Does the Use of Local Antibiotics Affect Clinical Outcome of Patients with Fracture-Related Infection?

This international, multi-center study evaluated the effect of antibiotic-loaded carriers (ALCs) on outcome in patients with a fracture-related infection (FRI) and evaluated whether bacterial resistance to the implanted antibiotics influences their efficacy. All patients who were retrospectively diagnosed with FRI according to the FRI consensus definition, between January 2015 and December 2019, and who underwent surgical treatment for FRI at any time point after injury, were considered for inclusion. Patients were followed-up for at least 12 months. The primary outcome was the recurrence rate of FRI at follow-up. Inverse probability for treatment weighting (IPTW) modeling and multivariable regression analyses were used to assess the relationship between the application of ALCs and recurrence rate of FRI at 12 months and 24 months. Overall, 429 patients with 433 FRIs were included. A total of 251 (58.0%) cases were treated with ALCs. Gentamicin was the most frequently used antibiotic (247/251). Recurrence of infection after surgery occurred in 25/251 (10%) patients who received ALCs and in 34/182 (18.7%) patients who did not (unadjusted hazard ratio (uHR): 0.48, 95% CI: [0.29–0.81]). Resistance of cultured microorganisms to the implanted antibiotic was not associated with a higher risk of recurrence of FRI (uHR: 0.75, 95% CI: [0.32–1.74]). The application of ALCs in treatment of FRI is likely to reduce the risk of recurrence of infection. The high antibiotic concentrations of ALCs eradicate most pathogens regardless of susceptibility test results

The effect of guideline-based antimicrobial therapy on the outcome of fracture-related infections (EAT FRI Study)

Aim: This study investigated the compliance with a guideline-based antibiotic regimen on the outcome of patients surgically treated for a fracture-related infection (FRI). Method: In this international multicenter observational study, patients were included when diagnosed with an FRI between 2015 and 2019. FRI was defined according to the FRI consensus definition. All patients were followed for at least one year. The chosen antibiotic regimens were compared to the published guidelines from the FRI Consensus Group and correlated to outcome. Treatment success was defined as the eradication of infection with limb preservation. Results: A total of 433 patients (mean age 49.7 ± 16.1 years) with FRIs of mostly the tibia (50.6%) and femur (21.7%) were included. Full compliance of the antibiotic regime to the published guidelines was observed in 107 (24.7%) cases. Non-compliance was mostly due to deviations from the recommended dosing, followed by the administration of an alternative antibiotic than the one recommended or an incorrect use or non-use of rifampin. Non-compliance was not associated with a worse outcome: treatment failure was 12.1% in compliant versus 13.2% in non-compliant cases (p = 0.87). Conclusions: We report good outcomes in the treatment of FRI and demonstrated that minor deviations from the FRI guideline are not associated with poorer outcomes.</p

Bruker matrix-assisted laser desorption/ionization time-of-flight mass spectrometry identification of Neisseria gonorrhoeae is improved by a database extension

Bruker MALDI-TOF MS identification of Neisseria gonorrhoeae may be affected by "B consistency categorization". A supplementary database of 17 N. gonorrhoeae main spectra was constructed. 12/64 N. gonorrhoeae identifications were categorized with B consistency, which disappeared using the supplementary database. Database extension did not result in misidentification of Neisseria meningitidis

Properties of CD4(+) T cells in human cytomegalovirus infection

The correlates of protective immunity to disease-inducing viruses in man remain to be elucidated. We determined the kinetics and properties of cytomegalovirus (CMV)-specific CD4(+) T cells in healthy individuals and renal transplant recipients during different stages of CMV infection. Our data reveal that circulating CMV-specific CD4(+) T cells displayed an effector-memory phenotype, and produced the T helper 1 cytokines interferon-gamma and tumor necrosis factor-alpha. In addition, they lacked molecules for secondary lymphoid organ homing and expressed the cytotoxic molecule granzyme B, inferring a direct role of these cells at target sites of infection. In asymptomatic individuals the CMV-specific CD4(+) T-cell response preceded CMV-specific CD8(+) T-cell responses, whereas in symptomatic individuals the CMV-specific effector memory CD4(+) T-cell response was delayed and only detectable after antiviral therapy. The appearance of disease symptoms in these patients suggests that functional CD8(+) T cell and antibody responses are insufficient to control viral replication and that formation of effector memory CD4(+) T cells is necessary for recovery of infectio

Bruker matrix-assisted laser desorption/ionization time-of-flight mass spectrometry identification of Neisseria gonorrhoeae is improved by a database extension

Bruker MALDI-TOF MS identification of Neisseria gonorrhoeae may be affected by "B consistency categorization". A supplementary database of 17 N. gonorrhoeae main spectra was constructed. 12/64 N. gonorrhoeae identifications were categorized with B consistency, which disappeared using the supplementary database. Database extension did not result in misidentification of Neisseria meningitidis

Two Cases of Mycobacterium microti-Induced Culture-Negative Tuberculosis▿

We present descriptions of two human Mycobacterium microti infections: one of a patient with pulmonary disease and one of a patient with osteomyelitis of the hip. Both patients had acid-fast bacilli and a positive Mycobacterium tuberculosis complex PCR from clinical specimens, but mycobacterial cultures remained negative. The microbiological diagnosis was established by molecular methods

The effect of guideline-based antimicrobial therapy on the outcome of fracture-related infections (EAT FRI Study)

Aim: This study investigated the compliance with a guideline-based antibiotic regimen on the outcome of patients surgically treated for a fracture-related infection (FRI). Method: In this international multicenter observational study, patients were included when diagnosed with an FRI between 2015 and 2019. FRI was defined according to the FRI consensus definition. All patients were followed for at least one year. The chosen antibiotic regimens were compared to the published guidelines from the FRI Consensus Group and correlated to outcome. Treatment success was defined as the eradication of infection with limb preservation. Results: A total of 433 patients (mean age 49.7 ± 16.1 years) with FRIs of mostly the tibia (50.6%) and femur (21.7%) were included. Full compliance of the antibiotic regime to the published guidelines was observed in 107 (24.7%) cases. Non-compliance was mostly due to deviations from the recommended dosing, followed by the administration of an alternative antibiotic than the one recommended or an incorrect use or non-use of rifampin. Non-compliance was not associated with a worse outcome: treatment failure was 12.1% in compliant versus 13.2% in non-compliant cases (p = 0.87). Conclusions: We report good outcomes in the treatment of FRI and demonstrated that minor deviations from the FRI guideline are not associated with poorer outcomes.</p

Differentiation of human alloreactive CD8(+) T cells in vitro

Expansion and differentiation of alloantigen-reactive CD8(+) T cells in mixed lymphocyte cultures was followed by measurement of the loss of carboxyfluorescein diacetate succinimidyl ester (CFSE) fluorescence of responder cells. Proliferation of CD8(+) T cells became detectable on day 4 of culture and, 2 days later, > 60% of the CD8(+) T cells in culture were dividing alloreactive lymphocytes. In parallel with expansion, CD8(+) T-cell differentiation was initiated, as evidenced by an increase in the number of CD45RA(−) and CD27(−) T cells and acquisition of the ability to produce interferon-γ after restimulation with the specific alloantigen. Finally, although short-term stimulation and measurement of intracellular cytokine production allowed visualization of alloreactive CD8(+) T cells expanded in vitro, this procedure did not detect circulating alloreactive CD8(+) T cells activated in vivo in recipients of allogeneic kidney grafts

The added value of the selective SuperPolymyxin™ medium in detecting rectal carriage of Gram-negative bacteria with acquired colistin resistance in intensive care unit patients receiving selective digestive decontamination

The objective of this study was to determine the value of using SuperPolymyxin™ selective medium (ELITech Group, Puteaux, France) in addition to conventional non-selective inoculation methods in the detection of acquired colistin resistance in a Dutch intensive care unit (ICU) that routinely uses selective decontamination of the digestive tract (SDD). We performed a cross-sectional study with prospective data collection in a tertiary-care ICU. All consecutive surveillance rectal swabs of ICU-patients receiving SDD were included and cultured in an observer-blinded approach using (1) a conventional culture method using non-selective media and (2) SuperPolymyxin™ selective medium. MIC values for colistin of non-intrinsically colistin-resistant Gram-negative isolates were determined with broth microdilution (BMD) using Sensititre™ and colistin resistance was confirmed using BMD according to EUCAST guidelines. One thousand one hundred five rectal swabs of 428 unique ICU-patients were inoculated using both culture methods, yielding 346 and 84 Gram-negative isolates for BMD testing with the conventional method and SuperPolymyxin™ medium, of which 308 and 80 underwent BMD, respectively. The number of identified rectal carriers of isolates with acquired colistin resistance was 3 (0.7%) for the conventional method, 4 (0.9%) for SuperPolymyxin™, and 5 (1.2%) for both methods combined. The number of isolates with acquired colistin resistance was 4 (1.0%) for the conventional method, 8 (2.1%) for SuperPolymyxin™ and 9 (2.3%) for both methods combined. In a surveillance setting of low prevalence of acquired colistin resistance in patients that receive SDD in a Dutch tertiary-care ICU, SuperPolymyxin™ had a higher diagnostic yield than conventional inoculation methods, but the combination of both had the highest diagnostic yield

The added value of the selective SuperPolymyxin™ medium in detecting rectal carriage of Gram-negative bacteria with acquired colistin resistance in intensive care unit patients receiving selective digestive decontamination

The objective of this study was to determine the value of using SuperPolymyxin™ selective medium (ELITech Group, Puteaux, France) in addition to conventional non-selective inoculation methods in the detection of acquired colistin resistance in a Dutch intensive care unit (ICU) that routinely uses selective decontamination of the digestive tract (SDD). We performed a cross-sectional study with prospective data collection in a tertiary-care ICU. All consecutive surveillance rectal swabs of ICU-patients receiving SDD were included and cultured in an observer-blinded approach using (1) a conventional culture method using non-selective media and (2) SuperPolymyxin™ selective medium. MIC values for colistin of non-intrinsically colistin-resistant Gram-negative isolates were determined with broth microdilution (BMD) using Sensititre™ and colistin resistance was confirmed using BMD according to EUCAST guidelines. One thousand one hundred five rectal swabs of 428 unique ICU-patients were inoculated using both culture methods, yielding 346 and 84 Gram-negative isolates for BMD testing with the conventional method and SuperPolymyxin™ medium, of which 308 and 80 underwent BMD, respectively. The number of identified rectal carriers of isolates with acquired colistin resistance was 3 (0.7%) for the conventional method, 4 (0.9%) for SuperPolymyxin™, and 5 (1.2%) for both methods combined. The number of isolates with acquired colistin resistance was 4 (1.0%) for the conventional method, 8 (2.1%) for SuperPolymyxin™ and 9 (2.3%) for both methods combined. In a surveillance setting of low prevalence of acquired colistin resistance in patients that receive SDD in a Dutch tertiary-care ICU, SuperPolymyxin™ had a higher diagnostic yield than conventional inoculation methods, but the combination of both had the highest diagnostic yield