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Health Technology Assessment... Jun 2024To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund...
BACKGROUND
To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of cefiderocol in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform the National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England.
METHODS
The health benefit of cefiderocol was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population values using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for cefiderocol.
RESULTS
Among isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase base-case network meta-analysis, cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time and rates of emergence of resistance. The population-level benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years.
CONCLUSION
This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS.
LIMITATIONS
Given existing evidence, the estimates of the value of cefiderocol are highly uncertain.
FUTURE WORK
Future evaluations of antimicrobials would benefit from improvements to NHS data linkages; research to support appropriate synthesis of susceptibility studies; and application of routine data and decision modelling to assess enablement value.
STUDY REGISTRATION
No registration of this study was undertaken.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in ; Vol. 28, No. 28. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Cephalosporins; Anti-Bacterial Agents; Quality-Adjusted Life Years; Cost-Benefit Analysis; England; Technology Assessment, Biomedical; Cefiderocol; Gram-Negative Bacterial Infections; State Medicine; Quality of Life
PubMed: 38938145
DOI: 10.3310/YGWR4511 -
Annals of Clinical Microbiology and... Jun 2024Detection of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) in humans is important to prevent transmission. However, the most optimal culture method to detect CR-PA... (Review)
Review
BACKGROUND
Detection of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) in humans is important to prevent transmission. However, the most optimal culture method to detect CR-PA is unknown. This systematic review aims to determine which culture method is most sensitive and which culture methods are used to detect CR-PA in humans. Second, to establish the most feasible culture method taking into account the turnaround time (TAT), and third, to provide an overview of the sampling sites used to detect carriage.
METHODS
We systematically searched the electronic databases Embase, Medline Ovid, Cochrane, Scopus, CINAHL, and Web of Science until January 27, 2023. All diagnostic accuracy studies comparing two or more culture methods to detect CR-PA and recent outbreak or surveillance reports on CR-PA carriage or infection in humans, which describe culture methods and their results, were eligible for inclusion. We used QUADAS-2 guideline for diagnostic accuracy studies and the STROBE or ORION guideline for outbreak-surveillance studies to assess the risk of bias.
RESULTS
Six diagnostic accuracy studies were included. An enrichment broth was found to increase the detection of CR-PA. Using an enrichment broth extended the TAT by 18-24 h, yet selective media could reduce the TAT by 24 h compared to routine media. In total, 124 outbreak-surveillance studies were included, of which 17 studies with surveillance samples and 116 studies with clinical samples. In outbreak-surveillance studies with surveillance samples, perianal, rectal swabs or stools were the most common sampling site/specimen (13/17, 76%). A large variety was observed in whether and which kind of enrichment broth and selective media were used.
CONCLUSIONS
We found a benefit of using an enrichment step prior to inoculation of the material onto selective media for the detection of CR-PA. More research is needed to determine the most sensitive sampling site and culture method.
TRAIL REGISTRATION
This study was registered in the PROSPERO International prospective register of systematic reviews (registration number: CRD42020207390, http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42020207390 ).
Topics: Humans; Pseudomonas aeruginosa; Carbapenems; Pseudomonas Infections; Anti-Bacterial Agents; Carrier State; Microbial Sensitivity Tests; Culture Media
PubMed: 38858708
DOI: 10.1186/s12941-024-00707-1 -
Infection Jun 2024The landscape of Pseudomonas infective endocarditis (IE) is evolving with the widespread use of cardiac implantable devices and hospital-acquired infections. This... (Review)
Review
BACKGROUND
The landscape of Pseudomonas infective endocarditis (IE) is evolving with the widespread use of cardiac implantable devices and hospital-acquired infections. This systematic review aimed to evaluate the emerging risk factors and outcomes in Pseudomonas IE.
METHODS
A literature search was performed in major electronic databases (PubMed, Scopus, and Google Scholar) with appropriate keywords and combinations till November 2023. We recorded data for risk factors, diagnostic and treatment modalities. This study is registered with PROSPERO, CRD42023442807.
RESULTS
A total of 218 cases (131 articles) were included. Intravenous drug use (IDUs) and prosthetic valve endocarditis (PVE) were major risk factors for IE (37.6% and 22%). However, the prosthetic valve was the predominant risk factor in the last two decades (23.5%). Paravalvular complications (paravalvular leak, abscess, or pseudoaneurysm) were described in 40 cases (18%), and the vast majority belonged to the aortic valve (70%). The mean time from symptom onset to presentation was 14 days. The incidence of difficult-to-treat resistant (DTR) pseudomonas was 7.4%. Valve replacement was performed in 57.3% of cases. Combination antibiotics were used in most cases (77%), with the aminoglycosides-based combination being the most frequently used (66%). The overall mortality rate was 26.1%. The recurrence rate was 11.2%. Almost half of these patients were IDUs (47%), and most had aortic valve endocarditis (76%).
CONCLUSIONS
This review highlights the changing epidemiology of Pseudomonas endocarditis with the emergence of prosthetic valve infections. Acute presentation and associated high mortality are characteristic of Pseudomonas IE and require aggressive diagnostic and therapeutic approach.
PubMed: 38856808
DOI: 10.1007/s15010-024-02311-z -
Frontiers in Immunology 2024According to the PRISMA criteria, a systematic review has been conducted to investigate the clinical relevance between patients with severe congenital neutropenia (SCN)...
INTRODUCTION
According to the PRISMA criteria, a systematic review has been conducted to investigate the clinical relevance between patients with severe congenital neutropenia (SCN) and cyclic congenital neutropenia (CyN) induced by ELANE mutations.
METHODS
We have searched PubMed, EMBASE, Web of Science, Scopus, Cochrane, CNKI, Wanfang Medicine, and VIP for ELANE mutation related literature published from 1997 to 2022. Using Microsoft Excel collect and organize data, SPSS 25, GraphPad Prism 8.0.1, and Omap analyze and plot statistical. Compare the gender, age, geography, mutation sites, infection characteristics, treatment, and other factors of SCN and CyN patients induced by ELANE mutations, with a focus on exploring the relationship between genotype and clinical characteristics, genotype and prognosis.
RESULTS
This study has included a total of 467 patients with SCN and 90 patients with CyN. The onset age of SCN and CyN are both less than 1 year old, and the onset and diagnosis age of SCN are both younger than CyN. The mutation of ELANE gene is mainly missense mutation, and hot spot mutations include S126L, P139L, G214R, c.597+1G>A. The high-frequency mutations with severe outcomes are A57V, L121H, L121P, c.597+1G>A, c.597+1G>T, S126L, C151Y, C151S, G214R, C223X. Respiratory tract, skin and mucosa are the most common infection sites, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli are the most common.
DISCUSSION
Patients with refractory G-CSF are more likely to develop severe outcomes. The commonly used pre-treatment schemes for transplantation are Bu-Cy-ATG and Flu-Bu-ATG. The prognosis of transplantation is mostly good, but the risk of GVHD is high.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/. PROSPERO, identifier CRD42023434656.
Topics: Humans; Neutropenia; Mutation; Congenital Bone Marrow Failure Syndromes; Prognosis; Male; Female; Clinical Relevance
PubMed: 38840904
DOI: 10.3389/fimmu.2024.1349919 -
The Journal of Hospital Infection Jun 2024With increasing awareness of water sinks as potential sources of outbreaks and transmission of multi-drug resistant (MDR) bacteria in intensive care units (ICUs), there... (Review)
Review
BACKGROUND
With increasing awareness of water sinks as potential sources of outbreaks and transmission of multi-drug resistant (MDR) bacteria in intensive care units (ICUs), there is growing interest in water-free patient care systems. This systematic review reviewed and synthesized available evidence on the effectiveness of sink removal with or without water-free activities in the ICU environment to reduce water-borne healthcare-associated infections.
METHODS
We searched five databases (PubMed, MEDLINE, Scopus, Web of Science and Embase) for studies published from 1st January 1980 to 2nd April 2024 that examined water-less or water-free activities in the ICU to reduce healthcare-associated infections and patient colonization.
RESULTS
Of 2,075 articles, seven quasi-experimental studies (total: 332 patient beds) met the study selection criteria. 6/7 studies (85.7%) were based in adult ICUs; one (14%) was in a neonatal ICU. 5/7 sites (71.4%) implemented water-less interventions after an outbreak. Water-free alternatives used included water-less bath products (6/7;85.7%), bottled water for consumption (3/7;42.9%), oral care (3/7;42.9%) and dissolving of oral medication (4/7;57.1%), designated 'contaminated' sink outside of patient and medication preparation areas for disposal of wastewater (4/7; 57.1%). Implicated pathogens studied included MDR gram-negative bacteria (4/7; 57.1%), MDR Pseudomonas aeruginosa only (2/7; 28.6%), and pulmonary non-tuberculous mycobacterium (NTB) (1/7; 14.3%). 5/7 (71.4%) studies reported outbreak cessation.
CONCLUSION
Preliminary evidence, from a limited number of studies of which the majority were conducted in an outbreak setting, suggest that sink removal and other water-free interventions in the ICU helped terminate outbreaks involving taps and decrease hospital-onset respiratory isolation of pulmonary NTB.
PubMed: 38830541
DOI: 10.1016/j.jhin.2024.05.012 -
Environmental Health Insights 2024Nosocomial pathogens are known to exacerbate morbidity and mortality in contemporary critical healthcare. Hospital fomites, which include inanimate surfaces, have been... (Review)
Review
BACKGROUND
Nosocomial pathogens are known to exacerbate morbidity and mortality in contemporary critical healthcare. Hospital fomites, which include inanimate surfaces, have been identified as "breeding grounds" for pathogens that cause nosocomial infections. This systematic review aimed to deliver incisive insights on nosocomial pathogens in intensive care units (ICUs) and the role of fomites as potential reservoirs for their transmission.
METHOD
An extensive exploration of electronic databases, including PubMed and Scopus, from 1990 to 2023, was carried out between 25 and 29 May 2023, per standard PRISMA guidelines. Information were extracted from articles that reported on fomites in the ICU. Studies that did not quantitatively report the fomite contamination, and those that exclusively took samples from patients in the ICU were excluded from the analysis.
RESULTS
About 40% of the total samples collected on fomites from all the studies yielded microbial growth, with species of being the most predominant. Other prevalent microbes were , , , spp., sp., and sp. The neonatal intensive care unit (NICU) had the highest proportion of contaminated fomites. Among known fomites, the sphygmomanometer exhibited a 100% detection rate of nosocomial pathogens. This included , , coagulase-negative (CoNS), , and Multidrug-resistant (MDR) bacteria, such as methicillin-resistant (MRSA), vancomycin-resistant (VRE), extended-spectrum beta-lactamase (ESBL)-producing , and MDR were commonly isolated on fomites in the ICUs.
CONCLUSION
Many fomites that are readily used in patient care in the ICU harbour nosocomial pathogens. The most common fomite appeared to be mobile phones, sphygmomanometers, and stethoscopes, with being the most common contaminant. Consequently, the need for rigorous disinfection and sterilization protocols on fomites in the ICU cannot be overemphasized. Additionally, heightened awareness on the subject among health professionals is crucial to mitigating the risk and burden of nosocomial infections caused by drug-resistant bacteria.
PubMed: 38828046
DOI: 10.1177/11786302241243239 -
Infectious Diseases and Therapy May 2024Ceftazidime-avibactam (CAZ-AVI) is a combination of the third-generation cephalosporin ceftazidime and the novel, non-β-lactam β-lactamase inhibitor avibactam that is...
INTRODUCTION
Ceftazidime-avibactam (CAZ-AVI) is a combination of the third-generation cephalosporin ceftazidime and the novel, non-β-lactam β-lactamase inhibitor avibactam that is approved for the treatment of pediatric (≥ 3 months) and adult patients with complicated infections including hospital-acquired and ventilator-associated pneumonia (HAP/VAP), and bacteremia. This systematic literature review and meta-analysis (PROSPERO registration: CRD42022362856) aimed to provide a quantitative and qualitative synthesis to evaluate the effectiveness of CAZ-AVI in treating adult patients with bacteremia or nosocomial pneumonia caused by carbapenem-resistant Enterobacterales (non metallo-β-lactamase-producing strains) and multi-drug resistant (MDR) Pseudomonas aeruginosa infections.
METHODS
The databases included in the search, until November 7, 2022, were Embase and PubMed. A total of 24 studies (retrospective: 22, prospective: 2) with separate outcomes for patients with bacteremia or pneumonia were included.
RESULTS
The outcomes assessed were all-cause mortality, clinical cure, and microbiological cure. Qualitative (24 studies) and quantitative (8/24 studies) syntheses were performed. The quality of the studies was assessed using the MINORS checklist and the overall risk of bias was moderate to high.
CONCLUSIONS
In studies included in the meta-analysis, lower all-cause mortality for patients with bacteremia (OR = 0.30, 95% CI 0.19-0.46) and improved rates of clinical cure for patients with bacteremia (OR = 4.90, 95% CI 2.60-9.23) and nosocomial pneumonia (OR = 3.20, 95% CI 1.55-6.60) was observed in the CAZ-AVI group compared with the comparator group. Data provided here may be considered while using CAZ-AVI for the treatment of patients with difficult-to-treat infections.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022362856.
PubMed: 38822167
DOI: 10.1007/s40121-024-00999-y -
Cancers May 2024We performed a systematic review of studies that compared beta-lactams vs. beta-lactams plus aminoglycosides for the treatment of febrile neutropenia in cancer patients. (Review)
Review
UNLABELLED
We performed a systematic review of studies that compared beta-lactams vs. beta-lactams plus aminoglycosides for the treatment of febrile neutropenia in cancer patients.
METHOD
We searched CENTRAL, MEDLINE, and Embase for studies published up to October 2023, and randomized controlled trials (RCTs) that compared anti-Pseudomonas aeruginosa beta-lactam monotherapy with any combination of an anti-Pseudomonas aeruginosa beta-lactam and an aminoglycoside were included.
RESULT
The all-cause mortality rate of combination therapy showed no significant differences compared with that of monotherapy (RR 0.99, 95% CI 0.84 to 1.16, high certainty of evidence). Infection-related mortality rates showed that combination therapy had a small positive impact compared with the intervention with monotherapy (RR 0.83, 95% CI 0.66 to 1.05, high certainty of evidence). Regarding treatment failure, combination therapy showed no significant differences compared with monotherapy (RR 0.99, 95% CI 0.94 to 1.03, low certainty of evidence). In the sensitivity analysis, the treatment failure data published between 2010 and 2019 showed better outcomes in the same beta-lactam group (RR 1.10 [95% CI, 1.01-1.19]). Renal failure was more frequent with combination therapy of any daily dosing regimen (RR 0.46, 95% CI 0.36 to 0.60, high certainty of evidence).
CONCLUSION
We found combining aminoglycosides with a narrow-spectrum beta-lactam did not spare the use of broad-spectrum antibiotics. Few studies included antibiotic-resistant bacteria and a detailed investigation of aminoglycoside serum levels, and studies that combined the same beta-lactams showed only a minimal impact with the combination therapy. In the future, studies that include the profile of antibiotic-resistant bacteria and the monitoring of serum aminoglycoside levels will be required.
PubMed: 38792012
DOI: 10.3390/cancers16101934 -
The Lancet Regional Health. Southeast... Jul 2024The WHO Global Antimicrobial Resistance Surveillance System (GLASS) aims to describe antimicrobial resistance (AMR) patterns and trends in common bacterial pathogens,...
BACKGROUND
The WHO Global Antimicrobial Resistance Surveillance System (GLASS) aims to describe antimicrobial resistance (AMR) patterns and trends in common bacterial pathogens, but data remain limited in many low and middle-income countries including Indonesia.
METHODS
We systematically searched Embase, PubMed and Global Health Database and three Indonesian databases for original peer-reviewed articles in English and Indonesian, published between January 1, 2000 and May 25, 2023, that reported antimicrobial susceptibility for the 12 GLASS target pathogens from human samples. Pooled AMR prevalence estimates were calculated for relevant pathogen-antimicrobial combinations accounting for the sampling weights of the studies (PROSPERO: CRD42019155379).
FINDINGS
Of 2182 search hits, we included 102 papers, comprising 19,517 bacterial isolates from hospitals (13,647) and communities (5870). In hospital settings, 21.6% of isolates, 18.3% of isolates, 35.8% of isolates and 70.7% of isolates were carbapenem-resistant; 29.9% of isolates were penicillin-resistant; and 22.2% of isolates were methicillin-resistant. Hospital prevalence of carbapenem-resistant and , and penicillin-resistant increased over time. In communities, 28.3% of isolates and 15.7% of isolates were carbapenem-resistant, 23.9% of isolates were penicillin-resistant, and 11.1% of isolates were methicillin-resistant. Data were limited for the other pathogens.
INTERPRETATION
AMR prevalence estimates were high for critical gram-negative bacteria. However, data were insufficient to draw robust conclusions about the full contemporary AMR situation in Indonesia. Implementation of national AMR surveillance is a priority to address these gaps and inform context-specific interventions.
FUNDING
Wellcome Africa Asia Programme Vietnam.
PubMed: 38778837
DOI: 10.1016/j.lansea.2024.100414 -
Infection and Drug Resistance 2024The World Health Organization (WHO) has classified carbapenem-resistant (), and () as high-priority pathogens, and carbapenem-resistant bacteria (CRB) have been... (Review)
Review
BACKGROUND
The World Health Organization (WHO) has classified carbapenem-resistant (), and () as high-priority pathogens, and carbapenem-resistant bacteria (CRB) have been reported to spread between humans, animals, and the environment.
OBJECTIVE
This study aimed to conduct a systematic review of carbapenem resistance in animals, foods, and the environment on the African continent and to provide recommendations and perspectives for better prevention and control of carbapenem resistance in Africa.
RESULTS
A total of 137 research articles collected from 2009 to 2023 were selected for this review, including articles reporting carbapenem-resistant bacteria in animals (81/137; 59.1%), the environment (66/137; 48.2%), and foods (26/137; 19%). Carbapenem-resistant bacterial species belonged to 31 genera and 17 families, including mainly spp. (68/127; 53.5%); spp. (45/127; 35.4%); spp. (20/127; 15.7%), spp. (19/127; 15%) and spp. (15/127; 11.8%). The prevalence of CRBs by country ranged from 1.1% to 48.5%, and the pooled prevalence of CRBs isolated from animal-environment-food in Africa was 19.1% (2804/14,684; Standard Deviation = 15). Twenty carbapenemase families belonging to A, B, C, and D Ambler classes were reported, including mainly carbapenemase genes from (44/84; 52.4%), (34/84; 40.5%), (23/84; 27.4%), (22/84; 26.2%), (19/84; 22.6%), and (12/84; 14.3%) families. The reported mobile genetic elements (MGE) carrying carbapenemase-encoding genes included plasmids (16/19; 84.2%), integrons (3/19; 15.8%), transposons (3/19; 15.8%), and insertion sequences (2/19; 10.5%). was often carried by (60kb-65kb) IncL/M-type pOXA-48 plasmids, while was often carried by (45-50kb) IncX-type plasmids. Moreover, 25 articles investigated and reported virulent and hypervirulent CRBs that carried multiple virulence factors.
CONCLUSION
Animal-environment-food ecosystems would constitute reservoirs of CRBs involved in human infections. The One Health approach and constant collaboration between governments are necessary to drastically reduce the mortality rates linked to antimicrobial resistance.
PubMed: 38715963
DOI: 10.2147/IDR.S458317