Antibiotic Consumption in a Cohort of Hospitalized Adults with Viral Respiratory Tract Infection.

Development of antibiotic resistance, a threat to global health, is driven by inappropriate antibiotic usage. Respiratory tract infections (RTIs) are frequently treated empirically with antibiotics, despite the fact that a majority of the infections are caused by viruses. The purpose of this study was to determine the prevalence of antibiotic treatment in hospitalized adults with viral RTIs, and to investigate factors influencing the antibiotic decision-making. We conducted a retrospective observational study of patients ≥ 18 years, hospitalized in 2015-2018 with viral RTIs. Microbiological data were taken from the laboratory information system and information on antibiotic treatment drawn from the hospital records. To investigate decisions for prescribing antibiotic treatment, we evaluated relevant factors such as laboratory and radiological results, in addition to clinical signs. In 951 cases without secondary bacterial RTIs (median age 73 years, 53% female), 720 (76%) were prescribed antibiotic treatment, most frequently beta-lactamase-sensitive penicillins, but cephalosporins were prescribed as first-line in 16% of the cases. The median length of treatment (LOT) in the patients treated with antibiotics was seven days. Patients treated with antibiotics had an average of two days longer hospital stay compared to patients with no such treatment, but no difference in mortality was found. Our study revealed that there is still a role for antimicrobial stewardship to further improve antibiotic use in patients admitted for viral RTIs in a country with relatively low antibiotic consumption.

High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19.

BACKGROUND: Immune dysregulation is a major factor in the development of severe coronavirus disease 2019 (COVID-19). The homeostatic chemokines CCL19 and CCL21 have been implicated as mediators of tissue inflammation, but data on their regulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is limited. We thus investigated the levels of these chemokines in COVID-19 patients. METHODS: Serial blood samples were obtained from patients hospitalized with COVID-19 (n = 414). Circulating CCL19 and CCL21 levels during hospitalization and 3-month follow-up were analyzed. In vitro assays and analysis of RNAseq data from public repositories were performed to further explore possible regulatory mechanisms. RESULTS: A consistent increase in circulating levels of CCL19 and CCL21 was observed, with high levels correlating with disease severity measures, including respiratory failure, need for intensive care, and 60-day all-cause mortality. High levels of CCL21 at admission were associated with persisting impairment of pulmonary function at the 3-month follow-up. CONCLUSIONS: Our findings highlight CCL19 and CCL21 as markers of immune dysregulation in COVID-19. This may reflect aberrant regulation triggered by tissue inflammation, as observed in other chronic inflammatory and autoimmune conditions. Determination of the source and regulation of these chemokines and their effects on lung tissue is warranted to further clarify their role in COVID-19. CLINICAL TRIALS REGISTRATION: NCT04321616 and NCT04381819.

Clinical Outcome of Viral Respiratory Tract Infections in Hospitalized Adults in Norway: High Degree of Inflammation and Need of Emergency Care for Cases With Respiratory Syncytial Virus.

Background: The clinical features and outcomes of viral respiratory tract infections (RTIs) in adults have not been thoroughly studied, especially the respiratory syncytial virus (RSV) disease burden. It has become apparent that outbreaks of RSV in the elderly are associated with increased hospitalization rates. However, little data exists on the severity of such viral RTIs in adults, particularly the need for hospitalization, respiratory support and intensive care. Methods: We conducted a retrospective observational single-center study at Østfold Hospital Trust, Norway, during three winter seasons 2015-2018. Patients ≥18 years with either influenza A, influenza B, RSV A/B, human metapneumovirus, parainfluenza virus 1-4 or adenovirus detected in respiratory specimens were included, if they were hospitalized 14 days prior or following the detection date, with signs of RTI. Hospital records on treatment and outcome were investigated, as well as mortality of all causes up to 30 days from discharge. Results: Of the 1222 infection events that were included, influenza A was the most frequent virus detected (39%), while 179 infection events (14.6%) were due to RSV. Influenza B counted for 24% of the infection events, human metapneumovirus 13%, parainfluenza virus 9% and adenovirus 1%. Patients admitted with RSV more often suffered from COPD and congestive heart failure than patients with influenza A. In addition, RSV patients were overrepresented in the urgent response NEWS score (National Early Warning Score) category ≥5. RSV patients also showed signs of more severe inflammation, with WBC ≥11.1 × 109/L and CRP >100 mg/L, and they were more often treated with antibiotic agents during their hospital stay. However, we found no differences in the need for ICU admission or mortality. Conclusion: Patients with RSV had more often high values for markers of inflammation and elevated NEWS score when compared to patients hospitalized with other common respiratory viruses. Taken into account that they suffered more frequently from comorbidities like COPD, these patients needed hospitalization more urgently. These findings highlight the need for further investigations on RSV disease in adults and the elderly.

Genetic diversity of rotavirus strains circulating in Norway before and after the introduction of rotavirus vaccination in children.

Globally, rotavirus (RV) is the leading cause of acute gastroenteritis (AGE) in young children under 5 years of age. Implementation of RV vaccination is expected to result in fewer cases of RV in the target population, but it is unknown if this also results in vaccine-induced virus strain replacement. Rotarix, a monovalent vaccine based on G1P[8] RV, was introduced in Norway in the children's immunization program in September 2014. The main aim of this study was to describe the diversity of RV circulating pre and post introduction of the RV vaccine in Norway and investigate changes in genotype distribution during the first 4 years after implementation. A total of 1108 samples were collected from children under 5 years enrolled with AGE from five large hospitals in Norway and were analyzed for RV by enzyme immunoassay (EIA). All positive results were genotyped by multiplex semi-nested reverse transcription PCR for identification of G and P types. In total, 487 of the 1108 (44%) samples, collected from the enrolled children, were positive for RV by EIA method which were further genotyped. G1P[8] was found to be the most common type of RV pre and post RV vaccine implementation followed by G9P[8]. There were neither geographical nor temporal differences in genotype dominance. Also, no apparent changes were shown in the genotype distribution in the postvaccine era for years from 2015 to 2018. In 21.4% of the cases, vaccine strains were detected. Continuous RV genotype surveillance is vital for assessing the effectiveness of a vaccine program and monitoring for any emergence of vaccine-escape strains. Genotyping is also necessary to detect vaccine strains to avoid reporting false-positive cases of active RV infection in newly vaccinated cases.

Etiology of viral respiratory tract infections in hospitalized adults, and evidence of the high frequency of prehospitalization antibiotic treatment in Norway.

BACKGROUND AND AIMS: Respiratory tract infections (RTIs) cause considerable morbidity and mortality in all age groups, but the epidemiology and role of several of the viral RTIs in the adult and elderly patients are still unclear, as is the extent of prehospitalization antibacterial drug use in this population. METHODS: We conducted a three-year (2015-2018) observational study of viral RTIs in hospitalized patients in a 500-bed hospital in Southeastern Norway, including all patients ≥18 years with RTI symptoms where one of the following viral agents was detected in a respiratory specimen (Seegene Allplex): Influenza A/B, RSV A/B, human metapneumovirus (hMPV), adenovirus and parainfluenza virus 1-4. Viral findings, demographical data, and information on prehospital antibiotic prescriptions were recorded. RESULTS: In 1182 patients 1222 viral infection events occurred. The mean patient age was 69.6 years, and 53% were females. Influenza virus A/B (63%), RSV A/B (15%) and hMPV (13%) were the most common agents detected. The proportional burden of influenza A H1 was found to be relatively high (65%) in the age groups <69 years, compared to older patients (P = .001, chi-square).As many as 20% of the patients had been treated with antibiotics prior to admission, with the lowest rate for influenza A H3 group at 17% (P = .036, chi-square), and highest for the RSV group at 28% (P = .004, chi-square).Oseltamivir was prescribed prior to hospitalization in only 3 cases (0.2%). CONCLUSIONS: We found a high rate of prehospital antibiotic prescription in adults hospitalized with viral RTIs, warranting better stewardship programs to tackle the increasing antibiotic resistance problem.

Tick-transmitted co-infections among erythema migrans patients in a general practice setting in Norway: a clinical and laboratory follow-up study.

BACKGROUND: Erythema migrans (EM) is the most common manifestation of Lyme borreliosis. Here, we examined EM patients in Norwegian general practice to find the proportion exposed to tick-transmitted microorganisms other than Borrelia, and the impact of co-infection on the clinical manifestations and disease duration. METHODS: Skin biopsies from 139/188 EM patients were analyzed using PCR for Neoehrlichia mikurensis, Rickettsia spp., Anaplasma phagocytophilum and Babesia spp. Follow-up sera from 135/188 patients were analyzed for spotted fever group (SFG) Rickettsia, A. phagocytophilum and Babesia microti antibodies, and tested with PCR if positive. Day 0 sera from patients with fever (8/188) or EM duration of ≥ 21 days (69/188) were analyzed, using PCR, for A. phagocytophilum, Rickettsia spp., Babesia spp. and N. mikurensis. Day 14 sera were tested for TBEV IgG. RESULTS: We detected no microorganisms in the skin biopsies nor in the sera of patients with fever or prolonged EM duration. Serological signs of exposure against SFG Rickettsia and A. phagocytophilum were detected in 11/135 and 8/135, respectively. Three patients exhibited both SFG Rickettsia and A. phagocytophilum antibodies, albeit negative PCR. No antibodies were detected against B. microti. 2/187 had TBEV antibodies without prior immunization. There was no significant increase in clinical symptoms or disease duration in patients with possible co-infection. CONCLUSIONS: Co-infection with N. mikurensis, A. phagocytophilum, SFG Rickettsia, Babesia spp. and TBEV is uncommon in Norwegian EM patients. Despite detecting antibodies against SFG Rickettsia and A. phagocytophilum in some patients, no clinical implications could be demonstrated.

Rotavirus detection in bulk stool and rectal swab specimens in children with acute gastroenteritis in Norway.

BACKGROUND: Bulk stool specimens are traditionally used for rotavirus detection but may be challenging to obtain from young children. Immediate and easy sampling may however be required in different situations, such as outbreak investigation. OBJECTIVES: We assessed the diagnostic performance of rectal swabs compared to bulk stools for the detection of rotavirus by Enzyme Immunoassay (EIA) and multiplex semi-nested reverse transcription PCR (semi-nested RT-PCR) in children recruited through active hospital-based surveillance of acute gastroenteritis in Norway. STUDY DESIGN: We obtained 265 paired bulk stool and rectal swab specimens from children under 5 years of age hospitalized with acute gastroenteritis (AGE). Both types of specimens were analyzed for rotavirus by EIA and semi-nested RT-PCR. In addition, VP6-spesific real-time PCR was used to evaluate the detection performance in the two specimen types. RESULTS: Concordant results were obtained in 257 (97%) paired specimens by EIA and in 248 (94%) pairs by semi-nested RT-PCR. Results of VP6-specific real-time PCR obtained from 100 pairs of specimens showed concordance in 91% of the pairs. Sensitivity and specificity for rectal swab specimens were 95% and 100% by EIA; 95% and 92% by semi-nested RT-PCR, respectively. CONCLUSION: Both EIA and semi-nested RT-PCR showed a high accuracy, and rectal swab specimens are appropriate for rotavirus diagnosis and may be used as an alternate specimen type when collection of bulk stool is not feasible.

Rapid Bedside Inactivation of Ebola Virus for Safe Nucleic Acid Tests.

Rapid bedside inactivation of Ebola virus would be a solution for the safety of medical and technical staff, risk containment, sample transport, and high-throughput or rapid diagnostic testing during an outbreak. We show that the commercially available Magna Pure lysis/binding buffer used for nucleic acid extraction inactivates Ebola virus. A rapid bedside inactivation method for nucleic acid tests is obtained by simply adding Magna Pure lysis/binding buffer directly into vacuum blood collection EDTA tubes using a thin needle and syringe prior to sampling. The ready-to-use inactivation vacuum tubes are stable for more than 4 months, and Ebola virus RNA is preserved in the Magna Pure lysis/binding buffer for at least 5 weeks independent of the storage temperature. We also show that Ebola virus RNA can be manually extracted from Magna Pure lysis/binding buffer-inactivated samples using the QIAamp viral RNA minikit. We present an easy and convenient method for bedside inactivation using available blood collection vacuum tubes and reagents. We propose to use this simple method for fast, safe, and easy bedside inactivation of Ebola virus for safe transport and routine nucleic acid detection.

[Disease caused by the new influenza A(H1N1) virus]. / Sykdom forårsaket av nytt A(H1N1)-influensavirus.

BACKGROUND: A new A(H1N1) influenza virus was detected in April 2009. The virus is now causing a pandemic of influenza. The article presents an overview of symptoms, complications, vulnerable groups, diagnosis and treatment. MATERIAL AND METHODS: The overview is based on literature identified through a search in PubMed (using PubMed's own search strategy) and on official reports from WHO and the disease control centres of EU and the USA. RESULTS: The new influenza A(H1N1) has so far mainly affected young people, only few people over 60 years. The clinical presentation is similar to that of ordinary influenza; but nausea, vomiting and diarrhoea seem to be more common. The reported risk of complications and case fatality are low, but hospitalisation, pneumonia and deaths have occurred, also in previously healthy young individuals. Antiviral treatment with oseltamivir or zanamivir is likely to be as effective as in ordinary influenza. INTERPRETATION: Mild cases may be underrepresented in the published literature. It is important to keep up-to-date on international reports on the nature of the disease in order to best prepare clinicians to diagnose and treat patients when the epidemic hits Norway with full force.

[Viral drug resistance]. / Resistens ved virusinfeksjoner.

BACKGROUND: More and more viral infections are treated with antiviral drugs, and resistance against these drugs is steadily increasing. Our aim is to give a general understanding of viral resistance and its clinical significance. MATERIAL AND METHODS: This article is based on review of published literature on the subject, international recommendations and our own experience as a national reference laboratory for hepatitis viruses. RESULTS AND INTERPRETATION: Development of viral resistance is an increasing problem with long-term treatment of both latent and chronic viral infections and may be one of the reasons for clinical treatment failure. Susceptibility testing is therefore an important diagnostic tool in cases of suspected failure during antiviral treatment, and is also necessary for customising of treatment to each individual patient. In Norway, susceptibility testing is offered for HIV, HBV, CMV and influenza, whereas systematic surveillance for the time being is only performed on HIV and influenza resistance. Surveillance on viral resistance is necessary in order to choose the adequate empirical therapy and to monitor the spread of resistant virus in the population. Prevalence of resistance can be limited with infection control measures and appropriate antiviral treatment, especially used in combinations of effective drugs directed at different enzymes and proteins within the virus.

[Resistance in influenza viruses]. / Resistens hos influensavirus.

BACKGROUND: Influenza virus infection can be prevented and treated with antiviral drugs. The usage of such drugs in Norway has been infrequent, however, they are an important component in our pandemic preparedness planning, as it will probably be difficult to get access to the appropriate vaccine in time before the pandemic reaches the country. The first generation of influenza drugs acquired resistance to a large degree, in contrast to the modern neuraminidase inhibitors that until recently have had minor problems with resistance. MATERIAL AND METHODS: This review is based on research found in relevant published literature, together with experience from a virology reference laboratory and participation in a national and international surveillance including susceptibility testing. RESULTS AND INTERPRETATION: While resistance has been a longstanding problem with the use of the "old" influenza drugs amantadine and rimantadine, only during the winter 2007/2008 did it become clear, that a certain type of virus acquired widespread resistance against the neuraminidase inhibitor oseltamivir. Resistance surveillance is crucial for the correct choice of empiric treatment for influenza infection, and will be one of the most important tasks at the National Influenza Centre in certain phases of a pandemic. The current situation with an increasing resistance problem strengthens the need to conduct continuous monitoring of antiviral susceptibility, as well as development of new antiviral drugs and treatment regimes.

[Whooping cough--an increasing problem in Norway]. / Kikhoste--et økende problem i Norge.

BACKGROUND: The incidence of whooping cough has increased in recent years in Norway, especially amongst older children and adults; in 2004 it was 168/100,000. MATERIAL AND METHODS: This article is based on our own experience and a review of available literature, identified on Medline with the search word "pertussis". RESULTS AND INTERPRETATION: Whooping cough, a disease caused by the bacterium Bordetella pertussis, is transmitted via respiratory droplets. Sources of infection for infants are often their parents and siblings. Older children and adolescents contract whooping cough mostly in school, whereas adults usually get the disease from children or colleagues. The typical symptoms are bouts of violent coughing with the classic whoop and post-tussive vomiting. A milder clinical picture can be seen in vaccinated persons, reinfected patients, and in persons above the age of 15. Infants are most at risk of developing serious disease and have the highest numbers of hospitalizations, complications and mortality. But complications are also seen in adolescents and adults, including urinary incontinence, rib fractures and pneumonia. The diagnosis is made by culture or PCR in nasopharyngeal secretions, as well as by detection of antibodies to B. pertussis in serum. If treatment is indicated, macrolides are the drugs of choice; these shorten the duration of symptoms and the period of contagiousness if given in the early stages of the disease. To help combat whooping cough in Norway, from 2006 an extra vaccine booster dose will be given to children at the age of seven.