A combination of laboratory, histopathological and microbiological tests for diagnosis of prosthetic joint infection (PJI) have been strongly recommended. This study aims to characterize the accuracy ...of individual or group tests, such as culture of sonicate fluid, synovial fluid and peri-implant tissue, C-reactive protein (CRP) and histopathology for detection of early, delayed and late PJI.
A prospective study of patients undergoing hip or knee arthroplasty from February 2009 to February 2014 was performed in a Spanish tertiary health care hospital. The diagnostic accuracy of the different methods was evaluated constructing receiver-operating-characteristic (ROC) curve areas.
One hundred thirty consecutive patients were included: 18 (13.8%) early PJI, 35 (27%) delayed PJI and 77 (59.2%) late PJI. For individual parameters, the area under the ROC curve for peri-implant tissue culture was larger for early (0.917) than for delayed (0.829) and late PJI (0.778), p = 0.033. There was a significantly larger difference for ROC area in the synovial fluid culture for delayed (0.803) than for early (0.781) and late infections (0.679), p = 0.039. The comparison of the areas under the ROC curves for the two microbiological tests showed that sonicate fluid was significantly different from peri-implant tissue in delayed (0.951 vs 0.829, p = 0.005) and late PJI (0.901 vs 0.778, p = 0.000). The conjunction of preoperative parameters, synovial fluid culture and CRP, improved the accuracy for late PJI (p = 0.01). The conjunction of histopathology and sonicate fluid culture increased the area under ROC curve of sonication in early (0.917 vs 1.000); p = 0.06 and late cases (0.901 vs 0.999); p < 0.001.
For early PJI, sonicate fluid and peri-implant tissue cultures achieve the same best sensitivity. For delayed and late PJI, sonicate fluid culture is the most sensitive individual diagnostic method. By combining histopathology and peri-implant tissue, all early, 97% of delayed and 94.8% of late cases are diagnosed. The conjunction of histopathology and sonicate fluid culture yields a sensitivity of 100% for all types of infection.
The aim of this study was to analyse the association between human immunodeficiency virus (HIV) related clinical and analytical parameters and the presence of subclinical atherosclerosis as well as ...endothelial dysfunction. This was a prospective cohort study of HIV-positive patients who underwent intima media thickness (IMT) determination and coronary artery calcium scoring to determine subclinical atherosclerosis. To detect endothelial dysfunction, the breath holding index, flow-mediated dilation and the concentration of endothelial progenitor cells (EPCs) were measured. Patients with an IMT ≥ 0.9 mm had an average of 559.3 ± 283.34 CD4/μl, and those with an IMT < 0.9 mm had an average of 715.4 ± 389.92 CD4/μl (p = 0.04). Patients with a low calcium score had a significantly higher average CD4 cell value and lower zenith viral load (VL) than those with a higher score (707.7 ± 377.5 CD4/μl vs 477.23 ± 235.7 CD4/μl (p = 0.01) and 7 × 10
± 5 × 10
copies/ml vs 23.4 × 104 ± 19 × 104 copies/ml (p = 0.02)). The number of early EPCs in patients with a CD4 nadir < 350/µl was lower than that in those with a CD4 nadir ≥ 350 (p = 0.03). In HIV-positive patients, low CD4 cell levels and high VL were associated with risk of developing subclinical atherosclerosis. HIV patients with CD4 cell nadir < 350/µl may have fewer early EPCs.
Mannose-binding lectin (MBL) is a key component of innate immunity. Low serum MBL levels, related to promoter polymorphism and structural variants, have been associated with an increased risk of ...infection. The aim of this work was to analyse the incidence and severity of infections and mortality in relation to the MBL2 genotype and MBL levels in patients underwent allogeneic haematopoietic stem cell transplantation (Allo-HSCT).
This was a prospective cohort study of 72 consecutive patients underwent Allo-HSCT between January 2007 and June 2009 in a tertiary referral centre. Three periods were considered in the patients' follow-up: the early period (0-30 days after Allo-HSCT), the intermediate period (30-100 days after Allo-HSCT) and the late period (> 100 days after Allo-HSCT). A commercial line probe assay for MBL2 genotyping and an ELISA Kit were used to measure MBL levels. A total of 220 episodes of infection were collected in the 72 patients. No association between donor or recipient MBL2 genotype and infection was found. The first episode of infection presented earlier in patients with pre-transplant MBL levels of < 1000 ng/ml (median 6d vs 8d, p = 0.036). MBL levels < 1000 ng/ml in the pre-transplant period (risk ratio (RR) 2.48, 95% CI 1.00-6.13), neutropenic period (0-30 days, RR 3.28, 95% CI 1.53-7.06) and intermediate period (30-100 days, RR 2.37, 95% CI 1.15-4.90) were associated with increased risk of virus infection. No association with bacterial or fungal disease was found. Mortality was associated with pre-transplant MBL levels < 1000 ng/ml (hazard ratio 5.55, 95% CI 1.17-26.30, p = 0.03) but not with MBL2 genotype.
Patients who underwent Allo-HSCT with low pre-transplant MBL levels presented the first episode of infection earlier and had an increased risk of viral infections and mortality in the first 6 months post-transplant. Thus, pre-transplant MBL levels would be important in predicting susceptibility to viral infections and mortality and might be considered a biomarker to be included in the pre-transplantation risk assessment.
D-dimer was introduced in 2018 as an alternative biomarker for C-reactive protein (CRP) in the diagnostic of prosthetic joint infection (PJI) criteria of the Musculoskeletal Infection Society. We ...assessed the accuracy of plasma D-dimer for the diagnosis of early, delayed, and late PJI according to Infectious Diseases Society of America (IDSA) criteria, and whether persistently high levels of D-dimer in cases of aseptic loosening (AL) may be predictive of subsequent implant-related infection.
A prospective study of a consecutive series of 187 revision arthroplasties was performed at a single institution. Septic (n = 39) and aseptic revisions (n = 141) were classified based on IDSA criteria. Preoperative assessment of CRP, erythrocyte sedimentation rate (ESR) and D-dimer was performed. Receiver operating curves were used to determine maximum sensitivity and specificity of the biomarkers. The natural progress of D-dimer for AL cases was followed up either until the date of implant-related infection at any time during the first year or 1 year after revision in patients without failure. Clinical outcomes for those AL cases included infection-related failure that required a new surgery or need for antibiotic suppression.
Preoperative D-dimer level was significantly higher in PJI cases than in AL cases (p = 0.000). The optimal threshold of D-dimer for the diagnosis of PJI was 1167 ng/mL. For overall diagnosis of PJI, C-reactive protein (CRP) achieved the highest sensitivity (84.6%), followed by erythrocyte sedimentation rate (ESR) and D-dimer (82% and 71.8%, respectively). Plasma D-dimer sensitivity was lower for all PJI types. When combinations of 2 tests were studied, the combined use of ESR and CRP achieved the best accuracy for all types of PJI (76.9%). 4.25% of AL cases had implant failure due to implant-related infection during the first year after the index revision arthroplasty, only the cases with early failure maintained high D-dimer levels.
Plasma D-dimer did not offer an improvement over the individual or combined diagnosis for any type of PJI according to IDSA criteria. Persistently raised levels of D-dimer after revision arthroplasty in AL cases might be used to effectively diagnose early postoperative infection.
We aimed to evaluate the impact of Staphylococcus aureus phenotype (vancomycin MIC) and genotype (agr group, clonal complex CC) on the prognosis and clinical characteristics of infective endocarditis ...(IE).
We performed a multicentre, longitudinal, prospective, observational study (June 2013 to March 2016) in 15 Spanish hospitals. Two hundred and thirteen consecutive adults (≥18 years) with a definite diagnosis of S. aureus IE were included. Primary outcome was death during hospital stay. Main secondary end points were persistent bacteraemia, sepsis/septic shock, peripheral embolism and osteoarticular involvement.
Overall in-hospital mortality was 37% (n = 72). Independent risk factors for death were age-adjusted Charlson co-morbidity index (OR 1.20; 95% CI 1.08–1.34), congestive heart failure (OR 3.60; 95% CI 1.72–7.50), symptomatic central nervous system complication (OR 3.17; 95% CI 1.41–7.11) and severe sepsis/septic shock (OR 4.41; 95% CI 2.18–8.96). In the subgroup of methicillin-susceptible S. aureus IE (n = 173), independent risk factors for death were the age-adjusted Charlson co-morbidity index (OR 1.17; 95% CI 1.03–1.31), congestive heart failure (OR 3.39; 95% CI 1.51–7.64), new conduction abnormality (OR 4.42; 95% CI 1.27–15.34), severe sepsis/septic shock (OR 5.76; 95% CI 2.57–12.89) and agr group III (OR 0.27; 0.10–0.75). Vancomycin MIC ≥1.5 mg/L was not independently associated with death during hospital nor was it related to secondary end points. No other genotype variables were independently associated with in-hospital death.
This is the first prospective study to assess the impact of S. aureus phenotype and genotype. Phenotype and genotype provided no additional predictive value beyond conventional clinical characteristics. No evidence was found to justify therapeutic decisions based on vancomycin MIC for either methicillin-resistant or methicillin-susceptible S. aureus.
Abstract Cytomegalovirus (CMV) infection remains a major complication of solid organ transplantation. Because of management of CMV is variable among transplant centers, in 2011 the Spanish ...Transplantation Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) developed consensus guidelines for the prevention and treatment of CMV infection in solid organ transplant recipients. Since then, new publications have clarified or questioned the aspects covered in the previous document. For that reason, a panel of experts revised the evidence on CMV management, including immunological monitoring, diagnostics, prevention, vaccines, indirect effects, treatment, drug resistance, immunotherapy, investigational drugs, and pediatric issues. This document summarizes the recommendations.
GES (Guiana Extended Spectrum) carbapenemases belong to “minor class A carbapenemases” and its prevalence could be underestimated due to the lack of specific tests. The aim of this study was to ...develop an easy PCR method to differentiate between GES β-lactamases with or without carbapenemase activity, based on an allelic discrimination system of SNPs that encode E104K and G170S mutations, without need of sequencing.
Two pair of primers and Affinity Plus probes, labeled with different fluorophores; FAM/IBFQ and YAK/IBFQ, were designed for each one of the SNPs.
This allelic discrimination assay allows to detect in real time the presence of all type of GES- β-lactamases, being able to differentiate between carbapenemases and extended-spectrum β-lactamase (ESBL), through a quick PCR test that avoid costly sequencing approaches and could help to decrease the current underdiagnosis of minor carbapenemases that scape of phenotypic screenings.
•Substitutions in residue ABL170 confer GES-carbapenemase activity.•Substitutions in residue ABL104 enhance GES-cephalosporinase activity.•Most commercial kits for carbapenemases detection do not include GES carbapenemases.•This allelic discrimination assay allows to detect and differentiate all type of GES beta-lactamases.
Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the ...healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.
Solid organ transplant recipients (SOTR) are at risk of serious influenza-related complications. The impact of respiratory co-infection in SOTR with 2009 pandemic influenza A(H1N1) is unknown. A ...multicentre prospective study of consecutive cases of pandemic influenza A(H1N1) in SOTR was carried out to assess the clinical characteristics and outcome and the risk factors for co-infection. Overall, 51 patients were included. Median time from transplant was 3.7 years, 5.9% of the cases occurred perioperatively and 7.8% were hospitalacquired. Pneumonia was diagnosed in 15 (29.4%) patients. Ten cases were severe (19.6%): 13.7% were admitted to intensive care units, 5.9% suffered septic shock, 5.9% developed acute graft rejection and 7.8% died. Co-infection was detected in 15 patients (29.4%): eight viral, six bacterial and one fungal. Viral co-infection did not affect the outcome. Patients with non-viral co-infection had a worse outcome: longer hospital stay (26.2 ± 20.7 vs. 5.5 ± 10.2) and higher rate of severe diseases (85.7% vs. 2.3%) and mortality (42.8% vs. 2.3%). Independent risk factors for non-viral co-infection were: diabetes mellitus and septic shock. Other factors associated with severe influenza were: delayed antiviral therapy, diabetes mellitus, time since transplantation <90 days and pneumonia. In conclusion, pandemic influenza A can cause significant direct and indirect effects in SOTR, especially in the early post-transplant period, and should be treated early. Clinicians should be aware of the possibility of non-viral co-infection, mainly in diabetic patients and severe cases. An effort should be made to prevent influenza with immunization of the patient and the environment.
The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study ...112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six‐ and 12‐week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio HR: 2.29; p‐value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p‐value = 0.017) were independent predictors for 6‐week all‐cause mortality, whereas the initial use of a voriconazole‐based regimen showed a protective effect (HR: 0.34; p‐value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.
Invasive pulmonary aspergillosis presents a high mortality rate in kidney transplant recipients, with diagnosis within the first 6 months posttransplantation and bilateral lung involvement as independent risk factors for mortality.
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