* ANTIMICROBIALS

Dr. Ahmed Mohammed Elamin

PHD of Clinical Pharmacolgy
* • Identify the classifications and actions of antimicrobial
medications
* • Give examples of when, how, and to whom antimicrobial
drugs may be administered
* • Identify the side effects and special considerations
associated with antimicrobial therapy
* • Include considerations and implications of using
antimicrobial medications across the lifespan
* • Include evidence-based concepts when using the nursing
process

*Learning Objectives
* A pathogen is defined as an organism causing disease to its
host. Pathogens, when overgrown, can cause significant health
problems or even death for your patients
* A culture is a test performed to examine different body
substances for the presence of bacteria or fungus. These
culture samples are commonly collected from a patient’s blood,
urine, sputum, wound bed, etc. Nurses are commonly
responsible for the collection of culture samples and must be
conscientious to collect the sample prior to the administration
of antibiotics. Antibiotic administration prior to a culture can
result in a delayed
* A sensitivity analysis is often performed to select an effective
antibiotic to treat the microorganism. If the organism shows
resistance to the antibiotics used in the test, those antibiotics
will not provide effective treatment for the patient’s infection.

*Definitions
* A gram stain is another type of test that is used to assist in
classification of pathogens.
* Gram stains are useful for quickly identifying if bacteria are
“gram positive” or “gram negative,” based on the staining
patterns of their cellular walls.
* Utilizing gram stain allows microbiologists to look for
characteristic violet (Gram +) or red/pink (Gram -) staining
patterns when they examine the organisms under a
microscope.
* Identification of bacteria as gram positive or gram negative
assists the healthcare provider in quickly selecting an
appropriate antibiotic to treat the infection.
* Spectrum of activity is one of the factors that providers use
when selecting antibiotics to treat a patient’s infection.
* A narrow-spectrum antimicrobial targets only specific
subsets of bacterial pathogens.
* For example, some narrow-spectrum drugs only target gram
positive bacteria, but others target only gram negative
bacteria.
* A broad-spectrum antimicrobial targets a wide variety of
bacterial pathogens, including both gram positive and gram
negative species, and is frequently used to cover a wide
range of potential pathogens.

* Broad-Spectrum vs. Narrow

Spectrum Antimicrobials
 *Antibacterial drugs can be either bacteriostatic or
bactericidal in their interactions with the
offending bacteria.
*Bacteriostatic drugs cause bacteria to stop
reproducing and growth.
*In contrast, bactericidal drugs kill their target
bacteria.

* Antibacterials Actions — Bacteriostatic

vs. Bactericidal
* Another consideration in the selection of an antibacterial
drug is the drug’s mechanism of action.
* Each class of antibacterial drugs has a unique mechanism of
action , the way in which a drug affects microbes at the
cellular level.
* For example, cephalosporins act on the integrity of the cell
wall.
* In contrast, aminoglycosides impact ribosome function and
inhibit protein synthesis, which stops the proliferation of
cells.

*Mechanism of Action
Figure Various mechanisms of actions of
antimicrobial medication
 * Penicillin was the first antibiotic discovered and its detection
came as a bit of an accident. In 1928, Alexander Fleming, a
professor of bacteriology at St. Mary’s Hospital in London,
discovered penicillin accidentally growing in a petri dish in his
lab.
* The penicillin was the result of mold juice that had grown there
inadvertently. Fleming noted that this “mold juice” inhibited the
growth of Staphylococcus bacteria that was previously growing in
the petri dish.
* Subsequently, the first antibiotic discovery was made.

*Penicillins
* Indications: Penicillins are prescribed to treat a variety of infectious
processes such as Streptococcal infections, Pneumococcal infections,
and Staphylococcal infections. Penicillins may be administered orally,
IV, or intramuscularly.
* Mechanism of Action: Penicillins are bactericidal and kill bacteria by
interfering with the synthesis of proteins needed in their cellular walls.
When the bacterial cell wall is impaired, the cell is rapidly broken down
and destroyed.
* Examples: penicillin V (PO), penicillin G (IV), amoxicillin,
piperacillin/tazobactam (combination product)
* Side effects: Common: nausea, vomiting, epigastric distress, diarrhea.
* Administration Considerations:
* Check for allergies to penicillin or cephalosporins
* Obtain culture, if ordered, before first dose
* Take w/ full glass of water; no acidic juice
* Best absorbed orally on empty stomach; give with food if stomach
upset
* If high doses; monitor INR, platelets,PT
*Cephalosporins are a slightly modified chemical “twin” to
penicillins due to their beta lactam chemical structure.
Because of similarities of the beta-lactam ring structure,
spectrum of activity, and route of administration across
different classes of medications, some patients who have
allergies to penicillins may experience cross-sensitivity to
cephalosporins.
*Indications: Cephalosporins are used to treat skin and skin-
structure infections, bone infections, genitourinary
infections, otitis media, and community-acquired
respiratory tract infections.
*Mechanism of Action: Cephalosporins are typically
bactericidal and are similar to penicillin in their action
within the cell wall.

*Cephalosporins
* Cephalosporins are grouped into “generations” by their
antimicrobial properties. The 1st-generation drugs are effective
mainly against gram-positive organisms.
* Higher generations generally have expanded spectra against
aerobic gram negative bacilli. The 5th-generation
cephalosporins are active against methicillin-resistant
Staphylococcus aureus (MRSA) or other complicated infections.
* 1st generation: cephalexin Cefazolin
* 2nd generation: cefuroxime
* 3rd generation: ceftriaxone
* 4th generation: cefepime
* 5th generation: ceftolozane
* Administration Considerations:
* Check for allergies, including if allergic to penicillin
* Dosage adjustment if renal impairment
* Use with caution with seizure disorder
* PO: Administer without regard to food; if GI distress, give with
food
* IV: Reconstitute drug with sterile water or normal saline; shake
well until dissolved. Inject into large vein or free-flowing IV
solution over 3-5 minutes
* Drug interaction: anticoagulants
* Side/ Adverse Effects:
* Common side effects: -Nausea –Vomiting -Epigastric distress –
Diarrhea
* Nephrotoxicity if preexisting renal disease
* Elevated INR and bleeding risk
* Development of hemolytic anemia
* Carbapenems are a beta- lactam “cousin” to penicillins and
cephalosporins.
* Indications: Carbapenems are useful for treating life-
threatening, multidrug-resistant infections due to their broad
spectrum of activity. These antibiotics are effective in treating
gram-positive and gram-negative infections. Because of their
broad spectrum of activity, these medications can be especially
useful for treating complex hospital-acquired infections or for
patients who are immunocompromised.
* Mechanism of Action: Carbapenems are typically bactericidal
and work by inhibiting the synthesis of the bacterial cell wall.

*Carbapenems
* Specific Administration Considerations: Carbapenems are
similar to cephalosporins. Cross sensitivity may occur in
patients allergic to pencillin orcephalosporins
* Side/Adverse Effects: Similar to cephalosporins
* Example:
* imipenem
*Like penicillins, cephalosporins, and carbapenems,
monobactams also have a beta-lactam ring structure.
*Indications: Monobactams are narrow-spectrum
antibacterial medications that are used primarily to treat
gram-negative bacteria such as Pseudomonas aeruginosa.
*Mechanism of Action: Monobactams are bactericidal and
work to inhibit bacterial cell wall synthesis.
*Specific Administration Considerations: Patients taking
monobactams may experience adverse effects similar to
other beta-lactam medications, so nurses should monitor
for GI symptoms, skin sensitivities, and coagulation
abnormalities.
*Example: aztreonam

*Monobactams
*Sulfonamides are one of the oldest broad-spectrum
antimicrobial agents that work by competitively
inhibiting bacterial metabolic enzymes needed for
bacterial function.
*Indications: Sulfonamides are used to treat urinary
tract infections, otitis media, acute exacerbations
of chronic bronchitis, and travelers’ diarrhea.
*Mechanism of Action: This mechanism of action
provides bacteriostatic inhibition of growth against
a wide spectrum of gram-positive and gram
negative pathogens.

*Sulfonamides
* Specific Administration Considerations: Allergic reactions to
sulfonamide medications are common and, therefore, patients
should be monitored carefully for adverse effects including
delayed hypersensitivity reactions. Sulfonamide medications
increase the risk of crystalluria that can cause kidney stones or
decreased kidney function; therefore, patients should increase
their water intake while taking these medications.
* Side/Adverse Effects:
* SAFETY:
* Sulfonamides, including sulfonamide-containing products such as
sulfamethoxaole /trimethoprim, should be discontinued at the
first appearance of skin rash of any sign of adverse reaction
* Examples:
* trimethoprim –
* sulfamethoxazole
* Indications: Fluoroquinolones may be used to treat pneumonia or
complicated skin or urinary tract infections.
* Mechanism of Action: Fluoroquinolones are a synthetic antibacterial
medication that work by inhibiting the bacterial DNA replication. They
are bacteriocidal due to the action they take against the DNA of the
bacterial cell wall. Many fluoroquinolones are broad spectrum and
effective against a wide variety of both gram-positive and gram-
negative bacteria.
* Specific Administration Considerations: Patients taking oral
fluoroquinolones should avoid the use of antacid medication as antacids
significantly impede absorption. Patients should also be instructed to
take oral fluoroquinolones with a full glass of water two hours before or
after meals to enhance absorption and prevent crystalluria.
Fluoroquinolone therapy is contraindicated in children except for
complicated UTIs, pyelonephritis, plague, or post Anthrax exposure and
should be used cautiously in pregnancy

*Fluoroquinolones
* IV: Infuse 500 mg or less over 60 minutes and doses of 750 mg
over 90 minutes
* Dosage adjustment if renal or hepatic impairment
* Use cautiously if history of seizures
* Side/Adverse Effects:
* Discontinue immediately if peripheral neuropathy, CNS effects,
or muscle weakness in patients with Myasthenia Gravis
* Monitor for: -GI upset –Hypersensitivity –Photosensitivity –
Hypoglycemia
* Examples: ciprofloxacin, norfloxacin, ofloxacin and levofloxacin
* Macrolides are complex antibacterial broad-spectrum
medications that are effective against both gram-positive and
gram-negative bacteria.
* Mechanism of Action: Macrolides inhibit RNA protein synthesis
and suppress reproduction of the bacteria. Macrolides are
bacteriostatic as they do not actually kill bacteria, but inhibit
additional growth and allow the body’s immune system to kill
the offending bacteria.
* Indications: Macrolides are often used for respiratory infections,
otitis media, pelvic inflammatory infections, and Chlamydia.
* Specific Administration Considerations: Macrolides can have
significant impact on liver function and should be used
cautiously in patients with liver disease or impairment.
* Cyp450 enzyme cytochrome

*Macrolides
* IV: Reconstitute and shake until well dissolved. Infuse a 500-mg
dose of azithromycin IV over 1 hour or longer. Never give as a
bolus or IM injection
* May prolong heart QT interval segment. Monitor for dysrhythmias
* PO: Reconstitute suspension with water. Can be given with or
without food. Take with food if GI upset occurs
* Side/ Adverse Effects:
* GI upset, Hypersensitivity, Photosensitivity
* Discontinue immediately if: -QT prolongation or dysrhythmias -
Signs of liver damage or jaundice- Onset or worsening of
myasthenia gravis
* Examples:
* erythromycin
* Azithromycin
* Clarrithomycin
* Aminoglycosides are a potent broad spectrum of antibiotics that are
useful for treating severe infections. Many aminoglycosides are poorly
absorbed in the GI tract; therefore, the majority are given IV or IM.
Aminoglycosides are potentially nephrotoxic and neurotoxic. They
should be administered cautiously.
* Indications: Streptomycin is used for streptococcal endocarditis and
a second line treatment for tuberculosis. Neomycin is used in the
treatment of hepatic encephalopathy as adjunct therapy to lower
ammonia levels and is also used as a bowel prep for colon
procedures.
* Mechanism of Action: Aminoglycosides are bactericidal and bind with
the area of the ribosome known as the 30S subunit, inhibiting protein
synthesis in the cell wall and resulting in bacterial death (see Figure.
Aminoglycosides may be given with beta-lactam medications to
facilitate transport of aminoglycoside across the cellular membrane,
resulting in a synergistic effect and increasing drug effectiveness.

*Aminoglycosides
* Special Administration Considerations: Aminoglycosides can result in
many adverse effects for the patient and, therefore, the nurse should
monitor the patient carefully for signs of emerging concerns.
* Aminoglycosides can be nephrotoxic (damaging to kidney), neurotoxic
(damaging to the nervous system), and ototoxic (damaging to the ear).
* Nurses should monitor the patient receiving aminoglycosides for signs of
decreased renal function such as declining urine output and increasing
blood urea nitrogen (BUN), creatinine, and declining glomerular filtration
rate (GFR).
* Indications of damage to the neurological system may be assessed as
increasing peripheral numbness or tingling in the extremities. Additionally,
the patient should be carefully assessed for hearing loss or hearing changes
throughout the course of drug administration.
* Check for allergies
* Obtain culture before administering
* IM: Blood sample for peak level should be obtained 1 to 2 hours after IM
injection;
* Inject in a large muscle
* Handle carefully; use gloves to prepare
* Side/Adverse Effects:
* GI upset, Rash. Report diarrhea immediately
* SAFETY:
* Nephrotoxicity: monitor renal function closely
* Risk for severe neurotoxic reactions, especially with renal
impairment. Can result in respiratory paralysis if given soon
after anesthesia or muscle relaxant
* Risk for ototoxicity, especially if administered with a loop
diuretic
* Can cause harm to fetus and breastfed infants
* Examples:
* Streptomycin
* Gentamicin
* Neomcin
*Tetracyclines are broad-spectrum antibiotics
that are bacteriostatic, subsequently inhibiting
bacterial growth.
*Indications: Tetracycline medications are useful
for the treatment of many gram-positive and
gram-negative infectious processes, yet are
limited due to the significance of side effects
experienced by many patients.
*Mechanism of Action: Tetracyclines work by
penetrating the bacterial cell wall and binding to
the 30S ribosome, inhibiting the protein synthesis
required to make the cellular wall.
*Tetracyclines
*Special Administration Considerations: Significant side
effects of tetracycline drug therapy include
photosensitivity, discoloration of developing teeth and
enamel hypoplasia, and renal and liver impairment.
*Tetracyclines are contraindicated in pregnancy and for
children ages 8 and under. Small amounts may be
excreted in breast milk.
*Side/Adverse Effects
*Gastrointestinal symptoms, Photosensitivity
*Oral candidiasis
*Permanent teeth discoloration if given to patients < 8 y.o.
*Intracranial hypertension: Monitor for headache, blurred
vision, diplopia, and vision loss
*Decreased effectiveness of oral contraceptives
* Unlike the complex structure of fungi or protozoa, viral structure
is simple.
* There are several subclasses of antiviral medications: antiherpes,
antiinfluenza, anti-hepatitis, and antiretroviral.
* Antiherpes
* Indications: Acyclovir (Zovirax) and its derivatives are frequently
used for the treatment of herpes and varicella virus infections,
including genital herpes, chickenpox, shingles, Epstein-Barr virus
infections, and cytomegalovirus infections.
* Mechanism of Action: Acyclovir causes termination of the DNA
chain during the viral replication process. Acyclovir can be
administered either topically or systemically, depending on the
infection.
* Special Administration Considerations: Acyclovir use may
result in nephrotoxicity.

*Antivirals
 * Indications: Tamiflu (oseltamivir) is used to target the
influenza virus by blocking the release of the virus from the
infected cells.
* Mechanism of Action: Tamiflu prevents the release of virus
from infected cells.
* Special Administration Considerations: This medication
does not cure influenza, but can decrease flu symptoms and
shorten the duration of illness if taken in a timely manner.
Patients are prescribed the medication for prophylaxis
against infection, known exposure, or to lesson the course of
the illness.
* If patients experience flu-like symptoms, it is critical that
they start treatment within 48 hours of symptom onset.

*AntiInfluenza
* Side/Adverse Effects:
* GI distress
* Serious skin/ hypersensitivity reactions; discontinue immediately
* Monitor for neuropsychiatric symptoms
* Use cautiously in patients with renal failure, chronic cardiac or
respiratory diseases, or any medical condition that may require
imminent hospitalization
* Example: oseltamivir
Figure Influenza virus réplications stages
* Viruses with complex life cycles, such as HIV, can be more
difficult to treat. These types of viruses require the use of
antiretroviral medications that block viral replication.
* Indications: Antiretrovirals are used for the treatment of
illnesses like HIV.
* Mechanism of Action: Antiretrovirals impede virus replication.
* Special Administration Considerations: Many antiretrovirals
may impact renal function; therefore, the patient’s urine output
and renal labs should be monitored carefully for signs of
decreased function.
* Side/Adverse Effects:
* Severe acute exacerbations of Hepatitis B Nephrotoxicity,
* Severe hepatomegally
* Example:adefovir

*Antiretrovirals
* Fungi are important to humans in a variety of ways. Both
microscopic and macroscopic fungi have medical relevance,
but some pathogenic species that can cause mycoses (illnesses
caused by fungi).
* Indications:
* Triazole drugs, including fluconazole, can be administered
orally or intravenously for the treatment of several types of
systemic yeast infections, including oral thrush and
cryptococcal meningitis, both of which are prevalent in
patients with AIDS.
* Mechanism of Action: Antifungals disrupt ergosterol
biosyntheses of the cell membrane increasing cellular
permeability and causing cell death.

*Antifungals
* Special Administration Considerations: Administration
guidelines will vary depending on the type of fungal infection
being treated. It is important to monitor response of the
affected area and examine class specific administration
considerations to monitor patient response.
* Side/Adverse Effects:
* Hepatotoxicity, Topical-skin irritation, rash
* Examples:
* Clotrimazole, fluconazole, nystatin, amphotericin B
* Antiprotozoal drugs target infectious protozoans such as
Giardia, an intestinal protozoan parasite that infects humans
and other mammals, causing severe diarrhea.
* Indications: Metronidazole is an example of an antiprotozoal
antibacterial medication gel that is commonly used to treat
acne rosacea, bacterial vaginitis, or trichomonas.
Metronidazole IV is used to treat Giardia and also serious
anaerobic bacterial infections such as Clostridium difficile (C-
diff).
* Mechanism of Action: Many antiprotozoal agents work to
inhibit protozoan folic acid synthesis, subsequently impairing
the protozoal cell.

*Antiprotozoals
* Special Administration Considerations: It can be
administered PO, i.v, or topically. Orally is the preferred route
for GI infections. The nurse should monitor the patient
carefully for side effects such as seizures, and dizziness.
Psychotic reactions have been reported with alcoholic patients
taking disulfiram.
* Side/Adverse Effects:
* Seizures
* Peripheral neuropathy
* Psychotic reactions
* Hepatotoxicity
* Example:
* metronidazole , Tinidazole
*M. tuberculosis is the causative agent of tuberculosis (TB),
a disease that primarily impacts the lungs but can infect
other parts of the body as well. It has been estimated that
one third of the world’s population has been infected with
M. tuberculosis and millions of new infections occur each
year.
*Treatment of M. tuberculosis is challenging and requires
patients to take a combination of drugs for an extended
time. Complicating treatment even further is the
development and spread of multidrug-resistant strains of
this pathogen.
*Indications: Antitubercular medications are selective for
mycobacteria work by inhibiting growth or selectively
destroying mycobacteria.

*Antituberculars
* Mechanism of Action: They work impacting the synthesis or
transcription of mycobacteria RNA or inhibiting the synthesis
of mycolic acids in the cellular wall. Mycobacteria can
develop resistance to antitubercular medications; therefore,
strict compliance to drug regimen must be emphasized.
* Special Administration Considerations: Antitubicular
medications require at least six months of treatment. Many
antitubercular medications may impact liver function, and
liver enzymes should be monitored carefully. Other side
effects to medication administration include GI symptoms,
peripheral neuropathy, and vision changes.
* Side/Adverse Effects:
* GI upset, Hepatotoxicity
* May decrease, effectiveness of oral contraceptives
* Examples:
* Isoniazid, Rifampicin, ethanbutol, pyrazinamide.