Thursday, June 1, 2023
| 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.
| 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.
| 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.
Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™
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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.
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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.
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).
