Christophe Guervilly*Antoine Roch

Aix-Marseille Universit�e, URMITE CNRS-UMR, APHM,Hopital Nord, R�eanimation, Marseille, France

*Corresponding author. Service de R�eanimation DRIS, HopitalNord, chemin des Bourrely, 13015 Marseille, France.

Tel.: þ33 0491965835; fax: þ33 0491965837.

E-mail address: christophe.guervilly@ap-hm.fr(C. Guervilly)

St�ephane RanqueAix-Marseille Universit�e, Parasitology and Mycology

Department, Marseille, France

Jean-Marie ForelSami Hraiech

Francois XeridatMelanie Adda

Laurent PapazianAix-Marseille Universit�e, URMITE CNRS-UMR, APHM,

Hopital Nord, R�eanimation, Marseille, France

Accepted 27 July 2012

ª 2012 The British Infection Association. Published by Elsevier Ltd.All rights reserved.

http://dx.doi.org/10.1016/j.jinf.2012.07.007

Anaerobes isolated from bone and joint infections andtheir susceptibility to antibiotics

Dear Editor,

In this journal, Cataldo et al. recently reported recentdevelopments in diagnosis and management of prostheticjoint infection.1

Involvement of anaerobes in bone and joint infections(BJI) has been well documented in children, and in diabeticfoot ulcers.2 We analyzed a large cohort of adult patientswith BJI involving anaerobes, with particular focus on or-thopaedic implants, to describe the isolated bacteria withtheir rate of resistance to antibiotics.

Anaerobes were recovered from 107 orthopaedic surgi-cal procedures performed on 99 patients between 2007 and2009 at Nantes University Hospital.

Deep specimens were processed within 2 h after collec-tion. Specific plates and anaerobic enrichment broths wereobserved for two weeks. Organisms were identified bycommercially available biochemical assays and 16S ribo-somal sequence analysis. Antibiotic susceptibility testingwas determined as recommended.3 MICs were then con-firmed using the Etest diagnostic with susceptibility break-points used by the European Committee on AntimicrobialSusceptibility testing and the CA-SFM.3

Diagnosis of BJI was based on converging clinical, micro-biological, and radiological arguments discussed by a multi-disciplinary team. Ninety patients (group A) developed a BJIon orthopaedic material, whereas nine patients (group B)developed a BJI in the absence of implant.

Group A was divided into 2 subgroups.Subgroup A1 patients had an infection on spinal in-

strumentation, articular prosthesis or osteosynthesis ma-terial (n Z 83, Table 1). Infections on spinalinstrumentation were caused by only anaerobic bacteriain 40 cases (78%, Propionibacterium acnes, n Z 39); 11 in-fections involved aerobes in association with P. acnes(n Z 8), Peptostreptococcus anaerobius (n Z 1), Parvimo-nas micra (n Z 1), and Bacteroides fragilis (n Z 1). Pros-thetic joint infections were monomicrobial infections withanaerobes in four cases: P. acnes (n Z 2), Bacteroides vul-gatus (n Z 1) and Clostridium perfringens (n Z 1); 8 pros-thetic joint infections involved aerobes in association withP. acnes (n Z 6), Actinobaculum schaalii (n Z 1), or Pep-toniphilus asaccharolyticus (n Z 1). Osteosynthetic infec-tions were monomicrobial infections with anaerobes in 13cases: P. acnes (n Z 12), and B. fragilis (n Z 1); 7

Table 1 Group A patients with a bone and joint infection on foreign implant.

Subgroup A1 Subgroup A2 Total

Spinal instrumentationinfections

Articular prosthesisinfections

Osteosynthesisinfections

Post-traumaticinfections

Number of patients 50 11 18 11 90Number of recurrent infections 1 1 1 3 6Total number of infections 51 12 20a 14 97a

Bacterial nature of infectionStrictly anaerobic 40 4 13 6 63Polymicrobial aerobic and anaerobic 11 8 7 8 34

Surgical treatmentComplete implant removal 31 7 14 10 62Partial implant removal 13 2 1 0 16Debridement with irrigation 7 3 5 2 17Amputation 0 0 0 2 2

Antibiotic treatment 40 11 17 13 81a One patient with infection at two different sites.

Letters to the Editor 473

infections involved aerobes in association with P. acnes(n Z 4), Anaerococcus prevotii with P. asaccharolyticus(n Z 1), Clostridium sporogenes (n Z 1), Bacteroides ure-alyticus (n Z 1).

Subgroup A2 patients had a post-traumatic infection(n Z 14) after an open fracture. Infections were polymicro-bial aero-anaerobic infections in 8 cases associating two orthree Clostridium species (n Z 5), P. asaccharolyticus(n Z 1), or A. prevotii (n Z 2) with aerobes. Six infectionsyielded only anaerobes: two or three isolates of variousClostridium species (n Z 4), Robinsoniella peoriensis(n Z 1), P. acnes (n Z 1), or A. prevotii (n Z 1).

The surgical treatment was combined with antimicrobialtherapy in 81 cases. Sixteen infections were surgicallytreated without receiving antibiotics, mostly monomicro-bial P. acnes infections with no signs of sepsis.

Group B patients had a BJI without implant (abscess orphlegmon, n Z 5; osteitis, n Z 2; osteoarthritis, n Z 3)(Table 2). Infections were aero-anaerobic in 6 cases associ-ating aerobes with F. magna (n Z 2), P. anaerobius and P.asaccharolyticus (n Z 1), Gram-negative anaerobic bacilli(n Z 2) or Eggerthella lenta (n Z 1). Four infectionswere monomicrobial with anaerobic bacteria: P. acnes(n Z 2), C. sporogenes (n Z 1) or P. asaccharolyticus(n Z 1). The surgical treatment was combined with antimi-crobial therapy in all the cases.

Seven out of 99 patients had a second infection at thesame site due to the same anaerobe in 5 cases.

All anaerobes were susceptible to amoxicillin plusclavulanic acid, cefoxitin, imipenem, and metronidazole(except P. acnes). Sixteen isolates were resistant to clinda-mycin (9 Clostridium strains), and 7 isolates to moxifloxacin(4 Clostridium strains). In aero-anaerobic infections,a beta-lactam with a beta-lactamase inhibitor, or a carba-penem, or a third-generation cephalosporin associated tometronidazole were used in association with a fluoroquino-lone. Clindamycin or rifampicin, in combination with a fluo-roquinolone, were used for P. acnes or GPAC inmonomicrobial or mixed infections with staphylococci.

We report a 3-year retrospective review of 99 patientswith 107 BJI involving anaerobes. P. acnes was the predom-inant anaerobe associated with orthopaedic implant mate-rial.4,5 P. acnes was isolated from at least three and as

many as seven samples per patient for 81% of infections,consistent with association with the infection rather thana contaminant.

Predominant anaerobes isolated from post-traumaticinfections in this study are Clostridium spp. Clostridiumfound in open fractures or puncture wounds were Clostrid-ium clostridioforme, C. sporogenes, or Clostridium bifer-mentans. In contrast to monomicrobial anaerobicinfections on spinal implants, multiple isolates of variousClostridium species with different antibiotic susceptibilitypatterns were recovered from the same patient. Bacterialeradication of Clostridium post-traumatic infections wasparticularly difficult.

GPAC, better known as peptostreptococci are dividedinto five major species. Here we report 15 BJI involvingGPAC from all 5 major species of GPAC. These findingscontrast with previous study indicating F. magna is the pre-dominant GPAC BJI pathogen.2

Clindamycin and fluoroquinolones are commonly usedantibiotics in BJI because of their high intraosseous con-centrations, and good activity against anaerobes.6,7 Levo-floxacin and moxifloxacin are not approved for use in BJIstricto sensu, but both are very effective against aero-anaerobic bacteria in combination with beta-lactams ormetronidazole.7 A high (45%) rate of resistance to clinda-mycin was observed. C. clostridioforme with C. sporogenesand Clostridium tertium make up most of the clindamycinresistant clinical isolates8 (http://www.medsafe.govt.nz/profs/datasheet/d/DalacinCcap.pdf). Our study underlinesthe need for rigorous susceptibility testing of all Clostrid-ium isolates.

Of 15 infections with GPAC, three (20%) yielded clinda-mycin resistant strains. The rate among the GPAC variedfrom 0 to 20% between European countries in 2008.9 In ourstudy, only two P. acnes strains were resistant toclindamycin.

The 5 recurrent infections were due to P. acnes (n Z 3),or Clostridium spp. (n Z 2). The recurrence of infectionswith P. acnes was observed after a partial or complete re-moval of implant. These findings suggest either a failurein the surgical strategy or lack of antibiotic diffusion inbone. Both recurrent post-traumatic infections due to Clos-tridium spp. required using successive lines of antibioticsfor several months.

This study highlights the importance of anaerobes inseveral types of BJI. Clinicians should be aware thatanaerobes isolated from post-traumatic infections oftendisplay a high level of clindamycin resistance. Antibiotictreatment must be reconsidered when the results fromanaerobic culturing are available.

References

1. Cataldo MA, Petrosillo N, Cipriani M, Cauda R, Tacconelle E. Pros-thetic joint infection: recent developments in diagnosis andman-agement. J Infect 2010;61:443e8. http://dx.doi.org/10.1016/j.jinf.2010.09.033.

2. Brook I. Microbiology and management of joint and boneinfections due to anaerobic bacteria. J Orthop Sci 2008;13:160e9.

3. Communiqu�e de l’Antibiogramme de la Soci�et�e Francaise de Mi-crobiologie. Bull Soc Fr Microbiol; 2008.

Table 2 Group B patients with a bone and joint infectionwithout foreign implant.

Number

Number of patients 9Number of recurrent infections 1Total number of infections 10

Bacterial nature of infectionStrictly anaerobic 4Polymicrobial aerobic and anaerobic 6

Surgical treatmentDebridement with irrigation 6Amputation 3None 1

Antibiotic treatment 10

474 Letters to the Editor

4. Bemer P, Corvec S, Tariel S, Asseray N, Boutoille D, Langlois C,et al. Significance of Propionibacterium acnes-positive samplesin spinal instrumentation. Spine 2008;33:E971e6.

5. Zeller V, Ghorbani A, Strady C, Leonard P, Mamoudy P,Desplaces N. Propionibacterium acnes: an agent of prostheticjoint infection and colonization. J Infect 2007;55:119e24.

6. Nicholas P, Meyer BR, Levy RN, Hirschman SZ. Concentration ofclindamycin in human bone. Antimicrob Agents Chemother1975;8(8):220.

7. Stein GE, Goldstein EJC. Review of in vitro activity and potentialclinical efficacy of levofloxacin in the treatment of anaerobic in-fections. Anaerobe 2003;9:75e81.

8. Alexander CJ, Citron DM, Brazier JS, Goldstein EJ. Identificationand antimicrobial resistance patterns of clinical isolates of Clos-tridium clostridioforme, Clostridium innocuum, and Clostridiumramosum compared with those of clinical isolates of Clostridiumperfringens. J Clin Microb 1995;33:3209e15.

9. Brazier J, Chmelar D, Dubreuil L, Feierl G, Hedberg M, Kalenic S,et al. The ESCMID study group on antimicrobial resistance in an-aerobic bacteria (ESGARAB). European surveillance study on an-timicrobial susceptibility of Gram-positive anaerobic cocci. Int JAntimicrob Agents 2008;31:316e20.

Marina IlliaquerSt�ephane Corvec

Service de Bact�eriologie-Hygi�ene, CHU de Nantes,Nantes, France

Sophie TouchaisClinique Chirurgicale Orthop�edique et Traumatologique,

CHU de Nantes, Nantes, France

David BoutoilleNathalie Asseray

Service des Maladies Infectieuses, CHU de Nantes,Nantes, France

Marie-Emmanuelle JuvinGhislaine le Gargasson

Alain ReynaudLise Cr�emet

Pascale B�emer*Service de Bact�eriologie-Hygi�ene, CHU de Nantes,

Institut de Biologie, 1 place Alexis Ricordeau,44093 Nantes, Cedex, France

*Corresponding author. Tel.: þ33 2 40 08 39 55;fax: þ33 2 40 08 39 28.

E-mail address: pascale.bemer@chu-nantes.fr (P. B�emer)

Accepted 18 August 2012

ª 2012 The British Infection Association. Published by Elsevier Ltd.All rights reserved.

http://dx.doi.org/10.1016/j.jinf.2012.08.012

Letters to the Editor 475