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Introduction to Antibiotics

In the year 1928 a researcher named Sir Alexander Fleming was studying petri dishes inoculated with colonies of Staphylococcus. He discovered that one of his dishes featured a blob of mold that appeared to resist the growth of the microbes. This mold was identified as Penicillium notatum – an organism secreting a substance that inhibited the growth of bacteria. From this point forward, the world would never be the same as Fleming had came across a lab accident that would soon lead to the creation of penicillin.

Infectious disease proves to be among the more challenging fields of medical practice based largely off the abundance of pathogens and antibiotics used to treat them. There are multiple classes of antibiotics that are used commonly in practice today – contributing to a vast spectrum of potency and adverse effect profiles. This NCLEX^® Pharmacology Review of Antibiotics will help to develop a firm grasp of the drug classes as well as commonly used medications as they play a key role in daily practice.

Indications for Antibiotics

Since the inception of penicillin researchers have developed many different drugs of various mechanisms. Penicillin and like antibiotics feature a beta-lactam structure disrupts the stability of bacterial cell walls leading to its antibacterial properties. Various penicillins like amoxicillin, nafcillin, and oxacillin were created which closely relate to penicillin specifically. From there cephalosporins were derived which exhibit broader antibacterial properties.

It is imperative to understand that certain antibiotics are more effective against specific microbes than others. Bacteria are classified based on gram stains which determines properties like gram-positive and gram-negative bacteria. Vancomycin for example is an antibiotic that exhibits strong antibacterial properties against gram positive organisms – where penicillins and cephalosporins often have more mixed gram negative and gram-positive killing ability.

Table 1: Refer to the chart below to see a list of common indications for specific antibiotic classes:

Drug Classes for Antibiotics:

Penicillins: Among some of the first types of antibiotics this class features drugs like penicillin, ampicillin, amoxicillin, and methicillin. Over-time it became evident that many pathogens would develop resistance to these medications which helped contribute to the creation of penicillins with beta-lactamase inhibitors which are equipped with the ability to fight bacterial resistance mechanisms.

• MOA: Penicillins work by interfering with the synthesis of bacterial cell walls – eventually leading to lysis.
• Adverse Effects:
  • Hypersensitivity: Anaphylaxis, rash, fever, wheezing
  • GI upset: Nausea, vomiting, diarrhea
  • Superinfections
• Warnings
  • Requires dosage reductions in renal impairment (piperacillin, ampicillin)
• Nursing Considerations:
  • Screen clients with claimed allergies for true hypersensitivity reactions (e.g. rash, wheezing, anaphylaxis) ensuring the client did not just have an adverse effect (e.g. diarrhea, nausea, vomiting). Adverse effects do not result in a contraindication to this class of medications.
    • Monitor pulmonary function and for signs of allergic reaction.
  • Clients should be instructed to complete the full antibiotic regimen to encourage eradication of infection and discourage resistance.
  • Most penicillins can be taken with food to mitigate GI symptoms.

• Common Key Generics (Brands): 
  • Penicillin G (IV)
  • Penicillin VK (oral)
  • Nafcillin, oxacillin
  • Ampicillin, Ampicillin-sulbactam (Unasyn)
  • Amoxicillin (Amoxil), Amoxicillin-clavulanate (Augmentin)
  • Piperacillin, piperacillin-tazobactam (Zosyn)

Cephalosporins: Modeled off penicillins – cephalosporins have become among the most common antibiotics used today in various settings. There are currently five generations of cephalosporins that are classified based on their spectrum of activity.

• MOA: Similar mechanism compared to penicillins – cephalosporins fall under the beta-lactam classification.
• Adverse Effects:
  • Hypersensitivity: Clients with true penicillin allergies develop reactions with cephalosporin usage. As cephalosporin generations increase the risk of allergic reactions to people with penicillin allergies decreases.
  • GI upset: Nausea, vomiting, diarrhea
  • CNS: Headache, dizziness
  • Nephrotoxicity
  • Superinfections
• Precautions:
  • Ceftriaxone should not be reconstituted or mixed with a calcium-containing product (e.g. Ringer’s or Hartmann’s solution) due to risk of precipitation in the lungs or kidneys
• Nursing Interventions:
  • Screen for true penicillin allergies – ensuring a real hypersensitivity reaction.
  • Monitor pulmonary function and for signs of allergic reaction.
  • Generally safe in pregnancy.
  • Monitor renal function
  • Potential interaction with anticoagulants → bleed risk

• Common Key Generics (Brands): 
  • 1st Gen: Cefazolin, cefadroxil, cephalexin (Keflex)
  • 2nd Gen: Cefoxitin, cefprozil, cefuroxime
  • 3rd Gen: Ceftriaxone, cefixime, ceftazidime, cefpodoxime, cefdinir, ceftriaxone (Rocephin)
  • 4th Gen: Cefepime (Maxipime)
  • 5th Gen: Ceftaroline

Tetracyclines: Semisynthetic antibiotics derived from a structure found in a common soil mold. Main examples include minocycline, doxycycline, and tetracycline.

• MOA: Inhibit protein synthesis → inhibition of bacterial cell growth.
• Adverse Effects:
  • Not pregnancy safe
  • Teeth discoloration
  • Sun sensitivity
  • Weakening of skeletal bone structure
  • Hepatotoxicity
• Warnings:
  • Tetracyclines given to children under the age of 8 can cause permanent tooth discoloration if given for prolonged courses.
  • Accumulation of antibiotics can occur in fetal bone and teeth in pregnancy
  • Risk of hepatotoxicity in pregnant women
• Nursing Interventions:
  • Consult on increased sensitivity to light – avoid excessive sun exposure or use sunscreen
  • Avoid antacids and multivitamins with this medication
  • Interaction with birth control – caution with oral contraceptives; additional birth control may be needed
• Common Key Generics (Brands): 
  • Minocycline (Minocin)
  • Doxycycline (Doryx, Periostat)
  • Tetracycline
  • Tigecycline

Macrolides: This class of medications is often prescribed as an adjunctive therapy with other antibiotics. Examples includes erythromycin, clarithromycin, and azithromycin.

• MOA:  Interferes with protein synthesis in susceptible bacteria inhibiting bacterial cell growth.
• Adverse Effect:
  • QT prolongation
    • Monitor ECG
    • Avoid other QT prolonging drugs including fluoroquinolones
  • Hepatotoxic
  • N/V since taken with empty stomach
• Warnings:
  • Practice caution when using these medications as the suffix “mycin” exists in other drug classes such as tobramycin which is an aminoglycoside.
  • Renal dosing adjustments required for clarithromycin
  • QT interval prolongation – increased risk of torsade de pointes
• Contraindication:
  • Azithromycin in clients with a history of cholestatic jaundice or hepatic dysfunction
• Nursing Interventions:
  • Monitor for signs of QT prolongation and risk of atrial fibrillation
  • Monitor ALT and AST
  • Should be taken on an empty stomach
• Common Key Generics (Brands): 
  • Azithromycin (Zithromax)
  • Clarithromycin (Biaxin)
  • Erythromycin (Ery-Tab)

Fluroquinolones: Very broad-spectrum antibiotics capable of treating a wide array of infections. However, increasing safety concerns regarding adverse effects in elderly may discourage use of these medications. Examples of these medications includes ciprofloxacin (Cipro), levofloxacin (Levaquin), and ofloxacin (Floxin).

• MOA: Interference with DNA enzymes that are required for the growth of bacterial cells.
• Adverse Effects:
  • GI: Nausea, vomiting, diarrhea
  • CNS: Headache, dizziness
  • Risk for tendinitis and tendon rupture in elderly and in renal impairment
  • Photosensitivity – avoid long exposure to sun or use sunscreen
  • Neurologic effects (e.g. headache, dizziness, altered mental status)
  • Peripheral neuropathy
  • Risk of aortic aneurysm → dangerous bleeding and death
  • QT prolongation
• Warning:
  • The use of these medications should be restricted to severe-complicated infections
  • Increased risk of toxicity (e.g. tendon rupture, QT prolongation) in elderly
  • Avoid use in clients with aortic aneurysms and those with risk factors for aneurysms including peripheral atherosclerotic vascular diseases, advanced age, and hypertension.
  • Avoid during pregnancy – use safer alternatives when able
  • Risk of musculoskeletal toxicity in children
  • Avoid in clients with myasthenia gravis – as macrolides may precipitate neuromuscular-blocking activity
  • Increased risk of C. difficile – clients on extended periods of these medications should be given probiotics to reduce risk
• Nursing Interventions: 
  • Avoid in pregnancy and lactation
  • Monitor for signs and symptoms QT prolongation, tendon rupture, and bleeding in elderly and renally impaired clients
  • Avoid with antacids or multivitamins as these may reduce the efficacy of the antibiotic increasing resistance
  • Ensure all the medication is taken to discourage resistance
• Common Key Generics (Brands): 
  • Ciprofloxacin (Cipro)
  • Gemifloxacin
  • Levofloxacin (Levaquin)
  • Moxifloxacin
  • Ofloxacin (Floxin)

Aminoglycosides: These medications exhibit profound nephrotoxic and ototoxic properties which limits its use in practice to more severe infections. Examples include tobramycin, gentamicin, neomycin, and amikacin.

• MOA: Powerful antibiotics which demonstrate bactericidal inhibition of protein synthesis – particularly gram-negative bacteria.
• Adverse Effects:
  • Ototoxicity (tinnitus, vertigo, irreversible deafness)
  • Renal toxicity
  • GI: Nausea, vomiting, diarrhea
  • Heart palpitations
  • Hypersensitivity
• Warnings:
  • High risk of nephrotoxicity and ototoxicity – careful monitoring should be in practice when clients are on these medications
  • Risk of neuromuscular blockade is rare but serious – caution with myasthenia gravis
• Nursing Interventions:
  • Avoid with preexisting hearing loss due to ototoxic effects
  • May worsen herpes or mycobacterial infections
  • Renal toxicity (monitor Scr for increases > 1)
  • Avoid in pregnancy and lactation
  • Ensure properly dose by monitoring trough levels periodically
• Common Key Generics (Brands): 
  • Amikacin (Amikin)
  • Gentamicin
  • Neomycin
  • Streptomycin
  • Tobramycin (Tobrex)

Vancomycin: A very commonly used medication prescribed empirically for the treatment of a variety of infections – especially those that are suspected to be gram-positive or containing MRSA. Vancomycin is like aminoglycosides in adverse effects and dosing. This medication is often dosed based on the measurement of trough vancomycin concentrations in the serum.

• MOA: Inhibition of cell wall synthesis leading to decrease in bacterial cell growth – bactericidal in most gram-positive bacteria.
• Adverse Effects:
  • Thrombophlebitis when given too quickly, given via PICC line as preferred route
    • Watch for pain, redness and swelling
  • Red man’s syndrome
    • Severe hypotension
    • Flushing
    • Pruitis on face, neck, and extremities = too fast infusion
      • At least over > 60 minutes
  • Nephrotoxic
  • Ototoxic
  • Anaphylaxis → administer EPI
    • Hives
    • Angioedema
    • Wheezing
    • Trough level check 15-30 minutes before admin
      • Range 10-20
    • Watch for signs of toxicity
• Warnings:
  • Renal dose adjustments in renal impairment (refer to hospital procedures)
  • Do not infuse more than 5 mg/mL in concentration in less than 60 minutes – to avoid infusion-related reactions
  • Risk of extravasation and thrombophlebitis – ensure proper needle or catheter placement prior to infusion
  • Neutropenia with prolonged use
  • High risk of superinfection
  • Formulations containing polyethylene glycol (PEG 400) or N-acetyl D-alanine (NADA) not recommended for use in pregnancy due to risk of fetal malformations
• Nursing Interventions:
  • Dosing based on trough levels – check 15-30 minutes prior to administration of antibiotics
    • Moderate infections: Trough goal = 10-15
    • Severe infections: Trough goal = 15-20
  • Trough is usually drawn before the 4th or 5th dose
    • Initial loading dose is based on clients’ weight
  • Infuse bolus slowly over an hour to avoid adverse effects
  • Nephrotoxic monitor for the following
    • Scr > 1.3 = Bad for kidney
    • BUN > 20
    • Urine output < 30 ml/hr or less = kidney in distress
• Common Key Generics (Brands): 
  • Vancomycin (Vanco)

Sulfonamides: Used to be a highly utilized class of antibiotics but has fallen out of favor due to higher risk of hypersensitivity as well as a less favorable adverse effect profile. The primary example in use is sulfamethoxazole trimethoprim (Bactrim).

• MOA: Inhibition of folic acid synthesis which are precursors for RNA and DNA synthesis → inhibiting bacterial cell growth
• Adverse Effects:
  • Hypersensitivity: Contraindicated when a known or suspected sulfa allergy is present (including allergies to sulfa containing drugs e.g. sulfonylureas, thiazides)
  • GI: Nausea, vomiting, diarrhea
  • Renal: Crystalluria
  • CNS: Headache, dizziness
  • Bone marrow depression
  • Photosensitivity, rash
• Warnings: 
  • Risk of serious hypersensitivity reactions – screen for sulfa allergies
  • Blood dyscrasia – fatalities associated with severe reactions including agranulocytosis and aplastic anemia
  • Hepatic necrosis
  • Hyperkalemia – caution in clients with heart conditions
  • Hypoglycemia – caution in diabetics
  • Risk of thrombocytopenia
• Nursing Interventions:
  • Screen for true sulfa allergies – monitor for signs and symptoms of hypersensitivity
  • Can take with food with upset stomach
  • Not safe for pregnancy
  • Nephrotoxic monitor for the following
    • Scr > 1.3 = Bad for kidney
    • BUN > 20
    • Urine output < 30 ml/hr or less = kidney in distress

Example NCLEX^® Question for NCLEX^® Pharmacology Review of Antibiotics:

Key Nursing Tips for Antibiotics:

Infectious disease proves to be among the most challenging fields to understand when practicing in the medical field. This NCLEX^® Pharmacology Review of Antibiotics hopefully serves as a good overview of the many drugs and disease states that will be encountered frequently in practice. Below is a list of key nursing interventions to keep in mind when practicing in this field.

• Watch for interactions between certain medications with birth control (e.g. penicillins, and tetracyclines)
• Double check before administration in pregnancy and lactation
• No food when taking macrolides, tetracyclines, or fluoroquinolones (generally okay to take with food for penicillins and sulfonamides)
• Avoid or limit alcohol consumption with antibiotics
• Monitor troughs for aminoglycosides and vancomycin
• Monitor kidney function
• Screen for risk of true allergies – understand the difference between adverse effects or allergies (rash, wheezing, dyspnea, swelling, etc.)

Another core concept to infectious disease involves antibiotic resistance. Resistance is a growing concern in the microbiological world as bacteria have been repeatedly found to demonstrate the capacity to develop mechanisms which fight back against antibiotics. This is especially true for penicillins with microbes that develop the ability to destroy the antibiotic before it can reach its target. For this reason, it is crucial that practitioners understand that under dosing or overusing antibiotics can lead to resistance. This limits the selection of antibiotic agents that will therefore be effective against specific pathogens like MRSA which is a highly resistant strain of Staphylococcus bacteria.

Conclusion for Antibiotics:

The field of infectious disease is vast and complex – yet continues to grow and expand in ways that will continue to influence medical practice for years to come. There is a lot to know and understand when it comes to antibiotics and the various disease states used to treat them. Initially the level of information to know for this subject may appear daunting but over-time it should become more familiar, especially with practice.

Before administering antibiotics there are many different interventions nurses can make to ensure the safety of their clients. Screening for allergies, kidney function, pregnancy status, and for the specific microbials selected for the infection are all key interventions for medical teams to implement into their daily practice. It is imperative to have a general understanding of the various classes and nursing considerations to help prepare for the NCLEX^® exam and for future practice.

Example NCLEX^® Question for NCLEX^® Pharmacology Review of Antibiotics:

References:

1. Gaynes R. The Discovery of Penicillin—New Insights After More Than 75 Years of Clinical Use. Emerging Infectious Diseases. 2017;23(5):849-853. doi:10.3201/eid2305.161556.
2. UpToDate. https://www.uptodate.com/contents/penicillin-antistaphylococcal-penicillins-and-broad-spectrum-penicillins. Accessed April 3, 2020.
3. UpToDate. https://www.uptodate.com/contents/cephalosporins. Accessed April 3, 2020.
4. UpToDate. https://www.uptodate.com/contents/tetracyclines. Accessed April 3, 2020.
5. UpToDate. https://www.uptodate.com/contents/Azithromycin and clarithromycin. Accessed April 3, 2020.
6. UpToDate. https://www.uptodate.com/contents/Fluroquinolones. Accessed April 3, 2020.
7. UpToDate. https://www.uptodate.com/contents/Aminoglycosides. Accessed April 3, 2020.
8. UpToDate. https://www.uptodate.com/contents/Vancomycin: Drug information. Accessed April 3, 2020.
9. UpToDate. https://www.uptodate.com/contents/Trimethoprim-sulfamethoxole (co-trimoxazole): Drug information. Accessed April 3, 2020.