Abstract

We present a case of a rapidly progressive pseudomembranous tracheobronchitis and pneumonia in a 52-year-old woman with severe aplastic anemia. Bacillus cereus was isolated from bronchoalveolar lavage fluids, blood cultures, and pseudomembrane biopsy specimens; despite intensive antibiotic treatment, the patient's condition deteriorated rapidly. To our knowledge, this is the first report of a B. cereus infection that has caused pseudomembranous tracheobronchitis, possibly because of the production of bacterial toxins.

Bacillus cereus is a part of the normal flora of our environment. It has long been considered to be a contaminant in culture materials, but it may also cause serious infections, particularly in immunosuppressed patients. We present the first case, to our knowledge, of B. cereus pseudomembranous tracheobronchitis, and we discuss the possible role of bacterial toxin production in the formation of pseudomembranes.

Case report. A 52-year-old woman developed petechiae, weakness, and dyspnea. A diagnosis of severe aplastic anemia was established (figure 1). Treatment with antilymphocyte globulin (Institute Mérieux Transplant), for 8 days; cyclosporine A; and intermediate-dose steroids (methylprednisolone, 1 mg/kg) was instituted, and prophylactic ofloxacin and amphotericin B were given orally.

Figure 1

Evidence of severe aplastic anemia in a bone marrow specimen obtained from a 52-year-old woman who had developed petechiae, weakness, and dyspnea (histological stain with hematoxylin-eosin).

Figure 1

Evidence of severe aplastic anemia in a bone marrow specimen obtained from a 52-year-old woman who had developed petechiae, weakness, and dyspnea (histological stain with hematoxylin-eosin).

Antilymphocyte globulin treatment was followed by an immediate drop in the leukocyte count to 0.1 × 109 cells/L and persistent thrombocytopenia (platelet count, 13 × 109 platelets/L). On treatment day 8, the patient developed fever, a productive cough with yellow sputum, chest pain, and progressive dyspnea. Twelve hours later, she was admitted to the intensive care unit with severe respiratory distress, with a partial pressure of oxygen (arterial value; PAO2) of 57 mm Hg (7.6 kPa) and a partial pressure of carbon dioxide (arterial value) of 25.3 mm Hg (3.4 kPa) with 100% oxygen. She was febrile (temperature, 38.9°C) and required intubation and intermittent positive-pressure ventilation. Although radiographs showed only minor bilateral perihilar alveolar infiltrates, PAO2 levels remained below 90 mm Hg (12 kPa), with a fraction of inspired oxygen value of 1.0.

Fiberoptic bronchoscopy revealed severely inflamed tracheal and bronchial mucosa with predominant left-side obstruction of the lower-lobe bronchi by white diphtheria-like membranes. Eight hours later, such membranes were found to be present throughout the entire visible bronchial system, causing obstruction of additional bronchi bilaterally. Complete bronchoscopic removal of these membranes was prevented by mucosal bleeding.

Blood cultures and bronchoalveolar lavage (BAL) were performed; broad-spectrum antibiotic, antiviral, and antifungal therapy with piperacillin-sulbactam, ciprofloxacin, acyclovir, and amphotericin B was instituted; granulocyte colony—stimulating factor was administered, and cyclosporine A was withdrawn. Gram-positive rods, which were subsequently identified as B. cereus, were isolated from the fluid of 2 BALs (105 cfu/mL and 106 cfu/mL), membrane biopsy specimens, and blood cultures. The results of tests for fungi, viruses, acid-fast bacilli, and Pneumocystis carinii remained negative. Microscopically, the membrane consisted of fibrin, necrotic epithelium, and bacteria. Disk antibiotic susceptibility testing demonstrated resistance to penicillins and cephalosporins but susceptibility to ciprofloxacin, vancomycin, imipenem, cotrimoxazole, and tetracycline. Piperacillin-sulbactam was replaced by vancomycin and imipenem. However, chest radiographs showed progressive diffuse bilateral infiltrates, and the patient's condition deteriorated. C-reactive protein levels rose to 580 mg/L, although leukocyte and platelet counts remained unchanged. Low-grade fever persisted, and the patient died of multiple-organ failure 7 days after admission to the intensive care unit.

Autopsy revealed severe pseudomembranous tracheobronchitis with focal necrosis (figure 2) and persistence of B. cereus. The lungs showed signs of diffuse alveolar damage and hemorrhage.

Figure 2

Severe pseudomembranous tracheobronchitis noted at autopsy in a 52-year-old woman.

Figure 2

Severe pseudomembranous tracheobronchitis noted at autopsy in a 52-year-old woman.

Discussion. B. cereus, a ubiquitous aerobic or facultatively anaerobic gram-positive rod, is associated primarily with toxin-mediated food poisoning. Systemic or respiratory infections with B. cereus are uncommon but life-threatening [1]. Cases of pneumonia, abscess, empyema, and pleuritis have been described. Most of these infections have occurred in patients with severe underlying diseases. Recently, 2 cases of fatal pneumonia that involved otherwise healthy adults were reported [2]. To our knowledge, this is the first case of pseudomembranous tracheobronchitis caused by B. cereus infection.

Pseudomembrane formation in the respiratory tract typically is seen in patients with diphtheria. In recent years, pseudomembranous tracheobronchitis caused by Aspergillus species or nondiphtherial corynebacteria in immunocompromised patients has been reported [3, 4]. In our case B. cereus was detected in BAL fluid, bronchial membranes, and blood cultures in the absence of other pathogens, which made it the most likely causative agent in this patient. A striking feature of this case was the initial presentation with chest pain and yellowish sputum, as well as the rapid progression of the infection. Within 12 h, the patient developed severe respiratory insufficiency, and 8 h after initial bronchoscopic detection, the number of pseudomembranes in the central airways had increased dramatically. Despite antibiotic treatment and attempted bronchoscopic removal of the membranes, B. cereus and the membranes persisted until death.

B. cereus is ubiquitous and can be found in the hospital environment [5]. As in most cases of pulmonary B. cereus infections, we were unable to identify a specific source of the infection [1]. No other patients were affected. The presentation with primary respiratory symptoms and the absence of diarrhea or emesis in our patient may indicate a respiratory rather than a gastrointestinal route of infection. In addition, the patient's symptoms were similar to those noted after inhalation of Bacillus anthracis, which causes pulmonary anthrax (woolsorters' disease) [6].

Infections with B. cereus tend to produce necrosis, because the organism produces necrotizing enterotoxin, phospholipases, and hemolysins [5]. The role of these factors in extra-intestinal disease is not clear, but it is likely that the enzymes and, in particular, the necrotizing enterotoxin played a role in inducing pseudomembrane formation in our patient. In animal models, the toxin is capable of increasing vascular permeability and producing necrosis, and in cell cultures, it has a cytotoxic effect [5]. Because of the severe immunosuppression in this patient, pathogens of normally low virulence could have led to overwhelming local and systemic infection. In addition, the immunosuppressive treatment implemented to reverse aplastic anemia would have further compromised the immune system. In particular, antilymphocyte globulin, which caused a dramatic reduction in leukocyte count, may have contributed to the fulminant course of the disease and may explain the differences from a case of aplastic anemia and B. cereus infection reported elsewhere [7]. That patient had no immunosuppressive therapy, a higher leukocyte count (1.2 × 109 cells/L vs. 0.1 × 109 cells/L), and survived pneumonia and empyema, but not pseudomembranous bronchitis or bacteremia.

Because B. cereus is usually resistant to β-lactam antibiotics, treatment with vancomycin, clindamycin, imipenem, or aminoglycosides is recommended [8]. Ciprofloxacin has been used with success in treating a patient with bronchiectasis [9]. Despite the administration of empirical antimicrobial therapy that included ciprofloxacin and subsequent intensive therapy with vancomycin and imipenem, we were unable to prevent the fatal outcome for our patient.

B. cereus may cause pseudomembranous tracheobronchitis and pneumonia in severely immunocompromised patients. We suggest that bacterial toxin may have significantly contributed to the rapid formation of bronchial pseudomembranes, which led to irreversible respiratory failure. Because of the longstanding immunoincompetence in patients with severe aplastic anemia, immunosuppressive treatment carries additional risks. When immunosuppressed patients develop chest pain and a productive cough with rapid deterioration of pulmonary function, B. cereus infection should be considered. Bronchoscopy with BAL may help not only to obtain adequate specimens but also to diagnose airway obstruction by tracheobronchial pseudomembranes.

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