anti biotica

1. Antimicrobial
Antimicrobials are the drugs that inhibit/kill the
infecting organism and to have no/minimal effect
on the recipient.
Antimicrobial are one of the most frequently used
as well as misused drugs.
This type of therapy is generally called
chemotherapy which has come to mean ‘treatment
of systemic infections with specific drugs that
selectively suppress the infecting microorganism
without significantly affecting the host.’

2. Antibiotics
These are substances produced by microorganisms,
which selectively suppress the growth or kill other
microorganisms at very low concentrations.
This definition excludes other natural substances
which also inhibit microorganisms but are produced
by higher forms (e.g.antibodies) or even those
produced by microbes but are needed in high
concentrations (ethanol,lactic acid, H2O2).

3. Chemotherapeutic agent
chemotherapeutic agent’ was restricted to
synthetic compounds, but now since many
antibiotics and their analogues have been
synthesized, this criterion has become
irrelevant; both synthetic and microbiologically
produced drugs need to be included together. It
would be more meaningful to use the term

4. SULFONAMIDES
Sulfonamides were the first antimicrobial
agents (AMAs) effective against pyogenic
bacterial
infections.
Sulfonamido-chrysoidine (Prontosil Red)
was one of the dyes included by Domagk to
treat experimental streptococcal infection in
mice and found it to be highly effective.

5. Chemistry
All sulfonamides may be considered to be
derivatives of sulfanilamide (p-
aminobenzene sulfonamide). Individual
members differ in the nature of
N1(Sulfonamido N) substitution, which
governs solubility, potency and
pharmacokinetic property. A free amino
group in the para position (N4) is required
for antibacterial activity.

6. Classification
1. Short acting (4–8 hr): Sulfadiazine
2. Intermediate acting (8–12 hr):
Sulfamethoxazole
3. Long acting (~7 days): Sulfadoxine,
Sulfamethopyrazine
4. Special purpose sulfonamides:
Sulfacetamide sod., Mafenide, Silver
sulfadiazine,Sulfasalazine

7. ANTIBACTERIAL SPECTRUM
Sulfonamides are primarily bacteriostatic
against many gram-positive and gram-
negative bacteria. However, bactericidal
concentrations may be attained in urine

8. Mechanism of action
1) inhibit bacterial folate synthase → FA is
not formed and a number of essential
metabolic reactions suffer.
2) Sulfonamides competitively inhibit the
union of PABA with pteridine residue
3) Sulfonamides chemically similar to
PABA, that may itself get incorporated to
form an altered folate which is
metabolically injurious

9. Resistance to sulfonamides
Most bacteria are capable of developing
resistance to sulfonamides.
(a) Produce increased amounts of PABA
(b) Their folate synthase enzyme has low
affinity for sulfonamides,
(c) Adopt an alternative pathway in folate
metabolism

10. PHARMACOKINETICS
Absorption: - rapidly and completely
absorbed from g.i.t.
Distribution: - widely distributed in the
body—enter serous cavities, CSF, placenta.
Metabolism: - in liver by acetylation.
Excretion: - mainly by the kidney through
glomerular filtration

11. ADVERSE EFFECTS
• Nausea, vomiting and epigastric pain.
• Crystalluria
• Hypersensitivity rashes, urticaria and drug fever. Photosensitization
Stevens-Johnson syndrome and exfoliative dermatitis
• Hepatitis
• Sulfonamides cause haemolysis in a dose dependent manner in
individuals with G-6-PD deficiency.
Neutropenia and other blood dyscrasias are rare.
• Kernicterus may be precipitated in the newborn, especially
premature, by displacement of bilirubin from plasma protein binding
sites and more permeable blood-brain barrier

12. Interactions
Sulfonamides inhibit the metabolism of
phenytoin, tolbutamide and warfarin
enhance their action.
They displace methotrexate from binding
and decrease its renal excretion—toxicity
can occur.
Fixed dose combinations of sulfonamides
with penicillin are banned in India.

13. USES
Systemic use of sulfonamides alone (not combined with trimethoprim
or pyrimethamine) is rare now.
For suppressive therapy of chronic urinary tract infection, for
streptococcal pharyngitis and gum infection
Combined with trimethoprim (as cotrimoxazole) sulfamethoxazole is
used for many bacterial
infections, P. jiroveci and nocardiasis Along with pyrimethamine,
certain sulfonamides are used for malaria and toxoplasmosis.
Ocular sulfacetamide sod. (10–30%) is a cheap alternative in
trachoma/inclusion conjunctivitis,
Topical silver sulfadiazine or mafenide are used for preventing
infection on burn Surfaces

14. COTRIMOXAZOLE
The fixed dose combination of
trimethoprim and sulfamethoxazole is
called cotrimoxazole
Trimethoprim is a diaminopyrimidine
related to the antimalarial drug
pyrimethamine which selectively inhibits
bacterial dihydrofolate reductase
(DHFRase).

15. COTRIMOXAZOLE
sulfonamide and trimethoprim are
bacteriostatic, but the combination becomes
cidal against many organisms. Maximum
synergism is seen when the organism is
sensitive to both the components, but even
when it is moderately resistant to one
component, the action of the other may be
enhanced.

16. COTRIMOXAZOLE
Sulfamethoxazole was selected for
combining with trimethoprim because both
have nearly the same t½ (~ 10 hr). Optimal
synergy in case of most organisms is
exhibited at a concentration ratio of
sulfamethoxazole 20 : trimethoprim 1, the
MIC of each component may be reduced by
3–6 times.

17. Mechanism of action

18. Spectrum of action
Antibacterial spectra of trimethoprim and
sulfonamides overlap considerably.
Additional organisms covered by the combination
are—Salmonella typhi, Serratia, Klebsiella,
Enterobacter, Yersinia enterocolitica,
Pneumocystis jiroveci and many
sulfonamideresistant strains of Staph. aureus,
Strep. pyogenes, Shigella, enteropathogenic E.
coli, H.influenzae, gonococci and meningococci.

19. Resistance
Mutational or plasmid mediated acquisition
of a DHFRase having lower affinity for the
inhibitor.

20. Adverse effects
All adverse effects seen with sulfonamides can be
produced by cotrimoxazole.
• Patients with renal disease may develop uremia. Dose
should be reduced in moderately severe renal impairment.
• A high incidence (upto 50%) of fever, rash and bone
marrow hypoplasia due to cotrimoxazole has been reported
among AIDS patients with Pneumocystis jiroveci
infection.
• The elderly are also at greater risk of bone marrow
toxicity from cotrimoxazole.
• Diuretics given with cotrimoxazole have produced a
higher incidence of thrombocytopenia

21. Uses
Urinary tract infections
Respiratory tract infections
Typhoid
Bacterial diarrhoeas and dysentery
Pneumocystis jiroveci
Chancroid
7. Cotrimoxazole is an effective alternative to penicillin for
protecting agranulocytosis patients and treating respiratory
and other infections in them.
Intensive parenteral cotrimoxazole therapy has been used
successfully in septicaemias, but other drugs are more
commonly employed now.

22. FLUOROQUINOLONES
These are quinolone antimicrobials having one
or more fluorine substitutions. The ‘first
generation’ fluoroquinolones (FQs) introduced
in 1980s have one fluoro substitution. In the
1990s, compounds with additional fluoro and
other substitutions have been developed—
further extending antimicrobial activity to gram-
positive cocci and anaerobes, and/or confering
metabolic stability (longer t½). These are
referred to as ‘second generation’ FQs.

23. Classification
First generation fluoroquinolones
Norfloxacin Ofloxacin Ciprofloxacin
Pefloxacin
Second generation fluoroquinolones
Lomefloxacin Sparfloxacin Levofloxacin
Gatifloxacin Moxifloxacin

24. Mechanism of action
FQs inhibit the enzyme bacterial DNA gyrase &
topoisomeraseIV, which nicks double-stranded
DNA, introduces negative supercoils and then
reseals the nicked ends. This is necessary to
prevent excessive positive supercoiling of the
strands when they separate to permit replication or
transcription.
The bactericidal action probably results from
digestion of DNA by exonucleases whose
production is signalled by the damaged DNA.

25. Higher potency against gram-positive bacteria
Greater affinity for topoisomerase IV
In gram-positive bacteria the major target of
FQ action is a similar enzyme
topoisomerase IV which nicks and separates
daughter DNA strands after DNA
replication.

26. Mechanism of resistance
Chromosomal mutation: - producing a DNA
gyrase or topoisomerase IV with reduced
affinity for FQs,
Due to reduced permeability/increased
efflux of these drugs across bacterial
membranes.

27. Absorption: - absorbed orally, but food
delays absorption, and first pass metabolism
occurs.
Distribution:-high tissue penetrability:
concentration in lung, sputum, muscle,
bone, prostate and phagocytes exceeds that
in plasma,
Excretion: - in urine. (by glomerular
filtration and tubular Secretion)
Pharmacokinetics

28. Adverse effects
Ciprofloxacin has good safety record: side
effects occur in ~10% patients, but are
generally mild; withdrawal is needed only
in 1.5%.
Gastrointestinal
CNS
Skin/hypersensitivity
Tendonitis and tendon rupture

29. Interactions
• Inhibits the metabolism of theophylline,
caffeine and warfarin
• NSAIDs may enhance the CNS toxicity of
FQs; seizures are reported.
• Antacids, sucralfate and iron salts given
concurrently reduce absorption of FQs.

30. Contraindication
Ciprofloxacin and other FQs are
contraindicated during pregnancy

31. Uses
Ciprofloxacin is effective in a broad range of
infections including some difficult to treat
ones.
Because of wide-spectrum bactericidal
activity, oral efficacy and good tolerability, it
is being extensively employed for blind
therapy of any infection, but should not be
used for minor cases or where gram-positive
organisms and/or anaerobes are primarily
causative

32. 1. Urinary tract infections:
2. Gonorrhoea:
3. Chancroid:
4. Bacterial gastroenteritis:
5. Typhoid:
6. Bone, soft tissue, gynaecological and wound infections:
7. Respiratory infections:
8. Tuberculosis
9. Gram-negative septicaemias:
10. Meningitis
11. Prophylaxis: of infections in neutropenic/ cancer and other susceptible
patients.
12. Conjunctivitis: by gram-negative bacteria: topical therapy is effective