Beta-lactamase Inhibitors

Drugs having beta lactam molecules are not clinically given alone. There are 3 beta lactamase
inhibitors:
1. Clavulanic acid
2. Sulbactam
3. Tazobactam

Mechanism of action
These drugs inhibit lactamse which degrades penicillin. They are more active against
lactamases produced by bacteria. Those bacteria grouped into class A are more susceptible to
inhibitory effects of these inhibitors. Such lactamases are produced by organisms like:
1. Salmonella
2. Shigella
3. H. influenza
4. Neisseria
5. E. coli
6. N. gonorrhea
7. K. pneumonia
Those grouped into class C are less susceptible.
These drugs have weak antibacterial activity so combined with penicillins to provide extended
spectrum of activity. Such combinations are especially used for empirical therapy.

Vancomycin
Vancomycin is a cell wall inhibitor. It is produced by Streptococcus orientalis
Chemistry -tricyclic glycopeptide
Mechanism of Action inhibits cell wall synthesis by binding D-ala-D-ala terminal,
inhibitingtransglycosylase.
Resistance
Resistance is produced when
1. D-alanine is replaced by D-lactate or D-serine
2. Metabolism is enhanced by bacteria.
Antibacterial activity

Against Gram positive organisms especially:

Staphylococci

Streptococci
E. facium
E. faecalis
C. difficile
Pharmacokinetics

Routinely given I/V, in dose of 1g 12 hourly. It is given in form of infusion over 1-2 hours.

Only indication oral administration is by pseudomembranous colitis enterocolitis. Drug of

choice is Metronidazole (flagyl). In resistant cases vancomycin is used.
PPB is 30%.
It is mainly excreted by glomerular filtration (more than 90%). Dose adjustment has to be done
in renal impairment.
Adverse effects

1. Hypersensitivity

Skin rash

Articaria

Fever

Chills
2. Local irritation at site of infusion
3. Phlebitis
4. Typical redman / red neck syndrome when given rapidly I/V. direct toxic effects on most
cells releasing histamine causing flushing, tachycardia and hypotension.
5. Ototoxicity
6. Nephrotoxicity
When combined with aminoglycosides, patient is closely monitored, as they also have similar
effects.
Uses

1. Endocarditis
2. Pneumonia
3. Empyema
4. Meningitis
5. Osteomyelitis
6. Soft tissue abscess
7. Disseminated infections
8. MRSA
9. Pseudomembranous enterocolitis
10. Given orally to enhance spectrum of aminoglycosides

Clindamycin
Produced by Streptomyces lincolnensis
Chemistry Cl substituted lincomycin
Mechanism of Action

Similar to macrolides. Inhibits protein synthesis by:

1. Interfering with formation of initiation complex

2. Inhibits aminoacyl translocation

Resistance
Resistance is produced by:
1.
Mutations bring about change in receptor site for drug or production of proteins
2.
Methylase alter receptor site for drug
3.
Enzymes produced by bacteria cause inactivation of drug
4.
Poor permeability in some bacteria of drug
Antibacterial activity

Gram positive and negative organisms including:

1.
2.
3.

Staphylococci
Streptococci
Bacterioides

4.
5.

P.jiroveci
Toxoplasma

Pharmacokinetics

Can be given Orally, I/V, I/M. also available as gel form for topical use e.g. acne or vaginal
infection.
Readily taken up by phagocytes in abscesses
In liver converted to active metabolites and excreted in urine and feces.
Adverse effects

1.
2.

Abdominal pain
Diarrhea

3.
Enterocolitis pseudomembranous colitis appearing as super-infections. In severe form
may be fatal, so drug is stopped and either metronidazole or vancomycin is used to treat colitis.
4.
Myelosuppression
5.
Impaired LFTs
6.
Local irritation in form of thrombophlebitis at site of injection
7.
Neuromuscular blocker
Clindamycin potentiates the effects of NM blockers as itself causes inhibition.
Uses

1.
a.
b.
c.
d.
e.
2.

Mainly used for treatment of anaerobic infections in different parts of body including:
Abdomen
genital tract
Pelvic abscess or septic abortion
Lung like lung abscess or aspiration pneumonia
Heart valvular heart disease
Dental treatment prophylactically given

3.
4.

Pneumonia caused by Pn. Jiroveci

In patients of AIDS with primaquine

5.

Encephalitis caused by Toxoplasma along with pyrimethamine