Chapter 4

Formulary sections

I. Antimicrobials, systemic

a. General considerations

Q. What is the difference between an antibiotic and chemotherapeutic agent?

A. An antibiotic denotes a substance that is of biological origin; whereas, a chemotherapeutic agent denotes a chemical made synthetically. The term “antimicrobial” agent is an inclusive term referring to either an antibiotic or chemotherapeutic agent.

Q. What factors are important in the choice of a suitable antibiotic for dental infections?

A. Before selecting an antibiotic for the treatment of an infection the dentist must first consider two major factors: the patient and the susceptibility of the bacteria. Factors related to the patient that must be considered when selecting the appropriate antibiotic include:

• history of allergy to antibiotics
• renal and hepatic function
• resistance to infection (e.g., whether a compromised host)
• ability to tolerate oral drugs
• severity of the infection
• age
• if female, whether pregnant, nursing or taking an oral contraceptive.

Q. How long should an antibiotic be prescribed?

A. Duration of therapy depends on the nature of the infection and the response to treatment. Courses should not be unjustifiably prolonged because it is wasteful and may lead to adverse effects including antibiotic resistance. If the patient has not clinically improved by the 3rd day, then the antibiotic should be stopped and another antibiotic started.

Q. What is the difference between bactericidal and bacteriostatic antibiotics?

A. First, antibiotics must enter the bacteria in order for it to be effective. Bactericidal antibiotics work by killing the bacteria as a result of inhibiting bacterial cell wall synthesis or interfering with bacterial DNA. Bacterial cells must be multiplying for a bactericidal antibiotic to be effective. A bacteriostatic antibiotic weakens, disables, and reversibly inhibits the growth and replication of bacteria thereby giving the body’s natural defense mechanisms time to become effective in overcoming an infection. If an infection is quiet without multiplying and forming new protein, the bacteriostatic antibiotic will not work.

Q. Does it make a difference when choosing the appropriate antibiotic?

A. Yes. In the majority of cases, and particularly in patients whose natural resistance is lowered by disorders of the immune system (e.g., HIV/AIDS, diabetes mellitus), it is preferable to choose a bactericidal agent resulting in a decrease in the number of bacteria, rather than simply preventing an increase with bacteriostatic agents. When a bacteriostatic antibiotic is used the duration of therapy must be sufficient to allow cellular and humoral host defense mechanisms to eradicate the bacteria. Bactericidal drugs are effective during the log phase of bacterial growth. If growth is slowed or stopped, then the bactericidal drugs will not have such an effect. As a result, combination therapy with a bactericidal and a bacteriostatic should not be used (Chambers, 2003).

    With bacteriostatic antibiotics it is important to maintain minimum inhibitory concentrations of the antibiotic during treatment.

Q. What are the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) and their importance in choosing an antibiotic?

A. MIC indicates the sensitivity of an antibiotic; it is the lowest concentration of an antibiotic that results in inhibition of visible bacterial growth on a plate or culture. The MBC is the lowest concentration of an antibiotic that kills 99.9% of the original inoculum (pool of bacteria). For an antibiotic to be effective the MIC or MBC must be achieved at the site of the infection. The MIC and MBC are important in laboratories to verify the resistance of bacteria to an antimicrobial agent. In simple terms, the MIC is a basic laboratory measurement of the activity of an antimicrobial agent against a bacteria. The MIC is determined in vitro and uses a standardized inoculum of about 10⁵ cells per mL. For example, an MIC₅₀ of 16 indicates that this is the concentration (16 µg/ml) of antibiotic required to inhibit 50% of the bacterial strains. MIC₉₀ of 128 indicates the concentration of antibiotic (128 µg/ml) required to inhibit 90% of the bacterial strains.

Q. Can a bacteriostatic antibiotic become bactericidal?

A. Yes. Either increasing the dose of the bacteriostatic antibiotic or combine it with another bacteriostatic antibiotic.

Q. Which bacteria are bacteriostatic and which are bactericidal?

A. Bacteriostatic: tetracyclines, macrolides (erythromycin), azilides (azithromycin, clarithromycin), clindamycin
Bactericidal: penicillins, cephalosporins, quinolones, metronidazole

Q. What is the difference between a narrow-spectrum and a broad-spectrum antibiotic?

A. Narrow-spectrum antibiotics are effective against only a limited range or organisms, such as Gram-negative or Gram-positive bacteria. Broad-spectrum antibiotics affect a wider range against Gram-negative and Gram-positive bacteria. It is recommended to choose a narrow spectrum antibiotic when treating non-life threatening dental infections. The primary indication for use of broad-spectrum antibiotics coverage is in severe life-threatening dental infections where identification of causative agent is unknown. Every time bacteria are exposed to antibiotics, the opportunity for development of resistant strains is present. If narrow-spectrum antibiotics are used fewer bacteria have the opportunity to become resistant. Also, specific narrow-spectrum antibiotics usually are more effective against specific susceptible bacteria than the broad-spectrum antibiotics. Extended-spectrum antibiotics have bacterial activity in between a narrow and a broad-spectrum agent.

Q. Which antibiotics are considered to be narrow-spectrum and which are broad-spectrum?

A. Narrow-spectrum antibiotics: penicillin VK, erythromycin, azithromycin, clarithromycin, clindamycin.
Extended-spectrum antibiotics: amoxicillin, amoxicillin/clavulanate (Augmentin).
Broad-spectrum antibiotics: tetracyclines (doxycycline, minocycline), ciprofloxacin (Cipro).

Q. How is it determined that an antibiotic is not working after its course?

A. The patient is not clinically responding in about 3 days and the infection is not clearing up. Resistance may develop in which case culture and sensitivity may be necessary. In this case another antibiotic or another antibiotic added should be prescribed. For example, if no clinical improvement is seen in a patient taking penicillin VK in 48 to 72 hours, then metronidazole (both are bactericidal) should be added.

Q. Why is combination antibiotic therapy sometimes better than monodrug therapy?

A. Combination therapy with two or more antibiotics is used in special cases to: prevent the emergence of resistant strains; treat emergency cases during the period when an etiological diagnosis is still in progress; andtake advantage of antibiotic synergism, which is defined when the effects of a combination of antibiotics is greater than the sum of the effects of the individual antibiotics. Sometimes when using combination drugs a lower dose of one or the other can be used.

Q. How do antibiotics get distributed in the body?

A. Through the plasma. Most antibiotics are well distributed in soft tissues.

Q. What adverse effects can occur with antibiotics that you need to warn the patient about and how is it managed?

A. Antibiotics, especially broad-spectrum, alter the microflora of the stomach resulting in diarrhea and fungal infections. To help avoid this problem it is beneficial to consume living organisms referred to as probiotics (Weinberg, 2002).

• Superinfections: fungal infections (e.g., vaginal) and infections by other bacteria include enteric rods, pseudomonads, and staphylococci are especially more prone with broad-spectrum antibiotics but can occur with any. The ­narrow-spectrum antibiotic will not kill as many of the normal microorganisms in the body as the broad spectrum ­antibiotics. So, it has less ability to cause superinfection. This occurs because the bacteria are targeted which allow for growth of Candida sp. To help avoid this it is recommended to all patients, especially females, to either eat yogurt (containing live and active cultures such as Kefir, Dannon or Yoplait). To prevent antibiotic-related suprainfections about 5 ounces of yogurt should be taken twice daily while on the antibiotic. An alternative method is to take acidophilus supplementation (capsule), which is available in the alternative therapy section of the store. As long as the product is produced by a reliable manufacturer, most acidophilus supplements are relatively equal, and should not cause unpleasant side effects; some cause slight bloating for the first few days or weeks of taking the product, but this does not usually last. Lactobacillus acidophilus is one of the bacteria found in these supplements, but the term acidophilus usually refers to a combination of L. acidophilus with other ­beneficial bacteria.
• Gastrointestinal problems (nausea, vomiting, and diarrhea): To help avoid antibiotic-related diarrhea it is recommended to all patients to eat yogurt (containing live and active cultures such as Kefir, Dannon or Yoplait). Approximately 4 to 8 ounces of yogurt should be taken twice daily while on the antibiotic. Yogurt should be taken at least 2 hours before or 2 hours after the antibiotic. However, antibiotic-associated diarrhea that is constant and watery/bloody diarrhea (new onset of >3 partially formed or watery stools per 24 hour period) can be caused by toxins released from Clostridium difficile resulting in pseudomembranous colitis or C. difficile-associated diarrhea. C. difficile is the leading known cause of nosocomial intestinal infections (McFarland et al., 1994). If this happens the patient should discontinue the antibiotic and call emergency services. The patient should not take antidiarrheal medications because it is advantageous to eliminate the bacterial toxins. Pseudomembranous colitis symptoms could appear after a few doses or from 2 to 9 days or even months after the start of antibiotic therapy; it could happen at any time while taking the antibiotic. Unless it is known that the patient has a proclivity toward pseudomembranous colitis, it is not known if the patient will develop it. In reality, any antibiotic can cause pseudomembranous colitis. Any antibiotic can cause pseudomembranous colitis, but if used appropriately there are fewer incidences.
• Antibiotic resistance: The narrow-spectrum antibiotic will cause less resistance of the bacteria as it will deal with only specific bacteria. This is the reason for initially choosing a narrow-spectrum antibiotic. Antibiotic resistance is an increasing problem worldwide.
• Allergic reactions: Allergic reaction ranging from a mild rash to wheezing and anaphylaxis. The antibiotic should be discontinued immediately.
• Photosensitivity: exaggerated sunburn when taking doxycycline. Avoid sunlight.

Q. How long after an antibiotic is taken can an allergic reaction occur?

A. Allergic reactions are classified based on the time of onset. Type I acute (anaphylactic) reactions can occur within minutes of taking the antibiotic and can be life-threatening. Accelerated reactions can occur between 30 minutes and 72 hours and are usually not life-threatening. Delayed allergic reactions can be seen up to 2 or more days later.

Q. What conditions may increase the risk of infection with antibiotic-resistant bacteria?

A. Indiscriminant use of antibiotics; recent (within 6 weeks) use of antibiotics for other conditions; previous antibiotic treatment that was not successful; and being in close contact with someone who recently was treated with an antibiotic. Patient must be compliant (adherent) with dosage regimen and avoid missing doses.

Q. What is the definition and symptoms of gastrointestinal distress?

A. Gastrointestinal distress is a term used to describe a variety of symptoms that arise from disturbances in the stomach/lower intestinal tract. Symptoms include nausea, vomiting, cramping and diarrhea. Most of the time GI symptoms are caused by the irritative properties of the antibiotic and can be minimized by taking it with food.

Q. What is the cause of gastrointestinal distress while taking antibiotics?

A. Gastrointestinal disturbances occur due to an alteration in the normal GI flora.

Q. Can combination antibiotics use used in dentistry?

A. Yes. Because multiple pathogens not just one type are present in a dental infection. Two of the same category of antibiotics can be used. For example, you can prescribe two bactericidal antibiotics but not a bactericidal and a bacteriostatic. Often amoxicillin and metronidazole are prescribed for aggressive periodontitis. Both are bactericidal antibiotics and the combination of metronidazole with penicillin VK or amoxicillin increases the bacterial susceptibility.

Q. Is the mouth sterile?

A. No. There are many bacteria present in the oral cavity: both beneficial and pathogenic (disease producing). It is clear that anaerobic bacteria both facultative and obligate are involved in the two major oral diseases, dental caries and periodontitis.

Q. Which oral bacteria are facultative (can live with or without oxygen) anaerobes?

A. Gram-positive facultative cocci: Streptococcus sanguis, S. mitis, S. salvarius, Staphylococcus aureus.
Gram-positive facultative rods: Actinomyces (including A. viscosus, A. naeslundii).
Gram-negative facultative rods: Eikenella corrodens, Capnocytophaga spp., Aggregatibacter actinomycetemcomitans (formerly Actinobacillus actinomycetemcomitans).

Q. Which oral bacteria are obligate or strict anaerobes?

A. Gram-positive obligate anaerobic coccus: Peptostreptococcus spp.
Gram-positive obligate anaerobic rods: Eubacterium spp.
Gram-negative obligate anaerobic rods: Porphyromonus gingivalis, Prevotella intermedia, Tannerlla forsynthensis (formerly Bacteroides forsythus), Fusobacterium nucleatum.
Gram-negative anaerobic spirochete: Treponema spp.

Q. Which bacteria are obligate aerobes?

A. Obligate aerobic: Mycobacterium tuberculosis, Pseudomonas aeruginosa.

Q. How is an antibiotic chosen for prophylaxis?

A. The choice of the antibiotic for prophylaxis is based on several factors. The antibiotic should be active against the bacteria most likely to cause an infection related to the dental procedure. Second, an antibiotic must be chosen that the patient is not allergic to or interacts with the patient’s other medications.

b. Antibiotics

Beta-lactam antibiotics

Q. What is the mechanism of action of the penicillins?

A. Penicillins cause bacterial lysis (breaking up) by interfering with the synthesis of peptidoglycan that is necessary for the formation of the bacterial cell wall. This results in the lysis of the cell wall and death to the bacteria. Therefore, penicillin is most active against rapidly dividing bacteria and has no effect on nonmultiplying organisms.

Q. What is the spectrum of bacterial activity of penicillin?

A. Even though narrow-spectrum penicillin VK (penicillin V potassium) inhibits both Gram-negative and Gram-positive organisms, the cell wall of Gram-negative bacteria is more complex, therefore these bacteria are more resistant to the lytic effects of penicillin. Some bacteria effective against penicillin include:
Gram-positive coccus: Streptococcus spp. (penicillin is the traditional drug of choice for treatment of streptococcal infections)
Gram-negative anaerobes associated with dental infections: Fusobacterium, peptostreptoccci, spirochetes, Actinomyces, and some Bacteroides.
Spirochetes (T. pallidum)

Q. Why is penicillin G never prescribed in dentistry?

A. Penicillin G is completely destroyed by acid in the stomach so that it is only available for parenteral administration.

Q. How is penicillin made?

A. An antibiotic is a natural substance produced by a microorganism that will kill or stop growth of another microorganism. Penicillin, discovered by Alexander Fleming in 1929 is made by the mold Penicillium chrysogenum. The mold forms the beta-lactam ring. Amoxicillin and ampicillin are considered to be semisynthetic antibiotics, consisting of a mixture of natural and synthetic substances; a substance produced by a microorganisms that is subsequently chemically modified to achieve desired properties. Some “antibiotics” such as fluoroquinolones are totally synthetically produced and are not really considered to be antibiotics by the true definition.

Q. What does the “V’ in penicillin V stand for?

A. Penicillin V is also known as phenoxymethyl penicillin and is the orally active form of penicillin (penicillin G is not orally active). The “V” stands for the Latin word vesco/vescor meaning “eat”. Sometimes it is written penicillin VK where the “K” stands for potassium.

Q. What is amoxicillin?

A. Amoxicillin is a semisynthetic analog of penicillin with a broader spectrum of antibacterial activity.

Q. What are other drug names for amoxicillin?

A. Amoxil, Trimox

Q. What is the spectrum of bacterial activity of amoxicillin?

A. Amoxicillin is an extended-spectrum analog of penicillin VK. However, it has limited activity against streptococci or oral anaerobes compared to penicillin VK. It is a broader spectrum against bacteria not in the oral cavity (e.g., Haemophilus influenzae, Streptococcus pneumoniae, Escherichia coli, Salmonella). Thus, it is not any more effective in oral odontogenic/periodontal infections than penicillin VK and actually since it is a broad-spectrum antibiotic it can cause many more adverse effects including superinfection. Penicillin VK is the drug of choice for odontogenic infections because of its superior bioavailability.

Q. What is the difference between penicillin and amoxicillin?

A. Amoxicillin has a broader spectrum of bacterial activity and it is completely absorbed (about 90% of an oral dose is absorbed) so that there is less gastrointestinal distress (e.g., diarrhea) because it does not stay in the intestine that long and it produces higher plasma and tissue concentrations. Also, absorption is not affected by food.

Q. How are the penicillins excreted?

A. Penicillin is actively excreted via the kidneys in the urine and about 80% of a penicillin dose is cleared from the body within 3–4 hours of administration.

Q. Can penicillin be given to a patient with renal impairment?

A. Yes, since penicillin is excreted by the kidneys, renal impairment may lead to high concentrations, and neurotoxicity (damage to nervous tissue) can develop from high concentrations in the cerebrospinal fluid. A reduction of dosing interval, not dosage is necessary if glomerular filtration rate (GFR) is 10–50: Administer q8–12 h. If GFR is <10 mL/min: Administer q12–16 h.

Q. What are the adverse effects of penicillins?

A. Hypersensitivity (anaphylactic reaction), gastrointestinal distress, nausea, vomiting, suprainfections (fungal infections), and Clostridium difficile-associated diarrhea (CDAD), which has been reported with use of nearly all antibacterial agents and not just penicillins.

Q. Why are individuals allergic to penicillin?

A. Approximately 5% of individuals are hypersensitive to penicillins. The breakdown products of the penicillin molecule act as the sensitizing agent for allergic reactions (Montgomery & Droeger, 1984). If the reaction is mild (rash) the penicillin should be discontinued and an antihistamine such as diphenhydramine (Benadryl) may be administered orally. This does not necessarily occur in a patient with a previous history of a reaction to penicillin. For more severe anaphylactic reaction emergency services should be contacted (Fairbanks, 2007).

Q. Is the incidence of developing a hypersensitive reaction to penicillin and amoxicillin the same?

A. No. Almost 7% of individuals can develop a rash-type reaction to aminopenicillins (e.g., amoxicillin) than do the other penicillins (Fairbanks, 2007).

Q. If someone is allergic to penicillin VK is he/she also allergic to amoxicillin and ampicillin?

A. Yes. The penicillin nucleus is the same of all penicillins including amoxicillin and ampicillin.

Q. What is the treatment of Clostridium difficile-associated diarrhea?

A. Metronidazole or oral vancomycin is effective in 80% of cases. The remaining 20% of patients will have more episodes of diarrhea or colitis up to 3 to 28 days after the antibiotic has been discontinued (Kekety et al., 1989). The patient can have repeated episodes of the disease for several years thereafter (Kekety & Shah, 1993).

Q. What drug interactions occur with the penicillins?

• Probenecid (anti-gout medication): Decreases renal tubular secretion of penicillin leading to higher and more prolonged serum concentrations.
• Bacteriostatic antibiotics (e.g., tetracyclines, erythromycins): Penicillin, a bactericidal antibiotic, requires the bacteria to be multiplying. If a bacteriostatic antibiotic, which stops multiplication of the bacteria, is taken concomitantly with penicillin, the penicillin will not be effective. To manage this interaction wait a few hours before taking one or the other antibiotic.
• Oral contraceptives: penicillins interfere with oral contraceptive efficacy.

Q. Can penicillin and amoxicillin be prescribed to a woman taking an oral contraceptive?

A. Some studies have shown that some antibiotics such as penicillin VK and amoxicillin can interfere with oral contraceptive efficacy. It is best to ask a woman if she is taking an oral contraceptive before prescribing antibiotics and to explain to either practice abstinence or choose another method of birth control.

Q. Can bacteria become resistant to penicillin?

A. Yes. Certain Gram-negative bacteria produce and secrete enzymes called beta-lactamases which break down the beta-lactam ring on the penicillin (including amoxicillin) and cephalosporin molecule. Penicillinase, a type of beta-­lactamase specially breaks down the beta-lactam ring on the penicillin molecule rendering the penicillin or amoxicillin inactive resulting in treatment failure.

Q. What can be given to a patient if penicillin or amoxicillin does not work?

A. Penicillins can be destroyed by beta-lactamases (penicillinases) produced by certain resistant bacteria. The enzyme attaches to the beta-lactam ring and breaks it up. This renders the penicillin ineffective and is a reason for the patient not getting clinically better. To prevent this type of resistance from occurring, Augmentin, a combination of amoxicillin and clavulanate, is prescribed (the generic is usually prescribed). Clavulanate is an inert ingredient that also has a beta-lactam ring similar to penicillin, which strongly irreversibly binds to the penicillinase blocking the actions of penicillinase from breaking down the amoxicillin molecule and restoring the antimicrobial activity to amoxicillin. It is an acid (clavulanic acid) and can cause gastrointestinal irritation (e.g., nausea, vomiting, and diarrhea). It is usually prescribed in refractory cases when absolutely no other antibiotic has been clinically successful.

Q. How can the gastrointestinal adverse effects be minimized when taking amoxicillin and clavulanic acid?

A. It is recommended to take amoxicillin/clavulanic acid with meals and lactobacillus preparations such as Lactinex, acidophilus or yogurt with active cultures, which should be taken 2 hours before or 2 hours after the antibiotic.

Q. Does penicillin VK have a wide margin of safety?

A. Yes, penicillin has a very wide margin of safety. It is ideal to select a drug that has a wide margin of safety. This means that a drug’s usual effective dose is not toxic and if a little more of the drug is given it still is not toxic. This is in contrast to antibiotics called aminoglycosides, which are not used in dental infections and have a narrow margin of safety so that even usual doses can be toxic.

Q. What is the usual dose of penicillin VK?

A. Supplied:
Tablet: 250, 500 mg
Dose: Loading dose (LD): 1000 mg (two 500 mg tablet) stat on day 1, followed by 500 mg (one 500 mg tablet) q6h after the LD, up to day 7 to 10.

Q. What is the usual dose of amoxicillin trihydrate?

A. Amoxicillin is supplied as capsules, oral suspension and chewable tablets.
Supplied:
Tablet: 500 mg, 875 mg
Chewable tablet: 125 mg, 400 mg
Capsule: 250 mg, 500 mg
Oral suspension: 125 mg/5 mL, 250 mg/5 mL, 400 mg/5 mL
Dose: LD: 1000 mg (two 500 mg capsules) stat, followed by 500 mg (one 500 mg capsule) q8h × 7 days.

Q. Why is the dosing interval of amoxicillin q8h and penicillin q6h?

A. The half-life (t_½) of amoxicillin is 1–1.3 hours and of penicillin 30 minutes. Dosing is less frequent with amoxicillin that has a longer t_½ and stays in the body longer than penicillin with a shorter half-life.

Q. What is the adult dosing for amoxicillin chewable tablet?

A. A loading dose of 1000 mg on day 1 is acceptable followed by 250–500 mg three times a day (every 8 hours) after the LD up to day 7 to 10.

Q. What is the usual dose of amoxicillin/clavulanate?

A. Supplied: (all tabs have 125 mg clavulanic acid)
Tablet: 250 mg, 500 mg, 875 mg
Chewable tablet: 125 mg, 200 mg, 400 mg chewable tab.
Dose: (can give a LD of 1000 mg) 250 to 500 mg q8h depending upon the severity of the infection. When writing the prescription only the strength (500 mg) needs to be designated because all dosage forms come with 125 mg clavulanate.

Q. Are two tablets of 250 mg amoxicillin/clavulanate equivalent to one 500 mg tablet?

A. No. Two amoxicillin/clavulanate 250 mg tablets are not equivalent to one 500 mg tablet and should not be substituted for one 500 mg tablet.

Cephalosporins

Q. Why are cephalosporins not a drug of choice in dental infections?

A. Cephalosporins are structurally related to penicillins with a similar mechanism of action. However, because most cephalosporins are poorly absorbed orally and display poor permeability into bacteria, routine use for dental infections is precluded. Additionally, cephalosporins’broader spectrum does not provide any advantage over penicillin V against principal odontogenic pathogens.

Q. Why is a cephalosporin indicated for total joint replacement prophylaxis?

A. Cephalosporins have very good bone penetration and increased activity against Staphylococcus aureus. Cephalexin is the first drug of choice along with amoxicillin for antibiotic prophylaxis for total joint replacement.

Q. Can a cephalosporin be given to a patient allergic to penicillin?

A. No. Cephalosporins should not be prescribed to patients allergic to penicillin since there is a 10% cross-reactivity with the cephalosporins. Penicillins share a common beta-lactam ring (Herbert et al., 2000).

Erythromycins

Erythromycin

Q. Erythromycins belong to which classification of drugs?

A. Macrolides

Q. How is erythromycin produced?

A. Erythromycin is produced from a bacterial strain of Streptomyces erythreus. It is very difficult to produce erythromycin synthetically.

Q. What is the mechanism of action of erythromycins?

A. Erythromycins are bacteriostatic antibiotics that inhibit bacterial protein synthesis by binding to the 50S subunit of bacterial ribosomes.

Q. What is the spectrum of activity of erythromycins?

A. Erythromycins are primarily active against Gram-positive facultative anaerobic and strict anaerobic bacteria.

Q. Are erythromycins bacteriostatic or bactericidal?

A. Erythromycin is usually bacteriostatic especially at standard low doses (e.g., doses prescribed in dentistry; about 1500 mg) and bactericidal at high doses (e.g., intravenous) (Engelkirk & Duben-Engelkirk, 2010).

Q. What is the spectrum of microbial activity of erythromycins?

A. Most erythromycins are primarily effective against Gram-positive bacteria and some Gram-negative.

Q. Does bacterial resistance develop to erythromycin?

A. Yes. Bacteria can become resistant especially group A streptococci. Most Gram-negative bacteria are resistant to macrolides. Also, cross resistance can occur between erythromycin and clindamycin.

Q. Can an individual be allergic to erythromycins?

A. Yes. Allergic reactions, ranging from mild skin reactions to anaphylaxis can occur with erythromycins. If an allergic reaction occurs the drug should be discontinued and management of the reaction either with an antihistamine such as diphenhydramine (Benadryl) for mild reactions to epinephrine and calling for emergency services for severe anaphylactic reactions.

Q. Is there crossover allergy between penicillins and erythromycins?

A. No. If an individual is allergic to penicillin any erythromycin is acceptable to prescribe without any crossover allergenicity.

Q. What are the different kinds of macrolides?

A. Erythromycin base (Ery-Tab; Eryc, E-Mycin), erythromycin ethyl succinate (EES), and erythromycin stearate (Erythrocin). The different salts of erythromycin have been developed in order to compensate for the poor bioavailability (absorption). The base and stearate forms are acid-labile (susceptible to breakdown and inactivation by acid in the stomach) so in order for it to be protected from stomach acid it is formulated as filmtabs (enteric coating). The ethylsuccinate form is absorbed first and then hydrolyzed in the blood to free erythromycin.

Q. Why is erythromycin not considered a preferred antibiotic in anaerobic odontogenic infections?

A. Erythromycin is usually bacteriostatic and resistance can develop very rapidly. Since erythromycins are bacteriostatic, the MIC must be maintained by diligently following dosage regimen and not missing doses. Additionally, since erythromycin does not penetrate the cell wall of Gram-negative bacteria, the antibiotic will be ineffective because it needs to enter the bacteria to have an effect.

Q. What are some precautions used when prescribing erythromycins?

A. Gastrointestinal distress is a cause for most patients not following the entire course of therapy. Also, all members of the erythromycins prolong the electrocardiographic QT-interval resulting in the development of ventricular arrhythmias, which can be fatal, including torsade de pointes. Erythromycins should be used with caution in patients with cardiac arrhythmias, uncorrected hypokalemia and with other drugs that are used in the management of arrhythmias that could prolong the QT-interval including quinidine, sotalol or procainamide (Fairbanks, 2007). Caution should be used in patients with severe liver disease because of high risk of hepatotoxicity.

Q. Why is nausea a common adverse effect of erythromycins?

Q. Are there any drug interactions with erythromycins?

A. Yes. Erythromycins are metabolized in the liver via cytochrome P450 enzymes to form a stable metabolite complex that inhibits the metabolism of other drugs that are metabolized by these enzymes including cholesterol lowering drugs: lovastatin (Mevacor), simvastatin (Zocor), and atorvastatin (Lipitor), cyclosporine (anti-organ rejection drug), theophylline (anti-asthma drug), and sildenafil (Viagra) (Fairbanks, 2007).

Azithromycin and clarithromycin

Q. What are azithromycin and clarithromycin?

A. Both are classified as azalides, which are 2nd generation macrolides. Azithromycin is a macrolide derivative and the first of the 15-membered ring azalide class of antimicrobials. Although its mechanism of action and susceptibility to resistance are similar to those of the macrolide antibiotics, azithromycin’s extended spectrum of activity includes Gram-positive and Gram-negative organisms. Azithromycin is stable at gastric pH and has a bioavailability of about 37% following oral administration. Although its serum concentrations are typically low, the drug concentrates to a high degree in tissues, including periodontal tissues. Azithromycin is cleared primarily by the biliary and fecal routes; its serum half-life is in excess of 60 hours. Azithromycin and clarithromycin are more completely absorbed than erythromycin with less gastrointestinal distress. The brand name of azithromycin is Zithromax and clarithromycin is Biaxin (Ballow & Amsden, 1992).

Q. What are advantages to prescribing azithromycin or clarithromycin?

A. Azithromycin and clarithromycin are more acid-stable than erythromycin, which means that they are not broken down in the acidity of the stomach before they reach the intestines where absorption occurs. There are few bacteria in the stomach because the high acidity inhibits bacterial growth. Both azalides have structural modifications, which result in better gastrointestinal tolerability and tissue penetration than erythromycin.

    Additionally, azithromycin concentrates higher in host (phagocytes) cells (e.g., polymorphonuclear leukocytes or PMNs) and in the periodontal tissues (gingiva) (Sefton et al., 1996). Because of its high concentration in PMNs, azithromycin is actively transported to the site of infection. During active phagocytosis, azithromycin is released in the tissues. Azithromycin has a post-antibiotic effect which means that it concentrates in the gingiva (about 50 times higher in the tissues than plasma) for days after the antibiotic is stopped providing microbial inhibition after the drug concentration has decreased below the MIC. This is a good feature when prescribing for aggressive periodontitis where the bacteria have been found in the gingival connective tissue. This high tissue concentration has been thought to overcome the high incidence of resistance seen with certain bacteria (Sefton et al., 1996).

Q. Is azithromycin adequate to prescribe in oral infections?

A. Yes. Azithromycin has activity against many Gram-positive and Gram-negative bacteria and anaerobic bacteria and in a good choice for mild infections when the patient is allergic to penicillin.

Q. What precautions should be followed when prescribing azithromycin or clarithromycin?

A. Azithromycin or clarithromycin should not be prescribed to patients with severe liver disease (e.g., hepatic failure, cirrhosis), severe kidney disease (e.g., renal failure, pyelonephritis, glomerulonephritis), severe cardiovascular disease, pregnancy, breastfeeding and myasthenia gravis).

Q. What is the usual dose of azithromycin?

A. Supplied:
Capsule: 250 mg
Tablet: 250 mg, 500 mg, 600 mg
Dose: Since azithromycin has a long t_½ of 60–70 hours the dose is only once a day. LD: 500 mg on day 1, then 250 mg for 4 days.

Q. Is there an oral suspension available?

A. Yes. Oral Suspension: 100 mg/5 mL (15 mL); 200 mg/5 mL (15 mL, 22.5 mL, 30 mL); Also available in single dose packet: 1 gram (1000 mg). For the single dose packet the entire contents of the packet is mixed with 2 ounces (60 mL) of water and drink the entire contents. Then add 2 oz more and mix and drink to make sure the entire dose was taken. It can be taken with or without food. Do not use packet for children. The single dose packet administers only 1000 mg or 1 g of azithromycin.

Q. Can I prescribe a Z-Pak?

A. Yes. The 250 mg tablets are dispensed in blister packages of six and commonly referred to as a Z-Pak (Zithromax), whereas the 500 mg tablets are available in a blister pack of three tablets, or Tri-Pak, which has a 3-day supply.

Q. When would I prescribe clarithromycin versus azithromycin?

A. Both clarithromycin and azithromycin can be prescribed when a patient is allergic to penicillin. Compared with clarithromycin, azithromycin has increased activity against Gram-negative bacilli. So, essentially, either one can be prescribed for dental infections. The bioavailability of clarithromycin is more than twice that of erythromycin and azithromycin is 1.5 times that of erythromycin. Azithromycin has a longer half-life than clarithromycin so the dosing interval is less. As mentioned in an earlier question, azithromycin also has a better uptake from the circulation into intracellular compartments (better tissue and cells penetration) followed by a slow release. For example, if azithromycin is prescribed for 5 days, it still has active therapeutic levels in the body at day 10. Thus, azithromycin may be more superior to clarithromycin.

Q. What is the usual dose of clarithromycin?

A. Supplied:
Tablet: 250 mg, 500 mg
Extended-release tablet: Biaxin XL 500 mg
Granules for oral suspension: Biaxin^®: 125 mg/5 mL, 250 mg/5 mL
Dose: Since the t½ is 3 to 7 hours dosing is 250–500 mg q12h. The extended-release formulation is given two 500 mg extended release tablets once daily.

Q. Are azithromycin and clarithromycin more expensive than erythromycin?

A. The brand names are more expensive, but there is less frequent dosing because of its long half-life (less frequent dosing), post-antibiotic effect and better tolerability, which may make them a better choice than erythromycin. With these advantages it is not necessary to prescribe a macrolide.

Q. What are some common adverse effects of azithromycin and clarithromycin?

A. Common adverse effects include diarrhea, nausea, vomiting, dyspepsia, rash, pruritus, and abdominal pain.

Q. Are there a lot of drug interactions with azithromycin and clarithromycin?

A. Clarithromycin and erythromycin are metabolized by the cytochrome P450 system in the liver resulting in many drug interactions. Clarithromycin is a CYP3A4 substrate (metabolized by this isoenzyme) and a strong inhibitor of 3A4. See Chapter 5 for more detailed information about drug interactions. However, azithromycin is unlikely to interact with drugs metabolized via the hepatic cytochrome P450 enzyme system, and few interactions have been reported clinically (Shakeri-Nejad & Stahlmann, 2006).

Q. What are some drug interactions with azithromycin?

A. See Table 5.5.

Q. Is there a potential interaction of azithromycin with warfarin?

A. Yes. In 2009, the FDA revised the label for azithromycin warning of a potential interaction with warfarin resulting in elevated international normalized ratio (INR) values. There is a risk that the patient can become over-anticoagulated. If azithromycin is given then patient should be monitored or treatment modified. Consult with the patient’s physician (Waknine, 2009; Glasheen et al., 2005; Schrader et al., 2004).

Lincomycins

Q. What is the mechanism of action of clindamycin?

A. Clindamycin is bacteriostatic at low doses but can be bactericidal at usual doses (600 mg) and extended-interval dosing (Klepser et al., 1997). It inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit.

Q. What is the spectrum of activity of clindamycin?

A. Clindamycin is a narrow-spectrum antibiotic effective against most Gram-positive organisms including, group A streptococci, staphylococci and pneumococci. Gram-negative aerobic microbes are resistant because clindamycin is poorly permeable to the outer membrane, but most anaerobes (Prevotella, Peptostreptococcus, Fusobacterium) are sensitive.

Q. Is clindamycin a good choice for odontogenic infections?

A. Yes. Clindamycin is superior to other antibiotics against anaerobes (chronic infection) making it a good choice in anaerobic infections especially if refractory to other antibiotics. It shows good distribution in soft tissues as well as penetration into bone. Clindamycin also shows high plasma concentrations.

Q. What are some common adverse effects of clindamycin?

A. Diarrhea, nausea, vomiting, abdominal pain, and rash. Serious reactions include clostridium difficile-associated diarrhea, Stevens Johnson syndrome, granulocytopenia (low concentration of white blood cells) and esophagitis.

Q. Is clindamycin the only antibiotic that causes Clostridium difficile colitis or pseudomembranous colitis?

A. No. Almost any antibiotic can cause pseudomembranous colitis, especially if two or more antibiotics are used together. Clindamycin was the first antibiotic reported to cause pseudomembranous colitis and that is why it is always associated with this condition.

Q. Is clindamycin contraindicated in any patients?

A. Yes. Precautions/contraindications in patients with inflammatory bowel disease, ulcerative colitis, and pseudomembranous colitis.

Q. If a patient is allergic to erythromycin can clindamycin be prescribed?

A. Yes. The mechanism of action of both antibiotics is relatively the same but they are two different antibiotics.

Q. What is the dose of clindamycin?

A. Supplied:
Capsule: 75 mg, 150 mg, 300 mg
Oral solution: 75 mg/5 mL (note that this is a solution, not a suspension as most other antibiotics)
Dose: LD: 600 mg stat, followed by 150–450 mg q6h–8 h.

Metronidazole

Q. What is the spectrum of antibacterial action for metronidazole?

A. Metronidazole is effective against Gram-negative obligate (strict) anaerobes such as Prevotella intermedia, Porphyomonas gingivalis, Bacteroides, Fusobacterium.

Q. What is the mechanism of action of metronidazole?

A. Metronidazole is taken up into the bacteria where it produces toxic products which accumulate in the anaerobes and interacts with DNA to cause a loss of the helical structure.

Q. Does metronidazole concentrate in the gingival crevicular fluid (GCF)?

A. Gingival crevicular fluid (GCF) or crevicular fluid is a serum transudate that originates in the gingival connective tissue. Irritation and inflammation of the gingival tissue increase the flow of GCF from the connective tissue into the gingival crevice. Metronidazole concentrates equally in the crevicular fluid and serum as well as in the gingival tissue.

Q. Can metronidazole be used in the management of chronic periodontitis?

A. Loesche & Grossman (2001) have shown in numerous studies documented that metronidazole plus scaling and root planing is statistically better than a placebo plus scaling and root planing. However, the majority of clinical studies have reported that the use of metronidazole or tetracycline or any systemic antibiotic in the treatment of chronic periodontitis cannot be justified unless it is refractory periodontitis where conventional therapy (the patient has attempted to maintain meticulous oral hygiene and regular maintenance or recare visits) has been unsuccessful (Vergani et al., 2004).

Q. Why is metronidazole not recommended for the treatment of odontogenic infections?

A. Metronidazole alone is mainly effective against Gram-negative anaerobic rods and is not effective against Streptococcus viridans, which is primarily isolated in odontogenic infections. However, when used together with amoxicillin there is an additive effectiveness against Gram-negative anaerobic rods.

Q. Is bacterial resistance to metronidazole common?

A. No. Metronidazole resistance is relatively uncommon.

Q. Does the ingestion of alcohol cause adverse effects when taking metronidazole?

A. Yes. Ingestion of alcohol when taking metronidazole and for 1 week after metronidazole is stopped can result in a disulfiram-like reaction. Disulfiram (Antabuse) is a medication used to wean individuals off alcohol. Chronic alcoholics are treated with disulfiram. If alcohol is ingested while on disulfiram an acute psychoses (hallucinations) and confusion, abdominal cramps, nausea, facial flushing and a headache can occur. This is a similar reaction with metronidazole.

Q. Can alcohol-containing mouthrinses be used while taking metronidazole?

A. No. Any product containing alcohol is contraindicated. This includes alcohol-containing mouthrinses, foods with alcohol and skin-to-skin contact with perfumes.

Q. How long after finishing the course of metronidazole can alcohol be started?

A. About 3 days after the metronidazole is finished.

Q. What is a commonly encountered oral adverse effect of metronidazole?

A. Metallic taste.

Q. Is there an interaction if metronidazole is taken with warfarin (Coumadin; an anticoagulant)?

A. Yes. Metronidazole can decrease the metabolism of warfarin resulting in bleeding. Dosage reduction of warfarin is necessary. Warfarin is metabolized by the cytochrome 2 C and 3A4 and metronidazole are potent inhibitors of CYP2C and 3A4 resulting in decreased metabolism of warfarin (Hersh, 1999). Consultation with the patient’s physician is necessary.

Q. What is the dose of metronidazole?

A. Supplied:
Tablet: 250 mg, 500 mg
Capsule: 375 mg
Dose: 500 mg q6–8 h × 7–14 days. For severe infections give a loading dose of 1000 mg on day 1 followed by 500 mg q6–8 hours after the LD on day 1 up to 5 to 7 or 10 days if needed.

Tetracyclines

Q. What is the microbial spectrum of activity of the tetracyclines?

A. Effect against many Gram-positive and Gram-negative bacteria.

Q. What is the mechanism of action of the tetracyclines?

A. Tetracyclines are broad-spectrum bacteriostatic antibiotics that inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit.

Q. What are doxycycline and minocycline?

A. Doxycycline and minocycline are semisynthetic members of the tetracycline group that are classified as longer acting tetracyclines with greater half-lives than the parent compound tetracycline HCl.

Q. Is doxycycline the same drug used in the treatment of acne?

A. No. Doxycycline is available in two different salts: hydrate, and monohydrate which is the form prescribed for acne.

Q. Why should doxycycline versus tetracycline be prescribed?

A. Doxycycline has a longer half-life so that dosing is much less frequent than with tetracycline which increases patient adherence.

Q. Why have tetracycline and its analogs, doxycycline and minocycline gained so much attention and popularity in the last two decades?

A. Tetracycline concentrations were found to be higher in GCF than in serum. When tetracycline is administered orally, high levels are found in the gingival crevice or periodontal pocket where it is desirable to have the antibiotic when treating periodontal diseases.

Q. Why is tetracycline prescribed for periodontal diseases?

A. A unique mechanism of action of the tetracyclines is inhibition of the synthesis and release of collagenase (anticollagenase) from human polymorphonuclear leukocytes (PMNs). This collagenase is destructive and breaks down collagen present in the periodontium (gingiva, bone, periodontal ligament). Doxycycline has the greatest anticollagenase activity. A subantimicrobial dose (20 mg) of doxycycline is used in the management of generalized chronic periodontitis in conjunction with scaling and root planing. It is prescribed to take one tablet twice a day (q12h) for up to 9 months. The brand name for doxycycline 20 mg is Periostat.

Q. Do the same adverse effects, precautions and contraindications follow with a subantimicrobial dose of doxycycline 20 mg?

A. Yes. It is still a tetracycline so it is contraindicated in pregnant women and children less than 8 years of age. Follow the same instructions to the patient as with antibiotic strength dose of doxycycline.

Q. Can doxycycline be taken at bedtime?

A. Doxycycline should not be taken at bedtime. Numerous reports have documented an increased incidence of esophageal erosions (ulcers). It is best to tell the patient to drink a full glass of water and not to lie down directly afterward (Segelnick & Weinberg, 2008).

Q. Can dairy products, iron and antacids be taken together with tetracycline?

A. Not at the same time. Divalent or trivalent cations including antacids containing aluminum (Amphojel), aluminum and magnesium combinations (Gelusil, Maalox, Mylanta), calcium including antacids (Tums, Citracal, Caltrate, Os-Cal) and dairy products (milk), iron and magnesium (Milk of Magnesia) reduce the absorption of tetracycline when taken concurrently by forming insoluble complexes or chelates with tetracycline resulting in a reduction of the amount of tetracycline. Note: the amount of tetracycline is reduced not the time of absorption. The tetracycline that is not absorbed into the bloodstream is eliminated in the feces. To manage this interaction, wait 1 hour before or 2 hours after taking the dairy product before tetracycline is taken.

Q. Can food and dairy products be taken with doxycycline?

A. It depends on the brand of doxycycline. With most brands there is only about a 30% decrease in bioavailability (absorption). The effects of dairy products, including milk, on doxycycline absorption are less than observed with other tetracycline derivatives, including tetracycline and minocycline.

Q. Can antacids and iron be taken with doxycycline?

A. No. Antacids, zinc and iron should not be taken at the same time of doxycycline, minocycline or tetracycline. Antacids (containing calcium, aluminum, magnesium) and iron markedly reduce absorption of the amount of tetracycline. Space the antacid apart about 1 hour or 2 hours after taking doxycycline.

Q. Why is it contraindicated to prescribe tetracyclines, including doxycycline and minocycline to a pregnant woman and children less than 8 years of age (children that do not have all permanent teeth)?

A. Tetracyclines are readily deposited into bone and teeth during calcification which can cause a yellow-gray-brown discoloration/fluorescence and can inhibit bone growth. The color of staining actually is dependent on which tetracycline was used, dosage and the length of time used. The tetracycline binds or chelates to calcium ions present on the hydroxyapatite crystals in the dentin forming a stable calcium orthophosphate complex (ADA, 2010).

Q. Can individuals taking tetracycline be exposed to sunlight?

A. Photosensitivity or a phototoxic reaction can occur when taking any tetracycline, especially doxycycline. Phototoxic reactions occur due to the damaging effects of light-activated compounds on cell membranes and DNA.

Q. Is dizziness an adverse effect of tetracycline?

A. Yes, especially with doxycycline (Segelnick & Weinberg, 2010). Care must be taken not to fall when taking doxycycline.

Q. Is there a problem if an expired tetracycline product is systemically taken?

A. Yes. Expired tetracyclines can become nephrotoxic at a pH less than 2 due to the formation of anhydro-4-epitetracycline, which can cause acquired Fanconi syndrome – a disorder with clinical features of polyuria, polydipsia and dehydration (Ubara et al., 2005; Fathallah-Shaykh, 2011).

Q. What is the dose of doxycycline?

A. Supplied: 50 mg, 100 mg capsule; 20 mg, 50 mg, 100 mg tablet. LD: 100 mg q12h on first day, followed by a maintenance dose of 100 mg once daily.

Fluoroquinolones

Q. What are fluoroquinolones?

A. Fluoroquinolones are not really considered to be antibiotics because they are entirely synthetic, but they are still classified as broad-spectrum antibiotics.

Q. What is the mechanism of action of fluoroquinolones?

A. Fluoroquinolones are bactericidal and block bacterial nucleic acid synthesis by inhibiting DNA gyrase.

Q. What is the microbial spectrum of activity of fluoroquinolones?

A. They are broad-spectrum drugs active against aerobic Gram-negative bacteria and many Gram-positive microorganisms. Anaerobes are usually resistant.

Q. If a patient is allergic to penicillin can a fluoroquinolone be prescribed?

A. Yes.

Q. Is there cross-resistance between a fluoroquinolone and other antibiotics such as penicillins?

A. No. Since fluoroquinolones have a different mechanism of action bacteria resistant to other antibiotics may be susceptible to fluoroquinolones.

Q. Why are fluoroquinolones useful for the treatment of pneumonia?

A. Because tissue and fluid concentrations exceed the serum drug concentration.

Q. When are fluoroquinolones prescribed in dentistry?

A. Fluoroquinolones are prescribed in dentistry if a patient is allergic to penicillin and/or has substantial gastrointestinal upset with erythromycins and clindamycin.

Q. What are some common fluoroquinolones used in dentistry?

A. Ciprofloxacin (Cipro) and levofloxacin (Levaquin)

Q. What are the adverse effects of fluoroquinolones?

A. Nausea, vomiting, diarrhea, headache, dizziness, phototoxicity (exaggerated sun reaction when exposed to the sun), insomnia, abnormal liver function tests, tendonitis and Achilles tendon rupture (especially in children and the elderly). Do not prescribe in patients younger than 18 years of age.

Q. Can fluoroquinolones be prescribed in pregnant patients?

A. Ciprofloxacin and levofloxacin are assigned a pregnancy category C. It is recommended not to prescribe either drug to pregnant or nursing women.

Q. Is there a Black Box Warning with fluoroquinolones?

A. Yes there are two Black Box Warnings.

Q. Does pseudomembranous colitis occur with fluoroquinolones?

A. Yes. There is a high association between fluoroquinolones and Clostridium difficile.

Q. Should fluoroquinolones be prescribed to a patient who is athletic and does a lot of running?

A. No. Fluoroquinolones can cause tendonitis and tendon rupture. The patient should be informed about this adverse effect and stop running while taking the medication.

Q. Can divalent and trivalent cations be taken concurrently with fluoroquinolone?

A. No. Similar to tetracyclines, divalent and trivalent cations [e.g., antacids containing aluminum and magnesium alone or in combination, iron and calcium (calcium supplements such as Caltrate, Citracal, Os-Cal, Tums) or dairy products] form insoluble complexes in the gut if they are taken concurrently with fluoroquinolones resulting in lower amounts of the antibiotic being absorbed. Management of this drug interaction involves spacing the antibiotic apart from the divalent or trivalent cation product for about 1 or 2 hours.

Q. Can a fluoroquinolone be prescribed to someone taking warfarin?

A. There is a drug interaction between levofloxacin and warfarin which may cause the patient to be over-anticoagulated with elevated INR values. If a fluoroquinolone is prescribed to a patient taking warfarin, the frequency of INR monitoring needs to be increased. Consult with the patient’s physician.

Q. What is the dosing for ciprofloxacin?

A. Supplied:
Tablet: 250 mg, 500 mg
Dose: 250–500 mg every 12 hours for 7–10 days.
Renal dosing: CrCL > 30: no changes
CrCL 5–30: 250 mg every 12 h or 250–500 mg every 18 to 24 hours

Q. What is the dosing for levofloxacin

A. Supplied:
Tablet: 250 mg, 500 mg 750 mg
Dose: 500 mg every 24 hours for 7–10 days
Renal dosing: CrCL > 50: no change
CrCL 20–49: 500 mg once, then 250 mg every 24 hours
CrCL 10–19 & <10: 500 mg once, then 250 mg every 48 hours

c. Specific instructions for taking antibiotics

Q. Does dosing “every 6 hour interval” for penicillin need to be strictly followed?

A. Bactericidal agents such as penicillins that inhibit bacterial cell wall synthesis, do not require constant blood levels to be maintained because at or above the minimal lethal concentration for susceptible bacteria, permanent damage to the cell wall occurs in growing bacteria resulting in the lysis (break down) of bacterial cells. Thus, pulse dosing, where the dose is given as four doses in 24 hours, is adequate to be taken as “every 6 hours while awake.” The patient does not need to follow the “every 6 hours, day and night” schedule and get up in the middle of the night. The dosing for bacteriostatic agents does need to be exactly followed as “every 6 hours.” The same follows for amoxicillin.

Q. Does the dosing interval need to be strictly followed for bacteriostatic antibiotics?

A. Yes. In contrast to bactericidal antibiotics, bacteriostatic antibiotics require constant blood levels, which need to be above the MIC for the pathogen be maintained. That means that the patient must follow the prescribed dosing interval strictly even if it means getting up in the middle of the night. Prescribing azalides such as azithromycin or clarithromycin is best to prescribe for the easiest dosing interval.

Q. If a patient is taking a bacteriostatic antibiotic such as azithromycin for a medical condition and a bactericidal antibiotic needs to be given (e.g., amoxicillin for antibiotic prophylaxis or bactericidal doses of clindamycin) how far apart should the antibiotics be given?

A. Allow at least a 6 hour interval between the bacteriostatic antibiotic and the bactericidal drug because if the two were given together a drug/drug interaction occurs whereby the bactericidal drug will not be effective because it requires active, multiplying bacteria (Ganda, 2008).

Q. Which antibiotics can cause dysgeusia (taste disturbances)?

A. Patients with dysgeusia have an alteration in the four taste sensations including excessively sweet, bitter, salty or metallic taste while eating. Some antibiotics that can cause dysgeusia are metronidazole, tetracycline and clarithromycin.

Q. How antibiotic-associated diarrhea best prevented?

A. To help prevent diarrhea resulting from antibiotic it is recommended that patients eat 4 ounces of yogurt containing “Live and Active Cultures” such as Dannon Activia, Yoplait, or Kefir twice a day while taking the antibiotic. It has been suggested to take the yogurt at least 2 hours before or 2 hours after the antibiotic.

Q. What is recommended to do if the patient has developed diarrhea?

A. First confirm that the patient does not have pseudomembranous colitis. If this is negative it is recommended to take 4 ounces of yogurt containing probiotic Lactobacillus casei twice a day.

Q. What should the patient be warned about pseudomembranous colitis?

A. If the patient experiences a watery or bloody diarrhea in addition to fever and abdominal cramps the antibiotic should be immediately stopped and medical attention sought. Dehydration, low blood pressure and low levels of potassium can occur due to significant loss of fluids and electrolytes due to diarrhea. Symptoms are caused by the bacterium Clostridium difficile releasing a powerful toxin. If it is truly pseudomembranous colitis it is life-threatening. The patient should not take an antidiarrheal medication such as Lomotil or Imodium because the objective of treatment is to rid the body of the toxins and antidiarrheal medications would only reduce the chances of eliminating of the toxins. Treatment involves discontinuing the offending antibiotic which may be enough to stop the diarrhea. If it continues then administering by mouth metronidazole or vancomycin is indicated. Signs and symptoms usually begin to improve within a few days.

Q. Should caution be used when prescribing antibiotics to women on oral contraceptives?

A. It is still a controversial issue. All women of child-bearing age should be asked if she is taking an oral contraceptive before prescribing an antibiotic. Even though there are limited cases reports regarding this interaction it is still considered to be a potential drug interaction. Ethinyl estradiol, an estrogen present in oral contraceptives, is only about 40% absorbed systemically in an inactive form. The remainder undergoes extensive first-pass metabolism. Inactive ethinyl estradiol becomes active in the gut by bacterial gut flora, which releases active ethinylestradiol. The active ethinylestradiol is then reabsorbed in the small intestine. Thus, there is a concern when taking antibiotics, especially broad-spectrum, because bacteria are needed to activate ethinylestradiol for the oral contraceptive to be effective. Antibiotics destroy the bacteria which dihyrolyze sulfate and glucuronide conjugates (metabolites of ethinylestradiol) (Gibson & McGowan, 1994). Thus, the enterohepatic recirculation of ethinylestradiol that usually occurs does not. There are conflicting reports on which antibiotics are the offending agents. Additionally, drug interactions may be more common with the low-dose estrogen oral contraceptives (Gibson & McGowan, 1994). However, The American College of Obstetricians and Gynecologists concluded that tetracycline, doxycycline, ampicillin and metronidazole do not affect oral contraceptive levels (Lomaestro, 2009; Archer & Archer, 2002). However, this activation by bacterial gut flora does not occur with progestins, the other component of oral contraceptives. The first reported published link between oral contraceptives and antibiotics occurred with rifampin, an antituberculosis drug in 1971 (Gibson & McGowan, 1994). Since it cannot be predicted which women will be at greater risk for this drug interaction, it has been suggested that women use an additional contraceptive method while taking the antibiotic and for at least 1 week after completing the antibiotic (Osborne, 2004). It is plausible that some women may have low levels of ethinyl estradiol due to differences in the pharmacokinetics of the drug which would result in oral contraceptive failure when taking antibiotics (Bauer & Wolf, 2005).

    In 2004, The World Health Organization (WHO) reported that there have been uncertainties that broad-spectrum antibiotics may lower oral contraceptive effectiveness; however, pregnancy rates are similar in women taking oral ­contraceptives concurrently with antibiotics or without antibiotics (WHO, 2004).

Q. What are specific instructions to the patient on how to take antibiotics?

A. Table 4.1 reviews patient counseling on how to take antibiotics?

Table 4.1 Patient counseling on how to take antibiotics.

Medical Economics Staff. 2000.

II. Antimicrobials, local

a. Chlorhexidine gluconate

Q. What is the difference between first generation and second generation oral rinses?

A. First generation mouth rinses have a high substantivity whereby the agent binds to oral structures and slowly is released over time and remains active. Chlorhexidine gluconate is an example of a first generation mouth rinse. The extending binding to oral soft tissues and tooth structure and slow release reduces bacterial recolonization for approximately 8 to 12 hours afterward. Second generation agents have low substantivity and are not as therapeutically effective as first generation agents. Examples of second generation agents include: Listerine, Scope, and Cepacol.

Q. What is the alcohol content of chlorhexidine gluconate?

A. Chlorhexidine gluconate 0.12% contains 11.6% alcohol. The alcohol present in oral rinses is ethyl alcohol. Isopropyl alcohol is present in the skin cleanser.

Q. Is chlorhexidine gluconate 0.12% available alcohol-free?

A. Yes. GUM^® chlorhexidine gluconate oral rinse 0.12%.

Q. What is the alcohol content of Listerine?

A. Listerine: 26.9% and Listerine Cool Mint or Freshburst: 21.6%

Q. What type of alcohol is present in oral rinses?

A. Ethanol.

Q. Does the alcohol in mouth rinses cause dry mouth?

A. Yes. The alcohol is a drying agent and can cause xerostomia.

Q. What is the mechanism of action of chlorhexidine?

A. Chlorhexidine is a cationic (positive charged) bisbiguanide. Chlorhexidine binds to the negative charged bacterial cell surface causing a disruption of the cytoplasmic membrane allowing for the chlorhexidine to enter the bacterial cytoplasm and kill the bacteria.

Q. What is the spectrum of antibacterial activity?

A. Chlorhexidine is active against Gram-positive and Gram-negative, facultative aerobic and anaerobic bacteria.

Q. What are the indications for chlorhexidine?

A. Chlorhexidine gluconate 0.12% is a prescription medication for gingivitis, not periodontitis.

Q. How should the patient use chlorhexidine?

A. Rinse bid with 15 mL of solution which is measured in the cap of the bottle. Rinse for 30 seconds and expectorate. The patient should not eat or drink for at least 30 minutes after rinsing.

Q. How is a prescription for chlorhexidine written?

A. See Figure 4.1.

Q. Can fluoride-containing toothpaste be used directly before or after rinsing with chlorhexidine?

A. No. Fluoride toothpaste that contains sodium lauryl sulfate should be spaced at least 30 minutes apart before using chlorhexidine. The positively charged chlorhexidine causes it to bind to the negatively charged sodium lauryl sulfate (a detergent) causing inactivation.

Q. What are some adverse effects of chlorhexidine that I should warn the patient?

A. Brown staining/>

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