American Journal of Gastroenterology ISSN0002-9270 C 2005by Am.Coll.of Gastroenterology doi:10.1111/j.1572-0241.2005.40310.x Published by Blackwell PublishingPyogenic Liver Abscess with a Focus on Klebsiella pneumoniae as a Primary Pathogen:An Emerging Disease with Unique Clinical CharacteristicsEdith R.Lederman,M.D.,and Nancy F.Crum,M.D.,M.P.H.U.S.Naval Medical Research Unit No2,Jakarta,Indonesia;and Naval Medical Center San Diego,San Diego,CaliforniaOBJECTIVES:Pyogenic liver abscess is a common intraabdominal infection.Historically,Escherichia coli(E.coli) has been the predominant causative agent.Klebsiella liver abscess(KLA)wasfirst reported inTaiwan and has surpassed E.coli as the number one isolate from patients with hepatic abscessesin that country and reports from other countries,including the United States,have increased.Weexamined the microbiologic trends of pyogenic liver abscess at our institution to determine if asimilar shift in etiologic agents was occurring.METHODS:We examined all cases of liver abscess at our institution from1999to2003via a retrospective chart review of inpatient records and reviewed the English literature via a MEDLINE search for allU.S.cases of KLA.RESULTS:Since1966,only12cases of KLA have been reported in the United States.We report six cases of KLA at our institution alone;2patients were not Asian,and4were not diabetic.Klebsiellapneumoniae(K.pneumoniae)was the most common cause of pyogenic hepatic abscess at ourinstitution over the last5-yr period.When comparing Klebsiella versus other causes of pyogenicliver abscess,there were no significant differences in demographics or laboratoryfindings;however,most of our Klebsiella cases occurred among Filipinos.Review of the18cases of K.pneumoniaeliver abscess in the United States showed that Klebsiella cases occurred predominantly amongmiddle-aged men;83%had concurrent bacteremia and28%had metastatic complications.Anincreasing number of cases were reported from the United States since the mid-1990s.CONCLUSIONS:These data suggest that KLA may represent an emerging disease in Western countries,such as the United States.The diagnosis of K.pneumoniae should be considered in all cases of liver abscess,and appropriate antibiotic therapy and a diagnostic work-up for metastatic complications should beemployed.(Am J Gastroenterol2005;100:322–331)INTRODUCTIONLiver abscess is a common intraabdominal infection that may be caused by bacterial,fungal,or parasitic organisms. Until the end of the last century,Escherichia coli(E.coli) was the predominant bacterial cause of pyogenic(bacterial or fungal)liver abscesses.In the1990s Klebsiella pneumo-niae liver abscess(KLA)wasfirst described as an emerg-ing disease in Taiwan,which affected diabetic,middle-aged men and led to metastatic complications,most notably en-dophthalmitis,in a large percentage of cases.Reports of KLA have been accumulating from Asian and Western coun-tries alike.In order to investigate this trend further,we examined the microbiologic causes of pyogenic liver ab-scess at our institution for the past5yr and reviewed all case reports of KLA in the United States through the year 2003.METHODSWe queried the inpatient records at the Naval Medical Cen-ter San Diego,San Diego,CA(a500-bed teaching insti-tution servicing active duty military members,their depen-dents,and retirees in the Southern California area)for all cases of liver abscess(discharge diagnosis of“liver abscess”and with corresponding radiographicfindings)between1999 and2003and compiled demographic and clinical informa-tion for these cases.In addition,a MEDLINE search was performed from1966to2003using key words Klebsiella and liver abscess(limited to English language)to identify all KLA reported in the United States.Descriptive statis-tics were performed as well as univariate analyses utiliz-ing Fisher’s exact tests for dichotomous variables and t-tests for continuous variables(Epi Info TM version3.2.2,Atlanta, GA).322Klebsiella Liver Abscess 323RESULTSCase 1A 50-yr-old Filipino male presented with a 5-day history of fevers,rigors,nausea,and myalgias.He was previously in good health except for noninsulin-dependent diabetes melli-tus and essential thrombocytosis,treated with glyburide and hydroxyurea,respectively.He denied abdominal pain,diar-rhea,or visual changes.On examination,his temperature was 101.1o F .He was in mild distress,but had a normal examina-tion except for scleral icterus and mild abdominal distension without tenderness or organomegaly.Laboratory values were remarkable for a leukocytosis of 23,100cells/mm 3,total bilirubin 3.7mg/dl,albumin 2.7g/dl,alkaline phosphatase 274IU/L,alanine transferase 589IU/L,and aspartate transferase 357IU/L.Glycosylated hemoglobin was 12.3%.A right upper quadrant ultrasound revealed mul-tiple foci of decreased echogenicity throughout the liver with-out gallbladder pathology.A CT scan showed too numerous to count,0.5–1.5-cm attenuations in the liver,especially in the right lobe consistent with multiple abscesses (Fig.1);other abdominal structures appeared normal.A biliary scan and MRI showed a nonobstructive biliary system.An upper and lower endoscopy were unrevealing.The patient was empirically treated with intravenous piperacillin-tazobactam (3.375g)every 6h and gentamicin (400mg)daily.Two of six blood cultures grew Klebsiella pneumoniae (K.pnemoniae )sensitive to all antibiotics ex-cept ampicillin.Entamoeba histolytica (E.histolytica )serol-ogy was negative.Antibiotics were switched to ceftriaxone (2g)daily and oral metronidazole (500mg)four timesdailyFigure 1.CT scan demonstrating numerous small hepatic abscesses due to K.pneumoniae .during his inpatient stay;he was treated as an outpatient with levofloxacin and metronidazole for 4wk.A repeat CT scan showed complete resolution of all liver abscesses,and he has remained healthy over an 18-month period.Case 2A 71-yr-old Caucasian male with a past medical history only significant for coronary artery disease acutely developed fevers of 102o F and abdominal pain followed by hypotension.The patient did not report any changes in vision.He denied any significant travel history.After stabilization in the inten-sive care unit with fluids and vasopressors,the patient was found to have positive blood cultures for K.pneumoniae ,and an abdominal CT scan revealed a 7-cm hepatic abscess in the left lobe.CT -guided percutaneous drainage revealed K.pneu-moniae sensitive to all tested antibiotics except ampicillin.E.histolytica serology was negative.Two days after discharge,the patient noted low-grade fevers up to 100.2o F ,chills,and recurrent abdominal boratory values were normal except for an albumin of 2.5g/dl,alkaline phosphatase of 469IU/L,alanine transferase 98IU/L,and aspartate transferase 170IU/L.Repeat blood cultures and a chest radiograph were unremarkable.A CT scan showed a 10×6×6.5cm multiloculated abscess in the left hepatic lobe.The patient was treated with intravenous ce-fotetan (2g)twice daily and oral levofloxacin (500mg)daily for 8wk.Right upper quadrant ultrasound showed no biliary pathology,and colonoscopy was normal.Imaging 6months later showed no abnormalities,and the patient has remained well except for recurrent angina over the past 4yr.Case 3A 53-yr-old Caucasian male with a history of mitral valve prolapse and hypercholesterolemia reported a 3-wk history of fatigue and malaise,as well as 1wk of fevers,rigors,night sweats,and tooth pain.His examination was remark-able for a temperature of 100.6o F ,a mid systolic click,and a normal S1and S2.There were no petechiae,Osler’s nodes,Janeway lesions,or Roth spots,and the remainder of his ex-amination was boratory values revealed a white blood count of 11,300cells/ml,total bilirubin of 1.2mg/dl,alkaline phosphatase of 137IU/L,alanine transferase of 68IU/L,aspartate transferase of 67IU/L,and albumin of 3.5g/dl.On day 1of hospitalization,one of eight blood cultures from admission grew gram-negative rods,later identified as K.pneumoniae .A follow-up transesophageal echocardio-gram was negative.A CT scan of the abdomen was performed to determine the source of the Klebsiella ;it revealed a 7×6cm abscess in the left lobe of the liver (Fig.2).A right upper quadrant ultrasound and biliary scan were normal.CT -guided drainage of the abscess yielded purulent material that grew K.pneumoniae .The patient received 4wk of ceftriaxone and metronidazole along with 2wk of gentamicin;he was then transitioned to oral ciprofloxacin for 1month.A follow-up324Lederman andCrumFigure 2.CT scan demonstrating a single large K.pneumoniae liver abscess.CT showed complete resolution of the abscess,and he has remained well over the past 3yr.Case 4A 64-yr-old Filipino female presented with a 2-day history of right upper quadrant abdominal pain,anorexia,and fever.Her past medical history was significant for peptic ulcer disease,coronary artery disease,and hypertension.She de-nied visual changes.Examination revealed a temperature of 101.1o F ,mild tenderness in the right upper quadrant and epi-gastrum without rebound tenderness,guarding,mass,or hep-atomegaly.Laboratory values were remarkable for a white blood count of 19,900cells/mm 3.Total bilirubin was 1.2mg/dl,albu-min 3.7g/dl,alkaline phosphatase 80IU/L,alanine trans-ferase 41IU/L,and aspartate transferase 30IU/L;all other chemistries were normal with a glucose of 120mg/dl.A right upper quadrant ultrasound revealed a 4.0cm ×2.4cm ×3.4cm lesion with multiple thick internal septations and a 1.0cm ×1.3cm ×1.4cm lesion both in the left lobe of the liver.A CT scan showed several lesions in the left lobe of the liver consistent with multiple abscesses;other abdomi-nal structures appeared normal.An upper endoscopy showed diffuse antral and duodenal erosions;colonoscopy was normal.The patient was empirically treated with intravenous ciprofloxacin (400mg)twice daily and metronidazole (500mg)three times daily.Eight blood cultures and E.histolytica serology were negative.Percutaneous drainage of a liver le-sion grew K.pneumoniae sensitive to all antibiotics except ampicillin.The patient clinically improved and was given a 6-wk course of oral ciprofloxacin and metronidazole.She re-turned to her usual state of health and was subsequently lost to follow-up.Case 5A 56-yr-old Filipino male presented with a 5-day history of fevers,chills,and night sweats,as well as 3days of epigastric pain and nausea.He denied recent travel or vi-sual changes.Examination revealed an initial temperature of 99.5o F and mild tenderness in the right upper quadrant and epigastrum without rebound or guarding;the remainder of the examination was unremarkable.During the first 6h,the patient became markedly hypotensive but responded to fluid boluses.Laboratory values were remarkable for a white blood count of 17,800cells/ml,total bilirubin 3.8mg/dl,direct bilirubin 2.4mg/dl,albumin 2.8g/dl,alkaline phosphatase 200IU/L,alanine transferase 156IU/L,aspartate transferase 116IU/L,and glucose 149mg/dl.Creatinine was elevated at 1.7mg/dl,and urine electrolyte studies were consistent with prerenal azotemia.A right upper quadrant ultrasound revealed a 5-cm lesion in the right lobe of the liver.A CT scan showed a 7.6×6.5×7.5cm low-attenuation mass in the right lobe consistent with an abscess;other abdominal structures were unremarkable.The patient was empirically treated with intravenous piperacillin/tazobactam every 6h,metronidazole (500mg)every 8h,and gentamicin (180mg)every 18h.T wo of four blood cultures grew K.pneumoniae sensitive to all antibiotics except ampicillin.A pigtail drain was placed into the liver ab-scess yielding 50cc of pus that also grew K.pneumoniae.E.histolytica serology was negative.A dilated fundoscopic ex-amination was unremarkable.The patient clinically improved and antibiotics were switched to oral levofloxacin (500mg)daily and metronidazole (500mg)three times daily for a 6-wk course.A follow-up CT scan after antibiotic therapy showed abscess boratories returned to baseline includ-ing the creatinine (1.0mg/dl).The patient has remained well over the past 30months.Case 6A 59-yr-old Filipino female presented with a 3-day history of fevers of 103◦F ,chills,anorexia,and fatigue.She noted no visual complaints.She had a history of noninsulin-dependent diabetes mellitus.She emigrated in 1967to the United States from Luzon,Philippines.Examination was remarkable for a temperature of 102.2◦F boratory findings included a white blood count of 19,800mm 3,creatinine 3.3mg/dl,glucose 120mg/dl,total bilirubin 1.8mg/dl,alanine trans-ferase 133IU/L,asparate transferase 156IU/L,alkaline phos-phatase 101U/L,and albumin 2.1g/dl.A CT scan of the abdomen showed an 8cm ×8cm ×4.4cm lesion,with internal higher attenuated septa/regions,in the anterior as-pect of the left lobe of the liver.The patient was empirically treated with piperacillin-tazobactam (3.375g)every 6h and metronidazole (500mg)every 8h.Klebsiella Liver Abscess325Table1.Demographics and Laboratory Values of Liver Abscess CasesAspartate Alanine Total Alkaline Age Causative Leukocytes Aminotransferase Aminotransferase Bilirubin Albumin Phosphatase No.(yr)Gender Race Organism(s)(mm3)(IU/L)(IU/L)(mg/dl)(g/dl)(IU/L) 150Male Filipino K.pneumoniae23.1357589 3.7 2.7274 271Male Caucasian K.pneumoniae9.6170980.9 2.5469 353Male Caucasian K.pneumoniae11.36768 1.2 3.5137 464Female Filipino K.pneumoniae19.93041 1.2 3.780 556Male Filipino K.pneumoniae17.8156116 3.8 2.8200 659Female Filipino K.pneumoniae19.8133156 1.8 2.1101 762Male Caucasian E.histolytica19.7107148 1.1 2.8278 829Female Caucasian E.histolytica12.425350.9 3.0196 971Male Caucasian E.coli K.oxytoca 4.530300.5 2.2119 1025Male Caucasian Fusobacterium10.83830 1.0 2.6309necrophorum1147Male Filipinoα-streptococcus,28.724571246 1.5 2.974E.coli1237Female Filipino E.coli7.824240.8 3.3124 1371Female Caucasian P.aeruginosa28.3808522.3 1.3228Enterococcus sp.1487Male Caucasian Enterococcus sp.44.22416 3.6 2.295 1544Male Africanα-streptococcus16.279139 1.3 3.0109 American1663Male Caucasian Unknown20.234480.6 2.595 1731Male Filipino Unknown10.64581 1.4 2.9350 1837Male African Unknown18.73048 1.0 2.2105 American1957Male Hispanic Unknown9.04176 1.0 2.776 2012Male Caucasian Unknown14.532450.5 2.8233One of four blood cultures grew K.pneumoniae,resis-tant to only ampicillin.CT-guided drainage of the abscess yielded purulentfluid,which grew K.pneumoniae.Urine cul-ture was negative.Antibiotics were switched to ceftriaxone (2g)daily and metronidazole(500mg)every8h for4wk, followed by oral levofloxacin(500mg)daily for3months. Follow-up imaging showed complete resolution of the liver abscess.We identified20cases of liver abscesses from our inpa-tient and outpatient hospital records between1999and2003. We identifiedfive other cases under this discharge diagno-sis,which we excluded based on patient record and radio-graphicfindings(two with hepatic candidiasis,one with an infected hepatic cyst,one with necrotic lesion after cryoab-lation,one with an infected biloma).The etiology,laborato-ries,and demographics of the20cases are summarized in Table1.KLA accounts for30%of liver abscesses for the past5yr at our institution,surpassing the incidence of E. coli as a liver abscess pathogen.Patients at our institution with KLA were predominantly male(2:1)and had an aver-age age of58.8yr(range50–71yr).Patients with pyogenic abscess due to other bacterial etiology were also predomi-nantly male(2:1)and had the same approximate age(mean age54.6yr with a range of25–87yr).Sixty-seven percent of KLA were Filipinos compared to29%of those with other types of bacterial liver abscesses,but this was not significantly different(p-value0.17).We compared the laboratory values between these groups and found no statistically significant differences.From our MEDLINE search,12cases of K.pneumo-niae case reports were identified(1–12).Demographics and clinical characteristics including our six cases are shown in Table2.In summary,the mean age of patients(excluding the newborn)was46yr;they were predominantly male(2:1),and one-third were diabetic.Sixty-seven percent of patients had a single abscess,83.3%had positive blood cultures,27.8% suffered metastatic complications,and the overall mortality rate was5.6%.Interestingly,more than75%of cases were reported since the mid-1990s.DISCUSSIONOne out of every4,500–7,000hospital admissions is due to a liver abscess(13,14).Liver abscesses may be separated into two major categories:pyogenic(bacterial and fungal)and amoebic;up to2.5%of amoebic liver abscesses may contain bacterial pathogens as well(15).Pyogenic abscesses account for three-quarters of liver abscesses in industrialized coun-tries(16).A bacterial pathogen may be identified in two-thirds of cases of liver abscesses(17).The most common bacteria isolated from liver abscess patients are gram-negative rods. Prior to the1980s,E.coli was the most commonly isolated organism from liver abscess patients,but more recently,K. pneumoniae has been found to be the number one pathogen in Taiwan(18).The average age of patients with KLA is55–60 yr(18,19)and KLAs are twice as likely to be diagnosed in men than women(19,20).Reports of KLA in children are rare(1).326Lederman and CrumT a b l e 2.K l e b s i e l l a L i v e r A b s c e s s C a s e s i n t h e U n i t e d S t a t e s ,1966–2003U n d e r l y i n g P o s i t i v e C a s e A g e M e d i c a l C u l t u r e (s )f o r H e p a t i c M e d i c a l P r o c e d u r e E x t r a h e p a t i c N o .R e f e r e n c e Y r(y r )S e x R a c eC o n d i t i o n (s )K l e b s i e l l aL e s i o n (s )T h e r a p y (s )C o m p l i c a t i o n s O u t c o m e1(1)1974N e w b o r n FA f r i c a n A m e r i c a n H y p o c a l c e m i a ,S G A ,u m b i l i c a l v e i n c a t h e t e r i n d u c e d p y l e p h l e b i t i sB l o o d a n d s p i n a l flu i d 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e A g e M e d i c a l C u l t u r e (s )f o r H e p a t i c M e d i c a l P r o c e d u r e E x t r a h e p a t i c N o .R e f e r e n c eY r(y r )S e x R a c eC o n d i t i o n (s )K l e b s i e l l aL e s i o n (s )T h e r a p y (s )C o m p l i c a t i o n s O u t c o m e9(9)200068MW e s t I n d i a n o r i g i n N o n i n s u l i n d e p e n d e n t d i a b e t e s m e l l i t u s B l o o d a n d l i v e r a s p i r a t e5-c m l i v e r a b s c e s s ,l e f t l o b e N R P e r c u t a n e o u s c a t h e t e r d r a i n a g e N o n eS u r v i v e d10(10)200157FA f r i c a n A m e r i c a n N o n i n s u l i n d e p e n d e n t d i a b e t e s m e l l i t u s ;c y s t i c d u c t o b s t r u c t i o nB l o o d a n d l i v e r a s p i r a t eM u l t i p l e l e s i o n s ,b o t h l o b e sC i p r o flo x a c i n a n d c l i n d a m y c i n ×26d a y s ,t h e n p i p e r -c i l l i n /t a z o b a c t a m a n d g e n t a m i c i n d u r a t i o n N RC h o l e c y s t e c t o m y a n d o p e n d r a i n a g e o f l a r g e l i v e r a b s c e s s f o l l o w e d b y p e r c u t a n e o u s d r a i n a g e o f s m a l l e r l i v e r l e s i o n s N o n e ∗S u r v i v e d11(11)200129M N R N o n eB l o o d a n d l i v e r a s p i r a t e7-c m s i n g l e a b s c e s s ,r i g h t l o b e P i p e r a c i l l i n /t a z o b a -c t a m a n d m e t r o -n i d a z o l e ×6w k P e r c u t a n e o u s d r a i n a g eN o n e ∗∗S u r v i v e d12(12)200362M C a u c a s i a nD i a b e t e s m e l l i t u sB l o o d a n d l i v e r a s p i r a t e S i n g l e l e s i o n ,r i g h t l o b eC i p r o flo x a c i n a n d I m i p e n e m P e r c u t a n e o u s c a t h e t e r d r a i n a g e N o n eS u r v i v e d13C u r r e n t C a s e 200350M F i l i p i n oN o n i n s u l i n d e p e n d e n t d i a b e t e s m e l l i t u sB l o o d a n d l i v e r a s p i r a t eM u l t i p l e l e s i o n s ,b o t h l o b e sP i p e r a c i l l i n /t a z o -b a c t a m a n d g e n t a m i c i n ,f o l l o w e d b y c e f t r i a x o n e a n d m e t r o n i d a z o l e ×4w k ,t h e n l e v o flo x a c i n a n d m e t r o n i d a z o l e ×4w k P e r c u t a n e o u s d r a i n a g eN o n eS u r v i v e d14C u r r e n t C a s e 200371M C a u c a s i a nC o r o n a r y a r t e r y d i s e a s e B l o o d a n d l i v e r a s p i r a t e 10-c m l i v e r a b s c e s s ,l e f t l o b e C e f o t e t a n a n d l e v o flo x a c i n ×8w k P e r c u t a n e o u s d r a i n a g eN o n eS u r v i v e d15C u r r e n t C a s e 200353M C a u c a s i a nN o n e B l o o d a n d l i v e r a s p i r a t e7-c m l i v e r a b s c e s s ,l e f t l o b e C e f t r i a x o n e a n d m e t r o n i d a z o l e ×4w k (g e n t a m i c i n g i v e n f o r 2w k ),t h e n c i p r o flo x a c i n ×4w k P e r c u t a n e o u s d r a i n a g eN o n eS u r v i v e d16C u r r e n t C a s e 200364F F i l i p i n oP e p t i c u l c e r d i s e a s e ,c o r o n a r y a r t e r y d i s e a s e ,h y p e r t e n s i o nL i v e r a s p i r a t e4-c m -a n d 1.5-c m l e s i o n s ,l e f t l o b e C i p r o flo x a c i n a n d m e t r o n i d a z o l e ×6w kP e r c u t a n e o u s d r a i n a g eN o n e S u r v i v e d328Lederman and CrumT a b l e 2.C o n t i n u e dU n d e r l y i n g P o s i t i v e C a s e A g e M e d i c a l C u l t u r e (s )f o r H e p a t i c M e d i c a l P r o c e d u r e E x t r a h e p a t i c N o .R e f e r e n c eY r(y r )S e x R a c eC o n d i t i o n (s )K l e b s i e l l aL e s i o n (s )T h e r a p y(s )C o m p l i c a t i o n s O u t c o m e17C u r r e n t C a s e 200356M F i l i p i n o H y p e r t e n s i o nB l o o d a n d l i v e r a s p i r a t e8-c m l e s i o n ,r i g h t l o b eP i p e r a c i l l i n /t a z o b a -c t a m ,g e n t a m i c i n a n d m e t r o n i d a z o -l e ×9d a y s ,t h e n l e v o flo x a c i n a n d m e t r o n i d a z o l e f o r 6w k P e r c u t a n e o u s d r a i n a g eN o n e †S u r v i v e d18C u r r e n t C a s e 200359FF i l i p i n o D i a b e t e s m e l l i t u s ,c o r o n a r y a r t e r y d i s e a s eB l o o d a n d l i v e r a s p i r a t e8-c m l e s i o n ,l e f t l o b eP i p e r a c i l l i n /t a z o b -a c t a m a n d m e t r o -n i d a z o l e ,t h e n c e f t r i a x o n e a n d m e t r o n i d a z o l eP e r c u t a n e o u s d r a i n a g eH y p o t e n s i o n (flu i d r e -s p o n s i v e )S u r v i v e d∗P a t i e n t i n i t i a l l y r e f u s e d s u r g i c a l d r a i n a g e r e s u l t i n g i n p e r s i s t e n t f e v e r s a n d a b s c e s s ;a f t e r s e c o n d a d m i s s i o n a s u r g i c a l p r o c e d u r e w a s p e r f o r m e d a n d t h e i n f e c t i o n c l e a r e d .∗∗F a i l e d p e r c u t a n e o u s d r a i n a g e o f m u l t i l o c u l a t e d a b s c e s s r e s u l t e d i n o p e n d e b r i d e m e n t a n d p a r t i a l l o b e c t o m y .†S e p s i s ,a c u t e r e n a l f a i l u r e ,a n d D I C w i t h f u l l r e c o v e r y .N R =n o t r e p o r t e d ;SG A =s m a l l f o r g e s t a t i o n a l a g e .Gram-positive organisms such as S.aureus and leri are reported less frequently (18,14)and are likely to be found in the setting of secondary hepatic lesions (i.e.,the primary source is from outside the abdomen).Recovery of anaerobic organisms is challenging,and therefore may not be identified in true mixed infections (17);in series where careful attention is paid to anaerobic organism recovery,they may be detected in 10–17%of cases,most often B.fragilis (18,20).Anaerobes were recovered from 20%of our non-KLA bacterial liver abscess patients.Recovery of organisms,particularly those that are anaerobic,is more likely from abscess aspiration than from blood cultures (14,18,21).All anaerobes from our series were recovered from abscess aspiration with the exception of the one case of Fusobacterium necrophorum .Mixed infections may be found in 14–55%of cases of routine pyogenic liver abscesses (18,20,22),but KLA cases are almost uniformly monobacterial.Prior to the era of rapid patient assessment and expeditious surgery,appendiceal pathology was the most common source of liver abscesses (23).In the modern era,biliary disease is the most common etiology (17,20).Other potential sources include penetrating trauma,distant sources (i.e.,outside the abdomen),and contiguous spread from lung,kidney,colon,or stomach.Still,many are deemed cryptogenic (14,17,19,20)(40–99%);abscesses containing only K.pneumoniae are much more likely to be cryptogenic (64%)(24).The first purported case of KLA with metastatic complica-tions reported in the United States was in an African Ameri-can diabetic man in 1999(7).However,Seeto et al.reported pure cultures of K.pneumoniae in 13of 140pyogenic liver abscess cases during the period 1979–1994;hence,a shift from E.coli to K.pneumoniae may have been present for over a decade in the United States but was unrecognized (14).In a case series by Hansen and Vargish,Klebsiella spp.was the most common bacterium isolated from liver abscesses,but it is unclear if these cases were polymicrobial (25)and thus would not be representative of KLA strictu sensu .In the past 5yr,we have observed six cases at our institution alone,four of which involved nondiabetic patients.This is an interesting institutional trend and may herald the beginnings of a shift in microbiologic etiology of liver abscess in the United States not unlike that seen in Taiwan over a decade ago.The first reports of a significant rise in incidence of KLA originated from Taiwan;however,other Asian (Japan (17,26,27),Singapore (28,29),Korea (30),India (31),Hong Kong (32)),and non-Asian (Spain (33),United States (7,10,12,58),England (34),Trinidad (35),Australia (36))coun-tries have followed suit.Many of the reports from non-Asian countries may involve patients of Asian descent but whether the patients are Asian or not,they nearly always have poorly controlled diabetes (19,24,26,34).Diabetes is a known risk factor for developing KLA,and it appears to be a signifi-cant risk factor for embolic complications (37),especially endophthalmitis (38).The diagnosis of diabetes may come to light because of the discovery of the KLA (7).In addition。
