Important Facts
Though ampicillin can be given orally, amoxicillin is a better choice. It is more bioavailable, better tolerated, and administered less frequently. Use ampicillin for IV therapy and amoxicillin for oral therapy. Europeans disagree; they use amoxicillin intravenously also.
Ampicillin is a drug of choice for susceptible enterococci. Enterococcus faecalis is almost always susceptible; Enterococcus faecium is often resistant.
These drugs are often listed as alternative regimens for urinary tract infections (UTIs) in pregnant women because they are pregnancy category B and eliminated renally. However, resistance in Escherichia coli to them is very high and susceptibility testing should be performed. Always perform follow-up cultures in pregnant women with UTIs since even asymptomatic bacteruria is dangerous for them.
What They’re Good For
Infections caused by susceptible GNRs, enterococci, and streptococci. Because resistance among GNRs is prevalent, aminopenicillins are used only infrequently in complicated nosocomial infections. Amoxicillin is frequently prescribed for infections of the upper respiratory tract, including streptococcal pharyngitis (strep throat) and otitis media (ear infection).
Don’t Forget!
To achieve bactericidal activity against enterococci, ampicillin (or any other beta-lactam) has to be combined with an aminoglycoside. This should be done in serious infections such as endocarditis.
Antipseudomonal Penicillins
Agents: piperacillin, ticarcillin
None of the penicillins we have discussed thus far offer appreciable activity against P. aeruginosa, a common nosocomial pathogen that is often resistant to multiple antibiotics. Enter the antipseudomonal penicillins. These agents are active against P. aeruginosa and other more drug-resistant GNRs. However, they are just as susceptible to beta-lactamases as penicillin and ampicillin, so they are not antistaphylococcal. Also, strains of GNRs that produce beta-lactamases are resistant to them. They do have activity against streptococci and enterococci. They are now relevant only for a discussion of pharmacology, since they are rarely if ever used clinically by themselves.
Mechanism of Action
All beta-lactams inhibit cross-linking of peptidoglycan in the cell wall, leading to autolysis and cell death.
Spectrum
Good: P. aeruginosa, streptococci, enterococci
Moderate: enteric GNRs, Haemophilus
Poor: staphylococci, anaerobes
Adverse Effects
Similar to those of other beta-lactams.
Important Facts
These drugs retain the Gram-positive activity of penicillin and are active against many streptococci and enterococci.
None of the antipseudomonal penicillins are commonly used except in combination with a beta-lactamase inhibitor (see the next section).
What They’re Good For
Taking up space in textbooks, since you won’t find them on the pharmacy shelf.
Don’t Forget!
When evaluating a penicillin/beta-lactamase inhibitor combination (see the next section), you need to understand the spectrum of the penicillin that the beta-lactamase inhibitor is protecting. That is why this section exists.
Penicillin/Beta-Lactamase Inhibitor Combinations Agents: ampicillin/sulbactam, amoxicillin/clavulanate, piperacillin/tazobactam
Though the aminopenicillins and antipseudomonal penicillins have good intrinsic activity against GNRs, they remain just as susceptible to betalactamases as penicillin G. This means that they are not useful against the vast majority of staphylococci or many GNRs and anaerobes, because these organisms have learned to produce beta-lactamase. In other words, it seemed we learned either how to make a penicillin resistant to betalactamase, or how to make it more active against GNRs, but not both. Betalactamase inhibitors counter beta-lactamases; these drugs mimic the structure of beta-lactams but have little antimicrobial activity on their own. They bind to beta-lactamases irreversibly, preventing the beta-lactamase from destroying any beta-lactams that are coadministered and enabling the therapeutic beta-lactam to be effective.
When considering the activity of the beta-lactamase inhibitor combination, remember that the beta-lactamase inhibitor only frees up the beta-lactam to kill the organism—it doesn’t enhance the activity. Therefore, the combination products are active only against the bacteria that the beta-lactam in the combination has intrinsic activity against. For example, ampicillin/sulbactam is active against beta-lactamase producing E. coli, because ampicillin alone is active against non-beta-lactamase producing E. coli. However, it has no useful activity against Pseudomonas aeruginosa, because ampicillin lacks activity against this organism. In contrast, piperacillin/tazobactam is active against P. aeruginosa because piperacillin alone is useful. Though these drugs have very broad spectra of activity, there are differences among the agents. Keep in mind the rule that beta-lactamase inhibitors restore activity, not add to it, to set them straight.
Mechanism of Action
All beta-lactams inhibit cross-linking of peptidoglycan in the cell wall, leading to autolysis and cell death. These beta-lactamase inhibitors structurally resemble beta-lactams and bind to many beta-lactamases, rendering them unable to inactivate the coadministered beta-lactam.
Spectrum
Good: MSSA, streptococci, enterococci, many anaerobes, enteric GNRs,
P. aeruginosa (only piperacillin/tazobactam)
Moderate: GNRs with advanced beta-lactamases
Poor: MRSA, extended-spectrum beta-lactamase (ESBL) producing GNRs
Adverse Effects
Similar to those of other beta-lactams.
Important Facts
Unlike the other members of this class, amoxicillin/clavulanate is available orally. Various doses are available, but higher doses are associated with more diarrhea. Note that the dose of clavulanate is fixed in all oral dosage forms (125 mg).
The beta-lactamase inhibitors packaged in these combinations are not active against all beta-lactamases. New beta-lactamases with the ability to destroy many types of beta-lactams are continually being discovered and are becoming more prevalent.
Except for study purposes, beta-lactamase inhibitors are not available outside of the combination products.
Sulbactam has useful activity against Acinetobacter baumannii, a highly drug-resistant GNR that causes nosocomial infections. For this reason, high doses of ampicillin/sulbactam can be used in the treatment of infections caused by this organism.
Amoxicillin/clavulanate and ampicillin/sulbactam have nearly identical spectra of activity, but clavulanate is more potent at inhibiting betalactamases than sulbactam and higher doses of sulbactam are given to account for this fact. Differences in susceptibility testing may be due to the low concentrations of sulbactam used in tests.
What They’re Good For
Empiric therapy of nosocomial infections, particularly nosocomial pneumonia (not aminopenicillin-based combinations). Because they have activity against aerobes and anaerobes, they are a good empiric choice for mixed infections, such as intra-abdominal infections, diabetic ulcers, and aspiration pneumonia. Amoxicillin/clavulanate is used for upper and lower respiratory tract infections when beta-lactamase–producing organisms are found or suspected. It can also be useful for UTIs when resistance to other drugs is seen, but it should not be given for a short 3-day course as with fluoroquinolones or TMP/SMX.