US Pharm. 2015;40(7):50-53.
ABSTRACT: Rates of pertussis (whooping cough) in adolescents and adults have been steadily increasing in the United States. Owing to the atypical presentation of symptoms in this population, proper prevention and treatment are particularly important to reduce the risk of transmission to young children and infants. Treatment of pertussis involves the use of antimicrobial therapy, particularly macrolide antibiotics. Infection prevention in adults is managed through scheduled vaccination with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap). Pharmacists are accessible sources of immunization education and administration, and they can impact infection outcome in patients through timely referrals for antimicrobial treatment and education regarding treatment options and expected outcomes.
Pertussis, an acute respiratory infection caused by Bordetella pertussis, is characterized by a paroxysmal cough lasting ≥2 weeks, an inspiratory whoop, posttussive emesis, and posttussive syncope. Its common name, whooping cough, is derived from the sound caused by a partially closed glottis obstructing a forceful inspiration. Although pertussis is typically considered a childhood disease, rates of infection in adults and adolescents have risen, currently accounting for more than half of all reported cases.1 Many more cases go unreported because the clinical presentation of symptoms in adolescents and adults often differs from the presentation of the classic symptoms observed in infants and children. In fact, a persistent cough may be the only symptom in adults and adolescents. Because the symptoms are nonspecific, providers may overlook pertussis as the source of infection in these patients.1
Rates of pertussis in the United States have increased steadily since the 1980s, peaking at 48,277 cases reported to the CDC in 2012—the highest incidence since 1955.2 However, the actual number of pertussis cases is estimated to be 1 to 3 million annually.3 Improved diagnostics and increased reporting of pertussis may be responsible for part of the rise, but a true increase in disease incidence is widely acknowledged to have occurred, most likely owing to waning immunity from childhood vaccinations.1,4
B pertussis is a small, aerobic, gram-negative coccobacillus that is transmitted via aerosolized respiratory droplets. No animal or environmental reservoirs have been identified, and transmission requires close contact or prolonged exposure to an infected human host.5 The pertussis toxin, as well as other antigenic factors produced by the bacterium, is primarily responsible for the clinical manifestations of the disease and the immunity that occurs following infection or vaccination.6
The incubation period for pertussis ranges from 4 to 21 days, and is most commonly 7 to 10 days.6 Initial symptoms may resemble those of the common cold or other upper respiratory tract infections, and may include rhinorrhea, lacrimation, mild cough, malaise, and/or low-grade fever.1,4 The nonspecific nature of the initial symptoms makes diagnosis difficult during this phase. Unfortunately, this is also the stage in which infected persons are most contagious.4 Undiagnosed adolescents and adults may spread the disease to each other, and, more significantly, to unimmunized or inadequately immunized infants or children. Although mortality rates from pertussis are low in adolescents and adults, infections are more severe in small children and lead to more serious complications, hospitalizations, and deaths.1,4
Clinical Presentation and Diagnosis
Both the CDC and the World Health Organization define a clinical case of pertussis as a cough lasting for 2 weeks with one classic symptom, such as paroxysmal cough, posttussive emesis, or inspiratory whoop, without any other apparent causes. Although prolonged cough is a hallmark of pertussis, diagnosis should be based on a combination of clinical presentation and laboratory measurements.7 Classic symptoms are seen more often in unimmunized children, whereas previously immunized adults and adolescents commonly have an atypical presentation.4 In symptomatic adults, the paroxysmal whooping is often absent, making the clinical presentation less severe than that seen in children.8
Typically, most adults have a prolonged cough and a lack of other symptoms.4 Therefore, pertussis should be suspected in any patient presenting with a cough that has persisted for more than 3 weeks. Other concomitant symptoms with cough are diaphoresis and syncope. Many cases remain unrecognized because of their atypical presentation, and these adolescents and adults are a potential reservoir of infection for infants and children.1,4 Infants aged <12 months are often only partly through their vaccine series and have only partial immunity to pertussis; therefore, they require special attention to prevent the development of severe complications, such as apnea and pneumonia.6,8 Unlike infants, adults and adolescents with pertussis rarely develop pneumonia or require hospitalization, but they may experience rib fracture, syncope, abdominal hernia, or other complications from the severe, chronic cough.
Laboratory tests for pertussis include B pertussis culture, polymerase chain reaction (PCR), serologic testing, and direct fluorescent antibody (DFA) testing. Culture is considered the gold standard laboratory test, with the highest specificity and moderately high sensitivity.4 B pertussis, however, has specific growth requirements that render it difficult to culture. Isolation rates are highest during the early stages of infection, but it may take as long as 2 weeks to obtain culture results, which can delay clinical decision making. Additionally, cultures are less likely to be positive if performed in patients who have been ill for >2 weeks, in those who have received a prior course of antibiotic treatment, and in those who have recently received a booster dose of pertussis vaccine. Since adolescents and adults usually have the cough for several weeks before seeking medical attention, culture is often too late to be useful.6
PCR can be used in combination with culture because of its rapid turnaround time of 1 to 2 days, its ability to diagnose pertussis after 4 weeks of symptom onset or within 5 days of previous antibiotic treatment, and its greater sensitivity.1 PCR does not require a viable organism, so results are not affected by prior antibiotic treatment or vaccination. PCR should be used only in combination with culture, owing to the variability of PCR assays.6 Culture should be considered in patients with a cough onset of ≤2 weeks. A combination of PCR and culture is advised in patients with a cough onset of ≤4 weeks.4 Neither DFA nor serologic testing is recommended for diagnosis of pertussis.6,8
Pharmacologic treatment of pertussis consists of antibiotics. Treatment is recommended within 3 weeks of symptom onset.9 The timing of antibiotic administration plays a role in the antibiotic’s effect. Administration during the initial phase—particularly within the first 7 days of symptom onset—may reduce symptom severity and duration, whereas later administration serves merely to reduce the risk of transmission.1,4 The majority of patients receiving antimicrobial therapy for pertussis do not experience substantial relief of clinical symptoms.8 There is no evidence that antimicrobial treatment leads to reduced mortality or prevents serious complications such as pneumonia; the main benefit is the reduced risk of transmission to other people due to more rapid eradication of B pertussis from the nasopharynx.1,4,8,10
Macrolide antibiotics have been established as the mainstay of therapy, and the three agents primarily administered are erythromycin, azithromycin, and clarithromycin (TABLE 1).1,9 Once administered, these antibiotics eradicate B pertussis within 5 days by inhibiting RNA-dependent protein synthesis. Although erythromycin is traditionally the drug of choice for pertussis treatment, it is associated with a higher incidence of adverse effects (primarily gastrointestinal upset) and a more frequent dosing regimen (four times daily for 14 days). Conversely, azithromycin and clarithromycin are better tolerated, have similar efficacy, and possess simpler dosing regimens (once daily for 5 days and twice daily for 7 days, respectively).1,9 Common adverse effects of macrolides include nausea, vomiting, and diarrhea.8,9
The addition of an antibiotic warrants a review of all concomitant drugs in order to avoid drug-drug interactions. Erythromycin and clarithromycin are strong CYP3A4 inhibitors; therefore, they may interact with numerous medications that are metabolized through this enzyme, requiring a change in dosage and/or additional monitoring.8,9 Azithromycin may be preferred in patients taking multiple medications, since it has the least potential for drug-drug interactions.4,9 Macrolides have been shown to possess a rare risk of QT prolongation, and therefore they should be avoided in patients with a prolonged QT interval, a history of torsades de pointes, uncorrected hypokalemia or hypomagnesemia, or the use of Class 1A or III antiarrhythmics.8
Conversely, in patients unable to tolerate macrolides because of allergy or drug-drug interactions, sulfamethoxazole-trimethoprim (SMX-TMP) is a suitable alternative (TABLE 1).1,4,9 SMX-TMP works by inhibiting dihydrofolic acid production, and its common adverse effects include gastrointestinal upset (i.e., nausea, vomiting, or loss of appetite) and rash.8,9 SMX-TMP is metabolized by CYP2C9, and therefore may be impacted by concurrent medications that inhibit or induce the enzyme. SMX-TMP should be avoided in patients with a sulfa allergy.9
The choice of antibiotic should be based upon efficacy, safety, tolerability, patient adherence, and patient preference. Although most patients can eradicate B pertussis from the nasopharynx without treatment within 1 month of symptom onset, the risk of transmission to others warrants the use of antimicrobial treatment when appropriate.1,9 Additionally, contact with young children and infants should be avoided until symptoms subside.
After the risks versus benefits of antimicrobial therapy have been evaluated, postexposure prophylaxis may be administered within 21 days of exposure to an individual infected with B pertussis. Persons who are immunocompromised, have a chronic pulmonary condition, or are in close contact with infants are at high risk for pertussis and should receive prophylactic treatment. Prophylactic therapy is identical to treatment for active pertussis (TABLE 1).4,9
Currently, there is no mainstay symptomatic treatment for B pertussis infection.11 Antihistamines, corticosteroids, antitussives, and bronchodilators have been considered as potential agents to reduce the frequency and severity of coughing bouts, but no statistically significant evidence has been found in their favor for the symptomatic treatment of pertussis.4,8,11 Therefore, these agents are not usually recommended.
Since pertussis is most infectious prior to development of the characteristic cough, immunization remains the most effective method of prevention.3 There are currently two FDA-approved Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccine formulations (TABLE 2).12 Also available are two DTaP (diphtheria and tetanus toxoids with acellular pertussis) vaccines, which are approved for use in children aged 6 weeks to <7 years. The lowercase letters in the acronym Tdap reflect the smaller doses of diphtheria and pertussis components, as compared with DTaP.
Although pertussis tends to be less severe in adults, booster vaccinations are critical for maintaining herd immunity and preventing the spread of infection, particularly to children. A booster is recommended during each of a woman’s pregnancies to confer temporary immunity to the infant. For adults aged ≥65 years, the CDC recommends the use of Boostrix when feasible, but states that both Tdap products are effective. Therefore, providers should administer whichever vaccine is available, rather than delaying vaccination in this age group.6 TABLE 3 summarizes CDC recommendations for adult pertussis vaccination.13 A schedule of recommended childhood vaccinations is available on the CDC’s website.13
Adverse reactions to the Tdap vaccine are generally mild and may include injection-site pain or redness, mild fever, fatigue, and headache. Contraindications to the Tdap vaccine include 1) encephalopathy occurring within 7 days of a previously administered pertussis vaccine and not attributable to another cause and 2) prior anaphylactic reaction to a vaccine or vaccine component.4,8 Symptoms of encephalopathy vary, but may include altered mental status, lethargy, tremors, seizures, altered breathing patterns, and coma.
Pertussis remains an imminent concern as rates of infection continue to increase, particularly in adults and adolescents. Prevention, accurate diagnosis, and treatment of pertussis are all important facets of infection management. Vaccination is a crucial aspect of infection prevention, and herd immunity throughout the community allows for decreased transmission and infection in people of all ages, principally infants.
The pharmacist’s role as a disseminator of information regarding the importance of vaccination and its proper timing is crucial for disease-prevention advocacy. Additionally, pharmacists can serve as accessible sources of vaccine administration within the community. They are often the first healthcare provider approached by patients for symptomatic treatment, so a proper assessment of medical history is essential for timely referral to a physician. Additionally, pharmacists may provide information regarding antibiotic treatment and prophylaxis and help healthcare providers assess patient-specific factors for antimicrobial selection.8
1. Cornia PB, Hersh AL, Lipsky BA, et al. Does this coughing adolescent or adult patient have pertussis? JAMA. 2010;304:890-896.
2. CDC. Pertussis outbreak trends. www.cdc.gov/pertussis/outbreaks/trends.html. Accessed March 27, 2015.
3. National Foundation for Infectious Diseases. Facts about whooping cough for adults. www.adultvaccination.org/vpd/pertussis/facts.html. Accessed March 27, 2015.
4. Spector TB, Maziarz EK. Pertussis. Med Clin North Am. 2013;97:537-552.
5. Warfel JM, Beren J, Merkel TJ. Airborne transmission of Bordetella pertussis. J Infect Dis. 2012;206:902-906.
6. Atkinson W, Wolfe S, Hamborsky J, et al. Pertussis. In: Atkinson W, Hamborsky J, Stanton A, et al, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed. Washington, DC: Public Health Foundation; 2012:215-230.
7. Rivard G, Viera A. Staying ahead of pertussis. J Fam Pract. 2014;63:658-669.
8. Kline JM, Lewis WD, Smith EA, et al. Pertussis: a reemerging infection. Am Fam Physician. 2013;88:507-514.
9. Tiwari T, Murphy TV, Moran J; National Immunization Program, CDC. Recommended antimicrobial agents for the treatment and postexposure prophylaxis of pertussis: 2005 CDC guidelines. MMWR Recomm Rep. 2005;54:1-16.
10. Altunaiji S, Kukuruzovic R, Curtis N, Massie J. Antibiotics for whooping cough (pertussis). Cochrane Database Syst Rev. 2007;(3):CD004404.
11. Wang K, Bettiol S, Thompson MJ, et al. Symptomatic treatment of the cough in whooping cough. Cochrane Database Syst Rev. 2014;(9):CD003257.
12. Diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine, adsorbed (DTaP/Tdap) [monograph]. In: Facts & Comparisons eAnswers [online database]. St. Louis, MO: Wolters Kluwer Health, Inc; 2015.
13. CDC. Pertussis: summary of vaccine recommendations. www.cdc.gov/vaccines/vpd-vac/pertussis/recs-summary.htm. Accessed March 27, 2015.
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