This document summarizes various classes of antimicrobials including lincosamide antibiotics, glycopeptide antibiotics, oxazolidinones, polypeptide antibiotics, and urinary antiseptics. It describes the mechanism of action, antimicrobial spectrum, pharmacokinetics, uses, and adverse effects of lincomycin, clindamycin, vancomycin, teicoplanin, linezolid, polymyxin B, colistin, bacitracin, nitrofurantoin, and methenamine. It also discusses the treatment of lower urinary tract infections with these urinary antiseptics and other antimicrobials like cotrimoxazole, quinolones

1. Miscellaneous Antimicrobials
Dr.Arka Mondal
Assistant Professor
(Pharmacology)

2. -:LINCOSAMIDE ANTIBIOTICS:-
• Derivatives of amino acid & a sulfur containing galactosidase
• Drugs – Lincomycin , Clindamycin
• Lincomycin:-
• First derived Lincosamide antibiotics
• Obtained from- Streptomyces lincolnenesis
• Antimicrobial spectrum:- Resemble macrolides
• Active against- Gm + ve cocci, mycoplasma, non spore forming anaerobic bacteria
• Pharmacokinetics:-
• Absorption:- Orally
• T1/2-5hr.

3. • Excretion:- Bile
• MOA:- Inhibit Protein synthesis by binding to 50S ribosomal subunit
• Less potent & higher incidence of Diarrhoea, colitis, Death
• Thus replaced by Clindamycin
• Semi-synthetic derivative of Lincomycin
• MOA:- Inhibit Protein synthesis by binding to 50S ribosomal subunit similar like
Erythromycin (Bacteriostatic)
• Anti-microbial Spectrum:-
• Sensitive against Most gm+ ve cocci like Pneumococci, Staph.(Except MRSA) C.
diphtheriae, Nocardia, Actinomyces, Plasmodial sp., toxoplasma gondii
• Resistant to -Gm-negative anaerobes
Clindamycin

4. • Resistance develop due to- Methylation of bacterial RNA in 50S unit
• Pharmacokinetics:-
Absorption-orally
T1/2-3hr.
Distribution- widely in body fluid, bone, phagocytes
Cross placental barrier
PPB- 90%
Metabolism-liver (N-dimethyl-clindamycin)
Excretion-urine, bile
In severe hepatic failure (dose adjustment)

5. • Therapeutic use:-
Skin and Soft-Tissue Infections:-
Especially in patients with β-lactam allergies, in Acne (as topically)
In gas gangrene by toxin-producing bacteria (e.g., streptococci, staphylococci,
clostridia)→ as Adjuvant therapy
Respiratory Tract Infections:-
Lung abscess, pleural space infections due to susceptible organisms
In AIDS patients:-
(1.) For P. jiroveci pneumonia-(Clindamycin + Primaquine)
(2.) For toxoplasmosis-(Clindamycin + Pyrimethamine)
Others:-
Prophylaxis of Bacterial endocarditis –in pt. allergic to penicillin
Pelvic, abdominal abscess

6. Bacterial vaginosis-vaginally
Osteomyelitis-use due to excellent bone penetration (as a alternative drug)
• Adverse effects:-
• Pseudomembranous colitis (superinfection) –due to toxin release by growth of
clost. difficile which alter gut flora
• Presented with diarrhoea with blood and mucus in the stools, fever, Abdominal
pain
• Rx- stoppage of drug
• Treated with metronidazole
• Skin rashes,
• Safe during pregnancy

7. GLYCOPEPTIDE ANTIBIOTICS:-
• Glycopeptide antibiotics → are cell wall synthesis inhibitors
• Bactericidal agents
• Drugs – Vancomycin , Teicoplanin
• Vancomycin:-
• Discover as a penicillin substitute due to efficacy against MRSA
• MOA:- Inhibit cell wall synthesis by binding with D-alanyl D-alanine to
peptidoglycan unit→ trans-glycosylation inhibited
• Resulted→ Elongation & cross linking of peptidoglycan is prevented
• Antimicrobial spectrum:-
• Sensitive against- gram+ bacteria Streptococcal pyrogenes, pneumoniae, Staph.
aureus including MRSA , S. viridans and Enterococcus.
• Gram-positive bacilli: Diphtheroids and Clostridium spp.

8. • Pharmacokinetics:-
• Absorption-poor so not preferred orally (Except-pseudomembranous colitis)
• T1/2-6hr.
• Distribution:-enters various body fluid like pleural, Pericardial, bile, CNS (in
meningitis)
• Metabolism- Liver
• Excretion- kidney
• USES:-
• MRSA infection (pneumonia, endocarditis, soft tissue abscess) →DOC
• Pseudomembranous colitis- not responding to Metronidazole (DOC)
Dose -125-250mg QID
• Enterococcus endocarditis→ Vancomycin+ Aminoglycoside

9. Adverse effect:-
• Systemic toxicity is high
• Skin rashes & ↓BP during IV injection (due to histamine release)
• Pain & phlebitis at site of injection
• “Red man syndrome or Red Neck syndrome” –orange discoloration of skin,
fluid, mucosal surface
• Upon Rapid i.v. injection→ due to histamine release
• Symptoms:- Chills, fever, urticaria, intense flushing
Treatment:- prevented by prolonging the infusion period by 1-2hrs.
• Nephrotoxicity
• Dose dependent ototoxicity

10. • Teicoplanin:-
• Chemical structure ,mechanism spectrum same as vancomycin
• More active against enterococcus sp. than vancomycin
• Highly bound to plasma protein
• T1/2-50hr.
• Used by i.v. or i.m. route in MRSA , MSSA
• Active against Vancomycin resistant enterococci (VRE)
• Safer than vancomycin
• Telavancin:-
• Semisynthetic derivatives of vancomycin
• Effective against→ VRSA
• MOA-same to vancomycin ‘
• Teratogenic & t1/2-8hr.

11. • OXAZOLIDINONES:-
• Drugs:- Linezolid, Torezolid
• Linezolid:- first drug in this group
• MOA:- bind at “P-site” to 23s part of 50s ribosomal subunit→ Prevent formation
of formylated methionine t-RNA→ inhibit protein synthesis (Bacteriostatic)
• AMS:- Gram + cocci ,bacilli ,VRE,MRSA,VRSA,M tuberculosis, Nocardia, clost.
Difficile.
• Not effective against gram-ve due to presence of membrane efflux pump
• Absorption-rapidly orally
• Oral BA-100%
• T1/2-5hr.
• Metabolism-partly by non enzymatic reaction
• Excretion-Urine

12. • USE:-
• Skin and Soft-Tissue Infections:- by VRSA(DOC), MRSA infection,
• VRE, Pneumonia due to MSSA
• Respiratory Tract Infections:- by MDR,XDR-TB
• Other:- Nocardiosis
• Adverse Effects:-
• Thrombocytopenia-upon prolong use(>2weeks)-bleeding, requires monitoring of
platelet count.
• Anemia
• Optic neuropathy- (>4 weeks)
• Nausea, abdominal pain, diarrhoea, altered taste
• Reversible MAO-I may case “Cheese reaction” with tyramine containing food
• “Serotonin syndrome”→ if use with serotonergic drugs

13. • Torezolid→ Recently approved for Acute bacterial infection of skin
• Mechanism of action is similar to linezolid
• Use- ventilator-associated Pneumonia cause by gram +ve bacteria
• Oral BA-is 90%
• T½ of 12 hours
• Polypeptide Antibiotics:-
• These are low molecular weight polypeptide antibiotics
• Bactericidal agents
• Not Used systemically due to toxicity
• Drugs- Polymyxin B, Colistin, Bacitracin
• Polymixin-B & Colistin :- Active against gram-ve bacteria
• Colistin is more potent against pseudomonas, salmonella , shigella

14. • MOA:- Both the agents have high affinity for phospholipids of cell membrane
• In gram-ve bacteria cell membrane cause distortion ion, Amino acids etc leak out.
sensitive bacteria take up more of antibiotic.
• USE:-
• Skin, eye & ear infections:- due to gram negative bacteria as a combination
therapy with other antimicrobial agents
• Diarrhoea – orally due to gram-negative organism like salmonella, shigella, E.
Coli
• Adverse effect:- GI symptoms on oral administration
• Bacitracin:-
• Polypeptide & topical antibiotics
• MOA:- Responsible for transfer of subunit of peptidoglycan to growing cell wall
• Inhibit cell wall synthesis (Bactericidal effect)
• ↑↑ efflux of ions by binding to cell membrane

15. • AMS:- Gram-positive organisms (both cocci and bacilli).
• Neisseria, H influenzae
• Not absorbed orally
• Parental use→ Nephrotoxicity (so used topically)
• USE:-
• Skin, eye, ear infection-Topically (Powder, Ointment, solution)
• Infected wound, ulcer
• Use along with neomycin, polymyxin-B
• Orally administered AMA attain antibacterial conc only in urine with no systemic
antibacterial effect →Indicated for UTI
• “Urinary Antiseptics”→ Considered as a form of local therapy
Urinary Antiseptics

16. • UTI:- Common(female) health problem in community & nosocomial setting
• Affects bladder, urethra, kidney, ureter
• Types- Upper or lower (most common)
• Lower UTI (uncomplicated):- urethra, Bladder, prostate
• Symptoms:- burning sensation (>3 time a day) , pain, frequency of micturition
bacteria multiplication due to low pH, high urea content
• Causative Organism:-Gram negative (bacilli-E.coli) common
• Others- Klebsiella, Proteus, Pseudomonas
• Risk factor-Catheterization during caesarian section, Traumatic injury to urethra
• Drug treatment should be base on organism causing UTI
• Pharmacotherapy:-
• Urinary antiseptics:- Nitrofurantoin, Methenamine
• URINARY ANALGESIC:- Phenazopyridine

17. • Nitrofurantoin:-
• Synthetic Bacteriostatic (32 μg/mL) drug but at high conc. & acidic pH-as cidal
effect (100 μg/mL)
• Antimicrobial action→ Restricted against E. Coli
• Low level of action in the blood (pH 7.4)
• More active in acidic pH
• Resistance develops rapidly
• Mechanism of Action :-
It is reduced by bacterial enzymes to DNA toxic compounds
↓↓
Damage to the DNA
↓↓
As a result cell Death occurs

18. • Pharmacokinetics:-
• Absorption:- Good Orally
• Excretion:- 50% is urine.(rate depends on creatinine clearance)
• t1/2-1hr.
• Probenecid →↓↓Excretion
• Urine becomes brown after a gap.
• Contraindication:- Pregnant, neonates and renal disorders
• Adverse effect–Nausea, vomiting, diarrhoea(common)
• Rare- acute pneumonitis, peripheral neuritis, hepatotoxicity.
• USES:-
• Lower UTI (uncomplicated)- 50-100mg QID for 2 wks. with meals & at Bedtime
• For long term prophylaxis 50-100mg HS for long period along with vit. C or
juices.

19. • Methenamine:-
• Urinary antiseptic and prodrug
• MOA:- At acidic pH activate by generating formaldehyde which inhibit bacteria
• Acidification of urine is needed for their action
• Rarely used drug
• No tissue action
• Ineffective in upper UTI
• USES:- 2nd line drug for acute lower UTI.
• Adverse effect:-
• Gastritis, Rashes, Albuminuria
• CNS symptoms- occasionally

20. • Urinary analgesic:-
• Phenazopyridine:-
• Orange dye which exerts analgesic action
• Symptomatic relief of burning symptoms
• Doesn’t have antibacterial property
• Adverse effect- Nausea, epigastric pain
• Others Antimicrobials:-
1. Cotrimoxazole:- use declined
• Empirically in UTI & recurrent cystitis (Women)
• Contraindicated in pregnancy
2. Quinolones:- Ciprofloxacin & Ofloxacin (Highly effective)
• Highly effective against Gm-ve bacilli & low cost
• Norfloxacin-chronic UTI & can be given in pregnancy

21. 3. Ampicillin/Amoxicillin:-
• Acute Infection- Amoxicillin+ Clavulanic acid(Parental)
• Acute Pyelonephritis:- Amoxicillin+ Clavulanic acid+ Gentamicin
• Safe in pregnancy
4. Cephalosporins:- ↑used in women with nosocomial Klebsiella and Proteus
infections
Safe in pregnancy
• Cephalexin- as alternative drug for Prophylaxis of recurrent cystitis
5. Gentamicin:- acute pyelonephritis along with others
• Effective against → Pseudomonas
• Prophylaxis of UTI:-
• Cotrimoxazole (480mg), Nitrofurantoin (100mg), Norfloxacin (400mg),
Cephalexin (250mg)→ OD,HS

22. Thank You