infections - HAART – highly active
 voriconazole other antiretroviral
antibiotics have failed therapy

 *Widely used  Tenofovir, emtricitabine, efavirenz

 Abacavir, lamivudine, efavirenz
--  Protease inhibitor: retinovir, lopinavir

Polyenes  1st line Tx:

1. Amphoterecin B  Regimens + protease inhibitor
 fungal pathogens – systemic
mycoses --
 more toxic but more effective
than itraconazole Herpes and CMV infection
 poorly absorbed in GIT- 1. HSV-1 (cold sores face, lips)
intravenous injection 2. HSV-2 (genital herpes)
2. Nystatin 3. Varicella zoster virus(chickenpox,
 orally transmitted, or by cream shingles)
 Tx C.albicans – intestine, mouth 4. Epstein-Barr virus(IM-glandular fever)
5. CMV(retinitis)
--
--
Echinocandins
1. Funjicidal Herpes infection
- Aspergillus sp. 1. Inosine pranobex
- Candida sp. 2. Idoxuridine
- Pneumocystis jirovecii (P.carinii) 3. Aciclovir – injection, tablet*, cream*
2. Caspofungin 4. Valaciclovir (prodrug)*
- Invasive aspergillosis, 5. peniciclovir
candidiasis
- Unresponsive toamphotericin B,  All 4 – used to Tx herpes simplex,
or itraconazole varicella, zoster infection
3. Anidulafungin & micafungin  Aciclovir * - administered 4-5x a day to
- Invasive candidiasis be effective
 Valaciclovir - * administered 2-3x a day
-- --
 CMV infection
1. Ganciclovir
2. Ganciclovir
3. Valganciclovir
4. Cidofovir – herpesvirus, AIDS pts
w/CMV
5. Foscarnet

--

Viral Hepatitis
1. HBV
 Lamivudine
 Tenofovir
 Adefovirdipivoxil
 Entecavir
 Telbivudine
 6-mos treatment or more
2. HCV
Interferon-a + ribavirin
Peginterferon –a2a + ribavirin
(more effective)
 Ribavirin alone – not effective
--

Influenza virus
 Influenza virus A, B, C
 Amantadine – influenza A
 2 neuramidase inhibitors:
 Oseltamivir – oral administration
 Zanamivir - inhalation

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Respiratory Syncytial virus

 RSV – related to measles, mumps
 Ribavirin
 Palivizumab – monoclonal antibody