On the importance of population-based serological surveys of SARS-CoV-2 without overlooking their inherent uncertainties

The SARS-CoV-2 epidemic has caused an unprecedented public health situation and more than ever it is important to be well informed on methods to monitor and analyse the progression of the epidemic. This brief note aims to explain the scope in conducting large-scale serological surveys of SARS-CoV-2 to define the landscape of population immunity, without overlooking the inherent uncertainty steaming from sampling design and diagnostic validity. The note completes with a succinct appendix of simple statistical methods for estimating prevalence from random population samples using imperfect diagnostic tests

Evaluation of health-related quality of life in patients receiving outpatient parenteral antimicrobial therapy (OPAT) in a UK setting

Background Studies assessing the benefits of outpatient parenteral antimicrobial therapy (OPAT) have paid less attention to patient-centered factors such as patients’ experiences and their health-related quality of life (HRQoL). Research design and methods Prospective before-and-after quasi-experimental study enrolled adult patients receiving OPAT at a tertiary hospital in Derbyshire, UK, between October 2022 and October 2023. Consenting patients completed paired EQ-5D-3 L questionnaires before OPAT initiation and upon completion of therapy or 30 days after its commencement (whichever occurred first). Changes and predictors of change in HRQoL indicators and associations with clinical outcomes (treatment failure, adverse events, and 30-day unplanned readmission) were examined. Results Health state index and visual analogue scale (EQ VAS) scores of 162 enrolled patients at baseline were significantly lower than the UK population averages, but the patients experienced significant improvements in both scores and in four EQ-5D dimensions (mobility, self-care, usual activities, and pain/discomfort). Baseline health index and EQ VAS scores were significant independent predictors of positive changes in HRQoL scores. Conclusions OPAT is associated with improved patient-reported quality of life and facilitates early return to work or school. Nevertheless, it is crucial to closely monitor patients with a lower baseline quality of life to optimize their overall OPAT experience

Editorial for the special issue: “Epidemiology, prognosis and antimicrobial treatment of extensively antibiotic-resistant bacterial infections”

The increasing consumption of broad-spectrum antimicrobials is fuelling a vicious cycle leading to extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria [...

Cefiderocol: systematic review of mechanisms of resistance, heteroresistance and in vivo emergence of resistance

Cefiderocol appears promising, as it can overcome most β-lactam resistance mechanisms (including β-lactamases, porin mutations, and efflux pumps). Resistance is uncommon according to large multinational cohorts, including against isolates resistant to carbapenems, ceftazidime/avibactam, ceftolozane/tazobactam, and colistin. However, alarming proportions of resistance have been reported in some recent cohorts (up to 50%). A systematic review was conducted in PubMed and Scopus from inception to May 2022 to review mechanisms of resistance, prevalence of heteroresistance, and in vivo emergence of resistance to cefiderocol during treatment. A variety of mechanisms, typically acting in concert, have been reported to confer resistance to cefiderocol: β-lactamases (especially NDM, KPC and AmpC variants conferring resistance to ceftazidime/avibactam, OXA-427, and PER- and SHV-type ESBLs), porin mutations, and mutations affecting siderophore receptors, efflux pumps, and target (PBP-3) modifications. Coexpression of multiple β-lactamases, often in combination with permeability defects, appears to be the main mechanism of resistance. Heteroresistance is highly prevalent (especially in A. baumannii), but its clinical impact is unclear, considering that in vivo emergence of resistance appears to be low in clinical studies. Nevertheless, cases of in vivo emerging cefiderocol resistance are increasingly being reported. Continued surveillance of cefiderocol’s activity is important as this agent is introduced in clinical practice

Risk of venous thromboembolism in outpatient parenteral antimicrobial therapy (OPAT): a systematic review and meta-analysis

The risk of venous thromboembolism (VTE) in outpatient parenteral antimicrobial therapy (OPAT) is not fully understood and the optimal strategy for thromboprophylaxis remains unclear. This systematic review investigated the incidence of VTE in OPAT settings (PROSPERO CRD42022381523). MEDLINE, CINAHL, EMCARE, EMBASE, Cochrane Library and grey literature were searched from earliest records to 18 January 2023. Eligible were primary studies reporting non-catheter-related or catheter-related thromboembolic (CRT) events in adults who received parenteral antibiotics in home or outpatient settings. In all, 43 studies involving 23,432 patient-episodes were reviewed. Four studies reported non-catheter related VTE while 39 included CRT. Based on generalised linear mixed-effects models, pooled risk estimates of non-catheter-related VTE and CRT were 0.2% (95% confidence interval [CI], 0.0 - 0.7%) and 1.1% (95% CI, 0.8 - 1.5%; prediction interval [PI], 0.2 - 5.4%), respectively. Heterogeneity was largely attributed to risk of bias by meta-regression (R2 = 21%). Excluding high-risk studies, CRT risk was 0.8% (95% CI, 0.5 - 1.2%; PI, 0.1 - 4.5%). From 25 studies, pooled CRT rate per 1,000 catheter-days was 0.37 (95% CI, 0.25 - 0.55; PI, 0.08 - 1.64). Our findings do not support universal thromboprophylaxis nor routine use of inpatient VTE risk assessment model in the OPAT setting. However, high index of suspicion should be maintained, especially for patients with known risk factors for VTE. An optimised protocol of OPAT-specific VTE risk assessment should be sought

Effectiveness and safety of a disposable elastomeric continuous infusion pump for outpatient parenteral antimicrobial therapy (OPAT) in a UK setting

We evaluated the effectiveness and safety of continuous antimicrobial infusion using a disposable elastomeric device in an outpatient parenteral antimicrobial therapy (OPAT) setting. We conducted a retrospective analysis of all patients who received either flucloxacillin (n = 131 episodes) or piperacillin/tazobactam (n = 301 episodes) as continuous infusion via elastomeric devices over 5 years (January 2018-December 2022) at a tertiary referral hospital in Derbyshire, UK. Overall, 81 adverse events were recorded in 77 (18%; 77/432) patient-episodes. Most adverse events were vascular access-related (59%; 4.6 events per 1000 OPAT-days), including one line-related infection (0.2%; 0.1 events per 1000 OPAT-days). 165 (38%) patient-episodes experienced at least one incident of incomplete infusion. Successful outcome (cure or improvement) occurred in 364 (84%) episodes. Our findings suggest that elastomeric infusion pumps are safe and effective for administering selected antimicrobial agents in OPAT. However, close monitoring of patients and the device are essential to ensure optimal delivery of prescribed therapy

Effectiveness of telemedicine in outpatient parenteral antimicrobial therapy (Tele-OPAT): a systematic review

Introduction: Telemedicine is increasingly used to deliver healthcare in many clinical specialities. However, the adoption of telemedicine in the delivery of outpatient parenteral antimicrobial therapy (OPAT) has been relatively slow and limited. This study aims to collate current evidence for telemedicine in OPAT regarding clinical efficacy, safety, acceptability and cost-effectiveness. Methods: We systematically searched the Cochrane Library, CINAHL, EMCARE, EMBASE and MEDLINE databases through 24 July 2022, for relevant studies published in English. Research articles and conference abstracts were included if they involved any form of telephone or video consultation in delivering parenteral antibiotics in the home or outpatient setting. Study findings were synthesised into three main themes: patient outcomes and safety, patient and provider satisfaction and cost-effectiveness. The mixed methods appraisal tool was used to review the methodological quality of the studies. PROSPERO CRD42022342874 Results: The literature search yielded 311 articles, of which 12 (five full-length articles and seven conference abstracts) reporting over 1245 telemedicine interventions were reviewed. The reported outcomes were heterogeneous. Telemedicine was cost-effective and associated with high patient satisfaction and comparable complication rates compared to conventional OPAT. Considering six comparative studies, rehospitalisation risk was lower for telemedicine than conventional OPAT (risk ratio, 0.58; 95% confidence interval, 0.38–0.88; I2  =  31%). Discussion: The results of this review demonstrate that telemedicine has a role in delivering safe and cost-effective OPAT care, especially for patients residing in remote and geographically isolated locations. Nevertheless, high-quality studies and publication of existing data and experiences are needed to further validate this model of care delivery

Pandrug-resistant Gram-negative bacteria : a systematic review of current epidemiology, prognosis and treatment options

Background: The literature on the epidemiology, mortality and treatment of pandrug-resistant (PDR) Gram-negative bacteria (GNB) is scarce, scattered and controversial. Objective: To consolidate the relevant literature and identify treatment options for PDR GNB infections. Methods: A systematic search in MEDLINE, Scopus and clinical trial registries was conducted. Studies reporting PDR clinical isolates were eligible for review if susceptibility testing for all major antimicrobials had been performed. Characteristics and findings of retrieved studies were qualitatively synthesized. Results: Of 81 studies reviewed, 47 (58%) were published in the last 5 years. The reports reflected a worldwide dissemination of PDR GNB in 25 countries in 5 continents. Of 526 PDR isolates reported, Pseudomonas aeruginosa (n=175), Acinetobacter baumannii (n=172) and Klebsiella pneumoniae (n=125) were most common. PDR GNB were typically isolated in intensive care units, but several studies demonstrated wider outbreak potential, including dissemination to long-term care facilities and international spread. All-cause mortality was high (range, 20%-71%), but appeared to be substantially reduced in studies reporting treatment regimens active in vitro. No controlled trial has been performed to date, but several case reports and series noted successful use of various regimens, predominantly synergistic combinations, and in selected patients increased exposure regimens and newer antibiotics. Conclusion: PDR GNB are increasingly being reported worldwide and are associated with high mortality. Several treatment regimens have been successfully used, of which synergistic combinations appear to be most promising and often the only available option. More pharmacokinetic/pharmacodynamic and outcome studies are needed to guide the use of synergistic combinations

Palliative outpatient parenteral antimicrobial therapy (OPAT): a single center experience and systematic scoping review

Traditionally, outpatient parenteral antimicrobial therapy (OPAT) is used to treat infections with predictable course and anticipated response to therapy. However, there has been little consideration of OPAT for palliation as opposed to cure. This study presents a scoping review of literature and the experience of palliative OPAT at a tertiary referral hospital in Derbyshire, UK. Over the 5.5-year study period, six patients received OPAT for palliation (mean age 61 years). They accounted for 0.6 % (6/1044) and 3.1 % (1135/36658) of the total numbers of OPAT patients and bed-days saved, respectively. The literature search yielded 2375 articles, of which 5 case studies were eligible for review. Palliative OPAT provided positive experiences and outcomes for patients and their families. However, delivering palliative OPAT could be complex, time-consuming, and associated with clinical complications. There is a need for more research to address significant gaps in knowledge, especially regarding patient experiences and perspectives