Page 809 - Basic _ Clinical Pharmacology ( PDFDrive )

C H A P T E R

Beta-Lactam & Other Cell 43

Wall- & Membrane-Active

Antibiotics

*
Camille E. Beauduy, PharmD, & Lisa G. Winston, MD

C ASE STUD Y

A 45-year-old man is brought to the local hospital emer- (38.7°C [101.7°F]), hypotensive (90/54 mmHg), tachypneic
gency department by ambulance. His wife reports that (36/min), and tachycardic (110/min). He has no signs of
he had been in his normal state of health until 3 days ago meningismus but is oriented only to person. A stat chest
when he developed a fever and a productive cough. Dur- x-ray shows a left lower lung consolidation consistent with
ing the last 24 hours he has complained of a headache and pneumonia. A CT scan is not concerning for lesions or
is increasingly confused. His wife reports that his medical elevated intracranial pressure. The plan is to start empiric
history is significant only for hypertension, for which he antibiotics and perform a lumbar puncture to rule out
takes hydrochlorothiazide and lisinopril, and that he is bacterial meningitis. What antibiotic regimen should be
allergic to amoxicillin. She says that he developed a rash prescribed to treat both pneumonia and meningitis? Does
many years ago when prescribed amoxicillin for bron- the history of amoxicillin rash affect the antibiotic choice?
chitis. In the emergency department, the man is febrile Why or why not?

■ BETA-LACTAM COMPOUNDS Structural integrity of the 6-aminopenicillanic acid nucleus (rings
A plus B) is essential for the biologic activity of these compounds.
PENICILLINS Hydrolysis of the β-lactam ring by bacterial β-lactamases yields
penicilloic acid, which lacks antibacterial activity.
The penicillins share features of chemistry, mechanism of action,
pharmacology, and immunologic characteristics with cephalospo- A. Classification
rins, monobactams, carbapenems, and β-lactamase inhibitors. Substituents of the 6-aminopenicillanic acid moiety determine the
All are β-lactam compounds, so named because of their four- essential pharmacologic and antibacterial properties of the result-
membered lactam ring. ing molecules. Penicillins can be assigned to one of three groups
(below). Within each of these groups are compounds that are
Chemistry relatively stable to gastric acid and suitable for oral administration,
eg, penicillin V, dicloxacillin, and amoxicillin. The side chains of
All penicillins have the basic structure shown in Figure 43–1. A some representatives of each group are shown in Figure 43–2.
thiazolidine ring (A) is attached to a β-lactam ring (B) that car-
ries a secondary amino group (RNH–). Substituents (R; examples 1. Penicillins (eg, penicillin G)—These have greatest activ-
shown in Figure 43–2) can be attached to the amino group. ity against Gram-positive organisms, Gram-negative cocci, and
non-β-lactamase-producing anaerobes. However, they have little
* activity against Gram-negative rods, and they are susceptible to
The authors thank Dr. Henry F. Chambers and Dr. Daniel Deck for
their contributions to this chapter in previous editions. hydrolysis by β-lactamases.
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