Evidence-based theory for drug prescribing
I. General considerations
Q. Is it appropriate to prescribe antibiotics against postsurgical infections in implant/periodontal surgery and oral/maxillofacial surgery?
A. Yes and No. It has been reported that presurgical antibiotics and good surgical technique reduced postoperative infection to 1%. The longer the surgical procedure, the higher the incidence of postoperative infection. A single prophylactic antibiotic dose is sufficient and using antibiotics after the surgery is not indicated unless extensive surgery is performed with soft tissue manipulation in which antibiotics is recommended to continue for 3 days following the surgery. The decision to use postsurgical antibiotics depends on the patient (e.g., diabetic patient). So, the clinical situation should be evaluated before any antibiotics are prescribed. Use of an antimicrobial rinse such as chlorhexidine gluconate can also be prescribed pre-and postsurgery (Resnik & Misch, 2008).
Q. For antibiotic prophylaxis how many hours or days before the dental procedure should the systemic antibiotic be administered?
A. To have the maximum effect, the antibiotic should be in the tissues when the bacterial contamination occurs, not after. In order for this to happen, the antibiotic needs to be administered only about 1 to 2 hours before surgery to attain plasma levels 3 to 4 times the minimum inhibitory concentration (MIC) needed to kill bacteria (Peterson, 1990). The antibiotic does not need and should not be given the day before or several days before the surgery (Classen et al., 1992).
Q. What is the usual prophylactic dose of antibiotic that should be prescribed preoperatively?
A. According to Peterson (1990), In order to attain high levels in the plasma for the maximal therapeutic response, the dose is usually twice that of the regular dose; it is equivalent to administering the loading dose. For example, if the usual dose of penicillin VK is 500, prescribe 1 g. or some dentists give the same dose that the American Heart Association recommends for prophylaxis against bacteremia which is 2 g one hours before the dental procedure.
Q. Should there be a concern with development of bacterial resistance when prescribing short-term prophylactic antibiotics before a surgical procedure?
A. No. Selective growth of resistant bacteria begins only once the host’s susceptible organisms are killed, which occurs in about 3 days of antibiotic use. Thus, one day/time of antibiotic use does not affect the development of resistant bacteria (Peterson, 1990).
Q. Does the selected antibiotic need to be effective against primarily anaerobic or aerobic bacteria?
A. Since the oral environment is usually 2:1 anaerobic to aerobic bacteria it is best to choose an antibiotic effect against both periodontal pathogens (Resnik & Misch, 2008). The rest of the chapter will give recommendations for using specific antibiotics with a specific bacterial infection.
The following reviews the classification of bacteria:
- Gram-positive facultative cocci: Streptococcus sanguis, mitis, 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).
- 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.
- Obligate aerobic: Mycobacterium tuberculosis, Pseudomonas aeruginosa.
Q. What can happen if antibiotics are used indiscriminately?
A. The indiscriminate use of systemic antibiotics could influence the emergence of resistant bacterial strains which would be resistant to eradication by antibiotics. However, as stated in a previous question, development of resistant strains after 1 day of antibiotic use will most likely not happen. Allergies to drugs may also develop.
Q. Is it best to use a single antibiotic or combinations?
A. Depending upon the results of antimicrobial testing and susceptibility combination antibiotic therapy may be necessary in mixed infections. It could be more advantageous to use combination drugs because the simultaneous use of two drugs of the same category (e.g., two bactericidal antibiotics) can achieve bactericidal synergism, allowing a reduction in dose or a shorter duration of therapy. For example, amoxicillin and metronidazole are effect against Aggregatibacter actinomycetemcomitans, where either antibiotic alone is ineffective (Jorgensen & Slots, 2000). Combination drugs can also help to reduce the emergence of resistant bacterial strains. A disadvantage of using multiple antibiotics is the increased incidence of adverse effects and potential drug-drug interactions. For example, prescribing a bacteriostatic antibiotic such as tetracycline with a bacteriostatic drug such as amoxicillin is not advised because the bactericidal antibiotic requires active multiplying bacteria in order to destroy the bacteria.
Q. Is it appropriate to start therapy with a broad-spectrum antibiotic?
A. When prescribing antibiotics the risk vs. benefits must be considered. Broad-spectrum antibiotics increase the incidence of superinfections with Candida sp., enteric rods, pseudomonads, and staphylococci and increase the emergence of resistant bacterial strains.
Q. Should the prophylactic antibiotic be bactericidal or bacteriostatic?
A. Bactericidal. The antibiotic should kill the bacteria rather than inhibiting multiplication and reproduction.
Q. What is the inoculum effect?
A. The maximum concentration to have a therapeutic effect may be insufficient even with the recommended prescribed dose because of the large number of bacteria present in untreated periodontal pockets. Thus, the minimum inhibitory concentration (MIC) of a certain antibiotic may actually be higher than the standard MIC for that drug.
II. Prescribing for inflammatory periodontal diseases and periodontal surgical procedures
Q. Do antibiotics have a role in the management of periodontal disease and periodontal therapy?
A. Yes. In some cases antibiotics have been shown to be helpful in the co-management of periodontal diseases and the selective use of antibiotics will help to avoid inappropriate prescribing.
Q. If systemic antibiotics are indicated in the adjunctive management of certain periodontal diseases, when should antibiotics be started during therapy?
A. Antibiotics should never be used alone without accompanied by mechanical debridement (scaling and root planing) and/or periodontal surgery. Sometimes antibiotics can be prescribed following initial therapy (scaling and root planing) and microbiological testing.
Q. Why is it necessary to use antibiotics in conjunction with scaling and root planing?
A. Mechanical debridement is necessary to disrupt the bacterial biofilm (colonies). This makes it easier for the antibiotic to penetrate the bacterial cell.
Q. What bacteria are primarily found in chronic gingivitis?
A. Predominant bacteria in chronic gingivitis includes Actinomyces spp., Capnocytophaga spp., Fusocbacterium spp. and Streptococcus spp. (S. mitis, S. oralis, S. sanguis, S. gordonii, S. intermedius) (Teles et al., 2007).
Q. Is antibiotic therapy used for chronic gingivitis?
A. Although chronic gingivitis is a bacterial infection, there is no current literature to support the use of systemic antibiotics because the infection is localized to the gingival unit with shallow probable depths which is easily treatable and reversible with mechanical debridement (scaling) and optimal oral hygiene.
Q. Is there any rationale for using antimicrobial agents for the treatment of chronic gingivitis?
A. There is no rationale for using systemic antibiotics in the treatment of chronic gingivitis. Topical antimicrobials including chlorhexidine gluconate may be used as an adjunct to scaling and root planing to help control the gingival inflammation but should never be used without mechanical debridement.
Q. Are there any cons for using systemic antibiotics in chronic gingivitis?
A. Yes. No literature supports the use of antibiotics. Indiscriminate use of antibiotics leads to adverse effects including bacterial resistance and unnecessary adverse effects.
b. Chronic periodontitis
Q. What are the bacteria found in inflammatory chronic periodontitis?
A. Predominant bacteria in chronic periodontitis (CP), previously referred to as adult periodontitis, include all of the bacteria in gingivitis in addition to obligate anaerobes: Porphyromonas gingivalis and Prevotella intermedii and facultative anaerobes: Fusobacterium spp., Eikinella corrodens, Tannerella forsythensis (formerly Bacteroides forsythus), Aggregatibacter actinomycetemcomitans (Aa) (formerly known as Actinobacillus actinomycetemcomitans), Actinomyces naseslundii, Peptostreptococcus spp., A. viscosus, Veillonella spp. and Treponema denticola.
Q. Do some bacteria actually invade the gingival tissues (junctional epithelium and gingival connective tissue)?
A. Some bacteria actually invade the inflamed gingival tissues rather than merely staying in the periodontal pocket. The prevalence of P. gingivalis and T. forsythensis was found not to be significantly different in chronic and aggressive periodontitis patients in either the plaque or the tissues. Prevalence of Aa in gingival tissue was higher in the localized aggressive periodontitis (63%) group than in either the chronic periodontitis (16%) or the generalized aggressive periodontitis (38%) group. A. actinomycetemcomitans serotype c was detected in 50% of localized aggressive periodontitis tissue samples (Thiha et al., 2007).
Q. Is systemic antibiotic therapy used in the treatment of inflammatory chronic periodontitis?
A. The use of systemic antibiotics in “garden variety” chronic periodontitis is very controversial. Some studies show that the addition of antibiotics to mechanical debridement may reduce the need for further treatment including surgery. In the 1980s Loesche showed a benefit of using antibiotics as an adjunct (or after subgingival debridement) to conventional periodontal treatment in “reducing the need for periodontal surgery” in patients with chronic periodontitis. Actually these patients although defined as having chronic periodontitis could have had refractory periodontitis. In Loesche’s studies the need for surgery or extractions was determined 4 to 6 weeks after initial treatment which consisted of scaling and root planing and metronidazole 250 mg, three times a day for 7 days. Results showed a decrease in teeth requiring surgery, pocket probing depths and subgingival bacteria (Bacteriodes and spirochetes) and an apparent gain in periodontal attachment (Loesche et al., 1984, 1991, 1992, 1996). Metronidzole is only effective against obligate anaerobes and not Aa, Eikenella corrodens, and Capnocytopha.
Other studies using amoxicillin plus metrondizole as an adjunct to mechanical debridement have resulted in improved clinical parameters and high percentage of eliminate of Aa and P.gingivalis in advanced chronic and refractory chronic periodontitis (van Winkelhoff et al., 1992).
Sefton et al., (1996), reported that azithromycin (500 mg once daily) consistently reduced spirochetes in chronic periodontitis patients throughout the 22 weeks of the study, but only reduced pigmented anaerobes at 3 and 6 weeks. Additional long-term studies using larger number of subjects need to be performed.
On the other hand, there are some clinical studies that have documented that there are no additional treatment outcome benefits when antibiotics are used as an adjunct to scaling and root planing and periodontal pocket elimination surgery (Slots & Rams, 1990). The first clinical periodontal studies using tetracycline was in chronic periodontitis patients, found no statistically significant differences in probing depth reduction but a slight improvement in attachment levels (Listgarten et al., 1978). Currently, systemic antibiotics are not indication for chronic periodontitis.
Q. Are there any cons for prescribing systemic antibiotics for chronic periodontitis?
A. Yes. Failing to recognize the patient has chronic periodontitis may cause the indiscriminate use of antibiotics which may increase the incidence of bacterial resistance and increased incidence of adverse effects. It must be determined that the chronic periodontitis patient is actually a refractory periodontitis patient and then antibiotics are indicated. For plain “garden variety” chronic periodontitis patients systemic antibiotics offer little or no advantage when used as an adjunct to conventional periodontal therapy.
Q. What is doxycycline 20 mg?
A. Doxycycline 20 mg is considered to be a subantimicrobial dose and is indicated for the management of generalized chronic periodontitis. The trade name was Periostat but it is now available generically as doxycycline hyclate 20 mg. Usual antibiotic doses are 100–200 mg but at 20 mg doxycycline exerts anticollagenase activity rather than antibacterial activity. Doxycycline 20 mg inhibits the synthesis and secretion of collagenase which is an enzyme that breaks down collagen which makes up the periodontium (bone, connective tissue). This anticollagenase property does not depend on the drug’s antibacterial actions. Doxycycline 20 mg is indicated for generalized chronic periodontitis especially in cases where scaling and root planing are ineffective in halting the progression of attachment loss.
Q. Clinically, what are the outcomes of prescribing doxycycline hyclate 20 mg?
A. Gain of clinical or periodontal attachment and decreased probing depth.
Q. What does gain of clinical attachment mean?
A. After periodontal therapy (e.g., scaling and root planing) reduction of probing depths as a result of gingival recession and/or removal of inflammatory infiltrate in the gingival connective tissue with reformation of collagen fibers. Healing after conventional periodontal therapy is usually via a long junctional epithelium.
Q. Do the same contraindications/precautions with doxycycline follow with doxycycline 20 mg?
A. Yes. Doxycycline 20 mg should not be used in pregnant women or breast feeding. Inform female patients on oral contraceptives. There is possible development of resistant bacterial strains.
Q. What is the recommended dosage for doxycycline hyclate 20 mg?
A. Taken twice a day (every 12 hours) as an adjunct to scaling and root planing for up to 9 months.
Q. What are specific instructions on how to take the drug?
A. Take on an empty stomach at least 1 hour before or 2 hours after meals. Do not take concurrently with antacids, iron, zinc or multivitamins (wait two hours before or two hours after). Swallow with a full glass of water to prevent esophageal irritation. Dairy products are alright to have with doxycycline.
Q. What should be done if a dose is missed?
A. If the missed dose is close to the next dose, skip the missed dose and proceed with regular dosing regimen. Do not take two doses at once to make up the missed dose.
c. Ulcerative periodontal diseases
Q. What are ulcerative periodontal diseases?
A. Ulcerative periodontal diseases (UPDs) including necrotizing ulcerative gingivitis (NUG) and necrotizing ulcerative periodontitis (NUP) are bacterial infections caused specifically by Treponema spp., Fusobacterium nucleatum, and Prevotella intermedia.
Q. Does necrotizing ulcerative gingivitis clinical look different from gingivitis?
A. Necrotizing ulcerative gingivitis (NUG) differs from the other periodontal diseases. Three criteria must be present for a diagnosis of NUG: interdental gingival necrosis or “punched out” ulcerative papillae, gingival bleeding and pain (Rowland, 1999). There is usually spontaneous bleeding which occurs when touched or during eating.
Q. Clinically what does NUG look like?
A. NUG is clinically characterized by small, gray, ulcerative lesions that begin at the tips of the interdental papillae and spread to the gingival margin to form punched-out or cratered lesions. There may be a grayish-white pseudomembrane covers the affected area.
Q. Is fever and a bad odor present in NUG?
A. Fever and fetid oral odor are variable findings are not always present.
Q. Why did the disease name change from acute ulcerative necrotizing gingivitis (ANUG) to NUG?
A. Armitage (1999) documented that the word “acute” is a clinical descriptive term and should not be used as a diagnostic classification (Rowland, 1999).
Q. What are some features of NUP?
A. Necrotizing ulcerative periodontitis has the same features as NUG except there is loss of clinical attachment and alveolar bone.
Q. Are necrotizing periodontal diseases seen in immunocompromised patients?
A. Yes. NUG/NUP may be the first sign of HIV infection. Although, not limited to HIV infection, NUPs is often seen in patients who have severe malnutrition and are immunosuppressed. In HIV patients with gingivitis the free gingiva often appears as a distinct red band about 2 to 3 mm in width and is known as linear gingival erythema.
Q. What is the treatment for NUPs?
A. It is the consensus that antibiotics are required to treat UPDs. However, many different antibiotic regimens have been suggested including metronidazole, tetracycline and penicillin (Rowland, 1999).
d. Refractory and recurrent periodontitis
Q. What is refractory periodontitis?
A. Refractory periodontitis was eliminated as a separate diagnostic term from the latest 1999 periodontal classification (American Academy of Periodontology, 2000). So, refractory periodontitis is not a single diagnostic term and can occur in all periodontal disease categories. It refers to destructive periodontal diseases (e.g., chronic periodontitis) in any patient who has additional attachment loss at one or more sites, despite all efforts and careful monitoring to stop the progression of the disease. Refractory patients generally do not respond to initial therapy (American Academy of Periodontology, 2000).
Q. Are systemic antibiotics indicated in refractory patients?
A. Yes. Antibiotic therapy is usually reserved for periodontal patients having continued periodontal destruction even after mechanical debridement and effective oral hygiene to help reduce the bacterial load and promote periodontal health in patient that do not respond to conventional therapy (American Academy of Periodontology, 2004). Antibiotic susceptibility testing is necessary to determine efficacy of antibiotics against the periodontal pathogens in the patient. (However, this is controversial due to varying lab results.)
Q. Where are oral microbiology testing labs located in the United States?
A. The Oral Microbiology Testing Service (OMTS) Laboratory at Temple University Maurice H. Kornberg School of Dentistry (Dr. Rams) in Philadelphia, Oral Microbiology Testing Laboratory at University of Southern California (Dr. Slots) and Oral Microbiology Laboratory (OML) at the University of North Carolina-Chapel Hill in North Carolina.
Q. What is a DNA probe?
A. DNA probes will detect specific species and determine the antibiotic susceptibility. Molecular DNA testing uses saliva to identify and measure specific types of bacteria in periodontal diseases. Oral DNA Labs (a Quest Diagnostics Company) (www.OralDNAtraining.com) is a company that does oral salivary DNA testing.
Q. What is the difference between recurrent periodontitis and refractory periodontitis?
A. Patients with recurrent periodontitis continue to have signs of periodontitis due poor compliance with oral hygiene and do not come to the office for regular periodontal maintenance. Patients with refractory periodontitis have regular periodontal care and perform adequate oral hygiene but continue to have periodontal tissue breakdown. The etiology of refractory periodontitis is most likely due to periodontal pathogens and the immune response of the host to the pathogens.
Q. Are systemic antibiotics indicated in recurrent periodontitis?
A. No. Managing the recurrent periodontitis patient involves working with the noncompliant patient on oral hygiene and motivation. Also, it is important to monitor the frequency of periodontal maintenance visits. Using a chlorhexidine rinse as an adjunct to tooth brushing and flossing can help to reduce oral biofilm on the tongue, tonsillar pillars, and gingiva and in saliva where the bacteria reside. After initial therapy is completed and the patient continues to have localized areas with ≥ 5 mm with bleeding on probing, localized controlled-delivery of Arestin, Atridox or PerioChip can be done (Low, 2006).
Q. What are some recommended antibiotics used in refractory periodontitis?
A. The decision of choice of antibiotic depends on the pathogens present which are determined from DNA testing. Antibiotic therapy is used to help reduce the bacterial load when used in conjunction with scaling and root planing.
Some antibiotics that can be prescribed for refractory periodontitis as an adjunct to scaling/root planing/periodontal surgery include (Table 6.1).
e. Aggressive periodontitis
Q. What is aggressive periodontitis?
A. The older term for aggressive periodontitis was juvenile periodontitis. There is a genetic predisposition to aggressive periodontitis and modified with certain risk factors such as smoking and diabetes. In localized aggressive periodontitis <30% of sites are involved and if >30% of periodontal sites are affected then it is generalized aggressive periodontitis.
Q. Should systemic antibiotics be prescribed in patients with aggressive periodontitis?
A. It is clearer substantiating the use of systemic antibiotics in aggressive periodontitis which has high levels of Aggregatibacter actinomycetemcomitans. The use of systemic antibiotics in periodontal infections is based solely on the fact that certain bacteria actually invade into the epithelial cells of the gingiva rather than just staying in the “pocket area” (Revert et al., 1990; Saglie et al., 1982). These bacteria including Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans, and spirochetes invade the gingival and avoid removal by scaling and root planing; hence, systemic antibiotics should be used. Porphyromonas gingivalis also has the ability to invade human gingival fibroblasts. Numerous papers supports the adjunctive use of systemic antibiotics in the treatment of localized and generalized aggressive periodontitis because of the invasion of these bacteria into the periodontal tissues, which cannot be eradicated by scaling and root planing or surgery alone.
Q. What systemic antibiotics are recommended in the management of aggressive periodontitis?
A. Since there are many different combinations of periodontal pathogens in periodontitis, at least 10 different antibiotic regimens may be required to specifically target the various pathogen complexes (Beikler et al., 2004). Antibiotics immediately after scaling and root planing can provide more probing depth reduction and gain of attachment with healing improved up to 6 months (Doğan et al., 2007; Söder et al., 1989). There is no controversy regarding the use of systemic antibiotics in the adjunctive treatment of aggressive periodontitis. However, there may be some questions regarding the selection of the antibiotic. Haffajee et al. (2003) reported a significant improvement in periodontal attachment levels with tetracycline, metronidazole and a borderline statistical significance for the combination of amoxicillin and metronidazole.
Q. Can Arestin or Atridox be applied into the periodontal pocket in aggressive periodontitis patients?
A. No. Locally-applied antibiotics have little or no effect on Aggregatibacter actinomycetemcomitans and do not penetrate deep into the gingival tissues.
Q. What are some suggested antibiotic dosages used in aggressive periodontics?
A. Some suggested systemic antibiotics in conjunction with scaling/root planing/surgery in aggressive periodontitis patients are given in Table 6.2 (recommendations are from Walker & Karpinia, 2002).
Q. Can metronidazole be prescribed alone?
A. Metronidazole is only effective against obligate or strict or obligate anaerobes so it should be prescribed with penicillin to have better antimicrobial coverage.
f. Periodontal therapy
Periodontal flap surgery: pocket reduction
Q. Are systemic antibiotics necessary after pocket reduction periodontal surgery?
A. The primary rationale for using systemic antibiotics during surgical therapy is based on the fact that there may be an increased risk of complications including infection, pain and delayed wound healing (Arab et al., 2006; Powell et al., 2005). Additionally, the bacterial burden of the host may be lessened with the use of systemic antibiotics (van Winkelhoff, 2005). However, the prevention of infections after periodontal surgery through the routine use of antibiotics seems to be primarily based on empiricism and is very controversial and generally not recommended.
The majority of the literature does not support the use of prophylactic antibiotics in preventing post-operative infection in patients undergoing periodontal osseous surgery including full thickness flaps, degranulation, osteoplasty or ostectomy and sutures (Arab et al., 2006; Checchi et al., 1992). Powell et al. (2005), reported that there was no statistical difference in the incidence of postoperative infections in patients undergoing periodontal surgery that did not take an antibiotic (1.81%) and those who received antibiotics pre- and/or postoperatively (2.85%). Very few studies support the use of antibiotics after periodontal osseous surgery to reduce pain swelling and improve wound healing (Peterson, 1990).
Q. Why do dentists prescribe antibiotics after periodontal surgery?
A. Many dentists may base their decision to use antibiotics pre- and/or postoperatively empirically. Do antibiotics reduce the incidence of infections post osseous surgery? According to Powell et al. (1990), the overall incidence of infections following different periodontal surgeries was 2.09%. Patients who received antibiotics had a 2.85% incidence of infections compared to 1.81% where antibiotics were not used. Thus, it is the consensus and the opinion of the authors that there is no benefit in using antibiotics for the sole purpose of only purpose of prevention of postosseous surgery infections.
Bone/bone substitutes grafting procedures
Q. Should antibiotics be prescribed for bone grafting procedures?
A. The difference between periodontal osseous resective surgery and periodontal surgery using bone grafts or bone substitute materials is that in osseous resective surgery native bone is being either removed (ostectomy) or reshaped (osteoplasty) and the remaining bone retains its blood and lymph supply. The concern is that in periodontal surgery which involves the placement of bone grafts (autogenous, bovine, freeze-dried bone) or bone substitutes (hydroxyapatite, anorganic bovine bone, bioactive glass) without an established blood supply into an infrabony defect that already has an intact blood supply. An infrabony defect is type of intrabony vertical defect with 3 bony walls bordering the tooth (Weinberg & Eskow, 2000). Thus, until this grafted bone material can establish a blood supply rich in inflammatory and immune cells antibiotics may be required to aid in preventing postsurgical infections. Additionally, optimal repair and regeneration of the periodontium has been shown to be enhanced when there is suppression of the microbiota during healing (Giannopoulou et al., 2006).
During the healing phase, by 18 hours there is an accumulation of polymorphonuclear leukocytes (PMNs) which are the first inflammatory cells to move into the wound area (Zipfel et al., 2003). After blood clot formation and inflammation, there is a 2-day period of fibroblast-like mesenchymal cell chemotaxis which is driven by growth factors (Zipfel et al., 2003). By 5 to 9 days, blood vessel components are observed. By day 10 the first osteoblasts with new bone formation observed (Zipfel et al., 2003). Thus, until inflammatory and immune cells are established with blood vessel formation, it may be prudent to give antibiotics 1 hour before the surgery and for 9 days after surgery to likely prevent postoperative infection. The reason for starting the antibiotic only 1 to 2 hours before is because most antibiotics are absorbed into the blood and show peak blood levels 1 to 2 hours after the first dose. This dose will also provide blood levels that will infiltrate the graft site. It is not necessary to start the antibiotic many days before. The duration of antibiotic therapy is for 10 days when new bone has formed.
Most of the research done on the preoperative and postoperative use of antibiotics with bone grafts/bone substitutes evaluated the clinical outcomes of the su/>