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Data suggests that favipiravir (FVP) could be used against SARS-CoV-2. Our aim was to investigate the role of FVP in COVID-19 treatment. A prospective sequential cohort study was performed among adults hospitalized at our center between March and August 2020 with moderate-to-severe, PCR-confirmed COVID-19. For diagnosis and severity, ECDC and WHO definitions were utilized. Patients were screened for inclusion by a priori criteria and included in the FVP cohort if standard-of-care (SOC) + FVP or the non-FVP cohort if SOC ± other antivirals without FVP were administered for > 48 h from diagnosis. Treatment allocation was done per national guidelines, based on severity and drug availability. Primary endpoint was disease progression, a composite of 14-day all-cause death, need for mechanical ventilation, or immunomodulatory therapy. The impact of FVP exposure on disease progression was analyzed by binomial logistic regression. In all, 150 patients were included, 75 in each cohort. Disease progression (17/75, 22.7% vs. 10/75, 13.3%, p = 0.13), 14-day all-cause death (9/75, 12.0% vs. 10/75, 13.3%, p = 0.8), and need for mechanical ventilation (8/75, 10.7% vs. 4/75, 5.3%, p = 0.22) were similar, while immunomodulatory therapies were required more frequently among patients receiving FVP (10/75, 13.3% vs. 1/75, 1.3%, p

[Scope] Despite the large availability of vaccines, coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2, continues to be a major threat for health-care providers and fragile people. A number of options are now available for outpatients with mild-to-moderate COVID-19 at the risk of disease progression for the prevention of deaths or hospitalization., [Methods] A European Society of Clinical Microbiology and Infectious Diseases COVID-19 guidelines task force was established by the European Society of Clinical Microbiology and Infectious Diseases Executive Committee. A small group was established, half appointed by the chair and the remaining selected based on an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the population, intervention, comparison, outcome format was developed at the beginning of the process. For each population, intervention, comparison, outcome, two panel members performed a literature search, with a third panelist involved in case of inconsistent results. Voting was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., [Recommendations] In this update, we focus on anti-viral agents, monoclonal antibodies (mAbs) and other treatment options proposed for patients with mild or moderate COVID-19 who are at the risk of hospitalization or death. Although the use of anti-virals is recommended, especially nirmatrelvir/ritonavir and remdesivir or, alternatively, molnupirarvir, the administration of mAbs against the spike protein strictly depends on circulating variants or the ability to test timely for variants and sub-variants. At the time of writing (April–June 2022), the only active mAb was tixagevimab/cilgavimab given the predominance of the Omicron BA.2, BA.3, BA.4 and BA.5 sub-lineages in Europe. However, considering that the epidemiological scenario is extremely dynamic, constant monitoring of variants of concern is mandatory.

Convalescent plasma therapy might be a feasible option for treatment of novel infections. During the early phases of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, several promising results were published with convalescent plasma therapy, followed by more disappointing findings of randomised controlled trials. In our single-centre, open-label, prospective, cohort study, we assessed the findings of 180 patients treated with convalescent plasma during the first four waves of the pandemic in Hungary. The primary outcome was all-cause mortality; secondary outcomes were clinical improvement and need for intensive care unit admission by day 28. Subgroup analysis comparing elderly and non-elderly (less than 65 years of age) was performed. Twenty (11.4%) patients died by day 28, at significantly higher rates in the elderly subgroup (3 vs. 17, p p

Összefoglaló. Bevezetés, célkitűzés: Az influenzaszezonban fellépő, elsősorban virális megbetegedések jelentős morbiditási és mortalitási teherrel rendelkeznek. Célunk volt az influenzaszerű betegséggel (ILI) és akut légúti betegséggel (ARI) kórházba felvett felnőtt betegek mikrobiológiai és klinikai karakterisztikájának leírása. Módszerek: Egycentrumos, obszervációs kohorszvizsgálatunk során a 2018/2019. évi légúti szezonban a Dél-pesti Centrumkórház – Országos Hematológiai és Infektológiai Intézet Infektológiai Osztályára ILI/ARI diagnózissal felvett betegek eseteit dolgoztuk fel a kórház elektronikus adatbázisának segítségével. Bevonásra azon betegek kerültek, akiknél légúti PCR-vizsgálat történt. A bevont betegeket alcsoportokra osztottuk: klinikai ILI/ARI, PCR-pozitív ILI/ARI influezavírussal, PCR-pozitív ILI/ARI más vírussal. Elsődleges kimenetelnek a komplikált betegséglefolyást, másodlagos kimenetelnek a kórházi összhalálozást, az intenzív osztályos (ICU-) felvételt, az osztályos ápolás hosszát (LOS) és az ICU LOS-t választottuk. Statisztikai összehasonlításra a Mann–Whitney-féle U-próbát, a Fisher-féle egzakt tesztet használtuk. Eredmények: A bevont 112 eset 42,8%-ában igazolódott influenza A- vagy B-vírus, 7,1%-ban egyéb légúti vírus, második leggyakrabban az RSV etiológiai szerepe. Megelőző kórházi ellátás szignifikánsan gyakrabban fordult elő PCR-pozitív ILI/ARI esetekben (23,2% vs. 42,8%; p = 0,04); ugyanezen betegek körében a panaszok kezdetétől a diagnózisig eltelt idő kb. 1 nappal rövidebb volt (3,0 ± 4,0 vs. 4,0 ± 5,0 nap; p = 0,02). A komplikációk gyakoriságát hasonló nagyságúnak találtuk (46,4% vs. 51,8%; p = 0,72), a leggyakoribb szövődmény a tüdőgyulladás volt (45,5%). ICU-felvételre az esetek 5,4%-ában volt szükség, a kórházi összhalálozás 3,6%-nak adódott. A medián LOS 8,5 ± 8,0 nap, a medián ICU LOS ideje 20,5 ± 30,5 nap volt. Következtetés: A vizsgált légúti szezonban ILI/ARI diagnózissal felvett betegek jelentős részében influenza-, kisebb hányadban egyéb légúti vírusok voltak felelősek a klinikumért. A leggyakoribb szövődmény a pneumonia volt. A légúti PCR-vizsgálat lehetőséget nyújthat az etiológia tisztázására. Orv Hetil. 2020; 161(52): 2179–2187. Summary. Introduction, objectives: A significant burden of morbidity and mortality is caused by seasonal outbreaks of respiratory viruses. Our aim was to identify clinical and microbiological differences among adult patients hospitalized with acute respiratory infection (ARI) or influenza-like illness (ILI). Methods: A single-center observational cohort study was conducted at South Pest Central Hospital, National Institute of Hematology and Infectious Diseases during the 2018/2019 influenza season. Patients were identified using the hospital database, and included in the study if respiratory PCR sampling was done during hospital stay. Subgroups were created according to the identified etiology: clinical ILI/ARI (no PCR positivity), PCR positive ILI/ARI with influenza, PCR positive ILI/ARI with other virus(es). Primary outcome was the occurrence of any complication, secondary outcomes were in-hospital all-cause mortality, intensive care unit (ICU) admission, length of stay (LOS) and ICU LOS. For statistical analysis, Mann–Whitney and Fisher’s tests were used. Results: From 112 identified cases, 42.8% were caused by influenza A or B, 7.1% by other viruses, notably RSV. PCR positivity frequently associated with prior hospitalization (23.2% vs. 42.8%; p = 0.04), and shorter time from symptom onset to diagnosis (3.0 ± 4.0 vs. 4.0 ±5.0 days, p = 0.02). Complication rates were similar among subgroups (46.4% vs. 51.8%; p = 0.72), with pneumonia as a leading complication (45.5%). ICU admission was necessary in 5.4%, in-hospital all-cause mortality was 3.6%. Median LOS and ICU LOS were 8.5 ± 8.0 and 20.5 ± 30.5 days, respectively. Conclusion: During the 2018/2019 season, most ILI/ARI cases were caused by influenza, but other respiratory viruses could also be detected in lower rates. Pneumonia was the most common complication. Respiratory PCR sampling might provide a feasible way of etiology identification. Orv Hetil. 2020; 161(52): 2179–2187.

Absztrakt: A COVID–19 a SARS-CoV-2 vírus által okozott, járványosan terjedő, légúti kiindulású betegség. A kórokozó magas patogenitású, zoonotikus eredetű humán coronavírus, mely hatékonyan terjed emberről emberre cseppfertőzéssel és közeli kontaktussal. A vírusdiagnosztika a légutakból vett minta PCR-vizsgálatán alapul, melynek ismétlésére szükség lehet a fertőzés kizárására. A PCR-eredményt a klinikummal egybe kell vetni, mivel a preszimptomatikus beteg már vírust üríthet, a gyógyultak PCR-pozitivitása pedig hetekig elhúzódik. A terápiás stratégiák két ágát az antivirális gyógyszerek, valamint a hiperinflammációt gátló immunmodulánsok adják. Jelen összefoglalásunk a második azon két társközlemény közül, melyek célja a 2020. május 25-ig elérhető legfőbb nemzetközi és hazai betegséggel kapcsolatos eredmények ismertetése, elsősorban, de nem kizárólag hematológus kollégák számára.

Absztrakt: A COVID–19 a SARS-CoV-2 vírus által okozott, járványosan terjedő, légúti kiindulású betegség. A kórokozó magas patogenitású, zoonotikus eredetű humán coronavírus, mely hatékonyan terjed emberről emberre cseppfertőzéssel és közeli kontaktussal. A medián lappangási idő 5 nap, a maximum 14 nap. A COVID–19 kardinális tünetei a láz, dyspnoe és száraz köhögés. Az esetek 80%-a enyhe lefolyású, 5%-ban azonban intenzív terápiás ellátás és gépi lélegeztetés válik szükségessé. A COVID–19 akár súlyos, az egész szervezetre kiterjedő citokinvihart is kiválthat, mely gyors beavatkozás nélkül végzetes kimenetelű lehet. Jelen összefoglaló – melyet a diagnosztikai és terápiás szempontokat tárgyaló társközlemény követ – a betegséggel kapcsolatban 2020. május 25-ig elérhető legfőbb nemzetközi és hazai irodalmi eredményeket ismerteti; elsősorban, de nem kizárólag hematológus kollégák számára.

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[Scope] In January 2021, the ESCMID Executive Committee decided to launch a new initiative to develop ESCMID guidelines on several COVID-19-related issues, including treatment of COVID-19., [Methods] An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search with a third panellist involved in case of inconsistent results. Voting was based on the GRADE approach., [Questions addressed by the guideline and recommendations] A synthesis of the available evidence and recommendations is provided for each of the 15 PICOs, which cover use of hydroxychloroquine, bamlanivimab alone or in combination with etesevimab, casirivimab combined with imdevimab, ivermectin, azithromycin and empirical antibiotics, colchicine, corticosteroids, convalescent plasma, favipiravir, remdesivir, tocilizumab and interferon β-1a, as well as the utility of antifungal prophylaxis and enoxaparin. In general, the panel recommended against the use of hydroxychloroquine, ivermectin, azithromycin, colchicine and interferon β-1a. Conditional recommendations were given for the use of monoclonal antibodies in high-risk outpatients with mild–moderate COVID-19, and remdesivir. There was insufficient evidence to make a recommendation for use of favipiravir and antifungal prophylaxis, and it was recommended that antibiotics should not be routinely prescribed in patients with COVID-19 unless bacterial coinfection or secondary infection is suspected or confirmed. Tocilizumab and corticosteroids were recommended for treatment of severe COVID-19 but not in outpatients with non-severe COVID-19., [Scope] The aim of the present guidance is to provide evidence-based recommendations for management of adults with coronavirus disease 2019 (COVID-19). More specifically, the goal is to aid clinicians managing patients with COVID-19 at various levels of severity including outpatients, hospitalized patients, and those admitted to intensive care unit. Considering the composition of the panel, mostly clinical microbiologists or infectious disease specialists with no pulmonology or intensive care background, we focus only on pharmacological treatment and do not give recommendations on oxygen supplement/support. Similarly, as no paediatricians were included in the panel; the recommendations are only for adult patients with COVID-19. Considering the current literature, no guidance was given for special populations such as the immunocompromised.

Abstract: Streptococcal toxic shock syndrome (STSS) is a hyperacute, life-threatening illness, a complication of invasive streptococcal (mostly group A, rarely groups B, G or C) infection. There is no portal of entry (skin, vagina, pharynx) in nearly half of the STSS cases. The initial signs and symptoms (fever, flu-like complaints, hypotension) are scarce and aspecific, but because of its rapid progression and poor prognosis, early high level of suspicion is necessary. Management has 3 crucial points: initiation of anti-streptococcal regimen (and intravenous immunoglobulin in some cases), aggressive intensive care support of multi-organ failure, and surgical control of the infective source. In this article, we present a case of a patient succumbing to streptococcal toxic shock syndrome which was preceded by primary S. pyogenes bacteremia, and review the key points of this potentially fatal disease for practising clinicians. Orv Hetil. 2019; 160(48): 1887–1893.

Abstract: We report a case of a 41-year-old female patient presenting with watery diarrhoea and myalgia in the winter-season. Before her symptoms started she had participated in a pig slaughtering with her family. Some of the family members also became ill. On her physical examination periorbital odema and myalgia were found. Eosinophilia, hypalbuminaemia, elevated lactate dehydrogenase and creatin kinase levels were detected on laboratory investigations. The clinical picture, the laboratory findings and background epidemiological data implied the diagnosis of trichinellosis and albendazol was started. Serum gained on the 22nd post-infectious day turned out to be equivocal for trichinellosis. For this reason and because of the refractory fever a muscle-biopsy was done. Granulomatous myositis described by histology and Trichinella seropositivity from the repeated serum sample on the 62nd post-infectious day finally confirmed the diagnosis. During the course of the disease, we experienced elevation of troponin I suggesting myocarditis, but it was accompanied neither with abnormal ECG signs nor characteristic symptoms. Almost a century ago, a case report was published in Hungarian with a similar introduction. Trichinellosis in that epidemic setting led to the death of five people. Orv Hetil. 2019; 160(24): 952–957.

Large randomized clinical trials in severe Coronavirus Disease 2019 (COVID-19) patients have proven efficacy of intravenous tocilizumab. Our aim was to describe the laboratory parameters predicting in-hospital mortality of patients with tocilizumab administration in COVID-19 associated cytokine release syndrome (CRS).We evaluated high-dose (8 mg/kg) intravenous tocilizumab administration in severe and critically ill COVID-19 adult patients fulfilling predefined strict CRS criteria. A single-centre, prospective, observational cohort study was carried out among consecutive adult (≥18 years of age) in-patients with COVID-19 between April 1 and December 31, 2020. The primary endpoint was 28-day all-cause mortality. The changes in laboratory parameters from baseline on day 7 and 14 after administration of tocilizumab were analysed.In total, 1801 patients were admitted to our centre during the study period. One hundred and six patients received tocilizumab, and among them 62 (58.5%) required intensive care unit admittance while 25 (23.6%) deceased. At day 7 after tocilizumab administration, inflammatory markers (CRP, IL-6, ferritin) and lactate dehydrogenase (LDH) values were significantly lower among survivors. Subsequently, at day 14, differences of IL-6 and LDH levels has become more pronounced between subgroups. Restoration of absolute lymphocyte count (ALC) by day 7 and 14 was insufficient among patients who died.In our cohort, administration of high-dose tocilizumab for COVID-19 patients with CRS demonstrated clinical and sustained biochemical parameter improvement in 76.4%. In this patient population high and increasing LDH, IL-6, and low ALC levels had a predictive role for mortality.

BackgroundPreliminary data suggests that favipiravir might have a role in COVID-19 treatment. Our aim was to assess the role of favipiravir in the treatment of COVID-19.MethodsA single-center, prospective, observational, sequential cohort study was performed among consecutive adults hospitalized with PCR-confirmed COVID-19 between March– July,2020. Patients were screened for inclusion by a priori criteria, and were included in the favipiravir cohort if SOC+FVP, or the non-favipiravir group if SOC±other antiviral medications without FVP were administered for >48 hours. Treatment allocation was done per national guidelines. For COVID-19 diagnosis and severity, ECDC and WHO definitions were utilized, and daily per protocol hospital follow-up was done. Primary composite end-point was disease progression (14-day all-cause death, need for mechanical ventilation, or immunomodulatory therapy). For statistical comparison, Fisher’s exact test and Mann– Whitney U-test were used.ResultsIn all, 75 patients were included per cohort. In the FVP cohort, chronic heart disease (36/75, 48.0% vs. 16/75, 21.3%, pConclusionsIn this study, favipiravir did not seem to affect disease progression. Further data are needed to position this drug among the anti-SARS-CoV-2 armamentarium.

Background: Preliminary data suggests that favipiravir might have a role in COVID-19 treatment. Our aim was to assess the role of favipiravir in the treatment of COVID-19.Methods: A single-center, prospective, observational, sequential cohort study was performed among consecutive adults hospitalized with PCR-confirmed COVID-19 between March–July,2020. Patients were screened for inclusion by a priori criteria, and were included in the favipiravir cohort if SOC+FVP, or the non-favipiravir group if SOC±other antiviral medications without FVP were administered for >48 hours. Treatment allocation was done per national guidelines. For COVID-19 diagnosis and severity, ECDC and WHO definitions were utilized, and daily per protocol hospital follow-up was done. Primary composite end-point was disease progression (14-day all-cause death, need for mechanical ventilation, or immunomodulatory therapy). For statistical comparison, Fisher's exact test and Mann–Whitney U-test were used.Results: In all, 75 patients were included per cohort. In the FVP cohort, chronic heart disease (36/75, 48.0% vs. 16/75, 21.3%, pConclusions: In this study, favipiravir did not seem to affect disease progression. Further data are needed to position this drug among the anti-SARS-CoV-2 armamentarium.

Our aim was to analyze characteristics of treatment failure with intravenous tigecycline monotherapy among adults with severe Clostridioides (Clostridium) difficile infection (CDI). A single-centre observational cohort study was performed between 2014 and 2018. Data were collected by charts review, diagnosis and severity were determined by ESCMID guidelines. Primary outcome was treatment failure, secondary outcomes were in-hospital mortality, relapse, colectomy, and complication rates. Independent predictors of failure were identified using logistic regression. Altogether 110 patients were included, failure occurred in 37.3%. Patients with failure frequently had chronic heart and pulmonary co-morbidities, peritonitis, higher CRP levels, ICU admittance rates and need for total parenteral nutrition and vasopressors. Mostly, CDI-specific mortality and complications contributed to failure. Relapse rates were similar. Chronic pulmonary disease, ileus, total parenteral nutrition, and duration of tigecycline therapy were predictors of failure. We conclude that severe CDI cases with higher risk for tigecycline monotherapy failure might be identified by contributing factors.

To describe the characteristics of adult invasive H. influenzae disease, 34 patients diagnosed at a single tertiary center between 2004 and 2017 were analyzed in a retrospective case series study. The annual estimated incidence was 0.1 cases/100.000 inhabitants. Dominant source of infection was pneumonia accompanied by sepsis (62%) and caused by nontypeable strains (74%) with low ampicillin resistance (14%). Survival (94%) and complication rates were high (35%). Main empirical treatments were ceftriaxone or levofloxacine.

Introduction Data suggests that invasive fungal infections (IFI) might complicate COVID-19. Our goal was to describe characteristics of IFI among critically ill COVID-19 adults. Methods A retrospective observational case-series analysis was done between March–July 2020. Consecutive patients with critical COVID-19 were eligible, and have been included when proven or putative/probable IFI could be confirmed during their course. For COVID-19 diagnosis, ECDC definitions and WHO severity criteria were followed. Candidaemia was diagnosed according to the ESCMID 2012 guideline. Invasive pulmonary aspergillosis (IPA) was defined following EORTC/MSG, ECMM/ISHAM and modified AspICU criteria. Outcome variables were rates of IFIs, in-hospital all-cause mortality, rate and time to negative respiratory SARS-CoV-2 PCR. Results From 90 eligible patients, 20 (22.2%) fulfilled criteria for IFI. Incidence rate for IFI was 2.02 per 100 patient-days at ICU. Patients were mostly elderly males with significant comorbidities, requiring mechanical ventilation because of ARDS. IFI could be classified as candidaemia in 7/20 (40%), putative/probable IPA in 16/20 (80.0%). Isolated species of candidaemia episodes were Candida albicans (4/9, 44.4%), Candida glabrata (3/9, 33.3%), Candida parapsilosis (1/9, 11.1%), Candida metapsilosis (1/9, 11.1%). Mold isolates from lower respiratory tract were Aspergillus fumigatus, BAL galactomannan positivity was prevalent (16/20, 80.0%). Mortality was 12/20 (60.0%) with a median time to death of 31.0±37.0 (5–89) days. Only 9/20 (45.0%) patients reached SARS-CoV-2 PCR negativity after a median time of 20.0±12.0 (3–38) days. Conclusion In this small cohort of critically ill COVID-19 adults, morbidity and mortality related to invasive fungal infections proved to be significant.

We aimed to develop a scoring system for predicting in-hospital mortality of community-acquired (CA) sepsis patients. This was a prospective, observational multicenter study performed to analyze CA sepsis among adult patients through ID-IRI (Infectious Diseases International Research Initiative) at 32 centers in 10 countries between December 1, 2015, and May 15, 2016. After baseline evaluation, we used univariate analysis at the second and logistic regression analysis at the third phase. In this prospective observational study, data of 373 cases with CA sepsis or septic shock were submitted from 32 referral centers in 10 countries. The median age was 68 (51-77) years, and 174 (46,6%) of the patients were females. The median hospitalization time of the patients was 15 (10-21) days. Overall mortality rate due to CA sepsis was 17.7% (n = 66). The possible predictors which have strong correlation and the variables that cause collinearity are acute oliguria, altered consciousness, persistent hypotension, fever, serum creatinine, age, and serum total protein. CAS (%) is a new scoring system and works in accordance with the parameters in third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). The system has yielded successful results in terms of predicting mortality in CA sepsis patients.

Incidence and mortality rates of infections caused by Streptococcus pneumoniae (pneumococcus) are high worldwide and in Hungary among paediatric as well as adult populations. Pneumococci account for 35–40% of community acquired adult pneumonias requiring hospitalization, while 25–30% of Streptococcus pneumoniae pneumonias are accompanied by bacteraemia. 5–7% of all infections are fatal but this rate is exponentially higher in high risk patients and elderly people. Mortality could reach 20% among patients with severe invasive pneumococcal infections. Complications may develop despite administration of adequate antibiotics. The authors summarize the epidemiology of pneumococcal infections, pathogenesis of non-invasive and invasive disease and present basic clinical aspects through demonstration of four cases. Early risk stratification, sampling of hemocultures, administration of antibiotics and wider application of active immunization could reduce the mortality of invasive disease. Anti-pneumococcal vaccination is advisable for adults of ≥50 years and high risk patients of ≥18 years who are susceptible to pneumococcal disease. Orv. Hetil., 2015, 156(44), 1769–1777.

Antimicrobial stewardship (AMS) is the cornerstone activity in the combat against antimicrobial resistance. In order to ensure sustainable deployment and development of AMS, a strategic and regulatory framework needs to be provided by national healthcare authorities. Experts from 32 European countries, Israel and Turkey were invited to participate in a cross-sectional internet-based survey from October 2016 to May 2017 on the legal framework and mandatory components (structures, activities) of AMS in hospitals, i.e. components required by legislation or regulations. We collected data from 25 countries and two regions (in countries with federal health administration). Laws regulating AMS existed in seven countries and one region. Other health ministry regulations were applicable in 13 countries and one region. National strategies and/or action plans approved by ministries of health were in place in 13 countries and one region. Conversely, five countries and one region had no regulation of AMS in hospitals. Funding for AMS in hospitals was provided in five countries and one region. Eight countries and one region reported mandatory AMS structures and activities complying with the Transatlantic Taskforce on Antimicrobial Resistance (TATFAR) structure, policy and practice indicators. In 10/27 cases, however, the mandatory AMS activities were not being fully carried out. The survey showed heterogeneous legal frameworks for AMS in hospitals, and in many countries it was even lacking. The situation may be critical in countries with poor control of antimicrobial use and resistance. Recent international initiatives calling on policy-makers to address the threat of antimicrobial resistance could yield improvement., peer-reviewed