Linezolid, Streptogramins, Fusidic Acid, Polymyxin, Bacitracin and Nitrofurantoin

Linezolid

Antimicrobial agent synthetically produced.

Chemistry – synthetic, belongs to oxazolidinones

Mechanism of Action – binds 23S rRNA in 50S unit. By this mechanism inhibit protein synthesis in bacteria.

Antibacterial activity

Gram positive organisms including:

a.      Staphylococci
b.      Streptococci
c.       Enterococci
d.      L. monocytogenes
e.       Mycobacterium Tuberculosis 

Given by oral or I/V route. Undergoes non-enzymatic oxidation.

Adverse effects

1. Myelosuppression (most common is thrombocytopenia) seen if treatment is undertaken for more than 2 weeks
2. Peripheral and optic neuropathies
3. Monoamine oxidase inhibition; care is taken when taking adrenergic or serotonergic drugs as can cause:
   • Headache
   • Palpitiations
   • Hypertension crisis

In these patients.

Uses

1. Mainly for resistant cases like Vancomycin resistant E.faecium
2. Community-acquired pneumonia
3. Skin infections by resistant strains of gram positive microorganisms
4. Usually drug of choice for MDR gram positive bacterial infections

Streptogramins

They are of two types; A and B.

Quinupristin (B)

Dalfopristin (A)

Used in combination in ration of  30:70 (B:A)

Mechanism of action

Protein synthesis inhibitor by binding 50S subunit of ribosomal RNA.

• Quinupristin binds same site as macrolides.
• Dalfopristin binds close by site.
• Thus have synergistic activity in inhibiting protein synthesis.

Antibacterial spectrum

Gram positive cocci –especially MDR strains.

Resistance

Resistance seen because of:

1. Mutation due to alteration in binding site
2. Inactivation by bacteria
3. In some drug is effluxed out.

Given I/V excreted in feces.

Streptogramins are CYP3A4 inhibitors

Adverse effects

1.      Local irritation
2.      Arthralgia
3.      Myalgia syndrome

Uses

1.      Staphylocci
2.      Vancomycin resistant E.faecium

Drugs are not given systemically but applied topically.

Fusidic Acid

• Inhibits protein synthesis
• Active against gram positive cocci esp. staphylocicci

Uses

Topically for:

1. boils
2. folliculitis

Systemically causes hepatocellular damage, so not given.

Polymyxin

• Surface active agent which disrupts cell membranes in bacteria.
• Effective against gram negative organisms.
• Used topically on skin, eye, ear and mucous membranes in combination with other antibacterial drugs like Bacitracin.
• It is not given systemically as is nephrotoxic. 

Bacitracin 

• Cell wall inhibitor.
• Active against gram positive organisms
• Topically given in combination with neomycin or polymyxin (which are effective against gram negative bacteria)
• Not given systemically because is nephrotoxic

Nitrofurantoin

Not an antibiotic actually is urinary antiseptic.

Mechanism of Action

When given orally in body there are enzymes which reduce nitrofurantoin into reactive intermediate. These damage DNA.

These enzymes are more in bacteria and this reaction takes  place at a much higher rate in bacteria. Thus there are less systemic effects.

Antimicrobial activity

1. Enterococci
2.  E.coli

Organisms like proteus, pseudomonas are resistant to this.

Pharmacokinetics

Administered orally.

Excretion – Glomerular Filtration and Tubular secretion.  Excreted in urine.

Action is better in acidic urine.

Adverse effects

1.      Hypersensitvity –articaria, skin rash, fever, chills
2.      Pneumonitis in form of pulmonary infiltrates and fibrosis
3.      Neuropathies, some neurological symptoms
4.      Hemolytic anemia in patients of G-6-PD deficiency
5.      Chronic hepatitis in some patients

Uses

1. Acidic urine
2. Uncomplicated  UTI
3. Prophylaxis – recurrent  UTI

Given in course of 2 weeks, then rest period, again course is repeated.

Not given to pregnant females and children under 14 years of age.