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INTRODUCTION: The global need for antifungal stewardship is driven by spreading antimicrobial and antifungal resistance. Triazoles are the only oral and relatively well-tolerated class of antifungal medications, and usage is associated with acquired resistance and species replacement with intrinsically resistant organisms. On a per-patient basis, hematology patients are the largest inpatient consumers of antifungal drugs, but are also the most vulnerable to invasive fungal disease. AREAS COVERED: In this review we discuss available and forthcoming antifungal drugs, antifungal prophylaxis and empiric antifungal therapy, and how a screening based and diagnostic-driven approach may be used to reduce antifungal consumption. Finally, we discuss components of an antifungal stewardship program, interventions that can be employed, and how impact can be measured. The search methodology consisted of searching PubMed for journal articles using the term antifungal stewardship plus program, intervention, performance measure or outcome before 1 January 2024. EXPERT OPINION: Initial focus should be on implementing effective antifungal stewardship programs by developing and implementing local guidelines and using interventions, such as post-prescription review and feedback, which are known to be effective. Technologies such as microbiome analysis and machine learning may allow the development of truly individualized risk-factor-based approaches to antifungal stewardship in the future.
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Antifungal Agents , Humans , Antifungal Agents/therapeutic use , Antimicrobial Stewardship/methods , Drug Resistance, Fungal , Mycoses/drug therapy , Leukemia/drug therapy , Invasive Fungal Infections/drug therapyABSTRACT
BACKGROUND: Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and ß-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing). METHODS: BioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC). The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking. The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed. DISCUSSION: The BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship. TRIAL REGISTRATION: ISRCTN11633399. Registered 24/06/2022.
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Antifungal Agents , Biomarkers , Cost-Benefit Analysis , Invasive Fungal Infections , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Humans , Antifungal Agents/therapeutic use , Antifungal Agents/economics , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/prevention & control , Invasive Fungal Infections/diagnosis , Biomarkers/blood , Galactose/analogs & derivatives , Mannans , Treatment Outcome , beta-Glucans , Antimicrobial Stewardship , Leukemia/drug therapy , Time Factors , Cost-Effectiveness AnalysisABSTRACT
Introduction: The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods: A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results: A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4â¯% and 85â¯% respectively between the JI Panel and synovial fluid cultures (SFCs). The JI Panel detected more positive samples and microorganisms than SFC, with a notable difference on Staphylococcus aureus, Streptococcus species, Enterococcus faecalis, Kingella kingae, Neisseria gonorrhoeae, and anaerobic bacteria. The study found that the BIOFIRE JI Panel has a high utility in the real-world clinical setting for suspected SA and PJI, providing diagnostic results in approximately 1â¯h. The user experience was positive, implying a potential benefit of rapidity of results' turnover in optimising patient management strategies. Conclusion: The study suggests that the BIOFIRE JI Panel could potentially optimise patient management and antimicrobial therapy, thus highlighting its importance in the clinical setting.
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Rapidly detecting and identifying pathogens is crucial for appropriate antimicrobial therapy in patients with sepsis. Conventional diagnostic methods have been a great asset to medicine, though they are time consuming and labor intensive. This work will enable healthcare professionals to understand the bacterial community better and enhance their diagnostic capacity by using novel molecular methods that make obtaining quicker, more precise results possible. The authors discuss and critically assess the merits and drawbacks of molecular testing and the added value of these tests, including the shift turnaround time, the implication for clinicians' decisions, gaps in knowledge, future research directions and novel insights or innovations. The field of antimicrobial molecular testing has seen several novel insights and innovations to improve the diagnosis and management of infectious diseases.
Sepsis is a life-threatening reaction to an infection. This infection is normally caused by a bacteria. Identifying the bacteria that has caused the infection is very important to choosing the best treatment. This is usually done using molecular testing. This article discusses the advantages and disadvantages of molecular testing, which tests are available and the value of these tests in clinical practice, the implication of molecular tests for clinicians' decisions and the gaps in our knowledge. It also discusses future innovations in molecular testing.
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Anti-Infective Agents , Sepsis , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Sepsis/diagnosis , Sepsis/drug therapy , Sepsis/microbiology , Bacteria/genetics , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Time FactorsABSTRACT
INTRODUCTION: Pneumococcal disease (PD) significantly contributes to morbidity and mortality, carrying substantial economic and public health burden. This article is a targeted review of evidence for pneumococcal vaccination in the UK, the definitions of groups at particular risk of PD and vaccine effectiveness. AREAS COVERED: Relevant evidence focusing on UK data from surveillance systems, randomized controlled trials, observational studies and publicly available government documents is collated and reviewed. Selected global data are included where appropriate. EXPERT OPINION: National vaccination programs have reduced the incidence of vaccine-type PD, despite the rising prominence of non-vaccine serotypes in the UK. The introduction of higher-valency conjugate vaccines provides an opportunity to improve protection against PD for adults in risk groups. Several incentives are in place to encourage general practitioners to vaccinate risk groups, but uptake is low-suboptimal particularly among at-risk individuals. Wider awareness and understanding among the public and healthcare professionals may increase vaccination uptake and coverage. National strategies targeting organizational factors are urgently needed to achieve optimal access to vaccines. Finally, identifying new risk factors and approaches to risk assessment for PD are crucial to ensure those at risk of PD can benefit from pneumococcal vaccination.
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Pneumococcal Infections , Vaccination Coverage , Adult , Humans , Pneumococcal Vaccines , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Vaccination , United Kingdom/epidemiology , Vaccines, Conjugate , Risk FactorsABSTRACT
Aims: The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit. Methods: We analyzed the retrospective record review from 2014 to 2020 of patients with long bone COM. All were managed by multidisciplinary infection team (MDT) protocol. Adequate debridement was employed for all cases, and no case of wide resection was included. Results: A total of 53 patients (54 bones) with median age of 45.5 years (interquartile range 31 to 55) and mean follow-up of 29 months (12 to 59) were included. In all, ten bones were Cierny-Mader type I, 39 were type III, and five were type IV. All patients were treated with single-staged management, except for one (planned two-stage stabilization). Positive microbial cultures grew in 75%. Overall, 46 cases (85%) had resolution of COM after index procedure, and 49 (90.7%) had resolution on last follow-up. Four patients (7%) underwent second surgical procedure and six patients (11%) had complications. Conclusion: We challenge the need for wide tumour-like resection in all cases of COM. Through detailed preoperative evaluation and planning with MDT approach, adequate debridement and local delivery of high concentration of antibiotic appears to provide comparable outcomes versus radical debridement.
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Septic arthritis is a serious condition with significant morbidity and mortality, routinely diagnosed using culture. The FDA has recently approved the rapid molecular BioFire® Joint Infection Panel (BJIP) for synovial fluid. We aimed to evaluate the BJIP compared to culture and its potential use in patient management. A multicentre retrospective evaluation of BJIP was conducted in the UK and Ireland. Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated between the BJIP and routine culture. A multidisciplinary team (MDT) discussion addressing the optimal or potential case use of the assay practice was facilitated. Three hundred ninety-nine surplus synovial fluid samples (~ 70% from native joints) from eight centres were processed using BJIP in addition to routine culture. An increased yield of positive results was detected using BJIP compared to routine culture (98 vs 83), giving an overall PPA of 91.6% and overall NPA of 93% for the BJIP compared to culture results. The BJIP detected resistant markers and additional organisms that could influence antibiotic choices including Neisseria gonorrhoeae and Kingella kingae. The MDT agreed that the assay could be used, in addition to standard methods, in adult and children patients with specialist advice use based on local needs. Rapid results from BJIP were assessed as having potential clinical impact on patient management. Organisms not included in the panel may be clinically significant and may limit the value of this test for PJI.
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Arthritis, Infectious , Kingella kingae , Child , Adult , Humans , Retrospective Studies , Arthritis, Infectious/diagnosis , Arthritis, Infectious/microbiology , Polymerase Chain Reaction , Synovial Fluid/microbiology , Kingella kingae/geneticsABSTRACT
OBJECTIVES: To analyse the adherence and impact of quality-of-care indicators (QCIs) in the management of Staphylococcus aureus bloodstream infection in a prospective and multicentre cohort. METHODS: Analysis of the prospective, multicentre international S. Aureus Collaboration cohort of S. Aureus bloodstream infection cases observed between January 2013 and April 2015. Multivariable analysis was performed to evaluate the impact of adherence to QCIs on 90-day mortality. RESULTS: A total of 1784 cases were included. Overall, 90-day mortality was 29.9% and mean follow-up period was 118 days. Adherence was 67% (n = 1180/1762) for follow-up blood cultures, 31% (n = 416/1342) for early focus control, 77.6% (n = 546/704) for performance of echocardiography, 75.5% (n = 1348/1784) for adequacy of targeted antimicrobial therapy, 88.6% (n = 851/960) for adequacy of treatment duration in non-complicated bloodstream infections and 61.2% (n = 366/598) in complicated bloodstream infections. Full bundle adherence was 18.4% (n = 328/1784). After controlling for immortal time bias and potential confounders, focus control (adjusted hazard ratio = 0.76; 95% CI, 0.59-0.99; p 0.038) and adequate targeted antimicrobial therapy (adjusted hazard ratio = 0.75; 95% CI, 0.61-0.91; p 0.004) were associated with low 90-day mortality. DISCUSSION: Adherence to QCIs in S. Aureus bloodstream infection did not reach expected rates. Apart from the benefits of application as a bundle, focus control and adequate targeted therapy were independently associated with low mortality.
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Bacteremia , Sepsis , Staphylococcal Infections , Humans , Staphylococcus aureus , Prospective Studies , Anti-Bacterial Agents/therapeutic use , Bacteremia/diagnosis , Bacteremia/drug therapy , Bacteremia/microbiology , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Sepsis/drug therapy , PrognosisABSTRACT
There have been numerous reports of patients initially misdiagnosed in the 2009 H1N1 influenza and coronavirus disease 2019 (COVID-19) pandemics within the literature. A systematic review was undertaken to collate misdiagnoses during the H1N1 and COVID-19 pandemics and identify which cognitive biases may contribute to this. MEDLINE, Embase, Cochrane and MedRxiv databases were searched for misdiagnoses or cognitive biases resulting in misdiagnosis, occurring during the H1N1 or COVID-19 virus pandemics. Eligible studies were assessed for quality using JBI criteria; primary outcome was the final diagnosis. Sixty-nine studies involving 2551 participants were included. We identified 686 cases of misdiagnosis, categorized as viral respiratory infection, other respiratory infection, non-respiratory infection, and non-infective. Misdiagnoses are listed and relevant investigations are offered. No article described prospective assessment of decision making in the pandemic setting or debiasing diagnostic thinking. Further research is required to understand why misdiagnoses occur and harm arises and how clinicians can be assisted in their decision making in a pandemic context.
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Mould-active antifungal prophylaxis is frequently used to prevent invasive fungal infection in patients with acute leukaemia being treated with intensive chemotherapy. Invasive fungal infections are difficult to diagnose, and despite the use of prophylaxis a high proportion of patients still receive therapeutic antifungals. Antifungal medications have important interactions, can cause serious adverse events, and may drive the proliferation of antifungal resistance. The use of two biomarkers, such as galactomannan in combination with the less-specific ß-d-glucan, can mitigate the risk of not detecting non-Aspergillus species, as well as improving pooled sensitivity and specificity. We argue that regular biomarkers could be used safely as part of an antifungal stewardship strategy to reduce antifungal use, by both screening for infection in patients not on prophylaxis and ruling out infection in patients treated empirically.
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INTRODUCTION: Antimicrobial resistance is an urgent medical challenge. In this two-part study, we investigated the epidemiology and management of carbapenem non-susceptible (Carb-NS) Gram-negative bacteria (GNB) in the UK. METHODS: We conducted a retrospective review of data from UK hospitals (ten in part 1, nine in part 2). In part 1, epidemiological data were collected from patients hospitalised between April 2017 and March 2018 with any laboratory detection of Carb-NS GNB, encompassing both colonisation and infection. In part 2, diagnosis and management pathways in a randomly selected population of adults from part 1 with confirmed Carb-NS GNB infection were assessed. Data were obtained from a detailed medical chart review for ≥ 3 months from index (collection date of first positive Carb-NS GNB sample). RESULTS: Of 42,340 GNB isolates from 36,098 patients colonised/infected with GNB in part 1, 7% were Carb-NS. In 157 patients included in part 2, 234 GNB index samples were collected, of which 197 (82%) were Carb-NS (median number of Carb-NS pathogens per patient, 1; range 1-3). The most frequent Carb-NS isolates were Pseudomonas aeruginosa (36%), Stenotrophomonas maltophilia (29%) and Klebsiella pneumoniae (10%). Median length of hospitalisation was 34 days. Median time from index to appropriate therapy was 3 days, with empirical therapy initiated a median of 1 day before index. Carb-NS infection was believed to contribute to 21 (28%) of 76 deaths during the study. CONCLUSIONS: This study highlights the high incidence of Carb-NS GNB colonisation and infection in the UK and the need for improved management of patients with Carb-NS GNB infection.
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Carbapenems , Gram-Negative Bacterial Infections , Adult , Anti-Bacterial Agents/therapeutic use , Carbapenems/therapeutic use , Gram-Negative Bacteria , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/epidemiology , Gram-Negative Bacterial Infections/microbiology , Humans , Retrospective Studies , United Kingdom/epidemiologyABSTRACT
Introduction. Fosfomycin has retained activity against many multi-drug resistant (MDR) Gram-negatives, and may be useful against extended spectrum beta-lactamase (ESBL) producing and carbapenem-resistant Enterobacterales to improve clinical outcomes.Hypothesis/Gap Statement. There are few data from the UK on the susceptibility of invasive Gram-negative isolates to fosfomycin, especially in the era of increasing use of oral fosfomycin for urinary tract infections (UTIs).Aim. We evaluated fosfomycin susceptibility against 100 consecutive Gram-negative bloodstream isolates, both individually, and in combination with other mechanistically similar and differing antibiotics. The aim was to investigate the synergy between antibiotic combinations against several E. coli, K. pneumoniae and P. aeruginosa isolates with variable levels of resistance.Methodology. Disc diffusion and MIC test strip methods applying revised EUCAST guidelines for Fosfomycin were used, followed by the MTS™ 'cross synergy' method for 'resistant' isolates as defined below: (a) Fosfomycin resistant by MIC test strip; (b) MDR isolates defined as being resistant to ≥3 classes of antibiotics (based on routine sensitivity testing; beta lactams were considered as a single class), and/or (c) AMP C or ESBL or carbapenemase producers (or carbapenem resistant). FIC Index (Fractional Inhibitory Concentration Index) calculations were used to interpret findings, whereby: FIC = (MICA combination A+B/ MIC agent A) + (MICB combination A+B/ MIC agent B). A result of ≤0.5 was taken to indicate 'synergy', >0.5 and ≤1.0 to indicate 'additive' effect, >1.0 and ≤4.0 to indicate 'indifference', and >4.0 to indicate 'antagonism'.Results. We found that 95/100 isolates were susceptible to fosfomycin by MIC test strip, with 88/100 isolates susceptible to fosfomycin by disc, based on EUCAST guideline breakpoints. A total of 30/100 isolates (the more 'resistant' of the 100) were eligible for synergy testing according to our definitions (see Methodology), with the remaining 70 isolates not tested further. Seventeen out of 30 were MDR, 2/30 were AMP C producers and 9/30 were ESBL producers. Overall, 34/300 (11â%) of all combination tests showed synergy and 161/300 (54â%) were additive. Synergy was most commonly detected between fosfomycin and beta-lactam antibiotics, including piperacillin/tazobactam (10/30; 33â%), ceftazidime/avibactam (10/30; 30â%), and temocillin (8/30; 27â%). An additive effect was most commonly detected with aztreonam (25/30; 83â%) and meropenem (25/30; 83â%), but 100â% indifference was found with tigecycline (30/30). No antagonism was identified with any antibiotic combination.Conclusion. Fosfomycin non-susceptibility by MIC test strip was unusual. Synergy was variable when combining fosfomycin with other antibiotics against the more 'resistant' isolates. Synergistic/additive effects were detected for beta-lactam/fosfomycin combinations in >80â% of all such combinations, suggesting beta-lactams may be the preferred partner for fosfomycin. Agents with a discordant site of action were more likely to result in indifference. Antagonism was not detected.
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Fosfomycin , Sepsis , Adenosine Monophosphate/pharmacology , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Drug Synergism , Escherichia coli , Fosfomycin/pharmacology , Hospitals, Teaching , Humans , Klebsiella pneumoniae , Microbial Sensitivity Tests , Pseudomonas aeruginosa , United KingdomABSTRACT
BACKGROUND: Antimicrobial resistance (AMR) is a global concern and better understanding of the gut microbiome, a known 'amplifier' of AMR, may allow future clinicians to tailor therapy to minimise this risk and offer a personalised medicine approach. To examine the gut microbiome, patients are required to provide faecal samples; more convenient and cheaper solutions need to be found. METHODS: As part of a pilot study looking at how routes of administration affect the gut microbiome in NHS patients undergoing routine clinical management for infections, we hypothesised that effects on the gut microbiome varied with the route and metabolism of antibiotic used, and these changes may be reflected in breath metabolites. We present a case report of a patient with an unusual clinical history, alongside breath metabolite and gut microbiome data taken before, during and after antibiotic therapy over a period of one year. RESULTS: We noted a shift in the dominant Bacteroides strain in the patient's gut microbiome between pre- and post-therapy samples, along with an alteration in the composition of breath metabolites. CONCLUSIONS: This study provides a framework for similar future work and highlights the need for further research on the relationships between changes in microbial gut communities and antimicrobial exposure, patient clinical status, and the metabolites of human breath.
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OBJECTIVES: To compare the performance of chest computed tomography (CT) scan versus reverse transcription polymerase chain reaction (RT-PCR) as the reference standard in the initial diagnostic assessment of coronavirus disease 2019 (COVID-19) patients. DESIGN: A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A search of electronic information was conducted using the following databases: MEDLINE, EMBASE, EMCARE, CINAHL and the Cochrane Central Register of Controlled Trials. SETTING: Studies that compared the diagnostic performance within the same patient cohort of chest CT scan versus RT-PCR in COVID-19 suspected patients. PARTICIPANTS: Thirteen non-randomised studies enrolling 4092 patients were identified. MAIN OUTCOME MEASURES: Sensitivity, specificity and accuracy were primary outcome measures. Secondary outcomes included other test performance characteristics and discrepant findings between both investigations. RESULTS: Chest CT had a median sensitivity, specificity and accuracy of 0.91 (range 0.82-0.98), 0.775 (0.25-1.00) and 0.87 (0.68-0.99), respectively, with RT-PCR as the reference. Importantly, early small, China-based studies tended to favour chest CT versus later larger, non-China studies. CONCLUSIONS: A relatively high false positive rate can be expected with chest CT. It is possible it may still be useful to provide circumstantial evidence, however, in some patients with a suspicious clinical presentation of COVID-19 and negative initial Severe Acute Respiratory Syndrome Coronavirus 2 RT-PCR tests, but more evidence is required in this context. In acute cardiorespiratory presentations, negative CT scan and RT-PCR tests is likely to be reassuring.
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INTRODUCTION: High-energy grade III open fractures of tibia are associated with significant complications and generate debate over the ideal fixation method. This study compares the clinical outcomes for circular frame fixation (CFF) vs intramedullary nail fixation (IMF) in grade III open tibial fractures. MATERIALS AND METHODS: Single-centre retrospective study of patients admitted from January 2008 to December 2016. All patients with grade III open diaphyseal tibial fractures (AO 42 A, B, C), treated with either CFF or IMF, were included. The primary outcome was deep bone infection (DBI). Secondary outcomes were delayed or non-union, secondary intervention, and amputation. RESULTS: A total of 48 limbs in 47 patients had CFF, and 25 limbs in 23 patients had IMF. Median time to definitive fixation was significantly longer for CFF at 9 days (IQR 3-13) compared to IMF at 1 day (IQR 0-3.5) (p <0.001). The DBI rate was significantly lower (2 vs 16%) in the CFF group (p = 0.04). There were 14 limbs (29%) with delayed or non-union in the CFF group vs 5 limbs (20%) in the IMF group. In the CFF group, significantly more limbs required bone grafting for delayed or non-union (p = 0.03). However, there was a greater proportion of limbs in the CFF group with segmental fractures or bone loss (46 vs 4%) and these high-energy fracture patterns were associated with secondary bone grafting (p = 0.005), and with delayed or non-union (p = 0.03). A subgroup analysis of patients without segmental fractures or bone loss treated with either CFF or IMF showed no significant difference in secondary bone grafting (p >0.99) and delayed or non-union rates (p = 0.72). Overall, one patient in each group went on to have an amputation. CONCLUSION: Our study found that CFF had a lower rate of DBI compared to IMF. Injuries with high-energy fracture patterns (segmental fractures or bone loss) were more likely to have delayed or non-union and require secondary bone grafting. These factors should be considered when selecting the appropriate method of definitive fixation. HOW TO CITE THIS ARTICLE: Natalwala I, Chuo CB, Shariatmadari I, et al. Outcomes and Incidence of Deep Bone Infection in Grade III Diaphyseal Open Tibial Fractures: Circular Fixator vs Intramedullary Nail. Strategies Trauma Limb Reconstr 2021;16(3):161-167.
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Tedizolid is a new oxazolidinone antibiotic with little real-life data on use outside of skin and soft tissue infections. There is a paucity of safety evidence in courses greater than 6 days. Our centre uses tedizolid predominantly when linezolid-associated adverse events have occurred. This service evaluation describes our experience to date. We performed a retrospective service evaluation by reviewing case notes, prescription charts, and laboratory system results for each patient prescribed tedizolid at our hospital and recording patient demographics, clinical details, and outcomes. Sixty patients received tedizolid between May 2016 and November 2018. Most were treated for bone or joint infections and had stopped linezolid prior to tedizolid prescription. Mean length of tedizolid therapy was 27 days. Haematological adverse effects were infrequent. Most patients (72%) finished the course and their clinical condition improved during treatment (72%). Adverse events were common, but often not thought to be tedizolid related. Tedizolid appears to be safe in prolonged courses within this context. It may be suitable for longer-term antibiotic therapy within a complex oral and parenteral outpatient antibiotic therapy (COPAT) service. Patients who do not tolerate linezolid can be safely switched to tedizolid if appropriate.
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Anti-Bacterial Agents/therapeutic use , Bone Diseases, Infectious/drug therapy , Oxazolidinones/therapeutic use , Tetrazoles/therapeutic use , Anti-Bacterial Agents/adverse effects , Female , Hospitals, Teaching , Humans , Linezolid/therapeutic use , Male , Middle Aged , Oxazolidinones/adverse effects , Retrospective Studies , Tetrazoles/adverse effects , Treatment Outcome , United KingdomSubject(s)
COVID-19 , Community-Acquired Infections , Sepsis , Humans , Organ Dysfunction Scores , SARS-CoV-2ABSTRACT
BACKGROUND: The number of different antimicrobial recommendations between hospital trusts for the same indication in England is unknown. AIM: We aimed to evaluate the heterogeneity of antimicrobial recommendations for seven common inpatient infections across hospital trusts in England and evaluate changes to recommendations following introduction of national (National Institute for Healthcare and Excellence, NICE) and international (WHO) antimicrobial guidelines. METHODS: Guidelines published on the MicroGuide smartphone application were collected from December 2017 to February 2018 and re-evaluated between December 2019 and February 2020. The following indications were assessed: community-acquired pneumonia (CAP) CURB65 score ≥3, hospital-acquired pneumonia (HAP), infective exacerbation of chronic obstructive pulmonary disease (iCOPD), cellulitis, uncomplicated urinary tract infection (uUTI), intra-abdominal infection (IAI) and sepsis of unknown source (SUS). On follow-up, compliance against WHO WATCH antibiotic and NICE recommendations was evaluated. RESULTS: Guidelines were obtained predominantly from England. Antibiotic regimens between hospitals became increasingly diverse across indications in the following order: uUTI, cellulitis, iCOPD, CAP, HAP, IAI and SUS. A piperacillin/tazobactam-based regimen was recommended in HAP (59%), SUS (39%) and IAI (30%). After 2 years, 107 changes were made to 357 antibiotic regimen recommendations; the overall number of regimens using piperacillin-tazobactam and WHO WATCH antibiotics remained similar. Compliance of recommendations with NICE guidelines as follows: iCOPD (100% adherent), uUTI (98%), cellulitis (90%), CAP (43%) and HAP (27%). CONCLUSION: The heterogeneity of antibiotic recommendations increased as the indicated infection was more severe, with broader underlying bacterial causes. Piperacillin-tazobactam remains favoured in antibiotic regimens, despite not recommended in WHO and NICE guidance.