Aetiological role of viral and bacterial infections in acute adult lower respiratory tract infection (LRTI) in primary care.

BACKGROUND: Lower respiratory tract infections (LRTI) are a common reason for consulting general practitioners (GPs). In most cases the aetiology is unknown, yet most result in an antibiotic prescription. The aetiology of LRTI was investigated in a prospective controlled study. METHODS: Eighty adults presenting to GPs with acute LRTI were recruited together with 49 controls over 12 months. Throat swabs, nasal aspirates (patients and controls), and sputum (patients) were obtained and polymerase chain reaction (PCR) and reverse transcriptase polymerase chain reaction (RT-PCR) assays were used to detect Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, influenza viruses (AH1, AH3 and B), parainfluenza viruses 1-3, coronaviruses, respiratory syncytial virus, adenoviruses, rhinoviruses, and enteroviruses. Standard sputum bacteriology was also performed. Outcome was recorded at a follow up visit. RESULTS: Potential pathogens were identified in 55 patients with LRTI (69%) and seven controls (14%; p<0.0001). The identification rate was 63% (viruses) and 26% (bacteria) for patients and 12% (p<0.0001) and 6% (p = 0.013), respectively, for controls. The most common organisms identified in the patients were rhinoviruses (33%), influenza viruses (24%), and Streptococcus pneumoniae (19%) compared with 2% (p<0.001), 6% (p = 0.013), and 4% (p = 0.034), respectively, in controls. Multiple pathogens were identified in 18 of the 80 LRTI patients (22.5%) and in two of the 49 controls (4%; p = 0.011). Atypical organisms were rarely identified. Cases with bacterial aetiology were clinically indistinguishable from those with viral aetiology. CONCLUSION: Patients presenting to GPs with acute adult LRTI predominantly have a viral illness which is most commonly caused by rhinoviruses and influenza viruses

Using domiciliary non-invasive ventilator data downloads to inform clinical decision-making to optimise ventilation delivery and patient compliance

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. Introduction Ventilation parameter data from patients receiving home mechanical ventilation can be collected via secure data cards and modem technology. This can then be reviewed by clinicians and ventilator prescriptions adjusted. Typically available measures include tidal volume (V T ), leak, respiratory rate, minute ventilation, patient triggered breaths, achieved pressures and patient compliance. This study aimed to assess the potential impact of ventilator data downloads on management of patients requiring home non-invasive ventilation (NIV). Methods A longitudinal within-group design with repeated measurements was used. Baseline ventilator data were downloaded, reviewed and adjustments made to optimise ventilation. Leak, V T and compliance data were collected for comparison at the first review and 3-7 weeks later. Ventilator data were monitored and amended remotely via a modem by a consultant physiotherapist between the first review and second appointment. Results Analysis of data from 52 patients showed increased patient compliance (% days used > 4 hours) from 90% to 96% (p=0.007), increased usage from 6.53 to 6.94 hours (p=0.211) and a change in V T (9.4 vs 8.7 mL/kg/ideal body weight, p=0.022). There was no change in leak following review of NIV prescriptions (mean (SD): 43 (23.4) L/min vs 45 (19.9)L/min, p=0.272). Conclusion Ventilator data downloads, via early remote assessment, can help optimise patient ventilation through identification of modifiable factors, in particular interface leak and ventilator prescriptions. However, a prospective study is required to assess whether using ventilator data downloads provides value in terms of patient outcomes and cost-effectiveness. The presented data will help to inform the design of such a study

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Cord formation in BACTEC(TM) medium aids rapid identification of Mycobacterium tuberculosis complex.

Mycobacterium tuberculosis complex (MTC) organisms form serpentine cords in fluid culture medium. Reporting of a presumptive identification of MTC based on cording allows rapid identification of patients with tuberculosis. A total of 612 positive mycobacterial cultures from 316 patients over 3 years (2008-2010) were evaluated for the presence of cord formation. Cording was identified in 426 (69.6%) specimens, while the reference laboratory confirmed M. tuberculosis in 424 specimens (69.3%). Sensitivity of the test in our laboratory was 99.1% (95%CI 97.4-99.7) and specificity was 96.8% (95%CI 92.8-98.7). Presumptive identification of M. tuberculosis by the presence of cording formation is both sensitive and specific

Fluoroquinolones and isoniazid resistant TB: implications for the 2018 WHO guidance

Introduction: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. / Methods: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009–2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). / Results: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60–1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14–2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). / Conclusions: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Competition and phylogeny determine community structure in Müllerian co-mimics

Until recently, the study of negative and antagonistic interactions (for example, competition and predation) has dominated our understanding of community structure, maintenance and assembly. Nevertheless, a recent theoretical model suggests that positive interactions (for example, mutualisms) may counterbalance competition, facilitating long-term coexistence even among ecologically undifferentiated species. Müllerian mimics are mutualists that share the costs of predator education and are therefore ideally suited for the investigation of positive and negative interactions in community dynamics. The sole empirical test of this model in a Müllerian mimetic community supports the prediction that positive interactions outweigh the negative effects of spatial overlap (without quantifying resource acquisition). Understanding the role of trophic niche partitioning in facilitating the evolution and stability of Müllerian mimetic communities is now of critical importance, but has yet to be formally investigated. Here we show that resource partitioning and phylogeny determine community structure and outweigh the positive effects of Müllerian mimicry in a species-rich group of neotropical catfishes. From multiple, independent reproductively isolated allopatric communities displaying convergently evolved colour patterns, 92% consist of species that do not compete for resources. Significant differences in phylogenetically conserved traits (snout morphology and body size) were consistently linked to trait-specific resource acquisition. Thus, we report the first evidence, to our knowledge, that competition for trophic resources and phylogeny are pivotal factors in the stable evolution of Müllerian mimicry rings. More generally, our work demonstrates that competition for resources is likely to have a dominant role in the structuring of communities that are simultaneously subject to the effects of both positive and negative interactions

On the Diagnosis and Management of Viral Respiratory Infections

Acute respiratory tract infections (ARTIs), are the most common infections in man, and represent a major global health burden. Viruses, most often causing a mild and self-limiting disease, yet with substantial morbidity and high costs for society, mainly cause upper respiratory tract infections. 70% of all infections in primary care in Sweden are due to ARTIs. Lower respiratory infections on the other hand constitute the third leading cause of death worldwide, mainly in children <5 years of age in resource poor settings. Distinguishing virus from bacteria can be difficult, and often lead to an over-prescription of antibiotics. Modern molecular based diagnostic methods have increased the possibility of an etiologic diagnosis of ARTIs significantly. This thesis aims to evaluate the use of a multiplex real time PCR assay targeting 13 respiratory viruses and two bacteria, from a clinical perspective. In paper I, a retrospective study of 954 nasopharyngeal samples, the PCR assay, which is based on automated specimen extraction and multiplex amplification, is described. Detection rate was 48%. Streamlined testing and cost limitation (€ 33 per sample) along with high accuracy and prompt result delivery, is key to successful implementation of broad molecular testing. Paper II evaluates in a prospective study of 209 adults with ARTI in primary care, and 100 asymptomatic controls, the impact duration of symptoms have on detection rate. Overall positive yield was 43% in patients and 2% in controls, with a significantly higher detection rate in patients with < 6 days duration of symptoms (51%) compared to ≥ 7 days (30%, p<0.01). Having access to the PCR assay reduced antibiotic prescription rates by 50%, in a prospective study (paper III) of 426 adults with ARTI. Patients receiving a result within 48 hours were prescribed antibiotics in 6,8% (n=14) compared to 15.1% (n=33, p<0.01) in the delayed result group. The diagnostic yield in paper IV, a retrospective study of 8753 patients of all ages during 36 consecutive months, was significantly higher during winter (54.7%) than in summer (31.1%, p<0.001), and in children (61.5%) compared with adults (30.5%, p<0.001). Rhinovirus was the most frequently found virus (32.5%), independent of season, and displayed a high genetic variability across seasons. The findings of this thesis support the implementation of similar methods in routine clinical care