In vitro activity of fusidic acid against streptococci isolated from skin and soft tissue infections

R. Leclercqa,b,*, R. Bismuthc, I. Casind, J. D. Cavalloe, J. Croizéf, A. Feltend, F. Goldsteing, H. Monteilh, C. Quentin-Nouryi, M. Reverdyj, M. Vergnaudb and R. Roironk

a Service de Bactériologie-Virologie, Hôpital Henri Mondor-Université Paris XII, 94010 Créteil; b Service de Microbiologie, Hôpital Côte de Nacre, Université de Caen, 14033 Caen; c Service de Bactériologie, Hôpital Pitié-Salpétrière, 74651 Paris cedex 13; d Service de Bactériologie, Hôpital Saint-Louis, 75475 Paris cedex 10; e Service de Biologie, Hôpital Bégin, 94160 Saint-Mandé; f Service de Bactériologie, CHU Grenoble, 38043 Grenoble cedex; g Service de Bactériologie, Hôpital Saint-Joseph, 75674 Paris cedex 14; h Institut de Bactériologie de la Faculté de Médecine, 67000 Strasbourg; i Service de Bactériologie, Hôpital Pellegrin-Tripode, 33076 Bordeaux cedex; j Service de Bactériologie, Hôpital Edouard Herriot, 69437 Lyon cedex 03; k Laboratoires Leo, 78054 Saint-Quentin-en-Yvelines, France


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The in vitro activity of fusidic acid was evaluated against 242 strains of streptococci isolated from skin and soft tissue infections during a prospective multicentre study. Nearly 90% of strains were isolated from dermatology, emergency and medicine units. Groups A, B, C and G streptococci represented, respectively, 41.9, 20.6, 4.4 and 27.8% of the strains. The activity of fusidic acid was dependent on the media used. MICs were generally one dilution lower with heart infusion agar than with Mueller–Hinton agar supplemented with 5% horse blood (MIC90 for the whole streptococcal population = 8 mg/L and 16 mg/L, respectively). The distribution of MICs was unimodal and only two strains displayed MICs of fusidic acid >= 64 mg/L. In both media, fusidic acid was moderately active against streptococci. However, antibiotic concentrations obtained in the skin exceed the MIC90 of fusidic acid for streptococci, possibly explaining its clinical efficacy in the treatment of common cutaneous infections.


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Oral fusidic acid has been shown to be effective for the treatment of patients with skin and soft tissues infections.1,2 These infections are often due to staphylococci, against which fusidic acid is active, and to a lesser extent to streptococci.3 Fusidic acid is often empirically prescribed as therapy for these infections, which are usually community acquired and are rarely bacteriologically documented. However, in contrast to staphylococci, the in vitro activity of fusidic acid against streptococci has seldom been studied. To the best of our knowledge, no recent data are available. We have studied the in vitro activity of fusidic acid against streptococci recently isolated from skin and soft tissue infections by the laboratories of 10 French hospitals.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Bacterial strains

From six to 50 streptococcal strains consecutively isolated from skin and soft tissue infections (one strain per patient) for a period of 3 months in 1995 were collected by each of the 10 participating centres in the hospitals of Bordeaux, Caen, Créteil, Grenoble, Lyon, Paris (three hospitals), Saint Mandé and Strasbourg. Only strains isolated from out-patients or in-patients hospitalized in medical and dermatological units were included in the study. Strains from surgical, intensive care or burns units were excluded. Strains were identified by the presence of ß-haemolysis, group antigen and biochemical characteristics (API 32 strep galleries, bioMérieux, La Balme les Grottes, France).

Antibiotic susceptibility testing

The in vitro activity of the antibiotics was tested in the co-ordinating centre of Créteil. MICs of fusidic acid were determined by the agar dilution method according to the recommendations of the Comité de l’Antibiogramme de la Société Française de Microbiologie (CA-SFM).4 Mueller– Hinton medium (Sanofi Diagnostics Pasteur, MarnesLa-Coquette, France) supplemented with 5% horse blood (MHBA) was used. The inoculum consisted of a suspension of colonies taken from Columbia agar plates into Mueller–Hinton broth and diluted to obtain 104 cfu/spot. The plates were incubated for 24 h at 37°C. In addition, MICs were determined with the same inoculum and incubation conditions on Heart Infusion Agar (HIA) (Difco Laboratories, Detroit, MI, USA), a medium devoid of blood. The disc diffusion technique was used to test susceptibility to ampicillin (10 µg), cephalothin (30 µg), erythromycin (15 IU), fusidic acid (10 µg), penicillin G (10 IU), pristinamycin (15 µg), tetracycline (30 IU) and vancomycin (30 µg) on MHBA and on HIA. Staphylococcus aureus ATCC 25923 and Enterococcus faecalis ATCC 29212 were included as controls. The breakpoints used were those of CA-SFM. 4


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Characteristics of strains

A total of 248 streptococcal strains were collected; 41.1% originated from dermatology units, 27.4% from emergency units and 22.2% from medicine departments. Of these, 45.2% were isolated as the primary agent of the infection (13.0 and 11.4% from abcesses and whitlows, respectively) and 54.9% were responsible for superinfections (21.5 and 17.1% from wounds and cutaneous ulcers, respectively). The vast majority of isolates included groups A (41.9% of strains), G (27.8%), B (20.8%) and C (4.4%) streptococci. Group F and oral streptococci represented only 2.8 and 2.4% of isolates, respectively. Fourteen isolates were from cases of erysipelas, due to six group A streptococci, seven group G streptococci and one group B streptococcus, and five isolates were from cases of necrotizing fasciitis, four due to group A and one to group G streptococci.

Antibiotic susceptibility

A total of 242 strains were studied for susceptibility to antibiotics. All were susceptible to ampicillin, cephalothin, penicillin G, pristinamycin and vancomycin; 50.8% of strains were resistant to tetracyclines (41.2% of group A streptococci) and 9.5% to eythromycin (6.9% of group A streptococci). MIC range, MIC50 and MIC90 of fusidic acid are shown in Table IGo. MICs of fusidic acid when determined in HIA were generally one dilution lower than that obtained in MHBA. Modal MIC of fusidic acid was 4 mg/L or 8 mg/L when determined in HIA and MHBA, respectively. Thus, with regard to MICs, 87.6% of streptococcal strains tested in MHBA were classified as intermediate to fusidic acid (6.6% susceptible), but only 57.4% in HIA (41.3% susceptible) (Table IIGo). A similar trend was observed with the disc diffusion method (Table IIGo). However, this latter method led to an overestimation of the intermediate and resistant strains in both agar media as compared with MICs (Table IIGo). The MIC distribution for the streptococcal population was unimodal with only two strains displaying MICs of fusidic acid equal to or greater than 64 mg/L whatever the medium used.


View this table:
[in this window]
[in a new window]
 
Table I. MICs (mg/L) of fusidic acid for streptococci, in MHBA or HIA, according to species
 

View this table:
[in this window]
[in a new window]
 
Table II. Categorization of strains according to MICs and zone diameters
 

    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The strains studied were collected mostly from outpatients and from dermatology and emergency units and therefore were probably responsible for community-acquired infections. As expected, groups A and G streptococci were predominant. The in vitro activity of fusidic acid appeared different according to the medium used. MICs determined in agar medium were one doubling dilution lower in HIA than in MHBA. The difference could be related to the presence or absence of blood in the medium. We confirmed this effect by further determination of MICs of fusidic acid for 25 strains of group A streptococci on trypticase soy and Mueller–Hinton agars either alone or supplemented with 5% horse blood or serum (data not shown). The high percentage of binding of fusidic acid to serum proteins, which exceeds 90%, could account for differences in the activity of the antimicrobial according to the medium.5 The disc diffusion technique showed a tendency to overestimate the intermediate or resistant strains as compared with the MIC techniques. Whatever the technique used, fusidic acid appears to be moderately active against streptococci, although acquired resistance was rare. Possibly, the use of media supplemented with blood correlated better with the in vivo conditions. Our results are in accord-ance with the few reports already published.3,6 Of note, the high skin concentrations obtained after twice-daily administration of fusidic acid 500 mg, i.e. mean peak equal to 79 mg/L and mean trough equal to 39 mg/L, are above the MIC90 for the streptococci isolated from cutaneous infections.5 Therefore, the clinical efficacy of fusidic acid in the treatment of skin and soft tissue infections, including those owing to streptococci, could possibly be related to the inhibitory quotient obtained.


    Acknowledgments
 
This study was supported in part by a grant from Laboratoires Leo.


    Notes
 
* Correspondence address. CHU de Caen, Service de Microbiologie, Avenue Côte de Nacre, 14033 Caen cedex, France. Tel: +33-2-31-06-45-72; Fax: +33-2-31-06-45-73; E-mail: leclercq-r{at}chu-caen.fr Back


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
1 . Goncalves, J. & Thorn, P. (1991). Fusidic acid and the treatment of patients with skin and soft tissue infections. European Journal of Clinical Research 1, 91–7.

2 . Nordin, P. & Mobacken, H. (1994). A comparison of fusidic acid and flucloxacillin in the treatment of skin and soft-tissue infection. European Journal of Clinical Research 5, 97–106.

3 . Reverdy, M. E., Coignard, S., Dubreuil, L., Bouvet, A. & Fleurette, J. (1994). In vitro activity of cloxacillin staphylococci, group A streptococci and Clostridium perfringens-seric inhibitor indexes. Médecine et Maladies Infectieuses 24, 898–905.[ISI]

4 . Comité de l’Antibiogramme de la Société Française de Microbiologie. (1996). 1996 report of the Comité de l’Antibiogramme de la Société Française de Microbiologie. Technical recommendations for in vitro susceptibility testing. Clinical Microbiology and Infection 2S1, 11–25.

5 . Vaillant, L., Machet, L., Taburet, A. M., Sorensen, H. & Lorette, G. (1992). Levels of fusidic acid in skin blister fluid and serum after repeated administration of two dosages (250 and 500 mg). British Journal of Dermatology 126, 591–5.[ISI][Medline]

6 . Tillotson, G. S. & Ganguli, L. A. (1984). Antibiotic susceptibility of clinical strains of Streptococcus milleri and related streptococci. Journal of Antimicrobial Chemotherapy 14, 557–8.[ISI][Medline]

Received 22 February 1999; returned 22 June 1999; revised 3 August 1999; accepted 10 September 1999





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 (2)
Disclaimer
Request Permissions
Google Scholar
Articles by Leclercq, R.
Articles by Roiron, R.
PubMed
PubMed Citation
Articles by Leclercq, R.
Articles by Roiron, R.