Antimicrobials and Pharmacotherapy

1

Describe the key factors that influence antibiotic choice.

• An antimicrobial active against the organism causing the infection should be used. If this is not known, then the typical organisms known to cause the infection should be considered and treatment directed toward these organisms.

• The anticipated resistance pattern of the organism must be considered. If the organism has been cultured, resistance testing should be done. If susceptibility testing is not possible, local resistance patterns should be taken into consideration when choosing antibiotics.

• The location of the infection and delivery and penetration of the antibiotic must be considered.

• The mechanism of action of the antibiotic is important. If the patient does not have an intact immune system, a bacteriocidal antibiotic should be chosen over a bacteriostatic one, if possible.

• Host factors such as age, history of drug allergy, renal or hepatic dysfunction, pregnancy, drug–drug interactions due to other medications the patient is taking, and immune status must be taken into consideration. Drug dosage adjustment is required for many antibiotics in the setting of renal or hepatic dysfunction.

2

What facts must the clinician consider when deciding between oral and intravenous antibiotic therapy?

Severity of infection: Oral antibiotics are typically used in mild infections whereas intravenous (IV) antibiotics are chosen for moderate to severe infections. Intravenous antibiotics should be given to patients who are in shock, because oral absorption can be erratic.

Degree of systemic absorption: If an oral antibiotic is given, the absorption of the antibiotic must be considered. For example, some antibiotics such as aminoglycosides are not given orally due to poor absorption. On the other hand, some antibiotics have excellent oral bioavailability and can be used almost interchangeably with IV antibiotics.

3

What are some advantages of topical antibiotics?

Some advantages are optimal delivery to the site, ability to deliver higher drug concentration, ability to overcome resistance mechanisms, and minimized systemic side effects. For example, topical eardrops are routinely used to treat otitis externa.

4

Describe the mechanism of action and spectrum of activity of the penicillin class of antibiotics.

Penicillins are β-lactam antibiotics and are bactericidal. They kill bacteria by inhibiting cell wall synthesis ( Table 4.1 ).

5

Explain the spectrum of activity of the different classes of cephalosporin antibiotics.

First-generation cephalosporins (intravenous cefazolin, oral cephalexin) primarily have activity against gram-positive cocci, such as Staphylococcus sp. and Streptococcus sp.

Second-generation cephalosporins (cefuroxime) have increased activity against gram-negative respiratory pathogens, including Haemophilus influenzae and Moraxella catarrhalis . However, second-generation cephalosporins have limited activity against many Enterobacteriaceae. Cefuroxime is active against penicillin-sensitive strains of Streptococcus pneumoniae .

Third-generation cephalosporins (intravenous ceftriaxone and ceftazidime, oral cefixime and cefditoren) demonstrate increased activity against gram-negative organisms. Some of the drugs in this class, such as ceftriaxone, also have activity against penicillin-resistant S. pneumoniae .

Fourth-generation cephalosporins (cefepime is the only drug in this class available in the United States) have the broadest activity against gram-negative organisms, including P. aeruginosa .

Fifth-generation or methicillin-resistant Staphylococcus aureus (MRSA) active cephalosporins (the only approved agent in this class is ceftaroline) have excellent activity against MRSA and other gram-positive organisms including S. pneumoniae . The gram-negative activity of this drug is similar to that of ceftriaxone.