Rapid and Point-of-Care Testing in Respiratory Tract Infections: An Antibiotic Guardian?

This is a narrative review on the potential of rapid and point-of-care microbiological testing in pneumonia patients, focusing particularly on hospital-acquired and ventilator-associated pneumonia, which have substantial mortality and diverse microbiology. This work is written from a United Kingdom perspective, but much of it is generalizable internationally. In a world where antimicrobial resistance is a major international threat, the use of rapid molecular diagnostics has great potential to improve both the management of pneumonia patients and the stewardship of antibiotics. Rapid tests potentially can distinguish patients with bacterial versus viral infection and can swiftly identify bacterial pathogens and their resistances. We seek to answer the question: "Can such tests be used as an antibiotic guardian?"Their availability at the bedside rather than in the laboratory should best ensure that results are swiftly used to optimize patient management but will raise new challenges, not the least with respect to maintaining quality control and microbiology/infection control input. A further challenge lies in assessing the degree of trust that treating clinicians will place in these molecular diagnostic tests, particularly when early de-escalation of antibiotic therapy is indicated

Review of health economic models exploring and evaluating treatment and management of hospital-acquired pneumonia and ventilator-associated pneumonia

BACKGROUND: Hospital-acquired pneumonia (HAP) is pneumonia that occurs ≥48 h after hospital admission; it is the most common hospital-acquired infection contributing to death. Ventilator-associated pneumonia (VAP) arises ≥48-72 h after intubation. Opinions differ on whether VAP is a subset of HAP; the same pathogens predominate in both. Compared with VAP-free controls, patients developing VAP are twice as likely to die and have significantly longer stays in intensive care units. Guidelines recommend that microbiological cultures should guide antibiotic treatment, but these lack sensitivity and take 48-72 h to process, meaning that initial therapy must be empiric, generally with broad-spectrum agents. Given increasing pressure to improve both antibiotic stewardship and patient outcomes, the National Institute for Health and Care Excellence and the Infectious Diseases Society of America recommend research into rapid molecular diagnostic tests to identify causative organisms and their antibiotic resistances. Ideally, these would supersede culture, being quicker and more sensitive. In the UK, the INHALE research programme, funded by the National Institute for Health Research, is exploring rapid molecular diagnostics to inform treatment of HAP/VAP and, given resource implications, incorporates a health economic component. AIM: To identify previous economic modelling of HAP/VAP costs to inform this component. METHODS: Literature review of HAP/VAP studies with economic modelling identified from three databases. FINDINGS: Twenty studies were identified. Only one study specifically evaluated strategies to improve diagnosis; the remaining 19 studies omitted this important aspect. CONCLUSION: HAP/VAP modelling would be improved by better awareness of long-term outcomes and treatment complexity. To the authors' knowledge, no similar literature reviews of economic modelling for HAP/VAP have been published

Comparative antimicrobial susceptibility of aerobic and facultative bacteria from community-acquired bacteremia to ertapenem in Taiwan

<p>Abstract</p> <p>Background</p> <p>Ertapenem is a once-a-day carbapenem and has excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. The susceptibility of isolates of community-acquired bacteremia to ertapenem has not been reported yet. The present study assesses the in vitro activity of ertapenem against aerobic and facultative bacterial pathogens isolated from patients with community-acquired bacteremia by determining and comparing the MICs of cefepime, cefoxitin, ceftazidime, ceftriaxone, ertapenem, piperacillin, piperacillin-tazobactam, ciprofloxacin, amikacin and gentamicin. The prevalence of extended broad spectrum β-lactamases (ESBL) producing strains of community-acquired bacteremia and their susceptibility to these antibiotics are investigated.</p> <p>Methods</p> <p>Aerobic and facultative bacteria isolated from blood obtained from hospitalized patients with community-acquired bacteremia within 48 hours of admission between August 1, 2004 and September 30, 2004 in Chang Gung Memorial Hospital at Keelung, Taiwan, were identified using standard procedures. Antimicrobial susceptibility was evaluated by Etest according to the standard guidelines provided by the manufacturer and document M100-S16 Performance Standards of the Clinical Laboratory of Standard Institute. Antimicrobial agents including cefepime, cefoxitin, ceftazidime, ceftriaxone, ertapenem, piperacillin, piperacillin-tazobactam, ciprofloxacin, amikacin and gentamicin were used against the bacterial isolates to test their MICs as determined by Etest. For <it>Staphylococcus aureus </it>isolates, MICs of oxacillin were also tested by Etest to differentiate oxacillin-sensitive and oxacillin-resistant <it>S. aureus</it>.</p> <p>Results</p> <p>Ertapenem was highly active in vitro against many aerobic and facultative bacterial pathogens commonly recovered from patients with community-acquired bacteremia (128/159, 80.5 %). Ertapenem had more potent activity than ceftriaxone, piperacillin-tazobactam, or ciprofloxacin against oxacillin-susceptible <it>S</it>. <it>aureus </it>(17/17, 100%)and was more active than any of these agents against <it>enterobacteriaceae </it>(82/82, 100%).</p> <p>Conclusion</p> <p>Based on the microbiology pattern of community-acquired bacteremia, initial empiric treatment that requires coverage of a broad spectrum of both gram-negative and gram-positive aerobic bacteria, such as ertapenem, may be justified in moderately severe cases of community-acquired bacteremia in non-immunocompromised hosts.</p

Understanding decisions about antibiotic prescribing in ICU: an application of the Necessity Concerns Framework

Background: Antibiotics are extensively prescribed in intensive care units (ICUs), yet little is known about how antibiotic-related decisions are made in this setting. We explored how beliefs, perceptions and contextual factors influenced ICU clinicians’ antibiotic prescribing. / Methods: We conducted 4 focus groups and 34 semistructured interviews with clinicians involved in antibiotic prescribing in four English ICUs. Focus groups explored factors influencing prescribing, whereas interviews examined decision-making processes using two clinical vignettes. Data were analysed using thematic analysis, applying the Necessity Concerns Framework. / Results: Clinicians’ antibiotic decisions were influenced by their judgement of the necessity for prescribing/not prescribing, relative to their concerns about potential adverse consequences. Antibiotic necessity perceptions were strongly influenced by beliefs that antibiotics would protect patients from deterioration and themselves from the ethical and legal consequences of undertreatment. Clinicians also reported concerns about prescribing antibiotics. These generally centred on antimicrobial resistance; however, protecting the individual patient was prioritised over these societal concerns. Few participants identified antibiotic toxicity concerns as a key influencer. Clinical uncertainty often complicated balancing antibiotic necessity against concerns. Decisions to start or continue antibiotics often represented ‘erring on the side of caution’ as a protective response in uncertainty. This approach was reinforced by previous experiences of negative consequences (‘being burnt’) which motivated prescribing ‘just in case’ of an infection. Prescribing decisions were also context-dependent, exemplified by a lower perceived threshold to prescribe antibiotics out-of-hours, input from external team members and local prescribing norms. / Conclusion: Efforts to improve antibiotic stewardship should consider clinicians’ desire to protect with a prescription. Rapid molecular microbiology, with appropriate communication, may diminish clinicians’ fears of not prescribing or of using narrower-spectrum antibiotics

Treatment of infections caused by multidrug-resistant Gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party

The Working Party makes more than 100 tabulated recommendations in antimicrobial prescribing for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) and suggest further research, and algorithms for hospital and community antimicrobial usage in urinary infection. The international definition of MDR is complex, unsatisfactory and hinders the setting and monitoring of improvement programmes. We give a new definition of multiresistance. The background information on the mechanisms, global spread and UK prevalence of antibiotic prescribing and resistance has been systematically reviewed. The treatment options available in hospitals using intravenous antibiotics and in primary care using oral agents have been reviewed, ending with a consideration of antibiotic stewardship and recommendations. The guidance has been derived from current peer-reviewed publications and expert opinion with open consultation. Methods for systematic review were NICE compliant and in accordance with the SIGN 50 Handbook; critical appraisal was applied using AGREE II. Published guidelines were used as part of the evidence base and to support expert consensus. The guidance includes recommendations for stakeholders (including prescribers) and antibiotic-specific recommendations. The clinical efficacy of different agents is critically reviewed. We found there are very few good-quality comparative randomized clinical trials to support treatment regimens, particularly for licensed older agents. Susceptibility testing of MDR GNB causing infection to guide treatment needs critical enhancements. Meropenem- or imipenem-resistant Enterobacteriaceae should have their carbapenem MICs tested urgently, and any carbapenemase class should be identified: mandatory reporting of these isolates from all anatomical sites and specimens would improve risk assessments. Broth microdilution methods should be adopted for colistin susceptibility testing. Antimicrobial stewardship programmes should be instituted in all care settings, based on resistance rates and audit of compliance with guidelines, but should be augmented by improved surveillance of outcome in Gram-negative bacteraemia, and feedback to prescribers. Local and national surveillance of antibiotic use, resistance and outcomes should be supported and antibiotic prescribing guidelines should be informed by these data. The diagnosis and treatment of both presumptive and confirmed cases of infection by GNB should be improved. This guidance, with infection control to arrest increases in MDR, should be used to improve the outcome of infections with such strains. Anticipated users include medical, scientific, nursing, antimicrobial pharmacy and paramedical staff where they can be adapted for local use

Dio-sensimedia: a novel culture medium for rapid detection of extended spectrum β-lactamases

BACKGROUND: Resistance to contemporary broad-spectrum β-lactams, mediated by extended-spectrum β-lactamases (ESBL), is an increasing problem worldwide. Many of the emerging antimicrobial resistance problems of this decade have been characterized by difficulty in the recognition of resistance in the laboratory, particularly by rapid susceptibility test methods. The plasmid-encoded ESBL represent such a resistance phenomenon that is difficult to recognize. We compared Dio-Sensimedia-ES (DSM-ES; Diomed, Istanbul, Turkey) and Mueller-Hinton (MH) agar in the double-disk synergy test (DDST) as a novel rapid system for detecting ESBL directly from bacterial culture. METHODS: Sixty ESBL-producing Klebsiella pneumoniae isolates cultured from blood (30), endotracheal aspirates (20), urine (5) and pus (5), as well as 40 Escherichia coli isolates cultured from endotracheal aspirates (15), urine (10), blood (8) and pus (7) were studied. Isolates positive for ESBL by the combined disk tests were tested with the DDST using MH and DSM-ES agar to detect ESBL-mediated resistance in K. pneumoniae and E. coli. DSM-ES agar was also used to determine the susceptibility of Enterobacteriaceae and staphylococci. RESULTS: Among 60 ESBL-producing K. pneumoniae isolates, 59 (98.3%) were identified as ESBL-positive by the DDST using MH, and 58 (96.6%), using DSM-ES agar. Of 40 ESBL-producing E. coli isolates, 38 (95%) were ESBL-positive by the DDST on MH agar, and 37 (92.5%), on DSM-ES agar. The average incubation period required for ESBL detection by the DDST on DSM-ES agar was 4 hours. CONCLUSIONS: Since the DDST results were available within 4 hours when DSM-ES agar was used, the use of this media may significantly lower the length of hospital stay, the total cost for patient care and even the mortality rate by fascilitating early treatment against ESBL-producing organisms

INHALE: the impact of using FilmArray Pneumonia Panel molecular diagnostics for hospital-acquired and ventilator-associated pneumonia on antimicrobial stewardship and patient outcomes in UK Critical Care—study protocol for a multicentre randomised controlled trial

BACKGROUND: Hospital-acquired and ventilator-associated pneumonias (HAP and VAP) are common in critical care and can be life-threatening. Rapid microbiological diagnostics, linked to an algorithm to translate their results into antibiotic choices, could simultaneously improve patient outcomes and antimicrobial stewardship. METHODS: The INHALE Randomised Controlled Trial is a multi-centre, parallel study exploring the potential of the BioFire FilmArray molecular diagnostic to guide antibiotic treatment of HAP/VAP in intensive care units (ICU); it identifies pathogens and key antibiotic resistance in around 90 min. The comparator is standard care whereby the patient receives empirical antibiotics until microbiological culture results become available, typically after 48-72 h. Adult and paediatric ICU patients are eligible if they are about to receive antibiotics for a suspected lower respiratory infection (including HAP/VAP) for the first time or a change in antibiotic because of a deteriorating clinical condition. Breathing spontaneously or intubated, they must have been hospitalised for 48 h or more. Patients are randomised 1:1 to receive either antibiotics guided by the FilmArray molecular diagnostic and its trial-based prescribing algorithm or standard care, meaning empirical antibiotics based on local policy, adapted subsequently based upon local microbiology culture results. Co-primary outcomes are (i) non-inferiority in clinical cure of pneumonia at 14 days post-randomisation and (ii) superiority in antimicrobial stewardship at 24 h post-randomisation (defined as % of patients on active and proportionate antibiotics). Secondary outcomes include further stewardship reviews; length of ICU stay; co-morbidity indicators, including septic shock, change in sequential organ failure assessment scores, and secondary pneumonias; ventilator-free days; adverse events over 21 days; all-cause mortality; and total antibiotic usage. Both cost-effectiveness of the molecular diagnostic-guided therapy and behavioural aspects determining antibiotic prescribing are being explored. A sample size of 552 will be required to detect clinically significant results with 90% power and 5% significance for the co-primary outcomes. DISCUSSION: This trial will test whether the potential merits of rapid molecular diagnostics for pathogen and resistance detection in HAP/VAP are realised in patient outcomes and/or improved antibiotic stewardship. TRIAL REGISTRATION: ISRCTN Registry ISRCTN16483855 . Retrospectively registered on 15 July 2019