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Clinical Experience With Minocycline and Rifampin—Impregnated Central Venous Catheters in Bone Marrow Transplantation Recipients: Efficacy and Low Risk of Developing Staphylococcal Resistance Author(s): Ioannis Chatzinikolaou , MD; Hend Hanna , MD; Linda Graviss , MT; Gassan Chaiban , BS; Cheryl Perego , MPH; Rebecca Arbuckle , RPh; Richard Champlin , MD; Rabih Darouiche , MD; George Samonis , MD; Issam Raad , MD, FACP Source: Infection Control and Hospital Epidemiology, Vol. 24, No. 12 (December 2003), pp. 961- 963 Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiology of America Stable URL: http://www.jstor.org/stable/10.1086/502167 . Accessed: 15/05/2014 22:31 Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at . http://www.jstor.org/page/info/about/policies/terms.jsp . JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact [email protected]. . The University of Chicago Press and The Society for Healthcare Epidemiology of America are collaborating with JSTOR to digitize, preserve and extend access to Infection Control and Hospital Epidemiology. http://www.jstor.org This content downloaded from 195.78.108.57 on Thu, 15 May 2014 22:31:03 PM All use subject to JSTOR Terms and Conditions

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Clinical Experience With Minocycline and Rifampin—Impregnated Central Venous Cathetersin Bone Marrow Transplantation Recipients: Efficacy and Low Risk of DevelopingStaphylococcal Resistance • Author(s): Ioannis Chatzinikolaou , MD; Hend Hanna , MD; Linda Graviss , MT; Gassan Chaiban, BS; Cheryl Perego , MPH; Rebecca Arbuckle , RPh; Richard Champlin , MD; Rabih Darouiche, MD; George Samonis , MD; Issam Raad , MD, FACPSource: Infection Control and Hospital Epidemiology, Vol. 24, No. 12 (December 2003), pp. 961-963Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiologyof AmericaStable URL: http://www.jstor.org/stable/10.1086/502167 .

Accessed: 15/05/2014 22:31

Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at .http://www.jstor.org/page/info/about/policies/terms.jsp

.JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range ofcontent in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new formsof scholarship. For more information about JSTOR, please contact [email protected].

.

The University of Chicago Press and The Society for Healthcare Epidemiology of America are collaboratingwith JSTOR to digitize, preserve and extend access to Infection Control and Hospital Epidemiology.

http://www.jstor.org

This content downloaded from 195.78.108.57 on Thu, 15 May 2014 22:31:03 PMAll use subject to JSTOR Terms and Conditions

Vol. 24 No. 12 INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY 961

Clinical Experience With Minocyclineand Rifampin–Impregnated CentralVenous Catheters in Bone MarrowTransplantation Recipients: Efficacy andLow Risk of Developing StaphylococcalResistance

Ioannis Chatzinikolaou, MD; Hend Hanna, MD;Linda Graviss, MT; Gassan Chaiban, BS; Cheryl Perego, MPH; Rebecca Arbuckle, RPh;Richard Champlin, MD; Rabih Darouiche, MD;George Samonis, MD; Issam Raad, MD

ABSTRACTIn this retrospective evaluation of the 4-year clinical use of

minocycline and rifampin–impregnated catheters in bone mar-row transplantation (BMT) patients, we report low risk of devel-opment of staphylococcal resistance to the antibiotics coating thecatheters and efficacy in preventing primary staphylococcalbloodstream infections (Infect Control Hosp Epidemiol 2003;24:961-963).

Central venous catheters (CVCs) impregnated withminocycline and rifampin are effective in preventingcatheter-related bloodstream infections (BSIs).1-3

The risk of microorganism resistance to the antibi-otics used for coating catheters is a concern.4,5 Althoughresistance was not evident in the clinical trials of minocy-cline and rifampin–impregnated CVCs,1,2 the clinical expe-rience with these catheters was limited at the time of pub-lication of those studies. Consequently, after 4 years ofusing minocycline and rifampin–impregnated CVCs, wewanted to evaluate the associated risk of development ofantibiotic resistance and their ability to reduce primarystaphylococcal BSIs in the bone marrow transplantationservice compared with the leukemia service, which doesnot use minocycline and rifampin–impregnated CVCs.

METHODS

The University of Texas, M. D. Anderson CancerCenter implemented the use of minocycline andrifampin–impregnated CVCs in July 1997 for all recipientsof bone marrow transplantation during the pre-engraft-ment period to prevent catheter-related BSI.

Four years after the introduction of minocycline andrifampin–impregnated CVCs, we conducted a 6-month (July1 to December 31, 2001) retrospective cohort study of allpatients hospitalized on the bone marrow transplantationand leukemia services to determine the efficacy of minocy-cline and rifampin–impregnated CVCs for preventing staphy-

lococcal BSI, as that is the pathogen most frequently associ-ated with catheter-related BSI.6 All primary staphylococcalBSIs occurring in both services during the study periodwere recorded and all implicated coagulase-negativestaphylococcus and Staphylococcus aureus organisms werecollected. All patients were evaluated for the duration of neu-tropenia, type and number of catheters and duration ofcatheterization, history and type of bone marrow transplan-tation, and history of graft-versus-host disease. All minocy-cline and rifampin–impregnated CVCs used were silicone orpolyurethane nontunneled catheters.

To evaluate the impact of the 4 years of use ofminocycline and rifampin–impregnated CVCs on the sus-ceptibility patterns of Staphylococcus species, we conduct-ed a retrospective resistance surveillance study. In thisstudy, we compared the collected (during the 6-monthperiod) staphylococcal organisms that caused primaryBSI in the bone marrow transplantation patients who usedthe minocycline and rifampin–impregnated CVCs with thestaphylococcal organisms causing primary BSI inleukemia patients who did not use the minocycline andrifampin–impregnated CVCs regarding susceptibility(MIC90—the lowest concentration of antibiotic at which90% of isolates are inhibited) to minocycline and rifampin.Additionally, we compared our current data with a histor-ical control group of staphylococcal catheter-related BSIisolates from patients of the University of Texas, M. D.Anderson Cancer Center between 1990 and 1992 (5 to 7years before the introduction of minocycline andrifampin–impregnated CVCs).7 Standard methods of test-ing were followed.8 Resistance to minocycline was docu-mented if the MIC90 was 16 mg/L or greater and sensitiv-ity if the MIC90 was 4 mg/L or less. Resistance to rifampinwas documented if the MIC90 was 4 mg/L or greater andsensitivity if the MIC90 was 1 mg/L or less.

To accurately evaluate the impact of the minocyclineand rifampin–impregnated CVCs on the susceptibility pat-tern of Staphylococcus species, we performed a 1-yearantibiotic surveillance study calculating the intensity ofsystemic use of minocycline and rifampin for 2001. Thedefined daily dose was defined as the assumed averagedaily dose of a drug used for its main indication in adults(200 mg for minocycline, 600 mg for rifampin, and 1 g fortetracycline).

A primary staphylococcal bacteremia was defined asa single positive blood culture of S. aureus, or more than50 colonies or 2 or more positive blood cultures of coagu-lase-negative staphylococcus with no other apparent clini-cal source.9 We defined neutropenia as an absolute neu-trophil count of less than 500 cells/µL.

Concise Communications

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962 INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY December 2003

For the statistical analysis of the data, the chi-square, Fisher’s exact, and Student’s t tests were used.SPSS statistical software was used (version 11.00; SPSS,Inc., Chicago, IL).

RESULTS

During the study period, there were 212 (122 allo-geneic and 90 autologous bone marrow transplantations)patients receiving bone marrow transplantation (9,378hospital-days) and 460 patients with leukemia (9,844 hos-pital-days) (Table 1). The two patient populations weresimilar in gender distribution, but the patients receivingbone marrow transplantation were younger (P < .001)(Table 1). All patients receiving bone marrow transplanta-tion had a CVC, compared with 90% of the patients whohad leukemia (P < .001), and the former group had alonger mean duration of catheterization (P = .03) (Table1). Fourteen patients with leukemia developed graft-ver-sus-host disease (bone marrow transplantation the yearbefore), compared with 42 patients receiving bone mar-row transplantation (P < .001) (Table 1). All patientsreceiving bone marrow transplantation experienced neu-tropenia, compared with 83% of the patients with leukemia(P < .001); however, the duration of neutropenia waslonger in the latter group (P < .001) (Table 1). The aver-age use of rifampin was the same, but there was moreintense use of tetracyclines in the bone marrow trans-plantation service (P = .02) (Table 1). During the studyperiod, there were 14 Staphylococcus species primaryBSIs in the bone marrow transplantation group (3 causedby S. aureus and 11 caused by coagulase-negative staphy-lococcus) and 53 in the leukemia group (4 caused by S.aureus and 49 caused by coagulase-negative staphylococ-

cus). The primary staphylococcal BSI rate in the bonemarrow transplantation service was 1.2 per 1,000 patient-days, compared with 5.4 per 1,000 patient-days in theleukemia service (P = .003) (Table 1). All 67 staphylococ-cal isolates were susceptible to minocycline, whereas onefrom the bone marrow transplantation service and 9 fromthe leukemia service were resistant to rifampin (P = .7).

After a 4-year period of using approximately 600minocycline and rifampin–impregnated CVCs (27,600catheter-days) in the bone marrow transplantation ser-vice, the susceptibility patterns of staphylococcal organ-isms to minocycline and rifampin were comparable to thebaseline ones7 reported 5 to 7 years before the use of suchcatheters (1990 to 1992) (Table 2).

DISCUSSION

Prospective randomized clinical studies demonstrat-ed the efficacy of minocycline and rifampin–impregnatedCVCs in reducing catheter colonization and preventingcatheter-related BSI for short-term1,2 and long-termcatheterization.3 Although patients receiving bone mar-row transplantation in our study had a significantly higherfrequency of graft-versus-host disease and a significantlylonger duration and higher frequency of catheterization,they were 4.5-fold less likely than patients with leukemiato develop staphylococcal BSIs (Table 1). Because prima-ry staphylococcal BSIs are frequently catheter related,6this significant difference in the frequency of staphylo-coccal BSIs is likely attributed to the use of minocyclineand rifampin–impregnated CVCs by the bone marrowtransplantation service. Although the degree and durationof neutropenia are known risk factors for the acquisitionof bacterial infections, neither has been found to be a riskfactor for acquiring catheter-related BSI.10 However, inthis study, neutropenia occurred more frequently inpatients on the bone marrow transplantation service,whereas the duration of neutropenia was longer in thepatients on the leukemia service (Table 1).

There has been concern related to the possibility ofmicroorganisms developing resistance to minocycline andrifampin.4,5 In two in vitro studies4,5 S. epidermidis and S.aureus were exposed to minocycline and rifampin in a set-ting of maximized conditions. Although a 10- to 16-foldincrease in the MIC of the combination of minocycline andrifampin against S. epidermidis organisms was observedafter 20 passages, S. epidermidis remained susceptible tothis combination at a MIC level of 0.31 µg/mL or less.4,5

Our study is the only clinical study to investigate theissue of microbial resistance to minocycline and rifampinafter long-term use and exposure to minocycline andrifampin–impregnated CVCs. Despite the use of approxi-mately 600 minocycline and rifampin–impregnated CVCsduring a 4-year period for approximately 27,600 catheter-days, all of the staphylococcal organisms causing BSIs inthe patients receiving bone marrow transplantationremained susceptible to minocycline and 93% remained sus-ceptible to rifampin. This occurred despite using minocy-cline and rifampin–impregnated CVCs and administering

TABLE 1CLINICAL CHARACTERISTICS OF THE TWO GROUPS OF PATIENTS

BMT LeukemiaCharacteristic (n = 212) (n = 460) P

Male (%) 124 (59) 278 (60) .63Mean age, y (± SD) 46 (± 15) 53 (± 17) < .001Central venous catheter (%) 212 (100) 414 (90) < .001Mean duration of catheteriza- 112 (± 53) 102 (± 63) .03

tion, d (± SD)Graft-versus-host disease (%) 42 (20) 14 (3) < .001Neutropenia of < 500 cells/mm3 212 (100) 382 (83) < .001

(%)Mean duration of neutropenia, 18 (± 18) 32 (± 31) < .001

d (± SD)Mean rifampin DDD (± SD) 4.7 (± 3.5) 4.7 (± 3.5) 1Mean tetracyclines DDD (± SD) 7.5 (± 8) 4 (± 3) .02Staphylococcal BSIs 1.2 5.4 .003

(per 1,000 patient-days)

BMT = bone marrow transplantation (122 allogeneic BMTs and 90 autologous BMTs); SD =standard deviation; DDD = number of defined daily doses; BSIs = bloodstream infections.

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Vol. 24 No. 12 CONCISE COMMUNICATIONS 963

more systemic tetracyclines in the bone marrow transplan-tation service. Additionally, despite the use of minocyclineand rifampin–impregnated CVCs in patients receiving bonemarrow transplantation (with equivalent use of systemicrifampin in both services), the risk of emergence of organ-isms resistant to rifampin was less in this group than in thepatients with leukemia (Table 2). Furthermore, the suscep-tibility patterns of staphylococcal organisms to minocyclineand rifampin after 4 years of using minocycline andrifampin–impregnated CVCs on the bone marrow trans-plantation service were comparable to baseline susceptibili-ty patterns from 1990 to 19927 (ie, 5 to 7 years prior to theintroduction of minocycline and rifampin–impregnatedCVCs) (Table 2). We believe that the impact of antibiotic-coated catheters on resistance rates in high-risk patient pop-ulations receiving a large volume of systemic antimicrobialshas been overestimated. Limiting antibiotic pressures tominimize the development of microbial resistance is a cru-cial concern: whether coated catheters contribute to orreduce these pressures remains an unanswered question.

In addition to their efficacy in preventing BSIscaused by Staphylococcus species, minocycline andrifampin–impregnated catheters are associated with a lowrisk of development of staphylococcal resistance to theantibiotics coating their surface.

Drs. Chatzinikolaou, Hanna, and Raad, Ms. Graviss, Mr.Chaiban, and Ms. Perego are from the Division of Internal Medicine,Department of Infectious Diseases, Infection Control and EmployeeHealth; Ms. Arbuckle is from the Division of Pharmacy; and Dr.Champlin is from the Department of Bone Marrow Transplantation,University of Texas, M. D. Anderson Cancer Center, Houston, Texas. Dr.Darouiche is from the Section of Infectious Diseases, VA Medical Centerand Baylor College of Medicine, Houston, Texas. Drs. Chatzinikolaouand Samonis are from the Division of Internal Medicine, Departmentof Infectious Diseases, School of Medicine, University of Crete, Greece.

Address reprint requests to Hend Hanna, MD, MPH,Department of Infectious Diseases, Infection Control and EmployeeHealth, The University of Texas, M. D. Anderson Cancer Center, 1515Holcombe Boulevard (Unit 402), Houston, TX 77030.

Drs. Raad and Darouiche are coinventors on two patents associat-ed with catheters coated with minocycline and rifampin. These patents arethe property of the University of Texas, M. D. Anderson Cancer Centerand Baylor College of Medicine. Both patents were licensed to CookCritical Care with royalty rights to the institutions involved. A percentageof the royalties goes to the inventors according to the royalty policies ofeach institution.

Presented at the 42nd Interscience Conference on AntimicrobialAgents and Chemotherapy; September 27-30, 2002; San Diego, CA.

REFERENCES1. Raad I, Darouiche R, Dupuis J, et al. Central venous catheters coated

with minocycline and rifampin for the prevention of catheter-related col-onization and bloodstream infections: a randomized, double-blind trial.Ann Intern Med 1997;127:267-274.

2. Darouiche RO, Raad II, Heard SO, et al. A comparison of two antimicro-bial-impregnated central venous catheters. N Engl J Med 1999;340:1-8.

3. Hanna H, Benjamin RS, Chatzinikolaou I, et al. The role of long-term sil-icone central venous catheters impregnated with rifampin and minocy-cline (S-CVC-RM) in preventing catheter-related infections: a prospec-tive randomized study. Presented at the 38th Annual Meeting of theAmerican Society of Clinical Oncology; May 18-21, 2002; Orlando, FL.

4. Tambe SM, Sampath L, Modak SM. In vitro evaluation of the risk ofdeveloping bacterial resistance to antiseptics and antibiotics used inmedical devices. J Antimicrob Chemother 2001;47:589-598.

5. Sampath LA, Tambe SM, Modak SM. In vitro and in vivo efficacy ofcatheters impregnated with antiseptics or antibiotics: evaluation of therisk of bacterial resistance to the antimicrobials in the catheters. InfectControl Hosp Epidemiol 2001;22:640-646.

6. Benezra D, Kiehn TE, Gold JW, Brown AE, Turnbull AD, Armstrong D.Prospective study of infections in indwelling central venous cathetersusing quantitative blood cultures. Am J Med 1988;85:495-498.

7. Darouiche RO, Raad II, Bodey GP, Musher DM. Antibiotic susceptibili-ty of staphylococcal isolates from patients with vascular catheter-relatedbacteremia: potential role of the combination of minocycline andrifampin. Int J Antimicrob Agents 1995;6:31-36.

8. National Committee for Clinical Laboratory Standards. Methods forDilution Antimicrobial Susceptibility Tests for Bacteria That GrowAerobically. Wayne, PA: National Committee for Clinical LaboratoryStandards; 2000.

9. Herwaldt LA, Geiss M, Kao C, Pfaller MA. The positive predictive valueof isolating coagulase-negative staphylococci from blood cultures. ClinInfect Dis 1996;22:14-20.

10. Hanna HA, Raad I. Blood products: a significant risk factor for long-termcatheter-related bloodstream infections in cancer patients. Infect ControlHosp Epidemiol 2001;22:165-166.

Roseomonas Infection Associated With aLeft Ventricular Assist Device

Amit Singal, BS; Preeti N. Malani, MD; Larry J. Day,MD; Francis D. Pagani, MD; Nina M. Clark, MD

ABSTRACTRoseomonas species have been increasingly noted as caus-

es of human infection. We present what we believe is the firstcase of left ventricular assist device (LVAD) infection secondaryto Roseomonas. The clinical characteristics of Roseomonas infec-tion and the pertinent features of LVAD infection are reviewed(Infect Control Hosp Epidemiol 2003;24:963-965).

TABLE 2STAPHYLOCOCCAL SUSCEPTIBILITY PATTERNS (MIC90 MG/L)*

Baseline Data (1990 to 1992)7 Study Susceptibilities (July to December 2001)Staphylococcus Leukemia BMT

aureus CNS S. aureus CNS S. aureus CNS(n = 60) (n = 30) (n = 4) (n = 49) (n = 3) (n = 11)

Minocycline 0.25 0.2 � 0.06 � 0.06 � 0.06 � 0.06Rifampin 0.5 0.03 � 0.06 128 � 0.06 � 0.06

BMT = bone marrow transplantation; CNS = coagulase-negative staphylococci.*MIC90 = the lowest concentration of antibiotic that inhibits the growth of 90% of the isolates.

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964 INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY December 2003

Left ventricular assist devices (LVADs) haveimproved patient outcomes and revolutionized ourapproach to cardiac transplantation. However, device-related infection remains a serious complication of LVADsand is associated with increased costs.1-4 An extendedduration of LVAD support, prolonged intensive care unitstay, need for hemodialysis, and delayed sternal closurehave been associated with LVAD infection.1

We present what we believe is the first case of LVADinfection secondary to Roseomonas, an uncommon butincreasingly described cause of human infection. Theinfection did not prevent successful cardiac transplanta-tion but did require an extended course of antimicrobialtherapy for treatment.

CASE REPORT

A 48-year-old man with long-standing nonischemic car-diomyopathy and severe aortic regurgitation presented tothe University of Michigan Health System with refractorycardiogenic shock. He underwent implantation of aHeartMate IP-1000 LVAD (Thoratec, Pleasanton, CA),repair of a patent foramen ovale, and replacement of the aor-tic valve with a Mosaic porcine bioprosthesis (Medtronic,Minneapolis, MN). Postoperatively, he developed mediasti-nal bleeding requiring reexploration and cautery of oozingvessels. He was discharged 11 days after implantation of theLVAD. Cefuroxime axetil was administered as prophylacticantibiotic coverage throughout the time the LVAD was inplace, a frequent practice at the University of MichiganHealth System after LVAD implantation. The patient’s sub-sequent course was complicated by the development of ahematoma in the preperitoneal pocket containing the bloodpump. This was evacuated on device-day 194 and cultures ofthe fluid were negative. Cefuroxime axetil was continuedand on device-day 217, the patient underwent cardiac trans-plantation. At the time of transplant, a 1-cm, walled-off col-lection of granulation tissue was found behind the ascend-ing aorta. Incision of this area revealed purulent materialthat underwent culture. Vancomycin and ampicillin–sulbac-tam were administered perioperatively.

Blood cultures performed at the time of the trans-plant were negative, but after 8 days of incubation onblood agar at 37°C, cultures of the periaortic fluid collec-tion grew pink mucoid colonies. Gram staining of thecolonies revealed short, fat gram-negative coccobacillithat were catalase positive and oxidase negative. Growthalso occurred on Sabouraud’s agar, but the colonies didnot fluoresce with Wood’s lamp.5 The culture was sent tothe Michigan state reference laboratory for further test-ing and the isolate was identified as Roseomonas species.

Susceptibility testing of the organism demonstratedresistance to trimethoprim–sulfamethoxazole, cef-tazidime, and piperacillin–tazobactam and intermediatesusceptibility to cefuroxime. The isolate was susceptibleto cefazolin, cefotetan, ceftriaxone, gentamicin, amikacin,doxycycline, ciprofloxacin, aztreonam, and meropenem.Based on these results, vancomycin and ampicillin–sul-bactam were discontinued and imipenem was begun.

Ciprofloxacin was also added for an unrelatedPseudomonas aeruginosa wound infection at the site of afemoral artery catheterization. The patient received 7weeks of meropenem and ciprofloxacin. He remains well1 year after the transplant with good graft function andcomplete healing of his surgical wounds.

DISCUSSION

Roseomonas is a newly designated genus of pink-pig-mented, mucoid, coccoid bacilli composed of threeunnamed and three named species, the latter including R.gilardii, R. cervicalis, and R. fauriae.6 Roseomonas hasbeen isolated from humans for many years but prior toRihs et al. naming the genus, the bacteria were referred toas the “pink coccoid” group.5,7 Although isolates haveoccasionally been recovered from environmental sourcessuch as potable water and contaminated saline, the natur-al reservoir of Roseomonas is currently unknown.6 Of theRoseomonas species, R. gilardii is the most frequently iso-lated, suggesting it may have the most pathogenic poten-tial.7 R. gilardii is typically found in patients with underly-ing clinical illness such as malignancy, renal disease, ordiabetes mellitus.5,7

The most common manifestation of Roseomonasinfection is bacteremia, often in association with sepsissyndrome, but Roseomonas species have also been isolat-ed from cerebrospinal fluid, the eyes, bone, and peritonealfluid, the latter in the setting of continuous ambulatoryperitoneal dialysis.7-9 Roseomonas has also been implicatedas an etiologic agent of respiratory tract infection and softtissue infection.6,7,9 Furthermore, intravenous catheterinfection is a manifestation of particular importance, as itmay be difficult to eradicate Roseomonas infection in thissetting with antibiotics alone.10-12

When Roseomonas species are cultured from non-sterile body sites such as the respiratory tract or the gen-itourinary tract, it can be difficult to determine their clini-cal significance. In one review of Roseomonas infection, upto 40% of the isolates were not associated with identifiabledisease.7 This finding as well as the uncommon nature ofRoseomonas infection suggest that the organism may existas a commensal or transient colonizer in humans or that itis of low pathogenic potential. In fact, reports of fatalRoseomonas infection appear to be rare.7,12 Still, there isclear evidence that Roseomonas can cause serious disease,particularly in patients with underlying illnesses. In addi-tion, our report and those of catheter-related bacteremiassuggest Roseomonas may be more likely to cause diseasein the setting of indwelling devices.

Roseomonas infection of an LVAD has not been pre-viously reported. Malani et al. performed a retrospectivereview of 36 cases of LVAD insertion at the University ofMichigan Health System.1 Nearly 45% of the cases werecomplicated by surgical-site infections, although only halfof these were deep space surgical-site infections involvingthe LVAD, sternum, or mediastinum. Surgical-site infec-tions developed a mean of 32 days after LVAD implanta-tion. Although no causative organism was isolated in

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Vol. 24 No. 12 CONCISE COMMUNICATIONS 965

approximately 40% of the cases, the most common causeof wound infection in this setting was found to be coagu-lase-negative staphylococcus. It is notable that LVADinfection does not necessarily preclude successful cardiactransplantation.1 In the case we have presented, pro-longed LVAD support may have been a risk factor predis-posing to infection.

A characteristic feature of Roseomonas is its slowgrowth in culture; colonies often do not appear until 4 to 5days of incubation.5,7 The organism may therefore bemissed if cultures are not held for a prolonged period.Because of this feature, it is not uncommon to isolateRoseomonas from only one of several blood cultures orfrom a central venous catheter line with negative periph-eral blood cultures.

The antibiotic susceptibility pattern of Roseomonasspecies is characteristic. For example, there appears to befrequent resistance to cephalosporins, including third-generation cephalosporins.5,6,8,9,11 However, this resis-tance has not been uniformly reported. Lewis et al. pre-sented a series of Roseomonas isolates with in vitro susceptibility to cefotaxime and, in some cases, clinicalresponse to this agent.13 Roseomonas isolates may also attimes exhibit susceptibility to first- and second-generationcephalosporins, as in the current report and that byRichardson.10 In the case we have described, it is notablethat the isolate was only intermediately susceptible tocefuroxime, an agent with which the patient had beenempirically treated for months prior to the appearance ofhis infection.

Roseomonas is also widely resistant to penicillinssuch as ampicillin, piperacillin, and ticarcillin, and theaddition of beta-lactamase inhibitors does not reliablyrestore susceptibility.5,6,8-10,12 On the other hand, imipen-em, tetracycline, and the aminoglycosides are nearly uni-versally active against Roseomonas strains.5,6,8-10,12

Although Roseomonas infection is uncommon, it cancause a variety of disease manifestations and is more oftenfound in patients with underlying illness. Indwellingdevices, including LVADs, may be an additional associa-tion. The characteristic slow growth of Roseomonas maymake it difficult to detect and usual empiric antibiotic reg-

imens such as penicillins or cephalosporins may be inef-fective. The current case adds to the growing body ofLVAD literature suggesting that device removal and trans-plant in the setting of LVAD infection is often success-ful.1,3,4

Mr. Singal is from the University of Michigan Medical School;Drs. Malani, Day, and Clark are from the Department of InternalMedicine, Division of Infectious Diseases; and Dr. Pagani is from theDepartment of Surgery, Section of Cardiothoracic Surgery, University ofMichigan Health System, Ann Arbor, Michigan.

Address reprint requests to Nina M. Clark, MD, University ofIllinois at Chicago, Department of Internal Medicine, Section ofInfectious Diseases, 808 S. Wood Street, Room 888, M/C-735, Chicago,IL 60612.

REFERENCES1. Malani PN, Dyke DB, Pagani FD, Chenoweth CE. Nosocomial infec-

tions in left ventricular assist device recipients. Clin Infect Dis2002;34:1295-1300.

2. McCarthy PM, Schmitt SK, Vargo RL, Gordon S, Keys TF, Hobbs RE.Implantable LVAD infections: implications for permanent use of thedevice. Ann Thorac Surg 1996;61:359-365.

3. Argenziano M, Catanese KA, Moazami N, et al. The influence ofinfection on survival and successful transplantation in patients withleft ventricular assist devices. J Heart Lung Transplant 1997;16:822-831.

4. Fischer SA, Trenholme GM, Costanzo MR, Piccione W. Infectious com-plications in left ventricular assist device recipients. Clin Infect Dis1997;24:18-23.

5. Shokar NK, Shokar GS, Islam J, Cass AR. Roseomonas gilardii infection:case report and review. J Clin Microbiol 2002;40:4789-4791.

6. Rihs JD, Brenner DJ, Weaver RE, Steigerwalt AG, Hollis DG, Yu VL.Roseomonas, a new genus associated with bacteremia and other humaninfections. J Clin Microbiol 1993;31:3275-3283.

7. Struthers M, Wong J, Janda JM. An initial appraisal of the clinical signif-icance of Roseomonas species associated with human infections. ClinInfect Dis 1996;23:729-733.

8. Nahass RG, Wisneski R, Herman DJ, Hirsh E, Goldblatt K. Vertebralosteomyelitis due to Roseomonas species: case report and review of theevaluation of vertebral osteomyelitis. Clin Infect Dis 1995;21:1474-1476.

9. Sandoe JA, Malnick H, Loudon KW. A case of peritonitis caused byRoseomonas gilardii in a patient undergoing continuous ambulatory peri-toneal dialysis. J Clin Microbiol 1997;35:2150-2152.

10. Richardson JD. Failure to clear a Roseomonas line infection with antibi-otic therapy. Clin Infect Dis 1997;25:155.

11. Alcala L, Vasallo FJ, Cercenado E, Garcia-Garrote F, Rodriguez-Creixems M, Bouza E. Catheter-related bacteremia due to Roseomonasgilardii spp. J Clin Microbiol 1997;35:2712.

12. Subudhi CP, Adedeji A, Kaufmann ME, Lucas GS, Kerr JR. FatalRoseomonas gilardii bacteremia in a patient with refractory blast crisis ofchronic myeloid leukemia. Clin Microbiol Infect 2001;7:573-575.

13. Lewis L, Stock F, Williams D, Weir S, Gill VJ. Infections with Roseomonasgilardii and review of characteristics used for biochemical identificationand molecular typing. Am J Clin Pathol 1997;108:210-216.

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