Drugs To Prevent Or Treat Infection

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NON-SPECIFIC DEFENSES

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-serves as barriers to microbes or environmental hazards; it is unable to distinguish one type of threat from anothers and is the same regardless of the pathogen; involves the phagocytes, natural killer cells, the complement system, fever, and interferons

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WHAT CELLS ARE INVOLVED IN NON-SPECIFIC IMMUNITY?

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MAINLY THE PHAGOCYTES:
-granulocytes (neutrophils, eosinophils, basophils, mast cell)
-agranulocytes (monocytes, macrophage)

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SPECIFIC IMMUNITY

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MAINLY INVOLVES THE LYMPHOCYTES
-Bone marrow=Humoral mediated, B lymphocyte
-Thymus=Cell-mediated, T lymphocytes

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ACTIVE IMMUNITY

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-the type of immunity achieved through the administration of a vaccine

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PASSIVE IMMUNITY

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-occurs when preformed antibodies are transferred from one person to another; antibodies or serum from immunized humans or animals fro immediate protection. DRUGS FOR PASSIVE IMMUNITY ARE ADMINISTERED WHEN THE CLIENT HAS ALREADY BEEN EXPOSED TO A VIRULENT PATHOGEN, OR IS AT VERY HIGH RISK TO EXPOSURE, AND THERE IS NOT SUFFICIENT TIME TO DEVELOP ACTIVE IMMUNITY.

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WHAT ARE THE VARIABLES IN EFFICACY OF ANTI-INFECTIVE DRUGS?

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-Drug interactions can lower effect of the anti-infective drug
-Other drugs such as glucocorticoids which suppress immunity
-Site of infection such as sinus cavity and CNS is very difficult for anti-infective to reach because of the blood brain barrier.
-effective immune system of the patient is important

Hint 6

D.O.S.E. Variables

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WHAT SHOULD NURSE TEACH PATIENT ABOUT ANTI-BIOTICS?

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-Do not overuse
-If given an antibiotic, take as directed for the full course
-Do not use for viral infections

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WHAT ARE THE GENERAL MODES OF ACTION FOR ANTI-INFECTIVE DRUGS?

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-modifies protein synthesis of the bacteria.(TCNs, AMINOGLYCOSIDES, MACROLIDES)
-modifies DNA synthesis of the bacteria.(QUINOLONES)
-damages the cell wall of the bacteria (BETA-LACTAMS=PENICILLIN, CEPHALOSPORINS, & CARBAPENEMS)
-modifies energy metabolism via folic acid (SULFONAMIDES)

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WHAT ARE THE THREE MAIN TYPES OF MICROORGANISM RESISTANCE?

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1.) Microbe develops enzyme that chemically alters and inactivates the antibiotic (ex: penicillinase)
2.) The antibiotic uptake is reduced (ex: tetracyclines)
3.) Bacteria mutates so the target of the antibiotic is resisted (ex: erythromycin)

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STAPHYLOCOCCUS AUREUS

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-can cause serious soft tissue infections.
-important when considering resistance because many strains are resistant to methicillin (MRSA)
-colonizes mainly in nasal passages
-can be cuase of many infections: boils, diarrhea, systitis, osteomyelitis, pneumonia, sinusitis, etc.
-can be found on many wounds and in sutures
-responsible for hospital acquired infections that often become resistan---now in the community, too!!!
-can cause toxic shock if in the blood.

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HEALTH-CARE ASSOCIATED MRSA

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-acquired and transmitted primarily in health care settings.
-well adapted to survival in hospital where in can multiple and colonize
-was first reported in 1961 after introduction of methicillin and resulted from inadequate hygiene and infection control.
-prevention efforts in US hospitals are largely unsuccessful.

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COMMUNITY-ACQUIRED MRSA

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-primarily skin and sof tissue with purulence
-many strains
-more sensitive to a greater number of antibiotics than hospital-associated
-NEW PROBLEM: community strains moving into hospital snad hospital strains moving in to community
-nasal colonization.

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WHAT CAN BE DONE TO PREVENT SPREAD OF MRSA?

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-Cover infected areas with dry, clean bandages
-Wash hands/alcohol preps
-Advise close contacts to do the same
-Avoid unnecessary use of antibiotics
-Donot share personal items

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WHAT IS THE MOST COMMON PROBLEM WITH ANTIBIOTICS?

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HYPERSENSITIVITY REACTIONS BY SOME PATIENTS.

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WHAT ARE THE DIFFERENT TYPES OF HYPERSENSITIVITY REACTIONS?

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TYPE 1=IgE-mediated. Example: anaphylaxis, urticaria, angeioedema)

TYPE 2=Cytotoxic meaning it destroys cells which can be due to antibody or toxin and usually not antibiotic)

TYPE 3=Immune complex mediated. Example: serum sickness which is an immune response where the glands sell from the drugs-not from the illness)

TYPE 4=Mediated by sensitized lymphocytes. Example: contact sensitivity

Hint 15

Most important is Type 1 & Type 3

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PENICILLINS

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-Belongs to the Beta-Lactam class tue to its chemical structure
-It is BACTERICIDAL
MOA:
-gets into bacteria
-finds target which is the penicillin-binding protein (PBP)
-it then binds to the PBP which results in interference with the normal cell-wall synthesis=CELL WALL LYSIS & BACTERIA DIES

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NARROW SPECTRUM PENICILLIN

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-does the normal MOA of penicillins which bind to PBP
-Example: penicillin G, penicillin V

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EXTENDED SPECTRUM PENICILLIN

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1.) PENICILLINASE-RESISTANT
Example: methicillin (Staphcillin)-however, genetic mutation in bacteria has created resistance (MRSA)

2.) BROAD-SPECTRUM (AMINOPENICILLINS)
-Penicillin+B-lactamase inhibitor
Example: amoxicillin+clavulanic acid=Augmentin p.o.

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EXTENDED SPECTRUM (ANTI-PSEUDOMONAL) PENICILLIN

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-ticarcillin (Ticar)
-piperacillin+tazobactam(a B-lactamase inhibitor)=Zosyn, which is often used w/ Vancomycin (IV) to treat MRSA

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BETA-LACTAMASE

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-an enzyme that bacteria resistant to beta-lactam produces which destroys penicillins and cephalosporins

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PENICILLINASE

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-enzyme produced by bacteria that destroys penicillin by cleaving the beta-lactam ring of the drug in turn the drug becomes inactive.

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CLAVULANIC ACID

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-enhances the activity of penicillins by binding to the active sites of the enzyme penicillinase.

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WHAT ARE THE COMMON SIDE EFFECTS OF PENICILLIN?

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ALLERGIES
-skin rash (most common)
-serum sickness (less common)
-anaphylaxis (rare but potentially fatal)
GASTROINTESTINAL DISTRESS

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WHY DO YOU NOT GIVE PENICILLIN TO A PERSON WITH MONONUCLEOSIS AND HOW IS THIS DIAGNOSTIC FOR PENICILLIN?

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If penicillin is given to a person with mononucleosis, it can cause a serious rash. It can be diagnostic for mononucleosis because some people don't know they have mono until they are given an antibiotic & turn out to have a serious rash as a reaction. NOTE: Antibiotics should not be given for mono because it is caused by a virus.

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CEPHALOSPORINS

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-semisynthetic derivative of a fungus
-structurally and pharmacologically similar to penicillins=Beta-lactam drug
-it is BACTERICIDAL.
-has a BROAD SPECTRUM vs. penicillin w/ NARROW SPECTRUM
-varies depending upon generation.

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WHAT MAJOR PRECAUTION SHOULD BE TAKEN BEFORE GIVING PATIENT A CEPHALOSPORIN DRUG?

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Ask if patient has had anaphylactic reaction to penicillin. Because PCN & cephalosporins are similar, patient may also have allergic reaction to cephalosporin if allergic to penicillin.

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FIRST GENERATION CEPHALOSPORINS

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-bacteria that produce beta-lactamase will usually be resistant to these drugs
-has poor CNS penetration
-most effective for gram+ bacteria.
-administered via IM

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SECOND GENERATION CEPHALOSPORINS

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-more resistant to bacterias that produce beta-lactamase
-has broader spectrum--both gram+ & gram- & also some anaerobic bacteria
-administered via IM & IV

NOTE: loracarbef (Lorabid)
-excellent drug for otitis, URI, pharyngitis, sinusitis. NOT FOR PT W/ HISTORY OF SEIZURE. This is an "other" class similar to cephalosporin.

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THIRD GENERATION CEPHALOSPORINS

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-resistant to bacteria that produces beta-lactamase
-capable of entering the cerebrospinal fluid to treat CNS infections.
-most effective for gram- bacteria and also covers the anaerobic bacterias.

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FOURTH GENERATION CEPHALOSPORINS

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-reserved and effective against organisims that have developed resistance to earlier cephalosporins.
-like 3rd gen, can enter the CSF to treat CNS infections

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CARBAPENEMS

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-new class of beta-lactam antibiotics
MOA: similar to penicillins and cephalosporins by weakening bacterial cell wall
NOTE: it is structurally similar to penicillin and cephalosporin, so it may also have a cross-over allergy.
-so far, this class is highly resistant to bacterials producing beta-lactamase, but other forms of resistance do occur.
-ALL ARE RESERVED FOR SERIOUS INFECTIONS and effective against anaerobes

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CARBAPENEM:
imipenem (Primaxin)

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-given via IM or IV
-for serious LRI, UTI, skin & bone(osteomyelitis), intraabdominal, gyn resistant bacteria.

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CARBAPENEM:
meropenem (Merrem)

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-given via IV only
-for intraabdominal infection and BACTERIAL MENINGITIS

Hint 33

NOTE: know that this is for only for BACTERIAL meningitis

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CARBAPENEM:
ertapenem (Invanz)

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-given via IM & IV
-has narrow spectrum but longer half-life
-for complicated UTI and acute pelvic infection.

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MONOBACTAM

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-new class of anti-biotic
-slight difference from beta-lactam
-because it is structurally different than penicillins & cephalosporins, it may not have cross-over allergic reactio. It is reserved for patients w/ allergic reaction to PCN & cephalosporins; HOWEVER, this is not the preferred alternative for patients w/ allergic reaction to PCN & cepahalosporins (Macrolides is the 1st choice!)
-used for serious infections

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MONOBACTAM:
aztreonam (Azactam)

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-given via IM & IV
-has small spectrum of activitly only against gram- aerobic organisms.

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QUINOLONE

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-this class is BACTERICIDAL
-it's the first ORAL anti-bio to kill gram- bugs
-effective against gram+, gram- & atypicals
-has excellent ORAL ABSORPTION; however, antacids can reduce the absorption.
-great gram- coverage and an excellent drug for kidneys
#great for treatment of UTIs and prostatitis
#good for Salmonella typhi & Shigella.

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QUINOLONE MODE OF ACTION

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-alters DNA of bacteria by interference of DNA enzyme necessary for synthesis of bacterial DNA
NOTE: It does not affect mammalian enzyme, thus it does not inhibit production of human DNA

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QUINOLONE THERAPEUTIC USES

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-recurrent UTIs and prostatitis
-infectious diarrhea
-lower respiratory tract infections
-bone and joint infections
-skin infections

Hint 39

NOTE: important to know that it's for recurrent UTIs and prostatitis

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QUINOLONE SIDE EFFECTS

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OTHER/INTERESTING:
-can cause tendonitis
-may cause false positive on toxicology urine screen for opiates
-Levofloxacin, moxifloxacin & levaquin can cuase long QT interval, so get EK before giving this drug.
-fever chills, blurred vision & tinnitus.
DERM: rash, pruritis, photosensitivity, flushing
GI: n/v/d, constipation & thrush
CNS: HA, dizziness, fatigue, depression & restlessness.

Hint 40

Note the unusual side effect of tendonitis. Nursing implication, stop med if patient reports tendon pain

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WHAT UNUSUAL SIDE EFFECT MUST THE NURSE BE ALERT FOR IN PATIENTS TAKING QUINOLONES?

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TENDONITIS

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NOTE: Also, note that it can cause +urine test for opiates & can cause long QT interval.

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MACROLIDES AND THE THREE MAIN DRUGS

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-this is the drug given for patients w/ allergies to penicillin and cephalosporins
A.C.E.
-Azithromycin
-Clarithromycin
-Erythromycin

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MACROLIDES MODE OF ACTION

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-this drug is BACTERIOSTATIC
-is an inhibitor of cytochrome 3A4 in the P45o system so it has great potential for many many drug interactions (except for Azithromycin)
MOA:
-binds to 50s ribosomal subunit thus INHIBITING THE PROTEIN SYNTHESIS necessary to make needed DNA

Hint 43

NOTE: Because this class of drugs are hepatotoxic and metabolized in the liver & can cause many drug-drug interactions, it should not be given to patients w/ liever/hepatic impairment.

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MACROLIDES THERAPEUTIC EFFECTS

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-used to treat mycoplasma (aka "walking pneumonia"-- for which PCN & cephalosporins are not effective)
-strep infections
-mild to moderate URTI
-spirochetal infections (syphilis & Lyme disease)
-gonorrhea and chlamydia

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MACROLIDES SIDE EFFECTS

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Main S/E:
-GI especially with Erythromycin
-n/v/d, hepatotoxicity, flatulence, jaundice & anorexia
NOTE: NEWER MACROLIDES (azithromycin) have less S/Es, longer DOA, better efficacy & excellent tissue penetration, less nausea

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TETRACYCLINE

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-drugs in this class is BACTERIOSTATIC
-can be natural or semi-synthetic and is obtained from cultures of Streptomyces
-BAD: can bind (chelate) to divalent [Ca++ & Mg++] and trivalent [Al+++) metallic ions to form insoluble complexes
-because of its strong affinity for calcium, it can permanently stain teeth if given to children under 8 yrs old.
-must also avoid dairy products, antacids & iron salts because these can reduce oral absorption of TCNs (due to TCNs high affinity for metallic ions that are in these substances)
-it is lipid soluble & able to enter the CSF.

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TETRACYCLINE MODE OF ACTION

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-inhibits protein synthesis by inhibiting the ribosome 30s resulting in prevention of RNA synthesis to DNA
-TCN stops many of the bacteria's essential features:
growth & repair--bacteria eventually stops growing and dies.

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TETRACYCLINE THERAPEUTIC EFFECTS

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Example drug:
doxycycline [Doryx, Vibramycine & VibraTabs]
-has a wide spectrum
-is a synthetic TCN
good for:
-acne
-Rickettsial infections, Chlamydial & Mycoplasma infections, Gonorrhea, and Spirochetal infections(Lyme dz).
-pleural effusions & many biologic agents.

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TETRACYCLINE ADVERSE EFFECTS

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-CNS side effects
-phototoxicity
-permanently stained teeth.

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SULFONAMIDES

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-this drug class is BACTERIOSTATIC
-mainly used for UTI(an alternative are the Quinolones due to growing resistance to the Sulfonamides)
-also used for treatment of bronchitis (Bactrim)
-a.k.a. antimetabolites

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SULFONAMIDES MODE OF ACTION

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-prevents synthesis of folic acid which is needed by the bacteria for synthesis of purines & nucleic acid thus inhibiting the growth of the bacteria
-does not affect the human cells because humans take up folic acid from diet
-is HIGHLY PROTEIN BOUND, so it may displace other drugs from protein-binding sites

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WHAT NURSE TEACHING SHOULD BE GIVEN TO PATIENT TAKING SULFONAMIDES?

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1.)Teach patient to drink plenty of fluids to prevent urinary crystals because this drug causes crystalluria.
2.)Caution for patients who are allergic to thiazide diuretics and sulfonylureas.
3.) Find out if pt is allergic to red dyes & betadine. Caution pt about red urine.

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SULFONAMIDES SIDE EFFECT

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HEME: hemolytic & aplastic anemia & thrombocytopenia.
DERM: photosensitivity, (rare) Steven's Johnson syndrome, epidermal necrolysis, & exfoliative dermatitis.
OTHER: (rare) convulsion, crystalluria, toxic nephrosis, peripheral neuritis and urticaria
FAIRLY COMMON: rash & urticaria