# An Abrasion, a Prosthetic Shoulder, and a Cat with a Licking Tendency: Case Report and Literature Review ofP. multocida Joint Seeding

Authors: William F. Abel; Christopher S. Eckman; Robert P. Summers; William S. Sessions; Amanda E. Schnee
Journal: Case Reports in Infectious Diseases
 (2020)

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## Abstract

Pasteurella multocida is a pathogen well known for its zoonotic transmission, most commonly by cats and dogs. When bacteremia ensures from an infection, patients with foreign objects present in their bodies, including prosthetic joints and mesh implants, become vulnerable to seeding. There have been multiple documented cases in which P. multocida bacteremia has resulted in infection of both native and prosthetic joints. Furthermore, cases have been documented in which patients with P. multocida bacteremia have developed meningitis and neurological complications. Here, we present a patient with multiple comorbidities including multifactorial immunocompromise, advanced age, and multiple prosthetic joints who developed prosthetic joint infection and spinal osteomyelitis after the development of Pasteurella bacteremia. Aggressive treatment was undertaken given her risk factors, and a combination of antibiotics and surgery was utilized, with the patient making a full recovery.


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## Body

## 1. Background

Pasteurella multocida was first isolated by Louis Pasteur in 1880. Since that time, it has been demonstrated as a common source of zoonotic infection with P. multocida isolated in up to 50% of dog bites and 75% of cat bites [1]. P. multocida infection has also been documented in the absence of bite wounds in patients with cat scratches present on physical examination [2]. Less commonly still are instances in which P. multocida is isolated from an individual where no wounds from animals are detected [3, 4]. We present a case of P. multocida bacteremia in an immunocompromised patient, with a history of close contact with both cats and dogs but no bites or scratches, resulting in subsequent septic arthritis of the shoulder, epidural abscess, and spinal osteomyelitis. We reviewed the available literature on P. multocida and pathogenicity, antibiotic susceptibility profiles, and propensity for metastatic foci of infection.


## 2. Case Presentation

A 67-year-old female with a past medical history of multiple myeloma status postautologous stem cell transplant 4 years prior with evidence of stringent complete response and maintained on lenalidomide presented with wrist pain, fevers, and altered mental status. The patient had been well until two days prior when she fell at home. She was found by a home aide to be confused, febrile, and with a swollen right wrist. Significant surgical history included bilateral knee surgeries, left shoulder arthroplasty, and right total hip arthroplasty. She reported living with a roommate and numerous domestic cats and dogs.In the emergency department, presenting vital signs revealed blood pressure 86/44 mmHg, temperature 101.1 F, heart rate 128, and oxygen saturation 94% on 3 liters nasal cannula. Examination of the patient revealed her to be alert and oriented only to herself. Respiratory examination revealed good air movement and normal breath sounds. The ulnar aspect of her right wrist revealed a small abrasion with mild erythema. The right wrist was edematous and tender to palpation. She had decreased strength and range of motion in the right wrist, but normal elbow and shoulder joints. There were no signs of otherwise broken or punctured skin. The remainder of her musculoskeletal examination was unremarkable.Initial complete blood count revealed a white blood cell count of 5.0 Th/mm3 (normal limit 4.0–11.0 Th/mm3), hemoglobin 10.4 g/dL (grams/deciliter) (normal limit 12.0–16.0 g/dL), platelets 132.0 Th/mm3 (normal limit 150–400 Th/mm3), and 21% bands (normal limit 3–5%). Complete metabolic panel was significant for sodium 126 mMol/L (millimoles per liter) (normal limit 136–145 mMol/L), AST 213 IU/L (international units per liter) (normal limit 8–20 IU/L), ALT 57 IU/L (normal limit 8–20 IU/L), and alkaline phosphatase 479 IU/L (normal limit 20–70 IU/L). Erythrocyte sedimentation rate and C-reactive protein were 104 mm/hr (normal limit 0–20 mm/hr) and 237 mg/L (normal limit < 10 mg/L), respectively. Procalcitonin was 5.48 ng/mL (normal limit < 0.05 ng/mL). Urinalysis returned negative for leukocyte esterase and nitrite, and moderate blood was noted. Blood, urine, and stool cultures were obtained. Lumbar puncture was attempted twice unsuccessfully. Aspiration of the right wrist resulted in a dry tap. Empiric antibiotic coverage with vancomycin and ceftriaxone was initiated. Table 1 illustrates lab values from the patient’s admission.Table 1
Laboratory values from the patient’s hospital admission.
Hospital dayDay 1Day 2Day 3Day 4Day 5Day 6Day 7Day 8Day 9Day 10Day 11Day 20WBC9.97.114.114.111.510.791010.48.38.76.0RBC2.82.762.93.062.653.013.052.922.812.72.812.69Hemoglobin9.69.19.79.98.89.89.99.79.38.69.38.5Hematocrit26.726.726.92824.528.328.328.527.726.827.926.3MCV95.496.792.891.592.59492.897.698.699.399.397.8MCH34.33333.432.433.232.632.533.233.131.933.131.6MCHC3634.136.135.435.934.6353433.632.133.3232.3RDW13.914.31414.414.514.614.114.513.913.713.213.6Platelets125109159256256311340331360358335255MPV9.59.9109.59.49.398.99.1998.5nRBC percentage000000000000nRBC abs000000000000Sodium126131132132133132127132130129130131Potassium4.32.93093.13.43.73.94.54.54.14.23.6Chloride931041069910196959697979596CO2171715242627242819212627Anion gap1610119698891198Glucose93809010499999390787888104BUN2114137778121212116Creatinine, serum0.710.60.620.560.550.550.540.60.570.570.590.52eGR non-African American88>90>90>90>90>90>90>90>90>90>90>90Calcium8.77.57.58.188.88.69.58.38.58.88.2Bilirubin, total1.61.01.21.21.01.01.00.80.6060.40.3Protein, total6.85.25.25.65.16.06.16.35.86.06.25.3Albumin2.51.91.92.01.82.12.12.32.52.12.21.9AST213206105492522242224192012ALT57765642241917151411107Alkaline phosphatase479415401426356453485487453415402253Magnesium1.81.41.81.41.51.41.61.61.71.72.1AmmoniaLactate1.940.8CRP, inflammatory237133.3Procalcitonin5.48CK, total6972Osmolality, measured262ESR10458Radiographs of the chest as well as the right wrist (Figure1), elbow, and humerus were obtained. Computed tomography (CT) of the head, abdomen, and pelvis were also obtained. Right upper extremity radiographs revealed no acute osseous or soft tissue abnormalities, and chest radiograph revealed clear lungs. CT imaging revealed no intracranial abnormalities but did note fluid levels in frothy secretions in the paranasal sinuses, as well as nonspecific perinephric edema and thickening of the renal pelvis bilaterally.Figure 1
(a) PA X-ray right wrist, (b) lateral X-ray right wrist, (c) T1 coronal MRI right shoulder, and (d) T1 sagittal lumbar spine.
(a)(b)(c)(d)The patient’s blood cultures grewPasteurella multocida in both sets of bottles. Susceptibilities included amoxicillin-clavulanate, ampicillin, ceftriaxone, levofloxacin, penicillin, and tetracycline. The organism was noted to be resistant to trimethoprim-sulfamethoxazole. Respiratory, stool, and urine cultures were negative. Antibiotic therapy was deescalated to monotherapy with ceftriaxone. Repeat blood cultures were obtained on hospital day four and were without growth.On hospital day seven, the patient reported worsening left shoulder pain, the site of her previous left total shoulder arthroplasty. Magnetic resonance imaging (MRI) (Figure1) revealed the presence of a small perihardware collection. Aspiration was performed, revealing approximately 70,000 white blood cells without crystals, and no subsequent growth on either aerobic or anaerobic cultures. Arthroscopy revealed purulent drainage from the anterior left shoulder, and subsequent lavage was performed by orthopedics out of concern for septic arthritis. Thick, purulent material was noted intraoperatively, but cultures remained without growth.On hospital day ten, the patient reported an acute worsening in pain and feeling overall unwell. Physical exam revealed extreme point tenderness to palpation of her cervical and lumbar spine. MRIs of the spine (Figure1) revealed multilevel osteomyelitis and septic arthritis of the facet joints L3-S1 bilaterally, as well as edema of the paraspinous soft tissues with epidural abscess. Laminectomy with incision and drainage was performed, and subsequent cultures revealed no growth. Additional imaging with contrast further demonstrated septic arthritis and epidural abscess.The patient was able to be successfully discharged to a rehabilitation facility with the follow-up arranged with infectious disease and orthopedic specialists. She was continued on levofloxacin at discharge to complete a total of 6 weeks of therapy.


## 3. Discussion

P. multocida is a Gram-negative organism found as a member of the normal flora in the oropharynx and nasopharynx of cats, dogs, cattle, and mice [5]. With 38.4% of households owning dogs and 25.4% of households owning cats in the United States, this is an organism that a relatively large proportion of the population is exposed to on a daily basis [6]. Of particular relevance is the danger of infection with P. multocida progressing to bacteremia, which has mortality rates up to 30% [7].


### 3.1. Virulence Factors

P. multocida possesses a number of virulence factors known to facilitate various diseases in both humans and animals. LPS (lipopolysaccharide) from P. multocida has been shown to cause hemorrhagic septicemia in ungulates, cholera in avian species, and atrophic rhinitis in pigs [8]. While there are no known exotoxins produced, the polysaccharide capsule is important for protection from host immune defenses, and the filamentous hemagglutinin surface adhesin allows for adherence to structures [8]. There are 5 capsular serogroups and 16 Heddleston serovars, with A:1 and A:3 (serogroup: serovar) being most commonly transmitted from cats to humans [9]. P. multocida possesses the ability to produce biofilms, although this ability depends on the conditions present and interferes with the production of serogroup A capsule [10]. It would seem plausible, then, that in an immunosuppressed host such as in our case, the need for capsule production to evade immune response would be lessened, allowing for the production of biofilms and potentially the ability to seed multiple sites within the same host. The ability to form biofilms in these hosts may also speak to the need for longer durations of therapy, more aggressive interventions where foreign bodies are involved, and the consideration for suppressive therapy in settings where foreign bodies cannot be removed. This hypothesis is substantiated by a case report by Guilbart et al. [11], where they report a patient who suffered fatal septicemia related to P. multocida cellulitis which was complicated by endocarditis as well as prosthetic joint infection. In this particular case, they attempted a salvage approach for the prosthetic joint but were unsuccessful at clearing the infection, indicating that the virulence factors discussed require more aggressive initial interventions for effective treatment.


### 3.2. Antibiotic Resistance

Drug resistance has been noted in a number of strains infecting bovine and avian species in China [12]. P. multocida strains known to infect humans and cats have been shown to possess resistance to cotrimoxazole (75.6%), sulfisoxazole (60.9%), and penicillin (7.3%), as well as others at very low rates [13]. Furthermore, β-lactamase production has been documented as well as the presence of plasmids that are associated with resistance to various antibiotic classes including tetracyclines and aminoglycosides [14]. The potential for beta-lactamase production should be noted by physicians when treating P. multocida infections or when P. multocida is suspected and treatment failure occurs, as beta-lactams are frequently the first line therapies for cellulitis and bacteremia.


### 3.3. Lenalidomide in the Setting of Infection

In our patient, a history of multiple prosthetic joints significantly elevated the risks associated with bacteremia due to her increased susceptibility to joint seeding. While most documented cases ofPasteurella bacteremia are in patients who suffered animal bites and scratches, there are documented cases in which the source of the infection was considered to be licking of an existing wound or kissing of the animal [3, 4, 13]. Of significant interest is the fact that the patient was taking lenalidomide at the time of hospitalization. In a meta-analysis conducted in 2017, the incidence of high-grade infection in patients with multiple myeloma taking lenalidomide was determined to be 14.32%, nearly twice the infection rate of the control group [15].While a mechanism for the way in which lenalidomide might lead to immunodeficiency has not yet been established, a number of confounding factors leading to immunodeficiency in patients with multiple myeloma include advanced median age of patients, effects of the disease on B cells, T cells, and natural killer cells, as well as additional medical therapies used in the treatment of multiple myeloma [16].


### 3.4. Prosthetic vs. Native Joint Seeding

The presence of a prosthetic joint in and of itself is an established risk factor for infection [17]. Furthermore, in bacteremia patients, the microbial load required to seed and infect a joint is lower [17]. In a review of literature regarding the seeding of joints by P. multocida from 1985 to 2019 (Table 2), there were 30 cases of infection reported involving a knee joint, seven cases of a hip joint, two cases of shoulder joint (including our patient in this report), one case of ankle joint, and one case of wrist joint. Of these, 28 of 30 (93%) knee infections were prosthetic, 7 of 7 (100%) hip infections were prosthetic, 1 of 2 (50%) shoulder infections was prosthetic, 0 of 1 (0%) ankle infection was prosthetic, and 0 of 1 (0%) wrist infection was prosthetic.Table 2
Previous findings and outcomes from case reports in relation to the presence of septic arthritis in patients withPasteurella bacteremia.
ReferenceSite of infectionAnimal exposure?ComorbiditiesDuration of therapyAntibiotic resistance?Bacteremia (y/n)?Outcome (surgical intervention?)Maurer et al. [18]Knee, prostheticYesRheumatoid arthritis—NoneNoCure, no interventionGriffin and Barber [19]Knee, prostheticYesRheumatoid arthritis—NoneNoCure, no interventionSugarmen et al. [20]Knee, prostheticYesRheumatoid arthritis—NoneNoCure, replacement of prosthesisArvan and Goldberg [21]Knee, prostheticYesAdvanced age—NoneNoCure, surgical debridementSpagnuolo [22]Knee, prostheticYesAdvanced age—NoneNoCure, surgical debridementGomez-Reino et al. [23]Knee, prostheticYesAdvanced age—NoneNoCure, replacement of prosthesisMellors and Schoen [24]Bl knees, prostheticYesNone—NoneNoCure, noneOrton and Fulcher [25]Bl knees, prostheticYesAdvanced age—NoneNoCure, replacement of prosthesisTaillan et al. [26]Knee, prostheticYesAdvanced age—NoneNoCure, noneBraithwaite and Giddins [27]Hip, prostheticYesDiabetes—NoneNoCure, replacement of prosthesisGuion and Sculco [28]Knee, prostheticYesRheumatoid arthritis—NoneNoCure, replacement of prosthesisGabuzda and Barnett [29]Knee, prostheticYesAdvanced age—NoneNoCure, replacement of prosthesisAntuña et al. [30]Knee, prostheticYesRheumatoid arthritis—NoneNoCure, surgical debridementTakwale et al. [31]Hip, prostheticYesRheumatoid arthritis—NoneNoCure, replacement of prosthesisMaradona et al. [32]L knee, prostheticYesAdvanced age, diabetes3 weeksNoneNoCure, surgical debridementChikwe et al. [33]R hip, prostheticYesAdvanced age—NoneNoCure, replacement of prosthesisCiampolini et al. [34]Knee, prostheticYesAdvanced age6 weeksNoneNoCure, replacement of prosthesisPolzhoferet al. [35]R knee, prostheticYesAdvanced age—NoneNoCure, surgical debridementStiehl et al. [36]Knee, prostheticYesAdvanced age—NoneNoCure, replacement of prosthesisMehta and Mackie [37]Hip, prostheticYesAdvanced age, rheumatoid arthritis—NoneNoCure, replacement of prosthesisMehta and Mackie [37]Hip, prostheticYesRheumatoid arthritis—NoneNoCure, replacement of prosthesisHeym et al. [38]Knee, prostheticYesAdvanced age2 monthsNoneYesCure, replacement of prosthesisKadakia and Langkamer [39]Knee, prostheticYesAdvanced age10 weeksNoneNoCure, surgical debridementHeydeman et al. [40]L knee, prostheticYesAdvanced age4 weeksNoneNoCure, removal of prosthesisRomano et al. [41]L knee, prostheticYesAdvanced age, rheumatoid arthritis6 weeksNoneYesCure, surgical debridementFurgeson et al. [42]L knee, prostheticYesAdvanced age8 weeksNoneNoCure, surgical debridementAyoade and Todd. [17]R knee, prostheticYesAdvanced age, obesity, aortic stenosis7 daysNoneYesDeath, surgical debridementArbefeville et al. [43]R knee, prostheticYesAdvanced age6 weeksNoneyesCure, replacement of prosthesisZahirovic and Siddique [44]L wrist, nativeYesDiabetes2 weeksYes (to erythromycin)YesCure, surgical debridementHonnerat et al. [45]Hip, prostheticYesAdvanced age8 monthsNoneNoCure, surgical debridementHonnerat et al. [45]Knee, prostheticYesAdvanced age, diabetes8 monthsNoneNoCure, replacement of prosthesisHonnerat et al. [45]Knee, prostheticYesAdvanced age, diabetes8 monthsNoneNoCure, replacement of prosthesisHonnerat et al. [45]Knee, prostheticYesAdvanced age, obesity8 monthsNoneNoCure, replacement of prosthesisHonnerat et al. [45]Knee, prostheticYesAdvanced age8 monthsNoneNoCure, surgical debridementHonnerat et al. [45]Knee, prostheticYesAdvanced age8 monthsNoneNoCure, replacement of prosthesisNitorslawski et al. [46]Knee, native; shoulder, nativeYesAdvanced age6 weeksNoneNoCure, surgical debridementFayyaz [47]L hip, prostheticNoCOPD, alcohol use6 weeksNoneYesCure, replacement of prosthesisKatechakis et al. [48]Ankle and knee, nativeYesNone20 daysNoneYesCure, below the knee amputationAlcohol use,The decision of whether to salvage or replace a prosthetic joint after seeding has occurred is a complicated one. In the review described above, 13 joints were debrided with antimicrobials and salvaged, while 29 joints were removed (Table2). Cost and associated risks with repeated arthroscopic surgery and spacer placement have to be weighed against the risk of chronic infection that a more conservative debridement and salvage may bring. Of the 13 cases in which the joint was salvaged, one death occurred leading to the conclusion that salvage of the joint (and other septic joints in the general population) was a poor decision due to the risk of sepsis that goes with retainment of an infected foreign body [11].


### 3.5. Meningitis and Septic Arthritis in the Setting ofPasteurella Bacteremia

Review of 13 cases in which meningitis occurred in the setting ofP. multocida infection from 1983 to 2018 was conducted to analyze the relationship between meningitis and bacteremia. 10 of 13 (77%) cases occurred in the setting of Pasteurella bacteremia, with the remaining 3 cases not documenting the presence (Table 3).Table 3
Previous findings and outcomes from case reports in relation to the presence of meningitis in patients withPasteurella bacteremia.
ReferenceYearPresenting compliantSite of infectionAnimal exposure?ComorbiditiesAntibiotic resistance?Bacteremia (y/n)?OutcomeNitoslawski et al. [46]2018FeverCNSYesDiabetes mellitusNoYesCureLarné et al. [49]2019FeverCNSYesNoYesCureClarke et al. [2]2017FeverCNSYesNoYesCure, residual hearing lossYamaguchi et al. [50]2014FeverCNSYesNoneNoYesCureSpadafora et al. [51]2011Status epilepticusCNSYesNoNoCureSoloaga et al. [52]2008FeverCNSYesNoYesCureHirsh et al. [53]2004FeverCNSYesNoneNoNoCureGreen et al. [54]2002CNSYesNoYesCureLayton [55]1999FeverCNSYesNoYesCureGuerin et al. [56]1994CNSYesHIV+NoYesDeathKumar et al. [57]1990CNSYesNoYesCureLevy et al. [58]1989FeverCNSYesNoneNoYesCure, residual neurological deficitPermezel et el. [59]1984FeverCNSYesRecent sinus surgeryNoNoCureBruun and Friis-Møller [60]1983FeverCNSYesChronic omNoNoCureBased on the review of outcomes from 13 cases, 10 patients had resolution of infection, two patients had negative long-term neurological outcomes, and one patient died (in the setting of HIV infection). These results support consideration of lumbar puncture in patients presenting with evidence of joint infection in the setting of animal contact and immunocompromising illness due to the risk of meningitis.


### 3.6. Risk Factors and Potential Mechanism

WhilePasteurella bacteremia in the absence of a bite or scratch is uncommon, most documented cases were in the presence of some form of immunodeficiency [3, 12]. A number of risk factors have been established including advanced age (mean age of 63), alcohol consumption, tobacco use, and chronic liver disease [61]. Our patient in this case report demonstrated both age and alcohol risk factors. Our patient denied any bites or scratches, and physical examination corroborated her story; however, there was an abrasion on her right wrist that she sustained from her prior fall. In support of the hypothesis that the licking of an already existing wound led to infection with P. multocida, the patient has multiple dogs and cats and reported that one cat has a tendency to lick people and objects. Cases in which licking was considered to be a likely mode of transmission have been documented [4, 62]. Additionally, one retrospective review noted that cases of P. multocida bacteremia where animal bites were not noted as the inciting event for infection were found to have poorer outcomes [63]. Given our patient’s hospital course, we would hypothesize that her infection was related to licking of a preexisting wound, with underlying comorbidities portending a more aggressive course and potentially a worse prognosis.


### 3.7. Thrombocytopenia in the Setting of Infection

The patient was thrombocytopenic on initial labs taken in the emergency department. This resolved by day 3 of admission, and the patient had a normal platelet count for the duration of her hospital stay. A number of mechanisms have been postulated to account for thrombocytopenia in systemic infection including the formation of thrombocyte/neutrophil complexes and the temporary reduction of thrombopoiesis due to LPS [64, 65]. The role of platelets in infection has been reviewed at length by Dewitte et al. [66]. Given that this patient had a Gram-negative bacteremia, we suspect her temporary thrombocytopenia may have been due to a combination of thrombocyte/neutrophil aggregation and the effects of LPS on thrombopoiesis.


## 3.1. Virulence Factors

P. multocida possesses a number of virulence factors known to facilitate various diseases in both humans and animals. LPS (lipopolysaccharide) from P. multocida has been shown to cause hemorrhagic septicemia in ungulates, cholera in avian species, and atrophic rhinitis in pigs [8]. While there are no known exotoxins produced, the polysaccharide capsule is important for protection from host immune defenses, and the filamentous hemagglutinin surface adhesin allows for adherence to structures [8]. There are 5 capsular serogroups and 16 Heddleston serovars, with A:1 and A:3 (serogroup: serovar) being most commonly transmitted from cats to humans [9]. P. multocida possesses the ability to produce biofilms, although this ability depends on the conditions present and interferes with the production of serogroup A capsule [10]. It would seem plausible, then, that in an immunosuppressed host such as in our case, the need for capsule production to evade immune response would be lessened, allowing for the production of biofilms and potentially the ability to seed multiple sites within the same host. The ability to form biofilms in these hosts may also speak to the need for longer durations of therapy, more aggressive interventions where foreign bodies are involved, and the consideration for suppressive therapy in settings where foreign bodies cannot be removed. This hypothesis is substantiated by a case report by Guilbart et al. [11], where they report a patient who suffered fatal septicemia related to P. multocida cellulitis which was complicated by endocarditis as well as prosthetic joint infection. In this particular case, they attempted a salvage approach for the prosthetic joint but were unsuccessful at clearing the infection, indicating that the virulence factors discussed require more aggressive initial interventions for effective treatment.


## 3.2. Antibiotic Resistance

Drug resistance has been noted in a number of strains infecting bovine and avian species in China [12]. P. multocida strains known to infect humans and cats have been shown to possess resistance to cotrimoxazole (75.6%), sulfisoxazole (60.9%), and penicillin (7.3%), as well as others at very low rates [13]. Furthermore, β-lactamase production has been documented as well as the presence of plasmids that are associated with resistance to various antibiotic classes including tetracyclines and aminoglycosides [14]. The potential for beta-lactamase production should be noted by physicians when treating P. multocida infections or when P. multocida is suspected and treatment failure occurs, as beta-lactams are frequently the first line therapies for cellulitis and bacteremia.


## 3.3. Lenalidomide in the Setting of Infection

In our patient, a history of multiple prosthetic joints significantly elevated the risks associated with bacteremia due to her increased susceptibility to joint seeding. While most documented cases ofPasteurella bacteremia are in patients who suffered animal bites and scratches, there are documented cases in which the source of the infection was considered to be licking of an existing wound or kissing of the animal [3, 4, 13]. Of significant interest is the fact that the patient was taking lenalidomide at the time of hospitalization. In a meta-analysis conducted in 2017, the incidence of high-grade infection in patients with multiple myeloma taking lenalidomide was determined to be 14.32%, nearly twice the infection rate of the control group [15].While a mechanism for the way in which lenalidomide might lead to immunodeficiency has not yet been established, a number of confounding factors leading to immunodeficiency in patients with multiple myeloma include advanced median age of patients, effects of the disease on B cells, T cells, and natural killer cells, as well as additional medical therapies used in the treatment of multiple myeloma [16].


## 3.4. Prosthetic vs. Native Joint Seeding

The presence of a prosthetic joint in and of itself is an established risk factor for infection [17]. Furthermore, in bacteremia patients, the microbial load required to seed and infect a joint is lower [17]. In a review of literature regarding the seeding of joints by P. multocida from 1985 to 2019 (Table 2), there were 30 cases of infection reported involving a knee joint, seven cases of a hip joint, two cases of shoulder joint (including our patient in this report), one case of ankle joint, and one case of wrist joint. Of these, 28 of 30 (93%) knee infections were prosthetic, 7 of 7 (100%) hip infections were prosthetic, 1 of 2 (50%) shoulder infections was prosthetic, 0 of 1 (0%) ankle infection was prosthetic, and 0 of 1 (0%) wrist infection was prosthetic.Table 2
Previous findings and outcomes from case reports in relation to the presence of septic arthritis in patients withPasteurella bacteremia.
ReferenceSite of infectionAnimal exposure?ComorbiditiesDuration of therapyAntibiotic resistance?Bacteremia (y/n)?Outcome (surgical intervention?)Maurer et al. [18]Knee, prostheticYesRheumatoid arthritis—NoneNoCure, no interventionGriffin and Barber [19]Knee, prostheticYesRheumatoid arthritis—NoneNoCure, no interventionSugarmen et al. [20]Knee, prostheticYesRheumatoid arthritis—NoneNoCure, replacement of prosthesisArvan and Goldberg [21]Knee, prostheticYesAdvanced age—NoneNoCure, surgical debridementSpagnuolo [22]Knee, prostheticYesAdvanced age—NoneNoCure, surgical debridementGomez-Reino et al. [23]Knee, prostheticYesAdvanced age—NoneNoCure, replacement of prosthesisMellors and Schoen [24]Bl knees, prostheticYesNone—NoneNoCure, noneOrton and Fulcher [25]Bl knees, prostheticYesAdvanced age—NoneNoCure, replacement of prosthesisTaillan et al. [26]Knee, prostheticYesAdvanced age—NoneNoCure, noneBraithwaite and Giddins [27]Hip, prostheticYesDiabetes—NoneNoCure, replacement of prosthesisGuion and Sculco [28]Knee, prostheticYesRheumatoid arthritis—NoneNoCure, replacement of prosthesisGabuzda and Barnett [29]Knee, prostheticYesAdvanced age—NoneNoCure, replacement of prosthesisAntuña et al. [30]Knee, prostheticYesRheumatoid arthritis—NoneNoCure, surgical debridementTakwale et al. [31]Hip, prostheticYesRheumatoid arthritis—NoneNoCure, replacement of prosthesisMaradona et al. [32]L knee, prostheticYesAdvanced age, diabetes3 weeksNoneNoCure, surgical debridementChikwe et al. [33]R hip, prostheticYesAdvanced age—NoneNoCure, replacement of prosthesisCiampolini et al. [34]Knee, prostheticYesAdvanced age6 weeksNoneNoCure, replacement of prosthesisPolzhoferet al. [35]R knee, prostheticYesAdvanced age—NoneNoCure, surgical debridementStiehl et al. [36]Knee, prostheticYesAdvanced age—NoneNoCure, replacement of prosthesisMehta and Mackie [37]Hip, prostheticYesAdvanced age, rheumatoid arthritis—NoneNoCure, replacement of prosthesisMehta and Mackie [37]Hip, prostheticYesRheumatoid arthritis—NoneNoCure, replacement of prosthesisHeym et al. [38]Knee, prostheticYesAdvanced age2 monthsNoneYesCure, replacement of prosthesisKadakia and Langkamer [39]Knee, prostheticYesAdvanced age10 weeksNoneNoCure, surgical debridementHeydeman et al. [40]L knee, prostheticYesAdvanced age4 weeksNoneNoCure, removal of prosthesisRomano et al. [41]L knee, prostheticYesAdvanced age, rheumatoid arthritis6 weeksNoneYesCure, surgical debridementFurgeson et al. [42]L knee, prostheticYesAdvanced age8 weeksNoneNoCure, surgical debridementAyoade and Todd. [17]R knee, prostheticYesAdvanced age, obesity, aortic stenosis7 daysNoneYesDeath, surgical debridementArbefeville et al. [43]R knee, prostheticYesAdvanced age6 weeksNoneyesCure, replacement of prosthesisZahirovic and Siddique [44]L wrist, nativeYesDiabetes2 weeksYes (to erythromycin)YesCure, surgical debridementHonnerat et al. [45]Hip, prostheticYesAdvanced age8 monthsNoneNoCure, surgical debridementHonnerat et al. [45]Knee, prostheticYesAdvanced age, diabetes8 monthsNoneNoCure, replacement of prosthesisHonnerat et al. [45]Knee, prostheticYesAdvanced age, diabetes8 monthsNoneNoCure, replacement of prosthesisHonnerat et al. [45]Knee, prostheticYesAdvanced age, obesity8 monthsNoneNoCure, replacement of prosthesisHonnerat et al. [45]Knee, prostheticYesAdvanced age8 monthsNoneNoCure, surgical debridementHonnerat et al. [45]Knee, prostheticYesAdvanced age8 monthsNoneNoCure, replacement of prosthesisNitorslawski et al. [46]Knee, native; shoulder, nativeYesAdvanced age6 weeksNoneNoCure, surgical debridementFayyaz [47]L hip, prostheticNoCOPD, alcohol use6 weeksNoneYesCure, replacement of prosthesisKatechakis et al. [48]Ankle and knee, nativeYesNone20 daysNoneYesCure, below the knee amputationAlcohol use,The decision of whether to salvage or replace a prosthetic joint after seeding has occurred is a complicated one. In the review described above, 13 joints were debrided with antimicrobials and salvaged, while 29 joints were removed (Table2). Cost and associated risks with repeated arthroscopic surgery and spacer placement have to be weighed against the risk of chronic infection that a more conservative debridement and salvage may bring. Of the 13 cases in which the joint was salvaged, one death occurred leading to the conclusion that salvage of the joint (and other septic joints in the general population) was a poor decision due to the risk of sepsis that goes with retainment of an infected foreign body [11].


## 3.5. Meningitis and Septic Arthritis in the Setting ofPasteurella Bacteremia

Review of 13 cases in which meningitis occurred in the setting ofP. multocida infection from 1983 to 2018 was conducted to analyze the relationship between meningitis and bacteremia. 10 of 13 (77%) cases occurred in the setting of Pasteurella bacteremia, with the remaining 3 cases not documenting the presence (Table 3).Table 3
Previous findings and outcomes from case reports in relation to the presence of meningitis in patients withPasteurella bacteremia.
ReferenceYearPresenting compliantSite of infectionAnimal exposure?ComorbiditiesAntibiotic resistance?Bacteremia (y/n)?OutcomeNitoslawski et al. [46]2018FeverCNSYesDiabetes mellitusNoYesCureLarné et al. [49]2019FeverCNSYesNoYesCureClarke et al. [2]2017FeverCNSYesNoYesCure, residual hearing lossYamaguchi et al. [50]2014FeverCNSYesNoneNoYesCureSpadafora et al. [51]2011Status epilepticusCNSYesNoNoCureSoloaga et al. [52]2008FeverCNSYesNoYesCureHirsh et al. [53]2004FeverCNSYesNoneNoNoCureGreen et al. [54]2002CNSYesNoYesCureLayton [55]1999FeverCNSYesNoYesCureGuerin et al. [56]1994CNSYesHIV+NoYesDeathKumar et al. [57]1990CNSYesNoYesCureLevy et al. [58]1989FeverCNSYesNoneNoYesCure, residual neurological deficitPermezel et el. [59]1984FeverCNSYesRecent sinus surgeryNoNoCureBruun and Friis-Møller [60]1983FeverCNSYesChronic omNoNoCureBased on the review of outcomes from 13 cases, 10 patients had resolution of infection, two patients had negative long-term neurological outcomes, and one patient died (in the setting of HIV infection). These results support consideration of lumbar puncture in patients presenting with evidence of joint infection in the setting of animal contact and immunocompromising illness due to the risk of meningitis.


## 3.6. Risk Factors and Potential Mechanism

WhilePasteurella bacteremia in the absence of a bite or scratch is uncommon, most documented cases were in the presence of some form of immunodeficiency [3, 12]. A number of risk factors have been established including advanced age (mean age of 63), alcohol consumption, tobacco use, and chronic liver disease [61]. Our patient in this case report demonstrated both age and alcohol risk factors. Our patient denied any bites or scratches, and physical examination corroborated her story; however, there was an abrasion on her right wrist that she sustained from her prior fall. In support of the hypothesis that the licking of an already existing wound led to infection with P. multocida, the patient has multiple dogs and cats and reported that one cat has a tendency to lick people and objects. Cases in which licking was considered to be a likely mode of transmission have been documented [4, 62]. Additionally, one retrospective review noted that cases of P. multocida bacteremia where animal bites were not noted as the inciting event for infection were found to have poorer outcomes [63]. Given our patient’s hospital course, we would hypothesize that her infection was related to licking of a preexisting wound, with underlying comorbidities portending a more aggressive course and potentially a worse prognosis.


## 3.7. Thrombocytopenia in the Setting of Infection

The patient was thrombocytopenic on initial labs taken in the emergency department. This resolved by day 3 of admission, and the patient had a normal platelet count for the duration of her hospital stay. A number of mechanisms have been postulated to account for thrombocytopenia in systemic infection including the formation of thrombocyte/neutrophil complexes and the temporary reduction of thrombopoiesis due to LPS [64, 65]. The role of platelets in infection has been reviewed at length by Dewitte et al. [66]. Given that this patient had a Gram-negative bacteremia, we suspect her temporary thrombocytopenia may have been due to a combination of thrombocyte/neutrophil aggregation and the effects of LPS on thrombopoiesis.


## 4. Conclusion

Given the relative abundance of cats and dogs as pets in the United States, it is prudent to remain aware of zoonotic pathogens.P. multocida is a microorganism with the capability of causing infection associated with significant morbidity and mortality. With pet ownership in the United States unlikely to decline in the near future, it is important to consider P. multocida in patients who have contact with pets and comorbid factors known to attenuate immunity. Physicians treating patients found to be infected with P. multocida should be aware of the potential for bacteremia, prosthetic joint infection, and meningitis, particularly in patients with advanced age and immunocompromised states as demonstrated by our patient.



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