Antibiotic resistance surveillance of Stenotrophomonas maltophilia, 1993–1999

Carmen Betriu,*, Ana Sánchez, M. Luisa Palau, María Gómez and Juan J. Picazo

Servicio de Microbiología Clínica, Hospital Clínico San Carlos, Plaza Cristo Rey s/n, 28040 Madrid, Spain

Sir,

Stenotrophomonas maltophilia has emerged as an increasingly important nosocomial pathogen capable of causing life-threatening infections. Risk factors associated with S. maltophilia infections include immunosuppressive and invasive therapies, admission to the intensive care unit, advanced age, prolonged hospitalization, surgical procedures and prior therapy with broad-spectrum ß-lactam antibiotics, aminoglycosides or quinolones.1,2 The treatment of these infections is often difficult because S. maltophilia is inherently resistant to most of the available antimicrobial agents, including ß-lactams, quinolones and aminoglycosides. In vitro susceptibility studies have shown co-trimoxazole, ticarcillin–clavulanate, doxycycline, minocycline and some new fluoroquinolones as the only agents with activity against these organisms.36

In order to determine the current antibiotic susceptibility patterns of S. maltophilia in our hospital, we studied the in vitro activities of 20 antimicrobial agents against 150 clinical strains isolated from 1997 to 1999. Each organism was identified using the ID 32 GN system (bioMérieux, Marcy l'Étoile, France). The clinical sources of isolates were as follows: skin and soft tissues (91), respiratory tract (23), urine (19), blood (7), catheter (6) and others (4). MICs were determined using a microdilution procedure (Sensititre; Trek Diagnostic Systems Ltd, East Grinstead, UK) in Mueller–Hinton broth according to NCCLS guidelines7 except for ticarcillin–clavulanate, which was tested by the NCCLS agar dilution method.7 The results were compared with those of previous studies obtained with 63 strains isolated in 1993–1994, and 95 strains isolated in 1995–1996. The method of susceptibility testing was the same as that used with the isolates obtained in 1997–1999 and the sources of isolates were comparable. Duplicate isolates from the same patient were excluded. Fisher's exact test was used for statistical analysis and P values <0.05 were considered significant.

The results of susceptibility testing are presented in the TableGo. Among the cephalosporins, ceftazidime was the most active, with 50% of the strains susceptible. As expected, cefotaxime, aztreonam and the two carbapenems tested were inactive. Our results agree with those of previously published reports, which show that aminoglycosides have poor activity against this organism.2,5 The old quinolones tested showed poor activity. By contrast, clinafloxacin was very active, with 90.7% of isolates susceptible at <=2 mg/L. Unfortunately, clinafloxacin is not yet available. Several studies have proved the high activity of new quinolones against S. maltophilia isolates.3,4 Clinical trials are warranted to study the effectiveness of these drugs. Given that mutants of S. maltophilia resistant to quinolones and unrelated drugs can be isolated in vitro at a high frequency,8 continued surveillance of antimicrobial resistance of these organisms is necessary.


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Table. Antimicrobial agents tested against S. maltophilia isolates
 
Susceptibility and intermediate susceptibility to ticarcillin–clavulanate were found in 53.3 and 32.7% of isolates, respectively. The other ß-lactam–ß-lactamase inhibitor combinations tested were less active than ticarcillin–clavulanate. However, slightly higher susceptibility rates to piperacillin–tazobactam have been reported elsewhere.5

The most active agent was co-trimoxazole (95.3% susceptible). For almost three decades, co-trimoxazole has been the agent of choice in S. maltophilia infections. Although it remains a useful antimicrobial agent against this organism, resistance to co-trimoxazole has been reported.2,3,5 Because of clinical failures observed with monotherapy in some cases, and the emergence of resistance during therapy, several combinations of antimicrobial agents that exhibit in vitro synergy have been proposed. Muder et al.2 suggest a combination of co-trimoxazole and either ticarcillin–clavulanate or a third-generation cephalosporin for patients who are neutropenic or seriously ill.

A comparison of susceptibilities between isolates in this study and those collected previously shows that resistance to co-trimoxazole decreased significantly from 16.8% in 1995–1996 to 4.7% in the present study (P < 0.005). We also observed an increasing trend in the rates of resistance to ciprofloxacin and norfloxacin (P < 0.05). Resistance to ciprofloxacin increased from 54% in 1993–1994 to 68.7% in the last study period and resistance to norfloxacin increased from 68.3 to 80.7% during the same period. Similar findings have been reported by Vartivarian et al.,3 who related these changes in susceptibilities to therapeutic and prophylactic practices in their hospital. The significant decrease in resistance to co-trimoxazole observed in the present study could be associated with the decreased use of this antibiotic in our hospital during the last 5 years. Furthermore, the increased resistance to ciprofloxacin among our S. maltophilia isolates could be linked to a rise in the prescription of quinolones among hospitalized patients. No appreciable changes in susceptibility to other antibiotics were noted over the study period.

The results of this study confirm that S. maltophilia remains highly resistant to several antibiotics and show co-trimoxazole and ticarcillin–clavulanate as the only currently available agents with good activity against these organisms. The high degree of resistance of S. maltophilia to many antibiotics emphasizes the importance of continued local surveillance of antimicrobial resistance. Prudent antibiotic usage and application of infection control measures are necessary in order to prevent cross-transmission of this organism within the hospital environment.

Acknowledgments

This study was presented in part at the Thirty-ninth Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, 26–29 September 1999.

Notes

* Corresponding author. Tel: + 34-91-3303484; Fax: +34-91-3303478; E-mail: cbetriu{at}efd.net Back

References

1 . Denton, M. & Kerr, K. G. (1998). Microbiological and clinical aspects of infection associated with Stenotrophomonas maltophilia. Clinical Microbiology Reviews 11, 57–80.[Abstract/Free Full Text]

2 . Muder, R. R., Harris, A. P., Muller, S., Edmond, M., Chow, J. W., Papadakis, K. et al. (1996). Bacteremia due to Stenotrophomonas (Xanthomonas) maltophilia: a prospective, multicenter study of 91 episodes. Clinical Infectious Diseases 22, 508–12.[ISI][Medline]

3 . Vartivarian, S., Anaissie, E., Bodey, G., Sprigg, H. & Rolston, K. (1994). A changing pattern of susceptibility of Xanthomonas maltophilia to antimicrobial agents: implications for therapy. Antimicrobial Agents and Chemotherapy 38, 624–7.[Abstract]

4 . Weiss, K., Restieri, C., De Carolis, E., Laverdière, M. & Guay, H. (2000). Comparative activity of new quinolones against 326 clinical isolates of Stenotrophomonas maltophilia. Journal of Antimicrobial Chemotherapy 45, 363–5.[Abstract/Free Full Text]

5 . Traub, W. H., Leonhard, B. & Bauer, D. (1998). Antibiotic susceptibility of Stenotrophomonas (Xanthomonas) maltophilia: comparative (NCCLS criteria) evaluation of antimicrobial drugs with the agar dilution and the agar disk diffusion (Bauer–Kirby) tests. Chemotherapy 44, 164–73.[ISI][Medline]

6 . Kurlandsky, L. E. & Fader, R. C. (2000). In vitro activity of minocycline against respiratory pathogens from patients with cystic fibrosis. Pediatric Pulmonology 29, 210–2.[ISI][Medline]

7 . National Committee for Clinical Laboratory Standards. (1997). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically—Fourth Edition: Approved Standard M7-A4. NCCLS, Villanova, PA.

8 . Lecso-Bornet, M., Pierre, J., Sarkis-Karam, D., Lubera, S. & Bergogne-Berezin, E. (1992). Susceptibility of Xanthomonas maltophilia to six quinolones and study of outer membrane proteins in resistant mutants selected in vitro. Antimicrobial Agents and Chemotherapy 36, 669–71.[Abstract]