Other beta lactam antibiotics

·        Carbapenams: imipenam, meropenam.

·        Monobactams: aztreonam.

Imipenam

1.       Imipenam has the widest spectrum of all currently available antimicrobials.

2.    It is bactericidal against:

a.    Most Gram-positive cocci.

b.       Gram-negative bacilli.

c.       Anaerobes including Bacteroides fragilis.

3.       Pharmacokinetics:

a.    Half-life: 1h.

b.    Not absorbed orally due to instability in gastric acid.

c.       Excreted in the urine where it is metabolized by an enzyme in the renal tubular cells to potential nephrotoxic products.

d.       Cilastatin inhibits dihydropeptidase, the enzyme responsible for its renal metabolism and prevent both inactivation and toxicity.

e.       Widely distributed but in the absence of inflammation, penetration into CNS is limited.

4.       Indications:

a.       Septicaemia, particularly of renal origin.

b.       Intra-abdominal infection.

c.       Nosocomial pneumonia.

5.       Adverse effects:

a.       Gastrointestinal upset.

b.    Skin rashes.

c.       Blood disorders.

d.       Confusion and convulsions.

6.       Meropenam is similar to imipenam in terms of spectrum of activity and pharmacokinetics except it is not metabolized by renal dihydropeptidase.

Aztreonam

1.       Active against Gram-negative bacilli including:

a.       Pseudomonas aeruginosa.

b.       Haemophilus influenzae.

c.       Neisseria spp.

2.       Inactive against gram-positive cocci and anaerobes.

3.    It is not absorbed after oral administration.

4.    It is metabolized only to a limited extent and is excreted mainly unchanged in the urine.

5.       Adverse effects:

a.    Skin rash.

b.       Nausea and vomiting.

c.       Diarrhoea.

d.       Hepatitis.

e.       Thrombocytopenia and neutropenia.

Vancomycin

1.       Chemistry:

a.       Complex glycopeptide produced by Streptococcus orientalis.

b.       Inhibits the biosynthesis of peptidoglycan.

2.       Pharmacokinetics:

a.    Oral bioavailability is poor.

b.    Half-life: 8h.

c.       Diffuses readily into pleural, pericardial and ascitic fluids.

d.    Poor penetration into CSF when meninges are normal; improved penetration when they are inflamed.

e.       Eliminated unchanged by the kidney.

3.       Spectrum of activity:

a.       Staphylococci: including beta-lactamase-producing species and MRSA.

b.       Streptococci including streptococcus viridans and enterococci.

c.       Clostridium difficile.

d.       Corynebacterium spp.

e.       Listeria monocytogenes.

4.       Therapeutic indications:

a.       Pseudomembranous colitis.

b.       Streptococcal endocarditis: combined with an aminoglycoside.

c.       Serious staphylococcal infections.

5.       Adverse effects:

a.       Thrombophlebitis: fever, chills.

b.       “Red-neck” syndrome: erythema or flushing or rash affecting the face, neck, upper chest and upper limbs (associated with rapid infusion).

c.       Auditory damage.

d.       Nephrotoxicity.

6.       Teicoplanin:

a.       Structurally related to vancomycin.

b.       Active against gram-positive bacteria.

c.    Used for endocarditis and peritonitis in patients undergoing chronic ambulatory peritoneal dialysis.