antimicrobial

1. Antimicrobial Drug

2. PENICILLINS
• Penicillin was the first antibiotic to be used clinically in 1941.
• The penicillin nucleus consists of fused thiazolidine and β-lactam rings
to which side chains are attached through an amide linkage.
• Sources: It was originally obtained from the fungus Penicillium
notatum.
• Mechanism of action:All β-lactam antibiotics interfere with the
synthesis of bacterial cell wall

3. Classification of Penicillin
1. Natural penicillin: PENICILLIN-G (BENZYL PENICILLIN)
2. SEMISYNTHETIC PENICILLINS:
1. Acid-resistant alternative to penicillin G
Phenoxymethyl penicillin (Penicillin V).
2. Penicillinase-resistant penicillins
Methicillin, Cloxacillin, Dicloxacillin.
3. Extended spectrum penicillins
(a) Aminopenicillins: Ampicillin, Bacampicillin, Amoxicillin.
(b) Carboxypenicillins: Carbenicillin.
(c) Ureidopenicillins: Piperacillin, Mezlocillin

4. PENICILLIN-G (BENZYL PENICILLIN)
It is a narrow spectrum antibiotic; activity is limited primarily to gram-
positive bacteria, few gram negative ones and anaerobes.
Pharmacokinetics:
Penicillin G is acid labile, therefore destroyed by gastric acid. As such, less
than 1/3rd of an oral dose is absorbed in the active form. Absorption of sod.
PnG from i.m. site is rapid and complete; peak plasma level is attained in 30
min. The pharmacokinetics of PnG is dominated by very rapid renal
excretion; about 10% by glomerular filtration and the rest by tubular
secretion.
Adverse effects:
Local irritancy and direct toxicity
Hypersensitivity

5. Indication
• Streptococcal infections
• Pneumococcal infections
• Meningococcal infections
• Gonorrhoea
• Syphilis
• Diphtheria
Contraindication:
It is contraindicated in a patients who have a previous history of severe
allergic reactions or penicillin and its derivatives.
Penicillin is also contraindicated in patients who have had Stevens-Johnson
syndrome after administering penicillin or a penicillin derivative.

6. CEPHALOSPORINS
• These are a group of semisynthetic antibiotics obtained from a fungus
Cephalosporium. They are chemically related to penicillins; the
nucleus consists of a β-lactam ring fused to a dihydrothiazine ring.
• All cephalosporins are bactericidal and have the same mechanism of
action as penicillin.

8. Pharmacokinetics
 Rout of administration:
 Oral
 Parenteral
 Distribution
 Body fluid
 Joint fluid
 Pleural fluid
 CNS
 Elimination
 Unchanged in urine
 Renal tubules
 Plasma Half-life: 1-4 hours mostly

9. Adverse Drug Reaction
 Allergic reaction
 Anaphaylaxis
 Serum sickness
 Urticaria
 Skin rash
 Haemolytic anaemia etc..
 GIT upset
 Nausia
 Vomiting
 Diarrhoea
 Nephrotoxicity:
 Interstitial Nephritis
 Renal Tubular necrosis
 Others:
 Disulfiram-like reaction
 Local irritation after I/M injection
 Thromboflavitis after repeated I/V
 Bleeding tendency
 Eosinophilia and thrombocytosis
 Defect of newborn babies
 Pharyngitis ( Throat infection)
 Stillbirth or Miscarriage

10. Indication
• UTI
• Infection of gut
• Respiratory tract infection
• Boils, abscess
• Prophylaxis in surgery
• Biliary sepsis
• Person allergic to penicillin
• Meningitis
• Gonorrhoea
• Infected burns

11. Contraindication
 These drugs are contraindicated in patient with known
hypersensitivity to cephalosporin & penicillin
• .
Renal failure
Hepatic impairment
Rheumatic fever
Lactating patient and anaerobic infections.
Pregnancy & Breastfeeding

12. Sulfonamides
⚫AKA “sulfadrugs”
⚫Effectiveagainsta broad rangeof microorganisms
⚫Block specific step in biosynthetic pathwayof folic
acid
⚫Interferewith PABAand folicacid formation, thereby
destroying bacteria

13. Sulfonamides

16. Pharmacokinetics
• A – Rapidly and well absorbed orally
• D - Widely distributed in the body
- Crosses BBB and placenta
- Accumulates in prostatic fluid
- Extent of plasma protein binding differs  Longer acting agents are highly protein
bound
• M – Acetylation in the Liver  acetylated metabolites are inactive
• E – Kidney by glomerular filtration

17. Indication
• UTI
• Ulcerative colitis
• Respiratory tract infections
• Burns and skin diseases
• Meningococcal meningitis
Contraindication:
The sulphonamides are contraindicated in patients with a history of
sulpha hypersensitivity and advance kidney disease
Adverse effects:
⚫Rash
⚫Nausea
⚫Drug fever
⚫Vomiting
⚫Jaundice
⚫Blood complications
⚫Kidneydamage

18. • Sulfamethoxazole + Trimethoprim
• This combination is BACTERICIDAL
(Both drugs are bacteriostatic when given alone)
Cotrimoxazole

19. Trimethoprim vs. Sulfamethoxazole
(Cotrimoxazole)
TRIMETHOPRIM SULFAMETHOXAZOLE
• Diaminopyrimadine related to antimalarial drug • Intermediate acting PABAstructural analogue
PYRIMETHAMINE
• MOA: Inhibits bacterial dihydrofolate • MOA: Inhibits folate synthase
reductase (DHFRase)
• Bacteriostatic • Bacteriostatic
Combination is BACTERICIDAL against many organisms
• Pharmacokinetics:
A – More rapidly absorbed
D – 40% plasma protein bound
M – Partly metabolized in Liver
E – Excreted in urine
• Pharmacokinetics:
A – Rapidly absorbed
D – 65% plasma protein bound
M – Acetylation in Liver
E – Renal excretion by glomerular filtration

20. • Both compounds have a similar half life (~10 hours)
• Two bacteriostatic drugs produces bactericidal action when combined
• The combination has a wider antibacterial spectrum
• The combination delays the development of bacterial resistance
• The MIC of each component can be reduced 3-6 times
• Trimethoprim enters many tissues and has a larger volume of distribution

22. Uses
(Cotrimoxazole)
*Cotrimoxazole is still used now… however, its popularity has decreased in the treatment
of systemic infections
1. Urinary Tract Infections
2. Respiratory Tract Infections
3. Bacterial Diarrheas + Dysentery
4. Pneumocystis jiroveci (Pneumonia in Neutropenic/AIDS patient)
5. Sexually transmitted Diseases
6. Typhoid

23. Adverse Effects
(Cotrimoxzole)
• All the adverse effects seen with Sulfonamides can be seen with Cotrimoxazole
• Nausea, Vomiting, Headache, Stomatitis
• Rashes
• Folate deficiency ONLY in patients with marginal folate levels
• Blood dyscrasias (RARE)

24. Contraindications
(Cotrimoxazole)
• AVOID IN PREGNANCY
• Trimethoprim is an antifolate  Theoretical teratogenic risk
• Uremia in renal disease
• Greater risk of bone marrow toxicity in the elderly
• Fever, Rash and bone marrow hypoplasia among AIDS patients with P. jiroveci infection

25. Macrolides
• The macrolide antibiotics structurally consist of a large lactone ring to
which sugars are attached. They include
• Erythromycin
• Azithromycin
• Clarithromycin
• Spiramycin

26. Mechanism of Action
• Bacteriostatic- usually
• Inhibit bacterial RNA-dependent protein synthesis
• Bound to the 50S ribosomal subunits and blocks the
execution of instruction coded by mRNA.

27. Pharmacokinetics
• Absorption (Oral)
• Erythromycin: variable absorption of 15% - 45%
• Clarithromycin: 55%
• Azithromycin: 38%
• Half Life (T1/2)
• Erythromycin 1.4 Hours
• Clarithromycin (250mg and 500mg 12hrly) 3-4 & 5-7 hours respectively
• Azithromycin 68hours
• Excellent tissue and intracellular concentrations
• Tissue levels can be 10-100 times higher than those in serum
• Poor penetration into brain and CSF
• Cross the placenta and excreted in breast milk
Metabolism & Elimination
• ALL hepatic elimination

28. Indications
• First line choice as an alternative to penicillin in the penicillin-
sensitive patients (example gonorrhoea, syphilis, streptococcal and
pneumococcal infections, rheumatic fever prophylaxis), alternative to
a tetracycline in mycoplasma pneumoniae infection, pertussis
(whooping cough), diphtheria.
• Second line choice in bronchitis and penicillin-resistant staphylococcal
infections.

29. Adverse Effects
• Gastrointestinal (up to 33 %) (especially Erythromycin)
• Nausea
• Vomiting
• Diarrhoea
• Dyspepsia
• Thrombophlebitis: IV Erythromycin & Azithromycin
• Other: ototoxicity with high dose erythromycin in renal impairment

30. Tetracyclines
• The first member of this family was chlortetracycline, derived from
the soil organism Streptomyces aureofaciens. This was followed by
oxytetracycline produced from Streptomyces rimosus. The
tetracyclines available for the clinical use are:
Doxycycline
Oxytetracycline
Minocycline
Demeclocycline

31. Mechanism of action
• It enter bacterial cells by either passive diffusion through pores on by
an active transport system. Inside the bacterial cells, they bind
specifically to 30S ribosomes, thereby blocking binding of transfer
RNA to the messenger RNA-ribosome complex, inhibiting protein
synthesis.

32. Pharmacokinetic
• Incompletely absorbed from GI, improved by fasting
• Metabolised by the liver and concentrated in bile (3-5X higher than
serum levels)
• Excretion primarily in the urine except doxycycline ( 60% biliary tract
into faeces,40% in urine)

33. Indications
Tetracyclines are the first choice drugs for:
• Chronic bronchitis
• Non specific urethritis
• Primarily atypical pneumonia
• Rickettsia infections
• Pustular acne
• Cholera
Second line choice for:
• Syphilis (in penicillin allergic patients it is first choice)
• Meningococcal carriers

34. Contraindications
• They are usually contraindicated in pregnancy, lactation, peptic ulcer
and hepatic disease.
Adverse effects:
Gastrointestinal upset: Anorexia, heartburn, nausea, vomiting
Organ toxicity: Liver damage, Kidney damage
Phototoxicity
Brown staining of teeth

35. Fluoroquinolones
• Nalidixic acid, 4-quinolone, and other related compounds exert
antimicrobial action by inhibiting DNA synthesis.
• Currently the Fluoroquinolones:
• Cinoxacin
• Enoxacin
• Norfloxacin
• Ciprofloxacin
• Levofloxacin
• Lomefloxacin
• Ofloxacin
• Pefloxacin

36. Pharmacokinetics
• Absorption
• Good bioavailability
• Oral bioavailability 60-95%
• Divalent and trivalent cations (Zinc, Iron, Calcium, Aluminum, Magnesium) and antacids
reduce GI absorption
• Distribution
• Extensive tissue distribution but poor CSF penetration
• Metabolism and Elimination
• Combination of renal and hepatic routes

37. Indications
• The fluoroquinolones are indicated for treatment of several bacterial
infections, including bacterial bronchitis, pneumonia, sinusitis, urinary
tract infections, septicemia and intraabdominal infections, joint and
bone infections, soft tissue and skin infections, typhoid fever, anthrax,
bacterial gastroenteritis, urethral and gynecological infections, and
pelvic inflammatory disease and several other infectious conditions.

38. Contraindications
• There is no absolute contraindication but a caution must be observed in
young children and in pregnant or nursing mothers.
Adverse Reactions:
• Nausea, headache, dizziness, abdominal discomfort, photosensitivity and
skin rash
• Palpitation, hypertension and angina
• Pain, burning, tingling, numbness, weakness
• nerve damage in hands, feet, arms, or legs
• Depression, anxiety or other changes in mental health

39. Aminoglycosides
• The aminoglycosides are so named because they are composed of
amino sugars connected by glycosidic linkages
Naturally occurring:
•Streptomycin
•Neomycin
•Kanamycin
•Tobramycin
•Gentamicin
Semisynthetic derivatives:
•Amikacin (from Kanamycin)
•Netilmicin (from Sisomicin)

40. Mechanism of action
• Inhibit bacterial protein synthesis by irreversibly binding to 30S
ribosomal unit and distort the mRNA translation of the genetic code,
thereby preventing the formation of normal complex required to
initiate protein synthesis.

41. Pharmacokinetics
They are poorly absorbed following oral administration thus
given by injection to treat systemic infection.
• Distribution: It is widely distributes into body fluids but very poorly into;
• CSF
• Vitreous fluid of the eye
• Biliary tract
• Prostate
• Tracheobronchial secretions
• Adipose tissue
• Elimination
• 85-95% eliminated unchanged via kidney
• t1/2 dependent on renal function
• In normal renal function t1/2 is 2-3 hours

42. Indications
• severe infections of the abdomen and urinary tract, as well as
bacteremia and endocarditis.
Contraindication: it should be avoided in pregnancy as it crosses
the placenta

43. Adverse Effects
• Nephrotoxicity
• Direct proximal tubular damage - reversible if caught early
• Ototoxicity
• 8th cranial nerve damage – irreversible vestibular and auditory
toxicity
• Neuromuscular paralysis
• Can occur after rapid IV infusion especially with;