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Bone and joint infections due to Haemophilus parainfluenzae: case report and review of the literature.

1. Case Presentation

A 56-year-old female presented to the emergency room with a three-day history of right hip pain. She reported decreased range of motion and difficulty ambulating. She denied constitutional symptoms or fever. She had undergone intra-articular steroid injection of her right hip three days prior. Review of systems was otherwise unremarkable. Her past medical history was relevant for hereditary spherocytosis with splenectomy at age 14 and chronic right hip osteoarthritis. Her only medication was celecoxib as needed. She denied any drug allergy. She was unaware of her immunization history. She worked as a flight attendant, denied smoking or recreational drug use, and had not recently travelled outside of Canada. On initial examination she was afebrile and her vital signs were within normal limits. On examination of her right hip she had limitation of internal rotation with reproducible pain, but her physical exam otherwise was unremarkable. Her initial investigations showed elevation in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at 22.9 mg/L and 25mm/hr, respectively. Her white blood cell count was not elevated. An X-ray of her right hip showed severe joint space narrowing with osteophytosis consistent with severe osteoarthritis. Arthrocentesis was performed and synovial fluid samples were directly inoculated onto solid culture media, including blood agar and chocolate agar. Two of three samples also underwent cytospin centrifugation and direct Gram stain. Gram-negative bacilli were observed in one sample though heavy neutrophils were observed in both. Synovial fluid analysis for cell count and chemistry was not performed due to insufficient sample. She was admitted to hospital for 24 hours of observation and was subsequently discharged with instructions to return to hospital if her symptoms worsened or if cultures subsequently grew a pathogenic organism.

Three days later she was seen in a follow-up clinic. In the interim she had developed a fever (38.3[degrees]C), had chills, and had worsening right hip pain. Repeat physical examination showed deterioration in range of motion at her right hip with significant pain. Cardiovascular examination was unremarkable with no appreciable murmur. Synovial fluid cultures from the initial arthrocentesis were now growing Haemophilus parainfluenzae with colonies observed on solid media within 24 hours of inoculation. She received one dose of ceftriaxone and subsequently underwent right hip arthrotomy with synovectomy and irrigation. The Infectious Disease service was consulted the following day. The organism was susceptible to ceftriaxone and cefuroxime and resistant to ampicillin and ciprofloxacin (Table 1). Blood cultures and intraoperative tissue cultures did not demonstrate growth, likely due to the administration of antibiotics prior to collection. The patient was treated with intravenous ceftriaxone and was subsequently discharged with outpatient follow-up for home intravenous antibiotics. Ongoing pain, difficulty ambulating, and persistently elevated inflammatory markers necessitated a prolonged, nine-week course of antimicrobial therapy (Figure 1). At the time of treatment discontinuation, she reported pain and her functional ability had not yet returned to baseline. She is currently awaiting evaluation for total hip arthroplasty.

2. Discussion

H. parainfluenzae is a pleomorphic Gram-negative coccobacillus with fastidious growth requirements, which require enriched media, usually containing blood (e.g., chocolate agar). It can be differentiated from other Haemophilus spp. by the requirement for V factor (i.e., NAD, nicotinamide adenine dinucleotide) for growth [1]. H. parainfluenzae is part of the normal flora of the oral cavity and respiratory tract [1]. It is an increasingly recognized opportunistic pathogen in serious infections such as endocarditis, meningitis, and pneumonia and has also been recognized as a rare cause of nongonococcal urethritis [2]. However, it is an uncommon pathogen in osteomyelitis and septic arthritis.

Inclusive of our case, there have been only 16 cases of bone and joint infections caused by H. parainfluenzae reported in the English literature (summarized in Table 2) [3-16]. Of these 16 patients, 10 (63%) had septic arthritis, four (25%) had osteomyelitis, and two (13%) had both septic arthritis and osteomyelitis. The median age was 65 (Interquartile Range [IQR]: 46-76) and 63% were male. Most (14/16, 88%) were immunocompetent and only one reported recent trauma [14]. Four patients (25%) had prosthetic joint infections. Most patients (10/16, 63%) reported a procedure in the previous three months (four dental, two nasopharyngeal, two gastrointestinal, one total knee arthroplasty, and one intraarticular steroid injection). The organism was identified on culture of aspirated synovial fluid (6/16, 38%), blood (4/16, 25%), and surgical or biopsy specimens (7/16, 44%). 8/16 (50%) of patients required surgical intervention and the rest (8/16, 50%) were managed with antibiotics alone. One patient with a prosthetic joint infection was treated with chronic, suppressive antibiotic therapy after having refused surgical intervention [10]. The median length of antibiotic therapy was 42 days (IQR: 14-70). Of patients with data reported, most (11/14, 79%) were treated with a beta-lactam antibiotic, the most common being ampicillin (7/14, 50%).

To our knowledge, we report the first case of septic arthritis due to a beta-lactamase producing strain of H. parainfluenzae (Table 1). Community surveillance studies of Haemophilus spp. isolated from respiratory samples have reported rates of beta-lactamase production as high as 70% [17, 18]. Beta-lactamase plasmids can transmit from less pathogenic strains of Haemophilus, such as H. parainfluenzae, to invasive pathogens such as Haemophilus influenza type b, suggesting H. parainfluenzae may be a reservoir for antimicrobial resistance in the nasopharyngeal tract [18]. More recently, increasing rates of antimicrobial resistance have also been reported in genitourinary isolates of H. parainfluenzae [2,19].

Moreover, it is well known that immuno compromised hosts are particularly susceptible to opportunistic pathogens, and it is within this context that we report the first case of septic arthritis due to H. parainfluenzae in a patient with asplenia. Patients with asplenia are at significant increased risk of sepsis due to encapsulated bacteria, such as Haemophilus spp., Neisseria spp., and Streptococcus pneumoniae [20]. Immunizations for pneumococcal disease, Haemophilus influenzae type b infection, and meningococcal disease are recommended for asplenic patients. However, they remain susceptible to less common potentially pathogenic bacteria, such as H. parainfluenzae. Prompt recognition and source control (e.g., surgical debridement) are particularly important in preventing disseminated infection in patients with asplenia. In our case, given her risk of disseminated infection, surgical intervention and antibiotics could have been initiated sooner, when Gram stain of the initial arthrocentesis was reported.

To the best of our knowledge, our case is the only example of H. parainfluenzae septic arthritis temporally associated with intra-articular steroid injection that is described in the literature. Septic arthritis is a rare but recognized complication following intra-articular steroid injection. Infection may result from lack of adherence to proper aseptic technique during the procedure and subsequent inoculation of the joint space, or through microbiological contamination of the steroid preparation used [21, 22]. Alternatively, transient bacteremia can lead to secondary seeding of a susceptible joint capsule, for example, in patients with underlying osteoarthritis or previous joint infection. However, localized immuno suppression from intra-articular steroid injections does not appear to be associated with increased rates of deep infection as demonstrated in patients receiving steroid injection prior to joint arthroplasty [23, 24].

H. parainfluenzae is an uncommon though increasingly recognized pathogen in bone and joint infections. In this series, patients with prosthetic joints and patients undergoing invasive procedures appear to be particularly susceptible to this pathogen. Furthermore, the rate of beta-lactamase producing strains of H. parainfluenzae may be increasing. Thus, accurate microbiologic diagnosis is key to providing tailored antibiotics, as patients often require a prolonged course of therapy.

http://dx.doi.org/10.1155/2016/4503025

Competing Interests

The authors have no conflict of interests regarding this paper.

Acknowledgments

The authors thank Dr. Julie Carson.

References

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[2] G. Deza, G. Martin-Ezquerra, J. Gomez, J. Villar-Garcia, A. Supervia, and R. M. Pujol, "Isolation of Haemophilus influenzae and Haemophilus parainfluenzae in urethral exudates from men with acute urethritis: a descriptive study of 52 cases," Sexually Transmitted Infections, vol. 92, no. 1, pp. 29-31, 2016.

[3] M. J. Hong, Y. D. Kim, and H. D. Ham, "Acute septic arthritis of the acromioclavicular joint caused by Haemophilus parainfluenzae: a rare causative origin," Clinical Rheumatology, vol. 34, no. 4, pp. 811-814, 2014.

[4] C. Bailey, S. Duckett, S. Davies, R. Townsend, and I. Stockley, "Haemophilus parainfluenzae prosthetic joint infection. The importance of accurate microbiological diagnosis and options for management," Journal of Infection, vol. 63, no. 6, pp. 474-476, 2011.

[5] T. W. Carey, K. Jackson, R. Roure, and B. E. Abell, "Acromioclavicular septic arthritis: a case report of a novel pathogen," The American Journal Of Orthopedics, vol. 39, no. 3, pp. 134-136, 2010.

[6] B.-S. Khor, S.-J. Liaw, H.-C. Liao, C.-C. Yang, and M.-H. Lee, "Bone and joint infections caused by Haemophilus parainfluenzae: report of two cases and literature review," Infectious Diseases in Clinical Practice, vol. 15, no. 3, pp. 206-208, 2007.

[7] P A. Jellicoe, A. Cohen, and P Campbell, "Haemophilus parainfluenzae complicating total hip arthroplasty: a rapid failure," Journal of Arthroplasty, vol. 17, no. 1, pp. 114-116, 2002.

[8] P Blanche, S. Abad, and D. Sicard, "Septic arthritis due to Haemophilus parainfluenzae in a patient infected with the human immunodeficiency virus type 1," Revue du Rhumatisme (English Edition), vol. 63, no. 5, article 380, 1996.

[9] C. Beauvais, F. Berenbaum, M. Spentchian, A. Prier, and G. Kaplan, "Early diagnosis of vertebral osteomyelitis due to a rare pathogen: Haemophilus parainfluenzae," Journal of Rheumatology, vol. 19, no. 3, pp. 491-493, 1992.

[10] F. A. Manian, "Prosthetic joint infection due to Haemophilus parainfluenzae after dental surgery," Southern Medical Journal, vol. 84, no. 6, pp. 807-808, 1991.

[11] G. M. Auten, C. S. Levy, and M. A. Smith, "Haemophilus parainfluenzae as a rare cause of epidural abscess: case report and review," Reviews of Infectious Diseases, vol. 13, no. 4, pp. 609-612, 1991.

[12] J. Pravda and E. Habermann, "Hemophilus parainfluenzae complicating total knee arthroplasty. A case report," Clinical Orthopaedics and Related Research, no. 243, pp. 169-171, 1989.

[13] D. G. Olk, R. J. Hamill, and R. A. Proctor, "Haemophilus parainfluenzae vertebral osteomyelitis," The American Journal of the Medical Sciences, vol. 294, no. 2, pp. 114-116, 1987

[14] S. T. Warman, E. Reinitz, and R. S. Klein, "Haemophilus parainfluenzae septic arthritis in an adult," The Journal of the American Medical Association, vol. 246, no. 8,pp. 868-869, 1981.

[15] P A. Oill, A. W. Chow, and L. B. Guze, "Adult bacteremic Haemophilus parainfluenzae infections. Seven reports of cases and a review of the literature," Archives of Internal Medicine, vol. 139, no. 9, pp. 985-988, 1979.

[16] J. W. Renne, H. B. Tanowitz, and J. D. Chulay, "Septic arthritis in an infant due to Clostridium ghoni and Hemophilus parainfluenzae," Pediatrics, vol. 57, no. 4, pp. 573-574, 1976.

[17] D. W. Scheifele, S. J. Fusell, and M. C. Roberts, "Characterization of ampicillin-resistant Haemophilus parainfluenzae" Antimicrobial Agents and Chemotherapy, vol. 21, no. 5, pp. 734-739, 1982.

[18] N. I. Leaves, I. Dimopoulou, I. Hayes et al., "Epidemiological studies of large resistance plasmids in Haemophilus," Journal of Antimicrobial Chemotherapy, vol. 45, no. 5, pp. 599-604, 2000.

[19] M. Giufre, L. Daprai, M. L. Garlaschi, R. Cardines, E. Torresani, and M. Cerquetti, "Genital carriage of the genus Haemophilus in pregnancy: species distribution and antibiotic susceptibility," Journal of Medical Microbiology, vol. 64, no. 7, pp. 724-730, 2015.

[20] L. G. Rubin and W. Schaffner, "Clinical practice. Care of the asplenic patient," The New England Journal of Medicine, vol. 371, no. 4, pp. 349-356, 2014.

[21] J. M. Ritter, A. Muehlenbachs, D. M. Blau et al., "Exserohilum infections associated with contaminated steroid injections: a clinicopathologic review of 40 cases," American Journal of Pathology, vol. 183, no. 3, pp. 881-892, 2013.

[22] M. R. Wong, P Del Rosso, L. Heine et al., "An outbreak of Klebsiella pneumoniae and Enterobacter aerogenes bacteremia after interventional pain management procedures, New York City, 2008," Regional Anesthesia and Pain Medicine, vol. 35, no. 6, pp. 496-499, 2010.

[23] D. Marsland, A. Mumith, and I. W. Barlow, "Systematic review: the safety of intra-articular corticosteroid injection prior to total knee arthroplasty," Knee, vol. 21, no. 1, pp. 6-11, 2014.

[24] C. P. Charalambous, A. D. Prodromidis, and T. A. Kwaees, "Do intra-articular steroid injections increase infection rates in subsequent arthroplasty? A systematic review and metaanalysis of comparative studies," Journal of Arthroplasty, vol. 29, no. 11, pp. 2175-2180, 2014.

Conar R. O'Neil, (1) Evan Wilson, (2) and Bayan Missaghi (2)

(1) Department of Internal Medicine, Cumming School of Medicine, Health Sciences Centre, University of Calgary, Foothills Campus, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1

(2) Department of Microbiology, Immunology and Infectious Disease, Cumming School of Medicine, Health Sciences Centre, University of Calgary, Foothills Campus, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1

Correspondence should be addressed to Bayan Missaghi; bayan.missaghi@albertahealthservices.ca

Received 2 July 2015; Accepted 15 December 2015

Caption: FIGURE 1: Inflammatory markers over time during a prolonged course of intravenous ceftriaxone for Haemophilus parainfluenzae septic arthritis. CRP: C-reactive protein; ESR: erythrocyte sedimentation rate. *CRP = mg/L; ESR = mm/hr.
TABLE 1: Haemophilus parainfluenzae susceptibility results.

Antibiotic             Result                   Method

Beta-lactamase        Positive         Nitrocefin SR112, Oxoid
                                        Microbiology Products

Ciprofloxacin         Resistant        MIC by Etest = 6 ug/mL
                                        Sensitive [less than
                                            or equal to] 1

Ceftriaxone      Susceptible (32 mm)         Kirby Bauer

Cefuroxime       Susceptible (30 mm)         Kirby Bauer

Meropenem        Susceptible (28 mm)         Kirby Bauer

Disk diffusion and Etest as per CLSI M100 S24 document;
Haemophilus test medium: 35[degrees]C [+ or -] 2[degrees]C in 5%
C[O.sub.2] for 16-18 hours.

TABLE 2: Summary of previously reported cases of bone and joint
infections caused by Haemophilus parainfluenzae.

                             Age/sex        Site of infection

Our case                      56 F                 Hip

Hong et al. [3]               53 M            AC joint (1)

Bailey et al. [4]             75 M                Knee

Carey et al. [5]              60s F        AC joint, clavicle

Khor et al. [6]             79 M 36 M       Spine, epidural,
                                        psoas SI joint (2), spine

Jellicoe et al. [7]           78 F                 Hip

Blanche et al. [8]            26 M                Knee

Beauvais et al. [9]           70 M                Spine

Manian [10]                   72 M                Knee

Auten et al. [11]             74 M           Spine, epidural

Pravda and Habermann [12]     78 F                Knee

Oik et al. [13]               49 M                Spine

Warman et al. [14]            95 F          Ankle, meningitis

Oill et al. [15]              18 M            Polyarticular

Renne et al. [16]            8 mo F               Knee

                            Prosthetic joint

Our case                           No

Hong et al. [3]                    No

Bailey et al. [4]                 Yes

Carey et al. [5]                   No

Khor et al. [6]

Jellicoe et al. [7]               Yes

Blanche et al. [8]                 No

Beauvais et al. [9]

Manian [10]                       Yes

Auten et al. [11]

Pravda and Habermann [12]         Yes

Oik et al. [13]

Warman et al. [14]                 No

Oill et al. [15]                   No

Renne et al. [16]                  No

                                    Procedure *

Our case                          Interarticular
                                 steroid injection

Hong et al. [3]                        None

Bailey et al. [4]                     TKA (3)

Carey et al. [5]                       None

Khor et al. [6]                  Gastroscopy None

Jellicoe et al. [7]                   Dental

Blanche et al. [8]             Nasopharyngeal biopsy

Beauvais et al. [9]         Gastroscopy and colonoscopy

Manian [10]                           Dental

Auten et al. [11]                     Dental

Pravda and Habermann [12]             Dental

Oik et al. [13]                  Nasal septoplasty

Warman et al. [14]                     None

Oill et al. [15]                       None

Renne et al. [16]                      None

                            Comorbidities

Our case                      Asplenic

Hong et al. [3]                 None

Bailey et al. [4]              CLL (4)

Carey et al. [5]                None

Khor et al. [6]               None None

Jellicoe et al. [7]             None

Blanche et al. [8]             HIV (5)

Beauvais et al. [9]         Colon cancer

Manian [10]                     None

Auten et al. [11]               None

Pravda and Habermann [12]       None

Oik et al. [13]                 None

Warman et al. [14]            Dementia

Oill et al. [15]                None

Renne et al. [16]           Otitis media

                                Positive cultures

Our case                          Synovial fluid

Hong et al. [3]                       Blood

Bailey et al. [4]                     Tissue

Carey et al. [5]                      Tissue

Khor et al. [6]                    Tissue Blood

Jellicoe et al. [7]         Synovial fluid and tissue

Blanche et al. [8]           Blood and synovial fluid

Beauvais et al. [9]                   Tissue

Manian [10]                         Wound swab

Auten et al. [11]                     Tissue

Pravda and Habermann [12]         Synovial fluid

Oik et al. [13]                       Tissue

Warman et al. [14]          Synovial fluid and CSF (6)

Oill et al. [15]                      Blood

Renne et al. [16]                 Synovial fluid

                            Surgical intervention

Our case                          Arthrotomy

Hong et al. [3]                       No

Bailey et al. [4]           2-stage revision of TKA

Carey et al. [5]            Incision and drainage

Khor et al. [6]                 Laminectomy No

Jellicoe et al. [7]           2-stage revision
                                  of THA (7)

Blanche et al. [8]                    No

Beauvais et al. [9]                   No

Manian [10]                           No

Auten et al. [11]                Laminectomy

Pravda and Habermann [12]         Arthrotomy

Oik et al. [13]                       No

Warman et al. [14]                    No

Oill et al. [15]                      No

Renne et al. [16]                 Arthrotomy

                             Beta-lactamase

Our case                        Positive

Hong et al. [3]               Not reported

Bailey et al. [4]               Negative

Carey et al. [5]              Not reported

Khor et al. [6]             Negative Negative

Jellicoe et al. [7]             Negative

Blanche et al. [8]            Not reported

Beauvais et al. [9]           Not reported

Manian [10]                     Negative

Auten et al. [11]               Negative

Pravda and Habermann [12]       Negative

Oik et al. [13]                 Negative

Warman et al. [14]              Negative

Oill et al. [15]              Not reported

Renne et al. [16]             Not reported

                                     Antibiotics

Our case                             Ceftriaxone

Hong et al. [3]                Cefazolin and gentamicin

Bailey et al. [4]           Flucloxacillin and rifampicin

Carey et al. [5]                     Levofloxacin

Khor et al. [6]                 Ampicillin Ampicillin

Jellicoe et al. [7]         Ampicillin and flucloxacillin

Blanche et al. [8]                   Not reported

Beauvais et al. [9]                  Not reported

Manian [10]                         Ciprofloxacin

Auten et al. [11]             TMP/SMX (8) and tobramycin

Pravda and Habermann [12]     Ampicillin and amoxicillin

Oik et al. [13]                      Ceftriaxone

Warman et al. [14]                    Ampicillin

Oill et al. [15]              Penicillin and ampicillin

Renne et al. [16]                     Ampicillin

                             Length of therapy          Outcome

Our case                          9 weeks                Cure

Hong et al. [3]                   4 weeks                Cure

Bailey et al. [4]                 10 weeks               Cure

Carey et al. [5]                  14 days                Cure

Khor et al. [6]              14 weeks 10 weeks         Cure Cure

Jellicoe et al. [7]               4 weeks                Cure

Blanche et al. [8]              Not reported             Cure

Beauvais et al. [9]             Not reported             Cure

Manian [10]                 Chronic, suppressive   Chronic infection

Auten et al. [11]                 7 weeks                Cure

Pravda and Habermann [12]         12 weeks               Cure

Oik et al. [13]                   6 weeks                Cure

Warman et al. [14]                14 days                Cure

Oill et al. [15]                   7 days          Lost to follow-up

Renne et al. [16]                 10 days                Cure

In the previous three months; Acromioclavicular joint, (2)
sacroiliac joint, (3) total knee arthroplasty, (4) chronic
lymphocytic leukemia, (5) human immunodeficiency virus, (6)
cerebrospinal fluid, (7) total hip arthroplasty, and (8)
trimethoprim/sulfamethoxazole.
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Title Annotation:Case Report
Author:O'Neil, Conar R.; Wilson, Evan; Missaghi, Bayan
Publication:Canadian Journal of Infectious Diseases and Medical Microbiology
Article Type:Case study
Date:Jan 1, 2016
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