Infectious Diseases in Clinical Practice:
Chryseobacterium indologenes Sepsis Due to an Infected Central Catheter in a Patient With Metastatic Breast Cancer to the Skin
Cone, Lawrence A. MD, DSc*†; Morrow, Ariella A. BA*; Benson, Mark MD*; Younes, Bachir MD, MPH*†; Gade-Andavolu, Radhika PhD†
*Eisenhower Medical Center, and †Genetic Research Institute of the Desert, Rancho Mirage, CA.
Address correspondence and reprint requests to Lawrence A. Cone, MD, DSc, Eisenhower Medical Center 39000 Bob Hope Dr, P308 Rancho Mirage, CA 92270. E-mail: firstname.lastname@example.org.
Chryseobacterium indologenes, previously called Flavobacterium, has been reported to cause hospital-acquired infections mostly in Taiwan but rarely elsewhere. Six cases have been recorded in Europe, 2 in Australia, and a single case in the United States. We report a second case in the United States in a patient with metastatic breast cancer who, while on chemotherapy, developed a bacteremia due to C. indologenes via an indwelling catheter. Initially described as a gram-negative rod, this led to treatment with carbapenems to which the isolate proved resistant. Once the definitive speciation and in vitro sensitivities became available, appropriate antimicrobial therapy led to resolution of the infection. Broth microdilution rather than disc diffusion correlates most accurately with minimum inhibitory concentrations.
Chryseobacterium, formerly known as Flavobacterium, was defined in 1994 by Vandamme et al.1 The genus originally comprised 6 species of yellow-pigmented, nonmotile, oxidase-positive, glucose-nonfermenting aerobic bacilli that are ubiquitous in nature and are found in plants, soil, food, and both fresh and marine water.2 The most commonly encountered species in patients with meningitis, bacteremia, and infection related to intravascular devices is Chryseobacterium meningosepticum, although Chryseobacterium indologenes is the most common Flavobacterium isolated from clinical specimens. Chryseobacterium gleum, Chryseobacterium odoratum, Chryseobacterium multivorum, and Chryseobacterium breve have more recently been reclassified into the genera Myroides, Sphingobacterium, and Empedobacter. In 1993, Bonten et al3 first isolated C. indologenes from a tracheal aspirate from a ventilator-associated pneumonia.
Recent studies by Hsueh et al,4,5 Lin et al,6 and Lu and Chan7 from Taiwan described 38 patients with C. indologenes infection, whereas only 6 cases have been described in Europe,3,8-12 2 cases in Australia,13 and a single instance in the United States.14 We report a patient with metastatic breast cancer and sepsis with C. indologenes due to an infected central line.
A 57-year-old white woman was diagnosed with right breast cancer in 1997 for which she underwent lumpectomy, radiation, and chemotherapy with adriamycin and cyclophosphamide. In 2005, she developed recurrent disease in the right side of the chest and again received radiation and chemotherapy with carboplatin and paclitaxel. This was done with stem cell transplantation. There was an incomplete response to therapy, and she developed cutaneous metastases to the skin surrounding and covering the right breast. Gemcitabine chemotherapy was initiated via an indwelling catheter in the right upper chest after another in the left upper chest clotted, became nonfunctional, and was removed. She received 2 doses of gemcitabine 1 week apart, the last dose 3 days before her subsequent hospitalization.
In mid-July 2006, she noted a tightness in the right side of the chest when taking a deep breath. A chest radiograph revealed atelectasis at the right base. On July 26, 2006, she was admitted to the Eisenhower Medical Center with fever and chills. On physical examination, aside from decreased breath sounds at the right lung base, multiple pea-sized nodules were noted involving the skin of the right breast which was warm and slightly edematous and moderately tender in addition to a yellowish-erythematous discoloration of the skin extending to the right anterior chest wall catheter. Her temperature was 101.3°F; pulse rate, 104/min; blood pressure, 100/60; and respirations, 18/min. After blood cultures were drawn from both the central catheter and periphery, intravenous antimicrobial therapy was initiated with vancomycin at a dosage of 1 g every 12 hours and imipenem at a dosage of 1 g every 6 hours. Laboratory studies revealed a white blood cell count of 4700/μL, with 97% granulocytes, hemoglobin/hematocrit level of 12/35, and platelets of 95,000/μL. All blood chemistries were normal other than for a slightly elevated alanine aminotransferase and aspartate aminotransferase of 83 and 67 U/L, respectively. The CA 15-3 and CA 27-29 tumor markers were normal.
On hospital day 2, blood cultures were growing gram-negative rods only from the central line, and the catheter was promptly removed. Peripheral blood cultures were sterile. Cultures were not taken from the yellowish-red rash on the right side of the chest wall. Vancomycin was stopped, and imipenem was continued. By the following day, her white blood cell count, hemoglobin/hematocrit level, and platelet count decreased further, and blood cultures from the central line only revealed C. indologenes. In vitro studies revealed susceptibility to ciprofloxacin (MIC, 0.5 μg/mL), levofloxacin (MIC, 0.75 μg/mL), trimethoprim/sulfamethoxazole (MIC, ≤20 μg/mL), and rifampin, whereas resistance was seen with vancomycin (MIC, 16 μg/mL), ceftriaxone (MIC, ≥64 μg/mL), cefepime (MIC, ≥64 μg/mL), tobramycin (MIC, ≥16 μg/mL), gentamicin (MIC, ≥16 μg/mL), piperacillin/tazobactam (MIC, ≥128 μg/mL), and aztreonam (MIC, ≥64 μg/mL). Intermediate susceptibility was seen with imipenem (MIC, 8 μg/mL). Consequently, imipenem was discontinued and replaced with ciprofloxacin at 500 mg twice daily. Within 24 hours of the administration of ciprofloxacin, the patient became afebrile, the tightness in the chest improved, and the yellowish-erythematous area surrounding the cutaneous metastases likewise began to resolve along with the cutaneous sensitivity extending to the former right-sided central catheter site. The neutropenia and thrombocytopenia which, in part, was secondary to previous chemotherapy resolved in 2 days. Repeat blood cultures were sterile, and the ciprofloxacin was discontinued after 4 weeks of therapy.
The patient then noted a mass in the left breast which was confirmed by palpation and mammography along with a left axillary mass. A biopsy of both the breast mass and axillary node revealed a second invasive ductal carcinoma. The new tumor was both estrogen and progesterone receptor positive and human epidermal growth factor receptor-2 negative. The patient's genetic analysis of peripheral blood for BRCA 1 and 2 was negative. She has been given gemcitabine and abraxane neoadjuvant and metastatic chemotherapy with a favorable clinical response and, in December 2006, underwent a left mastectomy without sequelae. She continued on chemotherapy.
Members of the genera Chryseobacterium, Myroides, Sphingobacterium, and Empedobacter were classified as Flavobacterium species. They are yellow-pigmented gram-negative rods that are not motile, nonfermentative, and oxidase positive. Six species have been defined including C. meningosepticum and C. indologenes, whereas C. gleum, C. odoratum, C. multivorum, and C. breve have been reclassified as Myroides, Sphingobacterium, and Empedobacter, respectively. Human infection is most commonly caused by C. meningosepticum15 and includes meningitis, pneumonia, bacteremia, soft tissue and indwelling catheter infections, and osteomyelitis,16 although C. indologenes is more commonly isolated from clinical specimens. The previously termed members of the Flavobacterium group IIb1,4 including Flavobacterium indologenes was first designated in 1983 by Yabuuchi et al,17 and, in 1990, it was clearly distinguished from Flavobacterium gleum.18 Although previous intravascular device-related bacteremias due to group IIb Flavobacterium species19 were recorded, they were never designated as F. indologenes or F. gleum.
Forty-seven cases of human infection caused by C. indologenes have been recorded worldwide since 1993: 38 in Taiwan, 6 in Europe, 2 in Australia, and 1 in the United States.3-14 Thirty-two were male patients, and 13 had a variety of neoplasms; however, only 1 was because of breast cancer. The remainder included hepatic tumors, leukemia, myeloma, and lung, esophageal, and pancreatic tumors, and squamous cell cancer of the nose and skin. In addition, 9 patients were diabetic, 7 have burns, 4 were azotemic, 3 had cardiac disease, 3 experienced biliary calculi, 1 had pancreatitis, 2 had corneal disease, and 1 had idiopathic thrombocytopenic purpura. Four patients had no underlying disease.
Approximately 50% of all the above infections were associated with various indwelling devices, most often central catheters. Mortality was directly attributed to infection in 14% of the patients.
Although C. meningosepticum produces either little or no pigment, C. indologenes produces a distinct yellowish pigment,2,20 which has been seen in burn infections13 and might have contributed to the skin color covering the right breast in our patient.
Although C. indologenes is a gram-negative bacillus, its antimicrobial sensitivity resembles that of gram-positive organisms.15 However, disc diffusion susceptibility testing correlates poorly with MIC determinations,2,15,20 and it has been recommended that broth microdilution be performed and that therapy be guided by those results. In our patient, disc sensitivity studies revealed sensitivity to vancomycin, rifampin, and ciprofloxacin with intermediate sensitivity to imipenem and resistance to all β-lactams and aminoglycosides. The MICs confirmed these findings except that the organism was resistant to vancomycin and imipenem. It is interesting to note that the initial treatment with vancomycin and imipenem and then imipenem alone when a gram-negative rod was initially isolated was unsuccessful as predicted by the MICs and not by disc susceptibility. It should be mentioned that other antimicrobials such as macrolides, chloramphenicol, clindamycin, quinupristin-dalfopristin, and linezolid are also ineffective agents, whereas other quinolones such as levofloxacin and sparfloxacin are effective.
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