Download Nur127 Unit 1 Lecture 3 Antibiotics

Antimicrobials
NUR 127
Prototype approach to teaching pharmacology:
Uses a prototype (a drug that is representative of it’s
class) to help students learn by grouping the
medications. It is a method of learning and organizing
large amounts of information.
OBJECTIVES:
1.Identify various types of pathogenic organisms
2.Identify and describe pathogenicity and virulence of common
bacterial pathogens
3.Discuss the development of anti-infective drug resistance and
identify the nurse/patient role in preventing development of
resistant pathogens
4.Discuss the development and common symptoms of
superinfections caused by anti-infective therapy
5.Identify prototype drugs within the anti-infective drug classes.
Discuss mechanism of action, indication for use,
contraindications, adverse effects and administration. Identify
drugs within each class with specific features differing from the
prototype.
Terminology
 Pathogenicity—ability of an organism to cause






disease in a human
Virulence—severity of disease that an organism is
able to cause; a highly virulent pathogens causes
disease when present in very small numbers
Acquired Resistance—when a microbe is no longer
affected by an anti-infective
Nephrotoxicity—an adverse effect on the kidneys
Hepatotoxicity—an adverse effect on the liver
Ototoxicity—an adverse effect on hearing
Superinfection—condition caused when a
microorganism grows rapidly as a result of having less
competition in its environment
Terminology
 Anti-infective aka antimicrobial—General term
referring to drugs active against pathogens
 Antibiotic aka antibacterial—Drugs active against
bacteria
 Bacteriocidal—kill bacteria
 Bacteriostatic—slow the growth of bacteria
 Chemoprophylaxis—prophylactic use of a
medication
Characteristics of Anti-Infectives
 Includes antibacterials, antivirals and antifungals
 Antibacterials (antibiotics) refer to drugs which treat
bacterial infections
 Narrow spectrum
 Broad spectrum
 Bactericidal (kills) vs. Bacteriostatic (inhibits)
Common Human Pathogens
 Viruses
 Gram+:

enterococci, streptococci and staphylococci
 Gram- organisms:

E.coli, Bacteroides, Klebsiella, Proteus, Pseudomonas
 Opportunistic
 Community-acquired vs. nosocomial
Common Bacterial Pathogens
 Staphylococci—Common in wounds , URI’s and







pneumonia (MRSA—resistant strain)
Streptococci—Common infection in URI’s, ear
infections & pneumonia
Enterococci—Common infection in UTI’s & wounds
(VRE—resistant strain)
Escherichia coli—UTI’s; GI infection most commonly
related to contaminated ground beef
Klebsiella—Causes respiratory tract infections, UTI’s,
bloodstream, burn wound infections
Pneumococci—Most common cause of pneumonia in
children; otitis media
Proteus—Cause UTI’s and wound infections
Pseudomonas—Cause respiratory tract infections,
UTI’s, wound & burn wound infections (high
resistance to many antibiotics)
Disease Process
 Pathogens generally cause disease by one of two
basic mechanisms
Rapid growth
2) Production of toxins
1)
Normal Bacterial Flora
 Colonized areas include the skin, upper respiratory
tract, colon and vagina
 Skin Flora (eg, staphylococci, streptococci)
 Upper Respiratory Tract (eg, staphylococci,
streptococci, pneumococci, Haemophilus
influenzae)
 Colon (eg, escherichia coli, Klebsiella, Enterobacter,
Proteus, Pseudomonas, Bacteroids, clostridia,
lactobacilli, strep, staph)
 Vaginal (eg, Candida, lactobacilli, Bacteroids)
Infectious Diseases
 Presence of a pathogen plus clinical s/sx of
infection
 Patient with a compromised immune system may
be prone to opportunistic infections caused by
endogenous or environmental flora
Drug Classification
Classified by their chemical structure or by their mechanism
of action
 Mechanism of action
 Cell-wall synthesis inhibitors, protein synthesis inhibitors,
RNA or DNA synthesis inhibitors, antimetabolites (
 Bacteriocidal vs. Bacteriostatic


Bactericidal drugs kill organisms
Bacteriostatic drugs inhibit growth of organisms
 Classification by chemical class
 Share similar mechanisms of action and side effects
(aminoglycoside, fluoroquinolone, sulfonamide)
Antimicrobials
 Used to prevent or treat infections caused by
pathogenic microorganisms
 Broad-spectrum drugs are effective against a
wide variety of microorganisms
 Narrow-spectrum drugs are effective against one
or a restricted group of microorganisms
Guidelines for use
 Collect specimens before beginning therapy
 Avoid use of broad-spectrum drugs
 Use with other interventions—universal
precautions, hand hygeine, isolation techniques,
preoperative skin and bowel cleansing
 Multidrug therapy should be avoided except in
specific circumstances
Anti-microbial Drug Administration
 Dosage should be individualized
 Dosages often determined by grams or milligrams
per kilogram of body weight
 Routes of administration
 Most PO or IV
 IM doses : deep and into a large muscle
(Ventrogluteal preferred for adults)
 Topical
 Duration of therapy varies from single dose to
years; most acute infections treated for 7 to 10
days
Anti-microbial Drug Reactions
 Hypersensitivity reactions
 Occur most often with the ____________
administration
 S/Sx: Low grade fever, rash, hives and swelling
 Anaphylactic reactions
 More likely to occur with IV route
 Most often occur within 5-30min of injection
 S/Sx: ________________________________________
______________________________________________
Common Adverse Effects
 Phlebitis at IV sites; pain at IM sites
 Nausea & Vomiting—Most Common Side Effect
 Diarrhea (severe colitis possible with some
antimicrobial therapy—s/sx blood stool, pus
mucous)
 Bone marrow suppression with thrombocytopenia
(decreased plt)—most common with penicillins and
cephalosporins
 Nephrotoxicity—esp aminoglycosides and
sulfonamides
Common Adverse Effects
 Neurotoxicity—IV penicillins or cephalosporins
 Ototoxicity: S/Sx: Tinnitus , vertigo, hearing loss
 Hepatoxicity
 Monitor Liver Function Tests: ALT, AST, Bilirubin
 S/Sx: Jaundice, dark urine, pale stools, abd pain, fever
 Photosensitivity
Age-Related ConsiderationsChildren
 Penicillins and Cephalosporins generally safe
 Fewer clinical trials on children
 Erythromycin, Zithromax (azithromycin) and Biaxin
(clarithromycin) considered safe
Antimicrobials and Children
 Aminoglycosides can cause ototoxicity and
nephrotoxicity.
 Tetracyclines are contraindicated in children younger
than 8 years old, effects on teeth
 Cleocin (clindamycin) admin. requires liver and
kidney monitoring in neonates and infants
Antimicrobials and Children
 Fluoroquinolones contraindicated in children under
18 yo. May have effects on weight bearing joints.
 Bactrim (trimethoprim-sulfamethoxazole) no longer
1st line due to resistance
Antimicrobials and Older Adults
 Penicillins are generally safe, IV admin. can cause
hyperkalemia
 Cephalosporins are considered sage but can affect or
worsen renal failure
 Macrolides are generally safe
 Aminoglycosides are contraindicated in severe renal
impairment
Antimicrobials and Older Adults
 Aminoglycosides can also cause
ototoxicity
 Cleocin (clindamycin)-diarrhea, colitis
 Bactrim (trimethoprimsulfamethoxazole) may be associated
with impaired liver or kidney function
 Tetracyclines (except doxycycline) and
Macrodantin (nitrofurantoin) are
contraindicated in impaired renal
function
In General
 With most oral antibiotics, liberal fluid intake is
recommended
 Always be aware of pregnancy category before
administering medication
Lab ID of Pathogens
 Culture and sensitivity
 Serology-measures antibody levels
 Polymerase Chain Reaction (PCR) detects the
specific DNA for a specific organism
Antibiotic-Resistant Microorganisms
Occurs when:
 Clinical condition of host is impaired
 Normal flora have been suppressed
 interrupted or inadequate tx
 Type of bacteria
 Widespread use of broad spectrum abx
 Environmental setting of host
Host Defense Weakened by
 Breaks in skin and mucous membranes
 Impaired blood supply
 Neutropenia
 Malnutrition
 Poor personal hygiene
 Suppression of normal flora
 Diabetes, advanced age or immunosuppression
Mechanisms of Action
 Inhibit cell wall synthesis
 Alter membrane permeability (PCNs,
Cephalosporins, Vancomycin_
 Inhibition of protein synthesis (EES,
tetracyclines, clindamycin, aminoglycosides)
Mechanisms of Action cont.
 Disruption of microbial cell membranes (anti-fungals)
 Inhibition of organism reproduction by interfering
w/nucleic acid synthesis (fluoroquinolones, HIV antiretrovirals)
 Inhibition of cell metabolism and growth
(sulfonamides)
Administration
 Labs to Monitor
 Blood levels of the antibiotic
 CBC (complete blood count)
 WBC (white blood cell) count

WBC should return to normal if med is effective
Prophylactic Therapy
 STD exposure
 Recurrent UTIs
 TB
 Perioperative infections in high risk patients or high
risk surgeries
Antibiotic Combination Therapy
 Used when infection is caused by multiple
microorganisms
 Nosocomial infections
 Serious infections in which a combination is
synergistic (aminoglycoside and antipseudomonal
PCN)
Antibiotic Combination Therapy cont.
 Likely emergence of drug resistant organisms
 In those who are immunosuppressed
Antibiotics Affecting the
Bacterial Cell Wall
 Penicillins

Penicillin (P)
 Cephalosporins

Cefotaxime (P)
 Vancomycins

vancomycin
 Carbapenems

meropenem
 Monobactam
Antibiotics
Beta Lactams
 Contain a beta-lactam ring that is part of their
chemical structure
 An intact beta-lactam ring is essential for
antibacterial activity
 Include: Penicillins, Cephalosporins, Carbapenems
 Cross-sensitivity
Penicillins
 Prototype is Penicillin G
 Most serious complication is hypersensitivity. Can
cause seizures and nephropathy.
 Contraindicated in patients with known allergy to
PCN, cephalosporins, or imipenem.
Indications for Penicillins
Examples of Penicillins
 Penicillins G and V (parenteral); dicloxacillin
(antistaph);
 Ampicillins—Principen, Amoxil
 Antipseudomonals—Geocillin (carbenicillin), Ticar
(ticaracillin), Pipracil (piperacillin)
 Combinations for beta lactamase—Unasyn
(ampicillin/sulbactam), Zosyn
(piperacillin/taxobactam)
Cephalosporins
 Also derived from a mold
 Broad spectrum with activity against both gram
positive and gram negative bacteria
 Cefotamine (P)- 3rd generation
Cephalosporins
 Indications-surgical prophy, tx infections of the
respiratory tract, skin, bone and joints, urinary tract,
brain and spinal cord and in septicemia
Cephalosporins
 Contraindicated in anaphylaxis to a penicillin
 May develop a delayed reaction or cross-sensitivity
 A/E:




Hypersensitivity
Anaphylaxis
GI: n/v/d
Pain at injection site
Examples
 Oral—Keflex (cephalexin); Ceclor (cefaclor), Lorabid
(lorcarbef); Omnicef (cefdinir)
 Parenteral—Ancef (kefzol); Mefoxin (cefoxitin);
Claforan (cefotaxime), Fortaz (ceftazidime), Rocephin
(ceftriaxone); Maxipime (cefepime)
Carbapenems
 Broad spectrum, bactericidal, beta-lactam anti-
microbials. Inhibit synthesis of cell walls.
 All are parenteral
 Indicated for organisms resistant to other drugs
 Examples: Merrem (meropenem) and Primaxin
(imipenem-cilastatin)
Monobactam Antibiotics
 Azactam (aztreonam) is active against gram-negative
bacteria and to many resistant strains
 Stable in presence of beta lactamase
 Preserves normal gram positive and anaerobic flora
FYI
 Penicillins may be given with Probenecid or
aminoglycosides for serious infections
 PCN can cause nephropathies
 Ticaracillin has been linked to hypernatremia
 PCN G can cause hyperkalemia
 Caution w/Augmentin in hepatic impairment
 Need to adjust dosages of all beta lactams in the
presence of renal impairment whether PCN,
cephalosporins, carbapenems and monobactams
Antibiotics affecting Protein
Synthesis
 Aminoglycosides
 Gentamicin (P)
 Tetracyclines
 Tetracycline (P)
 Macrolide Antibiotics
 Erythromycin (P)
Aminoglycosides
 Bactericidal agents to treat gram negative organisms
such as: Proteus, Klebsiella, Enterobacter, Serratia,
Escherichia coli, and Pseudomonas
 Narrow specturm
 Accumulate in kidneys and ears
 Gentamycin (P)
Aminoglycosides cont.
 MOA: penetrate cell walls of susceptible bacteria and
bind to 30S ribosomes. —prevent protein synthesis and
replication.
 Most often affect the respiratory, GU, skin, wound,
bowel and bloodstream
Aminoglycoside—Management Considerations
cont.
 Measurement of peak and trough levels helps to
maintain therapeutic serum levels w/o excessive
toxicity
 Daily dosing
 With impaired renal function, dosage of
aminoglycosides must be reduced. Dosages or
intervals may be reduced.
 In UTIs, may use lower dosage as excreted by kidneys
Tetracyclines
 Broad spectrum bacteriostatic
 Microbial resistance emerging
 Effective against Chlamydia, Mycoplasma, protozoa
(e.g. Malaria, Giardia, Leishmaniasis)
Indications for use
 Treatment of uncomplicated urethral, endocervical or
rectal infections caused by chlamydia
 Long term treatment of acne
 May be used as substitute for penicillin
 Doxycycline may be used for Traveller’s diarrhea
Tetracyclines cont.
 Contraindicated in renal failure except for doxy
and minocycline
 Not indicated in children less than 8 years of age
because can cause permanent discoloration of
teeth and can depress bone growth
 Can cause photosensitivity
 Avoid taking within 2 hours of dairy products,
w/iron or w/antacids
Macrolides
 Include: Zithromax (azithromycin), Biaxin
(clarithromycin), (erythromycin) (P) and Dynabac
(dirithromycin)
 Effective against gram positive cocci, Neisseria,
Treponema, Mycoplasma,Bacteroides, Clostridia and
Corynebacterium
Macrolide Management Considerations &
Contraindications
 Interacting drugs include: Coumadin, Theophylline,
Prednisone, Norpace, Lanoxin, Tegretol, Alfenta and
Parlodel (dopamine agonist)
 Contraindicated in liver disease
 Contraindicated in hypersensitivity
Fluoroquinolones
 Synthetic bactericidal drugs with activity against gram
positive and gram negative organisms
 Most are given orally
 Excreted via kidneys
 Contraindicated in liver disease
 Contraindicated in hypersensitivity
Fluoroquinolones
 Examples of floroquinolones: Cipro (ciprofloxacin),
Levaquin (levofloxacin), Floxin (ofloxacin)
 Monitor renal and liver function
 Ensure adequate fluid intake to prevent crystalluria
 Assess current medications for drugs that interact
 Avoid exposure to sunlight
Miscellaneous--Vancomycin
 Active against gram positives only
 Frequently used to treat MRSA
 Can cause hypotension, flushing and skin rash if
given too quickly
 Resistance is mounting
 Can cause “red man sydrome” if given too quickly
 Caution in patients w/myasthenia gravis
Miscellaneous
 Cleocin (clindamycin)—similar in actio to macrolides;
is effective against gram positive cocci and
pneumococci
 Effective in treating mixed infections
 Great for acne and bacterial vaginosis
 Can cause pseudomembranous colitis
Miscellaneous
 Flagyl (metronidazole)
 Effective against anaerobic bacteria, gram positive
bacilli such as clostridium and protozoa such as
Giardia, amebiasis, trichomoniasis
 Useful topically for rosacea
 Used for bacterial vaginosis
 Disulfiram-like reaction if taken w/alcohol
Drug interactions
 Amphotericin B, vancomycin, cephalosporins, loop
diuretics, neuromuscular blocking agents can increase
the effects of aminoglycosides
 Tagamet (cimetidine) and Probenecid increase the
effects of the fluoroquinolones
Sulfonamides
 Bacteriostatic against both gram positive and gram
negative bacteria
 Resistance is mounting
 Combination of Bactrim (trimethoprimsulfamethoxazole) is useful in the treatment of urinary
tract infections and in Pneumocystis carinii
Sulfonamides
 Contraindicated in renal failure
 Can cause bone marrow depression, especially in
elderly
 With Bactrim, can cause folic acid deficiency
 Can cause cholestatic jaundice in rare cases
Sulfonamide preparaions
 Azulfidine (sulfasalazine) is used in tx of ulcerative
colitis and in RA
 May cause crystalluria. Liberal fluids needed.
Sulfonamides cont.
 Sulfamylon used in burns—especially
w/Pseudomonas—can cause metabolic acidosis, is
painful w/application
 Silver sulfadiazine—useful in burns
Treating Viral & Fungal Infections
Viral and Fungal Diseases
 Hepatits
 Herpes Simplex
 Herpes Zoster
 Influenza
 HIV
 candidiasis
Antifungals: 2 types
1. Systemic antifungal
2. Superficial antifungal
Antifungals
 Fluconazole (Diflucan)
 Nystatin (P), (Mycostatin)
 May be used orally, topically, or vaginally
 Generally well tolerated
Viral Replication
Anti-Viral Agents
 Acycolvir (P)
 Indications: HSV, Herpes zoster
 A/E: lightheadedness, anorexia, n/v, HA.


Confusion, tremors, sz
IV may be nephrotoxic