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Introduction: Uropathogenic bacteria like Escherichia coli (UPEC) and Pseudomonas are the most common agents of Urinary Tract Infection (UTI). Recently, the ability of UPEC to invade urothelial cells and to form Intracellular Bacterial Communities (IBCs) has been described which can be missed out during routine diagnosis and can lead to recurrent infection despite antibiotic treatment. Aim: To study the presence of ICB in exfoliated urothelial cells using confocal microscopy. Materials and Methods: A cross-sectional observational study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India for detection of Isolated Intracellular Bacteria (IIB) and IBC. The study done for detection of IIB/IBC in urine samples suspected with UTI between January 2022 to December 2022. Four hundred ninety-five urine samples collected from women of age group 18-50 years visited at Central laboratory for suspected diagnosis of UTI. Urine samples were screened for detection of Gram-negative intracellular bacteria by using light microscopy. Urine samples showing intracellular gram-negative bacteria by Gram staining were further processed for fluorescence confocal microscopy followed by conventional culture and virulence detection by multiplex Polymerase Chain Reaction (PCR). Formation of biofilm ability was assessed by tube method. Quantitative data presented as mean and Standard Deviation (SD) while qualitative variables expressed as frequency (percentage). Results: Ninety-two Gram negative urine samples were processed for fluorescence staining and culture, out of that 24 were processed for virulence gene detection. Mean age of women was 36.2±9.5 years and 74 (80.4%) had fever, 19 (20.7%) had burning sensation and 16 (17.4%) had frequent micturition. Confocal microscopy examination showed 23 (25.0%) samples which were IIB and 11 (12.0%) were IBC. While the culture report showed 23 (25.0%) were E. coli, 29 (31.5%) were polymicrobial flora and 29 (31.05%) were negative for culture. Interestingly, out of 29 culture negative samples 9 (3.1%) were detected with IIB and IBC by confocal microscopy. Prevalence of virulent genes like iutA was higher 12 (50.0%). Conclusion: This study highlighted the importance of confocal microscopy for diagnosis of IIB/IBC which was missed by urine culture. Unrecognised bacterial colonisation might be maintained through intracellular reservoir. Hence diagnosis of IIB/IBC is crucial for the management of recurrent UTI and precise antibiotic therapy to avoid antibiotic resistance. [ABSTRACT FROM AUTHOR]

When treating chronic prosthetic joint infection after shoulder arthroplasty, removal of the implants and cement is typically pursued because they represent a potential nidus for infection. However, complete removal can increase morbidity and compromise bone stock that is important for achieving stable revision implants. The purpose of this study is to compare the rates of repeat infection after 2-stage revision for prosthetic joint infection in patients who have retained cement or hardware compared to those who had complete removal. We retrospectively analyzed all two-stage revision total shoulder arthroplasties performed for infection at 2 institutions between 2011 and 2020 with minimum 2-year follow-up from completion of the two-stage revision. Patients were included if they met the International Consensus Meeting criteria for probable or definite infection. Postoperative radiographs after the first-stage of the revision consisting of prosthesis and cement removal and placement of an antibiotic spacer were reviewed to evaluate for retained cement or hardware. Repeat infection was defined as either ≥2 positive cultures at the time of second-stage revision with the same organism cultured during the first-stage revision or repeat surgery for infection after the two-stage revision in patients that again met the International Consensus Meeting criteria for probable or definite infection. The rate of repeat infection among patients with retained cement or hardware was compared to the rate of infection among patients without retained cement or hardware. Thirty-seven patients met inclusion criteria and were included in the analysis. Six (16%) patients had retained cement and 1 patient (3%) had 2 retained broken glenoid baseplate screws after first-stage revision. Of the 10 cases of recurrent infection, 1 case (10%) involved retained cement/hardware. Age at revision (60.9 ± 10.6 vs. 65.0 ± 9.6, P =.264), body mass index (33.4 ± 7.2 vs. 29.7 ± 7.3, P =.184), Charlson Comorbidity Index (2 (0-8) vs. 3 (0-6), P =.289), male sex (7 vs. 16, P =.420), and presence of diabetes (1 vs. 3, P =.709) were not associated with repeat infection. Retained cement or hardware was also not associated with a repeat risk of infection (1 vs. 6, odds ratio = 0.389, P =.374). We did not find an increased risk of repeat infection in patients with retained cement or hardware compared to those without. Therefore, we believe that surgeons should consider leaving cement or hardware that is difficult to remove and may lead to increased morbidity and future complications. [ABSTRACT FROM AUTHOR]

Bronchogenic cysts, a rare congenital pulmonary disorder, typically affect young adults and are often managed conservatively. However, large cysts with recurrent infections require surgical intervention. This case study highlights the successful management of a large bronchogenic cyst. A 53-year-old female presented with a decade-long history of recurrent respiratory infections manifesting as cough, yellow purulent sputum, and shortness of breath. Chest computed tomography revealed a large bronchogenic cyst in the right middle lobe, causing cardiac compression. Despite conservative management, the recurrent symptoms persisted. After multidisciplinary consultation, a thoracoscopic right middle lobectomy was planned. Severe pleural adhesions and bleeding complicated the procedure; therefore, thoracotomy was performed. Postoperatively, the patient developed transient fever and elevated white blood cell count, both of which resolved with appropriate antibiotic therapy. The patient was discharged in stable condition, with no recurrence of symptoms at follow-up. Large, symptomatic bronchogenic cysts that cause recurrent infections require surgical resection. [ABSTRACT FROM AUTHOR]

Purpose: Patients with non-beta-hemolytic streptococcal bacteremia (NBHSB) are at risk of infective endocarditis (IE). Patients with cardiac implantable electronic device (CIED) have been described to have an increased risk of IE. The aim of the study was to describe a population-based cohort of patients with NBHSB and CIED and variables associated with IE and recurrent NBHSB. Methods: All episodes with NBHSB in blood culture from 2015 to 2018 in a population of 1.3 million inhabitants were collected from the Clinical Microbiology Laboratory, Lund, Sweden. Through medical records, patients with CIED during NBHSB were identified and clinical data were collected. Patients were followed 365 days after NBHSB. Results: Eighty-five episodes in 79 patients with CIED and NBHSB constituted the cohort. Eight patients (10%) were diagnosed with definite IE during the first episode, five of whom also had heart valve prosthesis (HVP). In 39 patients (49%) transesophageal echocardiography (TEE) was performed of which six indicated IE. Four patients had the CIED extracted. Twenty-four patients did not survive (30%) the study period. Four patients had a recurrent infection with NBHSB with the same species, three of whom had HVP and had been evaluated with TEE with a negative result during the first episode and diagnosed with IE during the recurrency. Conclusion: The study did not find a high risk of IE in patients with NBHSB and CIED. Most cases of IE were in conjunction with a simultaneous HVP. A management algorithm is suggested. [ABSTRACT FROM AUTHOR]

Abstract Antibacterial lysozyme hydrogels show attractive advantages in wound dressings due to their intrinsic antibacterial activity and excellent biochemical and mechanical properties. Unfortunately, the development of such hydrogels is still greatly limited due to the lack of universal gelation strategies. Herein, a universal gelation strategy between lysozyme‐nanofiber (LZF) and inorganic salts is proposed for the first time to construct functional nanofibrous lysozyme‐based hydrogels. In particular, divalent anions are found to universally drive LZF for the aggregation and transformation into three‐dimensional nanofibrous network hydrogels via electrostatic interaction, and the key role of divalent anions in the gelation is further proved by molecular dynamics simulation. In addition, near‐infrared light‐mediated photothermal characteristics are endowed with LZF to enhance its inhibitory activity of multidrug‐resistant bacteria by the skeleton modification with genipin to produce genipin‐conjuagted LZF (GLZF). As a distinct application paradigm, the brilliant immunomemory MnSO4‐crosslinked GLZF hydrogel is constructed to sensitize the cGAS‐STING pathway and skillfully establish an antibacterial immune microenvironment. It can excellently realize the anti‐recurrence of diabetic wound infection via photo‐enhanced bacterial killing and the cGAS‐STING pathway. Thereby, it paves the way to employ the universal divalent anion‐mediated gelation strategy for the future development of functional inorganic salt hybrid lysozyme hydrogels.

Abstract Background Idiopathic CD4 lymphocytopenia (ICL) is an underdiagnosed immunodeficiency syndrome characterised by persistent low CD4 counts in the absence of HIV and other causes of lymphocytopenia. ICL patients are susceptible to opportunistic infections, with human papillomavirus, cryptococcal, and tuberculosis being the most common infections reported. Nocardiosis is rarely reported in patient with ICL. Case Presentation We herein discuss a 46-year-old female presented with complaints of weight loss, low grade fever and cough with expectoration from last four months. The patient was diagnosed with pulmonary nocardiosis and aspergillosis co-infection four years back; in addition she also had ICL. Subsequently, the patient was lost in follow-up and readmitted four years later. Bronchoalveolar lavage sample shows the presence of acid-fast bacilli in modified gram stain, which later identified as Nocardia otitidiscaviarum by metagenomic next-generation sequencing. Her CD4 counts were still found low (298 cells/mm3). After an initial improvement with trimethoprim-sulfamethoxazole (TMP-SMX), she was commenced on indefinite secondary prophylaxis. Conclusions Nocardiosis without usual risk factors should be evaluated for ICL. This case emphasize the importance of periodic follow-up with CD4 count monitoring and secondary prophylaxis therapy to prevent recurrence or the emergence of new infections in ICL. Clinical trial number Not applicable.

Abstract There are currently no available data on the relationship between sonographic temporary nephromegaly in children during their first febrile urinary tract infection (fUTI) and recurrent fUTI. For this analysis, a multicenter retrospective cohort study of 343 children who underwent renal ultrasound during their first fUTI was conducted between 2013 and 2020. Sonographic temporary nephromegaly was defined as increased renal length during the initial fUTI, followed by normal renal length after antibiotic treatment. Compared with children without sonographic temporary nephromegaly (n = 307), the duration of fever and intravenous antibiotics was significantly longer, and C-reactive protein, creatinine, and the proportion of children who had recurrent fUTI were significantly higher, in those with sonographic temporary nephromegaly (n = 36). In an additional analysis of 100 patients who received voiding cystourethrography, a logistic regression model confirmed that the odds of vesicoureteral reflux (VUR) were significantly higher in children with temporary nephromegaly or those who experienced fUTI recurrence. In nine out of 16 children with VUR who had temporary nephromegaly, the reason for receiving voiding cystourethrography was recurrent fUTI. Our results suggest that sonographic temporary nephromegaly during an initial fUTI is predictive for recurrence and VUR, and that in children with temporary nephromegaly, VUR may be detectable before fUTI recurrence.

Background: Idiopathic CD4 lymphocytopenia (ICL) is an underdiagnosed immunodeficiency syndrome characterised by persistent low CD4 counts in the absence of HIV and other causes of lymphocytopenia. ICL patients are susceptible to opportunistic infections, with human papillomavirus, cryptococcal, and tuberculosis being the most common infections reported. Nocardiosis is rarely reported in patient with ICL. Case Presentation: We herein discuss a 46-year-old female presented with complaints of weight loss, low grade fever and cough with expectoration from last four months. The patient was diagnosed with pulmonary nocardiosis and aspergillosis co-infection four years back; in addition she also had ICL. Subsequently, the patient was lost in follow-up and readmitted four years later. Bronchoalveolar lavage sample shows the presence of acid-fast bacilli in modified gram stain, which later identified as Nocardia otitidiscaviarum by metagenomic next-generation sequencing. Her CD4 counts were still found low (298 cells/mm3). After an initial improvement with trimethoprim-sulfamethoxazole (TMP-SMX), she was commenced on indefinite secondary prophylaxis. Conclusions: Nocardiosis without usual risk factors should be evaluated for ICL. This case emphasize the importance of periodic follow-up with CD4 count monitoring and secondary prophylaxis therapy to prevent recurrence or the emergence of new infections in ICL. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Patients with cardiac implantable electronic device (CIED) and Staphylococcus aureus bacteraemia (SAB) are at risk of having CIED infection, pocket infection or endocarditis. To avoid treatment failures, guidelines recommend that the CIED should be extracted in all cases of SAB butrecent studies indicate low extraction rates and low risk of relapse. The aim of the study was to describe a Swedish population-based cohort of patients with CIED and SAB, the rate of extraction, and treatment failure measured as recurrent SAB. Patients identified to have SAB in the Karolinska Laboratory database, serving a population of 1.9 million, from January 2015 through December 2019 were matched to the Swedish ICD and Pacemaker Registry. Patients with CIED and SAB were included. Clinical data were collected from medical records. A cohort of 274 patients was identified and 38 patients (14%)had the CIED extracted. Factors associated with extraction were lower age, lower Charlson comorbidity index, shorter time since CIED implantation, and non-nosocomial acquisition, but not mortality. No patient was put on lifelong antibiotic treatment. Sixteen patients (6%) had a recurrent SAB within one year, two in patients subjected to extraction (5%) and 14 in patients not subjected to CIED-extraction (6%). Three of the 14 patients were found to have definite endocarditis during the recurrent episode. Despite a low extraction rate, there were few recurrences. We suggest that extraction of the CIED might be omitted if pocket infection, changes on the CIED, or definite endocarditis are not detected. [ABSTRACT FROM AUTHOR]

Burkholderia semiarida was previously identified solely as a plant pathogen within the Burkholderia cepacia complex. We present a case in China involving recurrent pneumonia attributed to B. semiarida infection. Of note, the infection manifested in an immunocompetent patient with no associated primary diseases and endured for >3 years.

AIM: To evaluate dry eye disease (DED) symptomatology and mental health status in different COVID-19 patients. METHODS: A cross-sectional observational design was used. Totally 123 eligible adults (46.34% of men, age range, 18-59y) with COVID-19 included in the study from August to November, 2022. Ocular Surface Disease Index (OSDI), Five-item Dry Eye Questionnaire (DEQ-5), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI) were used in this study. RESULTS: OSDI scores were 6.82 (1.25, 15.91) in asymptomatic carriers, 7.35 (2.50, 18.38) in mild cases, and 16.67 (4.43, 28.04) in recurrent cases, with 30.00%, 35.56%, and 57.89%, respectively evaluated as having DED symptoms (χ2=7.049, P=0.029). DEQ-5 score varied from 2.00 (0, 6.00) in asymptomatic carriers, 3.00 (0, 8.00) in mild cases, and 8.00 (5.00, 10.00) in recurrent cases, with 27.50%, 33.33%, and 55.26%, respectively assessed as having DED symptoms (χ2=8.532, P=0.014). The prevalence of clinical anxiety (50.00%) and depression (47.37%) symptoms were also significantly higher in patients with recurrent infection (χ2=24.541, P

Abstract Background Recurrent infections in childhood are the main cause of remission to the immunology service. T lymphocytes generated in the thymus are essential for fighting infection, making the thymus area an important predictor of the immune system’s competence. This study aimed to identify the possible relationship of the thymic area with clinical-epidemiological variables and values of subpopulations of T lymphocytes in the peripheral blood of children with recurrent infections. Methods We conducted applied research using a transversal analytical design at the National Medical Genetics Center (Havana, Cuba), from January to August 2022. The study covered 73 children of which we analyzed clinical-epidemiological variables and the size of the thymus through ultrasound. Furthermore, we determined the relative and absolute values of the subpopulations of T cells using flow cytometry. Results Of the children studied, 65.8% had thymic hypoplasia. The children who breastfed for less than 6 months showed four times the risk of developing moderate-severe thymus hypoplasia (OR = 3.90, 95% CI: 1.21–12.61). A direct relationship was found between the area of the thymus and the child’s size (r = 0.238, p = 0.043) and weight (r = 0.233, p = 0.047). The relative values of CD3+ T lymphocytes decreased in the cases of mild hypoplasia (p = 0.018) and moderate-severe hypoplasia (p = 0.049). The thymus area was associated with the absolute cell count of CD8+ effector memory T cells (rs = −0.263, p = 0.024) and of the central memory T cells (r = −0.283, p = 0.015). Conclusions Breastfeeding for less than 6 months, as well as the weight and size of the child, are related to their thymus area. The subpopulation values of T lymphocytes detected suggest that patients with thymic hypoplasia develop a contraction of CD3+ T cells, which can make them more vulnerable to infectious processes. This finding was combined with an expansion of the memory compartments of the subpopulations of CD8+ T cells, suggesting a greater susceptibility to intracellular viral and bacterial infections in these cases.

Objective To study and verify the function of de novo interferon regulatory factor (IRF8) frameshift mutation detected in an etiology screening of the cohort of children with recurrent pneumonia at the molecular level. Methods The recombinant overexpression plasmids with wildtype or mutated IRF8 genes were constructed to transiently transfect HEK293T cells, or packed into lentivirus to infect two kinds of immune cell lines. Q-PCR, Western blot, immunofluorescence and other experimental assays were performed to explore the differences of expression and the regulatory effect on downstream genes associated with inflammation. Results The recombinant vectors with wildtype or mutated IRF8 genes were constructed successfully, and the efficiency of transfection by plasmids and infection by packed lentivirus was remarkable as well. Compared with wildtype, the molecular weight of IRF8 variant was slightly increased, while the expression level presents in opposition, even if on transcription level. Moreover, the localization of IRF8 variant was detected in abundance in nucleus rather than cytoplasm, and its inhibition effect was enhanced on the downstream ISRE element in comparison with the wildtype IRF8 protein. Conclusion The de novo frameshift mutation was presumed as gain-of-function (GOF) mutation. [ABSTRACT FROM AUTHOR]

Background: Recurrent infections in childhood are the main cause of remission to the immunology service. T lymphocytes generated in the thymus are essential for fighting infection, making the thymus area an important predictor of the immune system's competence. This study aimed to identify the possible relationship of the thymic area with clinical-epidemiological variables and values of subpopulations of T lymphocytes in the peripheral blood of children with recurrent infections. Methods: We conducted applied research using a transversal analytical design at the National Medical Genetics Center (Havana, Cuba), from January to August 2022. The study covered 73 children of which we analyzed clinical-epidemiological variables and the size of the thymus through ultrasound. Furthermore, we determined the relative and absolute values of the subpopulations of T cells using flow cytometry. Results: Of the children studied, 65.8% had thymic hypoplasia. The children who breastfed for less than 6 months showed four times the risk of developing moderate-severe thymus hypoplasia (OR = 3.90, 95% CI: 1.21–12.61). A direct relationship was found between the area of the thymus and the child's size (r = 0.238, p = 0.043) and weight (r = 0.233, p = 0.047). The relative values of CD3+ T lymphocytes decreased in the cases of mild hypoplasia (p = 0.018) and moderate-severe hypoplasia (p = 0.049). The thymus area was associated with the absolute cell count of CD8+ effector memory T cells (rs = −0.263, p = 0.024) and of the central memory T cells (r = −0.283, p = 0.015). Conclusions: Breastfeeding for less than 6 months, as well as the weight and size of the child, are related to their thymus area. The subpopulation values of T lymphocytes detected suggest that patients with thymic hypoplasia develop a contraction of CD3+ T cells, which can make them more vulnerable to infectious processes. This finding was combined with an expansion of the memory compartments of the subpopulations of CD8+ T cells, suggesting a greater susceptibility to intracellular viral and bacterial infections in these cases. [ABSTRACT FROM AUTHOR]

Inborn errors in immunity (IEI), well known as primary immunodeficiency diseases (PID) in children, have a varied spectrum of presentation. As the normal immune development is key for programming various cell responses in the body, IEI results in significant infections due to defective cell function, auto-immunity, or auto-inflammatory syndromes due to loss of self-tolerance and immune dysregulation and predisposition to lymphoid malignancies due to the defective tumor surveillance by the lymphocytes or natural killer cells. High index of suspicion and knowledge of the myriad presenting features are very important for appropriate timely diagnosis and management. We present four children with B-cell immunodeficiency syndromes with initial presentation including arthritis or auto-immunity. [ABSTRACT FROM AUTHOR]

Background: Special antibiotics are prescribed against . However, sometimes the bacteria are not completely eliminated, or they are recurrent. Unlike most infections, it is very difficult to eliminate a infection. Heteroresistance is defined as the phenomenon in which subpopulations of the same colony of bacteria exhibit a range of susceptibilities to a particular antibiotic. Because of heteroresistant cells, antibiotic failure and chronic infection can occur; thus, the current research aimed to investigate presence of heteroresistant cells in collected from patients reffering to clinic in Ilam, Iran. Subsequently, patients who were infected with heteroresistant were treated with antibiotics effective against heteroresistant subpopulations.Methods: In this cross-sectional descriptive study, 100 patients with clinical symptoms and suspected of being infected with were studied in private clinics in Ilam, Iran. Fiftyisolates of accompanied by patients’ information were obtained from Ilam clinics. We cultured the bacteria to identify heteroresistance and to find the cause of recurrent infection in these patients. Results: Out of a total of 50 samples, 3 were heteroresistant to clarithromycin (6%). Levofloxacin was applied in cases of heteroresistant samples, and the effectiveness was determined after one month of follow-up of patients. Conclusion: Patients with heteroresistance showed sensitivity to levofloxacin. After one month of follow-up, it was found that the effectiveness of this antibiotic was good. Therefore, this antibiotic was introduced as a more effective drug in patients with heteroresistant .

Neonatal meningitis is a devastating disease associated with high mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis in full-term infants (herein NMEC) and the most common cause of meningitis in preterm neonates. Here, we investigated the genomic relatedness of a collection of 58 NMEC isolates spanning 1974–2020 and isolated from seven different geographic regions. We show NMEC are comprised of diverse sequence types (STs), with ST95 (34.5%) and ST1193 (15.5%) the most common. No single virulence gene profile was conserved in all isolates; however, genes encoding fimbrial adhesins, iron acquisition systems, the K1 capsule, and O antigen types O18, O75, and O2 were most prevalent. Antibiotic resistance genes occurred infrequently in our collection. We also monitored the infection dynamics in three patients that suffered recrudescent invasive infection caused by the original infecting isolate despite appropriate antibiotic treatment based on antibiogram profile and resistance genotype. These patients exhibited severe gut dysbiosis. In one patient, the causative NMEC isolate was also detected in the fecal flora at the time of the second infection episode and after treatment. Thus, although antibiotics are the standard of care for NMEC treatment, our data suggest that failure to eliminate the causative NMEC that resides intestinally can lead to the existence of a refractory reservoir that may seed recrudescent infection.

Background There is a need to understand the duration of infectivity of primary and recurrent coronavirus disease 2019 (COVID-19) and identify predictors of loss of infectivity. Methods Prospective observational cohort study with serial viral culture, rapid antigen detection test (RADT) and reverse transcription polymerase chain reaction (RT-PCR) on nasopharyngeal specimens of healthcare workers with COVID-19. The primary outcome was viral culture positivity as indicative of infectivity. Predictors of loss of infectivity were determined using multivariate regression model. The performance of the US Centers for Disease Control and Prevention (CDC) criteria (fever resolution, symptom improvement, and negative RADT) to predict loss of infectivity was also investigated. Results In total, 121 participants (91 female [79.3%]; average age, 40 years) were enrolled. Most (n = 107, 88.4%) had received ≥3 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine doses, and 20 (16.5%) had COVID-19 previously. Viral culture positivity decreased from 71.9% (87/121) on day 5 of infection to 18.2% (22/121) on day 10. Participants with recurrent COVID-19 had a lower likelihood of infectivity than those with primary COVID-19 at each follow-up (day 5 odds ratio [OR], 0.14; P <.001]; day 7 OR, 0.04; P =.003]) and were all non-infective by day 10 (P =.02). Independent predictors of infectivity included prior COVID-19 (adjusted OR [aOR] on day 5, 0.005; P =.003), an RT-PCR cycle threshold [Ct] value <23 (aOR on day 5, 22.75; P <.001) but not symptom improvement or RADT result. The CDC criteria would identify 36% (24/67) of all non-infectious individuals on day 7. However, 17% (5/29) of those meeting all the criteria had a positive viral culture. Conclusions Infectivity of recurrent COVID-19 is shorter than primary infections. Loss of infectivity algorithms could be optimized. [ABSTRACT FROM AUTHOR]

Background Recurrent Clostridioides difficile infection (rCDI) occurs frequently, and concomitant antibiotic (CA) during the initial episode for treatment of non-CDI is a major risk factor. We sought to address the comparative efficacy of fidaxomicin versus vancomycin in the setting of CA during the initial CDI episode. Methods We conducted a randomized, controlled, open-label trial at 2 hospitals in Ann Arbor, Michigan. We consecutively consented and enrolled hospitalized patients ≥18 years old with diarrhea, a positive test for C. difficile , and ≥1 qualifying CA. Complicated CDI, CDI treatment for >24 hours prior to enrollment, and planned long-term (>12 weeks) CA use were notable exclusions. Clinical cure was defined as resolution of diarrhea for 2 consecutive days maintained until 2 days after therapy, and rCDI as recurrent diarrhea with positive testing ≤30 days after initial treatment. Patients were randomized to fidaxomicin or vancomycin. Results Baseline characteristics were similar in the 2 groups of 144 patients. Rates of clinical cure (73% vs 62.9%, P =.195) and rCDI (3.3% vs 4.0%; P >.99) were similar for fidaxomicin and vancomycin in the intention-to-treat and per-protocol cohorts, respectively. Only 4 patients developed rCDI. Conclusions In this study of patients with CDI receiving CA, a numerically higher proportion were cured with fidaxomicin versus vancomycin, but this result did not reach statistical significance. Overall recurrence was lower than anticipated in both arms compared with previous studies that did not extend duration of CDI treatment during CA. Clinical Trials Registration www.clinicaltrials.gov (NCT02692651). [ABSTRACT FROM AUTHOR]

Introduction: Clostridioides difficile infection (CDI) is a major public health threat. Up to 40% of patients with CDI experience recurrent CDI (rCDI), which is associated with increased morbidity. This study aimed to define an at-risk population by obtaining a detailed understanding of the different factors leading to CDI, rCDI, and CDI-related morbidity and of time to CDI. Methods: We conducted a systematic literature review (SLR) of MEDLINE (using PubMed) and EMBASE for relevant articles published between January 1, 2016, and November 11, 2022, covering the US population. Results: Of the 1324 articles identified, 151 met prespecified inclusion criteria. Advanced patient age was a likely risk factor for primary CDI within a general population, with significant risk estimates identified in nine of 10 studies. Older age was less important in specific populations with comorbidities usually diagnosed at earlier age, such as bowel disease and cancer. In terms of comorbidities, the established factors of infection, kidney disease, liver disease, cardiovascular disease, and bowel disease along with several new factors (including anemia, fluid and electrolyte disorders, and coagulation disorders) were likely risk factors for primary CDI. Data on diabetes, cancer, and obesity were mixed. Other primary CDI risk factors were antibiotics, proton pump inhibitors, female sex, prior hospitalization, and the length of stay in hospital. Similar factors were identified for rCDI, but evidence was limited. Older age was a likely risk factor for mortality. Timing of primary CDI varied depending on the population: 2–3 weeks in patients receiving stem cell transplants, within 3 weeks for patients undergoing surgery, and generally more than 3 weeks following solid organ transplant. Conclusion: This SLR uses recent evidence to define the most important factors associated with CDI, confirming those that are well established and highlighting new ones that could help to identify patient populations at high risk. [ABSTRACT FROM AUTHOR]

Patients who undergo total shoulder arthroplasty usually have excellent long-term outcomes. However, a subset of patients is diagnosed with a prosthetic joint infection (PJI) requiring revision procedures and prolonged recovery. The purpose of this study was to evaluate rates of recurrent shoulder PJI in patients undergoing débridement, antibiotics, and implant retention (DAIR), single-stage revision, and 2-stage revision. We also sought to compare outcomes and complications across procedures. Retrospective chart review was conducted for patients diagnosed with PJI after primary shoulder arthroplasty between January 2010 and August 2021. Patients were included if they underwent treatment with DAIR, single-stage revision, or 2-stage revision. Demographic information, surgical details, complications, laboratory data, postoperative antibiotic regimen, and infectious pathogen were collected. Postoperative patient-reported outcomes were collected: American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Single Assessment Numeric Evaluation, Shoulder Activity Scale, and PROMIS Upper Extremity. Chi-square, t test, and 1-way analysis of variance were used as appropriate to evaluate each factor. Sixty-five patients were included in the study, 26% treated with DAIR, 9% treated with single-stage revision, and 65% treated with 2-stage revision. There were no significant differences in patient comorbidities. Patients undergoing DAIR were diagnosed significantly earlier than those undergoing single- and 2-stage revision procedures (12.6 ± 22.9 months vs. 49.6 ± 48.4 vs. 25.0 ± 26.6, P =.010). Recurrent PJI was noted in 23.1% of patients: 29.4% of DAIR patients, no single-stage patients, and 23.8% of 2-stage patients (P =.330). Patients undergoing 2-stage revision with treatment failure had a significantly higher Elixhauser Comorbidity Index (0.2 ± 3.7 vs. 3.7 ± 3.9, P =.027). There was no significant difference in patient-reported outcomes across groups. Patients undergoing treatment of shoulder PJI with DAIR did not have an increased rate of reinfection compared with single-stage and 2-stage revision procedures. Patients treated with DAIR were diagnosed with PJI significantly earlier than those undergoing single-stage and 2-stage revision procedures. There was no difference in complication rates between groups. This information adds to the body of work detailing outcomes after DAIR for shoulder PJI and provides encouraging data for use in this patient population. Future studies with a larger sample size may be conducted to further investigate specific pathogens, infection timelines, and antibiotic regimens that reduce the risk of treatment failure. [ABSTRACT FROM AUTHOR]

Background: Vitamin D, known for its immunoregulatory effects and antimicrobial properties, plays a crucial role in regulating inflammation and chemokine production. Zinc is influential for a healthy immune system and human health, influencing cell differentiation, proliferation, and apoptosis, which impact organism growth. Objectives: Determine the serum zinc and vitamin D3 levels in UTI patients and controls to detect the role of Vit. D3 and Zn in UTIs, and their levels in recurrent and non-recurrent infections. Methodology: Samples of 60 urinary tract infection patients, distributed between 30 females and 30 males, were collected from Imam Hassan Al-Mujtaba Hospital for the period from December 2022 to April 2023. After collecting venous blood samples from patients and the controls, the serum was separated to measure the concentrations of vitamin D3 and zinc. The concentration of vitamin D3 was measured using the Cobas system, while the concentration of zinc was measured using a Mindray device. Results: UTI patients have lower serum zinc levels than the controls group, with the patient group having 83.0 mg/dL compared to the control group. Vitamin D3 was also low in the patients group compared to controls (10.50, 12.58 respectively). Conclusion: Vitamin D3 and zinc levels can influence UTI development, with patients having lower serum vit. D3 and zinc than the controls group, indicating a potential risk of UTI. [ABSTRACT FROM AUTHOR]

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Summary: Colony‐stimulating factor 3 (CSF3) is a key factor in neutrophil production and function, and recombinant forms have been used clinically for decades to treat congenital and acquired neutropenia. Although biallelic inactivation of its receptor CSF3R is a well‐established cause of severe congenital neutropenia (SCN), no corresponding Mendelian disease has been ascribed to date to CSF3. Here, we describe three patients from two families each segregating a different biallelic inactivating variant in CSF3 with SCN. Complete deficiency of CSF3 as a result of nonsense‐mediated decay (NMD) could be demonstrated on RT‐PCR using skin fibroblasts‐derived RNA. The phenotype observed in this cohort mirrors that documented in mouse and zebrafish models of CSF3 deficiency. Our results suggest that CSF3 deficiency in humans causes a novel autosomal recessive form of SCN. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) may recur in approximately 10–30% of patients, and the risk of recurrence increases with each successive recurrence, reaching up to 65%. C. difficile can form biofilm with approximately 20% of the bacterial genome expressed differently between biofilm and planktonic cells. Biofilm plays several roles that may favor recurrence; for example, it may act as a reservoir of spores, protect the vegetative cells from the activity of antibiotics, and favor the formation of persistent cells. Moreover, the expression of several virulence genes, including TcdA and TcdB toxins, has been associated with recurrence. Several systems and structures associated with adhesion and biofilm formation have been studied in C. difficile, including cell-wall proteins, quorum sensing (including LuxS and Agr), Cyclic di-GMP, type IV pili, and flagella. Most antibiotics recommended for the treatment of CDI do not have activity on spores and do not eliminate biofilm. Therapeutic failure in R-CDI has been associated with the inadequate concentration of drugs in the intestinal tract and the antibiotic resistance of a biofilm. This makes it challenging to eradicate C. difficile in the intestine, complicating antibacterial therapies and allowing non-eliminated spores to remain in the biofilm, increasing the risk of recurrence. In this review, we examine the role of biofilm on recurrence and the challenges of treating CDI when the bacteria form a biofilm. [ABSTRACT FROM AUTHOR]

The dedicator of cytokinesis 2(DOCK2) protein, an atypical guanine nucleotide exchange factor (GEFs), is a member of the DOCKA protein subfamily. DOCK2 protein deficiency is characterized by early-onset lymphopenia, recurrent infections, and lymphocyte dysfunction, which was classified as combined immune deficiency with neutrophil abnormalities as well. The only cure is hematopoietic stem cell transplantation. Here, we report two patients harboring four novel DOCK2 mutations associated with recurrent infections including live attenuated vaccine-related infections. The patient's condition was partially alleviated by symptomatic treatment or intravenous immunoglobulin. We also confirmed defects in thymic T cell output and T cell proliferation, as well as aberrant skewing of T/B cell subset TCR-Vβ repertoires. In addition, we noted neutrophil defects, the weakening of actin polymerization, and BCR internalization under TCR/BCR activation. Finally, we found that the DOCK2 protein affected antibody affinity although with normal total serum immunoglobulin. The results reported herein expand the clinical phenotype, the pathogenic DOCK2 mutation database, and the immune characteristics of DOCK2-deficient patients. [ABSTRACT FROM AUTHOR]

Multiple episodes of Enterococcus faecalis bacteremia (EfsB) may indicate a relapse and be due to an undiagnosed infective endocarditis (IE). The aims were to study the clinical presentation of patients with EfsB with focus on the risk of recurrent infection and IE, identify potential improvements of the management, and to investigate whether E. faecalis isolates from different episodes in the same patient were identical. In a retrospective study, a cohort of patients with monomicrobial (M) EfsB episodes was analyzed. Clinical data from medical records were collected. Furthermore, blood culture isolates from patients with multiple episodes were subjected to whole genome sequencing and multilocus sequence typing. In 666 episodes of MEfsB, 69 patients with IE and 43 with recurrent infections were found. Patients without IE, but with a following episode diagnosed as IE, were compared to those without a following episode. Variables significantly correlated with IE were long duration of symptoms, growth in all blood cultures, unknown origin of infection, heart murmur, and predisposition for IE. Transesophageal echocardiography, all negative, was done in 4 out of 11 episodes during the first episodes, later diagnosed with IE. In 28 of 31 patients with two or more EfsB episodes, isolates with identical sequence type were found. Episodes of EfsB in patients later diagnosed with IE showed features of IE already during the first episodes, were not adequately evaluated, are due to identical isolates, and most likely represent true relapses. Risk factor analysis should guide the use of echocardiography. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the clinical outcomes associated with the use of highly bioavailable oral antibiotics (fluoroquinolones and trimethoprim-sulfamethoxazole) compared with the less-bioavailable oral antibiotics (β-lactams) in gram-negative bloodstream infections (BSIs). Among hospitalized older adult patients in Ontario, Canada, discharged home on oral treatment for gram-negative BSI between 1 January 2017 and 31 December 2019, we used a matched cohort design to compare outcomes among those receiving highly versus less-bioavailable agents; hard-matching 1:1 on sex, BSI pathogen (Escherichia coli vs. non– E. coli), and infection source (urinary vs. non-urinary/unknown source) along with a propensity score, incorporating specific pathogen, patient, and infection characteristics. The primary outcome was the composite of 90-day all-cause mortality, recurrent BSI with the same pathogen (genus and species), and re-admission to any Ontario hospital. A total of 2012 patients were included in the study (1006 in each bioavailability category). Those who received highly (compared with less) bioavailable antibiotics at discharge had lower rates of the composite outcome (171/1006 [17.0%] vs. 216/1006 [21.5%]), adjusted odds ratio being 0.74 (95% CI, 0.60–0.92). Recurrent BSI at 90 days was the main driver for the composite outcome occurring in 64 (5.4%) and 107 (9.4%) patients of the highly and less-bioavailable groups, respectively (p < 0.001) (adjusted odds ratio, 0.56; 95% CI, 0.40–0.78). Use of highly (compared with less) bioavailable antibiotics at discharge was associated with significantly better clinical outcomes among patients with gram-negative BSIs. [ABSTRACT FROM AUTHOR]

We report microbiological results from a cohort of recurrent bone and joint infection to define the contributions of microbial persistence or replacement. We also investigated for any association between local antibiotic treatment and emerging antimicrobial resistance. Microbiological cultures and antibiotic treatments were reviewed for 125 individuals with recurrent infection (prosthetic joint infection, fracture-related infection, and osteomyelitis) at two UK centres between 2007 and 2021. At re-operation, 48/125 (38.4%) individuals had an organism from the same bacterial species as at their initial operation for infection. In 49/125 (39.2%), only new species were isolated in culture. In 28/125 (22.4%), re-operative cultures were negative. The most commonly persistent species were Staphylococcus aureus (46.3%), coagulase-negative Staphylococci (50.0%), and Pseudomonas aeruginosa (50.0%). Gentamicin non-susceptible organisms were common, identified at index procedure in 51/125 (40.8%) and at re-operation in 40/125 (32%). Gentamicin non-susceptibility at re-operation was not associated with previous local aminoglycoside treatment (21/71 (29.8%) vs. 19/54 (35.2%); p = 0.6). Emergence of new aminoglycoside resistance at recurrence was uncommon and did not differ significantly between those with and without local aminoglycoside treatment (3/71 (4.2%) vs. 4/54 (7.4%); p = 0.7). Culture-based diagnostics identified microbial persistence and replacement at similar rates in patients who re-presented with infection. Treatment for orthopaedic infection with local antibiotics was not associated with the emergence of specific antimicrobial resistance. [ABSTRACT FROM AUTHOR]

AbstractBackground Urinary tract infection (UTI) is the most common bacterial infection in women. In Norwegian general practice, methenamine has been prescribed for many years as long-term prevention and accounted for 20% of the total antibiotic prescribing in 2015, as measured in defined daily dosages (DDDs). The efficacy of methenamine is unknown. If shown to be effective, this drug may become an important preventive against UTI.Objective To examine whether methenamine is preventive against recurrent UTI in women.Design Data for all antibiotics used for UTIs dispensed from all pharmacies from 2005 to 2015 were collected from the Norwegian prescription database (NorPD).Subjects Women aged ≥ 40 years with recurrent UTI, defined as ≥3 courses of UTI antibiotic/year, were included.Main outcome measures Patients using methenamine (cases) and those not using methenamine (controls) were compared. The numbers of UTI prescriptions during the 2 years before and after inclusion were analysed. Results: The yearly prevalence for recurrent UTI was 2.4% in women ≥ 40 years. The change in antibiotic use from 2 years before to 2 years after inclusion in the study differed significantly between groups: 44.6 and 34.9% reductions in the number of antibiotic prescriptions for UTI in the methenamine and control groups, respectively. The decrease in UTI antibiotic prescriptions (58.9%) was greater in patients with a higher consumption of antibiotics before starting methenamine.Conclusions Methenamine seems to be effective against recurrent UTI over the time span studied. The effect seems to be greater in patients with the highest number of recurrent UTIs. Key pointsMethenamine has been used for many years for prevention of recurrent UTI, but no studies have demonstrated a significant preventive effect of long time use.This study shows that methenamine seems to be effective for prevention in patients having recurrent UTI over 2 years or more.The effect seems to be larger in patients with a high number of UTIs over 2 years.

Abstract Management of infective endocarditis (IE) in intravenous drug users (IVDUs) can be challenging due to risk of reinfection following surgery. Although complex repair techniques that can be utilized to reconstruct the tricuspid valve after extensive debridement, treatment of active IVDU is incomplete without effective post‐operative harm reduction intervention program.

The bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a severe tropical disease associated with high mortality and relapse and persistent infections. Treatment of melioidosis requires prolonged antibiotic therapy; however, little is known about relapse and persistent infections, particularly the phenotypic and genetic alterations of B. pseudomallei in patients. In this study, we performed pulsed-field gel electrophoresis (PFGE) to compare the bacterial genotype between the initial isolate and the subsequent isolate from each of 23 suspected recurrent and persistent melioidosis patients in Northeast Thailand. We used whole-genome sequencing (WGS) to investigate multilocus sequence types and genetic alterations of within-host strain pairs. We also investigated the bacterial phenotypes associated with relapse and persistent infections, including multinucleated giant cell (MNGC) formation efficiency and intracellular multiplication. We first identified 13 (1.2%) relapse, 7 (0.7%) persistent, and 3 (0.3%) reinfection patients from 1,046 survivors. Each of the 20 within-host strain pairs from patients with relapse and persistent infections shared the same genotype, suggesting that the subsequent isolates arise from the infecting isolate. Logistic regression analysis of clinical data revealed regimen and duration of oral antibiotic therapies as risk factors associated with relapse and persistent infections. WGS analysis demonstrated 17 within-host genetic alteration events in 6 of 20 paired isolates, including a relatively large deletion and 16 single-nucleotide polymorphism (stocktickerSNP) mutations distributed across 12 genes. In 1 of 20 paired isolates, we observed significantly increased cellto-cell fusion and intracellular replication in the second isolate compared with the initial isolate from a patient with persistent infection. WGS analysis suggested that a non-synonymous mutation in the tssB-5 gene, which encoded an essential component of the type VI secretion system, may be associated with the increased intracellular replication and MNGC formation efficiency of the second isolate of the patient. This information provides insights into genetic and phenotypic alterations in B. pseudomallei in human melioidosis, which may represent a bacterial strategy for persistent and relapse infections. [ABSTRACT FROM AUTHOR]

Background: Two-stage exchange arthroplasty is considered the gold standard treatment for chronic periprosthetic joint infection (PJI). However, there is a scarcity of research investigating the major risk factors for infection recurrence and the prognosis after infection recurrence.Methods: This study included 203 patients who underwent 2-stage exchange arthroplasty between June 22, 2010 and January 24, 2017. The need of reoperation for infection-related or PJI-related mortality was considered treatment failure. Participant age, gender, body mass index, comorbidities, culture results, length of hospital stay, cause of treatment failure, operative procedure, and fate were analyzed.Results: Fifty-three patients experienced treatment failure (26.1%). Mean follow-up was 63 months (range, 26-103). Based on the multivariate analyses, risk factors for treatment failure included men and positive intraoperative culture during reimplantation. Recurrent infection was most commonly caused by Staphylococcus aureus (32.1%, 17/53), and new microorganisms caused recurrent infection in 34 of 53 (64.2%) patients. In 44 patients who had treatment failure, debridement, antibiotic therapy, irrigation, and retention of prosthesis (DAIR) performed within 6 months of reimplantation and at <3 weeks from symptom onset resulted in a significantly higher success rate than the use of other DAIR protocols (P = .031).Conclusion: Men and positive intraoperative culture are major risk factors for 2-stage exchange arthroplasty failure in patients who have knee PJI. Recurrent infection in these patients is usually caused by new microorganisms. DAIR within 6 months of reimplantation and at <3 weeks from symptom onset results in good outcomes in these patients. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine magnetic resonance imaging (MRI) features that could help differentiate the bone destruction due to persistent/recurrent spine infection from worsening bone destruction due to mechanical factors, which could help obviate the need for repeat spine biopsy. Material and methods: A retrospective study was performed on selected subjects who were more than 18 years of age, were diagnosed with infectious spondylodiscitis, underwent at least 2 spinal interventions for the diagnosis at the same level, and had MRI prior to each image-guided intervention. Both MRI studies were analysed for vertebral body changes, paravertebral collections, epidural thickening and collections, bone marrow signal changes, loss of vertebral body height, abnormal signal in intervertebral disc, and loss of disc height. Results: We observed that worsening of changes in paravertebral and epidural soft tissue were statistically more significant predictors of recurrent/persistent spine infection (p < 0.05). However, worsening destruction of vertebral body and intervertebral disc, abnormal vertebral marrow signal changes, and abnormal signal in intervertebral disc did not necessarily indicate worsening infection or recurrence. Conclusions: In patients of infectious spondylitis with suspected recurrence, the most common and pronounced MRI findings of worsening osseous changes can be deceiving and can result in negative repeat spinal biopsy. Changes in paraspinal and epidural soft tissues are more helpful in identifying the cause of worsening bone destruction. Correlation with clinical examination, inflammatory markers, and observing soft tissue changes on follow-up MRI is a more reliable way to identify patients who may benefit from repeat spine biopsy. [ABSTRACT FROM AUTHOR]

The bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a severe tropical disease associated with high mortality and relapse and persistent infections. Treatment of melioidosis requires prolonged antibiotic therapy; however, little is known about relapse and persistent infections, particularly the phenotypic and genetic alterations of B. pseudomallei in patients. In this study, we performed pulsed-field gel electrophoresis (PFGE) to compare the bacterial genotype between the initial isolate and the subsequent isolate from each of 23 suspected recurrent and persistent melioidosis patients in Northeast Thailand. We used whole-genome sequencing (WGS) to investigate multilocus sequence types and genetic alterations of within-host strain pairs. We also investigated the bacterial phenotypes associated with relapse and persistent infections, including multinucleated giant cell (MNGC) formation efficiency and intracellular multiplication. We first identified 13 (1.2%) relapse, 7 (0.7%) persistent, and 3 (0.3%) reinfection patients from 1,046 survivors. Each of the 20 within-host strain pairs from patients with relapse and persistent infections shared the same genotype, suggesting that the subsequent isolates arise from the infecting isolate. Logistic regression analysis of clinical data revealed regimen and duration of oral antibiotic therapies as risk factors associated with relapse and persistent infections. WGS analysis demonstrated 17 within-host genetic alteration events in 6 of 20 paired isolates, including a relatively large deletion and 16 single-nucleotide polymorphism (stocktickerSNP) mutations distributed across 12 genes. In 1 of 20 paired isolates, we observed significantly increased cell-to-cell fusion and intracellular replication in the second isolate compared with the initial isolate from a patient with persistent infection. WGS analysis suggested that a non-synonymous mutation in the tssB-5 gene, which encoded an essential component of the type VI secretion system, may be associated with the increased intracellular replication and MNGC formation efficiency of the second isolate of the patient. This information provides insights into genetic and phenotypic alterations in B. pseudomallei in human melioidosis, which may represent a bacterial strategy for persistent and relapse infections.

Clostridioides difficile infection (CDI) may recur in approximately 10–30% of patients, and the risk of recurrence increases with each successive recurrence, reaching up to 65%. C. difficile can form biofilm with approximately 20% of the bacterial genome expressed differently between biofilm and planktonic cells. Biofilm plays several roles that may favor recurrence; for example, it may act as a reservoir of spores, protect the vegetative cells from the activity of antibiotics, and favor the formation of persistent cells. Moreover, the expression of several virulence genes, including TcdA and TcdB toxins, has been associated with recurrence. Several systems and structures associated with adhesion and biofilm formation have been studied in C. difficile, including cell-wall proteins, quorum sensing (including LuxS and Agr), Cyclic di-GMP, type IV pili, and flagella. Most antibiotics recommended for the treatment of CDI do not have activity on spores and do not eliminate biofilm. Therapeutic failure in R-CDI has been associated with the inadequate concentration of drugs in the intestinal tract and the antibiotic resistance of a biofilm. This makes it challenging to eradicate C. difficile in the intestine, complicating antibacterial therapies and allowing non-eliminated spores to remain in the biofilm, increasing the risk of recurrence. In this review, we examine the role of biofilm on recurrence and the challenges of treating CDI when the bacteria form a biofilm.

Selective IgM deficiency is a rare immunological disorder, with patients presenting with recurrent infections and allergic manifestations. However, the association with early postoperative infection has not been widely reported in the literature. We describe a rare case of a patient who had an early wound infection 1 day after excision of a Merkel cell carcinoma from his right buttock and was later found to have decreased IgM levels. Selective IgM deficiency should therefore be considered in patients presenting with recurrent infections or in patients who have previously undergone surgery and subsequently developed early infection postoperatively. In this subset of patients, extra precautions may need to be taken pre‐ and postoperatively to reduce the risk of developing a postoperative infection. [ABSTRACT FROM AUTHOR]

Purpose: In all patients with cardiac implantable electronic devices (CIED) and Enterococcus faecalis bacteremia (EfsB), endocarditis (IE) and CIED infection should be suspected. Guidelines recommend extraction of the CIED when CIED infection or IE is diagnosed. Whether extraction of the CIED should be done in other situations with EfsB is not known. We aimed to describe the management and outcome of patients with CIED and monomicrobial EfsB, in relation to extraction and recurrent EfsB. Methods: A population-based cohort of patients with monomicrobial EfsB from January 2014 to November 2020 was identified through microbiology registers in the Region Skåne, Sweden. Data on CIED and other clinical features were collected from medical records. Results: Among 1087 episodes of EfsB, 72 patients with CIED and monomicrobial EfsB were identified. Five of these patients were diagnosed with IE (7%), three of whom had echocardiographic changes on the CIED. Four CIED were extracted (6%). Recurrences were found in seven of 68 patients (10%) not subjected to extraction and in none of the extracted. In the group of patients without extraction, community acquisition and predisposition for IE were significantly associated with recurrent infection in univariate analyses. No infections involving the CIED were diagnosed during the recurrences. Conclusions: In patient with monomicrobial EfsB, it seems safe to omit extraction if no structural changes are found on the CIED. [ABSTRACT FROM AUTHOR]

Hyper-IgE syndrome (HIES) is a rare group of primary immunodeficiency diseases characterized by elevated IgE levels, eosinophilia, recurrent pyoderma, ear infection, eczematous dermatitis, and pulmonary infection. The treatment depends on the clinical presentation of the disease. The eczematous skin lesions usually respond to a topical steroid, calcineurin inhibitors, and sometimes, based on severity, systemic drugs are given. The secondary infections are usually treated with oral and topical antibiotics. We are describing a case of HIES who presented with severe recalcitrant itchy oozy eczematous skin lesions which did not respond to conventional systemic drugs and were later on controlled with injection omalizumab. In addition, we have discussed the HIES in detail in the current article. [ABSTRACT FROM AUTHOR]

Background: Prior studies have shown that the majority of re-infections following two-stage revisions are due to organisms different from the initial organisms identified. It remains unknown whether these new organisms were susceptible to the antibiotics given (indicating the patient likely developed another infection following successful treatment) or not susceptible (indicating these organisms may have been initially present, but were not identified, and thus, inadequately treated). The purpose of this study was to determine if bacteria identified at time of re-infection following two-stage revisions were susceptible to the antibiotics administered during treatment of the index infection, in order to understand if these are new infections or from organisms that were present but not initially identified. Methods: Thirty failures (19 knees and 11 hips) following two-stage revisions from four institutions were identified. Cultures and antibiotic sensitivities were used to determine whether the re-infectious organisms were new and if they were susceptible to the antibiotics initially given. Results: Twenty-five (83.3%) re-infections were due to new organisms. Of these re-infections from new organisms, 16 (64.0%) were susceptible to the antibiotics previously administered, suggesting they were new infections rather than persistent infections from organisms that were not detected during initial treatment. No statistically significant differences in demographics or time to revision were observed when comparing by organism type (new vs. repeat) or by antibiotic susceptibility. Conclusions: Failures following two-stage revisions are frequently due to organisms different than those identified prior to two-stage revision and are likely new infections rather than persistent infections from undetected organisms.

Urinary tract infection (UTI) is the most common bacterial infection in women. In Norwegian general practice, methenamine has been prescribed for many years as long-term prevention and accounted for 20% of the total antibiotic prescribing in 2015, as measured in defined daily dosages (DDDs). The efficacy of methenamine is unknown. If shown to be effective, this drug may become an important preventive against UTI. To examine whether methenamine is preventive against recurrent UTI in women. Data for all antibiotics used for UTIs dispensed from all pharmacies from 2005 to 2015 were collected from the Norwegian prescription database (NorPD). Women aged ≥ 40 years with recurrent UTI, defined as ≥3 courses of UTI antibiotic/year, were included. Patients using methenamine (cases) and those not using methenamine (controls) were compared. The numbers of UTI prescriptions during the 2 years before and after inclusion were analysed. Results: The yearly prevalence for recurrent UTI was 2.4% in women ≥ 40 years. The change in antibiotic use from 2 years before to 2 years after inclusion in the study differed significantly between groups: 44.6 and 34.9% reductions in the number of antibiotic prescriptions for UTI in the methenamine and control groups, respectively. The decrease in UTI antibiotic prescriptions (58.9%) was greater in patients with a higher consumption of antibiotics before starting methenamine. Methenamine seems to be effective against recurrent UTI over the time span studied. The effect seems to be greater in patients with the highest number of recurrent UTIs. Methenamine has been used for many years for prevention of recurrent UTI, but no studies have demonstrated a significant preventive effect of long time use. This study shows that methenamine seems to be effective for prevention in patients having recurrent UTI over 2 years or more. The effect seems to be larger in patients with a high number of UTIs over 2 years. [ABSTRACT FROM AUTHOR]

Background Giant cell myocarditis (GCM) is a rare but well-known cause of fulminant myocarditis. Despite optimal medical therapy, many patients progress to orthotopic heart transplant (OHT). We present a case of recurrent GCM following OHT, including complex considerations in patient management and infectious sequelae. Case summary A 33-year-old previously healthy male presented with 2 months of worsening shortness of breath. Transthoracic echocardiogram (TTE) demonstrated a left ventricular ejection fraction of 30–35%. After ruling out an ischaemic aetiology, he was discharged on guideline-directed medical therapy and later presented with productive cough, worsening dyspnoea on exertion, and diarrhoea. He was found to have elevated troponins and N-terminal pro-brain natriuretic peptide, lactic acidosis, progression of severe bi-ventricular dysfunction on TTE and right heart catheterization, and low cardiac index (1.0 L/min/m2) requiring inotropes. He then required left ventricular assist device as a bridge to OHT. Pathology of the apical core diagnosed GCM as the cause of his fulminant heart failure. He eventually underwent heart transplantation, which was complicated by recurrent GCM. Treatment required intensification of his immunosuppressive regimen, which led to multiple infectious sequelae including norovirus, Shiga-like toxin producing Escherichia coli , and disseminated nocardia of the lung and brain. As of the most recent follow-up, the patient is currently clinically stable. Discussion Although recurrent GCM after OHT has been reported in the literature, the prognosis is not well understood and there are no clear guidelines regarding management. This case summarizes clinical considerations, treatment strategies, and adverse effects of recurrent GCM treatment. [ABSTRACT FROM AUTHOR]

Paenibacilli are gram-variable, endospore-forming bacteria that occupy various ecologic niches. These microorganisms have been known to infect humans occasionally at various anatomic sites. However, in humans, as well as in other vertebrate animals, the relationship between disease and isolation of Paenibacillus spp. remains poorly understood. We report here a case of infection in an adult Poodle dog. The animal had nodules in the lungs and multifocal osteolytic expansile bone lesions. From bone, Paenibacillus amylolyticus was recovered by culture and identified by MALDI-TOF mass spectroscopy and 16S rDNA sequencing; pyogranulomatous inflammation was observed in lung and bone specimens. The microorganism was resistant to clindamycin and imipenem. Four-month treatment with amoxicillin–clavulanate resulted in clinical resolution of disease in this dog. Nevertheless, therapy for more prolonged periods should be considered because recurrent infections can occur as a result of the transition of Paenibacillus spores to vegetative cells. Disease caused by a Paenibacillus species has not been reported previously in dogs, to our knowledge. [ABSTRACT FROM AUTHOR]

Management of infective endocarditis (IE) in intravenous drug users (IVDUs) can be challenging due to risk of reinfection following surgery. Although complex repair techniques that can be utilized to reconstruct the tricuspid valve after extensive debridement, treatment of active IVDU is incomplete without effective post‐operative harm reduction intervention program. [ABSTRACT FROM AUTHOR]

GATA2 deficiency is a disease with a broad spectrum of clinical presentation, ranging from lymphedema, deafness, pulmonary dysfunction to miscarriage and urogenital anomalies, but it is mainly recognized as an immune system and bone marrow disorder. It is caused by various heterozygous mutations in the GATA2 gene, encoding for a zinc finger transcription factor with a key role for the development and maintenance of a pool of hematopoietic stem cells; notably, most of these mutations arise de novo. Patients carrying a mutated allele usually develop a loss of some cell populations, such as B-cell, dendritic cell, natural killer cell, and monocytes, and are predisposed to disseminated human papilloma virus and mycobacterial infections. Also, these patients have a predisposition to myeloid neoplasms, including myelodysplastic syndromes, myeloproliferative neoplasms, chronic myelomonocytic leukaemia. The age of symptoms onset can vary greatly even also within the same family, ranging from early childhood to late adulthood; incidence increases by age and most frequently clinical presentation is between the second and third decade of life. Currently, haematopoietic stem cell transplantation represents the only curative treatment, restoring both the hematopoietic and immune system function. [ABSTRACT FROM AUTHOR]