Methicillin-resistant Staphylococcus aureus in children with cystic fibrosis: An eradication protocol.

A retrospective 12-year study (May 1988-July 2000) was undertaken in children with cystic fibrosis (CF) to evaluate 1) the magnitude of methicillin-resistant Staphylococcus aureus (MRSA) in these children; 2) the clinical impact of MRSA on CF; and 3) the efficacy of an MRSA protocol aimed at the eradication of the carrier state. The study maneuver comprised of 1) surveillance cultures of throat/rectum to detect the MRSA carrier state; 2) life-long cephradine rather than flucloxacillin to lift selection pressure; 3) topical application of oral and nebulized vancomycin for 5 days to clear the carriage of MRSA; and 4) a strict antistaphylococcal hygiene program, including handwashing and device policy. Fifteen children with CF (11 boys, with median age 117 months) positive for MRSA were enrolled. The current prevalence of MRSA among children with CF in our hospital is 6.5%. Of 15 children identified, only 12 (18 episodes of MRSA colonization) were treated according to protocol. Median age of MRSA acquisition was 73 months (interquartile range, 43-134 months). In 7 patients (55%), MRSA was eradicated. Of a total of 18 MRSA episodes, the protocol was successful in 10 episodes. The mean period of MRSA-free status was 12 months (range, 6-36 months). Pulmonary function (measured by FEV(1)) was not affected (68% of predicted before treatment, and 68% of predicted after treatment). All children were oropharyngeal carriers of both MRSA and ceftazidime-resistant P. aeruginosa. We believe that an effort has to be made to limit MRSA in CF clinics for the following reasons: 1) MRSA carriage in any individual is an abnormal condition; 2) limitation of systemic vancomycin use is desirable; 3) MRSA carriage may be a contraindication for lung transplantation; and 4) epidemiologically, a CF unit with a substantial MRSA problem functions as a source of dissemination for other patients.

Targeting of dornase alpha therapy in adult cystic fibrosis.

Although dornase alpha (recombinant human DNase) can thin the viscid pulmonary secretions of cystic fibrosis (CF), clinical trials in groups of unselected patients have shown only modest average improvements in pulmonary function. The product is very expensive, so in conjunction with purchasers we designed selection criteria and a protocol for a 2-week trial to target CF individuals who might gain most benefit. Treatment was to be continued in those showing > or = 10% improvement in pulmonary function. Those who had a trial of dornase alpha were followed up for 2 years. Of 25 patients who had a 2-week trial of dornase alpha, 17 met the criteria for continuation (average gain in forced expiratory volume 37%). The 11 of these who were still alive at 2 years had a greater initial average FEV1 improvement than those who had died (45% versus 22%), and still had an average improvement of 31% at 2 years. The 8 patients who did not meet the criteria for continuation were older and had required fewer intravenous antibiotic courses. All these were alive at 2 years with unchanged clinical indices. This method of selection for dornase alpha treatment allows targeting to those who gain most benefit without disadvantaging the remaining patients. Furthermore, production of such guidelines in conjunction with purchasers obviates funding difficulties and allows rational prescribing.

Growth during one year of treatment with fluticasone propionate or sodium cromoglycate in children with asthma.

The aim of this study was to compare accurately measured growth over 12 months in asthmatic children treated with either fluticasone propionate (FP) 50 micrograms twice daily (b.i.d.) or sodium cromoglycate (SCG) 20 mg four times daily (q.i.d.). After a 2-week run-in, asthmatic children aged 4-10 years from 15 UK centers were randomized in a 3:4 ratio to open-label FP (n = 52) or SCG (n = 70). After 8 weeks, those whose asthma was not adequately controlled were switched from SCG to FP or withdrawn. Standing height was measured (Holtain stadiometry) at baseline, after 8 weeks and at 6 weeks intervals thereafter for 1 year. Morning peak flows (PEFam) were recorded by patients for 2 weeks during baseline, and 1 week before each visit during treatment. Urinary free cortisol (24 h) was measured at baseline, 6 months, and 1 year. After 8 weeks, 22 patients were withdrawn from SCG group (and were switched to FP), and five patients were withdrawn from the FP group due to poor asthma control. A further 21 and 11 patients were withdrawn from the SCG and FP groups, respectively, during the course of the study. There were no significant differences between patients who received FP and SCG for 1 year (n = 34 and n = 26, respectively) in terms of height velocity adjusted for age and gender (HV), or height velocity standard deviation scores adjusted for gender (HVSDS). Mean HV (mean HVSDS) were 6.0 cm/yr (0.1) and 6.5 cm/yr (0.5) for FP and SCG, respectively. There were no treatment differences in mean 24 h urinary free cortisol levels at 6 and 12 months. Mean % predicted PEFam improved over 1 year in both groups but to a greater degree in the FP group. We concluded that growth was normal in mildly asthmatic children receiving FP (50 micrograms bid) for 1 year. There were fewer withdrawals and lung function improved to a greater extent in FP treated patients than in patients receiving SCG.

Spread of beta-lactam-resistant Pseudomonas aeruginosa in a cystic fibrosis clinic.

BACKGROUND: Pseudomonas aeruginosa colonisation of the airways of patients with cystic fibrosis (CF) is associated with considerable respiratory morbidity. Although segregation of colonised patients from non-colonised patients to prevent cross-infection has been recommended, there is little evidence that such cross-infection is widespread. We observed that a high proportion of children attending our CF clinic were colonised with P aeruginosa that was resistant to ceftazidime and other beta-lactam antibiotics. We used two genomic fingerprinting techniques to see whether this may have arisen from epidemic spread of a single strain. METHODS: The prevalence of P aeruginosa colonisation and the antibiotic susceptibility of the organisms was determined from review of laboratory reports in the case-notes of 120 children with CF. Isolates were cultured from the sputum of 65 children colonised with ceftazidime-resistant P aeruginosa. Polymorphisms in total bacterial DNA from 92 isolates were analysed with two molecular fingerprinting techniques--pulsed-field gel electrophoresis after restriction enzyme digestion and assessment of flagellin gene polymorphisms by amplification of the whole gene and restriction enzyme digestion. RESULTS: 92 (76.7%) of 120 children were colonised with P aeruginosa, and 65 of the 92 harboured isolates that were resistant to ceftazidime. Only three of the 92 children had never been treated with ceftazidime. The results of the two molecular-fingerprinting techniques were concordant and showed that 55 of 65 children harboured the same epidemic strain. This strain was resistant to ceftazidime, azlocillin, and imipenem, and sensitive to tobramycin and ciprofloxacin. INTERPRETATION: This study provides the first molecular evidence of a long-term outbreak of P aeruginosa in a CF centre. We suggest that careful surveillance of the prevalence of antibiotic resistance in CF centres should be instituted with measures to prevent cross-infection. We believe that antipseudomonal monotherapy should be considered with caution.

Effect of anaesthesia on lung function in children with asthma.

Spirometry was performed before operation, soon after recovery ("early") and the day after ("late") general anaesthesia for elective surgery in 20 children with asthma and 20 matched children without asthma. Pulse oximetry was recorded on the first postoperative night. The mean early peak expiratory flow rate (PEFR) decreased in the asthmatics by 19.91 (95% confidence intervals (CI) 10.84-28.97)% and in the controls by 19.25 (10.70-27.80)%. The mean early FEV1 decreased in the asthmatics by 16.02 (9.29-22.75)% and in the controls by 11.03 (2.86-19.19)%. The mean late decrease from baseline PEFR for the asthmatics was 18.55 (11.23-25.87)% but only 14.93 (7.89-21.97)% for the controls. The mean late FEV1 was 8.2 (0.83-15.56)% below baseline in the asthmatics but only 6.82 (-0.79 to 14.42)% in the controls. There were no differences in overnight pulse oximetry. We conclude that healthy children exhibited a decrease in FEV1 and PEFR after general anaesthesia for elective surgery, but this decline did not appear to be any greater in well controlled asthmatic children compared with children who did not have asthma.

Effect of respiratory virus infections including rhinovirus on clinical status in cystic fibrosis.

One hundred and eight patients with cystic fibrosis were investigated over one year to determine whether an association existed between rhinovirus or other respiratory virus infection and clinical status. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), Shwachman score, Chrispin-Norman chest radiograph score, and percentage weight for height were recorded at the beginning and end of the study; days of intravenous antibiotics were noted. Nasopharyngeal aspirates were taken for viral studies during respiratory exacerbations. Serum was collected at enrollment and 2-6 weeks after each respiratory exacerbation. One hundred and fifty seven exacerbations occurred in 76 patients. Respiratory virus infection was detected in 44 exacerbations and rhinovirus was present in 16% (25/157) of exacerbations. Patients with one or more respiratory virus infections were compared with those who had none. When all respiratory virus infections were considered, patients had a significantly greater deterioration in Shwachman score and received significantly more days of intravenous antibiotics. When rhinovirus was considered separately, patients received significantly more days of intravenous antibiotics, but showed no deterioration in clinical status. However, patients infected with another respiratory virus had a significant decline in FEV1, with trends towards significance for decline in FVC and Shwachman score.

Maternal asthma, premature birth, and the risk of respiratory morbidity in schoolchildren in Merseyside.

BACKGROUND: A study was carried out to analyse the impact of maternal asthma on the risk of preterm delivery and the contribution of preterm delivery to the development of childhood asthma. METHODS: Two cross sectional community studies of 1872 children (5-11 years) in 1991 and 3746 children in 1993 were performed. A respiratory health questionnaire was distributed throughout 15 schools in Merseyside and completed by the parents of the children. RESULTS: Asthmatic mothers were more likely to have a preterm delivery than non-asthmatic mothers (odds ratio (OR) 1.49; 95% CI 1.10 to 2.02). Smoking was a separate risk factor for preterm delivery (OR 1.35; 95% CI 1.10 to 1.65). Asthmatic mothers did not have an increased risk of delivering small, growth retarded babies. Maternal asthma, paternal asthma, and premature birth, in that order, increased the risk of later childhood respiratory morbidity (OR 3.13, 95% CI 2.36 to 4.16; 2.23, 95% CI 1.62 to 3.05; 1.40, 95% CI 1.10 to 1.79). Conversely, babies who were small for gestational age appeared less likely to develop doctor diagnosed asthma or the symptom triad of cough, wheeze, and breathlessness in childhood, although this was not statistically significant (OR 0.63, 95% CI 0.28 to 1.41). CONCLUSIONS: Maternal smoking during pregnancy and maternal asthma are independent risk factors associated with preterm delivery. Asthma in mothers predisposes to preterm delivery but not fetal growth retardation. Preterm birth, but not growth retardation, predisposes the child to the development of subsequent asthma.

Strictures of ascending colon in cystic fibrosis and high-strength pancreatic enzymes.

We have observed five children with cystic fibrosis, who presented over 2 months, with meconium ileus equivalent that failed to respond to medical management. At surgery, four had a stricture in the ascending colon, and all had histopathological changes of post-ischaemic ulceration repair, with mucosal and submucosal fibrosis. The only common change in the management of these children was a switch from conventional enteric-coated pancreatic enzymes to high-strength products 12-15 months before presentation.

Branhamella catarrhalis colonization in preschool asthmatics.

Branhamella catarrhalis has been associated with exacerbations of chronic bronchitis and asthma in adults. To investigate the possible role of B. catarrhalis in asthma of early childhood, we took posterior pharyngeal swabs from 24 normal children, 20 well asthmatics, and 20 acutely wheezy asthmatics, all between 1 and 4 years of age. On culture, 33% of the normal children were colonized with B. catarrhalis; colonization rates in the well asthmatics (70%) and in the wheezy asthmatics (75%) were significantly higher than in normals. The nature of this association requires further study.

Ceftazidime treatment in cystic fibrosis: resistant organisms in sputum and faeces.

Ceftazidime was used as the only intravenous agent for treating lower respiratory tract infections in patients with cystic fibrosis. The risks of inducing beta lactamases and conferring antibiotic resistance are high when monotherapy is used; so the emergence of resistant bacteria was studied prospectively in the sputum of 120 patients. The mean age of patients was 9.0 (range 0.3-25) years and there were equal number of male and female patients. Pseudomonas aeruginosa was the only ceftazidime resistant bacterium to be isolated from the respiratory tract, and was identified only in chronically colonised patients. Ceftazidime resistance occurred in 103 (14%) of 750 P aeruginosa isolates, and in 16 of 36 chronically colonised patients. Ceftazidime resistant organisms were isolated from the faeces of 17 of 64 patients investigated. Eighty two per cent of the resistant faecal organisms were single isolates: the same resistant organism in faeces was isolated from successive samples in only two patients. In no case was the ceftazidime resistant enteric isolate the same as that from sputum. Patients chronically colonised by P aeruginosa did not harbour ceftazidime resistant enteric organisms any more than non-colonised patients. The use of ceftazidime as a single intravenous agent in treating chest exacerbations in cystic fibrosis does not induce a reservoir of ceftazidime resistant bacteria.

Long term outcome of ventilated asthmatics.

Over a 25 year period, 31 asthmatic children received artificial ventilation for acute asthma at Alder Hey Children's Hospital on 48 occasions. Altogether 47 episodes occurred from 1971-89, with no decline in the number of episodes per year (mean 2.5) over this period. Eight children died during intermittent positive pressure ventilation (IPPV), and of the 23 survivors, three further children had subsequently died from asthma. Seventeen children were followed up for more than a year after IPPV. Sixteen still had symptoms of asthma and over half had symptoms every day. Ten cooperated with pulmonary function tests: mean forced expiratory volume in one second was 83% of predicted and geometric mean provocative histamine concentration (PC20) was 2.1 mg/ml. Since the follow up study a fourth patient had died from asthma. IPPV continues to be required for a small number of asthmatic children each year. The survivors remain a high risk group with significant continuing morbidity and mortality.

Cystic fibrosis, Pseudomonas aeruginosa, and selective decontamination.

We used an oral topical antibiotic preparation to try and prevent oropharyngeal carriage of Pseudomonas aeruginosa in patients with cystic fibrosis. Ten of 15 patients treated with a two week course of intravenous ceftazidime together with a 90 day course of an antibiotic containing gel continued to carry P aeruginosa in the oropharynx.

Fluorescein dilaurate test of exocrine pancreatic function in cystic fibrosis.

The fluorescein dilaurate test, a non-invasive test of exocrine pancreatic function, was carried out on 21 children with cystic fibrosis and pancreatic exocrine insufficiency, and 12 healthy siblings. The test clearly discriminated between the patients with cystic fibrosis and severe exocrine pancreatic insufficiency and the normal control subjects.

Small intestinal permeability and orocaecal transit time in cystic fibrosis.

Cellobiose and mannitol were used as probe molecules to measure intestinal permeability in 36 children with cystic fibrosis, and 25 age matched controls. Orocaecal transit was also evaluated for each subject using the lactulose/hydrogen breath test. There was a fourfold increase in permeability to disaccharide (cellobiose) in patients with cystic fibrosis, but permeability to the monosaccharide (mannitol) was similar to controls. The orocaecal transit time of lactulose was prolonged in patients with cystic fibrosis, but was unrelated to the percentage excretion of cellobiose or mannitol in cystic fibrosis patients or control subjects.

Pathology mimicking distal intestinal obstruction syndrome in cystic fibrosis.

Eight patients with cystic fibrosis had chronic abdominal pain and the other features of distal intestinal obstruction syndrome. Coexistent abdominal pathology was shown in six patients. Two had a small bowel volvulus, and the others had Crohn's disease, a small bowel fistula, appendix abscess, and an ovarian dermoid. Opiate abuse exacerbated symptoms in two other patients.

Oro-caecal transit time and intra-luminal pH in cystic fibrosis patients with distal intestinal obstruction syndrome.

Oro-caecal transit time assessed by the lactulose/hydrogen breath test was prolonged in cystic fibrosis patients experiencing distal intestinal obstruction syndrome (DIOS); compared to those without the syndrome, and normal controls. Jejunal intraluminal pH was lower in cystic fibrosis patients compared to controls, but no difference was observed between those patients experiencing DIOS, and those cystic fibrosis patients without the syndrome. The prolonged oro-caecal transit time observed in cystic fibrosis patients with DIOS may contribute to the syndrome, however intraluminal pH is unlikely to be a factor in the aetiology of DIOS.

Accident and emergency department attendance by asthmatic children.

Attendances at the accident and emergency department of a children's hospital for treatment of acute asthma were studied for one year to determine the characteristics of the children attending and their management. Eight hundred and twenty children, median age 5.5 years, made 1389 visits. Records were available from 1046 visits. Clinical information and assessment of the severity of the attack in the department was often inadequate. Peak flow records were available for 366 (35%). Attendances were most frequent in September and during the evening, but there was no significant day to day variation. Eight hundred and three children (78%) were self referred. Before attendance 962 (92%) had used a bronchodilator, including nebulised salbutamol (11%); 2% had taken prednisolone and 21% antibiotics. Five hundred and sixteen visits (49%) led to admission and 19% of those admitted required intravenous treatment. Probably some children who at present attend hospital for treatment of acute asthma could be managed at home, but this cannot be assumed without better understanding of the reasons for hospital attendance. More information is needed.