Fast multiplex bacterial PCR of bronchoalveolar lavage for antibiotic stewardship in hospitalised patients with pneumonia at risk of Gram-negative bacterial infection (Flagship II): a multicentre, randomised controlled trial.

BACKGROUND: PCR-based testing has transformed the management of suspected respiratory viral infections. We aimed to determine whether multiplex bacterial PCR of bronchoalveolar lavage fluid aids antibiotic stewardship in patients with pneumonia. METHODS: This investigator-initiated, multicentre, randomised controlled trial was conducted at two tertiary care centres in Switzerland (University Hospital of Basel and Kantonsspital St Gallen). Patients aged 18 years or older who were admitted to hospital with suspected pneumonia, had a clinical indication for bronchoscopy with bronchoalveolar lavage, and were at risk of Gram-negative bacterial infection were included. Patients were randomly assigned (1:1) to either the multiplex bacterial PCR group or the conventional microbiology control group using a random allocation sequence. Treating physicians were not masked, but the committee panel was masked to patient randomisation. All patients underwent bronchoscopy with bronchoalveolar lavage and samples were assessed by conventional microbiological culture (and additionally, in the PCR group, by multiplex bacterial PCR for Gram-negative rods using the Unyvero Hospitalized Pneumonia [HPN] Cartridge; Curetis, Holzgerlingen, Germany). Patients received empirical antibiotic therapy as clinically indicated by the treating physician. In the PCR group, a recommendation regarding antibiotic therapy was made approximately 5 h after taking the sample. The primary outcome was the time in hours on inappropriate antibiotic therapy from bronchoscopy to discharge or to 30 days after bronchoscopy. This trial was registered with the International Clinical Trials Registry Platform, ISRCTN95828556. FINDINGS: Between May 31, 2017, and Sept 25, 2019, 740 patients with pneumonia were screened for eligibility and 208 were included and randomly assigned to the PCR group (n=100) or conventional microbiology control group (n=108). The mean age of patients was 65·9 years (SD 14·0) and 135 (65%) were male. After daily follow-up until hospital discharge or for a maximum of 30 days, the duration of inappropriate antibiotic treatment was significantly shorter by 38·6 h (95% CI 19·5-57·7) in the PCR group than in the control group (adjusted mean 47·1 h [34·7-59·5] vs 85·7 h [78·8-95·6]; p<0·0001), which translates as a decrease in the duration of inappropriate antibiotic therapy of 45·0% (37·9-52·1). Adverse events due to antimicrobial therapy occurred in nine patients (five [5%] in the PCR group vs four [4%] in the control group) and due to bronchoscopy occurred in four patients (two [1%] vs two [1%]). There were eight (8%) deaths in the PCR group and 11 (10%) in the control group. All in-hospital deaths were attributed to a respiratory cause. INTERPRETATION: Multiplex bacterial PCR examination of bronchoalveolar lavage decreases the duration of inappropriate antibiotic therapy of patients admitted to hospital with pneumonia and at risk of Gram-negative rod infection. This approach warrants further consideration in future antibiotic stewardship strategies. FUNDING: Curetis and the Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Switzerland.

Bronchial hyperresponsiveness testing in athletes of the Swiss Paralympic team.

BACKGROUND: The aim of this study was to assess airway hyperresponsiveness to eucapnic voluntary hyperventilation and dry powder mannitol challenge in athletes aiming to participate at the Paralympic Games 2008 in Beijing, especially in athletes with spinal cord injury. METHODS: Forty-four athletes with a disability (27 with paraplegia (group 1), 3 with tetraplegia (group 2) and 14 with other disabilities such as blindness or single limb amputations (group 3) performed spirometry, skin prick testing, measurement of exhaled nitric oxide, eucapnic voluntary hyperventilation challenge test (EVH) and mannitol challenge test (MCT). A fall in FEV1 of ≥10% in either challenge test was deemed positive for exercise-induced bronchoconstriction. RESULTS: Fourteen (32%) athletes were atopic and 7 (16%) had a history of physician-diagnosed asthma. Absolute lung function values were significantly lower in patients of group 1 and 2 compared to group 3. Nine (20%) athletes were positive to EVH (8 paraplegics, 1 tetraplegic), and 8 (18%) athletes were positive to MCT (7 paraplegics, 1 tetraplegic). Fourteen (22.7%) subjects were positive to at least one challenge; only three athletes were positive to both tests. None of the athletes in group 3 had a positive test. Both challenge tests showed a significant association with physician-diagnosed asthma status (p = 0.0001). The positive and negative predictive value to diagnose physician-diagnosed asthma was 89% and 91% for EHV, and 75% and 86% for MCT, respectively. CONCLUSION: EVH and MCT can be used to identify, but especially exclude asthma in Paralympic athletes.

Chronic obstructive pulmonary disease--a treatable disease.

Chronic obstructive pulmonary disease (COPD) is a global health challenge and a leading cause of death worldwide. Several risk factors have been identified, with cigarette smoking being the most important. Diagnostic assessment is based on symptoms, risk of exacerbations and results of lung function testing. A fixed post-bronchodilator ratio for forced expiratory volume in one second to forced expiratory volume (FEV1/FVC) of <0.7 is required to make the diagnosis, and the severity of airflow obstruction defines the grade according to GOLD (Global Strategy for the Diagnosis, Management, and Prevention of COPD). The GOLD strategy makes therapeutic recommendations taking into account the grade, symptomatic assessment and future risk of exacerbations. This review focuses on the therapeutic options for COPD, in accordance with the GOLD strategy. Smoking cessation is the most effective treatment option in all COPD stages. Bronchodilators, namely long-acting antimuscarinic drugs and long-acting beta-agonists, form the mainstay of treatment in COPD. Patients with frequent exacerbations also benefited from the addition of inhaled corticosteroids. Roflumilast is an add-on option for patients with severe COPD. Several controversies are the subject of discussion: (1.) whether pharmacotherapy can modify the natural history of COPD; (2.) whether pharmacotherapy should be started in the early stages of COPD; (3.) the impact of therapy on comorbidities; (4.) whether patients benefit from a combination therapy with a long-acting beta-agonist, a long-acting antimuscarinic drug and an inhaled corticosteroid; (5.) step-down therapy. This overview also reviews the evidence for recommended vaccines in COPD, as well as nonpharmacological therapies. Rehabilitation is an essential part of COPD treatment. Oxygen therapy, noninvasive nocturnal ventilation and surgical treatment options only apply to a highly selected group of patients. Disease management programmes and guideline adherence are briefly discussed. In conclusion, although there is debate as to the extent with which pharmacological therapies influence mortality, adherence to the GOLD strategy is recommended.

Levosimendan as treatment option in severe verapamil intoxication: a case report and review of the literature.

Cardiovascular shock due to verapamil intoxication is often refractory to standard resuscitation methods. Recommended therapy includes prevention of further absorption of the drug, inotropic therapy, calcium gluconate, and hyperinsulinemia/euglycemia therapy. Often further measures are needed such as ventricular pacing or mechanical circulatory support. Still, mortality remains high. Levosimendan, an inotropic agent, that enhances myofilament response to calcium, increases myocardial contraction and could therefore be beneficial in verapamil intoxication. Here, we report the case of a 60-year-old patient with clinically severe verapamil poisoning who presented with shock, bradycardia, and sopor. Standard therapy including high-dose inotropes failed to ameliorate the signs of intoxication. But additional therapy with levosimendan led to rapid improvement. Based on this observation, the literature is reviewed focusing on utilization of levosimendan in the treatment of calcium channel blocker overdose. We suggest to consider levosimendan as additional treatment option in patients with cardiovascular shock due to verapamil intoxication that are refractory to standard management.

Management of chronic obstructive pulmonary disease patients after hospitalization for acute exacerbation.

The objective of this review is to sum up the literature regarding the management of patients with chronic obstructive pulmonary disease (COPD) after hospitalization for an acute exacerbation. Guidelines recommend a follow-up 4-6 weeks after hospitalization to assess coping strategies, inhaler technique, the need for long-term oxygen therapy and the measurement of FEV(1). This review discusses the follow-up of patients with exacerbations of COPD, the use and value of spirometry in their further management, the potential benefit of home monitoring, the value of long-term oxygen therapy, the value of self-management programs including the use of action plans, the potential benefit of noninvasive ventilation as well as the value of early rehabilitation. There is not enough literature to allow specific recommendations and to define components of a care plan after hospitalization for an acute exacerbation; however, early rehabilitation should be included.