A Comparison of Two Strategies to Prevent Pertussis in Vaccinated Healthcare Personnel Following Pertussis Exposure

Background:   Until the licensure of an effective acellular pertussis vaccine (Tdap) for use in adults in 2005, antibiotic post-exposure prophylaxis was the only method to reduce acquisition of pertussis by healthcare personnel following a pertussis exposure.  In 2006 the Centers for Disease Control and Prevention recommended healthcare personnel with direct patient contact receive a single booster dose of Tdap to reduce nosocomial spread of pertussis.  Pertussis vaccination may eliminate the need to provide antibiotic post-exposure prophylaxis in recently-vaccinated healthcare personnel. 

Objective:   To determine if close symptom monitoring following a pertussis exposure of Tdap-vaccinated healthcare personnel is non-inferior to routine antibiotic post-exposure prophylaxis.

Methods: Personnel with direct patient contact at a tertiary care 206-bed pediatric hospital were vaccinated with Tdap.  Personnel subsequently exposed to an index patient with pertussis were randomly assigned to receive standard antibiotic prophylaxis or no prophylaxis following the exposure.  Nasopharyngeal and serum specimens were obtained at baseline upon identification of the exposure and 21 days later.  Nasopharyngeal specimens were tested for Bordetella pertussis via polymerase chain reaction (PCR), while serum specimens were tested for anti-pertussis toxin (PT) antibodies.  Subjects in both arms were queried daily for symptoms, and an additional nasopharyngeal specimen was collected in symptomatic subjects for PCR and culture testing.  The primary outcome was laboratory-confirmed pertussis defined as a positive nasopharyngeal specimen (by either culture or PCR), a two-fold rise in anti-PT titers, or a single anti-PT titer of ≥94 EU/mL.  Close symptom monitoring without antibiotic prophylaxis was considered non-inferior to antibiotic post-exposure prophylaxis if the lower limit of the one-sided 95% confidence interval (CI) for the reduction in pertussis infection was greater than -7%.

Results: Between May 21, 2007, and October 8, 2009, 1,091 pediatric healthcare personnel were vaccinated with Tdap.  Eighty personnel were exposed a total of 94 times.  Twenty-four personnel were not eligible for randomization.  Thirty-four personnel were randomly assigned to receive azithromycin prophylaxis, and 36 received no prophylaxis.  Pertussis infection occurred following a healthcare exposure in 6 persons (16.7%) in the group without prophylaxis and 1 person (2.9%) in the antibiotic prophylaxis group (absolute risk difference -13.7%; lower bound of the one-sided 95% CI, -25.0%; p=0.06).

Conclusions:   Close symptom monitoring of healthcare personnel following a pertussis exposure did not meet the criteria for noninferiority.  However, the low rate of symptomatic pertussis in both groups warrants further study of this approach.