Cell wall inhibitors are antibiotics whose mechanism of action involves disruption of the bacterial cell wall, typically by preventing the peptidoglycan building blocks from being cross-linked together. Without an intact cell wall, bacteria cannot maintain normal metabolic functions and will either stop proliferating or die. Antibiotics under this category include the penicillins, cephalosporins, monobactams, carbapenems, and vancomycin.
Penicillins are a group of antibiotics typified by the presence of a beta-lactam ring in their molecular structure. Normally, bacteria create their cell wall by producing peptidoglycan subunits which are then cross-linked together by transpeptidase enzymes, also known as penicillin binding proteins. Penicillins bind to these enzymes, as their name suggests, and prevents the cell wall from being cross-linked together. This leads to bacterial cell death. There are different subclasses of penicillins. For example, oxacillin and nafcillin are resistant to the bacterial enzyme penicillinase and have activity against Staph aureus. Ticarcillin and piperacillin, conversely, have activity against Pseudomonas.
Cephalosporins are a class of antibiotics that are similar to penicillins in that both share a beta-lactam molecular structure and inhibit cross-linking of the bacterial cell wall. Cephalosporins are generally more broad spectrum, and have multiple generations which help define their activity. First generation cephalosporins like cefazolin have good gram positive coverage. As the generations go up, generally, more gram negative coverage is added. For example, second generation cephalosporins like cefuroxime have improved gram negative coverage. Check out our Cephalosporin Picmonics for more information.
Monobactams are another class of beta-lactam cell wall inhibiting antibiotics, and the only relevant member of this class is aztreonam. Aztreonam only has coverage against gram negative bacteria, in contrast to many other beta-lactam antibiotics. It is useful for patients with penicillin allergies.
Carbapenems, such as imipenem and meropenem, are a class of broad spectrum antibiotics. They share a beta-lactam molecular structure with the other cell wall inhibiting antibiotics and similarly work by preventing cell wall formation. Carbapenems are active against most bacteria including gram positive, gram negative, and anaerobic species. Cilastin is often given alongside these medications because it prevents their breakdown by the kidneys.
Beta-lactamase inhibitors are a type of medication given alongside certain penicillins to prevent breakdown of the antibiotic by the bacterial enzyme beta-lactamase. Beta-lactamase inhibitors include clavulanic acid, sulbactam, and tazobactam.
Protein synthesis inhibitors are antibiotics whose mechanism of action involves targeting ribosomes within bacteria and stopping production of vital proteins. The bacterial ribosome is composed of two parts named the 50S subunit and 30S subunit, and different antibiotics target different parts. Most are bacteriostatic, although some such as aminoglycosides are bactericidal.
Aminoglycosides are a class of antibiotic that inhibit the 30S subunit of the bacterial ribosome, leading to cell death or bactericidal activity. They are active against gram negative rods. Examples include gentamicin, neomycin and amikacin. Important side effects include nephrotoxicity and ototoxicity.
Macrolides are a class of antibiotic which bind to the 50S subunit of the bacterial ribosome and prevent protein production. This results in bacteriostatic activity and prevents bacteria from replicating. Macrolides include erythromycin, azithromycin and clarithromycin. They can treat multiple types of infections including Mycoplasma and Chlamydia.
Clindamycin inhibits the 50S ribosomal subunit and is an important antibiotic for its activity against gram positive bacteria and anaerobes. It is useful in cases of group A streptococcal infection as well as certain cases of MRSA. It can also be used in aspiration pneumonia or other infections where anaerobic organisms are suspected. An important side effect can be the development of pseudomembranous colitis, which occurs secondary to overgrowth of C. difficile.
Tetracyclines are another class of protein synthesis inhibitors and work by binding to the 30S bacterial subunit. Examples include tetracycline itself, doxycycline and minocycline. Tetracyclines are broad spectrum antibiotics and can treat various infections such as Lyme disease, Mycoplasma pneumonia, or Chlamydia infections. Side effects include photosensitivity and, in children, discoloration of teeth.
Linezolid inhibits the 50S ribosomal subunit and is only effective against gram positive bacteria. It is useful for treating cases of methicillin-resistant Staph aureus (MRSA) or vancomycin-resistant Enterococci (VRE). Side effects can include bone marrow suppression or peripheral neuropathy.
Chloramphenicol inhibits the 50S ribosomal subunit and has broad spectrum activity. However, due to significant side effects, it is not often used. Side effects include bone marrow suppression including aplastic anemia, as well as gray baby syndrome which is seen in exposed infants.
Fluoroquinolones are a class of antibiotic whose mechanism of action involves inhibition of the bacterial enzyme topoisomerase II (DNA gyrase) and topoisomerase IV. Inhibition of these enzymes prevents bacteria from properly replicating their DNA, resulting in cell death. These antibiotics often end with the suffix “-floxacin” and include ciprofloxacin, levofloxacin, and moxifloxacin. They are broad spectrum with excellent gram negative activity, including coverage of Pseudomonas in some cases. Side effects can include tendon rupture, cartilage damage in younger patients, and QT prolongation.
Sulfonamides are a class of antibiotic whose mechanism of action involves inhibition of bacterial DNA replication. Normally, bacteria require two enzymes in the folate pathway to carry out DNA synthesis: dihydropteroate synthase and dihydrofolate reductase. Sulfonamide antibiotics such as sulfamethoxazole inhibit the first enzyme, dihydropteroate synthase. Trimethoprim is often added to sulfonamides because it inhibits the second enzyme, dihydrofolate reductase. This combination results in broad spectrum activity against gram positive and negative organisms, including MRSA.
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