Enterococcal glycopeptide resistance at an Italian teaching hospital

Mario Bonadio*, Micaela Meini, Enrico Tagliaferri, Cristina Gigli and Armando Vigna

Insegnamento di Malattie Infettive, Università di Pisa, Ospedale S. Chiara, 56100 Pisa, Italy


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 References
 
Two thousand one hundred and thirteen strains of enterococci isolated at Pisa General Hospital in 1998 were analysed retrospectively to determine their glycopeptide resistance. Of all the microorganisms isolated in this period, 14.7% were enterococci (1405 Enterococcus faecalis, 19 Enterococcus faecium, six Enterococcus avium and 683 Enterococcus spp.). Two hundred and thirty (10.8%) of these enterococci were resistant or demonstrated reduced susceptibility to vancomycin and/or teicoplanin. The highest rate of resistance was found in outpatient enterococcal strains isolated from the urogenital tract. The frequency of enterococcal glycopeptide resistance at Pisa Hospital is higher than that reported from other areas of Italy.


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 References
 
Enterocci as a cause of nosocomial infection have become more prevalent over the last 20 years, both in North America and in most western European countries.12 Vancomycin-resistant enterococci (VRE) have been described as a cause of many bacterial infections.3 Glycopeptide antibiotics are being used increasingly in the hospital setting to combat infections caused by methicillin-resistant Gram-positive cocci. The increase in glycopeptide resistance among enterococci is of concern in itself but also because enterococci can transfer antibiotic resistance genes to Staphylococcus aureus.4 The aim of this study was to evaluate the role of enterococci in bacterial infections in the Pisa area and to estimate the rate of glycopeptide resistance among enterococci.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 References
 
All records of bacterial cultures performed in the microbiology laboratories at Pisa Hospital during 1998 were examined retrospectively. We reviewed all isolates for which susceptibility tests had been performed, with particular reference to enterococci. The hospital microbiology laboratories receive samples from all hospital departments and from community outpatients. Microbial cultures were performed using conventional techniques. Identification and susceptibility tests were performed with the automatic Vitek system (bioMerieux Vitek, Hazelwood, MO, USA) and NCCLS recommendations.5 Enterococcal isolates with MICs of >=32 mg/L were considered resistant to vancomycin, those with an MIC between 4 and 32 mg/L of intermediate susceptibility and those with an MIC <=4 mg/L fully susceptible. Enterococci with an MIC >=32 mg/L were considered resistant to teicoplanin, those with an MIC between 8 and 32 mg/L of intermediate susceptibility and those with an MIC <=8 mg/L fully susceptible.


    Results and discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 References
 
In 1998, a total of 14364 bacterial strains were isolated in the laboratories of Pisa Hospital; 2113 (14.7%) of these were enterococci (1147 from outpatients and 966 from inpatients). The frequencies of enterococcal isolates found in all urine, vaginal and seminal fluid samples cultured were 23.5, 25.9 and 31.3%, respectively. Enterococci were found in 4.8, 0.9 and 4.1% of blood samples, sputum samples and other specimens, respectively.

Most of the enterococci were Enterococcus faecalis (1405), 19 were Enterococcus faecium, six were Enterococcus avium and 683 were unspecified Enterococcus spp.

Over 90% of the strains studied were susceptible to nitrofurantoin, ampicillin, piperacillin and imipenem; 79% were susceptible to fosfomycin, 75.1% to penicillin, 74% to ciprofloxacin and norfloxacin, 72.6% to gentamicin, 90.3% to teicoplanin and 89.7% to vancomycin (Table IGo).


View this table:
[in this window]
[in a new window]
 
Table I. In vitro susceptibility of 2113 strains of enterococci (Pisa, 1998)
 
Resistance or intermediate susceptibility of enterococci to vancomycin and/or teicoplanin in vitro was found in 10.8% of isolates (230/2113); of these 230 isolates, 193 were resistant or showed intermediate susceptibility to vancomycin (MIC > 4 mg/L) and teicoplanin (MIC > 8 mg/L); 33 strains were resistant or had intermediate susceptibility to vancomycin; and four strains were resistant or had intermediate susceptibility to teicoplanin.

Of enterococci from inpatients and outpatients, 7.1% and 14%, respectively, were glycopeptide resistant. In 61 outpatients, glycopeptide-resistant enterococci were isolated from vaginal or urethral secretions or seminal fluid.

The sensitivity of vancomycin-resistant enterococci to the other antibiotics is shown in Table IIGo; only nitrofurantoin and imipenem showed good activity (>90% of the strains were sensitive). There was a striking contrast in susceptibility to fosfomycin between vancomycin-susceptible and vancomycin-resistant enterococci (79% versus 7.5%). Similar patterns of activity against the teicoplanin-resistant enterococcal strains were found for the other antibiotics.


View this table:
[in this window]
[in a new window]
 
Table II. In vitro susceptibility of vancomycin-resistant enterococci (Pisa, 1998)
 
The results of this study confirm the role of enterococci in bacterial infections, accounting for 14.7% of all the bacterial isolates studied. In particular, enterococci were frequently isolated from the urogenital tract (urine, seminal fluid and vaginal swabs) although some of these isolates could result from bacterial colonization without infection.

Sensitivity testing demonstrated excellent activity of nitrofurantoin, ampicillin, piperacillin and imipenem (>90% of the strains were sensitive), but poor activity of quinolones and gentamicin (only 72–74% of the strains were sensitive). The rates of resistance to vancomycin (10.3%) and teicoplanin (9.7%) are in accordance with the results of a study performed in Pisa in 1997, but significantly higher than those reported in two multicentre Italian studies during 19936 and 1996–97.7 Our data are similar to those of the National Infections Surveillance System of the USA, which reported in 1996 rates of glycopeptide resistance of about 12% in intensive care units and 10% in other non-intensive care units.8

In our study, glycopeptide-resistant enterococci were more frequently resistant to other antibiotics: only nitrofurantoin and imipenem were active against >90% of the glycopeptide-resistant enterococcal strains. The highest rates of resistance were detected in samples obtained from the urogenital tract (urine, seminal fluid and vaginal secretion) and, unexpectedly, in outpatients. This may be because the patients who undergo more frequent microbiological evaluations of the urogenital tract are those who have chronic or recurrent infections (cystitis, vaginitis or prostatitis), and may have received numerous courses of antibiotics.3 This may also partly explain the low numbers of VRE that were susceptible to ampicillin and penicillin. Enterococci may be resistant to penicillin and ampicillin because of the production of low-affinity penicillin-binding proteins (PBPs) or because of the production of ß-lactamase. The Vitek system we used in this study can detect isolates with altered PBPs, but it may not reliably detect ß-lactamase-producing strains. Based on the decreased susceptibility to ß-lactams observed in our VRE, it is likely that a significant number of the unspecified VRE are E. faecium, rather than E. faecalis, which are generally susceptible to ß-lactams. The very low percentage of VRE fully susceptible to fosfomycin could be explained by the use of this agent to treat recurrent urinary tract infections in our area.

In conclusion, the high frequency of glycopeptide-resistant enterococci that we observed in Pisa was largely unexpected. The cause of these high rates of resistance is not clear, especially if we consider the data reported in other Italian studies. The indiscriminate use of antibiotics may, in part, explain our results. We feel that continued surveillance in both hospital and outpatient settings is mandatory and that the use of glycopeptides needs to be rationalized.


    Notes
 
* Corresponding author. Fax: +39-050-533414; E-mail: m.bonadio{at}int.med.unipi.it Back


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results and discussion
 References
 
1 . Schaberg, D. R., Culver, D. H. & Gaynes, R. P. (1991). Major trends in the microbial etiology of nosocomial infection. American Journal of Medicine 91, Suppl. 3B, 72S–75S.[Medline]

2 . Spera, R. V. & Farber, B. F. (1992). Multiply-resistant Enterococcus faecium. The nosocomial pathogen of the 1990s. Journal of the American Medical Association 268, 2563–4.[ISI][Medline]

3 . Moellering, R. C. (1998). The specter of glycopeptide resistance: current trends and future considerations. American Journal of Medicine 104, 3S–6S.[Medline]

4 . Noble, W. C., Virani, Z. & Cree, R. G. (1992). Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus. FEMS Microbiology Letters 72, 195–8.

5 . National Committee for Clinical Laboratory Standards. (1997). Performance Standards for Antimicrobial Susceptibility Testing—Eighth Informational Supplement: Approved Standards M100-S8. NCCLS, Wayne, PA.

6 . Venditti, M. & Goglio, A. (1996). Vancomycin susceptibility in enterococcal blood isolates in Italy: a multicenter retrospective analysis. Journal of Chemotherapy 8, 33–6.[ISI][Medline]

7 . Cornaglia, G. & Fontana, R. (1999). Susceptibilities of strains isolated from outpatient urine specimens in Italy. Clinical Microbiology and Infection 5, Suppl. 3, 237.

8 . Centers for Disease Control. (1996). National Nosocomial Infection Surveillance Report. Data summary from October 1986 to April 1996. American Journal of Infection Control 24, 380–8.[ISI][Medline]

Received 9 November 1999; returned 21 January 2000; revised 28 February 2000; accepted 20 March 2000





This Article
Abstract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (5)
Disclaimer
Request Permissions
Google Scholar
Articles by Bonadio, M.
Articles by Vigna, A.
PubMed
PubMed Citation
Articles by Bonadio, M.
Articles by Vigna, A.