The effectiveness of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in relation to renal function.

OBJECTIVES: We evaluated the effect of renal function on clinical failure rates of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in primary care. METHODS: Data were retrospectively obtained from 78 Dutch general practitioner (GP) practices between 2013 and 2019. Eligible episodes in patients (>11 years) were those requiring 5 days of nitrofurantoin (NF5), single-dose fosfomycin-trometamol (FT1), 3 days of trimethoprim (TMP3) for uncomplicated cystitis, or 7 days of nitrofurantoin (NF7) or trimethoprim (TMP7) for complicated cystitis. Clinical failure was defined as second antibiotic prescription for cystitis or pyelonephritis within 28 days post-prescription. Mixed effects regression analysis was used, with patient and GP practice as random effects and demography, comorbidity, and cystitis history as fixed effects. RESULTS: Adjusted odds ratios (aORs) for clinical failure per 10mL/min decrease in estimated glomerular filtration rate (eGFR) were 1.05 (95% CI: 1.01-1.09) for NF5 (n = 24,591), 0.96 (95% CI: 0.92-1.01) for FT1 (n = 5359), 0.98 (95% CI: 0.89-1.08) for TMP3 (n = 1064), 1.05 (95% CI: 1.02-1.09) for NF7 (n = 10,628) and 1.02 (95% CI: 0.93-1.14) for TMP7 (n = 831). In uncomplicated cystitis and eGFR ≥60 mL/min, clinical failures occurred in 14.6% (1895/12 980) of NF5-treated, 20.7% (266/1283) of FT1-treated (aOR versus NF5 1.37, 95% CI 1.18-1.59) and 20.8% (66/318) of TMP3-treated patients (aOR 1.42, 95% CI 1.07-1.87 versus NF5). In uncomplicated cystitis and eGFR <60 mL/min, FT1 resulted in 16.0% (39/244) and NF5 in 23.3% clinical failures (110/472), aOR: 0.61, 95% CI: 0.39-0.95). CONCLUSIONS: In eGFR ≥60 mL/min treatment with fosfomycin or trimethoprim for uncomplicated cystitis was associated with more clinical failure than treatment with nitrofurantoin, while in eGFR <60 mL/min nitrofurantoin was associated with more clinical failure than fosfomycin-trometamol. Renal function, if known, should be considered in the clinical decision-making for cystitis treatment.

Risk factors for mortality in patients with pulmonary infections with non-tuberculous mycobacteria: a retrospective cohort study.

BACKGROUND: Infections with non-tuberculous mycobacteria (NTM) represent an increasing problem. Their clinical relevance is still largely unknown as well as predictors for mortality in affected patients. The objective was to describe prevalence and clinical relevance of different NTM and to identify risk factors for mortality. METHODS: Retrospective cohort study of 124 patients with NTM detection between January 2001 and December 2011. Clinical characteristics like symptoms and radiological appearance were assessed at presentation. The primary outcome was all cause mortality during the follow-up period. Univariate and multivariate survival analyses using Cox proportional hazard models were employed for statistical analysis. RESULTS: Over the study period, the frequency of NTM isolation varied from 4 to 12 patients per year. Twenty-nine out of 124 patients (23%) had a clinically relevant infection, according to the criteria of the American Thoracic Society (ATS). Mycobacterium avium was isolated most frequently, but Mycobacterium kansasii, Mycobacterium malmoense and Mycobacterium xenopi had the highest clinical relevance. Symptoms were mostly diverse and non-specific. On radiology, cavities were observed more frequently than a nodular-bronchiectatic variant or consolidation. In 75% of all patients, follow up time was more than two years. Median survival was 6.5 years (95%CI = 2.7-10.3). Factors significantly influencing survival time were haemoptysis (HR = 0.2, 95%CI = 0.1-0.6) and a consolidation on imaging (HR = 5.1, 95%CI 1.4-18.2). CONCLUSIONS: The presentation of an infection with NTM can be diverse and depends mainly on the causative NTM pathogen. The most important predictor for increased mortality is the radiological appearance of a consolidation.

Lung cancer in idiopathic pulmonary fibrosis patients diagnosed during or after lung transplantation.

Lung transplantation is an accepted therapy for patients with end-stage lung disease and offers a major survival benefit in selected patients. The most important indications are chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis besides cystic fibrosis and pulmonary arterial hypertension. The incidence of lung cancer in patients after Ltx is 20-25 times higher than in the general population. Diagnosis is often difficult in IPF patients because of the diffuse lung abnormalities due to the underlying fibrosis. Moreover, the lung cancer may mimic a pulmonary infection. Symptoms are often aspecific, diagnosis is difficult, and prognosis is extremely poor. We describe three patients who were transplanted for idiopathic pulmonary fibrosis and who developed a primary lung cancer.

[Surgical treatment of lung cancer with complete VATS lobectomy, new in the Netherlands]. / De chirurgische behandeling van longkanker via complete VATS-lobectomie, nieuw in Nederland.

* In view of the favourable results of lobectomy with complete 'video-assisted thoracoscopic surgery' (c-VATS) as described in literature, we started to perform these totally endoscopic lung resections in the Netherlands in March 2006. * Essential aspects of the procedure are that the ribs are not spread and that the procedure is performed using the image on the monitor only. * In the 23 c-VATS lobectomies performed, the advantages described in literature were confirmed. The operation was safe and entirely similar to the 'open' thoracotomy in an oncological sense. The effects for the patient were favourable. There was less pain after the operation, the function of the shoulder remained intact and the patients recovered rapidly. * It takes a considerable time before the learning curve reaches the plateau phase. The use of proper instruments is essential. * It is expected that the c-VATS lobectomy will be performed more often in the Netherlands in the coming years.

Maximal neutropenia during chemotherapy and radiotherapy is significantly associated with the development of acute radiation-induced dysphagia in lung cancer patients.

BACKGROUND: Acute dysphagia is a distressing dose-limiting toxicity after concurrent chemoradiation or high-dose radiotherapy for lung cancer. We therefore identified factors associated with the occurrence of acute dysphagia in lung cancer patients receiving radiotherapy alone or combined with chemotherapy. PATIENTS AND METHODS: Radiotherapy, chemotherapy and patient characteristics were analyzed using ordinal regression analysis as possible predictors for acute dysphagia (CTCAE 3.0) in 328 lung cancer patients treated with curative intent. RESULTS: The most significant association was seen between the maximal grade of neutropenia during chemoradiation and dysphagia, with an odds ratio increasing from 1.49 [95% confidence interval (CI) 0.63-3.54, P = 0.362] for grade 1-2 neutropenia to 19.7 (95% CI 4.66-83.52, P < 0.001) for patients with grade 4 neutropenia. Twice-daily schedule, mean esophageal dose and administration of chemotherapy were significant predictive factors. By combining these factors, a high-performance predictive model was made. On an individual patient level, 64% of patients were correctly classified and only 1.2% of patients were misclassified by more than one grade. CONCLUSIONS: The maximal neutrophil toxicity during concurrent chemotherapy and radiotherapy is strongly associated with the development of acute dysphagia. A multivariate predictive model was developed.

[Diagnosis and treatment of bronchiectasis]. / Diagnostiek en behandeling van bronchiëctasieën.

Patients with bronchiectasis usually have chronic pulmonary infection with secondary obstructive airway disease. This disease has to be distinguished from chronic obstructive pulmonary disease (COPD). The diagnosis is established with the help of high resolution CT scan of the thorax. Further diagnostic evaluation is necessary to identify aetiologic factors. The treatment is complicated and involves many aspects: treatment of underlying conditions, recognition of exacerbations, boosting of tracheobronchial clearance, treatment of haemoptysis, surgical resection of affected lung segments and antibiotic therapy. Antibiotic therapy can focus on treatment of exacerbations but chronic suppressive antibiotic therapy is also used. Favourable results have been reported for maintenance treatment with macrolids as well as anti-inflammatory therapy.

[Asthma and pregnancy]. / Astma en zwangerschap.

Pregnancy is accompanied by physiological hyperventilation that may be perceived as shortness of breath; causes are a reduced residual capacity and a reduced expiratory reserve volume due to the swelling uterus, and a larger tidal volume due to increase of the progesterone concentration and of the chemosensitivity to CO2 and O2. Fatigue, lowered exercise tolerance and orthopnoea also may occur, as do basal crepitations at auscultation. In pregnant asthma patients the symptoms may either improve greatly or become aggravated. During an asthma attack the foetus is exposed to hypoxaemia, which may be worsened by a decreased uteroplacental blood circulation in case of maternal alkalosis. Poorly controlled asthma has a stronger adverse effect on the unborn child than the judicious use of anti-asthma drugs. Safe drugs against asthma during pregnancy, around parturition and during breast feeding, are cromoglycic acid and ipratropium; relatively safe drugs are short-acting beta-sympathicomimetics, inhalation corticosteroids and systemic corticosteroids, as well as theophylline from the second trimester; use of long-acting beta-sympathicomimetics is advised against.

Association between Wegener's granulomatosis and Staphylococcus aureus infection?

Two patients are presented with Wegener's granulomatosis (WG) and lower respiratory tract infections with Staphyloccus aureus (SA). It is posulated that there is a relationship between the infection and the induction or relapse of the disease. We suggest that bronchoalveolar lavages should be performed in cases of suspected WG to identify SA-infections. The co-existence of WG and SA support the reported beneficial effects of sulfamethoxazole/trimethoprim, but needs further evaluation in patients with and without SA-infection of the airways.

The effects of the inhaled corticosteroid budesonide on lung function and bronchial hyperresponsiveness in adult patients with cystic fibrosis.

Bronchial hyperresponsiveness is present in 40-60% of adult patients with cystic fibrosis (CF). Drugs which alter airway hyperresponsiveness have not yet been studied in CF. In this randomized placebo-controlled study, we investigated the effects of an inhaled corticosteroid, budesonide, on lung function and bronchial hyperresponsiveness in adult CF patients, with proven bronchial hyperresponsiveness to histamine. Twelve patients were treated with budesonide, 1600 micrograms day-1, and with placebo during two periods of 6 weeks in a randomized, double-blind, cross-over study. Drug effects were assessed with regard to bronchial hyperresponsiveness to histamine, spirometry and clinical symptom scores. After treatment with budesonide, no significant differences in spirometry were seen, however, bronchial hyperresponsiveness to histamine significantly improved as compared to baseline. Fifty-eight percent of the patients showed at least one doubling-dose increase in PC20 histamine. Daily symptom scores showed small, but statistically significant, improvements in dyspnoea and cough after budesonide treatment. There is increasing evidence suggesting that excessive inflammatory responses contribute to the pulmonary damage that characterizes CF. Treatment with oral corticosteroids improved the clinical course of selected CF patients, but was associated with unacceptable adverse effects. We conclude that daily inhalation of 1600 micrograms day-1 budesonide for 6 weeks induced a small, but significant, improvement in bronchial hyperresponsiveness to histamine, and symptoms of cough and dyspnoea in adult CF patients. Longer observations are needed to establish whether inhaled corticosteroids improve the long term outcome of CF.

Bronchial vagal tone and responsiveness to histamine, exercise and bronchodilators in adult patients with cystic fibrosis.

Atopy and bronchial responsiveness to histamine, exercise and bronchodilators were investigated in 18 adult patients with cystic fibrosis (CF). Reversibility of airflow limitation was measured after ipratropium bromide and terbutaline, and histamine and exercise provocation tests were performed. Histamine hyperresponsiveness was observed in 10 out of 18 patients and was not confined to those with severe airway obstruction. The positive histamine responders showed significantly better bronchodilatation after terbutaline, when compared to negative histamine responders. Histamine responsiveness was not related to atopy or exercise responsiveness. Exercise challenge caused bronchodilatation without bronchoconstriction in all patients. The exercise-induced bronchodilatation correlated with bronchodilatation after ipratropium bromide. It is proposed that an increased vagal tone may lead to an increased resting bronchomotor tone which can be reduced by ipratropium bromide and by exercise in adult patients with cystic fibrosis.

Pancreatic morphology and function in adult patients with cystic fibrosis.

To determine the relation between pancreatic morphology and pancreatic exocrine and endocrine function, we have studied 8 adult cystic fibrosis patients and 14 normal control subjects by ultrasonography and pancreatic function testing. In the patients with cystic fibrosis the maximum anteroposterior diameter of the pancreatic head was significantly increased over that in control subjects (p less than 0.01), whereas the maximum diameter of the body was significantly decreased (p = 0.05). Increased echogenicity of the pancreatic body was observed in most patients. In the cystic fibrosis patients postprandial insulin secretion was reduced in the 1st h (p less than 0.005 versus control), whereas pancreatic polypeptide secretion was virtually abolished for at least 3 h (p less than 0.01 versus control). All cystic fibrosis patients had evidence of exocrine pancreatic dysfunction as reflected by a diminished urinary para-aminobenzoic acid excretion. Intraduodenal enzyme and bicarbonate output in response to secretin-cholecystokinin was reduced in all of three patients studied. It is concluded that loss of endocrine and exocrine pancreatic function in adult cystic fibrosis patients is accompanied by a small and echo-dense pancreatic body relative to a large pancreatic head.

Increased plasma cholecystokinin levels and small gall bladders in adult patients with cystic fibrosis.

1. In patients with cystic fibrosis, abnormalities in plasma cholecystokinin level and gall-bladder emptying may contribute to the development of maldigestion and gall-stones. 2. Therefore, we have measured plasma cholecystokinin levels and gall-bladder volumes before and after ingestion of a standard breakfast in eight adult patients with cystic fibrosis and in eight normal control subjects. 3. In the patients with cystic fibrosis basal (2.8 +/- 0.4 pmol/l; P less than 0.05, t-test) and maximum post-prandial (5.7 +/- 0.5 pmol/l; P less than 0.05, t-test) plasma cholecystokinin levels were significantly higher than those in the control subjects (1.9 +/- 0.1 pmol/l, and 4.5 +/- 0.2 pmol/l, respectively). On the other hand, integrated plasma cholecystokinin secretion in response to the meal was similar (t-test, P = 0.4 versus control subjects). The increased plasma cholecystokinin levels in the patients with cystic fibrosis were accompanied by reduced gallbladder volumes in both the basal (7.8 +/- 2.1 cm3 versus 20.9 +/- 2.3 cm3 in control subjects; P less than 0.005, t-test) and the post-prandial state (2.2 +/- 1.0 cm3 versus 4.8 +/- 0.8 cm3 in control subjects; P = 0.06, t-test). Gall-bladder emptying in the patients with cystic fibrosis was well preserved (70 +/- 7% versus 78 +/- 9% in control subjects; P = 0.4, t-test). 4. In comparison with normal control subjects, patients with cystic fibrosis have an increased basal plasma cholecystokinin level and a reduced gall-bladder volume, whereas post-prandial gall-bladder emptying and plasma cholecystokinin secretion are not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchodilator response in adult patients with cystic fibrosis: effects on large and small airways.

Spirometry, body plethysmography, maximal expiratory flow-volume curves (MEFV-curves) with air and with heliox (80% He + 20% O2) before and after inhalation of bronchodilators were studied in a group of 20 adult cystic fibrosis (CF) patients. Most of them showed prominent bronchial obstruction and seven also had evidence of restrictive pulmonary disease. Large differences were observed between total lung capacity as measured with body plethysmography and with a helium dilution technique. A calculated air trapping index correlated well with parameters of peripheral airway obstruction. Both inhalation of terbutaline and ipratropium bromide caused dose-related bronchodilatation. Density dependence of expiratory flow increased significantly after terbutaline but not after ipratropium bromide. We conclude that adult CF patients with varying degrees of obstructive and restrictive pulmonary function limitation show a dose-related improvement of lung function after terbutaline and ipratropium bromide with terbutaline being probably more effective on peripheral airways than ipratropium bromide.

Inhibition of cholesterol side-chain cleavage by intermediates of an alternative steroid biosynthetic pathway.

Mitochondrial preparations from endocrine tissues were incubated with radioactive cholesterol and the effect of hydroxylated metabolites of 23,24-dinor-5-cholen-3 beta-ol (23,24-dinor-5-cholene-3 beta,20-diol and 23,24-dinor-5-cholene-3 beta,21-diol) on the production of pregnenolone was measured. These compounds are intermediates in an alternative, sesterterpene pathway for steroid hormone biosynthesis. It was found that these materials, like the analogous side-chain-hydroxylated derivatives of cholesterol (20 alpha-hydroxycholesterol and 22S-hydroxycholesterol), inhibit cholesterol side-chain cleavage. The possibility that there could be a control mechanism whereby metabolites of 23,24-dinor-5-cholen-3 beta-ol inhibit steroidogenesis occurring by the cholesterol pathway is discussed.