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A colored electron microscopy image of methicillin-resistant staphylococcus aureus (MRSA), a bacteria commonly targeted by broad-spectrum antibiotics

The term broad-spectrum antibiotic can refer to an antibiotic that acts on the two major bacterial groups, gram-positive and gram-negative bacteria or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are used when a bacterial infection is suspected but the group of bacteria is unknown (also called empiric therapy), or when infection with multiple groups of bacteria is suspected. This is in contrast to a narrow-spectrum antibiotic, which is effective against only a specific group of bacteria. An example of a commonly used broad-spectrum antibiotic is ampicillin.

Uses

Broad-spectrum antibiotics are properly used in the following situations:

• Empirically, when the causative organism is unknown, but delays in treatment would lead to poor patient outcomes. This occurs, for example, in meningitis, where the patient can become fatally ill within hours if broad-spectrum antibiotics are not initiated.
• For drug resistant bacteria that do not respond to narrow-spectrum antibiotics.
• In the case of superinfections, where there are multiple types of bacteria causing illness, thus warranting either a broad-spectrum antibiotic or combination antibiotic therapy.
• For prophylaxis in order to prevent bacterial infections occurring. For example, this can occur before surgery, to prevent infection during the operation, or for patients with immunosuppression who are at high-risk for dangerous bacterial infections.

Bacterial targets

Although bacteria are biologically classified using taxonomy, disease-causing bacteria have historically been classified by their microscopic appearance and chemical function. The morphology of the organism may be classified as cocci, diplococci, bacilli (also known as "rods"), spiral-shaped or pleomorphic. Additional classification occurs through the organism's ability to take up the Gram stain and counter-stain; bacteria that take up the crystal violet dye stain are referred to as "gram-positive," those that take up the counterstain only are "gram-negative," and those that remain unstained are referred to as "atypical." Further classification includes their requirement for oxygen (ie, aerobic or anaerobic), patterns of hemolysis, or other chemical properties. The most commonly encountered groupings of bacteria include gram-positive cocci, gram-negative bacilli, atypical bacteria, and anaerobic bacteria. Antibiotics are often grouped by their ability to act on different bacterial groups. For example, 1st-generation cephalosporins are primarily effective against gram-positive bacteria, while 4th-generation cephalosporins are generally effective against gram-negative bacteria.

Empiric antibiotic therapy

Main article: Empiric therapy

Simplified diagram showing common disease-causing bacteria and the antibiotics which act against them.

Empiric antibiotic therapy refers to the use of antibiotics to treat a suspected bacterial infection despite lack of a specific bacterial diagnosis. Definitive diagnosis of the species of bacteria often occurs through culture of blood, sputum, or urine, and can be delayed by 24 to 72 hours. Antibiotics are generally given after the culture specimen has been taken from the patient in order to preserve the bacteria in the specimen and ensure accurate diagnosis. Alternatively, some species may be identified through a urine or stool test.

Selection of appropriate treatment

Clinicians often use a step-wise approach to determining appropriate empiric therapy. First, the potential diagnoses are established (for example, lobar pneumonia) and any predisposing risk factors are determined (for example, alcoholism puts patients at risk for Klebsiella pneumonia). Then, the most likely bacterial species for this type of infection are identified (for lobar pneumonia in healthy adults: S. pneumonia, H. influenzae, etc). Lastly, an antibiotic or group of antibiotics are chosen that are reliably effective against the potential species of bacteria (for example in lobal pneumonia, levofloxacin covers the majority of relevant bacteria). Clinicians aspire to choose empiric antibiotic combinations that cover all appropriate bacteria but minimize coverage of inappropriate bacteria, as to reduce the incidence of antimicrobial resistance (see below).

A community-wide antibiogram (that lists the susceptibility of community-acquired and hospital-acquired bacteria) is helpful in guiding empiric therapy. Many professional organizations (for example, the Infectious Disease Society of America) publish guidelines for empiric antibiotic therapy, as do hospitals, with their choices tailored for their specific resistance patterns. Many of these guidelines also offer guidance on antibiotic dose and duration of therapy.

Once a specific species has been identified and its susceptibilities determined, antibiotics can be "narrowed" to a medication which targets a more specific range of bacteria. If no specific species are identified, patients may continue on the empiric regimen.

Risks

Disruption of normal microbial flora

There are an estimated 10-100 trillion individual organisms that colonize the human body. As a side-effect of therapy, antibiotics can change the body's normal microbial content by attacking indiscriminately both the pathological and naturally occurring, beneficial or harmless bacteria found in the intestines, lungs and bladder. The destruction of the body's normal bacterial flora is thought to disrupt immunity, nutrition, and lead to a relative overgrowth in some bacteria or fungi. An overgrowth of drug-resistant microorganisms can lead to a secondary infection such as Clostridium difficile ("C. diff") or candidiasis ("thrush"). This side-effect is more likely with the use of broad-spectrum antibiotics, given their greater potential to disrupt a larger variety of normal human flora.

Antimicrobial resistance

Main article: Antimicrobial resistance

After continued exposure to an antibiotic, bacteria may develop changes in their structure or function that make them resistant to the antibiotic. These resistant organisms will live, while the susceptible organisms will die, leaving the population of bacteria entirely resistant to a given antibiotics. For example, after the discovery of penicillin and its subsequent use to treat bacterial infections, bacteria were found to have begun producing an enzyme, penicillinase, which rendered the penicillin molecule inactive. In response to this newly-acquired resistance, newer penicillins were produced that could not be de-activated by penicillinases. This cycle of bacteria evolving resistance to antibiotics and necessitating the development of new antibiotics has been referred to as a "bacterial arms race."

Some bacteria have developed resistance to multiple antibiotics, so-called "superbugs." Methicillin-resistant staphylococcus aureus (MRSA) is one example, and can be life-threatening without the appropriate therapy. Other examples of emerging resistant organisms include vancomycin-resistant enterococcus (VRE), Klebsiella pneumoniae carbapenemase (KPC), and extended-spectrum beta-lactamase producing E coli (ESBL).

In order to combat the rise of antimicrobial resistance, antimicrobial stewardship programs have begun that focus on educating clinicians to improve their use of antibiotics by focusing on evidence-based approaches to minimize resistance.

Examples of broad-spectrum antibiotics

In humans:

• Aminoglycosides (except for streptomycin)
• Ampicillin
• Amoxicillin
• Amoxicillin/clavulanic acid (Augmentin)
• Carbapenems (e.g. imipenem)
• Piperacillin/tazobactam
• Quinolones (e.g. ciprofloxacin)
• Tetracyclines
• Chloramphenicol
• Ticarcillin
• bactrim

In veterinary medicine, co-amoxiclav, (in small animals); penicillin & streptomycin and oxytetracycline (in farm animals); penicillin and potentiated sulfonamides (in horses).

References

[[Category:Antibiotics]]