Uses
Clarithromycin is used orally for the treatment of pharyngitis and tonsillitis, mild to moderate respiratory tract infections (acute bacterial exacerbation of chronic bronchitis, acute maxillary sinusitis, community-acquired pneumonia), uncomplicated skin and skin structure infections, and acute otitis media caused by susceptible organisms. Clarithromycin also is used orally in the treatment of disseminated infections caused by Mycobacterium avium complex (MAC) in patients with advanced human immunodeficiency virus (HIV) infection and for prevention of disseminated MAC infection (both primary and secondary prophylaxis) in HIV-infected individuals.
Oral clarithromycin is used in combination with amoxicillin and lansoprazole or omeprazole (triple therapy) for the treatment of Helicobacter pylori infection and duodenal ulcer disease. Clarithromycin also is used orally in combination with omeprazole (dual therapy) or ranitidine bismuth citrate for the treatment of H. pylori infection in patients with an active duodenal ulcer. Clarithromycin also has been used orally in other multiple-drug regimens (with or without amoxicillin, lansoproprazole, omeprazole, or ranitidine bismuth citrate) for the treatment of H. pylori infection associated with peptic ulcer disease.
Safety and efficacy of clarithromycin extended-release tablets have been established only for the treatment of certain respiratory tract infections in adults (acute bacterial exacerbations of chronic bronchitis, acute maxillary sinusitis, community-acquired pneumonia); safety and efficacy of the extended-release formulation of the drug have not been established for the treatment of other infections that are treated with clarithromycin conventional tablets or oral suspension.
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Acute Otitis Media
Clarithromycin (conventional tablets, oral suspension) is used for the treatment of acute otitis media (AOM) caused by Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae in children. 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, oral clarithromycin, and oral loracarbef, have been used in the treatment of AOM. The American Academy of Pediatrics (AAP), US 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.
Clarithromycin is not considered a first-line agent for treatment of AOM, but is recommended as an alternative 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 controlled clinical trials of therapy for children with otitis media in areas of the US where the rate of β-lactamase-producing bacteria is high, clarithromycin therapy was compared with cephalosporin therapy alone or other antibiotic therapy with a concomitant β-lactamase inhibitor. In these studies, the combined clinical success rate (i.e., cure plus improvement) for clarithromycin therapy ranged from 88-91%, while that for the comparison therapies was 91%. The overall clinical success rate (i.e., presumed bacterial eradication/clinical cure outcomes) for clarithromycin ranged from 81-83%, while that for the comparison agents ranged from 73-97%. In all studies, the adverse effects associated with any therapy were principally GI related (e.g., diarrhea, vomiting), with a similar or lower incidence of effects occurring in the clarithromycin-treated group as compared with group treated with the comparison agent.
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Pharyngitis and Tonsillitis
Clarithromycin (conventional tablets, oral suspension) is used for the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci) in adults and children. Although clarithromycin generally is effective in the 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 clarithromycin-resistant strains have been reported in the US.
(See Resistance: Resistance in Gram-positive Bacteria.) Because penicillin has a narrow spectrum of activity, is inexpensive, and generally 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 alternatives.
In a limited number of controlled, comparative studies, microbiologic and clinical response rates of approximately 90% or greater were achieved in patients 12 years of age or older who received oral therapy with either clarithromycin 250 mg every 12 hours, penicillin V 250 mg every 6 hours, or erythromycin 500 mg every 12 hours; most patients were treated for approximately 7-10 days. Comparable clinical and microbiologic response rates have been reported in children as young as 6 months of age who received clarithromycin 7.5 mg/kg (maximum dose: 250 mg) twice daily or penicillin V 13.3 mg/kg (maximum dose: 500 mg) 3 times daily as oral suspensions.
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Respiratory Tract Infections
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Acute Exacerbations of Chronic Bronchitis
Clarithromycin (conventional tablets, oral suspension, extended-release tablets) is used for the treatment of acute bacterial exacerbations of chronic bronchitis caused by H. influenzae, H. parainfluenzae, M. catarrhalis, or S. pneumoniae in adults. Data from a limited number of studies from which patients with β-lactamase-positive infections generally were excluded suggest similar clinical and microbiologic efficacy for oral clarithromycin and oral ampicillin in these infections.
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Acute Sinusitis
Clarithromycin (conventional tablets, oral suspension) is used for the treatment of acute maxillary sinusitis caused by H. influenzae, M. catarrhalis, or S. pneumoniae in adults or children; clarithromycin (extended-release tablets) is used for the treatment of these infections in adults.
In one study in patients with acute maxillary sinusitis caused principally by S. pneumoniae or Haemophilus spp., oral therapy with clarithromycin 500 mg every 12 hours or amoxicillin 500 mg every 8 hours for 9-11 days resulted in clinical response in 91% of patients in each group, with similar microbiologic responses. All microbiologic treatment failures in patients receiving clarithromycin involved Haemophilus spp. However, patients with β-lactamase-producing organisms were excluded from this study, and bacteriologic response rates may not be representative of those generally encountered in clinical practice. Limited data from another study in patients with acute maxillary sinusitis suggest that oral clarithromycin 500 mg every 12 hours or amoxicillin and clavulanate potassium 500 mg every 8 hours produce comparable clinical and bacteriologic responses.
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Community-acquired Pneumonia
Clarithromycin (conventional tablets, oral suspension) is used for the treatment of mild to moderate community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae, Chlamydophila pneumoniae (Chlamydia pneumoniae), or S. pneumoniae in adults and children; clarithromycin (conventional tablets, oral suspension) also is used in adults for the treatment of CAP caused by H. influenzae. In addition, clarithromycin (extended-release tablets) is used in adults for the treatment of CAP caused by H. influenzae, H. parainfluenzae, M. catarrhalis, M. pneumoniae, C. pneumoniae, or S. pneumoniae.
Limited data in patients with CAP caused by these pathogens suggest that oral therapy with clarithromycin given twice daily generally is as effective as erythromycin given 2-4 times daily.
Initial treatment of CAP generally involves use of an empiric anti-infective regimen based on the most likely pathogens; therapy may then be changed (if possible) to a pathogen-specific regimen 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.
For information on recommendations of the IDSA and American Thoracic Society (ATS) regarding use of clarithromycin and other macrolides in empiric regimens for the inpatient or outpatient treatment of CAP, see Community-acquired Pneumonia under Uses: Respiratory Tract Infections, in the Erythromycins General Statement 8:12.12.04.
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Skin and Skin Structure Infections
Clarithromycin (conventional tablets, oral suspension) is used in adults and children for the treatment of uncomplicated skin and skin structure infections caused by Staphylococcus aureus or S. pyogenes. Some data in adults and children suggest that oral clarithromycin has efficacy comparable to that of oral erythromycin or an oral cephalosporin (e.g., cefadroxil) in treating various bacterial skin and skin structure infections (e.g., impetigo, cellulitis). Further comparative studies are needed to determine the relative efficacy of clarithromycin versus other anti-infective agents in treating various skin and skin structure infections, and other drugs (e.g., an oral penicillinase-resistant penicillin or cephalosporin) generally are preferred for the treatment of these infections.
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Helicobacter pylori Infection and Duodenal Ulcer Disease
Clarithromycin (conventional tablets) is used in conjunction with amoxicillin and lansoprazole or omeprazole (triple therapy) for the treatment of Helicobacter pylori (formerly Campylobacter pylori or C. pyloridis) infection in patients with duodenal ulcer disease (active or up to 1-year history of duodenal ulcer). Clarithromycin also is used in conjunction with omeprazole (dual therapy) or ranitidine bismuth citrate for the treatment of H. pylori infection in patients with an active duodenal ulcer. Clarithromycin also has been used orally in other multiple-drug regimens (with or without amoxicillin, omeprazole, lansoprazole, or ranitidine bismuth citrate) for the treatment of H. pylori infection associated with peptic ulcer disease. While some evidence indicates that combined therapy with 2 drugs (e.g., clarithromycin-omeprazole, ranitidine bismuth citrate-omeprazole, amoxicillin-omeprazole) can successfully eradicate H. pylori infection and prevent recurrence of duodenal ulcer at least in the short term (e.g., at 6 months following completion of anti-H. pylori therapy), the American College of Gastroenterology (ACG) and some clinicians currently recommend anti-H. pylori regimens consisting of at least 3 drugs (e.g., 2 anti-infective agents plus a proton-pump inhibitor) because of enhanced H. pylori eradication rates, decreased treatment failures due to resistance, and shorter treatment periods compared with those apparently required with 2-drug regimens.
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Pathogenesis
Current epidemiologic and clinical evidence supports a strong association between gastric infection with H. pylori and the pathogenesis of duodenal and gastric ulcers; with the exception of ulcers associated with gastrinoma (Zollinger-Ellison syndrome) or use of NSAIAs, almost all cases of duodenal ulcer and most cases of gastric ulcer are associated with H. pylori infection.
Although H. pylori eradication (generally defined as the absence of H. pylori organisms in the stomach documented at least 1 month after completion of anti-H. pylori therapy) reduces ulcer relapse rates, other factors appear to be essential for the development of peptic ulcer because most individuals with H. pylori infection do not develop peptic ulcers, and such ulcers are healed by various other therapies despite the presence of the organism in the stomach. Once acquired, H. pylori infection may persist for decades or even for life, causing chronic inflammation, although most infected individuals reportedly are asymptomatic. Since type B active chronic gastritis is caused by H. pylori infection and may eventually progress to chronic atrophic gastritis, a well- recognized risk factor for gastric carcinoma, long-term H. pylori infection also has been implicated as a risk factor for gastric cancer. However, whether eradication of H. pylori ultimately will reduce the incidence of gastric carcinoma remains to be established, and most clinicians currently do not advocate the use of anti-H. pylori therapy solely as a potential means of lowering the risk of gastric cancer given the prevalence of H. pylori infection in the general population and the potential costs and complications of current treatment regimens.
Although H. pylori eradication (generally defined as the absence of H. pylori organisms in the stomach documented at least 1 month after completion of anti-H. pylori therapy) reduces ulcer relapse rates, other factors appear to be essential for the development of peptic ulcer because most individuals with H. pylori infection do not develop peptic ulcers, and such ulcers are healed by various other therapies despite the presence of the organism in the stomach. Once acquired, H. pylori infection may persist for decades or even for life, causing chronic inflammation, although most infected individuals reportedly are asymptomatic. Since type B active chronic gastritis is caused by H. pylori infection and may eventually progress to chronic atrophic gastritis, a well- recognized risk factor for gastric carcinoma, long-term H. pylori infection also has been implicated as a risk factor for gastric cancer. However, whether eradication of H. pylori ultimately will reduce the incidence of gastric carcinoma remains to be established, and most clinicians currently do not advocate the use of anti-H. pylori therapy solely as a potential means of lowering the risk of gastric cancer given the prevalence of H. pylori infection in the general population and the potential costs and complications of current treatment regimens.
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Therapeutic Regimens
Conventional antiulcer therapy with H2-receptor antagonists, proton-pump inhibitors, sucralfate, and/or antacids heals ulcers but generally is ineffective in eradicating H. pylori, and such therapy is associated with a high rate of ulcer recurrence (e.g., 60-100% per year). Several useful therapeutic regimens for H. pylori-associated peptic ulcer disease have been identified, and the ACG, the National Institutes of Health (NIH), and most clinicians currently recommend that all patients with initial or recurrent duodenal or gastric ulcer and documented H. pylori infection receive anti-infective therapy for treatment of the infection.
The optimum regimen for treatment of H. pylori infection has not been established; however, combined therapy with 3 drugs that have activity against H. pylori (e.g., a bismuth salt, metronidazole, and tetracycline or amoxicillin) has been effective in eradicating the infection, resolving associated gastritis, healing peptic ulcer, and preventing ulcer recurrence in many patients with H. pylori-associated peptic ulcer disease. Although such 3-drug regimens typically have been administered for 10-14 days, current evidence principally from studies in Europe suggests that 1 week of such therapy provides H. pylori eradication rates comparable to those of longer treatment periods. Other regimens that combine one or more anti-infective agents (e.g., clarithromycin, amoxicillin) with a bismuth salt and/or an antisecretory agent (e.g., omeprazole, lansoprazole, H2-receptor antagonist) also have been used successfully for H. pylori eradication, and the choice of a particular regimen should be based on the rapidly evolving data on optimal therapy, including consideration of the patient's prior exposure to anti-infective agents, the local prevalence of resistance, patient compliance, and costs of therapy.Current data suggest that eradication of H. pylori infection using regimens consisting of 1 or 2 anti-infective agents with a bismuth salt and/or an H2-receptor antagonist or proton-pump inhibitor (e.g., omeprazole, lansoprazole) is cost effective compared with intermittent or continuous maintenance therapy with an H2-receptor antagonist (considering the costs associated with ulcer recurrence, including endoscopic or other diagnostic procedures, physician visits, and/or hospitalization).
The ACG and some clinicians currently state that an H. pylori eradication rate of approximately 90% with a 1-week treatment period represents a realistic goal of therapy for H. pylori infection. However, some clinicians state that results of 1-week anti-H. pylori regimens in Europe generally have been superior to those conducted in the US to date and that additional US studies with these regimens are needed to confirm the efficacy of 1-week regimens in the US. Although high eradication rates have been achieved with standard 3-drug, bismuth-based regimens (e.g., bismuth-metronidazole-tetracycline or bismuth- metronidazole-amoxicillin), such regimens typically involve administration of many tablets/capsules and have been associated with a relatively high (although variable) incidence of adverse effects. In addition, the efficacy of these regimens generally is unacceptable in patients with H. pylori strains resistant to the imidazole anti-infective (e.g., metronidazole) component.
Current evidence suggests that inclusion of a proton-pump inhibitor (e.g., omeprazole, lansoprazole) in anti-H. pylori regimens containing 2 anti-infectives enhances effectiveness, and limited data suggest that such regimens retain good efficacy despite imidazole (e.g., metronidazole) resistance. Therefore, the ACG and many clinicians currently recommend 1 week of therapy with a proton-pump inhibitor and 2 anti-infective agents (usually clarithromycin and amoxicillin or metronidazole), or a 3-drug, bismuth-based regimen (e.g., bismuth-metronidazole-tetracycline) concomitantly with a proton-pump inhibitor, for treatment of H. pylori infection. Although few comparative studies have been performed, such regimens appear to provide high (e.g., 85-90%) H. pylori eradication rates, are well tolerated, and may be associated with better patient compliance than more prolonged therapy. The ACG states that in a cost-sensitive environment, an alternative regimen consisting of a bismuth salt, metronidazole, and tetracycline for 14 days is a reasonable choice in patients who are compliant and in whom there is a low expectation of metronidazole resistance (no prior exposure to the drug and a low regional prevalence of resistance).
Current data suggest that modification of bismuth-metronidazole-tetracycline regimens by substituting clarithromycin for metronidazole or amoxicillin (but not ampicillin) for tetracycline also results in effective therapy, but the substitution of either amoxicillin or another tetracycline derivative (i.e., doxycycline) for tetracycline hydrochloride in such regimens reduces efficacy. While azithromycin has been used in a limited number of multiple-drug regimens (e.g., with tetracycline, metronidazole, bismuth salts, and/or omeprazole) for the treatment of Helicobacter pylori infection and peptic ulcer disease, such combination regimens generally have been associated with a high incidence of adverse effects (principally GI effects) or low H. pylori eradication rates (e.g., 50-70%). Additional controlled, comparative studies and long-term follow-up are needed to determine optimal drug regimens for H. pylori-associated peptic ulcer and to elucidate the effects of H. pylori eradication on potential long- term complications of peptic ulcer disease such as GI bleeding and gastric carcinoma.
Current evidence suggests that eradication of H. pylori by anti-infective agents may be facilitated by increased gastric pH, and many clinicians recommend concomitant treatment with antisecretory agents (e.g., omeprazole, lansoprazole, H2-receptor antagonists) to enhance ulcer healing and symptom relief while allowing relatively short (e.g., 1-week) treatment periods in patients with active peptic ulcer disease. Eradication rates of almost 100% have been reported with addition of omeprazole to a 3-drug anti-H. pylori regimen. Therapy with an antisecretory drug and a single anti-infective agent (i.e., ''dual therapy'') also has been used successfully for treatment of H. pylori infection. However, rates of H. pylori eradication have varied considerably in some studies using combined therapy with 2 drugs (e.g., amoxicillin and omeprazole) depending on dosage, timing of administration, and possibly the age of the patient. An analysis of pooled data from a number of studies in which combined therapy with omeprazole and either amoxicillin or clarithromycin was used indicate H. pylori eradication rates averaging approximately 55-62% with amoxicillin-omeprazole and 67-75% with clarithromycin-omeprazole therapy.
In 4 randomized, controlled trials in patients with active duodenal ulcer, combined therapy with clarithromycin (500 mg 3 times daily for 14 days) and omeprazole (40 mg daily for 14 days followed by either 20 or 40 mg daily for an additional 14 days) was successful in eradicating H. pylori (defined as 2 negative tests for H. pylori 4 weeks after the end of treatment) in 64-83% of patients compared with 0-1% of patients receiving omeprazole alone or (in 2 trials) 31-39% of patients receiving clarithromycin alone. Ulcer healing rates at 4 weeks averaged 94-100% with clarithromycin-omeprazole treatment, 88- 99% with omeprazole alone, and (in 2 trials) 64-71% with clarithromycin alone. In addition, follow-up evaluations at 6 months in patients whose ulcers were healed demonstrated a reduction in ulcer recurrence in patients in whom H. pylori was eradicated. In 2 other randomized, controlled trials in patients with active duodenal ulcer, eradication of H. pylori (defined as 2 negative tests for H. pylori 4 weeks after the end of anti-H. pylori treatment) was achieved in 72 or 71% of patients receiving 2 weeks of combined therapy with clarithromycin (500 mg 2 or 3 times daily, respectively) and ranitidine bismuth citrate (400 mg twice daily) followed by 2 weeks of monotherapy with ranitidine bismuth citrate (400 mg 2 times daily). Follow-up evaluations demonstrated a twofold reduction in the risk of ulcer recurrence within 6 months of completing treatment in patients in whom H. pylori was eradicated compared with those in whom the infection was not eradicated. The contribution, if any, of bismuth citrate to the healing effects of ranitidine alone was not evaluated in these studies.
While some studies demonstrate that certain 2-drug anti-H. pylori regimens (e.g., clarithromycin-omeprazole, ranitidine bismuth citrate-omeprazole, amoxicillin-omeprazole) can successfully eradicate H. pylori infection and prevent recurrence of duodenal ulcer at least in the short term (e.g., at 6 months following completion of anti-H. pylori therapy), 3-drug regimens appear to be associated with higher H. pylori overall eradication rates than dual-therapy combinations. In 2 randomized, controlled trials in patients with H. pylori infection and duodenal ulcer disease (i.e., active ulcer or history of an ulcer within 1 year) who received triple therapy for 14 days with clarithromycin (500 mg twice daily), amoxicillin (1 g twice daily), and lansoprazole (30 mg twice daily), H. pylori was eradicated (defined as 2 negative tests for H. pylori by culture or histology 4-6 weeks after the end of anti-H. pylori treatment) in 92 or 86% of evaluable patients (86 or 83% of patients, respectively, by intent- to-treat analysis); while dual therapy with lansoprazole (30 mg 3 times daily) and amoxicillin (1 g 3 times daily) for 14 days produced H. pylori eradication in 77 or 66% of evaluable patients (70 or 61% of patients, respectively, by intent-to-treat analysis). Therapy with the 3-drug combination was more effective than all possible dual-therapy combination regimens with these drugs (i.e., lansoprazole-amoxicillin, lansoprazole-clarithromycin, and amoxicillin-clarithromycin).
In 3 randomized, double-blind trials in patients with H. pylori infection and duodenal ulcer disease (active ulcer or a history of duodenal ulcer in the previous 5 years) who were treated for 10 days, triple therapy with clarithromycin (500 mg twice daily), amoxicillin (1 g twice daily), and omeprazole (20 mg twice daily) eradicated H. pylori (defined as 2 negative and no positive tests for H. pylori as assessed by CLOtest, histology, and/or culture) in 77, 78, or 90% of evaluable patients (69, 73, or 83% of patients, respectively, by intent- to-treat analysis); dual therapy with clarithromycin and amoxicillin eradicated H. pylori infection in 43, 41, or 33% of evaluable patients (37, 36, or 32% of patients, respectively, by intent-to-treat analysis). In 2 of these studies, patients receiving the triple-therapy regimen for eradication of H. pylori continued omeprazole 20 mg daily for an additional 18 days.
The ACG and some clinicians currently state that anti-H. pylori regimens consisting of at least 3 drugs (e.g., 2 anti-infective agents plus a proton-pump inhibitor) are recommended because of enhanced H. pylori eradication rates, decreased failures secondary to resistance, and shorter treatment periods (e.g., 1 week) compared with those apparently required with 2-drug regimens (e.g., 10-14 days). Additional randomized, controlled studies comparing various anti-H. pylori regimens are needed to clarify optimum drug combinations, dosages, and duration of treatment for H. pylori infection.
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Duration of Therapy
The minimum duration of therapy required to eradicate H. pylori infection in peptic ulcer disease has not been fully established. In a randomized trial in patients with H. pylori infection and duodenal ulcer disease, 10 days of therapy with clarithromycin (500 mg twice daily), amoxicillin (1 g twice daily), and lansoprazole (30 mg twice daily) was as effective in eradicating H. pylori as 14 days of therapy with this drug regimen; H. pylori eradication was achieved in 85% of evaluable patients with the 14-day regimen compared with 84% of those receiving the 10-day regimen (82 versus 81% of patients, respectively, by intent-to-treat analysis). In patients with uncomplicated ulcers who receive a proton-pump inhibitor (e.g., omeprazole) plus 2 anti-infective agents or a proton-pump inhibitor and bismuth-tetracycline-metronidazole, the ACG and many clinicians state that treatment for longer than 1 week probably is not necessary. However, more prolonged anti-infective and/or antisecretory therapy is recommended for patients with complicated, large, or refractory ulcers; therapy in such patients should be continued at least until successful eradication of H. pylori has been confirmed.
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Resistant and Recurrent Infection
The optimum method of treating patients who fail to respond to currently recommended anti-H. pylori regimens is unknown. However, clarithromycin or metronidazole should not be used subsequently in patients with H. pylori infection who fail therapy that includes these drugs since resistance commonly emerges during such unsuccessful therapy.
Rapid development of resistance by H. pylori to certain drugs (e.g., metronidazole, clarithromycin and other macrolides, quinolones) has occurred when these drugs were used as monotherapy or as the only anti-infective agent in anti-H. pylori regimens. Resistance commonly emerges during therapy with clarithromycin or metronidazole when eradication of H. pylori is not achieved; therefore, prior exposure to these anti-infectives predicts resistance in individual patients and should be considered when selecting anti-H. pylori treatment regimens. Clarithromycin-containing regimens should not be used for eradication of H. pylori in patients with known or suspected clarithromycin-resistant isolates because of reduced efficacy in such patients.
(See Cautions: Precautions and Contraindications.) Some clinicians state that the same anti-infective regimen should not be used for retreatment of H. pylori infection even if antibiotic resistance has not developed. In clinical trials in patients who received clarithromycin as the sole anti-infective agent in combination regimens for H. pylori infection, some H. pylori isolates demonstrated an increase in clarithromycin MICs over time, indicating decreased susceptibility and increasing resistance to the drug. Agents that do not induce resistance in H. pylori include amoxicillin, tetracycline, and bismuth; 1 or 2 of these drugs generally are included in regimens that contain metronidazole or clarithromycin. The ACG states that possible regimens for treatment of metronidazole-resistant H. pylori infections include bismuth-clarithromycin-tetracycline or omeprazole-amoxicillin-clarithromycin. In patients who develop clarithromycin resistance, the ACG suggests potential alternative therapy consisting of omeprazole, a bismuth salt, metronidazole, and tetracycline; or omeprazole, amoxicillin, and metronidazole. A regimen consisting of amoxicillin (1 g twice daily), rifabutin (300 mg daily), and a proton-pump inhibitor (pantoprazole 40 mg twice daily) for one week reportedly was effective in eradicating H. pylori (according to the results of a C urea breath test) in about 79% of patients who had failed at least 2 prior courses of anti-H. pylori therapy. Some clinicians also suggest that a 3-drug, furazolidone-containing regimen could be used in patients with metronidazole- or clarithromycin-resistant H. pylori infection.The most common cause of ulcer recurrence after anti-infective therapy for H. pylori infection is failure to eradicate the organism since reinfection with H. pylori in developed countries appears to occur very infrequently. The ACG and some clinicians state that diagnostic confirmation of H. pylori eradication is important in patients with complicated, giant, or refractory ulcers but is controversial or generally not needed in those with uncomplicated ulcers who remain asymptomatic after anti-infective therapy. If diagnostic tests for H. pylori are used, such tests should be performed at least 1 month or, preferably, longer after discontinuance of anti-H. pylori therapy to minimize the potential for false-negative test results attributable to suppression rather than eradication of the organism.
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Therapy in Children
Combined therapy with 1 or 2 anti-infective agents (e.g., generally amoxicillin with or without metronidazole) and bismuth subsalicylate in children with H. pylori infection and associated peptic ulcer disease appears to promote healing and reduces ulcer recurrence. Although the prevalence of H. pylori infection is lower in children than in adults, the organism reportedly has been identified in approximately 50% of children with gastritis or gastric ulcers and in 60% of those with duodenitis or duodenal ulcers. Limited data suggest that therapy with H2-receptor antagonists or a single antibiotic is associated with a high risk of disease recurrence; in addition, reinfection with H. pylori has been reported to be more common in children than in adults. Because the prevalence of H. pylori infection and the incidence of H. pylori-associated gastroduodenal inflammation are much lower in children than in adults, H. pylori is more likely to be associated with peptic ulcer disease when found in a child. Therefore, some clinicians have recommended that children with symptoms suggesting gastroduodenal inflammation that do not respond to antacid therapy should be evaluated for the presence of H. pylori and, if the organism is found, given therapy aimed at eradicating the infection. In a study in a limited number of children (mean age: 12.2 years) with H. pylori-associated duodenal ulcer, treatment with a 6-week regimen of bismuth subsalicylate and amoxicillin, or these 2 drugs plus metronidazole in cases of initial treatment failure, resulted in endoscopically proved eradication of the organism in 100% of patients at long- term (mean: 6.5 months) follow-up.
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Nonulcer Dyspepsia
Although it has been suggested that patients with nonulcer dyspepsia and concomitant H. pylori infection also may benefit from eradicative therapy for H. pylori, evidence from several well-designed clinical trials has been conflicting regarding an association between this organism and nonulcer dyspepsia. Nevertheless, while therapy for H. pylori eradication in such patients generally is not routinely recommended, some evidence suggests that initial anti-H. pylori therapy may be a cost-effective management strategy compared with initial endoscopy for patients with simple dyspepsia who are H. pylori-positive on noninvasive (e.g., serologic) testing.
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Bartonella Infections
Clarithromycin has been used in a few patients, including HIV-infected patients, 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 erythromycin, doxycycline, ciprofloxacin, rifampin, co-trimoxazole, gentamicin, azithromycin, clarithromycin, or third generation cephalosporins.
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Cryptosporidiosis
It has been reported that use of clarithromycin or rifabutin in HIV-infected adults for prevention of MAC infection may also decrease the incidence of cryptosporidiosis is these patients. No anti-infective agent 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, National Institutes of Health (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.
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Legionella Infections
Clarithromycin has been 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 and doxycycline and co-trimoxazole are alternatives. An oral regimen (e.g., azithromycin, erythromycin, doxycycline, clarithromycin, a fluoroquinolone) may be effective for patients with mild to moderate Legionnaires' disease. However, a parenteral regimen (e.g., azithromycin or 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 of therapy in severely ill and/or immunocompromised patients; after a response is obtained, rifampin can be discontinued and therapy changed to an oral regimen.
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Lyme Disease
Clarithromycin (500 mg twice daily for 21 days) has been used with apparent success (based on a 6-month follow-up period) in a limited number of patients with early Lyme disease. However, some evidence in patients with early Lyme disease suggests that other macrolides (e.g., azithromycin, erythromycin) may be less effective than penicillins or tetracyclines, and the IDSA, AAP, and other clinicians recommend that macrolide antibiotics not be used as first-line therapy for early Lyme disease.
Oral doxycycline or oral amoxicillin is recommended as first-line therapy for the treatment of early localized or early disseminated Lyme disease associated with erythema migrans, in the absence of neurologic involvement or third-degree atrioventricular (AV) heart block; alternatively, oral cefuroxime axetil has been used. The IDSA and other clinicians state that macrolide antibiotics should be reserved for patients who are intolerant of doxycycline, amoxicillin, and cefuroxime axetil and that patients treated with macrolides should be monitored closely. For more detailed information on the manifestations of Lyme disease and the efficacy of various anti-infective regimens in early or late Lyme disease,
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Mycobacterial Infections
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Mycobacterium avium Complex (MAC) Infections
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Primary Prevention of Disseminated MAC Infection
Clarithromycin (conventional tablets, oral suspension) is used to prevent Mycobacterium avium complex (MAC) bacteremia and disseminated infections (primary prophylaxis) in patients with advanced HIV infection. The Prevention of Opportunistic Infections Working Group of the US Public Health Service and the Infectious Diseases Society of America (USPHS/IDSA) state that either clarithromycin or azithromycin is the preferred drug for primary prevention of disseminated MAC infection in adults and pediatric patients.
Results of a limited number of controlled studies in patients with HIV infection and absolute helper/inducer (CD4, T4) T-cell counts less than 100/ mm indicate that clarithromycin used alone is more effective than placebo in preventing disseminated MAC disease; clarithromycin prophylaxis also has been shown to reduce mortality in at least one placebo-controlled study. In a randomized, double-blind study in patients with acquired immunodeficiency syndrome (AIDS) and baseline median CD4 counts of 25-30 cells/ mm, the risk of MAC infection (defined as at least one positive culture for MAC bacteria from blood or another normally sterile site) was reduced by 69% in patients receiving clarithromycin 500 mg twice daily compared with that in patients receiving placebo (6 versus 16% incidence of MAC infection with clarithromycin or placebo prophylaxis, respectively). On an intent-to-treat basis, the 1- year cumulative incidence of MAC bacteremia was 5% for patients receiving clarithromycin and 19.4% for patients receiving placebo. Clarithromycin-resistant MAC isolates developed in 11 of 19 clarithromycin recipients who developed MAC infection compared with none of the 53 placebo recipients in whom MAC bacteremia developed. Despite this higher incidence of clarithromycin resistance, clarithromycin prophylaxis was associated with reduced mortality compared with placebo, particularly during the first 12 months of the study.
During a follow-up period of about 10 months, the incidence of mortality with clarithromycin prophylaxis was 32% versus 41% with placebo, a 26% reduction. The incidences of hospitalization and of certain complications of HIV infection (e.g., pneumonia, giardiasis) also were reduced in patients receiving clarithromycin prophylaxis. Patients receiving clarithromycin also showed reductions in the manifestations of disseminated MAC disease, including fever, night sweats, weight loss, and anemia. Although the incidence of adverse effects attributed to the study drug was higher in patients receiving clarithromycin (42%) than in those receiving placebo (26%), taste perversion (11 versus 2% with clarithromycin or placebo, respectively) and rectal disorders (8 versus 3%, respectively) were the only adverse effects that occurred more frequently with clarithromycin than with placebo. The incidence of severe adverse effects was similar with clarithromycin (7%) and placebo (6%), and discontinuance of clarithromycin prophylaxis because of adverse events (principally headache, nausea, vomiting, depression and taste perversion) was required in 18% of patients receiving the drug compared with 17% of those receiving placebo.
The USPHS/IDSA recommends primary prophylaxis against MAC disease for HIV-infected adults and adolescents (13 years 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 disease 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 infants younger than 1 year of age, less than 750 cells/ mm.
Although either azithromycin or clarithromycin is the preferred drug for primary prophylaxis against MAC, the USPHS/IDSA states that rifabutin may be used if the macrolides cannot be tolerated. There is evidence from placebo-controlled studies that concomitant use of clarithromycin and rifabutin for primary prophylaxis is no more effective than clarithromycin used alone and the combination regimen appears to be associated with an increased incidence of adverse effects. Therefore, the USPHS/IDSA does not recommend concomitant use of clarithromycin and rifabutin for primary MAC prophylaxis. Although the combination of azithromycin and rifabutin is more effective than azithromycin alone for primary MAC prophylaxis, the USPHS/IDSA does not recommend this combination regimen because of additional cost, increased incidence of adverse effects, and absence of a difference in survival in patients receiving the combination compared with azithromycin prophylaxis 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. The USPHS/IDSA states that 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, the USPHS/IDSA states that 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 primary prophylaxis against the infection 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, the USPHS/IDSA considers azithromycin the drug of choice for MAC prophylaxis in HIV-infected pregnant women because of the drug's safety profile in animal studies and anecdotal information on safety in humans. Clarithromycin has demonstrated adverse effects on pregnancy outcome and/or embryo-fetal development in animals and should be used during pregnancy only in clinical circumstances where no alternative therapy is appropriate.
(See Cautions: Pregnancy, Fertility, and Lactation.) .HIV-infected patients who develop MAC disease while receiving prophylaxis for the infection require treatment with multiple drugs since monotherapy results in drug resistance and clinical failure.
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Treatment and Prevention of Recurrence of Disseminated MAC Infection
Clarithromycin (conventional tablets, oral suspension) is used as part of a multiple-drug regimen for the treatment of disseminated MAC infections and for prevention of recurrence (secondary prophylaxis) of MAC infections. Although clarithromycin has been effective when used alone for the treatment of MAC, most authorities recommend the use of multiple-drug regimens for the treatment or secondary prevention of these infections.
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 can 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 more extensive experience and because it appears to be associated with more rapid clearance of MAC from blood; however, azithromycin can be substituted if clarithromycin cannot be used because of drug interactions or intolerance and is preferred in pregnant women. Rifabutin should be included in the treatment regimen if the patient has advanced immunosuppression (CD4 T-cell count less than 50/mm) or high mycobacterial load (exceeding 2 log10 colony forming units/mL of blood) or is not receiving effective antiretroviral therapy since there is an increased risk of mortality and emergence of drug resistance. If a third drug is indicated in the treatment regimen and rifabutin cannot be used (e.g., because of drug interactions or intolerance), use of a fluoroquinolone (ciprofloxacin or levofloxacin) or amikacin can be considered.
Limited data from comparative trials suggest that concomitant use of ethambutol and clarithromycin may decrease emergence of clarithromycin-resistant MAC; however, inclusion of clofazimine in multiple-drug regimens containing clarithromycin (e.g., with or without ethambutol) does not add to the efficacy (e.g., in terms of prevention of clarithromycin resistance) of such regimens and may even be associated with reduced survival. Therefore, clofazimine should not be used for the treatment of disseminated MAC disease.
Clarithromycin appears to be one of the most active single agents against MAC; however, monotherapy with clarithromycin has been associated with clinical and bacteriologic relapse and the development of clarithromycin-resistant MAC isolates. Randomized studies in adults and children infected with HIV and MAC who had peripheral blood absolute helper/inducer (CD4, T4) T-cell counts less than 100/ mm (with most patients having such T-cell counts less than 50/ mm), demonstrated that oral monotherapy with clarithromycin (0.5-2 g twice daily in adults, 3.75-15 mg/kg twice daily in children) resulted in clinical and laboratory improvement of the MAC infection. In 52-61% of treated patients in these studies, colony counts of MAC in sequential blood cultures decreased or became absent within 29-54 days; patients also experienced decreases in the incidence of fever, night sweats, weight loss, diarrhea, splenomegaly, and hepatomegaly. However, effects of clarithromycin monotherapy were not sustained; only 8-25% of treated patients maintained negative blood cultures for 12 weeks or longer and median duration of clinical improvement was 2-6 weeks. In addition, development of drug resistance has been reported after 2-7 months of clarithromycin monotherapy.
High clarithromycin dosages (e.g., 1 or 2 g twice daily) for the treatment of disseminated MAC infection have been associated with reduced survival in some studies compared with that in patients receiving clarithromycin 500 mg twice daily; while these findings are not fully understood, dosages exceeding 500 mg twice daily currently are not recommended in HIV-infected patients with disseminated MAC infection. In randomized studies in HIV-infected patients who had peripheral blood absolute helper/inducer (CD4, T4) T-cell counts less than 100/ mm (with most patients having such T-cell counts less than 50/ mm), median survival was 199-249 or 179-215 days in adults receiving clarithromycin dosages of 0.5 or 1 g twice daily, respectively. Higher dosages (e.g., 1-2 g twice daily) of clarithromycin were associated with better bacteriologic improvement during the first 4 weeks of therapy; median time to achieve negative blood culture was 54, 41, or 29 days in patients receiving 0.5, 1, or 2 g of the drug twice daily, respectively. However, no substantial differences in the time required to achieve negative blood cultures were observed later in therapy.
To prevent recurrence of MAC disease in HIV-infected adults, adolescents, or children who have previously been treated for an acute episode of MAC infection and in whom macrolide resistance has not been documented, the USPHS/IDSA, CDC, NIH, and IDSA recommend a regimen consisting of a macrolide (clarithromycin or azithromycin) given with ethambutol (with or without rifabutin). Azithromycin usually is the preferred macrolide for use in conjunction with ethambutol for secondary prophylaxis of disseminated MAC infection in pregnant women. Secondary MAC prophylaxis generally is administered for life in adults and adolescents unless immune recovery has occurred as a result of potent antiretroviral therapy. Limited data indicate that secondary MAC prophylaxis can be discontinued in adults and adolescents who have immune recovery in response to potent antiretroviral therapy. Based on these data and more extensive cumulative data on safety of discontinuing secondary prophylaxis for other opportunistic infections, the USPHS/IDSA, CDC, NIH, and IDSA state that it may be reasonable to consider discontinuance of secondary MAC prophylaxis in adults and adolescents who have successfully completed at least 12 months of MAC therapy, have remained asymptomatic with respect to MAC, and have CD4 T-cell counts exceeding 100/ mm as the result of potent antiretroviral therapy and this increase has been sustained (e.g., for 6 months or longer). Some experts would obtain a blood culture for MAC (even in asymptomatic patients) prior to discontinuing secondary MAC prophylaxis to substantiate that the disease is no longer active. Secondary MAC prophylaxis should be restarted in adults or adolescents if CD4 T-cell counts decrease to less than 100/ mm. The safety of discontinuing secondary MAC prophylaxis in HIV-infected children receiving potent antiretroviral therapy has not been studied and children with a history of disseminated MAC should receive lifelong secondary prophylaxis.
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Treatment of Pulmonary MAC Infections in HIV-negative Adults
Clarithromycin has been used in multiple-drug regimens for the treatment of pulmonary MAC infections in patients not infected with HIV.
The ATS recommends that pulmonary MAC infections in HIV-negative adults be treated with a regimen that includes at least 3 drugs, including clarithromycin (500 mg twice daily) or azithromycin (250 mg daily or 500 mg 3 times weekly), rifabutin (300 mg daily) or rifampin (600 mg daily), and ethambutol (25 mg/kg daily for 2 months, then 15 mg/kg daily). For patients with a small body mass and/or who are older than 70 years of age, clarithromycin 250 mg twice daily or azithromycin 250 mg 3 times weekly may be better tolerated. The ATS states that the addition of streptomycin given intermittently (2 or 3 times weekly) for the first 2-3 months may be considered for patients with extensive disease.
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Other Mycobacterial Infections
Clarithromycin has been used with some success in the treatment of various other mycobacterial infections; however, further experience and study are needed to establish the role of clarithromycin in the treatment of these infections.
The ATS and other clinicians suggest that clarithromycin can be used as an alternative agent for the treatment of infections caused by M. kansasii. Although a regimen of isoniazid, rifampin, and ethambutol usually is recommended for the treatment of pulmonary or extrapulmonary infections caused by M. kansasii, the ATS states that clarithromycin is a reasonable alternative in patients who are unable to tolerate one of these drugs or when retreatment is necessary. It also has been suggested that clarithromycin may be substituted for rifampin for the treatment of M. kansasii infections in HIV-infected individuals who are receiving indinavir and therefore cannot receive concomitant rifampin. Although M. kansasii generally are susceptible to clarithromycin in vitro, clinical experience is limited and efficacy of the drug for the treatment of infections caused by this organism has not been established.
The ATS suggests that use of clarithromycin can be considered for the treatment of cutaneous infections caused by M. abscessus or M. chelonae and states that treatment of these infections should be based on results of in vitro susceptibility testing. Although there is some evidence that clarithromycin monotherapy may be effective for the treatment of cutaneous M. chelonae infections in adults, preliminary studies indicate that monotherapy with macrolides is insufficient to produce microbiologic cure for pulmonary M. abscessus infection. In an open, noncomparative trial evaluating clarithromycin in cutaneous (disseminated) infection caused by M. chelonae in a limited number of patients with immunosuppression secondary to disease (e.g., organ transplant, autoimmune disease) or drug therapy (e.g., corticosteroids, cyclophosphamide), clarithromycin (0.5-1 g twice daily for 6 months) resolved the infection in all patients completing therapy; 82% of patient who completed therapy had complete remission of the infection. Oral clarithromycin has been used in the treatment of an outbreak of cutaneous M. abscessus infections involving the hands and feet that occurred in children and one adult as the result of exposure at a public wading pool; however, the benefits of the drug in this infection are unclear since lesions eventually resolved in all patients, including those who did not receive clarithromycin treatment (with or without incision and drainage of lesions).
The ATS and others suggest that clarithromycin monotherapy is one of several acceptable regimens for the treatment of cutaneous infections caused by M. marinum.
Limited in vitro and in vivo studies suggest that clarithromycin has bactericidal activity against M. leprae, and the drug has been used with some success in multiple-drug regimens for short periods in a few patients with leprosy.
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Pertussis
Clarithromycin has been effective when used for the treatment of pertussis caused by Bordetella pertussis. In a randomized study in children 1 month to 16 years of age with culture-proven B. pertussis infection or a cough illness suspected of being pertussis, a 7-day regimen of oral clarithromycin (7.5 mg/kg twice daily) was as effective and better tolerated than a 14-day regimen of oral erythromycin (13.3 mg/kg 3 times daily).
A 14-day regimen of oral erythromycin usually is considered the drug of choice for the treatment of pertussis and for prevention in contacts of patients with pertussis. However, other macrolides (azithromycin, clarithromycin) appear to be as effective and may be associated with better compliance since they are better tolerated.
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Toxoplasmosis
Clarithromycin has been used in conjunction with pyrimethamine for the treatment of encephalitis caused by Toxoplasma gondii in a few patients with AIDS. The USPHS/IDSA states that use of clarithromycin for primary or secondary prophylaxis of toxoplasmosis in HIV-infected individuals cannot be recommended based on current data. The CDC, NIH, IDSA, and other clinicians usually recommend a regimen of pyrimethamine in conjunction with sulfadiazine and leucovorin for the treatment of toxoplasmosis in adults and children, especially immunocompromised patients (e.g., HIV-infected individuals).
For information on recommendations regarding treatment and prophylaxis of toxoplasmosis,
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Prevention of Bacterial Endocarditis
Clarithromycin has been recommended for prevention of α-hemolytic (viridans group) streptococcal endocarditis in penicillin-allergic adults and children with congenital heart disease, rheumatic or other acquired valvular heart dysfunction (even after valvular surgery), prosthetic heart valves (including bioprosthetic or allograft valves), surgically constructed systemic pulmonary shunts or conduits, hypertrophic cardiomyopathy, mitral valve prolapse with valvular regurgitation and/or thickened leaflets, or previous bacterial endocarditis (even in the absence of heart disease) who undergo dental procedures that are likely to result in gingival or mucosal bleeding (e.g., dental extractions; periodontal procedures such as scaling, root planing, probing, and maintenance; dental implant placement or reimplantation of avulsed teeth; root-filling procedures; subgingival placement of antibiotic fibers or strips; initial placement of orthodontic bands; intraligamentary local anesthetic injections; routine professional cleaning) or minor upper respiratory tract surgery or instrumentation (e.g., tonsillectomy, adenoidectomy, bronchoscopy with a rigid bronchoscope). The AHA recognizes that its current recommendations for prevention of bacterial endocarditis are empiric, since no controlled efficacy studies have been published, and that prophylaxis of endocarditis is not always effective. However, the AHA, the ADA, and most clinicians generally recommend routine use of prophylactic anti-infectives in patients at risk for bacterial endocarditis. When selecting anti-infectives for prophylaxis of recurrent rheumatic fever or prophylaxis of bacterial endocarditis, the current recommendations published by the AHA should be consulted.
