Case Report Multidrug-Resistant Bacteroides fragilis Bacteremia...

Case ReportMultidrug-Resistant Bacteroides fragilis Bacteremiain a US Resident: An Emerging Challenge

Cristian Merchan,1 Sunita Parajuli,2 Justin Siegfried,1 Marco R. Scipione,1

Yanina Dubrovskaya,1 and Joseph Rahimian2

1Department of Pharmacy, NYU Langone Medical Center, New York, NY 10016, USA2Department of Infectious Diseases, NYU Langone Medical Center, New York, NY 10016, USA

Correspondence should be addressed to Cristian Merchan; [email protected]

Received 30 March 2016; Accepted 30 May 2016

Academic Editor: Janak Koirala

Copyright © 2016 Cristian Merchan et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

We describe a case of Bacteroides fragilis bacteremia associated with paraspinal and psoas abscesses in the United States. Resistanceto b-lactam/b-lactamase inhibitors, carbapenems, and metronidazole was encountered despite having a recent travel history toIndia as the only possible risk factor for multidrug resistance. Microbiological cure was achieved with linezolid, moxifloxacin, andcefoxitin.

1. Brief Case Report

An 82-year-old male with no significant past medical his-tory was admitted to the intensive care unit for acutehypoxic respiratory failure, fever, hypotension, and confu-sion. Laboratory findings were significant for leukocytosisand elevated liver function tests. He was empirically startedon vancomycin, cefepime, amikacin, and azithromycin forseptic shock secondary to pneumonia. Within 24 hoursof admission, 3 out of 6 blood cultures grew anaerobicGram-negative rods, prompting a switch in antibiotics topiperacillin-tazobactam andmetronidazole, pending suscep-tibility results. A computed tomography scan of the abdomenand a colonoscopy revealed no significant findings; however,the patient remained persistently febrile.

In the following two days, the patient’s mental statusimproved and he began to report lower back pain. Amagneticresonance image (MRI) of the lower back was ordered andrevealed discitis at the level of L2–L5 as well as paraspinal,epidural, and psoas abscesses. Bacteroides fragilis was iden-tified from the blood cultures with resistance to ampicillin-sulbactam (MIC 32mg/L), clindamycin (MIC 32mg/L),metronidazole (MIC 32mg/L), penicillinG (MIC> 32mg/L),cefoxitin (MIC 12mg/L), imipenem-cilastatin (MIC 1mg/L),

ertapenem (MIC 12mg/L), and meropenem (MIC 32mg/L).Further susceptibility testing demonstrated an increasedMICof 6 to imipenem, linezolid (MIC 2mg/L), ceftazidime-avibactam (MIC 24mg/L), ceftolozane-tazobactam (MIC256mg/L), and tigecycline (MIC 256mg/L). All susceptibili-ties were confirmed by E test. High dose imipenem-cilastatin(1 gram intravenously every 6 hours) was initiated along withlinezolid 600 milligrams intravenously every 12 hours. Giventhe high level of resistance, the patient was asked about anyrisk factors associated with multidrug-resistant pathogens.He reported having traveled throughout India four monthsprior to admission but was never hospitalized nor did hereceive any antibiotics during his time abroad. In an attemptto obtain source control, general surgery was consultedand determined that the harm of a surgical interventionoutweighed the benefits. Only a small amount of fluid wasaspirated by Interventional Radiology and the culture wasnegative.

Thebacteremia cleared after 3 days and the fevers resolvedafter 7 days. The patient was discharged after 2 weeks onthe following antibiotics: cefoxitin, linezolid, and high doseimipenem-cilastatin. Linezolid was stopped a month laterdue to thrombocytopenia. Follow-up susceptibilities revealedthat the B. fragilis was sensitive to moxifloxacin (MIC

Hindawi Publishing CorporationCase Reports in Infectious DiseasesVolume 2016, Article ID 3607125, 4 pageshttp://dx.doi.org/10.1155/2016/3607125

2 Case Reports in Infectious Diseases

Table1:Previous

case

repo

rtso

fB.fragilis

resistancea

ndtre

atmentregim

ens.

Case

repo

rts

Source

ofinfection

Resistancem

echanism

sDefinitiv

etreatmentregim

enOutcome

UnitedStatescasereports

Sherwoo

detal.[1]

Bacterem

ia+wou

ndnimE

Moxifloxacin

400m

gIV

q24h

+lin

ezolid

600m

gIV

q12h

Duration:

8weeks

Survived

Kapalpila

etal.[2]

Bacterem

ia+intra-abdo

minalflu

idNomolecular

investigatio

n;resistant

toMTZ1,imipenem

,PTZ1,clin

damycin,

cefotetan,

amp/sul1,m

oxifloxacin

Ertapenem

1gIV

q24h

r+Linezolid

600m

gIV

q12h

rDuration:

4weeks

Survived

Non-Un

itedStatescase

reports

Ank

etal.[3]

Bacterem

iacfiA,

nimE,

ermF,tetQ

Moxifloxacin

400m

gIV

q24h

+piperacillin-tazobactam

4.5g

IVq8

hrDuration:

7days

Survived

Urban

etal.[4]

Abdo

minalflu

idcfiA,

nimA,

erm,cepA,

tetQ

Locally

appliedantib

iotic

therapy/wou

ndcare

Survived

Hartm

eyer

etal.[5]

Bacterem

ia+intra-abdo

minalflu

idcfiA,

nimD,

ermF,tetQ,tetX

Merop

enem

+metronidazole

Duration:

6days,disc

ontin

uatio

ndu

etodeath

Died

Katsandrietal.(2

case

repo

rts)

[6]

Case

1:bacterem

iafro

mac

olitis

Case

2:esop

hagojejunalanasto

moticleak

cfiA

Case

1:metronidazole500m

gIV

q8h+cefotaxime

2gIV

q8h

Case

2:im

ipenem

500m

gIV

q8h

Case

1:died

Case

2:died

Wareham

etal.[7]

Bacterem

iafro

mpancreatitis

cfiA,

ermF,tetQ,efflux

pumpbm

eB9/B15

Linezolid

600m

gIV

q12h

Died

Rotim

ietal.(3

case

repo

rts)

[8]

Case

1:paracolic

abscess

Case

2:surgicalwou

ndCa

se3:groinandscrotalabscess

Nomolecular

investigatio

n;resistant

toMTZ

Case

1:im

ipenem

500m

gIV

q8h

Case

2:am

oxicillin-clavulanateacid

600m

gPO

q8h

Case

3:merop

enem

500m

gIV

q8h+cefepime+

amikacin

500m

gIV

q12h

Case

1:survived

Case

2:survived

Case

3:died

Turner

etal.[9]

Bacterem

iafro

mperiton

itisa

ndem

pyem

aNomolecular

investigatio

n;resistant

toMTZ

,imipenem

,amoxicillin-clav

ulanate

acid

Gentamicin

andclind

amycin

Survived

1MTZ

:metronidazole;P

TZ:piperacillin-ta

zobactam

.

Case Reports in Infectious Diseases 3

0.125mg/L) which was then added to the patient’s regimen.The patient completed a total 12-week course of antibioticsand had normalization of his c-reactive protein and erythro-cyte sedimentation rate. Follow-up MRI at 12 weeks showedsignificant reduction in the patient’s paraspinal, epidural, andpsoas abscesses.

2. Discussion

The B. fragilis group is the most common anaerobic organ-ism recovered in blood cultures to date [10]. They arefrequently isolated from the gastrointestinal tract but arerarely present in the oral cavity, upper respiratory tract,and female genitalia. Their slow in vitro growth, associationwith polymicrobial infections, and potential for antimicrobialresistance tend to complicate the treatment course [11].

The variation in susceptibilities for B. fragilis isolatesdepends on the individual species, country, medical institu-tion, and antibiotic use within a geographic location [12].Thenumber of reports of multidrug-resistant B. fragilis strainshas increased in the past decade as highlighted in Table 1 [1–9]. In particular, at NYU Langone Medical Center, resistancerates for 361 Bacteroides isolates were evaluated over a 5-yeartime period which demonstrated overall resistance rates of5% (17/361) to metronidazole, 4% (13/361) to carbapenems,and 0.3% (1/361) to both carbapenems andmetronidazole. Ofnote, 96% (16/17) of the isolates that were resistant tometron-idazole were susceptible to carbapenems. Additionally, 94%(12/13) of the isolates that were resistant to carbapenemswere susceptible to metronidazole. Our institution’s higherresistance rates are in direct contrast to the rates reportedin the USA for metronidazole (<1%) and carbapenems (1%)from 2008 to 2013 [12].

Themechanisms of antibiotic resistance in B. fragilis havebeen well described for carbapenems and metronidazole.Resistance to carbapenems is mainly mediated throughthe production of class b metallo-beta-lactamase enzymesencoded by the cfiA gene in the presence of an insertionsequence [12]. Metronidazole resistance has been associatedwith the presence of nitroimidazole resistance gene, nim A-G, that prevents the activation of metronidazole throughthe production of nitroimidazole reductase. The B. fragilisisolated from this patient revealed high-level resistance tomultiple antibiotics including metronidazole, meropenem,and ertapenem. Resistance was also observed for ampicillin-sulbactam, clindamycin, and tigecycline. The only risk factorfor a multidrug-resistant organism was a recent trip to India;however, he was not hospitalized or exposed to antibiotics asseen in other published reports. The B. fragilis isolates fromour patient were analyzed by the Center for Disease Controland Prevention for Genomic Epidemiology database whichidentified that the isolates contained the following resistancegenes: cfiA, cfxA, erm (F), erm (B), and sul2. From theanalysis done using CLCbio andGeneious, it seems that thereare no insertion sequences upstream of the gene; thereforethe resistance to B-lactams seen phenotypically is most likelydue to the cfxA gene. The cfx A gene leads to the productionof a class a serine beta lactamase responsible for high-level

resistance to cephalosporins [12]. In addition, the B. fragilisisolates did not contain nim genes conferring metronidazoleresistance, suggesting that alternative resistance mechanismslike efflux pumps may be present [3].

In conclusion, this is the third case of MDR B. fragilisinfection reported in a US hospital with resistance to bothcarbapenems and metronidazole; however, it is the first casein which the patient was not hospitalized abroad beforereturning to the USA [1, 2]. In addition, this is the firstcase that describes a monomicrobial B. fragilis bacteremiaassociated with a paraspinal, epidural, and psoas abscesses.Our case report suggests that physicians can no longerrely on the assumption of metronidazole or carbapenemsusceptibility and should consider requesting susceptibilitytesting when treating severe infections caused by B. fragilis.

Competing Interests

The authors declare that they have no competing interests.

References

[1] J. E. Sherwood, S. Fraser, D. M. Citron et al., “Multi-drugresistant Bacteroides fragilis recovered from blood and severeleg wounds caused by an improvised explosive device (IED) inAfghanistan,” Anaerobe, vol. 17, no. 4, pp. 152–155, 2011.

[2] A. Kapalpila, S. Pergam, P. Pottinger et al., Multidrug-ResistantBacteroides Fragilis, MMWR, Seattle, Wash, USA, 2013.

[3] N. Ank, T. V. Sydenham, L. H. Iversen, U. S. Justesen, and M.Wang, “Characterisation of a multidrug-resistant Bacteroidesfragilis isolate recovered from blood of a patient in Den-mark usingwhole-genome sequencing,” International Journal ofAntimicrobial Agents, vol. 46, no. 1, pp. 117–120, 2015.

[4] E. Urban, Z. Horvath, J. Soki, and G. Lazar, “First Hungariancase of an infection caused by multidrug-resistant Bacteroidesfragilis strain,” Anaerobe, vol. 31, pp. 55–58, 2015.

[5] G. N. Hartmeyer, J. Soki, E. Nagy, and U. S. Justesen,“Multidrug-resistant Bacteroides fragilis group on the rise inEurope?” Journal of Medical Microbiology, vol. 61, no. 12, pp.1784–1788, 2012.

[6] A. Katsandri, J. Papaparaskevas, A. Pantazatou et al., “Two casesof infections due to multidrug-resistant Bacteroides fragilisgroup strains,” Journal of Clinical Microbiology, vol. 44, no. 9,pp. 3465–3467, 2006.

[7] D. W. Wareham, M. Wilks, D. Ahmed, J. S. Brazier, and M.Millar, “Anaerobic sepsis due tomultidrug-resistant Bacteroidesfragilis: microbiological cure and clinical response with line-zolid therapy,”Clinical Infectious Diseases, vol. 40, no. 7, pp. e67–e68, 2005.

[8] V. O. Rotimi, M. Khoursheed, J. S. Brazier, W. Y. Jamal, and F. B.Khodakhast, “Bacteroides species highly resistant tometronida-zole: an emerging clinical problem?” Clinical Microbiology andInfection, vol. 5, no. 3, pp. 166–169, 1999.

[9] P. Turner, R. Edwards, V. Weston, P. Ispahani, D. Greenwood,and A. Gazis, “Simultaneous resistance to metronidazole, co-amoxiclav, and imipenem in clinical isolate of Bacteroidesfragilis,”The Lancet, vol. 345, no. 8960, pp. 1275–1277, 1995.

[10] B. Lassmamn, D. R. Gustafson, C. M. Wood, and J. E.Rosenblatt, “Reemergence of anaerobic bacteremia,” ClinicalInfectious Diseases, vol. 44, no. 7, pp. 895–900, 2007.

4 Case Reports in Infectious Diseases

[11] I. Brook, H. M. Wexler, and E. J. C. Goldstein, “Antianaerobicantimicrobials: spectrum and susceptibility testing,” ClinicalMicrobiology Reviews, vol. 26, no. 3, pp. 526–546, 2013.

[12] L. Boyanova, R. Kolarov, and I. Mitov, “Recent evolution ofantibiotic resistance in the anaerobes as compared to previousdecades,” Anaerobe, vol. 31, pp. 4–10, 2015.

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