4
101 CASE REPORT Bacillus cereus Necrotizing Pneumonia in a Patient with Nephrotic Syndrome Jun Miyata 1 , Sadatomo Tasaka 1 , Masaki Miyazaki 1 , Syuichi Yoshida 1 , Katsuhiko Naoki 1 , Koichi Sayama 1 , Koichiro Asano 1 , Hiroshi Fujiwara 2 , Kiyofumi Ohkusu 3 , Naoki Hasegawa 2 and Tomoko Betsuyaku 1 Abstract Bacillus cereus (B. cereus) is a Gram-positive rod that is widely distributed in the environment and can be a cause of food poisoning. We herein present a case of B. cereus necrotizing pneumonia in a patient with nephrotic syndrome under corticosteroid treatment after developing transient gastroenteritis symptoms. B. cereus was isolated from bronchial lavage fluid and transbronchial biopsy specimens. A multiplex polymerase chain reaction analysis of the toxin genes revealed a strain possessing enterotoxicity. The patient recovered after one week of intravenous meropenem followed by a combination of oral moxifloxacin and clindamycin. B. cereus is a pathogen that causes necrotizing pneumonia in immunocompromised hosts. Key words: Bacillus cereus, necrotizing pneumonia, nephrotic syndrome, corticosteroid, hypogammaglobu- linemia (Intern Med 52: 101-104, 2013) (DOI: 10.2169/internalmedicine.52.7282) Introduction Bacillus cereus (B. cereus) is a Gram-positive, aerobic-to- facultative, spore-forming rod that is widely distributed in the environment (1). Although it is well known as a cause of food poisoning (2), the clinical relevance of B. cereus is often disregarded. When isolated from clinical specimens, it is usually considered a culture contaminant. However, severe hematogenous infections caused by B. cereus have been re- ported, especially in drug addicts, premature neonates and patients with severe underlying diseases or compromised im- munity (3). B. cereus rarely causes lower respiratory tract infections, although most reported cases of B. cereus pneu- monia involve fatal outcomes despite intensive antibiotic therapy. We herein describe a case of B. cereus necrotizing pneu- monia in an immunocompromised patient with nephrotic syndrome under treatment with high-dose corticosteroids. The definitive diagnosis of B. cereus pneumonia was made based on cultures of bronchial lavage fluid and transbron- chial lung biopsy specimens. Case Report A 43-year-old man presented with a 3-month history of progressive edema in both lower extremities and the face. On examination, his urinary protein level was 6.0 g/day and his serum albumin level was 1.1 g/dL. His renal function was mildly impaired (estimated glomerular filtration rate: 61.1 mL/min/1.73 m 2 ) and hypogammaglobulinemia (immu- noglobulin G (IgG): 224 mg/dL, immunoglobulin A (IgA): 322 mg/dL and immunoglobulin M (IgM): 58 mg/dL) was present. After obtaining the results of a renal biopsy, the pa- tient was diagnosed with minimal change nephrotic syn- drome. Following three days of pulsed steroid therapy with 500 mg/day of methylprednisolone, oral prednisolone (PSL) was administered at a dose of 50 mg/day. Diarrhea and Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Japan, Center for Infectious Diseases and In- fection Control, Keio University School of Medicine, Japan and Department of Microbiology, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Japan Received for publication January 10, 2012; Accepted for publication June 11, 2012 Correspondence to Dr. Sadatomo Tasaka, [email protected]

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Page 1: Bacillus cereus Necrotizing Pneumonia in a Patient with

101

□ CASE REPORT □

Bacillus cereus Necrotizing Pneumonia in a Patientwith Nephrotic Syndrome

Jun Miyata 1, Sadatomo Tasaka 1, Masaki Miyazaki 1, Syuichi Yoshida 1, Katsuhiko Naoki 1,

Koichi Sayama 1, Koichiro Asano 1, Hiroshi Fujiwara 2, Kiyofumi Ohkusu 3,

Naoki Hasegawa 2 and Tomoko Betsuyaku 1

Abstract

Bacillus cereus (B. cereus) is a Gram-positive rod that is widely distributed in the environment and can be

a cause of food poisoning. We herein present a case of B. cereus necrotizing pneumonia in a patient with

nephrotic syndrome under corticosteroid treatment after developing transient gastroenteritis symptoms. B.cereus was isolated from bronchial lavage fluid and transbronchial biopsy specimens. A multiplex polymerase

chain reaction analysis of the toxin genes revealed a strain possessing enterotoxicity. The patient recovered

after one week of intravenous meropenem followed by a combination of oral moxifloxacin and clindamycin.

B. cereus is a pathogen that causes necrotizing pneumonia in immunocompromised hosts.

Key words: Bacillus cereus, necrotizing pneumonia, nephrotic syndrome, corticosteroid, hypogammaglobu-

linemia

(Intern Med 52: 101-104, 2013)(DOI: 10.2169/internalmedicine.52.7282)

Introduction

Bacillus cereus (B. cereus) is a Gram-positive, aerobic-to-

facultative, spore-forming rod that is widely distributed in

the environment (1). Although it is well known as a cause

of food poisoning (2), the clinical relevance of B. cereus is

often disregarded. When isolated from clinical specimens, it

is usually considered a culture contaminant. However, severe

hematogenous infections caused by B. cereus have been re-

ported, especially in drug addicts, premature neonates and

patients with severe underlying diseases or compromised im-

munity (3). B. cereus rarely causes lower respiratory tract

infections, although most reported cases of B. cereus pneu-

monia involve fatal outcomes despite intensive antibiotic

therapy.

We herein describe a case of B. cereus necrotizing pneu-

monia in an immunocompromised patient with nephrotic

syndrome under treatment with high-dose corticosteroids.

The definitive diagnosis of B. cereus pneumonia was made

based on cultures of bronchial lavage fluid and transbron-

chial lung biopsy specimens.

Case Report

A 43-year-old man presented with a 3-month history of

progressive edema in both lower extremities and the face.

On examination, his urinary protein level was 6.0 g/day and

his serum albumin level was 1.1 g/dL. His renal function

was mildly impaired (estimated glomerular filtration rate:

61.1 mL/min/1.73 m2) and hypogammaglobulinemia (immu-

noglobulin G (IgG): 224 mg/dL, immunoglobulin A (IgA):

322 mg/dL and immunoglobulin M (IgM): 58 mg/dL) was

present. After obtaining the results of a renal biopsy, the pa-

tient was diagnosed with minimal change nephrotic syn-

drome. Following three days of pulsed steroid therapy with

500 mg/day of methylprednisolone, oral prednisolone (PSL)

was administered at a dose of 50 mg/day. Diarrhea and

1Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Japan, 2Center for Infectious Diseases and In-

fection Control, Keio University School of Medicine, Japan and 3Department of Microbiology, Regeneration and Advanced Medical Science,

Gifu University Graduate School of Medicine, Japan

Received for publication January 10, 2012; Accepted for publication June 11, 2012

Correspondence to Dr. Sadatomo Tasaka, [email protected]

Page 2: Bacillus cereus Necrotizing Pneumonia in a Patient with

Intern Med 52: 101-104, 2013 DOI: 10.2169/internalmedicine.52.7282

102

Figure 1. Chest radiograph performed on day 22 showing infiltrates in the left lower lung field.

Figure 2. (A) Chest radiograph performed on day 46 showing infiltrates with cavitations in the left lower lung field. (B) Chest computed tomography performed on day 46 showing a cavity with a thick, irregular wall surrounded by consolidation in the left lower lobe, indicating the development of necrotizing pneumonia.

vomiting were noted on day 2 of oral steroid therapy; how-

ever, there were no symptoms suggestive of sepsis. As the

patient’s proteinuria and hypoalbuminemia gradually im-

proved, the dose of PSL was reduced to 40 mg/day on day

43 from the start of PSL treatment.

On day 22, chest roentgenogram (Fig. 1) showed infil-

trates in the left lower lung field. Due to the absence of fe-

ver, cough or sputum and normal physical examination find-

ings, no antibiotics were administered. On day 46, chest

roentgenogram (Fig. 2A) and chest computed tomography

(CT) (Fig. 2B) revealed a cavitary lesion surrounded by in-

filtrates in the left lower lung lobe. On day 47, broncho-

scopic examinations were performed, followed by antibiotic

therapy with intravenous meropenem (2.0 g/day). No patho-

genic organisms were identified by sputum cultures. Seven

days later, B. cereus was isolated from the bronchial lavage

fluid and transbronchial lung biopsy specimens. After under-

going eight days of intravenous meropenem treatment, the

patient received 400 mg/day of moxifloxacin and 900 mg/

day of clindamycin orally for 15 days. Chest roentgenogram

and chest CT performed three months after discharge

showed a reduction in the size of the cavity.

To identify B. cereus toxin genes, we performed multiplex

polymerase chain reaction (PCR). The strain isolated from

our patient exhibited the presence of nhe and cesB and the

absence of nblA, hblC, hblD, cap, cya, lef, pag and Ba813,

which indicates that the strain possessed strong cytotoxity

among the various strains of B. cereus (4) and was different

from outbreak strains (5).

Discussion

B. cereus plays a well-known pathogenic role in food poi-

soning. It leads to toxin-mediated (6, 7), self-limited illness

characterized by emetic or diarrheal syndromes. Systemic or

localized infections encompass bacteremia (8), endocardi-

tis (9), meningitis (10) and pneumonia (11-23). In this re-

port, we described a case of B. cereus necrotizing pneumo-

nia in a patient with nephrotic syndrome under treatment

with high-dose corticosteroids. Previously reported cases of

B. cereus pneumonia in adults are summarized in Table.

Most of these cases occurred in patients with hematological

disorders (e.g., leukemia and aplastic anemia) or alcohol

abuse; however, four lethal cases of B. cereus pneumonia in

immunocompetent welders and metalworkers have been re-

cently reported (12, 15). Our patient was not neutropenic,

although he could have been immunocompromised owing to

hypogammaglobulinemia and the use of corticosteroids.

B. cereus is generally considered to be a saprophytic con-

taminant when isolated from clinical samples. Therefore, de-

tection of the microorganism in multiple samples is neces-

sary to make a definitive diagnosis of B. cereus pneumonia.

In the present case, the pathogenic role of B. cereus in

pneumonia was indicated because the bacteria were isolated

from two different specimens that were sampled aseptically.

However, the two specimens were obtained with the same

Page 3: Bacillus cereus Necrotizing Pneumonia in a Patient with

Intern Med 52: 101-104, 2013 DOI: 10.2169/internalmedicine.52.7282

103

Tab

le.  

Clin

ical

Cha

ract

eris

tics

, Treat

men

t an

d O

utco

me

of 1

6 Pat

ients

of B

. cer

eus P

neum

onia

in Adu

lts

Patie

ntA

ge/S

exR

isk

fact

orSe

ptic

emia

Neu

trope

nia

Rad

iogr

aphi

c ch

arac

teris

tics

Trea

tmen

tO

utco

me

Ref

eren

ce1

NA

none

NA

NA

NA

NA

died

232

52/M

acut

e le

ukem

iaye

sye

sin

filtra

te, e

ffus

ion

Abx

(pen

icill

in, m

ethi

cilli

n, g

enta

mic

in)

died

223

63/M

acut

e le

ukem

iaye

sye

sin

filtra

teA

bx (o

xaci

llin,

car

beni

cilli

n, g

enta

mic

in)

died

214

29/M

leuk

emia

noye

sin

filtra

te, c

avita

tion,

eff

usio

nA

bx (p

enic

illin

, cef

alot

in, c

arbe

nici

llin)

, pne

umoc

ente

sis

reco

vere

d20

560

/Mal

coho

l abu

seno

noin

filtra

te, c

avita

tion,

eff

usio

nA

bx (p

enic

illin

, chl

oram

phen

icol

), lu

ng re

sect

ion

reco

vere

d19

618

/Mal

coho

l abu

seno

noin

filtra

te, p

neum

otho

rax,

eff

usio

nA

bx (t

obra

myc

in, c

efam

ando

le, c

efal

otin

, clin

dam

ycin

,er

ythr

omyc

in, a

mpi

cilli

n), t

hora

cost

omy,

rese

ctio

nre

cove

red

18

754

/Mle

ukem

iaye

sye

sin

filtra

te, c

avita

tion

Abx

(mox

alac

tam

, naf

cilli

n, to

bram

ycin

)re

cove

red

178

21/M

bron

chie

ctas

isN

AN

Ain

filtra

teA

bx (a

zloc

illin

, gen

tam

icin

, cip

roflo

xaci

n)re

cove

red

169

46/M

none

(wel

der)

yes

noin

filtra

teA

bx (c

ipro

floxa

cin,

cef

otax

ime)

died

1510

41/M

none

(wel

der)

yes

noin

filtra

te, e

ffus

ion

Abx

(am

pici

llin-

sulb

acta

m, e

ryth

rom

ycin

, clin

dam

ycin

, van

com

ycin

)di

ed15

1152

/Fap

last

ic a

nem

iaye

sye

sin

filtra

teA

bx (p

iper

acill

in-s

ulba

ctam

, van

com

ycin

, im

ipen

em)

died

1412

37/F

leuk

emia

yes

yes

infil

trate

, eff

usio

nA

bx (c

efep

ime,

am

ikac

in, v

anco

myc

in)

died

1313

39/M

none

(met

al w

orke

r)ye

sno

infil

trate

Abx

(azi

thro

myc

in, v

anco

myc

in, c

efep

ime)

died

1214

56/M

none

(met

al w

orke

r)ye

sno

infil

trate

Abx

(cef

triax

one,

levo

floxa

cin)

died

1215

60/M

acut

e le

ukem

iaye

sye

sin

filtra

te, n

odul

eA

bx (c

efep

ime,

pan

ipen

em/b

etam

ipro

n, a

mik

acin

)di

ed11

1643

/Mne

phro

tic sy

ndro

me

nono

infil

trate

, cav

itatio

nA

bx (m

erop

enem

, mox

iflox

acin

, clin

dam

ycin

)re

cove

red

Pres

ent c

ase

NA

: not

ava

ilabl

e, A

bx: a

ntib

iotic

s

bronchoscope and the possibility for contamination cannot

be ruled out.

As in most of the reported cases of B. cereus pulmonary

infection, we were unable to identify the route of the infec-

tion (18). We observed no respiratory symptoms such as

cough, hemoptysis or chest pain, whereas gastrointestinal

symptoms (diarrhea and emesis) were present. Therefore, in

the present case, it was indicated that the B. cereus pulmo-

nary infection might have resulted from transient bacteremia

from a gastrointestinal infection.

B. cereus produces β-lactamase and is therefore resistant

to penicillin and cephalosporins (1). B. cereus is usually sus-

ceptible to clindamycin, vancomycin, fluoroquinolones,

carbapenems and aminoglycosides. After isolating B. cereus,

we changed the antibiotics to a combination of clindamycin

and moxifloxacin, which was effective.

A multiplex PCR analysis revealed that the strain of B.cereus isolated from our patient was different from outbreak

strains possessing Ba813 (5). The present strain, which was

positive for nhe and ces and negative for hbl, possesses

strong cytotoxic capacity and accounts for 28.6% of B.cereus strains (4). These results are compatible with the de-

velopment of necrotizing pneumonia in our patient and did

not present a life-threatening condition.

In summary, this is a rare case of B. cereus necrotizing

pneumonia in a patient with nephrotic syndrome. The pre-

sent case indicates the importance of performing a broncho-

scopic assessment of lung infiltrates, especially in immuno-

compromised hosts, even if the inflammatory reaction is not

significant.

The authors state that they have no Conflict of Interest (COI).

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