1. Introduction
Clindamycin, 7(s)-chlor-7-deoxy lincomycin, is a semisynthetic, lincosamide antibiotic. Clindamycin has proven to be efficient against Gram- negative, -positive and anaerobic bacteria, rendering it a dependable medication in the treatment of streptococcal and staphylococcal infections (1-4).
Its antibacterial activity is mediated by attachment to the 50S rRNA of bacterial ribosomes, thus inhibiting the synthesis of proteins and disrupting the proper construction of the cellular wall (5). This disruption results in a reduced adherence to the host cell surface, enhancing the intracellular killing of some strains of gram positive and negative organisms as well as anaerobic bacteria, such as B. fragilis (6).
Clindamycin is the preferred antimicrobial agent in the treatment of the infectious diseases of the female genital tract, cases of pelvic inflammatory disease, post-cesarean section endometritis, post-hysterectomy vaginal cuff infections and septic abortions (7, 8).
A number of side effects have been reported following the administration of clindamycin. These include: maculopapular rash, nausea, diarrhea, vomiting, flatulence, esophagitis, erythema multiforme, metallic taste, anorexia, fever and also hematopoietic and, although occurring rarely, cardiopulmonary effects (9). We describe the case of a patient who developed chest pain and sinus bradycardia following the administration of clindamycin.
2. Case Presentation
A 19-year-old primigravid woman presented herself at Shahid Motaharri Hospital (Urmia, Iran) with a complaint of high grade fever and severe pain in the hypogastrium. The pain was associated with nausea and vomiting since the morning of the same day. She exhibited orientation regarding time, place and person. She was gravida 1, para 0, and with a gestational age of 8 weeks.
She had a thin physique and her features were pale. The physical examination revealed a pyrexia of 39°C (axillary), a feeble pulse, tachycardia (PR: 120) and a blood pressure of 90/60 mmHg (obtained from the right hand in a supine position). Bimanual abdominal examination revealed an enlarged uterus with an estimated age of 8 - 10 weeks. The abdomen was tender to the physician’s touch. Vaginal examination revealed active bleeding, dilation of the external cervical os equivalent to one finger and putrid smelling vaginal discharge. Her menstrual cycle had resumed following a delay of 8 weeks.
Laboratory investigations reported a positive HCG level for pregnancy, a hemoglobin value of 9 gm/dL, White blood cell count of 30000/mm3 with 99% neutrophils, platelet count of 150000 and 3+ qualitative C-reactive protein. All electrolytes were reported to be in their respective range of normal values. Ultrasonography revealed the presence of retained products of conception. Based on the presented evidence, septic abortion was decided as the primary diagnosis.
Treatment was initiated with the administration of intravenous clindamycin (900 mg TID) and gentamicin (80 mg TID). Two liters of lactated Ringer’s was used as volume replacement. Despite the administration of 6 liters of normal saline blood pressure levels exceeding 80/60 mmHg could not be achieved. Evacuation of the retained products of conception was performed via suction. During the operation two units of blood were transfused (due to an atonic uterus and excessive vaginal bleeding). Oxytocin drop was administered drop (30 units in one liter Ringer’s lactate). The patient was taken to the intensive care unit and concurrent resuscitation and investigation was done. The following morning, the patient exhibited bradycardia (PR: 40) and complained of pain in the left side of her chest. Her blood pressure was 100/70 and respiratory rate: 18/min. An ECG was obtained, which represented a sinus bradycardia. Troponin I and creatine kinase-MB values were analyzed and determined to pertain to values within the normal range. Echocardiography revealed an ejection fraction of 50% and the presence of mild mitral regurgitation.
Due to a pulse rate of 50 bpm, an intravenous administration of 4 mg of atropine was performed. The patient remained febrile (T: 37.9°C axillary) despite 48h of antibiotic therapy. Therefore the medications were switched to intravenous administrations of meropenem (1 gr TID) vancomycin (1 gr BID) and metronidazole (500 mg TID). No further modifications were made to daily treatment regimen. The following afternoon, the pulse rate was 65 and normal blood pressure was obtained.
3. Discussion
Fortunately, despite the widespread use of clindamycin in the treatment of the infections of the female genital tract, there have been minor reports on the topic of the side effects caused by its administration. Sinus bradycardia is amongst the less commonly reported adverse effects of clindamycin.
The administration of clindamycin is indicated in patients suffering from serious infections arising from anaerobic bacteria, due to its excellent coverage against gram negative and positive organisms, cocci, anaerobic bacteria such chlamydia trachomatis (10). Zambrano reported the successful use of clindamycin in septic abortion, alone or alongside aminoglycosides (8). Wegner and et al. reported that in healthy subjects, the half-life of clindamycin is 2 hours and 38 minutes (11). Common adverse effects of clindamycin use include gastrointestinal unease, vomiting, nausea, diarrhea, hepatotoxicity, maculopapular rash, anorexia, flatulence, drug fever and Stevens-Johnson syndrome (12, 13). Less common adverse effects include elevated liver transaminase levels, jaundice, monoarthritis, neutropenia, leukopenia, agranulocytosis, hematopoietic, cardiopulmonary arrest and hypotension (9, 14).
Lee et al., have reported that gentamicin and clindamycin stimulate rocuronium-induced neuromuscular blockade. In addition, it was found that these drugs pertain synergistic features when administered concomitantly (7). Fiekers et al. reported that clindamycin affects neural pre and post junctional sites (15). Clindamycin stimulates muscle relaxation and enhances the action of activating neuromuscular agents. Different explanations for clindamycin-induced neuromuscular mechanisms have been proposed (7, 16).
Therefore, the bradycardia was more likely to be related to the administration of clindamycin and professionals should be fully aware of the mechanisms of action and side effects of the antibiotics which they choose to administer. It is suggested that clinical trials be conducted on the side effects of clindamycin.
3.1. Conclusions
We conclude that bradycardia was a result of clindamycin administration and physicians should be aware that this medication may have the potential to induce severe bradycardia and be prepared in case such an adverse effect presents itself.
