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1.
J Infect Dis ; 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38235716

ABSTRACT

BACKGROUND: Pseudomonas aeruginosa is a frequent pathogen isolated from bacterial bloodstream infection (BSI) and is associated with high mortality. To survive in the blood, P aeruginosa must resist the bactericidal action of complement (ie, serum killing). Antibodies usually promote serum killing through the classical complement pathway; however, "cloaking antibodies" (cAbs) have been described, which paradoxically protect bacteria from serum killing. The relevance of cAbs in P aeruginosa BSI is unknown. METHODS: Serum and P aeruginosa were collected from a cohort of 100 patients with BSI. Isolates were tested for sensitivity to healthy control serum (HCS). cAb prevalence was determined in sera. Patient sera were mixed with HCS to determine if killing of the matched isolate was inhibited. RESULTS: Overall, 36 patients had elevated titers of cAbs, and 34 isolates were sensitive to HCS killing. Fifteen patients had cAbs and HCS-sensitive isolates; of these patients, 14 had serum that protected their matched bacteria from HCS killing. Patients with cAbs were less likely to be neutropenic or have comorbidities. CONCLUSIONS: cAbs are prevalent in patients with P aeruginosa BSI and allow survival of otherwise serum-sensitive bacteria in the bloodstream. Generation of cAbs may be a risk factor for the development of BSI.

2.
Article in English | MEDLINE | ID: mdl-38842523

ABSTRACT

Extended hospitalization for infection management increases inpatient care costs and the risk of healthcare-associated adverse events, including infections. The growing global demand for healthcare, the diminishing availability of hospital beds and an increasing patient preference for care within their own home have been the primary drivers of the expansion of hospital-in-the-home programmes. Such programmes include the use of IV antimicrobials in outpatient settings, known as outpatient parenteral antimicrobial therapy (OPAT). However, OPAT practices vary globally. This review article aims to describe the current OPAT practices and challenges worldwide. OPAT practice begins with patient evaluation and selection using eligibility criteria, which requires collaboration between the interdisciplinary OPAT team, patients and caregivers. Depending on care requirements, eligible patients may be enrolled to various models of care, receiving medication by healthcare professionals at outpatient infusion centres, hospital clinics, home visits or through self-administration. OPAT can be used for the management of many infections where an effective oral treatment option is lacking. Various classes of parenteral antimicrobials, including ß-lactams, aminoglycosides, glycopeptides, fluoroquinolones and antifungals such as echinocandins, are used globally in OPAT practice. Despite its benefits, OPAT has numerous challenges, including complications from medication administration devices, antimicrobial side effects, monitoring requirements, antimicrobial instability, patient non-adherence, patient OPAT rejection, and challenges related to OPAT team structure and administration, all of which impact its outcome. A negative outcome could include unplanned hospital readmission. Future research should focus on mitigating these challenges to enable optimization of the OPAT service and thereby maximize the documented benefits for the healthcare system, patients and healthcare providers.

3.
Infection ; 51(4): 1003-1012, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36571672

ABSTRACT

BACKGROUND: P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P. aeruginosa bacteremia among old adults (≥ 80 years). METHODS: We included the 464/2394 (19%) older adults from a retrospective multinational (9 countries, 25 centers) cohort study of individuals hospitalized with P. aeruginosa bacteremia. Bivariate and multivariable logistic regression models were used to evaluate risk factors for 30-day mortality among older adults. RESULTS: Among 464 adults aged ≥ 80 years, the mean age was 84.61 (SD 3.98) years, and 274 (59%) were men. Compared to younger patients, ≥ 80 years adults had lower Charlson score; were less likely to have nosocomial acquisition; and more likely to have urinary source. Thirty-day mortality was 30%, versus 27% among patients 65-79 years (n = 894) and 25% among patients < 65 years (n = 1036). Multivariate analysis for predictors of mortality among patients ≥ 80 years, demonstrated higher SOFA score (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.23-1.51, p < 0.001), corticosteroid therapy (OR 3.15, 95% CI: 1.24-8.01, p = 0.016) and hospital acquired P. aeruginosa bacteremia (OR 2.30, 95% CI: 1.33-3.98, p = 0.003) as predictors. Appropriate empirical therapy within 24 h, type of definitive anti-pseudomonal drug, and type of regimen (monotherapy or combination) were not associated with 30-day mortality. CONCLUSIONS: In older adults with P. aeruginosa bacteremia, background conditions, place of acquisition, and disease severity are associated with mortality, rather than the antimicrobial regimen. In this regard, preventive efforts and early diagnosis before organ failure develops might be beneficial for improving outcomes.


Subject(s)
Bacteremia , Pseudomonas Infections , Male , Aged, 80 and over , Humans , Aged , Female , Anti-Bacterial Agents/therapeutic use , Retrospective Studies , Pseudomonas aeruginosa , Cohort Studies , Nonagenarians , Octogenarians , Pseudomonas Infections/drug therapy , Bacteremia/drug therapy , Bacteremia/epidemiology , Bacteremia/complications , Risk Factors
4.
Acta Obstet Gynecol Scand ; 102(7): 811-820, 2023 07.
Article in English | MEDLINE | ID: mdl-37067195

ABSTRACT

With increasing rates of cesarean section worldwide and international guidelines advising pre-incision antibiotics, neonatal exposure to pre-birth antibiotics is higher than ever before. Emerging evidence has raised concern regarding the impact of such antibiotics on the neonatal intestinal microbiota, immune system development and health conditions later in life. This narrative review investigates current protocols for intrapartum prophylactic antibiotics in cesarean section, how this and other factors may affect the neonatal intestinal microbiota and whether intrapartum antibiotics used for cesarean section are linked to the development of allergic disease.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Infant, Newborn , Infant , Humans , Pregnancy , Female , Anti-Bacterial Agents/therapeutic use , Cesarean Section , Parturition
5.
BMC Nephrol ; 24(1): 195, 2023 06 29.
Article in English | MEDLINE | ID: mdl-37386464

ABSTRACT

RATIONALE & OBJECTIVE: Shared decision making (SDM) is a collaborative effort between healthcare professionals, individuals with CKD whereby clinical evidence, expected outcomes and potential side-effects are balanced with individual values and beliefs to provide the best mutually decided treatment option. Meaningful SDM is supported by effective training and education. We aimed to identify the available evidence on SDM training and education of healthcare professionals caring for people with chronic kidney disease. We aimed to identify existing training programs and to explore what means are used to evaluate the quality and effectiveness of these educational efforts. METHODOLOGY: We performed a scoping review to study the effectiveness of training or education about shared decision making of healthcare professionals treating patients with kidney disease. EMBASE, MEDLINE, CINAHL and APA PsycInfo were searched. RESULTS: After screening of 1190 articles, 24 articles were included for analysis, of which 20 were suitable for quality appraisal. These included 2 systematic reviews, 1 cohort study, 7 qualitative studies, and 10 studies using mixed methods. Study quality was varied with high quality (n = 5), medium quality (n = 12), and low quality (n = 3) studies. The majority of studies (n = 11) explored SDM education for nurses, and physicians (n = 11). Other HCP profiles included social workers (n = 6), dieticians (n = 4), and technicians (n = 2). Topics included education on SDM in withholding of dialysis, modality choice, patient engagement, and end-of-life decisions. LIMITATIONS: We observed significant heterogeneity in study design and varied quality of the data. As the literature search is restricted to evidence published between January 2000 and March 2021, relevant literature outside of this time window has not been taken into account. CONCLUSIONS: Evidence on training and education of SDM for healthcare professionals taking care of patients with CKD is limited. Curricula are not standardized, and educational and training materials do not belong to the public domain. The extent to which interventions have improved the process of shared-decision making is tested mostly by pre-post testing of healthcare professionals, whereas the impact from the patient perspective for the most part remains untested.


Subject(s)
Education, Professional , Renal Insufficiency, Chronic , Humans , Cohort Studies , Decision Making, Shared , Renal Dialysis , Patient Participation , Renal Insufficiency, Chronic/therapy
6.
Nephrol Dial Transplant ; 37(11): 2080-2089, 2022 10 19.
Article in English | MEDLINE | ID: mdl-35671088

ABSTRACT

BACKGROUND: Availability of assisted PD (asPD) increases access to dialysis at home, particularly for the increasing numbers of older and frail people with advanced kidney disease. Although asPD has been widely used in some European countries for many years, it remains unavailable or poorly utilized in others. A group of leading European nephrologists have therefore formed a group to drive increased availability of asPD in Europe and in their own countries. METHODS: Members of the group filled in a proforma with the following headings: personal experience, country experience, who are the assistants, funding of asPD, barriers to growth, what is needed to grow and their top three priorities. RESULTS: Only 5 of the 13 countries surveyed provided publicly funded reimbursement for asPD. The use of asPD depends on overall attitudes to PD, with all respondents mentioning the need for nephrology team education and/or patient education and involvement in dialysis modality decision making. CONCLUSIONS AND CALL TO ACTION: Many people with advanced kidney disease would prefer to have their dialysis at home, yet if the frail patient chooses PD most healthcare systems cannot provide their choice. AsPD should be available in all countries in Europe and in all renal centres. The top priorities to make this happen are education of renal healthcare teams about the advantages of PD, education of and discussion with patients and their families as they approach the need for dialysis, and engagement with policymakers and healthcare providers to develop and support assistance for PD.


Subject(s)
Kidney Diseases , Kidney Failure, Chronic , Peritoneal Dialysis , Humans , Renal Dialysis , Kidney Failure, Chronic/therapy , Europe
7.
Blood Purif ; 51(12): 1022-1030, 2022.
Article in English | MEDLINE | ID: mdl-35477096

ABSTRACT

INTRODUCTION: Peritoneal dialysis (PD) remains underutilised in the West. The proportion of patients in the UK starting renal replacement therapy (RRT) with PD fell from 7.2% in 2011 to 6.0% in 2016. At our centre, 8.4% of dialysis patients received PD in April 2014. Evidence suggests that home dialysis improves patient clinical outcomes; therefore, a target was agreed to achieve 25% of dialysis patients receiving PD by 2018. METHODS: A rapid improvement process was introduced, as a quality improvement tool, to increase and sustain the PD programme. With multidisciplinary team support for PD growth, a nephrologist was trained to insert PD catheters. Nurses were trained to provide patients with balanced pre-dialysis information and discuss alternative dialysis modalities with haemodialysis (HD) patients. The "Acceptance, Choice and Empowerment" project raised awareness of home therapy choices, using a peer educator model specifically for ethnic minority patients. Lean methodologies were used to ensure continuous quality improvement. RESULTS: PD uptake increased from 37 to 84 patients, giving a PD penetration increase from 8.4% to 19.1% between April 2014 and March 2018. Catheter insertions increased from 94 at the end of QI Period 1 to 185 at the end of QI Period 2, representing a 97% increase, with the medical/surgical split remaining stable. Peritonitis rates remained stable, and PD drop off to HD reduced from 52% to 41% during the same period. CONCLUSIONS: By implementing a rapid improvement process and embedding a quality improvement programme, the number of incidents and prevalent PD patients increased and was sustained.


Subject(s)
Kidney Failure, Chronic , Peritoneal Dialysis , Humans , Kidney Failure, Chronic/therapy , Quality Improvement , Ethnicity , Minority Groups , Renal Dialysis , United Kingdom
8.
J Antimicrob Chemother ; 76(8): 2172-2181, 2021 07 15.
Article in English | MEDLINE | ID: mdl-33993273

ABSTRACT

BACKGROUND: Pseudomonas aeruginosa bacteraemia is a common and serious infection. No consensus exists regarding whether definitive combination therapy is superior to monotherapy. We aimed to evaluate the impact of combination therapy on mortality. METHODS: This was a multicentre retrospective study (nine countries, 25 centres), including 1277 patients with P. aeruginosa bacteraemia during 2009-15. We evaluated the association between ß-lactam plus aminoglycoside or quinolone combination therapy versus ß-lactam monotherapy and mortality. The primary outcome was 30 day all-cause mortality. Univariate and multivariate Cox regression analyses were conducted, introducing combination as a time-dependent variable. Propensity score was conducted to adjust for confounding for choosing combination therapy over monotherapy. RESULTS: Of 1119 patients included, 843 received definitive monotherapy and 276 received combination therapy (59% aminoglycoside and 41% quinolone). Mortality at 30 days was 16.9% (189/1119) and was similar between combination (45/276; 16.3%) and monotherapy (144/843; 17.1%) groups (P = 0.765). In multivariate Cox regression, combination therapy was not associated with reduced mortality (HR 0.98, 95% CI 0.64-1.53). No advantage in terms of clinical failure, microbiological failure or recurrent/persistent bacteraemia was demonstrated using combination therapy. Likewise, adverse events and resistance development were similar for the two regimens. CONCLUSIONS: In this retrospective cohort, no mortality advantage was demonstrated using combination therapy over monotherapy for P. aeruginosa bacteraemia. Combination therapy did not improve clinical or microbiological failure rates, nor affect adverse events or resistance development. Our finding of no benefit with combination therapy needs confirmation in well-designed randomized controlled trials.


Subject(s)
Bacteremia , Pseudomonas Infections , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Cohort Studies , Drug Therapy, Combination , Humans , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa , Retrospective Studies , Treatment Outcome
9.
Clin Infect Dis ; 70(11): 2270-2280, 2020 05 23.
Article in English | MEDLINE | ID: mdl-31323088

ABSTRACT

BACKGROUND: The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Although ß-lactam monotherapy is common, data to guide the choice between antibiotics are scarce. We aimed to compare ceftazidime, carbapenems, and piperacillin-tazobactam as definitive monotherapy. METHODS: A multinational retrospective study (9 countries, 25 centers) including 767 hospitalized patients with P. aeruginosa bacteremia treated with ß-lactam monotherapy during 2009-2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate, including propensity-adjusted, analyses were conducted introducing monotherapy type as an independent variable. RESULTS: Thirty-day mortality was 37/213 (17.4%), 42/210 (20%), and 55/344 (16%) in the ceftazidime, carbapenem, and piperacillin-tazobactam groups, respectively. Type of monotherapy was not significantly associated with mortality in either univariate, multivariate, or propensity-adjusted analyses (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.52-2.46, for ceftazidime; OR, 1.3; 95% CI, 0.67-2.51, for piperacillin-tazobactam, with carbapenems as reference in propensity adjusted multivariate analysis; 542 patients). No significant difference between antibiotics was demonstrated for clinical failure, microbiological failure, or adverse events. Isolation of P. aeruginosa with new resistance to antipseudomonal drugs was significantly more frequent with carbapenems (36/206 [17.5%]) versus ceftazidime (25/201 [12.4%]) and piperacillin-tazobactam (28/332 [8.4%] (P = .007). CONCLUSIONS: No significant difference in mortality, clinical, and microbiological outcomes or adverse events was demonstrated between ceftazidime, carbapenems, and piperacillin-tazobactam as definitive treatment of P. aeruginosa bacteremia. Higher rates of resistant P. aeruginosa after patients were treated with carbapenems, along with the general preference for carbapenem-sparing regimens, suggests using ceftazidime or piperacillin-tazobactam for treating susceptible infection.


Subject(s)
Pseudomonas Infections , Pseudomonas aeruginosa , Anti-Bacterial Agents/therapeutic use , Carbapenems/therapeutic use , Ceftazidime/therapeutic use , Humans , Microbial Sensitivity Tests , Penicillanic Acid/therapeutic use , Piperacillin/therapeutic use , Pseudomonas Infections/drug therapy , Retrospective Studies
10.
Aust Prescr ; 43(2): 45-48, 2020 04.
Article in English | MEDLINE | ID: mdl-32346210

ABSTRACT

Intravenous antibiotics are overused in hospitals. Many infections can be managed with oral antibiotics Oral antibiotics avoid the adverse effects of intravenous administration. They are also usually less expensive When intravenous antibiotics are indicated, it may be possible to switch to oral therapy after a short course. There are guidelines to aid the clinician with the timing of the switch so that there is no loss of efficacy Infections that may be suitable for a short course of intravenous antibiotic include pneumonia, complicated urinary tract infections, certain intra-abdominal infections, Gram-negative bacteraemia, acute exacerbations of chronic lung disease, and skin and soft tissue infections Bone and joint infections and infective endocarditis are managed with prolonged courses of intravenous antibiotics. However, there is research looking at the feasibility of an earlier switch to oral antibiotics in these conditions

11.
Psychooncology ; 26(11): 1860-1865, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28195672

ABSTRACT

OBJECTIVE: Breast reconstruction is associated with multiple psychological benefits. However, few studies have identified clinical and psychological factors associated with improved satisfaction and quality of life. This study examined factors, which predict satisfaction with breast appearance, outcome satisfaction and quality of life following post-mastectomy breast reconstruction. METHODS: Women who underwent post-mastectomy breast reconstruction between 2010 and 2016 received a postal questionnaire consisting of The BREAST-Q Patient Reported Outcomes Instrument, The European Organisation for Research and Treatment of Cancer QLQ-30 Questionnaire, The Patient and Observer Scar Assessment Scale, and a series of Visual-Analogue Scales. One hundredforty-eight women completed the questionnaire, a 56% response rate. RESULTS: Hierarchical multiple regression analyses revealed psychosocial factors accounted for 75% of the variance in breast satisfaction, 68% for outcome satisfaction, and 46% forquality of life. Psychosocial well-being emerged as a significant predictor of satisfaction with breast appearance (ß = .322) and outcome satisfaction (ß = .406). Deep inferior epigastric perforator flap patients reported greater satisfaction with breast appearance (ß = .120) and outcome satisfaction (ß = .167). CONCLUSIONS: This study extends beyond the limited research by distinguishing between satisfaction with breast appearance and outcome satisfaction. The study provides evidence for the role of psychosocial factors predicting key patient reported outcomes and demonstrates the importance of psychosocial well-being and reconstruction type. The findings also highlight the need for healthcare providers to consider the psychosocial well-being of patients both preoperatively and post operatively and provide preliminary evidence for the use of deep inferior epigastric perforator reconstructions over other types of reconstructive procedures.


Subject(s)
Breast Neoplasms/psychology , Mammaplasty/methods , Mammaplasty/psychology , Mastectomy/psychology , Personal Satisfaction , Quality of Life/psychology , Adult , Aged , Breast Neoplasms/surgery , Female , Humans , Middle Aged , Surveys and Questionnaires , Treatment Outcome
14.
Curr Diab Rep ; 15(11): 101, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26411924

ABSTRACT

Diabetes distress (DD) represents a significant clinical burden in which levels of DD are related to both glycated haemoglobin (HbA1c) and some self-management behaviours. DD is related to, but different from, depression. Differences in DD experienced in people with type 1 and type 2 diabetes have been observed. Commonly measured using the Problem Areas in Diabetes Scale (PAID) and the Diabetes Distress Scale (DDS), rates of elevated DD in research study participants range from 20 to 30 %. Risk factors for elevated DD in type 1 diabetes are longer duration of diabetes, severe hypoglycaemia, younger age and being female. A systematic review of intervention studies assessing DD identified eight randomised controlled trials (RCTs) and nine pre-post design studies. Only three studies targeted DD with the intervention. Intervention types were diabetes self-management education (DSME), psychologically informed self-management and devices. DSME pre-post studies, namely the Dose Adjustment For Normal Eating (DAFNE) programme, produced more consistent improvements in DD and HbA1c at follow-up. Psychologically informed self-management was more heterogeneous, but several RCTs were effective in reducing DD. Group interventions offered the greatest benefits across intervention designs.


Subject(s)
Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 2/therapy , Glycated Hemoglobin/analysis , Humans , Hypoglycemia , Self Care
15.
Semin Respir Crit Care Med ; 36(1): 44-55, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25643270

ABSTRACT

Pseudomonas aeruginosa is a formidable pathogen in the infection arena. It is able to easily adapt to the environment which it inhabits and can also colonize and invade the human host to cause serious infections. In 2011, it was responsible for 7.1% of all health care-associated infection in the United States. The morbidity and mortality of both blood stream infections and ventilator-associated pneumonia are significant. On a global scale, we have seen the development of not only multidrug resistance but also extensive and pan drug resistance in this organism. This is often associated with limited clonal types of which we now have epidemiological evidence of spread. With this has come reduced antibiotic treatment options. Consideration of antibiotic infusions, combination therapy, and inhalational therapy has occurred in an attempt to gain the upper ground. Gram-negative resistance has appropriately been described as a global emergency.


Subject(s)
Drug Resistance, Bacterial , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/pathogenicity , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Bacteremia/microbiology , Humans , Pneumonia, Ventilator-Associated/drug therapy , Pneumonia, Ventilator-Associated/microbiology , Pseudomonas Infections/microbiology
16.
Diagnostics (Basel) ; 14(1)2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38201422

ABSTRACT

BACKGROUND: Pneumocystis jirovecii pneumonia is increasingly diagnosed with highly sensitive PCR diagnostics in immunocompromised, HIV-negative individuals. We assessed the performance of our in-house quantitative PCR with the aim to optimise interpretation. METHODS: Retrospective audit of all positive P. jirovecii qPCRs on induced sputum or BAL fluid at a single centre from 2012 to 2023. Medical and laboratory records were analysed and people with HIV were excluded. Cases were categorised as colonisation, high-probability PCP or uncertain PCP infection against a clinical gold standard incorporating clinico-radiological data. Quantitative PCR assay targeting the 5s gene was utilised throughout the time period. RESULTS: Of the 82 positive qPCRs, 28 were categorised as high-probability PCP infection, 30 as uncertain PCP and 24 as colonisation. There was a significant difference in qPCR values stratified by clinical category but not respiratory sample type. Current assay performance with a cutoff of 2.5 × 105 copies/mL had a sensitivity of 50% (95% CI, 30.65-69.35%) and specificity of 83.33% (95% CI, 62.62-95.26%). Youden Index calculated at 6.5 × 104 copies/mL had a sensitivity of 75% (56.64-87.32%, 95% CI) and specificity of 66.67% (46.71-82.03%, 95% CI). High and low cutoffs were explored. Significant variables associated with infection were age > 70 years old, the presence of fever, hypoxia or ground glass changes. CONCLUSIONS: A single qPCR cutoff cannot reliably determine P. jirovecii infection from colonisation. Low and high cutoffs are useful, however, a large "possible infection" cohort will remain where interpretation of clinic-radiological factors remains essential. Standardisation of assays with prospective validation in specific immunocompromised groups will allow greater generalisability and allow large-scale prospective assay validation to be performed.

17.
Genome Med ; 16(1): 78, 2024 06 07.
Article in English | MEDLINE | ID: mdl-38849863

ABSTRACT

BACKGROUND: Antimicrobial resistance (AMR) is an intensifying threat that requires urgent mitigation to avoid a post-antibiotic era. Pseudomonas aeruginosa represents one of the greatest AMR concerns due to increasing multi- and pan-drug resistance rates. Shotgun sequencing is gaining traction for in silico AMR profiling due to its unambiguity and transferability; however, accurate and comprehensive AMR prediction from P. aeruginosa genomes remains an unsolved problem. METHODS: We first curated the most comprehensive database yet of known P. aeruginosa AMR variants. Next, we performed comparative genomics and microbial genome-wide association study analysis across a Global isolate Dataset (n = 1877) with paired antimicrobial phenotype and genomic data to identify novel AMR variants. Finally, the performance of our P. aeruginosa AMR database, implemented in our AMR detection and prediction tool, ARDaP, was compared with three previously published in silico AMR gene detection or phenotype prediction tools-abritAMR, AMRFinderPlus, ResFinder-across both the Global Dataset and an analysis-naïve Validation Dataset (n = 102). RESULTS: Our AMR database comprises 3639 mobile AMR genes and 728 chromosomal variants, including 75 previously unreported chromosomal AMR variants, 10 variants associated with unusual antimicrobial susceptibility, and 281 chromosomal variants that we show are unlikely to confer AMR. Our pipeline achieved a genotype-phenotype balanced accuracy (bACC) of 85% and 81% across 10 clinically relevant antibiotics when tested against the Global and Validation Datasets, respectively, vs. just 56% and 54% with abritAMR, 58% and 54% with AMRFinderPlus, and 60% and 53% with ResFinder. ARDaP's superior performance was predominantly due to the inclusion of chromosomal AMR variants, which are generally not identified with most AMR identification tools. CONCLUSIONS: Our ARDaP software and associated AMR variant database provides an accurate tool for predicting AMR phenotypes in P. aeruginosa, far surpassing the performance of current tools. Implementation of ARDaP for routine AMR prediction from P. aeruginosa genomes and metagenomes will improve AMR identification, addressing a critical facet in combatting this treatment-refractory pathogen. However, knowledge gaps remain in our understanding of the P. aeruginosa resistome, particularly the basis of colistin AMR.


Subject(s)
Genome, Bacterial , Pseudomonas aeruginosa , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/drug effects , Drug Resistance, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Humans , Genomics/methods , Pseudomonas Infections/microbiology , Pseudomonas Infections/drug therapy , Microbial Sensitivity Tests , Databases, Genetic , Phenotype
18.
BMJ Open ; 14(7): e084313, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013653

ABSTRACT

INTRODUCTION: Peripheral intravenous catheters (PIVCs) are the most commonly used vascular access device in hospitalised patients. Yet PIVCs may be complicated by local or systemic infections leading to increased healthcare costs. Chlorhexidine gluconate (CHG)-impregnated dressings may help reduce PIVC-related infectious complications but have not yet been evaluated. We hypothesise an impregnated CHG transparent dressing, in comparison to standard polyurethane dressing, will be safe, effective and cost-effective in protecting against PIVC-related infectious complications and phlebitis. METHODS AND ANALYSIS: The ProP trial is a multicentre, superiority, randomised clinical and cost-effectiveness trial with internal pilot, conducted across three centres in Australia and France. Patients (adults and children aged ≥6 years) requiring one PIVC for ≥48 hours are eligible. We will exclude patients with emergent PIVCs, known CHG allergy, skin injury at site of insertion or previous trial enrolment. Patients will be randomised to 3M Tegaderm Antimicrobial IV Advanced Securement dressing or standard care group. For the internal pilot, 300 patients will be enrolled to test protocol feasibility (eligibility, recruitment, retention, protocol fidelity, missing data and satisfaction of participants and staff), primary endpoint for internal pilot, assessed by independent data safety monitoring committee. Clinical outcomes will not be reviewed. Following feasibility assessment, the remaining 2624 (1312 per trial arm) patients will be enrolled following the same methods. The primary endpoint is a composite of catheter-related infectious complications and phlebitis. Recruitment began on 3 May 2023. ETHICS AND DISSEMINATION: The protocol was approved by Ouest I ethic committee in France and by The Queensland Children's Hospital Human Research Ethics Committee in Australia. The findings will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05741866.


Subject(s)
Bandages , Catheter-Related Infections , Catheterization, Peripheral , Chlorhexidine , Adult , Child , Humans , Anti-Infective Agents, Local/administration & dosage , Australia , Catheter-Related Infections/prevention & control , Catheterization, Peripheral/adverse effects , Catheterization, Peripheral/methods , Chlorhexidine/analogs & derivatives , Chlorhexidine/administration & dosage , Chlorhexidine/therapeutic use , Cost-Benefit Analysis , France , Phlebitis/prevention & control , Phlebitis/etiology , Randomized Controlled Trials as Topic
19.
Medicine (Baltimore) ; 102(13): e32662, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-37000062

ABSTRACT

Pseudomonas aeruginosa infective endocarditis (IE) is a rare disease associated with high mortality and complications. Here, we describe a contemporary set of patients aiming to improve the understanding of risk factors, clinical features, treatments, and outcomes. This retrospective case series reviewed cases from 3 tertiary metropolitan hospitals between January 1999 and January 2019. prespecified data were collected for each case, with a review of risk factors, valve involvement, acquisition, treatment, and complications. Fifteen patients were identified over a 20 years period. All patients presented with fever, 5/15 had preexisting prosthetic valve with valvular heart disease in 7/15 patients making it the most common risk factor. Intravenous drug use (IVDU) was the source in only 6/15 cases with healthcare associated infection and left-sided valvular involvement being more common than previous reports both occurring in 9/15 cases. Complications occurred in 11/15 patients with a 30 days mortality of 13%. Surgery was performed in 7/15 patients and 9/15 patients received antibiotic combination therapy. One year mortality was higher in those with increasing age, comorbidities, left-sided valve involvement, presence of predefined complications, and antibiotic monotherapy. Development of resistance occurred in 2 cases that received monotherapy. P aeruginosa IE remains a rare disease with high mortality and secondary complications.


Subject(s)
Endocarditis, Bacterial , Endocarditis , Humans , Pseudomonas aeruginosa , Retrospective Studies , Rare Diseases , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/drug therapy , Endocarditis, Bacterial/surgery , Endocarditis/diagnosis , Endocarditis/drug therapy , Anti-Bacterial Agents/therapeutic use
20.
Infect Dis Health ; 28(4): 259-264, 2023 11.
Article in English | MEDLINE | ID: mdl-37142538

ABSTRACT

BACKGROUND: Midline catheter (MC) use has increased in acute-care settings, particularly for patients with difficult venous access or requiring peripherally compatible intravenous therapy for up-to 14 days. Our aim was to assess feasibility and generate clinical data comparing MCs with Peripherally Inserted Central Catheters (PICCs). METHODS: A two-arm parallel group pilot randomised controlled trial (RCT), comparing MCs with PICCs, was conducted in a large tertiary hospital in Queensland between September 2020 and January 2021. The primary outcome was study feasibility, measured against rates of eligibility (>75%), consent (>90%), attrition (<5%); protocol adherence (>90%) and missing data (<5%). The primary clinical outcome was all-cause device failure. RESULTS: In total, 25 patients were recruited. The median patient age was 59-62 years; most patients were overweight/obese, with ≥2 co-morbidities. PRIMARY OUTCOMES: The eligibility and protocol adherence criteria were not met; of 159 screened patients, only 25 (16%) were eligible, and three patients did not receive their allocated intervention post-randomisation (88% adherence). All-cause failure occurred in two patients allocated to MC (20%) and one PICC (8.3%). CONCLUSIONS: Our study found that a fully powered RCT testing MCs compared with PICCs is not currently feasible in our setting. We recommend a robust process evaluation before the introduction of MCs into clinical practice.


Subject(s)
Catheterization, Central Venous , Central Venous Catheters , Humans , Middle Aged , Catheterization, Central Venous/adverse effects , Catheterization, Central Venous/methods , Pilot Projects , Central Venous Catheters/adverse effects , Catheters, Indwelling/adverse effects , Patients
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