A short-term course of erythromycin, azithromycin, or clarithromycin is as effective as a long-term (2-week) erythromycin therapy in eradicating Bordetella pertussis from the nasopharynx (strength of recommendation [SOR]: A; based on one meta-analysis of randomized controlled trials [RCTs]). Evidence is insufficient to determine the benefit of antibiotic prophylaxis for pertussis contacts. However, due to high mortality and morbidity, prophylaxis is recommended for families who have an infant less than 6 months old (SOR: C; based on expert opinion)

Mayo, Helen G.

Niemi, Heli

Tubbs, Charles G.

University of Missouri: MOspace

1096 VOL 54, NO 12 / DECEMBER 2005  THE JOURNAL OF FAMILY PRACTICEFrom the Family Practice Inquiries NetworkCLINICAL INQUIRIESWhat is the best treatment for pertussis?■ Evidence summaryA 2005 Cochrane review of 11 RCTs and1 quasi-randomized trial, with a total of1720 adults and children, investigated sev-eral antibiotics for treatment and prophy-laxis of pertussis. The outcome measuresused to assess the efficacy of antibiotictreatment or prophylaxis vary between thetrials and most of them did not report the immunization status of the partici-pants. The Cochrane review included 1meta-analysis of 3 studies with 252 partic-ipants, comparing azithromycin for 3 days, erythromycin estolate for 7 days, and A short-term course of erythromycin, azithromycin,or clarithromycin is as effective as a long-term (2-week) erythromycin therapy in eradicatingBordetella pertussis from the nasopharynx(strength of recommendation [SOR]: A; based onone meta-analysis of randomized controlled trials[RCTs]). Evidence is insufficient to determine thebenefit of antibiotic prophylaxis for pertussis contacts. However, due to high mortality and morbidity, prophylaxis is recommended for families who have an infant less than 6 months old (SOR: C; based on expert opinion). E V I D E N C E - B A S E D A N S W E RFewer doses and lower cost make compliance more likelyI found this Clinical Inquiry on the treatment andprophylaxis of Bordetella pertussis invaluable asit addresses ease of dosing and cost, 2 thingsimportant in my pediatric community health practice with its inherent financial and social constraints. The alternatives suggested are easyto use and are as equally effective as the first-linetherapy of erythromycin estolate, the long-termtreatment recommended by the CDC and the AAP. These alternatives, clarithromycin andazithromycin, require either twice a day or a once a day dosing for 7 days or 3 days respectively,can be accommodated in busy households, thuspromoting better compliance. The cost of medication also relates to compli-ance. The cost difference between the first-linetherapy and the alternative therapy is significant,and may be as much as $89. In an underinsuredpopulation, this out-of-pocket cost for the alternatives would prove prohibitive, resulting in decreased compliance. Where cost is not agreat issue and concerns of compliance impor-tant, choosing the short-term treatment may be apreferable option. For the financially strapped, the 1-week regimen of erythromycin estolatewould be preferable. The importance of counsel-ing cannot be overstated in all dosing regimens, especially in those with a more difficult dosingschedule and in cases of prophylaxis in a house-hold with an infant less than 6 months old. Marcia Warren, MDDepartments of Family and Community Medicine andPediatrics, Baylor College of Medicine, Houston, TexC L I N I C A L C O M M E N T A R YC O N T I N U E DCharles Tubbs, MD, Heli Niemi, MDDepartment of Family Practice and Community Medicine, University of Texas Southwestern, DallasHelen G. Mayo, MLSUniversity of Texas Southwestern Medical Center Library, DallasJFP_1205_CI.Final  11/16/05  2:39 PM  Page 1096What is the best treatment for pertussis? ▲VOL 54, NO 12 / DECEMBER 2005 1097w w w. j f p o n l i n e . c o mDue to high mortality, pertussisprophylaxis is recommendedfor families withan infant <6 months oldFAST TRACKclarithromycin for 7 days (short-termtreatment) with erythromycin estolate forfourteen days (long-term treatment). Thestudy showed equal efficacy in eradicationof B pertussis from the nasopharynx of99.2% to 97.7% (absolute risk reduction[ARR]=1.44%; 95% confidence interval[CI], –1.58 to 4.46). There were fewer sideeffects with the short-term treatment(32.1% vs 48.9%; ARR=16%; 95% CI,7.84 to 25.84).1A large, multicenter RCT of 477 chil-dren of 6 months to 16 years of agedemonstrated that a 5-day treatment withazithromycin eradicated B pertussis fromthe nasopharynx as effectively as a 10-daycourse of erythromycin estolate.2 Similarly,trimethoprim/sulfamethoxazole proved aseffective as erythromycin in eliminating Bpertussis from the nasopharynx. Although tetracycline and chloram-phenicol are effective treatments for per-tussis, they are not recommended becauseof their side effects.1 Six randomized trialsfailed to show any statistically significantdifference between antibiotics and placeboon frequency and severity of cough orduration of pertussis disease.1 A random-ized, placebo-controlled trial studied 300household contacts of children with culture-positive pertussis. There was nostatistically significant difference in eitherthe frequency of pertussis disease or rate ofpositive cultures in household contactsbetween the erythromycin group (2.1%)and the placebo group (5.1%)(ARR=2.95%; 95% CI, –1.21 to 7.11).1Another Cochrane review of 8 trialsexamined the effectiveness of the sympto-matic treatment of cough in children andadults with pertussis. There were manyproblems with the methodological qualityof these trials, including small sample sizesand poor reporting of the methods.T A B L EAntibiotics for treatment and prophylaxis of pertussis in children and adultsFIRST-LINE THERAPY DOSAGE FOR CHILDREN DOSAGE FOR ADULTS COST*Erythromycin 40–50 mg/kg orally or 1–2 g orally or 56 tabs (500 mg),intravenously in 4 divided intravenously in 4 divided $16 (generic) doses for 14 days5,7 doses for 14 days5,7ALTERNATIVE THERAPY IF PATIENT DOESN’T TOLERATE ERYTHROMYCINClarithromycin 15–20 mg/per kg orally 500 mg orally every 12 20 tabs (500 mg), $78 divided every 12 hours hours for 7 days5 28 tabs (500 mg),for 10–14 days7 or $109 (generic)14-15 mg/kg orally divided every 12 hours for 7 days1,5Azithromycin 10–12 mg/kg orally as 500 mg orally once, then 5 tabs (500 mg), $75 single daily dose for 5 to 250 daily on days 2–55,7 7 tabs (500 mg),7 days5,7 or $105 (no generic)10 mg/kg orally single daily dose for 3 days1Trimethoprim- 8 mg of TMP, 40 mg/kg 160 mg of TMP, 800 mg 28 tabs $8 (generic) sulfamethoxazole SMX per kg orally divided SMX orally (1 tab DS)every 12 hours for 14 every 12 hours for 14 days5,7 days5,7All these therapies have gastrointestinal side effects and risk for hypersensitivity reactions. *Approximate retail price for adult dose. Available at: http://www.drugstore.com. Accessed on June 28, 2005. JFP_1205_CI.Final  11/16/05  2:39 PM  Page 1097Good news for the underinsured:relatively inexpensiveantibiotics areamong the drugseffective againstpertussis1098 VOL 54, NO 12 / DECEMBER 2005  THE JOURNAL OF FAMILY PRACTICECLINICAL INQUIRIESFAST TRACKDiphenhydramine, pertussis immuno-globulin, corticosteroids and salbutamolwere compared with placebo. There were no statistically significant differencesin coughing paroxysms, mean number of whoops per 24 hours or in duration ofhospital stay between these interventionsand placebo.3Extracorporeal circulatory life supporthas been used to maintain perfusion forpatients with severe disease. The mortalityof these patients is very high.4 No RCTs ofthe effectiveness of this intervention hasbeen performed.Recommendations from othersThe Centers for Disease Control andPrevention recommends erythromycin for14 days as a first choice for the treatmentand prophylaxis of pertussis. Antibioticsshould be started no later than 3 weeksafter the onset of cough. Trimethoprim-sulfamethoxazole can be used as an alter-native treatment for patients who do nottolerate erythromycin. Prophylaxis is rec-ommended for all household and closecontacts if pertussis is highly suspected.5The American Academy of Pediatricsrecommends the use of azithromycin andclarithromycin as an alternative treatmentfor patients who do not tolerate erythro-mycin.5A national consensus conference onpertussis held in Canada recommendedprophylaxis for household contacts of aninfant aged <1 year, pregnant women dur-ing the third trimester, and for vulnerableindividuals who have had face-to-faceexposure, or have shared confined air for>1 hour.6R E F E R E N C E S1. Altunaiji S, Kukuruzovic R, Curtis N, Massie J.Antibiotics for whooping cough (pertussis) (CochraneReview). Cochrane Database Syst Rev 2005;(1):CD004404. 2. Langley JM, Halperin SA, Boucher FD, Smith B,Pediatric Investigators Collaborative Network onInfections in Canada (PICNIC). Azithromycin is as effec-tive as and better tolerated than erythromycin estolatefor the treatment of pertussis. Pediatrics 2004;114:e96–101. 3. Pillay V, Swingler G. Symptomatic treatment of thecough in whooping cough (Cochrane Review).Cochrane Database Syst Rev 2003; (4):CD003257. 4. Williams GD, Numa A, Sokol J, Tobias V, Duffy BJ.ECLS in pertussis: does it have a role? Intensive CareMed 1998; 24:1089-1092. 5. Guris D. Treatment and Chemoprophylaxis. Guidelinesfor the Control of Pertussis Outbreaks. Atlanta, Ga:Centers for Disease Control and Prevention, 2000. Lastupdated January 2005. Available at:www.cdc.gov/nip/publications/pertussis/guide.htm.Accessed on November 14, 2005.6. National consensus conference on pertussis. CanCommun Dis Rep 2003; 29 (Suppl 3): S1–S33 (English),S1–S36 (French). Last updated June 5, 2003. Availableat: www.phac-aspc.gc.ca/publicat/ccdr-rmtc/03vol29/29s3/index.html. Accessed on November 14, 2005.7. Pertussis Information for Physicians: Diagnostic andTreatment Criteria. Texas Department of HealthPertussis Treatment Guidelines. TDH ImmunizationDivision; 2004. Last updated January 26, 2004.Available at: www.tdh.state.tx.us/immunize/html/pert_physician_txt.htm. Accessed on November 14,2005.JFP_1205_CI.Final  11/16/05  2:39 PM  Page 1098

What is the best treatment for pertussis?

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