RevIew
Pulmonary Involvement in Brucellosis, a Rare Complication
of Renal Transplant: Case Report and Brief Review
Nurettin Ay,1 Şafak Kaya,2 Melih Anıl,3 Vahhac Alp,1 Ünal Beyazıt,4 Enver Yüksel,3
Ramazan Danış3
Abstract
Brucellosis, a disease endemic in many countries
including Turkey, is a systemic infectious disease.
Brucellosis is rare in renal transplant recipients. Only 4
cases have been reported in the literature. In this
report, we describe the clinical manifestations and
laboratory findings of a brucellosis case with pulmonary
involvement in a renal transplant recipient. A 20-year-
old man who had a living-donor kidney transplant 4
months earlier presented to our transplant clinic with
fever, cough, and right flank pain. Clarithromycin
and ceftriaxone were started for the diagnosis of
pneumonia. However, piperacillin/tazobactam, mero-
penem plus teicoplanin, and antituberculosis
treatment were continued because the patient was
unresponsive to the initial therapy. Serum Brucella
agglutination titer was found to be 1/320. Treatment
was started with a 6-week course of oral doxycycline
and rifampin, resulting in cure. Brucellosis and
especially its pulmonary involvement are rare after
kidney transplant. However, in endemic areas, it
should be considered as it mimics several other
infectious diseases.
Key words: Kidney transplant, Brucellosis, Pulmonary,
Doxycycline, Rifampin
Introduction
Brucellosis is one of the most common systemic
zoonotic diseases (with 500 000 new cases annually)
and is particularly endemic in the Mediterranean
region, the Middle East, the Arabian Peninsula,
Central and South America, Asia, and Africa.1,2
From the 1Transplantation Center, Diyarbakır Education and Research Hospital, the
2Department of Infectious Disease and the 4Department of General Surgery, Diyarbakır Gazi
Yaşargil Training and Research Hospital, and the 3Department of Nephrology, Diyarbakır Gazi
Yaşargil Education and Research Hospital, Diyarbakır, Turkey
Corresponding author: Nurettin Ay, Diyarbakır Education and Research Hospital,
Transplantation Center, Diyarbakır, Turkey
Phone: +90 505 661 4260 E-mail: nurettinay77@hotmail.com
Experimental and Clinical Transplantation (2016)
Copyright © Başkent University 2016
Printed in Turkey. All Rights Reserved.
According to data from the Turkish Ministry of
Health in 2004, the disease is most common in the
southeastern region of Turkey.3 Humans are infected
after close contact with an animal or after
consumption of meat or dairy products infected by
bacteria of the genus Brucella.4 This is a multisystem
infection that may present with a broad spectrum of
clinical symptoms, organ involvement, and other
complications.5-7 Brucellosis is rare in renal transplant
recipients. To the best of our knowledge, only 4 cases
have been reported in the literature.8-11 In this report,
we describe the clinical manifestations and laboratory
findings of a brucellosis case with pulmonary
involvement in a renal transplant recipient.
Case Report
A 20-year-old man who had received a living-donor
kidney transplant (the donor was his 43-year-old
mother) was hospitalized due to coughing, dyspnea,
sputum production, right flank pain, nausea, and
vomiting. He had fever (> 38°C), shivering, and night
sweating for 1 week. The cause of the patient’s
chronic kidney disease was unknown; however,
before transplant he had hemodialysis for 4 months.
He had no other comorbid disease. Informed consent
was obtained from the patient.
The patient was taking 1 mg twice daily
tacrolimus, 360 mg twice daily mycophenolate
sodium, 10 mg daily prednisolone, 80/400 mg/d
trimethoprim/sulfamethoxazole, and 30 mg/d
lansoprazole. His body temperature was 38.1°C,
blood pressure was 112/75 mm Hg, pulse was 102
beats/min, rhythmic respiratory rate was 16
breaths/min. There was tenderness on his right
lateral side of the chest by palpation and decreased
lung sounds in the lower portion of the right chest
by auscultation. Other findings during physical
examination were unremarkable. Laboratory results
at admission showed white blood cell count of
DOI: 10.6002/ect.2015.0324
 Nurettin Ay et al/Experimental and Clinical Transplantation (2016)
5600/μL (53% neutrophils and 37.9% lymphocytes),
hemoglobin level of 9.9 g/dL, platelet count of
238 000/μL, C reactive protein level of 295 mg/L,
erythrocyte sedimentation rate of 43 mm/h, aspartate
aminotransferase level of 16 U/L, alanine amino-
transferase level of 10 U/L, alkaline phosphatase level
of 66 U/L, gamma-glutamyl transpeptidase level of
23 U/L, lactate dehydrogenase level of 671 U/L, and
creatinine level of 1.46 mg/dL. Pleural effusion
(5 cm) was observed by radiologic and ultraso-
nographic imaging (Figures 1 and 2). Pleural fluid
was taken for laboratory and bacteriologic
examinations. Biochemistry values showed that
pleural fluid was compatible with exude; Gram and
acid-fast stain tests and cultures were negative.
Adenosine deaminase level in pleural fluid was
26 U/L. Transthoracic echocardiography result was
normal.
Figure 1. Pleural Effusion Imaging on Chest Radiography
Figure 2. Pleural Effusion Imaging on USG
Specimens from urine, blood, and sputum were
taken for microbiologic examination. A triple sputum
examination for acid-fast bacteria was negative.
Antibody for Cytomegalovirus was negative. We
started the patient on 500 mg twice daily
clarithromycin and 1 g twice daily ceftriaxone due to
suspicion of pneumonia, with mycophenolate
sodium dose reduced. Culture results were negative.
After 5 days on this regimen, fever continued. Both
clarithromycin and ceftriaxone were stopped, and
4.5 g piperacillin/tazobactam 3 times per day was
started. Repeat bacteriologic cultures were negative.
After 5 days on this regimen, piperacillin/tazobactam
was stopped and 1 g meropenem 3 times per day and
400 mg/d teicoplanin were administered due to
continued fever. After meropenem and teicoplanin
were introduced, fever disappeared and C-reactive
protein levels decreased to 32 mg/L; however,
erythrocyte sedimentation rate was 98 mm/h.
Although bacteriologic tests did not yield positive
results, empiric antituberculosis treatment was
started. Our region is an endemic area for
tuberculosis; therefore, 300 mg/d isoniazid, 450 mg/d
rifampicin, 1000 mg/d ethambutol, and 1000 mg/d
pyrazinamide were started12 because pleural
effusion of the patient did not resolve and fever
relapsed after day 14 of meropenem and teicoplanin
treatment. Fever continued even after 12 days of anti-
tuberculosis treatment.
The patient’s family had a dairy farm. The patient
denied any contact with raw milk and milk products
and stated that after the renal transplant he did not
get close to the farm and animals. However, after a
detailed history was obtained, we learned that
approximately 30 to 35 days before admission there
were abortus and deaths among the sheep and goats.
Brucella agglutination was studied and found to be
1/320 titer positive. Antituberculosis treatment was
stopped, and 600 mg/d rifampicin and 200 mg/d
doxycycline were started. Fever disappeared after
day 3 of the treatment, with no relapse shown with
treatment continued to the 6-week follow-up.
Discussion
Brucellosis is a systemic infectious disease. Because
of its high degree of morbidity, for both animals and
humans, it is a significant cause of economic loss and
represents a serious public health problem in many
developing countries.13 Incidence of the disease in
Turkey is 0.59 per 100 000 per year.6 Pulmonary
involvement of brucellosis is rare.14 Brucellosis may
cause abscess of lungs, empyema, pneumonia, pleural
 Nurettin Ay et al/Experimental and Clinical Transplantation (2016)

Table 1. Brucellosis in Renal Transplant Recipients

Bishara et al10 Yousif and Nelson11 Einollahi et al9 Ting et al8 Present Case
Age (y)/sex/ country 41/M/Israel 56/F/Saudi Arabia 44/F/Iran 58/M/Taiwan 20/M/Turkey
Time posttransplant 3 years 13 years 17 months 3 years 4 months
Immunosuppressive therapy AZT + prednisolone Cyclosporine + Cyclosporine + AZT + Tacrolimus + MMF Tacrolimus + MMF +
AZT + prednisolone AZT + prednisolone prednisolone
Clinical features Fever, weakness Fever, confusion Fever, right knee Fever, sweats, Cough, right flank pain,
swelling malaise fever, weakness
White blood cell count, 5200 NA 20 000 3160 5600
per mm3
Platelets, per mm3 130 000 NA NA 74 000 238 000
Alanine aminotransferase, U/L Normal NA NA 156 Normal
Creatinine, mg/dL 1.6 6.0 (admission), 3.8 (admission), 1.25 1.4 (admission),
2.71 (discharge) 1.71 (discharge) 1.08 (discharge)
Diagnosis Blood culture Brucella titer (1:320) Synovial fluid, blood Blood culture Brucella titer (1:320)
(Brucella melitensis) culture (Brucella melitensis)
Complication Infective endocarditisa Neuro-brucellosis Brucellosis arthritis Hematologic, Brucellosis pneumonia
hepatobiliary
Treatment Doxycycline, rifampin, Doxycycline and Doxycycline, rifampin, Tigecycline for 2 wk; Doxycycline and
TMP/SMX for 6 wk rifampin for 6 wk and ciprofloxacin minocycline and rifampin for 6 wk
TMP/SMX for 3 mo
Outcome Cure Cure Cure Cure Cure
Abbreviations: AZT, azathioprine; MMF, mycophenolate sodium; NA, not available; TMP/SMX, trimethoprim/sulfamethoxazole
aA 3-mm vegetation on mitral valve.

effusion, granulomas, solitary nodules, and hilar and
paratracheal lymphadenopathies.15-17 Gur and
associates,6 Lubani and associates,14 and Hatipoglu
and associates15 found that lung involvement of
brucellosis was 5%, 0.6%, and 10%.
Lulu and associates presented 4 patients (1%),
with 1 patient having pneumonia and 1 patient
having pleural effusion.18 Our finding of brucellosis
with subsequent pleural effusion was in a living-
donor kidney transplant recipient. This is the first
report of such a case in the literature.
To the best of our knowledge, only 4 cases with
brucellosis after kidney transplant have been
reported in the literature.8-11 Clinical and laboratory
features of our case and the other 4 cases in the
literature are summarized in Table 1.
The purpose of brucellosis treatment is to cure the
disease, decrease symptoms, and prevent com-
plications and relapses. There are several com-
binations for the treatment of brucellosis: (1)
doxycycline for 6 weeks and gentamicin or
streptomycin for 2 weeks, (2) doxycycline and
rifampin for 6 weeks, or (3) doxycycline and
trimethoprim/sulfamethoxazole for 6 weeks.19 The
best results are obtained with doxycycline and
rifampin or doxycycline and streptomycin. We
preferred doxycycline and rifampin because of the
potential nephrotoxicity of gentamicin and
streptomycin. Rifampin is a potential inducer of
cytochrome P450, which metabolizes tacrolimus.20
Therefore, we closely monitored tacrolimus levels,
with our patient receiving 3 mg/kg tacrolimus and
120 mg/d verapamil to ensure serum tacrolimus
level of 6 to 8 mg/dL. After 6 weeks of brucellosis
treatment, complete cure was observed.
Conclusions
Brucellosis and especially its pulmonary involvement
are rare after kidney transplant. However, it should be
considered, especially in endemic areas, because this
disease mimics several other infectious diseases.
References
1. World Health Organization. Fact Sheet N173. Geneva, Switzerland:
World Health Organization; 1997.
2. Madkour MM. Madkour’s Brucellosis. 2nd ed. New York, NY:
Springer; 2001.
3. Turkish Ministry of, Health. Statistics/Study Yearbook of the General
Directorate of Primary Health Care. Ankara, Turkey: Ministry of
Health; 2004.
4. Kaya S, Eskazan AE, Elaldi N. Brucellar pericarditis: a report of four
cases and review of the literature. Int J Infect Dis. 2013;17(6):e428-
e432.
5. Young EJ. Brucella species. In: Mandell GL, Bennett JE, Dolin R, eds.
Principles and Practice of Infectious Diseases. 6th ed. Philadelphia,
PA: Elsevier, Churchill Livingstone; 2005:2669-2674.
6. Gur A, Geyik MF, Dikici B, et al. Complications of brucellosis in
different age groups: a study of 283 cases in southeastern Anatolia
of Turkey. Yonsei Med J. 2003;44(1):33-44.
7. Celen MK, Ulug M, Ayaz C, Geyik MF, Hosoglu S. Brucellar
epididymo-orchitis in southeastern part of Turkey: an 8 year
experience. Braz J Infect Dis. 2010;14(1):109-115.
8. Ting IW, Ho MW, Sung YJ, et al. Brucellosis in a renal transplant
recipient. Transpl Infect Dis. 2013;15(5):E191-E195.
9. Einollahi B, Hamedanizadeh AK, Alavian SM. Brucellosis arthritis--
a rare complication of renal transplantation: a case report.
Transplant Proc. 2003;35(7):2698.
 Nurettin Ay et al/Experimental and Clinical Transplantation (2016)
10. Bishara J, Robenshtok E, Weinberger M, Yeshurun M, Sagie A, Pitlik
S. Infective endocarditis in renal transplant recipients. Transpl Infect
Dis. 1999;1(2):138-143.
11. Yousif B, Nelson J. Neurobrucellosis--a rare complication of renal
transplantation. Am J Nephrol. 2001;21(1):66-68.
12. World Health Organization. Global Tuberculosis Control:
Surveillance, Planning, Financing. Who Report 2008. Geneva,
Switzerland, World Health Organization; 2008.
13. Ulug M, Can-Ulug N. Pulmonary involvement in brucellosis. Can J
Infect Dis Med Microbiol. 2012;23(1):e13-e15.
14. Lubani MM, Lulu AR, Araj GF, Khateeb MI, Qurtom MA, Dudin KI.
Pulmonary brucellosis. Q J Med. 1989;71(264):319-324.
15. Hatipoglu CA, Bilgin G, Tulek N, Kosar U. Pulmonary involvement
in brucellosis. J Infect. 2005;51(2):116-119.
Exp Clin Transplant
16. Pappas G, Bosilkovski M, Akritidis N, Mastora M, Krteva L, Tsianos
E. Brucellosis and the respiratory system. Clin Infect Dis. 2003;37(7):
e95-e99.
17. Olukman O. Pulmonary involvement in childhood brucellosis: a
case report. Vector Borne Zoonotic Dis. 2008;8(2):245-248.
18. Lulu AR, Araj GF, Khateeb MI, Mustafa MY, Yusuf AR, Fenech FF.
Human brucellosis in Kuwait: a prospective study of 400 cases. Q
J Med. 1988;66(249):39-54.
19. Skalsky K, Yahav D, Bishara J, Pitlik S, Leibovici L, Paul M. Treatment
of human brucellosis: systematic review and meta-analysis of
randomised controlled trials. BMJ. 2008;336(7646):701-704.
20. Paterson DL, Singh N. Interactions between tacrolimus and
antimicrobial agents. Clin Infect Dis. 1997;25(6):1430-1440.