Nationwide surveillance of nasopharyngeal Streptococcus pneumoniae isolates from children with respiratory infection, Switzerland, 1998-1999

The surveillance of pneumococcal antibiotic resistance and serotype distribution is hampered by the relatively low numbers of invasive pneumococcal infections. In Switzerland, a nationwide sentinel surveillance network was used to assess antibiotic resistance and serotype distribution among 1179 pneumococcal isolates cultured from 2769 nasopharyngeal swabs obtained from outpatients with acute otitis media or pneumonia during 1998 and 1999. The proportion of penicillin-susceptible pneumococcal isolates overall (87%) and among infants <2 years old (81%) was comparable to that of invasive isolates (90% and 81%, respectively). The high number of nasopharyngeal isolates allowed for the detection of a rapid increase in the number of penicillin-nonsusceptible pneumococcal (PNSP) strains in the West region of Switzerland, partly because of an epidemic caused by the 19F clone of Streptococcus pneumoniae. Clustering of risk factors for the carriage of PNSP isolates further explained the geographic variation in resistance rates. The nationwide sentinel surveillance of nasopharyngeal pneumococcus proved to be valuable for the monitoring of antibiotic resistance, risk factors for carriage of PNSP isolates, and serotype distribution and for the detection of the emergence of a new epidemic clone.

[Antibiotic resistance: infections of the upper respiratory tract and bronchi. When are antibiotics necessary?]

Antimicrobial resistance among respiratory tract pathogens has become an increasing problem worldwide during the last 10-20 years. The wide use of antimicrobial agents in ambulatory practice has contributed to the emergence and spread of antibiotic-resistant bacteria in the community, namely Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The pneumococcus has developed resistance to most antibiotics used for its treatment. Classes with important resistance problems include the beta-lactams, the macrolides, the lincosamides, trimethoprim-sulfamethoxazole, and the tetracyclines. Unfortunately, resistance to more than one class of antibiotics is common. In Haemophilus influenzae and Moraxella catarrhalis, resistance to beta-lactam antibiotics is the main concern currently. It is important to know the local resistance pattern of the most common respiratory tract pathogens in order to make reasonable recommendations for an empirical therapy for respiratory tract infection, when antibiotic therapy is indeed indicated.

Comparison of magnetic resonance imaging of inhaled SF6 with respiratory gas analysis

Magnetic resonance imaging of inhaled fluorinated inert gases ((19)F-MRI) such as sulfur hexafluoride (SF(6)) allows for analysis of ventilated air spaces. In this study, the possibility of using this technique to image lung function was assessed. For this, (19)F-MRI of inhaled SF(6) was compared with respiratory gas analysis, which is a global but reliable measure of alveolar gas fraction. Five anesthetized pigs underwent multiple-breath wash-in procedures with a gas mixture of 70% SF(6) and 30% oxygen. Two-dimensional (19)F-MRI and end-expiratory gas fraction analysis were performed after 4 to 24 inhaled breaths. Signal intensity of (19)F-MRI and end-expiratory SF(6) fraction were evaluated with respect to linear correlation and reproducibility. Time constants were estimated by both MRI and respiratory gas analysis data and compared for agreement. A good linear correlation between signal intensity and end-expiratory gas fraction was found (correlation coefficient 0.99+/-0.01). The data were reproducible (standard error of signal intensity 8% vs. that of gas fraction 5%) and the comparison of time constants yielded a sufficient agreement. According to the good linear correlation and the acceptable reproducibility, we suggest the (19)F-MRI to be a valuable tool for quantification of intrapulmonary SF(6) and hence lung function.

Viral etiology of acute respiratory infections with cough in infancy: a community-based birth cohort study

BACKGROUND: Acute respiratory infections (ARI) are a major cause of morbidity in infancy worldwide, with cough and wheeze being alarming symptoms to parents. We aimed to analyze in detail the viral aetiology of ARI with such symptoms in otherwise healthy infants, including rhinoviruses and recently discovered viruses such as human metapneumovirus (HMPV), coronavirus NL63 and HKU1, and human bocavirus (HBoV). METHODS: We prospectively followed 197 unselected infants during their first year of life and assessed clinical symptoms by weekly standardized interviews. At the first ARI with cough or wheeze, we analyzed nasal swabs by sensitive individual real time polymerase chain reaction assays targeting 16 different respiratory viruses. RESULTS: All 112 infants who had an ARI had cough, and 39 (35%) had wheeze. One or more respiratory viruses were found in 88 of 112 (79%) cases. Fifteen (17%) dual and 3 (3%) triple infections were recorded. Rhino- (23% of all viruses) and coronaviruses (18%) were most common, followed by parainfluenza viruses (17%), respiratory syncytial virus (RSV) (16%), HMPV (13%), and HBoV (5%). Together rhinoviruses, coronaviruses, HMPV, and HBoV accounted for 60% (65 of 109) of viruses. Although symptom scores and need for general practitioner (GP) consultations were highest in infants infected with RSV, they were similar in infants infected with other viruses. Viral shedding at 3 weeks occurred in 20% of cases. CONCLUSIONS: Rhinoviruses, coronaviruses, HMPV, and HBoV are common pathogens associated with respiratory symptoms in otherwise healthy infants. They should be considered in the differential diagnosis of the aetiology of ARI in this age group.

Mannose-binding lectin cord blood levels and respiratory symptoms during infancy: a prospective birth cohort study

Respiratory infections cause considerable morbidity during infancy. The impact of innate immunity mechanisms, such as mannose-binding lectin (MBL), on respiratory symptoms remains unclear. The aims of this study were to investigate whether cord blood MBL levels are associated with respiratory symptoms during infancy and to determine the relative contribution of MBL when compared with known risk factors. This is a prospective birth cohort study including 185 healthy term infants. MBL was measured in cord blood and categorized into tertiles. Frequency and severity of respiratory symptoms were assessed weekly until age one. Association with MBL levels was analysed using multivariable random effects Poisson regression. We observed a trend towards an increased incidence rate of severe respiratory symptoms in infants in the low MBL tertile when compared with infants in the middle MBL tertile [incidence rate ratio (IRR) = 1.59; 95% confidence interval (CI): 0.95-2.66; p = 0.076]. Surprisingly, infants in the high MBL tertile suffered significantly more from severe and total respiratory symptoms than infants in the middle MBL tertile (IRR = 1.97; 95% CI: 1.20-3.25; p = 0.008). This association was pronounced in infants of parents with asthma (IRR = 3.64; 95% CI: 1.47-9.02; p = 0.005). The relative risk associated with high MBL was similar to the risk associated with well-known risk factors such as maternal smoking or childcare. In conclusion the association between low MBL levels and increased susceptibility to common respiratory infections during infancy was weaker than that previously reported. Instead, high cord blood MBL levels may represent a so far unrecognized risk factor for respiratory morbidity in infants of asthmatic parents.

Clinical characteristics associated with isolation of small-colony variants of Staphylococcus aureus and Pseudomonas aeruginosa from respiratory secretions of patients with cystic fibrosis

During a 3-month period, small-colony variant phenotypes of both Staphylococcus aureus and Pseudomonas aeruginosa were isolated from respiratory secretions of 8.2% and 9.2%, respectively, of 98 patients with cystic fibrosis, particularly those with advanced pulmonary disease and prolonged antibiotic exposure.

Air pollution during pregnancy and lung function in newborns: a birth cohort study

Post-natal exposure to air pollution is associated with diminished lung growth during school age. The current authors aimed to determine whether pre-natal exposure to air pollution is associated with lung function changes in the newborn. In a prospective birth cohort of 241 healthy term-born neonates, tidal breathing, lung volume, ventilation inhomogeneity and exhaled nitric oxide (eNO) were measured during unsedated sleep at age 5 weeks. Maternal exposure to particles with a 50% cut-off aerodynamic diameter of 10 microm (PM(10)), nitrogen dioxide (NO(2)) and ozone (O(3)), and distance to major roads were estimated during pregnancy. The association between these exposures and lung function was assessed using linear regression. Minute ventilation was higher in infants with higher pre-natal PM(10) exposure (24.9 mL x min(-1) per microg x m(-3) PM(10)). The eNO was increased in infants with higher pre-natal NO(2) exposure (0.98 ppb per microg x m(-3) NO(2)). Post-natal exposure to air pollution did not modify these findings. No association was found for pre-natal exposure to O(3) and lung function parameters. The present results suggest that pre-natal exposure to air pollution might be associated with higher respiratory need and airway inflammation in newborns. Such alterations during early lung development may be important regarding long-term respiratory morbidity.

Relative impact of respiratory muscle activity on tidal flow and end expiratory volume in healthy neonates

INTRODUCTION: It has been suggested that infants dynamically regulate their tidal flow and end-expiratory volume level. The interaction between muscle activity, flow and lung volume in spontaneously sleeping neonates is poorly studied, since it requires the assessment of transcutaneous electromyography of respiratory muscles (rEMG) in matched comparison to lung function measurements. METHODS: After determining feasibility and repeatability of rEMG in 20 spontaneously sleeping healthy neonates, we measured the relative impact of intercostal and diaphragmatic EMG activity in direct comparison to the resulting tidal flow and FRC. RESULTS: We found good feasibility, repeatability and correlation of timing indices between rEMG activity and flow. The rEMG amplitude was significantly dependent on the resistive load of the face mask. Diaphragm and intercostal muscle activity commenced prior to the onset of flow and remained active during the expiratory cycle. The relative contribution of intercostal and diaphragmatic activity to flow was variable and changed dynamically. CONCLUSION: Using matched rEMG, air flow and lung volume measurements, we have found good feasibility and repeatability of intercostal and diaphragm rEMG measurements and provide the first quantitative measures of the temporal relationship between muscle activity and flow in spontaneously sleeping healthy neonates. Lung mechanical function is dynamically regulated and adapts on a breath to breath basis. So, non-invasive rEMG measurements alone or in combination with lung function might provide a more comprehensive picture of pulmonary mechanics in future studies. The data describing the timing of EMG and flow may be important for future studies of EMG triggered mechanical ventilation.

Negative impact of the noseclip on high-frequency respiratory impedance measurements

The noseclip is conventionally used in lung function testing to prevent leakage via the nasal compartments. However, some subjects exhibit a velum-opening reflex which may affect results. We performed forced oscillation measurements at frequencies (8-256 Hz) that include the first antiresonance, comparing the noseclip with a cotton wool nose plug to eliminate upper airway contribution. Three sets of measurements were made in 18 adults: with and without noseclip, and with cotton wool. Velum opening during noseclip measurements was monitored using a nasal pressure transducer. A significantly greater proportion of subjects produced a characteristic distortion to the first antiresonance with the noseclip than with either no noseclip or with cotton wool. Distortion of the spectrum coincided with the transmission of oscillations into the nasal cavity. Thus, the noseclip cannot be used in high-frequency forced oscillation measurements because of the velum reflex. The cotton wool plug offers a simple alternative. This effect has unknown impact in other lung function tests.

On the modeling of drug induced respiratory depression in the non-steady-state

The ability of anesthetic agents to provide adequate analgesia and sedation is limited by the ventilatory depression associated with overdosing in spontaneously breathing patients. Therefore, quantitation of drug induced ventilatory depression is a pharmacokinetic-pharmacodynamic problem relevant to the practice of anesthesia. Although several studies describe the effect of respiratory depressant drugs on isolated endpoints, an integrated description of drug induced respiratory depression with parameters identifiable from clinically available data is not available. This study proposes a physiological model of CO2 disposition, ventilatory regulation, and the effects of anesthetic agents on the control of breathing. The predictive performance of the model is evaluated through simulations aimed at reproducing experimental observations of drug induced hypercarbia and hypoventilation associated with intravenous administration of a fast-onset, highly potent anesthetic mu agonist (including previously unpublished experimental data determined after administration of 1 mg alfentanil bolus). The proposed model structure has substantial descriptive capability and can provide clinically relevant predictions of respiratory inhibition in the non-steady-state to enhance safety of drug delivery in the anesthetic practice.

Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication

We observed opioid-related respiratory depression in a patient receiving tramadol via patient-controlled analgesia. Predisposing factors were the patient's genetic background and renal impairment. Complete recovery occurred after naloxone administration, thus confirming opioid intoxication. Analysis of the patient's genotype revealed a CYP2D6 gene duplication resulting in ultra-rapid metabolism of tramadol to its active metabolite (+)O-desmethyltramadol. Concomitant renal impairment resulting in decreased metabolite clearance enhanced opioid toxicity. This genetic CYP2D6 variant is particularly common in specific ethnic populations and should be a future diagnostic target whenever administration of tramadol or codeine is anticipated, as both drugs are subject to a comparable CYP2D6-dependent metabolism.