versión impresa ISSN 0325-7541
Rev. argent. microbiol. vol.44 no.2 Ciudad Autónoma de Buenos Aires abr./jun. 2012
Two cases of urinary tract infection caused by Shiga toxin-producing Escherichia coli 0157:H7 strains
María Del P. Gadea1, Natalia Deza2, María I. Mota1,3, Carolina Carbonari2, Mitila Robatto3, Beatriz D'astek2, Victoria Balseiro1, Cristina Bazet3, Eduardo Rügnitz4, Valérie Livrelli5, Felipe Schelotto1, Marta Rivas2, Gustavo Varela1*
1Departamento de Bacteriología y Virología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;
2 Servicio Fisiopatogenia, INEI-ANLIS "Dr. Carlos G Malbrán", Buenos Aires, Argentina;
3Laboratorio de Patología Clínica. Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;
4 Departamento de Medicina Interna, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;
5 Clermont Université, Université d'Auvergne,JE 2526, Clermont-Ferrand, France. *Correspondence. E-mail: firstname.lastname@example.org
STEC strains can infect extra-intestinal sites such as the human urinary tract and sometimes cause severe complications. We report two cases of urinary tract infection caused by STEC in two elderly women with comorbidities. Although both strains belonged to the 0157:H7 serotype and carried genes associated with severe illness, none of the patients developed hemolytic uremic syndrome (HUS). These findings provide additional evidence for the presence of these agents in our country and in the region, and highlight the need to maintain an active surveillance system of HUS cases, placing special emphasis on the study of other sites of infection in patients with non-diarrheal HUS.
Key words: E. coli 0157:H7; STEC; Urinary tract infection.
RESUMEN Dos casos de infección del tracto urinario causados por cepas de Escherichia coli 0157:H7 productoras de toxina Shiga. En los seres humanos, las cepas STEC pueden producir infección en sitios extraintestinales, como el tracto urinario, y causar complicaciones graves. Comunicamos dos casos de infección urinaria por STEC en dos mujeres ancianas con comorbilidades. Aunque ambas cepas correspondieron al serotipo 0157:H7 y portaban los genes asociados con enfermedad grave, ninguna de las pacientes desarrolló síndrome urémico hemolítico (SUH). Estos hallazgos constituyen una evidencia adicional de la presencia de estos agentes en nuestro país y en la región, y destacan la necesidad de mantener un sistema activo de vigilancia, con especial énfasis en el estudio de otros sitios de Infección en pacientes que presentan SUH no asociado a diarrea.
Palabras clave: E. coli 0157:H7; STEC; Infección del tracto urinario.
Shiga toxin (Stx)-producing Escherichia coli (STEC) can cause diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Post-enteric HUS, a life-threatening complication, is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. Moreover, STEC strains can infect the human urinary tract and also cause non-diarrheal HUS (1, 6).
The ability of STEC strains to cause severe disease in humans is related to the capacity to secrete Stx1, Stx2, and/or variant toxins (1), encoded by lysogenic bacteriophages. Another virulence factor of STEC strains is a 94-kDa outer membrane protein, called intimin. It is encoded by an eae gene located on a 34-kb chromosomal pathogenicity island termed Locus of Enterocyte Effacement (LEE). This locus is associated with intimate adherence to epithelial cells, initiation of host signal transduction pathways, and formation of attaching-and-effacing intestinal lesions (1). Some STEC strains produce also an enterohemorraghic hemolysin (EHEC-Hly), encoded by a large plasmid-borne (90-kb) ehxA gene, which has been associated with severe clinical disease in humans (1).
In this report we describe two cases of urinary tract infection (UTI) caused by STEC O157:H7 in adults who did not develop HUS.
First case. An 84-years-old woman with medical history of hypertension, vaginal prolapse and a stage 3 chronic kidney disease was admitted to the hospital on July 5, 2010 with fever and anorexia. She had watery diarrhea during 48 hours before the admission; without fever, nausea or vomiting. Diuresis was maintained.
Laboratory tests yielded the following results: serum potassium 8.5 mEq/L (normal range 3.5-5.5 mEq/L), azotemia 1.65 g/L (normal range 0.2-0.6 g/L), creatinine 1.78 mg/dL (normal range 0.2-0.6) mg/dL, and hemoglobin 9.6 mg/dL (normal range 12-16 mg/dL). The blood cell count, peripheral blood smear and liver function tests were normal.
The urine analysis showed some polymorphonuclear leukocytes. Clean-catch midstream urine specimen yielded a pure culture with a count of 105 CFU/mL. She received 3 g of ceftriaxone i/v per day, with good clinical outcome. The isolate (IH1) was identified with 99% probability using the Vitek 2 Compact System (bioMérieux, Inc., Marcy l'Etoile, France) as E. coli O157 and then was sent to the Bacteriology and Virology Department-Institute of Hygiene, Universidad de la República and to the National Reference Laboratory of Argentina , to complete its characterization.
Second case. A 72-years-old woman with a medical history of urinary incontinence and repeated urinary infections, living in an elderly long term care facility located at the same town than the first patient, was admitted to the hospital with symptoms of acute cystitis on October 25, 2010.
In 2002, she underwent total hysterectomy and bilateral anexectomy due to an ovarian mucinous cystadenoma.
The urine analysis showed leukocytes, erythrocytes and proteinuria of 0.3 g/L. Clean-catch midstream urine specimen yielded a pure culture with a count higher than 105 CFU/mL and the isolate (IH2) was identified with 99% probability using the Vitek 2 Compact System as E. coli O157. She received 15 mg/Kg of cefuroxime axetil orally every 24 hours, with good clinical outcome. The strain was submitted also to the above-mentioned laboratories to complete its characterization.
Confirmation of isolates as E. coli was performed through biochemical tests and the serotyping was conducted using antisera provided by the Instituto Nacional de Producción de Biológicos- ANLIS "Dr. Carlos G. Malbrán".
Antimicrobial susceptibility to amikacin, ampicillin, ceftriaxone, cefuroxime, ciprofloxacin, cloramphenicol, colistin, gentamicin, nalidixic acid, nitrofurantoin, streptomycin, tetracycline, and trimethoprim-sulfamethoxazole was established according to Clinical Laboratory Standards Institute (CLSI) guidelines (2).
The stx1, stx2, and rfbO157 genes were detected by a multiplex PCR as described by Leotta et al. (4), while the ehxA, eae, and fliCH7 genes were investigated according to previously described procedures (5).
In order to determine Stx production, bacterial supernatant and periplasmic cell extracts were used on Vero cells for cytotoxicity assays(5).
The orientation of the invertible DNA element containing the fimA promoter was determined using a PCR-RFLP assay (7).
Phage typing was performed by the method described by Khakhria et al. (3).
The strain IH1 was characterized as E. coli O157:H7 harboring the stx1, eae-?1, ehxA, flicH7 and fimA (phase off) genes of phage type (PT) 39. Meanwhile, the strain IH2 was characterized as E. coli O157:H7 harboring the stx1/stx2, eae-?1, flicH7 and fimA (phase off) genes of PT40. Expression of toxicity in Vero cells assays and of flagellar antigens by slide agglutination were demonstrated in both isolates.
Both strains were susceptible to all antibiotics tested.
Unusual cases of HUS involving patients who presented UTI have been previously reported. The O-groups of the STEC strains involved were OX3, O5, O103, O138, O145, and O157 (6).
Although both strains belonged to the O157:H7 serotype and carried genes associated with severe illness, neither patient developed HUS.
Neither the origin and the reservoir of the recovered O157:H7 STEC strains, nor the epidemiologic link between both UTI cases could not be established. Furthermore, both strains showed different stx-genotypes and PTs.
We can assume that the STEC O157:H7 strains reached the urinary tract by the ascending route from the gastrointestinal tract. Both patients had known predisposing factors that favored it.
Between 2002 and 2008 we studied 36 children with clinical diagnosis of post-enteric HUS; in three cases we recovered STEC strains of serotypes O157:H7, O111:NM, and O26:H11, and in a fourth case an STEC O26:H11/O145:HNT co-infection was detected (8). However, there have been no previous local or regional reports of non-diarrheal HUS caused by STECor episodes of UTI due to this pathogen.
The detection of STEC O157:H7 in urine infections provides additional evidence about the presence of this serotype in the region, reinforcing the importance of performing an active surveillance of gastrointestinal and urinary infections caused by STEC.
Both patients have given their informed consent for the cases report to be published.
This work was partially supported by a grant from the Comisión Sectorial de Investigación Científica (CSIC)-UdelaR, Montevideo, Uruguay and by and by the ECOS-Sud Program (U08B02).
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RECIBIDO: 29/11/2011 - ACEPTADO: 7/05/2012