There are many advantages to shorter and simpler antibiotic treatment regimens. Patients find them more convenient and the compliance rate, which is as low as 50 percent for four-times-a-day regimens, is greatly increased with a once-a-day dose. When single-dose therapy is used, compliance can approach 100 percent, particularly when it can be administered under direct observation.
Because prolonged, suboptimal concentrations of antibiotics are theoretically most likely to promote antimicrobial resistance, single-dose therapy may lessen this risk by providing brief, high, effective concentrations. Another advantage of directly observed therapy is that treatment begins sooner than when the patient must obtain the medication at an outside facility.
While these advantages make single-dose therapy desirable, several conditions must be met before advising this regimen. The antibiotics must be readily available, and the caregiver time necessary for administration must be considered. The therapeutic choice must be cost-effective, and the route of administration and side effects must be acceptable to the patient or the parents. There also must be adequate tissue penetration, and data must support the probable success of a single dose. Finally, the potential failure rate must be acceptable, which means that single-dose therapy is generally not recommended for severe or life-threatening infections. Singer et al provide a nice review of single-use antibiotics in pediatric patients. (Pediatr Emerg Care 2005;21[1]:50.)
While single-dose antimicrobial therapy is already the preferred treatment for some infections in the ED, some recently suggested indications are controversial. There also is a new formulation of azithromycin being evaluated which may greatly expand the use of single-dose therapy in the emergency department.
Single-Dose Therapy
Sexually transmitted infections are frequently treated with single-dose therapy, and direct observation of treatment protects the public health. Uncomplicated gonococcal infection (urethritis, cervicitis, proctitis, but not PID) can be treated with a single IM dose of ceftriaxone (125 mg) or a single oral dose of a fluoroquinolone, plus a single oral dose of azithromycin (1 gm). Chlamydia trachomatis can be treated with a single dose of azithromycin (1 gm PO).
Some studies have indicated that a single-dose of azithromycin alone may be adequate to treat gonorrhea. (International J STD AIDS 2004;15[4]:240.) While this may turn out to be a reasonable, cost-effective treatment, it is not currently recommended as the sole treatment for presumed or established gonorrhea. Vaginal candidiasis can be treated with a single oral dose of fluconazole (150 mg), and vaginal trichomoniasis can be treated with a single oral dose of metronidazole (2 g).
While single, high-dose therapy with amoxicillin or sulfamethoxazole/trimethoprim has been shown to be effective to treat uncomplicated lower urinary tract infections, the cure rate is higher with three-day therapy, and the side effects are not significantly increased. For these reasons, single-dose therapy for urinary tract infections is no longer recommended.
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Table: Single-Dose Treatments for Various Infections
The primary treatment of scabies remains the application of permethrin left in place for eight to 10 hours and repeated in a week. A single oral dose of ivermectin (200 mcg/kg) is an attractive alternative treatment because it is reasonably effective and much more convenient. (New Engl J Med 1995;333[1]:26.)
Other Infections
Exudative pharyngitis, presumed to be caused by group A beta hemolytic streptococcus, can be treated with a single IM dose of benzathine penicillin G (600,000 units for patients under age 6; 1.2 million units for those over age 6). The clinical response is comparable with oral 10-day regimens. While allergic reactions are probably more common than with oral administration of beta lactams, they are still quite infrequent. There is, however, a high incidence of pain and tenderness at the site of injection with up to 50 percent of children refusing to ambulate for several days. (Pediatrics 1996;97:960.) The pain of injection can be decreased without changing the pharmacokinetics by adding 3.2 ml of 1% lidocaine to 2 ml of the Bicillin LA. (Pediatr Infect DisJ 1998;17:890.)
Shorter antibiotic regimens are more convenient and have higher compliance
There are two single-dose antimicrobial treatments approved for acute otitis media. Neither, however, is considered to be first-line treatment, which instead is high-dose amoxicillin (80–90 mg/kg per day) for at least five days (10 days for children under age 6 or sicker patients at any age). Patients who have failed other treatment or are unable to take oral medications can receive ceftriaxone 50 mg/kg IM. This is approved as a one-time dose treatment for otitis media. (American Academy of Pediatrics and American Academy of Family Physicians, Clinical Practice Guide: Diagnosis and Management of Acute Otitis Media, Pediatrics, 2004;113[5]:1451.)
It should be remembered, however, that three daily doses are more effective so the patient needs to be assessed in follow-up for the need of additional doses. (Pediatr Infect Dis J 2000;19:1040.) The pain of injection can be ameliorated by adding 0.9 ml of 1% lidocaine to 2ml (500 mg) of ceftriaxone. (Arch Pediatr Adolesc Med 1994;148:72.)
Patients with a history of a severe type I allergic reaction to a beta lactam might be considered for azithromycin as initial therapy for otitis media. A single 30 mg/kg oral dose has been approved for otitis media. A recent multicenter, double-blind study of children ages 6 to 30 months with acute otitis media found a single dose of azithromycin (30 mg/kg) to be as effective as a 10-day course of high-dose oral amoxicillin. (Pediatr Infect Dis J 2005;24[2]:153.) There is, however, a fairly high incidence of nausea, abdominal pain, and vomiting.
A new formulation of azithromycin that binds the drug to microspheres seems to make single, high-dose therapy significantly more tolerable. The formulation is administered as a small volume of alkaline slurry (pH=10.5). The drug is not released until the pH becomes acidic. This tends not to occur until the drug reaches the small intestine. Gastric side effects are significantly less common than with the original formulation of azithromycin, which is absorbed in the stomach. The primary side effect is diarrhea, which occurs in approximately 10 percent of patients and tends to resolve within 24 hours. (Intern Med News 2004:37[24].) Preliminary studies indicate that single, high-dose therapy with this formulation is tolerable and effective to treat acute sinusitis, community-acquired pneumonia, and acute exacerbation of chronic bronchitis. (Infect Dis Clin Pract 2005;13[3]:115.)
Single-dose therapy can be quite desirable, particularly in the emergency department population for which access to medications and follow-up care may be limited. Many times we are able to provide definitive antimicrobial therapy with a single dose of antibiotics which can be administered in the emergency department. Careful utilization of this treatment modality can lead to markedly increased compliance, presumably better outcomes, and even theoretically, less antimicrobial resistance.
