Gonococcal Septic Shock Associated With Eculizumab Treatment

Abstract

To the Editors: A 19-year-old female with paroxysmal nocturnal hemoglobinuria and aplastic anemia presented with fever of 39.4°C, lightheadedness, nausea, vomiting, right upper quadrant abdominal pain and headache that began 1 day before admission. There was no arthralgia, rash, genital lesions or discharge but she was having a menstrual period and was using pads. She had been receiving intravenous eculizumab every other week for the past 2 years for paroxysmal nocturnal hemoglobinuria with last dose 6 days before admission. She received meningococcal conjugate vaccine before starting eculizumab. She has been sexually active for 3 years, and the recent sexual contact was 2 weeks earlier; condom use was inconsistent. Her temperature was 38.5°C. Pulse rates of 131, 147 and 164/min and blood pressures of 106/54, 111/55 and 106/53 mm 14;Hg were measured during supine, sitting and standing positions, respectively, with a respiratory rate of 30/min. Physical examination revealed cool extremities, weak peripheral pulses, tachycardia, right upper quadrant tenderness and unsteadiness on standing. A complete blood count showed hemoglobin of 7.8 g/dL, white blood cells of 4400/mm3 with 72.7% neutrophils and 15.9% band forms and platelets of 68,000/mm3. Coagulation profiles were prolonged. Dopamine, norepinephrine and blood transfusion were required to maintain perfusion. Meropenem and vancomycin were given for a concern of septic shock. Magnetic resonance imaging of the brain was normal, but lumbar puncture was unsuccessful. She also developed respiratory failure requiring mechanical ventilation. Ceftriaxone was given due to the positive blood culture; however, it was discontinued because of extensive rash. The initial blood culture grew Neisseria gonorrhoeae. Chlamydia and gonorrhea DNA amplification tests and cultures from rectal and genital swabs obtained after 3 days of antibiotic treatment were negative. Hepatitis C antibody, HIV antibody, rapid plasma reagin and the urine test for trichomonas were negative. She received meropenem for 7 days, and she improved with a negative blood culture on the third day of treatment. She was advised to practice safe sex and to have her partners evaluated for sexually transmitted infections. Eculizumab is a humanized monoclonal antibody approved for the treatment of paroxysmal nocturnal hemoglobinuria in 2007. It blocks the activation of terminal complement C5, thereby inhibiting intravascular hemolysis and decreasing transfusion requirements. Eculizumab reduces the formation of cytolytic membrane attack complex and can impair neutrophil and monocyte functions,1,2 so this drug can predispose patients to N. meningitidis and N. gonorrhoeae infections.3,4 In the eculizumab study, 3 of 196 patients developed meningococcal sepsis.5 It is recommended that patients receive meningococcal vaccine at least 2 weeks before beginning eculizumab and be revaccinated every 3–5 years.3 Gonococcal sepsis, although theoretically possible, has not been reported in patients receiving eculizumab. In general, gonococcemia rarely presents with septic shock. The severe disease seen in our patient raises the possibility that eculizumab could increase the morbidity and even the mortality of gonococcal sepsis. If so, it is crucial to counsel the patients about avoidance of risky sexual behaviors to prevent gonococcal infections. Julie Gleesing, BSc Michigan State College of Osteopathic Medicine East Lansing, MI Saurabh Chiwane, MD Children’s Hospital of Michigan Chokechai Rongkavilit, MD The Carman and Ann Adams Department of Pediatrics Wayne State University School of Medicine Detroit, MI