PHARMACOLOGY FOR DENTAL HYGIENE: DEHY34
Instructor (who to blame and contact): Jim Middleton, RPh
Module Three: ANTIMICROBIAL AGENTS


By the completion of this section, the participant should be able to:
 1. Discuss the differences between "bactericidal" and "bacteriostatic"
 2. Identify those portions of the bacterial cell acted upon by antimicrobial, based on classification
 3. Identify the antibiotic that is contraindicated in 2 year olds, and discuss the reason why
 4. Discuss the general side effects of antibiotic therapy and their possible treatments
 5. Define "Spectrum of Activity"
 6. Identify the characteristics of an ideal antibiotic
 7. Identify the causes of bacterial resistance to therapy
 8. Understand the concept of "crossover" allergy and identify those classes of antibiotics where this is possible
 9. Discuss the options for premedicating a patient with mitral valve disease and how it relates to bacterial endocarditis
 10. Identify the substance "penicillinase" and its effect on antibacterial therapy
 11. Discuss cost-benefit differences between antibiotic therapy choices


I. General discussions
    A. Antibiotics
        1. most often prescribed class of drugs these days
        2. subtypes--DEFINITION TIME!
            a. bacteriostatic – slows down the growth of bacteria–drug removed, bug grows!
   examples: chlroamphenicol, clindamycin, “macrolides”, spectinomycin, sulfonamides, tetracyclines, trimethoprim

            b. bactericidal – kills the microbe
   examples: aminoglycosides, bacitracin, cephalosporins, penicillins, high dose macrolides, quinolones, vancomycin, rifampin

   B. Characteristics of an ideal antibiotic
 --remember that these are ideal characteristics, and no currently-marketed antibiotic meets all these criteria, but we can still dream--
       1. effective against microbe without harming host
       2. bactericidal (preferentially)
       3. no bacterial resistance
          --at one time, there was no resistance to penicillin
       4. quickly reaches a peak concentration and stays there for a sustained period
          --patient compliance, reduced number of doses/day
       5. minimal side effects
       6. not inactivated by enzymes (a problem with penicillin) secreted by microbes, plasma proteins, or body fluids (many antibiotics are ineffective if taken orally)

   C. Possible mechanisms of action
        1. inhibit bacterial cell wall synthesis (bactericidal)
        2. alter permeability of a microbe's cell membrane (bactericidal)
              --increase in permeability can cause rupture of the microbe and destruction of the cell
        3. alter synthesis of the cellular components of the microbe (bacteriostatic): slow down microbial synthesis
        4. inhibit bacterial cell metabolism ('static)
              --metabolism is slowed, therefore duplication of the cell is slowed (but not stopped)

    D. Resistance: "the microbe is not affected by the antibiotic"
        1. two types of resistance are possible
           RESISTANCE TYPES
            a. natural
               --not due to contact with the drug
               --microbe is simply not within the spectrum of activity of the antibiotic

              SPECTRUM OF ACTIVITY: “those microbes against which an antibiotic is effective”

  NARROW spectrum–effective only against a few microbes
  BROAD spectrum–effective against many types

           b. acquired resistance
               --results from contact with the drug
               --the microbe mutates at the DNA level, passing the change on as the microbe reproduces

               ACQUIRED RESISTANCE CAN DEVELOP BY
                  i. inactivating enzyme (e.g., penicillinase)
                  ii. alternative metabolic pathways not affected by the antibiotic
                  iii. microbe undergoes a biochemical change and antibiotic no longer has access to microbial cell (the drug cannot bind or cannot be absorbed)
                                –ie, changing the cell wall of the microbe to prevent penetration of the drug

    E. Effectiveness of Therapy depends upon
        1. appropriate antibiotic
        2. appropriate dosing
        3. THEREFORE, CONSIDER
            a. improper antibiotic choice and the results
                   –infections associated with high rates of resistance include lower respiratory tract infections and those associated with osteomyelitis or cystic fibrosis
            b. inadequate dose
            c. resistance and "selective pressure" (survival of the fittest)-- both gram-positive and gram-negative bacteria are developing resistance; gram-positive organisms include staphylococci, streptococci, and enterococci.  Gram-negative organisms with high rates of antibiotic resistance are Pseudomonas aeruginosa, Serratia, Enterobacter, and Acineobacter

            d. "take until gone" not just "until I feel better" (general therapy is 7 to 10 days)
            e. drug interactions (calcium and "heavy metals" with tetracycline)
            f. condition of the host: patients with malnutrition, immunocompromised systems, or on mechanical ventilation or other mechanical devices (dialysis machines)



   Factors that can affect the host’s defenses
   1. breaks in skin or mucous membranes
   2. impaired blood supply
   3. neutropenia or blood disorders
   4. malnutrition
   5. poor personal hygiene
   6. suppression of bacterial flora by antibiotics
   7. suppression of immune system by immunosuppressive drugs (ie chemotherapies for cancer, corticosteroids)
   8. diabetes and other chronic diseases
   9. advanced age


4. Complications of proper therapy

            a. killing off body flora results in: DIARRHEA!
               --can treat with– ACIDOPHILUS, YOGURT with active cultures –the re-establishment of intestinal flora can take several weeks to months


A brief Digression on "NORMAL BODY FLORA" (sounds so pastoral, doesn't it?)
Bacteria colonies exist on the skin, in the upper respiratory tract, and in the colon.
The upper respiratory tract contains
 staphylococci
 streptococci
 pneumococci
 diphteriods
 Haemophilus influenzae
The vaginal membranes contain
 lactobacilli
 Candida albicans
 Bacteroides
The colon contains
 Eschericia coli
 Klebsiella
 Enterobacter
 Proteus
 Pseudomonas
 Bacteroides
 Clostirdia
 lactobacilli
 streptococci
 staphylococci

ANOTHER COMPLICATION POTENTIAL AT THERAPEUTIC DOSING:
            b. superinfection (sometimes called “suprainfection”)
  Normal flora protects the human host by occupying space and consuming nutrients; if suppressed, potential pathogens may thrive.  For example, the yeast Candida albicans is a normal resident of the vaginal membranes and intestinal tract.  Without normal flora present, Candida albicans can grow unchecked and become THE organism of the area.
    And from this you can get:
               "black tongue" "thrush" yeast infections
   can treat this with: NYSTATIN (mycostatin)

  AND IF THAT ISN’T ENOUGH
   c. VITAMIN K is produced by GI bacteria–killing off the body’s natural flora will reduce vitamin K levels.  Vitamin K is part of the body’s clotting process; without it, the body could experience increased bleeding times.  Patients taking a blood thinner such as warfarin (Coumadin) could experience increased anticoagulation effects as well...

    F. Spectrum of activity
        a. broad vs narrow spectrum

        b. effectiveness depends on microbe involved



QUESTION
Mouthwashes containing commonly used systemic antibiotics make ideal mouthwashes because systemic antibiotics show little tendency toward antibiotic sensitization when used topically.
 BOTH STATEMENT AND REASONING ARE FALSE!!!


G. Combination therapy
        1. synergism or antagonism

        2. physiological antagonism: bacteriostatic and bactericidal given together
NOSOCOMIAL INFECTIONS are becoming an increasingly serious problem in the health care settings.  These infections grow in institutional settings where antibiotic use is very common--hospitals, nursing homes--and the likelihood for bacterial resistance is high.  These infections are very, very difficult to treat and often require multiple antibiotics, prolonged duration of therapy, and hospitalization.


Another Digression
THE DEADLY E-coli:
One strain of the gram-negative bacteria E. coli, called 0157:H7, causes hemorrhagic colitis, a disease resulting in severe abdominal cramping, copious bloody diarrhea, and possibly hemolytic-uremia syndrome (hemolytic anemia, thrombocytopenia, and acute renal failure; the syndrome is more common among children).  The main location for this strain of E. coli is in the intestinal tracts of animals, notably cattle; epidemics have resulted from eating undercooked beef.  Other sources include contaminated water and person to person contact.  Because it cannot survive in nature, the presence of E. coli in milk or water indicates fecal contamination!And while talking about nosocomial infections, consider IATROGENIC infections---
Iatrogenic infections are those that occur because of the treatment–namely, when the caregiver has a lax approach to handwashing (or other hygiene issues) and spreads the infection to the patient.


II. THE ACTUAL ANTIBIOTICS!!!
YET ANOTHER RUDE INTERRUPTION IN THE OUTLINE:
There has been a long standing concern of diminished effectiveness of oral contraceptives when co-administered with antibiotics.  While this concern initially involved only tetracycline and drugs in that classification, the general warning now encompasses all antibiotics.
Women are to be urged to use additional forms of birth control while using antibiotics as a result.

A. Penicillin– Fleming of England
         1. oldest, from: bread mold
  2. spectrum MAINLY GRAM POSITIVE
  3. bactericidal
           a. works on growing cell walls, therefore, with a bacteriostatic antibiotic.....antagonism!
  4. better absorption on an empty stomach (improved blood levels)
  5. adverse effects (mainly allergies, 1-5%)
  If you’re allergic to one drug in the penicillin class, there's about a 10% chance you’ll be allergic to ALL drugs in the penicillin class, depending on the severity of your allergic reaction (obviously, the more severe the reaction, the greater likelihood of "crossover allergies")
  6. excreted by kidney, mostly unchanged (odor often noted)
  7. DRUG OF CHOICE FOR PROPHYLAXIS IN RHEUMATIC FEVER
  8. types
             a. penicillin G--the original penicillin, buffered, developed in Britain
                   (injection and oral, orally also known as “Pentids”)

             b. penicillin V--more rapidly absorbed, acid stable (meaning, it doesn't break apart in stomach acid), developed in the US
                   (oral only, known as “Pen-Vee K” “V-Cillin K” or “Veetids”)

BOTH ARE GOOD CHOICES TO HIT MICROBES THAT DO NOT PRODUCE THAT NASTY ENZYME PENICILLINASE



QUESTION
A histamine type reaction can be combated by administration of any of the following drugs except...
 a. penicillin
 b. epinephrine
 c. prednisolone (or prednisone or methylprednisolone)
 d. diphenhydramine (Benadryl)
Granted, this section is not covering cardiac or medical emergencies, however, you should be able to recognize an antibiotic used out of context when you see it.  Here, the examiner wants to know whether you think an antibiotic would be effective in treating an allergic reaction.  Your response is “of course not.”

IF you have to treat an infection whose microbe does produce penicillinase, you have to use a penicillinase-resistant penicillin, such as
             c. methicillin (Staphcillin)  inj
             d. oxacillin (Prostaphlin)    oral and inj
             e. dicloxicillin (Dynapen)    oral and inj
             f. nafcillin  (Unipen)        oral and inj

 THE FOLLOWING PENICILLINS are considered "broad spectrum" but are not penicillinase-resistant
             g. ampicillin (Amcil)
             h. amoxicillin (Amoxil, Trimox)
   –note: an “augmented” version of amoxicillin is on the market, representing a combination with clavulanic acid to inactivate beta-lactam enzymes (ie penicillinase) is available as well; this product is known as Augmentin
             i. carbenicillin (Geocillin)

    B. CEPHALOSPORINS
        1. related to the penicillins, therefore
        2. ALLERGY CROSSOVER POSSIBLE if patient is allergic to penicillins
           --depends on severity of penicillin allergy; about a 10% likelihood



 QUESTION
A patient who is allergic to penicillin will have an allergic reaction to which of the following drugs?
   a. neomycin
   b. cefalexin
   c. erythromycin


         3. activity
            a. gram positive and some gram negative
            b. E. Coli, Proteus mirabilis, Klebsiella, Enterobacter

        4. Bactericidal
   in dental use, these antibiotics have a questionable advantage over the penicillins, especially in light of crossover allergies and COST!!! ($$$$$$$$$)

        5. specific agents,
            a. orally: cefalexin (Keflex), cefachlor (Ceclor), cefadroxil (Duricef), cephradine (Anspor/Velosef), cefpodoxime (Vantin)
            b. injections:cefazolin (Ancef/Kefzol),cefoxitin (Mefoxin), cefamandol (Mandol), cefoperazone (Cefobid), ceftriaxone (Rocephin),ceftazidime (Fortaz)

A HINT IN REMEMBERING IF A DRUG IS A CEPHALOSPORIN: look for the prefix "cef" in its name.

    C. Erythromycins “The Macrolides”
  --“Erythromycin” also goes under the names of EryPed, EES, Eryc, Ilosone, PCE, E-Mycin
  –Erythromycins are also often called MACROLIDE ANTIBIOTICS.  They have been known to interfere with the metabolism of certain other drugs, such as the theophyllines (used in asthma), Propulcid (used to maintain a steady peristalsis in the stomach and GI tract), and the antihistamine Hismanal.–fortunately, these last two have been pulled from the market...however, other drugs are emerging to demonstrate a similar interaction, most recently, some of the SSRI agents for depression and sildenafil (Viagra) for... well...
  In addition, the combination can result in increased levels of carbamazepine (Tegretol) and warfarin (Coumadin).
  DIMINISHED effectiveness of birth control pills.

        1. bactericidal: an alternative to the penicillins
                  Therapy also for Legionnaire’s bacillus and Mycoplasmosis avii
        2. effective against penicillinase?

        3. injection, liquids, capsules, tablets
        4. main side effect: GI distress and diarrhea– should be taken with food

  OTHER VARIETIES OF ERYTHROMYCINS or “Macrolide antibiotics” include clarithromycin (Biaxin) and azithromycin (Zithromax).   Azithromycin (Zithromax) is the exception to the “take with food” rule of erythromycin drugs--it is absorbed best on an empty stomach.   Azithromycin (Zithromax) comes in a “Z pack” for dosing convenience: 2 tablets on the first day, followed by one tablet daily for days 2 through 5
  Clarithromycin (Biaxin), however, ALWAYS needs to be given with food!
  Also, both clarithromycin (Biaxin) and azithromycin (Zithromax), when dispensed in suspension form, do NOT need to be refrigerated.  In fact, refrigeration makes both suspensions taste worse than they already do!

    D. Tetracyclines
       The original tetracycline has the trade names of Tetracyn, Achromycin, and Panmycin; later, Vibramycin (doxycycline), Terramycin, Minocin (minocycline) were introduced for their proclaimed resistance to chelation to "heavy metals"

        1. broad spectrum, alternative for penicillins or erythromycins
        2. tetracyclines are BACTERIOSTATIC
        3. FALCONI'S SYNDROME
           --from outdated tetracyclines
           --the organ affected by this syndrome: kidneys

  4. crossover tetracycline allergy – if allergic to one, allergic to all
        5. photosensitivity
            definition of photosensitivity: sensitivity to sunlight, from overexaggerated sunburn to painful, itchy rashes

        6. teratogenic
            definition of teratogenic: causes birth defects in developing fetus

        7. effect on teeth and bone
  binding with calcium AND WHICH OTHER ELEMENTS? LITHIUM, IRON, ZINC, MAGNESIUM, ALUMINUM...need to administer tetracycline 1 hour before or 2 hours after ingesting these materials or drugs that contain them... less of an issue with doxycycline or minocycline – the goal is to prevent the formation of non-absorbable chelates



QUESTION
A two-year old boy contracts an infection that requires antibiotic therapy.  With this information alone, which drug below wouldn't you use?
   a. penicillin
   b. erythromycin
   c. tetracycline
   d. cephalothin


E. Clindamycin (Cleocin)
        1. used against gram-positive and anaerobic Bacteroides species of bacteria, occasionally an alternative to penicillin when allergies present
   a. oral anaerobic infections–Bacteroides oralis, Peptostreptococcus, Fusobacterium
        2. spectrum similar to erythromycin–food does not affect absorption
        3. side effects
            a. diarrhea 10%
            b. nausea/vomiting
            c. hemorrhagic colitis
               --even when used topically for acne
     d. glossitis and stomatitis
     e. neutropenia, thrombocytopenia, and agranulocytosis have been reported
  4. cross-resistance to erythromycin has been noted
  5. renal dysfunction reports have resulted in encouraging increased fluid intake while using clindamyicn

 F. Vancomycin
        1. IV alternative to penicillin for preoperative use in penicillin-allergic patients
        2. treat bacterial endocarditis
        3. phlebitis, renal toxicity, 8th cranial nerve damage

 QUESTION: WHAT DOES DAMAGE TO THE 8TH CRANIAL NERVE CAUSE?

        4. not a useful oral substitute for penicillin; when given orally, it is poorly absorbed through the GI tissue, if at all

    G. Streptomycin
        1. prophylaxis for patient with rheumatic fever history
        2. 8th cranial nerve damage
        3. topical solution

    H. Sulfonamides–introduced in the 1930s
        1. not often used in dentistry; mainly for UTIs (urinary tract infections), although effective for otitis media or exacerbations of chronic bronchitis
        2. photosensitivity–most common side effect
        3. DRINK LOTS OF WATER (cleared through the kidney) 2 liters per day!
           –microscopically, sulfonamides resemble clear needles when they precipitate from solution...imagine clear little needles passing through the kidneys....imagine childbirth...
        4. bacteriostatic–inhibits the synthesis of folic acid from PABA in the bacteria; bacteria cannot use pre-formed folic acid
           Many gram-positive and some gram-negative bacteria susceptible
       5. Examples--single entity products
           Sulfisoxazole (Gantrisin), sulfamethoxazole (Gantanol), sulfasalazine (Azulfidine)
       6. Examples--combination products
           Sulfamethoxazole/trimethoprim (Bactrim, Bactrim DS; Septra, Septra DS)
              the combination is a double whammy against the production of folic acid by the bacteria, especially that of E. Coli,    the  main cause of UTIs
        7. NO crossover allergies to “sulfites” “sulfates” or “sulfur”

  A note here: long term use of sulfonamides, or any antibiotic for that matter, can diminish the amount of “natural flora” in the colon.  The loss of “natural flora” can result in a decrease in Vitamin K production, of concern in patients prone to bleeding.  B vitamin complexes are also synthesized by bowel flora.



QUESTION
Protracted use ("prolonged use") of sulfa drugs may produce symptoms of vitamin K deficiency because sulfa drugs
   a. are detoxified in the liver
   b. combine chemically with vitamin K
   c. inhibit growth of intestinal bacteria
   d. interfere with the conversion of prothrombin to thrombin
   e. inhibit calcium absorption which is essential to enzyme systems
  Also, supplements of folic acid can interfere with the effectiveness of the sulfonamide antibiotics, since that is their main site of action against the bacteria.


   I. NEW CLASS OF DRUGS: THE ORAL QUINOLONES –lots of recent PR in this category
  Chemically, related to nalidixic acid (NegGram)
  Broad spectrum, possible dental applications in extreme cases
  Should be reserved to prevent resistance...
        1. more on market now
               a. norfloxacin (Noroxin), 400mg
               for urinary tract infections
               b. ciprofloxacin (Cipro), 250mg, 500mg tablets, 750mg tablets, and injection
               --broad spectrum, some Pseudomonal coverage
               c. ofloxacin (Floxin) 200, 300, 400mg tablets
               d. temafloxacin (Omniflox): withdrawn in 1992 (tended to cause the occasional annoying fatality)
  other newer agents:
               e. enoxacin (Penetrex),200-400mg once daily
               f. lomefloxacin (Maxaquin) 400mg once daily
               g. levofloxacin (Levaquin) 250 or 500mg tablets  (also a once daily dosage)
               h. trovafloxacin (Trovan), 400mg daily

        2. they cost a pretty penny!!! (well, actually $5 to $15 per tablet)

  3. Side effects
       a. photosensitivity
       b. renal accumulation–drink lots of water
       c. should not be given concurrently with antacids
       d. SLOWS DOWN THE METABOLISM OF CAFFEINE!
       e. rash, pruritus, urticaria, hyperpigmentation, and edema of the lips have been noted



QUESTIONS
Which of the following drugs is used to treat an infection with CANDIDA ALBICANS (a fungal infection):
 a. nystatin (Mycostatin)
 b. gentamicin
 c. tetracycline
 d. penicillin G or V
The only antifungal listed here is nystatin.  The other antibiotics could actually cause a fungal “superinfection.”  In addition to nystatin, you might see the drugs DIFLUCAN (generic name FLUCONAZOLE) , SPORANOX (generic name ITRACONAZOLE), NIZORAL (generic name NIZORAL) or GRISEOFULVIN.  These are other antifungal agents.

Fungal infections of the oral cavity can develop with systemic administration of
 a. insulin
 b. antibiotics (can result in a superinfection)
 c. antipyretics
 d. corticosteroids (due to immune suppression from steroids)
 e. antihistamines
 f. tricyclic antidepressants (or any drug that can cause xerostomia--dry gums, irritation, and bingo! Thrush!)



    J. Antifungal agents
     –for candidiasis, Candida albicans or “thrush” infections
     --can be used to kill "fungi on oral prosthetic devices" (so sez one of the DEHY p’col books!)
        1. Nystatin (Nilstat)
            a. suspension, vaginal suppositories, tablets
        2. ketoconazole (Nizoral)
               200mg tablets, topical cream
        3. griseofulvin (Fulvicin)
        4. fluconazole (Diflucan)--oral and injection
   orally, now offers a one-dose treatment for yeast infections (150mg)
        5. amphotericin B (Fungizone)--injection
        6. clotrimazole (Mycelex)
        7. flucytosine (5-FC) (Ancobon) for serious infections caused by strains of Candida or Cryptococcus
        8. Miconazole (Monistat)
        9. Itraconazole (Sporanox) for superficial and systemic mycoses (fungal infections); also for severe, nonresponsive fingernail infections
   Severe drug interactions with Sporanox can be expected with erythromycin, the recently withdrawn antihistamines Hismanal and Seldane, and Propulcid

    K. Antiviral products
        1. acyclovir (Zovirax)
      --available in capsules, injection, and ointment (both regular and sterile formulations; sterile formulations for ophthalmic use)
      --therapy for herpes simplex, herpes type II, and herpes zoster
      --still trying for over the counter status on the ointment as a lip balm (11-99)

        2. Famvir (new, 1995)
      --oral treatment for herpes zoster ("Shingles")
      --reduces the duration of the lesions and recurrence

        3. Valcyclovir (Valtrex)
      –an alternative to acyclovir from the same manufacturer since the patent ran out

        4. HIV antivirals
           a. zidovudine (AZT, Compound S) (Retrovir)
           b. stavudine (d4T) (Zerit)
           c. ritonavir (Norvir)
           d. indinavir sulfate (Crixivan)
           e. lamivudine (3TC) (Epivir)
           f. saquinavir mesylate (Invirase)
           g. didanosine (ddl; dideoxyinosine) (Videx)

    L. Metonidazole (Flagyl)
          a. injection, intravaginal cream, tablets
          b. bactericidal to susceptible bacteria and bacteroides (obligate anaerobic bacteria), also useful against Fusobacterium, Veillonella, Treponema, Clostridum, Peptococcus, Camplyobacter, and Peptostreptococcus– however, resistance is emerging
          c. tricohomonocidal (against trichomonas vaginalis)
          d. CAUSES DISULFRAM (Antabuse) REACTIONS WITH ALCOHOL!
          e. 12% of patients experience GI disturbances
          f. polyuria and occasional urinary incontinence have been reported; darkened urine as well
          g. sometimes combined with amoxicillin as “the poor man’s Augmentin”

    M. NATURAL PRODUCTS
 The following are purported to have either some antibiotic activity or possess the ability to stimulate the body's own immune response systems
       1. Echinecea "Coneflower"
  --stimulates the body's immune system with continuous use; under a controversial European investigation for adjunct treatment in AIDS (note on latest study: while echinacea may enhance T cell function, there is no evidence to support this)
  –no known side effects, although there is a possibility of crossover allergy among patients with pre-existing allergies to daisies; also, because of its immune-stimulating effect, it is not recommended for use in diseases where the immune system itself is causing the disease disturbances: this would include TB, leucosis, collagenoses, multiple sclerosis, AIDS and HIV infections, and other auto-immune disorders
  --for periods of cold symptoms, the usual dose is 1-2 capsules three times daily for up to 10 days; it should be reserved for times of need as prolonged use diminishes the effectiveness
  --alternately, a daily dose of 2 capsules for 2 weeks, with 2 weeks off, has been used for prevention  --useful in preventing susceptibility to viral infections; used as a Native American cure for infections
  --often combined with Golden Seal Root

        2. Golden Seal Root
   --antibiotic activity has been noted, especially with upper respiratory infections
   --popularity is the misguided notion that it can mask signs of drug usage in urine tests (not effective, but it sells a lot of capsules)
   --major side effect--elevated blood pressure! (has caused deaths in those overusing the raw herb to achieve the illicit response listed immediately above)
   --contraindicated with pregnancy
   –used topically as paste for oral lesions, or mixed with ethanol as an antifungal for athlete’s foot

        3. Garlic
 --a clove of garlic has the antibiotic potency of one 250mg tablet of penicillin
 --has been used topically as a wound disinfectant (but, oh, what an aroma on dressing changes three days later!)
 –dried or whole? allicin or no allicin? oh the controversy rages on
 –also for reduction in blood pressure and cholesterol
 –external use as an insect repellant (hmm!) and fungicide
 –typical doses for therapeutic effect: 1-2 tsp garlic oil, 1/4-1/2 tsp powdered garlic, or one to two cloves fresh raw garlic daily
 –not recommended for long term use in patients with diabetes, acute inflammation, dehydration and insomnia, as well as those taking anticoagulants

        4. Capsicum (Capsicum frutescens)
   --a "traditional" component of liniments, most notably "Sloan's Liniment"
   --rediscovered as a means to treat herpes zoster in the early 1990s; the topical extract is available in many forms, strengths, and prices (Zostrix, Theragen, RxCreme, Drs Cream, Arthur-Itis, et al)
   –also appears in topical patches, ie Salonpas

      5. Ginseng (Panax ginseng)
 --many varieties on the market, with the popularity resulting in dilution and adulteration
 --originally from the Orient, especially mainland China; ironically, today most ginseng is exported to the Orient from the West Coast of the US of A; customers going to Chinese apothecaries looking for the native herb usually end up getting something grown in Oregon
 --known as an "adaptogen," meaning it gives the body the ability to adapt to external stresses; used as an energy source and illness preventer; available in tablets and capsules, although purists prefer to steep the root shavings as a tea

    6. Australian tea tree oil
  –in creams, lotions, ointments, soaps, shampoos, deodorants
  –significant in vitro antibacterial and antifungal activity
   –long used as a local antiseptic
   –another name: melaleuca oil
   –oil should not be ingested; topical use only
 

III. Prophylactic Antibiotic use in certain cardiac patients and patients with joint surgery history...

      A. Considerations
  1. patients may be on prophylactic antibiotics to prevent bacteremias (infections in the blood) – consider cardiac infections
  2. therefore, extra preventative cautions are needed with procedures that could result in GINGIVAL BLEEDING
  3. Streptococcus veridans -->  gingival crevice --> heart valves or weakened cardiac tissue with scar tissue --> BACTERIAL ENDOCARDITIS!!!!!!!
         sometimes, due to its appearance, called “vegetative endocarditis”
 

IV.  RECOMMENDATIONS FOR PROPHYLACTIC ANTIBIOTIC USE PRIOR TO DENTAL VISITS:
* Bacterial endocarditis is a relatively uncommon, but nonetheless life-threatening infection of the endotheilal surface of the heart, including the heart valves.
* Infection most likely in individuals with underlying structural cardiac defects
* Bacteremia can be spontaneous (via food chewing or tooth brushing)
* Bacteremia can be a complication of an infection (periodontal, periapical, UTI)
* Bacteremia from dental procedures or instrumentations can cause transient bacteremia that rarely persists for more than a few minutes
* Two independent events are required for endocarditis to occur
 1. area of endothelium must be damaged
 2. bacteremia by adherent organisms must occur
*The following situations do not represent the only procedures of concern regarding bacterial endocarditis–these are the ones applicable to the dental field

V. CARDIAC CONDITIONS AND ENDOCARDITIS PROPHYLAXIS
 A. Endocarditis prophylaxis recommended
 High Risk Category
  1. Prosthetic cardiac valves
  2. Previous history of bacterial endocarditis
  3. Complex cyanotic congenital heart disease
  4. Surgically-constructed systemic-pulmonary shunts
 Moderate Risk Category
  1.. Congenital cardiac malformations
  2. Acquired valvular dysfunctions (such as rheumatic heart disease)
  3. Hypertrophic cardiomyopathy
  4. Mitral valve prolapse with valvular regurgitation

 B. Endocarditis prophylaxis not recommended
 Negligible risk category
  1. Isolated, secondary atrial septral defect
  2. Surgical repair of atrial septral defect, ventricular septal defect, or patent ductus arteriosis
  3. Previous coronary artery bypass graft surgery
  4. Mitral valve prolapse without valvular regurgitation
  5. Physiologic, functional, or “innocent” heart murmur
  6. Previous Kawasaki disease without valvular dysfunction
  7. Previous rheumatic fever without valvular dysfunction
  8. Cardiac pacemakers and implanted defibrillatiors

VI. DENTAL PROCEDURES AND ENDOCARDITIS PROPHYLAXIS
 A. Endocarditis prophylaxis recommended
 1. Dental extractions
 2. Periodontal procedures, including surgery, scaling, root planing, probing, and recall maintenance
 3. Dental implant replacement and reimplantation of avulsed teeth
 4. Endodontic (root canal) instrumentation or surgery only beyond the apex
 5. Subgingival placement of antibioitc fibers or strips
 6. Initial placement of orthodontic bands (but not brackets)
 7. Intraligamentary local anesthetic injections
 8. Prophylactic cleaning of teeth or implants, where bleeding is anticipated

 B. Endocarditis prophylaxis not recommended
 1. Restorative dentistry (operative and prosthodontic
 2. Local anesthetic injections (nonintraligamentary)
 3. Intracanal endodontic treatment
 4. Placement of rubber dams
 5. Postoperative suture removal
 6. Placement of removable prosthodontic or orthodontic appliances
 7. Oral impressions
 8. Fluoride treatments
 9. Oral radiographs
 10. Orthodontic appliance adjustments
 11. Shedding of primary teeth

VII. ENDOCARDITIS PROPHYLACTIC REGIMENS FOR DENTAL, ORAL, RESPIRATORY TRACT, AND ESOPHAGEAL PROCEDURES
 A. Standard, general prophylaxis
  –Amoxicillin, 2gm, taken orally one hour before the procedure
  –for children, the dose is 50mg per kg body weight
  –Amoxicillin comes in capsules of 250mg and 500mg, chewable tablets of 250mg, and in suspensions of 125mg/5ml and 250mg/5ml concentrations

 B. Patient unable to take oral medication
  –Ampicillin 2gm, IV or IM within 30 minutes before the procedure
  –for children, again the dose is 50mg per kg body weight
  –note that the drug here is ampicillin and NOT amoxicillin–injectable amoxicillin is not available in the U.S.

 C. Patient is allergic to penicillin, but can take oral medication
  1. Clindamycin (Cleocin) 600mg, taken orally one hour before the procedure
   –for children, the dose is 20mg per kg body weight
   –clindamycin comes in 150mg capsules, thus 4 capsules required for 600mg dose

  2. Cefadroxil (Duricef) or cephalexin (Keflex) sometimes substituted
   –not a popular alternative, due to that 10% possible crossover allergy with penicillins certainly not if allergy to penicillin is anaphylaxis
   –2gm orally, one hour before the procedure
   –for children, the dose is 50mg per kg of body weight

  3. Azithromycin (Zithromax) or clarithromycin (Biaxin)
   –500mg taken orally one hour before the procedure
   –for children, 15mg per kg body weight
   Regarding erythromycin–
   –some dentists still use erythromycin as an alternative, but this has been dropped from the recommended protocols due to its higher level of GI side effects and potential for drug interactions

 D. Patient is allergic to penicillin, and is unable to take oral medication
  1. Clindamycin (Cleocin)
   –adults 600mg IV within 30 minutes before the procedure
   –for children, 20mg per kg body weight

  2. Cefazolin (Ancef)
   –1gm IM or IV within 30 minutes before procedure
   –for children, 25mg per kg body weight
 

VIII. PATIENTS WITH JOINT OR HIP REPLACEMENT SURGERY IN THEIR BACKGROUNDS
* 450,000 patients undergo joint replacement surgery annually.  The scarring from this procedure offers an additional breeding ground for bacteria once a bacteremia sets in.
* The following recommendations come from JADA, 128:1006, July 1997, for patients who have a history of joint surgery.  These recommendations were based on literature reviews, since there has not been a specific prospective study regarding antibiotic prophylaxis in these particular cases.
* Prophylaxis is indicated if
          • the patient is immuno-compromised
          • the dental procedure is likely to have a higher incidence of bacteremia such as routine cleaning, tooth extraction, root canal or dental implants.
          • the higher risk dental procedures are performed within two years of the total joint replacement.
          • the patient has had a previous prosthetic joint infection.

* A recent study published in Clinical Orthopaedics and Related Research showing an association      between total knee arthroplasty infections and dental procedures underscores these recommendations. However, it also points out that infections occur in patients who are not immuno-compromised.
Antibiotic prophylaxis in these cases:
 1. No existing medication allergies,
  Give 2 grams of Amoxicillin 1 hour prior to dental procedure
 2. No existing allergy, but patient is not able to take oral meds,
  Give cefazolin (Ancef) 1gm or Ampicillin 2 grams, IM or IV 1 hour prior to procedure
 3. Penicillin Allergy present:
  Give 600mg of clindamycin (Cleocin) 1 hour prior to procedure
 4. Penicillin Allergy present AND patient is unable to take oral meds:
  Give 600mg of clindamycin (Cleocin) 1 hour prior to procedure



QUESTION
When performing deep scaling procedures, prophylactic antibiotic therapy is necessary for patients with each of the following conditions EXCEPT
   a. a prosthetic hip
   b. a prosthetic heart valve
   c. coronary heart disease
   d. rheumatic heart disease
   e. congenital heart disease


KCC Dental Hygiene Students: to send your homework, highlight the questions below, go to "edit," click on "copy," then click onto my email address below...when the email appears, go to "edit" in the email menu, click on "paste," and the questions will appear as the body of the email.  Answer the questions and then press "send." Your homework will be reviewed and returned via email within 72 hours.  Or just do it all on paper and bring your work to the next class session.

REVIEW QUESTIONS UP TO HERE!

1. What is the difference between bacteriostatic and bactericidal?
2. What are the six characteristics of an ideal antibiotic?
3. What is “Spectrum of activity?”
4. Given that a patient is allergic to amoxicillin, what crossover allergies are possible to other antibiotics?  5. What is a good antibiotic alternative to penicillin for a patient allergic to penicillin who also needs anaerobic bacteria coverage?
6. What is a recommendation for taking clindamycin (Cleocin)?  Why?
7. How can you identify a penicillin when given a list of antibiotic names?
8. How can you identify a cephalosporin when given a list of antibiotic names?
9. What recommendation can you make for taking erythromycin?
10. What recommendation can you make regarding drug storage for Biaxin or Zithromax suspensions?
11. You have a two year old patient.  With this amount of information alone, what antibiotic would be contra-indicated?  Why?
12. What other metals besides calcium form “chelates” with tetracyclines?
13. There are  two recommendations to give a patient taking a “sulfa” (ie sulfamethoxazole --trimethoprim combination [Bactrim DS]) antibiotic. What are they?
14.  Metronidazole (Flagyl) has a potential effect on the urine.  What is it?
15. Metronidazole (Flagyl) has a dietary restriction associated with it.  What is it and what is the result of the combination?
16. A physician wants to give his patient amoxicillin (Amoxil) and tetracycline (Achromycin).  Explain why this might not be a good idea.
17. List five cardiac conditions that come with the recommendation for endocarditis prophylaxis
18. List five cardiac conditions where endocarditis prophylaxis is not recommended
19. What is the standard endocarditis prophylaxis regimen for a patient able to take oral meds and who does NOT have a penicillin allergy?
20. What is the protocol when that patient has a penicillin allergy?
21. What is the protocol when that patient has a penicillin allergy AND cannot take oral meds?
22. How many years after hip replacement is antibiotic prophylaxis recommended?
23. What is the primary causative agent involved with bacterial endocarditis?
24. What is the difference between “broad” and “narrow” spectrum antibiotics?
25. Name two herbal supplements that help the body fight infection.
 
 

End of Module Three: Antimicrobial Therapy
Responsible party and contact: Jim Middleton, Pharmacist
KCC Pharmacology for Dental Hygiene
January 2002