Ciprofloxacin

Pharmacology
Ciprofloxacin is a quinolone that is active against gram-negative rods,
including all facultative and some anaerobic putative periodontal
pathogens.

Clinical Use
Because it demonstrates a minimal effect on Streptococcus species,
which are associated with periodontal health, ciprofloxacin therapy
may facilitate the establishment of a microflora that is associated with
periodontal health. At present, ciprofloxacin is the only antibiotic in
periodontal therapy to which all strains of A. actinomycetemcomitans
are susceptible. It has also been used in combination with
metronidazole.

Side Effects
Nausea, headache, metallic taste in the mouth, and abdominal discom-
fort have been associated with ciprofloxacin. Quinolones inhibit the
metabolism of theophylline, and caffeine and concurrent
administration can produce toxicity. Quinolones have also been
reported to enhance the effects of warfarin and other anticoagulants

Macrolides

Pharmacology
Macrolide antibiotics contain a many-membered lactone ring to which
one or more deoxy sugars are attached. They inhibit protein synthesis
by binding to the 50S ribosomal subunits of sensitive microorganisms.
Macrolides can be bacteriostatic or bactericidal, depending on the
concentration of the drug and the nature of the microorganism. The
macrolide antibiotics used for periodontal treatment include eryth-
romycin, spiramycin, and azithromycin.

Clinical Use
Erythromycin does not concentrate in GCF and is not effective against
most putative periodontal pathogens. For these reasons, erythromycin
is not recommended as an adjunct to periodontal therapy.
Spiramycin is active against gram-positive organisms; it is excreted in
high concentrations in saliva. It is used as an adjunct to periodontal
treatment in Canada and Europe but is not available in the United
States. Spiramycin has a minimal effect on attachment levels.
Azithromycin is a member of the azalide class of macrolides. It is
effective against anaerobes and gram-negative bacilli. After an oral
dosage of 500 mg 4 times daily for 3 days, significant levels of
azithromycin can be detected in most tissues for 7 to 10 days.7,30 The
concentration of azithromycin in tissue specimens from periodontal
lesions is significantly higher than that of normal gingiva.40 It has been
proposed that azithromycin penetrates fibroblasts and phagocytes in
concentrations that are 100 to 200 times greater than that of the
extracellular compartment. Azithromycin is actively transported to
sites of inflammation by phagocytes, where it is released directly into
the sites of inflammation as the phagocytes rupture during
phagocytosis.23 Therapeutic use requires a single dose of 250 mg/day
for 5 days after an initial loading dose of 500 mg.62
Data have suggested that azithromycin may be an effective adjunctive
therapy for increasing attachment levels in patients with aggressive
periodontitis27 as well as for reducing the degree of gingival
enlargement.15 These data must be carefully considered, because they
were derived from small subject populations. Currently, the literature
presents conflicting reports regarding the efficacy of this antibiotic as
an adjunct to periodontal therapy. One study concluded that adjunctive
azithromycin provides no additional benefit over nonsurgical
periodontal treatment for the parameters investigated in patients with
severe generalized chronic periodontitis. Furthermore, an additional
study reported that there was an increase in cardiovascular deaths
among patients who received azithromycin; this increase was most
pronounced among patients with a high baseline risk of cardiovascular
disease. As a result of this study, the US Food and Drug Administration
issued a warning that the drug can alter the electrical activity of the
heart, which may lead to a potentially fatal heart rhythm known as
prolonged QT interval. This rhythm causes the timing of the heart’s
contractions to become irregular. The warning stated that physicians
should use caution when giving the antibiotic to patients who are
known to have this condition or who are at risk for cardiovascular
problems.
To ascertain the efficacy of azithromycin for the management of
periodontal diseases, future studies will need to increase the number of
subjects, improve diagnostic methods and tools, and determine the
appropriate dose, duration, and frequency of azithromycin therapy.