REVIEWS OF INFECTIOUS DISEASES • VOL. 12, NO.2. MARCH-APRIL 1990 © 1990 by The University of Chicago. All rights reserved. 0162-0886/90/1202-0007$02.00
Pietro Martino, Alessandra Micozzi, Mario Venditti, Giuseppe Gentile, Corrado Girmenia, Ruggero Raccah, Stefania Santilli, Nicola Alessandri, and Franco Mandelli
in Bone Marrow Transplant Recipients From the Cattedra di Ematologia, Dipartimento di Biopatologia Umana, III Patologia Medica, and the Istituto dt Chirurgia del Cuore e Grossi Vasi, Universita "La Sapienza," Rome, Italy
Patients and Methods
Central venous access is necessary for administration of antineoplastic agents, blood components, and intravenous fluids in patients with hematologic malignancies, especially those undergoing bone marrow transplantation . Septicemia due to grampositive cocci, especially coagulase-negative Staphylococcus, is being noted with increased frequency in granulocytopenic patients . Despite frequent bacteremic episodes, endocarditis appears to be uncommon in leukemic patients . On the other hand, right-sided infective endocarditis due to several microorganisms has been described as a likely complication of intracardiac catheters placed for diagnostic or therapeutic purposes [4~6]. Recently, sporadic cases of catheter-related staphylococcal endocarditis have been clinicallydocumented in leukemic patients undergoing intensive chemotherapy or bone marrow transplantation [3, 7]. In light of this documentation, even though right-sided infective endocarditis is a difficult-to-establish diagnosis (particularly in bone marrow recipients where fever and pulmonary infiltrates may be due to several causes), we actively sought it, and in eight cases we have observed a syndrome compatible with this disease.
All patients admitted to the Institute of Hematology of Rome between January 1986 and December 1987 and scheduled to receive either autologous or allogeneic bone mar~ow infusion were included in this study [8, 9]. At least 48 hours before starting cytotoxic chemotherapy, a Hickman catheter was placed, with use of a previously described technique . Selective intestinal decontamination with norfloxacin  or cotrimoxazole (trimethoprim-sulfamethoxazole)  plus oral amphothericin B  was started as the polymorphonuclear cells decreased to 38°C) and granulocytopenia «1,000 cells/rum"), empiric b-Iactam and aminoglycoside therapy was started after blood was drawn for three cultures (at least one sample from a peripheral vein) . Catheter-related infections were defined according to Press et al. . In the event of relapsing bacteremia from the same organism, the catheter was always removed and two-dimensional echocardiography performed on Ultramark 8 3.0MHz transources (Advanced Technology Laboratories, Bothwell, Wash.) to detect endocardial vegetations according to published criteria . The syndrome compatible with catheter-related right-sided infective endocarditis was distinguished as follows: definite, in the case of direct evidence of infective endocarditis based on histology from autopsy; probable, in the case of persistent fever and
Received for publication 17 March 1989 and in revised form 18 July 1989. Please address requests for reprints to Dr. Pietro Martino, Cattedra di Ematologia, Dipartimento di Biopatologia Umana, Universita "La Sapienza," Via Benevento 6, 00161 Rome, Italy.
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Bone marrow transplant recipients are at increased risk of severe central venous cath.eter-related septicemias that may be complicated by endocardial infectio~. In viewof this, we prospectively evaluated 141 consecutive patients receiving alloge~eIc or autol~g?us bone marrow infusion. Seven (5070) of 141 patients developed eight epIsod~s.of a ~hn!cal syndrome compatible with catheter-related right-sided infective endocarditis; ~hIS dI~~ nosis was confirmed at autopsy in two patients who died. Staphylococcus epidermidis was the most frequent isolate (four cases). Other offending pathogens were, ~n one case each, Enterococcus faecalis, Corynebacterium jeikeium, Pseudomonasalcallgenes: and Achromobacterxylosoxidansplus Candida species. Three- to 7-weekcourses of antlb~c terial therapy wereassociated with a favorable outcome in six of the sevencases. Infective endocarditis may be a complication of the use of central venous catheters and should be actively sought in septicemic bone marrow transplant recipients.
Endocarditis in Bone Marrow Recipients
Microbiologic Studies The catheter tip was cultured with use of the semiquantitative method of Maki et al. . All isolates wereidentified by standard microbiologic techniques . Coagulase-negative Staphylococcus isolates were examined for slime production by the method of Christensen et al. . Case Reports Patient 1. A 33-year-old man with myelofibrosis had a Hickman catheter inserted on 8 March 1986 and 12 days later received an allogeneic bone marrow infusion. On 22 March during cytotoxicityinduced aplasia (30 PMNs/mm3 ) , he developed fe-
ver and a P. alcaligenes infection at the catheter exit site. Under empiric antibiotic therapy with piperacillin plus amikacin, only a transient clinical improvement was obtained. Therefore, on 30 March ceftazidime was added to the antibacterial regimen, but only a new transient improvement was obtained, without eradication of the offending organism from the catheter exit site. On 14April the patient was febrile and aplastic (20 PMNs/mm 3 , 23,000 platelets/rnm"), and a chest roentgenogram showed triangular infiltrates suggestive of embolic lesions in both peripheral lung fields. The Hickman catheter was removed; culture of the catheter tip yielded P. alcaligenes. Fever promptly disappeared, and the patient improved with a 28-day course of piperacillin, amikacin, and ceftazidime. On 7 May because of unsuccessful bone marrow engraftment, the patient receiveda new bone marrow infusion, and 15days later he was successfully treated with ceftazidime plus amikacin for two bacteremic episodes caused by Serratia marcescens and Acinetobacter lwoffi, respectively. On 1 June the patient developed fever and hypotension during a platelet transfusion. A. xylosoxidans was isolated from blood cultures and from the platelet apparatus. Despite therapy with aztreonam plus amikacin, the patient remained persistently febrile. On subsequent days 10additional blood cultures still yielded A. xylosoxidans, and new bilateral lung infiltrates became apparent on chest roentgenograms. The patient died on 2 July. The autopsy showed right atrial thrombosis with secondary pulmonary embolism. A. xylosoxidans and Candida species were cultured from atrial thrombi and from the pulmonary infiltrates. Both of these lesions presented hyphal invasion consistent with candidal infection. Patient 2. A 34-year-old man with chronic myeloid leukemia had a Hickman catheter inserted on 21 July 1986 and 9 days later received an allogeneic bone marrow infusion. During cytotoxicity-induced aplasia «100 PMNs/mm3 ,