Upload
others
View
4
Download
0
Embed Size (px)
Citation preview
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.
Submit your manuscripts athttp://www.hindawi.com
Stem CellsInternational
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Disease Markers
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014
Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014
Parkinson’s Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com