Afatinib-induced toxic epidermal necrolysis: A case report with a literature review.

We present a 70-year-old female patient diagnosed with epidermal growth factor receptor-mutated metastatic non-small cell lung cancer (T4N2M1a), who developed afatinib-induced toxic epidermal necrolysis (TEN). We have also performed a PubMed/Medline literature review to detect other possible cases of TEN/Stevens-Johnson syndrome associated with afatinib treatment and found only 5 other cases reported. To our best knowledge, this is the first case of afatinib-induced TEN successfully treated with cyclosporine.

Rebound in community antibiotic consumption after the observed decrease during the COVID-19 pandemic, EU/EEA, 2022.

We observed a rebound in consumption of antibacterials for systemic use (ATC J01) in the community sector in the European Union/European Economic Area during 2021 and 2022, after an observed decrease between 2019 and 2020. The rates in 2022 returned to pre-COVID-19-pandemic levels and were exceeded in 13 countries. Although these patterns could partly be a result of changes in disease transmission during the study period, it could also reflect a lost opportunity to strengthen and reinforce prudent antibiotic use.

Impact of the COVID-19 pandemic on hospital antimicrobial consumption in Croatia.

OBJECTIVES: The aim of the study was to assess the impact of the COVID-19 pandemic on antimicrobial consumption (AMC) in the hospital sector in Croatia by analysing data reported to the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) between 2016 and 2020. METHODS: AMC was measured as the number of DDDs/1000 inhabitants/day and as the number of DDDs/100 bed days. To assess trends, linear regression was performed. To assess the impact of the pandemic on AMC, the compound annual growth rate was calculated for the years preceding the pandemic based on which AMC for 2020 was forecasted and compared with the actual consumption. RESULTS: While hospital AMC expressed as DDDs/1000 inhabitants/day between 2019 and 2020 decreased by 17%, when expressed as DDDs/100 bed days, an 8% increase was observed. Hospital consumption of antibacterials for systemic use in the 5 year period did not significantly change when expressed as DDDs/1000 inhabitants/day, while it statistically significantly increased when expressed as DDDs/100 bed days. An increasing trend in consumption of broad-spectrum antimicrobials was found. CONCLUSIONS: During the pandemic there was an increase in hospital AMC with a shift towards broad-spectrum antimicrobials requiring further in-depth qualitative analysis based on patient-level data. Contrasting results obtained using different denominators indicate that the metric DDDs/1000 inhabitants/day is not sensitive enough to evaluate hospital AMC. When assessing hospital AMC, the population under surveillance should be relevant for healthcare context. Antimicrobial stewardship remains one of the most important strategies to tackle antimicrobial resistance and antimicrobial surveillance methods must be as sensitive as possible.

Importance of antimicrobial stewardship in solid organ transplant recipients: An ESCMID perspective.

BACKGROUND: In the last decades, solid organ transplantation (SOT) has emerged as an important method in the management of chronic kidney, liver, heart, and lung failure. Antimicrobial use has led to a significant reduction of morbidity and mortality due to infectious complications among patients with SOT; however, it can lead to adverse events and drive the development of antimicrobial resistance; thus, antimicrobial stewardship is of extreme importance. Even though there are ongoing efforts of transplant societies to implement principles of antimicrobial stewardship in everyday practice in SOT, there is still a lack of guidelines in this patient population. AIM: The aim of this study was to review the status of antimicrobial stewardship in patients with SOT, highlight its importance from the perspective of an ongoing vivid dialogue among ESCMID experts in the field of antimicrobial stewardship, and depict opportunities for future study in the field. REVIEW: Antimicrobial stewardship programs are important in order to allow appropriate initiation and termination of antimicrobials in SOT recipients, and also aid in the most appropriate dosing and choosing of the route of administration of antimicrobials. Application of already known antimicrobial stewardship principles and application of currently used biomarkers and newly developed molecular rapid diagnostic testing tools can aid to the rationalization of antimicrobial prescribing and to a more targeted treatment of infections. Finally, physicians caring for SOT recipients should be actively involved in antimicrobial stewardship in order to assure optimization of antimicrobial prescribing and become familiar with the principles of antimicrobial stewardship.

Trends in the hospital-sector consumption of the WHO AWaRe Reserve group antibiotics in EU/EEA countries and the United Kingdom, 2010 to 2018.

BackgroundIn 2019, the World Health Organization published the 21st Model list of Essential Medicines and updated the Access, Watch Reserve (AWaRe) antibiotics classification to improve metrics and indicators for antibiotic stewardship activities. Reserve antibiotics are regarded as last-resort treatment options.AimWe investigated hospital-sector consumption quantities and trends of Reserve group antibiotics in European Union/European Economic Area countries and the United Kingdom (EU/EEA/UK).MethodsHospital-sector antimicrobial consumption data for 2010-2018 were obtained from the European Centre for Disease Prevention and Control. Antibacterials' consumption for systemic use (Anatomical Therapeutic Chemical classification (ATC) group J01) were included in the analysis and expressed as defined daily doses (DDD) per 1,000 inhabitants per day. We defined reserve antibiotics as per AWaRe classification and applied linear regression to analyse trends in consumption of reserve antibiotics throughout the study period.ResultsEU/EEA/UK average hospital-sector reserve-antibiotic consumption increased from 0.017 to 0.050 DDD per 1,000 inhabitants per day over the study period (p = 0.002). This significant increase concerned 15 countries. In 2018, four antibiotics (tigecycline, colistin, linezolid and daptomycin) constituted 91% of the consumption. Both absolute and relative (% of total hospital sector) consumption of reserve antibiotics varied considerably (up to 42-fold) between countries (from 0.004 to 0.155 DDD per 1,000 inhabitants per day and from 0.2% to 9.3%, respectively).ConclusionAn increasing trend in reserve antibiotic consumption was found in Europe. The substantial variation between countries may reflect the burden of infection with multidrug-resistant bacteria. Our results could guide national actions or optimisation of reserve antibiotic use.

An international inventory of antimicrobial stewardship (AMS) training programmes for AMS teams.

BACKGROUND: Healthcare professionals are increasingly expected to lead antimicrobial stewardship (AMS) initiatives. This role in complex healthcare environments requires specialized training. OBJECTIVES: Little is known about the types of AMS training programmes available to clinicians seeking to play a lead role in AMS. We aimed to identify clinicians' awareness of AMS training programmes, characteristics of AMS training programmes available and potential barriers to participation. METHODS: AMS training programmes available were identified by members of the ESCMID Study Group for Antimicrobial Stewardship (ESGAP) via an online survey and through an online search in 2018. Individual training programme course coordinators were then contacted (September-October 2018) for data on the target audience(s), methods of delivery, intended outcomes and potential barriers to accessing the training programme. RESULTS: A total of 166/250 ESGAP members (66%) responded to the survey, nominating 48 unique AMS training programmes. An additional 32 training programmes were identified through an online search. AMS training programmes were from around the world. Less than half (44.4%) of respondents were aware of one or more AMS training programmes available, with pharmacists more aware compared with medical doctors and other professionals (73% versus 46% and 25%, respectively). AMS training programmes were most commonly delivered online (59%) and aimed at medical doctors (46%). Training costs and a lack of recognition by health professional societies were the most frequently cited barriers to participation in AMS training programmes. CONCLUSIONS: The development of a systematic inventory of AMS training programmes around the globe identifies opportunities and limitations to current training available. Improving access and increasing awareness amongst target participants will support improved education in AMS.

Impact of guidelines on antibiotic prescribing approach in primary care-a 10-year study.

BACKGROUND: Publication and implementation of clinical guidelines is an important educational measure that considerably helps physicians in choosing appropriate antimicrobial drug. OBJECTIVES: To evaluate long-term changes in antimicrobial prescribing habits before and after publishing the guidelines and to determine the factors that influence physician's decision to prescribe an antimicrobial drug. METHODS: The study among general practitioners in Primorsko-Goranska County was conducted in three periods (January 2009, January 2011 and April 2019) by using a structured questionnaire that included general data about the physician, questions about their habits in antibiotic prescribing, criteria that influenced decision to prescribe antibiotics and antimicrobial agent(s) preferred in treating common infections. RESULTS: Concomitant chronic (non-pulmonary) disease was the most important factor influencing decision to prescribe an antimicrobial drug. Over 88% of physicians that completed the survey declared themselves as rational prescribers of antimicrobials but more than half of them (53.3%) sometimes prescribed an antibiotic even though it was not indicated compared to 75% of self-reported non-rational prescribers (P ˂ 0.05). Self-reported adherence to the guidelines increased from 34.6% in 2011 to 51.8% in 2019. CONCLUSION: The research showed improvement in physicians' knowledge in choosing the right antibiotic based on the analysis of answers but indicated the necessity for improving communication skills and empowering physicians not to prescribe antibiotics 'just in case' because of diagnostic uncertainty or patient demand. Further qualitative research is needed to understand physicians' prescribing behaviour and decision-making processes in order to develop interventions that will effectively improve the use of antibiotics.

Decrease in community antibiotic consumption during the COVID-19 pandemic, EU/EEA, 2020.

We present a European Union/European Economic Area-wide overview of the changes in consumption of antibacterials for systemic use (ATC J01) in the community between 2019 and 2020 as reported to the European Surveillance of Antimicrobial Consumption Network. Overall antibiotic consumption decreased by 18.3% between 2019 and 2020, the largest annual decrease in the network's two-decade history. We observed a strong association between the level of community antibiotic consumption in 2019 and the size of the decrease between 2019 and 2020.

What is the most appropriate metric for the assessment of volume of antibiotic use?

One of the core elements of antibiotic stewardship is surveillance and monitoring of quantity of antibiotic use. This requires tools for measuring the quantity of antibiotic use. However, these metrics have not been standardized, and different metrics are used across different countries, regions and individual healthcare settings. In the literature, there is much controversy on the most appropriate metric for monitoring antibiotic use. Several authors have questioned the relevance of DDDs, which are recommended by the WHO, while others still prefer using DDDs as the best available metric. The results of the recent DRIVE-AB project suggest that a combination of metrics may be the best approach, since all metrics have limitations and provide different perspectives.

Decreasing and stabilising trends of antimicrobial consumption and resistance in Escherichia coli and Klebsiella pneumoniae in segmented regression analysis, European Union/European Economic Area, 2001 to 2018.

Investments to reduce the spread of antimicrobial resistance (AMR) in the European Union have been made, including efforts to strengthen prudent antimicrobial use. Using segmented regression, we report decreasing and stabilising trends in data reported to the European Surveillance of Antimicrobial Consumption Network and stabilising trends in data reported to the European Antimicrobial Resistance Surveillance Network. Our results could be an early indication of the effect of prioritising AMR on the public health agenda.

Quality indicators assessing antibiotic use in the outpatient setting: a systematic review followed by an international multidisciplinary consensus procedure.

Objectives: Quality indicators (QIs) assessing the appropriateness of antibiotic use are essential to identify targets for improvement and guide antibiotic stewardship interventions. The aim of this study was to develop a set of QIs for the outpatient setting from a global perspective. Methods: A systematic literature review was performed by searching MEDLINE and relevant web sites in order to retrieve a list of QIs. These indicators were extracted from published trials, guidelines, literature reviews or consensus procedures. This evidence-based set of QIs was evaluated by a multidisciplinary, international group of stakeholders using a RAND-modified Delphi procedure, using two online questionnaires and a face-to-face meeting between them. Stakeholders appraised the QIs' relevance using a nine-point Likert scale. This work is part of the DRIVE-AB project. Results: The systematic literature review identified 43 unique QIs, from 54 studies and seven web sites. Twenty-five stakeholders from 14 countries participated in the consensus procedure. Ultimately, 32 QIs were retained, with a high level of agreement. The set of QIs included structure, process and outcome indicators, targeting both high- and middle- to low-income settings. Most indicators focused on general practice, addressing the common indications for antibiotic use in the community (particularly urinary and respiratory tract infections), and the organization of healthcare facilities. Twelve indicators specifically addressed outpatient parenteral antimicrobial therapy (OPAT). Conclusions: We identified a set of 32 outpatient QIs to measure the appropriateness of antibiotic use. These QIs can be used to identify targets for improvement and to evaluate the effects of antibiotic stewardship interventions.

Metrics to assess the quantity of antibiotic use in the outpatient setting: a systematic review followed by an international multidisciplinary consensus procedure.

Background: The international Innovative Medicines Initiative (IMI) project DRIVE-AB (Driving Reinvestment in Research and Development and Responsible Antibiotic Use) aims to develop a global definition of 'responsible' antibiotic use. Objectives: To identify consensually validated quantity metrics for antibiotic use in the outpatient setting. Methods: First, outpatient quantity metrics (OQMs) were identified by a systematic search of literature and web sites published until 12 December 2014. Identified OQMs were evaluated by a multidisciplinary, international stakeholder panel using a RAND-modified Delphi procedure. Two online questionnaires and a face-to-face meeting between them were conducted to assess OQM relevance for measuring the quantity of antibiotic use on a nine-point Likert scale, to add comments or to propose new metrics. Results: A total of 597 articles were screened, 177 studies met criteria for full-text screening and 138 were finally included. Twenty different OQMs were identified and appraised by 23 stakeholders. During the first survey, 14 OQMs were excluded and 6 qualified for discussion. During the face-to-face meeting, 10 stakeholders retained five OQMs and suggestions were made considering context and combination of metrics. The final set of metrics included defined daily doses, treatments/courses and prescriptions per defined population, treatments/courses and prescriptions per defined number of physician contacts and seasonal variation of total antibiotic use. Conclusions: A small set of consensually validated metrics to assess the quantity of antibiotic use in the outpatient setting was obtained, enabling (inter)national comparisons. The OQMs will help build a global conceptual framework for responsible antibiotic use.

Quality indicators for responsible antibiotic use in the inpatient setting: a systematic review followed by an international multidisciplinary consensus procedure.

Background: This study was conducted as part of the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project and aimed to develop generic quality indicators (QIs) for responsible antibiotic use in the inpatient setting. Methods: A RAND-modified Delphi method was applied. First, QIs were identified by a systematic review. A complementary search was performed on web sites of relevant organizations. Duplicates were removed and disease and patient-specific QIs were combined into generic indicators. The relevance of these QIs was appraised by a multidisciplinary international stakeholder panel through two questionnaires and an in-between consensus meeting. Results: The systematic review retrieved 70 potential generic QIs. The QIs were appraised by 25 international stakeholders with diverse backgrounds (medical community, public health, patients, antibiotic research and development, regulators, governments). Ultimately, 51 QIs were selected in consensus. QIs with the highest relevance score included: (i) an antibiotic plan should be documented in the medical record at the start of the antibiotic treatment; (ii) the results of bacteriological susceptibility testing should be documented in the medical record; (iii) the local guidelines should correspond to the national guidelines but should be adapted based on local resistance patterns; (iv) an antibiotic stewardship programme should be in place at the healthcare facility; and (v) allergy status should be taken into account when antibiotics are prescribed. Conclusions: This systematic and stepwise method combining evidence from literature and stakeholder opinion led to multidisciplinary international consensus on generic inpatient QIs that can be used globally to assess the quality of antibiotic use.

Variation in antibiotic use among and within different settings: a systematic review.

Objectives: Variation in antibiotic use may reflect inappropriate use. We aimed to systematically describe the variation in measures for antibiotic use among settings or providers. This study was conducted as part of the innovative medicines initiative (IMI)-funded international project DRIVE-AB. Methods: We searched for studies published in MEDLINE from January 2004 to January 2015 reporting variation in measures for systemic antibiotic use (e.g. DDDs) in inpatient and outpatient settings. The ratio between a study's reported maximum and minimum values of a given measure [maximum:minimum ratio (MMR)] was calculated as a measure of variation. Similar measures were grouped into categories and when possible the overall median ratio and IQR were calculated. Results: One hundred and forty-three studies were included, of which 85 (59.4%) were conducted in Europe and 12 (8.4%) in low- to middle-income countries. Most studies described the variation in the quantity of antibiotic use in the inpatient setting (81/143, 56.6%), especially among hospitals (41/81, 50.6%). The most frequent measure was DDDs with different denominators, reported in 23/81 (28.4%) inpatient studies and in 28/62 (45.2%) outpatient studies. For this measure, we found a median MMR of 3.7 (IQR 2.6-5.0) in 4 studies reporting antibiotic use in ICUs in DDDs/1000 patient-days and a median MMR of 2.3 (IQR 1.5-3.2) in 18 studies reporting outpatient antibiotic use in DDDs/1000 inhabitant-days. Substantial variation was also identified in other measures. Conclusions: Our review confirms the large variation in antibiotic use even across similar settings and providers. Data from low- and middle-income countries are under-represented. Further studies should try to better elucidate reasons for the observed variation to facilitate interventions that reduce unwarranted practice variation. In addition, the heterogeneity of reported measures clearly shows that there is need for standardization.

Metrics for quantifying antibiotic use in the hospital setting: results from a systematic review and international multidisciplinary consensus procedure.

Background: Quantifying antibiotic use is an essential element of antibiotic stewardship since it allows comparison between different settings and time windows, and measurement of the impact of interventions. However, quantity metrics (QMs) and methods have not been standardized. Objectives: To propose a set of QMs for antibiotic use in inpatients (IQMs) that are accepted globally by professionals in a range of disciplines. The study was conducted within the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project. Methods: A systematic literature review using MEDLINE identified articles on measuring inpatient antibiotic use, published up to 29 January 2015. A consensually selected list of national and international web sites was screened for additional IQMs. IQMs were classified according to the type of numerator used and presented to a multidisciplinary panel of stakeholders. A RAND-modified Delphi consensus procedure, which consisted of two online questionnaires and a face-to-face meeting, was performed. Results: The systematic literature review and web site search identified 168 eligible articles from which an initial list of 20 IQMs, composed of 20 different numerators and associated denominators was developed. The consensus procedure resulted in a final set of 12 IQMs. Among this final set, DDDs per 100(0) patient-days and days of therapy per patient-days were most frequently found in the review. The panel recommended that antibiotic use should be expressed in at least two metrics simultaneously. Conclusions: Our consensus procedure identified a set of IQMs that we propose as an evidence-based global standard.

Potentially inappropriate prescribing to the elderly: comparison of new protocol to Beers criteria with relation to hospitalizations for ADRs.

PURPOSE: Screening tools for detecting potentially inappropriate medications (PIMs) represent an important way to assess drug prescribing in the elderly. Recently, we introduced a new comprehensive tool to detect both PIMs and clinically important drug-drug interactions (DDI). The aim of the study was to assess the applicability of the new tool. METHODS: The new tool was used to detect PIMs and DDI and to assess their relation to morbidity and hospital admissions. It was also compared to the widely used Beers criteria. The study population included 454 consecutive patients aged ≥65 years who were acutely admitted to the Department of Internal Medicine of the University Hospital of Osijek. The Naranjo protocol was used to analyze the causal relationship between a drug and an adverse event. RESULTS: According to the new protocol, 44 % patients were taking PIMs, while 33 % patients were taking drugs with potentially serious DDIs. In 11 % of the overall number of patients, the cause of admission was adverse drug reaction (ADR), and among contributing drugs, 44 % were potentially inappropriate according to our protocol. Gastrointestinal bleeding was the most common diagnosis causing ADR-associated admission, and in 72 % cases, either PIM or a potentially serious DDI was involved. CONCLUSION: The new Croatian tool detected a high number of patients taking PIMs and/or having potentially important drug-drug interactions. The tool also detected almost half of the drugs contributing to ADR-associated admission. We expect the tool to be useful in prescription evaluation for the elderly inpatient and outpatient population.

Potentially inappropriate prescribing in elderly outpatients in Croatia.

PURPOSE: The purpose of this study was to determine the prevalence of inappropriate prescribing to the elderly and to identify possible gender-related differences in prescribing certain potentially inappropriate medications (PIMs) to outpatients by using large administrative prescription database. METHODS: Medications prescribed for elderly outpatients (≥ 65 years) in Primorsko-Goranska County, Croatia, who received five or more different drugs simultaneously in 2010, were analyzed. The prevalence of potentially inappropriate drugs prescribed to the elderly was assessed using the new comprehensive protocol developed by authors Mimica Matanovic and Vlahovic-Palcevski. RESULTS: A total of 62.4 % of patients received at least one medication with unfavorable benefit/risk ratio in the elderly. Female patients were given inappropriate medications in a significantly higher percentage than men (69.3 % vs. 50.5 %; p < 0.001). The average number of prescriptions for PIMs that should have been avoided with certain diseases or conditions was 0.88 per patient in the survey. The most common drug combination potentially leading to serious drug-drug interactions (DDIs) included an angiotensin-converting enzyme (ACE) inhibitor and a potassium supplement. CONCLUSIONS: Our study has shown that every tenth medication prescribed to a patient > 65 years and receiving five or more drugs was potentially inappropriate. Elderly women were prescribed PIMs more often than men. Drugs of concern in female patients were benzodiazepines, antidepressants, and nonsteroidal anti-inflammatory drugs (NSAIDs). In male patients, there was a significantly higher proportion of possible interactions with warfarin, theophylline, and medications affecting the cardiovascular system, such as ACE inhibitors and amiodarone.

Personalizing health care: feasibility and future implications.

Considerable variety in how patients respond to treatments, driven by differences in their geno- and/ or phenotypes, calls for a more tailored approach. This is already happening, and will accelerate with developments in personalized medicine. However, its promise has not always translated into improvements in patient care due to the complexities involved. There are also concerns that advice for tests has been reversed, current tests can be costly, there is fragmentation of funding of care, and companies may seek high prices for new targeted drugs. There is a need to integrate current knowledge from a payer's perspective to provide future guidance. Multiple findings including general considerations; influence of pharmacogenomics on response and toxicity of drug therapies; value of biomarker tests; limitations and costs of tests; and potentially high acquisition costs of new targeted therapies help to give guidance on potential ways forward for all stakeholder groups. Overall, personalized medicine has the potential to revolutionize care. However, current challenges and concerns need to be addressed to enhance its uptake and funding to benefit patients.

Antimicrobial Prescribing Preparedness of Croatian Medical Students-Did It Change between 2015 and 2019?

BACKGROUND: Antimicrobials are some of the most prescribed drugs by junior doctors, but studies suggest most medical graduates feel unprepared for their future prescribing tasks. The aim of the present study was to compare the self-reported preparedness to prudently prescribe antimicrobials of final-year medical students in Croatia in 2015 and 2019. METHODS: The same self-reported web-based survey on the preparedness to prescribe antibiotics was used in both 2015 and 2019. All final-year students at all four medical schools in Croatia (Osijek, Rijeka, Split, and Zagreb) were invited to participate in both 2015 and 2019. Preparedness scores were divided into "topic preparedness scores" and "global preparedness scores". Topic preparedness scores represented the percentage of students at a medical school who felt sufficiently prepared for each topic. They were first established at a medical school level and then at the national level. Global preparedness scores were determined for each student separately and then calculated at the medical school and national levels. RESULTS: The country's global preparedness score, representing the average proportion of topics in which students felt sufficiently prepared, was slightly higher in 2015 compared with the 2019 results (62.7% vs. 56.5%; p = 0.191). Croatian students reported higher preparedness in 2015 than in 2019 for 25 out of 27 topics included in the survey. The majority of students reported a need for more education on antibiotic use both in 2015 and 2019 (78.0% vs. 83.0%; p = 0.199). CONCLUSIONS: Despite increasing antimicrobial stewardship activities in various healthcare settings, medical students who are about to start prescribing antibiotics on their own do not feel sufficiently prepared to do so. Antimicrobial stewardship programs should be designed to incorporate undergraduate medical student education, for instance, as a specific, mandatory course or integrated into other courses, such as clinical pharmacology.

Analysis of the Gut Microbiome and Dietary Habits in Metastatic Melanoma Patients with a Complete and Sustained Response to Immunotherapy.

Immunotherapy has improved the prognosis of metastatic melanoma patients, although most patients do not achieve a complete response. While specific gut microbiome and dietary habits might influence treatment success, there is a lack of concordance between the studies, potentially due to dichotomizing patients only into responders and non-responders. The aim of this study was to elucidate whether metastatic melanoma patients with complete and sustained response to immunotherapy exhibit differences in gut microbiome composition among themselves, and whether those differences were associated with specific dietary habits. Shotgun metagenomic sequencing revealed that patients who exhibited a complete response after more than 9 months of treatment (late responders) exhibited a significantly higher beta-diversity (p = 0.02), with a higher abundance of Coprococcus comes (LDA 3.548, p = 0.010), Bifidobacterium pseudocatenulatum (LDA 3.392, p = 0.024), and lower abundance of Prevotellaceae (p = 0.04) compared to early responders. Furthermore, late responders exhibited a different diet profile, with a significantly lower intake of proteins and sweets and a higher intake of flavones (p < 0.05). The research showed that metastatic melanoma patients with a complete and sustained response to immunotherapy were a heterogeneous group. Patients with a late complete response exhibited microbiome and dietary habits which were previously associated with an improved response to immunotherapy.