Human inherited CCR2 deficiency underlies progressive polycystic lung disease.

We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca2+ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.

Timing and Predictors of Loss of Infectivity Among Healthcare Workers With Mild Primary and Recurrent COVID-19: A Prospective Observational Cohort Study.

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.

An Open-Label, Randomized Trial Comparing Fidaxomicin With Oral Vancomycin for the Treatment of Clostridioides difficile Infection in Hospitalized Patients Receiving Concomitant Antibiotics for Concurrent Infections.

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).

Burkholderia semiarida as Cause of Recurrent Pulmonary Infection in Immunocompetent Patient, China.

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.

Non-betahemolytic streptococcal bacteremia, cardiac implantable electronic device, endocarditis, extraction, and outcome; a population-based retrospective cohort study.

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.

Recurrent pulmonary nocardiosis due to Nocardia Otitidiscaviarum in a patient with isolated CD4 lymphocytopenia: a case report.

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.

Does retained cement or hardware during 2-stage revision shoulder arthroplasty for infection increase the risk of recurrent infection?

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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). DISCUSSION: 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.

Outcomes after débridement, antibiotics, and implant retention for prosthetic joint infection in shoulder arthroplasty.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Early postoperative infection in patient with IgM deficiency.

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.

[Urinary tract infection and overactive bladder. Is there an association?]

A discussion of key research findings dedicated to the relationship between urinary tract infection (UTI) and overactive bladder (OAB) is presented in the article. The results of the publications support the concept that UTI may be an underappreciated contributor to the development of OAB in some patients and vice versa. This information raises a number of questions regarding the treatment and diagnosis of OAB and UTI. The main question is the potential use of antibiotics, anti-inflammatory drugs, and other drugs in the treatment of patients with OAB, as well as the rationale for the use of therapy that normalize lower urinary tract (LUT) function in the presence of chronic recurrent UTI.

[A case of neonatal Netherton syndrome]. / 新生儿Netherton综合征1例.

A male infant, aged 6 days, was admitted to the hospital due to respiratory distress and systemic desquamative rash after birth. The infant presented with erythema and desquamative rash, respiratory failure, recurrent infections, chronic diarrhea, hypernatremic dehydration, and growth retardation. Comprehensive treatment, including anti-infection therapy, intravenous immunoglobulin administration, and skin care, resulted in improvement of the rash, but recurrent infections persisted. Second-generation sequencing revealed a homozygous mutation in the SPINK5 gene, consistent with the pathogenic variation of Netherton syndrome. The family opted for palliative care, and the infant died at the age of 2 months after discharge. This report documents a case of Netherton syndrome caused by the SPINK5 gene mutation in the neonatal period, and highlights multidisciplinary diagnosis and therapy for this condition.

Human 'knockouts' of CSF3 display severe congenital neutropenia.

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.

Multiple Immune Defects in Two Patients with Novel DOCK2 Mutations Result in Recurrent Multiple Infection Including Live Attenuated Virus Vaccine.

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-Vß 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.

Recurrent bacteremia with Enterococcus faecalis, the clinical findings predicting endocarditis, and genomic characterization of the isolates: a retrospective cohort study.

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.

Risk Factors for Treatment Failure in Patients Who Have Knee Periprosthetic Joint Infection Treated With Two-Stage Exchange Arthroplasty as Well as Their Fate.

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.

A case of recurrent human Dirofilaria repens infection in Uzbekistan.

Dirofilaria repens is a zoonotic mosquito-borne filarioid that parasitizes in the subcutaneous tissues of carnivores, that has been incriminated in the great majority of human dirofilariasis cases reported throughout the Old World. From the Republic of Uzbekistan, recent data showed that this parasite is endemic in domestic and wild carnivores. In contrast, information regarding human infection is scarce and mostly outdated, with a single case report being published during the last decades. The present paper reports a case of recurrent autochthonous infection with D. repens in a patient living in the rural area of the Sirdaryo Region of Uzbekistan and having no international travel history. The first diagnosis was in 2019, when the patient presented with what was suspected to be a tumour of the left breast. Three years later, in 2022, she presented for a consultation after experiencing redness, occasional swelling and persistent itching in the umbilical region of the abdomen. The ultrasound indicated the presence of a living, motile nematode. Following anthelmintic therapy, the parasite was surgically removed and identified as a female D. repens. The present report highlights the possibility of human re-infection with D. repens and further underlines the necessity of raising public awareness and implementing of solid control strategies in carnivores.

Finding MRI features to obviate the need of repeat spinal biopsies in clinically suspected persistent or recurrent spinal osteomyelitis.

Purpose: The aim of this study was to determine magnetic resonance imaging (MRI) features that could help differen-tiate 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.

Novel mutations of TYK2 leading to divergent clinical phenotypes.

BACKGROUND: TYK2 deficiency is a rare primary immunodeficiency disease caused by loss-of-function mutations of TYK2 gene, which is initially proposed as a subset of hyper-IgE syndrome (HIES). However, accumulating evidence suggests TYK2-deficient patients do not necessarily present with HIES characteristics, indicating a vacuum of knowledge on the exact roles of TYK2 in human immune system. METHOD: Pathogenic effects of patients were confirmed by qRT-PCR, Western blot, and protein stability assays. The responses to cytokines including IFN-α/ß/γ, IL-6, IL-10, IL-12, and IL-23 of peripheral blood mononuclear cells (PBMCs) from these patients were detected by Western blot, qRT-PCR, and flow cytometry. The differentiation of T and B cells was detected by flow cytometry. RESULTS: We described five more TYK2-deficient cases presenting with or without hyper-IgE levels, atopy, and distinct pathogen infection profile, which are caused by novel TYK2 mutations. These mutations were all found by high-throughput sequencing and confirmed by Sanger sequencing. The patients showed heterogeneous responses to various cytokine treatments, including IFN-α/ß/γ, IL-6, IL-10, IL-12, and IL-23. The homeostasis of lymphocytes is also disrupted. CONCLUSION: Based on our findings, we propose that TYK2 works as a multi-tasker in orchestrating various cytokine signaling pathways, differentially combined defects which account for the expressed clinical manifestations.

Enterococcus faecalis bacteremia, cardiac implantable electronic device, extraction, and the risk of recurrence.

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.

Preventive effect of methenamine in women with recurrent urinary tract infections - a case-control study.

BACKGROUND: 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.