Lincosamides

General adverse effects and adverse reactions

The direct toxicity of the lincosamides is relatively low [ ]. The frequency of adverse reactions to clindamycin may be well below 1%. In a tertiary care center, adverse reactions to clindamycin were reported in 0.47% of 3896 courses, and in half of these events an effect of other medications could not be excluded [ ]. However, clindamycin has not been given in as high doses as lincomycin.

The most common adverse reaction is diarrhea, which occurs in as many as 10–20% of patients. The most serious gastrointestinal complication is colitis due to Clostridium difficile , which occurs with about equal frequency after oral and parenteral treatment [ , ]. Rashes, urticaria, and angioedema have been reported with lincomycin, but are rare. In contrast, maculopapular and pruritic eruptions occur after 1–2 weeks of treatment in up to 10% of patients taking clindamycin. Clindamycin has also been incriminated in one case of Stevens–Johnson syndrome and in one of anaphylaxis; in the latter, hemagglutinating antibodies were found against clindamycin and lincomycin [ ]. Leukocytoclastic angiitis associated with clindamycin is rare. If a similar angiitis can also occur in the colon, the question arises whether some cases of antibiotic-associated colitis might be caused by the drug itself rather than by bacterial toxins. Tumor-inducing effects have not been reported.

Observational studies

Long-term oral clindamycin therapy has been successfully used in a 36-year-old woman with late-stage AIDS who presented with disseminated, nodular cutaneous lesions and underlying osteomyelitis due to a microsporidial infection with an Encephalitozoon-like species [ ].

In 123 patients with uncomplicated falciparum malaria, intravenous clindamycin 5 mg/kg every 8 hours and quinine 8 mg/kg every 8 hours for 3 days, 12 patients had minor adverse effects, including transient hypoacusis (4%), nausea (3.2%), transient hypoglycemia (1%), anxiety (0.8%), diarrhea (0.8%), and transient rash (0.8%). Treatment was withdrawn in two cases on day 2 because one patient had severe diarrhea and the other had intense abdominal pain. In both of these, the clindamycin was withdrawn and the patients completed therapy with a 7-day course of quinine and remained well [ ].

In a retrospective review of the records of 50 consecutive patients with active toxoplasmic chorioretinitis treated with clindamycin, five had gastrointestinal adverse events and six had rashes [ ].

Comparative studies

In a multicenter, double-blind, randomized trial in 87 patients, clindamycin + primaquine was compared with co-trimoxazole as therapy for AIDS-related Pneumocystis jiroveci pneumonia; efficacy was similar. In patients with a PaO ₂ under 70 mmHg, clindamycin + primaquine was associated with fewer adverse events and less glucocorticoid use, but more rashes [ ].

In a prospective, open, randomized trial clindamycin (600 mg tds) and quinine (650 mg tds) were compared with atovaquone (750 mg bd) plus azithromycin (500 mg on day 1 followed by 250 mg/day) in 58 patients with non-life-threatening babesiosis [ ]. Bacterial response was complete 3 months after the end of treatment. Adverse reactions were reported by 72% of those who received clindamycin and quinine compared with 15% of those who received atovaquone and azithromycin. The most common adverse effects with clindamycin and quinine were tinnitus (39%), diarrhea (33%), and impaired hearing (28%); the symptoms had resolved in 73% of the patients assigned to clindamycin/quinine 3 months after the start of therapy and in 100% after 6 months.

In 233 women with bacterial vaginosis, a 3-day regimen of clindamycin (intravaginal ovules, 100 mg/day) was as effective as a 7-day regimen of oral metronidazole (500 mg bd) and better tolerated [ ]. Treatment-related adverse events were reported more often with metronidazole, and systemic symptoms, such as nausea and taste disturbance, accounted for most of the difference between the groups.

Placebo-controlled studies

In a 10-week, multicenter, double-blind study 480 patients with moderate to moderately severe acne were randomized to receive twice-daily 5% benzoyl peroxide, 1% clindamycin, 5% benzoyl peroxide plus 1% clindamycin, or vehicle, all topically [ ]. There were significantly greater reductions in the numbers of inflammatory and total lesions in patients who used combination therapy compared with those who used any of its three individual components. The most frequent adverse reaction, dry skin, occurred to a similar extent with the combination and with benzoyl peroxide alone.

Cardiovascular

Rapid intravenous infusion of large doses of lincomycin (600 mg in 5–10 minutes) can cause flushing and a sensation of warmth for about 10 minutes.

• A patient who received 200 mg/kg of lincomycin experienced nausea, vomiting, hypotension, dyspnea, and electrocardiographic changes for 20 minutes [ ].

Rapid intravenous infusion of lincomycin 1–2 g can cause phlebitis.

Clindamycin can prolong the QT interval and cause ventricular fibrillation [ ]. Cardiac arrest associated with rapid intravenous administration of clindamycin has been reported [ ].

Respiratory

The benzyl alcohol component of clindamycin injection can cause “gasping syndrome” in premature neonates. A baby boy born at 24 weeks gestation weighing 710 g was given intravenous clindamycin [ ]. The first two doses were given without problem, but after the third and fourth doses he had profound desaturation and chest splinting, requiring resuscitation. The clindamycin was withdrawn and he had no obvious sequelae.

Nervous system

Clindamycin, either alone or in combination with neuromuscular blocking drugs or aminoglycosides, has been associated with neuromuscular blockade.

• A 58-year-old woman who was accidentally overdosed with 2400 mg (40 mg/kg) of clindamycin during anesthesia (with tubocurarine and suxamethonium induction) developed prolonged neuromuscular blockade, unresponsive to intravenous calcium or cholinesterase inhibitors (edrophonium and neostigmine), and required assisted ventilation for 11 hours [ ]. It seems likely that the large dose of clindamycin used in this case produced sustained neuromuscular blockade in the absence of non-depolarizing relaxants and after full recovery from suxamethonium.

• A 14-year-old girl with autism developed hiccup-like movements after receiving clindamycin 300 mg bd and risperidone 5.5 mg/day for 1 day; 3 days after withdrawal of clindamycin the abnormal movements resolved [ ].