Clinical relevance of Proteus mirabilis in hospital patients: a two year survey

C. de Champs*, R. Bonnet, D. Sirot, C. Chanal and J. Sirot

Laboratoire de Bactériologie, Faculté de Médecine, 28, place Henri Dunant, 63001 Clermont-Ferrand Cedex, France


    Abstract
 Top
 Abstract
 Introduction
 Material and methods
 Results and discussion
 References
 
A retrospective study was performed on 1072 non-duplicate isolates of Proteus mirabilis, taken in the period April 1996 to March 1998, and on 100 patient charts randomly selected during the same period. P. mirabilis isolates accounted for 7.7% of Enterobacteriaceae. The isolates were predominantly from urine (70.2%); of the total, 38.0% were penicillinase-producing isolates, 6.9% were extended-spectrum ß-lactamase (ESBL)-producing isolates and 3.6% produced inhibitor-resistant ß-lactamase (IRB). ESBL-producing isolates were observed in long-stay and intensive care and IRB-producing isolates in paediatric units. Of the 95 patients whose charts were examined, 69 had a confirmed infection, which in 42 cases was nosocomial.


    Introduction
 Top
 Abstract
 Introduction
 Material and methods
 Results and discussion
 References
 
Proteus mirabilis, an organism that is often considered to be implicated in contamination and colonization, is occasionally isolated in severe infections.1 In hospitals it is the second most frequently isolated Enterobacteriaceae species after Escherichia coli.2 Wild-type isolates of this species are susceptible to ß-lactams. Acquired resistance is usually enzyme mediated and the most common plasmid-mediated ß-lactamases reported are TEM-penicillinases. Mutant TEM-type ß-lactamases have been observed in France in P. mirabilis since 1991 for extended-spectrum ß-lactamases (ESBLs)3,4 and since 1996 for inhibitorresistant TEM (IRT).5

A survey was carried out to assess the recent evolution of antibiotic susceptibility of P. mirabilis isolates, and to determine the level of implication of this species in infections.


    Material and methods
 Top
 Abstract
 Introduction
 Material and methods
 Results and discussion
 References
 
A retrospective study was conducted on data from the period 1 April 1996 to 31 March 1998. For each patient, two or more isolates of the same species and the same susceptibility pattern in the same specimen type, separated by less than 7 days, were counted once. Only isolates from diagnostic specimens were included. No additional samples were taken for the detection of P. mirabilis. Clinical isolates were identified with rapid ID32 E galleries (bioMérieux SA, Marcy-l'Étoile, France). Antibiotic susceptibility was determined by the rapid ATBE System (bioMérieux SA). IRT enzyme was detected in AMC-resistant isolates by the disc diffusion method.6 The ESBLs were detected by a modified double disc synergy test7 for isolates resistant to cephalothin and to amikacin–tobramycin and netilmicin (AAC(6')-1 producers).

The charts of 100 patients were selected using a table of random digits. Infections and their nosocomial character were defined according to the recommendations of the CDC.8 The McCabe score, for severity of underlying illness, was determined from data recorded on the day of isolation, and the severity of sepsis from the criteria of the European Study Group on Nosocomial Infections.9

Statistical analysis was made with SPSS Base 8.0 Software using Fisher's exact test, the median test and {chi}2 test to compare nosocomial (Group I) with community-acquired infections (Group II).


    Results and discussion
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 Abstract
 Introduction
 Material and methods
 Results and discussion
 References
 
Over the whole study period, P. mirabilis accounted for 1147 out of 14,886 (7.7%) Enterobacteriaceae isolates, a figure similar to that reported in a French multicentre study in 1996 (8.3%).10 The percentage was higher in long-stay care and surgical units (14.9 and 14.7%, respectively) and lower in paediatric and gynaecology–obstetric departments (5.2 and 4.1%, respectively), as observed elsewhere.10 These rates could be explained by the frequency of urinary tract infections observed in these units and by the presence of P. mirabilis infections in patients with severe underlying diseases and in those who were chronically ill.1 Most isolates were from urine (70.2%); others came from wounds (11.9%), bronchopulmonary samples (6.1%), blood cultures (2.2%) and various other samples (9.6%).

After exclusion of the repeated isolates of P. mirabilis, 1072 isolates were included. The frequency of amoxycillin-resistant P. mirabilis in this study was 48.5%, higher than the values reported in 1991–1992 (<32%).11

The ß-lactam resistance phenotypes were wild for 552 isolates (51.5%), penicillinase for 407 isolates (38.0%), ESBL for 74 isolates (6.9%) and inhibitor-resistant ß- lactamase (IRB) for 39 isolates (3.6%) (Table IGo).


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Table I. ß-Lactam resistance phenotypes of 1072 P. mirabilis isolates
 
In France the proportion of ESBL-producing isolates rose from 0.8% of P. mirabilis isolates in 199111 to 2.4% in 199610 and 3.7% in 1998.2 The highest prevalences of the ESBL were in long-stay (18.1%) and intensive care units (15.1%). No ESBL-producing isolates were observed in paediatric and gynaecology units, where IRB-producing isolates were predominant (12.5 and 9.8%, respectively).

Of the 1072 isolates, 7.6% were resistant to amikacin, 21.1% to gentamicin, 24.8% to nalidixic acid, 21.7% to pefloxacin and 43.9% to co-trimoxazole (Table IIGo). The resistance to amikacin may be associated with ESBL-producing isolates, which were often resistant to amikacin (85.1%), and the resistance to gentamicin may be associated with penicillinase- and IRB-producing isolates, whose resistance rates to gentamicin were 43.6 and 94.4%, respectively.


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Table II. Percentage of isolates resistant to other antibiotics in each ß-lactam resistance phenotype
 
The frequency of resistance to pefloxacin in IRBproducing isolates was low (5.4%), perhaps because quinolones are rarely prescribed in paediatric and gynaecology– obstetric units.

Documented information was obtained for 95 of the 100 randomly selected patients. In 69/95 patients P. mirabilis was implicated in an infection. However, in 29/75 sites (38.7%), it was associated with another microorganism (and in 6/7 in respiratory tract infections), and so it is difficult to determine its significance precisely.

Of the 69 patients, 42 had fever with or without multivisceral failure (n = 1), shock (n = 1) or sepsis (n = 23). In 58 patients, P. mirabilis was implicated in a monomicrobial infection and in 13/58 in sepsis. Some of the infections were notable by their seriousness or location (septicaemia n = 2, pyelonephritis n = 4, maternofetal infection n = 1, coxarthritis n = 1). This underlines the pathogenic potential of P. mirabilis.

In 42 (60.9%) patients this infection was nosocomial (Group I) and in 27 (39.1%) it was community-acquired (Group II). The sex ratio did not differ between the groups (about 59% female). In comparison with those of Group II, the patients of Group I were characterized by a more severe status: 19 versus two patients had a rapidly or ultimately fatal McCabe score (P < 0.005), a median age of 71 versus 41 years (P < 0.005) and a median length of stay of 28 versus 6 days (P < 0.001). Predisposing factors were present in 39/42 (69.0%) versus 3/27 (11.1%) (P < 0.001) patients: indwelling urinary catheter 29/42 (69%) versus 3/27 (11.1%), surgical intervention 19/42 (45.2%) versus 2/27 (7.4%), intravascular catheter 15/42 (35.7%) versus 1/27 (3.7%), respiratory assistance 14/42 (33.3%) versus 0/27 (0.0%) and corticosteroid therapy 9/42 (21.4%) versus 0/27 (0.0%).

All ESBL-producing isolates (n = 7) were from patients with nosocomial infections and the single IRB-producing isolate was from a patient with a community-acquired infection. IRB-producing isolates may have occurred as the result of the selection pressure of amoxycillin–clavulanate, an antibiotic widely used in out-patients and in infants, as previously reported for E. coli isolates.

During the 15 days before isolation of P. mirabilis, 21 of the 27 patients on antibiotics were receiving ß-lactams (penicillin n = 13, imipenem n = 2, cephalosporins n = 6).

Of the 57 treated for P. mirabilis infection, 43 (75.4%) were receiving ß-lactams (penicillins n = 26, oxyimino-cephalosporins n = 13, imipenem n = 3, cefoxitin n = 1), seven aminoglycosides (12.3%), 29 quinolones (50.9%) and 15 another antibiotic (26.3%). Microbiological samples were taken 3 days after the first isolation of P. mirabilis in 27 patients. Eradication was obtained in 15 (55.6%). Seven patients died. Death was not related to P. mirabilis infection.

Since 1990 there has been a notable increase in the frequency of resistance of P. mirabilis to ß-lactams, aminoglycosides and quinolones. Although the pathogen is often isolated in combination with another, our report is of clinical relevance, in that P. mirabilis was the sole organism involved in 60% of cases of infection, some of which were severe. These factors should be taken into account in the choice of antibiotic treatment.


    Acknowledgments
 
This work was supported in part by a grant from the Direction de la Recherche et des Études doctorales, Ministère de l'Éducation Nationale, France.


    Notes
 
* Corresponding author. Tel: +33-4-73-60-80-18; Fax: +33-4-73-27-74-94; E-mail: Christophe.DECHAMPS{at}u-clermont1.fr Back


    References
 Top
 Abstract
 Introduction
 Material and methods
 Results and discussion
 References
 
1 . Rozalski, A., Sidorczyk, Z. & Kotelko, K. (1997). Potential virulence factors of Proteus bacilli. Microbiology and Molecular Biology Reviews 61, 65–89.[Abstract]

2 . De Champs, C., Sirot, D., Chanal, C., Sirot, J. & French Study Group (1999). A survey of extended-spectrum ß-lactamase in Enterobacteriaceae in France. In Program and Abstracts of the Thirty-Ninth Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, 1999. Abstract 1485, p. 168. American Society for Microbiology, Washington, DC.

3 . Mariotte, S., Nordmann, P. & Nicolas, M. H. (1994). Extended-spectrum ß-lactamase in Proteus mirabilis. Journal of Antimicrobial Chemotherapy 33, 925–35.[Abstract]

4 . Chanal, C., Sirot, D., Romaszko, J. P., Bret, L. & Sirot, J. (1996). Survey of prevalence of extended spectrum ß-lactamases among Enterobacteriaceae. Journal of Antimicrobial Chemotherapy 38, 127–32.[Abstract]

5 . Bret, L., Chanal, C., Sirot, D., Labia, R. & Sirot, J. (1996). Characterization of an inhibitor-resistant enzyme IRT-2 derived from TEM-2 ß-lactamase produced by Proteus mirabilis strains. Journal of Antimicrobial Chemotherapy 38, 183–91.[Abstract]

6 . Romaszko, J. P., Bret, L., Henquell, C., Sirot, D., Chanal, C. & Sirot, J. (1995) Detection of ß-lactamases resistant to inhibitors (IRT) by the disk diffusion method. Pathologie Biologie 43, 306–9.[ISI][Medline]

7 . Sirot, J. (1996). Detection of extended-spectrum plasmidmediated ß-lactamases by disc diffusion. 1996 Report of the Comité de l'Antibiogramme de la Société Française de Microbiologie. Clinical Microbiology and Infection 2, Suppl. 1, 35–9.

8 . Garner, J. S., Jarvis, W. R., Emori, T. G., Horan, T. C. & Hughes, J. M. (1988). CDC definitions for nosocomial infections, 1988. American Journal of Infection Control 16, 128–40.[ISI][Medline]

9 . Bouza, E., Pérez-Molina, J. & Munoz, P. (1999). Bloodstream infections in Europe. Report of ESGNI-001 and ESGNI-002 studies. On behalf of the Cooperative Group of the European Study Group on Nosocomial Infections (ESGNI). Clinical Microbiology and Infection 5, 2S01–12.

10 . Nicolas-Chanoine, M. H., Chardon, H., Avril, J. L., Cattoen, Y., Croix, J. C., Dabernat, H. et al. (1997). Susceptibility of Enterobacteriaceae to betalactams and fluoroquinolones: a French multicenter study. Journal of Clinical Microbiology and Infection 3, Suppl. 2, Abstract P 338, 74.

11 . Goldstein, F. W., Péan, Y., Rosato, A., Gertner, J. & Gutmann, L. (1993). Characterization of ceftriaxone-resistant Enterobacteriaceae: a multicentre study in 26 French hospitals. Vigil'Roc Study Group. Journal of Antimicrobial Chemotherapy 32, 595–603.[Abstract]

Received 30 June 1999; returned 23 September 1999; revised 1 November 1999; accepted 13 December 1999