Approximately 10,000 persons were recommended for at least 60 days of antimicrobial prophylaxis to prevent inhalational anthrax. The largest number of persons on antimicrobial prophylaxis was associated with the Brentwood facility (n=2,743) and the smallest with the Hart Senate Building (n=600). We completed interviews on 6,178 persons; participation rates varied by site ().
Response rates for persons recommended for at least 60 days of postexposure antimicrobial prophylaxis, 2001–2002
Most of the respondents were 40–64 years of age, and 60% were men. Of 2,444 women, 2% reported being pregnant or having been pregnant while taking antimicrobial prophylaxis. Median age was lowest at the Hart Senate Building site and highest at the Brentwood facility. Approximately 150 persons were <18 years of age at the start of the antimicrobial prophylaxis campaign; the Florida site had the most children (n=88). The number of children was estimated based on data collected at 10 and 30 days. Persons <18 years were not interviewed as part of the program evaluation after 60 days. Forty-one percent of respondents reported their race as white and 42% as African-American, but marked variation existed by site. Members of the Florida and Hart Senate Building cohorts were primarily Caucasian, while persons at Brentwood facility were primarily African-American ().
Demographic data for persons recommended for at least 60 days of postexposure prophylaxis, 2001–2002
Almost all (97%) respondents obtained an initial supply of antimicrobial prophylaxis. Three percent (n=182) of respondents reported difficulty in obtaining their supply of prophylaxis, and of these, most (83%) were able to get 60 days of prophylaxis. Ten percent of respondents took no antimicrobial prophylaxis, although they collected an initial supply. This group and those who never obtained antimicrobial prophylaxis compose the overall group of 787 respondents who reported not taking any of their prophylaxis. Forty-eight respondents did not provide any adherence information. Persons who took at least one dose of antimicrobial prophylaxis numbered 5,343 (86%); fewer than half of these respondents took only one agent as antimicrobial prophylaxis. Fifty-nine percent of respondents taking at least one dose of antimicrobial prophylaxis (n=3,156) took two antimicrobial agents as prophylaxis; 56% (n=2,984) took ciprofloxacin for one part of their course and doxycycline for the rest. Data from 10, 30, and post-60 days show an overall shift in the most recent antimicrobial agent used from ciprofloxacin (84% at day 10) to doxycycline (61% at day 60).
Of the 5,343 persons who reported taking at least one dose of antimicrobial prophylaxis, 57% (n=3,032) reported adverse events during the first 60 days of antimicrobial prophylaxis use. Reporting of adverse events varied by site, ranging from 42% of respondents at the Connecticut facility to 65% at the Brentwood facility. Thirty-two percent of respondents with adverse events reported diarrhea or stomach pain with their most recent antibiotic, 27% nausea or vomiting, 25% headache, and 22% dizziness. The most commonly reported categories of symptoms were gastrointestinal (44%, including nausea or vomiting, diarrhea or stomach pain, heartburn, and pain with swallowing) and neurologic (33%, including headache, dizziness, lightheadedness, fainting, and seizure). Of the 3,032 persons reporting at least one adverse event, 23% identified “diarrhea or stomach pain” and 19% “nausea or vomiting” as their “most serious” symptom. Among persons reporting adverse events, 17% graded them as severe, 45% as moderate, and 41% as none/mild. Twenty-six percent of persons with adverse events reported missing at least 1 day of work because of symptoms.
At 10 days, the rate of one or more adverse events among persons taking ciprofloxacin most recently (45%) did not differ significantly from that of persons taking doxycycline most recently (49%). At day 30, this rate was slightly higher (77%) among persons taking ciprofloxacin most recently than persons taking doxycycline most recently (71%, p<0.01) ().
Adverse events at 10 and 30 days, by most recent antimicrobial agent, all sites,a 2001–2002
Univariate analysis of factors associated with the presence of adverse events showed male respondents were less likely to report adverse events than were female respondents in all sites except Connecticut. Compared with the youngest age group, persons who reported adverse events were less likely to be >65 years of age. Persons with adverse events were significantly more likely to enroll in the IND protocol in the Brentwood facility ().
Univariate analysis of factors associated with adverse events, post 60-day program evaluation data, 2001–2002a
Multivariable analysis also showed that persons reporting adverse events were less likely to be male in all sites except Connecticut. At the Hart Senate Building site, persons with adverse events were less likely to be African-American. At the Brentwood site, persons with adverse events were more likely to have enrolled in the IND protocol.
Medical Attention for Adverse Events and Serious Adverse Events
Of 2,907 persons participating in 10-day follow-up, 7% reported seeking medical attention. Follow-up at 10 days for serious adverse events in the Florida, New Jersey, and New York City facilities found no hospitalizations attributable to antimicrobial prophylaxis in persons seeking medical care for symptoms consistent with anaphylaxis (difficulty breathing, rash or itchy skin, throat tightness, or lip and tongue swelling) (11)
. Of 3,374 persons participating in 30-day follow-up, 13% reported seeking medical attention. Of 2,135 persons with follow-up information available at 30 days in the Florida, New Jersey, New York City, and the Hart Senate Building facilities, seven persons (0.3%) were found to have had a serious adverse event, including three persons hospitalized. Ten- and 30-day follow-up data were not available for Connecticut. Four persons had reactions in which the relationship to antimicrobial prophylaxis was judged to be definite or probable, while the remaining three were classified as not related or could not assess. Two of four serious adverse events with a definite or probable relationship to antimicrobial prophylaxis were characterized by diffuse rash and systemic symptoms; the remaining two involved swelling of the face and neck. Two persons were treated as outpatients, one was treated in the emergency department, and the remaining patient was briefly hospitalized. All four recovered without sequelae.
At the post 60-day evaluation, 16% of respondents who took at least one dose of antimicrobial prophylaxis (n=842) reported seeking medical care for adverse events caused by prophylaxis at some time during their 60-day course. Nine percent (n=493) reported that their physician or other health-care provider advised them to stop taking antibiotics; 54% of these persons (n=267) reported that the presence of adverse events was the only reason for the recommendation to discontinue. Medical follow-up of persons reporting potentially serious adverse events after 60 days is ongoing.
Fewer than half of respondents (44%, n=2,712) reported taking antimicrobial prophylaxis for at least 60 days. Adherence through 60 days was highest at the Brentwood facility (64%) and lowest at the New York City facility (21%) (). Of persons who took at least one dose of antimicrobial prophylaxis, 72% (n=3,873) reported taking their medicine daily as prescribed, and 19% (n=1,027) reported taking prophylaxis “almost every day.” Eighty-six percent of all respondents were aware of the IND.
Percentage of persons completing at least 60 days of antimicrobial prophylaxis, by U.S. site, 2001–2002.
Of 2,631 persons taking at least one dose of antimicrobial prophylaxis but stopping before 60 days, 43% stated that adverse events were the most important reason they discontinued prophylaxis, 25% reported perception of a low risk for anthrax, and 7% identified fear of long-term side effects from antimicrobial prophylaxis. Of the 172 who never obtained their prophylaxis, 54% reported perception of a low personal risk for anthrax as the most important reason for not obtaining the recommended antimicrobial agent.
On univariate analysis, in some sites nonadherent respondents were more likely to be African-American, and in other sites they were more likely to be Hispanic. In New York City, nonadherent persons were more likely to have sought medical care and were more likely to have been advised by a health-care provider to stop taking their antimicrobial prophylaxis. In all sites, respondents who enrolled in the IND were more likely to have been adherent. These associations were statistically significant in all but one site (Connecticut) ().
Univariate analysis of factors associated with nonadherence, post 60-day program evaluation data, 2001–2002a
Six site-specific logistic regression models showed an adverse event to be associated with <60 days’ adherence in two sites only (Florida and New York City). Respondents who enrolled in the IND were more likely to have been adherent in all sites except Connecticut. Hispanic persons were more likely to be nonadherent in New Jersey and New York City; African-American persons were more likely to be nonadherent in New Jersey and the Hart Senate Building site. Persons in the 40- to 64-year age group were less likely to be nonadherent in the Florida, New Jersey, Brentwood, and New York City sites ().
Factors associated with nonadherence, multivariable analysis, post 60-day data, 2001–2002a