Prosthetic Joint Infections due to Candida Species: A Multicenter International Study.

BACKGROUND: Prosthetic joint infection (PJI) caused by Candida spp is a severe complication of arthroplasty. We investigated the outcomes of Candida PJI. METHODS: This was a retrospective observational multinational study including patients diagnosed with Candida-related PJI between 2010 and 2021. Treatment outcome was assessed at 2-year follow-up. RESULTS: A total of 269 patients were analyzed. Median age was 73.0 (interquartile range [IQR], 64.0-79.0) years; 46.5% of patients were male and 10.8% were immunosuppressed. Main infection sites were hip (53.0%) and knee (43.1%), and 33.8% patients had fistulas. Surgical procedures included debridement, antibiotics, and implant retention (DAIR) (35.7%), 1-stage exchange (28.3%), and 2-stage exchange (29.0%). Candida spp identified were Candida albicans (55.8%), Candida parapsilosis (29.4%), Candida glabrata (7.8%), and Candida tropicalis (5.6%). Coinfection with bacteria was found in 51.3% of cases. The primary antifungal agents prescribed were azoles (75.8%) and echinocandins (30.9%), administered for a median of 92.0 (IQR, 54.5-181.3) days. Cure was observed in 156 of 269 (58.0%) cases. Treatment failure was associated with age >70 years (OR, 1.811 [95% confidence interval {CI}: 1.079-3.072]), and the use of DAIR (OR, 1.946 [95% CI: 1.157-3.285]). Candida parapsilosis infection was associated with better outcome (OR, 0.546 [95% CI: .305-.958]). Cure rates were significantly different between DAIR versus 1-stage exchange (46.9% vs 67.1%, P = .008) and DAIR versus 2-stage exchange (46.9% vs 69.2%, P = .003), but there was no difference comparing 1- to 2-stage exchanges (P = .777). CONCLUSIONS: Candida PJI prognosis seems poor, with high rate of failure, which does not appear to be linked to immunosuppression, use of azoles, or treatment duration.

Hydroxyapatite-coated compared with stainless steel external fixation pins did not show impact in the rate of pin track infection: a multicenter prospective study.

PURPOSE: Infection at the pin site remains the most common complication of external fixators (EFs). It is known that hydroxyapatite (HA)-coated pins increase bone adhesion and may lead to reduced rates of reported infections. The present study compares the rates of pin track infection associated with stainless steel and HA-coated pins. METHODS: This is a prospective, multicenter, nonrandomized, comparative intervention study among patients undergoing surgical treatment with EFs of any type between April 2018 and October 2021. Patients were followed up until the removal of the EF, or the end of the study period (ranging from 1 to 27.6 months). The definition of pin track infection was based upon the Maz-Oxford-Nuffield (MON) pin infection grading system. RESULTS: Overall, 132 patients undergoing external fixation surgery were included. Of these, 94 (71.2%) were male, with a mean age of 36.9 years (SD ± 18.9). Infection of any type (score > 1) was observed in 63 (47.7%) patients. Coated and uncoated-pin track-infection occurred in 45.7% and 48.5% of patients, respectively (P= 0.0887). The probability of developing infection (defined as a score ≥ 2) adjusted for comorbidities and follow-up time was not statistically higher among those who received uncoated pins compared to those who received pins coated with HA (odds ratio (OR) = 1.56, 95% confidence interval (95% CI): 0.67-3.67, p <0.05). CONCLUSION: In the present study, the external fixator pin infection rates were similar when using HA coating and standard steel pins.

Type of antibiotic but not the duration of prophylaxis correlates with rates of fracture-related infection.

PURPOSE: The issue of optimal prophylactic antibiotic administration for closed and open fracture surgeries remains controversial. The purpose of this study was to assess the role of type and duration longer than 48 h of antibiotic prophylaxis on the rates of fracture-related infection (FRI). METHODS: This is a single-center, prospective observational cohort study carried out with patients undergoing surgery for implants insertion to fracture stability. Risk estimates were calculated on the variables associated with factors for FRI and reported as a prevalence ratio (PR) with respect to the 95% confidence interval (CI). RESULTS: Overall, 132 patients were analyzed. The global rate of FRI was 15.9% (21/132), with open and closed fractures accounting for 30.5% (11/36) and 10.4% (10/96), respectively. The FRI rates in patients undergoing orthopedic surgery for fracture stabilization who received prophylactic antibiotic for up to and longer than 48 h were 8.9% and 26.4%, respectively. This difference did not reach statistical significance (prevalence ratio [PR] = 2.6, 95% confidence interval [95% CI]: 0.9-7.3. p = 0.063). CONCLUSIONS: Duration of antibiotic prophylaxis for surgical orthopedic fractures was not correlated with rates of FRI.

Prior use of antibiotics and immunosuppression are risk factors for fracture-related infection during the COVID-19 pandemic period: a Brazilian prospective cohort study.

BACKGROUND: Little is known about the role of COVID-19 pandemic period on the epidemiology of fracture-related infection (FRI). The present study summarizes the changes in the prevalence, microbiology, and risk factors of FRI during this period. METHODS: A prospective single-center cohort study assessed in the setting of COVID-19 pandemic (2020-2021), clinical, microbiological aspects, and independent risk factors (RF) of FRI. RFs were estimated by bivariate and multivariable analyses using prevalence ratio (PR) with significance at P < 0.05. Kaplan-Meier analysis was performed to evaluate treatment outcomes. RESULTS: Overall, 132 patients were analyzed, with patients with age over 65 years accounting 65.1%. FRI was diagnosed in 21(15.9%) patients. Independent RFs for FRI were recent and preoperative use of systemic antibiotics (PR: 7.0, 95% confidence interval (95% CI): 2.2 - 22.4, p = 0.001) and cancer (PR: 9.8, 95% CI: 2.0 - 48.8, p = 0.005). Cultures yielded Gram-negative bacteria in 77.8%, 33.3% were MDR. CONCLUSIONS: We found higher rates of FRI, predominating in the elderly with closed femoral fractures during the COVID-19 pandemic. Prior use of antibiotics and immunosuppression conditions were independent factor for FRI. Our outcomes provide evidence to avoid the empirical use of antibiotics prior to surgery for fracture stabilization.

How to Handle Concomitant Asymptomatic Prosthetic Joints During an Episode of Hematogenous Periprosthetic Joint Infection, a Multicenter Analysis.

BACKGROUND: Prosthetic joints are at risk of becoming infected during an episode of bacteremia, especially during Staphylocococcus aureus bacteremia. However, it is unclear how often asymptomatic periprosthetic joint infection (PJI) occurs, and whether additional diagnostics should be considered. METHODS: In this multicenter study, we retrospectively analyzed a cohort of patients with a late acute (hematogenous) PJI between 2005-2015 who had concomitant prosthetic joints in situ. Patients without at least 1 year of follow-up were excluded. RESULTS: We included 91 patients with a hematogenous PJI and 108 concomitant prosthetic joints. The incident PJI was most frequently caused by Staphylococcus aureus (43%), followed by streptococci (26%) and Gram-negative rods (18%). Of 108 concomitant prosthetic joints, 13 were symptomatic, of which 10 were subsequently diagnosed as a second PJI. Of the 95 asymptomatic prosthetic joints, 1 PJI developed during the follow-up period and was classified as a "missed" PJI at the time of bacteremia with S. aureus (1.1%). Infected prosthetic joints were younger than the noninfected ones in 67% of cases, and prosthetic knees were affected more often than prosthetic hips (78%). CONCLUSIONS: During an episode of hematogenous PJI, concomitant asymptomatic prosthetic joints have a very low risk of being infected, and additional diagnostic work-up for these joints is not necessary.

Non-elective and revision arthroplasty are independently associated with hip and knee prosthetic joint infection caused by Acinetobacter baumannii: a Brazilian single center observational cohort study of 98 patients.

BACKGROUND: Prosthetic joint infection (PJI) caused by Acinetobacter baumannii (Ab) has become a growing concern due to its overwhelming ability to express resistance to antibiotics and produce biofilm. AIM: This study aimed to identify independent risk factors (RFs) associated with Ab-associated PJI and their role in the treatment outcome. METHODS: This was a single-centre, retrospective cohort study of PJI patients diagnosed between January 2014 and July 2018. A PJI diagnosis was made based upon the MSIS 2018 criteria. To estimate RFs associated with Ab-associated PJI, multivariate analyses with a level of significance of p < 0.05 were performed. To evaluate treatment failure, Kaplan-Meier analysis and log-rank test were performed. RESULTS: Overall, 98 PJI cases were assessed, including 33 with Ab-associated PJI and 65 with PJI involving other microorganisms (non-Ab-associated PJI). Independent RFs associated with Ab-associated PJI were revision arthroplasty [odds ratio (OR) = 3.01; 95% confidence interval (CI) = 1.15-7.90; p = 0.025] and nonelective arthroplasty (OR = 2.65; 95% CI = 1.01-7.01; p = 0.049). Ab-associated PJI was also more likely than non-Ab-associated PJI to be classified as a chronic late infection (OR = 5.81; 95% CI = 2.1-16.07; p = 0.001). Ab-associated PJI was not associated with treatment failure (p = 0.557). CONCLUSIONS: Late chronic infections, surgical revision and nonelective arthroplasty are well-known predictors of PJI but were also independently associated with Ab-associated PJI. Infections caused by Ab and surgical treatment with debridement, antibiotics and implant retention were not associated with PJI treatment failure. TRIAL REGISTRATION: Study data supporting our results were registered with the Brazilian Registry of Clinical Trials ( https://www.ensaiosclinicos.gov.br/rg/RBR-6ft5yb/ ), an open-access virtual platform for the registration of studies on humans performed in Brazil. Registration no. RBR-6ft5yb .

Microbiological diagnosis of intramedullary nailing infection: comparison of bacterial growth between tissue sampling and sonication fluid cultures.

BACKGROUND: Intramedullary nailing (IMN) has been frequently indicated to treat long bone open and closed fractures, but IMN infection (IMNI) may have devastating consequences. Sonication has been regarded as an important add-on for microbial identification on a variety of orthopaedic implant-associated infections, but its role in the IMNI is poorly studied. We aim at evaluating the accuracy obtained by conventional peri-implant tissue culture (TC) samples with sonication fluid cultures (SCs) of IMNI. METHODS: Longitudinal prospective cohort study ongoing since June 2014, which included patients with indication for IMN removal due to any reason. Clinical diagnosis of INMI was defined according to publication addressing fracture-related infections. Minimal of two samples from TC were cultured. SCs followed the protocol previously published. Statistical analysis was performed using McNemar's test for related proportions. RESULTS: We included 54 patients submitted to IMN retrieval, of whom 47 presenting clinical signs of IMNI. Sensitivity for detecting microorganisms using TC and SC was 89.4% (42/47) and 97.6% (40/41), and specificity was 71.4% (5/7) for both TC and SC (p = 1.00). Positive and negative predictive values for TC and SC were 95.5% (42/44), 95.2% (40/42), 50% (5/10), and 83.3% (5/6), respectively. The most frequent organisms isolated in both TC and SC were Staphylococcus aureus, S. epidermidis, and Enterococcus sp. Polymicrobial infection was diagnosed in 14.8% (8/54) and 25% (12/48) by TC and SC, respectively (p = 0.19). CONCLUSION: Sonication fluid and tissue samples presented similar accuracy on the diagnosis of IMNI, but SC was advantageous of detecting polymicrobial infection.

In vitro antibacterial activity of bioactive glass S53P4 on multiresistant pathogens causing osteomyelitis and prosthetic joint infection.

BACKGROUND: Conventional local treatment for medullary osteomyelitis (OM) includes insertion of antibiotic-loaded polymethylmethacrylate (PMMA) cement. Nevertheless, PMMA may delivery irregular concentration of antibiotic to surrounding tissue. We aimed to compare the in vitro antibacterial activity of Bioactive Glass (BAG) S53P4, which is a compound showing local antibacterial activity, to that of antibiotic-loaded PMMA against multidrug resistant bacteria from OM isolates. METHODS: We studied convenience samples of multidrug resistant (MDR) microorganisms obtained from patients presenting OM and prosthetic joint infection (PJI). Mixtures containing tryptic soy broth (TSB) and inert glass beads (2 mm), BAG-S53P4 granules (0.5-0.8 mm and < 45 mm) and Gentamicin or Vancomycin-loaded PMMA beads were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MR-CoNS), Pseudomonas aeruginosa or Klebsiella pneumoniae isolates. Glass beads (2.0 mm) were used as a control. Antibacterial activity was evaluated by means of time-kill curve, through seeding the strains on blood agar plates, and subsequently performing colony counts after 24, 48, 72, 96, 120 and 168 h of incubation. Differences between groups were evaluated by means of two-way analysis of variance (ANOVA) and Bonferroni's t test. RESULTS: Inhibition of bacterial growth started soon after 48 h of incubation, reached zero CFU/ml between 120 and 168 h of incubation for both antibiotic-loaded PMMA and BAG S53P4 groups, in comparison with inert glass (p < 0.05). No difference regarding time-kill curves between antibiotic-loaded PMMA and BAG S53P4 was observed. CONCLUSIONS: BAG S53P4 presented antibacterial properties as much as antibiotic-loaded PMMA for MDR bacteria producing OM and PJI.

Interferon-γ release assay as a sensitive diagnostic tool of latent tuberculosis infection in patients with HIV: a cross-sectional study.

BACKGROUND: In developing countries, tuberculosis (TB) is a major public health problem and the leading cause of death among patients with HIV (Human Immunodeficiency Virus). Until 2001, the tuberculin skin test (TST) was the only available tool for the diagnosis of latent tuberculosis infection (LTBI), but false-negative TST results are frequently reported. Recently, the interferon-γ (IFN-γ) release assay (IGRA) has gained ground because it can detect the IFN-γ secreted by circulating lymphocytes T cells when stimulated by specific TB antigens. However, the role of IGRA in the diagnosis of LTBI in HIV-infected patients has not been well established. METHODS: This cross-sectional study compared the accuracy of TST (performed by the Mantoux method) and IGRA (QuantiFERON-TB Gold In-Tube, Cellestis, Carnegie, Australia) on the diagnosis of LTBI among patients with HIV. LTBI is defined by LTBI risk and at least one positive test (TST or IGRA), without clinical evidence of active TB. We also assessed the accuracy of TST and IGRA among HIV patients with high and low risk for LTBI. RESULTS: Among 90 HIV patients, 80 met the study criteria for LTBI, fifty-nine (73.7%) patients were TST positive, 21 (26.2%) were negative, whereas 75 patients (93.7%) were IGRA positive, and five (6.2%) were negative. TST showed poor agreement with the diagnosis of LTBI (Kappa: 0.384), while IGRA demonstrated good agreement (Kappa: 0.769). Among 69 patients with high risk and 21 with low risk for LTBI, TST was positive in 48 (69.5%) and 11 (52.4%), while IGRA was positive in 68 (98.5%) and 7 (33.3%) patients, respectively. There were no association between TST and the level of risk (P = 0,191). Conversely, we observed a strong association between the IGRA and risk for LTBI (p < 0.001). CONCLUSIONS: Compared to TST, IGRA positivity is consistent with the risk of TB infection and seems to be a better diagnostic tool for LTBI in HIV-infected patients.

Concentration of Sonication Fluid through Centrifugation Is Superior to Membrane Filtration for Microbial Diagnosis of Orthopedic Implant-Associated Infection.

Microbial identification of orthopedic implant-associated infections using sonication fluid (SF) submitted to a concentration step by membrane filtration (SMF) was compared with the standard centrifugation (SC) method. Among 33 retrieved infected implants, sonication identified microorganisms in 26 (78.8%). The sensitivity of SC was higher than that of SMF (78.8% versus 30.3%; P < 0.001).