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Research Letter |

Prevention of Hemolytic Uremic Syndrome With Daily Bowel Lavage in Patients With Shiga Toxin–Producing Enterohemorrhagic Escherichia coli O104:H4 Infection FREE

Stefan Lüth, MD1; Thorben W. Fründt, MD1; Thomas Rösch, MD2; Christoph Schlee, MS1; Ansgar W. Lohse, MD1
[+] Author Affiliations
1Department of Medicine I, University Hospital Hamburg-Eppendorf, Hamburg, Germany
2Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany
JAMA Intern Med. 2014;174(6):1003-1005. doi:10.1001/jamainternmed.2014.1175.
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Published online

Infection with Shiga toxin–producing enterohemorrhagic Escherichia coli (EHEC) can cause hemorrhagic colitis and hemolytic uremic syndrome (HUS).1 An epidemic outbreak of EHEC O104:H4 started in May 2011 in northern Germany, affecting 3842 patients and causing 855 cases of HUS.2 There is little evidence in the literature that HUS can be effectively prevented. In this case-series, we present our experience of daily intestinal lavage with polyethylene glycol (PEG) for prevention of HUS in an at-risk group of patients with EHEC.

Between May 13 and June 6, 2011, 33 patients with bloody diarrhea and proven EHEC O104:H4 infection diagnosed via stool cultures were considered to be at risk for HUS development and were subsequently admitted to the First Department of Medicine of the University Medical Center Hamburg-Eppendorf, Hamburg Germany. Institutional review board approval was obtained from the Ethics Committee of the Hamburg Chamber of Physicians, and we conducted a retrospective study.

The first 12 patients (control group [patient 1-12]) were treated symptomatically with intravenous fluids. Because of the positive response to treatment with PEG solution in patient 13, all 20 patients subsequently admitted (treatment group [patient 13-33]) received PEG solution for intestinal lavage daily during the hospital course in addition to symptomatic therapy. Hemolytic uremic syndrome was diagnosed in patients fulfilling all of the following criteria: platelet count lower than 100 × 103/μL (to convert to ×109/L, multiply by 1), evidence of hemolytic anemia with hemoglobin level lower than 13 g/dL (to convert to g/L, multiply by 10) for male patients or lower than 12 g/dL for female patients, and acute renal insufficiency, defined as a 1.5-fold increase of serum creatinine level within 48 hours. The t test was used to compare interval variables after assuring that they met the assumptions of normality, and the Fisher exact test was used for comparing proportions.

No significant difference was found between the control group and the treatment group regarding laboratory findings on admission (Table). Hemolytic uremic syndrome developed in 8 of 12 patients (66%) in the control group vs 4 of 21 patients (19%) in the treatment group (P = .01).

Table Graphic Jump LocationTable.  Baseline Demographic and Laboratory Characteristics and Clinical Course in Both Groupsa

The 2011 German O104:H4 outbreak was characterized by a high rate of patients developing HUS.3 To identify patients at risk of HUS development, we established risk criteria, reflecting the clinical symptoms and laboratory abnormalities of severe EHEC infection and indicating admission for further treatment. The admission procedure is shown in the Figure.

Place holder to copy figure label and caption
Figure.
Patient Management and Admission Procedures in All 122 Patients With Proven O104:H4 Infection Who Presented to the Outpatient Department of the University Medical Center Hamburg-Eppendorf Within the Observation Period

CRP indicates C-reactive protein; HUS, hemolytic uremic syndrome; and LDH, lactate dehydrogenase. SI conversion factors: To convert platelets and leukocytes to ×109/L, multiply by 1; lactate dehydrogenase to microkatals per liter, multiply by 0.0167; CRP to nanomoles per liter, multiply by 9.524.

Graphic Jump Location

Treatment of EHEC-associated bloody diarrhea is usually symptomatic and consists of adequate volume substitution.4 Following admission, all 33 patients received standard therapy, consisting of 2 to 3 L of intravenous fluids (crystalloids [isotonic saline and Ringer solution]) daily. Because the use of antibiotics is associated with an increased risk of developing HUS,5 none of the 33 patients received antibiotic therapy.

Patient 13, who developed symptoms of a paralytic ileus with simultaneously increasing leukocyte and declining platelet counts, reflecting the progressed infection, successfully responded to repetitive intestinal lavage with PEG solution as an attempt to treat the ileus. Her clinical status improved gradually after the first lavage, and thrombocytes and leukocytes returned to normal levels within the next 3 days. We believed it was likely that the PEG solution was effective by enhancing clearance of intestinal bacteria and toxins through dilution and large-volume lavage. On the basis of this theoretical rationale and our successful experience, we treated all subsequent patients with PEG solution lavage and found a lower rate of development of HUS compared with the control group.

Although all 33 patients tested positive for O104:H4 prior to hospitalization, stool cultures were not taken regularly following admission, so we cannot determine if patients in the treatment group had an accelerated clearance of EHEC bacteria. Also, we cannot rule out the possibility that the organism became less pathogenic over the time of the outbreak. Nonetheless, we believe that daily bowel lavage with PEG solution combined with intravenous rehydration is a promising treatment to prevent HUS in patients with EHEC and should be further studied.

Corresponding Author: Stefan Lüth, MD, Department of Medicine I, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany (s.lueth@uke.de).

Published Online: April 28, 2014. doi:10.1001/jamainternmed.2014.1175.

Author Contributions: Drs Lüth and Fründt had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Lüth and Fründt contributed equally to the manuscript.

Study concept and design: Lüth, Fründt, Lohse.

Acquisition, analysis, or interpretation of data: Lüth, Fründt, Rösch, Schlee, Lohse.

Drafting of the manuscript: Lüth, Fründt, Rösch, Schlee.

Critical revision of the manuscript for important intellectual content: Lüth, Rösch, Lohse.

Statistical analysis: Lüth, Fründt, Schlee, Lohse.

Obtained funding: Lüth.

Administrative, technical, or material support: Lüth, Lohse.

Study supervision: Lüth, Rösch, Lohse.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by the Deutsche Forschungsgemeinschaft (grant LU B62/2-1) and the Federal Ministry of Health (grant 1501/544 01).

Role of the Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Moritz Tacke, MD (Department of Pediatrics, Ludwig-Maximilians University, Munich, Germany), Johannes Kluwe, MD, and Katharina Freadrich-Zimmermann, MD (Department of Medicine I, University Hospital Hamburg-Eppendorf), and Marina Nesselrode, MD (Department of Medicine III, University Hospital Hamburg-Eppendorf), collaborated on the study. Ulf Panzer, MD (Department of Medicine III, University Hospital Hamburg-Eppendorf), and Karl Wegscheider, PhD (Department of Medical Biometry and Epidemiology, University Hospital Hamburg-Eppendorf), provided administrative assistance in preparing the manuscript. No compensation was received by any of the persons listed.

Karmali  MA, Steele  BT, Petric  M, Lim  C.  Sporadic cases of haemolytic-uraemic syndrome associated with faecal cytotoxin and cytotoxin-producing Escherichia coli in stools. Lancet. 1983;1(8325):619-620.
PubMed   |  Link to Article
Robert Koch-Institut. Bericht: Abschließende Darstellung und Bewertung der epidemiologischen Erkenntnisse im: EHEC O104:H4 Ausbruch, Deutschland 2011. Berlin, Germany 2011. http://edoc.rki.de/documents/rki_ab/reeFNxULvsdZo/PDF/262b4Pk2TGGs.pdf. Accessed September 6, 2013.
Frank  C, Werber  D, Cramer  JP,  et al; HUS Investigation Team.  Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med. 2011;365(19):1771-1780.
PubMed   |  Link to Article
Tarr  PI, Gordon  CA, Chandler  WL.  Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet. 2005;365(9464):1073-1086.
PubMed
Wong  CS, Jelacic  S, Habeeb  RL, Watkins  SL, Tarr  PI.  The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med. 2000;342(26):1930-1936.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure.
Patient Management and Admission Procedures in All 122 Patients With Proven O104:H4 Infection Who Presented to the Outpatient Department of the University Medical Center Hamburg-Eppendorf Within the Observation Period

CRP indicates C-reactive protein; HUS, hemolytic uremic syndrome; and LDH, lactate dehydrogenase. SI conversion factors: To convert platelets and leukocytes to ×109/L, multiply by 1; lactate dehydrogenase to microkatals per liter, multiply by 0.0167; CRP to nanomoles per liter, multiply by 9.524.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable.  Baseline Demographic and Laboratory Characteristics and Clinical Course in Both Groupsa

References

Karmali  MA, Steele  BT, Petric  M, Lim  C.  Sporadic cases of haemolytic-uraemic syndrome associated with faecal cytotoxin and cytotoxin-producing Escherichia coli in stools. Lancet. 1983;1(8325):619-620.
PubMed   |  Link to Article
Robert Koch-Institut. Bericht: Abschließende Darstellung und Bewertung der epidemiologischen Erkenntnisse im: EHEC O104:H4 Ausbruch, Deutschland 2011. Berlin, Germany 2011. http://edoc.rki.de/documents/rki_ab/reeFNxULvsdZo/PDF/262b4Pk2TGGs.pdf. Accessed September 6, 2013.
Frank  C, Werber  D, Cramer  JP,  et al; HUS Investigation Team.  Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med. 2011;365(19):1771-1780.
PubMed   |  Link to Article
Tarr  PI, Gordon  CA, Chandler  WL.  Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet. 2005;365(9464):1073-1086.
PubMed
Wong  CS, Jelacic  S, Habeeb  RL, Watkins  SL, Tarr  PI.  The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med. 2000;342(26):1930-1936.
PubMed   |  Link to Article

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