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a p o l l o m e d i c i n e 1 1 ( 2 0 1 4 ) 1 1 5e1 1 8

Available online at w

ScienceDirect

journal homepage: www.elsevier .com/locate/apme

Case Report

Successful treatment of two cases of Elizabethkingiameningoseptica septicemia and a review of theliterature

Ujjwayini Ray a,*, Soma Dutta b, Chandrashish Chakravarty c,Indrajit Kumar Tiwari c

a Consultant Microbiologist, Apollo Gleneagles Hospitals, 58, Canal Circular Road, Kolkata 54, West Bengal, Indiab Registrar Microbiology, Apollo Gleneagles Hospitals, 58, Canal Circular Road, Kolkata 54, West Bengal, Indiac Consultant Critical Care Medicine, Apollo Gleneagles Hospitals, 58, Canal Circular Road, Kolkata 54, West Bengal,

India

a r t i c l e i n f o

Article history:

Received 12 February 2014

Accepted 7 May 2014

Available online 2 June 2014

Keywords:

Elizabethkingia meningoseptica

Septicemia

Adults

Immunocompromised

* Corresponding author. Tel.: þ91 983063948E-mail address: dr_uray@rediffmail.com

http://dx.doi.org/10.1016/j.apme.2014.05.0120976-0016/Copyright © 2014, Indraprastha M

a b s t r a c t

Elizabethkingia meningoseptica is emerging as a cause of hospital acquired infection partic-

ularly in immunocompromised adults. The treatment of this bacterium is difficult since it

is intrinsically resistant to a number of antibiotics. Here we report two cases of septicemia

in patients who were critically ill and were successfully treated with appropriate antibi-

otics. Cotrimoxazole, quinolones, and rifampicin seem to be drugs effective against E.

meningoseptica. Antibiotic susceptibility results are ineffective in guiding treatment. The

bacterium particularly colonizes water pipelines and tap faucets and occurrence of infec-

tion by this bacterium should direct attention towards eradicating the source of this

bacterium.

Copyright © 2014, Indraprastha Medical Corporation Ltd. All rights reserved.

1. Introduction

An aging population, the AIDS epidemic, the growth of

chemotherapeutic options for cancer treatment, a growing

transplant population and high end critical care medicine

with multiple interventions has resulted in a large population

of immunocompromised patients. In immunocompromised

patients, micro organisms with low pathogenic potential that

is usually efficiently controlled by the immune system can

suddenly cause life-threatening diseases that may be difficult

0 (mobile).(U. Ray).

edical Corporation Ltd. A

to treat with currently available anti-infectives. Elizabethkingia

meningoseptica is one such bacteria which is emerging as an

important cause of serious opportunistic infection in immu-

nocompromised hosts.1,2 E. meningoseptica has undergone

several taxonomic changes and was previously known as

Flavobacterium meningosepticum and Chryseobacterium meningo-

septicum and finally it was named after bacteriologist Elizabeth

O. King who first isolated the bacteria.3 E. meningoseptica is a

non-motile, non-fermenting, oxidase positive, aerobic bacilli.

We here report two cases of serious infection by E. meningo-

septica which were successfully treated.

ll rights reserved.

a p o l l o m e d i c i n e 1 1 ( 2 0 1 4 ) 1 1 5e1 1 8116

2. Case report

2.1. Case 1

An 18-year-old female patient suffering from refractory

Hodgkin's lymphoma (STAGE IV B) underwent autologous

bone marrow transplant (BMT). She was put on immunosup-

pressive therapy with tacrolimus and mycophenolate mofetil

to prevent graft rejection. She engrafted successfully initially

with neutrophil on day 9th followed by platelets on day 12th

post transplant. On day 10th post transplant she became

septic and was managed with broad spectrum antibiotics

meropenem and teicoplanin after sending samples for cul-

ture. Both the aerobic blood culture and urine culture samples

showed growth of gram negative bacilli. The isolates were

oxidase positive, non-motile and non-fermenter. Further

identification and sensitivity was done in VITEK 2C (Bio-

merieux) automated system. The isolates were identified as E.

meningoseptica .The isolateswere sensitive only to levofloxacin

[Minimum Inhibitory Concentration (MIC) 2 mg/ml] when

tested in VITEK using AST N090 cards and were resistant to all

other commonly used antibiotics. E. meningoseptica was also

isolated from the throat swab of this patient during routine

pre-transplant surveillance. In view of the above findings

levofloxacin was added. Subsequently blood culture became

sterile. On day 15th post transplant the patient developed

severe respiratory distress and had to be intubated and

ventilated to support her respiratory functions. A broncho-

alveolar lavage was performed at that time. BAL fluid culture

also showed heavy growth of E. meningoseptica. But she

continued to have repeated episodes of respiratory distress

and her condition deteriorated and was shifted to the ICU

(Intensive Care Unit). Levofloxacin was discontinued and

vancomycin, trimethoprim/sulphamethoxazole and rifam-

picin (drugs which are effective against E. meningoseptica ac-

cording to various literature.) were started on day 22 post

transplant. Urine culture still showed growth of E. meningo-

septica and Chest X ray had persistent infiltrates. Vancomycin

was added on day 30th post transplant since it is reported to

have therapeutic effect on E. meningoseptica .After about a

week of above therapy the patient started improving and

thereafter E. meningoseptica was not isolated from any of the

clinical samples. Rifampicin and trimethoprim/sulphame-

thoxazole was continued for 10 more days and thereafter

rifampicin was stopped and trimethoprim/sulphamethox-

azole was continued for one month. Vancomycin was

administered for a week. Her condition improved gradually

and she was extubated on Day 37 post transplant and

remained well with minimum oxygen requirement.

2.2. Case 2

A 25-year-old patient following caesarean section two days

back was admitted to the hospital with abdominal pain and

distention. The CAT scan of abdomen revealed severe acute

pancreatitis (Balthazer E, CTSI 4/10) along with blood clots in

pelvis with pleural and peritoneal effusion. At the time of

admission she had features of disseminated intra vascular

coagulation (DIC) for which she was treated with fresh frozen

plasma. She underwent surgical intervention for removal of

pelvic blood clots and adhesionolysis. But despite her

pancreatitis and coagulation parameters improving, her con-

dition worsened and she developed fever and respiratory

distress and was put onmechanical ventilation on day 10th of

hospitalization. She started having spikes of high tempera-

ture. Suspecting sepsis with multidrug resistant bacteria she

was empirically treated with polymyxin B, teicoplanin and

caspofungin. Her chest X-ray showed presence of bilateral

infiltrates. Blood and Endotracheal (E.T) secretion sent for

culture showed growth of E. meningoseptica. The isolate was

moderately sensitive to levofloxacin (MIC 4 mg/ml) and resis-

tant to other antibiotics such as quinolones, beta lactams,

aminoglycosides, trimethoprim/sulphamethoxazole, doxycy-

cline. Following the isolation of E. meningoseptica the poly-

myxin B was substituted with rifampicin and trimethoprim/

sulphamethoxazole. A repeat blood culture sent three days

later again showed growth of E. meningoseptica. Gradually the

patient started improving and she was extubated four days

after starting E. meningoseptica specific antibiotics. The rifam-

picin was continued for two weeks and trimethoprim/sul-

phamethoxazole was continued for a total of three weeks.

Repeat blood and urine cultures after 14 days were sterile and

the patient was discharged in a haemodynamically stable

condition.

3. Discussion

E. meningoseptica used to be implicated as a cause of infection

in neonates. The literature is replete with cases of E. menin-

goseptica primarily in pediatric patients with neonates in

particular.3 E. meningoseptica is a well known cause of neonatal

meningitis particularly in premature infants and often occurs

as outbreaks with a very high mortality rate.4 But recent

literature search has shown that E. meningoseptica is emerging

as a cause of infection in hospitalized adults as well. In adults

E. meningosepticahas beenmainly responsible for blood stream

and respiratory infection unlike pediatric patients where

meningitis is the most common presentation.2 In adults E.

meningoseptica is increasingly being reported as a cause of

nosocomial infection in immunocompromised hosts. Respi-

ratory infection in adults is mostly associated with mechani-

cal ventilation.5

In both the above mentioned cases the patients were

immunocompromised e one being a BMT recipient heavily on

immunosuppressant therapy and the other was a patient with

multiorgan involvement in the form of pancreatitis, acute

respiratory distress syndrome, and DIC with multiple blood

transfusions.

Respiratory route seems to be the portal of entry of the

bacteria .Both our patients had severe chest infection and E.

meningoseptica was isolated from BAL (Broncho Alveolar

Lavage) and E.T secretion in significant numbers.

In the first case E. meningoseptica was isolated from the

throat swab sample during routine surveillance days before

infection by E. meningoseptica was detected. E. meningoseptica

was also isolated from the tap water of Bone Marrow Trans-

plant unit where the first case initially was admitted.

a p o l l o m e d i c i n e 1 1 ( 2 0 1 4 ) 1 1 5e1 1 8 117

It is well documented that contaminated respiratory

equipment has been the source of infection in ventilated pa-

tients.6 This may be true for this bacterium as well.

Environmental studies have shown that E. meningoseptica

can survive in chlorinated water supplies, often colonize sink

basins and taps and thus becomes a potential reservoir for

infection in the hospital environment and can infect patients

via contaminated medical devices.7 A recent study by Balm

et al has shown that 44% of taps in the critical care units are

colonized with E. meningoseptica.8

Treatment with E. meningoseptica infection is difficult and

challenging as this organism is inherently resistant to many

antimicrobial agents such as beta lactams including carba-

penems and aztreonam (due to production of beta lactamases

and metallobetalactamases), polymyxins, aminoglycosides,

and chloramphenicol that are the mainstay of treatment for

gram negative sepsis. They are often susceptible to agents

generally used to treat gram positive bacterial infections such

as rifampicin, clindamycin, cotrimoxazole, quinolones and

vancomycin.9 However use of Rifampicin alone in countries

like India where tuberculosis is endemic is not advocated.

The difficulty in treating this infection is compounded by

the fact that MIC breakpoints have not being established for

this bacterium by Clinical and Laboratory Standards Institu-

te(CLSI). Moreover results of susceptibility testing vary when

different methods are used thus adding to the difficulty of

selecting the appropriate antibiotic. Disc diffusion method is

unreliable .The use of inactive drugs may be the cause of poor

outcome in many patients.9

Hsu et al have studied 118 patients with bacteremia and

have concluded that institution of effective antibiotic therapy

after the availability of culture results is an independent

predictor of mortality. They have also shown that E. menin-

goseptica septicemia patients treated with carbapenems have

higher mortality than when they are treated with other anti-

biotics such as fluoroquinolones.10

The SENTRY antimicrobial surveillance programme which

was initiated in 1997 to monitor antimicrobial resistance for

both community acquired and nosocomial infection has

revealed Chryseobacterium strains exhibit resistance to ami-

noglycosides, tetracyclines, chloramphenicol, erythromycin,

clindamycin and teicoplanin.11The same study has shown

that fluoroquinolones have favorable susceptibility pattern

against E. meningosepticawith levofloxacin being slightly more

effective than ciprofloxacin and that the susceptibility to

doxycycline and trimethoprim/sulphamethoxazole appears

variable. Rifampicin and vancomycin in combination has

been used successfully in meningitis cases. But recently in-

vestigators have questioned the usefulness of vancomycin

since in vitro susceptibility data points towards a high MIC of

vancomycin against E. meningoseptica.12,13

In the first case the patient was initially treated with lev-

ofloxacin and subsequently with rifampicin and trimetho-

primesulphamethoxazole and the organism was successfully

eradicated from blood, urine and respiratory samples. In the

second case the cure was affected with rifampicin and tri-

methoprimesulphamethoxazole. Both the patients were

successfully treated with the proper antibiotics after the cor-

rect identification was made. Thus timely identification of E.

meningoseptica is very crucial since appropriate antibiotic

therapy is vital for eradicating infection. All oxidase positive

organism resistant to Polymyxin group (Poly B & Poly E) of

antibiotics should be further characterized. Reporting of all

non-fermenter oxidase positive organisms as Pseudomonas

sp may result in inappropriate antibiotic therapy resulting in

poor outcome. E. meningoseptica septicemia can be life

threatening if not detected and treated with appropriate an-

tibiotics. A study by Lin et al from Taiwan has shown high

mortality of patients with nosocomial bloodstream infection

due to E. meningoseptica. They have further shown that shock

and use of inappropriate antibiotics in these patients are

significantly associated with mortality.14

Isolation of E. meningoseptica should necessitate enhanced

environmental surveillance since E. meningoseptica has the

potential to cause outbreaks and any incriminating source

should be dealt appropriately. In our case flushing of pipelines

and changing of tap faucets resulted in eradication of organ-

ism from the water source and no new infection with E.

meningoseptica was reported.

In conclusions it can be said that E. meningoseptica is an

emerging bacteria causing infection in critically ill adult pa-

tients. The use of Polymyxin group of drugs that are the main

stay of treatment for carbapenem resistant bacteria may have

resulted in the emergence of these intrinsic polymyxin resis-

tant bacteria. Contaminated equipments and water is the

possible source of infection. Infection with E. meningoseptica

necessitates enhanced microbiological surveillance particu-

larly of the water and hand washing sinks so as to be able to

identify the source of the bacteria. Identification of this bac-

terium is difficult and may be wrongly reported as Pseudo-

monas sp. A high index of suspicion should be present in order

to be able to identify this bacterium. Antibiotic therapy is

challenging as E. meningoseptica is intrinsically resistant to

many of the high end antibiotics used in critical care units

particularly Polymyxin group of drugs to which this is intrin-

sically resistant. The currently used CLSI guideline for anti-

biotic susceptibility testing is not helpful for guiding antibiotic

therapy against this organism. Rifampicin, trimetho-

primesulphamethoxazole and levofloxacin alone or in com-

bination seem to be effective against E. meningoseptica.

However the use of Rifampicin alone for the treatment of E.

meningoseptica is to be discouraged. Timely identification and

appropriate therapy is crucial in eradicating this bacterium

and there by improving patients' outcome.

Conflicts of interest

All authors have none to declare.

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