Ceftriaxone treatment of spondylodiscitis and other serious infections with Cutibacterium acnes.

OBJECTIVES: To establish testing and treatment recommendations for a ceftriaxone once-daily dose regimen for systemic infections with Cutibacterium acnes. METHODS: A review of the literature and a retrospective evaluation of patients diagnosed with C. acnes spondylodiscitis and treated with ceftriaxone were performed. Ceftriaxone and penicillin MICs were determined for C. acnes isolates from blood and biopsies and the epidemiological cut-off (ECOFF) was determined with surveillance data from the UK Anaerobe Reference Laboratory in Cardiff. RESULTS: Limited clinical data exist from endocarditis and prosthetic joint infections using treatment with ceftriaxone 2 g once daily for C. acnes with ceftriaxone MICs ≤0.5 mg/L. In this case study, five patients were successfully treated with ceftriaxone as part of the treatment for spondylodiscitis with C. acnes. Ceftriaxone and penicillin MICs of the C. acnes isolates from the patients were 0.016-0.125 mg/L and 0.012-0.032 mg/L, respectively. The ceftriaxone ECOFF was 0.5 mg/L and the penicillin ECOFF was 0.25 mg/L based on available surveillance data. CONCLUSIONS: From the data presented in this study it would be acceptable to consider treatment with a once-daily dose of ceftriaxone 2 g for systemic infections, including endocarditis, spondylodiscitis and prosthetic joint infections with C. acnes using a clinical breakpoint of ≤0.5 mg/L (the ECOFF). However, clinical data are still limited and the response of patients treated with ceftriaxone for serious infections with C. acnes should be monitored closely.

Quantitative B-lymphocyte deficiency and increased TCRγδ T-lymphocytes in acute infectious spondylodiscitis.

Acute infectious spondylodiscitis (AIS) is a serious infection of the spine with rising incidence and a mortality of 3-6%. The role of the immune system in AIS is largely unknown. We performed extensive B and T-lymphocyte phenotyping in patients with AIS at diagnosis and after treatment cessation. In this prospective multicentre study, flow cytometric analysis of T and B-lymphocyte subsets was performed in 35 patients at diagnosis and 3 months after treatment cessation. We additionally analysed levels of immunoglobulins and IgG subclasses, serum level and genetic variants of mannose-binding lectin, and somatic hypermutation. A total of 22 (61%) patients had B-lymphocytes below reference limit at baseline, persisting in 7 (30%) patients at follow-up. We found a lower proportion of CD19 + CD27 + IgD+ marginal zone B-lymphocytes and a higher proportion of γδ+ T-lymphocyte receptors compared with controls at both time points. Immunoglobulin levels were elevated at baseline compared to follow-up, and not associated with absolute B-lymphocyte count. In conclusion, a large proportion of AIS patients presented with profound B-lymphocyte deficiency, only partly reversible at follow-up. Identification of immune dysfunction related to AIS may allow for future targeted therapeutic interventions to restore host immunity.

Mycobacterium marinum infections in Denmark from 2004 to 2017: A retrospective study of incidence, patient characteristics, treatment regimens and outcome.

Mycobacterium marinum (M. marinum) is a slowly growing nontuberculous mycobacterium. The incidence of M. marinum infections in Denmark is unknown. We conducted a retrospective nationwide study including all culture confirmed cases of M. marinum from 2004 to 2017 in Denmark. All available medical records were reviewed. Demographics, clinical characteristics, and treatment regiments were analyzed. Fifty-five patients were identified, 40 (72.7%) were men with a median age of 50 years. Aquatic exposure was reported by 48 (90.6%) of the patients. Site of infection was upper extremities in 49 (92.5%) patients and 49 (92.5%) had superficial infection. The median time from symptom presentation to diagnosis was 194 days. All patients received antibiotics. Median time of treatment duration among all patients was 112 days. Treatment outcome was classified as improved in 40 (75%), improved with sequela in 4 (7.6%) patients and only 3 patients (3.8%) were classified as failed. Infection with M. marinum is rare and there is a long delay from symptom manifestation to diagnosis. The infection is predominantly related to aquatic exposure. M. marinum should be a differential diagnose in patients with slow-developing cutaneous elements and relevant exposure. Treatment outcomes are overall good and severe sequela are rare.

Reduced ability to work both before and after infectious spondylodiscitis in working-age patients.

BACKGROUND: As little is known about the ability to work in patients with infectious spondylodiscitis, we compared the relation between the workforce before infection with that of a reference population and described the patients' ability to work after infection including predictors of return to work (RTW). METHODS: We identified all patients aged 20-57 years treated for infectious spondylodiscitis January 1994-May 2009 at hospitals in Funen County, Denmark. The work status of each week from 2 years before until 2 years after index date was compared with that of a reference population. Time to RTW was described using cumulative incidence curves and univariate cause-specific Cox-regression analyses (hazard ratios - HRs). RESULTS: Of 112 identified patients, 8 (7%) died within the first year and 48 (43%) were part of the workforce 1 year before index. Through the entire observation period, the patients had lower affiliation to the workforce compared with the reference population. During the observation period, the proportion of patients on permanent disability pension increased from 24% to 38% and the proportion of self-supporters decreased from 58% to 33%. Seventy-three per cent of the patients being part of the workforce 1 year before index returned to the workforce within the 2 year follow-up. Main predictor of RTW was being part of the workforce 1 year before index (HR = 7.8; CI: 2.4-25.3). CONCLUSIONS: Patients with infectious spondylodiscitis were less likely to be part of the workforce before infection compared with a reference population and infection further lowered their ability to RTW.

Characteristics and Clinical Outcome of Bone and Joint Tuberculosis From 1994 to 2011: A Retrospective Register-based Study in Denmark.

BACKGROUND: Most information on bone-joint (BJ)-tuberculosis is based on data from high-incidence areas. We conducted a nationwide register-based analysis of BJ-tuberculosis in Denmark from 1994 to 2011. METHODS: We linked data from the national tuberculosis surveillance system on BJ-tuberculosis, hospital records, the Danish Hospital and Civil Registration System. RESULTS: We identified 282 patients with BJ-tuberculosis, 3.6% of all tuberculosis cases (n = 7936). Spinal tuberculosis was found in 153 of 282 patients (54.3%); 83.3% of all cases were immigrants. Danes were older and had higher Charlson comorbidity index scores than immigrants (P < .01). C-reactive protein and erythrocyte sedimentation rates were elevated in most cases. Median time to diagnosis after first hospital contact was 19.5 days for spinal tuberculosis and 28 days for other forms of BJ-tuberculosis (P = .01). Of patients with spinal tuberculosis, 54/133 (40.6%) had neurologic deficits at admission and 17.3% presented with cauda equina. Diagnosis was culture verified in 87%. (Resistance to any drug was found in 10.2%). Median time on antituberculous treatment for patients with spinal and other forms of BJ-tuberculosis was 9 months and 7 months, respectively (P < .01). Surgery was required in 44.4% patients with spinal tuberculosis and in 32.6% patients with other forms of BJ-tuberculosis (P = .04). Sequelae were reported in 57.5% of patients with spinal tuberculosis and 29.1% of patient with other forms of BJ-tuberculosis (P < .01). One-year mortality was 25.5% among Danes compared with 1.3% among immigrants (P < .01). CONCLUSIONS: BJ-tuberculosis was rare and seen mainly in younger immigrants in Denmark. More than half of cases were spinal tuberculosis, presenting with more severe symptoms and worse outcome, compared with other forms of BJ-tuberculosis.

Increased short- and long-term mortality among patients with infectious spondylodiscitis compared with a reference population.

BACKGROUND CONTEXT: Information on short- and especially long-term mortality among patients with infectious spondylodiscitis is sparse. PURPOSE: To analyze mortality, factors associated with death, and cause-specific mortality rates among patients with infectious nonpostoperative spondylodiscitis. STUDY DESIGN: A case-cohort study. PATIENT SAMPLE: We identified all patients aged 18 years or older treated for infectious spondylodiscitis from January 1994 to May 2009 at hospitals in Funen County, Denmark. OUTCOME MEASURES: Overall and cause-specific mortality. METHODS: Mortality rates among patients were compared with rates among a reference population using Kaplan-Meier plots and mortality rate ratios (MRRs). Short-term mortality was defined as deaths within first year after admission and long-term mortality was deaths thereafter. Factors associated with death were determined. RESULTS: Among 298 identified patients, 61 (20%) died within the first year. Adjusted MRRs were 16.8 (95% confidence interval: 9.9-28.5) for 0 to 90 days; 4.2 (2.5-7.0) for 91 to 365 days; 2.2 (1.6-2.9) for 1 to 4 years; and 1.7 (1.2-2.5) for 5 to 14 years. Mortality rate ratios stratified on microbiological etiology were 8.8 (3.3-22.1) for 0 to 90 days; 1.4 (0.3-5.8) for 91 to 365 days; 3.2 (2.0-5.1) for 1 to 4 years; and 1.1 (0.5-2.4) for 5 to 14 years for unknown etiology and 24.0 (13.0-44.2) for 0 to 90 days; 6.0 (3.1-11.5) for 91 to 365 days; 1.9 (1.1-3.2) for 1 to 4 years; and 2.7 (1.5-4.7) for 5 to 14 years among Staphylococcus aureus infections. The main factors associated with short-term mortality were severe neurologic deficits at the time of admission, epidural abscess, and comorbidities. Long-term mortality seemed independent of microbiological etiology. CONCLUSIONS: Mortality remained high the first year after admission and thereafter decreased with time to a level close to the reference population. Short-term mortality was especially related to infection with abscess formation and neurologic deficits and long-term mortality was related to alcohol dependency.

No transmission of blood-borne viruses among hospital staff despite frequent blood exposure.

INTRODUCTION: Exposure to blood and body fluids (BBF) is a major concern for health-care workers (HCWs) and implies a risk of infection with blood-borne pathogens. However, in Denmark, no exposure incidence studies among HCWs have been reported for the past ten years. The aims of this study were to provide an updated evaluation of the annual frequency of registered exposures during the 2003-2012 period, the prevalence and incidence of transmission of HIV, HBV and HCV among HCWs, the prevalence of HIV, HBV and HCV among source patients, the follow-up by HBV vaccination and blood sampling in exposed HCWs and, finally, reporting habits. MATERIAL AND METHODS: All registered first-time cases of BBF exposure at Odense University Hospital during the 2003-2012 period were included. The exposed HCW and source patient were linked to a laboratory database to obtain the test results for HIV, HBV, HCV and the anti-HBs level at baseline and after exposure. For 2012, a detailed analysis of BBF exposure was performed. RESULTS: A total of 2,274 first-time BBF exposures were analysed. We observed a 35% increase in the reported incidence of exposures in the period. The prevalence and incidence of HIV, HBV and HCV among HCWs was zero. The prevalence of anti-HIV among source patients was 0.9%, HBsAg 1.2% and anti-HCV/HCV-RNA 3.8%. In 2003-2012, 31.3% of the tested HCWs had an anti-HBs ≥ 10 IU/l at baseline and this increased to 76.1% after vaccination. In 2012, 95% of the HCWs had blood samples at the time of exposure, 35% had a three-month blood test and 17% had a six-month test. CONCLUSION: Despite a high rate of exposure to BBF among HCWs, the risk of infection was low. FUNDING: no external funding received. TRIAL REGISTRATION: not relevant.

Increasing incidence of pyogenic spondylodiscitis: a 14-year population-based study.

OBJECTIVES: Smaller studies indicate that the incidence of pyogenic spondylodiscitis is increasing, possible related to a growing elderly population. Data supporting this is sparse, and we therefore studied patient characteristics and changes in spondylodiscitis incidence 1995-2008. METHODS: In a population-based study we identified all patients aged ≥18 years treated for pyogenic spondylodiscitis in Funen County, Denmark (population 483 123). Annual incidences were determined. Demographics, symptoms and diagnostic methods were recorded. RESULTS: We found 192 cases: median age 66.6 years; 57.3% men; 76.6% culture positive cases. Staphylococcus aureus was the most common pathogen (55.1%). During 1995-2008 the overall incidence, incidence of culture negative cases, and incidence of cases due to S. aureus increased 2.2-5.8, 0.3-1.8, and 1.6-2.5 cases per 100 000 person years, respectively. The elderly had the highest incidence compared to those aged ≤70 years (rate ratio for men 5.9 (95% CI: 4.2-8.5) and for women 3.5 (95% CI: 2.3-5.3)). CONCLUSIONS: During 1995-2008 the overall incidence of S. aureus and culture negative cases of spondylodiscitis increased and remained highest among the elderly. Whether the increase is real or is a result of improved diagnostic methods and workup remains unknown.

[Endogenous Clostridium septicum panophthalmitis associated with gastrointestinal malignancy]. / Endogen Clostridium septicum-panoftalmitis associeret med gastrointestinal malignitet.

Endogenous panophthalmitis due to Clostridium septicum (C. septicum) is a rare, but life-threatening condition. There is a known association between infection and malignancy. Our patient presented with panophthalmitis - with visual loss, proptosis, raised intraocular pressure and air bubble in the anterior chamber. C. septicum was found in cultures of pus. He was treated with antibiotics and surgery, and recovered. Further investigations showed carcinoma of the colon. This case stresses the need for urgent treatment and subsequent investigation for occult malignancy.