in october 2007 , a 37-year - old woman from thailand sought treatment at siriraj hospital ( a 2,400-bed university hospital in bangkok , thailand ) with a history of fever for 1 week . she was a hairdresser residing in a suburban area of prachuap khiri khan , a southern province of thailand . there was no incidence of unusual animal death in the area in which she resided . five months before seeking treatment , she received a diagnosis of advanced stage clear cell adenocarcinoma of the ovary with metastasis to peritoneum , spleen , uterus , and multiple abdominal lymph nodes . initial laboratory screening showed increased liver enzyme levels and abnormal hepatitis markers confirming chronic active hepatitis b virus infection . chemotherapy was delayed while she was treated with lamivudine . a follow - up visit in early september showed that her liver function biochemistry results had returned to within normal limits . 25 days after the start of chemotherapy , the patient had fever ( 39c ) , blood pressure 90/60 mm hg , and pulse rate 75 beats / min . it was believed that fever and gastrointestinal bleeding were complications from chemotherapy ; thus , microbiologic investigation was not promptly initiated . course of illness in a thai patient with francisella novicida bacteremia . solid line , leukocyte count with percentage of neutrophils ; dashed line , temperature . two samples of blood cultures from peripheral lines were obtained using bact / alert fa bottles ( biomrieux , durham , nc , usa ) on day 10 of hospital admission and incubated in the continuous monitoring bact / alert 3d system ( biomrieux ) . both blood culture bottles grew small pleomorphic gram - negative coccobacillus after incubation for 2 days . samples from positive bottles were subcultured onto 5% ( vol / vol ) sheep blood agar , macconkey agar , and chocolate agar . a slow - growing bacterium was recovered on both blood agar and chocolate agar after 2-day incubation at 35c with 5% co2 . bacterial identification was delayed because the organism was unidentifiable based on the conventional biochemical keys and the vitek 2 system ( biomrieux , marcy letoile , france ) . using the api 20ne ( biomrieux ) , the organism was identified as mannheimia haemolytica / pasteurella trehalosi with good confidence level ( 94.5% probability ) . the identification of this isolate was further determined by the 16s rdna gene analysis that used screening primers sqe1 and sqe3 ( 6 ) and the 1,445-bp gene sequencing procedure as described elsewhere ( 7 ) . the dna sequence was analyzed by using the standard nucleotide - nucleotide blast algorithm ( www.ncbi.nlm.nih.gov ) . the 16s rdna sequence of this isolate , called strain rb401 , was most closely related ( 99.9% homology ) to the novicida - like subspecies of f. novicida strain 3523 ( genbank accession no . ay243028 ) and was deposited to the genbank database under the accession no . eu365864 . identification of strain rb401 was further confirmed by analyzing dna sequences of tul4 and ppiase genes as previously described for strain 3523 ( 5 ) . the fragment containing tul4 amplicon ( 363 nt ) from strain rb401 shared the highest similarity ( 98% ) to the matching region from strain 3523 . comparing the 267-nt coding region sequence of the 3 end of ppiase gene nt 733259733525 to the genome sequence of f. novicida strain u112 ( genbank accession no . cp000439 ) showed the highest similarity to all subspecies of f. tularensis , e.g. , f. tularensis subsp . the sequences of tul4 and ppiase genes from strain rb401 were deposited to genbank under accession nos . eu786119 and eu786120 , respectively . antimicrobial drug susceptibility testing was performed by disk diffusion method and interpreted based on the clsi criteria for acinetobacter spp . results showed that strain rb401 was susceptible to piperacillin / tazobactam , third - generation cephalosporins , cefepime , imipenem , meropenem , aminoglycosides , fluoroquinolones , and tetracycline , but resistant to co - trimoxazole . due to the delay in organism identification and lack of awareness of its significance , antimicrobial treatment ( piperacillin / tazobactam 4.5 g intravenously every 8 h ) however , on day 21 , the patient requested to be referred to her hometown hospital and died 2 days after referral . all laboratory technicians who processed culture and identified the bacterium received doxycycline ( 100 mg twice a day for 14 days ) for prophylaxis , and none reported fever or abnormal symptoms . novicida , is rarely attributed to human infection and is not readily recognized in most clinical laboratories . because of the unreliable results of phenotypic identification methods , unfamiliarity of the bacterium and close genetic relatedness among francisella spp . a clinical diagnosis of francisella infection is highly nonspecific , and it seems that the underlying disease with immunosuppression was an important factor to contracting the disease in the described case and previous case reports ( 35 ) . there is no clear explanation regarding route of acquisition and the pathogenic role of this organism . additionally , there is no evidence for human - to - human transmission . in our case , given that our patient had severe complicated underlying diseases while the potentially low - virulence organism was recovered , it was thus difficult to claim that the patient s death was solely due to f. novicida infection . notably , the 16s rdna , tul4 , and ppiase sequences of our isolate are most closely related to the strain earlier reported from australia ( 5 ) . these areas are not known to be endemic for f. novicida , and therefore , these strains represent the emergence of f. novicida in the asia - pacific region . the earlier case - patient was successfully treated with flucloxacillin and doxycycline , followed by dicloxacillin and doxycycline ( 5 ) . . the standard protocol of 5-day incubation for automated blood culture ( 9 ) is supposedly sufficient for detection of f. novicida bacteremia . identification of f. novicida , however , is often difficult because the bacterium can be easily misidentified as a non - francisella species or as a highly pathogenic f. tularensis . it was also indicated that this organism could not be detected by a direct fluorescent antibody test used for the identification of f. tularensis types a and b ( 5 ) . as a preliminary result , our 16s rdna sequence was closely related to subspecies of f. tularensis , and thus doxycycline prophylaxis for the organism - exposed laboratory personnel could not be avoided . there is high risk for laboratory - acquired tularemia when handling f. tularensis cultures ( 10 ) . in retrospect , prophylactic treatment may have been unnecessary because our isolate proved to be f. novicida , which is not known to cause laboratory - acquired infections . most f. tularensis strains were susceptible to aminoglycosides , quinolones , and tetracyclines ( 11 ) . our isolate was similarly susceptible to these agents , which suggests that they may be considered as therapeutic options for francisella spp . initial treatment with piperacillin / tazobactam was based on the preliminary report of gram - negative bacilli , but later antimicrobial susceptibility testing showed this isolate to be susceptible to this agent . however , previous reports ( 1113 ) suggested that piperacillin / tazobactam and other -lactams are generally considered ineffective in vivo against francisella spp . and given that the organism is believed to be of low virulence , particularly that it does not pose a substantial risk for immunocompetent persons , its role as a human pathogen remains controversial . further studies to gain better understanding of pathogenic mechanism and transmission route of f. novicida are necessary to provide appropriate guidelines for the treatment and prophylaxis .
we report isolation of francisella novicida  causing bacteremia in a woman from thailand who was receiving chemotherapy for ovarian cancer . 
 the organism was isolated from blood cultures and identified by 16s rdna and ppiase gene analyses . 
 diagnosis and treatment were delayed due to unawareness of the disease in this region .