Antimicrobial Therapy for Head & Neck Infection: Introduction
A summary of empiric antimicrobial therapy for common conditions encountered in otolaryngology can be found in Table 2–1. In general, when culture and susceptibility data are finalized, it is important to use the narrowest agent possible. This may not only be cost effective in many cases but will also decrease selection pressure for the development of antimicrobial resistance.
| Suspected Clinical Diagnosis | Likely Etiologic Diagnosis | Treatment of Choice | Comments |
|---|---|---|---|
| Infections of the Ear | |||
| External otitis | Gram-negative rods (Pseudomonas, Enterobacteriaceae, Proteus) or fungi (Aspergillus) | Otic drops containing a mixture of an aminoglycoside and corticosteroids, such as neomycin sulfate and hydrocortisone | In refractory cases, particularly if there is cellulitis of the adjacent periauricular tissue, oral fluoroquinolones such as ciprofloxacin 500 mg twice a day can be used for their antipseudomonal activity. However, there is increasing resistance being reported. Acute infection may be due to Staphylococcus aureus; dicloxacillin 500 mg 4 times a day may be used. |
| Malignant external otitis | Pseudomonas aeruginosa | Antibiotics with antipseudomonal activity (such as ciprofloxacin) for a prolonged period until there is radiographic evidence of improvement. | Surgical debridement may be necessary if medical therapy is unsuccessful. It may also be necessary to rule out osteomyelitis by CT scan or MRI, as osteomyelitis requires prolonged therapy for 4–6 weeks. |
| Acute otitis media | Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and viruses (RSV, rhinoviruses) | Amoxicillin is the first drug of choice at 45 mg/kg/d in two or three divided doses. If drug resistance is suspected, a higher dose of amoxicillin or amoxicillin–clavulanate (90 mg/kg/d) may be used. Prevention of recurrent acute otitis media may be treated with oral doses of sulfisoxazole 50 mg/kg or amoxicillin 20 mg/kg at bedtime. If this strategy fails, the insertion of ventilating tubes may be necessary. | Treatment is a combination of antibiotics and nasal decongestants. Without treatment, there may be a spontaneous resolution of illness (less likely with S pneumoniae). |
| Mastoiditis | S pneumoniae, Streptococcus pyogenes, H influenzae, and P aeruginosa | Myringotomy for culture and drainage and ceftriaxone, 1 g IV every 24 hours. | Antibiotics may be modified based on culture results. |
| Infections of the Nose & Paranasal Sinuses | |||
| Rhinitis (common cold) | Can be caused by a variety of viruses, including several serologic types of rhinoviruses and adenoviruses | Mainly reassurance of the patient and supportive therapy, such as decongestants (pseudoephedrine 30–60 mg every 4–6 hours). Nasal sprays such as oxymetazoline or phenylephrine can be immediately effective but must not be used for more than a few days at a time since rebound congestion may occur. | Secondary (bacterial) infection may occur and present as acute sinusitis. |
| Acute sinusitis | S pneumoniae, H influenzae, M catarrhalis, Group A streptococcus, anaerobes, viruses, and S aureus | Amoxicillin or amoxicillin–clavulanate 500 mg by mouth 3 times a day is a reasonable first choice. If drug-resistant S pneumoniae is suspected, an oral fluoroquinolone such as levofloxacin may be used. | Because two-thirds of untreated patients will improve symptomatically within 2 weeks, antibiotic treatment is usually reserved for those who have maxillary or facial pain (or both), and purulent nasal discharge after 7 days of decongestants and analgesics. In cases of clinical failure, endoscopic sampling or maxillary sinus puncture can yield a specimen for microbiologic evaluation and the targeted selection of antibiotics. |
| Sinusitis in an immunocompromised host | Various molds, including Aspergillus and Mucormycosis | Wide surgical debridement and amphotericin B. Liposomal amphotericin, the echinocandins, and the new broad-spectrum azoles may be alternatives in appropriate patients. | These molds are highly angioinvasive and rapid dissemination and death can occur if they are not recognized in a timely fashion. |
| Infections of the Oral Cavity & Pharynx | |||
| Candidiasis (thrush) | Candida albicans (usually) | Fluconazole (100 mg by mouth daily for 7–14 days) or an oral solution of itraconazole (200 mg by mouth once daily) | AIDS patients may have fluconazole-resistant disease and may be treated with higher doses of fluconazole or itraconazole solution, or with amphotericin B administered intravenously. |
| Necrotizing ulcerative gingivitis (trench mouth, Vincent infection) | Usually coinfection with spirochetes and fusiform bacilli | Penicillin, 250 mg 3 times a day orally, with peroxide rinses | Clindamycin for patients with penicillin allergies. |
| Aphthous stomatitis (canker sore, aphthous ulcers) | Unknown, although human herpesvirus 6 is suspected | Mainly untreated. Options include topical steroids (eg, Kenalog in Orabase), other compounds such as mouthwashes containing amyloglucosidase and glucose oxidase, or a short course of systemic steroids. | Immunocompromised hosts, such as HIV-positive patients, may have more severe disease. |
| Herpetic stomatitis | Reactivation of herpes simplex virus 1 or 2 | Oral acyclovir 400 mg 3 times daily, famciclovir 125 mg 3 times daily for 5 days, or valacyclovir 500 mg twice a day for 5 days may decrease healing time if initiated within 48 hours from the onset of symptoms. For recurrent disease, suppression with acyclovir 400 mg twice a day, famciclovir 250 mg twice daily, or valacyclovir 1 g daily is effective. | Most adults require no intervention. Immunocompromised hosts, such as HIV-positive patients, may have more severe and acyclovir-resistant disease and should be treated. |
| Pharyngitis | Group A, C, and G (β-hemolytic) streptococci, viruses (EBV-related infectious mononucleosis), Neisseria gonorrhoeae, Mycoplasma pneumoniae, human herpesvirus 6, Corynebacterium diphtheriae, Arcanobacterium haemolyticum, and Chlamydia trachomatis | Penicillin V (500 mg orally twice a day for 10 days), a single dose of benzathine penicillin intramuscularly (1–2 million units), or clarithromycin 500 mg by mouth twice a day for 10 days. If gonococcus is diagnosed, this may be treated with ceftriaxone 125 mg intramuscularly once, cefixime 400 mg orally in one dose, or cefpodoxime 400 mg orally in one dose. All patients with gonorrhea must also be treated for the possibility of concomitant genital Chlamydia trachomatis with azithromycin 1 g orally once, or doxycycline 100 mg orally twice daily for 7 days. | One of the main goals in management is to diagnose and treat Group A streptococcal infection and decrease the risk of rheumatic fever. |
| Epiglottitis | H influenzae, Group A streptococcus, S pneumoniae, and S aureus | Ceftriaxone (50 mg/kg daily for children) or cefuroxime. Adjunctive steroids are sometimes given but are not of proven benefit. Urgent tracheostomy in children or intubation in adults may be necessary. | |
| Parapharyngeal space infection (including Ludwig angina) | Often polymicrobial and include streptococcal species, anaerobes, and Eikenella corrodens | Clindamycin 600–900 mg intravenously every 8 hours, or a combination of penicillin and metronidazole | External drainage is sometimes necessary. |
| Jugular vein septic phlebitis (Lemierre disease) | F necrophorum | Clindamycin, or a combination of penicillin and metronidazole | Surgical drainage of the lateral pharyngeal space and ligation of the internal jugular vein may be performed as well. |
| Laryngitis | Viral (>90% of cases) | Antibiotics are not usually indicated | |
| Sialadenitis | S aureus | Antistaphylococcal intravenous antibiotics such as nafcillin 2 g every 4 hours | |
| Acute cervical lymphadenitis | Bartonella henselae (catscratch disease), Group A streptococcus, S aureus, anaerobes, M tuberculosis (scrofula), Mycobacterium avium, toxoplasmosis, and tularemia | Depends on the specific diagnosis after fine-needle aspiration is performed | |
Antibacterial Agents
Penicillins are a large group of β-lactam antibiotics. All share a common nucleus (6-aminopenicillanic acid) that contains a β-lactam ring, which is the biologically active moiety. The drugs work by binding to penicillin-binding proteins on the bacterial cell wall, which inhibits peptidoglycan synthesis. They also activate autolytic enzymes in the cell wall, resulting in cell lysis and death.
This class includes parenteral penicillin G (eg, aqueous crystalline, procaine, and benzathine penicillin G) and oral formulations (eg, penicillin V).
The most common side effect of agents in the penicillin family is hypersensitivity, with anaphylaxis presenting in 0.05% of cases.
These drugs are most active against gram-positive organisms, but resistance is increasing. Natural penicillins are still widely used for streptococci, such as in streptococcal pharyngitis; however, 30–35% of pneumococci have intermediate- or high-level resistance to penicillin. They are also used for meningococci, Treponema pallidum and other spirochetes, and actinomyces.
This extended-spectrum group includes ampicillin, which is administered intravenously, and amoxicillin (only oral formulation in the United States). These agents are susceptible to destruction by β-lactamases produced by staphylococci and other bacteria.
A maculopapular rash may occur in 65–100% of patients with infectious mononucleosis who are prescribed amoxicillin. This symptom is not a true penicillin allergy.
In addition to having the same spectrum of activity against gram-positive organisms as the natural penicillins, aminopenicillins also have some activity against gram-negative rods. Because of its pharmacokinetics, amoxicillin is active against strains of pneumococcus with intermediate resistance to penicillin, but not against strains with high-level resistance; it is therefore a first-line drug for the treatment of sinusitis and otitis.
This class includes methicillin, dicloxacillin, and nafcillin. They are relatively resistant to β-lactamases produced by staphylococci.
Nafcillin in high doses can be associated with a modest leukopenia, particularly if given for several weeks.
These agents are used as antistaphylococcal drugs because they are less active than the natural penicillins against other gram-positives. They are still adequate in streptococcal infections.
This class includes the carboxypenicillins, such as ticarcillin (Ticar), and the ureidopenicillins, such as piperacillin (Pipracil).
These agents are used primarily for their activity against many strains of Pseudomonas. They also have better enterococcal coverage compared with penicillin, with piperacillin having better activity than ticarcillin.
The addition of β-lactamase inhibitors to aminopenicillins and antipseudomonal penicillins can prevent inactivation by bacterial β-lactamases. These agents inactivate β-lactamases produced by S aureus, H influenzae, Moraxella catarrhalis, and Bacteroides fragilis, extending the activity of the parent drug to include these organisms. Augmentin (amoxicillin and clavulanic acid) is given orally. Unasyn (ampicillin and sulbactam), Zosyn (piperacillin and tazobactam), and Timentin (ticarcillin and clavulanic acid) are administered intravenously.
Augmentin is associated with some gastrointestinal intolerance, particularly diarrhea, which is decreased if administered twice a day.
Augmentin is used clinically for the treatment of refractory cases of sinusitis and otitis media that have not responded to less costly agents and may be due to anaerobes or S aureus. Unasyn, Zosyn, and Timentin are used as general broad-spectrum agents, with Zosyn having the most broad-spectrum activity. They are not active against methicillin-resistant S aureus and atypical organisms such as chlamydia and mycoplasma. Unasyn has no activity against Pseudomonas.
Other β-lactam drugs include monobactams (aztreonam [Azactam]), and carbapenems (imipenem [Primaxin], meropenem [Merrem], doripenem [Doribax], and ertapenem [Invanz]). Monobactams have activity limited to gram-negative organisms, including Pseudomonas. Carbapenems have a wider spectrum. Imipenem is a broad-spectrum antibiotic and covers most gram-negative organisms, gram-positive organisms, and anaerobes, with the exception of Stenotrophomonas maltophilia, Enterococcus faecium, and most methicillin-resistant S aureus and Staphylococcus epidermidis. Meropenem and doripenem has a similar spectrum of activity. Ertapenem has a narrower spectrum of activity, with no coverage against Pseudomonas, Acinetobacter, or Enterococcus faecalis.
Despite the structural similarity of aztreonam to penicillin, cross-reactivity is limited and the drug can be given to those with a history of penicillin allergy, including IgE-mediated reactions. Patients allergic to penicillins may be allergic to imipenem and meropenem. Imipenem is associated with seizures, particularly if used in higher doses in elderly patients with decreased renal function, cerebrovascular disease, or seizure disorders. Meropenem is less likely to cause seizures and is associated with less nausea and vomiting than imipenem.
Aztreonam is useful for the treatment of confirmed pseudomonal infections in patients with allergies to penicillin and cephalosporins. Imipenem and meropenem should not be routinely used as a first-line therapy unless treating known multidrug-resistant organisms that are sensitive to these agents. However, in an appropriate patient who has been hospitalized for a prolonged period and who may experience infection with organisms resistant to multiple drugs, imipenem or meropenem may be used while awaiting culture results.
