Group A Escherichia coli-Related Purpura Fulminans: an Unusual Manifestation Due to an Unusual Strain?

Abstract

We describe an exceptional case of life-threatening group A Escherichia coli-induced purpura fulminans. Genotyping of common polymorphisms in genes involved in innate immunity or coagulation did not reveal known susceptibility to such a manifestation. Genetic analysis of the strain revealed an unusual conserved virulence plasmidic region, pointing out its potential virulence.

CASE REPORT

A 53-year-old woman had a medical history of penicillin allergy and morbid obesity (body mass index [BMI], 46 kg/m²), treated by a banding gastroplasty in 2007. In 2009, she suffered from gastric necrosis complicated by peritonitis associated with a first episode of Escherichia coli bacteremia. At that time, she presented with septic shock without disseminated intravascular coagulation (DIC). She underwent a total gastrectomy with esojejunal anastomosis. Following gastrectomy, her BMI decreased dramatically, to 16 kg/m².

In May 2013, she presented at the emergency department with weakness. Her central body temperature was 38.6°C, with a heart rate of 144 beats/min and blood pressure of 85/52 mm Hg. A physical exam did not point to a particular site of infection. A thoracoabdominal computed tomography (CT) scan did not show an infectious process. Laboratory results showed evidence of severe sepsis: a C-reactive protein level of 113 mg/liter, leukocyte count of 1.8 × 10⁹/liter, prothrombin ratio of 59%, and arterial lactate level of 7.3 mmol/liter. The other results were normal: creatininemia at 80 μmol/liter, platelet count of 201 × 10⁹/liter, factor V level of 81%, and creatine phosphokinase (CPK) level of 111 IU/liter. Administration of vancomycin, aztreonam, and gentamicin was initiated, along with fluid loading of 3 liters crystalloids and continuous noradrenalin infusion up to 2.4 μg/kg of body weight/min. The patient was referred to the intensive care unit (ICU), and 6 h after admission, she suddenly developed diffuse map-like purple skin lesions that were particularly prominent in the lower limbs (Fig. 1A and B). The legs became cold and mottled. Simultaneously, she developed multiorgan failure and severe DIC (platelet count, 36 × 10⁹/liter; prothrombin rate, 32%; factor V, 31%; d dimers, 1,830 ng/ml). Arterial Doppler examination of the legs ruled out arterial thrombosis. The diagnosis of purpura fulminans was made. Fresh frozen plasma and platelet concentrate were transfused. The patient's status slowly improved; the coagulation tests normalized at day 3, and the patient was weaned off norepinephrine at day 7. By day 20, the patient underwent surgical debridement of cutaneous and subcutaneous tissues. After 12 weeks in the ICU, she was discharged in the hospital ward for renutrition. A skin graft was performed after 5 months. The two blood cultures drawn at ICU admission, as well as a cutaneous biopsy specimen of a necrotic lesion, grew with a penicillinase-producing E. coli strain identified using a Microflex matrix-assisted laser desorption ionization–time-of-flight (MALDI-TOF) mass spectrometer (Bruker, Germany). Histopathological exam of the skin was in accordance with the diagnosis of purpura fulminans (Fig. 1C). The cytobacteriological examination of urine was negative. Following written consent, 32 well-characterized human genetic polymorphisms associated with severe sepsis susceptibility were searched for (1). The patient's genotyping did not reveal any variant of the genes associated with Gram-negative detection (Toll-like receptor 2 [TLR2], TLR4, and CD14 genes) (2), severity of sepsis (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], and IL-10 genes) (3), and coagulation disorders (coagulation factor V, tissue factor, protein C receptor endothelial, thrombin, and PAI-1 genes) (4). The 2009 and 2013 E. coli strains were further characterized by multilocus sequence typing (MLST). Both the 2009 and 2013 strains belonged to phylogenetic group A, and they harbored sequence types ST398 and ST10, respectively. The search for 14 virulence factors (VFs) was performed by PCR as previously described (5, 6). The 2013 strain did not carry any of the adhesin/invasin (Pap, Sfa, and IbeA) nor any of the toxin (Hly, Cnf-1, Sat, Vat, and colibactin) genes sought. Interestingly, it harbored two iron acquisition systems, yersiniabactin and salmochelin, and the sit system; plasmidic ompT (ompTp), encoding a putative outer membrane protease (omptin), and cva, encoding colicin V, hlyF, encoding α-hemolysin, a pore-forming toxin, the ets operon, encoding a type I secretion system, and iss, the increased serum survival gene. This combination of genes, together with the aerobactin gene, lacking in this observation, is considered to be the signature of the conserved virulence plasmidic (CVP) region, which contains eight operons or genes amplified by multiplex PCR, as previously described (7). A complete or almost-complete CVP region has been identified in sequenced plasmids of human, avian, and environmental origins (7–11). The 2009 strain carried neither the CVP region genes nor any of the VFs sought.

FIG 1.

(A and B) Bilateral necrotic leg lesions of purpura fulminans. (C) Histopathological exam of the skin revealed a sparse infiltrate of often altered neutrophils around the vessels, extravasated erythrocytes, and edema of the dermis.

Purpura fulminans is a life-threatening condition caused by a sudden and severe DIC, typically caused by meningococcemia and sometimes pneumococcemia, but Escherichia coli-related purpura fulminans remains exceptional (12, 13). Extraintestinal pathogenic Escherichia coli (ExPEC) infections represent a growing public health concern (14, 15). Strains commonly belong to phylogenic groups B2 and D (16) and lead to various clinical features, such as urinary tract infections, meningitis, and occasionally severe skin infections (17), (18). Phylogenic group A is, along with the B1 group, the group to which almost all commensal strains belong (19). However, some of these strains may be responsible for severe invasive infections, and we recently showed that the CVP region contributes to the extraintestinal virulence of E. coli isolates belonging to these phylogroups (7).

We describe herein an unusual case of commensal group A E. coli-related purpura fulminans in a patient that had previously exhibited an episode of E. coli bacteremia without such presentation. At the time of the second bacteremia, the patient had experienced a total gastrectomy and severe weight loss. The alteration of the gastrointestinal tract anatomy may predispose to bacterial translocation, and malnutrition could increase the severity of the infection; however, neither of these two factors is involved in DIC. The absence of DIC during the first episode of bacteremia, together with the fact that known genetic markers for increased susceptibility to DIC were lacking in the host, suggest that the unusual presentation was related to the pathogen's genotype and possibly to the presence of the CVP region, since the strain does not carry other particular VFs.

In conclusion, this observation points out the potential virulence associated with the CVP region, which could be involved in the emergence of “unconventional” ExPEC belonging to human commensal phylogroups A/B1 (7) and should be explored in further studies. The role of bacterial genetic determinants such as the CVP region in this life-threatening syndrome remains to be elucidated.