A Textbook of Clinical Pharmacology and Therapeutics

ofpenicillin. This interaction may be used therapeutically to
produce higher and more prolonged blood concentrations of
penicillin. Antibiotics in this group include the penicillins,
monobactams, carbapenems and cephalosporins.

PENICILLINS

Use

Benzylpenicillin(penicillin G) is the drug of choice for strep-
tococcal, pneumococcal, gonococcal and meningococcal infec-
tions, and is also useful for treatment of anthrax, diphtheria,
gas gangrene, leptospirosis, syphilis, tetanus, yaws and Lyme
disease in children.

Adverse effects

The adverse effects include:

1. anaphylaxis (in approximately 1 in 100 000 injections);
   2.rashes (3–5% of patients) can, rarely, be severe (e.g.
   Stevens–Johnson syndrome – see Chapter 12);
   3.serum sickness – type III hypersensitivity;
   4.other idiosyncratic reactions including haemolytic
   anaemia and thrombocytopenia;
   5.in renal failure, high-dose penicillincauses
   encephalopathy and seizures.
   Limitations of benzylpenicillininclude:


2. It is acid labile and so must be given parenterally
   (inactivated in gastric acid).
   2.It has a short half-life, so frequent injections are required.
   3.Development of resistant β-lactamase-producing strains
   can occur.
   4.It has a narrow antibacterial spectrum.

Two preparations with similar antibacterial spectra are
used to overcome the problems of acid lability/frequent
injection:

1. Procaine benzylpenicillin– this complex releases
   penicillinslowly from an intramuscular site, so a twice
   daily dosage only is required.
   2.Phenoxymethylpenicillin(‘penicillin V’) – this is acid
   stable and so is effective when given orally (40–60%
   absorption). Although it is useful for mild infections,
   blood concentrations are variable, so it is not used in
   serious infections or with poorly sensitive bacteria.
   Tablets are given on an empty stomach to improve
   absorption.

β-LACTAMASE-RESISTANT PENICILLIN

Flucloxacillinwas developed to overcome β-lactamase-produc-
ing strains. Otherwise, it has a similar antibacterial spectrum to
benzylpenicillin. It is effective against β-lactamase-producing
organisms. It is used for the treatment of staphylococcal infec-
tions (90% of hospital staphylococci are resistant to benzylpeni-
cillinand 5–10% are resistant to flucloxacillin).

EXTENDED-RANGE PENICILLINS

AMPICILLIN/AMOXICILLIN

Uses

In addition to streptococcal (including pneumococcal) strains,

ampicillinandamoxicillinare also effective against many

strains of Haemophilus influenzae,E. coli,Streptococcus faecalisand

Salmonella. They are used for a variety of chest infections (e.g.

bronchitis, pneumonia), otitis media, urinary tract infections,

biliary infections and the prevention of bacterial endocarditis

(amoxicillin).Amoxicillin is somewhat more potent than

ampicillin, penetrates tissues better and is given three rather

than four times daily. Both are susceptible to β-lactamases.

Adverse effects

Rashes are common and may appear after dosing has stopped.

There is an especially high incidence in patients with infec-

tious mononucleosis or lymphatic leukaemia.

Pharmacokinetics

The half-life of each drug is about 1.5 hours and they are pre-

dominantly renally excreted.

CO-AMOXICLAV

Co-amoxiclavis a combination of amoxicillinandclavulanic

acid, a β-lactamase inhibitor. In addition to those bacteria that

are susceptible to amoxicillin, most Staphylococcus aureus, 50% of

E. coli, some Haemophilus influenzaestrains and many Bacteroides

andKlebsiellaspecies are susceptible to co-amoxiclav. Adverse

effects are similar to those of amoxicillin, but abdominal dis-

comfort is more common.

ANTIPSEUDOMONAL PENICILLINS

Standard penicillins are not effective against Pseudomonas. This

is not usually a problem, as these organisms seldom cause dis-

ease in otherwise healthy people. However, Pseudomonasinfec-

tion is important in neutropenic patients (e.g. those undergoing

cancer chemotherapy) and in patients with cystic fibrosis.

Penicillins with activity against Pseudomonashave been devel-

oped and are particularly useful in these circumstances. These

includepiperacillin,azlocillinandticarcillin.

Uses

These expensive intravenous penicillins are not used routinely.

Their efficacy against Gram-positive organisms is variable and

poor. They are useful against Gram-negative infections, partic-

ularly with Pseudomonasand they are also effective against

many anaerobes. These drugs have a synergistic effect when

combined with aminoglycosides in Pseudomonassepticaemias.

Combinations of ticarcillinor of piperacillinwithβ-lactamase

inhibitors designed to overcome the problem of β-lactamase

formation by Pseudomonasare commercially available.

Adverse effects

These drugs predispose to superinfection. Rashes, sodium over-

load, thrombocytopenia and platelet dysfunction can occur.

326 ANTIBACTERIALDRUGS