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Antimicrobial postexposure prophylaxis for anthrax: adverse events and adherence. (Bioterrorism-Related Anthrax).


We collected data during postexposure antimicrobial antimicrobial /an·ti·mi·cro·bi·al/ (-mi-kro´be-al)
1. killing microorganisms or suppressing their multiplication or growth.

2. an agent with such effects.
 prophylaxis prophylaxis (prō'fĭlăk`sĭs), measures designed to prevent the occurrence of disease or its dissemination. Some examples of prophylaxis are immunization against serious diseases such as smallpox or diphtheria; quarantine to confine  campaigns and from a prophylaxis program evaluation Program evaluation is a formalized approach to studying and assessing projects, policies and program and determining if they 'work'. Program evaluation is used in government and the private sector and it's taught in numerous universities.  60 days after start of antimicrobial prophylaxis involving persons from six U.S. sites where Bacillus anthracis Bacillus anthracis Infectious disease A gram-positive organism which causes often fatal infections when its endospores–resistant to heat, drying, UV light, gamma radiation, and many disinfectants–enter the body and cause septicemia Military medicine  exposures occurred. Adverse events associated with antimicrobial prophylaxis to prevent anthrax anthrax (ăn`thrăks), acute infectious disease of animals that can be secondarily transmitted to humans. It is caused by a bacterium (Bacillus anthracis  were commonly reported, but hospitalizations and serious adverse events as defined by Food and Drug Administration criteria were rare. Overall adherence during 60 days of antimicrobial prophylaxis was poor (44%), ranging from 21% of persons exposed in the Morgan postal facility in New York City New York City: see New York, city.
New York City

City (pop., 2000: 8,008,278), southeastern New York, at the mouth of the Hudson River. The largest city in the U.S.
 to 64% of persons exposed at the Brentwood postal facility in Washington, D.C. Adherence was highest among participants in an investigational new drug protocol to receive additional antibiotics Antibiotics Definition

Antibiotics may be informally defined as the subgroup of anti-infectives that are derived from bacterial sources and are used to treat bacterial infections.
 with or without anthrax vaccine--a likely surrogate surrogate n. 1) a person acting on behalf of another or a substitute, including a woman who gives birth to a baby of a mother who is unable to carry the child. 2) a judge in some states (notably New York) responsible only for probates, estates, and adoptions.  for anthrax risk perception. Adherence of <60 days was not consistently associated with adverse events.

**********

Bioterrorist attacks involving the use of Bacillus anthracis in the fall of 2001 caused 22 cases of cutaneous cutaneous /cu·ta·ne·ous/ (ku-ta´ne-us) pertaining to the skin.

cu·ta·ne·ous
adj.
Of, relating to, or affecting the skin.


Cutaneous
Pertaining to the skin.
 and inhalational anthrax and placed many more persons at risk for this disease because of workplace exposures (1). The massive public health response to these events included an unprecedented prevention program in which approximately 10,000 persons across the eastern United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area.  were offered >60 days of postexposure antimicrobial prophylaxis to prevent inhalational anthrax (2). We describe the exposed population and the provision of postexposure antimicrobial prophylaxis and analysis of data for associated adverse events and adherence to prophylaxis.

The large-scale use of antimicrobial prophylaxis to prevent anthrax within the setting of a bioterrorist attack has never been reported. While ineffective in killing B. anthracis spores, antibiotics are effective against replicating bacteria that develop from the spore following germination germination, in a seed, process by which the plant embryo within the seed resumes growth after a period of dormancy and the seedling emerges. The length of dormancy varies; the seed of some plants (e.g. . After being inhaled in·hale  
v. in·haled, in·hal·ing, in·hales

v.tr.
1. To draw (air or smoke, for example) into the lungs by breathing; inspire.

2.
, B. anthracis spores may not germinate immediately but can remain dormant Latent; inactive; silent. That which is dormant is not used, asserted, or enforced.

A dormant partner is a member of a partnership who has a financial interest yet is silent, in that he or she takes no control over the business.
 in the lung and lymphatic system lymphatic system (lĭmfăt`ĭk), network of vessels carrying lymph, or tissue-cleansing fluid, from the tissues into the veins of the circulatory system.  for weeks to months as they are slowly cleared by the immune system immune system

Cells, cell products, organs, and structures of the body involved in the detection and destruction of foreign invaders, such as bacteria, viruses, and cancer cells. Immunity is based on the system's ability to launch a defense against such invaders.
. As long as spores remain in the body, the risk of germination, replicating B. anthracis, and clinical anthrax exists. Based on initial risk assessments and the estimated efficacy of prophylaxis, antimicrobial postexposure prophylaxis Postexposure prophylaxis (PEP)
Any treatment given after exposure to a disease to try to prevent the disease from occurring. In the case of rabies, PEP involves a series of vaccines given to an individual who has been bitten by an unknown animal or one that is
 was recommended during the 2001 anthrax outbreak (3,4).

Public health and military officials involved in bioterrorism bi·o·ter·ror·ism
n.
The use of biological agents, such as pathogenic organisms or agricultural pests, for terrorist purposes.


Bioterrorism 
 preparedness pre·par·ed·ness  
n.
The state of being prepared, especially military readiness for combat.

Noun 1. preparedness - the state of having been made ready or prepared for use or action (especially military action); "putting them
 initiatives had identified antimicrobial agents Antimicrobial agents

Chemical compounds biosynthetically or synthetically produced which either destroy or usefully suppress the growth or metabolism of a variety of microscopic or submicroscopic forms of life.
 of choice for this purpose before the 2001 outbreak (5). Largely through the efforts of these officials, ciprofloxacin ciprofloxacin /cip·ro·flox·a·cin/ (sip?ro-flok´sah-sin) a synthetic antibacterial effective against many gram-positive and gram-negative bacteria; used as the hydrochloride salt.

cip·ro·flox·a·cin
n.
 and doxycycline doxycycline /doxy·cy·cline/ (dok?se-si´klen) a semisynthetic broad-spectrum tetracycline antibiotic, active against a wide range of gram-positive and gram-negative organisms; used also as d. calcium and d. hyclate.  were approved by the Food and Drug Administration in 2000 and 2001, respectively, for use as antimicrobial prophylaxis to prevent anthrax and were offered as first-line agents to exposed persons (6,7). Because of safety concerns over the use of ciprofloxacin and doxycycline, amoxicillin amoxicillin /amox·i·cil·lin/ (ah-mok?si-sil´in) a semisynthetic derivative of ampicillin effective against a broad spectrum of gram-positive and gram-negative bacteria.

a·mox·i·cil·lin
n.
, to which B. anthracis is known to be susceptible (8), was offered as prophylaxis to infants, children, and breastfeeding mothers, although it is not approved by the Food and Drug Administration for this indication (2).

In 2001, as soon as the risk for inhalational anthrax was identified, announcements were made recommending antimicrobial prophylaxis to exposed groups at risk; persons in these exposed groups were instructed to obtain prophylaxis from a central distribution point, where antibiotics were supplied from the National Pharmaceutical Stockpile stock·pile  
n.
A supply stored for future use, usually carefully accrued and maintained.

tr.v. stock·piled, stock·pil·ing, stock·piles
To accumulate and maintain a supply of for future use.
 (9). In December 2001, as vaccine became available, the Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center.  offered persons who were recommended for 60 days of antimicrobial prophylaxis the opportunity to receive 40 additional days of antibiotics (ciprofloxacin, doxycycline, or amoxicillin), with or without three doses of anthrax vaccine An´thrax vac´cine

1. (Veter.) A fluid vaccine obtained by growing a bacterium (Bacillus anthracis, formerly Bacterium anthracis) in beef broth. It is used to immunize animals, esp. cattle.
, through an investigational new drug (IND) protocol. Exposed persons were encouraged to consult with their physicians regarding their individual risk for anthrax and the benefits of participation in the IND protocol (10).

Methods

Antimicrobial prophylaxis campaigns were centered in six sites where persons were exposed: American Media, Inc. employees and visitors in Palm Beach County, Florida Palm Beach County is a county located in the state of Florida. As of 2007, the county had a population of 1,351,236 according to the University of Florida, Bureau of Economic and Business Research[1]. ; workers and visitors at the United States Postal Service postal service, arrangements made by a government for the transmission of letters, packages, and periodicals, and for related services. Early courier systems for government use were organized in the Persian Empire under Cyrus, in the Roman Empire, and in medieval  Trenton Processing and Distribution Center in Hamilton Township, New Jersey Hamilton Township is the name of two similarly named, but distinct, places in the U.S. state of New Jersey:
  • Hamilton Township, Atlantic County, New Jersey
  • Hamilton Township, Mercer County, New Jersey
; employees and visitors at specific parts of the Hart Senate Office Building The Hart Senate Office Building, the third U.S. Senate office building, was built in the 1970s. First occupied in November 1982, the Hart Building is the largest of the Senate office buildings. It is named for Philip A. Hart, long-time senator from Michigan.  in Washington, D.C., as well as congressional mail workers who handled mail for that site; employees and visitors at the Brentwood postal facility in Washington, D.C.; employees working in selected areas of the Morgan postal facility in New York City; and workers and visitors with exposure to the Wallingford and Seymour postal facilities in Connecticut (2). Also among the cohort recommended for at least 60 days of antimicrobial prophylaxis were employees and visitors of the Department of State Annex an·nex  
tr.v. an·nexed, an·nex·ing, an·nex·es
1. To append or attach, especially to a larger or more significant thing.

2.
 32 mailroom mail·room  
n.
A room in which ingoing and outgoing mail is handled for a company or other organization.
 facility in Sterling, Virginia Sterling, Virginia is an unincorporated Washington, D.C. suburb, northwest of Herndon, east of Ashburn, and west of Reston, close to Dulles International Airport in Loudoun County. , and media workers associated with cutaneous cases in New York City. Ciprofloxacin was initially provided to all persons unless a specific contraindication contraindication /con·tra·in·di·ca·tion/ (-in?di-ka´shun) any condition which renders a particular line of treatment improper or undesirable.

con·tra·in·di·ca·tion
n.
 existed. At the first and second refill refill noun A second allotment of a prescription agent obtained from a pharmacy, which is allowed by the original prescription verb Pharmacology To obtain more of a particular drug, after the initially prescribed amount of the agent has been used or  visits at the New York City, New Jersey, Brentwood, and Connecticut sites (after antimicrobial susceptibility testing susceptibility test Antimicrobial susceptibility test, see there  results were available), persons who had been taking ciprofloxacin were encouraged to change to doxycycline, provided no contraindications to doxycycline existed. Persons at the Hart Senate Building were provided a 60-day supply of ciprofloxacin during the first week that antimicrobial prophylaxis was distributed. In Florida, doxycycline was primarily provided at 30-day refill. At all sites, amoxicillin was provided to pregnant women, breastfeeding mothers, children, and some persons who had adverse events associated with ciprofloxacin and doxycycline.

Data Collection

At each site, we used questionnaires distributed primarily at 10- and 30-day refill clinics to collect demographic, clinical, and adherence information. An adverse event was defined as any self-reported symptom while on antimicrobial prophylaxis. Respondents were asked to identify the antimicrobial agent taken most recently and select symptoms experienced while taking this agent from a list of possible adverse events. Early questionnaires used in the first antimicrobial prophylaxis campaign in Florida focused on the presence of a few specific symptoms and medical attention sought for adverse events. Later, in conjunction with 10-day refill clinics, a standardized standardized

pertaining to data that have been submitted to standardization procedures.


standardized morbidity rate
see morbidity rate.

standardized mortality rate
see mortality rate.
 questionnaire administered at the New Jersey, New York City, and Brentwood facilities collected information on a broader list of adverse events. We did not analyze 10-day New York City data because a large number of persons completed the questionnaires who had discontinued dis·con·tin·ue  
v. dis·con·tin·ued, dis·con·tin·u·ing, dis·con·tin·ues

v.tr.
1. To stop doing or providing (something); end or abandon:
 postexposure prophylaxis as recommended at, 10-day follow-up. Modified versions of this initial questionnaire were used at 30 days at the Florida, New Jersey, Hart Senate Building, Brentwood, and New York City facilities. Questionnaires were self-administered in all sites except New Jersey, where they were administered by a health-care worker.

Potentially serious adverse events were identified based on adverse event data collected at 10- and 30-day follow-up (11,12). Persons who reported seeking medical attention because of adverse events associated with antimicrobial prophylaxis were further investigated. The definition of a serious adverse event, based on the Code of Federal Regulations The New Deal program of legislation enacted during the administration of President franklin roosevelt established a large number of new federal agencies, which generated a shapeless and confusing mass of new regulations.  (21 CFR CFR

See: Cost and Freight
 314.80), was applied to any of the following events associated with antimicrobial prophylaxis: death, life-threatening adverse event, inpatient inpatient /in·pa·tient/ (in´pa-shent) a patient who comes to a hospital or other health care facility for diagnosis or treatment that requires an overnight stay.

in·pa·tient
n.
 hospitalization hospitalization /hos·pi·tal·iza·tion/ (hos?pi-t'l-i-za´shun)
1. the placing of a patient in a hospital for treatment.

2. the term of confinement in a hospital.
 or prolongation PROLONGATION. Time added to the duration of something.
     2. When the time is lengthened during which a party is to perform a contract, the sureties of such a party are in general discharged, unless the sureties consent to such prolongation. See Giving time.
 of an existing hospitalization, persistent or substantial disability/ incapacity The absence of legal ability, competence, or qualifications.

An individual incapacitated by infancy, for example, does not have the legal ability to enter into certain types of agreements, such as marriage or contracts.
, congenital congenital /con·gen·i·tal/ (kon-jen´i-t'l) existing at, and usually before, birth; referring to conditions that are present at birth, regardless of their causation.

con·gen·i·tal
adj.
1.
 anomaly/birth defect, or an important medical event that requires medical or surgical intervention to avert one of these outcomes. A clinician clinician /cli·ni·cian/ (kli-nish´in) an expert clinical physician and teacher.

cli·ni·cian
n.
 interviewed healthcare providers and reviewed medical charts to assess the severity of the adverse events and determine whether they met the case definition. The relationship of the adverse event to the antimicrobial agent used was categorized cat·e·go·rize  
tr.v. cat·e·go·rized, cat·e·go·riz·ing, cat·e·go·riz·es
To put into a category or categories; classify.



cat
 as definite, probable, possible, remote, not related, and cannot assess. At day 30, a standardized data collection form was used.

Program Evaluation after 60 Days

Beginning in late January 2002, after persons at each site had completed at least 60 days of antimicrobial prophylaxis, we evaluated the program for all persons in the exposed cohort. In our analysis, we included only persons who stated that they were recommended for at least 60 days of prophylaxis during the program evaluation interview. Through brief telephone interviews using a standardized questionnaire, we collected information on the ability of exposed persons to obtain antimicrobial prophylaxis and informational materials, associated adverse events, and adherence to prophylaxis. Adherence was defined as self-reported use of antimicrobial prophylaxis for at least 60 days. Respondents indicating the presence of adverse events were asked to identify their most severe or "single most serious" symptom, then identify other associated symptoms from a list of potential adverse events. Adverse events identified after the 60-day follow-up could be associated with overall use of antimicrobial prophylaxis, meaning respondents were attributing adverse events to one or more agents used as antimicrobial prophylaxis. Measures of perceived severity of symptoms, including whether medical attention was sought for adverse events, were included. Persons reporting nonadherence were asked to give the most important reason for not taking the antibiotic antibiotic, any of a variety of substances, usually obtained from microorganisms, that inhibit the growth of or destroy certain other microorganisms. Types of Antibiotics
. We made multiple attempts to reach identified persons; follow-up to determine characteristics of nonrespondents is ongoing. Investigation of potentially serious adverse events reported after the 60-day follow-up is planned in a manner similar to prior serious adverse event evaluations.

Data Analysis

Statistical analyses were conducted by using SAS (1) (SAS Institute Inc., Cary, NC, www.sas.com) A software company that specializes in data warehousing and decision support software based on the SAS System. Founded in 1976, SAS is one of the world's largest privately held software companies. See SAS System.  version 8 (SAS Institute SAS Institute Inc., headquartered in Cary, North Carolina, USA, has been a major producer of software since it was founded in 1976 by Anthony Barr, James Goodnight, John Sall and Jane Helwig. , Inc., Cary, NC) statistical software. We used the [c.sup.2] test to compare proportions across each of the six sites; p<0.05 was considered statistically significant.

We conducted two separate analyses for each of the six sites after 60 days using program evaluation data: one for nonadherence and one for occurrence of adverse events. The dependent (outcome) variable for the first analysis was nonadherence (nonadherence [1-59 days of antimicrobial prophylaxis] versus adherence [[greater than or equal to] 60 days of antimicrobial prophylaxis]). The dependent (outcome) variable for the adverse event analysis was self-reported adverse events (a symptom reported versus no symptom reported). We excluded persons who reported not obtaining their prophylaxis or not taking any of it, as well as those for whom adherence information was not available. We constructed a logistic regression In statistics, logistic regression is a regression model for binomially distributed response/dependent variables. It is useful for modeling the probability of an event occurring as a function of other factors.  model for each dependent variable for each of the six sites. The independent (predictor) variables used in the logistic models logistic models,
n.pl statistical models that describe the relationship between a qualitative dependent variable (that is, one that can take only certain discrete values, such as the presence or absence of a disease) and an independent variable.
 included demographic and clinical variables from the 60-day program evaluation, including gender, age group, race, ethnicity, presence of adverse events, and participation in the IND protocol. Independent variables were retained in each of the site-specific models if their estimated parameters were statistically significant (p<0.05) in any model for the same dependent variable. We assessed colinearity and two-way interactions for all variables in each of the final multivariable models.

Results

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 (Table 1).

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 (Table 2).

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 com·pose  
v. com·posed, com·pos·ing, com·pos·es

v.tr.
1. To make up the constituent parts of; constitute or form:
 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).

Adverse Events

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 nausea, sensation of discomfort, or queasiness, in the stomach. It may be caused by irritation of the stomach by food or drugs, unpleasant odors, overeating, fright, or psychological stress. It is usually relieved by vomiting.  or vomiting vomiting, ejection of food and other matter from the stomach through the mouth, often preceded by nausea. The process is initiated by stimulation of the vomiting center of the brain by nerve impulses from the gastrointestinal tract or other part of the body. , 25% headache, and 22% dizziness dizziness: see vertigo. . The most commonly reported categories of symptoms were gastrointestinal (44%, including nausea or vomiting, diarrhea or stomach pain, heartburn heartburn, burning sensation beneath the breastbone, also called pyrosis. Heartburn does not indicate heart malfunction but results from nervous tension or overindulgence in food or drink. , and pain with swallowing) and neurologic neurologic /neu·ro·log·ic/ (-loj´ik) pertaining to neurology or to the nervous system.
Neurologic
Having to do with the nervous system.
 (33%, including headache, dizziness, lightheadedness, fainting, and seizure Forcible possession; a grasping, snatching, or putting in possession.

In Criminal Law, a seizure is the forcible taking of property by a government law enforcement official from a person who is suspected of violating, or is known to have violated, the law.
). 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, 14% 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) (Table 3).

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 [greater than or equal to] 65 years of age. Persons with adverse events were significantly more likely to enroll in the IND protocol in the Brentwood facility (Table 4).

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 anaphylaxis (ăn'əfəlăk`sĭs), hypersensitive state that may develop after introduction of a foreign protein or other antigen into the body tissues.  (difficulty breathing, rash or itchy itch·y
adj.
Having or causing an itching sensation.
 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 diffuse /dif·fuse/
1. (di-fus´) not definitely limited or localized.

2. (di-fuz´) to pass through or to spread widely through a tissue or substance.


dif·fuse
adj.
 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 sequelae Clinical medicine The consequences of a particular condition or therapeutic intervention .

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 dis·con·tin·ue  
v. dis·con·tin·ued, dis·con·tin·u·ing, dis·con·tin·ues

v.tr.
1. To stop doing or providing (something); end or abandon:
. Medical follow-up of persons reporting potentially serious adverse events after 60 days is ongoing.

Adherence

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%) (Figure). Of persons who took at least one dose of antimicrobial prophylaxis, 72% (n=3,873) reported taking their medicine daily as prescribed pre·scribe  
v. pre·scribed, pre·scrib·ing, pre·scribes

v.tr.
1. To set down as a rule or guide; enjoin. See Synonyms at dictate.

2. To order the use of (a medicine or other treatment).
, and 19% (n=1,027) reported taking prophylaxis "almost every day." Eighty-six percent of all respondents were aware of the IND.

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 Side effects

Effects of a proposed project on other parts of the firm.
 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 healthcare provider to stop taking their antimicrobial prophylaxis. In all sites, respondents who enrolled in the IND were more likely to have been adherent adherent /ad·her·ent/ (-ent) sticking or holding fast, or having such qualities. . These associations were statistically significant in all but one site (Connecticut) (Table 5).

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 (Table 6).

Discussion

The anthrax outbreak of 2001 represents the first bioterrorist attack in the United States using B. anthracis and the first recorded mass postexposure antimicrobial prophylaxis campaign to prevent inhalational anthrax. Monitoring for adverse events and adherence during this campaign offers a unique opportunity to evaluate associated adverse events and adherence to antimicrobial agents in a mass prophylaxis campaign. Our data show that the rate of serious adverse events was low, and adverse event monitoring In computer science, event monitoring is the process of collecting, analyzing, and signalling event occurrences to subscribers such as operating system processes, active database rules as well as human operators.  to date has shown no deaths due to antimicrobial prophylaxis. Mild adverse events or adverse events that did not fulfill criteria as serious were common, and adherence to recommendations for at least 60 days of antimicrobial prophylaxis was poor.

The overall rate of reported adverse events during this campaign was higher than the rate (16.5%) listed on the usage information provided with ciprofloxacin (13). (The information provided for doxycycline does not include a rate for adverse events, so a similar comparison cannot be made with this agent.) However, comparison of these rates with adverse event rates associated with antimicrobial prophylaxis must be made with caution. Adverse events reported in the ciprofloxacin literature are categorized by their likelihood to be drug related, while this relationship was assessed only for the small proportion of potentially serious adverse events resulting from antimicrobial prophylaxis. Adverse event rates are ideally derived from data collected under controlled circumstances, including the presence of a control group, while these data were collected as part of a response to a public health emergency. Published adverse event rates among patients taking ciprofloxacin or doxycycline in clinical settings where a similar definition of adverse event is used provide a closer comparison of adverse event rates to antimicrobial prophylaxis. A recent published review of adverse events among patients taking long-term (>30 days) ciprofloxacin in clinical trials found an overall rate of 32% and a rate of gastrointestinal adverse events of 22% (14). In several small studies, the rate of adverse events among patients on doxycycline has been sh6wn to be >30% and as high as 50%, with rates of nausea and vomiting Nausea and Vomiting Definition

Nausea is the sensation of being about to vomit. Vomiting, or emesis, is the expelling of undigested food through the mouth.
 of 31%, depending on the reporting method used (15-20).

Adverse events to antimicrobial prophylaxis in this event may be attributed to the known pharmacology pharmacology, study of the changes produced in living animals by chemical substances, especially the actions of drugs, substances used to treat disease. Systematic investigation of the effects of drugs based on animal experimentation and the use of isolated and  of the drugs taken. However, some portion of the adverse events may also be ascribed to above-average symptom awareness related to fear of contracting anthrax. Data from focus groups of exposed workers support this hypothesis and suggest that self-reports of stress were frequent (21). Anxiety may have led to symptoms or physiologic changes that cannot be explained on the basis of the known pharmacology of the antimicrobial agents given but are temporally related to antimicrobial prophylaxis (22). Regardless of their relation to antimicrobial prophylaxis or fulfillment of criteria for serious adverse events, high rates of reported adverse events during this event suggest the need for a management strategy in addition to monitoring efforts for future antimicrobial prophylaxis campaigns.

While overall adverse events rates were high, differences in rates of adverse events associated with ciprofloxacin compared with those associated with doxycycline were not substantial. Many exposed persons were encouraged to change from ciprofloxacin to doxycycline midway through their course for reasons not related to adverse events (23). Because more than half of persons switched from ciprofloxacin to doxycycline or vice versa VICE VERSA. On the contrary; on opposite sides. , attribution at·tri·bu·tion  
n.
1. The act of attributing, especially the act of establishing a particular person as the creator of a work of art.

2.
 of adverse events to a specific antimicrobial agent is possible only with data collected at the first and second refill visits; adverse event data collected at the program evaluation after 60 days reflect overall adverse events to antimicrobial prophylaxis. Nonetheless, available agent-specific adverse event data do not show differences between ciprofloxacin and doxycycline of the magnitude to warrant preference for one agent over the other in a future antimicrobial prophylaxis campaign.

Overall adherence to recommendations to take at least 60 days of antimicrobial prophylaxis was poor. While adherence to any medical treatment or prophylaxis regimen regimen /reg·i·men/ (rej´i-men) a strictly regulated scheme of diet, exercise, or other activity designed to achieve certain ends.

reg·i·men
n.
1.
 is essential for treatment to be successful, adherence to antimicrobial prophylaxis is thought to be particularly important because of the risk among persons exposed to B. anthracis aerosols for developing anthrax while spores are slowly cleared from lung and thoracic thoracic /tho·rac·ic/ (thah-ras´ik) pectoral; pertaining to the thorax (chest).

tho·rac·ic
adj.
Of, relating to, or situated in or near the thorax.
 lymphatic systems (4). For this analysis we chose premature discontinuation dis·con·tin·u·a·tion  
n.
A cessation; a discontinuance.

Noun 1. discontinuation - the act of discontinuing or breaking off; an interruption (temporary or permanent)
discontinuance
 of antimicrobial prophylaxis as a surrogate for nonadherence, although errors in amount, timing, or frequency can also constitute nonadherence to a medication regimen (24). We found the factor most consistently associated with adherence to be IND participation, which we interpret as a surrogate for perception of individual risk. Because exposed persons were asked to consider their risk for anthrax and the guidance of their health-care provider when making their decision, IND participation is a marker for an person's perception of risk for inhalational anthrax. Some of the respondents who perceived their risk for anthrax to be high may have been reluctant to enroll in the IND at the end of the initial 60-day regimen because of adverse events in response to antimicrobial prophylaxis, but our univariate analysis did not demonstrate that persons with adverse events were less likely to enroll in the IND protocol. The strong association between risk perception and adherence to antimicrobial prophylaxis is consistent with previous studies of a variety of health conditions, which have demonstrated that effective risk communication based on a close patient-provider relationship is a crucial determinant determinant, a polynomial expression that is inherent in the entries of a square matrix. The size n of the square matrix, as determined from the number of entries in any row or column, is called the order of the determinant.  of adherence (24-26).

The presence of adverse events was not consistently associated with nonadherence on univariate and multivariable analysis. When asked directly, a higher proportion of nonadherent respondents indicated that the most important reason for their premature discontinuation was adverse events, rather than a low personal risk for anthrax (43% vs. 25%, p<0.01). Of the 1,120 respondents who reported discontinuing antimicrobial prophylaxis because of adverse events, at another point in the interview 16% said that they did not have any adverse events. Despite the fact that many persons recall discontinuing antimicrobial prophylaxis because of adverse events, our analysis showed that risk perception is a stronger and more consistent predictor of adherence across the six exposed cohorts.

Data on adverse events and adherence must be interpreted in light of the unusual circumstances of the bioterrorist attacks of 2001. The difference in clinical and demographic variables between the six sites prevented us from identifying factors related to nonadherence or adverse events for the exposed cohort as a whole. In any future bioterrorist-related B. anthracis exposure, site-specific circumstances of the attack and the nature of the exposed population must be taken into account during antimicrobial prophylaxis campaigns. Future adherence promotion activities should consider existing theoretical models developed to predict health behaviors, which often stress the importance of understanding persons' interest and concern about their health, their perception of the level of risk to their health, and education regarding the consequences of the health problem (27). Adverse event management efforts should help exposed persons manage adverse events regardless of whether they are serious or related to antimicrobial prophylaxis or the terrorism itself. The threat of bioterrorism remains, and we must incorporate lessons learned from the bioterrorist attacks of 2001 to prepare for any future attacks. The data presented here offer public health decision-makers reassurance REASSURANCE. When an insurer is desirous of lessening his liability, he may procure some other insurer to insure him from loss, for the insurance he has made this is called reassurance.  regarding the low proportion of serious adverse events to antimicrobial prophylaxis and guidance regarding the expected level of adherence during prophylaxis campaigns. Adherence promotion and adverse events management will be essential components to providing this potentially life-saving intervention.
Table 1. Response rates for persons recommended for at least 60
days of postexposure antimicrobial prophylaxis, 2001-2002

                          No. of
                         persons       Response rates for prophylaxis
                        prescribed
Anthrax                  prophyl-    10 days   30 days   60 days (b,c)
investigation site       axis (a)      (%)       (%)          (%)

Florida                   1,082        81        40           78
New Jersey                1,402        25        64           76
Hart Senate Building,      600       n/a (d)     59           82
Washington, D.C.
Brentwood facility,       2,743        60        45           62
Washington, D.C.
New York City             2,259        n/a       23           58
Connecticut               1,217        n/a       n/a          69

(a) When determining the number of persons prescribed prophylaxis, we
excluded program evaluation respondents who indicated that they were
not recommended for [greater than or equal to] 60 days of antimicrobial
prophylaxis. This number may vary from estimates using other data.

(b) Lists of persons in groups recommended for
[greater than or equal to] 60 days of antimicrobial prophylaxis
were sometimes available only later in the campaign, so denominators
may vary slightly for each collection period.

(c) No 60-day follow-up available on persons <18 years of age at time
of 60-day evaluation.

(d) n/a, not available.

Table 2. Demographic data for persons recommended for at least 60 days
of postexposure prophylaxis, 2001-2002

                                                  Hart Senate Building,
                   Florida (%)   New Jersey (%)   Washington, D.C. (%)
Characteristic       (n=780)       (n=1,061)             (n=485)

Male                   62              66                  59
Pregnant                2               1                   3
Caucasian              84              63                  76
African-American        4              23                  16
Median age (yrs)       40              46                  34
Age range (yrs)      (17-86)        (18-77)              (17-75)

                    Brentwood
                   facility,
                   Washington,
                    D.C. (%)     New York City (%)   Connecticut (%)
Characteristic      (n=1,694)        (n=1,315)           (n=843)

Male                   58               55                 67
Pregnant                2                2                  3
Caucasian               5               17                 63
African-American       87               45                 21
Median age (yrs)       51               46                 44
Age range (yrs)      (19-79)          (18-78)            (17-85)

Table 3. Adverse events at 10 and 30 days, by most recent antimicrobial
agent, all sites, (a) 2001-2002

                                        Day 10

                        Ciprofloxacin (%)    Doxycycline (%)
Adverse events              (n=2,446)            (n=165)        p value

[greater than or               45                  49            0.27
equal to] 1 adverse
event
Gastrointestinal               26                  26            0.89
symptoms (nausea,
vomiting, diarrhea,
abdominal pain, or
heartburn)
Fainting, dizziness,           18                  11            0.08
light-headedness, or
seizures (b)
Rash, hives, or                 7                   7            0.8
itchy skin
Joint problems (b)              8                   7            0.6

                                        Day 30

                        Ciprofloxacin (%)    Doxycycline (%)
Adverse events               (n=737)            (n=2,050)       p value

[greater than or               77                  71            <0.01
equal to]1 adverse
event
Gastrointestinal               42                  49            <0.01
symptoms (nausea,
vomiting, diarrhea,
abdominal pain, or
heartburn)
Fainting, dizziness,           23                  18             0.01
light-headedness, or
seizures (b)
Rash, hives, or                14                  14             0.6
itchy skin
Joint problems (b)             25                  16            <0.01

(a) Day 10 data includes the Florida, New Jersey, and Washington, D.C.,
Brentwood sites; Day 30 data includes the Florida, New Jersey,
Washington, D.C., Hart Senate Building, and New York City sites.

(b) Day 10 reports of these symptoms not collected at the Florida site.

Table 4. Univariate analysis of factors associated with adverse events,
post 60-day program evaluation data, 2001-2002 (a)

                                    Reports of adverse events among
                                    persons taking at least one dose
                                            of prophylaxis

                                      Florida           New Jersey
                                      (n=744)           (n=1,028)

Variable                            (%)    p value    (%)    p value

Gender
Male                                50      <0.01     54      <0.01
Female                              63       Ref      68       Ref

Age group
17-39 yr                            55       Ref      58       Ref
40-64 yr                            55       0.99     59       0.75
[greater than or equal to] 65 yr    41       0.19     39       0.03

Race
African-American                    54       0.88     61       0.35
All others                          55       Ref      58       Ref

Ethnicity
Hispanic                            55       1.00     60       0.87
Non-Hispanic                        55       Ref      59       Ref

IND enrollment
Yes                                 48       0.29     61       0.34
No                                  56       Ref      57       Ref

Received printed materials about adverse events
No                                  70       0.03     61       0.73
Yes                                 54       Ref      58       Ref

                                    Reports of adverse events among
                                    persons taking at least one dose
                                            of prophylaxis

                                      Hart Senate        Brentwood
                                       Building,         facility,
                                      Washington,        Washington,
                                     D.C. (n = 472)    D.C. (n=1,619)

Variable                            (%)    p value    (%)    p value

Gender
Male                                54       0.01     60      <0.01
Female                              65       Ref      74       Ref

Age group
17-39 yr                            61       Ref      69       Ref
40-64 yr                            53       0.10     66       0.38
[greater than or equal to] 65 yr    40       0.34     52       0.04

Race
African-American                    46       0.02     67       0.36
All others                          61       Ref      63       Ref

Ethnicity
Hispanic                            44       0.38     57       0.38
Non-Hispanic                        59       Ref      66       Ref

IND enrollment
Yes                                 68       0.11     71      <0.01
No                                  57       Ref      63       Ref

Received printed materials about adverse events
No                                  73      <0.01     78       0.02
Yes                                 54       Ref      66       Ref

                                    Reports of adverse events among
                                    persons taking at least one dose
                                            of prophylaxis

                                     New York City      Connecticut
                                       (n=882)           (n=598)

Variable                            (%)    p value    (%)    p value

Gender
Male                                44      <0.01     41      0.53
Female                              61       Ref      44       Ref

Age group
17-39 yr                            56       Ref      40       Ref
40-64 yr                            51       0.20     44      0.37
[greater than or equal to] 65 yr    37       0.04     19      0.10

Race
African-American                    52       0.74     36      0.14
All others                          51       Ref      44       Ref

Ethnicity
Hispanic                            56       0.12     39      0.65
Non-Hispanic                        50       Ref      42       Ref

IND enrollment
Yes                                 56       0.40     50      0.13
No                                  51       Ref      41       Ref

Received printed materials about adverse events
No                                  29       0.01     53      0.36
Yes                                 53       Ref      42       Ref

(a) IND, investigational new drug; Ref, referent.

Table 5. Univariate analysis of factors associated with nonadherence,
post 60-day program evaluation data, 2001-2002 (a)

                                                    Reports of nonad-
                                                    herence (b) among
                                                   persons who took at
                                                    least one dose of
                                                      postexposure
                                                       prophylaxis

                                                     Florida (n=744)

Variable                                             (%)    p value

Gender
Male                                                 67       0.57
Female                                               69       Ref

Age group
17-39 yr                                             75       Ref
40-64 yr                                             61      <0.01
[greater than or equal to] 65 yr                     64       0.23

Race
African-American                                     82       0.10
All others                                           67       Ref

Ethnicity
Hispanic                                             65       0.52
Non-Hispanic                                         68       Ref

Adverse events
Yes                                                  75      <0.01
No                                                   59       Ref

Severity of adverse events
None                                                 64       Ref
Mild                                                 66       0.58
Moderate/severe                                      72       0.05

IND enrollment
Yes                                                  46      <0.01
No                                                   70       Ref

Missed [greater than or equal to] 1 day of work
Yes                                                  72       0.47
No                                                   68       Ref

Sought medical attention
Yes                                                  72       0.36
No                                                   67       Ref

                                                    Reports of nonad-
                                                    herence (b) among
                                                   persons who took at
                                                    least one dose of
                                                      postexposure
                                                       prophylaxis

                                                        New Jersey
                                                        (n=1,028)

Variable                                             (%)    p value

Gender
Male                                                 32      <0.01
Female                                               47       Ref

Age group
17-39 yr                                             53       Ref
40-64 yr                                             32      <0.01
[greater than or equal to] 65 yr                     26      <0.01

Race
African-American                                     44       0.02
All others                                           35       Ref

Ethnicity
Hispanic                                             60      <0.01
Non-Hispanic                                         37       Ref

Adverse events
Yes                                                  38       0.40
No                                                   36       Ref

Severity of adverse events
None                                                 37       Ref
Mild                                                 29       0.07
Moderate/severe                                      44       0.09

IND enrollment
Yes                                                  19      <0.01
No                                                   46       Ref

Missed [greater than or equal to] 1 day of work
Yes                                                  40       0.28
No                                                   36       Ref

Sought medical attention
Yes                                                  40       0.42
No                                                   37       Ref

                                                    Reports of nonad-
                                                    herence (b) among
                                                   persons who took at
                                                    least one dose of
                                                       postexposure
                                                        prophylaxis

                                                        Hart Senate
                                                         Building,
                                                     Washington, D.C.
                                                         (n=472)

Variable                                             (%)    p value

Gender
Male                                                 39       0.71
Female                                               41       Ref

Age group
17-39 yr                                             42       Ref
40-64 yr                                             37       0.33
[greater than or equal to] 65 yr                      0       0.08

Race
African-American                                     53       0.02
All others                                           38       Ref

Ethnicity
Hispanic                                             60       0.19
Non-Hispanic                                         40       Ref

Adverse events
Yes                                                  39       0.72
No                                                   41       Ref

Severity of adverse events
None                                                 45       Ref
Mild                                                 34       0.07
Moderate/severe                                      43       0.66

IND enrollment
Yes                                                   7      <0.01
No                                                   46       Ref

Missed [greater than or equal to] 1 day of work
Yes                                                  33       0.39
No                                                   41       Ref

Sought medical attention
Yes                                                  34       0.18
No                                                   42       Ref

                                                    Reports of nonad-
                                                    herence (b) among
                                                   persons who took at
                                                    least one dose of
                                                      postexposure
                                                       prophylaxis

                                                   Brentwood facility,
                                                    Washington, D.C.
                                                        (n=1,619)

Variable                                             (%)    p value

Gender
Male                                                 32       0.27
Female                                               34       Ref

Age group
17-39 yr                                             52       Ref
40-64 yr                                             29      <0.01
[greater than or equal to] 65 yr                     29      <0.01

Race
African-American                                     33       0.83
All others                                           32       Ref

Ethnicity
Hispanic                                             29       0.67
Non-Hispanic                                         33       Ref

Adverse events
Yes                                                  32       0.49
No                                                   34       Ref

Severity of adverse events
None                                                 33       Ref
Mild                                                 27       0.06
Moderate/severe                                      36       0.38

IND enrollment
Yes                                                  16      <0.01
No                                                   43       Ref

Missed [greater than or equal to] 1 day of work
Yes                                                  32       0.44
No                                                   34       Ref

Sought medical attention
Yes                                                  32       0.58
No                                                   33       Ref

                                                    Reports of nonad-
                                                    herence (b) among
                                                   persons who took at
                                                    least one dose of
                                                      postexposure
                                                       prophylaxis

                                                      New York City
                                                         (n=882)

Variable                                             (%)    p value

Gender
Male                                                 62      <0.01
Female                                               77       Ref

Age group
17-39 yr                                             80       Ref
40-64 yr                                             67      <0.01
[greater than or equal to] 65 yr                     33      <0.01

Race
African-American                                     72       0.15
All others                                           67       Ref

Ethnicity
Hispanic                                             76       0.03
Non-Hispanic                                         67       Ref

Adverse events
Yes                                                  75      <0.01
No                                                   63       Ref

Severity of adverse events
None                                                 63       Ref
Mild                                                 65       0.58
Moderate/severe                                      79      <0.01

IND enrollment
Yes                                                  49      <0.01
No                                                   72       Ref

Missed [greater than or equal to] 1 day of work
Yes                                                  77       0.03
No                                                   67       Ref

Sought medical attention
Yes                                                  86      <0.01
No                                                   67       Ref

                                                    Reports of nonad-
                                                    herence (b) among
                                                   persons who took at
                                                    least one dose of
                                                      postexposure
                                                       prophylaxis

                                                       Connecticut
                                                         (n=598)

Variable                                             (%)    p value

Gender
Male                                                 68       0.68
Female                                               70       Ref

Age group
17-39 yr                                             71       Ref
40-64 yr                                             68       0.62
[greater than or equal to] 65 yr                     31      <0.01

Race
African-American                                     72       0.37
All others                                           68       Ref

Ethnicity
Hispanic                                             75       0.30
Non-Hispanic                                         67       Ref

Adverse events
Yes                                                  72       0.13
No                                                   66       Ref

Severity of adverse events
None                                                 65       Ref
Mild                                                 63       0.73
Moderate/severe                                      76       0.01

IND enrollment
Yes                                                  60       0.08
No                                                   70       Ref

Missed [greater than or equal to] 1 day of work
Yes                                                  74       0.23
No                                                   67       Ref

Sought medical attention
Yes                                                  65       0.62
No                                                   69       Ref

(a) IND, investigational new drug.

(b) 1-59 days of postexposure prophylaxis.

Table 6. Factors associated with nonadherence, multivariable analysis,
post 60-day data, 2001-2002 (a)

                                  Participants reporting non-adherence
                                       (1-59 days of antimicrobial
                                  prophylaxis) among persons taking at
                                             least one dose

                                                         New Jersey
                                  Florida (n=744)       (n=1,028) OR
Variable                            OR (95% CI)           (95% CI)

Gender
Male                             1.00 (0.71, 1.41)    0.56 (0.42, 0.76)
Female                               Referent             Referent

Age
17-39 yr                             Referent             Referent
40-64 yr                         0.51 (0.36, 0.72)    0.54 (0.40, 0.73)
[greater than or equal to] 65
  yr                             0.73 (0.28, 1.89)    0.51 (0.23, 1.12)

Race
African-American                 1.80 (0.66, 4.92)    1.47 (1.06, 2.05)
All others                           Referent             Referent

Ethnicity
Hispanic                         0.78 (0.47, 1.29)    2.42 (1.21, 4.86)
Non-Hispanic                         Referent             Referent

Adverse events
Yes                              2.23 (1.61, 3.09)    1.08 (0.82, 1.44)
No                                   Referent             Referent

IND enrollment
Yes                              0.36 (0.21, 0.64)    0.27 (0.19, 0.38)
No                                   Referent             Referent

                                  Participants reporting non-adherence
                                       (1-59 days of antimicrobial
                                  prophylaxis) among persons taking at
                                               least one dose

                                    Hart Senate        Brentwood faci-
                                 Building (n=472)      lity (n=1,619)
Variable                            OR (95% CI)          OR (95% CI)

Gender
Male                             0.92 (0.61, 1.38)    0.90 (0.71, 1.13)
Female                               Referent             Referent

Age
17-39 yr                             Referent             Referent
40-64 yr                         0.82 (0.53, 1.28)    0.42 (0.32, 0.56)
[greater than or equal to] 65
  yr                                    n/a           0.49 (0.24, 1.02)

Race
African-American                 1.87 (1.08, 3.25)    0.90 (0.63, 1.28)
All others                           Referent             Referent

Ethnicity
Hispanic                         1.58 (0.42, 6.01)    0.62 (0.23, 1.69)
Non-Hispanic                         Referent             Referent

Adverse events
Yes                              1.07 (0.71, 1.62)    0.98 (0.77, 1.24)
No                                   Referent             Referent

IND enrollment
Yes                              0.09 (0.04, 0.24)    0.28 (0.22, 0.36)
No                                   Referent             Referent

                                  Participants reporting non-adherence
                                      (1-59 days of antimicrobial
                                  prophylaxis) among persons taking at
                                             least one dose

                                   New York City         Connecticut
                                    (n=882) OR           (n=598) OR
Variable                             (95% CI)             (95% CI)

Gender
Male                             0.57 (0.41, 0.79)    0.99 (0.67, 1.46)
Female                               Referent             Referent

Age
17-39 yr                             Referent             Referent
40-64 yr                         0.61 (0.41, 0.90)    0.96 (0.64, 1.44)
[greater than or equal to] 65
  yr                             0.17 (0.08, 0.39)    0.21 (0.07, 0.65)

Race
African-American                 1.08 (0.76, 1.52)    1.39 (0.86, 2.24)
All others                           Referent             Referent

Ethnicity
Hispanic                         1.57 (1.03, 2.39)    1.42 (0.68, 2.93)
Non-Hispanic                         Referent             Referent

Adverse events
Yes                              1.58 (1.16, 2.16)    1.32 (0.92, 1.90)
No                                   Referent             Referent

IND enrollment
Yes                              0.33 (0.21, 0.52)    0.64 (0.39, 1.05)
No                                   Referent             Referent

(a) OR, odds ratio; CI, confidence interval; IND, investigational new
drug.

Figure. Percentage of persons completing at least 60 days of
antimicrobial prophylaxis, by U.S. site, 2001-2002.

                        Percent
                          (%)

Florida                   31
New Jersey                61
Hart Senate Building      58
Brentwood facility        64
New York City             21
Connecticut               22


Acknowledgments

We thank the persons (1) and organizations involved in the distribution of antimicrobial prophylaxis and evaluation of adverse events, especially the United States Postal Service, Food and Drug Administration, Palm Beach County Health Department, Florida Department of Health Florida Department of Health is a category of Government of Florida. Orange County Health Department is one of the branches of Florida Department of Health and Government of Florida. , New Jersey Department of Health and Senior Services, New York City Department of Health, Maryland Department of Health and Hygiene, District of Columbia District of Columbia, federal district (2000 pop. 572,059, a 5.7% decrease in population since the 1990 census), 69 sq mi (179 sq km), on the east bank of the Potomac River, coextensive with the city of Washington, D.C. (the capital of the United States).  Department of Health, Virginia Department of Health, and the Office of the Attending Physician, U.S. Capitol.

Dr. Shepard is an Epidemic Intelligence Service The Epidemic Intelligence Service is a program of the United States' Centers for Disease Control and Prevention. Established in 1951 due to biological warfare concerns arising from the Korean War, it has become a hands-on two-year postgraduate training program in epidemiology, with  officer, assigned to the National Center for Infectious Diseases infectious diseases: see communicable diseases. , Division of Bacterial and Mycotic mycotic /my·cot·ic/ (mi-kot´ik)
1. pertaining to mycosis.

2. caused by a fungus.


my·cot·ic
adj.
1. Relating to mycosis.

2.
 Diseases, Meningitis meningitis (mĕnĭnjī`tĭs) or cerebrospinal meningitis (sĕr'əbrōspī`nəl), acute inflammation of the meninges, the membranes that cover and protect the brain and spinal cord.  and Special Pathogens Branch, Centers for Disease Control and Prevention.

(1) Paul Abomonte, Denise Allen, Veronica Alvarez, Alina Alonso, Mary Kate Appicelli, Mike Beach, Beth Bell, Susan Blank, Amy Bloom, Jennifer Brooks Jennifer Brooks is an American publisher, actress, producer and distributor of fetish videos.

Brooks produces and appears in pornographic content focusing on the fetish of erotic spanking.
, Jane Buckner, Jim Buehler, Heather Burke, Louise Causer, Eleanor Cawthorne, Marty Cetron, Shadi Chamany, Charles Chamberlain, Isa Chines, Bruce Clemons, Gary Cobb, Pat Cook, Margaret Cooke, Sara Critchley, Donita Croft CROFT, obsolete. A little close adjoining to a dwelling-house, and enclosed for pasture or arable, or any particular use. Jacob's Law Dict. , Colleen col·leen  
n.
An Irish girl.



[Irish Gaelic cailín, diminutive of caile, girl, from Old Irish.
 Crowley, Valerie J.Curry, Nick Deluca, Catherine Dentinger, Bob DiGregorio, William Duck, Peter Dull, Jeff Efird, Evelyn Finch finch, common name for members of the Fringillidae, the largest family of birds (including over half the known species), found in most parts of the world except Australia. , Bridgette Finkelstein, Robert Fireall, Mike Fraser, Cindy Friedman, Kathi Gallagher, Julie Gerberding Julie Louise Gerberding, M.D., M.P.H. (born August 22, 1955, Estelline, South Dakota), an infectious disease expert, is the current director of the Centers for Disease Control and Prevention (CDC) and administrator of the Agency for Toxic Substances and Disease Registry (ATSDR), , Dawn Gnesda, Missy Goveia, Carolyn Greene, Kevin Griffith, Rana Hajjeh, Jennifer Hamborsky, Darryl Hardge, Daniel John Hewett, Kelly Holton, Mariaelena Jefferds, Greg Jones Greg Jones may refer to:
  • Greg Jones (Entrepreneur) (born 1969)
  • Greg Jones (baseball player) (born 1976)
  • Greg Jones (football player) (born 1981)
  • Greg Jones (tennis) (born 1989)
  • Greg Jones (wrestler) (born 1982)
  • Greg Jones (FBI agent) (born 1982)
, Jim Jones For other persons named Jim Jones, see Jim Jones (disambiguation).

James Warren "Jim" Jones (May 13, 1931 – November 18, 1978) was the American founder of the Peoples Temple, which became synonymous with group suicide after the November 18, 1978 mass murder-suicide by
, Sean Kaufmann, Michael Keith Michael Keith is a Canadian jazz guitarist, and a resident of Toronto, Ontario. Keith is a practitioner of freely improvised music. His most recent work is a CD with John Oswald and Roger Turner called "Number Nine". It is available on the British label Emanem Records. , Jonathan King, Linda Koenig, Lara Lamprecht, Kayla Laserson, Marci Layton, Suzanne Lebovit, Chang Lee, Norman Lee, Steven W. Lenhart, Mark Long, Jean Malecki, Greg Martin, Thomas Matte, Veronica McCant, Peter McElroy, Shawn McMahon, Theodies Mitchell, Juliette Morgan, Robin Moseley, Tim Morris Timothy Bryce Morris (born 10 January 1955, Alexandra, Victoria) is an Australian politician. He has been a Tasmanian Greens member of the Tasmanian House of Assembly since the 2002 election, representing the Lyons electorate. , Dianne Murphy, Joyce Neale, Stephanie Noviello, John Painter John Painter (Tennessee, September 20, 1888 - March 1, 2001) was posthumously recognized as the world's oldest man and oldest American veteran, as a result of the U.S.'s SSA supercentenarian study. , Margaret Patterson, Lisa Pealer, Cindy Pecoraro, Bradley Perkins, Bobble bob·ble  
v. bob·bled, bob·bling, bob·bles

v.intr.
To bob up and down.

v.tr.
To lose one's grip on (a ball, for example) momentarily.

n.
A mistake or blunder.
 Person, Joe Perz, Lyle Petersen, Bob Pinner, Gabriel Ponce De Leon Ponce de Le·ón   , Juan 1460-1521.

Spanish explorer who sailed with Columbus on his second voyage (1493-1494) and discovered Florida (1513) while looking for the legendary Fountain of Youth.

Noun 1.
, Pratima Raghunathan, Jennita Reefhuis, Julia Rhodes, Taraz Samandari, Anne Schuchat, James Sejvar, Curt Senft, Douglas Shaffer, Tanya Sharpe, Arlene Shaw, Wrenn Slocum, Julia Smith Julia Smith (26 May 1927 – 19 June 1997) was an English television director and producer. Early career
London-born Smith became involved in television production when she directed the series Suspense in 1962.
, John Stamper, Stefanie Steele, Jennifer Stevenson, David Swerdlow, Tins Tan, Kathryn Testes testes
 or testicles

Male reproductive organs (see reproductive system). Humans have two oval-shaped testes 1.5–2 in. (4–5 cm) long that produce sperm and androgens (mainly testosterone), contained in a sac (scrotum) behind the penis.
, Alison Tepper, Peg Tipple, Beth Tohill, Marc Traeger, Scott Tulloch, Reuben Varghese, Wands Walton, Dana White Dana White (born July 28, 1969 in Manchester, Connecticut) is the current President of the Ultimate Fighting Championship (UFC), a mixed martial arts organization based in the United States. , Sara Whitehead whitehead /white·head/ (hwit´hed)
1. milium.

2. closed comedo.


white·head
n.
1.
, Steve Wiersma, Holly Williams Holly Williams (born March 12, 1981) is an American singer/songwriter. Biography
Raised in Nashville, Tennessee, considered the home of country music, she is the granddaughter of Hank Williams, the daughter of Hank Williams, Jr., and the half-sister of Hank Williams III.
, Jennifer Williams, Leigh Winston, Heather Wurtzel, and Weigong Zhou.

References

(1.) Centers for Disease Control and Prevention. Update: investigation of bioterrorism-related anthrax--Connecticut, 2001. MMWR MMWR Morbidity & Mortality Weekly Report Epidemiology A news bulletin published by the CDC, which provides epidemiologic data–eg, statistics on the incidence of AIDS, rabies, rubella, STDs and other communicable diseases, causes of mortality–eg,  Morb Mortal Wkly Rep 2001;50:1077-9.

(2.) Centers for Disease Control and Prevention. Update: investigation of bioterrorism-related anthrax, 2001. MMWR Morb Mortal Wkly Rep 2001;50:1008-10.

(3.) Friedlander AM, Welkos SL, Pitt ML, Ezzell JW, Worsham PL, Rose KJ, et al. Postexposure prophylaxis against experimental inhalation anthrax inhalation anthrax Pulmonary anthrax, woolsorter's disease Pulmonology Occupational anthrax caused by inhalation of Brucella anthracis spores, affecting those exposed to aerosols during early processing of goat or other infected animal hair Clinical . J Infect infect /in·fect/ (in-fekt´)
1. to invade and produce infection in.

2. to transmit a pathogen or disease to.


in·fect
v.
1.
 Dis 1993;167:1239-43.

(4.) Henderson DW, Peacock S peacock or peafowl, large bird of the genus Pavo, in the pheasant family, native to E Asia. There are two main species, the common (Pavo cristatus), and the Javanese (P. , Belton FC. Observations on the prophylaxis of experimental pulmonary anthrax pulmonary anthrax Inhalation anthrax, see there  in the monkey. J Hyg 1956;54:28-36.

(5.) Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, et al. Anthrax as a biological weapon: medical and public health management. Working group on civilian biodefense. JAMA JAMA
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Journal of the American Medical Association
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(6.) Food and Drug Administration. Prescription drug prescription drug Prescription medication Pharmacology An FDA-approved drug which must, by federal law or regulation, be dispensed only pursuant to a prescription–eg, finished dose form and active ingredients subject to the provisos of the Federal Food, Drug,  products; doxycycline and penicillin G Procaine penicillin G procaine

Ayercillin (CA), Crysticillin-AS (CA), Wycillin

Pharmacologic class: Penicillin

Therapeutic class: Anti-infective

Pregnancy risk category B

Action

 administration for inhalational anthrax (postexposure). Federal Register 2001;66:55679.

(7.) Food and Drug Administration. Medical review. Available from: URL URL
 in full Uniform Resource Locator

Address of a resource on the Internet. The resource can be any type of file stored on a server, such as a Web page, a text file, a graphics file, or an application program.
: http://www.fda.gov/cder/foi/nda/2000/19-537SO38_cipro.htm. Accessed November 2001.

(8.) Lightfoot NF, Scott RJD RJD Rashtriya Janata Dal (Indian political party)
RJD Ronnie James Dio (singer)
RJD Little Skate (FAO fish species code) 
, Turnbull PCB PCB: see polychlorinated biphenyl.
PCB
 in full polychlorinated biphenyl

Any of a class of highly stable organic compounds prepared by the reaction of chlorine with biphenyl, a two-ring compound.
. Antimicrobial susceptibility susceptibility

the state of being susceptible. Refers usually to infectious disease but may be to physical factors such as wetting or to psychological factors such as harassment.
 of Bacillus anthracis. Salisbury Medical Bulletin 1990;68:95-8.

(9.) Centers for Disease Control and Prevention. National pharmaceutical stockpile program. Available from: URL: http://www.cdc.gov/nceh/nps/. Accessed July 3, 2002.

(10.) Centers for Disease Control and Prevention. Notice to readers: additional options for preventive treatment preventive treatment
n.
See prophylactic treatment.
 for persons exposed to inhalational anthrax. MMWR Morb Mortal Wkly Rep 2001;50:1142,1151.

(11.) Centers for Disease Control and Prevention. Update: adverse events associated with anthrax prophylaxis among postal employees--New Jersey, New York City, and the District of Columbia Metropolitan Area, 2001. MMWR Morb Mortal Wkly Rep 2001;50:1051-4.

(12.) Shepard CW. Adverse events associated with post-exposure antimicrobial prophylaxis for the prevention of anthrax--Florida, New Jersey, New York City, Maryland, Virginia, and Washington, D.C., 2001. In: 51st Annual Epidemic Intelligence Service Conference program and abstracts book. Atlanta: Centers for Disease Control and Prevention: 2002. p. 51.

(13.) Physicians Desk Reference. Available from: URL: http://www.pdrel.com. Accessed July 3, 2002.

(14.) Segev S, Yaniv I, Haverstock D, Reinhart M. Safety of long-term therapy with ciprofloxacin: data of controlled clinical trials controlled clinical trial,
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(15.) Bryant SG, Fisher S, Kluge (jargon) kluge - /klooj/, /kluhj/ (From German "klug" /kloog/ - clever and Scottish "kludge") 1. A Rube Goldberg (or Heath Robinson) device, whether in hardware or software.  RM. Increased frequency of doxycycline side effects. Pharmacotherapy pharmacotherapy /phar·ma·co·ther·a·py/ (-ther´ah-pe) treatment of disease with medicines.

phar·ma·co·ther·a·py
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Treatment of disease through the use of drugs.
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(16.) McCormack WM, Martin DH, Hook EW, Jones RB. Daily oral grepafloxacin vs. twice daily oral doxycycline in the treatment of Chlamydia trachomatis Chlamydia tra·cho·ma·tis
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A species of Chlamydia that causes trachoma, inclusion conjunctivitis, lymphogranuloma venereum, nonspecific urethritis, and proctitis in humans.
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(17.) Ragnar NS. Atypical pneumonia atypical pneumonia
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See primary atypical pneumonia.


atypical pneumonia Chest medicine A clinically 'atypical' form of pneumonia, which lacks the classic signs and Sx of pneumonia Types Chlamydia pneumonia,
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see etiology.
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(18.) Phillips MA, Kass RB. User acceptability patterns for mefloquine mefloquine /mef·lo·quine/ (mef´lo-kwin) an antimalarial effective against chloroquine-resistant strains of Plasmodium falciparum and P. vivax; used as the hydrochloride salt.  and doxycycline malaria malaria, infectious parasitic disease that can be either acute or chronic and is frequently recurrent. Malaria is common in Africa, Central and South America, the Mediterranean countries, Asia, and many of the Pacific islands.  chemoprophylaxis chemoprophylaxis /che·mo·pro·phy·lax·is/ (-pro?fi-lak´sis) prevention of disease by means of a chemotherapeutic agent.

che·mo·pro·phy·lax·is
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Disease prevention by use of chemicals or drugs.
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(19.) Raoult D, Houpikian P, Tissot Dupont H, Riss JM, Arditi-Djiane J, Brouqui P, et al. Treatment of Q fever Q fever: see rickettsia.  endocarditis endocarditis (ĕn'dōkärdī`tĭs), bacterial or fungal infection of the endocardium (inner lining of the heart) that can be either acute or subacute. : comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine. Arch Intern intern /in·tern/ (in´tern) a medical graduate serving in a hospital preparatory to being licensed to practice medicine.

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(20.) Schuhwerk M, Behrens RH. Doxycycline as first line malarial ma·lar·i·a  
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1. An infectious disease characterized by cycles of chills, fever, and sweating, caused by a protozoan of the genus Plasmodium
 prophylaxis: how safe is it? J Travel Med 1998;5:102.

(21.) Jefferds MD, Roy S, Hayslett J, Frye A, Laserson K, Schuchat A, et al. Promoting postal workers' adherence to antibiotic prophylaxis to prevent inhalational anthrax--Washington, DC, 2001. In: 51st Annual Epidemic Intelligence Service Conference program and abstracts book. Atlanta: Centers for Disease Control and Prevention: 2002. p. 73.

(22.) Barsky AJ, Saintfort R, Rogers MP, Borus JF. Nonspecific nonspecific /non·spe·cif·ic/ (non?spi-sif´ik)
1. not due to any single known cause.

2. not directed against a particular agent, but rather having a general effect.


nonspecific

1.
 medication side effects and the nocebo nocebo /no·ce·bo/ (no-se´bo) [L.] an adverse, nonspecific side effect occurring in conjunction with a medication but not directly resulting from the pharmacologic action of the medication.  phenomenon. JAMA 2002;287:622-7.

(23.) Centers for Disease Control and Prevention. Notice to readers: interim guidelines guidelines,
n.pl a set of standards, criteria, or specifications to be used or followed in the performance of certain tasks.
 for investigation of and response to Bacillus anthracis exposures. MMWR Morb Mortal Wkly Rep 2001;50:987-90.

(24.) Sanson-Fisher R, Bowman J, Armstrong S. Factors affecting nonadherence with antibiotics. Diagn Microbiol Infect Dis 1992;15:103S-9S.

(25.) Lam F, Stevenson FA, Britten N, Stell IM. Adherence to antibiotics prescribed in an accident and emergency department: the influence of consultation factors. Eur J Emerg Med 2001;8:181-8.

(26.) Shea S, Misra D, Ehrlich MH, Field L, Francis CK. Correlates of nonadherence to hypertension treatment in an inner-city minority population. Am J Public Health 1992;82:1607-12.

(27.) Trick LR. Patient compliance--don't count on it! J Am Optometric Assoc 1993;64:264-70.

Address for correspondence: Colin W. Shepard, Meningitis and Special Pathogens Branch, Centers for Disease Control and Prevention, Mailstop C09, 1600 Clifton Road Clifton Road is main street in Clifton neighborhood of Saddar Town in Karachi, Sindh, Pakistan.

Its name dates from the British Colonial rule, and its market is posh areas of Karachi.
 NE, Atlanta, GA 30333, USA; fax: 404-639-3059; e-mail: cvs8@cdc.gov

Colin W. Shepard, * Montse Soriano-Gabarro, * Elizabeth R Elizabeth R is a BBC television drama serial that was broadcast in six, 85 minute parts on terrestrial channel BBC Two from February to March 1971. Starring Glenda Jackson in the title role, it was a largely accurate, historical portrayal of the life of Elizabeth I of . Zell, * James Hayslett, * Susan Lukacs, * Susan Goldstein, * Stephanie Factor, * ([dagger]) Joshua Jones This article may violate Wikipedia's policy on biographies of living persons.

Articles may not contain unsourced or poorly sourced controversial claims about living people.
, * Renee Ridzon, * Ian Williams Ian Williams (born 1970 in Johnstown, Pennsylvania) is an American rock guitarist.

Williams is most well known for his unique approach to finger tapping on guitar and utilizing two Akai Headrush guitar pedals.
, * Nancy Rosenstein, * and the CDC Adverse Events Working Group (1)

* Centers for Disease Control and Prevention, Atlanta, Georgia, USA; and ([dagger]) New York Academy of Medicine The New York Academy of Medicine was founded in 1847 by a group of leading New York City metropolitan area physicians as a voice for the medical profession in medical practice and public health reform. , New York New York, state, United States
New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of
, New York, USA

(1) Michael Bales, Judith Cobb, Leigh Farrington, Alicia Fry, Emily Zielinski Gutierrez, Renee Joskow, Pavani Kalluri, Aileen Kenneson, Savita Kumar, Jill Morris, Melanie F. Myers, Robert Newman Robert Newman can refer to:
  • Robert Newman (actor), known for his long-running role on Guiding Light
  • Robert Newman (comedian), also known as Rob Newman
  • Robert Newman (impresario) - manager of the Queen's Hall and founder of the Promenade Concerts
, Chima Ohuabunwo, John T. Redd, Sharon Roy, Stephanie Schrag, Andi Shane, Reina Turcios, Kevin Winthrop, and Mitchell Wolfe.
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Author:Rosentein, Nancy
Publication:Emerging Infectious Diseases
Geographic Code:1USA
Date:Oct 1, 2002
Words:7763
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