Lung abscess: an update on the current knowledge and call for future investigations.

PURPOSE OF REVIEW: Lung abscess is a severe and complex respiratory infection. The purpose of this review is to discuss recent publications on lung abscess, covering topics such as epidemiology, clinical presentation, diagnosis, and treatment and prevention. RECENT FINDINGS: Risk factors associated with lung abscess include structural lung disease, poor dental hygiene, and ventilator-associated pneumonia, while concerns are now raised regarding the potential of electronic cigarettes use as a risk factor. The complexity of lung abscess is reflected by the relative high number of case reports describing rare and complex cases. Early transthoracic drainage could improve in-hospital outcomes, while next-generation sequencing could become an important tool in diagnostics and future clinical studies. SUMMARY: High-quality evidence and guidelines to support treatment of lung abscess are lacking. Despite advancements, we call for prospective studies to evaluate the use of invasive procedures and antibiotic treatment regimens.

Prevalence estimates of tuberculosis infection in adults in Denmark: a retrospective nationwide register-based cross-sectional study, 2010 to 2018.

BackgroundTuberculosis (TB) elimination requires identifying and treating persons with TB infection (TBI).AimWe estimate the prevalence of positive interferon gamma release assay (IGRA) tests (including TB) and TBI (excluding TB) in Denmark based on TBI screening data from patients with inflammatory bowel disease (IBD) or inflammatory rheumatic disease (IRD).MethodsUsing nationwide Danish registries, we included all patients with IBD or IRD with an IGRA test performed between 2010 and 2018. We estimated the prevalence of TBI and positive IGRA with 95% confidence intervals (CI) in adolescents and adults aged 15-64 years after sample weighting adjusting for distortions in the sample from the background population of Denmark for sex, age group and TB incidence rates (IR) in country of birth.ResultsIn 13,574 patients with IBD or IRD, 12,892 IGRA tests (95.0%) were negative, 461 (3.4%) were positive and 221 (1.6%) were indeterminate, resulting in a weighted TBI prevalence of 3.2% (95% CI: 2.9-3.5) and weighted positive IGRA prevalence of 3.8% (95% CI: 3.5-4.2) among adults aged 15-64 years in the background population of Denmark. Unweighted TBI prevalence increased with age and birthplace in countries with a TB IR higher than 10/100,000 population.ConclusionEstimated TBI prevalence is low in Denmark. We estimate that 200,000 persons have TBI and thus are at risk of developing TB. Screening for TBI and preventive treatment, especially in persons born in high TB incidence countries or immunosuppressed, are crucial to reduce the risk of and eliminate TB.

Comorbidities, mortality and causes of death among patients with tuberculosis in Denmark 1998-2010: a nationwide, register-based case-control study.

OBJECTIVE: To evaluate the impact of comorbidities, age and clinical presentation of TB on mortality among Danish patients with TB. METHODS: Danish patients with an ICD-10 (International Statistical Classification of Diseases and Related Health Problems 10th Revision) diagnosis of TB in 1998-2010 were identified in the National Patient Registry and matched with controls (1:4) on age, gender, civil status and geography. Comorbid diagnoses up to 3 years before and after TB diagnosis or enrolment as control as well as survival data were obtained from national databases RESULTS: We included 8433 cases and 33 707 controls. Respiratory diseases were the most common comorbidities among cases (12.4% of cases, 3.8% of controls (p<0.001)). Overall HR of death was 2.45 (2.31; 2.59). Relative mortality was especially increased among younger adults (HR 8.70 (95% CI 5.53 to 13.69) among the 30 to 39-year-olds). While overall mortality increased with Deyo-Charlson comorbidity (DCC) score, relative mortality among cases was highest in the low-DCC group. Additionally, male gender, low income and central nervous system TB were risk factors for death among TB cases. The most common cause of death in both groups was non-lung cancers, among TB cases followed by COPD, TB and lung cancer, all being significantly more common among TB cases. CONCLUSION: In Denmark, TB carries substantial mortality. Among those who die, 12% are reported to die from TB. A high relative mortality among younger adults underscores the importance of continually targeting high-risk TB groups in low-incidence countries.

Co-morbidity and mortality among patients with interstitial lung diseases: A population-based study.

BACKGROUND AND OBJECTIVE: Co-morbidities are frequent among patients with interstitial lung diseases (ILD). The objective of this study was to investigate their impact on mortality. METHODS: We used the Danish National Patient Registry (DNPR) to identify all patients with a first-time diagnosis of ILD between 1998 and 2010. Patients with ILD were matched 1:4 with controls from the background population. The burden of co-morbidity was assessed using the Deyo-Charlson co-morbidity score (DCcs). Mortality risks were assessed using Kaplan-Meier survival curves, and hazard rate ratios (HRR) for death were estimated using Cox proportional hazards regression models. RESULTS: We identified 10 629 patients with ILD with a corresponding incidence estimate of ILD in Denmark of 17.6 per 100 000 inhabitants (95% CI: 16.5-18.7). Mean age was 72 years and 45.6% of the patients were females. Co-morbidity (DCcs ≥ 1) was present in 30% of the ILD patients and 12% of the controls (P < 0.001). The 5-year survival was 56.0% (95% CI: 54.6-56.6) among ILD patients and 84.0% (95% CI: 83.7-84.4) among controls. HRR for death among patients with ILD was 3.82 for males (95% CI: 3.63-4.02) and 3.85 for females (95% CI: 3.62-4.09) with matched controls as reference. Decreasing survival was seen with increasing DCcs for both groups. The 5-year survival for DCcs = 0 was 61% for ILD and 87% for controls compared with 41% versus 58% for DCcs = 2. CONCLUSION: Survival was impaired for patients with ILD for all levels of the DCcs, although increasing burden of co-morbidity tended to close the mortality gap.

Development of an epitope panel for consistent identification of antigen-specific T-cells in humans.

We aimed to establish a panel of MHC-peptide multimers suitable as a positive control in the detection of HLA A*0201 restricted antigen specific T cells (ASTC) by flow cytometry. MHC Dextramers were loaded with HLA A*0201 binding peptides from viral antigens and melanoma targets identified from a literature search and in silico prediction. Peripheral blood mononuclear cells (PBMC) from healthy donors were analysed with the MHC Dextramers using flow cytometry. The best performing epitopes were tested on PBMC from patients undergoing testing for Mycobacterium tuberculosis infection to assess the coverage of this epitope panel. Of 21 candidate epitopes, ASTC could be detected against 12 (57·1%) in at least one of 18 healthy blood donors. Reactivity to two or more epitopes was seen in 17 of the 18 donors (94·4%). We selected the six best-performing epitopes and demonstrated a positive response in 42 (97·7%) of 43 patient samples (healthy, latent and active M. tuberculosis infection). The selected panel of six antigenic epitopes sufficed as a positive control in the detection of ASTC in HLA A*0201. Performance was robust in different stages of latent and active M. tuberculosis infection, indicating reliability also during infection.

Risk Assessment of Tuberculosis in Contacts by IFN-γ Release Assays. A Tuberculosis Network European Trials Group Study.

RATIONALE: Latent infection with Mycobacterium tuberculosis is defined by a positive IFN-γ release assay (IGRA) result in the absence of active tuberculosis. Only few, mostly monocentric studies have evaluated the role of IGRAs to predict the development of tuberculosis in recent contacts in low-incidence countries of tuberculosis. OBJECTIVES: To analyze IGRA results and the effect of preventive chemotherapy on tuberculosis progression rates among recent contacts. METHODS: Results from contact investigations at 26 centers in 10 European countries including testing for latent infection with M. tuberculosis by the QuantiFERON-TB Gold In-Tube (QFT) test or the T-SPOT.TB (TSPOT) were prospectively collected and analyzed. MEASUREMENTS AND MAIN RESULTS: Among 5,020 contacts of 1,023 index cases, 25 prevalent secondary cases were identified at screening. Twenty-four incident cases occurred among 4,513 contacts during 12,326 years of cumulative follow-up. In those with a positive IGRA result, tuberculosis incidence was 0.2 (QFT) and 0 (TSPOT) per 100 patient-years when contacts received preventive chemotherapy versus 1.2 (QFT) and 0.8 (TSPOT) per 100 patient-years in those not treated (38 and 37 patients needed to be treated to prevent one case, respectively). Positive and negative predictive values were 1.9% (95% confidence interval [CI], 1.1-3.0) and 99.9% (95% CI, 99.7-100) for the QFT and 0.7% (95% CI, 0.1-2.6) and 99.7% (95% CI, 99.1-99.9) for the TSPOT. CONCLUSIONS: Tuberculosis rarely developed among contacts, and preventive chemotherapy effectively reduced the tuberculosis risk among IGRA-positive contacts. Although the negative predictive value of IGRAs is high, the risk for the development of tuberculosis is poorly predicted by these assays.

Shortening Isolation of Patients With Suspected Tuberculosis by Using Polymerase Chain Reaction Analysis: A Nationwide Cross-sectional Study.

BACKGROUND: Isolation of patients suspected for pulmonary tuberculosis is guided by serial sputum smears. This can result in isolation for days for patients with noncontagious tuberculosis. To determine whether a single sample negative for Mycobacterium tuberculosis complex at polymerase chain reaction (PCR) can guide isolation. METHODS: We retrospectively evaluated sputum samples analyzed for M. tuberculosis complex at the International Reference Laboratory of Mycobacteriology, Copenhagen, Denmark in 2002-2011. We selected culture-confirmed tuberculosis cases with ≥3 samples within 14 days before or after the initial culture-positive sample. We repeated the process for those with ≥2 samples within 28 days. The primary outcome was PCR-negative, smear-positive patients. RESULTS: We included 53 533 sputum samples from 20 928 individuals; 1636 had culture-confirmed tuberculosis. Of these, 856 had ≥3 sputum samples analyzed within the 28 days, and 482 had ≥1 PCR result. Nine patients (2.5% of smear-positive patients) were smear positive/PCR negative; 8 of the 9 had a smear-positive result in only 1 of 3 samples, and 5 had a low smear grade. Of 722 patients with 2 samples, 7 (1.3% of smear-positive patients) were smear positive/PCR negative. Overall, none were smear positive for the sample that produced the negative PCR result. CONCLUSIONS: Primary PCR identified >97% of serial smear-positive cases. The majority of the missed cases had low-grade smears. Nevertheless, the occurrence of smear-positive/PCR-negative cases underlines the importance of increasing the quantity and quality of samples. Moreover, it is important that samples analyzed with PCR are cultured, owing to higher-sensitivity drug susceptibility testing, differential diagnosis, and surveillance.

Pulmonary infections with nontuberculous mycobacteria.

This review focuses on the treatment of nontuberculous pulmonary disease caused by Mycobacterium avium complex and M. abscessus. It covers treatment indications, antibiotic choice, resistance and side effects. Treatment of nontuberculous pulmonary disease is complex, lengthy, and fraught with side effects. Increased attention on this disease is needed in order to alleviate the severe consequences of this growing disease. Cooperation between pulmonologists and infectious disease specialists is needed to ensure uniform treatment, and to account for the heterogeneity seen in patients and mycobacteria alike.

Nationwide Increasing Incidence of Nontuberculous Mycobacterial Diseases Among Adults in Denmark: Eighteen Years of Follow-Up.

BACKGROUND: The epidemiology of nontuberculous mycobacteria (NTM) infections is not well described. In this study, we sought to determine the incidence and prevalence of NTM infections and focus on social risk factors. In addition, we describe people with pulmonary and extrapulmonary NTM. RESEARCH QUESTION: What are the incidence and prevalence of NTM in Denmark, and what are the characteristics of the affected patients? STUDY DESIGN AND METHODS: This is a nationwide retrospective register-based cohort study in Denmark. Adult patients in the Danish national registers who received a diagnosis of NTM disease from 2000 to 2017 were classified as having either pulmonary or extrapulmonary NTM disease. RESULTS: We identified 1,146 adults with an NTM diagnosis. Of these, 661 patients had pulmonary NTM, of whom 50.4% were male, whereas 485 had extrapulmonary NTM, of whom 59.6% were male. The median age (interquartile range) was 66 (18) years and 57 (32) years, respectively. The yearly incidence rate per 100,000 increased between 2000 and 2017 for both pulmonary NTM (0.4 to 1.3) and extrapulmonary NTM (0.3 to 0.6). The annual prevalence per 100,000 inhabitants increased from 0.4 to 3.5 for pulmonary NTM and from 0.3 to 1.0 for extrapulmonary NTM. The incidence rate increased with age. The incidence of pulmonary NTM was highest among those who were aged 70 years or older (19.3 per 100,000 inhabitants). Compared with patients with pulmonary NTM, patients with extrapulmonary NTM were more likely to be employed and had a higher educational level. INTERPRETATION: This study indicates that the prevalence of NTM disease in Denmark increased between 2000 and 2017. We found that patients with pulmonary NTM and patients with extrapulmonary NTM represent two distinct groups that differ in age, sex, education, and employment status. Increased suspicion of pulmonary NTM disease is warranted in older adults after exclusion of more common lung infections.

The role of whole genome sequencing in identifying occupational tuberculosis among healthcare workers: two case reports.

In this case report, we present case reports for two nurses, both working in departments of respiratory medicine, who developed tuberculosis (TB). For each individual case, whole genome sequencing (WGS) revealed only one specific match within a genomic distance of <6 single-nucleotide polymorphisms. The subsequent epidemiological investigations confirmed that both nurses had relevant exposures to their corresponding match 1139 and 1704 days before presenting with TB symptoms, respectively. Twenty-two studies were identified that reported using genotyping to identify occupational transmission of Mycobacterium tuberculosis to healthcare workers. Only two studies applied WGS, both conducted in resource-rich countries, comparable to the present Danish investigation. When comparing the two WGS studies to the other studies that used older genotyping techniques, WGS provided a higher resolution and much more detailed information. Consequently, the epidemiological investigations were more straightforward. In conclusion, WGS is a powerful tool for determining whether M. tuberculosis transmission is occupational as demonstrated for the two cases in this study.

Inhaled Corticosteroids Particle Size and Risk of Hospitalization Due to Exacerbations and All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease. A Nationwide Cohort Study.

Background: Extra-fine particle inhaled corticosteroids (ICS) improve peripheral airway distribution, but their effect on risk of exacerbations and all-cause mortality in patients with chronic obstructive pulmonary disease (COPD) is unclear. Methods: This observational cohort study compares patients with COPD who received extra-fine particle ICS to those who received standard particle size ICS from 2010 to 2017 while followed in outpatient clinics. The primary outcome was the time to a COPD exacerbation that required hospitalization, with all-cause mortality as a secondary outcome. Data were analyzed using an adjusted Cox proportional hazards model and a competing risk analysis. Two predefined subgroup analyses of patients treated with pressurised metered dose inhalers (pMDIs) and patients with a previous exacerbation history, was carried out. Lastly, we created a propensity score matched cohort as a sensitivity analysis. Results: Of the 40,489 patients included, 38,802 (95.8%) received stand particle size ICS and 1,687 (4.2%) received extra-fine particle ICS. In total 7,058 were hospitalized with a COPD exacerbation, and 4,346 died. No significant protective effect of extra-fine particle ICS against hospitalization due to COPD exacerbations (HR 0.93, 95% CI 0.82-1.05, p=0.23) or all-cause mortality (HR 1.00, 95% CI 0.85-1.17, p=0.99) was found when compared to standard particle size ICS. However, in the subgroup analysis of patients treated with pMDIs, extra-fine particle ICS was associated with reduction in risk of exacerbations (HR 0.72, 95% CI 0.63-0.82, p<0.001) and all-cause mortality (HR 0.72, 95% CI 0.61-0.86, p<0.001). Conclusion: The administration of extra-fine particle ICS was not associated with reduced risk of exacerbations or all-cause mortality in our primary analysis. A subgroup consisting of patients treated with pMDIs suggested potential protective benefits.

Mycobacterium avium complex pulmonary disease patients with limited treatment options.

How to identify MAC-PD patients with limited treatment options: an expert consensus https://bit.ly/3QwLQ8T.

Nontuberculous mycobacterial infections in a Danish region between 2011 and 2021: evaluation of trends in diagnostic codes.

INTRODUCTION: Nontuberculous mycobacteria (NTM) are emerging as human pathogens at increasing rates. In Denmark, few studies of NTM exist, but these have not been able to confirm an increasing trend. Existing studies have not utilised clinical data or investigated geographical variations. METHODS: A retrospective cohort study of patients with an ICD-10 diagnostic code of NTM infection in a Danish region, Central Denmark Region, between 2011 and 2021. Incidence rates per 100,000 citizens were calculated using data from Statistics Denmark. A Spearman's rank correlation coefficient was computed to assess the linear relationship between years and annual incidence rates. RESULTS: We identified 265 patients, 53.2% (n = 141) females, with a median age of 65.0 years (IQR 47-74). The age distribution was bimodal with peaks in extreme age groups between 0-14 years of age (n = 35, 13.2%) and above 74 years (n = 63, 23.8%). Most patients were coded with a pulmonary infection (51.3%, n = 136), 35.1% (n = 93) with other/unspecified infection and 13.6% (n = 36) with a skin infection. Incidence rates ranged from 1.3 (2013) to 2.5 (2021) per 100,000 citizens. There was a highly positive linear correlation of NTM incidence rates over the years (r = 0.75, p = 0.010) suggesting an increasing trend. CONCLUSION: More than one-third with an NTM infection based on ICD-10 codes were found in extreme age groups. At least half of the patients had a pulmonary infection. Contradicting previous data from Denmark, we found an increasing trend of NTM, potentially suggesting an increase in clinically relevant disease, a higher awareness and test rate, or improved coding.

Pulmonary Mycobacterium abscessus infection treated in combination with inhaled tigecycline.

Pulmonary disease caused by Mycobacterium abscessus is difficult to treat, as there is currently no reliable evidence-based treatment. Treatment is long, complex and has many side effects. In this case, we report a patient with treatment-refractory pulmonary M abscessus disease, treated with inhaled tigecycline. Treatment with inhaled tigecycline lasted 15 months with comparably limited side effects. There were no positive mycobacterial cultures in the follow-up period of 2 years. Inhaled tigecycline is an option in the treatment of pulmonary M. abscessus when first-line treatment fails. Additional research should investigate this further.

Disseminated Mycobacterium genavense infection in a patient with a history of sarcoidosis.

We present a case of Mycobacterium genavense infection in a man in his 60s with a history of sarcoidosis, treated for 24 years with systemic corticosteroids and later methotrexate as monotherapy. He presented with low grade fever, dyspnoea and right-sided thoracic pain and was admitted due to a treatment-refractory infection. After a prolonged period of symptoms and diagnostics, acid-fast bacilli were demonstrated in pleural fluid and PCR revealed M. genavense The patient was treated with intravenous amikacin, peroral azithromycin, rifampicin and ethambutol for a total of 18 months, with a good clinical and radiological treatment response. Infection with M. genavense is rare in HIV-negative immunocompromised hosts. Diagnosing and treating mycobacterial infections, especially for more rare species, remains a challenge as clinical evidence is sparse. Nonetheless, the disease-causing infection must be considered in symptomatic and immunocompromised patients.

Lung abscess: Clinical characteristics of 222 Danish patients diagnosed from 2016 to 2021.

INTRODUCTION: Lung abscess (LA) is a serious respiratory infection often followed by several weeks of antibiotic treatment. This study described the clinical presentation of LA, treatment duration and mortality in a contemporary Danish population. METHODS: In a retrospective multicenter cohort study at four Danish hospitals, patients diagnosed with LA were identified using the International Classification of Diseases and Related Health Problems 10th revision (ICD-10) between 2016 and 2021. A predefined data collection tool was used to extract data on demographics, symptoms, clinical findings and treatment. RESULTS: Of 302 patients, 222 with LA were included after review of patient records (76%). Mean age was 65 years (54-74), 62.9% was male and 74.9% were ever-smokers. Chronic obstructive pulmonary disease (COPD) (35.1%), use of sedatives (29.3%) and alcohol abuse (21.8%) were common risk factors. Dental status was reported in 51.4%, whereof 41.6% had poor dental status. Patients presented with cough (78.8%), malaise (61.3%) and fever (56.8%) Patients were hospitalized for a median of 14 days (interquartile ranges, IQR 7-21) and median duration of antibiotic treatment was 38 days (IQR 30-51). All-cause mortality after 1, 3 and 12 months was 2.7%, 7.7% and 15.8%, respectively. CONCLUSION: Risk factors for LA include COPD and use of sedatives, alcohol abuse, and poor dental status. Despite long-term antibiotic treatment, long-term mortality is markedly high.

Twelve-month follow-up after hospitalization for SARS-COV-2: Physiology improves, symptoms remain.

OBJECTIVES: Persistent symptoms on short-term follow-up after infection with COVID-19 are common, but long-term consequences have been insufficiently studied. The aim of this study was to characterize pulmonary function and ongoing symptoms 12 months after hospitalization with COVID-19. METHODS: This prospective multicenter study included 222 patients hospitalized with PCR-confirmed COVID-19 in the Central Denmark Region. Disease severity was stratified using WHO Clinical Progression Scale. Clinical characteristics, pulmonary function test (PFT), 6-minute walk test (6MWT), and patient-reported outcome measures were collected at follow-up 3 and 12 months after discharge. Outcome measures from follow-up 3 months after discharge have previously been published. RESULTS: A total of 179 (81%) patients completed the 12-month follow-up. Median age was 60 years (IQR 51, 69) and 58% were male patients. At 12-month follow-up 49.7% had a normal diffusion capacity for carbon monoxide (DLCO), while 39.4% had DLCO < 80%. The 6MWT distance increased significantly (29 m 95% CI 19, 40; p < 0.01). An mMRC score of 0 was reported by 51% and an mMRC ≥ 2 by 20%. The frequency and severity of fatigue, depression, and anxiety did not improve over time. CONCLUSIONS: The study found that impaired DLCO percentage is common 12 months after hospitalization with SARS-CoV-2 and reduction in DLCO percentage is associated to dyspnea.

Global trends of pulmonary infections with nontuberculous mycobacteria: a systematic review.

OBJECTIVES: To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease. METHODS: A systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated. RESULTS: Most studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 100,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%). CONCLUSION: Our data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation.

The cascade of care in tuberculosis infection screening and management in newly arrived refugees in Aarhus, Denmark.

BACKGROUND: Screening for tuberculosis (TB) disease and infection is often a part of health screening programs offered to refugees, but the yield of screening varies and losses along the steps from screening to treatment completion was reported. METHODS: A retrospective cohort study was performed investigating a newly arrived refugee population offered a systematic refugee health assessment in Aarhus, Denmark. Data was collected on screening, referral, diagnosis and treatment for TB disease and infection. RESULTS: Among both adults and children IGRA positivity was associated with origin in a high TB incidence country and increasing age. The number needed to screen (NNS) to find one case of TB infection was 7 among adult refugees and 19 among children, while NNS for TB disease was 266 and 164 respectively. The proportion of the eligible population with a valid result was 78.1% for adults and 71.3% for children, while 43.1% and 50% of adults and children with presumed TB infection completed preventive treatment. DISCUSSION: Screening for TB disease and infection among refugees in Aarhus had a high yield in terms of diagnosis, however significant losses were seen during screening, follow-up and preventive treatment completion.