A 49-year-old woman with a persistent cough

Direct fluorescence antibody testing

The CDC does not recommend direct fluorescence antibody testing to diagnose pertussis. This test is commercially available and is sometimes used to screen patients for B pertussis infection, but it lacks sensitivity and specificity for this organism. Cross-reaction with normal nasopharyngeal flora can lead to a false-positive result.¹⁸ In addition, the interpretation of the test is subjective, so the sensitivity and specificity are quite variable: the sensitivity is reported as 52% to 65%, while the specificity can vary from 15% to 99%.

Enzyme-linked immunosorbent assay

ELISA testing has been used in epidemiologic studies to measure serum antibodies to B pertussis. Many serologic tests exist, but none is commercially available. Many of these tests are used by the CDC and state health departments to help confirm the diagnosis, especially during outbreaks. Generally, serologic tests are more useful for diagnosis in later phases of the disease. Currently used ELISA tests use both paired and single serology techniques measuring elevated immunoglobulin G serum antibody concentrations against an array of antigens, including pertussis toxin, filamentous hemagglutinin, pertactin, and fimbrae. As a result, a range of sensitivities (33%–95%) and specificities (72%–100%) has been reported.^12,14,19

TREATING PERTUSSIS

Our patient’s PCR test result comes back positive. In view of her symptoms and this result, we decide to treat her empirically for pertussis, even though she has had no known contact with anyone with the disease and there is currently no outbreak of it in the community.

3. According to the most recent evidence, which of the following would be the treatment of choice for pertussis in this patient?

• Azithromycin (Zithromax)
• Amoxicillin (Moxatag)
• Levofloxacin (Levaquin)
• Sulfamethoxazole-trimethoprim (Bactrim)
• Supportive measures (hydration, humidifier, antitussives, antihistamines, decongestants)

Azithromycin and the other macrolide antibiotics erythromycin and clarithromycin are first-line therapies for pertussis in adolescents and adults. If given during the catarrhal phase, they can reduce the duration and severity of symptoms and lessen the period of communicability.^20,21 After the catarrhal phase, however, it is uncertain whether antibiotics change the clinical course of pertussis, as the data are conflicting.^20–22

Factors to consider when selecting a macrolide antibiotic are tolerability, the potential for adverse events and drug interactions, ease of compliance, and cost. All three macrolides are equally effective against pertussis, but azithromycin and clarithromycin are generally better tolerated and are associated with milder and less frequent side effects than erythromycin, including lower rates of gastrointestinal side effects.

Erythromycin and clarithromycin inhibit the cytochrome P450 enzyme system, specifically CYP3A4, and can interact with a great many commonly prescribed drugs metabolized by this enzyme. Therefore, azithromycin may be a better choice for patients already taking other medications, like our patient.

Azithromycin and clarithromycin have longer half-lives and achieve higher tissue concentrations than erythromycin, allowing for less-frequent dosing (daily for azithromycin and twice daily for clarithromycin) and shorter treatment duration (5 days for azithromycin and 7 days for clarithromycin).

An advantage of erythromycin, though, is its lower cost. The cost of a recommended course of erythromycin treatment for pertussis (ie, 500 mg every 6 hours for 14 days) is roughly $20, compared with $75 for azithromycin.

Amoxicillin is not effective in clearing B pertussis from the nasopharynx and thus is not a reasonable option for the treatment of pertussis.²³

Levofloxacin is also not recommended for the treatment of pertussis.

Sulfamethoxazole-trimethoprim is a second-line agent for pertussis. It is effective in eradicating B pertussis from the nasopharynx²⁰ and is generally used as an alternative to the macrolide agents in patients who cannot tolerate or have contraindications to macrolides. Sulfamethoxazole-trimethoprim can also be an option for patients infected with rare macrolide-resistant strains of B pertussis.

Supportive measures by themselves are reasonable for patients with pertussis beyond the catarrhal phase, since antibiotics are typically not effective at that stage of the disease.

From 80% to 90% of patients with untreated pertussis spontaneously clear the bacteria from the nasopharynx within 3 to 4 weeks from the onset of cough symptoms.²⁰ However, supportive measures, including antitussives (both over-the-counter and prescription), tend to have very little effect on the severity or duration of the illness, especially when used past the early stage of the illness.

POSTEXPOSURE CHEMOPROPHYLAXIS FOR CLOSE CONTACTS

Postexposure chemoprophylaxis should be given to close contacts of patients who have pertussis to help prevent secondary cases.²² The CDC defines a close contact as someone who has had face-to-face exposure within 3 feet of a symptomatic patient within 21 days after the onset of symptoms in the patient. Close contacts should be treated with antibiotic regimens similar to those used in confirmed cases of pertussis.

In our patient’s case, the diagnosis of pertussis was reported to the Ohio Department of Health. Shortly afterward, the department contacted the patient and obtained information about her close contacts. These people were then contacted and encouraged to complete a course of antibiotics for postexposure chemoprophylaxis, given the high secondary attack rates.

PERTUSSIS VACCINES

4. Which of the following vaccines could have reduced our patient’s chance of contracting the disease or reduced the severity or time course of the illness?

• DTaP
• Tdap
• Whole-cell pertussis vaccine
• No vaccine would have reduced her risk

It is important to prevent pertussis, given its associated morbidities and its generally poor response to drug therapy. Continued vigilance is imperative to maintain high levels of vaccine coverage, including the timely completion of the pertussis vaccination schedule.

The two vaccines in current use in the United States to produce immunity to pertussis—DTaP and Tdap—also confer immunity to diphtheria and tetanus. DTaP is used for children under 7 years of age, and Tdap is for ages 10 to 64. Thus, our patient should have received a series of DTaP injections as an infant and small child, and a Tdap booster at age 11 or 12 years and every 10 years after that.

The upper case “D,” “T,” and “P” in the abbreviations signifies full-strength doses and the lower case “d,” “t,” and “p” indicate that the doses of those components have been reduced. The “a” in both vaccines stands for “acellular”: ie, the pertussis component does not contain cellular elements.