Case report

Severe Legionnaire’s disease caused by Legionella

longbeachae in a long-term renal transplant patient:

the importance of safe living strategies after

transplantation

A.J. Wright, A. Humar, S. Gourishankar, K. Bernard, D. Kumar.Severe Legionnaire’s disease caused by Legionella longbeachae in along-term renal transplant patient: the importance of safe livingstrategies after transplantation.Transpl Infect Dis 2012. All rights reserved

Abstract: Legionella species are intracellular gram-negative bacillithat require specific culture media for growth. Transplant recipientswith impaired cellular immunity are at particular risk for infectionwith this pathogen. Most human disease is caused by Legionellapneumophila; disease caused by non-L. pneumophila species isreported mainly in immunosuppressed patients with the exceptionof Legionella longbeachae. L. longbeachae is a common cause ofLegionnaires’ disease in Australia and New Zealand, and isassociated with exposure to potting soil. We report the case of apatient, 26 years post kidney transplant, who presented with severeand rapidly progressive respiratory illness. L. longbeachaeserogroup 1 was isolated from respiratory cultures. Furtherinvestigation revealed that she had significant soil exposure beforethe onset of illness. We highlight the importance of following safeliving strategies to prevent exposure-related illness even in long-term transplant recipients.

A.J. Wright1, A. Humar2,S. Gourishankar2, K. Bernard3,D. Kumar21Division of Infectious Diseases, University of BritishColumbia, Vancouver, British Columbia, Canada,2Alberta Institute for Transplant Sciences, University ofAlberta, Edmonton, Alberta, Canada, 3National MicrobiologyLaboratory, Public Health Agency of Canada, Winnipeg,Manitoba, Canada

Key words: pneumonia; organ transplantation;exposure; Legionnaire’s; Legionalla

Correspondence to:Deepali Kumar, MD, MSc, FRCPC, Transplant InfectiousDiseases, University of Alberta, 6-030 Katz Center forHealth Research, Edmonton, Alberta T6G 2E1, CanadaTel: (780) 492 3885Fax: (780) 492 4805E-mail: deepali.kumar@ualberta.ca

Received 25 September 2011, revised 18 January 2012,accepted for publication 14 February 2012

DOI: 10.1111/j.1399-3062.2012.00755.xTranspl Infect Dis 2012: 0: 1–4

Legionnaire’s disease was named after the first recog-nized outbreak of disease due to Legionella pneumo-phila, which occurred during a 1976 Pennsylvania StateAmerican Legion convention in Philadelphia (1).Although it is a clinical syndrome resulting from anacute pneumonia, the primary manifestations may notbe pulmonary. Systemic symptoms, such as abdominalpain and diarrhea, or laboratory findings, such ashyponatremia and elevated transaminases, can confusethe initial clinical picture (2). Risk factors for diseaseinclude immunosuppression and, particularly, impairedcellular immunity (3, 4). We describe a long-termkidney transplant patient who had severe systemicdisease due to Legionella longbeachae serogroup 1, and

highlight the importance of disease caused by environ-mental exposure in this setting.

Case report

A 54-year-old female kidney transplant recipient wasadmitted to a rural hospital with a 1-week history offever, headache, and severe nausea, vomiting, andwatery diarrhea. She had undergone deceased-donorkidney transplant 26 years earlier for end-stage renaldisease due to post-streptococcal glomerulonephritis.Her immunosuppression at the time of admission wascyclosporine (CsA) 150 mg twice daily, mycophenolic

1

© 2012 John Wiley & Sons A/S

Transplant Infectious Disease, ISSN 1398-2273

acid (MPA) 360 mg twice daily, and prednisone 5 mgdaily and had not been modified recently. Four daysbefore admission, outpatient blood work was donebecause of her symptoms, which revealed a leukocyto-sis (white blood cell count [WBC] of 21.9 9 109 cells/L). Upon presentation to the emergency room, herWBC had decreased to 4.7 9 109 cells/L. Bloodcultures were drawn and she was started on intrave-nous cefuroxime. She was noted to have had a declinein renal function (creatinine of 395 lmol/L and glo-merular filtration rate [GFR] of 10 mL/min/1.73 m2)prompting her transfer to our transplant center.On admission to the transplant center, she continued

to have complaints of headache, generalized malaise,and diarrhea. Her WBC count had further reduced to2.3 9 109 cells/L. She was hyponatremic (serumsodium 129 mmol/L) with a mild transaminitis (aspar-tate aminotransferase 158 U/L, alanine aminotransfer-ase 108 U/L), and her creatinine had risen to433 lmol/L (GFR of 9 mL/min/1.73 m2). Chest x-rayrevealed a dense right lower lobe consolidation. Shewas started on intravenous piperacillin-tazobactam andoral standard dose azithromycin (500 mg followed by250 mg, total of 2 doses given). Her MPA was discon-tinued and prednisone increased to 60 mg daily.Within hours, the patient rapidly declined, and she

required intensive care unit (ICU) admission andmechanical ventilation. Continuous renal replacementtherapy was initiated for persistent metabolic acidosisand acute renal failure. The next day the patient’sdiarrhea resolved. However, progressive decline in thepatient’s respiratory parameters continued, with pro-gression of diffuse pulmonary infiltrates on chest x-ray.A bronchoalveolar lavage (BAL) was performed on day6, which was negative for bacterial, viral, or fungalpathogens. Specific cultures for Legionella were notrequested at this time. She subsequently requiredventilator support with an oscillator. Severe neutrope-nia developed (absolute neutrophil count 0.2 9 109

cells/L) and her CsA was discontinued. Her antibioticregimen was changed to meropenem and ciprofloxacin.Vancomycin and fluconazole were added for additionalcoverage as well as granulocyte-colony stimulatingfactor and prophylactic-dose trimethoprim-sulfameth-oxazole.On day 8, the patient began to improve; she was

removed from the oscillator on day 10. A second BALwas done on this day. This was also negative for allbacterial, viral, or fungal pathogens. Legionella culturewas specifically performed, but was negative.Because of concern about her persistent pulmonary

infiltrates and frequent mucus plugging, a third BALwas done on day 16. This culture ultimately grew

Legionella species 7 days later. This was identifiedfurther as L. longbeachae by 16S rRNA and mip genesequence analysis, and as L. longbeachae serogroup 1by antibody typing (m-Tech, Milton, Georgia, USA).Her initial BAL specimen from day 6 was then set-up forLegionella culture, and this grew the same organismafter 5 days. Her therapy was changed to high-doseazithromycin (500 mg daily), to complete a full 21-daycourse of therapy.The patient improved slowly, as she had suffered

from critical illness polyneuropathy. Dialysis wasstopped on day 15 of ICU admission; her creatinineeventually settled to 123 lmol/L (GFR of 39 mL/min/1.73 m2). Her steroids were tapered to her baselineprednisone dose. CsA and MPA were re-introduced forimmunosuppression. She was later discharged from theICU for a prolonged stay on the ward to rehabilitate.Post-ICU questioning revealed that the patient lived

on a ranch with her family, where she was activelyinvolved in raising horses and cattle. Her property hadextensive gardens, which she personally maintained,and she had her own greenhouse on the property.Although she primarily used decomposed cattle fecesfor fertilizer, in the 2 weeks before her illness, she hadbeen re-seeding her lawn, which required commercialpotting soil. She did not wear gloves or a mask duringthese activities, and only intermittently washed herhands after potting soil use. The patient was anon-smoker.

Discussion

We describe an unusual case of severe legionellosisafter organ transplantation due to L. longbeachae. Ourpatient was a kidney transplant recipient who had beenwell for several years and presented with a subacutemulti-system illness. Although broad-spectrum antimi-crobials were instituted, the diagnosis was not madeuntil several days into her ICU stay. She had severalpreviously described features consistent with Legion-naire’s disease including a presentation with prominentsystemic and gastrointestinal symptoms, but minimalrespiratory symptoms. Her epidemiologic history sup-ported recent exposure to commercial potting soil,which previously has been reported to harbor thispathogen (5–7). She recovered after aggressive sup-portive care and a prolonged ICU stay. In the absenceof other pathogens, with the isolation of L. longbeachaeon 2 occasions from BAL, and a consistent clinicalpresentation and exposure history, we conclude thatthis patient had clinical infection with L. longbeachae

2 Transplant Infectious Disease 2012:0: 1–4

Wright et al: Legionella in transplant

likely acquired as a result of recent exposure to pottingsoil.Although L. pneumophila serogroup 1 is responsible

for causing between 70% and 90% of legionellosis, thisepidemiology is variable world-wide (8, 9). Severalother Legionella species have been reported in theliterature to cause disease. In 1980, a new species ofLegionella was first isolated from a woman in LongBeach, California – subsequently named L. longbeachae(10). In 2000, 3 patients with L. longbeachae diseasetransmitted from potting soil were reported by the U.S.Centers for Disease Control (11). All patients resided inthe Western United States. Subsequently, this specieshas been reported to be a cause of legionellosis aroundthe world, but particularly in Australia, where it isquoted to cause up to 42% of legionellosis cases(12–14). More recent reports of L. longbeachae infectionsuggest either that the disease frequency is increasing,or that the disease is increasingly recognized andreported (15).Unlike other species of Legionella, L. longbeachae has

a unique epidemiology, in that it is not transmitted viasources of water (15, 16). Instead, it appears to betransmitted from some commercial potting soil andother decomposing materials, including some homecomposts (16, 17). This was confirmed in a case studyfrom Australia, where 25 cases with L. longbeachaeinfection were compared with 75 controls. Use of acommercial potting mix was associated with a signifi-cantly increased risk of infection with L. longbeachae, aswas lack of hand washing after gardening, smoking,and being near dripping hanging flower pots (6). Not allpotting mixes have been shown to contain L. longbe-achae, and we did not test the potting soil handled bythis patient for L. longbeachae. The life cycle ofL. longbeachae in potting soil includes an amplificationcycle in amoebae, and a requirement for storage of thepotting soil at higher ambient temperatures (17). Forour patient, the soil exposure took place in July 2011, atwhich time the average daytime temperature in thearea was 22°C (~72°F). L. longbeachae infections aredocumented rarely in Canada; since 2006, 10 strainsfrom 8 patients, including the case presented here,have been referred to the National MicrobiologyLaboratory for characterization (K. Bernard, personalcommunication, September 21, 2011). We used 16SrRNA sequence analysis for species identification.Literature on the use of polymerase chain reaction(PCR) for detection of Legionella species in clinicalsamples is increasing. PCR of the 16S or 23S rRNAgenes followed by sequencing for species identificationcan be done using a real-time or multiplex formats andhas a sensitivity ranging from 80% to 100% and

specificity of >90%, and has a rapid turnaround time(12, 18, 19).L. longbeachae has been described only once previ-

ously, to our knowledge, in the setting of transplanta-tion (20). In that case report, a 61-year-old femaleorthotopic heart transplant recipient developed respi-ratory failure 10 days after surgery. Although left upperlobe opacity was noted on chest x-ray, the initial Gramstain of respiratory specimens showed no bacteria.The patient’s immunosuppression was subsequentlyincreased for presumed humoral rejection, and multi-system failure and death resulted. Upon autopsy,L. longbeachae was isolated from pulmonary specimens.The infection was presumed nosocomial, althoughenvironmental cultures were negative.Our patient did poorly despite the azithromycin

therapy. However, this was a short course and only 2doses were given. Nevertheless, the patient waschanged to ciprofloxacin, which also has activityagainst this pathogen and she began to improve after48 h of this therapy. Although the role of targetedantimicrobials is important, the role of immunosup-pression in a transplant patient is also equally impor-tant. Although the MPA was discontinued, prednisonewas increased, and this may have contributed to overallincreased immunosuppression and the slowness of herrecovery.Our case illustrates several important teaching

points, and highlights the value of the traditionaltimeline of infection post transplant (21). A patientdoing well several years from transplant will likelynot have an opportunistic infection unless intenseexposure has occurred. Therefore, it is important toobtain a complete risk-factor history. An exposurehistory was difficult to obtain during our patient’sadmission, and her clinical features suggested aprimary gastrointestinal illness.Another issue illustrated by this case is the ongoing

education of transplant patients on measures to preventinfections after transplant. These are described in detailin guidelines by the American Society of Transplanta-tion (22). Specifically, when working with soil, trans-plant patients should wear long-sleeve shirts and pantswhile out in the garden, and should don gloves for anydirect contact with soil. Frequent and thorough handwashing should be employed both during and afterthese activities. Consideration should also be given towearing a mask, if aerosolization of particulate mattercould potentially occur. Although usually thought of asa recommendation to reduce the risk of fungal infec-tions, the case of our patient highlights that this alsoapplies to other pathogens that can be transmittedthrough the soil. Patients should be reminded of these

Transplant Infectious Disease 2012:0: 1–4 3

Wright et al: Legionella in transplant

tips regularly after transplant as they may become lessvigilant as they get further from their transplant, andreturn to normal activities.In summary, we present a case of a patient with a

remote history of renal transplant who presented with amultisystem illness due to a Legionella species, likelyacquired from exposure to potting soil. Although shehad epidemiological risk factors for acquisition of thisparticular infection, the link was only made retrospec-tively. We believe our case highlights the importance ofobtaining an epidemiologic history, considering unu-sual pathogens during severe illness, and remindinglong-term transplant patients about the importance ofsafe living strategies.

Acknowledgements:

The authors thank Ian Cunningham, Tamara Burdz,Deborah Wiebe, Betty Ng, and Ana Luisa Pacheco fromthe Canadian National Microbiology Laboratory, Winni-peg,Manitoba, Canada, for providing excellent technicalassistance, as well as Dr. Natalia Solomon from theProvincial Laboratory for PublicHealth, Alberta, Canada.

References

1. McDade JE, Shepard CC, Fraser DW, Tsai TR, Redus MA,Dowdle WR. Legionnaires’ disease: isolation of a bacterium anddemonstration of its role in other respiratory disease. N Engl JMed 1977; 297 (22): 1197–1203.

2. Mandell GL, Bennet JE, Dolin R, eds. Mandell, Douglas, andBennett’s Principles and Practice of Infectious Diseases. (7thedn.) Philadelphia, PA: Churchill Livingstone, 2009.

3. Singh N, Stout JE, Yu VL. Prevention of Legionnaires’ disease intransplant recipients: recommendations for a standardizedapproach. Transpl Infect Dis 2004; 6 (2): 58–62.

4. Gudiol C, Garcia-Vidal C, Fernandez-Sabe N, et al. Clinicalfeatures and outcomes of Legionnaires’ disease in solid organtransplant recipients. Transpl Infect Dis 2009; 11 (1): 78–82.

5. Casati S, Gioria-Martinoni A, Gaia V. Commercial potting soils asan alternative infection source of Legionella pneumophila andother Legionella species in Switzerland. Clin Microbiol Infect2009; 15 (6): 571–575.

6. O’Connor BA, Carman J, Eckert K, Tucker G, Givney R, CameronS. Does using potting mix make you sick? Results from a

Legionella longbeachae case-control study in South Australia.Epidemiol Infect 2007; 135 (1): 34–39.

7. Steele TW, Lanser J, Sangster N. Isolation of Legionellalongbeachae serogroup 1 from potting mixes. Appl EnvironMicrobiol 1990; 56 (1): 49–53.

8. Ng V, Tang P, Jamieson F, Guyard C, Low DE, Fisman DN.Laboratory-based evaluation of legionellosis epidemiology inOntario, Canada, 1978 to 2006. BMC Infect Dis 2009;9: 68.

9. Fields BS, Benson RF, Besser RE. Legionella and Legionnaires’disease: 25 years of investigation. Clin Microbiol Rev 2002; 15 (3):506–526.

10. McKinney RM, Porschen RK, Edelstein PH, et al. Legionellalongbeachae species nova, another etiologic agent of humanpneumonia. Ann Intern Med 1981; 94 (6): 739–743.

11. Centers for Disease Control and Prevention (CDC). Legionnaires’disease associated with potting soil–California, Oregon, andWashington, May–June 2000. MMWR Morb Mortal Wkly Rep2000; 49 (34): 777–778.

12. Blyth CC, Adams DN, Chen SC. Diagnostic and typing methodsfor investigating Legionella infection. N S W Public Health Bull2009; 20 (9–10): 157–161.

13. Lim I, Sangster N, Reid DP, Lanser JA. Legionella longbeachae

pneumonia: report of two cases. Med J Aust 1989; 150 (10):599–601.

14. Amodeo MR, Murdoch DR, Pithie AD. Legionnaires’ diseasecaused by Legionella longbeachae and Legionella pneumophila:comparison of clinical features, host-related risk factors, andoutcomes. Clin Microbiol Infect 2010; 16 (9): 1405–1407.

15. Whiley H, Bentham R. Legionella longbeachae and legionellosis.Emerg Infect Dis 2011; 17 (4): 579–583.

16. Hughes MS, Steele TW. Occurrence and distribution of Legionellaspecies in composted plant materials. Appl Environ Microbiol1994; 60 (6): 2003–2005.

17. Steele TW, Moore CV, Sangster N. Distribution of Legionellalongbeachae serogroup 1 and other Legionellae in potting soils inAustralia. Appl Environ Microbiol 1990; 56 (10): 2984–2988.

18. Cloud JL, Carroll KC, Pixton P, Erali M, Hillyard DR. Detection ofLegionella species in respiratory specimens using PCR withsequencing confirmation. J Clin Microbiol 2000; 38 (5):1709–1712.

19. Nazarian EJ, Bopp DJ, Saylors A, Limberger RJ, Musser KA.Design and implementation of a protocol for the detection ofLegionella in clinical and environmental samples. Diagn MicrobiolInfect Dis 2008; 62 (2): 125–132.

20. Korman TM, Fuller A, Ibrahim J, Kaye D, Bergin P. FatalLegionella longbeachae infection following heart transplantation.Eur J Clin Microbiol Infect Dis 1998; 17 (1): 53–55.

21. Fishman JA. Infection in solid-organ transplant recipients. N EnglJ Med 2007; 357 (25): 2601–2614.

22. Avery RK, Michaels MG; AST Infectious Diseases Community ofPractice. Strategies for safe living following solid organtransplantation. Am J Transplant 2009; 9 (Suppl 4): S252–S257.

4 Transplant Infectious Disease 2012:0: 1–4

Wright et al: Legionella in transplant