Non-respiratory Infections Research Articles

Clinical case review: A method to improve identification of true clinical and radiographic pneumonia in children meeting the World Health Organization definition for pneumonia

BackgroundThe World Health Organization's (WHO) case definition for childhood pneumonia, composed of simple clinical signs of cough, difficult breathing and fast breathing, is widely used in resource poor settings to guide management of acute respiratory infections. The definition is also commonly used as an entry criteria or endpoint in different intervention and disease burden studies.MethodsA group of paediatricians conducted a retrospective review of clinical and laboratory data including C-reactive protein concentration and chest radiograph findings among Filipino children hospitalised in the Bohol Regional Hospital who were enrolled in a pneumococcal vaccine efficacy study and had an episode of respiratory disease fulfilling the WHO case definition for clinical pneumonia. Our aim was to evaluate which disease entities the WHO definition actually captures and what is the probable aetiology of respiratory infections among these episodes diagnosed in this population.ResultsAmong the 12,194 children enrolled to the vaccine study we recorded 1,195 disease episodes leading to hospitalisation which fulfilled the WHO criteria for pneumonia. In total, 34% of these episodes showed radiographic evidence of pneumonia and 11% were classified as definitive or probable bacterial pneumonia. Over 95% of episodes of WHO-defined severe pneumonia (with chest indrawing) had an acute lower respiratory infection as final diagnosis whereas 34% of those with non-severe clinical pneumonia had gastroenteritis or other non-respiratory infection as main cause of hospitalisation.ConclusionThe WHO definition for severe pneumonia shows high specificity for acute lower respiratory infection and provides a tool to compare the total burden of lower respiratory infections in different settings.Trial registrationISRCTN62323832

Reverse causation and confounding‐by‐indication: do they or do they not explain the association between childhood antibiotic treatment and subsequent development of respiratory illness?

Reverse causation and confounding‐by‐indication: do they or do they not explain the association between childhood antibiotic treatment and subsequent development of respiratory illness?

Increased Risk of Childhood Asthma From Antibiotic Use in Early Life

To address the major methodological issues of reverse causation and selection bias in epidemiologic studies of antibiotic use in early life and the development of asthma, we undertook a cohort study of this association in a complete population of children. Using the health-care and prescription databases of Manitoba, Canada, this longitudinal study assessed the association between antibiotic prescription use during the first year of life and asthma at age 7 years in a 1995 birth cohort of 13,116 children. Independent of well-known asthma risk factors, asthma was significantly more likely to develop in children who had received antibiotics in the first year of life at age 7 years. The association with asthma was observed for antibiotic use in non-respiratory tract infections (adjusted odds ratio [OR], 1.86; 95% confidence interval [CI], 1.02 to 3.37). The risk of asthma was highest in children receiving more than four courses of antibiotics (adjusted OR, 1.46; 95% CI, 1.14 to 1.88), especially among rural children, and in the absence of maternal asthma or a dog in the birth year. Broad-spectrum (BS) cephalosporin use was more common in these subpopulations of children. Antibiotic use in early life was associated with the development of childhood asthma, a risk that may be reduced by avoiding the use of BS cephalosporins.

Important HIV-associated conditions in HIV-infected infants and children

This article is the last in a series of 6 articles that discussed the management of HIV-infected children in a clinically orientated, practical and concise fashion. The topics covered previously include; 1) Preventing and diagnosing HIV-infection in infants and children, 2) Initiating anti-retroviral therapy in HIV-infected infants and children, 3) Maintaining HIV-infected infants and children on anti-retroviral therapy, 4) Common opportunistic infection in HIV-infected children: Part 1-respiratory infections and 5) Part 2 non-respiratory infections.

Common opportunistic infections in HIV infected infants and children Part 2 non-respiratory infections

Increased susceptibility to infections is the major cause of disease, end organ damage and death in human immunodeficiency virus (HIV)-infected children. This article will focus on prevention, diagnosis and management of the most common and less common severe infections that are specifically associated with HIV-related immune compromise, as well as some aspects relating to immune reconstitution inflammatory syndrome (IRIS).

Early life exposure to antibiotics for non-respiratory infections is associated with asthma

Early life exposure to antibiotics for non-respiratory infections is associated with asthma

Intravenous immunoglobulin replacement prevents severe and lower respiratory tract infections, but not upper respiratory tract and non‐respiratory infections in common variable immune deficiency

Although the dose of 400 mg/kg body weight intravenous immunoglobulins (IVIG) every 3-4 weeks is now standard for treating patients with common variable immune deficiency, studies demonstrating its long-term benefits over low 200 mg/kg dose and its effects on infectious subsets (upper vs lower respiratory vs non-respiratory infections) are rare. All patients from a single center with the diagnosis of common variable immune deficiency and whose clinical chart was available during three successive therapeutic periods [a pre-IVIG replacement period, a low-dose (200 mg/kg every 3 weeks) and a standard-dose replacement period (400 mg/kg every 3 weeks)] were screened retrospectively. Seven patients followed up for a total of 116 patient-years over the three defined periods of observation were recruited. When compared with low-dose therapy, standard-dose intravenous immunoglobulin therapy raised trough IgG levels from 4.3 to 6.5 g/l and significantly decreased the overall frequency of infections, with marked effects on lower respiratory tract and severe infection number. In contrast, non-respiratory and upper respiratory infections were, in comparison, resistant to therapy. Overall, these data support the use of standard-dose 400 mg/kg intravenous immunoglobulin therapy, despite the high cost, to raise trough IgG levels to 5-7 g/l, but underlines that some categories of infectious events (non-respiratory, upper respiratory) may need parallel surgical or pharmacological approaches to be optimally prevented or treated.

Use of Pegylated Interferons is Associated with An Increased Incidence of Infections during Combination Treatment of Chronic Hepatitis C: A Side Effect of Pegylation?

Standard interferon treatment is known to increase the risk of infections; this risk also needs to be evaluated in clinical practice for pegylated interferon. To this end, we studied 255 patients treated with standard (103) or pegylated (152) interferon, in combination with ribavirin, for hepatitis C. Overall, 31 anti-hepatitis C virus treatment-related infections were observed. Neutropenia (neutrophil counts below 1x10(3) cells/ml) was observed in a significantly higher proportion of patients treated with pegylated interferons (48% vs 9%; P=0.0009). Of the 31 infections, eight were respiratory infections and were observed only in patients with neutropenia. None of the non-respiratory infections was observed in patients with neutropenia. Multivariate analysis, using Cox's proportional hazards regression model, found a higher risk of all infections associated with both use of pegylated interferons [hazard ratio (HR) 4.6] and neutropenia (HR 2.46). However, neutropenia was independently associated with acute respiratory infections only and use of pegylated interferons with non-respiratory infections. In summary, use of pegylated interferon appears to increase the risk of non-respiratory infections independently from neutropenia.

Antibacterials for Viral Respiratory Infections

To determine the effectiveness of a multi-component managed-care intervention in reducing inappropriate antibacterial prescribing for viral respiratory infections (VRIs). An episode-based retrospective analysis of administrative claims data between 1998, the year prior to the initiation of the first component of the intervention, and 2001, the year after full implementation. Patient group studied: All health plan members of the Hawaii Medical Service Association (Blue Cross Blue Shield Hawaii) in the US who sought care for an upper respiratory infection. To ensure that changes in the rate of antibacterial prescriptions were not because of viral-related infections being coded as bacterial, we measured, in parallel, diagnoses of similar bacterial respiratory infections. Persons with chronic bronchitis, emphysema, and asthma were excluded. Episodes temporally associated with any diagnosis for a non-respiratory bacterial infection were also excluded. The main study outcome was change in VRI-associated antibacterial utilization. Secondary outcomes included episode-related outpatient, emergency department and inpatient utilization, and estimated cost savings related to changes in antibacterial prescribing rates. The population-based rate of antibacterial use for VRIs decreased significantly between 1998 and 2001, from 39.9% to 33.5%. There was no observed increase in the proportion of bacterial to viral episodes over the same period of time, suggesting that the observed decrease in rates was not a result of coding changes. This reduction in antibacterial prescribing for VRIs was not associated with an increase in emergency department or inpatient utilization. A reduction in VRI-related outpatient visits was observed. The reduction in inappropriate antibacterial prescriptions was estimated to result in a cost saving of approximately $US500 000 over the 4-year study period, assuming the antibacterials prescribed were similar over time (1998 values). The majority of savings were found in the last year, after full implementation of the intervention. While this study did not offer evidence that one component of the intervention was effective by itself, the combination of all components was associated with decreased antibacterial prescribing for VRIs. The observed reduction in antibacterial prescribing for viral episodes was not associated with increased healthcare visit utilization, and is estimated to be associated with a sizable cost saving. While further research is recommended, this study offers preliminary evidence that multi-component physician feedback programs may be effective in reducing the inappropriate prescribing of antibacterials, and managed care organizations can use claims-based, episode-defined analyses to evaluate the effectiveness of their initiatives.

Klebsiella and Enterobacter: Antibiotic resistance and treatment implications

KLEBSIELLA: spp. and Enterobacter spp. are widespread throughout the environment and also carried by humans. Both genera are well-recognized community and nosocomial pathogens and cause significant infections. They are a common cause of respiratory and nonrespiratory infections. Klebsiella spp. is responsible for 1% to 5% of all cases of community-acquired pneumonia and between 0% to 23% of those acquired in the hospital, and its frequency is greater in alcoholic patients. The majority of cases are unilateral in the posterior segment of the right upper lobe. Lung abscess can occur after a pneumonic process or secondarily to Klebsiella spp. infections and have high rates of morbidity and mortality. K. pneumoniae is one of the most common microorganisms responsible for empyema. Klebsiella spp. and Enterobacter spp. rank fourth and third, respectively, as causes of hospital-acquired pneumonia mainly in patients during the early period of mechanical ventilation. Klebsiella spp. are intrinsically resistant to penicillins and can acquire resistance to third- and fourth-generation cephalosporins owing to the production of plasmid-mediated extended-spectrum beta-lactamases (ESBLs). These plasmids frequently carry aminoglycoside-modifying enzymes. Enterobacter spp. are intrinsically resistant to ampicillin, amoxicillin, amoxicillin-clavulanate, first-generation cephalosporins, and cefoxitin owing to the production of constitutive AmpC beta-lactamase. The derepression of this enzyme is increasingly frequent among clinical isolates and confers resistance to third-generation cephalosporins, and ureido- and carboxypenicillins; fourth-generation cephalosporins retain reasonable activity against depressed strains. Most isolates of Klebsiella spp. and Enterobacter spp. are susceptible to fluoroquinolones, trimethoprimsulfamethoxazole, aminoglycosides, and carbapenems. In some instances, treatment of severe infections caused by these microorganisms may benefit from the combination of beta-lactams (or fluoroquinolones) with aminoglycosides. Because of the high risk for developing resistance during treatment, all severe infections should be carefully watched during therapy.

Exhaled breath condensate and serum levels of hepatocyte growth factor in pneumonia

Hepatocyte growth factor (HGF) is a protein produced by mesenchymal cells in many organs, which can stimulate epithelial growth. An enhanced production and concentration of HGF is observed after injuries. The lung is one of the major sources of HGF. By cooling exhaled air, a condensate is formed containing molecules from bronchi and alveoli. In order to investigate HGF concentration and time course in pneumonia, paired serum and exhaled breath condensate was collected from 10 patients with pneumonia, 10 patients with non-respiratory infections and 11 healthy controls. The concentration of HGF was measured by an immunoassay kit. In the acute phase HGF-levels in breath condensate and serum were significantly higher in the patients with pneumonia compared to the control groups. Similar concentrations in breath condensate were seen in healthy controls and in patients with non-respiratory infections. In the patients with pneumonia a decrease in serum HGF was seen already after 4–7 days while HGF values in breath condensate remained elevated even after 4–6 weeks. These results might imply local production of HGF in the lungs and a long repair and healing process after pneumonia.

Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study.

Delirium impedes communication and contributes to symptom distress in patients with advanced cancer. There are few prospective data on the reversal of delirium in this population. To evaluate the occurrence, precipitating factors, and reversibility of delirium in patients with advanced cancer. Prospective serial assessment in a consecutive cohort of 113 patients with advanced cancer. Precipitating factors were examined using standardized criteria; 104 patients met eligibility criteria. Acute palliative care unit in a university-affiliated teaching hospital. Delirium occurrence and reversal rates, duration, and patient survival. Strengths of association of various precipitating factors with reversal were expressed as hazard ratios (HRs) in univariate and multivariate analyses. On admission, delirium was diagnosed in 44 patients (42%), and of the remaining 60, delirium developed in 27 (45%). Reversal of delirium occurred in 46 (49%) of 94 episodes in 71 patients. Terminal delirium occurred in 46 (88%) of the 52 deaths. In univariate analysis, psychoactive medications, predominantly opioids (HR, 8.85; 95% confidence interval [CI], 2.13-36.74), and dehydration (HR, 2.35; 95% CI, 1.20-4.62) were associated with reversibility. Hypoxic encephalopathy (HR, 0.39; 95% CI, 0.19-0.80) and metabolic factors (HR, 0.44; 95% CI, 0.21-0.91) were associated with nonreversibility. In mulitivariate analysis, psychoactive medications (HR, 6.65; 95% CI, 1.49-29.62), hypoxic encephalopathy (HR, 0.32; 95% CI, 0.15-0.70), and nonrespiratory infection (HR, 0.23; 95% CI, 0.08-0.64) had independent associations. Patients with delirium had poorer survival rates than controls (P<.001). Delirium is a frequent, multifactorial complication in advanced cancer. Despite its terminal presentation in most patients, delirium is reversible in approximately 50% of episodes. Delirium precipitated by opioids and other psychoactive medications and dehydration is frequently reversible with change of opioid or dose reduction, discontinuation of unnecessary psychoactive medication, or hydration, respectively.

Bacterial vaccines: anything but placebo.

Bacterial vaccines: anything but placebo.

FulminantBranhamella catarrhalistracheitis

Branhamella catarrhalis, a well known commensal of the normal respiratory flora, is being increasingly implicated as an aetiological agent in various acute respiratory and non-respiratory infections. B. catarrhalis has demonstrated a particular predilection for turning pathogenic in the immunocompromised host. Bacterial tracheitis, presenting as an acute airway obstruction, is commonly caused by Staphylococcus aureus and Haemophilus influenzae. The unusual occurrence of a fulminant B. catarrhalis bacterial tracheitis in a previously normal and healthy Indian child is the subject of this communication.

Respiratory Complications of Cardiac Transplantation

The authors evaluated all respiratory complications of cardiac transplantation in a 10-year study of 94 consecutive recipients. Mean follow-up time was 20 +/- 17 months. The initial 20 patients were treated with azathioprine and prednisone, while the subsequent 74 patients received cyclosporine and prednisone. In the azathioprine group, respiratory infections accounted for 24 of 60 (40%) infections. Two-thirds of the respiratory infections occurred in the first 3 postoperative months and were generally localized processes (focal pneumonitis, nodule(s), abscess, or empyema). Gram-positive and gram-negative bacteria (8/30) and aspergillus (8/30) were the predominant pathogens. Respiratory failure occurred in 29% of infectious episodes. In the cyclosporine group, there were significantly fewer respiratory infections. There was also a reduction in the number of nonrespiratory infections; hence, the percentage of total infections due to respiratory causes, 26 of 50 (52%), was not significantly different. In contrast, however, nearly two-thirds of the respiratory infections in cyclosporine-treated patients occurred after the first 3 postoperative months, and were usually diffuse processes. Despite diffuse disease, respiratory failure was observed with similar frequency (19%). Pneumocystis carinii (9/31) and cytomegalovirus (CMV) (7/31) were the predominant pathogens. CMV pneumonitis tended to occur earlier than that due to P. carinii (2.9 +/- 1.9 mo vs. 9.8 +/- 11.2 mo, respectively), but there was considerable overlap. In comparison with infectious processes, there were 50% fewer noninfectious respiratory complications in both groups. These were primarily pleural (46%) or thromboembolic (18%) disorders. Four of five pulmonary emboli occurred in patients with intercurrent cardiorespiratory illness, and were detected only at autopsy. The authors conclude that respiratory infections account for one-half of all infections observed in cardiac transplant recipients, despite the reduced infection rate associated with the use of cyclosporine. Furthermore, respiratory infections in cyclosporine-treated patients exhibit different clinical and etiologic features than those seen in azathioprine-treated patients. Finally, occult thromboemboli may be difficult to recognize in cardiac transplant recipients because of the high incidence of coexisting cardiorespiratory disease.

Surveillance in a surgical intensive care unit: patient and environment.

Microbiologic surveillance of both the patients and the ambient environment of a surgical intensive care unit allowed us to relate the incidence of nosocomial respiratory tract infection to levels of airborne bacteria. Over the study period respiratory tract nosocomial infection rates varied from 0.7% to 17.0%, and nonrespiratory infection rates varied from 1.0% to 25.0%. Airborne bacteria counts during that time varied from 1.0 +/- 0.8 S.E. CFU/ft3 to 96.0 +/- 6.8 S.E. CFU/ft3. There was a reasonably close correlation between airborne bacteria levels and the incidence of nosocomial pneumonia (r = 0.81, p less than 0.05). Furthermore, there was a close correlation between a specific organism nosocomial infection rate and the number of colonies of that organism present in the air (r = 0.88, p less than 0.05). In contrast, there was no significant relationship between airborne bacteria counts and nonrespiratory attack rates (r = 0.60, p less than 0.05). If the bacteria traveled from the air to the patients, there appear to be at least three possible explanations for this significant relationship: (1) direct inoculation of the airway by the airborne bacteria; (2) inoculation of the airway by direct contact, which is related to the degree of "cleanliness" of the environment; and (3) an increased incidence of contaminated respiratory equipment and airway inoculation because of high counts of airborne bacteria. It is also possible that high bacterial air counts represent contamination of the air from patients with respiratory infections. Regardless of the pathway(s), surveillance of the ambient environment may prove to be a useful epidemiologic tool in the study and control of nosocomial respiratory tract infections in certain high-risk patient care areas.

Office treatment of infection. 2. Nonrespiratory bacterial infections, antibiotic prophylaxis, fungal and viral infections.

Office treatment of infection. 2. Nonrespiratory bacterial infections, antibiotic prophylaxis, fungal and viral infections.

Sexual bias in drug advertisements

This study was based on drug advertisements appearing in two leading American medical journals in 1975. The sex distribution of patients shown in advertisements for drugs for various conditions was compared with the sex distribution of those people who are actually afflicted with these conditions. Sexual bias was found in advertisements for medications for hypertension. anxiety, insomnia, angina, depression, and hyperlipidemia. In each case there were significantly more male patients shown in the advertisements than was warranted. No bias was found in advertisements for drugs for respiratory problems, non-respiratory infections. arthritis, and pain.