Economic impact of managing invasive mold disease with isavuconazole compared with liposomal amphotericin B followed by posaconazole in Spain.

BACKGROUND: Invasive fungal infections (IFI) are associated with significant morbidity and mortality. The objective of this work was to compare the costs per adult patient, associated with intravenous isavuconazole (ISAV) followed by oral ISAV versus the regimen of liposomal amphotericin B followed by posaconazole (L-AMB→POSA) in the treatment of IFI. The comparison was conducted from the perspective of the Spanish National Health System (SNS). METHODS: As indirect comparisons have demonstrated similar efficacy between the comparators, a cost-minimization approach was taken. Drug acquisition, administration, hospitalization, laboratory tests and adverse events costs were evaluated from SNS perspective. Deterministic and probabilistic sensitivity analyzes were performed. RESULTS: Total costs per-patient were €24,715.54 with ISAV versus €29,753.53 with L-AMB→POSA, resulting in cost-savings per patient treated with ISAV of €5,037.99 (-16.9%). Treatment costs of IFI remained lower for ISAV than for L-AMB→POSA across all sensitivity analyses (-7,968.89€ to -326.59€), being treatment duration the most influential parameter. CONCLUSION: According to the present model, the treatment of IFIs with ISAV would generate savings for the SNS compared to L-AMB→POSA. These savings are attributed to the shorter duration of IV treatment, reduced use of healthcare resources and lower costs associated with managing adverse effects when ISAV was employed.

Safety of fluoroquinolones.

Fluoroquinolones (FQs) are one of the most commonly prescribed classes of antibiotics. Although they were initially well tolerated in randomized clinical trials, subsequent epidemiological studies have reported an increased risk of threatening, severe, long-lasting, disabling and irreversible adverse effects (AEs), related to neurotoxicity and collagen degradation, such as tendonitis, Achilles tendon rupture, aortic aneurysm, and retinal detachment. This article reviews the main potentially threatening AEs, the alarms issued by regulatory agencies and therapeutic alternatives.

Recommendations for the prevention of healthcare-associated infections in nursing homes.

Nursing homes (NH) conceptually should look as much like a home as possible. However NH have unquestionable similarities with a nosocomium as they are places where many patients with underlying diseases and comorbidities accumulate. There is evidence of transmission of microorganisms between residents and between residents and caregivers. We have not found any recommendations specifically aimed at the prevention of nosocomial infections in NH by the major Public Health Agencies and, therefore, the Health Sciences Foundation (Fundación de Ciencias de la Salud) has convened a series of experts and 14 Spanish scientific societies to discuss recommendations that could guide NH personnel in establishing written programs for the control and reduction of these infections. The present document is the result of these deliberations and contains suggestions for establishing such control programs on a voluntary and flexible basis in NH. We also hope that the document can help the health authorities to encourage this control activity in the different territorial areas of Spain. In our opinion, it is necessary to draw up a written plan and establish the figure of a coordinator or person responsible for implementing these projects. The document includes measures to be implemented and ways of quantifying the reality of different problems and of monitoring the impact of the measures established.

Recommendations on the use of azole antifungals in hematology-oncology patients.

The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.

Antimicrobial resistance in Gram-negative bacilli in Spain: an experts' view.

BACKGROUND: Antibiotic resistance in Gram-negative bacilli poses a serious problem for public health. In hospitals, in addition to high mortality rates, the emergence and spread of resistance to practically all antibiotics restricts therapeutic options against serious and frequent infections. OBJECTIVE: The aim of this work is to present the views of a group of experts on the following aspects regarding resistance to antimicrobial agents in Gram-negative bacilli: 1) the current epidemiology in Spain, 2) how it is related to local clinical practice and 3) new therapies in this area, based on currently available evidence. METHODS: After reviewing the most noteworthy evidence, the most relevant data on these three aspects were presented at a national meeting to 99 experts in infectious diseases, clinical microbiology, internal medicine, intensive care medicine, anaesthesiology and hospital pharmacy. RESULTS AND CONCLUSIONS: Subsequent local debates among these experts led to conclusions in this matter, including the opinion that the approval of new antibiotics makes it necessary to train the specialists involved in order to optimise how they use them and improve health outcomes; microbiology laboratories in hospitals must be available throughout a continuous timetable; all antibiotics must be available when needed and it is necessary to learn to use them correctly; and the Antimicrobial Stewardship Programs (ASP) play a key role in quickly allocating the new antibiotics within the guidelines and ensure appropriate use of them.

Interactions listed in the Paxlovid fact sheet, classified according to risks, pharmacological groups, and consequences.

Paxlovid (nirmatrelvir plus ritonavir) is a new oral antiviral therapeutic for the treatment and post-exposure prophylaxis of COVID-19. Nirmatrelvir is an inhibitor of SARS-CoV-2 main protease, while ritonavir is used as a CYP3A inhibitor in low doses to slow the metabolism of nirmatrelvir, thus enhancing their therapeutic effect. The isoenzyme CYP3A4 is responsible for at least part of the oxidative metabolism of approximately 60% of available medications and ritonavir is therefore a significant source of drug interactions. We describe here the drugs that are contraindicated or should be used with or without precautions when Paxlovid (nirmaltrevir plus ritonavir) should be administered according to each fact sheet in force at the Spanish Agency for Medicines and Health Products.

Decalogue for the selection of oral antibiotics for lower respiratory tract infections.

Lower respiratory tract infections, including chronic obstructive pulmonary disease exacerbations (COPD-E) and community acquired pneumonia (CAP), are one of the most frequent reasons for consultation in primary care and hospital emergency departments, and are the cause of a high prescription of antimicrobial agents. The selection of the most appropriate oral antibiotic treatment is based on different aspects and includes to first consider a bacterial aetiology and not a viral infection, to know the bacterial pathogen that most frequently cause these infections and the frequency of their local antimicrobial resistance. Treatment should also be prescribed quickly and antibiotics should be selected among those with a quicker mode of action, achieving the greatest effect in the shortest time and with the fewest adverse effects (toxicity, interactions, resistance and/or ecological impact). Whenever possible, antimicrobials should be rotated and diversified and switched to the oral route as soon as possible. With these premises, the oral treatment guidelines for mild or moderate COPD-E and CAP in Spain include as first options beta-lactam antibiotics (amoxicillin and amoxicillin-clavulanate and cefditoren), in certain situations associated with a macrolide, and relegating fluoroquinolones as an alternative, except in cases where the presence of Pseudomonas aeruginosa is suspected.

Dalbavancin.

Dalbavancin is a long-acting antimicrobial agent with an excellent in vitro activity against Gram-positive pathogens, including staphylococcal biofilms. The unusually long terminal half-life ranging from 149 to 250 hours in human subjects, allows a weekly dose. Currently is indicated in acute bacterial skin and skin structure infections (ABSSSIs), but in real-life clinical practice it has already been used successfully and safely in other infections, especially as consolidation therapy.

Recommendations for antibiotic selection for severe nosocomial infections.

Severe infection and its evolution to sepsis are becoming more prevalent every day and are among the leading causes of critical illness and mortality. Proper management is crucial to improve prognosis. This document addresses three essential points that have a significant impact on this objective: a) early recognition of patients with sepsis criteria, b) identification of those patients who suffer from an infection and have a high risk of progressing to sepsis, and c) adequate selection and optimization of the initial antimicrobial treatment.

[Safety in the selection of oral antibiotic treatment in community infections, beyond COVID-19]. / Seguridad en la selección del tratamiento antibiótico oral en las infecciones comunitarias, más allá de la COVID-19.

Oral antibiotics are among the most frequently used medications in the community. Its adverse effects are generally considered to be infrequent and mild, and include allergies, toxicities and drug interactions. Antibiotics are able to harm patients by various mechanisms, not always well known. Knowledge of the clinically relevant antibiotic-associated adverse effects can allow a judicious use based on the principle first do no harm, primun non nocere. In this review we explore the main adverse effects of oral antibiotics with specific focus on ß-lactams, macrolides, and fluoroquinolones.

Clinical characteristics and outcomes of 1,331 patients with COVID-19: HM Spanish Cohort.

OBJECTIVE: Spain is one of the European countries most affected by the COVID-19 pandemic. Epidemiologic studies are warranted to improve the disease understanding, evaluate the care procedure and prepare for futures waves. The aim of the study was to describe epidemiologic characteristics associated with hospitalized patients with COVID-19. METHODS: This real-world, observational, multicenter and retrospective study screened all consecutive patients admitted to 8 Spanish private hospitals. Inclusion criteria: hospitalized adults (age≥18 years old) with clinically and radiologically findings compatible with COVID-19 disease from March 1st to April 5th, 2020. Exclusion criteria: patients presenting negative PCR for SARS-CoV-2 during the first 7 days from hospital admission, transfer to a hospital not belonging to the HM consortium, lack of data and discharge against medical advice in emergency departments. RESULTS: One thousand and three hundred thirty-one COVID-19 patients (medium age 66.9 years old; males n= 841, medium length of hospital stayed 8 days, non-survivors n=233) were analyzed. One hundred and fifteen were admitted to intensive care unit (medium length of stay 16 days, invasive mechanical ventilation n= 95, septic shock n= 37 and renal replacement therapy n= 17). Age, male gender, leukocytes, platelets, oxygen saturation, chronic therapy with steroids and treatment with hydroxychloroquine/azithromycin were independent factors associated with mortality. The proportion of patients that survive and received tocilizumab and steroids were lesser and higher respectively than those that die, but their association was not significant. CONCLUSIONS: Overall crude mortality rate was 17.5%, rising up to 36.5% in the subgroup of patients that were admitted to the intensive care unit. Seven factors impact in hospital mortality. No immunomodulatory intervention were associated with in-hospital mortality.

Community-acquired pneumonia: similarities and differences between European and American guidelines - A narrative review.

Community-acquired pneumonia (CAP) is severe disease. Early prescription of an adequate treatment has a positive impact in the CAP outcome. Despite the evidence of existing relevant differences between CAP across geographical areas, general guidelines can be designed to be applied everywhere. Eight years have passed between the publication of the European (EG) and American (AG) CAP guidelines, thus the aim of this narrative review is to compare both guidelines and summarize their recommendations. The main similarity between both guidelines is the antibiotics recommendation with the exception that AG mention new antimicrobials that were not available at the time of EG publication. Both guidelines recommend against routinely adding steroids as an adjuvant treatment. Finally, both guidelines acknowledge that the decision to hospitalize a patient is clinical and should be complemented with an objective tool for risk assessment. EG recommend the CRB-65 while AG recommend the Pneumonia Severity Index (PSI). EG and AG share a similar core of recommendations and only differ in minor issues such as new antibiotics. Likewise, both guidelines recommend against the routine prescription of steroids as an adjuvant therapy.

Risk factors for methicillin-resistant Staphylococcus aureus and extended-spectrum ß-lactamase producing Enterobacterales in patients with diabetic foot infections requiring hospital admission.

OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) may complicate the treatment of diabetic foot infections (DFIs). The aim of this study was to determine the risk factors for these pathogens in DFIs. METHODS: This was a prospective observational study of 167 consecutive adult patients with DFIs. The diagnosis and severity of DFIs were based on the Infectious Disease Society of America (IDSA) classification system. Multivariate analyses were performed in order to identify risk factors for MRSA and ESBL-E infections. RESULTS: S. aureus was the most isolated pathogen (n=82, 37.9 %) followed by Escherichia coli (n= 40, 18.5%). MRSA accounted for 57.3% of all S. aureus and 70% of Klebsiella pneumoniae and 25% of E. coli were ESBL producers, respectively. Deep ulcer [OR 8,563; 95% CI (1,068-4,727)], previous use of fluoroquinolones [OR 2,78; 95% CI (1,156-6,685)] and peripheral vasculopathy [OR 2,47; 95% CI (1.068-4.727)] were the independent predictors for MRSA infections; and osteomyelitis [OR 6,351; 95% CI (1,609-25,068)] and previous use of cephalosporins [OR 5,824; 95% CI (1,517-22,361)] for ESBL-E infections. CONCLUSIONS: MRSA and ESBL-E have adquired a great clinical relevance in DFIs. The availability of their risk factors is very convenient to choose the empirical treatment in severe forms.

Recommendations for use of antigenic tests in the diagnosis of acute SARS-CoV-2 infection in the second pandemic wave: attitude in different clinical settings.

The high transmissibility of SARS-CoV-2 before and shortly after the onset of symptoms suggests that only diagnosing and isolating symptomatic patients may not be sufficient to interrupt the spread of infection; therefore, public health measures such as personal distancing are also necessary. Additionally, it will be important to detect the newly infected individuals who remain asymptomatic, which may account for 50% or more of the cases. Molecular techniques are the "gold standard" for the diagnosis of SARS-CoV-2 infection. However, the massive use of these techniques has generated some problems. On the one hand, the scarcity of resources (analyzers, fungibles and reagents), and on the other the delay in the notification of results. These two facts translate into a lag in the application of isolation measures among cases and contacts, which favors the spread of the infection. Antigen detection tests are also direct diagnostic methods, with the advantage of obtaining the result in a few minutes and at the very "pointof-care". Furthermore, the simplicity and low cost of these tests allow them to be repeated on successive days in certain clinical settings. The sensitivity of antigen tests is generally lower than that of nucleic acid tests, although their specificity is comparable. Antigenic tests have been shown to be more valid in the days around the onset of symptoms, when the viral load in the nasopharynx is higher. Having a rapid and real-time viral detection assay such as the antigen test has been shown to be more useful to control the spread of the infection than more sensitive tests, but with greater cost and response time, such as in case of molecular tests. The main health institutions such as the WHO, the CDC and the Ministry of Health of the Government of Spain propose the use of antigenic tests in a wide variety of strategies to respond to the pandemic. This document aims to support physicians involved in the care of patients with suspected SC2 infection, in the context of a growing incidence in Spain since September 2020, which already represents the second pandemic wave of COVID-19.

[Development of a predictive model for hospital mortality and re-admission in a cohort of infected patients that require hospitalization]. / Desarrollo de un modelo predictivo para mortalidad y otro para reingreso hospitalario en una cohorte de paciente con infección que requieren hospitalización.

OBJECTIVE: The aims of the study were: to develop a predictive model for hospital mortality and another for hospital re-admission, to identify the impact of antibiotic delay in the mortality rate and, to report the rate of inappropriate antibiotic therapy. METHODS: A cohort and retrospective study was conducted at the HM Sanchinarro University Hospital during the period September 1st, 2012 to March 31th, 2013. The inclusion criteria were: age> 18 years, hospital admission from the ED with a diagnosis of bacterial infection. The exclusion criteria were: suspected viral infection, negative bacteriological cultures, life expectancy less than 6 months, lack of clinical information, assistance exclusively by the trauma emergency department. Two logistic models were made (hospital mortality and hospital re-admission). RESULTS: A total of 517 patients were included. The final mortality model (30 deaths) include the following variables: respiratory rate (OR 1.12; IC95% 1.02; 1.22), oxygen saturation (OR 0.92; IC95% 0.87; 0.98), creatinine (OR 2.33; IC95% 1.62; 3.36), COPD (OR 3.02; IC95% 1.06; 8.21), cancer (OR 3.34; IC95% 1.07; 9.98) and chemotherapy in the last 3 months (OR 4.83; IC95% 1.54; 16.41). The final model for hospital re-admission (28 re-admissions) include the following variables: hepatopathy (OR 5.51; IC95% 1.57; 16.88), GPT (OR 1.005; IC95% 1.003; 1.008), history of stroke (OR 5.06; IC95% 1.04; 18.80) and arterial hypertension (OR 3.15; IC95% 1.38; 7.56). The antibiotic therapy delays not influenced the mortality or re-admission rate. In 24.3% the causative microorganism was identified and antibiotic treatment was inappropriate 19.6%. CONCLUSIONS: Hospital mortality rate was 5.8% and readmission rate was 5.7%. Variables associated with mortality differ from those associated with re-admission. The delay in the antibiotic initiation was not associated with a deleterious effect. Antibiotic therapy was inadequate in almost 20% of patients.

Recommendations for the diagnosis and treatment of Clostridioides difficile infection: An official clinical practice guideline of the Spanish Society of Chemotherapy (SEQ), Spanish Society of Internal Medicine (SEMI) and the working group of Postoperative Infection of the Spanish Society of Anesthesia and Reanimation (SEDAR).

This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at high risk of recurrence. Surgery is becoming less and less necessary and prevention with vaccines is under research. Probiotics have so far not been shown to be therapeutically or preventively effective. The therapeutic strategy should be based, rather than on the number of episodes, on the severity of the episodes and on their potential to recur. Some data point to the efficacy of oral vancomycin prophylaxis in patients who reccur CDI when systemic antibiotics are required again.

[Three keys to the appropriate choice of oral antibiotic treatment in the respiratory tract infections]. / Tres claves para seleccionar el antibiótico oral adecuado en las infecciones respiratorias.

Exacerbation of chronic obstructive pulmonary disease and community-acquired pneumonia are the most frequent infections of the lower respiratory tract in daily clinical practice. Antibiotic selection is a crucial component in its treatment and, in most cases, it is performed empirically. Scientific societies make therapeutic recommendations based on scientific evidence and / or expert recommendations that are of great help to clinicians. Beta-lactams, fluoroquinolones and macrolides are the most commonly used drugs for oral administration. From a practical point of view, there are three keys to the appropriate choice of oral antibiotic treatment, which are the effectiveness, safety and the ecological impact on the patient's microbiota, including the development of resistance, which will be assessed in depth in this review.