Hepatic abscess due to Burkholderia ( Pseudomonas ) cepacia in cystic fibrosis

811rk/10/dcria (Pse11do111011as) ce11acia has been cultured from bronchial secretions of patients with cystic fibrosis with varying freq uency. The overall prevalence in patients over 18 years old at the authors' centre in Toronto is 51 %. Extrapulmonary infections are rare in non immunosuppressed patients with cystic fibrosi s and B ccpacia has been the causative organism in only three pre vious reports. Two patients with cystic fibrosis are described who developed hepatic abscesses clue to B cc11acia. One patient is the sibling of two brothers in whom this complication was previously described.

reported in only thrc•c cases (2,3 ).Two brothers from Toronto developed hepatic abscesses and one male from Toronto was treated for recurrent neck abscesses due to this organism.The present report describes two further Toronto patients who were treated for hepatic abscesses due to B c1'fwcia.

CASE PRESENTATIONS Case 1
A 28 -year-old woman with CF was admitted to hospital with a two-week history of fever.chills.weight loss and dyspnea.She was diagnosed with CF in infancy based on a positive sweat chloride test.a clinical history of panneatic insufficiency and a positive family history.Her clinical course was one of slowly progressive pulmonary disease with two infLctious exacerbations requiring hospitali zati on over the preceding IO years.She was known to have chronic pulmonary infection with P .,ewlomo nas lla11g i110.1ll and B l'l'/hlcill s ince age 17.At age 18 she developed diabetes mellitus.She was malnourished with a weight and height less than the With percentile since age 6.Her last recorded body mass index (BMI) was 19.0.Liver function tests had previously heen normal.Baseline pulmonary function showed moderately severe disease with forced vital capacit y (FYC) 2.16 L (47 %, predicted) and forced expiratory volume in I s (FEY 1) 1.44 L (36% predicted).
Ahdominal ultrasound demonstrated mild he patomegaly and the liver contained at least six poorly defined hypoechoic nodules occupying hoth right and left lobes, the largest measuring 3.7 cm in maximum diameter.An abdominal c om puterized tomogram (CT) with contrast confirmed these findings (Figure I) and purulent tluid was aspirated under CT guidance.Gram stain w;.is remarkable for polymononuclear cells and Gram-negative bacilli.Suhsequcnt culture gre w /3 CC'/Jllcill, sensitive to ecft:uidime.irnipenem.pipcracillin and resistant to tohramycin, tri111ethoprim-sult'amc thoxazolc.gcntamycin.ciprofloxacin and a111picillin.Serology was negative for echinocnccus and amochiasis.Pre v ious testi ng for qu;.intitative immunoglohulins was normal :md a human immunodeficiency virus (HIV) test was negative.
The patient was treated for six weeks with parenteral ceftazidime and tohramycin at high closes adjusted according to hloocl levels.After three weeks.the liver function tests had improved (ALP 366 U/L, GGT 98 U/L) and ultrasound examin;itinn revealed complete resolution of the abscess: however.a concom itant CT scan revealed multiple remaining hypodense lesions within the liver.although reduced in size (Figure 2).Intrave nous therapy was continued for a total of six weeks.followed by oral ofloxacin for six weeks more.Follow-up imag ing with CT at three and e ight months revealed complete resolution of the lesions al though ALP remained e levated at 220 U/L.Her nutritional status improved to a BMI of 20 .':i .Three years later there was no ev idcncL' Df recurrence.

Case 2
A 3.1-ycar-old male diag nosed with CF in infancy was chronically infec ted with B ccpacia and P acmg i11osa .He had moderate lung d isease requiring admission to hospital approximate ly once yearly for pulmonary exacerbations .Baseline pulmonary fu nction tests showed F YC 2.47 L (52% predicted) and FEY 1 1.43 L (59% predicted).H is usual weig ht was 65. 3 kg and he measured 173 cm, re presenting a B MI of 21.8.Hi s fam ily history was significant fo r CF in a twin brothL'I' who died in 199 I a nd a younge r brother ,vim died in 1993.Both brotht'rs had been treated for hepatic absc esses felt to be clue to B C'l'f)uciu (sec Discussion).
In May l lJ95. he was admitted to another hospital complaining of scvnal months of fever.chills.cough.sputum . .left upper quadrant and qiigastric pleuritic pain.An abdominal CT scan revealed a hepatic lesion and percutaneous drainage was performed.Shortly thereafter the patient developed diffuse abdominal pain with peritoneal signs and underwent laparotomy.peritoneal lavage and biopsy.
Parenteral nutrition and antibiotics werL' administered in an intensive care unit for six days.W hile culture rl."sults we rt' awaited.piperacillin.tobramycin and metronida1ole were given.After IO days of improvement.the antibiotic., were discontinued.l'otir days later the fever recurred accompanied by abJominal pain.The abdominal incision was partly dehisccd, draining purulent fluid .lntraopcrativc cultures returned growing B cepacia.Antibiotics we re restarted anJ the paliL•nl was transferred to the authors • centre three wed.slollowing hi s initial admi ssion.
At the time of admi ssion he appeared chronically ill.He weighed 60.0 kg and was febrile.There was some epigastrie tL•ndcrncss and the pncutaneous dr:1in was in place.Air entry was decreased hilaterally in the chest.L1horatory results rcwak-LI k•ukoeytosis (while hlooJ cell count I 2.2X 10 9 /L) " .
with I 0.4x IO / L PMNs.ALP was 50 I U/L (normal le.,s than I 00 U/L).and i\ST anJ A LT we re mildly elevated at 43 U/L (nL>Irnal less than 40 U/L) and Ti U/L (normal less than 45 ll/L).respectively.Bilirubin was normal and albumin was JO g/L (normal greate r than 35 g/Ll.The chest rndiogra ph was unchanged from previous studies.
The patient was treated c•mpirically for 8 0•1wciu infection of liver.lungs and abdominal wound with pipcracillin.imi pene m and tobramycin.Ciprotloxacin and ccftazidirne could not be used due to pn~vious seve re allergic reactions.A CT scan showed multiple small hepatic fluid collel'lions not significan tly changed compa red with the CT from the other hospital perfom1cd one week previously.A slight increase in the size of one small collection anterior to the stomach was noted but this a rea could not be reached percutaneou sly.
Unfortunately. the patient de veloped a severe urticaria!ra.,h after five days or treatment.This was felt most likely to be due to a beta-lactam age nt so the tobramycin was contin-ueJ alone.Four days later aztreonam became available and was added to the regimen.Over the next wee k. abdominal pain and feve r s ubsided.Liver enzyme te sts improved (AST 4 2 U/ L, ALT 61 U/L.ALP 389 U/L) and a re peat CT scan showed reso lution or fluid between the stomach and liver and one pers istent low de ns ity focus in the left lobe or the li ver.The patient was discharged home on pare nteral tobramycin and aztreonam .
After one month ALP remained elevated at 416 U/L but the CT scan was compatible with comple te resol ution of

DISCUSSION
n n'fhlciu is recognized as an important pathogen in CF patients with prevalence rates in some clinics of 20 to 30% (I ).In l lJ\JJ.the prevalence of B cepuciu in the Toronto CF clinics was 126/ 502 (25 % ).This organism wa s grown in 20/295 ( 7'/c. ) children under the age of 18 years and I Oci/207 (51 % ) or those 18 years and olde r.T he clinical course or er: patie nts colonized by B ccpacia is variable.Three distinct patterns have been described: chronic asymptomatic carriage: progress ive deterioration over many months .with recurrent hospital admissions: and rapid.usually fatal Jctcrioralion characteri1ed by fever, el e vated while blood cl'il count.elevated erythrocyte sedimentation rate, weight loss anJ Jctcrioration in pulmonary function.a pattern known as the •eepacia syndrome• (4).BactL:rcmia is rnrc but has lwcn reported in casts of acute de terioration (5).
The prognosis is generally worse for patients who arc colonized than for those who arc rnllurc-negative (I).A revi e w of the publis hed litera ture and of the Toronto data base identified four patients with extrathoracic infections due to I> cc1wciu.ThreL' cases have been reported in adults from the CF clinics in Toronto.Two brothers were siblings of our second case.They were chronicall y inkctcd with IJ n •puciu and bulh deve lnpcd hc•patiL• abscesses .although aspiration failed to reveal a responsible p,llhogcn.They were treated with intravenou., antibiotics for four weeks.and ultrasound follow-up rL•vealed eompit't e re.,olution of abscess cavities (2l.I fowevn.one patient suffered recurrent abscess fonnation and. on the second occasion, 8 ccpuciu was isolated from the :1spiratc.This suggested to the authors that the cause of livn abscess in both brothers was metastatic infection with B ,•1•1)(1,)a from the lower respiratory tract with recurrence due lo incomplete treatment (6).The ml'chanism of abscess fnnnalion in our patients was likely the same.
Recurrent neck abscesses dUL'.to N n•11uciu have been described in a 19-ycar-old Toronto patirnl with CF (3 ).He was known to lwvc severe lung disease.pancreatic insufficiency and diabetes mcllitus hut was we ll nourished with a weig ht for hei ght percentile ol I I 0 % .The isolate was only sens itive to ceftaziclime.SurgiG!l drainage and intravenous ceftazidime were rqx~atedly administered but infection recurred .Quantitative serum immunoglobulins.compleme nt screen.nitroblue telrazolium a. ,say.neutrophil cl1L'.motaxis.ingestion.killingol Stu/Jhylococrns mm'us in vitro and lymphoc yte markers we re normal.Recombinant interferon-gamma therapy resulted in a relatively prolonged response to treatment.
The reasons for the broad spectrum of disease caused by this organism arc not well understood .Alterations in host defences and variations in bacterial virulence arc the most attractive hypothesL'S.
The immune system in patients with CF has been l' :x tcnsi vely stud ied and no eonsi stent defect has been found in humoral, cellular, ehcmotactic, phagocytic or complemL•nt mechani sms ( 10, 11 ).In fact, patients with CF and chronic infection with P aerngi11osa or B cepacia commonly have elevated immunoglobulins.High IgG levels and the presence of circulating immune complexes are associated with progres ive, more severe pulmonary di sease ( 12).
Extrathoracic infections can be explained by the i111munornmpromised status of lung transplant recipients.However. in our two patients as well as the other three Toronto cases of extrapulmonary infections with B ccpacia.no defect in immunoglobulins or complement could be demonstratcJ.More sophisticalL'J tests of immune function were not readily available at our institution.Although the young woman in our first case was chronically malnourished, our seconJ pati ent had a normal baseline BM! and the patient with recurrent neck abscesses was welt nourished.
B cepacia is a ubiquitous environmental organism and it is believed that patients become infL'C ted hy person to person transmiss ion.The high prevalence of chronic infection with B ccpacia in Toronto suggests the presence of a highly transmi ss ible strain, and the clustering of cxtrapulmonary infections in the To ronto clinic may suggest involvement or a particularly virulent st rain of B ccpacia.The epidemiology of this organism is being investi gated through the application of genotyping using pulse field gel electrophoresis.However, the marked predisposition of one family to the dt'velopment of hepatic abscesses is more consistent with a familial defect in host re ponse rather than a function of bacterial virulence.
Three of four repo rted cases of hepatic abscess duL' to B cepacia have occurred within the same family and the fourth has also been from Toronto.Cl inicians need to he aware of the rare but definite capability of this organism to cause extrapulmonary infection in noni mmunocompromised patie nts with chronic infection.Further insight into the virulence fac tors and host immune response could facilitate the clinic ians• approach to prevention and treatment of this complication.