Enteroviruses in Respiratory Samples from Paediatric Patients of a Tertiary Care Hospital in Germany

Enteroviruses are associated with various diseases accompanied by rare but severe complications. In recent years, outbreaks of enterovirus D68 and enterovirus A71 associated with severe respiratory infections and neurological complications have been reported worldwide. Since information on molecular epidemiology in respiratory samples is still limited, the genetic diversity of enteroviruses was retrospectively analysed over a 4-year period (2013–2016) in respiratory samples from paediatric patients. Partial viral major capsid protein gene (VP1) sequences were determined for genotyping. Enteroviruses were detected in 255 (6.1%) of 4187 specimens. Phylogenetic analyses of 233 (91.4%) strains revealed 25 different genotypes distributed to Enterovirus A (39.1%), Enterovirus B (34.3%), and Enterovirus D (26.6%). The most frequently detected genotypes were enterovirus D68 (26.6%), coxsackievirus A6 (15.9%), and enterovirus A71 (7.3%). Enterovirus D68 detections were associated with lower respiratory tract infections and increased oxygen demand. Meningitis/encephalitis and other neurological symptoms were related to enterovirus A71, while coxsackievirus A6 was associated with upper respiratory diseases. Prematurity turned out as a potential risk factor for increased oxygen demand during enterovirus infections. The detailed analysis of epidemiological and clinical data contributes to the non-polio enterovirus surveillance in Europe and showed high and rapidly changing genetic diversity of circulating enteroviruses, including different enterovirus D68 variants

What is the burden of osteomyelitis in Germany? An analysis of inpatient data from 2008 through 2018

Background The epidemiology of osteomyelitis in Germany is unknown, which makes it difficult to estimate future demands. Therefore, we aimed to analyse how the numbers of cases have developed over the last decade as a function of osteomyelitis subtype, age group, gender, and anatomical localization. Methods Osteomyelitis rates were quantified based on annual ICD-10 diagnosis codes from German medical institutions between 2008 through 2018, provided by the Federal Statistical Office of Germany (Destatis). Results Overall osteomyelitis prevalence increased by 10.44% from 15.5 to 16.7 cases per 100,000 inhabitants between 2008 through 2018. Out of 11,340 cases in 2018, 47.6% were diagnosed as chronic, 33.2% as acute and 19.2% as unspecified osteomyelitis. Men were often affected than women with 63.4% of all cases compared to 36.6%. The largest proportion of patients comprised the age group 60–69 years (22.1%), followed by 70–79 years (21.7%). A trend towards more osteomyelitis diagnoses in older patients was observed. Lower extremities were most frequently infected with 73.8% of all cases in 2018 (+ 10.8% change). Conclusions Osteomyelitis remains a serious problem for orthopedic and trauma surgery. Prevention methods and interdisciplinary approaches are strongly required

Comment on Lunz et al. Impact and Modification of the New PJI-TNM Classification for Periprosthetic Joint Infections. J. Clin. Med. 2023, 12, 1262

We read with great interest the article by Lunz et al. [1], in which the authors dealt with the new Periprosthetic Joint Infection (PJI)-TNM classification that was recently published by our group (Table 1) [2–4]. PJI represents one of the most feared complications in the orthopedic field, resulting in impaired quality of life, repeated and prolonged hospital stays, and significant morbidity and mortality in affected patients. Still, there is no commonly used classification system that could facilitate the comparison of treatment strategies and patient outcomes [5,6]. Therefore, we are delighted with the authors’ conclusions that “clinicians and researchers should be familiar with the new PJI-TNM classification and start implementing it into their routine practice” [1]. The work of Lunz et al. [1] retrospectively assessed 80 consecutive PJI patients treated with a two-stage exchange and was the first to correlate the PJI-TNM classification to surgical parameters and some clinical outcome parameters, such as need for revision surgery after stage one surgery, the duration of the interim period, and mortality. In addition, Lunz et al. [1] believed that the initial PJI-TNM publication from our group could be improved through certain modifications to the TNM backbone, resulting in a “pTNM” version. An additional “p-status” (type of prosthesis) was proposed to distinguish between standard implants (p0), revision implants (p1), and megaprostheses (p2). Further suggestions were to add an “x” in front of the “p-status” to indicate a loosened implant and to limit the criteria parameters for p, T, N, and M to only 0 = least serious, 1 = moderate, and 2 = most serious by eliminating the letters for the subclassifications of the 0, 1, and 2 categories of our initially proposed classification. They also proposed the replacement of the CCI for the assessment of patients’ comorbidities with the American Society of Anesthesiologists (ASA) Physical Status Classification System [7]

What Is the Most Effective Empirical Antibiotic Treatment for Early, Delayed, and Late Fracture-Related Infections?

Antibiotic treatment strategies for fracture-related infections (FRI) are often extrapolated from periprosthetic joint infections (PJI), although, in contrast to PJI, detailed analysis of pathogens and their antibiotic resistance is missing. Therefore, this study aimed to investigate antibiotic susceptibility profiles to identify effective empiric antibiotic treatment for early-, delayed-, and late-onset FRI. Patients treated for FRI from 2013 to 2020 were grouped into early (10 weeks) onset of infection. Antibiotic susceptibility profiles were examined with respect to broadly used antibiotics and antibiotic combinations. In total, 117 patients (early n = 19, delayed n = 60, late n = 38) were enrolled. In early-onset FRI, 100.0% efficacy would be achieved by meropenem + vancomycin, gentamicin + vancomycin, co-amoxiclav + glycopeptide, ciprofloxacin + glycopeptide and piperacillin/tazobactam + glycopeptide. For patients with delayed FRI, the highest susceptibility was revealed for meropenem + vancomycin, gentamicin + vancomycin and ciprofloxacin + glycopeptide (96.7%). Meropenem + vancomycin was the most effective empiric antimicrobial in patients with late-onset of infection with 92.1% coverage. No subgroup differences in antibiotic sensitivity profiles were observed except for the combination ciprofloxacin + glycopeptide, which was significantly superior in early FRI (F = 3.304, p = 0.04). Across all subgroups meropenem + vancomycin was the most effective empiric treatment in 95.7% of patients with confirmed susceptibility. Meropenem + vancomycin, gentamicin + vancomycin, co-amoxiclav + glycopeptide are the best therapeutic options for FRI, regardless of the onset of infection. To avoid multidrug resistance, established antibiotic combinations such as co-amoxiclav with a glycopeptide seem to be reasonable as a systemic antibiotic therapy, while vancomycin + gentamicin could be implemented in local antibiotic therapy to reduce adverse events during treatment

Treatment of Periprosthetic Joint Infection and Fracture-Related Infection With a Temporary Arthrodesis Made by PMMA-Coated Intramedullary Nails – Evaluation of Technique and Quality of Life in Implant-Free Interval

Background: Antimicrobial coating of intramedullary nails with polymethyl methacrylate (PMMA) bone cement promises infection control and stabilization for subsequent bone healing. However, when removing the implant, bone cement can debond and remain in the medullary cavity of the long bones, representing a nidus for reinfection. This work presents a technique comprising reinforcement of PMMA-coated intramedullary nails with cerclage wire to prevent such problems in patients treated for fracture-related infection (FRI) or knee periprosthetic joint infection (PJI) with a static spacer as temporary arthrodesis allowing weight-bearing in the implant-free interval. Outcomes of this surgical treatment were evaluated in terms of (i) associated complications and (ii) patient-reported quality of life. Methods: In this retrospective case series, 20 patients with PJI (n = 14, 70%) and FRI (n = 6, 30%) treated with PMMA-coated intramedullary nails reinforced with cerclage wire between January 2021 and July 2021 were included. Quality of life during the implant-free interval was evaluated with the EQ-5D, SF-36, and an ICD-10 based psychological symptom rating and compared with previously analyzed cohorts of successfully treated PJI and FRI patients in whom eradication of infection and stable bone consolidation was achieved. Results: Complications during the implant-free interval comprised a broken nail in one case (5.0%) and a reinfection in one case (5.0%). Coating-specific side effects and cement debonding during removal did not occur. The mean physical health component score of SF-36 was 26.1 ± 7.6, and the mean mental health component score reached a value of 47.1 ± 18.6. The mean EQ-5D index value was 0.36 ± 0.32 and the mean EQ-5D visual analogue scale rating was 47.4 ± 19.4. The scores were significantly lower than those in the successfully treated FRI cohort but not in the PJI cohort. The mean ICD-10-based symptom rating scores revealed psychological symptom burden on the depression scale and enhanced levels of anxiety in comparison with healed FRI and PJI patients. Conclusion: Reinforcement of PMMA bone cement-coated implants seems to be a reasonable treatment option to create a temporary arthrodesis, preventing detachment of the bone cement when the implant was removed. Level of Evidence: IV

Long-term patient-related quality of life outcomes and ICD-10 symptom rating (ISR) of patients with pyogenic vertebral osteomyelitis: What is the psychological impact of this life-threatening disease?

Purpose We aimed to evaluate the long-term impact of the treatment of pyogenic vertebral osteomyelitis (VO) on functional outcomes and patients' quality of life (QoL) with a special focus on psychological well-being. Methods A total of 156 patients with VO with a minimum clinical follow-up of 12 months were retrospectively identified and asked to participate. Patient-reported outcome measures were evaluated with the EuroQol five-dimension questionnaire (EQ-5D) and German Short-Form 36 (SF-36) outcome instruments as well as with an ICD-10 based symptom rating (ISR) and compared to normative data. Spine-specific outcomes were assessed with the Core Outcome Measure Index and the Oswestry disability index (ODI) or the Neck disability index (NDI), respectively. Results From n = 156 eligible patients, n = 129 patients could be contacted and n = 40 returned questionnaires, yielding a response rate of 31.0%. The mean time from hospital discharge to follow-up was 83.0 ± 3.8 (13–193) months. Spine-specific outcomes showed mild to moderate disability. The mean physical health component score of the SF-36 (37.1 ± 16.7), the mean mental health component score (38.2 ± 14.0) and the mean EQ-5D VAS rating (57.1 ± 21.5) were significantly lower in comparison with the scores of an age-matched reference population (all p < 0.05). The mean total score of the ISR was 0.53 ± 0.23. On average, the cohort did not cross the threshold of clinically relevant symptom burden on any subscale. Conclusion Even almost seven years on average after completed treatment of VO, patients report impaired QoL. Assessment of psychological disorders should be implemented in clinical practice and future prospective studies

The Epidemiology of Spondylodiscitis in Germany: A Descriptive Report of Incidence Rates, Pathogens, In-Hospital Mortality, and Hospital Stays between 2010 and 2020

Background: Spondylodiscitis can lead to significant morbidity and mortality. Understanding its up-to-date epidemiological characteristics and trends is important to improve patient care. Methods: This study analyzed trends in the incidence rate of spondylodiscitis cases in Germany between 2010 and 2020, as well as the pathogens, in-hospital mortality rate, and length of hospital stay. Data were obtained from the Federal Statistical Office and the Institute for the Hospital Remuneration System database. The ICD-10 codes “M46.2-”, “M46.3-” and “M46.4-” were evaluated. Results: The incidence rate of spondylodiscitis increased to 14.4/100,000 inhabitants, with 59.6% cases occurring in patients 70 years or older and affecting mainly the lumbar spine (56.2%). Absolute case numbers increased from 6886 by 41.6% to 9753 in 2020 (IIR = 1.39, 95% CI 0.62–3.08). Staphylococci and Escherichia coli were the most coded pathogens. The proportion of resistant pathogens was 12.9%. In-hospital mortality rates increased to a maximum of 64.7/1000 patients in 2020, intensive care unit treatment was documented in 2697 (27.7%) cases, and the length of stay per case was 22.3 days. Conclusion: The sharply increasing incidence and in-hospital mortality rate of spondylodiscitis highlights the need for patient-centered therapy to improve patient outcomes, especially in the geriatric, frail population, which is prone to infectious diseases

The clinical use of bone graft substitutes in orthopedic surgery in Germany—A 10‐years survey from 2008 to 2018 of 1,090,167 surgical interventions

Aim of the study was to evaluate (1) the overall use of bone graft substitutes, autografts and allografts, (2) of different types of bone graft substitutes (calcium sulfate, calcium phosphate, calcium phosphate ceramics or polymethyl methacrylate) and of different bone grafts (cancellous vs. cortical), and (3) the use of antibiotic-loading of bone graft substitutes in orthopedic surgery in Germany. Gross data were provided from the Federal Statistical Office of Germany and revealed an overall increase in bone defect reconstruction procedures using bone graft substitutes, autografts and allografts from 86,294 in 2008 to 99,863 cases in 2018 (+15.7%). The relative use of bone graft substitutes for these interventions strongly increased from 11.8% in 2008 (10,163 cases) to 23.9% in 2018 (23,838 cases) with an increase of +134.4%. Furthermore, antibiotic-loaded bone graft substitutes were implanted more frequently with an overall increase of +194% (2008: n = 2,657; 2018: n = 7,811). The work shows an increasing use of bone graft substitutes and antibiotic-loaded bone graft substitutes over the last 10 years in Germany

Comment on Lunz et al. Impact and Modification of the New PJI-TNM Classification for Periprosthetic Joint Infections. <i>J. Clin. Med.</i> 2023, <i>12</i>, 1262

We read with great interest the article by Lunz et al. [...

Is There a Difference in Microbiological Epidemiology and Effective Empiric Antimicrobial Therapy Comparing Fracture-Related Infection and Periprosthetic Joint Infection? A Retrospective Comparative Study

This study aims to investigate (1) microbial patterns in fracture-related infections (FRIs) in comparison to microbiological patterns of periprosthetic joint infections (PJIs), (2) the identification of effective empiric antibiotic therapy for FRIs and PJIs and (3) analysis of difficult-to-treat (DTT) pathogens. Patients treated for FRIs or PJIs from 2017 to 2020 were evaluated for pathogens detected during treatment. Antibiotic susceptibility profiles were examined with respect to broadly used antibiotics and antibiotic combinations. Resistance rates to rifampicin or fluoroquinolone were determined. A total of 81 patients with PJI and 86 with FRI were included in the study. For FRIs Staphylococcus aureus was the most common infection-causing pathogen (37.4% vs. 27.9% for PJI). Overall, there was no statistical difference in pathogen distribution (p = 0.254). For FRIs, combinations of gentamicin + vancomycin (93.2%), co-amoxiclav + glycopeptide and meropenem + vancomycin (91.9% each) would have been effective for empiric therapy, similar to PJIs. Difficult to treat pathogens were more frequently detectable in PJIs (11.6% vs. 2.3%). Empiric therapy combinations such as gentamicin + vancomycin, co-amoxiclav + glycopeptide or meropenem + vancomycin, are effective antibiotic strategies for both FRI and PJI patients. More DTT pathogens were detectable in PJIs compared to FRIs