Chemotherapeutics: Drugs for Various Infections

Key Terms

• Bactericidal: A substance that causes the death of bacteria, usually by interfering with cell membrane stability or with proteins or enzymes necessary to maintain the cellular integrity of the bacteria.
• Bacteriostatic: A substance that prevents or slows the replication of bacteria, usually by interfering with proteins or enzyme systems necessary for the reproduction of the bacteria.
• Culture: A sample of the bacteria (e.g., from sputum, cell scrapings, urine) to be grown in a laboratory to determine the species of bacteria causing a particular infection.
• Prophylaxis: Treatment to prevent an infection before it occurs or to prevent a second infection, as in the use of antibiotics to prevent bacterial endocarditis in high-risk patients or antiprotozoals to prevent malaria.
• Resistance: The ability of pathogens over time to adapt to an anti-infective to produce cells that are no longer affected by a particular drug.
• Selective Toxicity: The ability to affect certain proteins or enzyme systems that are used by the infecting organism but not by human cells.
• Sensitivity Testing: Evaluation of pathogens obtained in a culture to determine which anti-infectives will be effective against the organisms causing a particular infection.
• Spectrum: Range of bacteria against which an antibiotic is effective (e.g., broad-spectrum antibiotics are effective against a wide range of bacteria; narrow-spectrum antibiotics are effective only against very selective bacteria).
• Superinfection: Infections that occur when opportunistic pathogens have the opportunity to invade tissues and cause infections because the normal flora bacteria that kept them in check have been destroyed by antibiotic therapy.
• Aerobic: Bacteria that depend on oxygen for survival.
• Anaerobic: Bacteria that survive without oxygen, which are often found in chronic infections and in the GI tract.
• Antibiotic: Chemical that inhibits the growth of specific bacteria or causes the death of susceptible bacteria.
• Gram-negative: Bacteria that have only a thin layer of peptidoglycan, making them less likely to absorb stain or become decolorized by alcohol; these bacteria are frequently associated with infections of the genitourinary or gastrointestinal (GI) tract.
• Gram-positive: Bacteria that have cell walls with more peptidoglycan layers, which absorb more stain or resist decolorization with alcohol during preliminary identification; these bacteria are frequently associated with infections of the respiratory tract and soft tissues.
• Gram Staining: A process used to identify between types of bacteria based on differences of components in their cell walls.
• Synergistic: Drugs that work together to increase drug effectiveness.

Pathogens

• Pathogens are microbes that cause disease.
• Types of pathogens:
  • Viruses
  • Bacteria
  • Fungi
  • Unicellular organisms
  • Multicellular animals
• Pathogenicity: The ability of an organism to cause infection.
• Virulence: Minute numbers of microbes can produce disease
• How pathogens enter the body: broken skin, inhalation, ingestion, or via a mucous membrane

Micro-Organism Identification

1. Gram Stain: Examination of the body fluid aspirate under a microscope to ID the organism.
   • This is done by traditional laboratory testing of body fluid (blood, urine, sputum, wound drainage, or other fluid).
2. Culture: A portion of the host’s body fluid aspirate is applied to a medium and growth of the organism is promoted over several days.
   • This technique must be used if the gram stain produces no definitive ID.
   • The sample of body fluid MUST be taken PRIOR to treatment with antimicrobial medications!
   • The nurse MUST use great care to take the sample using aseptic technique to prevent cross-contamination.
   • A correction/adjustment of the prescribed broad-spectrum antiinfective may need to be changed after culture results.

Classifying Bacteria

• Gram stain – crystal violet stain color
  • Gram positive
  • Gram negative
• Cellular shape
  • Bacilli - rods
  • Cocci - spheres
  • Spirilla – spirals
• Oxygenation
  • Aerobic – thrive in oxygen
  • Anaerobic – thrive without oxygen

Resistance

• Resistance to conventional drug therapy.
• Resistance to bacteria, not patient resistance.
• The longer an antibiotic is used, and the more often it is prescribed, the larger the percentage of resistant strains.

Acquired Resistance

• Mutations: Bacteria replication with errors in genetic code.
• Mutated bacteria survive in more harsh conditions.
• Insensitive to anti-infective medications used for destruction of original parent bacteria.

Treating Resistance

• The microorganism can survive and even produce cells that are no longer affected by a drug.
• Antiinfective therapy should consider developing resistance and use one that is known to affect the specific microorganism.
• Can lead to uncontrollable epidemics.
• Antiinfective prescriptions should be strong enough to kill microorganisms and for long enough to prevent recurrence.

Classifying Medications for Infection

• Either antibiotic, antifungal, antimicrobial, antiseptic.
• First we need to define/identify which microbes are susceptible to each medication.
• Once we know this, we can choose which type of antibiotic to use: Either narrow-spectrum or broad-spectrum.
  • Narrow-spectrum – Only a few bacteria are sensitive.
  • Broad-spectrum – A wide variety of bacteria are sensitive.
• Then, ID the mechanism of action of each antibacterial medication.
• This will allow us to make a decision as to which antibacterial medication is best suited to combat the bacteria: kill it, or slow its growth allowing the host to kill the bacteria.
  • Bactericidal medications – directly lethal to the microbe.
  • Bacteriostatic medications – slow the microbe growth enough to allow the host’s natural immune system to attack and destroy the microbe.

How Antimicrobials Work

1. Destroy the bacterial cell wall without affecting mammalian cells.
2. Inhibit a bacteria’s enzyme necessary for the bacteria’s survival.
3. Impair protein synthesis in the bacteria’s ribosomes, again without affecting mammalian cells.

• Critical that all anti-infectives be finished as prescribed (unless adverse effects arise). Stopping the medication early promotes resistant strains.

Adverse Reactions to Anti-Infectives

• Host cells can be damaged, particularly if immunocompromised.
• NO ANTI-INFECTIVE AGENT IS COMPLETELY FREE OF ADVERSE EFFECTS.
• Most common adverse reactions:
  • Toxic effects on kidney, GI tract, nervous system.
  • Hypersensitivity reaction.
  • Superinfections.

Superinfection/Suprainfection

• Secondary infection that develops during the treatment of the primary infection.
• Cause: normal microorganisms or host flora in body destroyed.
• Host flora is body’s own defense mechanism against bacteria.
• Allows for overgrowth of pathogenic microbes.
• Mainly caused by broad-spectrum antibiotics or use of multiple antibiotics, worsened by compromised immunity.
• It is the provider’s responsibility to:
  1. Be aware of the emergence of resistant strains.
  2. Use ABX prescriptions responsibly.
  3. Avoid prescribing newer ABX.
  4. Ensure dose is strong enough and for a long enough period of time to eradicate the infection.

Superinfections Examples

• MRSA- Methicillin Resistant Staphylococcus Aureus- Typically found on the skin
• Cdiff- Clostridioides Difficile- Causes a colitis found in the stool. Severe Diarrhea
• VRE- Vancomycin Resistant- Typically found in Urine and Stool
• ESBL (Extended spectrum Betalactamase resistant- Found in Urine Typically

Host Factors Affecting Treatment

1. The host’s immune system
2. The host’s site of infection
3. The host’s age
4. Is the host complicated by pregnancy
5. Has the host had an allergic reaction to an antimicrobial in the past
6. Does treatment require more than one antimicrobial (combination therapy)

Host Factors Cont’d

• The host’s immune system
  • With an INTACT immune system, the host will automatically work to suppress the organism.
    • It is appropriate for the provider to prescribe EITHER bactericidal or bacteriostatic
  • With COMPROMISED immune system, the host may or may not work to suppress the organism, but will often become overwhelmed
    • The provider MUST prescribe a strong bactericidal medication, and often more than one for expanded coverage

Host Factors Cont’d - Site of Infection

• The host’s site of infection
  • Not all sites are easy to treat – based on location
    • Infections in the CSF – this requires the medication to cross the BBB (think meningitis)
    • Bacterial infection in the heart – the heart is injured, a thrombus forms, bacteria infect the thrombus, and then new thrombus forms over the infected one, making it hard for antimicrobials to fight the infection.
    • Abscesses (pus/hematoma) –block antimicrobials from working
    • Anywhere there is poor circulation/blood supply
    • Surgical intervention can improve effect of antimicrobials
    • Phagocytes that attack foreign objects (like a pacemaker, graft, heart valve, prosthesis, surgical mesh) have less ability to destroy micro-organisms that colonize the foreign object

Host Factors Cont’d - Age

• The Host’s Age
  • Dose must be tailored to size, age, and liver/kidney function (usually reduced dose)
  • Infants have underdeveloped kidney and liver function
    • This causes SLOW excretion of medications
    • Increased risk for toxicity
  • Elderly have slow metabolism and excretion
    • Increased risk for toxicity

Host Factors Cont’d - Pregnancy

• Pregnancy
  • Damage and harm to a developing fetus
    • Sulfonamides – kernicterus
    • Gentamicin – hearing loss
    • Tetracyclines – tooth discoloration
  • Lactation can also transfer dangerous levels of medication to the newborn

Host Factors Cont’d - Allergic Reaction

• Previous Allergic Reaction
  • Some are life threatening
  • Usually penicillins
  • Should not be given again after any true allergy, or potential allergy, unless benefit greatly outweighs the risk
  • Significantly narrows treatment options and antibiotic choices

Host Factors Cont’d - Combination Therapy

• Combination Therapy
  • Combination therapy can be either ADDITIVE, POTENTIATING "synergistic", or ANTAGONISTIC
  • Soooo….why do it?
    • Used for severe infections, or infections with more than one organism, or for immunocompromised persons
    • Potentially delays the emergence of resistant strains (like when treating TB or HIV)
    • Allows for smaller doses of each medication, lessening chance of toxicity
    • More effective than just one medication
  • Soooo…..why not do it?
    • ADVERSE EFFECTS – Increased resistance to antimicrobials, increased cost, more adverse/toxicities, antagonistic effect among antimicrobials, increased risk of superinfection

Prophylaxis

• Antimicrobials can be given for prophylaxis.
• Prevention of development of infection
• Useful for surgeries involving the heart, GI/GU tract, peripheral vascular areas, orthopedic, or gynecological.
• Prevention of STD’s after exposure.
• Antimicrobials for:
  • Recurring UTI’s
  • Patients with known cardiac valve disease or prosthetic heart valves, prior to ANY dental or other invasive procedure (prevent endocarditis).

Nosocomial Infections

• Acquired in hospital or other healthcare setting.
• Often MORE resistant to common antibiotics

Principles of Preventing Infection

• Wash hands, before/after patient care
• Remove invasive catheters as soon as it’s safe to do so
• Maintain up-to-date immunization status
• Follow transmission-based precautions to prevent the spread of resistant micro-organisms

Nursing Considerations and Education

• Recognition of invasive procedures requiring strict aseptic technique – If it’s sterile, keep it sterile!
• Educate patients on the importance of taking ALL the medication to prevent recurrence of infection or development of resistance.
• Educate patients not to use left-over antibiotics for other infections.
• Prevent transmission of infection by keeping individuals isolated.
• As cultures grow, make sure the patient’s current prescription is appropriate for the pathogen.
• Monitor patient for improvement of symptoms.
• Instruct all women of child-bearing age to use a backup contraceptive.
• ALWAYS, ALWAYS, ALWAYS ASK FOR HISTORY OF PREVIOUS ALLERGY!
• Careful monitoring of peak and trough when indicated.

Peak vs Trough

• The therapeutic window is the range of drug concentrations within which a drug is effective without causing significant toxicity.
• Peak: C Max
• Trough: C Min

Anti-Infective Agents Across the Lifespan

• Children
  • Use anti-infectives with caution; early exposure can lead to early sensitivity.
  • Controversy is widespread regarding the use of antibiotics to treat ear infections, a common pediatric problem. Some believe that the habitual use of antibiotics for what might well be a viral infection has contributed greatly to the development of resistant strains.
  • Because children can have increased susceptibility to anti-infectives' effects on the gastrointestinal (GI) and nervous systems, carefully monitor their hydration and nutritional status.
• Adults
  • Adults often demand anti-infectives for a "quick cure" of various signs and symptoms. Drug allergies and the emergence of resistant strains can be a challenge with this group.
  • Extreme caution must be exercised in the use of anti-infectives in people who are pregnant or lactating. Many anti-infectives can affect the fetus and cross into human milk, leading to toxic effects in the neonate.
• Older Adults
  • Older patients often do not present with the same signs and symptoms of infection that are seen in younger people.
  • The older patient is susceptible to severe adverse GI, renal, and neurological effects and must be monitored for nutritional status and hydration during drug therapy.
  • Anti-infectives that adversely affect the liver and kidneys must be used with caution in older patients, who may have decreased organ function.