Azithromycin is used orally in adults for the treatment of mild to moderate upper and lower respiratory tract infections and uncomplicated skin and skin structure infections caused by susceptible organisms. Oral azithromycin also is used for the treatment of urethritis or cervicitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae, and for the treatment of chancroid caused by Haemophilus ducreyi. Azithromycin is used orally for the treatment of disseminated infections caused by Mycobacterium avium complex (MAC) in patients with human immunodeficiency virus (HIV) infection and for prevention of disseminated MAC infection (both primary and secondary prophylaxis) in HIV-infected individuals.
Azithromycin is used orally in children for the treatment of acute otitis media, community-acquired pneumonia, and pharyngitis or tonsillitis caused by susceptible organisms.
IV azithromycin is used for the treatment of community-acquired pneumonia and acute pelvic inflammatory disease (PID) caused by susceptible organisms when initial IV therapy is considered necessary.
Potential advantages of azithromycin compared with erythromycin include improved oral bioavailability and tissue penetration, increased activity against infections caused by gram-negative organisms (e.g., Haemophilus influenzae), fewer adverse GI effects, and less frequent and less prolonged dosing (promoting better compliance with therapy). Controlled and uncontrolled clinical studies in patients with community-acquired upper or lower respiratory tract infections suggest that 3-5 days of oral therapy with azithromycin generally is as effective as 7-10 days of oral therapy with other macrolides (erythromycin, clarithromycin), a natural penicillin, amoxicillin (with or without clavulanic acid), or a cephalosporin (e.g., cefaclor). In addition, single-dose therapy with azithromycin for urethritis or cervicitis caused by Chlamydia trachomatis may be more cost-effective than longer courses of therapy with another anti-infective (e.g., doxycycline) in populations where noncompliance may be a problem.
Considering the relative costs of drug therapy, erythromycin generally would be preferred for most infections in which oral macrolide therapy was indicated unless azithromycin would be expected to be more effective than erythromycin, the patient is intolerant of erythromycin (e.g., secondary to GI toxicity), or compliance with 3- or 4-times daily erythromycin dosing is considered a problem.
Prior to initiation of azithromycin therapy, appropriate specimens should be obtained for identification of the causative organism(s) and in vitro susceptibility tests. Azithromycin may be started pending results of susceptibility tests, but should be discontinued and other appropriate anti-infective therapy substituted if the organism is found to be resistant to the drug.
Acute Otitis Media
Azithromycin is used orally in children for the treatment of acute otitis media (AOM) caused by H. influenzae, M. catarrhalis, or S. pneumoniae. Safety and efficacy of azithromycin for the treatment of AOM in children has been established when the drug is given in a single-dose regimen (a single 30-mg/kg dose), a 3-day regimen (10 mg/kg once daily for 3 days), or a 5-day regimen (10 mg/kg on day 1, then 5 mg/kg on days 2-5).
Various anti-infectives, including oral amoxicillin, oral amoxicillin and clavulanate potassium, various oral cephalosporins (cefaclor, cefdinir, cefixime, cefpodoxime proxetil, cefprozil, ceftibuten, cefuroxime axetil, cephalexin), IM ceftriaxone, oral co-trimoxazole, oral erythromycin-sulfisoxazole, oral azithromycin, and oral clarithromycin, have been used in the treatment of AOM. The American Academy of Pediatrics (AAP), Centers for Disease Control and Prevention (CDC), and other clinicians state that, despite the increasing prevalence of multidrug-resistant S. pneumoniae and presence of β-lactamase-producing H. influenzae or M. catarrhalis in many communities, amoxicillin remains the anti-infective of first choice when treatment of uncomplicated AOM is indicated since amoxicillin is highly effective, has a narrow spectrum of activity, is well distributed into middle ear fluid, and is well tolerated and inexpensive.
Azithromycin is not considered a first-line agent for treatment of AOM, but is recommended as an alternative, especially for individuals with type I penicillin hypersensitivity. Because S. pneumoniae resistant to amoxicillin also frequently are resistant to co-trimoxazole, clarithromycin, and azithromycin, these drugs may not be effective in patients with AOM who fail to respond to amoxicillin. For additional information regarding treatment of AOM and information regarding prophylaxis of recurrent AOM, treatment of persistent or recurrent AOM, and treatment of otitis media with effusion (OME), .
In a multicenter, randomized, comparative trial in children 1-15 years of age, oral azithromycin therapy (10 mg/kg as a single dose on day 1, followed by 5 mg/kg once daily for 4 days) produced a favorable clinical response (i.e., cure or improvement) in 88 or 73% of patients 11 or 30 days after initiation of therapy, respectively, while therapy with amoxicillin and clavulanate potassium produced a favorable clinical response in 88 or 71% of patients, respectively, at these time points. In another study in children 2-15 years of age with acute otitis media in areas of the US with a high incidence of β-lactamase-producing bacteria, azithromycin therapy produced a favorable clinical response (i.e., cure or improvement) in 84 or 70% of patients 11 or 30 days, respectively, after initiation of therapy. At day 11 or 30, a presumptive bacteriologic/clinical cure was evident in 82 or 71%, respectively, of children with S. pneumoniae infections, 80 or 64% of those with H. influenzae infections, 80 or 73% of those with M. catarrhalis infections, and 100% of those with S. pyogenes infections; 14.3% were considered treatment failures. In one open-label comparative study, the overall clinical success rate (i.e., presumed bacteriologic eradication/clinical cure outcomes) 11 or 30 days after initiation of therapy was 88 or 82%, respectively, in azithromycin-treated patients and 82 or 81%, respectively, in patients receiving amoxicillin and clavulanate potassium. In all studies, the adverse effects associated with any of the therapies were principally GI related (e.g., diarrhea), with a substantially lower incidence of adverse effects in the azithromycin-treated group compared with the group receiving amoxicillin and clavulanate potassium.
Pharyngitis and Tonsillitis
Azithromycin is used orally for the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci) in adults and children when first-line therapy (penicillins) cannot be used. Although azithromycin generally is effective in eradicating S. pyogenes from the nasopharynx, efficacy of the drug in the subsequent prevention of rheumatic fever has not been established. Strains of S. pyogenes resistant to macrolides are common in some areas of the world (e.g., Italy, Japan, Korea, Finland, Spain, Taiwan) and azithromycin-resistant strains have been reported in the US.
(See Resistance: Resistance in Gram-positive Bacteria.)Therefore, the manufacturer recommends that in vitro susceptibility tests be performed prior to use of azithromycin in patients with streptococcal pharyngitis.
Because penicillin has a narrow spectrum of activity, is inexpensive, and generally is effective, the CDC, AAP, American Academy of Family Physicians (AAFP), Infectious Diseases Society of America (IDSA), American Heart Association (AHA), American College of Physicians (ACP), and others consider natural penicillins (i.e., 10 days of oral penicillin V or a single IM dose of penicillin G benzathine) the treatment of choice for streptococcal pharyngitis and tonsillitis and prevention of initial attacks (primary prevention) of rheumatic fever, although oral amoxicillin often is used instead of penicillin V in small children because of a more acceptable taste. Other anti-infectives (e.g., oral cephalosporins, oral macrolides) generally are considered alternative agents. A 10-day regimen of oral erythromycin usually is considered the preferred alternative for the treatment of streptococcal pharyngitis in patients hypersensitive to penicillin. It has been suggested that azithromycin offers an advantage over erythromycin in terms of ease of administration (i.e., fewer daily doses and a 5-day regimen) and better GI tolerance. However, because of limited data to date, the IDSA states that use of anti-infective regimens administered for 5 days or less for the treatment of S. pyogenes pharyngitis cannot be recommended at this time. Because of lower relative rates of bacteriologic eradication reported in some studies, azithromycin should not be administered in a 3-day regimen for the treatment of streptococcal pharyngitis.
In a controlled comparative study in patients 16 years of age or older with streptococcal pharyngitis, microbiologic and clinical response rates of approximately 91% or greater were achieved with either a 5-day, 5-dose course of azithromycin or a 10-day, 40-dose course of penicillin V. In several double-blind, controlled trials in children 2 years of age or older with streptococcal pharyngitis, clinical and microbiologic response with azithromycin (12 mg/kg once daily for 5 days) was superior to that with penicillin V (250 mg 3 times daily for 10 days). In these trials, bacteriologic eradication at day 14 or 30 occurred in a combined 95 or 77%, respectively, of azithromycin-treated children and 73 or 63%, respectively, of penicillin-treated children; clinical success (i.e., cure or improvement) at day 14 or 30 was achieved in a combined 98 or 94%, respectively, of children given azithromycin and 84 or 74%, respectively, of children given penicillin V. Approximately 1% of azithromycin-susceptible S. pyogenes isolates were resistant to the drug following therapy. In another study in children 1.5-14 years of age with streptococcal pharyngitis, oral therapy with azithromycin (10 mg/kg once daily for 3 days) or penicillin V (56 mg/kg daily in 3 divided doses for 10 days) produced clinical success (cure or improvement) in 93 or 89% of patients, respectively. However, bacteriologic eradication was reported in substantially fewer azithromycin-treated patients (65%) than penicillin-treated patients (82%).
Azithromycin has been used as a first-line agent for the treatment of symptomatic enteric infections caused by Campylobacter jejuni. The CDC, National Institutes of Health (NIH), IDSA, AAP, and other clinicians recommend oral erythromycin or azithromycin or fluoroquinolones (e.g., ciprofloxacin) for empiric treatment of these infections; tetracyclines (doxycycline) also can be used. However, increasing emergence of fluoroquinolone-resistant strains of Campylobacter should be considered when selecting a first-line agent.
When initiated early in the course of the Campylobacter infection, erythromycin or azithromycin shortens the duration of illness and prevents relapse. Either macrolide usually eradicates the organism from the stool within 2-3 days; however, a longer duration of treatment (5-7 days) is recommended for treatment of gastroenteritis.
Azithromycin has been used in the treatment of cryptosporidiosis in HIV-infected adults, adolescents, or children. Oral azithromycin in conjunction with paromomycin was used with some success (i.e., reduction in oocyst excretion, improvement in diarrhea) in a limited number of patients with AIDS-related cryptosporidiosis. In addition, azithromycin monotherapy may have contributed to resolution of symptoms in a few HIV-infected children with cryptosporidiosis. However, no anti-infective has been found to reliably eradicate Cryptosporidium, although several drugs (e.g., paromomycin, azithromycin, nitazoxanide) may improve symptoms or suppress the infection.
HIV-infected individuals at greatest risk for cryptosporidiosis are those with advanced immunosuppression (i.e., CD4 T-cell counts less than 100/mm) and fulminant infections usually have occurred in those with CD4 T-cell counts less than 50/mm. The CDC, NIH, IDSA, and other clinicians state that the most appropriate treatment for cryptosporidiosis in HIV-infected individuals is the use of potent antiretroviral agents and symptomatic treatment of diarrhea. A highly potent antiretroviral regimen can result in immune restoration (CD4 T-cell counts exceeding 100/mm), which usually results in resolution of the infection. Symptomatic treatment of diarrhea in HIV-infected or immunocompetent individuals with cryptosporidiosis should include oral or IV fluids and electrolyte replacement to correct dehydration and nutritional supplementation when necessary; severe diarrhea may require intensive support. Adjunctive use of antimotility agents may be indicated, but these agents are not consistently effective and should be used with caution in young children.
Escherichia coli Infections
Azithromycin has been recommended for use in the treatment of GI infections caused by Escherichia coli.
Diarrhea caused by enterotoxigenic E. coli (ETEC) generally is of moderate severity and self-limited, but may be severe. Although anti-infectives are not usually indicated, the AAP, CDC, and others suggest that an anti-infective (e.g., azithromycin, co-trimoxazole, a fluoroquinolone, rifamycin) can be considered in addition to supportive care if diarrhea is severe or intractable and the causative organism is susceptible.
For the treatment of dysentery caused by enteroinvasive E. coli (EIEC), the AAP suggests than an oral anti-infective (e.g., azithromycin, ciprofloxacin, co-trimoxazole) can be used and, whenever possible, the anti-infective should be selected based on results of in vitro tests.
There is some evidence that azithromycin may shorten the course of diarrhea associated with enteroaggregative E. coli (EAEC) in adults and the drug has been recommended as a drug of choice for children with severe or persistent illness caused by this organism.
The role of anti-infectives in patients with hemorrhagic colitis caused by shiga toxin-producing E. coli (STEC; formerly known as enterohemorrhagic E. coli [EHEC] or verotoxin-producing E. coli) is unclear, and most experts do not recommend use of anti-infectives in the treatment of enteritis caused by E. coli 0157:H7 since there is no evidence of benefit from such therapy.
Azithromycin has been used in adults and children for the treatment of shigellosis caused by susceptible strains of Shigella dysenteriae, S. boydii, S. flexneri, or S. sonnei.
Fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin) usually are considered the drugs of choice for the treatment of shigellosis; alternatives are azithromycin, ampicillin, ceftriaxone, or co-trimoxazole. Because of increasing resistance, the choice of anti-infective should be based on susceptibility patterns of locally circulating Shigella. In the US, about 50% of S. flexneri and S. sonnei isolates are resistant to ampicillin and co-trimoxazole.
Oral azithromycin is used as an alternative to fluoroquinolones for the treatment of travelers' diarrhea.
The most common cause of travelers' diarrhea worldwide is noninvasive enterotoxigenic strains of E. coli (ETEC), but travelers' diarrhea also can be caused by various other bacteria including enteroaggregative E. coli (EAEC), Campylobacter jejuni, Shigella, Salmonella, Aeromonas hydrophila, Plesiomonas shigelloides, Yersinia enterocolitica, Vibrio parahaemolyticus, or non-O-group 1 Vibrio cholerae. In some cases, travelers' diarrhea is caused by a parasitic enteric pathogen (e.g., Giardia duodenalis, Cryptosporidium parvum, Cyclospora cayetanensis, Entamoeba histolytica, Dientamoeba fragilis) or viral enteric pathogen (e.g., rotavirus, norovirus).
Countries where travelers are at low risk of travelers' diarrhea include the US, Canada, Australia, New Zealand, Japan, and countries in Northern and Western Europe. Travelers are at intermediate risk for travelers' diarrhea in Eastern Europe, South Africa, and some of the Caribbean islands, but are at high risk in Asia, the Middle East, Africa, and Central and South America.
Travelers' diarrhea usually is self-limited and may resolve within 3-4 days without anti-infective treatment. If diarrhea is moderate or severe, persists for longer than 3 days, or is associated with fever or bloody stools, short-term treatment (1-3 days) with an anti-infective may be indicated. A fluoroquinolone (e.g., ciprofloxacin, levofloxacin, norfloxacin, ofloxacin) generally is recommended when treatment, including self-treatment, of travelers' diarrhea is indicated in adults. Azithromycin can be used as a treatment alternative for individuals who should not receive fluoroquinolones (e.g., children, pregnant women) and may be a drug of choice for travelers in areas with a high prevalence of fluoroquinolone-resistant Campylobacter (e.g., Thailand, Nepal) or those who have not responded after 48 hours of fluoroquinolone treatment. Rifaximin is another alternative for the treatment of travelers' diarrhea caused by noninvasive E. coli. Bismuth subsalicylate or an antimotility agent may be used as an adjunct to anti-infective treatment to provide symptomatic relief; oral rehydration therapy should be used if indicated, especially in young children or geriatric adults. Travelers should consult a physician if diarrhea persists despite treatment.
Respiratory Tract Infections
Azithromycin is used in adults and children 6 months of age or older for the treatment of acute bacterial sinusitis caused by H. influenzae, M. catarrhalis, or S. pneumoniae.
In a randomized, controlled study in patients with acute bacterial sinusitis who received azithromycin (500 mg once daily for 3 days) or amoxicillin and clavulanate (500 mg of amoxicillin and 125 mg of clavulanate 3 times daily for 10 days), the clinical cure rate (modified intent-to-treat analysis) at day 10 was 88% in those who received azithromycin and 85% in those who received amoxicillin and clavulanate; the clinical cure rate at day 28 was 71.5% in both groups.
Safety and efficacy of a single-dose azithromycin regimen for the treatment of acute bacterial maxillary sinusitis were evaluated in a randomized, double-blind study in 270 adults. Patients were randomized to receive a single 2-g dose of azithromycin as an extended-release oral suspension (Zmax) or a 10-day regimen of oral levofloxacin (500 mg once daily). The clinical cure rate was 94.5% in those who received the single-dose azithromycin regimen and 92.9% in those who received the multiple-dose levofloxacin regimen. When patients were stratified according to causative organism, the single-dose azithromycin regimen cured 97.3% of infections caused by S. pneumoniae, 96.3% of those caused by H. influenzae, and 100% of those caused by M. catarrhalis.
Acute Bacterial Exacerbations of Chronic Obstructive Pulmonary Disease
Azithromycin is used orally for the treatment of acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) caused by Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis when anti-infective therapy is considered appropriate.
Current data from a limited number of randomized, comparative studies suggest similar clinical and microbiologic efficacy for oral azithromycin and oral cefaclor, erythromycin, clarithromycin, or amoxicillin (with or without clavulanic acid) for treatment of acute bacterial exacerbations of COPD. In addition, eradication of H. influenzae in patients with chronic bronchitis has occurred more frequently in those receiving azithromycin than in those receiving cefaclor. In these studies, azithromycin generally was administered once daily for 3-5 days, while other anti-infective therapy was given 2 or more times daily for 5-10 days. Although co-trimoxazole generally is considered the drug of choice for the treatment of upper respiratory tract infections and bronchitis caused by H. influenzae or M. catarrhalis, azithromycin is considered by many clinicians to be alternative therapy for the treatment of these infections.
Azithromycin is used in adults for the treatment of acute bacterial exacerbations of COPD caused by H. influenzae, M. catarrhalis, or S. pneumoniae. In a randomized, double-blind, controlled study in patients with acute exacerbation of chronic bronchitis who received azithromycin (500 mg once daily for 3 days) or clarithromycin (500 mg twice daily for 10 days), the clinical cure rate (modified intent-to-treat analysis) at day 21-24 was 85% in those who received azithromycin and 82% in those who received clarithromycin. When results from patients who received azithromycin were stratified according to causative organism, the cure rate was 86% for those with H. influenzae infections and 91-92% for those with S. pneumoniae or M. catarrhalis infections.
Azithromycin is used orally for the treatment of mild to moderate community-acquired pneumonia (CAP) caused by susceptible S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae (formerly Chlamydia pneumoniae) in adults and children 6 months of age or older when oral therapy is indicated. Limited data in patients with CAP caused by these pathogens suggest that oral azithromycin given for 3-5 days is as effective as a 10-day regimen of oral cefaclor or clarithromycin. When an oral regimen is appropriate, a single-dose regimen of azithromycin given as an extended-release oral suspension (Zmax) can be used for the treatment of mild to moderate CAP caused by susceptible C. pneumoniae, H. influenzae, M. pneumoniae, or S. pneumoniae.
Oral azithromycin should not be used in patients who have moderate to severe pneumonia or when there are risk factors that make oral therapy inappropriate (e.g., cystic fibrosis, nosocomial infection, known or suspected bacteremia, illness requiring hospitalization, geriatric or debilitated status, immunodeficiency or functional asplenia or other underlying conditions that may compromise ability to respond to treatment). Although azithromycin is highly distributed into tissues and phagocytes, some clinicians suggest that oral azithromycin is unsuitable for the treatment of CAP bacteremia or potentially resistant organisms (e.g., penicillin-resistant S. pneumoniae) may be involved because of the relatively low serum concentrations achieved with oral administration of the drug; parenteral therapy with IV azithromycin or another anti-infective agent may be preferred in such situations.
IV azithromycin is used for the treatment of CAP caused by susceptible C. pneumoniae, H. influenzae, Legionella pneumophila, M. catarrhalis, M. pneumoniae, S. aureus, or S. pneumoniae when initial IV drug therapy is considered necessary. In a comparative study in patients with CAP, clinical success (i.e., cure or improvement) 10-14 days after completion of therapy reportedly occurred in 78% of patients receiving azithromycin (500 mg IV once daily for 2-5 days followed by azithromycin 500 mg orally once daily to complete 7-10 days of therapy) and in 74% of patients receiving cefuroxime (750 mg IV every 8 hours for 2-5 days followed by cefuroxime 500 mg orally every 12 hours to complete 7-10 days of therapy) with or without erythromycin (up to 2 g daily IV or oral). In an uncontrolled study, clinical success (i.e., cure or improvement) was reported in 89% of patients receiving the same regimen of IV and oral azithromycin. In these studies, presumptive bacteriologic eradication (determined according to microbiologic data available at the patient's last completed clinic visit) was evident in 96% of evaluable patients with S. pneumoniae infections (including 79% of those with positive blood cultures for S. pneumoniae), 95% of those with H. influenzae infection, 90% of those with M. catarrhalis or S. aureus infection. At 10-14 days after azithromycin therapy, presumptive bacteriologic/clinical success was evident in 89% of patients with M. pneumoniae infection, 82% of those with C. pneumoniae infection, and 81% of those with L. pneumophila infection.
Initial treatment of CAP generally involves use of an empiric anti-infective regimen based on the most likely pathogens and local susceptibility patterns, but should be modified to provide more specific therapy (pathogen-directed therapy) based on results of in vitro culture and susceptibility testing, especially in hospitalized patients. The most appropriate empiric regimen varies depending on the severity of illness at the time of presentation and whether outpatient treatment or hospitalization in or out of an intensive care unit (ICU) is indicated and the presence or absence of cardiopulmonary disease and other modifying factors that increase the risk of certain pathogens (e.g., penicillin- or multidrug-resistant S. pneumoniae, enteric gram-negative bacilli, Ps. aeruginosa). For both outpatients and inpatients, most experts recommend that an empiric regimen for the treatment of CAP include an anti-infective active against S. pneumoniae since this organism is the most commonly identified cause of bacterial pneumonia and causes more severe disease than many other common CAP pathogens. Macrolides should not be used alone for empiric treatment of CAP in hospitalized patients.
For empiric outpatient treatment of CAP in previously healthy adults without risk factors for drug-resistant S. pneumoniae (DRSP), IDSA and ATS recommend monotherapy with a macrolide (azithromycin, clarithromycin, erythromycin) or, alternatively, doxycycline. If risk factors for DRSP are present (e.g., chronic heart, lung, liver, or renal disease, diabetes mellitus, alcoholism, malignancy, asplenia, immunosuppression, history of anti-infective treatment within the last 3 months), IDSA and ATS recommend monotherapy with a fluoroquinolone with enhanced activity against S. pneumoniae (gemifloxacin, levofloxacin, moxifloxacin) or, alternatively, a combination regimen that includes a β-lactam active against S. pneumoniae (high-dose amoxicillin or fixed combination of amoxicillin and clavulanic acid or, alternatively, ceftriaxone, cefpodoxime, or cefuroxime) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline.
For empiric inpatient treatment of CAP when treatment in an intensive care unit (ICU) is not necessary, IDSA and ATS recommend adults receive monotherapy with a fluoroquinolone with enhanced activity against S. pneumoniae (gemifloxacin, levofloxacin, or moxifloxacin) or, alternatively, a combination regimen that includes a β-lactam (usually cefotaxime, ceftriaxone, or ampicillin) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline. For empiric inpatient treatment of CAP in ICU patients when Pseudomonas and oxacillin-resistant (methicillin-resistant) Staphylococcus aureus are not suspected, IDSA and ATS recommend a combination regimen that includes a β-lactam (cefotaxime, ceftriaxone, fixed combination of ampicillin and sulbactam) given in conjunction with either azithromycin or a fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin).
For empiric treatment of CAP in adults with risk factors for Ps. aeruginosa, IDSA and ATS recommend a combination regimen that includes an antipneumococcal, antipseudomonal β-lactam (cefepime, imipenem, meropenem, fixed combination of piperacillin and tazobactam) and ciprofloxacin or levofloxacin; one of these β-lactams, an aminoglycoside, and azithromycin; or one of these β-lactams, an aminoglycoside, and an antipneumococcal fluoroquinolone.
Skin and Skin Structure Infections
Azithromycin is used in adults for the treatment of uncomplicated skin and skin structure infections caused by susceptible Staphylococcus aureus, S. pyogenes, or S. agalactiae (group B streptococci). Results of comparative studies indicate that oral azithromycin is as effective as oral cloxacillin, oral cephalexin, or oral erythromycin in the treatment of bacterial skin and skin structure infections (e.g., cellulitis, pyoderma, erysipelas, wound infections). However, some clinicians state that azithromycin or any macrolide should not be used for serious staphylococcal infections because of the propensity for development of resistance during therapy. Skin structure infections resulting in abscess formation may require surgical or needle drainage in addition to antibacterial therapy.
A combination regimen of atovaquone and azithromycin is recommended as a regimen of choice for the treatment of babesiosis caused by Babesia microti. The other regimen of choice for this infection is clindamycin and quinine. The clindamycin and quinine regimen may be preferred for severe babesiosis; in those with mild or moderate illness, the atovaquone and azithromycin regimen may be as effective and better tolerated than the quinine and clindamycin regimen. Use of exchange transfusions also should be considered in severely ill patients with high levels of parasitemia (at least 10%), substantial hemolysis, or compromised renal, hepatic, or pulmonary function.
Limited data in animals suggest that a regimen of azithromycin and quinine also may be effective in the management of babesiosis.
Azithromycin has been used for the treatment of infections caused by Bartonella henselae (formerly Rochalimaea henselae) (e.g., cat scratch disease, bacillary angiomatosis, peliosis hepatitis). Cat scratch disease generally is a self-limited illness in immunocompetent individuals and may resolve spontaneously in 2-4 months; however, 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 such therapy 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. While the optimum anti-infective regimen for the treatment of cat scratch disease or other B. henselae infections has not been identified, some clinicians recommend use of azithromycin, ciprofloxacin, erythromycin, doxycycline, rifampin, co-trimoxazole, gentamicin, or third generation cephalosporins.
Azithromycin has been used in conjunction with IM or IV ceftriaxone for the treatment of bacteremia caused by Bartonella quintana (formerly Rochalimaea quintana).B. quintana, a gram-negative bacilli, can cause cutaneous bacillary angiomatosis, trench fever, bacteremia, endocarditis, and chronic lymphadenopathy.B. quintana infections have been reported most frequently in immunocompromised patients (e.g., individuals with HIV infection), homeless individuals in urban areas, and chronic alcohol abusers. Optimum anti-infective regimens for the treatment of infections caused by B. quintana have not been identified, and various drugs have been used to treat these infections, including doxycycline, erythromycin, azithromycin, clarithromycin, or chloramphenicol. There is evidence that these infections tend to persist or recur and prolonged therapy (several months or longer) usually is necessary.
Azithromycin is used orally in the treatment of chancroid (genital ulcers caused by Haemophilus ducreyi).
The CDC and others state that a single oral dose of a conventional formulation of azithromycin, a single IM dose of ceftriaxone, a 3-day regimen of oral ciprofloxacin (contraindicated in pregnant or lactating women), or a 7-day regimen of oral erythromycin are the regimens of choice for the treatment of chancroid. The AAP states that a single oral dose of a conventional formulation of azithromycin or a single IM dose of ceftriaxone is the preferred regimen in infants, children, and adolescents. All 4 regimens generally are effective for the treatment of chancroid; however, patients with human immunodeficiency virus (HIV) infection and patients who are uncircumcised may not respond to therapy as well as those who are HIV-negative or circumcised. Because data on the efficacy of the single-dose azithromycin and single-dose ceftriaxone regimens for treatment of chancroid in patients with HIV infection are limited, the CDC recommends that these regimens be used in HIV-infected patients only if follow-up can be ensured; some experts recommend that HIV-infected individuals with chancroid receive the 7-day erythromycin regimen.
Chancroid occurs more frequently in men (90% of infections) than in women and experience with azithromycin treatment of this infection in women is limited. Consequently, efficacy of the drug in the treatment of chancroid in women has not been established to date, and the drug is labeled by the US Food and Drug Administration (FDA) for this use only in men. However, azithromycin has been used successfully for the treatment of chancroid in women, and chancroid treatment guidelines from CDC, AAP, and other authorities do not provide gender-based recommendations.
In the US, chancroid usually occurs in discrete outbreaks, but the disease is endemic in some areas. Approximately 10% of patients with chancroid acquired in the US also are coinfected with Treponema pallidum or herpes simplex virus (HSV); this percentage is higher in individuals who acquired the infection outside the US. In addition, high rates of HIV infection have been reported in patients with chancroid, and the disease appears to be a cofactor for HIV transmission. Evaluation of the physical features of genital ulcers (without laboratory evaluation and testing) usually is inadequate to provide a differential diagnosis between chancroid, primary syphilis, and genital HSV infection. Ideally, diagnostic evaluation of patients with genital ulcers should include a serologic test for syphilis and darkfield examination or direct immunofluorescence test for T. pallidum, culture for H. ducreyi, and culture or antigen test for HSV. A definitive diagnosis of chancroid requires identification of H. ducreyi on special culture media that is not widely available. The presence of a painful ulcer and tender suppurative inguinal adenopathy suggests a diagnosis of chancroid. However, a probable diagnosis of chancroid can be made if the patient has one or more painful genital ulcers, there is no evidence of T. pallidum infection based on a negative darkfield examination of ulcer exudate or a negative serologic test for syphilis (performed at least 7 days after onset of ulcers), culture or antigen test for HSV is negative, and the clinical presentation, appearance of genital ulcers, and regional lymphadenopathy (if present) are typical for chancroid.
Patient Follow-up and Management of Sexual Partners
The CDC recommends that all patients diagnosed with chancroid be tested for HIV and, if the test is negative, retested for HIV and for syphilis 3 months later. Patients with chancroid should be examined 3-7 days after initiation of anti-infective therapy. If the regimen was effective, symptomatic improvement in the ulcers is evident within 3 days and objective improvement is evident within 7 days. If clinical improvement is not evident within 3-7 days, consideration should be given to the possibility that the diagnosis was incorrect, there is coinfection with another sexually transmitted disease, the patient was noncompliant with the anti-infective regimen, the strain of H. ducreyi is resistant to the anti-infective agent used, or the patient is HIV seropositive.
The time required for complete ulcer healing is related to the size of the ulcer; large ulcers may require more than 2 weeks to heal. Healing of ulcers may be slower in uncircumcised men who have ulcers under the foreskin. Resolution of fluctuant lymphadenopathy is slower than that of ulcers, and needle aspiration or incisional drainage may be necessary even during otherwise effective anti-infective therapy. While needle aspiration of buboes is a simpler procedure, incision and drainage of buboes may be preferred.
The CDC recommends that any individual who had sexual contact with a patient with chancroid within 10 days before the onset of the patient's symptoms should be examined and treated for the disease, even if no symptoms are present.
Urogenital Chlamydial Infections
Azithromycin is used orally for the treatment of urogenital infections caused by C. trachomatis.
Urogenital Chlamydial Infection in Adults and Adolescents
Azithromycin is used orally for the treatment of urethritis and cervicitis caused by C. trachomatis.
In the US, urogenital chlamydial infection is the most frequently reported infectious disease and these infections occur most frequently in individuals 25 years of age or younger. Urogenital C. trachomatis infection in women can result in serious sequelae, including pelvic inflammatory disease (PID), ectopic pregnancy, and infertility. Asymptomatic infection is common, and some women with uncomplicated cervical infection already have subclinical upper reproductive tract infection. There is evidence that routine screening for chlamydial infection in women can reduce the prevalence of infection and rates of PID. Therefore, the CDC recommends annual screening of all sexually active women 25 years of age or younger and also recommends screening of older women who have risk factors for chlamydial infection (e.g., new or multiple sex partners). Although data are insufficient to date to recommend routine screening for C. trachomatis in sexually active young men, the CDC states that screening of such men should be considered in clinical settings with a high prevalence of chlamydial infection (e.g., adolescent clinics, correctional facilities, sexually transmitted disease clinics).
For the treatment of urogenital chlamydial infections in nonpregnant adults and adolescents, the CDC, AAP, and other clinicians recommend a single oral dose of a conventional formulation of azithromycin or a 7-day regimen of oral doxycycline. Alternatively, these adults and adolescents can receive a 7-day regimen of oral erythromycin base or ethylsuccinate or a 7-day regimen of oral ofloxacin or levofloxacin. While doxycycline is highly effective and experience with the drug is more extensive than that with azithromycin, azithromycin may be particularly useful and cost-effective when compliance with a multiple-day (e.g., 7-day) anti-infective regimen cannot be ensured. Results from controlled clinical studies in individuals 15 years of age or older indicate that a single 1-g oral dose of a conventional formulation of azithromycin is as effective as a 7-day course of doxycycline in the treatment of uncomplicated chlamydial genital infections.
The CDC, AAP, and others recommend that urogenital chlamydial infections in pregnant women be treated with a single-dose regimen of a conventional formulation of azithromycin or a 7-day regimen of oral amoxicillin. Alternative regimens recommended for these infections in pregnant women are a 7- or 14-day regimen of oral erythromycin base or ethylsuccinate. The CDC states that clinical experience and studies suggest that the single-dose azithromycin regimen is safe and effective, and some clinicians suggest that this is the regimen of choice for treatment of urogenital chlamydial infections in pregnant women.
Individuals with HIV infection who also are infected with chlamydia should receive the same treatment regimens recommended for other individuals with chlamydial infections.
When given in the usual dosage for the treatment of uncomplicated sexually transmitted chlamydial infections, azithromycin alone should not be relied on for effective therapy against possible concomitant syphilis and the possibility that the regimen may mask or delay development of the signs and symptoms of incubating syphilis should be considered. Appropriate serologic tests for syphilis and cultures for gonorrhea should be performed prior to initiating azithromycin therapy for chlamydial infection; appropriate anti-infective therapy and follow-up should be initiated if either infection is confirmed.
Urogenital Chlamydial Infection in Infants and Children
For the treatment of uncomplicated urogenital chlamydial infections in children 8 years of age and older, the CDC recommends a single-dose of a conventional formulation of azithromycin or a 7-day regimen of oral doxycycline. For children younger than 8 years of age, the CDC recommends that those weighing at least 45 kg receive a single-dose azithromycin regimen and that those weighing less than 45 kg receive a 14-day regimen of oral erythromycin base or ethylsuccinate. The AAP recommends that infants younger than 6 months of age with urogenital chlamydial infections receive an erythromycin regimen and that those 6 months to 12 years of age receive either azithromycin or erythromycin.
Presumptive Treatment of Chlamydial Infection in Patients with Gonorrhea
Because of the risks associated with untreated coexisting chlamydial infection, the CDC and most clinicians recommend that patients being treated for uncomplicated gonorrhea or disseminated gonococcal infection also receive an anti-infective regimen effective for presumptive treatment of uncomplicated urogenital chlamydial infection. For presumptive treatment of chlamydia in adults and adolescents being treated for uncomplicated or disseminated gonococcal infections, the CDC and many clinicians recommend use of a single oral dose of azithromycin or a 7-day regimen of oral doxycycline. The strategy of routine administration of a regimen effective against chlamydia in patients being treated for gonococcal infection has been recommended by the CDC for more than 10 years and appears to have resulted in substantial decreases in the prevalence of genital chlamydial infection in some populations. In addition, since most N. gonorrhoeae isolated in the US are susceptible to doxycycline and azithromycin, dual therapy may delay the development of resistance in N. gonorrhoeae. Nucleic acid amplification tests (NAAT) for C. trachomatis are highly sensitive and patients with a negative chlamydial NAAT result at the time of treatment for gonorrhea do not need to be treated for chlamydia. However, if test results are not available or if a test other than a NAAT was performed and was negative for chlamydia, patients should receive treatment for both gonorrhea and chlamydia.
Although some clinicians suggest that azithromycin may be effective for the treatment of lymphogranuloma venereum caused by invasive serotypes of C. trachomatis (serovars L1, L2, L3), safety and efficacy of the drug for this use have not been established. The CDC recommends a 21-day regimen of doxycycline as the treatment of choice and a 21-day regimen of erythromycin base as an alternative for the treatment of lymphogranuloma venereum. Although oral azithromycin also may be effective, the CDC states that clinical safety and efficacy data are lacking. Effective treatment cures the infection and prevents ongoing tissue damage, although tissue reaction can result in scarring. Aspiration of buboes through intact skin or incision and drainage may be necessary to prevent the formation of inguinal/femoral ulcerations.
The CDC recommends that individuals who had sexual contact with a lymphogranuloma venereum patient within 60 days before onset of the patient's symptoms should be examined, tested for urethral or cervical chlamydial infection, and treated with a regimen usually recommended for the treatment of urogenital chlamydial infections (a single 1-g dose of azithromycin or 100 mg of doxycycline twice daily for 7 days).
While HIV-infected individuals with lymphogranuloma venereum should receive the same treatment regimens recommended for other patients, there is some evidence that HIV-infected patients may require more prolonged therapy and resolution may be delayed.
Chlamydial Pneumonia in Infants
Some clinicians recommend azithromycin for the treatment of chlamydial pneumonia in infants.
Trachoma and Other Ocular Chlamydial Infections
Some clinicians recommend azithromycin for the treatment of chlamydial conjunctivitis in neonates.
Azithromycin is used in the treatment of ocular trachoma caused by C. trachomatis and is considered a drug of choice for this infection. Azithromycin is recommended for use in mass treatment programs, usually as a single-dose regimen; however, the optimal number of doses required to minimize reservoirs of infection when mass treatment programs are undertaken in high-prevalence areas is unclear.
Other Chlamydial Infections
Azithromycin is used for the treatment of C. pneumoniae respiratory tract infections.
(See Uses: Respiratory Tract Infections.)IV azithromycin is used for the treatment of pelvic inflammatory disease (PID) caused by C. trachomatis. (See Uses: Pelvic Inflammatory Disease.)
Although tetracyclines are the drugs of choice for the treatment of psittacosis caused by Chlamydophila psittaci (formerly Chlamydia psittaci), macrolides (erythromycin, azithromycin, clarithromycin) are possible alternatives in children younger than 8 years of age who should not receive tetracyclines.
Azithromycin has been used to treat adults with coronary artery disease (CAD) who have elevated anti-C. pneumoniae antibody titers (a possible risk factor for myocardial infarction [MI] or CAD) in an attempt to reduce recurrent ischemic events. In a randomized, placebo-controlled study in men who had survived an MI and who had elevated anti-C. pneumoniae antibody titers, the risk of subsequent adverse cardiovascular events (i.e., MI, unstable angina requiring IV therapy, coronary angioplasty, or coronary artery bypass, cardiovascular death) during a follow-up period averaging 18 months was reduced in individuals who received azithromycin (500 mg daily for 3-6 days) compared with C. pneumoniae-seropositive individuals who received placebo and was similar to that in men who were C. pneumoniae seronegative. However, these results were not confirmed in other studies. In a large study in stable patients with documented MI (at least 6 weeks previously) and serologic evidence of exposure to C. pneumoniae, those who received azithromycin (600 mg daily for 3 days then once weekly for 11 weeks) had a 7% (nonsignificant) reduction in the risk of the primary endpoint (death, MI, coronary revascularization procedure, hospitalization for angina) compared with placebo. Because efficacy has not been proven to date, use of azithromycin for prevention of recurrent CAD is not recommended.
Azithromycin has been used in the treatment of cholera caused by Vibrio cholerae O1 or O139.
A tetracycline or, alternatively, a fluoroquinolone or co-trimoxazole generally is used for the treatment of cholera in conjunction with fluid and electrolyte replacement therapy. Although further study is needed, azithromycin may be an alternative, especially for treatment of cholera in children or infections caused by V. cholerae resistant to tetracyclines and fluoroquinolones.
Gonorrhea and Associated Infections
Azithromycin is used orally for the treatment of uncomplicated gonorrhea (i.e., urethritis and/or crevices) caused by susceptible N. gonorrhoeae.
The CDC and many clinicians currently recommend that uncomplicated gonorrhea in adults and adolescents be treated with a single IM dose of ceftriaxone or a single oral dose of cefixime given in conjunction with an anti-infective regimen effective for presumptive treatment of chlamydia (e.g., a single dose of oral azithromycin or a 7-day regimen of oral doxycycline). Although not recommended for routine use, the CDC and other clinicians state that the single 2-g azithromycin regimen of a conventional preparation can be used as an alternative for the treatment of uncomplicated gonorrhea when preferred drugs cannot be used (e.g., in patients hypersensitive to cephalosporins when spectinomycin is unavailable and desensitization to cephalosporins is not an option).
Limited data suggest that a single 2-g oral dose of a conventional formulation of azithromycin is as effective as a single 250-mg IM dose of ceftriaxone in the treatment of uncomplicated gonorrhea. However, the 2-g azithromycin regimen has been associated with a relatively high incidence of adverse GI effects and does not appear to offer any advantages over IM ceftriaxone for the treatment of uncomplicated gonorrhea.
Although a single 1-g oral dose of a conventional formulation of azithromycin also has been effective in some patients for the treatment of uncomplicated gonorrhea, this lower single-dose regimen has been associated with a substantial incidence of therapeutic failure in some studies. Therefore, the CDC does not recommend use of a 1-g single-dose azithromycin regimen.
The fact that N. gonorrhoeae with reduced susceptibility to azithromycin have been isolated in the US should be considered.
(See Resistance: Resistance in Neisseria and Treponema.)Because of concerns related to emerging resistance to macrolides, the CDC recommends that azithromycin be used for the treatment of gonorrhea only when considered necessary.
Granuloma Inguinale (Donovanosis)
Oral azithromycin (1 g once weekly) reportedly has been effective in the treatment of granuloma inguinale (donovanosis), a chronic, progressively destructive sexually transmitted disease caused by Klebsiella granulomatis (formerly Calymmatobacterium granulomatis).
The CDC and AAP recommend that donovanosis be treated with a regimen of oral doxycycline or, alternatively, an oral regimen of azithromycin, ciprofloxacin, erythromycin, or co-trimoxazole. Anti-infective treatment of donovanosis should be continued until all lesions have healed completely; a minimum of 3 weeks of treatment usually is necessary. If lesions do not respond within the first few days of therapy, the CDC recommends that a parenteral aminoglycoside (e.g., 1 mg/kg of gentamicin IV every 8 hours) be added to the regimen. Anti-infective therapy appears to halt progressive destruction of tissue, although prolonged duration of therapy often is required to enable granulation and re-epithelization of ulcers. Despite effective anti-infective therapy, donovanosis may relapse 6-18 months later.
Individuals with HIV infection should receive the same treatment regimens recommended for other individuals with donovanosis; however, the CDC suggests that addition of a parenteral aminoglycoside to the regimen should be strongly considered in HIV-infected patients.
Any individual who had sexual contact with a patient with donovanosis should be examined and treated if they had sexual contact with the patient during the 60 days preceding the onset of symptoms in the patient and they have clinical signs and symptoms of the disease. The value of empiric therapy in the absence of clinical signs and symptoms has not been established.
Helicobacter pylori Infection and Duodenal Ulcer Disease
Azithromycin has been used in multiple-drug regimens for the treatment of Helicobacter pylori infection and peptic ulcer disease. However, data from a limited number of clinical studies indicate that such combination regimens generally are associated with a high incidence of adverse effects (principally GI effects) or low H. pylori eradication rates (i.e., 50-70%). For more information on the treatment of H. pylori infection and peptic ulcer disease, .
Oral or IV azithromycin is used for the treatment of Legionnaires' disease caused by Legionella pneumophila. Macrolides (usually azithromycin) or fluoroquinolones are considered the drugs of choice for the treatment of pneumonia caused by L. pneumophila; alternatives are doxycycline or co-trimoxazole. An oral regimen (e.g., azithromycin, clarithromycin, doxycycline, erythromycin, a fluoroquinolone) may be effective for patients with mild to moderate Legionnaires' disease. However, a parenteral regimen (e.g., azithromycin, a fluoroquinolone) usually is necessary for the initial treatment of severe Legionnaires' disease and the addition of oral rifampin is recommended during the first 3-5 days therapy in severely ill and/or immunocompromised patients; after a response is obtained, rifampin can be discontinued and therapy changed to an oral regimen.
Some clinicians suggest that azithromycin may be the preferred macrolide for the treatment of severe Legionnaires' disease and may also be preferred for empiric therapy in patients with severe community-acquired pneumonia that may be caused by Legionella.
(See Community-acquired Pneumonia under Uses: Respiratory Tract Infections.)
Azithromycin is considered an alternative for the treatment of leptospirosis caused by Leptospira. Penicillin G is the drug of choice for severe infections; tetracyclines (usually doxycycline) or ceftriaxone are recommended as alternatives for less severe infections. Azithromycin also has been effective.
Although further study is needed, azithromycin has been used in conjunction with an antimalarial agent (e.g., chloroquine, quinine, artesunate [not commercially available in the US]) for the treatment of uncomplicated malaria caused by Plasmodium falciparum, including multidrug-resistant strains. Azithromycin should not be used alone as monotherapy for the treatment of malaria.
Although further study is needed, azithromycin has been used for the treatment or prevention of P. vivax malaria. When used for treatment of such infections, the rate of resolution of parasitemia reported for azithromycin was considerably slower than that reported for chloroquine.
Mycobacterium avium Complex (MAC) Infections
Primary Prevention of Disseminated MAC Infection
Oral azithromycin is used to prevent Mycobacterium avium complex (MAC) bacteremia and disseminated infections (primary prophylaxis) in adults, adolescents, and children with advanced HIV infection. Azithromycin and clarithromycin are the preferred drugs for primary prevention of disseminated MAC infections in adults, adolescents, and children.
In controlled trials, azithromycin monotherapy was more effective than placebo or rifabutin monotherapy in preventing disseminated MAC infection in patients with advanced HIV infection (CD4 T-cell counts less than 100/mm) and infrequently resulted in the development of resistant organisms. In a placebo-controlled trial, the cumulative incidence rate of MAC infection at 1 year in patients receiving azithromycin 1.2 g once weekly as a conventional formulation was 10.9% less than that in patients receiving placebo (19.1 versus 8.2% incidence, respectively), while both groups had a comparable incidence of adverse effects. In a randomized, comparative study in patients with advanced HIV infection (CD4 T-cell counts less than 100/mm), prophylaxis with rifabutin (300 mg daily), azithromycin (1.2 g once weekly as a conventional formulation), or both drugs concomitantly was associated with a cumulative incidence of MAC infection at 1 year of 15.2, 7.6, or 2.8%, respectively. All patients also received fluconazole (200 mg daily or 400 mg once weekly) for prevention of fungal infections. The risk of MAC infection (after adjustment for baseline CD4 T-cell counts) in patients receiving azithromycin prophylaxis was 47% lower than that with rifabutin prophylaxis, while prophylaxis with both drugs reduced the risk by 72% compared with rifabutin alone.
The incidences of bacterial infections (e.g., pneumonia, sinusitis) and of manifestations of disseminated MAC infection (e.g., fever, night sweats, weight loss, anemia) in this study were lower with azithromycin or azithromycin-rifabutin prophylaxis than with rifabutin prophylaxis or placebo. Analyses of the occurrence of Pneumocystis carinii pneumonia in these patients indicated that prophylaxis with azithromycin (alone or combined with rifabutin) provided additional protection against this opportunistic infection (45% risk reduction) compared with that provided by rifabutin alone in patients without previous P. carinii episodes; no additional benefit from azithromycin was observed to enhance when azithromycin was used as secondary prophylaxis (i.e., in patients with prior P. carinii episodes). Of patients in whom prophylaxis with azithromycin was unsuccessful, resistance to azithromycin (and clarithromycin) was found in 11%. The overall incidence of adverse effects was similar among the 3 groups (i.e., 76, 88, or 90% of patients receiving rifabutin, azithromycin, or combined rifabutin-azithromycin prophylaxis, respectively), although dose-limiting adverse effects (principally GI effects) occurred more frequently with combined azithromycin-rifabutin prophylaxis (23% of patients) than with rifabutin (16%) or azithromycin (13%) prophylaxis.
Primary prophylaxis against MAC disease is recommended for HIV-infected adults and adolescents (13 years of age or older) who have CD4 T-cell counts less than 50/mm. Severely immunocompromised HIV-infected children younger than 13 years of age also should receive primary prophylaxis against MAC according to the following age-specific CD4 T-cell counts: children 6-13 years of age, less than 50 cells/mm; children 2-6 years of age, less than 75 cells/mm; children 1-2 years of age, less than 500 cells/mm; and children less than 1 year of age, less than 750 cells/mm.
There is evidence that the combination of azithromycin and rifabutin is more effective than azithromycin alone for primary MAC prophylaxis; however, routine prophylaxis with the combination is not recommended because of additional cost, increased incidence of adverse effects, and absence of a difference in survival in patients receiving the combination compared with azithromycin alone.
Current evidence indicates that primary MAC prophylaxis can be discontinued with minimal risk of developing disseminated MAC disease in HIV-infected adults and adolescents who have responded to highly active antiretroviral therapy (HAART) with an increase in CD4 T-cell counts to greater than 100/mm that has been sustained for at least 3 months. Discontinuance of primary prophylaxis against MAC is recommended in adults and adolescents meeting these criteria because prophylaxis in these individuals appears to add little benefit in terms of disease prevention for MAC or bacterial infections, and discontinuance reduces the medication burden, the potential for toxicity, drug interactions, selection of drug-resistant pathogens, and cost. However, primary MAC prophylaxis should be restarted in adults and adolescents if CD4 T-cell counts decrease to less than 50-100/mm. The safety of discontinuing MAC prophylaxis in children whose CD4 T-cell counts have increased as a result of highly active antiretroviral therapy has not been studied to date.
HIV-infected pregnant women are at risk for MAC disease, and chemoprophylaxis should be given to such women who have T-cell counts less than 50/mm. However, some clinicians may choose to withhold prophylaxis during the first trimester of pregnancy because of general concerns regarding drug administration during this period. Of the available agents, azithromycin usually is considered the drug of choice for MAC disease prophylaxis in HIV-infected pregnant women because of the drug's safety profile in animal studies and anecdotal information on safety in humans.
HIV-infected patients who develop MAC disease while receiving prophylaxis for the infection require treatment with a multiple-drug regimen since monotherapy results in drug resistance and clinical failure.
Treatment and Prevention of Recurrence of Disseminated MAC Infection
Azithromycin is used as part of a multiple-drug regimen for the treatment of disseminated MAC infections and for prevention of recurrence (secondary prophylaxis or chronic maintenance therapy) of MAC infections in HIV-infected patients.
For the treatment of disseminated MAC infections in HIV-infected adults, adolescents, and children, the ATS, CDC, NIH, IDSA, and other clinicians recommend a regimen of clarithromycin (or azithromycin) and ethambutol and state that consideration may be given to adding a third drug (preferably rifabutin). Some clinicians state that clarithromycin is the preferred macrolide for the initial treatment regimen because of mo