The second patient was a man, age 60, with a two-week history of abdominal pain and a six-month history of effective etanercept use for persistent psoriatic arthritis. Contrast-enhanced CT revealed a large splenic abscess, and blood cultures identified infection with S aureus. Management began with unsuccessful high-dose IV antibiotics, followed by laparotomy and splenectomy, postsurgical sepsis, and finally, high-dose inotropic therapy that proved effective.8
Infection With Listeria monocytogenes
Listeria monocytogenes, a pathogen sometimes identified in patients who receive anti-TNF-a therapy, has been the focus of several case reports. For example, Gluck et al9 describe a 60-year-old woman with a history of RA and previous treatment with multiple therapies who had recently completed a five-month regimen with infliximab (10 mg/kg every 4 weeks). Fourteen days after receiving her last dose, she presented to a hospital with anemia, fever (measurement undisclosed), and abdominal pain. She was given multiple diagnoses, including a gastric ulcer without hemorrhage, a pulmonary infiltrate, and acute cholecystitis. After she underwent cholecystectomy, her condition deteriorated, and head CT revealed several small subarachnoid hemorrhages and severe brain edema.
The patient experienced multi–organ system failure and died after a brain-stem herniation. What should be noted is that a blood culture taken one day after her surgery was positive for L monocytogenes, as was an intraoperative gallbladder swab-culture for the same organism—this, despite presumed antibiotic therapy.
A second patient described by Gluck et al9 was a 62-year-old woman with RA who developed cholecystitis after her second dose of infliximab, administered over a two-week period (200 mg IV/dose). As in the previous case, the patient manifested cerebral edema and had a fever after undergoing cholecystectomy. Blood cultures performed after the surgery were positive for L monocytogenes. The patient recovered slowly with proper antibiotic therapy, including ampicillin and gentamicin.
A third example of listeriosis involved a 52-year-old patient with RA who presented with symptoms including fever and abdominal pain. CT led to a diagnosis of terminal ileitis. One of two blood cultures taken was positive for L monocytogenes.6
Finally, a 79-year-old patient with a long-standing diagnosis of RA and prosthetic hips reported a fever of three weeks’ duration and left leg pain. As the patient had no fever on initial presentation, blood cultures were not drawn until five days after he was admitted. Three of four blood cultures were positive for L monocytogenes.6
Less Common Infections
Other less common bacterial etiologies have also been reported in the literature, including a fatal case of Salmonella enteritidis septicemia with a pleural empyema after treatment with infliximab.10 Another fatality was reported in a 54-year-old man who had necrotizing fasciitis, with a group A hemolytic streptococcus that grew in blood cultures. The patient, who had been taking infliximab, had no report of fever before or during his hospitalization.11
Discussion
Although infliximab is effective for controlling the symptoms of RA, clinicians must be attentive to fever in patients who use it—even a patient-reported fever that may not be present on physical exam. Due to the potential blunting of the immune response associated with infliximab use, a serious underlying infection can occur without fever. General malaise may be the only symptom a patient reports.
Infliximab and other anti-TNF medications are included in a textbook list of immunosuppressive medications whose use warrants special attention for patients who are evaluated for infection in an emergency setting. According to Burns,1 “Rapid diagnosis and early initiation of therapy are essential in preventing serious morbidity and mortality in immunocompromised patients who often have subtle or unusual presentations and are difficult to diagnose.”1
Active tuberculosis (ATB) is another serious illness that has been reported with infliximab use.12,13 Patients should be screened for TB before taking infliximab, but clinicians must also be aware that ATB can develop as an unwanted result of infliximab therapy. Standard blood cultures may not be an effective means of identifying ATB.
Several types of infection may occur, with or without confirmation by positive blood cultures, including viral and fungal infections. Even bacterial infections, such as a urinary tract infection or bacterial pneumonia, may not yield positive blood cultures immediately, if ever. Each of these has been included among serious illnesses associated with use of anti-TNF medications.4 Nevertheless, blood cultures—Gram-stain, anaerobic, and aerobic blood cultures with sensitivities—should be considered an important component of any comprehensive infectious disease evaluation.
Although the purpose of this article has been to emphasize the importance of blood cultures in the timely diagnosis and treatment of patients taking anti-TNF medications who present with symptoms of infectious disease, it is important to remember that blood cultures are only part of a full infectious disease workup.