Prophylactic Antibiotic Use in Head and Neck Surgery

Prophylaxis with antimicrobials has decreased the high incidence of wound infection after head and neck operations that involve incisions through oral or pharyngeal mucosa. Prophylactic administration of antibiotics can decrease postoperative morbidity, shorten hospitalization, and reduce overall costs attributable to infections. ^{[1, 2, 3]}

Principles of prophylaxis include providing optimal and effective dosing of antibiotics at the time of wound exposure and effective prophylactic regimens. The regimen should be only be directed against the most likely pathogens. Selecting the antibiotic regimen should largely be based on location of the surgical incision; however, the need to assess for epidemiological factors such as common offending bacteria and their respective susceptibility panels should also be addressed.

Many antimicrobials require a single dose given within 60 minutes of skin incision to provide adequate tissue concentration throughout the operation. Additional doses during the procedure are advisable if surgery is prolonged (ie, > 4 h), major blood loss occurs, or an antimicrobial with a short half-life is used. The antibiotics should be discontinued 24 hours after surgery, as the prolonged use of prophylaxis leads to bacterial resistance and increased hospital costs. ^[4]

The immunocompetency of the patient should also be evaluated, which includes attentiveness to factors such as history of previous surgery creating scarring, radiation exposure, malnourishment, or HIV infection, among others. However, a diagnosis of diabetes mellitus remains controversial in assessing complication risk specific to head and neck surgery. This review therefore highlights the multifactorial nature of administering appropriate and efficacious antibiotic prophylaxis to reduce postsurgical complications. ^[5]

See the image below.

Choosing an antibiotic for prophylaxis is multifactorial and should be based on the following:

• Type of operation

• Kinetics and toxicity of the drugs

• Microbiologic characteristics of the operative site

• Antibiotic sensitivities specific to the particular hospital environment

In operations in which mucosa is not violated, antimicrobial prophylaxis needs to cover only gram-positive skin flora, primarily Staphylococcus epidermidis and Staphylococcus aureus.

In operations that feature postoperative infections with aerobic and anaerobic flora, an antibiotic regimen effective against this broad spectrum of pathogens should be used.

If a number of drugs appear equally acceptable for prophylaxis, the agent least likely to be used for definitive therapy in postoperative wound infection should be chosen. This strategy should minimize the selection of organisms resistant to valuable therapeutic agents. Recent studies have shown that high dose parenteral first generation cephalosoprins have equal efficacy as third generation options in patients undergoing a procedure in clean-contaminated oncologic surgery. This could allow for the opportunity to continue to use first generation cephalosporins while preserving resistance rates in the third generation class. Therefore, the need to assess susceptibility profiles while selecting antibiotics is emphasized. ^[5]

The regimen chosen should be compatible with findings from the hospital's infection control wound surveillance report. This regimen is particularly important in hospitals with high incidence of infection with methicillin-resistant organisms (eg, S aureus [MRSA], S epidermidis [MRSE]) or with organisms exhibiting vancomycin or clindamycin resistance.

A recent article described the importance of determining MRSA susceptibility profiles when choosing an antibiotic. A regimen consisting of linezolid and gentamicin was shown to be more efficacious than trimethoprim/sulfamethoxazole and gentamicin in treating MRSA otorrhea; highlighting the need to assess for resistance in head and neck antibiotic selection as TMP/SMX is typically first-line. The epidemiology of clindamycin resistance should also be regarded, as studies have shown MRSA resistance rates as high as 22% for clindamycin, an antibiotic typically implemented to cover for this organism in addition to anaerobes. ^{[6, 7]}

Consider cost and total expenses, including those of laboratory monitoring, drug administration (eg, supplies, personnel), and treatment of adverse effects.

Penicillin

Mechanism of action

• Affects actively dividing cells by causing abnormal peptidoglycan formation in cell wall development

• Inhibits third stage of cell wall synthesis by inhibiting DD-transpeptidase

Resistance

• Alterations in penicillin-binding proteins

• Inability to penetrate bacterial cell walls

• Enzymatic hydrolysis of penicillin molecule by beta lactamase

Spectrum

• Gram-positive cocci - Group A and group B Streptococcus

• Gram-positive bacilli -Corynebacterium diphtheriae

• Gram-negative cocci -Neisseria meningitidis

• Gram-negative bacilli -Streptobacillus moniliformis

• Anaerobes -Clostridium, Bacteroides, Fusobacterium, and Peptostreptococcus species

• Miscellaneous -Treponema pallidum and Leptospira, Enterobacter, and Acinetobacter species

Adverse reactions

• Hypersensitivity (1-5%) - Irritant properties that affect the peripheral nervous system

• Nephropathy - Allergic reaction manifested by interstitial nephritis and hypokalemia

Cephalosporin

Mechanism of action

• Binds to penicillin binding proteins

• Inhibits third step of bacterial wall synthesis by inhibiting DD-transpeptidase

• Alters cell permeability

• Inhibits protein synthesis

• Releases autolysins

Resistance

• Decrease in bacterial cell wall permeability to antibiotics and production of beta-lactamase

• Less susceptible to beta-lactamase than penicillin

Spectrum

• First generation (eg, Ancef, Keflin, Kefzol) - Have the greatest degree of activity against gram-positive organisms, such as Staphylococcus and Streptococcus (not MRSA); have the same coverage against gram-positive, anaerobic, and aerobic bacilli as penicillin

• Second generation (eg, Ceclor, Zinacef, Mefoxin) - Less active against gram-positive bacteria, but have an advantage against Haemophilus influenzae organisms and some gram-negative bacilli, including Proteus and Enterobacter species

• Third generation (eg, Ceftazidime, Cefotaxime, Cefoperazone) - Have the greatest activity against gram-negative aerobes, with variable activity against Pseudomonas organisms

• Fourth generation (eg, Cefepime, Cefclidine) - Extended-spectrum with almost equal efficacy against gram-positive organisms as first-generation cephalosporins, and greater resistance to beta-lactamase than third generation cephalosporins. They are bactericidal against gram-negatives such as Pseudomonas.

Adverse reactions

• Hypersensitivity - Highest incidence in those allergic to penicillin

• Hematologic - Neutropenia, leukopenia, and thrombopenia

• GI disturbances - Nausea, vomiting, anorexia, and diarrhea

• Reversible renal impairment

Erythromycin

Mechanism of action

• Inhibits bacterial protein synthesis by binding to 50s ribosomal subunit

Resistance

• Alteration in protein component of 50s ribosomal subunit

• Plasmid-mediated resistance

Spectrum

• Similar to that of penicillin G

• Effective against Mycoplasma, Legionella, and Actinomyces species

• Combined with sulfisoxazole to make Pediazole, which is used in the pediatric population

• Effective against H influenzae organisms

Adverse reactions

• GI disturbances

• Hypersensitivity

• Cholestatic hepatitis

Clindamycin

Mechanism of action

• Binds to 50s ribosomal subunit, thereby inhibiting protein synthesis

Resistance

• Similar to that of erythromycin

Spectrum

• Active against most aerobic and anaerobic gram-positive organisms

• Anaerobic gram-negative organisms, although some staphylococcal organisms have developed resistance

Adverse reactions

• Pseudomembranous colitis

• Mild nausea and diarrhea

• Hypersensitivity

• Leukopenia

• Transient increase

• Hepatotoxicity (rare)

Metronidazole (Flagyl)

Mechanism of action

• Reduced intracellularly to its active metabolite that is bactericidal

• May be administered orally, intravenously, or rectally

• Metabolized in the liver and excreted by the kidneys

Adverse reactions (most of which are dose related and are not seen with regular short-term use)

• CNS toxicity

• GI disturbance

• Neutropenia

• Drug fever

• Synergistic alcohol effect

• Prolonged activated partial thromboplastin time (aPTT)

Antibiotic prophylaxis is indicated in some surgeries but not in others. The appropriate use of antibiotic prophylaxis in the different types of head and neck surgery is discussed herein. An algorithm of appropriate antibiotic prophylaxis is shown in the image below.

Noncontaminated head and neck surgery

Noncontaminated surgery refers to violation of prepared skin only and no mucosal exposure or incision (eg, neck dissection, parotidectomy, thyroidectomy).

Clean surgical procedures are those in which no infection exists prior to surgery. During surgery, sterility of the wound is maintained. Following closure of the wound at completion of surgery, the wound is never again exposed to direct contact with bacteria. The risk of postoperative wound infection under these circumstances is less than 5%.

Because the mucosa is not violated, antimicrobial prophylaxis needs to cover only gram-positive skin flora, primarily Staphylococcus epidermidis and Staphylococcus aureus. Antibiotics such as cephalosporins or other beta-lactamase resistant drugs are encouraged to use in the regimen.

The inefficacy of antibiotics administrated to patients undergoing clean operations of the head and neck was demonstrated in a study by Johnson et al. In fact, there has been a reported increase in morbidity when using clindamycin for free flap surgical prophylaxis including flap suture site infection and resulting partial or complete flap loss. This could be attributed to clindamycin’s broad spectrum of action; an antibiotic not typically used in noncontaminated surgery prophylaxis. ^{[8, 9]}

A meta-analysis by Medas et al, which included 6 studies with a total of 4428 patients, showed that antibiotic prophylaxis is not effective in decreasing the incidence of surgical site infections in thyroid and parathyroid surgery. The incidence of infections was 0.6% in the case group and 0.4% in the control group. ^[10]

Contaminated head and neck surgery

Contaminated surgery refers to transmucosal operations (eg, composite resection, glossectomy, maxillectomy). Saliva contains 108 bacteria per milliliter, 90% of which are anaerobic. Ninety-six percent of wound infections in the head and neck are polymicrobial. In a study by Johnson et al, organisms involving oropharyngeal flora included anaerobic organisms (Bacteroides, 76%), gram-negative rods (eg, Escherichia coli and Klebsiella, Serratia, and Proteus species), and gram-positive organisms (ie, Staphylococcus, Streptococcus). Isolation of aerobic gram-negative bacilli and fungi from postoperative wounds after head and neck surgery is generally representative of colonization. Therefore, antimicrobial prophylaxis for these microorganisms remains questionable. ^[8]

Clindamycin (600 mg PO/IV q8h for 4 doses) is the recommended antibiotic to prevent anaerobic and gram-positive wound contamination in extensive surgeries of the head and neck.

Aerobic gram-negative coverage remains controversial as these bacteria are not part of the normal upper GI flora, however aerobic gram-negative bacilli commonly colonize the oropharynx of hospitalized patients. Because Clindamycin does not protect against aerobic gram-negative bacilli the question of additional antibiotic coverage has been explored. Studies have failed to show decreased post-surgical infection rates when using Clindamycin + Gentamycin vs Clindamycin alone, indicating unnecessary coverage for aerobic gram negatives. Implementing this restriction in practice can preserve coverage in an antibiotic class with growing resistance. ^{[5, 11]}

There has been controversy regarding prophylaxis use in tonsillectomy patients to improve post operative outcomes and quality of life. In recent trials, researchers failed to show a significant reduction in pain, the need for analgesics, or hemorrhage rates when using antimicrobials. However, they were able to show significant fever reduction in treated patients. If prophylaxis is used, recent data has shown oral azithromycin to be of equal efficacy as intravenous cefazolin in preventing surgical site infection in tonsillectomy patients. The implementation of this change in common practice could allow for more cost-effective antimicrobial prophylaxis. ^{[12, 13]}

In summary, a single antibiotic with excellent anaerobic coverage (eg, clindamycin) is probably as effective as multiple or broad-based spectrum antibiotics covering aerobes and anaerobes. Appropriate antibiotic choices also include a combination of ampicillin and sulbactam (3 g IV followed by 1.5 g q8h for 3 doses) and a combination Ancef and Flagyl. As an oral mouth rinse, use of clindamycin (75-mg caps stirred in 8 oz of tap water) or chlorhexidine (Peridex) provides rapid and sustained reductions in the concentrations of aerobic and anaerobic oral flora.

A retrospective study by Langerman et al indicated that in employing antibiotic prophylaxis in clean-contaminated head and neck surgery, ampicillin/sulbactam may offer greater protection against surgical site infection than clindamycin when administered not just on the day of surgery but after as well. The investigators found that protection from ampicillin/sulbactam did not differ significantly from that provided by other antibiotics on the day of surgery but that when given on both the day of surgery and the next day, ampicillin/sulbactam reduced the likelihood of surgical site infection by more than two thirds. Administration of clindamycin past the day of surgery was not found to offer the same advantage. ^[14]

Nasal and sinus surgery

Nasal bacterial flora primarily consists of diphtheroids, coagulase-negative cocci, and enterobacteria. Coagulase-positive staphylococcal organisms reside in the nasal cavities of approximately 50% of patients undergoing nasal surgery.

The nose is a contaminated field. Prophylactic antibiotics should be used to prevent devastating postoperative infections. Intranasal packing causes sinusitis that can be prevented with antibiotics.

Facial fractures

Open fractures have an increased incidence of infection in the absence of antibiotic prophylaxis when compared to closed or open fractures treated with prophylactic antibiotics.

The infection rates of mandible fractures treated with closed or open reduction are similar, provided that antibiotics are used in the perioperative period.

Studies have concluded that antibiotic prophylaxis significantly reduce the incidence of postoperative infections in facial fractures, especially mandible fractures of the body or parasymphyseal region.

The infection rates in zygoma fractures, LeFort fractures, and mandibular subcondylar fractures are similar.

High risk patients

Risk factors for surgical site infections in head and neck surgery include cancer at advanced stages, smoking, comorbidities, major reconstruction of the surgical wound, tracheotomy procedure, malnourished patients, or those who were submitted to inadequate antibiotic prophylaxis. Furthermore, increased duration of prophylaxis has failed to decrease infection in many of these high risk groups. ^{[15, 16]}

The issue of diabetic prophylactic efficacy remains controversial, as studies have failed to show a correlation between diabetes and increased surgical site infection post head and neck surgery. However, postoperative complications in free tissue transfer flaps have increased in diabetic patients, at a rate equivocal to patients treated with immunosuppressive drugs. The majority of these diabetic patients had concomitant peripheral vascular disease, allowing us to appreciate the impact that short and long-term glycemic control have on post surgical morbidity. The reported increases in diabetic complications have been attributed to decreased innate and acquired immunity and even renal failure with uremia-induced immunosuppression. Regardless, the topic of diabetic head and neck surgical outcomes, opposed to well documented peripheral complications, remains to be explored. ^{[15, 17, 18, 19]}

Disadvantages of antibiotics

The use of antibiotics may encourage laxity of good surgical technique. It promotes antibiotic resistance and contributes to superinfection. Antibiotic use is also costly and associated with allergic reactions, toxic reactions, and adverse effects. Studies have shown increased hospital stay and morbidity with extended oral prophylaxis; which could be attributed to adverse side effects of the antibiotic regimen or opportunistic infection such as Clostridium Difficile, which Clindamycin is notorious for inducing. Regardless, when considering extensive or complicated procedures, such as bone surgery with reconstruction, extending prophylaxis for 48-72 hours continues to be encouraged. ^{[20, 4]}