Introduction to antibiotics

Explain the difference between antibiotics and anti-infective drugs.

"Anti-infective drug" (a.k.a. "antimicrobial") is a broad term that includes antibiotics, antivirals, antifungals, and so on. The term "antibiotic" has a much stricter definition. The strict definition of an antibiotic is a chemical produced by a microorganism that kills or inhibits other microorganisms, but in clinical practice, most people just use "antibiotic" to mean any kind of substance that kills or inhibits bacteria (with the exception of antiseptics and disinfectants).

Describe the sources of antibiotics.

Antibiotics can be naturally-derived, semisynthetic, or fully synthetic. Some antibiotics are derived from natural sources- for instance, penicillin is derived from the Penicillum fungus. Semisynthetic antibiotics are essentially these natural antibiotics with a few modifications to make them better, whereas synthetic antibiotics (which are relatively uncommon) are synthesised in the lab.

Describe the different mechanisms of action of antibiotics, and for each give an example of an antibiotic utilising the mechanism.

• Chemotherapy II: Antibacterial Drugs

Examples of antibiotics of each class:

• Beta-lactam (cell wall synthesis inhibitors acting on transpeptidase)
• Penicillins- e.g. penicillin, ampicillin, amoxicillin (and many other drugs ending in -cillin)
• Cephalosporins- e.g. cephalexin, cefazolin (and many other drugs beginning with ceph- or cef-)
• Monobactams- e.g. aztreonam
• Carbapenems- e.g. imipenem, meropenem (and many other drugs ending in -penem)
• Glycopeptides (cell wall synthesis inhibitors binding to the D-ala-D-ala end of precursor side chains)- e.g. vancomycin
• Rifamycins (inhibits the enzyme that produces mRNA)- e.g. rifampin (and many other drugs beginning with rif-)
• 50S inhibitors (prevent protein elongation)
• Macrolides- e.g. azithromycin, erythromycin (and many other drugs ending in -mycin, but note that not all drugs ending in -mycin are macrolides)
• Clindamycin (surprise! A drug ending in -mycin that isn't a macrolide- Google says that it's a lincosamide)
• Streptogramins- e.g. quinupristin-dalfopristin
• Oxazolidinones- e.g. linezolid
• Aminoglycosides (bind to the 30S ribosomal subunit and cause misreading of the genetic code)- e.g. gentamicin, amikacin
• Tetracyclics (bind to the 30S subunit and block binding of tRNA)- e.g. doxycycline, minocycline
• Folate synthesis inhibitors (basically what it says on the box)
• Sulfonamides- e.g. sulfamethoxazole
• Trimethoprim- often co-administered with sulfamethoxazole to form co-trimoxazole
• Quinolones (inhibit DNA gyrase and topoisomerase)- e.g. ciprofloxacin (technically a fluoroquinolone, but close enough :P)
• Lipopeptides (insert into the lipid membrane, disrupting it)- e.g. daptomycin

Define “spectrum of activity” and give an example of a broad spectrum and narrow spectrum antibiotic.

"Spectrum of activity" refers to whether an antibiotic is broad-spectrum (affects a wide range of bacteria) or narrow-spectrum (affects only a select few types of bacteria). An example of a broad-spectrum antibiotic is ampicillin, which can be used against a lot of gram-positive and gram-negative bacteria, and has some resistance to beta-lactamases (an enzyme that often threatens to break down beta-lactams like ampicillin). An example of a narrow spectrum antibiotic is isoniazid, which pretty much only works against mycobacteria species, such as M. tuberculosis.

Explain the difference between empirical and targeted antibiotic therapy.

Empirical antibiotic therapy involves treatment based on symptoms and likely causes of those symptoms. Since you often don't know for sure what the causative agent is, empirical therapy tends to be more broad-spectrum. Targeted antibiotic therapy involves treatment based on information from laboratory tests, and as such can be more narrow-spectrum and targeted towards the specific organism. Often, you would start with empirical therapy (as it can take days to get a result from the lab). Then, once the causative agent is known, you would switch to targeted therapy.

Define the term Minimum Inhibitory Concentration.

The Minimum Inhibitory Concentration (MIC) is the minimum concentration of an antibiotic needed to inhibit growth of bacteria in vitro. There are different types of tests for determining MIC, which I have written about here.

Outline the four broad mechanisms by which bacteria can be resistant to antibiotics.

• Antibiotic Resistance

Describe in detail the resistance mechanisms of S. aureus to beta-lactam antibiotics.

As mentioned earlier, the main target of beta-lactams is the transpeptidase enzyme, which is involved in cell wall formation. If the transpeptidase is modified in a way that beta-lactams cannot bind, then that bacteria will become resistant to beta-lactams. In fact, this is how Staphylococcus aureus can develop a resistance to beta-lactams.

Usually, the transpeptidase (a.k.a. Penicillin Binding Protein, or PBP) in S. aureus is PBP2, encoded by the gene pbpB. However, if S. aureus acquires the mecA gene, it can create a new transpeptidase, called PBP2a. Beta-lactams cannot bind to and inhibit PBP2a, so S. aureus is now resistant to beta-lactams. Such strains of S. aureus are also known as Methicillin-resistant S. aureus, or MRSA for short.