Difficult-to-treat Research Articles

Outcomes of Revision Hip Replacement After Resection Arthroplasty With a Non-Free Muscle Flap Transfer for Difficult-To-Treat Periprosthetic Infection

Background. Resection arthroplasty with non-free muscle flap transfer allows to quickly eliminate the infection, but resulting in functional impairment of hip joint. To date, there are only a few publications with a small number of observations, where the proportion of patients who underwent the second stage of the revision hip arthroplasty (rTHA) is extremely small.
 The aim of the study was to evaluate the effect of resection arthroplasty on the functional outcomes and incidence of adverse outcomes in patients with difficult-to-treat (DTT) periprosthetic infection who had previously undergone resection arthroplasty with a non-free transfer of the axial flap fom the vastus lateralis muscle.
 Methods. The prospective study included 24 patients. During the period 20112021, at the first stage of the treatment for chronic recurrent DTT PJI of the hip, resection arthroplasty was performed with a non-free transfer of an island flap from the vastus lateralis muscle. Subsequent reimplantation of the endoprosthesis was performed in at least 1 year after the infection remission. The functional outcomes, degree of the lower limb shortening immediately before and in two or more years after revision arthroplasty (rTHA), the results of the microbiological cultures at the first and second stages of PJI treatment, technical aspects of the surgery as well as the postoperative period and long-term PJI remission were studied.
 Results. Revision arthroplasty resulted in a statistically significant improvement of the postoperative functional outcome and quality of life in patients. The average Harris score agter rTHA increased from 53 to 83 points after surgery, EQ-5D degree of the quality of life increased from 50 points to 80, the overall score from 0.61 to 0.74 and average intensity of pain via VAS decreased from 3 points to 1 point in 3.1 years after rTHA (p0.05). After reEP, complete restoration of the limb length was achieved in 29.1% of cases (n = 7) with an average compensation of the limb length for 4.5 cm. In 66.7% of patients (n = 16), the results of the intraoperative tissue biopsy microbiological analysis during reEP were culture negative. The recurrence rate of PJI was 12.5% (n = 3) up to 30 days after rTHA and 4.2% (n = 1) with a follow-up period of 3.1 years (IQR 2.14.1). With a single revision surgery performed without a delay, stable remission of DTT PJI was 95.8%.
 Conclusion. Complex two-stage surgical treatment using resection arthroplasty with a non-free muscle flap transfer at the stage of debridement and subsequent revision has demonstrated high efficiency in eliminating the infectious process as well as restoring weight-bearing capacity and extremity function. It could be recommended as a method of choice in the treatment of patients with DTT PJI of hip joint.

In vitro activity of imipenem/relebactam against Pseudomonas aeruginosa isolates recovered from ICU patients in Spain and Portugal (SUPERIOR and STEP studies).

To study the in vitro activity of imipenem/relebactam and comparators and the imipenem/relebactam resistance mechanisms in a Pseudomonas aeruginosa collection from Portugal (STEP, 2017-18) and Spain (SUPERIOR, 2016-17) surveillance studies. P. aeruginosa isolates (n = 474) were prospectively recovered from complicated urinary tract (cUTI), complicated intra-abdominal (cIAI) and lower respiratory tract (LRTI) infections in 11 Portuguese and 8 Spanish ICUs. MICs were determined (ISO broth microdilution). All imipenem/relebactam-resistant P. aeruginosa isolates (n = 30) and a subset of imipenem/relebactam-susceptible strains (n = 32) were characterized by WGS. Imipenem/relebactam (93.7% susceptible), ceftazidime/avibactam (93.5% susceptible) and ceftolozane/tazobactam (93.2% susceptible) displayed comparable activity. The imipenem/relebactam resistance rate was 6.3% (Portugal 5.8%; Spain 8.9%). Relebactam restored imipenem susceptibility to 76.9% (103/134) of imipenem-resistant isolates, including MDR (82.1%; 32/39), XDR (68.8%; 53/77) and difficult-to-treat (DTR) isolates (67.2%; 45/67). Among sequenced strains, differences in population structure were detected depending on the country: clonal complex (CC)175 and CC309 in Spain and CC235, CC244, CC348 and CC253 in Portugal. Different carbapenemase gene distributions were also found: VIM-20 (n = 3), VIM-1 (n = 2), VIM-2 (n = 1) and VIM-36 (n = 1) in Spain and GES-13 (n = 13), VIM-2 (n = 3) and KPC-3 (n = 2) in Portugal. GES-13-CC235 (n = 13) and VIM type-CC175 (n = 5) associations were predominant in Portugal and Spain, respectively. Imipenem/relebactam showed activity against KPC-3 strains (2/2), but was inactive against all GES-13 producers and most of the VIM producers (8/10). Mutations in genes affecting porin inactivation, efflux pump overexpression and LPS modification might also be involved in imipenem/relebactam resistance. Microbiological results reinforce imipenem/relebactam as a potential option to treat cUTI, cIAI and LRTI caused by MDR/XDR P. aeruginosa isolates, except for GES-13 and VIM producers.

Impact of Ceftolozane-Tazobactam vs. Best Alternative Therapy on Clinical Outcomes in Patients with Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Lower Respiratory Tract Infections.

Infections caused by multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat (DTR) Pseudomonas aeruginosa are increasingly challenging to combat. Ceftolozane-tazobactam (C/T) is a novel β-lactam-β-lactamase inhibitor combination now commonly used to treat MDR and XDR P.aeruginosa. Lower respiratory tract infections (LRTIs) remain the most common source of infection caused by MDR/XDR P.aeruginosa. Comparative effectiveness studies to date have been limited by the type of comparator agents (i.e., aminoglycosides and polymyxins) and the inclusion of multiple infection sources (i.e., urinary tract, abdominal, skin and soft tissue, etc.). We performed a multicenter, retrospective analysis of adults with LRTI caused by MDR or XDR P.aeruginosa admitted from January 2014 to December 2019. We aimed to compare clinical outcomes between patients who received C/T (n = 118) versus best alternative therapy (n = 88). The primary outcome was clinical failure, defined as 30-day mortality and/or an adverse drug reaction on antibiotic therapy. Two hundred and six patients met inclusion criteria. The C/T group had a significantly higher proportion of XDR P.aeruginosa and ventilator-associated bacterial pneumonia (VABP). After multivariable logistic regression, C/T treatment was independently associated with a 73.3% reduction in clinical failure compared to those who received best alternative therapy (P < 0.001). The number needed to harm with best alternative therapy was 3. Our results suggest that C/T is a safe and effective therapeutic regimen for patients with MDR and XDR P.aeruginosa LRTI.

New Perspectives on Antimicrobial Agents: Imipenem-Relebactam.

Imipenem (IMI)/cilastatin/relebactam (REL) (I/R) is a novel β-lactam/β-lactamase inhibitor combination with expanded microbiologic activity against carbapenem-resistant non-Morganellaceae Enterobacterales (CR-NME) and difficult-to-treat (DTR) Pseudomonas aeruginosa. Relebactam, a bicyclic diazabicyclooctane, has no direct antimicrobial activity but provides reliable inhibition of many Ambler class A and class C enzymes. It is currently approved for the treatment of adult patients with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) and those with complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) when limited or no alternative treatments are available. Given the number of recently approved β-lactams with expanded activity against highly resistant Gram-negative pathogens, this review summarizes the published literature on I/R, with a focus on its similar and distinguishing characteristics relative to those of other recently approved agents. Overall, available data support its use for the treatment of patients with HABP/VABP, cUTI, and cIAI due to CR-NME and DTR P. aeruginosa. Data indicate that I/R retains some activity against CR-NME and DTR P. aeruginosa isolates that are resistant to the newer β-lactams and vice versa, suggesting that susceptibility testing be performed for all the newer agents to determine optimal treatment options for patients with CR-NME and DTR P. aeruginosa infections. Further comparative PK/PD and clinical studies are warranted to determine the optimal role of I/R, alone and in combination, for the treatment of patients with highly resistant Gram-negative infections. Until further data are available, I/R is a potential treatment for patients with CR-NME and DTR P. aeruginosa infections when the benefits outweigh the risks.

Real-world effectiveness after initiating fremanezumab treatment in US patients with episodic and chronic migraine or difficult-to-treat migraine

BackgroundFremanezumab, a fully humanized monoclonal antibody (mAb; IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for the preventive treatment of migraine in adults. The efficacy and safety of fremanezumab for migraine prevention have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world effectiveness data are needed to complement clinical trial data. This study assessed the effectiveness of fremanezumab across different subgroups of adult patients with episodic migraine (EM), chronic migraine (CM), or difficult-to-treat (DTT) migraine in real-world clinical settings.MethodsThis retrospective, panel-based online chart review used electronic case report forms. Patient inclusion criteria were a physician diagnosis of EM or CM; age ≥ 18 years at the time of first fremanezumab initiation; ≥ 1 dose of fremanezumab treatment; ≥ 1 follow-up visit since first initiation; and ≥ 2 measurements of monthly migraine days (MMD; with 1 within a month before or at first initiation and ≥ 1 after first initiation). Changes in MMD and monthly headache days were assessed during the follow-up period. These endpoints were evaluated in subgroups of patients by migraine type (EM/CM) and in subgroups with DTT migraine (diagnosis of medication overuse [MO], major depressive disorder [MDD], generalized anxiety disorder [GAD], or prior exposure to a different CGRP pathway–targeted mAb [CGRP mAb]).ResultsData were collected from 421 clinicians and 1003 patients. Mean (percent) reductions from baseline in MMD at Month 6 were − 7.7 (77.0%) in EM patients, − 10.1 (68.7%) in CM patients, − 10.8 (80.6%) in the MO subgroup, − 9.9 (68.3%) in the MDD subgroup, − 9.5 (66.4%) in the GAD subgroup, and − 9.0 (68.7%) in the prior CGRP mAb exposure subgroup. Improvements in MDD or GAD severity were reported by 45.5% and 45.8% of patients with comorbid MDD or GAD, respectively.ConclusionsIn this real-world study, fremanezumab demonstrated effectiveness for migraine regardless of migraine type or the presence of factors contributing to DTT migraine (MO, GAD, MDD, or prior exposure to a different CGRP mAb).

Resistance to Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam in Gram-Negative MDR Bacilli: Molecular Mechanisms and Susceptibility Testing.

Multidrug resistance (MDR) represents a serious global threat due to the rapid global spread and limited antimicrobial options for treatment of difficult-to-treat (DTR) infections sustained by MDR pathogens. Recently, novel β-lactams/β-lactamase inhibitor combinations (βL-βLICs) have been developed for the treatment of DTR infections due to MDR Gram-negative pathogens. Although novel βL-βLICs exhibited promising in vitro and in vivo activities against MDR pathogens, emerging resistances to these novel molecules have recently been reported. Resistance to novel βL-βLICs is due to several mechanisms including porin deficiencies, increasing carbapenemase expression and/or enzyme mutations. In this review, we summarized the main mechanisms related to the resistance to ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam in MDR Gram-negative micro-organisms. We focused on antimicrobial activities and resistance traits with particular regard to molecular mechanisms related to resistance to novel βL-βLICs. Lastly, we described and discussed the main detection methods for antimicrobial susceptibility testing of such molecules. With increasing reports of resistance to novel βL-βLICs, continuous attention should be maintained on the monitoring of the phenotypic traits of MDR pathogens, into the characterization of related mechanisms, and on the emergence of cross-resistance to these novel antimicrobials.

What Doesn't Kill Them Makes Them Stronger: The Impact of the Resistance Patterns of Urinary Enterobacterales Isolates in Patients from a Tertiary Hospital in Eastern Europe.

(1) Background: The evolution of bacterial resistance to antibiotics is one of the factors that make infectious pathology an extremely dynamic field, also inducing a significant burden on public health systems; therefore, continuous updates on the bacterial resistance to antibiotics and their particular regional patterns is crucial for the adequate approach of various infectious diseases. (2) Methods: We retrospectively analyzed 354 patients with Enterobacterales urinary tract infections (UTIs), determined their antibiotic resistance pattern, thus aiming to correlate them with the outcome and other specific markers of poor prognosis. (3) Results: The most frequent causative agent was Escherichia coli, representing 64.6% of all UTIs. We identified 154 patients resistant to multiple antibiotic classes, of which 126 were multidrug-resistant (MDR), 17 were extensive drug-resistant (XDR) and 11 were pandrug-resistant (PDR). Moreover, 25 isolates were resistant to carbapenems (CRE), 25 were difficult-to-treat (DTR), and 84 were extended-spectrum cephalosporin-resistant (ESC), with only 95 isolates susceptible to all tested antibiotics. Mortality ranged from 1% for UTIs caused by isolates susceptible to all tested antibiotics, to 24% for the ones caused by DTR or CRE isolates. Other significant risk factors associated with mortality were: prolonged hospital stay (p = 0.0001), Charlson comorbidity index ≥ 3 (p = 0.02), urinary catheterization (p = 0.001), associated respiratory pathologies (p = 0.004), obesity (p = 0.047), a history of previous hospitalizations (p = 0.007), inappropriate empiric antibiotic regimen (p = 0.001), or hyper inflammatory status (p = 0.006). Basically, we observed that a multiple regression model comprising urinary catheterization, inappropriate empiric anti-biotherapy, obesity, and respiratory comorbidities exhibits the best correlation with mortality rate in patients with UTI (R = 0.347, R2 = 0.12). (4) Conclusions: By focusing on the novel resistance patterns, our study provides complementary evidence concerning the resistance profiles found in an Eastern European region, as well as their prognostic implications in patients with UTI.

Antifungal Activity of Green and Red Brazilian Propolis Extracts

Background: Diseases associated to Candida spp. are recurrent and can be difficult to treat, mainly due to the new strains resistant to the limited number of available antifungals. Objective: The objective of this study is to evaluate the in vitro and in vivo activity of Brazilian green propolis (GrProp) and red propolis (RdProp) ethanolic extracts against standard strains of Candida albicans, C. tropicalis, C. krusei, C. glabrata, C. parapsilosis and 10 clinical isolates of C. albicans. Methods: Antifungal activity in vitro was tested using the M-27-A3/CLSI protocol. The in vivo antifungal activity was evaluated using Tenebrio molitor model and, the effect of extracts on adhesion of C. albicans in human buccal epithelial cells (BECs) was also studied. Results: GrProp and RdProp exhibited antifungal activity against at least one of the Candida strains tested. The adhesion inhibition of C. albicans in BECs was 45% (GrProp28), 60% (Gr- Prop50) and 82% (RdProp), in comparison to amphotericin B (82%). All propolis extracts showed synergistic activity with fluconazole and amphotericin B. GrProp50 (10 mg/kg) showed better protection of T. molitor, blocking the progression of C. albicans infection, increasing survival and delayed the larvae death. Conclusion: Brazilian GrProp and RdProp extracts inhibit the in vitro C. albicans growth and protect T. molitor against infection by this yeast. The physiochemical parameters found for the analyzed samples were in accordance to the standards established by the Brazilian Legislation for propolis and derivatives. GrProp and RdProp have potential to be used against Candida spp. infections, mainly in association with fluconazole or amphotericin B.

Association of Proteus mirabilis and Providencia stuartii Infections with Diabetes.

Background and Objectives: Proteus and Providencia are related genera of opportunistic pathogens belonging to the Morganellaceae family, often a cause of infections in the immunocompromised hosts, such as diabetic patients. Their clinical significance has increased due to their intrinsic resistance to polymyxins, which is often associated with acquired resistance mechanisms. In this study we evaluated the infections caused by Proteus mirabilis and Providencia stuartii in two groups of patients, with diabetes (group 1) and without diabetes (group 2) admitted to the intensive care unit and surgical wards. The infections were investigated in terms of infection type, risk factors, clinical course, predictive factors for unfavourable outcomes and antibiotic resistance profile. Materials and Methods: An observational, retrospective, cross-sectional study was conducted, comprising all patients infected with these pathogens. Bacterial identification and antibiotic sensitivity testing were performed using the Vitek2C automated system. Results: Comparison of the two groups showed that the statistically significant common infectious risk factors were found less frequently among diabetic patients when compared with non-diabetic patients, and that antimicrobial resistance was significantly lower in the diabetic patient group. However, survival rates did not differ between the two groups, drawing attention to the implications of diabetes as comorbidity. Additionally, with regard to the antibiotic resistance profile, 38.89% of P. stuartii strains isolated from diabetic patients belonged to the difficult-to-treat (DTR) phenotype, contributing to the severity of these infections compared with those caused by P. mirabilis, of which 32% were wild type strains and 0% were DTR phenotype. The DTR/extended spectrum beta-lactamase producing P. stuartii isolates more than doubled the risk of mortality, while the presence of nasogastric nutrition tripled the risk. Conclusions: P. stuartii infections that occurred in diabetic patients proved to be more difficult to treat, the majority of them being healthcare-associated bacteremias.

Treatment by biomarker-informed endotype vs guideline care in children with difficult-to-treat asthma

BackgroundAsthma is heterogeneous, contributing to difficulty in disease management. ObjectiveTo develop a biomarker-informed treatment model for difficult-to-treat (DTT) asthma and conduct a pilot feasibility study. MethodsSchool-aged children (n = 21) with DTT asthma were enrolled and completed 3 medical visits (V1-V3). V2 and V3 were completed approximately 3.5 months and 12 months after V1, respectively. At V1, guideline care and adherence interventions were initiated, and blood samples were collected for asthma biomarker assessment. A personalized treatment algorithm was developed based on biomarkers (treatment by endotype) and was implemented at V2. Asthma outcomes were compared from V1 to V2 (guideline-based care) to V2 to V3 (guideline + biomarker-informed care). ResultsOverall retention was 86%. There was an even distribution of participants with allergy, without allergy, and with mixed allergies. The participants received an average of 5.9 interventions (range, 3-9). The allergic phenotype was characterized by increased CDHR3 risk genotype and high transepidermal water loss. High serum interleukin-6 level was most notable in the mixed allergic subgroup. The nonallergic phenotype was characterized by vitamin D deficiency and poor steroid treatment responsiveness. The personalized treatment plans were associated with decreased emergency department visits (median, 1 vs 0; P = .04) and increased asthma control test scores (median, 22.5 vs 23.0; P = .01). ConclusionThe biomarker-based treatment algorithm triggered interventions on top of guideline care in all children with DTT asthma studied, supporting the need for this type of multipronged approach. Our findings identify the minimal biomarker set that is informative, reveal that this treatment-by-endotype intervention is feasible and may be superior to guideline care alone, and provide a strong foundation for a definitive trial. Trial RegistrationClinicalTrials.gov identifier: NCT04179461.

Longitudinal Adherence to Inhaled Corticosteroids in Pediatric Patients with Difficult to Control Asthma

The purpose of this study is to examine adherence to inhaled corticosteroids in children with difficult-to-treat (DTT) asthma, in whom poor adherence is known to lead to poor outcomes. Participants received multi-modal treatment strategy including a digital adherence intervention.

Treatment by Biomarker-Informed Endotype Versus Guideline Care in Children with Difficult to Treat Asthma

Asthma is heterogeneous contributing to difficultyindisease management. We sought to develop a biomarker-informed treatment model for difficult-to-treat (DTT) asthma and conduct a pilot feasibility study.

Protein-Energy Malnutrition as a Predictor of Early Recurrent Revisions After Debridement Surgery in Patients With Difficult-to-Treat Periprosthetic Infection

Background. Protein-energy malnutrition (PEM) is an established risk factor of postoperative complications in orthopedic disorders, including arthroplasty of the large joints.&#x0D; The study aimed to evaluate PEM prevalence and its association with the early postoperative revision in patients with the difficult-to-treat (DTT) prosthetic joint infection (PJI) of the hip.&#x0D; Methods. The retrospective study included 132 patients with chronic DTT PJI of the hip. The patients underwent orthopedic implant removal, radical debridement of the infected tissues, and resection arthroplasty with non-free transplantation of an axial vastus lateralis muscle flap (n = 57) or installation of an antimicrobial spacer (n = 75). DTT PJI was defined as an infection caused by rifampicin-resistant staphylococcal strains, ciprofloxacin-resistant gram-negative bacteria, fungi of the genus Candida, and their associations. The assessment of the patients protein-energy status included the evaluation of reference laboratory parameters, such as levels of hemoglobin, total protein, and albumin and number of lymphocytes. The degree of PEM was determined by the number of laboratory markers below the threshold values. The statistical comparison was performed using Fishers test. The odds ratio (OR, 95% confidence interval [CI]) was calculated to assess the risk of PJI recurrence. Differences were considered significant at p0.05.&#x0D; Results. More than 70% of patients with chronic DTT PJI included in the study were diagnosed with preoperative PEM of varying degrees of severity. Hypoalbuminemia and decreased hemoglobin levels were diagnosed more often: 64.3% and 57.1% in the muscle flap plasty and 57.3% and 31.1% in the antimicrobial spacer group, respectively. In muscle plasty and antimicrobial spacer groups, a decrease in the values of three or more reference PEM markers was detected in 28.5% and 16.0% of patients, and this advanced impairment of the nutritional status increased the risk of early revision intervention by two (OR 2.0; CI 95% 0.478.56; p = 0.35) and six times (OR 6.11; 95% CI 1.0635.35; p0.04), respectively.&#x0D; Conclusion. In general, the analysis of publications and results of our study show that PEM is associated with the development of surgical site infection and recurrence of PJI after revision surgery. A decrease in the values of three or more reference PEM markers is a significant predictor of repeated revisions after debridement surgery with the installation of an antimicrobial spacer. PEM complicates the postoperative course in patients with resection arthroplasty. Given the high incidence of PEM in patients with DTT PJI of the hip joint, further research is needed to develop methods for nutritional status correction and assessment of their effect on the outcomes of debridement surgery.

Hemiarthroplasty in Unstable Intertrochanteric Fractures in Elderly: A Prospective Study

Background: Grossly comminuted intertrochanteric fractures in osteoporotic bones are highly unstable and difficult totreat. Hemiarthroplasty is a popular choice because it provides stability and enables for immediate complete weightbearing.Objectives: The goal of this trial was to see how effective cemented hemiarthroplasty was at treating proximal femoralfractures in older people with severe osteoporosis.Methods: Thirty patients who had bipolar hemiarthroplasty for unstable intertrochanteric fractures were studiedprospectively. The posterior (Moore’s) technique was used to treat all of the patients with cemented bipolar prostheses.The average time of follow-up was 12 months. The modified Harris hip score was used to evaluate the patients.Results: Abductor weakness was present in 5 of the individuals. At the 12-month follow-up, 21 cases (70%) had badresults, while three cases (10%) had poor results. The average length of stay in the hospital was 10.9 days. Excellent to fairresults were observed in 24 patients, as measured by the modified Harris hip score.Conclusion: In older individuals with significant osteoporosis, the therapy of unstable intertrochanteric fractures differsfrom the treatment of other proximal femoral fractures. Internal fixation is not as effective as cemented hemiarthroplastyin treating these fractures. This approach has a clear advantage in terms of early full weight bearing and recovery. Hipsthat have undergone cemented hemiarthroplasty are stable and mobile. Weight bearing can begin earlier than with othertreatment approaches, avoiding any recumbency-related problems.

Superinfection with Difficult-to-Treat Pathogens Significantly Reduces the Outcome of Periprosthetic Joint Infections.

Periprosthetic joint infection (PJI) is a serious complication after total joint arthroplasty. In the course of a PJI, superinfections with pathogens that do not match the primary infecting micro-organism may occur. To our knowledge, there are no published data on the outcome of such infections in the literature. The aim of this study was to assess the outcome of PJI with superinfections with a difficult-to-treat (DTT) pathogen. Data of 169 consecutive patients with PJI were retrospectively analyzed in this single-center study. Cases were categorized into: Group 1 including non-DTT-PJI without superinfection, Group 2 DTT-PJI without superinfection, Group 3 non-DTT-PJI with DTT superinfection, and Group 4 non-DTT-PJI with non-DTT superinfection. Group 3 comprised 24 patients and showed, after a mean follow-up of 13.5 ± 10.8 months, the worst outcome with infection resolution in 17.4% of cases (p = 0.0001), PJI-related mortality of 8.7% (p = 0.0001), mean revision rate of 6 ± 3.6 (p < 0.0001), and duration of antibiotic treatment of 71.2 ± 45.2 days (p = 0.0023). PJI caused initially by a non-DTT pathogen with a superinfection with a DTT pathogen is significantly associated with the worst outcome in comparison to non-DTT-PJI, PJI caused initially by a DTT pathogen, and to non-DTT-PJI with a non-DTT superinfection.

Trends of Multidrug-Resistant Pathogens, Difficult to Treat Bloodstream Infections, and Antimicrobial Consumption at a Tertiary Care Center in Lebanon from 2015-2020: COVID-19 Aftermath.

Introduction: We studied the trend of antimicrobial resistance and consumption at Saint George Hospital University Medical Center (SGHUMC), a tertiary care center in Beirut, Lebanon, with a focus on the SARS-CoV-2 pandemic. Materials and Methods: We calculated the isolation density/1000 patient-days (PD) of the most isolated organisms from 1 January 2015–31 December 2020 that included: E. coli (Eco), K. pneumoniae (Kp), P. aeruginosa (Pae), A. baumannii (Ab), S. aureus (Sau), and E. faecium (Efm). We considered March–December 2020 a surrogate of COVID-19. We considered one culture/patient for each antimicrobial susceptibility and excluded Staphylococcus epidermidis, Staphylococcus coagulase-negative, and Corynebacterium species. We analyzed the trends of the overall isolates, the antimicrobial susceptibilities of blood isolates (BSI), difficult-to-treat (DTR) BSI, carbapenem-resistant Enterobacteriaceae (CRE) BSI, and restricted antimicrobial consumption as daily-defined-dose/1000 PD. DTR implies resistance to carbapenems, beta-lactams, fluoroquinolones, and additional antimicrobials where applicable. Results and Discussion: After applying exclusion criteria, we analyzed 1614 blood cultures out of 8314 cultures. We isolated 85 species, most commonly Eco, at 52%. The isolation density of total BSI in 2020 decreased by 16%: 82 patients were spared from bacteremia, with 13 being DTR. The isolation density of CRE BSI/1000 PD decreased by 64% from 2019 to 2020, while VREfm BSI decreased by 34%. There was a significant decrease of 80% in Ab isolates (p-value < 0.0001). During COVID-19, restricted antimicrobial consumption decreased to 175 DDD/1000 PD (p-value < 0.0001). Total carbapenem consumption persistently decreased by 71.2% from 108DDD/1000 PD in 2015–2019 to 31 DDD/1000 PD in 2020. At SGHUMC, existing epidemics were not worsened by the pandemic. We attribute this to our unique and dynamic collaboration of antimicrobial stewardship, infection prevention and control, and infectious disease consultation.

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.

554 Utilization of Pediatric Sleep Questionnaire to Screen for Obstructive Sleep Apnea in a Difficult-to-treat Asthma Cohort

Abstract Introduction Early detection and management of obstructive sleep apnea(OSA) could improve asthma control in children with difficult-to-treat(DTT) asthma. The purpose of this study was to assess the effectiveness of the pediatric sleep questionnaire(PSQ) to screen for OSA in children with DTT asthma, and to compare clinical characteristics between those with positive and negative PSQ scores. Methods A prospective study of 81 children with DTT asthma was completed from 2015–2017. The PSQ, Epworth sleepiness scale(ESS), Pediatric Quality of Life(PQL), and the academic performance questionnaires(APQ) were administered during clinic visits. Polysomnography(PSG) was recommended for PSQ score&amp;gt;0.33. Medical records were reviewed for asthma clinical characteristics. The cohort was separated into positive(PSQ&amp;gt;0.33) and negative PSQ score(PSQ≤0.33) groups for analysis. Results The mean age of the cohort was 11.3±4.5 years and the mean body mass index was 22±7.6 kg/m2. Sixty-two percent were male and 68% were African-American. Forty-nine(53%) subjects had positive PSQ (0.5[0.4 – 0.7]). The positive group had higher ESS score (10.5[8 – 13] vs. 6[2 – 8], p&amp;lt;0.0001) and lower total PQL score (58.7[47.8–72.8] vs. 79.4[70.7 – 87], p&amp;lt;0.0001) than the negative group. There was no difference between APQ scores(p=0.07). The positive group had lower asthma control test(ACT) scores than the negative group (17.5[15 – 20.5] vs. 21[19 – 22], p&amp;lt;0.0001). Furthermore, the positive group was more likely to have gastroesophageal reflux (OR: 3.97, 95%CI: 1.7 to 9.1, p=0.0018). Twenty-nine(59%) subjects in the positive group had subsequent PSG, and 17(58.6%) subjects were diagnosed with OSA (14 mild OSA, 1 moderate OSA, 2 severe OSA). The mean obstructive index in the positive group was 3±5.5 events/hour. There was 1 subject with central apnea and alveolar hypoventilation. Of the 17 subjects with OSA, all received treatment with nasal steroids, 3 were treated with non-invasive positive pressure ventilation, and 4 had surgical intervention. Conclusion Children with DTT asthma who have positive PSQ have higher degree of daytime sleepiness, lower quality of life and worse asthma control. The positive group was more likely to have GERD, which may suggest a relationship between nighttime asthma symptoms and OSA. Further studies are needed to evaluate the effects of OSA treatment on asthma control. Support (if any):

Treatment response and age of onset as risk indicators for parkinson disease in patients with major depressive disorder: A nationwide longitudinal study

BackgroundIndividuals with major depressive disorder (MDD) have a higher risk of developing Parkinson disease (PD). This study investigated whether response to treatment with antidepressants for MDD can determine patients at risk of developing PD later in life. MethodsWe enrolled 3303 patients with newly-diagnosed MDD and 13,212 controls between 2002 and 2004 using Taiwan's Nationwide Health Insurance Research Database. We stratified patients with MDD according to the number of antidepressant regimens prescribed to them and the age at MDD onset and followed all participants until the end of 2013. During follow-up, we evaluated patients for the possibility of developing PD. ResultsPatients with MDD had a greater likelihood of developing PD than controls. Patients with difficult-to-treat (DTT) MDD had a higher risk of developing PD than the other MDD subgroups (hazard ratio [HR] = 3.44, 95% confidence interval [95% CI]: = 1.99–5.95). When stratified by age (<50, 50–65, >65 years), DTT patients with middle-age or late-onset MDD exhibited elevated risks of developing PD (50–65 years: HR: 7.03, 95% CI: 2.95–16.76; >65 years: HR: 2.89, 95% CI: 1.26–6.65). DiscussionPatients with MDD and an onset age of >50 years who responded poorly to antidepressant treatment have an associated higher risk of subsequently developing PD. Therefore, when treating patients with MDD, clinicians should provide intensive antidepressant treatment and evaluations for PD so that risk-prevention measures can be implemented upon MDD diagnosis.

Difficult to Treat Proteeae strains in high risk Romanian hospital departments

Abstract Introduction: Resistance to first-line antibiotics of the Proteeae strains within the difficult-to-treat (DTR) phenotype is a cause of limitation of therapeutic options. The study aimed to characterize these strains, to identify the factors that influence their acquisition and the predictive factors for the patient’s evolution. Material and methods: Between July 2017 and January 2019, 400 of Proteeae strains were isolated from samples of patients admitted to intensive care units (ICUs) and surgical wards of a university hospital in Romania. The identification and testing of antibiotic sensitivity was performed using the Vitek 2 Compact system. The DTR phenotype was defined as the resistance (or intermediate resistance) to all categories of β-lactams, carbapenems and fluoroquinolones. Results: Out of 400 Proteeae strains, 21% were of the DTR type, most of them from the species Providencia stuartii and Proteus mirabilis, identified predominantly on the ICUs. The excess fatality in the DTR subsample compared to the non-DTR subsample was 16.37%. The multivariate analysis identified as independent risk factors: the number of antibiotics administered, the number of days of urinary catheterization, the presence of tracheostomy, nasogastric nutrition, respectively belonging to the species P. stuartii. The probabilities of survival were reduced by the presence of the central venous catheter (CVC), tracheostomy, by the increase of the number of hospitalization days respectively of the number of antibiotics administered. Conclusion: The DTR phenotype in the case of Proteeae strains has been associated especially with the species P. stuartii, with invasive exogenous factors and with an increased fatality.