Recommendations for antibacterial therapy in adults with COVID-19 e an evidence based guideline

The Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19). We performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology. We assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic.

Management of community-acquired pneumonia in adults: 2016 guideline update from the Dutch Working Party on Antibiotic Policy (SWAB) and Dutch Association of Chest Physicians (NVALT).

The Dutch Working Party on Antibiotic Policy in collaboration with the Dutch Association of Chest Physicians, the Dutch Society for Intensive Care and the Dutch College of General Practitioners have updated their evidence-based guidelines on the diagnosis and treatment of community-acquired pneumonia (CAP) in adults who present to the hospital. This 2016 update focuses on new data on the aetiological and radiological diagnosis of CAP, severity classification methods, initial antibiotic treatment in patients with severe CAP and the role of adjunctive corticosteroids. Other parts overlap with the 2011 guideline. Apart from the Q fever outbreak in the Netherlands (2007-2010) no other shifts in the most common causative agents of CAP or in their resistance patterns were observed in the last five years. Low-dose CT scanning may ultimately replace the conventional chest X-ray; however, at present, there is insufficient evidence to advocate the use of CT scanning as the new standard in patients evaluated for CAP. A pneumococcal urine antigen test is now recommended for all patients presenting with severe CAP; a positive test result can help streamline therapy once clinical stability has been reached and no other pathogens have been detected. Coverage for atypical microorganisms is no longer recommended in empirical treatment of severe CAP in the non-intensive care setting. For these patients (with CURB-65 score >2 or Pneumonia Severity Index score of 5) empirical therapy with a 2nd/3rd generation cephalosporin is recommended, because of the relatively high incidence of Gram-negative bacteria, and to a lesser extent S. aureus. Corticosteroids are not recommended as adjunctive therapy for CAP.

SWAB/NVALT (Dutch Working Party on Antibiotic Policy and Dutch Association of Chest Physicians) guidelines on the management of community-acquired pneumonia in adults.

The Dutch Working Party on Antibiotic Policy (SWAB) and the Dutch Association of Chest Physicians (NVALT) convened a joint committee to develop evidence-based guidelines on the diagnosis and treatment of community acquired pneumonia (CAP). The guidelines are intended for adult patients with CAP who present at the hospital and are treated as outpatients as well as for hospitalised patients up to 72 hours after admission. Areas covered include current patterns of epidemiology and antibiotic resistance of causative agents of CAP in the Netherlands, the possibility to predict the causative agent of CAP on the basis of clinical data at first presentation, risk factors associated with specific pathogens, the importance of the severity of disease upon presentation for choice of initial treatment, the role of rapid diagnostic tests in treatment decisions, the optimal initial empiric treatment and treatment when a specific pathogen has been identified, the timeframe in which the first dose of antibiotics should be given, optimal duration of antibiotic treatment and antibiotic switch from the intravenous to the oral route. Additional recommendations are made on the role of radiological investigations in the diagnostic work-up of patients with a clinical suspicion of CAP, on the potential benefit of adjunctive immunotherapy, and on the policy for patients with parapneumonic effusions.

[Guideline 'Diagnosis and treatment of community-acquired pneumonia' from the Dutch Thoracic Society]. / Richtlijn 'Diagnostiek en behandeling van "community-acquired" pneumonie' van de Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose.

Community-acquired pneumonia (CAP) is associated with considerable morbidity and mortality. The incidence of CAP in the Netherlands is estimated to be 5-10 per 1000 per year. This guideline can be used for the scientifically-based diagnosis and antibiotic treatment of adults with CAP. Streptococcus pneumoniae is the most frequent causative agent In 30-50% of patients, the aetiological pathogen cannot be identified. In the Netherlands, the resistance of S. pneumoniae to penicillin is less than 1%. In addition to patient history and physical examination, chest radiography is indispensable to the diagnosis of CAP. Cultures of sputum, blood, and, if present, pleural effusion are needed to detect the causative agent. Bronchoscopy can be considered if the patient's condition deteriorates during antibiotic therapy. Urinary antigen detection is important if signs of legionellosis are present; only Legionella pneumophila serotype can be identified with this technique. The severity of CAP and the risk factors can be measured by the pneumonia severity index, which may be helpful in deciding whether to hospitalise a patient. The choice of antibiotic therapy is based on the intention of providing optimal therapy, the epidemiological features ofvarious microorganisms in the Netherlands, and an inference of the most likely pathogen, based on comorbidity. Empirical antibiotic therapy should target primarily S. pneumoniae because of its high incidence. In both seriously ill patients and those suspected of having legionellosis, antibiotic therapy should also target L. pneumophila. Antibiotic therapy should be adjusted if the pathogen is subsequently identified. Parapneumonic effusion frequently occurs in cases of CAP. Drainage is indicated if the pleural fluid contains bacteria or yields a pH < 7.0. Influenza vaccination is recommended in the elderly to prevent CAP.

A chromosomal abnormality in hyaline vascular Castleman's disease: evidence for clonal proliferation of dysplastic stromal cells.

The pathogenesis of the hyaline vascular variant of Castleman's disease is currently unknown; however, vascular and dendritic cell proliferations are common in this disorder. We report a clonal karyotypic abnormality (46,XX,t(1;16) (p11;p11), del(7)(q21q22),del(8)(q12q22)) in 15 of 20 cells obtained after short-term stromal cultures of a typical case of hyaline vascular Castleman's disease (HVCD). There was no histologic, immunohistochemical, or genotypic evidence of a clonal lymphoid or plasma cell proliferation supporting origin of this aberration from the stromal component, possibly dendritic cells. We re-examined 15 previous cases of HVCD and identified a spectrum of dysplastic changes in the follicular dendritic cells (FDC) of atrophic lymphoid follicles, with some cases showing expansions of FDC networks by CD21 immunostaining. We propose that localized clonal proliferations of stromal elements, particularly follicular dendritic cells, occur in typical HVCD and likely explain the increased incidence of FDC sarcomas in these patients.

Submucosa 1.0 x 0.1 mm in size is sufficient to count inflammatory cell numbers in human airway biopsy specimens.

Counting of inflammatory cells in human airway biopsy specimens is difficult because immunopositive cells are present in varying density in lung tissue. The goal of our study was to assess the minimal amount of tissue that is necessary for the counting of constant cell numbers. In bronchial biopsy specimens from 5 healthy controls and 5 patients with asthma, we evaluated 20 successive areas of submucosa 0.1 x 0.1 mm in size. We recorded positive and negative changes of more than 10% in the counted numbers of CD4-, CD8-, and EG2-positive cells. We demonstrated that tissue 1.0 x 0.1 mm in size, along 1-mm basement membrane, is sufficient to obtain constant cell numbers.

Techniques in human airway inflammation: quantity and morphology of bronchial biopsy specimens taken by forceps of three sizes.

BACKGROUND: In recent years, fiberoptic bronchoscopy has been introduced successfully in the research of bronchial asthma. Bronchial biopsy specimens obtained by this procedure are small, and an optimal biopsy technique is necessary to obtain high-quality tissue samples, as sufficient length of intact basement membrane and sufficient depth of submucosal tissue are required. METHODS: We compared size and qualitative aspects of bronchial biopsy specimens from nonasthmatic subjects, obtained by forceps of three different sizes, types FB-19C, FB-21C, and FB-35C (Olympus; Tokyo, Japan). RESULTS AND CONCLUSIONS: We conclude from this study that the hypothesis that the bigger the biopsy forceps, the larger the biopsy specimen and the better the quality of the tissue does not hold. Bronchial biopsy specimens obtained with forceps type FB-35C and FB-21C were equal in size, but the FB-35C biopsy specimens showed more damage and crush artifacts, whereas biopsy specimens obtained with forceps type FB-21C had more intact basement membrane, more submucosal depth, and well-preserved morphology.

Techniques in human airway inflammation: differences in plastic-embedded and snap-frozen sections for CD3, CD4, and CD8 immunostaining of bronchial biopsy specimens.

Today, the quantification of inflammatory cells in human airway biopsies might be facilitated by better morphologic resolution provided by special resin (plastic)-embedding techniques. The present study compares the numbers of CD3-, CD4-, and CD8-positive cells in glycolmethacrylate-embedded versus snap-frozen biopsy specimens of normal bronchial mucosa in 10 patients with various pulmonary diseases. In general, larger numbers of CD3-, CD4-, and CD8-positive cells were counted in snap-frozen specimens than in plastic-embedded ones. Loss of antigenic properties during storage of plastic-embedded tissue (blocks) might have contributed to the weak correlation between both methods. An additional study showed that the number of CD3-, CD4-, and CD8-positive cells decreased significantly within a few months after embedding in glycolmethacrylate. Therefore, we recommend processing glycolmethacrylate-embedded specimens as soon as possible. For standard evaluation of established inflammatory cell parameters such as CD3, CD4, CD8, and EG2, frozen tissue is preferable because of the ease of the method and its reliable cell counting. Because glycolmethacrylate-embedded tissue shows superior morphologic resolution, under strict rules, this method seems attractive for the study, in particular, of cell-cell and cell-matrix relationships.

Occupational asthma caused by a hardener containing an aliphatic and a cycloaliphatic diamine.

An otherwise healthy 44-yr-old man experienced a serious attack of bronchial obstruction after working with resins and hardeners, releasing fumes of a mixture of an alipathic and a cycloaliphatic diamine hardener. Eight hours after deliberate challenge with the hardener a large increase of airway resistance was found. Seventy-two hours after challenge, eosinophilia in the bronchoalveolar lavage (BAL) fluid together with a decrease of peripheral eosinophils was seen. After cessation of contact with this hardener, no more acute episodes occurred, although maintenance treatment with a topical corticosteroid and a beta 2-agonist remained necessary. A BAL performed 1 yr later showed a normal cell distribution. The results suggest that these aliphatic and cycloaliphatic diamine hardeners may be occupational hazards. Eosinophil inflammation may play a causal role.

Late onset asthma?

A 77 yr old male was referred for dyspnoea and recurrent infections of the lower airways for the previous five months. On the lateral chest roentgenogram a process in the tracheal area was found, and during bronchoscopy a polypoid tumour was seen about four centimetres above the main carina. It appeared to be a benign endotracheal tumour which was removed after coagulation by a Neodymium yttrium aluminium garnet (YAG) laser.