AHFS Class:

• Lincomycins 8:12.28.20

Generic Name(s):

• Clindamycin Hydrochloride

• Clindamycin Palmitate Hydrochloride

• Clindamycin Phosphate

Clindamycin, a lincosamide antibiotic, is a derivative of lincomycin.121,126,139,140,141

Clindamycin is used for the treatment of certain serious infections caused by susceptible aerobic gram-positive bacteria (staphylococci, streptococci, pneumococci) and for the treatment of certain serious infections caused by susceptible anaerobic bacteria.121,126,139 Use of clindamycin generally should be reserved for the treatment of serious infections when less toxic anti-infectives cannot be used (e.g., penicillin-allergic patients or other patients for whom a penicillin is inappropriate).126,139,201 Because clindamycin has been associated with potentially fatal colitis (see Cautions: GI Effects), the manufacturer recommends that clinicians consider the nature of the infection and the suitability of less toxic alternatives (e.g., erythromycin).121,126,139

Certain infections may require incision and drainage or other indicated surgical procedures in addition to anti-infective treatment.139 Use of clindamycin does not eliminate the need for surgical procedures when indicated.121,126,139

Because clindamycin does not distribute adequately into the CNS, the drug should not be used for the treatment of meningitis.121,126,139

Gram-positive Aerobic Bacterial Infections

Clindamycin is used orally or parenterally for the treatment of serious respiratory tract infections caused by susceptible staphylococci, Streptococcus pneumoniae , or other streptococci121,126,139,512,513,514 or serious skin and skin structure infections caused by susceptible staphylococci, S. pneumoniae , or S. pyogenes (group A β-hemolytic streptococci; GAS).121,126,139,514,543 Clindamycin also is used parenterally for the treatment of septicemia caused by susceptible Staphylococcus aureus or streptococci,139 treatment of serious bone and joint infections (including acute hematogenous osteomyelitis) caused by susceptible S. aureus ,139,590 and as adjunctive therapy in the surgical treatment of chronic bone and joint infections caused by susceptible bacteria.139 However, clindamycin generally should be reserved for use in penicillin-allergic or other patients when less toxic alternatives cannot be used.121,126,139

Anaerobic Bacterial Infections

Clindamycin is used orally or parenterally for the treatment of serious lower respiratory tract infections (e.g., empyema, pneumonia, lung abscess), serious skin and skin structure infections, septicemia, intra-abdominal infections (e.g., peritonitis, intra-abdominal abscess), and gynecologic infections (e.g., endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis, postsurgical vaginal cuff infections) caused by susceptible anaerobic bacteria.121,126,139 Parenteral clindamycin also is used for the treatment of serious bone and joint infections (including acute hematogenous osteomyelitis) caused by susceptible anaerobes and as adjunctive therapy in the surgical treatment of chronic bone and joint infections caused by susceptible bacteria.139 Although previously considered a drug of choice for the treatment of infections caused by Bacteroides ,246 clindamycin is no longer routinely recommended for the treatment of intra-abdominal infections because of the increasing incidence of B. fragilis resistant to the drug.708 In the treatment of mixed aerobic-anaerobic bacterial infections (e.g., pelvic inflammatory disease), clindamycin has been used in conjunction with an IM or IV aminoglycoside.344,345

Acute Otitis Media

Oral clindamycin is used as an alternative for the treatment of acute otitis media† (AOM).499

When anti-infective therapy is indicated for the treatment of AOM, the American Academy of Pediatrics (AAP) recommends high-dose amoxicillin or amoxicillin and clavulanate as the drug of first choice for initial treatment.499 These experts recommend certain cephalosporins (cefdinir, cefpodoxime, cefuroxime, ceftriaxone) as alternatives for initial treatment in penicillin-allergic patients who do not have a history of severe and/or recent penicillin-allergic reactions.499

AAP states that clindamycin (with or without a third generation cephalosporin) is a possible alternative for the treatment of AOM in patients who fail to respond to initial treatment with first-line or preferred alternatives.499 When retreatment of AOM is indicated after failure of initial treatment, high-dose amoxicillin and clavulanate or IM ceftriaxone usually is recommended.499 Although clindamycin may be effective in infections caused by penicillin-resistant S. pneumoniae , the drug may not be effective against multidrug-resistant S. pneumoniae and usually is inactive against Haemophilus influenzae .499 If clindamycin is used for retreatment of AOM, concomitant use of an anti-infective active against H. influenzae and Moraxella catarrhalis (e.g., cefdinir, cefixime, cefuroxime) should be considered.499

For additional information regarding treatment of AOM, including information on diagnosis and management strategies, anti-infectives for initial treatment, duration of initial treatment, and anti-infectives after initial treatment failure, see Acute Otitis Media under Uses: Otitis Media, in the Cephalosporins General Statement 8:12.06.

Pharyngitis and Tonsillitis

Oral clindamycin is used as an alternative for the treatment of pharyngitis and tonsillitis† caused by S. pyogenes (group A β-hemolytic streptococci; GAS).135,149,292,375,580 Although clindamycin usually is effective in eradicating S. pyogenes from the nasopharynx,135,147,149,580 it is reserved for use as an alternative in patients who cannot receive β-lactam anti-infectives.292,375,580 In addition, clindamycin is recommended as one of several possible alternatives for the treatment of symptomatic patients who failed to respond to initial penicillin treatment or have multiple, recurrent episodes of pharyngitis known to be caused by S. pyogenes .292,375,580

Selection of an anti-infective for the treatment of S. pyogenes pharyngitis and tonsillitis should be based on the drug's spectrum of activity, bacteriologic and clinical efficacy, potential adverse effects, ease of administration, patient compliance, and cost.292,375,580 No regimen has been found to date that effectively eradicates group A β-hemolytic streptococci in 100% of patients.375

Because the drugs have a narrow spectrum of activity, are inexpensive, and generally are effective with a low frequency of adverse effects, AAP,292 Infectious Diseases Society of America (IDSA),580 and American Heart Association (AHA)375 recommend a penicillin regimen (i.e., 10 days of oral penicillin V or oral amoxicillin or a single dose of IM penicillin G benzathine) as the treatment of choice for S. pyogenes pharyngitis and tonsillitis and prevention of initial attacks (primary prevention) of rheumatic fever.292,375,580 Other anti-infectives (e.g., oral cephalosporins, oral macrolides, oral clindamycin) are recommended as alternatives in penicillin-allergic patients.292,375,580

Respiratory Tract Infections

Clindamycin is used for the treatment of serious respiratory tract infections (e.g., pneumonia, empyema, lung abscess) caused by susceptible S. aureus , S. pneumoniae , other streptococci, or anaerobes.121,126,139,512,513,514

IDSA and American Thoracic Society (ATS) consider clindamycin an alternative agent for the treatment of community-acquired pneumonia (CAP) caused by S. pneumoniae or S. aureus (methicillin-susceptible strains) in adults.512 IDSA also considers clindamycin an alternative for the treatment of CAP caused by S. pneumoniae , S. pyogenes , or S. aureus in pediatric patients.513 For the treatment of pneumonia caused by methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA), IDSA states that clindamycin is one of several options, unless the strain is resistant to clindamycin.513,514

For information regarding the treatment of CAP, including infections caused by MRSA, the current clinical practice guidelines from IDSA available at [Web] should be consulted.512,513,514

Skin and Skin Structure Infections

Clindamycin is used for the treatment of serious skin and skin structure infections caused by susceptible staphylococci, S. pneumoniae , other streptococci, or anaerobes.121,126,139,543 Clindamycin is recommended as one of several options for the treatment of staphylococcal and streptococcal skin and skin structure infections, including those known or suspected to be caused by susceptible MRSA.514,543

Clindamycin is used in conjunction with or as an alternative to penicillin G for the treatment of clostridial myonecrosis† (gas gangrene) caused by Clostridium perfringens or other Clostridium .197,292,543

Although the fixed combination of amoxicillin and clavulanate usually is the drug of choice for the treatment of infected human or animal (e.g., dog, cat, reptile) bite wounds, alternative regimens include clindamycin in conjunction with either an extended-spectrum cephalosporin or co-trimoxazole.292,543 Purulent bite wounds usually are polymicrobial and broad-spectrum anti-infective coverage is recommended.292,543 Nonpurulent infected bite wounds usually are caused by staphylococci and streptococci, but can be polymicrobial.543

For information regarding the treatment of skin and skin structure infections, including infections caused by MRSA, the current clinical practice guidelines from IDSA available at [Web] should be consulted.514,543

Actinomycosis

Clindamycin has been recommended as an alternative to penicillin G or ampicillin for the treatment of actinomycosis†, including infections caused by Actinomyces israelii .197,292

Anthrax

Although limited clinical data are available regarding use of clindamycin in the treatment of anthrax†, clindamycin was included in a multiple-drug regimen that was effective for the treatment of several patients in the US who developed anthrax during September and October 2001 following exposure to an intentional release of anthrax spores (biologic warfare, bioterrorism).116,120 At least 2 patients were treated with a parenteral regimen of ciprofloxacin (400 mg every 8 hours), rifampin (300 mg every 12 hours), and clindamycin (900 mg every 8 hours).119

Because of the rapid course of symptomatic inhalational anthrax and high mortality rate, prompt recognition of symptoms and early initiation of anti-infective therapy is essential.116,117 The US Centers for Disease Control and Prevention (CDC) and other experts (e.g., US Working Group on Civilian Biodefense) recommend that treatment of inhalational anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism should be initiated with a multiple-drug parenteral regimen that includes ciprofloxacin or doxycycline and 1 or 2 additional anti-infective agents predicted to be effective.117,120 Multiple-drug parenteral regimens also are recommended for the treatment of cutaneous anthrax if there are signs of systemic involvement, extensive edema, or lesions on the head and neck.120 Based on in vitro data, drugs that have been suggested as possibilities to augment ciprofloxacin or doxycycline in such multiple-drug regimens include chloramphenicol, clindamycin, rifampin, vancomycin, clarithromycin, imipenem, penicillin, or ampicillin.117,120,292 Strains of Bacillus anthracis that were associated with cases of inhalational or cutaneous anthrax† that occurred in the US (Florida, New York, District of Columbia) during September and October 2001 following bioterrorism-related anthrax exposures were susceptible to clindamycin in vitro.120

Based on in vitro data, clindamycin also has been suggested as a possible alternative for postexposure prophylaxis following a suspected or confirmed exposure to aerosolized anthrax spores† (inhalational anthrax) when the drugs of choice (ciprofloxacin, doxycycline) are not tolerated or cannot be used.118

For information on treatment of anthrax and recommendations for prophylaxis following exposure to anthrax spores, see Uses: Anthrax, in Ciprofloxacin 8:12.18.

Babesiosis

Oral or IV clindamycin is used in conjunction with oral quinine sulfate for the treatment of babesiosis† caused by Babesia microti 101,105,111,134,292,329 or other Babesia .134

Although several species of Babesia can infect humans (e.g., B. microti , B. divergens , B. duncani , B. venatorum ), B. microti is the most common cause of babesiosis in the US.134,329 B. microti is transmitted by Ixodes scapularis ticks, which also may be simultaneously infected with and transmit Borrelia burgdorferi (causative agent of Lyme disease) and Anaplasma phagocytophilum (causative agent of human granulocytotropic anaplasmosis [HGA, formerly known as human granulocytic ehrlichiosis]).329 Therefore, the possibility of coinfection with B. burgdorferi and/or A. phagocytophilum should be considered in patients who have severe or persistent symptoms despite appropriate anti-infective treatment for babesiosis.329

IDSA states that all patients with active babesiosis (i.e., symptoms of viral-like infection and identification of babesial parasites in blood smears or by polymerase chain reaction [PCR] amplification of babesial DNA) should receive anti-infective treatment because of the risk of complications; however, symptomatic patients whose serum contains antibody to babesia but whose blood lacks identifiable babesial parasites on smear or babesial DNA by PCR should not receive treatment.329 In addition, these experts state that treatment is not generally recommended initially for asymptomatic individuals, regardless of the results of serologic examination, blood smears, or PCR, but should be considered if parasitemia persists for longer than 3 months.329

When anti-infective treatment of babesiosis is indicated, IDSA and other clinicians recommend that either a regimen of clindamycin and quinine or a regimen of atovaquone and azithromycin be used.111,134,292,329 There is some evidence that, in patients with mild or moderate illness, the atovaquone and azithromycin regimen may be as effective and better tolerated than the clindamycin and quinine regimen.111,134,292,329 However, the clindamycin and quinine regimen generally is preferred for the treatment of severe babesiosis caused by M. microti 134,329 and infections caused by M. divergens , B. duncani , B. divergens -like organisms, or B. venatorum .134 Patients with moderate to severe babesiosis should be monitored closely during treatment to ensure clinical improvement.329 Exchange transfusions have been used successfully in asplenic patients with life-threatening babesiosis and should be considered, especially in severely ill patients with high levels of parasitemia (10% or more), significant hemolysis, or compromised renal, hepatic, or pulmonary function.134,292,329

Bacterial Vaginosis

Oral clindamycin is used in the treatment of bacterial vaginosis† (formerly called Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, or anaerobic vaginosis).180,181,182,194,196,203,344,345 The drug also is used intravaginally as a vaginal cream or vaginal suppository for the treatment of bacterial vaginosis (see Clindamycin Phosphate 84:04.04).174,175,178,184,185,187,190,191,192,193,194,195,196,203,344,345

Bacterial vaginosis is a polymicrobial syndrome that can occur when normal hydrogen peroxide-producing Lactobacillus in the vagina are replaced by overgrowth of various anaerobic bacteria (e.g., Prevotella , Mobiluncus ), Gardnerella vaginalis , Ureaplasma urealyticum , Mycoplasma hominis , Atopobium vaginae , or other bacteria.344,345 Treatment of bacterial vaginosis usually is recommended to relieve signs and symptoms of infection, regardless of pregnancy status.344,345

For the treatment of bacterial vaginosis, CDC and other experts recommend a 7-day regimen of oral metronidazole (500 mg twice daily); a 5-day regimen of intravaginal metronidazole 0.75% gel; or a 7-day regimen of intravaginal clindamycin 2% cream.344,345 Alternative regimens include a 2-day regimen of oral tinidazole (2 g once daily); a 5-day regimen of oral tinidazole (1 g once daily); a 7-day regimen of oral clindamycin (300 mg twice daily); or a 3-day regimen of intravaginal clindamycin 100-mg suppositories.344,345 CDC and other clinicians state that the oral or intravaginal metronidazole or clindamycin regimens can be used to treat symptomatic bacterial vaginosis in pregnant women.344,345

Regardless of the treatment regimen used, relapse or recurrence of bacterial vaginosis is common.188,192,193,194,195,344,345 Retreatment with the same regimen or an alternative regimen (e.g., oral therapy when topical therapy was used initially) can be effective for treating persistent or recurrent bacterial vaginosis after the first occurrence.344,345 Maintenance suppressive therapy with intravaginal metronidazole (0.75% gel twice weekly for 4-6 months) may reduce recurrences,344,345 but this benefit may not persist after suppressive therapy is discontinued.344

Malaria

Treatment of Uncomplicated Malaria

Oral clindamycin is used in conjunction with oral quinine sulfate for the treatment of uncomplicated chloroquine-resistant Plasmodium falciparum malaria† or when the plasmodial species has not been identified.113,114,115,134,143,144 Clindamycin is not effective when used alone for the treatment of malaria.114

For the treatment of uncomplicated malaria caused by chloroquine-resistant P. falciparum or the treatment of uncomplicated malaria when the plasmodial species has not been identified, CDC and other clinicians recommend the fixed combination of atovaquone and proguanil hydrochloride (atovaquone/proguanil), the fixed combination of artemether and lumefantrine (artemether/lumefantrine), or a regimen that includes quinine sulfate in conjunction with doxycycline, tetracycline, or clindamycin.134,143,144 Although mefloquine is another option for treatment in these patients,134,143,144 CDC states that mefloquine should only be considered when other options cannot be used143 and is not recommended if malaria was acquired in Southeast Asia.144

When a quinine sulfate regimen is used, concomitant doxycycline or tetracycline generally is preferable to concomitant clindamycin because more efficacy data exist regarding regimens that include tetracyclines.143 However, for pregnant women with uncomplicated malaria caused by chloroquine-resistant P. falciparum , a regimen of quinine sulfate and clindamycin is recommended.113,115,134,143,144 Although tetracyclines generally are contraindicated in pregnant women, in rare circumstances (e.g., if other treatment options are not available or are not tolerated) quinine sulfate may be used in conjunction with doxycycline or tetracycline if the benefits outweigh the risks.143,144

Pediatric patients with uncomplicated malaria generally can receive the same treatment regimens recommended for adults using age- and weight-appropriate drugs and dosages.143 However, because doxycycline and tetracycline generally are contraindicated in children younger than 8 years of age, children in this age group with uncomplicated chloroquine-resistant P. falciparum malaria or when the plasmodial species has not been identified may receive a regimen of oral quinine sulfate alone for a full 7 days (regardless of geographic area where infection was acquired) or atovaquone/proguanil, artemether/lumefantrine, or a regimen of oral quinine sulfate in conjunction with oral clindamycin.113,115,143,144 Mefloquine should only be considered in these children when other options cannot be used143 and is not recommended if malaria was acquired in Southeast Asia.144 In rare circumstances when other treatment options are unavailable or are not tolerated, CDC states that doxycycline or tetracycline may be used in conjunction with quinine sulfate in children younger than 8 years of age if the benefits of tetracycline therapy outweigh the risks.143,144

Treatment of Severe Malaria

Oral or IV clindamycin is used in conjunction with IV quinidine gluconate for the treatment of severe P. falciparum malaria† in adults and children.143,144

Patients with severe malaria require aggressive antimalarial treatment initiated as soon as possible after the diagnosis using a parenteral regimen.143,144 CDC recommends that severe malaria be treated with IV quinidine gluconate therapy in conjunction with a 7-day course of doxycycline, tetracycline, or clindamycin administered orally or IV as tolerated.143,144 After parasitemia is reduced to less than 1% and the patient can tolerate oral therapy, IV quinidine gluconate can be discontinued and oral quinine sulfate initiated to complete 3 or 7 days of total quinidine and quinine therapy as determined by the geographic origin of the infecting parasite (7 days if acquired in Southeast Asia or 3 days if acquired elsewhere).143,144

Assistance with diagnosis or treatment of malaria is available by contacting the CDC Malaria Hotline at 770-488-7788 or 855-856-4713 from 9:00 a.m. to 5:00 p.m. Eastern Standard Time or the CDC Emergency Operation Center at 770-488-7100 after hours and on weekends and holidays.143,144

Pelvic Inflammatory Disease

IV clindamycin used in conjunction with IV or IM gentamicin is one of several possible parenteral regimens for the treatment of acute pelvic inflammatory disease (PID) in adults and adolescents.344,345 PID is a polymicrobial infection most frequently caused by Neisseria gonorrhoeae and/or Chlamydia trachomatis ; however, organisms that can be part of the normal vaginal flora (e.g., anaerobic bacteria, G. vaginalis , H. influenzae , enteric gram-negative bacilli, S. agalactiae ) or mycoplasma (e.g., M. hominis , U. urealyticum ) also may be involved.344,345 PID is treated with an empiric regimen that provides broad-spectrum coverage.344,345 The regimen should be effective against N. gonorrhoeae and C. trachomatis and also probably should be effective against anaerobes.344,345 In addition, women with PID often have bacterial vaginosis concurrently, a polymicrobial infection that can include anaerobes.344 (See Uses: Bacterial Vaginosis.)

The optimum regimen for the treatment of PID has not been identified.344 A variety of parenteral and oral regimens have been recommended by CDC and other clinicians.344,345 When a parenteral regimen is used, these experts recommend a regimen of IV cefotetan in conjunction with oral or IV doxycycline; IV cefoxitin in conjunction with oral or IV doxycycline; or IV clindamycin in conjunction with IM or IV gentamicin.344,345 The parenteral regimen should be continued until 24-48 hours after the patient improves clinically and then an oral regimen of either doxycycline (100 mg twice daily) or clindamycin (450 mg 4 times daily) is used to complete 14 days of therapy.344,345 If tubo-ovarian abscess is present, at least 24 hours of inpatient observation is recommended344 and use of oral clindamycin or oral metronidazole in addition to oral doxycycline is preferred for follow-up oral therapy since this provides more effective coverage against anaerobes than doxycycline alone.344,345

Pneumocystis jirovecii Pneumonia

Treatment of Pneumocystis jirovecii Pneumonia

Clindamycin is used in conjunction with primaquine for the treatment of Pneumocystis jirovecii (formerly Pneumocystis carinii ) pneumonia† (PCP) in individuals with human immunodeficiency virus (HIV) infection.134,145,146,148,150,152,153,157,158,159,169,170,206,440 Clindamycin is designated an orphan drug by FDA for the treatment of PCP associated with acquired immunodeficiency syndrome (AIDS).212

Co-trimoxazole is the drug of choice for the treatment of mild, moderate, or severe PCP, including PCP in HIV-infected adults, adolescents, and children.134,440,441 CDC, National Institutes of Health (NIH), and IDSA state that a regimen of primaquine and clindamycin is an alternative for the treatment of mild, moderate, or severe PCP in HIV-infected adults and adolescents who have had an inadequate response to co-trimoxazole or when co-trimoxazole is contraindicated or not tolerated.440 Although data are not available regarding use in children, CDC, NIH, IDSA, and AAP state that a regimen of primaquine and clindamycin also can be considered an alternative to co-trimoxazole for the treatment of PCP in HIV-infected children based on data in adults.441

Results of clinical studies indicate that clindamycin administered IV (1.8-3.6 g given in 3 or 4 divided doses daily) or orally (1.2-3.6 g in 3 or 4 divided doses daily [in some cases oral clindamycin was administered after initial IV administration]) in conjunction with oral primaquine (15 or 30 mg daily) for a total 21 days of therapy is effective for the treatment of PCP in HIV-infected adults.145,146,148,150,152,153,158,169,170,206 Most patients exhibit clinical improvement within 2-7 days,146,148 and the combination generally appears to be well tolerated.146,148,153,158,159,170

Prevention of Pneumocystis jirovecii Pneumonia

Co-trimoxazole is the drug of choice for prevention of initial episodes (primary prophylaxis) of PCP in HIV-infected adults, adolescents, and children.440,441 CDC, NIH, and IDSA state that a regimen of primaquine and clindamycin is not recommended for primary PCP prophylaxis because data are insufficient to determine efficacy of the regimen for such prophylaxis.440

Although a regimen of clindamycin and primaquine has been used as an alternative to co-trimoxazole for long-term suppressive or chronic maintenance therapy (secondary prophylaxis) of PCP† in a limited number of AIDS patients,150,159 this regimen is not included in CDC, NIH, IDSA, and AAP recommendations for secondary prophylaxis of PCP in HIV-infected adults, adolescents, or children.440,441 Co-trimoxazole is the drug of choice for secondary PCP prophylaxis in HIV-infected adults, adolescents, and children.440,441

Toxoplasmosis

Treatment of Toxoplasmosis

Clindamycin is used in conjunction with pyrimethamine (and leucovorin) as an alternative for the treatment of toxoplasmosis caused by Toxoplasma gondii .129,131,132,134,138,164,166,167,172,440,441

Pyrimethamine (and leucovorin) in conjunction with sulfadiazine is the regimen of choice for initial treatment of toxoplasmosis, including toxoplasmic encephalitis in HIV-infected adults, adolescents, and children.134,440,441 A regimen of pyrimethamine (and leucovorin) in conjunction with clindamycin is the preferred alternative in HIV-infected adults and adolescents who are unable to tolerate sulfadiazine or who failed to respond to an initial regimen of pyrimethamine and sulfadiazine.440 When a parenteral regimen is required for initial treatment of toxoplasmosis in severely ill adults or adolescents, some experts suggest parenteral co-trimoxazole or a regimen of oral pyrimethamine (and leucovorin) in conjunction with parenteral clindamycin.440

Pyrimethamine (and leucovorin) in conjunction with sulfadiazine also is the regimen of choice for the treatment of congenital toxoplasmosis and the treatment of acquired CNS, ocular, or systemic toxoplasmosis in HIV-infected children.441 The preferred alternative for the treatment of toxoplasmosis in neonates or HIV-infected children with sulfonamide sensitivity is pyrimethamine (and leucovorin) in conjunction with clindamycin.441 Empiric treatment of congenital toxoplasmosis should be strongly considered in infants born to HIV-infected women who had symptomatic or asymptomatic toxoplasmosis during pregnancy, regardless of whether the mother received toxoplasmosis treatment during the pregnancy.441 Pregnant women with suspected or confirmed primary toxoplasmosis and neonates with possible or documented congenital toxoplasmosis should be managed in consultation with an appropriate infectious disease specialist.441

Prevention of Recurrence of Toxoplasmosis

CDC, NIH, IDSA, and AAP state that HIV-infected adults, adolescents, and children who have completed initial treatment of T. gondii encephalitis should receive chronic maintenance therapy (secondary prophylaxis) to prevent relapse.440,441

Pyrimethamine (and leucovorin) in conjunction with sulfadiazine is the regimen of choice for long-term suppressive or chronic maintenance therapy (secondary prophylaxis) of toxoplasmosis in HIV-infected adults, adolescents, and children.440,441 A regimen of pyrimethamine (and leucovorin) in conjunction with clindamycin is one of several alternatives for secondary prophylaxis of toxoplasmosis in HIV-infected adults, adolescents, and children who cannot tolerate sulfonamides.440,441

CDC, NIH, and IDSA state that secondary prophylaxis against toxoplasmosis generally can be discontinued in HIV-infected adults and adolescents who have successfully completed initial therapy for toxoplasmic encephalitis, remain asymptomatic with respect to toxoplasmic encephalitis, and have CD4⁺ T-cell counts that have remained greater than 200/mm³ for more than 6 months in response to antiretroviral therapy.440 Some experts recommend obtaining a magnetic resonance image (MRI) of the brain as part of the evaluation to determine whether discontinuance of secondary prophylaxis is appropriate.440 Secondary prophylaxis against toxoplasmosis should be reinitiated in HIV-infected adults and adolescents if CD4⁺ T-cell counts decrease to less than 200/mm³, regardless of plasma HIV viral load.440

The safety of discontinuing secondary toxoplasmosis prophylaxis in HIV-infected children receiving potent antiretroviral therapy has not been extensively studied.441 However, based on data from adults, CDC, NIH, IDSA, and AAP state that discontinuance of secondary prophylaxis against toxoplasmosis can be considered in HIV-infected children 1 to less than 6 years of age who have completed toxoplasmosis treatment, have received more than 6 months of stable antiretroviral therapy, are asymptomatic with respect to toxoplasmosis, and have CD4⁺ T-cell percentages that have remained greater than 15% for more than 6 consecutive months.441 In HIV-infected children 6 years of age or older who have received more than 6 months of antiretroviral therapy, consideration can be given to discontinuing secondary prophylaxis against toxoplasmosis if CD4⁺ T-cell counts have remained greater than 200/mm³ for more than 6 consecutive months.441 Prophylaxis should be reinitiated in HIV-infected children if these parameters are not met.441

Perioperative Prophylaxis

IV clindamycin is recommended as an alternative for perioperative prophylaxis† to reduce the incidence of infections in patients undergoing certain clean, contaminated surgeries when the drugs of choice (e.g., cefazolin, cefuroxime, cefoxitin, cefotetan) cannot be used because the patient is hypersensitive to β-lactam anti-infectives.360,374

Some experts state that clindamycin or vancomycin is a reasonable alternative for perioperative prophylaxis in patients allergic to β-lactam anti-infectives who are undergoing cardiac surgery (e.g., coronary artery bypass grafting, valve repairs, cardiac device implantation), neurosurgery (e.g., craniotomy, spinal and CSF-shunting procedures, intrathecal pump placement), orthopedic surgery (e.g., spinal procedures, hip fracture, internal fixation, total joint replacement), non-cardiac thoracic surgery (e.g., lobectomy, pneumonectomy, lung resection, thoracotomy), vascular surgery (e.g., arterial procedures involving a prosthesis, the abdominal aorta, or a groin incision), lower extremity amputation for ischemia, or certain transplant procedures (e.g., heart and/or lung).360,374 These experts state that clindamycin also is a reasonable alternative for perioperative prophylaxis in patients allergic to β-lactam anti-infectives who are undergoing head and neck surgery (e.g., incisions through oral or pharyngeal mucosa).360,374

For procedures that might involve exposure to enteric gram-negative bacteria, some experts state that clindamycin or vancomycin used in conjunction with an aminoglycoside (e.g., amikacin, gentamicin, tobramycin), aztreonam, or a fluoroquinolone is a reasonable alternative in patients allergic to β-lactam anti-infectives.360,374 These procedures include certain GI and biliary tract procedures (e.g., esophageal or gastroduodenal procedures, appendectomy for uncomplicated appendicitis, surgery involving unobstructed small intestine, colorectal procedures), gynecologic and obstetric surgery (e.g., cesarean section, hysterectomy), urologic procedures involving an implanted prosthesis, and certain transplant procedures (e.g., liver, pancreas and/or kidney).360,374

Prevention of Bacterial Endocarditis

Clindamycin is used as an alternative to amoxicillin or ampicillin for prevention of α-hemolytic (viridans group) streptococcal bacterial endocarditis† in penicillin-allergic adults and children undergoing certain dental or upper respiratory tract procedures who have cardiac conditions that put them at highest risk of adverse outcomes from endocarditis.451

The cardiac conditions identified by AHA as those associated with highest risk and for which endocarditis prophylaxis is reasonable are prosthetic cardiac valves or prosthetic material used for cardiac valve repair, previous infective endocarditis, cardiac valvulopathy after cardiac transplantation, and certain forms of congenital heart disease (i.e., unrepaired cyanotic congenital heart disease including palliative shunts and conduits; a completely repaired congenital heart defect where prosthetic material or device was placed by surgery or catheter intervention within the last 6 months; repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device that inhibit endothelialization).451

AHA states that anti-infective prophylaxis for prevention of α-hemolytic (viridans group) streptococcal bacterial endocarditis is reasonable for patients with the above cardiac risk factors if they are undergoing any dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa (e.g., biopsies, suture removal, placement of orthodontic bands).451 AHA states that anti-infective prophylaxis is not needed for routine anesthetic injections through noninfected tissue, dental radiographs, placement of removable prosthodontic or orthodontic appliances, adjustment of orthodontic appliances, placement of orthodontic brackets, shedding of deciduous teeth, or bleeding from trauma to the lips or oral mucosa.451

AHA states that anti-infective prophylaxis for prevention of bacterial endocarditis also is reasonable for patients with these cardiac risk factors if they are undergoing invasive procedures of the respiratory tract that involve incision or biopsy of respiratory mucosa (e.g., tonsillectomy, adenoidectomy) and may be reasonable for such patients if they are undergoing surgical procedures that involve infected skin, skin structure, or musculoskeletal tissue.451 However, anti-infective prophylaxis solely to prevent infective endocarditis is no longer recommended by AHA for GI or genitourinary tract procedures.451

For additional information on which cardiac conditions are associated with the highest risk of adverse outcomes from endocarditis and more specific information regarding use of prophylaxis to prevent endocarditis in these patients, the current recommendations published by AHA should be consulted.451

Prevention of Perinatal Group B Streptococcal Disease

IV clindamycin is used as an alternative to parenteral penicillin G or ampicillin for prevention of perinatal group B streptococcal (GBS) disease† in certain women who are hypersensitive to penicillins.292,359,362

Pregnant women who are colonized with GBS in the genital or rectal areas can transmit GBS infection to their infants during labor and delivery, resulting in invasive neonatal infection that can be associated with substantial morbidity and mortality.292,359,362 Intrapartum anti-infective prophylaxis for prevention of early-onset neonatal GBS disease is administered selectively to women at high risk for transmitting GBS infection to their neonates.292,359,362 CDC and AAP recommend routine universal prenatal screening for GBS colonization (e.g., vaginal and rectal cultures) in all pregnant women at 35-37 weeks of gestation, unless GBS bacteriuria is known to be present during the current pregnancy or the woman had a previous infant with invasive GBS disease.292,359 Intrapartum anti-infective prophylaxis for prevention of perinatal GBS is indicated in pregnant women identified as GBS carriers during the routine prenatal GBS screening performed at 35-37 weeks during the current pregnancy, in women with GBS bacteriuria identified at any time during the current pregnancy, and in women who had a previous infant diagnosed with invasive GBS disease.292,359 Intrapartum anti-infective prophylaxis also is indicated in women with unknown GBS status at the time of onset of labor (i.e., culture not done, incomplete, or results unknown), if delivery is at less than 37 weeks of gestation, the duration of amniotic membrane rupture is 18 hours or longer, intrapartum temperature is 38°C or higher, or an intrapartum nucleic acid amplification test (NAAT) was positive for GBS.359

When intrapartum anti-infective prophylaxis is indicated in the mother for prevention of GBS in the neonate, it should be initiated at the onset of labor or rupture of membranes.359 CDC, AAP, and others recommend penicillin G as the drug of choice and ampicillin as the preferred alternative for such prophylaxis.292,359,362 If intrapartum prophylaxis is indicated in a penicillin-allergic woman who is not at high risk for anaphylaxis (i.e., does not have a history of anaphylaxis, angioedema, respiratory distress, or urticaria after receiving a penicillin or cephalosporin), CDC, AAP, and others recommend IV cefazolin.292,359,362 If intrapartum prophylaxis is indicated in a penicillin-allergic woman who is at high risk for anaphylaxis (e.g., history of anaphylaxis, angioedema, respiratory distress, or urticaria after receiving a penicillin or cephalosporin), IV clindamycin is recommended if the GBS isolate is tested and found to be susceptible to clindamycin and erythromycin.292,359,362 GBS isolates susceptible to clindamycin but resistant to erythromycin in vitro should be evaluated for inducible clindamycin resistance.359 IV vancomycin can be used as an alternative in penicillin-allergic women if the GBS isolate is intrinsically resistant to clindamycin, demonstrates inducible resistance to clindamycin, or if susceptibility to clindamycin and erythromycin is unknown.292,359,362

For additional information regarding prevention of perinatal group B streptococcal disease, the current guidelines from CDC or AAP should be consulted.359,362

Topical Uses

For topical uses of clindamycin, see Clindamycin Phosphate 84:04.04.

Reconstitution and Administration

Clindamycin hydrochloride126 and clindamycin palmitate hydrochloride121 are administered orally.

Clindamycin phosphate is administered by IM injection or by intermittent or continuous IV infusion.139 Clindamycin phosphate should not be administered by rapid IV injection.139

In the treatment of serious anaerobic infections, the parenteral route is usually used initially but may be switched to the oral route when warranted by the patient's condition.121,126 In clinically appropriate circumstances, the oral route may be used initially.121,126

Oral Administration

Clindamycin hydrochloride capsules126 and clindamycin palmitate hydrochloride oral solution121 can be administered without regard to food.

Capsules

Clindamycin hydrochloride capsules should be administered orally with a full glass of water to avoid the possibility of esophageal irritation.126

The capsules should be swallowed whole and are not suitable for use in pediatric patients who are unable to swallow capsules.126

Oral Solution

Clindamycin palmitate hydrochloride powder (granules) for oral solution must be reconstituted by adding 75 mL of water to the 100-mL bottle.121 A large portion of the 75 mL should be added initially and the bottle shaken vigorously; the remainder of the water should then be added and the bottle shaken until the solution is uniform.121

The reconstituted oral solution contains 75 mg of clindamycin per 5 mL.121

IM Injection

For IM injection, commercially available clindamycin phosphate solution containing 150 mg of clindamycin per mL is administered undiluted.139

Single IM doses should not exceed 600 mg.139

IV Infusion

Prior to IV infusion, commercially available clindamycin phosphate solution (including solutions provided in ADD-Vantage^® vials) must be diluted with a compatible IV solution to a concentration not exceeding 18 mg/mL.139

Clindamycin phosphate usually is administered by intermittent IV infusion.139 As an alternative, clindamycin phosphate may be given by continuous IV infusion after the first dose of the drug has been given by rapid IV infusion.139 (See Table 1.)

Commercially available premixed solutions of clindamycin phosphate in 5% dextrose are administered only by IV infusion.139 Clindamycin phosphate in 5% dextrose injection should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.139 Premixed solutions provided in flexible containers should be checked for minute leaks by firmly squeezing the bag.139 Premixed solutions should be discarded if the container seal is not intact or leaks are found or if the solution is not clear.139 Additives should not be introduced into containers of premixed solutions of clindamycin phosphate in 5% dextrose.139 Flexible containers should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.139

Dilution

When commercially available clindamycin phosphate solution containing 150 mg of clindamycin per mL is used for IV infusion, the appropriate dose should be diluted in a compatible IV infusion solution and administered using the recommended rate of administration.139 (See Rate of Administration under Reconstitution and Administration: IV Infusion, in Dosage and Administration.)

Clindamycin phosphate solution provided in ADD-Vantage^® vials must be diluted prior to IV infusion according to the directions provided by the manufacturer.139 The ADD-Vantage^® vials are for IV infusion only.139

Commercially available clindamycin phosphate pharmacy bulk packages are not intended for direct IV infusion; doses of the drug from the bulk package must be further diluted in a compatible IV infusion solution.139 The bulk package is intended for use only in a laminar flow hood.139 Entry into the bulk pharmacy vial should be made using a sterile transfer set or other sterile dispensing device, and the contents dispensed in aliquots using appropriate technique; multiple entries with a syringe and needle are not recommended.139 After entry into a pharmacy bulk package vial, the entire contents of the vial should be used promptly; any unused portion should be discarded within 24 hours after initial entry into the pharmacy bulk package vial.139

Rate of Administration

Intermittent IV infusions of clindamycin phosphate solutions should be given over a period of at least 10-60 minutes and at a rate less than 30 mg/minute.139 No more than 1.2 g should be given by IV infusion in a single 1-hour period.139

The manufacturer recommends that 300-mg doses should be diluted in 50 mL of compatible diluent and infused over 10 minutes; 600-mg doses should be diluted in 50 mL of diluent and infused over 20 minutes; 900-mg doses should be diluted in 50-100 mL of diluent and infused over 30 minutes; and 1.2-g doses should be diluted in 100 mL of diluent and infused over 40 minutes.139

As an alternative to intermittent IV infusions, the manufacturer states that the drug can be given by continuous IV infusion in adults after an initial dose is given by IV infusion over 30 minutes.139 (See Table 1.)

Dosage

Dosage of clindamycin hydrochloride, clindamycin palmitate hydrochloride, and clindamycin phosphate is expressed in terms of clindamycin.121,126,139

Dosage and duration of treatment depend on the severity of the infection.121,126,139 If clindamycin is used in infections caused by Streptococcus pyogenes (group A β-hemolytic streptococci; GAS), therapy should be continued for at least 10 days.121,126,139 At least 6 weeks of therapy may be required for certain serious infections (e.g., osteomyelitis).590

Oral Dosage

General Dosage for Neonates

When clindamycin oral solution is used in pediatric patients, the manufacturer recommends 8-12 mg/kg daily for the treatment of serious infections, 13-16 mg/kg daily for severe infections, and 17-25 mg/kg daily for more severe infections;121 daily dosage is given in 3 or 4 equally divided doses.121 In pediatric patients weighing 10 kg or less, the manufacturer recommends a minimum clindamycin dosage of 37.5 mg 3 times daily.121

When oral clindamycin is used in neonates 7 days of age or younger, the American Academy of Pediatrics (AAP) recommends a dosage of 5 mg/kg every 12 hours in those weighing 2 kg or less or 5 mg/kg every 8 hours in those weighing more than 2 kg.292

In neonates 8-28 days of age, AAP recommends an oral clindamycin dosage of 5 mg/kg every 8 hours in those weighing 2 kg or less or 5 mg/kg every 6 hours in those weighing more than 2 kg.292 In extremely low-birthweight neonates (less than 1 kg), a dosage of 5 mg/kg every 12 hours can be considered until 2 weeks of age.292

General Dosage for Infants and Children

When clindamycin capsules are used in pediatric patients able to swallow capsules, the manufacturer recommends 8-16 mg/kg daily given in 3 or 4 equally divided doses for the treatment of serious infections or 16-20 mg/kg daily given in 3 or 4 equally divided doses for more severe infections.126

When the oral solution is used in pediatric patients, the manufacturer recommends 8-12 mg/kg daily for the treatment of serious infections, 13-16 mg/kg daily for severe infections, and 17-25 mg/kg daily for more severe infections; daily dosage is given in 3 or 4 equally divided doses.121 In pediatric patients weighing 10 kg or less, the manufacturer recommends a minimum dosage of 37.5 mg 3 times daily.121

When oral clindamycin is used in pediatric patients beyond the neonatal period, AAP recommends a dosage of 10-25 mg/kg daily given in 3 equally divided doses for the treatment of mild to moderate infections or 30-40 mg/kg daily given in 3 or 4 equally divided doses for the treatment of severe infections.292

General Adult Dosage

The usual adult dosage of oral clindamycin is 150-300 mg every 6 hours for the treatment of serious infections or 300-450 mg every 6 hours for the treatment of more severe infections.126

Acute Otitis Media

If oral clindamycin is used as an alternative for the treatment of acute otitis media† (AOM) in children 6 months through 12 years of age, AAP recommends a dosage of 30-40 mg/kg daily given in 3 divided doses (with or without a third generation cephalosporin).499 (See Uses: Acute Otitis Media.)

Pharyngitis and Tonsillitis

If oral clindamycin is used as an alternative for the treatment of pharyngitis and tonsillitis caused by S. pyogenes † (group A β-hemolytic streptococci; GAS) (see Uses: Pharyngitis and Tonsillitis), AAP recommends a dosage of 10 mg/kg 3 times daily (up to 900 mg daily) for 10 days.292 The Infectious Diseases Society of America (IDSA) recommends a dosage of 7 mg/kg (up to 300 mg) 3 times daily for 10 days.580 The American Heart Association (AHA) recommends a dosage of 20 mg/kg daily (up to 1.8 g daily) given in 3 divided doses for 10 days.375

Although anti-infective treatment is not recommended for most individuals identified as chronic pharyngeal GAS carriers, AAP and IDSA state that oral clindamycin can be given in a dosage of 20-30 mg/kg daily in 3 equally divided doses (up to 300 mg per dose or up to 900 mg daily) for 10 days when treatment is indicated in such patients.292,580

Respiratory Tract Infections

If oral clindamycin is used in adults for the treatment of healthcare-associated or community-acquired pneumonia (CAP) caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA), IDSA recommends a dosage of 600 mg 3 times daily for 7-21 days.514

If oral clindamycin is used for the treatment of CAP caused by susceptible gram-positive bacteria (e.g., S. pneumoniae , S. pyogenes , S. aureus ) in children older than 3 months of age, IDSA recommends a dosage of 30-40 mg/kg daily given in 3 or 4 divided doses.513

Babesiosis

For the treatment of babesiosis† caused by Babesia microti or other Babesia species, IDSA and other experts recommend that adults receive clindamycin in a dosage of 600 mg orally every 8 hours (or 300-600 mg IV every 6 hours) in conjunction with oral quinine sulfate (650 mg every 6 or 8 hours) given for 7-10 days.134,329

For the treatment of babesiosis in pediatric patients, IDSA recommends an oral (or IV) clindamycin dosage of 7-10 mg/kg (up to 600 mg) every 6-8 hours in conjunction with oral quinine sulfate (8 mg/kg [up to 650 mg] every 8 hours) given for 7-10 days.329 Other clinicians recommend an oral (or IV) clindamycin dosage of 20-40 mg/kg (up to 600 mg) daily given in 3 or 4 divided doses for 7-10 days in conjunction with oral quinine sulfate (24 mg/kg daily given in 3 divided doses for 7-10 days).134

Patients with mild to moderate babesiosis should have clinical improvement within 48 hours after treatment is initiated; symptoms should resolve completely within 3 months.329 Patients with severe babesiosis should receive IV clindamycin rather than oral clindamycin.329 Some patients may have persistent low-grade parasitemia for months after anti-infective treatment.329 Some experts suggest that anti-infective treatment in immunosuppressed patients should be continued for a minimum of 6 weeks and at least 2 weeks after the last positive smear.134 Regardless of the presence or absence of symptoms, IDSA suggests that retreatment be considered if babesial parasites or amplifiable babesial DNA is detected in blood 3 months or longer after initial treatment.329

Bacterial Vaginosis

When oral clindamycin is used as an alternative for the treatment of bacterial vaginosis† in symptomatic women, the US Centers for Disease Control and Prevention (CDC) and other clinicians recommend a dosage of 300 mg twice daily for 7 days.344,345

Malaria

If clindamycin is used in conjunction with quinine sulfate for the treatment of uncomplicated malaria caused by chloroquine-resistant Plasmodium falciparum † or when the plasmodial species has not been identified, CDC and other clinicians recommend that adults receive oral clindamycin in a dosage of 20 mg/kg daily in 3 equally divided doses given for 7 days in conjunction with oral quinine sulfate (650 mg 3 times daily given for 7 days if acquired in Southeast Asia or for 3 days if acquired elsewhere).134,143,144 Children with uncomplicated chloroquine-resistant P. falciparum malaria can receive oral clindamycin in a dosage of 20 mg/kg daily in 3 equally divided doses given for 7 days in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 7 days if acquired in Southeast Asia or 3 days if acquired elsewhere).134,143,144

If clindamycin is used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) for the treatment of severe malaria caused by P. falciparum † and if the patient is intolerant of oral therapy, treatment may be initiated in adults and children with a 10-mg/kg loading dose of IV clindamycin followed by 5 mg/kg IV every 8 hours continued until treatment can be switched to oral clindamycin (given in dosages recommended for uncomplicated malaria).143,144 The total duration of clindamycin therapy should be 7 days.143,144

Pneumocystis jirovecii Pneumonia

If a regimen of oral clindamycin and primaquine is used as an alternative for the treatment of mild to moderate Pneumocystis jirovecii pneumonia† (PCP), CDC, National Institutes of Health (NIH), and IDSA recommend that adults and adolescents receive oral clindamycin in a dosage of 450 mg every 6 hours or 600 mg every 8 hours for 21 days in conjunction with oral primaquine (30 mg once daily for 21 days).440

If a regimen of oral clindamycin and primaquine is used as an alternative for the treatment of moderate to severe PCP†, CDC, NIH, and IDSA recommend that adults and adolescents receive oral clindamycin in a dosage of 450 mg every 6 hours or 600 mg every 8 hours for 21 days in conjunction with oral primaquine (30 mg once daily for 21 days).440

Although data regarding use in children are not available, if a regimen of oral clindamycin and primaquine is used as an alternative for the treatment of PCP in pediatric patients, some clinicians recommend that oral clindamycin be given in a dosage of 10 mg/kg (up to 300-450 mg) every 6 hours for 21 days in conjunction with oral primaquine (0.3 mg/kg once daily [up to 30 mg daily] for 21 days).441

Toxoplasmosis

For the treatment of toxoplasmosis† caused by Toxoplasma gondii in HIV-infected adults and adolescents who cannot receive sulfadiazine or did not respond to an initial regimen, CDC, NIH, and IDSA recommend an oral (or IV) clindamycin dosage of 600 mg every 6 hours in conjunction with oral pyrimethamine (200-mg loading dose followed by 50 mg once daily in those weighing less than 60 kg or 75 mg once daily in those weighing 60 kg or more) and oral leucovorin (10-25 mg once daily; may be increased to 50 mg once or twice daily).440 Treatment should be continued for at least 6 weeks; a longer duration may be appropriate if disease is extensive or there is an incomplete response at 6 weeks.440

For the treatment of congenital toxoplasmosis† or the treatment of acquired CNS, ocular, or systemic toxoplasmosis† in HIV-infected children who cannot receive sulfadiazine, CDC, NIH, and IDSA recommend an oral (or IV) clindamycin dosage of 5-7.5 mg/kg (up to 600 mg) 4 times daily in conjunction with oral pyrimethamine (2 mg/kg once daily for 2 days followed by 1 mg/kg once daily) and oral or IM leucovorin (10 mg with each pyrimethamine dose).441 Although optimal duration of treatment of congenital toxoplasmosis has not been determined, some clinicians recommend that the treatment regimen be continued for 12 months.441 In HIV-infected children with acquired CNS, ocular, or systemic toxoplasmosis, the treatment regimen should be continued for at least 6 weeks; a longer duration may be appropriate if disease is extensive or there is an incomplete response at 6 weeks.441

For long-term suppressive therapy or chronic maintenance therapy† (secondary prophylaxis) to prevent relapse of toxoplasmosis in HIV-infected patients when the regimen of first choice (pyrimethamine and sulfadiazine) cannot be used, CDC, NIH, and IDSA recommend that adults and adolescents receive oral clindamycin in a dosage of 600 mg every 8 hours with pyrimethamine (25-50 mg once daily) and leucovorin (10-25 mg once daily).440 For secondary prophylaxis in HIV-infected infants and children, CDC, NIH, IDSA, and AAP recommend an oral clindamycin dosage of 7-10 mg/kg 3 times daily with oral pyrimethamine (1 mg/kg or 15 mg/m² [up to 25 mg] once daily) and oral leucovorin (5 mg once every 3 days).441 Long-term suppressive therapy for prophylaxis against relapse of toxoplasmosis in HIV-infected individuals generally can be discontinued if immune recovery has occurred as the result of potent antiretroviral therapy.440,441 (See Prevention of Recurrence of Toxoplasmosis under Uses: Toxoplasmosis.)

Prevention of Bacterial Endocarditis

When oral clindamycin is used as an alternative for prevention of bacterial endocarditis† in penicillin-allergic patients with certain cardiac conditions who are undergoing certain dental procedures or certain other procedures (see Uses: Prevention of Bacterial Endocarditis), AHA recommends that adults receive a single 600-mg dose and that children receive a single 20-mg/kg dose of the drug 30-60 minutes before the procedure.451

Parenteral Dosage

General Dosage for Neonates

The manufacturer recommends that neonates younger than 1 month of age receive IM or IV clindamycin in a dosage of 15-20 mg/kg daily given in 3 or 4 equally divided doses.139 The lower dosage may be adequate for small, premature neonates.139

When IM or IV clindamycin is used in neonates 7 days of age or younger, AAP recommends 5 mg/kg every 12 hours in those weighing 2 kg or less or 5 mg/kg every 8 hours in those weighing more than 2 kg.292

In neonates 8-28 days of age, AAP recommends an IM or IV clindamycin dosage of 5 mg/kg every 8 hours in those weighing 2 kg or less or 5 mg/kg every 6 hours in those weighing more than 2 kg.292 In extremely low-birthweight neonates (less than 1 kg), a dosage of 5 mg/kg every 12 hours can be considered until 2 weeks of age.292

General Dosage for Infants and Children

The IM or IV dosage of clindamycin recommended by the manufacturer for infants and children 1 month of age or older is 20-40 mg/kg daily administered in 3 or 4 equally divided doses;139 the higher dosage should be used for more severe infections.139 Alternatively, the manufacturer states that these infants and children may receive 350 mg/m² daily for the treatment of serious infections or 450 mg/m² daily for the treatment of more severe infections.139

In pediatric patients beyond the neonatal period, AAP recommends an IM or IV clindamycin dosage of 20-30 mg/kg daily given in 3 equally divided doses for the treatment of mild to moderate infections or 40 mg/kg daily given in 3 or 4 equally divided doses for the treatment of severe infections.292

General Adult Dosage

The recommended adult dosage of IM or IV clindamycin is 600 mg to 1.2 g daily given in 2-4 equally divided doses for the treatment of serious infections or 1.2-2.7 g daily given in 2-4 equally divided doses for the treatment of more severe infections.139 In the treatment of life-threatening infections, adult IV dosage may be increased to a maximum of 4.8 g daily.139

If continuous IV infusion of clindamycin is used to maintain serum clindamycin concentrations above 4-6 mcg/mL in adults, an initial dose is given by rapid IV infusion prior to continuous IV infusion.139 (See Table 1.)

Respiratory Tract Infections

If IV clindamycin is used in adults for the treatment of healthcare-associated pneumonia or CAP caused by susceptible methicillin-resistant S. aureus (MRSA), IDSA recommends a dosage of 600 mg 3 times daily for 7-21 days.514

If parenteral clindamycin is used for the treatment of CAP caused by susceptible gram-positive bacteria (e.g., S. pneumoniae , S. pyogenes , S. aureus ) in children older than 3 months of age, IDSA recommends a dosage of 40 mg/kg daily given in divided doses every 6-8 hours.513,514

Anthrax

Although the optimum regimen for the treatment of inhalational anthrax† remains to be established, several patients who developed inhalational anthrax in the context of an intentional release of anthrax spores (biologic warfare, bioterrorism) were treated successfully with a multiple-drug regimen that included IV clindamycin (900 mg every 8 hours), IV ciprofloxacin (400 mg every 8 hours), and IV rifampin (300 mg every 12 hours).119 (See Uses: Anthrax.)

Duration of treatment is 60 days if anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.117,120

Babesiosis

For the treatment of babesiosis† caused by B. microti or other Babesia species, IDSA and other experts recommend that adults receive clindamycin in a dosage of 300-600 mg IV every 6 hours (or 600 mg orally every 8 hours) in conjunction with oral quinine sulfate (650 mg every 6 or 8 hours) given for 7-10 days.134,329

For the treatment of babesiosis in pediatric patients, IDSA recommends an IV (or oral) clindamycin dosage of 7-10 mg/kg (up to 600 mg) every 6-8 hours in conjunction with oral quinine sulfate (8 mg/kg [up to 650 mg] every 8 hours) given for 7-10 days.329 Other clinicians recommend an IV (or oral) clindamycin dosage of 20-40 mg/kg (up to 600 mg) daily given in 3 or 4 divided doses for 7-10 days in conjunction with oral quinine sulfate (24 mg/kg daily given in 3 divided doses for 7-10 days).134

Patients with mild to moderate babesiosis should have clinical improvement within 48 hours after treatment is initiated; symptoms should resolve completely within 3 months.329 Patients with severe babesiosis should receive IV clindamycin rather than oral clindamycin.329 Some patients may have persistent low-grade parasitemia for months after anti-infective treatment.329 Some experts suggest that anti-infective treatment in immunosuppressed patients should be continued for a minimum of 6 weeks and at least 2 weeks after the last positive smear.134 Regardless of the presence or absence of symptoms, IDSA suggests that retreatment be considered if babesial parasites or amplifiable babesial DNA is detected in blood 3 months or longer after initial treatment.329

Pelvic Inflammatory Disease

For the treatment of acute pelvic inflammatory disease (PID) when a parenteral regimen is indicated, adults and adolescents may receive 900 mg of clindamycin IV every 8 hours.344,345 Gentamicin sulfate should be administered concomitantly (initial IM or IV gentamicin dose of 2 mg/kg followed by 1.5 mg/kg every 8 hours;344,345 alternatively, 3-5 mg/kg of gentamicin can be given as a single daily dose).344 Both parenteral drugs can be discontinued 24-48 hours after there is clinical improvement and therapy continued with oral clindamycin in a dosage of 450 mg 4 times daily to complete 14 days of therapy.344,345 Alternatively, oral doxycycline (100 mg twice daily) can be given to complete 14 days of therapy.344,345 (See Uses: Pelvic Inflammatory Disease.)

Patients with PID who do not demonstrate substantial clinical improvement (e.g., defervescence; reduction in direct or rebound abdominal tenderness; reduction in uterine, adnexal, and cervical motion tenderness) within 72 hours of initiating parenteral or oral therapy usually require additional diagnostic tests and/or surgical intervention.344

Pneumocystis jirovecii Pneumonia

If a regimen of IV clindamycin and oral primaquine is used as an alternative for the treatment of moderate to severe PCP†, CDC, NIH, and IDSA recommend that adults and adolescents receive IV clindamycin in a dosage of 600 mg every 6 hours or 900 mg every 8 hours for 21 days in conjunction with oral primaquine (30 mg once daily for 21 days).440

Although data regarding use in children are not available, if a regimen of IV clindamycin and oral primaquine is used as an alternative for the treatment of PCP in pediatric patients, some clinicians recommend that IV clindamycin be given in a dosage of 10 mg/kg (up to 600 mg) every 6 hours for 21 days in conjunction with oral primaquine (0.3 mg/kg once daily [up to 30 mg daily] for 21 days).441

Toxoplasmosis

For the treatment of toxoplasmosis† in HIV-infected adults and adolescents who cannot receive sulfadiazine or did not respond to an initial regimen, CDC, NIH, and IDSA recommend that adults and adolescents receive IV (or oral) clindamycin in a dosage of 600 mg every 6 hours in conjunction with oral pyrimethamine (200-mg loading dose followed by 50 mg once daily in those weighing less than 60 kg or 75 mg once daily in those weighing 60 kg or more) and oral leucovorin (10-25 mg once daily; may be increased to 50 mg once or twice daily).440

For the treatment of congenital toxoplasmosis† or the treatment of acquired CNS, ocular, or systemic toxoplasmosis† in HIV-infected children, CDC, NIH, and IDSA recommend an IV (or oral) clindamycin dosage of 5-7.5 mg/kg (up to 600 mg) 4 times daily in conjunction with oral pyrimethamine (2 mg/kg once daily for 2 days followed by 1 mg/kg once daily) and oral or IM leucovorin (10 mg with each pyrimethamine dose).441 Although optimal duration of treatment has not been determined, some experts recommend that treatment of congenital toxoplasmosis be continued for 12 months.441 The treatment regimen should be continued for at least 6 weeks in HIV-infected children with acquired CNS, ocular, or systemic toxoplasmosis; a longer duration may be appropriate for extensive disease or if there is an incomplete response at 6 weeks.441

Perioperative Prophylaxis

If clindamycin is used alone or in conjunction with another anti-infective for perioperative prophylaxis in patients undergoing certain surgeries when the drugs of choice cannot be used (see Uses: Perioperative Prophylaxis), some clinicians recommend that adults receive 900 mg of the drug360,374 and that pediatric patients receive 10 mg/kg of the drug374 given IV within 60 minutes prior to the initial incision.360,374

During prolonged procedures, some clinicians suggest that additional intraoperative doses of clindamycin can be given every 6 hours for the duration of the procedure in patients with normal renal function.360,374 Postoperative doses of prophylactic anti-infectives generally are not recommended.360

Prevention of Bacterial Endocarditis

When IM or IV clindamycin is used as an alternative for prevention of bacterial endocarditis† in penicillin-allergic patients (or patients unable to take oral medication) with certain cardiac conditions who are undergoing certain dental procedures or certain other procedures (see Uses: Prevention of Bacterial Endocarditis), AHA recommends that adults receive a single 600-mg dose and that children receive a single 20-mg/kg dose of the drug given 30-60 minutes before the procedure.451

Prevention of Perinatal Group B Streptococcal Disease

If clindamycin is used for intrapartum anti-infective prophylaxis for prevention of perinatal group B streptococcal (GBS) disease† in women with penicillin hypersensitivity who should not receive a β-lactam anti-infective, CDC and AAP recommend that 900 mg of clindamycin be given IV at the time of onset of labor or rupture of membranes followed by 900 mg IV every 8 hours until delivery.292,359 Because S. agalactiae (group B streptococci; GBS) with resistance to clindamycin has been reported with increasing frequency, clinical isolates obtained during GBS prenatal screening should be tested for in vitro susceptibility to clindamycin whenever use of the drug is being considered for prevention of perinatal GBS disease.292,359,362 (See Uses: Prevention of Perinatal Group B Streptococcal Disease.)

Dosage in Renal and Hepatic Impairment

Renal Impairment

Dosage adjustments are not usually necessary in patients with renal impairment.121,126,139

Hepatic Impairment

Dosage adjustments are not usually necessary in patients with hepatic impairment.121,126,139 However, because the plasma half-life of clindamycin may be prolonged, hepatic function should be monitored if the drug is used in those with severe hepatic impairment.121,126,139

GI Effects

Adverse GI effects frequently occur with oral, IM, or IV clindamycin and may be severe enough to necessitate discontinuance of the drug. Adverse GI effects reported in patients receiving clindamycin include nausea,121,126 vomiting,121,126 diarrhea,121,126 abdominal pain,121,126 and esophagitis.121,126 In addition, tenesmus, flatulence, bloating, anorexia, and weight loss have been reported.

An unpleasant or metallic taste has been reported in patients receiving oral clindamycin121,126 and also has been reported following IV administration of high doses of the drug.139

Clostridium difficile-associated Diarrhea and Colitis

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile .121,126,139,302,303,304

C. difficile infection (CDI) and C. difficile -associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported with nearly all anti-infectives, including clindamycin, and may range in severity from mild diarrhea to fatal colitis.121,126,139,302,303,304C. difficile produces toxins A and B, which contribute to the development of CDAD; hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.121,126,139,302(See Superinfection/Clostridium difficile-associated Diarrhea and Colitis under Cautions: Precautions and Contraindications.)

Sensitivity and Dermatologic Reactions

Anaphylactic shock and anaphylactoid reactions with hypersensitivity have been reported in patients receiving clindamycin.121,126,139

Other severe hypersensitivity reactions, including severe skin reactions such as toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome, have been reported and have been fatal in some cases.121,126,139 Acute generalized exanthematous pustulosis and erythema multiforme also have been reported.121,126,139

Generalized mild to moderate morbilliform-like (maculopapular) rash is the most frequently reported adverse reaction to clindamycin.121,126,139 Vesiculobullous rash,121,126 urticaria,121,126 pruritus,121,126 angioedema,121,126 and rare instances of exfoliative dermatitis121,126 also have been reported.

Local Effects

Thrombophlebitis,139 erythema, pain, and swelling have occurred with IV administration of clindamycin.

IM administration of clindamycin has caused pain,139 induration,139 and sterile abscess139 at the injection site. Reversible increases in serum creatine kinase (CK, creatine phosphokinase, CPK) concentrations have been reported.

Local reactions can be minimized by giving deep IM injections or avoiding prolonged use of indwelling IV catheters.139

Other Adverse Effects

Cardiopulmonary arrest and hypotension have been reported when IV clindamycin was administered too rapidly.139

Although renal damage has not been directly attributed to clindamycin, renal dysfunction manifested as azotemia, oliguria, and/or proteinuria has been observed in patients receiving clindamycin.121,126,139

Transient neutropenia (leukopenia) and eosinophilia, agranulocytosis, and thrombocytopenia have been reported in patients receiving clindamycin; however, a causal relationship was not established.121,126,139

Jaundice,121,126,139 abnormal liver function tests,121,126,139 polyarthritis,121,126,139 and vaginitis121,126,139 also have been reported.

Precautions and Contraindications

Clindamycin is contraindicated in patients hypersensitive to clindamycin or lincomycin.121,126,139

Prior to initiation of clindamycin, the patient should be questioned regarding prior hypersensitivity to drugs and other allergens.121,126,139 Clindamycin should be used with caution in atopic individuals.121,126,139

If an anaphylactic or severe hypersensitivity reaction occurs during clindamycin therapy, the drug should be permanently discontinued and appropriate therapy instituted as necessary.121,126,139

Superinfection/Clostridium difficile-associated Diarrhea and Colitis

As with other anti-infectives, use of clindamycin may result in overgrowth of nonsusceptible organisms, especially yeasts.121,126,139 If superinfection occurs, appropriate therapy should be instituted.121,126,139

Because CDAD has been reported with the use of nearly all anti-infectives, including clindamycin, it should be considered in the differential diagnosis in patients who develop diarrhea during or after clindamycin therapy.121,126,139,302,303,304 Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.121,126,139 If CDAD is suspected or confirmed, anti-infective therapy not directed against C. difficile should be discontinued whenever possible.121,126,139,302,303,304 Patients should be managed with appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.121,126,139,302,303,304

Patients should be advised that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued; however, it is important to contact a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.121,126,139

Clindamycin should always be discontinued if clinically important diarrhea occurs.121,126,139 The drug should be used with caution in patients with a history of GI disease, particularly colitis.121,126,139

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of clindamycin and other antibacterials, the drug should be used only for the treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.121,126,139 When selecting or modifying anti-infective therapy, results of culture and in vitro susceptibility testing should be used.121,126,139 In the absence of such data, local epidemiology and susceptibility patterns should be considered when selecting anti-infectives for empiric therapy.121,126,139 Culture and susceptibility testing performed periodically during therapy provides information on the therapeutic effect of the anti-infective agent and the possible emergence of bacterial resistance.121,126,139

Patients should be advised that antibacterials (including clindamycin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).121,126,139 Patients also should be advised about the importance of completing the full course of therapy, even if feeling better after a few days, and that skipping doses or not completing therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with clindamycin or other antibacterials in the future.121,126,139

Other Precautions and Contraindications

Some commercially available capsules of clindamycin hydrochloride (e.g., Cleocin HCl^® 75- and 150-mg capsules) contain the dye tartrazine (FD&C yellow No. 5), which may cause allergic reactions, including bronchial asthma, in susceptible individuals.126 Although the incidence of tartrazine sensitivity is low, it frequently occurs in patients who are sensitive to aspirin.126

Because clindamycin does not distribute adequately into the CNS, the drug should not be used for the treatment of CNS infections.121,126

During prolonged clindamycin therapy, liver and renal function tests and blood cell counts should be performed periodically.121,126,139

If clindamycin is used in patients with hepatic impairment, dosage adjustments may not be necessary; however, liver enzymes should be monitored periodically when the drug is used in those with severe hepatic impairment.121,126,139

Pediatric Precautions

When clindamycin is used in pediatric patients (birth to 16 years of age), organ system functions should be monitored.121,126,139

Each mL of clindamycin phosphate injection contains 9.45 mg of benzyl alcohol.139 Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates, including potentially fatal “gasping syndrome.”106,107,108,109,139 Toxicity appears to have resulted from administration of large amounts (i.e., about 100-400 mg/kg daily) of benzyl alcohol in these neonates.106,107 Although the amounts of benzyl alcohol in recommended dosages of IM or IV clindamycin are substantially lower than amounts reported in association with “gasping syndrome,” the minimum amount of benzyl alcohol at which toxicity may occur is unknown.139 The risk of benzyl alcohol toxicity depends on the quantity administered and capacity of the liver and kidneys to detoxify the chemical.139 Premature and low-birthweight infants may be more likely to develop toxicity.139 Although use of drugs preserved with benzyl alcohol should be avoided in neonates whenever possible,106,107 the American Academy of Pediatrics (AAP) states that the presence of small amounts of the preservative in a commercially available injection should not proscribe its use when indicated in an infant.106

Geriatric Precautions

Clinical studies of clindamycin did not include sufficient numbers of patients 65 years of age or older to determine whether geriatric patients respond differently than younger patients.121,126,139 Clinical experience indicates that C. difficile -associated diarrhea and colitis (see Cautions: GI Effects) seen in association with most anti-infectives may occur more frequently and be more severe in patients older than 60 years of age.121,126,139,302 Therefore, geriatric patients receiving clindamycin should be carefully monitored for the development of diarrhea (e.g., changes in bowel frequency).121,126,139

Studies to date have not revealed any clinically important differences in the pharmacokinetics of oral or parenteral clindamycin between younger adults and geriatric patients with normal hepatic function and normal (age-adjusted) renal function.121,126,139 Dosage adjustments are not usually necessary if clindamycin is used in geriatric patients with normal hepatic function and normal (age-adjusted) renal function.121,126,139

Mutagenicity and Carcinogenicity

Clindamycin was not mutagenic in a rat micronucleus test or the Ames Salmonella reversion test.121,126,139

Long-term studies in animals have not been performed to date to evaluate the carcinogenic potential of clindamycin.121,126,139

Pregnancy, Fertility, and Lactation

Pregnancy

Reproduction studies in rats and mice using oral or parenteral dosages of clindamycin up to 600 mg/kg daily (3.2 and 1.6 times, respectively, the maximum recommended human oral dosage or 2.1 and 1.1 times, respectively, the maximum recommended human parenteral dosage on a mg/m² basis) have not revealed evidence of teratogenicity.121,126,139

In clinical trials that included pregnant women, systemic clindamycin administered during the second and third trimesters was not associated with an increased frequency of congenital abnormalities.126,139 There are no adequate and well-controlled studies to date using clindamycin in pregnant women during the first trimester of pregnancy.121,126,139 Because animal reproduction studies are not always predictive of human response, clindamycin should be used during pregnancy only when clearly needed.121,126,139

Clindamycin phosphate injection contains benzyl alcohol as a preservative; benzyl alcohol can cross the placenta.139 (See Cautions: Pediatric Precautions.)

Fertility

Fertility studies in rats treated with oral clindamycin doses up to 300 mg/kg daily (about 1.1-1.6 times the maximum recommended human dose on a mg/m² basis) have not revealed evidence of impaired fertility or mating ability.121,126,139

Lactation

Clindamycin is distributed into milk (see Pharmacokinetics: Distribution),100,121,126,139 and has the potential to cause adverse effects on the GI flora of breast-fed infants.121,126,139

The manufacturer states that use of oral or IV clindamycin in the mother is not a reason to discontinue breast-feeding; however, it may be preferable to use an alternate anti-infective.121,126,139 If clindamycin is used in a breast-feeding mother, the infant should be monitored for possible adverse effects on GI flora, including diarrhea and candidiasis (thrush, diaper rash) or, rarely, blood in the stool indicating possible antibiotic-associated colitis.121,126,139 The benefits of breast-feeding and the importance of clindamycin to the woman should be considered along with potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition.121,126,139

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

In vitro studies indicate that clindamycin is a moderate inhibitor of cytochrome P-450 (CYP) isoenzyme 3A4 and does not inhibit CYP1A2, 2C9, 2C19, 2E1, or 2D6.121,126,139

Clindamycin is a substrate of CYP3A4 and, to a lesser extent, CYP3A5.121,126,139 Concomitant use with CYP3A4 or 3A5 inhibitors may result in increased plasma concentrations of clindamycin, and concomitant use with CYP3A4 or 3A5 inducers may result in decreased plasma concentrations of clindamycin.121,126,139 If clindamycin is used concomitantly with a potent CYP3A4 inhibitor, the patient should be monitored for adverse effects.121,126,139 If clindamycin is used concomitantly with a potent CYP3A4 inducer (e.g., rifampin), the patient should be monitored for loss of clindamycin effectiveness.121,126,139

Neuromuscular Blocking Agents

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the neuromuscular blocking action of other agents (e.g., ether, tubocurarine, pancuronium).121,126,139,198,199 Clindamycin should be used with caution in patients receiving such agents,121,126,139,198,199 and such patients should be observed for prolongation of neuromuscular blockade.199

Acute Toxicity

Convulsions, depression, and death have been reported in mice receiving IV clindamycin doses of 855 mg/kg; death has been reported in rats receiving oral or subcutaneous clindamycin doses of 2.6 mg/kg.121,126,139

Clindamycin is not removed by hemodialysis or peritoneal dialysis.121,126,139

Mechanism of Action

Clindamycin palmitate hydrochloride and clindamycin phosphate are inactive until hydrolyzed to free clindamycin. This hydrolysis occurs rapidly in vivo.

Clindamycin usually is bacteriostatic in action, but may be bactericidal depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism.

Clindamycin inhibits protein synthesis in susceptible bacteria by binding to the 23S RNA of the 50S ribosomal subunits;121,126,139,140 the primary effect is inhibition of peptide bond formation. The site of action appears to be the same as that of erythromycin, chloramphenicol, and lincomycin.

Spectrum

Clindamycin is active in vitro against many gram-positive aerobic and anaerobic bacteria and some gram-negative anaerobic bacteria.121,126,139,140,141 Clindamycin generally is inactive against most gram-negative aerobic bacteria.140

Clindamycin is active in vitro against Staphylococcus aureus (methicillin-susceptible strains),121,126,139,140,141 S. epidermidis (methicillin-susceptible strains),121,126,139,141 Streptococcus pneumoniae (penicillin-susceptible strains),121,126,139,140,141 S. pyogenes (group A β-hemolytic streptococci; GAS),121,126,139,140,141 S. agalactiae (group B streptococci; GBS),121,126,139 S. anginosus ,121,126,139 S. mitis ,121,126,139 and S. oralis .121,126,139 The drug is not active against Enterococcus faecalis or E. faecium .140

Clindamycin is active in vitro against some anaerobic and microaerophilic organisms including Actinomyces israelii ,121,126,139,140 Clostridium clostridioforme ,121,126,139 C. perfringens ,121,126,139 Eggerthella lenta (previously known as Eubacterium lentum ),121,126,139 Finegoldia anaerobius ,121,126,139 Finegoldia magna ,121,126,139 Fusobacterium necrophorum ,121,126,139 F. nucleatum ,121,126,139 Micromonas micros ,121,126,139 Mobiluncus ,173,176,177 Prevotella ( P. disiens , P. intermedia , P. melaninogenica , P. vivia ),121,126,139,140,173 Porphyromonas ,140,173 and Propionibacterium acnes .121,126,139

Clindamycin is active in vitro and in vivo against Gardnerella vaginalis .140,173,178,179,180

Clindamycin has in vitro activity against Toxoplasma gondii in infected human fibroblasts.141 The drug has been reported to have some activity against Plasmodium falciparum in vitro.140

Clindamycin generally is inactive against gram-negative aerobic bacteria, including Enterobacteriaceae,140,141 Pseudomonas ,140 Acinetobacter ,140 and most strains of Haemophilus influenzae 140,141 and Neisseria .140,141

In Vitro Susceptibility Testing

When in vitro susceptibility testing is performed according to the standards of the Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards [NCCLS]), clinical isolates identified as susceptible to clindamycin are inhibited by drug concentrations usually achievable when the recommended dosage is used for the site of infection.209 Clinical isolates classified as intermediate have minimum inhibitory concentrations (MICs) that approach usually attainable blood and tissue concentrations and response rates may be lower than for strains identified as susceptible.209 Therefore, the intermediate category implies clinical applicability in body sites where the drug is physiologically concentrated or when a higher than usual dosage can be used.209 This intermediate category also includes a buffer zone which should prevent small, uncontrolled technical factors from causing major discrepancies in interpretation, especially for drugs with narrow pharmacotoxicity margins.209 If results of in vitro susceptibility testing indicate that a clinical isolate is resistant to clindamycin, the strain is not inhibited by drug concentrations generally achievable with usual dosage schedules and/or MICs fall in the range where specific microbial resistance mechanisms are likely and clinical efficacy of the drug against the isolate has not been reliably demonstrated in clinical studies.209

Disk Susceptibility Tests

When the disk-diffusion procedure is used to test susceptibility to clindamycin, a disk containing 2 mcg of the drug should be used.121,126,139,209

When disk susceptibility testing is performed according to CLSI standardized procedures, Staphylococcus with growth inhibition zones of 21 mm or greater are susceptible to clindamycin, those with zones of 15-20 mm have intermediate susceptibility, and those with zones of 14 mm or less are resistant to the drug.121,126,139,209

When susceptibility of Streptococcus is evaluated according to CLSI standardized procedures, Streptococcus (including S. pneumoniae ) with growth inhibition zones of 19 mm or greater are susceptible to clindamycin, those with zones of 16-18 mm have intermediate susceptibility, and those with zones of 15 mm or less are resistant to the drug.121,126,139,209

Dilution Susceptibility Tests

When dilution susceptibility testing (agar or broth dilution) is performed according to CLSI standardized procedures, Staphylococcus with MICs of 0.5 mcg/mL or less are susceptible to clindamycin, those with MICs of 1-2 mcg/mL have intermediate susceptibility, and those with MICs of 4 mcg/mL or greater are resistant to the drug.121,126,139,209

When broth dilution susceptibility testing is performed according to CLSI standardized procedures, Streptococcus (including S. pneumoniae ) with MICs of 0.25 mcg/mL or less are susceptible to clindamycin, those with MICs of 0.5 mcg/mL have intermediate susceptibility, and those with MICs of 1 mcg/mL or greater are resistant to the drug.121,126,139,209

When broth dilution susceptibility testing is performed according to CLSI standardized procedures, anaerobic bacteria with MICs of 2 mcg/mL or less are susceptible to clindamycin, those with MICs of 4 mcg/mL have intermediate susceptibility, and those with MICs of 8 mcg/mL or greater are resistant to the drug.121,126,139,209

Resistance

Resistance to clindamycin has been induced in vitro in staphylococci and has been shown to be acquired in a stepwise manner. Clindamycin resistance has been reported in clinical isolates of Staphylococcus aureus , especially methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA).141

S. agalactiae (group B streptococci; GBS) clinical isolates resistant to clindamycin have been reported with increasing frequency.140,292,359 Data from 2006-2011 indicated that 13-30% of GBS clinical isolates in the US were resistant to clindamycin.292,359,362 Because GBS isolates that appear susceptible to clindamycin but resistant to erythromycin in vitro may have inducible resistance to clindamycin, appropriate in vitro susceptibility testing methods should be used whenever in vitro susceptibility of GBS to clindamycin is being evaluated.359

Clinical isolates of Bacteroides fragilis with resistance or reduced susceptibility to clindamycin have been reported with increasing frequency.140,141

Resistance to clindamycin is most frequently caused by modification of specific bases of the 23S ribosomal RNA.121,126,139

Complete cross-resistance occurs between clindamycin and lincomycin.121,126,139,141 Because of overlapping binding sites, partial cross-resistance has been reported between clindamycin and macrolides (e.g., erythromycin) and streptogramin B.121,126,139,140,141 In vitro, bacteria resistant to erythromycin and susceptible to clindamycin may exhibit a dissociated type of resistance to clindamycin during susceptibility testing if erythromycin is also present. This phenomenon may be the result of competition between erythromycin and clindamycin for the ribosomal binding site.

Pharmacokinetics

Absorption

Following oral administration of clindamycin hydrochloride, approximately 90% of the dose is rapidly absorbed from the GI tract.126 Following oral administration of a single 150-mg dose of clindamycin hydrochloride to healthy fasting adults, peak serum concentrations of clindamycin average 1.9-3.9 mcg/mL and are attained within 45-60 minutes; serum concentrations of clindamycin average 1.5 mcg/mL at 3 hours and 0.7 mcg/mL at 6 hours. Serum concentrations of clindamycin appear to be predictable, increasing linearly with increased doses.

Following oral administration of clindamycin palmitate hydrochloride oral solution, the drug is rapidly hydrolyzed in the GI tract to active clindamycin.121 Oral doses of clindamycin palmitate hydrochloride produce serum concentrations of clindamycin similar to those achieved with oral clindamycin hydrochloride. In a study in healthy children receiving 2, 3, or 4 mg/kg of clindamycin every 6 hours as the clindamycin palmitate hydrochloride oral solution, mean peak serum clindamycin concentrations were 1.24, 2.25, or 2.44 mcg/mL, respectively, 1 hour after the first dose.121 After the fifth dose, peak serum concentrations of the drug averaged 2.46, 2.98, or 3.79 mcg/mL, respectively.121

Clindamycin is not inactivated by gastric acidity. Administration of clindamycin hydrochloride capsules126 or clindamycin palmitate hydrochloride oral solution121 with food does not appreciably affect absorption121 or serum concentrations of the drug.126 Accumulation in plasma does not occur following multiple oral doses,121,126 including in neonates and infants up to 6 months of age.121

Following IM or IV administration, clindamycin phosphate is rapidly hydrolyzed in plasma to active clindamycin.139 Following IM administration of clindamycin phosphate, peak serum concentrations occur within 3 hours in adults and 1 hour in children.139 In healthy adult males, IM doses of 600 mg of clindamycin every 12 hours resulted in average peak serum clindamycin concentrations of 9 mcg/mL.139 IV doses of 600 mg of clindamycin infused over 30 minutes every 6 or 8 hours in healthy adult males resulted in average peak serum clindamycin concentrations of 11 mcg/mL and IV doses of 900 mg infused over 30 minutes every 8 hours resulted in average peak serum clindamycin concentrations of 14 mcg/mL.139 In a study in pediatric patients with infections, a single IM dose of 3-5 mg/kg resulted in average peak serum clindamycin concentrations of 4 mcg/mL and single IV or IM doses of 5-7 mg/kg resulted in average peak serum clindamycin concentrations of 10 or 8 mcg/mL, respectively.139

Distribution

Clindamycin is widely distributed into body tissues and fluids,121,126,140 including saliva,140 ascites fluid,140 peritoneal fluid,140 pleural fluid,140 synovial fluid,140 bone,121,126,140 and bile.140 The concentration of clindamycin in synovial fluid and bone is reported to be 60-80% of concurrent serum concentrations of the drug; the degree of penetration does not appear to be affected by joint inflammation.

Clinically important concentrations of clindamycin are not attained in CSF, even in the presence of inflamed meninges.121,126,139,140

Clindamycin readily crosses the placenta,140,141 and cord blood concentrations of the drug have been reported to be up to 50% of concurrent maternal blood concentrations.140

Clindamycin is distributed into milk.100,121,126,139,140 Breast milk concentrations of 0.7-3.8 mcg/mL121,126,139 have been reported following clindamycin dosages of 150 mg orally to 600 mg IV.139 In one study in women who received oral clindamycin in a dosage of 150 mg 3 times daily, breast milk concentrations of the drug ranged from less than 0.5 to 3.1 mcg/mL.100

At a concentration of 1 mcg/mL, clindamycin is approximately 93% bound to serum proteins.

Elimination

Clindamycin is partially metabolized to bioactive and inactive metabolites. In vitro studies indicate that clindamycin is predominantly metabolized by cytochrome P-450 (CYP) isoenzyme 3A4 and, to a lesser extent, by CYP3A5 to the major bioactive metabolite clindamycin sulfoxide and minor metabolite N -desmethylclindamycin.121,126,139

The serum half-life of clindamycin is 2-3 hours in adults and children.121,126,139 In neonates, the serum half-life of clindamycin depends on gestational and chronologic age and body weight.102 Half-life of the drug reportedly averages 8.7 or 3.6 hours in premature or full-term neonates, respectively, and about 3 hours in infants 4 weeks to 1 year of a serum half-life was longer in infants weighing less than 3.5 kg than in heavier infants.102

Pharmacokinetic studies using IV clindamycin phosphate in healthy older adults (61-79 years of age) and younger adults (18-39 years of age) indicate that age alone does not alter clindamycin pharmacokinetics (clearance, elimination half-life, volume of distribution, area under the serum concentration-time curve [AUC]).121,126,139 Following oral administration of clindamycin hydrochloride, elimination half-life increased to approximately 4 hours (range: 3.4-5.1 hours) in geriatric patients compared with 3.2 hours (range: 2.1-4.2 hours) in younger adults.121,126,139 Following oral administration of clindamycin palmitate, the elimination half-life in geriatric adults was 4.5 hours.121

The serum half-life of clindamycin is increased slightly in patients with markedly reduced renal or hepatic function.121,126,139

Clindamycin sulfoxide and N -desmethylclindamycin are excreted in urine, bile, and feces. Approximately 10% of an oral dose of clindamycin is excreted in urine and 3.6% is excreted in feces as active drug and metabolites;121,126 the remainder is excreted as inactive metabolites.121,126

Clindamycin is not appreciably removed by hemodialysis or peritoneal dialysis.121,126,139

Chemistry and Stability

Chemistry

Clindamycin is a semisynthetic derivative of lincomycin121,126,139,140 that differs structurally from lincomycin by the presence of a methoxy group instead of the hydroxyl group at position 7 on the molecule.140

Clindamycin is commercially available as the hydrochloride hydrate,126 the palmitate hydrochloride,121 and the phosphate ester.139 Potency of clindamycin hydrochloride, clindamycin palmitate hydrochloride, and clindamycin phosphate is expressed in terms of clindamycin.103,121,126,139 Each mg of the hydrochloride hydrate, palmitate hydrochloride, or phosphate has a potency of not less than 800, 540, or 758 mcg of clindamycin, respectively; potency of the phosphate is calculated on the anhydrous basis.103 The hydrochloride, palmitate hydrochloride, and phosphate occur as a white or practically white crystalline powder, a white to off-white amorphous powder, and a white to off-white hygroscopic crystalline powder, respectively, which may have faint, characteristic odors and are freely soluble in water.103 Clindamycin phosphate reportedly has a solubility of about 400 mg/mL in water at 25°C.103 The pK_a of clindamycin is 7.45.

Clindamycin hydrochloride is commercially available for oral administration as capsules.126 Clindamycin palmitate hydrochloride is commercially available as a powder (granules) for oral solution;121 when reconstituted as directed, each 5 mL of oral solution contains 75 mg of clindamycin.121

Clindamycin phosphate is commercially available as a sterile solution containing 150 mg of clindamycin that must be diluted prior to IV administration;139 each mL of the solution also contains 0.5 mg of disodium edetate per mL and 9.45 mg of benzyl alcohol as a preservative.139 Clindamycin phosphate also is commercially available as a premixed solution for IV infusion containing 300, 600, or 900 mg of clindamycin in 5% dextrose.139 The premixed solutions contain 0.04 mg of disodium edetate per mL and sodium hydroxide and/or hydrochloric acid may have been added to adjust pH.139

Stability

Clindamycin hydrochloride capsules should be stored at 20-25°C.126

Clindamycin palmitate hydrochloride powder (granules) for oral solution should be stored at 20-25°C.121 Following reconstitution with water, clindamycin palmitate hydrochloride oral solution is stable for 2 weeks at room temperature.121 The reconstituted oral solution should not be refrigerated since it will thicken if chilled and become difficult to pour.121

Clindamycin phosphate solutions containing 150 mg of clindamycin per mL (including ADD-Vantage^® vials) should be stored at a controlled room temperature of 20-25°C.139

Premixed solutions containing clindamycin phosphate in 5% dextrose injection should be stored at room temperature (25°C), and exposure to temperatures warmer than 30°C should be avoided.139 Some premixed solutions of clindamycin phosphate in 5% dextrose are provided in plastic containers fabricated from specially formulated multilayered plastic PL 2501.139 Solutions in contact with the plastic can leach out some of the chemical components in very small amounts within the expiration period of the injection; however, safety of the plastic has been confirmed in tests in animals as well as by tissue culture studies.139

At a concentration of 6, 9, or 12 mg of clindamycin per mL, clindamycin phosphate is physically and chemically compatible for at least 16 days at 25°C or at least 32 days when refrigerated at 4°C in glass or polyvinyl chloride (PVC) containers, or for at least 8 weeks when frozen at -10°C in PVC containers of the following IV solutions: 5% dextrose, 0.9% sodium chloride, or lactated Ringer's.139 At a concentration of 18 mg of clindamycin per mL, clindamycin phosphate is physically and chemically compatible for at least 16 days at 25°C in PVC containers of 5% dextrose.139

Clindamycin phosphate is physically and microbiologically compatible for 24 hours at room temperature in IV solutions containing sodium chloride, dextrose, potassium, or vitamin B complex in concentrations used clinically.139 However, certain concentrations or admixtures of calcium salts may result in physical incompatibility. Clindamycin phosphate has been reported to be incompatible with various drugs (e.g., aminophylline, barbiturates, ceftriaxone, ciprofloxacin, magnesium sulfate, phenytoin sodium);139,300 however, the compatibility depends on several factors (e.g., concentration of the drugs, specific diluents used, resulting pH, temperature).139 Specialized references should be consulted for specific compatibility information.300

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