Clindamycin. a potent lincosamide antibiotic is similar in mechanism of action (inhibits protein synthesis by binding to 50S ribosome) and spectrum of activity to erythromycin. Oral absorption of clindamycin is good. It penetrates into most skeletal and soft tissues, but not in brain and CSF; accumulates in neutrophils and macrophages. It is largely metabolized and metabolites are excreted in urine and bile. The t½ is 3 hr. Vancomycin is a glycopeptide antibiotic discovered in 1956 as a penicillin substitute which assumed special significance due to efficacy against MRSA, Strep. viridans, Enterococcus and Cl. difficile. Bactericidal action is exerted on gram-positive cocci, Neisseria, Clostridia and diphtheroids. However, in hospitals where it has been extensively used for surgical prophylaxis, etc. URINARY ANTISEPTICS Some orally administered AMAs attain antibacterial concentration only in urine, with little or no systemic antibacterial effect. Like many other drugs, they are concentrated in the kidney tubules, and are useful mainly in lower urinary tract infection. They have been called urinary antiseptics because this may be considered as a form of local therapy. Nitrofurantoin and methenamine are two such agents; infrequently used now. Nalidixic acid can also be considered to be a urinary antiseptic.

1. LINCOSAMIDES
GLYCOPEPTIDES &
URINARY TRACT INFECTION
28 January 2018 1
VINAY GUPTA
DEPT OF PHARMACOLOGY
UP UNIVERSITY OF MEDICAL SCIENCES,
SAIFAI, ETAWAH (UP) INDIA

2. 1
4
5
3
2
Modes of Antimicrobial Action of AMAs

3. LINCOSAMIDES
28 January 2018 3

4. 1) Lincomycin
2) Clindamycin
3) Pirlimycin
 MOA:
 Similar to Macrolides.
 Binds with 23rd portion of 50 S ribosome
subunit of bacterial ribosome & prevents
protein synthesis.
 Lincosamides don't interfere with protein
synthesis in humans.
LINCOSAMIDE

5.  Its first Lincosamide AB
 Absorbed Orally
 Eliminated in faeces through bile.
 Colitis is more common in comparison to
Clindamycin.
 Dose: 500 mg Orally
600 mg (iv/im) 6-8 hourly
LINCOMYCIN

6.  Clindamycin palmitate – Clindamycin
 Clindamycin phosphate – Clindamycin
 Strains resistant to macrolides are may be
sensitive to clinda as clinda is not a substrate for
macrolides efflux mechanism resistance.
 Resistance in Clinda may occur d/t alternation
in metabolism & also d/t methylation of bacterial
RNA +nt in 50 S ribosomal subunit of Bacteroides
fragilis.
CLINDAMYCIN

7.  Strains resistant to macrolides are may be
sensitive to clinda as clinda is not a substrate for
macrolides efflux mechanism resistance.
 Resistance in Clinda may occur d/t alternation
in metabolism & also d/t methylation of bacterial
RNA +nt in 50 S ribosomal subunit of Bacteroides
fragilis.
CLINDAMYCIN

8.  Oral absorption is Good.
 Absorption is not affected by presence of Food.
 Plasma t1/2 is 3 hrs
 Plasma protein binding is > 90%
 Distribution -
PKaCLINDAMYCIN

9.  About 10% of drug
excreted unchanged in
Urine.
 It undergoes
intrahepatic circulation &
the metabolites are
excreted in urine, bile &
faeces.
 Dose reduction is
required in case of hepatic
dysfunction.
PKaCLINDAMYCIN

10. Sensitive
Anaerobic Bact.
 MSSA
Therapeutic Uses -CLINDAMYCIN
Resistant
 Gm –ve Bacilli
 MRSA
Effective for infections caused by-
 Bacteroides fragilis
 Bact. melanenogenicus
 Clost. perfringens
 Fusobacterium
 Peptostreptococcus

11. Therapeutic Uses -CLINDAMYCIN
 as an alternative drug for bacterial endocarditis.
 1 % cream – Acne vulgaris.
 with Primaquine – Pneumosystis
 with Pyrimethamine – Encephalitis (Toxoplasma
gondii)
 with Quinine/ Artesunate – Maleria
 with Aminoglycosides/ Cephalosporins – non
sexually transmitted infection of genital tract of
females.

12.  600 – 1200 mg/ day
 1200 – 2400 mg/day *
*(in severe cases by IV route, in 4 divided
dose)
CLINDAMYCIN DOSE -

13.  Pseudomembranous colitis d/t Clost. difficile -
 Hypersensitivity Reactions -
 Liver enzymes -
 Thrembophlebitis -
CLINDAMYCIN ADVERSE EFFECTS -

14.  Active only against GM +ve bact.
 MOA same as Clinda
 Preferably used for treatment of Mastitis.
PIRLIMYCIN

15. GLYCOPEPTIDES
28 January 2018 15

16.  Inhibitors of Cell wall synthesis
 bactericidal for all susceptible bacteria
except Enterococci
 Only active against Gm +ve bact.
 Except Flavobacterium all Gm –ve bact
including pseudomonas & mycobacterium are
resistant.
GLYCOPEPTIDES

17.  Tricyclic glycopeptide
 Obtained from Streptococcus orientalis in
1956
 Its not susceptible to any of the Beeta-
lactamases.
 Inhibits cell wall synthesis
 Bactericidal
VANCOMYCIN

18.  has high affinity & binds with D-alanyl- D-
alanine dipeptide terminus of nascent
peptidoglycon & prevents its release.
 Elongation of peptidoglycon or polymerization
is inhibited d/t inhibition of transglycosylase, so
the further step of cross linking is not possible,
leading to cell damage.
MOA -VANCOMYCIN

19.  Resistant to Enterococci
 Resistance is d/t alteration of dipeptide from
D-alanyl- D-alanine to D-alanyl - D- lactate OR
to D-alanyl - D- serine.
RESISTANCE -VANCOMYCIN
Vancomycin +
Aminoglycosides

20.  Oral absorption is poor bt used orally in case of
Pseudomembranous colitis.
 also used orally for Staphylococcal enterocolitis.
 water soluble.
 t1/2 is 6 hr, used at 6 hourly.
 Distribution – body fluids
 Reaches to CNS
 90% of drug is excreted unchanged through
kidneys.
PKa -VANCOMYCIN

21.  Sensitive for-
•Streptococcal bact. like-
• S. pyogenes
• S. pneumoniae
• S. viridans
 MRSA
 MRSE
 Corynebacterium
 Clostridium spp. (difficile)
THERAPEUTIC USES -VANCOMYCIN
Gm +ve
Only

22.  It should be only used for serious nosocomial
infections where other agents are not effective.
 It can be used in pts allergic to penicillins or
cephalosporins & also for surgical prophylaxis for
MRSA infections.
 its drug of choice for MRSA like-
 Pneumonia
 Endocarditis
 Soft tissue abscess
 Osteomyelitis
THERAPEUTIC USES -VANCOMYCIN

23.  Vancomycin + Cefotaxime/ Ceftriaxone/
Rifampicin – for treatment of penicillin resistant
Pneumococcal meningitis caused by
Streptococcus pneumoniae.
 also used for vascular catheter infections d/t
Gm +ve organism.
 Drug of choice for Pseudomembranus colitis
caused by Clost. difficile
THERAPEUTIC USES -VANCOMYCIN

24.  Glycopeptide
 Active against both MSSA & MRSA
 its more active against Enterococci than
Vanco & also active against VRE.
 t1/2 is long – 100 hrs, OD
 Highly bounded with plasma proteins
TICOPLANIN

25.  Skin Rashes
 Pain & Phlebitis-
 Rapid IV infusion / higher doses –
 Ototoxicity –
 Nephrotoxicity -
RESISTANCE-VANCOMYCIN

26.  Used for Osteomylitis d/t MSSA & MRSA.
 equally effective as Vanco for
Pseudomembranus colitis caused by Clost. difficile
 with Gentamicin – Enterococcal Endocarditis.
 Dose:
 400 mg im/iv / day Loading dose
 200 mg im/iv / day Maintenance dose
TICOPLANIN

27.  Lypo-glycopeptide.
 effective against VRSA.
t1/2 – 8 hr
 Indicated for complicated skin & soft tissue
infections as/as hospital acquired infections &
ventilator associated bacterial pneumonia d/t
S. aureus.
TELAVANCIN

28.  Lipo-glycopeptide.
 effective against MRSA & VRE
 t1/2 is too long – 6-11 Days
 used once in a week
 Drug is still under evaluation.
DALBAVANCIN

29. URINARY TRACT INFECTION
28 January 2018 29

30.  Bact may +nt in distal urethra as transient flora,
most of which are derived from faecal flora.
 Types of UTI-
UTI
Lower UTI
• Uretheritis
•Cystitis
•Prostatitis
Upper UTI
• Acute Pyelitis
• Acute Pyelonephritis

31. 1) GENDER-
• Shorter length of urethra
• Sexual intercourse
2) Pregnancy
3) Obstruction to flow of urine
4) Neurogenic bladder
5) upward reflux of urine
6) Genetic factors
UTI Predisposing Factors-

32.  Asymptomatic
 Symptomatic
• Increased frequency of micturation
• dysuria
• suprapubic pain
• fever with rigors
• enlarged prostate in male – more susceptible.
UTI Clinical Features-

33. Gm –ve Bacilli
• E. coli
70-80% acute infection
50% hospital acquired
• Klebsella
• Protius
• Psuedomonas
• Schigela
• Enterobactor
• Aerobactor
UTI Causative Organism-
Gm +ve Cocci
• Enterococci
• Streptococci
• Staphylococci
95% 5%
Miscll.
• M. tuberculosis
• Citrobacter
• Salmonellae
• Candida albicans

34. - Antibiotics which specifically act at urinary tract
 Methenamine
 Nitrofurantoin
 Nalidixic acid
• They r mainly used for prophylactic purpose.
• Show remarkable potency in suitable pH of
urine.
UTI URINARY ANTISEPTICS

35.  Hexa Methylene tetramine / Hexamine
 Its a Pro drug.
 Acids used are
•Mandelic acid
•Hippuric acid
• Ascorbic acid
URINARY ANTISEPTICS
METHENAMINE
METHENAMINE FORMALDEHYDE
Acidic pH
Decomposition
+ Ammonia

36.  Favorable urinary pH-
UTI
ACIDIC
• Cloxacillin
• Tetracycline
•Nitrofuratoin
• Methenamine
ALKALINE
• Cephalosporin
• Cotrimoxazole
• Aminoglycosides
• Fluroquinolones
No effect
• Chloramphenicol
• Ampicillin

37.  GIT discomfort / gastritis with dose > 2gm/day.
Higher dose > 3gm/day for longer duration may
cause –
• Painful micturation
• Albuminuria
• Haematuria
• Increased frequency of micturation
Side Effects -
URINARY ANTISEPTICS
METHENAMINE

38.  Highly useful against E. coli, Staph. aureus, Staph.
epidermidis & other Gm –Ve bact.
 Protius vulgaris is resistant, produces Ammonia
which raises pH of urine.
 Psuedomonas are resistant.
 Not effective for Upper UTI as drug is eliminated
before converting to Formaldihyde.
Not useful for tt of acute UTI.
 Mainly used for prophylaxis of resistance, chronic
recurrent UTI including post catheterization or
Instrumentation.
URINARY ANTISEPTICS
METHENAMINE

39.  Absorbed orally.
 Enteric coated preparation preferred (20% of
drug decomposed).
 pH – 5 (20% drug decomposed).
 Urine pH – 6, Urine output – 1.5 Ltr, Dose -2 gm
 Dose 0.5 – 1 gm QID with fluid restriction.
PKa -
URINARY ANTISEPTICS
METHENAMINE

40.  Used for both therapeutic & prophylaxis
purpose in Lower UTI.
 During course of treatment, Resistance does not
develop easily in susceptible bact.
 Bacteriostatic but at higher c/n may exert
Bactericidal effect, especially in acidic pH
URINARY ANTISEPTICS
NITROFURANTOIN

41.  Active against E. coli & Enterococci
 Many Gm –ve bact are susceptible.
 Duration of treatment should not exceed > 2
weeks.
 Antagonizes activity of Nalidixic acid which is a
Bactericidal UA drug
 Resistant for –
• Protius
• Psuedomonas
• Klebsella
• Enterobacter
URINARY ANTISEPTICS
NITROFURANTOIN

42.  Absorbed orally.
 about 40% excreted unchanged in urine.
 undergo rapid hepatic metabolism.
 t1/2 is < 1 Hr, hence therapeutic antibacterial
concentration is not achieved in plasma.
 Dose: 50 – 100 mg TDS/QID for 5-10 days
URINARY ANTISEPTICS
NITROFURANTOIN PKa-

43.  GIT upset, Anorexia
 Haemolysis may occur in persons with G-6-PD
deficiency.
 Colour of urine turns brown on exposure to air.
 Acute pulmonary toxicity may occur in elderly.
 Polyneuropathy may occur on prolonged treatment
in impaired renal function patients.
 Probenecid decreases its action by inhibiting renal
tubular secreations.
URINARY ANTISEPTICS
NITROFURANTOIN S/E-

44.  Non Fluorinated Quinolones.
 Acts by inhibiting bacterial DNA gyrase.
 Absorbed orally, excreted in Urine, t1/2 – 8 Hrs
 Active against Gm –ve like
• E. coli
• Protius
• Klebsella
• Enterobacter
• Shigella but not Pseudomonas
URINARY ANTISEPTICS
NALIDIXIC ACID

45. To be continued.....

46. UTI I

47. UTI I