This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Arpin, C.
Right arrow Articles by Quentin, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arpin, C.
Right arrow Articles by Quentin, C.

 Previous Article  |  Next Article 

Journal of Clinical Microbiology, August 2002, p. 3032-3034, Vol. 40, No. 8
0095-1137/02/$04.00+0     DOI: 10.1128/JCM.40.8.3032-3034.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Cross-Infection Due to Imipenem-Resistant Bacteroides fragilis Associated with a Totally Implantable Venous Port

Corinne Arpin,1 Véronique Dubois,1 Anne-Marie Rogues,2 Fanny Menard,3 Anne-Marie Gavinet,3 Jean-Pierre Maire,4 Jean-Pierre Gachie,2 Marie-Christine Bezian,3 and Claudine Quentin1*

Laboratoire de Microbiologie, Faculté de Pharmacie,1 Service d'Hygiène Hospitalière, Université de Bordeaux 2,2 Laboratoire de Bactériologie,3 Service d'Oncologie, Hôpital Saint-André, Bordeaux, France4

Received 12 October 2001/ Returned for modification 25 February 2002/ Accepted 26 April 2002


arrow
ABSTRACT
 
Four patients in an oncology ward developed Bacteroides fragilis bacteremia over a 12-day period. Cross-infection between two of them, due to an imipenem-resistant strain, was demonstrated by epidemiological investigation and genotypic typing methods (arbitrarily primed PCR fingerprinting and nucleotide sequencing of the cfiA genes and upstream IS1186/IS1168 elements).


arrow
TEXT
 
Bacteroides fragilis is often responsible for intra-abdominal sepsis and as such is an important cause of nosocomial infections (7-9, 12, 14, 17). However, very few studies have been conducted on the possible dissemination of this organism within hospitals, probably because it is typically an endogenous pathogen (6, 25). Earlier studies based on serotyping suggested that strains of B. fragilis might spread between hospitalized patients (4, 5). But more recently, by using molecular typing techniques, no clonal distribution could be detected within B. fragilis hospital isolates (13). We report here a case of cross-infection due to an imipenem-resistant B. fragilis strain, as demonstrated by epidemiological investigation and genotypic typing methods.

Over a 12-day period in September 2001, four patients hospitalized in the oncology ward of Saint-André Hospital in Bordeaux, France, presented B. fragilis bacteremia (Fig. 1) despite the low incidence of this organism among bloodstream isolates (ca. 3%) (14, 17). Of the four patients, only patients A (kidney carcinoma) and D (colic adenocarcinoma), both admitted for a subocclusive syndrome, were likely to develop B. fragilis bacteremia. Indeed, members of the B. fragilis group reside in the gut and, from this reservoir, can colonize the female genital tract but they are virtually absent in the upper respiratory tract (6, 12). Accordingly, B. fragilis bacteremia originates much more frequently from abdominal (60 to 70%) rather than pelvic (3 to 5%) processes (patient B, cervical cancer) and almost never from respiratory disease (patient C, bronchial epidermoid carcinoma) (7-9, 14, 17). Nevertheless, all four patients had risk factors for B. fragilis bacteremia that included malignancy and use of immunosuppressive therapy (14, 17).



View larger version (24K):
[in this window]
[in a new window]
  		FIG. 1. Clinical cases. Abbreviations: M, male; F, female; y, years old; sd, syndrome; BC, blood culture; d, day; {dagger}, death.

No epidemiological link could be found between the four patients, except for the insertion of a totally implantable venous port (IVP) in patients B and C on the same day, in the same operating room. The timetable for the event in this room on this day included a gastro-jejunal derivation with cholecystectomy performed in the morning by a surgical team in patient X (7:35 to 12:20 a.m.) which ended with compressive dressing of the wound with Mefix tape (Molnlycke Health Care, Warenne, Belgium). After a period during which the room was cleaned and thereafter not entered by anyone (12:20 a.m. to 3:00 p.m.), three Port-A-Cath systems (Sims, Orly, France) were implanted in patient B (3:00 to 3:45 p.m.), an unrelated patient Y (4 to 5 p.m.), and patient C (5:15 to 6:00 p.m.) by a second surgical team. In contrast to patient Y, patients B and C had an IVP outfit with a Huber needle secured by the sticking Mefix bandage instead of an ordinary dressing and they subsequently developed an IVP-related infection, as defined by bacteremia without another apparent infection focus and/or inflammation or discharge at the insertion site (15). Infection is a rare complication of IVPs, and the predominant pathogens are staphylococci (10, 15).

The nonsterile bandage used to fix the IVP and the Huber needle was suspected to be the source of the contamination. Actually, adhesive tapes that secure Huber needles are applied in close contact with the intravascular insertion site for extended periods of time and can contribute to local infections (23). A sampling campaign (12 sites), carried out in the same operating room 1 month after the initial episode showed that several articles of noncleanable, nonsterilizable equipment, including the Mefix tape, were contaminated by skin-commensal and environmental organisms. The roll of tape may have been contaminated by the digestive flora of the patient operated on in the morning (patient X). Anaerobes substantially outnumber aerobic organisms in the digestive flora, and B. fragilis appears to be one of the most virulent (6, 7-9, 25). Moreover, the B. fragilis strain Bf1149 was demonstrated to remain viable on the adhesive tape for at least 8 h when present at levels higher than 106 CFU/ml (data not shown), in agreement with the fact that B. fragilis is only a moderate obligate anaerobe (26).

The four strains of B. fragilis isolated from patients A to D gave identical or similar biochemical reactions (12) (Table 1). Antibiotyping by the disk diffusion method (23 tested antibiotics) showed that Bf1149 and Bf1150 were resistant to all ß-lactams including imipenem, in contrast with the two other strains (MICs of 128 mg/liter and 0.5 mg/liter, respectively) (Table 1). Imipenem resistance is an exceptional trait among B. fragilis strains (0 to 3%) (6, 16, 21). This resistance is due to the production of a group 3a class B metallo-ß-lactamase encoded by the silent cfiA chromosomal gene, the expression of which is promoted by the insertion of an insertion element (IS) immediately upstream (1, 18, 19, 21).


View this table:
[in this window]
[in a new window]
  		TABLE 1. Characteristics of the B. fragilis strains used in this study

In order to type the four strains of B. fragilis by a molecular method, arbitrarily primed PCR fingerprinting with four primers was undertaken (2, 18). Bf1149 and Bf1150 gave strictly identical patterns, whereas Bf1148 and Bf1151 yielded different and distinct profiles (Fig. 2). Previous PCR fingerprinting experiments have demonstrated that the cfiA-positive B. fragilis strains yield a homogeneous DNA fragment pattern (2, 18). The same data were obtained with reference genotypic typing methods (18). Thus, conventional genotypic methods are inadequate for typing the genetically homogenous cfiA-positive B. fragilis.



View larger version (44K):
[in this window]
[in a new window]
  		FIG. 2. Arbitrarily primed PCR fingerprinting of B. fragilis strains. Fragments were generated with AP12h (5'-CGGCCCCTGT-3'), AP2 (5'-ATTGCGTCCA-3'), ERIC1R (5'-ATGTAAGCTCCTGGGGATTCAC-3'), and ERIC2 (5'-AAGTAAGTGACTGGGGTGAGCG-3'). Lanes ATCC, 1148, 1149, 1150, and 1151 were patterns obtained from B. fragilis strains ATCC 25285, Bf1148, Bf1149, Bf1150, and Bf1151, respectively. Lanes M were size marker profiles (PstI fragments from the {lambda} phage DNA).

The presence of the cfiA gene and an upstream IS in Bf1149 and Bf1150 was confirmed by PCR (27). Sequence analysis of the 2,250-bp amplified DNA fragment (GenBank sequence database accession number AF429432) showed that the 747-bp cfiA genes of Bf1149 and Bf1150 were identical and differed from the most closely related cfiA sequence available in GenBank by eight mismatches, including two missense mutations (Met-79->Thr and Arg-113->Lys) (22). In addition, both Bf1149 and Bf1150 strains harbored an identical 1,320-bp IS 8 bp upstream of the cfiA gene which differed from IS1186 and IS1168 by three and seven mismatches, respectively, including one (Glu-200->Lys) and two (Ala-178->Glu and Arg-46->Cys) missense mutations, respectively. IS1186 is one of the five elements reported at present to promote the expression of cfiA (19). IS1168 is 99.7% identical to IS1186 and has been identified upstream of 5-nitroimidazole resistance genes (11). Multiple isoforms of these ISs and various sites of insertion upstream of cfiA have been described previously (3, 19, 20, 24). Since Bf1149 and Bf1150 possessed strictly identical and original sequences encompassing the cfiA gene and the upstream IS1186/IS1168-related element, these isolates were concluded to be a single strain.

In conclusion, the cluster of four cases of B. fragilis bacteremia analyzed in this study appeared to include two independent endogenous cases (patients A and D) and two cross-transmitted cases (patients B and C). This is the first demonstration of B. fragilis cross-infection by genotypic typing methods. The sticking bandage fixing the IVP and the Huber needle is speculated to be the source of cross-transmission. This observation emphasizes the need for careful assessment of all items that come in contact with multiple patients.

This work was supported by grants from the Ministère de l'Education Nationale et de la Recherche (EA525) and the Programme de Recherche Fondamentale en Microbiologie et Maladies Infectieuses et Parasitaires (Réseau ß-lactamase).


arrow
FOOTNOTES
 
* Corresponding author. Mailing address: Laboratoire de Microbiologie, Faculté de Pharmacie, Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France. Phone: (33) 5 57 57 10 75. Fax: (33) 5 56 90 90 72. E-mail: claudine.quentin{at}bacterio.u-bordeaux2.fr. Back


arrow
REFERENCES
 
    1
  1. Bush, K. 1998. Metallo-ß-lactamases: a class apart. Clin. Infect. Dis. 27(Suppl. 1):S48-S53.
    2. 2
  2. Claros, M. C., D. M. Citron, S. Hunt Gerardo, E. J. C. Goldstein, G. Schönian, T. Montag, B. Hampel, and A. C. Rodloff. 1996. Characterization of indole-negative Bacteroides fragilis group species with use of polymerase chain reaction fingerprinting and resistance profiles. Clin. Infect. Dis. 23(Suppl. 1):S66-S72.
    3. 3
  3. Edwards, R., and P. N. Read. 2000. Expression of the carbapenemase gene (cfiA) in Bacteroides fragilis. J. Antimicrob. Chemother. 46:1009-1012.[Abstract/Free Full Text]
    4. 4
  4. Elhag, K. M., and A. Senthilselvan. 1988. A serogrouping scheme for the study of the epidemiology of Bacteroides fragilis. J. Med. Microbiol. 27:199-205.
    5. 5
  5. Elhag, K. M., and S. Tabaqchali. 1978. The distribution of Bacteroides fragilis serotypes amongst clinical strains. J. Hyg. 81:89-97.
    6. 6
  6. Falagas, M. E., and E. Siakavellas. 2000. Bacteroides, Prevotella, and Porphyromonas species: a review of antibiotic resistance and therapeutic options. Int. J. Antimicrob. Agents 15:1-9.[CrossRef][Medline]
    7. 7
  7. Gorbach, S. L., and J. G. Bartlett. 1974. Anaerobic infections (first of three parts). N. Engl. J. Med. 290:1177-1184.
    8. 8
  8. Gorbach, S. L., and J. G. Bartlett. 1974. Anaerobic infections (second of three parts). N. Engl. J. Med. 290:1237-1245.
    9. 9
  9. Gorbach, S. L., and J. G. Bartlett. 1974. Anaerobic infections (third of three parts). N. Engl. J. Med. 290:1289-1294.
    10. 10
  10. Groeger, J. S., A. B. Lucas, H. T. Thaler, H. Friedlander-Klar, A. E. Brown, T. E. Kiehn, and D. Armstrong. 1993. Infectious morbidity associated with long-term use of venous access devices in patients with cancer. Ann. Intern. Med. 119:1168-1174.[Abstract/Free Full Text]
    11. 11
  11. Haggoud, A., G. Reysset, H. Azeddoug, and M. Sebald. 1994. Nucleotide sequence analysis of two 5-nitroimidazole resistance determinants from Bacteroides strains and of a new insertion sequence upstream of the two genes. Antimicrob. Agents Chemother. 38:1047-1051.[Abstract/Free Full Text]
    12. 12
  12. Jousimies-Somer, H. R., P. H. Summanen, and S. M. Finegold. 1999. Bacteroides, Porphyromonas, Prevotella, Fusobacterium, and other anaerobic gram-negative rods and cocci, p. 690-711. In P. R. Murray, E. J. Baron, M. A. Pfaller, F. C. Tenover, and R. H. Yolken (ed.), Manual of clinical microbiology, 7th ed. American Society for Microbiology, Washington, D.C.
    13. 13
  13. Kleivdal, H., and T. Hofstad. 1995. Chromosomal restriction endonuclease analysis and ribotyping of Bacteroides fragilis. APMIS 103:180-184.[Medline]
    14. 14
  14. Lombardi, D. P., and N. C. Engleberg. 1992. Anaerobic bacteremia: incidence, patient characteristics, and clinical significance. Am. J. Med. 92:53-60.[CrossRef][Medline]
    15. 15
  15. Mallaret, M. R., F. Olive, J. Fauconnier, A. Bosseray, J. P. Brion, J. Croizé, and M. Micoud. 1996. Surveillance épidémiologique des infections de cathéters à chambre implantable. Méd. Mal. Infect. 26:752-756.
    16. 16
  16. Mory, F., A. Lozniewski, S. Bland, A. Sedallian, G. Grollier, F. Girard-Pipau, M. F. Paris, and L. Dubreuil. 1998. Survey of anaerobic susceptibility patterns: a French multicentric study. Int. J. Antimicrob. Agents 10:229-236.[CrossRef][Medline]
    17. 17
  17. Patey, O., J. Breuil, T. Prazuck, J. E. Malkin, L. Ouedraogo, A. Dublanchet, and C. Lafaix. 1992. Epidémiologie des infections à Bacteroides du groupe fragilis en France. Méd. Mal. Infect. 22:42-46.
    18. 18
  18. Podglajen, I., J. Breuil, I. Casin, and E. Collatz. 1995. Genotypic identification of two groups within the species Bacteroides fragilis by ribotyping and by analysis of PCR-generated fragment patterns and insertion sequence content. J. Bacteriol. 177:5270-5275.[Abstract/Free Full Text]
    19. 19
  19. Podglajen, I., J. Breuil, and E. Collatz. 1994. Insertion of a novel DNA sequence, IS1186, upstream of the silent carbapenemase gene cfiA, promotes expression of carbapenem resistance in clinical isolates of Bacteroides fragilis. Mol. Microbiol. 12:105-114.[Medline]
    20. 20
  20. Podglajen, I., J. Breuil, A. Rohaut, C. Monsempes, and E. Collatz. 2001. Multiple mobile promoter regions for the rare carbapenem resistance in Bacteroides fragilis. J. Bacteriol. 183:3531-3535.[Abstract/Free Full Text]
    21. 21
  21. Rasmussen, B. A., K. Bush, and F. P. Tally. 1997. Antimicrobial resistance in anaerobes. Clin. Infect. Dis. 24(Suppl. 1):S110-S120.
    22. 22
  22. Rasmussen, B. A., Y. Gluzman, and F. P. Tally. 1991. Escherichia coli chromosomal mutations that permit direct cloning of the Bacteroides fragilis metallo-ß-lactamase gene. Mol. Microbiol. 5:1211-1219.[CrossRef][Medline]
    23. 23
  23. Redelmeier, D. A., and N. J. Livesley. 1999. Adhesive tape and intravascular-catheter-associated infections. J. Gen. Intern. Med. 14:373-375.[CrossRef][Medline]
    24. 24
  24. Smith, C. J., G. D. Tribble, and D. P. Bayley. 1998. Genetic elements of Bacteroides species: a moving story. Plasmid 40:12-29.[CrossRef][Medline]
    25. 25
  25. Tabaqchali, S., and M. Wilks. 1992. Epidemiological aspects of infections caused by Bacteroides fragilis and Clostridium difficile. Eur. J. Clin. Microbiol. Infect. Dis. 11:1049-1057.[CrossRef][Medline]
    26. 26
  26. Tang, Y. P., M. M. Dallas, and M. H. Malamy. 1999. Characterization of the BatI (Bacteroides aerotolerance) operon in Bacteroides fragilis: isolation of a B. fragilis mutant with reduced aerotolerance and impaired growth in in vivo model systems. Mol. Microbiol. 32:139-149.[CrossRef][Medline]
    27. 27
  27. Yamazoe, K., N. Kato, H. Kato, K. Tanaka, Y. Katagiri, and K. Watanabe. 1999. Distribution of the cfiA gene among Bacteroides fragilis strains in Japan and relatedness of cfiA to imipenem resistance. Antimicrob. Agents Chemother. 43:2808-2810.[Abstract/Free Full Text]

Journal of Clinical Microbiology, August 2002, p. 3032-3034, Vol. 40, No. 8
0095-1137/02/$04.00+0     DOI: 10.1128/JCM.40.8.3032-3034.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Katsandri, A., Papaparaskevas, J., Pantazatou, A., Petrikkos, G. L., Thomopoulos, G., Houhoula, D. P., Avlamis, A. (2006). Two Cases of Infections Due to Multidrug-Resistant Bacteroides fragilis Group Strains.. J. Clin. Microbiol. 44: 3465-3467 [Abstract] [Full Text]  
  • Ayala, J., Quesada, A., Vadillo, S., Criado, J., Piriz, S. (2005). Penicillin-binding proteins of Bacteroides fragilis and their role in the resistance to imipenem of clinical isolates. J Med Microbiol 54: 1055-1064 [Abstract] [Full Text]  
  • Dubois, V., Arpin, C., Noury, P., Andre, C., Coulange, L., Quentin, C. (2005). Prolonged Outbreak of Infection Due to TEM-21-Producing Strains of Pseudomonas aeruginosa and Enterobacteria in a Nursing Home. J. Clin. Microbiol. 43: 4129-4138 [Abstract] [Full Text]  
  • Piriz, S., Vadillo, S., Quesada, A., Criado, J., Cerrato, R., Ayala, J. (2004). Relationship between penicillin-binding protein patterns and {beta}-lactamases in clinical isolates of Bacteroides fragilis with different susceptibility to {beta}-lactam antibiotics. J Med Microbiol 53: 213-221 [Abstract] [Full Text]  

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Arpin, C.
Right arrow Articles by Quentin, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arpin, C.
Right arrow Articles by Quentin, C.

Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»