Macrolides and ketolides are classes of antibiotics prescribed to combat bacterial infections. They function by interfering with the bacteria’s ability to produce proteins, which are necessary for their survival and multiplication.
How These Antibiotics Work
Macrolides and ketolides target the bacterial ribosome, a complex molecular machine responsible for protein synthesis. Specifically, they bind to the 50S ribosomal subunit. This binding action obstructs the ribosome’s ability to move along the messenger RNA (mRNA) and add amino acids to the growing protein chain, a process known as translocation.
By inhibiting this step, macrolides and ketolides prevent bacteria from synthesizing the proteins they require for growth and reproduction. This interference with protein production can either stop the bacteria from multiplying (a bacteriostatic effect) or, in some cases, lead to the bacteria’s death (a bactericidal effect). The targeted nature of this mechanism ensures that human cells, which have different ribosomal structures, are largely unaffected.
Common Uses
Macrolides and ketolides are used for bacterial infections, particularly those affecting the respiratory tract. These include such as community-acquired pneumonia, bronchitis, and sinusitis. They also treat skin and soft tissue infections.
Beyond respiratory and skin ailments, these antibiotics are effective against sexually transmitted infections. Their broad spectrum also extends to atypical microorganisms, such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila, which are common causes of pneumonia. Macrolides can also be an alternative for patients who have allergies to penicillin.
Understanding the Differences
Ketolides are a newer generation of antibiotics derived from macrolides, specifically erythromycin A. The primary structural modification distinguishing ketolides from macrolides is the replacement of a sugar molecule (L-cladinose) at position 3 of the macrolactone ring with a keto group. This change provides ketolides with greater acid stability and enhances their ability to bind to the bacterial ribosome.
This structural alteration in ketolides like telithromycin allows them to maintain activity against bacterial strains that have developed resistance to macrolides. Telithromycin exhibits increased potency and a lower risk of inducing bacterial resistance compared to macrolides. It achieves this by binding to two distinct regions (domains II and V) of the 23S ribosomal RNA, whereas macrolides typically bind only to domain V. This dual binding helps ketolides overcome resistance mechanisms like ribosomal methylation, which can alter the macrolide binding site.
Important Considerations for Patients
Patients taking macrolides or ketolides may experience side effects, with gastrointestinal upset being common, including nausea, vomiting, and diarrhea. Dizziness can also occur. Less common but serious side effects include liver toxicity, particularly with ketolides like telithromycin, which necessitates regular monitoring of liver function for patients on these drugs.
These antibiotics can also interact with other medications, potentially leading to increased drug levels and adverse effects. For example, macrolides, especially erythromycin and clarithromycin, can interfere with the cytochrome P450 CYP3A4 enzyme in the liver, which metabolizes many drugs, including statins and anticoagulants like warfarin. Complete the entire prescribed course of antibiotics, even if symptoms improve, to ensure the infection is fully eradicated and to help prevent the development of antibiotic resistance. Patients should always consult their healthcare professional about any concerns regarding side effects or potential drug interactions.