From Medscape Family Medicine
John H. Powers, MD; Janet A. Phoenix, MD, MPH; Diana M. Zuckerman, PhD
Introduction to Antibiotic Uses and Challenges
This review is intended to help primary care physicians prescribe the appropriate antibiotics for their patients. It provides background information on the origins of antibiotics, the classes of drugs, their mechanisms of action, and the organisms and diseases for which they are used. It includes information on when certain medications should be prescribed and in what order medications should be considered. Available antibiotics are a limited resource, and issues of resistance seem to be emerging faster than new antibiotics can become available. For that reason, prescription decisions by each physician for their patients can influence the effectiveness of antibiotics given to all patients, including patients of other physicians. The goal is to use antibiotics prudently, reserving antibiotics not intended for first-line use for instances when older, more commonly used medications fail. In addition, the adverse event profiles of various antibiotics differ, so administration of these drugs to individual patients should be based on the risk-benefit evaluation for each patient.
Background
Antibiotics are molecules used to treat or prevent disease in humans and animals. Their mechanism of action is to kill microbes or at least stop them from growing. Strictly speaking, the term antibiotics refers to naturally occurring molecules, and the term antimicrobials encompasses both naturally occurring and synthetically derived molecules. However, since the term antibiotic is so widely used, this review refers to all antimicrobials as "antibiotics."
The review concentrates on agents used to treat or prevent bacterial infections, rather than fungal or viral infections.
The term bacteriostatic is used to describe antibiotics that stop bacteria from growing.
The term bactericidal refers to antibiotics that kill bacterial or fungal cells outright.[1]
The clinical significance of bactericidal compared with bacteriostatic drugs is not clear in most infectious diseases. The human immune system also is important in curing infections, and stopping organisms from growing may be sufficient to allow the immune system time to cure the infection.[2]
Of note, antibiotics that appear potent in the test tube are not necessarily more beneficial in people when treating or preventing disease.
That is why data from human clinical trials are so important for understanding the benefits and risks of prescribing these powerful but often misused drugs.
Basic Principles of Prescribing Antibiotics
If used appropriately, antibiotics can help patients live longer and feel better. However, the idea that antibiotics "can’t hurt" is incorrect.
Antibiotics can cause serious and life-threatening adverse reactions, such as anaphylaxis and liver toxicity.
In fact, antibiotics are the second most common cause of anaphylaxis in the United States after food allergies.[3]
Less serious but more common adverse events include nausea, vomiting, diarrhea, and skin rash.
Antibiotics have no efficacy against viral infections, such as the common cold or flu. Therefore, prescribing for a viral infection is not warranted. There is no benefit to potentially exposing the patient to adverse events from the antibiotic. In addition, prescribing antibiotics for conditions when they are not needed contributes to antimicrobial resistance, thereby increasing the risk that these drugs will not be effective when they are needed. Resistance can affect not only the person who takes the drug but others to whom resistant bacteria may spread.
It is important to use these drugs only when the benefits outweigh the risks.
The first principle in prescribing antibiotics is to correctly diagnose a bacterial infection for which specific antibiotics are known to be effective compared with placebo.
Even when a bacterial infection is present, in some cases (eg, skin abscesses or asymptomatic bacteriuria), antibiotics may have no effect, and other therapy (eg, drainage of the abscess) may be indicated.
In other cases, such as ear infections, sinus infections, or bronchitis, the benefit of antibiotics is unclear and may be small, so it is necessary to determine the likely risks and benefits for that individual patient.
The second principle is to choose a drug that has the fewest adverse events for that patient. This maximizes the benefit and minimizes the risk.
Third, clinicians should choose a drug that has efficacy in treating or preventing the disease but leaves other bacteria in the body intact. This minimizes the spread of resistance and leaves intact the body’s own organisms that are a natural defense against other invading organisms.
Finally, the clinician should choose a drug that is convenient and inexpensive. Surprisingly, there is no clear evidence that drugs taken once each day have better adherence rates than twice-daily drugs.
In addition to the cost to the patient, antibiotics are one of the largest expenditures of hospital pharmacies, so cost-effective use of these drugs is important to contain healthcare costs.[4]
Gram Classification of Bacterial Cells
Bacterial cells are often grouped into categories on the basis of characteristics of their cell wall structure.
The terms gram-positive and gram-negative reflect the staining technique used to distinguish these differences.
Gram-positive cells retain crystal violet in an ethanol solution and thus appear purplish-blue when viewed under the microscope. Gram-negative bacteria do not retain crystal violet but do retain a counterstain, safranin, and so appear pinkish-red under the microscope.
One cannot classify all bacteria by using this technique. The differences in staining are due to differences in the structures of the outer surfaces of bacteria. Gram-positive and gram-negative cells both have a peptidoglycan layer as part of their cell wall structure. Gram-negative cells have an intact outer membrane that provides a barrier to the uptake of the stain. The membrane displays proteins and carbohydrates and provides a structural barrier to the force of osmotic pressure that could disrupt the cell. In gram-positive organisms, the peptidoglycan layer itself is usually thicker and multilayered than in gram-negative bacteria and displays proteins and carbohydrates that provide the osmotic structural barrier. These outer membrane proteins can act as binding sites, permitting the bacterial cells to penetrate human tissues.
Mechanisms of Bacteriostatic or Bactericidal Action
Many mechanisms exist by which antibiotics exert their effect on bacterial cells (Table 1). These differ depending on the characteristics of the bacterial organisms. Some antibiotics act by inhibiting the synthesis of the cell wall constituents, and so disrupt peptidoglycan substrates or enzymes involved in peptidoglycan assembly or cross-linking of the cell wall. Others block the synthesis of proteins essential for the functioning of bacterial or fungal cells. This activity generally takes place in the ribosomes at the 30S or 50S subunit sites through blockade of one or more of the biosynthetic steps. Another mechanism of action is the blockade of DNA synthesis or repair. This is generally accomplished through inhibition of the topoisomerases, which are essential for cell viability.
Table 1. Examples of Common Antibiotics and Their Mechanism of Action
Mechanisms of Action Antibiotics
Inhibitors of cell wall biosynthesis Penicillins, cephalosporins, vancomycin, bacitracin
Inhibitors of protein synthesis Tetracyclines, macrolides, aminoglycosides, lincosamides, streptogramins, oxazolidinones
Inhibition of DNA replication/repair Ciprofloxacin, rifampin, fluoroquinolones
Data from Walsh.[1]
http://www.medscape.com/viewarticle/723457?src=mp&spon=9&uac=71630FV
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