THE PRINCIPLES OF ANTIBIOTIC THERAPY

MICROBE
 Unicellular or small multicellular organisms

PATHOGEN
 Microbes capable of producing disease

BACTERIA
 Prokaryotes, single celled organisms lacking a true nucleus and nuclear membrane
 Have rigid cell walls
 The cell walls determine the shape of the bacteria
 Reproduce by cell division about every 20 minutes

Classification of Bacteria

(1) Shape under a Microscope (2) Staining Properties

- Bacillus or Rod shaped - Gram (+) retains purple stain

- Cocci or Spherical shaped
S. aureus
Streptococcus pneumoniae
a. In clusters - Staphylococcus
b. In chains – Streptococcus - Gram (-) not stained
Neisseria meningitides
Escherichia coli

(3) Toxins produced (4) Production of Beta lactamase enzymes

ANTIMICROBIALS / ANTI-INFECTIVES

 Substances that inhibit growth or kill microorganisms

 Drugs used to manage infections
 Drugs may be bacteriostatic or bactericidal depending on the dose and serum level

Classification by Susceptible Organism Classification by Mechanism of Action

Antibacterial drugs • Inhibition of bacterial cell wall synthesis

Narrow spectrum
Broad spectrum • Inhibition of protein synthesis
Myocobacterium
• Inhibition of nucleic acid synthesis
Antiviral drugs
Antiretroviral • Inhibition of metabolic pathways (Antimetabolites)
Antifungal drugs • Disruption of cell wall permeability
Antiparasitic drugs
• Inhibition of viral enzymes
Antihelmintic drugs

SELECTIVE TOXICITY

 The ability to suppress or kill an infecting microbe without injury the host
 An action of a drug on biochemical processes is more harmful to the microbe than to host cells
 The body’s defense mechanism works together with the antimicrobials to the stop the infectious process
 The body’s defense mechanism is influenced by age, nutrition, WBCs, Immunoglobulins, organ function, and
circulation

ANTIMICROBIAL SENSITIVITY
 The pathogen is inhibited and destroyed by a particular antimicrobial drug

ANTIMICROBIAL RESISTANCE
 The pathogen continues to grow despite the administration of drugs
 An ever present danger to effectively managing infection

Contributing Factors to Antimicrobial Resistance

Production of Drug-Inactivating - Beta lactamase enzymes affect the beta lactam structure of penicillins
Enzymes
and cephalosporins

Changes in Receptor Structure - Alteration in penicillin-binding proteins (PCBs) decreases the affinity for
binding beta lactam antibiotics
-

Changes in Drug Permeation and - Mechanisms developed to make passing through the cell wall difficult
Transport

Development of Alternative - Sulfonamides is an antimetalite that inhibits the enzyme necessary to

Metabolic Pathways
metabolize folic acid
- Some bacteria maybe able to bypass this inhibitory action
Acquiring Resistance
1. Spontaneous Mutation
2. Conjugation
Factors that Facilitate the
Development of Resistance
Methicillin-Resistant
Staphylococcus Aureus (MRSA)
Penicillin Resistant Streptococcus
Pneumoniae
Vancomycin-Resistant Enterococci
Multiple Drug-Resistant
Tuberculosis (MDR-TB)
General Considerations for Selecting Antimicrobial Therapy
1. Identification of the
Pathogen
2. Drug Susceptibility
3. Drug Spectrum
4. Drug Dose
5. Time to affect the
pathogen
6. Site of Infection
7. Patient Assessment
- Caused by prior and repeated exposure to an antimicrobial
- Change in the genetic composition of the microbe, a random occurrence or
DNA may have been acquired from an external source
- A form of sexual reproduction in which 2 individual microbes join in
temporary union to transfer genetic material
- Drug concentration too low to kill microorganism, below MIC
- Improper dosage or improper dosing interval
- Insufficient duration of therapy
- Prophylactic use should be limited to exposure to STDs, Recurrent UTIs,
Neutropenia, Surgery, and Bacterial Endocarditis
Common Antibiotic-Resistant Microbes
- Penicillin binding proteins have been altered
- Vancomycin is the drug of choice
- Penicillin is frequently used in infections like Otitis media, Community-
acquired Pneumonia and Meningitis
- Avoid using as prophylaxis in children and elderly
- Immunization of patients over 65 and under 2 yrs will decrease
development of resistance
- Enterococci are generally treated with combination antibiotics:
Aminoglycoside with penicillin or ceh-phalosporin
- Linezolid (Zyvox), dalfopristin-quinupristin (Synercid, and
daptomycin (Cubicin), have been developed to treat vancomycin
resistant microbes
- Resistance is developed over the long course of TB treatment, which can
last as long as 2 years
- The cause is inadequate therapy, duration too short, dose too low, and
poor patient adherence
- No less than four drugs are given at one time
“ The Right Drug for the Right Bug”
• A Culture test determines which pathogen is present
• A Sensitivity test determines the susceptibility of the pathogen to a
particular antibiotic
• Narrow spectrum drugs affects only few microorg., it limits the potential for
adverse effects, such as superinfection
• A Superinfection occurs during the course of treatment for a primary
infection. Two consequences can occur: (1) Secondary infection and the (2)
development of drug-resistant microbes
• Combination therapy is used as an alternative to broad spectrum
antimicrobials, in mixed infections, to prevent drug resistance, and for
enhanced antibacterial action
• Disadvantages of Combination therapy include an increased risk of toxic and
allergic reaction, for development of resistance, and for superinfection
• The lowest effective dose (= / >MIC)
• Choose the agent that takes the shortest time to affect the pathogen
• It will depend on the (1) type of pathogen, the (2) site of the infection, and
the (3) presence or absence of host defenses
• Generally 7 to 10 days, but may last as long as 30 days or more
• Sites that are difficult to achieve therapeutic concentration
a) Meninges – drugs cannot cross blood brain barrier
b) Abscess – poorly vascularized, pus impedes drug concentrations
c) Endocarditis – vegetative growths are hard to penetrate
d) Foreign objects like pacemaker or prosthetic joints, while phagocytosis are
busy attacking the foreign object, they are less able to attack the bacteria
multiplying at the site
  Health Status
• Immune status of the patient and Previous allergic reaction
 Life Span and Gender
• Elderly and Infants, populations most vulnerable to drug toxicity, may
request for lower doses
• During pregnancy; Tetracycline induced gray mottled enamel
Environment

• Nursing child; Sulfonamide induced kernicterus (hyperbilirubinemia)

 Culture and Inherited • IV route achieves the highest serum concentration of the antimicrobial but
Traits also the high potential for severe adverse effect (Amphotericin B IV
administration requires hospital admission)

• Predisposition to glucose-6-phosphate deficiency (G6PD), avoid antimicrobials

that induce RBC lysis like sulfonamides

Monitoring Antimicrobial Therapy

 Keep the serum level within the therapeutic margin

 Monitor CBCs if antimicrobial causes anemia
 Liver and kidney function test for the very young and old

 The most important element of patient education is to advise the patient to complete the entire course of the
therapy, Taking the prescribed dose at the prescribed intervals

General Adverse Reactions to Antibacterial Drugs

TYPE Considerations

Allergy or
- Mild allergic reaction: rash, pruritus,and hives. It is treated with an antihistamine
Hypersensitivity - Severe is Anaphylactic shock: It results in vascular collapse, laryngeal edema,
bronchospasm, and cardiac arrest.
- SOB is frequently the 1st symptom of anaphylaxis, It requires treatment with
epinephrine, bronchodilators, and antihistamines

- A secondary infection that occurs when normal microflora of the body are disturbed
during antibiotic therapy
- Rarely develops when drug therapy last < a week
Superinfection
- Commonly occurs with the use of broad spectrum antibiotics
- Superinfections can occur in the mouth, respiratory tract, intestine, GUT or skin
- Nystatin is used for fungal infections of the mouth

Organ toxicity - Liver and Kidney

- Aminoglycosides is neprotoxic and ototoxic

Mechanism of Actions of Antibacterial Drugs

ACTION EFFECT

Inhibition of cell wall synthesis - Bactericidal effect

Enzymatic breakdown of cell wall

• Penicillin ; Cephalosporin
-
- Inhibition of enzyme in synthesis of cell wall
• Bacitracin ; Vancomycin

Alteration of membrane permeability - Bacteriostatic or bactericidal

Membrane permeability increased, Loss of cellular substances
• Amphotericin B ; Nystatin
-
causes lysis of the cell
• Polymyxin ; Colistin

Inhibition of protein synthesis - Bacteriostatic or bactericidal effect

• Aminoglycoside ; Lincomycin - Interferes with protein synthesis without affecting normal
cell, Inhibits steps of protein synthesis
• Tetracycline ; Erythromycin

Inhibition of synthesis of bacterial RNA and - Inhibits synthesis of RNA and DNA in bacteria, Binds to
DNA nucleic acid and enzymes needed for nucleic acid synthesis
• Fluoroquinolones

Interference of cellular metabolism

• Sulfonamides - Bacteriostatic effect.
- Interferes with the steps of metabolism within the cells
• Trimethoprim ; Nalixidic acid
• Isoniazid (INH) ; Rifampicin
 PENICILLINS

 1st antibiotic introduced for clinical use (1929)

 Alexander Fleming (Nobel Prize winner),derived them from Penicillum molds
 Beta lactam antibiotic, beta lactam structure essential for antibacterial activity
 Difficult to maintain therapeutic levels because they are rapidly cleared from the plasma by the kidneys
 Contraindicated for any known allergy to penicillin or cephalosporin

Classification Considerations

- Gram + bacteria, anaerobes, spirochetes, Streptococci, Non-penicillinase

producing Staphylococci, Treponema pallidum (Syphilis)
(1) Narrow Spectrum - Prophylaxis to prevent Bacterial endocarditis
- Useful in treating meningitis

Penicillin G ( IM / IV ) • Unstable in gastric acid

 Salts of Na
• Salts of Na and K are aqueous and crystalline forms
 Salts of K • Salts of Procaine and Benzanthine are repository forms
Salts of Procaine (IM only)

 Salts of Benzanthine
• Procaine is milky in color, stored in the refrigerator, absorbed overs
hours
• Benzanthine is absorbed over days, low solubility (duration 12 weeks).
1º used to treat Syphilis

• Acid stable form of Penicillin G

Penicillin V (Oral) • Given on empty stomach 1 hr before or 2-3 hrs after meals with a full
glass of water

- Effective against many gram negative microrg.

- Haemophilus influenza, E. coli, Salmonella, Shigella, Proteus mirabilis
(2) Broad Spectrum - Ineffective against penicillinase producing Staphylococcus aureius
- Oral dosage is indicated for many pediatric infections like Otitis media,
“Aminopenicillins”
Pneumonia, Tonsillitis, skin infections
- Advantages : higher oral absorption, higher serum levels and longer
half lives
- Route: All Oral, only Ampicillin is available PO and IV

(3) Extended Spectrum

- Broader spectrum than aminoampicillins
“Antipseudomonal - Easily inactivated by penicillinase produced by S. aureus
penicillins”
- Combined with aminoglycosides to combat Pseudomonas
- PO, IV, IM

(4) Penicilinase- Resistant

- Resistance to Methicillin implies resistance to this class of penicillin
“Antistaphylococcal - PO, IM, IV
penicillins”

PENICILLINS

 Mechanism of Action: Inhibits bacterial wall synthesis

Adverse Effects Signs and Symptoms Nursing Intervention

• Skin test
Allergic reaction - Itching, rash, fever, wheezing (SOB), • Monitor vital signs first 30 mins after IV
anaphylaxis administration
• Epinephrine and Respiratory support must
be available

- N & V, diarrhea, abdominal pain, • Small frequent meals

glossitis, gastritis
GI Upset
- Caused by loss of normal flora and • Mouth care with nonirritating (non-
subsequent opportunistic infection alcoholic) solution

- Mouth ulcers, stomatitis, furry tongue • Ice chips for stomatitis and sore mouth or
Superinfections - Yeast infections (antifungal meds) pain
• Report and arrange for appropriate
- Genital discharge (vaginitis), anal or treatment
genital itching
• Culture and Sensitivity test (C&S) before
treatment

- Local pain or inflammation (monitor & • Aspirate to avoid injection of vasculature

rotate injection sites) (IM)
• Assess landmarks to avoid injection of
Injection sites nerve
- Phlebitis
Reactions • Provide warm compress and gentle
massage to painful and swollen injection
- Abscess formation sites
• Observe sterile technique
 Sodium overload - Potential fluid overload • Monitor vital signs especially blood
- Hypertension pressure
- CI: cardiovascular problems
• Monitor serum electrolytes

Potassium overload - Cardiac arrhythmias • Monitor ECG and vital signs

PENICILLINS

Drug-Drug Interactions Effect and Significance Nursing Interventions

Tetracyline - Decrease effectiveness of Penicillin • Avoid combination therapy

G

Aminoglycoside IV - Deactivated by Pen G • Administer 2 hours apart

Probenecid PO - Slows excretion of Pen G • Beneficial reaction

- Longer t1/2

Anticoagulants - Prolongs bleeding • Monitor for signs of bleeding

Oral contraceptives - Decreases plasma levels of • Use up back up method of birth

contraceptive control

Food - Impairs absorption of Pen G • Administer 1 hour before and 2

hours after meals

CEPHALOSPORINS

 Beta lactam antibiotics

 Similar to Penicillin in structure and activity (interferes with bacterial wall synthesis)
 Contraindicated for those allergic to penicillins (increased risk of cross sensitivity) , renal failure, pregnant and
lactating women

Four Generations of Cephalosporins

Major Differences 1st 2nd 3rd 4th

Activity against Gram - Least activity - Most activity

(-) bacteria

Resistance of Beta - Little - Less sensitive - Highly resistant - Most resistant

lactamase resistance

Ability to distribute in - poor - poor - good - good

CSF

Four Generations of Cephalosporins

Spectrum of Activity

1st
• Most active against gram + bacteria affected by Pen G, Staphylococci, Non-enterococcal streptococci
• Minor activity against gram (-) bacteria, PEcK – Proteus mirabilis, E. coli, Klebsiella pneumoniae

2nd
• HENPEcK- Haemophilus influenza, Enterobacter aerogenes, Neisseria species

3rd
• Weak against gram + bacteria but are more potent against gram (-) bacilli HENPEcKs –Serratia
marcescens

4th
• Active against gram (-) and gram (+) organisms, cephalosporin resistant Staphylococci and P.
aeruginosa

First Generation Cephalosporins

Adverse Effects Signs and Symptoms Nursing Intervention

N & V, diarrhea, abdominal pain,

GI
-
flatulence
• Taken with foods or fluid to decrease GI distress,
• Monitor hydration status
• Replace fluids lost
- Pseudomembranous colitis
(bloody violent diarrhea)

• Skin test
Hypersensitivity - Rash, urticaria, anaphylaxis • Monitor vital signs first 30 mins after IV
reaction administration
• Epinephrine and Respiratory support must be
available

CNS - Headache, dizziness, lethargy, • Safety precautions

paresthesia

Thrombophlebitis
IV site reaction
-
• Inject IM preparations into large muscle mass;
- Abscess formation Obsserve sterile technique
• IV: dilute with IV fluids, infuse over 30-45mins 2-
4X/day

Serum sickness - Fever, hives, swollen glands, • Monitor vital signs, WBC, urine input and output
like reaction neutropenia, arthralgia, edema

Nephrotoxicity - oliguria • monitor serum blood urea nitrogen and creatinine

levels

Second Generation Cephalosporins

Adverse Effects Signs and Symptoms Nursing Intervention

- Decrease Prothrombin levels • Advise patient about signs and

symptoms of bleeding
Thrombocytopenia - “Warfarin –like “ and antiplatelet
Bleeding • Adjust dosage of anticoagulants
activity, Interferes with Vitamin K
metabolism • Have Vitamin K available

- Bleeding gums, bruised skin • Avoid aspirin and NSAIDS

- Inhibits enzyme alcohol dehydrogenase • Avoid alcohol for 72 hours after

“Disulfiram-like” completing drug therapy
(Antabuse)
reaction
- Flushing, SOB, N & V, chest pains, • Educate patient about hidden
palpitations, dizziness, faintness, sources of alcohol like OTC cough
confusion, sweating, blurred vision, and cold remedies
respiratory depression, seizure,
unconsciousness

Third Generation Cephalosporins

 Indicated for bacterial strains resistant to aminoglycosides, severe infections or in immunocompromised

patients
 Active against P. aeruginosa
 Ceftriaxone is the drug of choice for Gonorrhea
 Induces bleeding tendencies like 2nd generation cephalosporins

CEPHALOSPORINS

Drug-Drug Interactions Effect and Significance Nursing Interventions

Anticoagulant Prolonged bleeding

-
• Monitor for signs of bleeding

Aminoglycosides - Increased risk of nephrotoxicity • Avoid coadministration

Probenecid - Prolongs effect of antibiotic • Beneficial reaction

MACROLIDES

 Used as penicillin substitutes for a clients allergic to penicillin

 Examples: Erythromycin, clarithromycin, azithromycin
 Broad spectrum antibiotics characterized by molecules made up of large ring lactones
 Derived from fungus-like bacteria Streptomyces erythreus, first introduced in 1952
 Mechanism of Action: binds to the 50S ribosomal subunits and inhibits protein synthesis
 Route: Administered orally and IV but not IM, because it is too painful
 IV macrolides should be infused slowly to avoid painful phlebitis
 Gastric acid destroys erythromycin in the stomach; acid resistant salts are added (e.g., ethylsuccinate, stearate,
 estolate) –Acid resistant macrolides
 Elimination: via bile and feces, NOTE: Renal insufficiency is not a contraindication
 Spectrum of activity: active against gram (+) bacteria, less effective against gram (-) bacteria
 Uses: Respiratory tract infections, sinuses, GIT, skin and soft tissue, diphtheria, STDs
 Drug of choice: Mycoplasma pneumonia and Legionnaire’s disease
 Extended macrolide group: longer t1/2 and administered once a day; clarithromycin and azithromycin

Adverse Reaction of Macrolides Nursing Intervention

Allergic reaction - Epinephrine, bronchodilators, antihistamine available

- Prepare for respiratory support

N &V, Diarrhea, - Small frequent meals

abdominal pain, - Replace fluids lost
Pseudomembranous colitis - Oral- administer azithromycin 1 hr before and 2 hrs after meals with a
full glass of water

Phleitis, Burning sensation at the IV - IV administration irritating to veins, infuse over 30 to 60 mins
injection site - Dilute drug with normal saline or D5W
- Apply cold compress if pain persist
- Reconstitute with sterile water and observe aseptic techniques
Abscess formation

QT interval prolongation - IV infusion rate should not be > 15mg/min

Ventricular tachycardia - Monitor vital signs and ECG findings

Hepatoxicity - Monitor for elevated liver enzymes (alkaline phosphatase, alanine

(large doses of azithromycin)
aminotransferase, aspartate aminotransferase) and jaundice (bilirubin
levels)

Tinnitus, - Safety precautions

reversible hearing loss

Drug – Drug Interactions Effect and Significance (Macrolides)

• Digoxin - Inhibits metabolism of many drugs increasing their serum concentration

• Warfarin - Increased risk of adverse effects and toxic reactions
• SSRI
• Theophylline
• Clozapine - Sudden cardiac death
• Ca channel blockers
- QT interval prolongation
• Benzodiazepine
• Pimozide - Additive hepatotoxic effect
• Acetomenophen

LINCOSAMIDES

 Used as penicillin substitutes for a clients allergic to penicillin

 Examples: Clindamycin (Cleocin) and lincomycin (Lincocin), very toxic drugs
 Mechanism of Action: Inhibits protein synthesis
 Route: Oral, IM, IV, Topical, opthalmic
 Elimination: metabolized in liver, excreted in bile and urine
 Spectrum of Activity: life threatening infections caused by aerobic gram (+) cocci, anaerobic gram (+) and (-)
microbes
 Uses: Septicemia, Acute hematogenous osteomyelitis; Topical forms: acne vulgaris and bacterial vaginosis
 Contraindications: Allergy ot lincosamide and tartrazine (component of some clindamycin), hepatic/renal
dysfunction, history of colitis, pregnancy, neonates

Adverse Reactions of Lincosamides Nursing Interventions

N & V, abdominal pain (PO)

- Administer on anempty stomach with a full glass of water
- Give with small meals if there is GI upset

Superinfection: - Monitor for signs of diarhea, abdominal cramps or tenderness

Antibiotic associated colitis - Stool examination for WBC, blood and mucus
“Pseudomembranous colitis” or Clostridium - Replace fluid lost, monitor hydration status
difficile colitis

- Assess for reaction to drugs with “mycin” or “micin”

Hypersensitivity reaction - Monitor for rash, itchiness, erythema, anaphylactoid reaction

Blood dyscrasia - Monitor for signs of fever, sore throat

- Monitor CBC
 Dryness of skin (xeroderma) - Use of topical preparations
Dryness of conjunctiva (xeropththalmia) - Apply lotion for skin and artificial tear for eyes
Dryness of mucous membrane - Suck sugarless candy

L I N C O SA M I D E S

Drug-Drug Interactions Effect and Significance Nursing Interventions

Neuromusclar Blockers Potentiates its action

-
• Mark “Warning” on chart
• Extended monitoring and support after
surgery

Erythromycin - Antagonizes effect of clindamycin • Avoid coadministration

Chloramphenicol

Opiates - Enhances its effect, respiratory • Monitor respiration

depression

Aluminum salts or - Decreases GI absorption of clindamycin • Administer 2 hrs before and 3-4 hrs after
Kaolin oral clindamycin dose

Pyrimethanine - Synergistic effect in treating toxopasmic • Beneficial reaction

encephalitis in patients with AIDS

VANCOMYCIN

 A complex and unusual tricyclic glycopeptide

 Mechanism of Action: inhibits cell wall synthesis
 Route: oral administration limited to treating GI infections, not absorbed systemically: generally given IV for severe
infections due to MRSA, septicemia
 Elimination: mainly feces
 Uses: (PO) antibiotic associated Peudomembranous colitis due to Clostridum difficile, not absorbed systemically
but excreted in the feces; (IV) Methicillin resistant staphylococcus aureus
 Contraindications: Elderly due to age related decrease in renal function, hypersensitivity, pregnancy,
inflammatory bowel disease

Adverse Reactions to Vancomycin Nursing Interventions

- Tinnitus, hearing loss (cochlear)

Ototoxicity - Ataxia, vertigo, N & V, nystagmus (vestibular)
- Periodic audiometric testing
- Keep serum levels < 60 to 80ug/ml
- Lower dosage, infuse IV slowly
- Avoid coadministration of other ototoxic drugs

Nephrotoxicity - Monitor I & O, Kidney function test, Lower dosage

“Red Man” or “Red Neck”

- Red blotching of the face, neck and chest due to histamine release, a toxic
and not an allergic reaction
Syndrome
- Hypotension, tachycardia, generalized tingling (paresthesia)
- Administer IV dose over 60 minutes

IV injection site reaction - Use large vein and administer slowly

Thrombophlebitis

Leukopenia, Thrombocytopenia - Periodic CBC testing for prolonged use, blood monitoring

VANCOMYCIN

Drug-Drug Interactions Effect and Significance Nursing Interventions

Antihyperlipidemic (Statins) - ↓ effectiveness of • Separate administration by 3-4 hrs

vancomycin

Nephrotoxic drugs - Additive risk • Lower dosage of vancomycin

• Monitor renal function

Ototoxic drugs - Additive risk • Monitor hearing function

Nondepolarizing muscle relaxants - Additive blockade • Avoid combination

NURSING DIAGNOSIS DESIRED OUTCOME

VANCOMYCIN
• Risk for injury R/T drug induced histamine release
reactions
• Disturbed sensory perception (auditory) r/t drug
induced ototoxicity
• Fluid excess volume r/t nephrotoxicity from drug
therapy
• Risk of infection r/t overgrowth of non-susceptible
organisms
 The patient will experience no preventable reaction r/t
vancomycin
 The patient will report any unusual auditory sensations
and have periodic audiograms to detect ototoxicity
 The patient will remain normovolemic throughout the
therapy
 The patient will report signs and symptoms of
superinfection ot the prescriber

TETRACYCLINES ( T C Ns )

 Isolated from Streptomyces aureofaciens in 1948

 A semisynthtic antibiotic based on the structure of a common soil mold
 A broad spectrum antibiotic that affects both gram (+) and gram (-) bacteria
 They have a 4 ring structure
 Examples: doxycycline, minocycline, methacycline
 Mechanism of Action: Act by inhibiting bacterial protein synthesis
 Route: Oral, most common and 100% absorbed; Opthalmic- prophylactic for opthalmia neonatorum (Neisseria
gonorrhea): Topical preparations for acne vulgaris and periodontal disease: IV route is used for treating severe
infections: IM route seldom used because it causes pain and tissue irritation
 Elimination: primarily excreted in the urine
 Uses: Rickettsiae, Mycoplasma pneumaniae, Syphilis, Chlamydia, Gonorrhea, Malaria prophylaxis, chronic
Periodontitis, Acne; treatment of Anthrax (Doxycyclline); as part of combination therapy to eliminate H. pylori
infections; drug of choice to stage 1 Lyme disease
 Contraindication: Pregnancy, breastfeeding, children younger than 8 yrs; Known allergy to tetracycline or to
tartrazine; Renal or hepatic dysfunction: Non-bacterial ocular infection

Adverse Reactions to Tetracyclines Nursing Interventions

N & V, diarrhea - Small frequent meals

- Increase fluid intake

Discoloration and mottling of teeth - Should not be taken by pregnant women and children younger than
8 years old

Photosensitivity (Sun burn reaction) - Avoid direct sunlight, remain indoors

- Use sunscreen with SPF >15, cover up with clothing

Nephrotoxicity / Hepatotoxicity - Monitor liver and renal function test (azotemia)

Sore mouth and throat, stomatitis

- Signs of Superinfection from the drug
- Effective oral hygiene several times a day
- Suck on ice chips or sugarless candy

Toxicity from Decomposed TCN - Light and heat decomposes TCN

- Expired TCN is toxic
- Becomes nephrotoxic

TETRACYCLINES ( T C Ns )

Drug-Drug Interactions Effect and Significance Nursing Interventions

Penicillin G - ↓ effectiveness of Pen G • Avoid combination

Oral contraceptive - Less effective • Use additional form of birth control

Antacids containing Ca, Mg • Separate administration by 3-4 hrs

and Al salts; - ↓ absorption of TCN • Administer 1 hr before or 2 hrs after
Dairy products; meals
Iron preparations

Insulin - ↑ hypoglycemia • Monitor blood glucose

Digoxin ↓ Metabolism of digoxin by GIT

-
• Monitor digoxin levels and toxicity

Anticoagulant - TCN eliminates Vit K • Monitor for signs of bleeding

- Increases activity of anticoagulant

AMINOGLYCOSIDES

 Powerful antibiotics used to treat serious infections caused by gram (-) aerobic bacilli
 Ineffective against Aneorobes (Gentamicin must be transported across the membrane in order to enter the cell
and disrupt protein synthesis-this requires oxygen)
 It is poorly absorbed in the gastrointestinal tract
 Mechanism of Action: inhibits protein synthesis
 Route: Oral, Ophthalmic, Topical, primarily administered IM or IV, Liposomal injections
 Elimination: Urine (IV, IM)
 Contraindication: Hepatic / Renal dysfunction, pregnant and lactating women

Aminoglycoside Route/ Dosage Forms Use / Significance

Amikacin • IV, IM
• Pseudomonas infection and a wide variety of gram (-)
infections
• IV, dilute in 50-200ml of normal saline of D5W solution
and administer over 30-60 mins
Gentamycin • Intrathecal • Meningitis
• Impregnated beads on • Chronic Osteomyelitis
surgical wire
• Liposomal injections
• Ophthalmic
• Topical • Skin wounds of infection

• To reduce normal GI flora (7-10) days only

Kanamycin • Oral • To reduce ammonia forming bacteria in hepatic coma

• Oral but not absorbed • Suppression of GIT flora preoperatively

Neomycin systemically from the GIT • Treatment of hepatic coma
• OTC Topical
• Skin ifections

Tobramycin • Ophthalmic form • Ocular infections

• For nebulization • Respiratory infection

Streptomycin • Oral
• 4th drug in combination therapy for Tuberculosis, Ototoxic
and Nephrotoxic

AMINOGLYCOSIDES

Adverse Effects Signs and Symptoms Nursing Intervention

• Diminished urinary excretion • Measure I & O

• Azotemia (urea in blood), proteinuria, ↓
CREA clearance, pyuria (↑ WBC)
Nephrotoxicity • Electrolyte imbalance ( ↓K, ↓Mg)
• Urinalysis – check for protein, cast, blood
cells
• Monitor BUN & CREA
• Careful dosing especially for younger and
older clients
• Therapeutic drug monitoring

• Hearing loss, Tinnitus, balance • CI: hearing problems

Ototoxicity problems • Safety measures
• Persistent headache • Avoid concomitant use of other ototoxic
drugs
• Dizziness, vertigo

Neuromuscular •
blockade
• Profound Respiratory depression
CI: Myasthenia gravis, Parkinson’ s,
Concomitant use of succinylcholine
• Warning on chart for preoperative
patients

GIT effect •
• N & V, diarrhea, weight loss
Small frequent meals

Bone marrow • Blood dyscrasia • Monitor CBC and for signs of anemia
depression •

• Confusion, depression, numbness, • Safety precautions

CNS effect tingling or weakness

Cardiovascular •
• Palpitaions, hypotension, hypertension
Monitor vital signs

• Rash, pruritus, • Antihistamines

Hypersensitivity • pholtosensitivity • Sunblock

•
Superinfections
• Fever, Stomatitis (mouth ulcers)
Monitor vital signs
• Genital ulcers (vaginitis) • Drink lots of water ; Mouth care
• Anal and genital itching • Antifungal medication
 AMINOGLYCOSIDES

Drug-Drug Interactions Effect and Significance Nursing Interventions

Penicillin - Decreased effect of aminoglycoside • Given several hours apart

Warfarin - Drug action of warfarin increased • Decrease dosage of warfarin

Ethacrynic acid (Loop - Increased ototoxicity • Avoid coadministration

diuretic)

CHLORAMPHENICOL

 Isolated from Streptomyces venezuelae “1947”

 Broad spectrum antibiotic, relatively toxic and reserved for serious infections
 Mechanism of Action: Inhibits protein synthesis,
 NOTE: affects both bacterial and human cells. In humans, rapidly proliferating cells like erythrocytes
 Route: Oral: Chloramphenicol Base; IV: Chroramphenicol succinate; Opthalmic; Otic; Topical
 Distribution: Highest concentration in liver and kidney, substantial CSF concentrations in patients with inflamed
meninges
 Elimination: Kidney, bile, feces

Indications / Uses Contraindication

1. Active against gram (+) and gram (-) 1. Hypersensitivity to the drug
2. Pregnant, infants, children
infections (anaerobic bacteria
3. Hepatic/renal impairment
4. Glucose 6 phosphate dehydrogenase deficiency (G6PD)
2. Meningitis caused by Streptococcus 5. Acute intermittent porphyria
pneumoniae, Neisseria meningitides or 6. Anemia
haemophilus influenzae 7. Patients with depressed marrow function (Cytotoxic drug and
Radiation therapy)
3. Brain abscess 8. Dental disease with dental work, myelosuppression
4. Rickettsial infection 9. Drugs that cause hematologic, nephrotoxicity and hepatotoxicity
5. Acute Typhoid fever (Outbreak)

CHLORAMPHENICOL

Adverse Effects Signs and Symptoms Nursing Intervention

- Failure to feed, abdominal - CI: premature infants and newborns

“Gray Baby Syndrome” distension, vomiting, blue gray skin, - Measure I & O, monitor renal & hepatic
-Life threatening vasomotor collapse
function

- Aplastic anemia, pancytopenia, - Monitor plasma levels, once a week,

“Reversible Bone Marrow thrombocytopenia
Monitor CBC
Depression”
- Plasma levels of drug increase
- Keep plasma levels below 25ug/ml to
Blood dyscrasia decrease adverse hematogic reactions
with renal and hepatic
- Monitor for signs of anemia and blood
dysfunction (newborn, infants,
dyscrasia
premature baby)

Opthalmic effects - Burning and itching of the eyes - Monitor for signs
- Optic neuritis-blindness - Safety measures

GIT effects - N & V, diarrhea, stomatitis, glossitis, - Small frequent meals

- Mouth care
enterocolitis
- Fluid replacement

- Monitor for signs

Peripheral neuritis - Vitamin B6 deficiency - Administer Pyridoxine as prophylaxis

Neurotoxic effects - Headache, mild depression, - Monitor for signs

confusion, delirium - Safety measures

Topical use/Systemic effect - Rash, pruritus, dermatitis, burning - Avoid rubbing, tight clothing, harsh
soaps, perfumed lotions
- Topical antihistamines or corticosteroids

CHLORAMPHENICOL
 Interference with hepatic metabolism and clearance of other drugs

Drug-Drug Interactions Effect and Significance Nursing Interventions

Oral anticoagulants - ↑ risk of bleeding • Dosage adjustment

Oral hypoglycemics - Clinical hypoglycaemia • Dosage adjustment

Hydantoins - ↑ toxicity • Dosage adjustment

 Iron overload and anemia
Iron salts
-
- ↓ iron clearance and erythropoesis
• Adjustment of iron dosage
• Monitoring of CBC

Vitamin B12 - ↓ hematologic effects of Vit B12bin • Monitor Vit B12 response
patients with pernicious anemia • Consider alternative antibiotic

Antibiotics:
Aminoglycosides,
cephalosporins,penicillin, - Altered bactericidal effects • Avoid concurrent administration
erythromycin↑

FLUOROQUINOLONES

 Synthetic antibacterials effective against aerobic gram (-) and gram (+) infections. These include urinary tract,
respiratory and skin infections

 Ciprofloxacin, the most widely used fluoroquinolones.

 Mechanism of Action: Interferes with the function of DNA gyrase enzyme necessary for the growth and
reproduction of bacteria

 Route: Oral, Parenteral, Topical ophthalmic and otic preparations

 Elimination: metabolized in the liver, excreted in urine and feces

 Uses: It is indicated for respiratory, dermatologic, urinary tract, eye, ear, bone, and joint infections. Treatment
after anthrax exposure and typhoid fever

 Contraindication: Known allergy, renal dysfunction, pregnant or lactating women, children under 18 years old

Four Generations of Fluoroquinolones

First Generation QUINOLONES

• Cinoxacin - Indicated for uncomplicated UTIs

• Nalidixic acid

Second Generation FLUOROQUINOLONES

• Lomefloxacin - Fluorine atom is added to the Quinolone structure

• Norfloxacin
• Ofloxacin - Increased gram (-) and systemic activity

Third Generation

• Gatifloxacin - Extended activity against gram (+) pathogens

• Gemifloxacin
• Levofloxacin - Less active than 2nd generation fluoroquinolones against Pseudomonas species
• Moxifloxacin
• Sparfloxacin

Fourth Generation

• Alatrofloxacin - Same spectrum as 3rd generation fluoroquinolones

• Trovafloxacin - Active against Pseudomonas species and anaerobic bacteria

Adverse Effects of Signs and Symptoms

Fluoroquinolones

CNS effects
- Headache, dizziness, restlessness, insomnia, depression, fatigue
- Avoid caffeinated products
- Avoid activities that require alertness

Gastrointestinal effects - Nausea, vomiting, diarrhea, flatulence, dry mouth

- Give with a full glass of water, may be taken with food if GI upset occurs

Laboratory changes - Elevated BUN, CREA, AST (SGOT), ALT (SGPT), Alkaline phosphatase
- Decreased WBC and hematocrit

Crystalluria - Fluid intake should be > 2000ml/day

- Urine pH should be < 6.7
- Monitor I & O; Urine output should be at least 750 ml/day

Tinnitus - Monitor hearing ability

Dermatologic effects - Rash, flushing, photosensitivity

Arthropathy - Joint disease that occurs in children under 18 yrs old

 -

Tendon rupture - Cartilage deterioration when administered to immature animals

- Report any tendon pain

IV site reaction - IV administration infused over 60 mins into a large vein

FLUOROQUINOLONES

Drug-Drug Interactions Effect and Significance Nursing Interventions

Antacid; iron salts - ↓ absorption • Separate administration by 4 hrs

Drugs that increase QT intervals

(e.g., procaineamide, amiodarone, - Fatal cardiac reaction • Cardiac monitoring
phenothiazine)

• Decrease dosage of theophylline

Theophylline - ↑ theophylline toxicity
• Monitor for signs of CNS stimulation

NSAIDS - ↑ CNS stimulation • Check for history of seizure and CNS

problems
Caffeine - ↓ hepatic metabolism • CNS stimulation and cardiovascular
effects
Hydantoins - ↑ phenytoin concentration • Dosage adjustment
- ↓ seizure activity
Oral contraceptives - Decrease effectiveness • Backup birth control

SULFONAMIDES

 One of the oldest antibacterial agents used to combat infection

 Isolated from a coal tar derivative compound in the early 1900s
 Clinically used against coccal infection in 1935
 NOT classified as an antibiotic (Not obtained from a biologic substance)
 Not used alone but in combination with Trimethoprim
 Mechanism of Action: It inhibits the bacterial synthesis of Folic acid which is essential for bacterial growth.
Folic acid is required by cells for biosynthesis of RNA, DNA and proteins
 Selectively inhibits bacterial growth without affecting human cells. Human do not synthesize folic acid, they derive
it from their diet
 Route: Oral- well absorbed from GIT; Ophthalmic: solution or ointment; Cream for burns
 Highly protein bound
 Elimination: Urine
 Uses: (1) Urinary tract infections, 90% effective against E. coli; (2) Against organisms like Chlamydia and
Toxoplasma; (3) Meningococcal meningitis; (4) prophylaxis in clients with rheumatic fever who are allergic to
penicillin
 Contraindication: Hypersensitivity to sulfonamides; hepatic and renal disease; 3rd trimester pregnancy

Classification according to their Duration of Action

Short-acting Sulfonamide Intermediate-acting Sulfonamide

(Rapid absorption and excretion rate) (Slow absorption and excretion rate)

• Sulfadiazine • Sulfamethoxazole
• Sulfamethizole • Sulfasalazine
• Sulfizoxazole (Gantrisin) • Trimethoprim-sulfamethoxazole (Bactrim, Septra)

Topical Sulfonamides Ophthalmic sulfonamides

• Mafenide acetate (Sulfamylon) – Creams for • Sulfacetamide sodium- eye drops or ointment
prevention of sepsis in 2nd or 3rd degree burns • Indicated for conjunctivitis and corneal ulcers;
• Silver sulfadiazine (Silvadine)
prophylactic treatment after an eye surgery

• Sulfacetamide sodium – skin ointment indicated

for seborrheic dermatitis secondary bacterial
infection

Adverse Reactions of Signs and Symptoms

Sulfonamides

Allergic Reactions - Skin rash, skin eruptions, itching

- Anaphylaxis is not common

Gastrointestinal disorders - Anorexia, nausea and vomiting

Blood disorders - Haemolytic anemia, aplastic anemia, low WBC and platelet count

- Poor urine solubility

Crystalluria - Recommend increase fluid intake > 2000 ml/day
- Administer with a full glass of water 1hr before or 2 hours after meals
- Urine output should be at least 1200ml/day

- Excessive reaction to direct sunlight or UV light leading to redness and burning of

Photosensitivity skin
 - Avoid sunbathing

Cross sensitivity - Sensitivity to on sulphonamide may lead to sensitivity to another sulfonamide

C O T R I M O X A Z O LE (BACTRIM, SEPTRA)

 TRIMETHOPRIM (TMP) and SULFAMETHOXAZOLE (SMZ) combination

 Drug ratio: (1:5) TMP:SMZ, synergistic effect; bacterial resistance develops more slowly

 Trimethoprim (TMP) is classified as a urinary tract anti-infective, maybe used alone for uncomplicatied UTIs
and affects gram negative bacteria. ACTION: It interferes with bacterial folic acid synthesis just like sulphonamide

 Mechanism of Action: Inhibition of protein synthesis of nucleic acid; bactericidal

 Route: Oral and IV

 Elimination: Urine

 Uses: UTIs, Intestinal, Lower respiratory tract infections, otitis media, prostatitis, gonorrhea, Pneumocystis carinii
(clients with AIDS)

 Contraindication: Hypersensitivity to sulfonamides; hepatic and renal disease

 LAB test: ↑ BUN, CREA, AST, ALT, ALP

Adverse Reactions of Signs / Symptoms and Nursing Interventions

Cotrimoxazole

Gatrointestinal - Anorexia, nausea, vomiting, diarrhea

Secondary infection - Stomatitis, vaginitis
Rash - Topical antihistamines
Crystalluria - Increase fluid intake not > 200ml/day
Photosensitivity - Use sunglass, sun block, protective clothing
Blood dyscrasia - Life threatening agranulocytosis, haemolytic anemia

C O T R I M O X A Z O LE (BACTRIM, SEPTRA)

Drug-Drug Interactions Effect and Significance Nursing Interventions

Sulfonylureas - ↑ hypoglycemic response • Dosage adjustment

Warfarin - ↑ anticoagulant activity • Monitor for signs of bleeding
Antacid - Decreased absorption • Allow 4 hr interval

CYCLIC L I P O P E P T I D E S – D A P T O M Y C I N ( CUBICIN )

 Reserved for infections that do not respond to other antibiotics

 It has the ability to retain potency against antibiotic-resistant gram positive bacteria
 There is no known transferable element (plasmids) that can confer resistance
 No known report of cross-resistance
 Mechanism of Action: Interferes with the integrity of the cell wall
 Route: IV once daily, at 4-8 mg/kg/day
 Administration: with 0.9% NaCl or Lactated Ringer’s solution, administer over 30 mins without any other IV
substances; NOT compatible with Dextrose solution
 Elimination: Urine
 Uses: Serious aerobic gram (+) complicated skin and skin structure infection caused by Enterococcus feacales, S.
aureus, Infective endocarditis due to MRSA, Streptococcus species
 Contraindication: Hypersensitivity to the drug

CYCLIC L I P O P E P T I D E S - DAPTOMYCIN (CUBICIN)

Adverse Effect Signs and Symptoms Nursing Interventions

Gastrointestinal - Nausea and vomiting, diarrhea, • Small frequent meals
dyspepsia • Monitor hydration status

Rhabdomyolysis
- Myalgia (muscle cramps or pain)
- Muscle weakness (fatigue)
Myopathy
- Numbness and tingling
• Avoid coadministration with Statin
drugs (HMG-CoA) or stop during
antibiotic therapy
• D/C if CK is 5-10X the upper limit
• Administer IV over 30 mins

Metabolic disturbances - Electrolyte imbalance (↓↑ • Renal and liver function test
• Monitor Metabolic panel
 K, ↓ Mg, ↑ Bicarbonate) • Monitor blood glucose
- Hyperglycemia

Laboratory results Elevation of Creatinine Kinase, hepatic

-
enzymes, alkaline phosphatase and INR
• Obtain baseline CK
• Weekly CK monitoring (myopathy)
• Avoid warfarin

Blood dyscrasia Anemia, bleeding

-
• Monitor CBC

CNS effects - Headache, dizziness, insomnia • Safety precautions

O X A Z O L I D I N O N E S – L I N E Z O L I D ( ZYVOX )

 Developed specifically for treating MRSA

 Mechanism of Action: Inhibits protein synthesis
 Route: Oral and IV, both 100% bioavailable, both forms interchangeable without dosage adjustment
 Elimination:
 Uses: Infection/Bacteremia caused by Vancomycin resistant Enterococcus faecalis (VRE), MRSA, and penicillin-
susceptible Streptococcus pneumonia; Skin infections, Nosocomial and community acquired pneumonia
 Contraindication: hypersensitivity to drug, phenylketonuria ( oral suspension has 20 mg phenylalanine/5ml),
hypertension, blood dyscrasia

Adverse Effect of Linezolid Signs/Symptoms and Nursing Intervention

Gastrointestinal - Nausea, vomiting, diarrhea

- Pseudomembranous colitis

Bone marrow depression - Blood dyscrasia (e.g., thrombocytopenia)

- Drug induced MAO inhibition

- Monitor blood pressure
Hypertension - Contraindicated in clients with HPN, hyperthyroidism, pheochromocytoma
- Monitor intake of tyramine rich foods, caffeine, alcohol, OTC drugs

Hepatic - Elevated liver enzymes, obtain liver function test

O X A Z O L I D I N O N E S – L I N E Z O L I D ( ZYVOX)

Drug-Drug Interactions Effect and Significance Nursing Interventions

MAO Inhibitors - Hypertensive crisis • Avoid coadministration

Levodopa • Do not administer linezolid 14 days
SSRI after these drugs
Sympathomimetics • Monitor BP
- May cause serotonin syndrome • Avoid OTC drugs
Tyrosine, Tryptophan

STREPTOGRAMINS
QUINUPRISTIN / DALFOPRISTIN (SYNERCID)

 Designed to eradicate “Super bugs” resistant to other antibiotics

 Mechanism of Action: Inhibits bacterial protein synthesis
 Route: IV only; Onset rapid: half life- 1 hr

 Administration Precautions:

1. Should be diluted with 250 ml of D5W and infused over one hour
2. DO NOT FLUSH the IV line with saline or heparin (NOT compatible), flush line with D5W
3. Should not be administered with Y-site infusion unless compatibility of drug and diluent is established
4. Administer through Peripherally inserted central catheter (PICC) or central line if possible

 Elimination: converted to several major active metabolites and excreted primarily through bile
 Uses: for VRE bacteremia and for complicated skin and skin structure infections due to Staphylococcus aureus
 Contraindication: hypersensitivity and decreased hepatic function

Adverse Effect of Synercid Signs and Symptoms Nursing Interventions

- Pain, swelling • Monitor for signs
- Phlebitis • Ask patient regarding pain at the injection site
Injection Site Reactions - Edema • Administer through PICC or central line when
- Infiltration possible
 • Asses history of liver dysfunction
Hepatotoxicity - Hyperbilirubinemia • Monitor for signs and symptoms
• Liver function test, bilirubin test

Gastrointestinal effects - Nausea, vomiting, diarrhea • Taken with foods or fluid to decrease GI distress,
- Pseudomembranous colitis • Monitor hydration status
• Replace fluids lost

Musculoskeletal effects - Arthralgina, myalgia • Report

• Avoid rubbing, tight clothing, harsh soaps,

Dermatologic effect - Rash, pruritus perfumed lotions
• Topical antihistamines or corticosteroids

QUINUPRISTIN / DALFOPRISTIN (SYNERCID)

 Drug-Drug Interaction: Potent inhibitor of cytochrome P 450 liver enzymes

 Serum concentration of drugs metabolized through this pathway maybe increased
 Avoid coadministration of drug if possible
 Monitor for toxicity if coadministration is unavoidable