2021 update of the AGIHO guideline on evidence-based management of COVID-19 in patients with cancer regarding diagnostics, viral shedding, vaccination and therapy.

The worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated infectious coronavirus disease (COVID-19) has posed a unique challenge to medical staff, patients and their families. Patients with cancer, particularly those with haematologic malignancies, have been identified to be at high risk to develop severe COVID-19. Since publication of our previous guideline on evidence-based management of COVID-19 in patients with cancer, research efforts have continued and new relevant data has come to light, maybe most importantly in the field of vaccination studies. Therefore, an update of our guideline on several clinically important topics is warranted. Here, we provide a concise update of evidence-based recommendations for rapid diagnostics, viral shedding, vaccination and therapy of COVID-19 in patients with cancer. This guideline update was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology by critically reviewing the currently available data on these topics applying evidence-based medicine criteria.

Mucormycosis treatment: Recommendations, latest advances, and perspectives.

Mucormycosis are life-threatening fungal infections especially affecting immunocompromised or diabetic patients. Despite treatment, mortality remains high (from 32 to 70% according to organ involvement). This review provides an update on mucormycosis management. The latest recommendations strongly recommend as first-line therapy the use of liposomal amphotericin B (≥5mg/kg) combined with surgery whenever possible. Isavuconazole and intravenous or delayed-release tablet forms of posaconazole have remained second-line. Many molecules are currently in development to fight against invasive fungal diseases but few have demonstrated efficacy against Mucorales. Despite in vitro efficacy, combinations of treatment have failed to demonstrate superiority versus monotherapy. Adjuvant therapies are particularly complex to evaluate without prospective randomized controlled studies, which are complex to perform due to low incidence rate and high mortality of mucormycosis. Perspectives are nonetheless encouraging. New approaches assessing relationships between host, fungi, and antifungal drugs, and new routes of administration such as aerosols could improve mucormycosis treatment.

Immune-related (IR)-pneumonitis during the COVID-19 pandemic: multidisciplinary recommendations for diagnosis and management.

Immune-related (IR)-pneumonitis is a rare and potentially fatal toxicity of anti-PD(L)1 immunotherapy. Expert guidelines for the diagnosis and management of IR-pneumonitis include multidisciplinary input from medical oncology, pulmonary medicine, infectious disease, and radiology specialists. Severe acute respiratory syndrome coronavirus 2 is a recently recognized respiratory virus that is responsible for causing the COVID-19 global pandemic. Symptoms and imaging findings from IR-pneumonitis and COVID-19 pneumonia can be similar, and early COVID-19 viral testing may yield false negative results, complicating the diagnosis and management of both entities. Herein, we present a set of multidisciplinary consensus recommendations for the diagnosis and management of IR-pneumonitis in the setting of COVID-19 including: (1) isolation procedures, (2) recommended imaging and interpretation, (3) adaptations to invasive testing, (4) adaptations to the management of IR-pneumonitis, (5) immunosuppression for steroid-refractory IR-pneumonitis, and (6) management of suspected concurrent IR-pneumonitis and COVID-19 infection. There is an emerging need for the adaptation of expert guidelines for IR-pneumonitis in the setting of the global COVID-19 pandemic. We propose a multidisciplinary consensus on this topic, in this position paper.

[Revision of guideline on Q fever fatigue syndrome (QFS)]. / Herziene richtlijn Q-koortsvermoeidheidssyndroom (QVS).

In 2012 the multidisciplinary guideline Q fever fatigue syndrome was developed for the Netherlands. The availability of new research data and developments and experiences from daily clinical practice made it necessary to revise this guideline. The multidisciplinary working group that has revised the guideline is composed of representatives from all medical professions involved in the care of patients with QFS and representatives of the patients' association. The revised guideline incorporates a number of changes, including refinement of the QFS diagnostic criteria and updates regarding advice on support and reintegration.

Recommendations for infectious disease screening in migrants to Western Europe with inflammatory arthropathies before starting biologic agents. Results from a multidisciplinary task force of four European societies (SIR, SER, SIMET, SEMTSI) facing the largest impact of the flow of migrants today.

OBJECTIVES: Inflammatory arthritis needs infectious disease screening before starting a biologic agent, however, few data are known about migrant patients, who represent a peculiar population which requires a multidisciplinary approach among international health specialists and should also be considered by health authorities. For this reason, the Italian and Spanish Societies of Rheumatology (SIR and SER) and Tropical Medicine (SIMET and SEMTSI) promoted a multidisciplinary task force in order to produce specific recommendations about screening and advices to be considered in migrant patients with inflammatory arthritis candidate to receive biological therapy, according to their geographical origin. METHODS: The experts provided a prioritised list of research questions and the eligible spectrum of inflammatory arthritis, biologic drugs and infectious disease were defined in order to perform a systematic literature review. A search was made in Medline, Embase and Cochrane library, updated to March 2015. Ubiquitous infections and HBV, HCV, HIV and tuberculosis that are already considered in national and international recommendations, were not included. The strength of each recommendation was determined. RESULTS: The task force members agreed on 7 overarching principles. The risk of reactivation of selected potentially latent infectious disease was addressed in migrants with inflammatory arthritis candidates for biologics was considered and 15 potentially relevant infections were identified. CONCLUSIONS: Fifteen disease-specific recommendations were formulated on the basis of high level of agreement among the experts panel.

Executive summary of the diagnosis and treatment of urinary tract infection: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC).

Most urinary tract infections (UTI) are uncomplicated infections occurring in young women. An extensive evaluation is not required in the majority of cases, and they can be safely managed as outpatients with oral antibiotics. Escherichia coli is by far the most common uropathogen, accounting for >80% of all cases. Other major clinical problems associated with UTI include asymptomatic bacteriuria, and patients with complicated UTI. Complicated UTIs are a heterogeneous group associated with conditions that increase the risk of acquiring infection or treatment failure. Distinguishing between complicated and uncomplicated UTI is important, as it influences the initial evaluation, choice, and duration of antimicrobial therapy. Diagnosis is especially challenging in the elderly and in patients with in-dwelling catheters. The increasing prevalence of resistant uropathogens, including extended-spectrum ß-lactamases and carbapenemase-producing Enterobacteriaceae, and other multidrug-resistant Gram-negative organisms further compromises treatment of both complicated and uncomplicated UTIs. The aim of these Clinical Guidelines is to provide a set of recommendations for improving the diagnosis and treatment of UTI.

[Infection Prevention in Premature Infants and Newborns in Thuringia: Implementation of Recommendation of the Commission for Hospital Hygiene and Infection Prevention (KRINKO)]. / Infektionsprävention bei Früh- und Neugeborenen in Thüringen: Umsetzung der Empfehlung der Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO).

Systematic recording of practical implementation of current recommendations of KRINKO for the prevention of nosocomial infections in premature and newborn infants in children's hospitals in Thuringia. All neonatal treatment centers in Thuringia (n=18) were included in this survey. Answer were received from 83% (15/18). Degree of compliance was 100% in level-1 (3/3) and level-2 centers (5/5), and 70% in level-3 centers (7/10). The aim of the questionnaire was to evaluate infection prevention measures as well as structural/organizational parameters in neonatal centers in Thuringia. Preventive measures as well as weekly screening for colonization was fully performed in patients with a birth weight <1 500 g (n=205) at all centers. Additionally, prolonged screening and colonization surveillance measures were performed in 60% of all units until discharge from the hospital. Results related to structural/organizational parameters and especially structural conditions in neonatal centers in Thuringia pointed up challenges (2 m minimum distance between incubators in 27% (n=4/15), isolation in single room in 53% (n=8/15)). Insufficient number of staff also hamper the complete implementation of KRINKO recommendations (intensive care unit: patient/staff ratio (MW±SD) 2.5±1.1; newborn area 4.3±0.9). Analysis shows actual rate of implementation of KRINKO recommendations as well as structural/organizational parameters in neonatal treatment centers in Thuringia. It provides important points for discussion regarding necessary staff numbers and structural conditions. Analysis could also be used for future surveys in other regions in Germany.

[Treatment of hepatitis C: what is known?]. / Therapie der Hepatitis C: Was ist gesichert?

BACKGROUND: Treatment of hepatitis C is changing dramatically. Various new direct-acting antivirals (DAA) against HCV have recently been approved or will become available during the next months. OBJECTIVES: To summarize the efficacy of DAAs and to describe optimal treatment regimens for chronic hepatitis C. METHODS: Review of selected phase 2 and 3 trials investigating anti-HCV drugs and recent HCV guidelines. RESULTS: New HCV therapies are interferon-free and lead to sustained HCV clearance in >90% of cases. DAAs include HCV protease inhibitors, NS5A inhibitors as well as nucleotide and non-nucleoside HCV polymerase inhibitors. Depending on the stage of liver disease, HCV genotype and viral load, treatment duration is 8-24 weeks. Ribavirin is not needed anymore in every case. Resistance against HCV drugs is not a major factor determining treatment response, but resistance testing is recommended in case of treatment failures before re-treatment is considered. CONCLUSIONS: Chronic hepatitis C is a curable disease. It remains to be determined to what extent HCV clearance will alter liver function and the risk for hepatocellular carcinoma in patients with liver cirrhosis.

Variability and accuracy in interpretation of consolidation on chest radiography for diagnosing pneumonia in children under 5 years of age.

BACKGROUND: Consolidation on chest radiography is widely used as the reference standard for defining pneumonia and variability in interpretation is well known but not well explored or explained. METHODS: Three pediatric sub-specialists (infectious diseases, radiology and respiratory medicine) viewed 3,033 chest radiographs in children aged under 5 years of age who presented to one Emergency Department (ED) with a febrile illness. Radiographs were viewed blind to clinical information about the child and blind to findings of other readers. Each chest radiograph was identified as positive or negative for consolidation. Percentage agreement and kappa scores were calculated for pairs of readers. Prevalence of consolidation and reader sensitivity/specificity was estimated using latent class analysis. RESULTS: Using the majority rule, 456 (15%) chest radiographs were positive for consolidation while the latent class estimate was 17%. The radiologist was most likely (21.3%) and respiratory physician least likely (13.7%) to diagnose consolidation. Overall percentage agreement for pairs of readers was 85-90%. However, chance corrected agreement between the readers was moderate, with kappa scores 0.4-0.6 and did not vary with patient characteristics (age, gender, and presence of chronic illness). Estimated sensitivity ranged from 0.71 to 0.81 across readers, and specificity 0.91 to 0.98. CONCLUSIONS: Overall agreement for identification of consolidation on chest radiographs was good, but agreement adjusted for chance was only moderate and did not vary with patient characteristics. Clinicians need to be aware that chest radiography is an imperfect test for diagnosing pneumonia and has considerable variability in its interpretation.

Challenges in diagnosing extrapulmonary tuberculosis in the European Union, 2011.

In the European Union (EU) 72,334 tuberculosis (TB) cases were notified in 2011, of which 16,116 (22%) had extrapulmonary tuberculosis (EPTB). The percentage of TB cases with EPTB ranged from 4% to 48% in the reporting countries. This difference might be explained by differences in risk factors for EPTB or challenges in diagnosis. To assess the practices in diagnosis of EPTB we asked European Union/European Economic Area (EU/EEA) countries to participate in a report describing the diagnostic procedures and challenges in diagnosing EPTB. Eleven EU Member States participated and reports showed that in the majority EPTB is diagnosed by a pulmonologist, sometimes in collaboration with the doctor who is specialised in the organ where the symptoms presented. In most countries a medical history and examination is followed by invasive procedures, puncture or biopsy, to collect material for confirmation of the disease (by culture/histology/cytology). Some countries also use the tuberculin skin test or an interferon-gamma-release-assay. A wide variety of radiological tests may be used. Countries that reported challenges in the diagnosis of EPTB reported that EPTB is often not considered because it is a rare disease and most medical professionals will not have experience in diagnosing EPTB. The fact that EPTB can present with a variety of symptoms that may mimic symptoms of other pathologies does pose a further challenge in diagnosis. In addition, obtaining an appropriate sample for confirmation of EPTB was frequently mentioned as a challenge. In summary, diagnosis of EPTB poses challenges due to the diversity of symptoms with which EPTB may present, the low level of suspicion of clinicians, and due to the difficulty in obtaining an adequate sample for confirmation.

Operational scores in the diagnosis of chronic hepatitis. A semi-quantitative assessment.

Starting from the quantification of the specific lesions for chronic hepatitis B and C, our study focused on (i) the correspondence between the necroinflammatory activity and the fibrosis stage ascertained through the Ishak scoring system, (ii) the classification overlaps and differences of Ishak vs. METAVIR score. The study group consisted of 202 cases with chronic hepatitis B and 751 cases with chronic hepatitis C, diagnosed based on liver biopsies. The fragments of hepatic tissue were routinely processed and stained with Hematoxylin-Eosin, trichrome Szekely, Gordon-Sweet silver impregnation, and Periodic Acid-Schiff. A semiquantitative evaluation was performed using the Ishak (for hepatitis B and C) and the METAVIR (for hepatitis C) scoring systems. Our results revealed that the comparison between hepatitis B and C, based on the necroinflammatory activity and fibrosis, is able to offer through the numeric values of the Ishak scoring system accurate proofs, which support the aggressivity of hepatitis C, because it develops fibrosis more quickly, even on the background of mild necroinflammatory activity. Also, our data showed that the necroinflammatory activity and the fibrosis are not processes which progress in a consistent pattern. The application of the METAVIR scoring system for the cases with chronic hepatitis C confirmed that there is not a direct correlation between necroinflammation and fibrosis. The Ishak scoring system provides through the wide range of numeric values attributed for the evaluation of necroinflammatory activity and fibrosis far more precise criteria for the appraisal of the degree of damage to the hepatic parenchyma at the time of the diagnosis. Supplementary, the METAVIR scoring system allows for the hepatitis C an assessment of the entire histologic activity, including the interface hepatitis and the associated lobular necrosis components. The scoring systems have unavoidably strengths and weaknesses, but the choice of a specific one must reflect the consensus between the pathologists and the clinicians, relying on their experience.

[Fluoroquinolones use at the Saint-Louis Hospital: investigations before and after diffusion of recommendations and interventions of the anti-infectious referent]. / Prescription des fluoroquinolones à l'hôpital Saint-Louis: enquête avant et après diffusion de recommandations et interventions du référent anti-infectieux.

OBJECTIVE: The increase of bacterial resistance and of fluoroquinolones consumption led to set up an action plan in order to improve the use of fluoroquinolones. METHODS: Two audits "on a given day" in February 2005 (before action) and January 2007 (after action) allowed evaluating the effects of several interventions: restitution of the results from the first audit and antibiotics counselling by an infectious diseases expert, conception and diffusion of local recommendations and follow-up of antibiotic consumption. RESULTS: The prevalence of the fluoroquinolones' prescriptions was 49/503 hospitalized patients in 2005 (1st audit) and 30/482 in 2007 (2nd audit). Global conformity to the recommendations was 47% in 2005 and 40% in 2007. The number of inappropriate indications remained stable between 2005 (12, 25%) and 2007 (10, 33%) with a reduction in the use of fluoroquinolones for empirical treatments: 74% in 2005 and 50% in 2007. The use of the intravenous route decreased from 45% in 2005 to 27% in 2007. Consumption of antibiotics and fluoroquinolones decreased by 7% and 30% between 2005 and 2007 respectively. CONCLUSION: The interventions allowed to decrease the use of fluoroquinolones in empirical treatments and to limit the use of the intravenous route. The impact on the fluoroquinolones and antibiotics consumption has been demonstrated. However, the proportion of inappropriate indications remained unchanged. The impact of the fluoroquinolones consumption decrease on the bacterial resistance will be the next step of our action.

Immunization programs for infants, children, adolescents, and adults: clinical practice guidelines by the Infectious Diseases Society of America.

Evidence-based guidelines for immunization of infants, children, adolescents, and adults have been prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). These updated guidelines replace the previous immunization guidelines published in 2002. These guidelines are prepared for health care professionals who care for either immunocompetent or immunocompromised people of all ages. Since 2002, the capacity to prevent more infectious diseases has increased markedly for several reasons: new vaccines have been licensed (human papillomavirus vaccine; live, attenuated influenza vaccine; meningococcal conjugate vaccine; rotavirus vaccine; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis [Tdap] vaccine; and zoster vaccine), new combination vaccines have become available (measles, mumps, rubella and varicella vaccine; tetanus, diphtheria, and pertussis and inactivated polio vaccine; and tetanus, diphtheria, and pertussis and inactivated polio/Haemophilus influenzae type b vaccine), hepatitis A vaccines are now recommended universally for young children, influenza vaccines are recommended annually for all children aged 6 months through 18 years and for adults aged > or = 50 years, and a second dose of varicella vaccine has been added to the routine childhood and adolescent immunization schedule. Many of these changes have resulted in expansion of the adolescent and adult immunization schedules. In addition, increased emphasis has been placed on removing barriers to immunization, eliminating racial/ethnic disparities, addressing vaccine safety issues, financing recommended vaccines, and immunizing specific groups, including health care providers, immunocompromised people, pregnant women, international travelers, and internationally adopted children. This document includes 46 standards that, if followed, should lead to optimal disease prevention through vaccination in multiple population groups while maintaining high levels of safety.