Group A Escherichia coli-related purpura fulminans: an unusual ...
Transcript of Group A Escherichia coli-related purpura fulminans: an unusual ...
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Group A Escherichia coli-related purpura fulminans: an unusual manifestation due to an 1
unusual strain? 2
Marlène Amara (1), Stéphane Bonacorsi (2, 3, 4), Jérôme Bedel (5), Jean-Paul Mira (6), Virginie 3
Laurent (5), Koryna Socha (7), Fabrice Bruneel (5), Béatrice Pangon (1), Jean-Pierre Bédos (5) 4
and David Grimaldi (5) 5
Corresponding author : Dr David Grimaldi 6
Mailing address : Centre Hospitalier Versailles, Service de réanimation, 177 rue de Versailles 7
78157 Le Chesnay, France. Phone : +33 1 39 63 88 42. Fax : +33 1 39 63 86 88. 8
Email : [email protected] 9
1. Laboratoire de Microbiologie, CH Versailles – Site André Mignot, Le Chesnay, France 10
2. IAME, UMR 1137, INSERM, F-75018 Paris, France 11
3. IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France 12
4. AP-HP, Hôpital Robert-Debré, Service de Microbiologie, Centre National de Référence 13
associé Escherichia coli, F-75018 Paris, France 14
5. Service de Réanimation, CH Versailles – Site André Mignot, Le Chesnay, France 15
6. Service de Réanimation, Centre Hospitalier Universitaire Cochin Saint Vincent de Paul, AP-16
HP, Paris, France 17
7. Service d’anatomo-pathologie, CH Versailles – Site André Mignot, Le Chesnay, France 18
Intended category: Case report 19
JCM Accepts, published online ahead of print on 17 September 2014J. Clin. Microbiol. doi:10.1128/JCM.01362-14Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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Words count: 818 20
Keywords: Escherichia coli, purpura fulminans, CVP region, group A, ExPECs 21
Running title: Group A E. Coli purpura fulminans 22
Abstract: 23
We report an exceptional case of life-threatening group A Escherichia coli-induced purpura 24
fulminans. Genotyping of common polymorphisms in genes involved in innate immunity or 25
coagulation did not reveal known susceptibility to such manifestation. Genetic analysis of the 26
strain revealed an unusual Conserved Virulence Plasmidic region, pointing out its potential 27
virulence. 28
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Case report 30
A 53-year-old woman had a medical history of penicillin allergy and morbid obesity (Body Mass 31
Index, BMI: 46 kg/m2) treated by a Banding Gastroplasty in 2007. In 2009, she suffered from a 32
gastric necrosis complicated by a peritonitis associated with a first episode of E. coli bacteraemia. 33
At that time, she presented a septic shock without disseminated intravascular coagulation (DIC). 34
She underwent a total gastrectomy with oeso-jejunal anastomosis. Following gastrectomy, her 35
BMI decreased dramatically to 16 kg/m2. 36
In May 2013, she presented at the emergency department with weakness. Her central body 37
temperature was 38.6°C, heart rate: 144 beats/min and blood pressure 85/52 mmHg. Physical 38
exam did not point to a particular site of infection. Thoraco-abdominal CT scan did not show an 39
infectious process. Laboratory results showed evidence of severe sepsis: C-reactive protein 113 40
mg/L, leukocyte count 1.8x106 /L, arterial lactate level 7.3 mmol/L. The other results were 41
subnormal: creatininemia 80 µmol/L, platelet count 201x106/L, prothrombine ratio 59%, factor V 42
81 %, CPK 111 IU/ L (N <200). Vancomycin, aztreonam and gentamicin were initiated along 43
with a fluid loading of 3L crystalloids and continuous noradrenalin infusion up to 2,4 g/kg/min. 44
The patient was referred to the intensive care unit (ICU) and, 6 hours after admission, she 45
suddenly developed diffuse map-like purple skin lesions particularly prominent in the lower 46
limbs (Figure 1, A and B). The legs became cold and mottled. Simultaneously, she developed 47
multiorgan failure and severe DIC (platelet count 36x106/L, prothrombin rate 32%, factor V 31 48
%, D-dimers 1830 ng/mL). Arterial Doppler examination of the legs ruled out arterial thrombosis. 49
The diagnosis of purpura fulminans was made. Fresh frozen plasma and platelet concentrate were 50
transfused. The patient’s status slowly improved, the coagulation tests normalized at day 3, 51
norepinephrine was weaned off at day 7. By day 20, the patient underwent surgical debridement 52
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of cutaneous and subcutaneous tissues. After 12 weeks in the ICU, she was discharged in hospital 53
ward for renutrition. A skin graft was performed after 5 months. The two blood cultures drawn at 54
ICU admission as well as cutaneous biopsy of a necrotic lesion grew with a Penicillinase-55
producing E. coli strain identified using a MALDI-TOF mass spectrometer Microflex (Brucker, 56
Germany). Histopathological exam of the skin was in accordance with the diagnosis of purpura 57
fulminans (Figure 1, C). The cytobacteriological examination of urine was negative. Following 58
written consent, 32 well-characterized human genetic polymorphisms associated with severe 59
sepsis susceptibility were searched for (1). The patient’s genotyping did not reveal any variant of 60
the genes associated with Gram-negative detection (TLR2, TLR4 and CD14) (2) severity of 61
sepsis (TNF-α, IL-6, IL-10) (3) and coagulation disorders (coagulation factor V, Tissue Factor, 62
Protein C Receptor Endothelial, Thrombin and PAI-1) (4). The 2009 and 2013 E. coli strains 63
were further characterized by MLST sequence typing. Both of the 2009 and 2013 strains 64
belonged to the phylogenetic group A and harbored the sequence type ST398 and ST 10 65
respectively. The search for 14 virulence factors (VFs) was performed by PCR as previously 66
described (5,6). The 2013 strain did not carry any of the adhesin/invasin (Pap, Sfa, and IbeA) nor 67
any of the toxin (Hly, Cnf-1, Sat, Vat and colibactin) genes sought. Interestingly, it harbored two 68
iron acquisition systems, yersiniabactin and salmochelin, as well as the sit system ; plasmidic 69
OmpT (OmpTp) encoding a putative outer membrane protease (omptin) and cva encoding 70
colicinV, hlyF encoding α-haemolysin, a poreforming toxin, ets operon encoding a type I 71
secretion system and iss, the increased serum survival gene. This combination of genes, together 72
with the aerobactin gene, lacking in this observation, is considered to be the signature of the 73
Conserved Virulence Plasmidic (CVP), which contains eight operons or genes amplified by 74
multiplex PCR as previously described (7). Complete or almost complete CVP region was 75
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identified in sequenced plasmids, from human, avian and environmental origin (7–11). The 2009 76
strain did carry neither the CVP region genes nor any of the VFs sought. 77
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Purpura fulminans is a life-threatening condition caused by a sudden and severe DIC, typically 79
caused by meningococcemia and sometimes pneumococcemia, but Escherichia coli-related 80
purpura fulminans remains exceptional (12,13). Extraintestinal pathogenic Escherichia coli 81
(ExPECs) infections represent a growing public health concern (14,15). Strains commonly belong 82
to phylogenic groups B2 and D (16) and lead to various clinical features, such as urinary tract 83
infections, meningitis and occasionally severe skin infections (17), (18). Phylogenic group A is, 84
with the B1 group, the group to whom belong almost all commensal strains (19). However, some 85
of these strains may be responsible for severe invasive infections and we recently showed that 86
CVP region contributes to the extra intestinal virulence of E. coli isolates belonging to these 87
phylogroups (7). 88
We report herein an unusual case of commensal group A E. coli-related purpura fulminans in a 89
patient that had previously exhibited an episode of E. coli bacteraemia without such presentation. 90
At the time of the second bacteraemia, the patient had experienced a total gastrectomy and a 91
severe weight loss. The alteration of the gastrointestinal tract anatomy may predispose to 92
bacterial translocation and malnutrition could increase the severity of the infection, however none 93
of these two factors are involved in DIC. The absence of DIC during the first episode of 94
bactaeremia, together with the fact that known genetic markers for increased susceptibility to DIC 95
were lacking in the host suggest that the unusual presentation was related to the pathogen’s 96
genotype and possibly to the presence of CVP region, since the strain does not carry other 97
particular VFs. 98
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In conclusion, this observation points out the potential virulence associated with the CVP region, 99
which could be involved in the emergence of “unconventional” ExPECs belonging to human 100
commensal phylogroups A/B1 (7) and should be explored in further studies. The role of bacterial 101
genetic determinants such as the CVP region in this life threatening syndrome remains to be 102
elucidated. 103
Acknowledgments: We thank Mr Christophe Rousseau for his technical help for the genotyping 104
and Dr Maher Anous for his help in the redaction of this manuscript. 105
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Figure caption: 170
FIG. 1 Bilateral necrotic legs lesions of Purpura fulminans (A and B). Histopathological exam of 171
the skin revealed a sparse infiltrate of often altered neutrophils around the vessels, extravasated 172
erythrocytes and edema of the dermis (C). 173
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