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Volume 27, Number 7—July 2021

Shiga Toxin–Associated Hemolytic Uremic Syndrome in Adults, France, 2009–2017

Benoît Travert1, Antoine Dossier1, Matthieu Jamme, Aurélie Cointe, Yahsou Delmas, Sandrine Malot, Alain Wynckel, Amélie Seguin, Claire Presne, Miguel Hie, Ygal Benhamou, David Ribes, Gabriel Choukroun, Steven Grangé, Alexandre Hertig, Emilie Cornec Le Gall, Lionel Galicier, Eric Daugas, Lila Bouadma, François-Xavier Weill, Elie Azoulay, Fadi Fakhouri, Agnès Veyradier, Stéphane Bonacorsi, Julien Hogan, Véronique Frémeaux-Bacchi, Eric Rondeau, Patricia Mariani-Kurkdjian, Paul CoppoComments to Author , and Centre de Référence des Microangiopathies Thrombotiques2
Author affiliations: Centre de Référence des Microangiopathies Thrombotiques, Paris, France (B. Travert, A. Dossier, M. Jamme, Y. Delmas, S. Malot, A. Wynckel, A. Seguin, C. Presne, M. Hie, Y. Benhamou, G. Choukroun, S. Grangé, A. Hertig, L. Galicier, E. Azoulay, F. Fakhouri, A. Veyradier, V. Frémeaux-Bacchi, E. Rondeau, P. Coppo); Université de Paris, Paris (B. Travert, A. Dossier, A. Cointe, L. Galicier, E. Daugas, L. Bouadma, E. Azoulay, A. Veyradier, S. Bonacorsi, J. Hogan, V. Frémeaux-Bacchi, P. Mariani-Kurkdjian); Hôpital Bichat—Claude Bernard, Paris (B. Travert, A. Dossier, E. Daugas, L. Bouadma); Sorbonne-Université, Paris (M. Jamme, M. Hie, A. Hertig, E. Rondeau, P. Coppo); Hôpital Tenon, Paris (M. Jamme, E. Rondeau); Hôpital Robert-Debré, Paris (A. Cointe, S. Bonacorsi, J. Hogan, P. Mariani-Kurkdjian); Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France (Y. Delmas); Hôpital Maison Blanche, Reims, France (A. Wynckel); Centre Hospitalier Universitaire de Caen, Caen, France (A. Seguin); Centre Hospitalier Universitaire d’Amiens, Amiens, France (C. Presne, G. Choukroun); Groupement Hospitalier Pitié-Salpêtrière, Paris (M. Hie, A. Hertig); Centre Hospitalier Universitaire de Rouen, Rouen, France (Y. Benhamou, S. Grangé); Centre Hospitalier Universitaire de Toulouse, Toulouse, France (D. Ribes); Centre Hospitalier Universitaire de Brest, Brest, France (E. Cornec-Le Gall); Hôpital Saint-Louis, Paris (L. Galicier, E. Azoulay); I; nstitut Pasteur, Paris (F.-X. Weill); Centre Hospitalier Universitaire de Nantes, Nantes, France (F. Fakhouri); Hôpital Lariboisière, Paris (A. Veyradier); Hôpital Européen Georges Pompidou, Paris (V. Frémeaux-Bacchi); Hôpital Saint Antoine, Paris (P. Coppo)

Main Article

Table 3

Survival analysis of 96 adults with Shiga toxin–associated hemolytic uremic syndrome, France, 2009–2017*

Characteristic Outcome

Univariate analysis

Multivariate analysis†
Survived Died Unadjusted HR (95% CI) p value Adjusted HR (95% CI) p value
Demographic data
Median age, y (IQR)‡ 58.0 (43.0–68.0) 69.0 (58.5–78.0) 1.04 (1.01–1.07) 0.01 1.03 (1.00–1.06) 0.09
Age quartile, y
20–47 24 (31.2) 1 (5.3) 1 Ref
47–60.5 18 (23.4) 5 (26.3) 6.31 (0.74–54.05) 0.09
60.5–71 21 (27.3) 4 (21.1) 4.64 (0.52–41.50) 0.17
71–99 14 (18.2) 9 (47.4) 12.93 (1.63–102.31) 0.02
M 26 (33.8) 9 (47.4)
51 (66.2)
10 (52.6)
0.66 (0.27–1.63)
0.36 (0.13–1.02)
Medical history
>1 underlying condition 50 (64.9) 19 (100.0) <0.01§
Median age-weighted CCI (IQR)‡ 2.0 (0.0–4.0) 5.0 (3.0–6.0) 1.15 (1.03–1.28) 0.02
Digestive disease 18 (23.4) 11 (57.9) 4.07 (1.63–10.14) <0.01 2.04 (0.70–5.90) 0.19
Cardiovascular disease 36 (46.8) 12 (63.2) 2.04 (0.80–5.19) 0.14 1.31 (0.43–3.98) 0.63
Heart disease 14 (18.2) 6 (31.6) 1.75 (0.66–4.59) 0.26
Renal disease 12 (15.6) 3 (15.8) 0.87 (0.25–3.01) 0.83
Neurologic disease 12 (15.6) 6 (31.6) 1.94 (0.74–5.11) 0.18 1.14 (0.37–3.52) 0.81
Autoimmune disease 8 (10.4) 3 (15.8) 1.45 (0.42–4.97) 0.56
15 (19.5)
12 (63.2)
4.36 (1.72–11.07)
3.54 (1.24–10.14)
Indicators of organ involvement
Median platelet count, × 109 cells/L (IQR)‡¶ 56.0 (32.5–122.0) 59.5 (45.8–95.0) 1.00 (1.00–1.00) 0.83
Median serum creatinine, µmol/L (IQR)¶ 222 (140–396) 221 (190–352) 1.00 (1.00–1.00) 0.45
Stage 3 acute kidney injury# 55 (71.4) 19 (100.0) 0.01§
Dialysis 44 (57.1) 17 (89.5) 5.57 (1.29–24.16) 0.02 3.49 (0.77–15.79) 0.10
Stroke, coma, or seizure 36 (46.8) 14 (73.7) 2.90 (1.04–8.06) 0.04 3.40 (1.05–11.04) 0.04
Mechanical ventilation 23 (29.9) 11 (57.9) 2.71 (1.09–6.74) 0.03
High troponin**
19 (54.3)
7 (87.5)
5.06 (0.62–41.14)

Microbiological findings
Shiga toxin genotypes††
stx1+/stx2 8 (12.1) 4 (22.2) 1 Ref
stx2+/stx1 50 (75.8) 13 (72.2) 0.64 (0.21–1.96) 0.43
stx1+/stx2+ 8 (12.1) 1 (5.6) 0.31 (0.04–2.81) 0.30
Serogroup‡‡ 0.05§
O157 9 (17.3) 1 (6.7)
O104 8 (15.4) 0
O91 8 (15.4) 4 (26.7)
O26 1 (1.9) 3 (20.0)
O80 2 (3.8) 2 (13.3)
24 (46.2)
5 (33.3)

BSC 7 (9.1) 3 (15.8) 1.52 (0.44–5.23) 0.51
TPE 63 (81.8) 16 (84.2) 1.25 (0.36–4.29) 0.72
ECZ 33 (42.9) 5 (26.3) 0.49 (0.18–1.36) 0.17
Time from admission to ECZ treatment, d§§
<7 16 (50.0) 2 (66.7)
>7 16 (50.0) 1 (33.3)
Macrolides 21 (27.3) 5 (26.3) 0.86 (0.31–2.39) 0.77
Other antimicrobial drugs¶¶
43 (55.8)
14 (73.7)

2.02 (0.73–5.62)

Therapeutic strategy## 0.43§
BSC 7 (9.1) 3 (15.8)
TPE without ECZ 37 (48.1) 11 (57.9)
ECZ without TPE 7 (9.1) 0
TPE and ECZ 26 (33.8) 5 (26.3)

*Values are no. (%), except as indicated. BSC, best supportive care; CCI, age-weighted Charlson Comorbidity Index; ECZ, eculizumab; HR, hazard ratio; IQR, interquartile range; ref, referent; TPE, therapeutic plasma exchange. †Akaike Information Criterion = 149.20; 19 events. ‡Shapiro-Wilk Normality test was used to check normality for age distribution (p = 0.30), CCI (p<0.01), and platelet count (in logarithmic form; p = 0.41 by log-normal distribution). §By log-rank test. ¶Samples taken at admission. #According to Kidney Disease Improving Global Outcomes criteria (15). **According to upper thresholds defined by respective laboratories. Out of 43 patients with known troponin level. ††Out of 84 patients with known Shiga toxin subgroups, 18 died. ‡‡Out of 67 patients with known serogroups, 15 died. §§The first day of ECZ administration was not reported in the medical records of 3 patients. ¶¶Including β-lactams, quinolones, and aminoglycosides. ##Multivariate comparison of BSC, TPE without ECZ, ECZ without TPE, and ECZ+TPE treatment regimens.

Main Article

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Main Article

1These first authors contributed equally to this article.

2Members of this group are listed at the end of this article.

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