Bone and joint infections due to Haemophilus parainfluenzae: case report and review of the literature.
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.
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 . H. parainfluenzae is part of the normal flora of the oral cavity and respiratory tract . 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 . 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 . 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 . 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 . 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 . 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.
The authors have no conflict of interests regarding this paper.
The authors thank Dr. Julie Carson.
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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; email@example.com
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.  53 M AC joint (1) Bailey et al.  75 M Knee Carey et al.  60s F AC joint, clavicle Khor et al.  79 M 36 M Spine, epidural, psoas SI joint (2), spine Jellicoe et al.  78 F Hip Blanche et al.  26 M Knee Beauvais et al.  70 M Spine Manian  72 M Knee Auten et al.  74 M Spine, epidural Pravda and Habermann  78 F Knee Oik et al.  49 M Spine Warman et al.  95 F Ankle, meningitis Oill et al.  18 M Polyarticular Renne et al.  8 mo F Knee Prosthetic joint Our case No Hong et al.  No Bailey et al.  Yes Carey et al.  No Khor et al.  Jellicoe et al.  Yes Blanche et al.  No Beauvais et al.  Manian  Yes Auten et al.  Pravda and Habermann  Yes Oik et al.  Warman et al.  No Oill et al.  No Renne et al.  No Procedure * Our case Interarticular steroid injection Hong et al.  None Bailey et al.  TKA (3) Carey et al.  None Khor et al.  Gastroscopy None Jellicoe et al.  Dental Blanche et al.  Nasopharyngeal biopsy Beauvais et al.  Gastroscopy and colonoscopy Manian  Dental Auten et al.  Dental Pravda and Habermann  Dental Oik et al.  Nasal septoplasty Warman et al.  None Oill et al.  None Renne et al.  None Comorbidities Our case Asplenic Hong et al.  None Bailey et al.  CLL (4) Carey et al.  None Khor et al.  None None Jellicoe et al.  None Blanche et al.  HIV (5) Beauvais et al.  Colon cancer Manian  None Auten et al.  None Pravda and Habermann  None Oik et al.  None Warman et al.  Dementia Oill et al.  None Renne et al.  Otitis media Positive cultures Our case Synovial fluid Hong et al.  Blood Bailey et al.  Tissue Carey et al.  Tissue Khor et al.  Tissue Blood Jellicoe et al.  Synovial fluid and tissue Blanche et al.  Blood and synovial fluid Beauvais et al.  Tissue Manian  Wound swab Auten et al.  Tissue Pravda and Habermann  Synovial fluid Oik et al.  Tissue Warman et al.  Synovial fluid and CSF (6) Oill et al.  Blood Renne et al.  Synovial fluid Surgical intervention Our case Arthrotomy Hong et al.  No Bailey et al.  2-stage revision of TKA Carey et al.  Incision and drainage Khor et al.  Laminectomy No Jellicoe et al.  2-stage revision of THA (7) Blanche et al.  No Beauvais et al.  No Manian  No Auten et al.  Laminectomy Pravda and Habermann  Arthrotomy Oik et al.  No Warman et al.  No Oill et al.  No Renne et al.  Arthrotomy Beta-lactamase Our case Positive Hong et al.  Not reported Bailey et al.  Negative Carey et al.  Not reported Khor et al.  Negative Negative Jellicoe et al.  Negative Blanche et al.  Not reported Beauvais et al.  Not reported Manian  Negative Auten et al.  Negative Pravda and Habermann  Negative Oik et al.  Negative Warman et al.  Negative Oill et al.  Not reported Renne et al.  Not reported Antibiotics Our case Ceftriaxone Hong et al.  Cefazolin and gentamicin Bailey et al.  Flucloxacillin and rifampicin Carey et al.  Levofloxacin Khor et al.  Ampicillin Ampicillin Jellicoe et al.  Ampicillin and flucloxacillin Blanche et al.  Not reported Beauvais et al.  Not reported Manian  Ciprofloxacin Auten et al.  TMP/SMX (8) and tobramycin Pravda and Habermann  Ampicillin and amoxicillin Oik et al.  Ceftriaxone Warman et al.  Ampicillin Oill et al.  Penicillin and ampicillin Renne et al.  Ampicillin Length of therapy Outcome Our case 9 weeks Cure Hong et al.  4 weeks Cure Bailey et al.  10 weeks Cure Carey et al.  14 days Cure Khor et al.  14 weeks 10 weeks Cure Cure Jellicoe et al.  4 weeks Cure Blanche et al.  Not reported Cure Beauvais et al.  Not reported Cure Manian  Chronic, suppressive Chronic infection Auten et al.  7 weeks Cure Pravda and Habermann  12 weeks Cure Oik et al.  6 weeks Cure Warman et al.  14 days Cure Oill et al.  7 days Lost to follow-up Renne et al.  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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