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Table 1.  

Characteristic Case
1 2 3 4[10] 5[11] 6[11] 7[12] 8[13]
Country France France France United States Switzerland Czech Republic United States Canada
Region Vendée Gironde Aube Colorado NS NS Illinois Ontario
Age, y 49 70 68 58 84 84 77 68
Sex M M M M F M M M
Exposure factors Rural residence, dog Hunter Retired butcher, cooking with wild game Farmer, possible rabbit carcass handling Airborne transmission (rabbit barn in neighbor’s house) Walk in tularemia- endemic area Hunter Hunter, tick bite 6 mo before surgery
Type of surgery Left THR Left TKA Left THR Left TKA Right knee prosthesis Right TKA Right THR Right TKA
Delay between diagnosis and prosthesis implantation 35 d 12 y 19 y 9 mo 12 y 8 y 7 d 6 mo
Clinical symptoms Infected scar, fever Feverish confusion, bilateral mediastinal and hilar lymphadenopathy, knee swelling Joint pain Repeated joint effusion Erythema, joint pain Fever, abdominal pain, confusion, painful knee effusion Fever, joint pain and swelling, bullous skin lesion with itching Joint pain, warm and swollen knee
CRP, mg/L 21 100 58 NA 81 98 16 NA
Leukocytes, G/L 4.45 4 NA NA NA NA NA NA
Sample type Abscess Joint aspiration 3 tissues Joint aspiration 7 tissues Joint aspiration Joint aspiration Joint aspiration
No. positive samples/total 1/1 1/1 2/3 1/1 6/7 1/1 1/1 1/1
Delay to positivity NA 7 d 5 d 24 h–48 h 12 d 4 d 7 d 3 d
Identification Vitek 2 GN Biochemical assay; ISFtu2 PCR +; specific F. tularensis subspeciesholarctica PCR Specific Francisella PCR; ISFtu2 PCR +; 16S-23S PCR + sequencing MALDI-TOF MS (Microflex LT); ISFtu2 PCR +; specific F. tularensis subspecies holarctica PCR Sequencing 16S rRNA gene sequencing 16 S rRNA gene sequencing MALDI-TOF MS Sequencing
Serologic results MAT 640; IFA IgG 1,280; IgM 640 ELISA IgG 1.5; IgM 3.58; IFA IgG 640; IgM 640 MAT 160 ND IgM 232.6 U/mL; IgG 126.4 U/mL MAT 80 Positive (titers NA) MAT 320

Table 1. Clinical and biologic characteristics of patients with Francisella tularensis–related prosthetic joint infection*

*CRP, C-reactive protein; IFA, immunofluorescence assay; MALDI-TOF MS, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; MAT, microagglutination test; Microflex LT, Bruker Daltonics; NA, not available; ND, not done; NS, not specified; THR, total hip replacement; TKA, total knee arthroplasty; +, positive.

Table 2.  

Characteristic Case
1 2 3 4[10] 5[11] 6[11] 7[12] 8[13]
Surgery 1-stage revision joint replacement 1-stage revision joint replacement 1-stage revision with partial joint replacement Repeated joint aspiration 2-stage revision joint replacement Repeated joint aspiration DAIR 2-stage revision joint replacement
Antibiotic treatment
Before surgery DOX 100 mg 2×/d until surgery OFX 200 mg 2×/d for 6 wk ND ND AMC AMC ND IV cloxacillin 2 g/6 h for 10 d, oral cloxacillin 500 mg 4×/d
After surgery CIP 750 mg 2×/d + DOX 100 mg x2 2×/d for 9 wk IV CIP 500 mg 2×/d + IV AMK 1,200 mg for 5 d, CIP 500 mg 2×/d for 6 wk CIP 750 mg 2×/d 3 mo, lifetime treatment by DOX 100 mg 2×/d DOX, dosage NA DOX 100 mg 2×/d for 6 wk DOX 100 mg 2×/d for 20 d + GEN 240 mg for 10 d, CIP 500 mg 2×/d for 20 d DOX 100 mg 2×/d for 12 mo IV CFZ 2g/8h 6 wk + RIF 300 mg 2×/d, CIP 500 mg 2×/d + RIF 300 mg 2×/d >6 mo
Progress at follow up No relapse, nqqqo biologic inflammatory limp, chronic joint pain Biologic surveillance, favorable evolution qqqFavorable evolution with mild limp No relapse, persistence of knee swelling Favorable evolution Small pain-free effusion at 24 mo Resolution of pain and skin lesion Resolution of symptoms under treatment
Staff monitoring or prophylaxis Prophylactic DOX or CIP NA Clinical and serologic NA Serologic Prophylactic DOX NA NA

Table 2. Surgery, antibiotic treatment, and follow-up of patients with Francisella tularensis-related prosthesis joint infection

*AMC, amoxicillin/clavulanic acid; AMK, amikacin; CFZ, cefazolin; CIP, ciprofloxacin; DOX, doxycycline; DAIR, debridement, antibiotics, implant retention; GEN, gentamicin; IV, intravenous; NA, not available; ND, not done; OFX, ofloxacin; RIF, rifampin.

Table 3.  

Antibiotics MICs, mg/L Breakpoints for susceptibility, mg/L
Case 1 Case 2 Case 3
Gentamicin 0.5 0.5 0.5 4†
Ciprofloxacin 0.016 0.032 0.016 0.25†
Levofloxacin 0.032 0.032 0.032 0.5†
Rifampin 0.5 0.5 0.5 1‡
Erythromycin 2 2 2 16‡
Azythromycin 1 1 1 4‡
Doxycycline 0.25 0.25 0.25 4†

Table 3. MICs of 3 strains of Francisella tularensis subspecies holarctica obtained by broth microdilution method, France*

*The assay medium was CAMHB supplemented with 2% PolyViteX (CAMHB-PVX; bioMérieux) and adjusted to pH 7.1+0.1 as recommended (17). MICs were read after 48 h of incubation and were interpreted using the Clinical and Laboratory Standards Institute susceptibility breakpoints for Francisella tularensis when available or the Haemophilus influenzae European Committee on Antimicrobial Susceptibility Testing breakpoints. †Clinical and Laboratory Standards Institute breakpoint. ‡H. influenzae European Committee on Antimicrobial Susceptibility Testing breakpoint.

CME / ABIM MOC

Three Unusual Cases of Francisella tularensis-Related Prosthetic Joint Infection in France, and a Literature Review of 5 Cases

  • Authors: Léa Ponderand, PharmD; Thomas Guimard, MD; Estibaliz Lazaro, MD, PhD; Henry Dupuy, MD; Olivia Peuchant, PharmD, PhD; Nathalie Roch, MD; Philippe Deroche, MD; Tristan Ferry, MD, PhD; Max Maurin, MD, PhD; Aurélie Hennebique, PharmD, PhD; Sandrine Boisset, PharmD, PhD; Isabelle Pelloux, MD; Yvan Caspar, PharmD, PhD
  • CME / ABIM MOC Released: 5/18/2023
  • Valid for credit through: 5/18/2024, 11:59 PM EST
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  • Credits Available

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    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for infectious disease clinicians, rheumatologists, orthopedists, internists, and other clinicians who treat and manage patients with Francisella tularensis subsp. holarctica-related prosthetic joint infection.

The goal of this activity is for learners to be better able to describe clinical presentation, diagnosis, and treatment of Francisella tularensis prosthetic joint infection, based on a case series of 3 cases of F tularensis subsp. holarctica-related prosthetic joint infection in France between 2016 and 2019 and a review of 5 other cases reported in the literature.

Upon completion of this activity, participants will:

  • Assess clinical presentation and course of Francisella tularensis prosthetic joint infection, based on a case series of 3 cases of F tularensis subsp. holarctica-related prosthetic joint infection in France between 2016 and 2019 and a review of 5 other cases reported in the literature
  • Evaluate the diagnosis and laboratory findings of Francisella tularensis prosthetic joint infection, based on a case series of 3 cases of F tularensis subsp. holarctica-related prosthetic joint infection in France between 2016 and 2019 and review of 5 other cases reported in the literature
  • Examine the treatment of Francisella tularensis prosthetic joint infection, based on a case series of 3 cases of F tularensis subsp. holarctica-related prosthetic joint infection in France between 2016 and 2019 and review of 5 other cases reported in the literature


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Faculty

  • Léa Ponderand, PharmD

    Grenoble Alpes University Hospital Center
    Grenoble, France

  • Thomas Guimard, MD

    Departmental Hospital Center of Vendée
    La Roche sur Yon, France

  • Estibaliz Lazaro, MD, PhD

    University Hospital Center of Haut-Lévêque
    Pessac, France

  • Henry Dupuy, MD

    University Hospital Center of Haut-Lévêque
    Pessac, France

  • Olivia Peuchant, PharmD, PhD

    University Hospital Center of Bordeaux
    Bordeaux, France

  • Nathalie Roch, MD

    William Morey Hospital Center
    Chalon-sur-Saône, France

  • Philippe Deroche, MD

    Dracy-le-Fort Orthopedic Center
    Dracy le Fort, France

  • Tristan Ferry, MD, PhD

    Claude Bernard Lyon 1 University, CNRS UMR5308 – ENS Lyon – INSERM U1111
    Lyon, France
    Croix-Rousse University Hospital Center, Hospices Civils de Lyon
    Lyon, France

  • Max Maurin, MD, PhD

    Grenoble Alpes University Hospital Center
    Grenoble, France
    Univ. Grenoble Alpes, CNRS – Grenoble INP – TIMC-IMAG
    Grenoble, France

  • Aurélie Hennebique, PharmD, PhD

    Grenoble Alpes University Hospital Center
    Grenoble, France
    Univ. Grenoble Alpes, CNRS – Grenoble INP – TIMC-IMAG
    Grenoble, France

  • Sandrine Boisset, PharmD, PhD

    Grenoble Alpes University Hospital Center
    Grenoble, France

  • Isabelle Pelloux, MD

    Grenoble Alpes University Hospital Center
    Grenoble, France

  • Yvan Caspar, PharmD, PhD

    Laboratoire de Bactériologie-Hygiène hospitalière
    Centre National de Référence des Francisella
    Centre Hospitalier Universitaire Grenoble Alpes
    Grenoble, France

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has no relevant financial relationships.

Editor

  • Jill Russell, BA

    Copyeditor
    Emerging Infectious Diseases

Compliance Reviewer

  • Yaisanet Oyola, MD

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Yaisanet Oyola, MD, has no relevant financial relationships.


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CME / ABIM MOC

Three Unusual Cases of Francisella tularensis-Related Prosthetic Joint Infection in France, and a Literature Review of 5 Cases

Authors: Léa Ponderand, PharmD; Thomas Guimard, MD; Estibaliz Lazaro, MD, PhD; Henry Dupuy, MD; Olivia Peuchant, PharmD, PhD; Nathalie Roch, MD; Philippe Deroche, MD; Tristan Ferry, MD, PhD; Max Maurin, MD, PhD; Aurélie Hennebique, PharmD, PhD; Sandrine Boisset, PharmD, PhD; Isabelle Pelloux, MD; Yvan Caspar, PharmD, PhDFaculty and Disclosures

CME / ABIM MOC Released: 5/18/2023

Valid for credit through: 5/18/2024, 11:59 PM EST

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Abstract and Introduction

Abstract

Tularemia is a zoonotic infection caused by Francisella tularensis. Its most typical manifestations in humans are ulceroglandular and glandular; infections in prosthetic joints are rare. We report 3 cases of F. tularensis subspecies holarctica–related prosthetic joint infection that occurred in France during 2016–2019. We also reviewed relevant literature and found only 5 other cases of Francisella-related prosthetic joint infections worldwide, which we summarized. Among those 8 patients, clinical symptoms appeared 7 days to 19 years after the joint placement and were nonspecific to tularemia. Although positive cultures are typically obtained in only 10% of tularemia cases, strains grew in all 8 of the patients. F. tularensis was initially identified in 2 patients by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; molecular methods were used for 6 patients. Surgical treatment in conjunction with long-term antimicrobial treatment resulted in favorable outcomes; no relapses were seen after 6 months of follow-up.

Introduction

Francisella tularensis is a fastidious, gram-negative coccobacillus that can cause tularemia, a zoonotic disease. Two subspecies are responsible for human cases: F. tularensis subspecies tularensis (type A strains) and F. tularensis subsp. holarctica (type B strains)[1]. Tularemia is a reemerging disease that has occurred recently both sporadically and in outbreaks worldwide. No vaccines are available, and antibiotic classes effective in treatment are limited to aminoglycosides, fluoroquinolones, and tetracyclines[2,3].

Potential reservoirs and vectors in both the terrestrial and aquatic cycles of this bacterium are varied. Six main clinical forms of tularemia have been described (glandular, ulceroglandular, oropharyngeal, oculoglandular, pneumonic, and typhoidal), depending on the route of bacterial inoculation. Tularemia can be transmitted through direct contact with infected animals (hares, rabbits, small rodents, etc.); through the bites of blood-sucking arthropods; through consumption of contaminated food or water; through conjunctival inoculation with contaminated fingers, materials, or aerosolized particles; or through the lungs, either by inhaling infectious aerosols or by the hematogenous spread of bacteria[4–7].

Severe infections are predominantly associated with F. tularensis subsp. tularensis, which is present only in North America, whereas F. tularensis subsp. holarctica, the only subspecies found in both Europe and North America, largely causes incapacitating and chronic disease with large or multiple lymphadenopathies[8]. According to data from the French National Reference Center for Francisella (FNRCF) and from mandatory notifications to the French Public Health Agency, the ulceroglandular and glandular forms account for most (72%) clinical forms of the disease[9]. Bone and joint infections (BJIs) and prosthetic joint infections (PJIs) related to F. tularensis are extremely rare and have been reported sporadically in literature[10–13]. BJIs are primarily related to staphylococci, streptococci, or gram-negative rods, but any bacterial species can cause an infection in the presence of prosthetic material[14,15]. We report 3 cases of F. tularensis–related PJIs occurring during 2016–2019 in France, as well as the results of a literature review on BJIs and PJIs related to this highly pathogenic bacterium (Table 1, Table 2).