RECENT FINDINGS: Optimal antibiotic treatment is challenging in critically ill patients with nosocomial pneumonia; most dosing guidelines do not consider the altered physiology and illness severity associated with severe lung infections. Antibiotic dosing can be guided by plasma drug concentrations, which do not reflect the concentrations at the site of infection. The application of aggressive dosing regimens, in accordance to the antibiotic's pharmacokinetic/pharmacodynamic characteristics, may be required to ensure rapid and effective drug exposure in infected lung tissues.
SUMMARY: Conventional antibiotic dosing increases the likelihood of therapeutic failure in critically ill patients with nosocomial pneumonia. Alternative dosing strategies, which exploit the pharmacokinetic/pharmacodynamic properties of an antibiotic, should be strongly considered to ensure optimal antibiotic exposure and better therapeutic outcomes in these patients.
METHODS: This was a prospective study conducted at a tertiary hospital in Malaysia, from 1st August 2010 until 31st July 2011. Children aged between 1 mo and 12 y who were admitted for CAP and had blood cultures performed before starting intravenous antibiotics were recruited. Children with congenital pneumonia, immunodeficiency, chronic cardiac or respiratory disorders, nosocomial pneumonia or those on corticosteroids, were excluded. Decision for admission was made by the attending Accident and Emergency physician.
RESULTS: One hundred and seventy-one children were enrolled. The median age was 13 mo (range: 38 d-10 y 3 mo) and 59 % were males. Blood cultures were positive in 1.2 % (2/171) of patients while the contamination rate was 1.8 % (3/171). Doctors altered antibiotics based on blood culture results in only one patient.
CONCLUSIONS: Both the yield and the impact of blood culture results on the adjustment of empiric antibiotic treatment were very small. There was a high contamination rate. The recommended practice of performing blood cultures in all children admitted with CAP should be reviewed.
METHODOLOGY: A follow-up in prospective cohort surveillance was conducted on patients admitted to an adult medical-surgical ICU of a university hospital and two governmental hospitals in Malaysia from October 2003 to December 2006. VAP was detected using CDC criteria which included clinical manifestation and confirmed endotracheal secretion culture results.
RESULTS: In total, 215 patients (2,306 patient-days) were enrolled into the study. The incidence of ICU-acquired device-related NI was 29.3 % (n = 63). The device-related VAP infection rate was 27.0 % (n = 58), with a mechanical ventilator utilization rate of 88.7%. The death rate due to all ICU-acquired NI including sepsis was 6.5%. The most common causative pathogen was Klebsiella pneumoniae (n = 27). Multivariate analysis using Cox regression showed that the risk factors identified were aspiration pneumonia (HR = 4.09; 95% CI = 1.24, 13.51; P = 0.021), cancer (HR = 2.51; 95% CI = 1.27, 4.97; P = 0.008), leucocytosis (HR=3.43; 95% CI= 1.60, 7.37; P=0.002) and duration of mechanical ventilation (HR=1.04; 95% CI = 1.00, 1.08; P = 0.030). Age, gender and race were not identified as risk factors in the multivariable analysis performed.
CONCLUSION: The incidence of VAP was comparable to that found in the National Nosocomial Infection Surveillance (NNIS) System report of June 1998. The incidence of VAP was considered high for the three hospitals studied.
MATERIALS AND METHODS: We studied the samples of the pharyngeal mucosa smears taken from children aged 1-15 years with X-ray confirmed pneumonia. The selection of DNA probes for specific detection of community-acquired pneumonia pathogens (S. pneumoniae, H. influenzae, M. pneumoniae, C. pneumonia, and L. pneumophila) and development of the microarray design were carried out using the disprose program. The nucleotide sequences of pathogens were obtained from NCBI Nucleotide database. In the research we used CustomArray microarrays (USA). For a pooled sample containing S. pneumoniae and H. influenzae DNA, we performed a sequential selection of the best combinations of hybridization parameters: DNA fragment size, DNA amount, hybridization temperature. The selection criteria were: the percentage of effective probes with a standardized hybridization signal (SHS) ≥3 Z, and the excess of SHS levels of effective specific probes compared to SHS of effective nonspecific probes. We selected the probes to detect of S. pneumoniae and H. influenzae characterized by an effective hybridization signal under optimal conditions. The developed microarray was tested under the selected conditions on clinical samples containing S. pneumoniae or H. influenzae DNA. Using ROC analysis there were established threshold values for the signals of specific probes at optimal sensitivity points and the test specificity, the excess of which was interpreted as the evidence of pathogen presence in a sample.
RESULTS: A microarray design included 142 DNA probes to detect S. pneumoniae, H. influenzae, M. pneumoniae, C. pneumoniae, and L. pneumophila, the probes being synthesized onto slides. Using the example of clinical samples containing S. pneumoniae and/or H. influenza DNA, we selected optimal parameters for DNA hybridization on microarrays, which enabled to identify bacterial pathogens of community-acquired pneumonia with sufficient efficiency, specificity and reproducibility: the amount of hybridized DNA was 2 μg, the DNA fragment size: 300 nt, hybridization temperature: 47°C. There was selected a list of probes for specific detection of S. pneumoniae and H. influenzae characterized by an effective hybridization signal under the identified conditions. We determined the threshold values of standardized probe signals for specific detection of S. pneumoniae (4.5 Z) and H. influenzae (4.9 Z) in clinical samples.
CONCLUSION: A DNA microarray was developed and synthesized for parallel indication of bacterial pathogens of community-acquired pneumonia. There were selected the optimal parameters for DNA hybridization on a microarray to identify bacterial pathogens - S. pneumoniae and H. influenzae, and determined the threshold values of significant probe signals for their specific detection. The interpretation of the microarray hybridization results corresponds to those obtained by PCR. The microarray can be used to improve laboratory diagnostics of community-acquired pneumonia pathogens.
OBJECTIVES: To determine the a) aetiology, b) factors associated with bacterial pneumonia and c) association between co-infections (bacteria + virus) and severity of disease, in children admitted with severe pneumonia.
METHODS: A prospective cohort study involving children aged 1-month to 5-years admitted with very severe pneumonia, as per the WHO definition, over 2 years. Induced sputum and blood obtained within 24 hrs of admission were examined via PCR, immunofluorescence and culture to detect 17 bacteria/viruses. A designated radiologist read the chest radiographs.
RESULTS: Three hundred patients with a mean (SD) age of 14 (±15) months old were recruited. Significant pathogens were detected in 62% of patients (n = 186). Viruses alone were detected in 23.7% (n = 71) with rhinovirus (31%), human metapneumovirus (HMP) [22.5%] and respiratory syncytial virus (RSV) [16.9%] being the commonest. Bacteria alone was detected in 25% (n = 75) with Haemophilus influenzae (29.3%), Staphylococcus aureus (24%) and Streptococcus pneumoniae (22.7%) being the commonest. Co-infections were seen in 13.3% (n = 40) of patients. Male gender (AdjOR 1.84 [95% CI 1.10, 3.05]) and presence of crepitations (AdjOR 2.27 [95% CI 1.12, 4.60]) were associated with bacterial infection. C-reactive protein (CRP) [p = 0.007]) was significantly higher in patients with co-infections but duration of hospitalization (p = 0.77) and requirement for supplemental respiratory support (p = 0.26) were not associated with co-infection.
CONCLUSIONS: Bacteria remain an important cause of very severe pneumonia in developing countries with one in four children admitted isolating bacteria alone. Male gender and presence of crepitations were significantly associated with bacterial aetiology. Co-infection was associated with a higher CRP but no other parameters of severe clinical illness.