Biomedical Engineering Reference
In-Depth Information
TABLE 25.1
Penicillins
O
S
CH
3
CH
3
C
R
1
C
NH
COONa (K)
N
C
O
H
R
1
C
8
H
5
CH
2
Benzylpenicillin (Penicillin G)
CH
3
CH
2
CH
CH
CH
2
Penicillin F
C
6
H
5
O
CH
2
Phenoxymethylpenicillin
OCH
3
Methicillin
OCH
3
Cl
Cloxacillin
CH
3
N
O
Cl
CH
3
Dicloxacillin
NO
Cl
Cl
CH
3
Flucloxacillin
NO
F
Another important development was the discovery of penicillins resistant to penicillinase.
Around 1960, quite a number of staphylococci were resistant to penicillin, because they produced
an enzyme, penicillinase, which opens the b-lactam ring. Methicillin was the i rst penicillin found
to be resistant against Staphylococcal penicillinase. More important are the oxacillins discovered
by Doyle and Nayler in the Beecham Laboratories (1952-1962), which may also be administrated
orally. The introduction of one chlorine (cloxacillin) and two chlorine atoms (dicloxacillin) improves
not only the oral absorption but also increases their protein binding. Flucloxacillin seems to be the
best compromise for optimum activity and protein binding (Table 25.1).
Carbenicillin (1967), which contains a carboxyl group in the a-position of the side chain, was
the i rst penicillin with antipseudomonal activity. Its activity is rather low (MIC ± 30
g/mL) and
large doses must be injected (500 mg/kg). Ticarcillin is approximately twice as active as carbenicil-
lin against
Pseudomonas aeruginosa
. The acylureido penicillins, mezlocillin and piperacillin, are
8-10 times more active than carbenicillin against
P. aeruginosa
, and also have activity against
K. pneumoniae, S
.
marcescens, H. inl uenzae
, and
Neisseria
. Temocillin, with a 6a-methoxy group,
μ
