Colonization with the Man's Escherichia coli Strain among Female Sex Partners of Men with

Transcription

1 JCM Accepted Manuscript Posted Online 1 April 2015 J. Clin. Microbiol. doi: /jcm Copyright 2015, American Society for Microbiology. All Rights Reserved. 1 2 Colonization with the Man's Escherichia coli Strain among Female Sex Partners of Men with Febrile Urinary Tract Infection Peter Ulleryd 1,2, * (#), Torsten Sandberg 2, Flemming Scheutz 3, Connie Clabots 4, Brian D. Johnston 4,5, Paul Thuras 4,6, and James R. Johnson 4,5 1 Department of Communicable Disease Control and Prevention, Region Västra Götaland, Sweden 2 Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 3 WHO Collaborating Centre for Reference and Research on Escherichia and Klebsiella, Statens Serum Institute, Copenhagen, Denmark 4 Veterans Affairs Medical Center, Minneapolis, Minnesota, USA 5 Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA 6 Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, USA Keywords: UTI, sex partners, E. coli, colonization, transmission, typing Running title: E. coli in sex partners of men with UTI Corresponding author: (#) Peter Ulleryd, Department of Communicable Disease Control and Prevention, Region Västra Götaland, Kaserntorget 11 B, Gothenburg, Sweden. *At present working at WHO HQ, Geneva, Switzerland (ullerydk@who.int) 1

2 26 ABSTRACT Of 23 unique Escherichia coli strains from 10 men with febrile urinary tract infection (UTI) and their female sex partners, 6 strains (all UTI-causing) were shared between partners. Molecularly, the 6 shared strains appeared more virulent than the 17 non-shared strains, being associated with phylogenetic group B2, sequence types ST73 and ST127, and multiple specific virulence genes. This supports UTI as sometimes being sexually transmitted. Downloaded from on March 16, 2019 by guest 2

3 Introduction. Escherichia coli is the leading cause of urinary tract infections (UTIs), a tremendously common and costly illness (1). Although the causative E. coli strains usually derive from the host's own gastrointestinal microbiota (2, 3), their more proximate reservoirs are poorly understood Sharing of E. coli strains, whether pathogenic or not, is common among closely associated hosts, including pets and sex partners (4-19). However, strain sharing between a man with E. coli UTI and his healthy female sexual partner (FSP) has not been reported. We capitalized on a large cohort of men with E. coli febrile UTI (FUTI) to assess this phenomenon's frequency and the characteristics of any such shared strains. Subjects and specimens. Ten men with community-acquired E. coli FUTI and a FSP who was willing to participate in the study were identified within a larger cohort study of male FUTI at Sahlgrenska University Hospital, Gothenburg, Sweden, (21, 22). Men had to have a temperature 38.0 C, at least one urinary-tract-referable symptom or sign (frequency, dysuria, flank pain, or costovertebral angle tenderness), and 10 4 colony-forming units (cfu)/ml of a uropathogen on urine culture (21, 22). Consenting subjects underwent culture surveillance of urine, feces, and (for FSPs) the vagina initially and with any subsequent UTI episode in either partner. Midstream urine samples, collected per protocol, were kept at 4 C until cultured semiquantitatively on blood and cysteine lactose electrolyte-deficient agar. Significant growth was defined as 10 4 cfu/ml of E. coli. The last free-lying colony was saved. 3

4 Males self-collected rectal samples per protocol. An author (P.U.) collected vaginal and rectal samples from FSPs. Swabs were streaked to modified Conradi-Drigalski agar, for overnight incubation. The last three free-lying colonies on each plate, plus any morphologically distinct colonies, were picked for analysis; this provides 97% sensitivity for detecting the quantitatively predominant clone in rectal samples (23). Confirmed E. coli isolates were stored in agar stabs (24). Isolate characterization. E. coli isolates underwent O-typing or full O:K:H-serotyping at Statens Serum Institute, Copenhagen, DK. One colony per O:K:H-serotype per specimen, and colonies differing by O-type from the index FUTI isolate, underwent molecular typing, including XbaI pulsed-field gel electrophoresis (PFGE) profiling (25). Pulsotypes (here equated with strains) were assigned based on 94% profile similarity to index profiles within a large PFGE database (26). One representative per sample per PFGE type underwent PCR-based major phylogenetic group determination (25). Extended virulence genotypes were determined by multiplex PCR (27-29). Sequence type (ST) and clonal complex (CC; cluster of closely-related STs) was determined by PCR (27), fumc-fimh sequence-analysis (30), and/or multi-locus sequence typing ( Statistical methods. Comparisons of proportions and virulence score were tested using Fisher's exact test and the Mann-Whitney U test, respectively, with significance set at P <.05. Study population. The 10 index men with FUTI had a median age of 55 (range, 37 69) and a median temperature of 39.3 C (range, ) (Table S1). None affirmed anal intercourse 4

5 during the preceding 6 months. Two patients had voiding problems suggesting prostatism. Only 3 had possible UTI-predisposing conditions: post-operative urethral catheterization 3 days pre-futi episode, diabetes mellitus, and a small bladder adenoma. The 10 FSPs' median age was 48.5 years (range, 32 62). All denied UTI symptoms and antibiotic treatment in the preceding three months. Culture results. Culture surveillance was done once for 7 couples and repeatedly (over 1 to 22 months) for 3 couples. Of the 76 total rectal, vaginal, and urine cultures, 59 (78%) yielded E. coli. Sequential serotyping and PFGE analysis resolved 23 unique E. coli strains (Figure 1), which were predominantly from phylogroup B2 (12, 52%) and represented 15 CCs. Seventeen (74%) qualified molecularly as ExPEC. Strain sharing. Of the 23 strains, 6 occurred in both members of a particular couple, and only in that couple (Figure 1). All 6 (100%) shared strains, vs. 4 (24%) non-shared strains, represented the male's index FUTI isolate (P =.002) (Table 1). Shared strains also were more likely to cause asymptomatic bacteriuria (ABU) or acute cystitis, and to colonize the woman's rectum and/or vagina. Longitudinal follow-up. During serial surveillance, in couples #10 and #29 the shared strains caused sustained co-colonization and recurrent symptomatic UTI and/or ABU (Table S2-3). In couple #95, at the time of the man's E. coli FUTI episode the FSP was colonized extensively with the index E. coli strain, which 3 weeks later persisted in her despite being undetectable in the man. 5

6 Characteristics of shared strains. Compared with non-shared strains, the 6 shared strains more often represented phylogroup B2 and uropathogenic lineages CC73 or CC127, and more often contained papg III, sfa/foc, sfas, hlyd, cnf1, iron, and malx (Table S4) Comment. This in-depth microbiological survey of 10 men with E. coli FUTI and their healthy FSPs identified frequent (60%) co-colonization of FSPs with the man's index E. coli strain. This equals or exceeds the prevalence of such co-colonization among male partners of women with E. coli cystitis (5, 11, 12). Such strain sharing may result from person-to-person transmission or parallel acquisition. Cocolonization between sex partners has been associated with specific sex practices (12). We lacked data regarding sexual practices other than anal intercourse (which our subjects denied), so cannot comment on behavioral correlates of co-colonization. The potential clinical implications of co-colonization include risks of (i) acute UTI in a FSP due to the male's UTI strain, and (ii) reintroduction of the strain into the index subject from a co-colonized partner. The first scenario occurred here (couple #10). Whether decolonization of co-colonized sex partners is warranted deserves study. As in previous studies (6, 7, 12, 31), shared strains were distributed more broadly, caused more infections, and exhibited more uropathogenic traits than non-shared strains. This supports that certain E. coli traits and lineages promote both UTI pathogenesis and intestinal colonization (32). Conceivably, interventions directed toward these traits and/or lineages could prevent UTI by blocking both proceesses. 6

7 Since we investigated middle-aged male FUTI patients without serious medical or urological compromise, and their middle-aged FSPs, our results cannot be extrapolated to other forms of UTI or host populations. Additionally, since our rectal sampling method detects mainly dominant fecal E. coli clones (23), we likely underestimated the true frequency of cocolonization (33). Summary. We demonstrated frequent sharing of the causative E. coli strain between men with FUTI and their FSPs, which supports male UTI as sometimes being sexually transmitted. Strain sharing was more common and extensive for classical urovirulent strains, suggesting that "urovirulence" traits may also promote colonization and transmission. Downloaded from on March 16, 2019 by guest 7

8 142 ACKNOWLEDGMENTS This material is based upon work supported by The Medical Society of Gothenburg, Sweden (P.U.), and the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, USA (J.R.J.). The technical assistance of Susanne Jespersen, Statens Serum Institute, Copenhagen, Denmark is highly appreciated. Downloaded from on March 16, 2019 by guest 8

9 149 REFERENCES Russo TA, Johnson JR Medical and economic impact of extraintestinal infections due to Escherichia coli: focus on an increasingly important endemic problem. Microbes Infect. 5: Yamamoto S, Tsukamoto T, Terai A, Kurazono H, Takeda Y, Yoshida O Genetic evidence supporting the fecal-perineal-urethral hypothesis in cystitis caused by Escherichia coli. J. Urol. 157: Nielsen KL, Dynesen P, Larsen P, Frimodt-Moller N Faecal Escherichia coli from patients with E. coli urinary tract infection and healthy controls who have never had a urinary tract infection. J. Med. Microbiol. 63: Caugant DA, Levin BR, Selander RK Distribution of multilocus genotypes of Escherichia coli within and between host families. J. Hyg. 92: Manges AR, Johnson JR, Riley LW Intestinal population dynamics of UTIcausing Escherichia coli within heterosexual couples. Curr. Issues. Intest. Microbiol. 5: Johnson JR, Clabots C, Kuskowski MA Multiple-host sharing, long-term persistence, and virulence of Escherichia coli clones from human and animal household members. J. Clin. Microbiol. 46: Johnson JR, Owens K, Gajewski A, Clabots C Escherichia coli colonization patterns among human household members and pets, with attention to acute urinary tract infection. J. Infect. Dis. 197: Johnson JR, Miller S, Johnston B, Clabots C, Debroy C Sharing of Escherichia coli sequence type ST131 and other multidrug-resistant and Urovirulent E. coli strains among dogs and cats within a household. J. Clin. Microbiol. 47:

10 Damborg P, Nielsen SS, Guardabassi L Escherichia coli shedding patterns in humans and dogs: insights into within-household transmission of phylotypes associated with urinary tract infections. Epidemiol. Infect. 137: Stamey TA, Timothy M, Millar M, Mihara G Recurrent urinary infections in adult women. The role of introital enterobacteria. Calif. Med. 115: Foxman B, Zhang L, Tallman P, Andree BC, Geiger AM, Koopman JS, Gillespie BW, Palin KA, Sobel JD, Rode CK, Bloch CA, Marrs CF Transmission of uropathogens between sex partners. J. Infect. Dis. 175: Foxman B, Manning SD, Tallman P, Bauer R, Zhang L, Koopman JS, Gillespie B, Sobel JD, Marrs CF Uropathogenic Escherichia coli are more likely than commensal E. coli to be shared between heterosexual sex partners. Am. J. Epidem. 156: Johnson JR, Clabots C Sharing of virulent Escherichia coli clones among household members of a woman with acute cystitis. Clin. Infect. Dis. 43:e Ender PT, Gajanana D, Johnston B, Clabots C, Tamarkin FJ, Johnson JR Transmission of an extended-spectrum-beta-lactamase-producing Escherichia coli (sequence type ST131) strain between a father and daughter resulting in septic shock and Emphysematous pyelonephritis. J. Clin. Microbiol. 47: Johnson JR, Anderson JT, Clabots C, Johnston B, Cooperstock M Withinhousehold sharing of a fluoroquinolone-resistant Escherichia coli sequence type ST131 strain causing pediatric osteoarticular infection. Pediatr. Infect. Dis. 29: Wong ES, Stamm WE Sexual acquisition of urinary tract infection in a man. JAMA 250:

11 Bailey RR, Peddie BA, Swainson CP, Kirkpatrick D Sexual acquisition of urinary tract infection in a man. Nephron 44: al-wali W, Hamilton-Miller JM, Joshi S, Brumfitt W A case of recurrently sexually transmitted urinary tract infection. Genitourin. Med. 65: Hebelka M, Lincoln K, Sandberg T Sexual acquisition of acute pyelonephritis in a man. Scand. J. Infect. Dis. 25: Johnson JR, Delavari P Concurrent fecal colonization with extraintestinal pathogenic Escherichia coli in a homosexual man with recurrent urinary tract infection and in his male sex partner. Clin. Infect. Dis. 35:E Ulleryd P, Zackrisson B, Aus G, Bergdahl S, Hugosson J, Sandberg T Selective urological evaluation in men with febrile urinary tract infection. BJU Int. 88: Ulleryd P, Sandberg T Ciprofloxacin for 2 or 4 weeks in the treatment of febrile urinary tract infection in men: a randomized trial with a 1 year follow-up. Scand. J. Infect. Dis. 35: Lidin-Janson G, Kaijser B, Lincoln K, Olling S, Wedel H The homogeneity of the faecal coliform flora of normal school-girls, characterized by serological and biochemical properties. Med. Microbiol. Immunol. (Berl.) 164: Ørskov I, Ørskov F, Birch-Andersen A, Kanamori M, Svanborg-Eden C O, K, H and fimbrial antigens in Escherichia coli serotypes associated with pyelonephritis and cystitis. Scand. J. Infect. Dis. Suppl. 33: Clermont O, Christenson JK, Denamur E, Gordon DM The Clermont Escherichia coli phylo-typing method revisited: improvement of specificity and detection of new phylo-groups. Environ. Microbiol. Rep. 5:

12 Johnson JR, Nicolas-Chanoine MH, DebRoy C, Castanheira M, Robicsek A, Hansen G, Weissman S, Urban C, Platell J, Trott D, Zhanel G, Clabots C, Johnston BD, Kuskowski MA; MASTER Investigators Comparison of Escherichia coli ST131 pulsotypes, by epidemiologic traits, Emerg. Infect. Dis. 18: Johnson JR, Menard M, Johnston B, Kuskowski MA, Nichol K, Zhanel GG Epidemic clonal groups of Escherichia coli as a cause of antimicrobial-resistant urinary tract infections in Canada, 2002 to Antimicrob. Agents Chemother. 53: Johnson JR, Johnston B, Kuskowski MA, Nougayrede JP, Oswald E Molecular epidemiology and phylogenetic distribution of the Escherichia coli pks genomic island. J. Clin. Microbiol. 46: Johnson JR, Stell AL Extended virulence genotypes of Escherichia coli strains from patients with urosepsis in relation to phylogeny and host compromise. J. Infect. Dis. 181: Weissman SJ, Johnson JR, Tchesnokova V, Billig M, Dykhuizen D, Riddell K, Rogers P, Qin X, Butler-Wu S, Cookson BT, Fang FC, Scholes D, Chattopadhyay S, Sokurenko E High-resolution two-locus clonal typing of extraintestinal pathogenic Escherichia coli. Appl. Environ. Microbiol. 78: Murray AC, Kuskowski MA, Johnson JR Virulence factors predict Escherichia coli colonization patterns among human and animal household members. Ann. Intern. Med. 140: Johnson JR, Scheutz F, Ulleryd P, Kuskowski MA, O'Bryan TT, Sandberg T Host-pathogen relationships among Escherichia coli isolates recovered from men with febrile urinary tract infection. Clin. Infect. Dis. 40:

13 Lautenbach E, Bilker WB, Tolomeo P, Maslow JN Impact of diversity of colonizing strains on strategies for sampling Escherichia coli from fecal specimens. J. Clin. Microbiol. 46:

14 TABLE 1. Colonization and clinical characteristics of 23 Escherichia coli strains from 10 men with FUTI a and their female sexual partners in relation to strain sharing. 253 Prevalence of characteristic, no. (column %) Characteristic Total (n = 23) Non-shared strains (n = 17) Shared strains (n = 6) P value, nonshared vs. shared b Male, any site 18 (78) 12 (71) 6 (100) Rectum 11 (48) 10 (59) 1 (17) FUTI a 10 (44) 4 (24) 6 (100).002 ABU during follow-up c 2 (9) 0 (0) 2 (33).06 Female, any site 11 (48) 5 (29) 6 (100).005 Rectum 10 (44) 5 (29) 5 (83).052 Vagina 4 (17) 0 (0) 4 (67).002 Acute cystitis during follow-up 1 (4) 0 (0) 1 (17) ABU during follow-up c 2 (9) 0 (0) 2 (33) a FUTI, febrile urinary tract infection. b P values (by Fisher's exact test) are shown when P <.10. c ABU, asymptomatic bacteriuria. 14

15 FIG 1. Pulsed-field gel electrophoresis (PFGE) profiles of Escherichia coli isolates from 10 men with febrile urinary tract infection and their female sex partners. Dendrogram is based on pairwise similarity relationships among XbaI PFGE profiles, as reflected in Dice similarity coefficients. Colored rectangles enclose profiles of the same pulsotype. Labels to right of dendrogram show the couple #. PFGE column lists pulsotype designation, which for shared strains is shown also to the right of each rectangle. The red circle identifies the sole instance of putative strain sharing across couples (couples 29 vs. 95), which likely was spurious (based on differences in virulence genotype). (Image on next page) Downloaded from on March 16, 2019 by guest 15

16 Downloaded from on March 16, 2019 by guest 16

17 PFGExba PFGExba PFGE YHost Sample Symptoms Sampling 4th Cystitis 2nd 4th Cystitis 5th Male 29 Male 29 Male 29 Male 29 Male 29 Male 125 Male 125 Female 149 Male 149 Male 10 Male 10 Male 10 Male 10 Male 10 Female 10 Female 10 Female 10 Female 82 Female 10 Male 103 Male 103 Male 82 Male 82 Male 121 Male 95 Male 95 Female 95 Female 95 Female 95 Female 81 Male 81 Female 131 Male 131 Female 103 Female 103 Female 125 Male Blood Cystitis Cystitis 4th 4th 4th 2nd 3rd 5th 4th 2nd 3rd 4th 4th 2nd 5th 2nd 5th 2nd 5th 2nd 5th Male Male Female 121 Female Female Male Male Male