Clindamycin development

To prevent development of resistance and promote synergy, inhaled tobramycin or colistin is usually added to an oral fluoroquinolone for P. aeruginosa coverage.1,3 Methicillin-sensitive S. aureus (MSSA) may be treated with oral amoxiciUin-clavulanic acid, dicloxacillin, first- or second-generation cephalosporins, trimethoprim-sulfamethoxazole, or clindamycin, depending on sensitivity. Likewise, methiciUin-resistant S. aureus (MRSA) may be treated with oral trimethoprim-sulfamethoxazole, clindamycin, minocycline, or linezolid. H. influenzae often produces... 

Although tetracycline, doxycycline, and minocycline are the most commonly prescribed oral antibiotics for acne, erythromycin and clindamycin are appropriate second-line agents for use when patients cannot tolerate or have developed resistance to tetracycline or its derivatives.3 See Table 62-3 for antibiotic dosing guidelines. 

Although their effectiveness is similar to the tetracyclines, the use of erythromycin and clindamycin is often limited due to their potential adverse outcomes. Erythromycin has treatment failure due to resistance and a high incidence of gastrointestinal intolerance, while clindamycin causes diarrhea and carries a risk of developing pseudomembranous colitis with long-term use.3,8... 

If a patient aspirates his or her oral contents and pneumonia develops, then anaerobes and Streptococcus spp. are the primary pathogens. Antibiotics active against these organisms include penicillin G, ampicillin/sulbactam, clindamycin, and metronidazole. 

Cefazolin or cefuroxime are appropriate for prophylaxis in cardiothoracic and vascular surgeries. In the case of 3-lactam allergy, vancomycin or clindamycin are advised. Debate exists on the duration of antimicrobial prophylaxis. The National Surgical Infection Prevention Project cites data that extending prophylaxis beyond 24 hours does not decrease SSI rates and may increase bacterial resistance.1 American Society of Health-System Pharmacists guidelines from 1999 allow for the continuation of prophylaxis for up to 72 hours.22 Duration of therapy should be based on patient factors and risk of development of an SSI. SSIs are rare after cardiothoracic operations, but the potentially devastating consequences lead some clinicians to support longer periods of prophylaxis. 

The answer is c. (Hardman, pp 996-997r 1145—1146. Ka tzung, p 8455 Metronidazole is often used to treat antibiotic-associated enterocolitis, especially when caused by C difficile. Vancomycin is no longer preferred because it induces selection of resistant staphylococci. Clindamycin is also associated with C difficile colitis, but in another way a higher percentage of patients taking this over other antibiotics develop antibiotic-associated enterocolitis. 

Antibiotics also are active against other protozoans. Tetracycline and erythromycin are alternative therapies for the treatment of intestinal amebiasis. Clindamycin, in combination with other agents, is effective therapy for toxoplasmosis, pneumocystosis, and babesiosis. Spiramycin is a macrolide antibiotic that is used to treat primary toxoplasmosis acquired during pregnancy. Treatment lowers the risk of the development of congenital toxoplasmosis. 

A 5-year-old child with diabetes, Pierre Robin syndrome, cleft palate, allergic rhinitis, recurrent sinusitis, and obstructive sleep apnea, who had previously had skin rashes after penicillin, sulfonamides, and clindamycin, was given soluble and isophane human insulins (131). Three years later she developed local reactions, 2-5 cm areas, 30-120 minutes after injection. Skin-prick tests were negative for the diluent, isophane, and soluble insulin, but intradermal testing was positive with both insulins. Cetirizine and dexamethasone added to the insulin gave temporary relief. She was... 

Variations in the local prevalence of C difficile may account for the great differences in incidence of antibiotic-associated colitis. For unknown reasons, neonates given clindamycin may become colonized with toxigenic C difficile but do not develop colitis. 

Platzer DJ, White BA. 2006. Development and validation of a gradient HPLC method for the determination of clindamycin and related compounds in a novel tablet formulation. J. Pharm. Biomed. Anal. 41 84-88. 

A 44-year-old HIV-1 infected woman from the Ivory Coast, who was taking stavudine, lamivudine, efavirenz, and pyrimethamine plus sulfadiazine for Toxoplasma encephalitis, developed a maculopapular rash on both arms. The sulfadiazine was withdrawn and clindamycin was added. Ten days later her condition had worsened. Her temperature was 40 C, pulse rate 137/minute, and respiratory rate 26/minute. She had a generalized maculopapular rash without mucosal involvement, moderate abdominal tenderness, hepatomegaly, jaundice, and bilateral crackles. Her white cell count was 16 x 10 /1 with 9% eosinophils and 51% lymphocytes. A chest X-ray showed moderate bilateral interstitial pneumonitis. All drugs were withdrawn and she was given intravenous methylprednisolone. The skin rash and aU systemic manifestations resolved within 1 week and HIV treatment was restarted uneventfully with lamivudine, stavudine, and nehinavir. 

In a retrospective cohort study of patients hospitalized in a Canadian teaching hospital during January 2003 to June 2004 there were 7421 episodes of care in 5619 patients, who were observed until they developed Clostridium difficile-s s,ocmt d diarrhea, or died, or for 60 days after discharge (107). Fluoroquinolones were the antibiotics that were most strongly associated with Clostridium di aJe-associated diarrhea (adjusted hazard ratio = 3.44 95% Cl = 2.65, 4.47). Almost one-quarter of all in-patients received quinolones, for which the population-attributable fraction of Clostridium difficile-as,s,odsAed diarrhea was 36%. All three generations of cephalosporins, macrolides, clindamycin, and intravenous beta-lactam/beta-lactamase inhibitors were intermediate-risk antibiotics, with similar hazard ratios (1.56-1.89). 

The most prominent adverse reaction of the lincosamides is diarrhea, which varies from mildly loose bowel movements to life-threatening pseudomembranous colitis (see monograph on Beta-lactam antibiotics). Almost all antimicrobial drugs have been associated with severe diarrhea and colitis however, lincomycin and clindamycin have been particularly incriminated. The incidence of clindamycin-induced diarrhea in hospital is 23%. Diarrhea resolves promptly after withdrawal in most cases. It seems to be dose-related and may result from a direct action on the intestinal mucosa. Severe colitis due to C. difficile is not dose-related and occurs in 0.01-10% of recipients. Clustering of cases in time and place suggests the possibility of cross-infection. Even low doses of clindamycin, in some cases after topical administration, can cause marked alterations in several intestinal functions related to bowel flora (23). There was reduced susceptibility of C. difficile to clindamycin in 80% of French isolates in 1997 (24). Lincomycin was among the antibiotics that were most often associated with the development of antibiotic-associated diarrhea in a Turkish study of 154 patients other associated antibiotics were azithromycin and ampicillin (25). 

In a one-year retrospective study at a tertiary hospital in Spain, 17% of 148 episodes of diarrhea associated with C. difficile developed after therapy with clindamycin (26). The possible association of toxin-positive C. difficile-induced colitis and the use of clindamycin phosphate vaginal cream for bacterial vaginosis has been reported in a 25-year-old white woman postpartum (27). 

A 57-year-old Caucasian woman with a history of ocular toxoplasmosis, treated with intravitreal clindamycin (1 mg/0.1 ml) and dexamethasone (0.4 mg/0.1 ml), developed a generalized eiythematous macular rash over the scalp, face, arms, thighs, and trunk 2 days after the start of treatment (37). 

In a 38-year-old non-atopic man, a generalized prurigi-nous maculopapular eruption with hp edema and facial erythema developed after 10 days of treatment with oral clindamycin phosphate (300 mg qds) and amoxicillin (500 mg qds) for bronchopneumonia (24). A patch test was positive 2 months later for clindamycin phosphate but negative for peniciUin, amoxiciUin, ampiciUin, and erythromycin. Prick tests and intradermal tests were all negative. Oral rechallenge with chndamycin phosphate 300 mg was positive. 

Successful desensitization has been described in a 35-year-old woman who developed a generalized rash after taking clindamycin (600 mg 6-hourly) and pyrimethamine for 12 days for AIDS-associated cerebral toxoplasmosis the rash resolved after withdrawal of clindamycin (44). Subsequent oral rechallenge was performed (without pretreatment with glucocorticoids or antihistamines), starting with three doses of 20 mg on day 1, 40 mg on day 2, 80 mg on day 3, and so on, until a dose of 600 mg qds was reached on day 7. A transient rash lasting 5 hours developed after the second dose of... 

---