Orthopedics

Case Reports 

Salmonella Osteomyelitis in New-onset Diabetes Mellitus

Joseph S. Gondusky, MD; Christina J. Gondusky, MD; Scott W. Helmers, MD

Abstract

Salmonella species are rare bacterial isolates in osteomyelitis. This article describes a case of an otherwise healthy, active duty male military member with an insidious onset of right knee pain during a deployment to Kuwait. His work-up revealed an infectious process in the distal femur. Operative treatment and intravenous antibiotics resolved the infection. Intraoperative cultures revealed the rare isolate Salmonella enterica serotype C2 (Newport). Postoperative medical management revealed new-onset diabetes mellitus, possibly making this otherwise healthy host susceptible to this rare infection.

Salmonella are gram-negative bacteria. Infection with nontyphoidal Salmonella species most commonly manifests as intestinal illness. Although it may be difficult for clinicians to accurately predict this rare entity as the causative organism in osteomyelitis, they may be aided by a history of travel to endemic regions or exposure to animal carriers. Comorbidities that seem to increase susceptibility include diabetes mellitus, human immunodeficiency virus, hemoglobinopathies, and immunosuppression. Blood cultures are reported to be frequently positive in cases of Salmonella osteomyelitis. Identification of Salmonella species from intraoperative cultures should prompt consultation with the infectious disease department for culture-specific antibiotic tailoring. Many common antibiotic agents active against gram-negative organisms seem efficacious. As in this case, following the basic tenets of osteomyelitis management should lead to an acceptable outcome.

Salmonella osteomyelitis is a rare entity. Salmonella species make up only 0.45% of isolates in osteomyeilitis.1 It is commonly associated with sickle cell patients, in whom multifocal disease is common.2 The most common isolates in Salmonella osteomyelitis are from subtypes Typhirium, Typhi, and Enteritidis.3 Salmonella serotype C2 (Newport), as seen in this case, is rarely isolated as the etiologic subspecies.

Salmonella infections are more common in the immunocompromised.4 Diabetes mellitus is a known risk factor for Salmonella infections,2 but we found no literature documenting Salmonella osteomyelitis as the presenting sign of new-onset diabetes mellitus. This article presents a case of a healthy, active duty United States military member who returned to the United States from the Middle East for definitive care after being diagnosed with a distal femoral lesion.

An otherwise healthy 38-year-old male active duty service member in the United States Navy presented to his primary care clinic in Kuwait with a 1-week history of right knee pain. He reported no history of injury or constitutional symptoms. An otherwise benign examination revealed a mild knee effusion. Due to unremitting pain and persistent effusion, plain radiographs were obtained, and revealed a large destructive lesion in the distal femur. Subsequent magnetic resonance imaging (MRI) demonstrated an extensive permeative process in the distal femur with posterior extension into the soft tissues. Post-contrast imaging showed multiple septations with a rim enhancement pattern, suggestive of osteomyelitis. Laboratory data revealed a white blood cell count of 9.3 (×103/mm3).

The patient was medically evacuated from Kuwait and arrived at our institution in the United States approximately 3 months after the onset of his symptoms. The delay in definitive care was likely caused by low clinical suspicion given the patient’s initial mild symptoms and a lack of easily accessible radiographic modalities at the patient’s overseas location. At presentation to our institution, his history revealed a recent onset of fevers, chills, and night sweats and a 20-pound weight loss over the prior 3 months. Examination showed a knee effusion with no abnormal skin findings. His knee range of motion (ROM) was limited, showing a pain-free arc of motion from 20° to 80°. Repeat laboratory data revealed a white blood cell count of 9.8, hemoglobin of 12 g/dL, increased erythrocyte sedimentation rate (96 mm/hour) and C-reactive protein (12 mg/dL). Bone scan revealed isolated increased metabolic activity in the distal femur. Computed tomography…

Abstract

Salmonella species are rare bacterial isolates in osteomyelitis. This article describes a case of an otherwise healthy, active duty male military member with an insidious onset of right knee pain during a deployment to Kuwait. His work-up revealed an infectious process in the distal femur. Operative treatment and intravenous antibiotics resolved the infection. Intraoperative cultures revealed the rare isolate Salmonella enterica serotype C2 (Newport). Postoperative medical management revealed new-onset diabetes mellitus, possibly making this otherwise healthy host susceptible to this rare infection.

Salmonella are gram-negative bacteria. Infection with nontyphoidal Salmonella species most commonly manifests as intestinal illness. Although it may be difficult for clinicians to accurately predict this rare entity as the causative organism in osteomyelitis, they may be aided by a history of travel to endemic regions or exposure to animal carriers. Comorbidities that seem to increase susceptibility include diabetes mellitus, human immunodeficiency virus, hemoglobinopathies, and immunosuppression. Blood cultures are reported to be frequently positive in cases of Salmonella osteomyelitis. Identification of Salmonella species from intraoperative cultures should prompt consultation with the infectious disease department for culture-specific antibiotic tailoring. Many common antibiotic agents active against gram-negative organisms seem efficacious. As in this case, following the basic tenets of osteomyelitis management should lead to an acceptable outcome.

Salmonella osteomyelitis is a rare entity. Salmonella species make up only 0.45% of isolates in osteomyeilitis.1 It is commonly associated with sickle cell patients, in whom multifocal disease is common.2 The most common isolates in Salmonella osteomyelitis are from subtypes Typhirium, Typhi, and Enteritidis.3 Salmonella serotype C2 (Newport), as seen in this case, is rarely isolated as the etiologic subspecies.

Salmonella infections are more common in the immunocompromised.4 Diabetes mellitus is a known risk factor for Salmonella infections,2 but we found no literature documenting Salmonella osteomyelitis as the presenting sign of new-onset diabetes mellitus. This article presents a case of a healthy, active duty United States military member who returned to the United States from the Middle East for definitive care after being diagnosed with a distal femoral lesion.

Case Report

An otherwise healthy 38-year-old male active duty service member in the United States Navy presented to his primary care clinic in Kuwait with a 1-week history of right knee pain. He reported no history of injury or constitutional symptoms. An otherwise benign examination revealed a mild knee effusion. Due to unremitting pain and persistent effusion, plain radiographs were obtained, and revealed a large destructive lesion in the distal femur. Subsequent magnetic resonance imaging (MRI) demonstrated an extensive permeative process in the distal femur with posterior extension into the soft tissues. Post-contrast imaging showed multiple septations with a rim enhancement pattern, suggestive of osteomyelitis. Laboratory data revealed a white blood cell count of 9.3 (×103/mm3).

The patient was medically evacuated from Kuwait and arrived at our institution in the United States approximately 3 months after the onset of his symptoms. The delay in definitive care was likely caused by low clinical suspicion given the patient’s initial mild symptoms and a lack of easily accessible radiographic modalities at the patient’s overseas location. At presentation to our institution, his history revealed a recent onset of fevers, chills, and night sweats and a 20-pound weight loss over the prior 3 months. Examination showed a knee effusion with no abnormal skin findings. His knee range of motion (ROM) was limited, showing a pain-free arc of motion from 20° to 80°. Repeat laboratory data revealed a white blood cell count of 9.8, hemoglobin of 12 g/dL, increased erythrocyte sedimentation rate (96 mm/hour) and C-reactive protein (12 mg/dL). Bone scan revealed isolated increased metabolic activity in the distal femur. Computed tomography (CT) scan of the chest, abdomen, and pelvis showed no abnormalities. Repeat plain radiographs and MRI showed findings similar to those noted in Kuwait. (Figures 1, 2).

Figure 1: Arthroscopic view of the anteromedial and posterolateral bundles of the ACL Figure 2: Fetal knee specimen demonstrating evidence of the 2 ACL bundles

Figure 1: Preoperative AP radiograph of the distal femur revealing a large area of multiple lytic foci. Figure 2: Preoperative sagittal MRI of the distal femur demonstrating multiple peripherally rim-enhancing intramedullay foci with posterior soft tissue involvement.

Through a lateral approach to the distal femur, a trephine biopsy was initially performed and sent for frozen section. Upon findings consistent with infection, a 5×3-cm oval of the lateral femoral cortex was removed. Irrigation, debridement, and curettage of the lesion were performed. The clinical findings were consistent with gross purulence. A large intraosseous cavity was evacuated. Posterior cortical breech was found, as suggested on preoperative MRI. The cavity was packed with vancomycin- and tobramycin-impregnated antibiotic cement beads (Figure 3). A negative-pressure wound vacuum sponge was applied to the open surgical wound. The intra-articular space was not irrigated or invasively evaluated due to low clinical suspicion on preoperative examination and MRI and intraoperative findings consistent with an extra-articular source of infection. Intraoperative cultures revealed Salmonella enterica serotype C2 (Newport). Pathologic findings showed tissue consistent with necrotizing osteomyelitis. Blood cultures taken preoperatively showed no bacterial growth.

Figure 3: Postoperative AP radiograph of the distal femur Figure 4: Final postoperative AP radiograph of the distal femur

Figure 3: Postoperative AP radiograph of the distal femur. After irrigation and debridement through a lateral cortical window, multiple antibiotic-impregnated cement beads were placed into the osseous cavity and the involved surrounding soft tissues. Figure 4: Final postoperative AP radiograph of the distal femur. One year after iliac crest bone grafting to the distal femoral defect, graft incorporation and continued bony remodeling are demonstrated.

Postoperatively, abnormal blood sugars prompted a consultation with the internal medicine department. Initial glycemic control was obtained with subcutaneous insulin. A hemoglobin A1C near 10% during the workup confirmed the chronicity of his hyperglycemia. Further workup confirmed type-2 diabetes mellitus. Additionally, infectious disease specialists recommended the patient be placed on ceftriaxone and ciprofloxacin. Four days postoperatively, the patient underwent repeat irrigation, debridement, and delayed primary closure of the wound over a drain. The antibiotic beads were retained. The remainder of the patient’s postoperative course was uneventful.

Over the ensuing months, the patient was managed by the orthopedic, internal medicine, and infectious disease departments on an outpatient basis. He was converted from insulin to oral agents for diabetes control. Retrospectively, the patient noted a history of weight loss and some polydypsia and polyuria but attributed these symptoms to the extreme heat of the Middle East. The infectious disease department followed downward trending infectious labs. Ceftriaxone was discontinued after 8 weeks. Although the patient was doing well clinically, due to a persistent draining sinus at the operative site, he underwent repeat irrigation, debridement, and antibiotic bead replacement approximately 10 weeks after the index procedure. A large subcutaneous seroma was evacuated. No infectious debris was found, and cultures showed no growth. Ciprofloxacin was discontinued after 3 months.

Continued outpatient management was uneventful. The patient underwent antibiotic bead removal and iliac crest bone grafting to the defect 6 weeks after the last irrigation and debridement (16 weeks after initial surgery; Figure 4). At latest follow-up, approximately 28 months after the onset of initial symptoms, and 9 months after his latest surgery, the patient is doing well. His diabetes continues to be controlled with oral agents. He has remained free of infectious symptoms with normal follow-up labs. He is able to run with a current ROM of 0° to 90°.

Discussion

Salmonella are gram-negative, nonspore-forming bacteria. Typhoidal and nontyphoidal species exist. Typhoidal species, which are endemic in some regions and are responsible for a human enteric febrile illness, include Salmonella Typhi and Salmonella Paratyphi. Nontyphoidal species are found in many animals, and humans are vulnerable to infection through their consumption or interaction. Infection with nontyphoidal Salmonella species most commonly manifests as intestinal illness.2 The most common sources of infection from consumption include poultry, beef, and eggs. Multiple reports document infection from exposure to reptiles and amphibians, up to 90% of which harbor Salmonella in their gastrointestinal tracts.5 Transient bacteremia from ingestion or exposure can rarely lead to infectious sequelae throughout the body, more commonly in the immunocompromised host. Extraintestinal manifestations of Salmonella infection include sepsis and involvement of major organ systems including the central nervous, pulmonary, gastrointestinal, musculoskeletal, urinary, and reproductive.3 Nontyphoidal illness can infrequently become life-threatening and is responsible for between 400 and 600 deaths in the United States annually.5

Extraintestinal Salmonella infections are frequently associated with underlying medical conditions. Sickle cell disease and other hemoglobinopathies are well-documented risk factors.4 Other risk factors include malignancy, steroids, antimicrobial therapy, use of immunosuppressants, diabetes, and human immunodeficiency virus (HIV).6 Some authors feel that cell-mediated immunologic dysfunction may contribute to patient susceptibility in the above disorders.4 Diabetes has been found to be associated with 28% of focal Salmonella infections.2 We found no cases in the literature reporting Salmonella osteomyelitis as the presenting sign of diabetes mellitus. Our patient’s environment, the Kuwaiti desert, may have masked the usual clinical findings associated with new-onset diabetes mellitus. It is possible that this case of Salmonella osteomyelitis was unrelated to the onset of diabetes mellitus. It would be impossible to prove a direct causal link, but it seems likely that this rare bacterial isolate in osteomyelitis was aided by the known risk factor of hyperglycemia and its resultant immunomodulatory effect in this otherwise healthy young man.

Osteomyelitis is a reported, but relatively uncommon, manifestation of Salmonella infection.7-15 In a review of 142 extraintestinal Salmonella infection cases in a United Kingdom hospital, 5 were found to have osteomyelitis (3.5%).2 No clinical or radiographic hallmarks aid the diagnosis of osteomyelitis due to Salmonella species. The clinical symptoms may be underwhelming for an acute infectious process, but most patients will present with pain and variable swelling. Although our preoperative blood cultures showed no growth, blood cultures have been reported to be frequently positive (71%) in patients with Salmonella osteomyelitis.3 Our intraoperative culture results revealed the nontyphoidal strain Salmonella serogroup C2 (Newport). The Newport serogroup is not frequently isolated in cases of Salmonella osteomyelitis.3 In their review of extraintestinal salmonella cases, Ispahani and Slack2 identified the Newport serogroup in only 2 of 104 isolates (2%).

In our case, the etiology of osteomyelitis caused by the rare bacterial isolate Salmonella enterica serotype C2 (Newport) is unknown, but the immunomodulatory effect of hyperglycemia from new-onset diabetes mellitus likely played a role. It would be difficult for clinicians to accurately predict this rare entity as the causative organism in osteomyelitis. They may be aided by a history of travel to endemic regions or exposure to animal carriers. Comorbidities that seem to increase susceptibility include diabetes mellitus, HIV, hemoglobinopathies, and immunosuppression. Blood cultures, although negative in our case, are reported to be frequently positive in cases of Salmonella osteomyelitis. Identification of Salmonella species from intraoperative cultures after standard open irrigation and debridement when indicated should prompt consultation with the infectious disease department for culture-specific antibiotic tailoring. Many common antibiotic agents active against gram-negative organisms seem efficacious. As in our case, following the basic tenets of osteomyelitis management should lead to an acceptable outcome.

References

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  2. Ispahani P, Slack RC. Enteric fever and other extraintestinal salmonellosis in University Hospital, Nottingham, UK, between 1980 and 1997. Eur J Clin Microbiol Infect Dis. 2000; 19(9):679-687.
  3. Arora A, Singh S, Aggarwal A, Aggarwal PK. Salmonella osteomyelitis in an otherwise healthy adult male—successful management with conservative treatment: a case report. J Orthop Surg (Hong Kong). 2003; 11(2):217-220.
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  11. Santos EM, Sapico FL. Vertebral osteomyelitis due to salmonellae: report of two cases and review. Clin Infect Dis. 1998; 27(2):287-295.
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Authors

Drs Gondusky (Joseph) and Helmers are from the Department of Orthopedic Surgery, and Dr Gondusky (Christina) is from the Department of Radiology, Naval Medical Center San Diego, California.

Drs Gondusky (Joseph), Gondusky (Christina), and Helmers have no relevant financial relationships to disclose.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or United States government.

Correspondence should be addressed to: Joseph S. Gondusky, MD, Department of Orthopedic Surgery, Naval Medical Center San Diego, 34800 Bob Wilson Dr, Ste 112, San Diego, CA 92134-1112.

DOI: 10.3928/01477447-20090728-42

10.3928/01477447-20090728-42

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