Adenovirus Vaccine and Doxycycline Calcium

• Generic Name: adenovirus vaccine
• Dosage Forms: n.a.
• Other Brand Names: Adenovirus Type 4 and Type 7 Vaccine Live Oral

Prevention of febrile acute respiratory disease caused by adenovirus type 4 and type 7. Labeled by FDA for use in military populations 17 through 50 years of age; not commercially available for use in other individuals. (See Restricted Distribution under Dosage and Administration.)

Adenoviruses, especially adenovirus type 4 and type 7, commonly cause acute respiratory disease (e.g., runny nose, fever, sore throat, breathing problems, cough, headache, croup, bronchitis). Certain adenovirus serotypes cause other illnesses (e.g., conjunctivitis, keratoconjunctivitis, otitis media, gastroenteritis, cystitis). Disseminated or life-threatening infections can occur (e.g., severe pneumonia, hepatitis, meningitis, encephalitis). Adenoviruses spread person to person via direct contact, respiratory droplet transmission, or food and/or water contaminated with feces. Fomites also may be involved in transmission since adenoviruses survive for long periods outside of the body, including on environmental surfaces, and are unusually stable when exposed to chemical and physical agents or adverse pH conditions.

Military recruits are at increased risk of acute respiratory illnesses during basic training because of several factors, including close sleeping and training environments where transmission of respiratory pathogens is facilitated, congregation of young adults arriving from wide geographic distributions who may enter basic training carrying pathogens capable of being spread to others who are immunologically susceptible, and stressful nature of basic training and military operations. Adenoviruses, especially adenovirus type 4 and type 7, are a well documented cause of acute respiratory illness in military recruits; adenoviruses reportedly cause 50–80% of cases of acute respiratory disease in this population. Outbreaks of adenovirus-associated disease also occur in other populations (e.g., healthcare-associated outbreaks), but the combination of sustained transmission and relatively high and predictable attack rates of adenovirus-associated respiratory disease appears to be unique to military basic trainees.

US Department of Defense (DOD) requires that all enlisted US military recruits 17 through 50 years of age receive a single dose of adenovirus type 4 and type 7 vaccine live oral at the earliest opportunity upon arrival at initial entry training (basic military training), unless contraindicated (see Contraindications under Cautions). May also be recommended for other military personnel at high risk for adenovirus infection, but not required for cadre working at enlisted basic training sites.

• Generic Name: doxycycline
• Dosage Forms: n.a.
• Other Brand Names: Acticlate, Adoxa CK, Adoxa Pak, Adoxa TT, Alodox, Avidoxy, Doryx, Mondoxyne NL, Monodox, Morgidox, Oracea, Oraxyl, Periostat Targadox, Vibramycin Calcium, Vibramycin Hyclate, Vibramycin monohydrate, Vibra-Tabs, Adox Pak 2/100, Adoxa, Adoxa Pak 1/100, Adoxa Pak 1/150, Avidoxy, TargaDOX, Vibramycin, Doxy 100, TargaDOX

Treatment of respiratory tract infections caused by Mycoplasma pneumoniae.

Treatment of respiratory tract infections caused by Haemophilus influenzae, Streptococcus pneumoniae, or Klebsiella. Should only be used for treatment of infections caused by these bacteria when in vitro susceptibility tests indicate the organism is susceptible.

Empiric treatment of community-acquired pneumonia (CAP) in conjunction with other anti-infectives. Tetracyclines provide coverage against C. pneumoniae, M. pneumoniae, H. influenzae, and Legionella, but S. pneumoniae may be resistant. Doxycycline is the preferred tetracycline for empiric treatment of CAP.

Alternative for treatment of infections caused by Legionella pneumophila; used with or without rifampin.

Acne

Adjunctive treatment of moderate to severe inflammatory acne. Not indicated for treatment of noninflammatory acne.

Actinomycosis

Treatment of actinomycosis caused by Actinomyces israelii. Alternative to penicillin G; oral tetracyclines (usually doxycycline or tetracycline) also used as follow-up after initial parenteral penicillin G.

Amebiasis

Adjunct to amebicides for treatment of acute intestinal amebiasis. Tetracyclines not included in current recommendations for treatment of amebiasis caused by Entamoeba.

Anthrax

Postexposure prophylaxis to reduce the incidence or progression of disease following a suspected or confirmed exposure to aerosolized Bacillus anthracis spores (inhalational anthrax). Initial drug of choice for such prophylaxis is ciprofloxacin or doxycycline; doxycycline is the preferred tetracycline because of ease of administration and proven efficacy in monkey studies.

Treatment of inhalational anthrax. Monotherapy may be effective for anthrax that occurs as the result of natural or endemic exposures, but a multiple-drug parenteral regimen (ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective) is recommended for inhalational anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism. Although tetracyclines not usually used in children <8 years of age or in pregnant women, the benefits of doxycycline outweigh the risks and CDC and others state doxycycline can be used when necessary for treatment of inhalational anthrax in these individuals.

Treatment of GI and oropharyngeal anthrax. If occurring in the context of biologic warfare or bioterrorism, use parenteral regimens recommended for inhalational anthrax.

Treatment of cutaneous anthrax. Multiple-drug regimen recommended for initial treatment when there are signs of systemic involvement, extensive edema, or lesions on the head or neck or when cutaneous anthrax occurs in children <2 years of age.

Bartonella Infections

Treatment of bartonellosis caused by Bartonella bacilliformis.

Treatment of infections caused by B. henselae (e.g., cat scratch disease, bacillary angiomatosis, peliosis hepatitis). Cat scratch disease generally is self-limited in immunocompetent individuals and may resolve spontaneously in 2–4 months; some clinicians suggest that anti-infective therapy be considered for acutely or severely ill patients with systemic symptoms, particularly those with hepatosplenomegaly or painful lymphadenopathy, and probably is indicated in immunocompromised patients. Anti-infectives also are indicated in patients with B. henselae infections who develop bacillary angiomatosis, neuroretinitis, or Parinaud’s oculoglandular syndrome. Optimum regimens have not been identified; some clinicians recommend erythromycin, azithromycin, doxycycline, ciprofloxacin, rifampin, co-trimoxazole, gentamicin, or third generation cephalosporins.

Treatment of infections caused by B. quintana. Optimum anti-infective regimens have not been identified; various drugs have been used, including doxycycline, erythromycin, azithromycin, chloramphenicol, or cephalosporins.

A drug of choice for treatment of bartonellosis in HIV-infected adults and adolescents, especially CNS bartonellosis. USPHS/IDSA, CDC, and others suggest that long-term suppression with erythromycin or doxycycline should be considered to prevent recurrence of bartonellosis in HIV-infected adults and adolescents with relapse or reinfection.

Brucellosis

Treatment of brucellosis; considered a drug of choice. Used in conjunction with other anti-infectives (e.g., streptomycin or gentamicin and/or rifampin), especially for severe infections or when there are complications (e.g., endocarditis, meningitis, osteomyelitis).

Postexposure prophylaxis following a high-risk exposure to Brucella (e.g., needle-stick injury, inadvertent laboratory exposure, confirmed exposure in the context of biologic warfare or bioterrorism). Postexposure prophylaxis not generally recommended after exposure to endemic brucellosis.

Burkholderia Infections

Treatment of melioidosis caused by Burkholderia pseudomallei. Although optimum regimens not identified, doxycycline monotherapy may be effective for mild, localized disease without toxicity, and doxycycline in conjunction with co-trimoxazole may be effective for localized disease with toxicity. Severe illness requires an initial parenteral regimen of ceftazidime, imipenem, or meropenem (with or without concomitant co-trimoxazole or doxycycline), followed by a prolonged oral maintenance regimen of doxycycline (in conjunction with co-trimoxazole) or amoxicillin-clavulanate.

Treatment of glanders caused by B. mallei. Experience is limited regarding treatment of human cases; optimum regimens not identified. Some clinicians suggest streptomycin used in conjunction with tetracycline or chloramphenicol or imipenem monotherapy. Others suggest that, pending results of in vitro susceptibility tests, regimens used for treatment of melioidosis can be used for initial empiric treatment of glanders.

The US Army Medical Research Institute of Infectious Diseases (USAMRIID) and European Commission’s Task Force on Biological and Chemical Agent Threats (BICHAT) state that the same treatment regimens recommended for naturally occurring melioidosis or glanders should be used if these Burkholderia infections occur in the context of biologic warfare or bioterrorism. These experts suggest that postexposure prophylaxis with doxycycline or co-trimoxazole for ≥10 days can be attempted in such situations, but is of unproven benefit.

Campylobacter Infections

Treatment of infections caused by Campylobacter fetus. Tetracyclines (usually doxycycline) are alternatives, not drugs of choice for C. fetus.

Chancroid

Treatment of chancroid caused by Haemophilus ducreyi. Not included in CDC recommendations for treatment of chancroid.

Chlamydial Infections

Treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis. A drug of choice for presumptive treatment of chlamydial infections in patients with gonorrhea.

Treatment of trachoma and inclusion conjunctivitis caused by C. trachomatis. Consider that anti-infectives may not eliminate C. trachomatis in all cases of chronic trachoma.

Treatment of lymphogranuloma venereum (genital, inguinal, or anorectal infections) caused by C. trachomatis. Recommended as drug of choice by CDC and others.

Treatment of psittacosis (ornithosis) caused by C. psittaci. A drug of choice recommended by CDC.

Clostridium Infections

Treatment of infections caused by Clostridium. Tetracyclines are alternatives to metronidazole or penicillin G for adjunctive treatment of C. tetani infections.

Ehrlichiosis

Treatment of human granulocytotropic (or granulocytic) anaplasmosis (HGA; formerly human granulocytic ehrlichiosis [HGE]) caused by Anaplasma phagocytophilum (formerly Ehrlichia phagocytophila, E. equi, agent of HGE); drug of choice.

Treatment of human monocytotropic (or monocytic) ehrlichiosis (HME) caused by E. chaffeensis; drug of choice.

Treatment of ehrlichiosis caused by E. ewingii or E. canis; drug of choice.

Enterobacteriaceae Infections

Treatment of infections caused by susceptible Escherichia coli, Enterobacter aerogenes, Klebsiella, or Shigella. Should only be used for treatment of infections caused by these common gram-negative bacteria when other appropriate anti-infectives are contraindicated or ineffective and when in vitro susceptibility tests indicate the organism is susceptible.

Fusobacterium Infections

Alternative to penicillin G for treatment of infections caused by Fusobacterium fusiforme (Vincent’s infection).

Gonorrhea and Associated Infections

Alternative for treatment of uncomplicated gonorrhea caused by susceptible Neisseria gonorrhoeae. However, tetracyclines are considered inadequate therapy and are not recommended by CDC for treatment of gonorrhea.

Empiric treatment of epididymitis most likely caused by N. gonorrhoeae or C. trachomatis; used in conjunction with IM ceftriaxone.

Granuloma Inguinale (Donovanosis)

Treatment of granuloma inguinale (donovanosis) caused by Calymmatobacterium granulomatis. CDC recommends doxycycline or co-trimoxazole as drugs of choice.

Leptospirosis

Alternative to penicillin G for treatment of leptospirosis.

Prevention of leptosporosis in travelers to areas where leptospirosis is endemic or epidemic who are at increased risk (e.g., those who engage in recreational water activities such as whitewater rafting, adventure racing, kayaking).

Can be used for combined prophylaxis in travelers at increased risk of leptospirosis who also require malaria chemoprophylaxis.

Listeria Infections

Alternative for treatment of listeriosis caused by Listeria monocytogenes. Not usually considered a drug of choice or alternative for these infections.

Lyme Disease

Treatment of early disseminated Lyme disease associated with erythema migrans, in the absence of neurologic involvement or third-degree AV heart block. IDSA, AAP, and others recommend oral doxycycline or oral amoxicillin as first-line therapy for treatment of early localized or early disseminated Lyme disease when oral therapy is appropriate.

Treatment of uncomplicated Lyme arthritis without objective evidence of neurologic involvement (e.g., meningitis or radiculopathy).

Alternative for treatment of neurologic manifestations of Lyme disease when β-lactams (e.g., ceftriaxone, penicillin G) cannot be used.

Malaria

Prevention (prophylaxis) of malaria caused by Plasmodium falciparum, including chloroquine-resistant strains. Recommended by CDC and others as a drug of choice for prophylaxis in individuals traveling to areas where chloroquine-resistant P. falciparum malaria has been reported; recommended by CDC as an alternative in those traveling to areas where chloroquine-resistant P. falciparum has not been reported and who are unable to take chloroquine or hydroxychloroquine.

Treatment of uncomplicated malaria caused by chloroquine-resistant Plasmodium falciparum or chloroquine-resistant P. vivax and when the plasmodial species has not been identified. Used in conjunction with quinine; not effective alone.

CDC and others state treatments of choice for uncomplicated chloroquine-resistant P. falciparum malaria are a regimen of oral quinine in conjunction with oral doxycycline, tetracycline, or clindamycin or a regimen of atovaquone and proguanil. A regimen of quinine and doxycycline (or tetracycline) generally preferred over quinine and clindamycin, except for young children or pregnant women who should not receive tetracyclines. Quinine in conjunction with tetracycline (or doxycycline) also a regimen of choice for chloroquine-resistant P. vivax malaria.

Treatment of severe malaria caused by P. falciparum; used in conjunction with IV quinidine gluconate initially and then with oral quinine when an oral regimen is tolerated.

Presumptive self-treatment of malaria in travelers who elect not to use prophylaxis, those who require or choose to use a prophylaxis regimen that may not have optimal efficacy, or for long-term travelers receiving effective prophylaxis but who plan to visit very remote areas; used in conjunction with quinine. Not recommended by CDC for presumptive self-treatment of malaria; CDC recommends the fixed combination of atovaquone and proguanil.

Active only against the asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages) and cannot prevent delayed primary attacks or relapse of P. ovale or P. vivax malaria or provide a radical cure; primaquine usually also indicated to eradicate hypnozoites and prevent relapse in patients exposed to or being treated for P. ovale or P. vivax malaria.

Assistance with diagnosis or treatment of malaria available from CDC Malaria Epidemiology Branch by contacting CDC Malaria Hotline at 770-488-7788 from 8:00 a.m. to 4:30 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours, on weekends, and holidays.

Mycobacterial Infections

Alternative for treatment of infections caused by Mycobacterium fortuitum.

Treatment of cutaneous infections caused by M. marinum; a drug of choice.

Nocardiosis

Alternative to co-trimoxazole for treatment of nocardiosis caused by Nocardia.

Nongonococcal Urethritis

Treatment of nongonococcal urethritis (NGU) caused by Ureaplasma urealyticum, C. trachomatis, or Mycoplasma.

Consider that some cases of recurrent urethritis following doxycycline treatment may be caused by tetracycline-resistant U. urealyticum.

Pelvic Inflammatory Disease

Treatment of acute pelvic inflammatory disease (PID); used in conjunction with other anti-infectives. Doxycycline is included in PID regimens to provide coverage against Chlamydia.

When a parenteral regimen is indicated for PID, CDC and others recommend IV cefotetan (or cefoxitin) in conjunction with IV or oral doxycycline as a regimen of choice. A regimen of IV ampicillin and sulbactam and IV doxycycline is an alternative since it provides good coverage against C. trachomatis, N. gonorrhoeae, and anaerobes and is effective for tubo-ovarian abscess. Doxycycline also used as follow-up after a parenteral regimen of clindamycin and gentamicin.

When an oral regimen is indicated, CDC and others recommend a single IM dose of ceftriaxone or cefoxitin (or other parenteral cephalosporin) followed by oral doxycycline (with or without oral metronidazole) as a regimen of choice. Although experience is limited, oral amoxicillin and clavulanate and oral doxycycline may be an alternative oral regimen.

Plague

Treatment of plague caused by Yersinia pestis, including naturally occurring or endemic bubonic, septicemic, or pneumonic plague and plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism. Regimen of choice is streptomycin or gentamicin; alternatives are doxycycline, tetracycline, ciprofloxacin, or chloramphenicol. For plague meningitis, some experts recommend that treatment regimen include chloramphenicol.

Postexposure prophylaxis following a high-risk exposure to Y. pestis (e.g., household, hospital, or other close contact with an individual who has pneumonic plague; laboratory exposure to viable Y. pestis; confirmed exposure to plague aerosol in the context of biologic warfare or bioterrorism). Doxycycline may be drug of choice; alternatives are tetracycline, ciprofloxacin, or chloramphenicol. Prophylaxis not required for asymptomatic contacts of individuals with bubonic plague, but observe such contacts for 1 week and initiate treatment if symptoms occur.

Pleural Effusions

Management of pleural effusions associated with metastatic tumors.

Rat-bite Fever

Treatment of rat-bite fever caused by Streptobacillus moniliformis or Spirillum minus. Tetracyclines (usually doxycycline) are alternatives to penicillin G.

Relapsing Fever

Treatment of relapsing fever caused by Borrelia recurrentis. A drug of choice.

Rickettsial Infections

Treatment of rickettsial infections including Rocky Mountain spotted fever (RMSF), typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae. Drug of choice for treatment of most rickettsial infections.

Syphilis

Alternative to penicillin G benzathine for treatment of primary, secondary, latent, or tertiary syphilis (not neurosyphilis) in nonpregnant adults and adolescents hypersensitive to penicillins, including HIV-infected patients. Use tetracyclines only if compliance and follow-up can be ensured since efficacy not well documented.

Tularemia

Treatment of tularemia caused by Francisella tularensis, including naturally occurring or endemic tularemia or tularemia that occurs following exposure to F. tularensis in the context of biologic warfare or bioterrorism. Drugs of choice are streptomycin or gentamicin; alternatives are tetracyclines (usually doxycycline), ciprofloxacin, or chloramphenicol. Risk of relapse and primary treatment failure may be higher with the alternatives.

Postexposure prophylaxis of tularemia following a high-risk laboratory exposure to F. tularensis (e.g., spill, centrifuge accident, needlestick injury) or in individuals exposed to the organism in the context of biologic warfare or bioterrorism. Drugs of choice are doxycycline, tetracycline, or ciprofloxacin. Postexposure prophylaxis usually not recommended after exposure to natural or endemic tularemia (e.g., tick bite, rabbit or other animal exposure) and is unnecessary in close contacts of tularemia patients since human-to-human transmission does not occur.

Preexposure prophylaxis of tularemia. Based on results of in vitro susceptibility data, use of doxycycline or ciprofloxacin before exposure possibly may protect against tularemia in the context of biologic warfare or bioterrorism.

Vibrio Infections

Treatment of cholera caused by Vibrio cholerae. A drug of choice; used as an adjunct to fluid and electrolyte replacement in moderate to severe disease.

Treatment of severe V. parahaemolyticus infection when anti-infective therapy is indicated in addition to supportive care.

Treatment of infections caused by V. vulnificus. Optimum anti-infective therapy has not been identified; a tetracycline or third generation cephalosporin (e.g., cefotaxime, ceftazidime) is recommended. Because the case fatality rate associated with V. vulnificus is high, initiate anti-infective therapy promptly if indicated.

Yaws

Alternative to penicillin G for treatment of yaws caused by Treponema pertenue.

Yersinia Infections

Treatment of plague caused by Yersinia pestis.

Treatment of GI infections caused by Yersinia enterocolitica or Y. pseudotuberculosis. These infections usually are self-limited, but IDSA, AAP, and others recommend anti-infectives for severe infections or when septicemia or other invasive disease occurs. Some suggest the role of oral anti-infectives in management of enterocolitis, pseudoappendicitis syndrome, or mesenteric adenitis caused by Yersinia needs further evaluation.

Prophylaxis in Sexual Assault Victims

Empiric anti-infective prophylaxis in sexual assault victims; used in conjunction with a drug effective for gonorrhea (IM ceftriaxone) and a drug effective for bacterial vaginosis and trichomoniasis (oral metronidazole).