Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.

Practical recommendations for home-nebulized corticosteroid use in children aged ≤ 5 years with asthma: A review and advisory group consensus.

BACKGROUND: Despite nebulized budesonide being identified by the Global Initiative for Asthma report as a viable alternative to inhaled corticosteroids (ICS) delivered by pressurized metered-dose inhalers (pMDIs) with spacers, practical guidance on nebulized corticosteroid use in the pediatric population remains scarce. OBJECTIVE: To review the current literature and provide practical recommendations for nebulized budesonide use in children aged ≤ 5 years with a diagnosis of asthma. METHODS: A group of 15 expert pediatricians in the respiratory and allergy fields in Thailand developed Delphi consensus recommendations on nebulized budesonide use based on their clinical expertise and a review of the published literature. Studies that evaluated the efficacy (effectiveness) and/or safety of nebulized budesonide in children aged ≤ 5 years with asthma were assessed. AR patients. RESULTS: Overall, 24 clinical studies published between 1993 and 2020 met the inclusion criteria for review. Overall, results demonstrated that nebulized budesonide significantly improved symptom control and reduced exacerbations, asthma-related hospitalizations, and the requirement for oral corticosteroids compared with placebo or active controls. Nebulized budesonide was well tolerated, with no severe or drug-related adverse events reported. Following a review of the published evidence and group consensus, a treatment algorithm as per the Thai Pediatric Asthma 2020 Guidelines was proposed, based on the availability of medications in Thailand, to include nebulized budesonide as the initial treatment option alongside ICS delivered by pMDIs with spacers in children aged ≤ 5 years. CONCLUSIONS: ThNebulized budesonide is an effective and well-tolerated treatment option in children aged ≤ 5 years with asthma.

Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS).

BACKGROUND: There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design. METHODS AND FINDINGS: Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily observational data was collected on clinical signs, supportive care, antibiotic treatment, microbiology, and 28-day mortality. Two prediction models were developed for (1) 28-day mortality from baseline variables (baseline NeoSep Severity Score); and (2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1-Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2-"Low" Watch). The largest group (34.0%, n = 1,068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3-"Medium" Watch), 18.0% (n = 566) started a carbapenem (Group 4-"High" Watch), and 1.8% (n = 57) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability. CONCLUSION: Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT03721302).

Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting.

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network.

Practical considerations of nebulized corticosteroid in children with acute asthmatic exacerbation: A consensus.

BACKGROUND: Acute asthmatic exacerbation in children causes economic burdens both directly and indirectly. The GINA guideline does mention the use of inhaled or oral corticosteroids in the treatment of asthmatic exacerbation, it provides little practical guidance on the use of nebulized corticosteroid. OBJECTIVE: To review and recommend the practical considerations in the use of nebulized corticosteroid in children with acute asthmatic exacerbation. METHODS: This consensus was developed by a group of expert pediatricians in respiratory and allergy fields in Thailand. The recommendations were made based on a review of published studies and clinical opinions. The eligible studies were confined to those published in English, and randomized controlled trials and meta-analyses involving nebulized corticosteroids in asthmatic exacerbation in children aged between 1-18 years. RESULTS: There were 13 randomized controlled-trial studies published from 1998 to 2017. Nine of the 13 studies compared nebulized with systemic corticosteroid conducted in moderate to severe exacerbation, while the remaining four compared nebulized corticosteroid with placebo conducted in mild to severe exacerbation. The admission rate was significantly lower in severe exacerbation (one study) and pooled four mild to severe exacerbation studies comparing with placebo (p 0.022). Other clinical parameters were significantly improved with nebulized corticosteroid such as clinical scores, systemic corticosteroid/bronchodilator use, or shorter ER stays. Only one study used fluticasone, while the other 12 studies conducted by budesonide (92.31%). CONCLUSIONS: Nebulized corticosteroid may offer an effective therapeutic option for the management of acute exacerbation of asthma in all severities. Nebulized budesonide is the preferred corticosteroid.

Bacterial etiology of empyema thoracis and parapneumonic pleural effusion in Thai children aged less than 16 years.

This study aimed to identify the bacterial etiology of empyema thoracis or parapneumonic pleural effusions in Thai children, with a focus on pneumococcus. This hospital-based, descriptive study included children aged < or = 16 years, diagnosed with empyema thoracis or parapneumonic pleural effusion, from whom a pleural fluid (PF) sample was taken between January 2008 and November 2009. PF and blood samples were cultured and PF samples were also tested by polymerase chain reaction (PCR) to assess whether evidence of an infection might be identified among culture-negative samples. Serotyping of Streptococcus pneumoniae-positive samples was performed by molecular techniques and Quellung reaction. In this study, 29 children with empyema thoracis and 42 children with parapneumonic pleural effusion were enrolled. Potentially pathogenic bacteria were cultured in 13/71 samples at local or central laboratories; the most common bacteria were Staphylococcus aureus (8 children) and S. pneumoniae (2 children). Molecular techniques detected one or more targeted respiratory pathogens in 18/71 PF samples. S. pneumoniae and Haemophilus influenzae were identified by PCR in 13 and 6 children, respectively; PCR for S. aureus was not performed. The pneumococcal serotypes identified were 1, 3, 5, 6A/B, 9A/V, 14, 15A, 19F and 23A. This study shows that among Thai children with empyema thoracis and parapneumonic pleural effusions, S. aureus and S. pneumoniae were the most common pathogens identified by culture and PCR, respectively. These findings confirmed that molecular techniques are more sensitive for identification of S. pneumoniae and H. influenzae and enhance detection of important bacterial causes of empyema.

Effects of temperature and time delay on arterial blood gas and electrolyte measurements.

OBJECTIVE: To determine the changes in pH, PaO2, PaCO2 and Na, K, Cl in arterial blood samples stored at room temperature or on ice, at 0, 15, 30, 45 and 60 minutes. MATERIAL AND METHOD: Arterial blood samples were collected in heparinized capillary tubes and stored at room temperature (24-26 degrees C) and on ice (0-4 degrees C). ABG and electrolytes were measured at 0, 15, 30, 45 and 60 minute intervals. RESULTS: There were significant decreases in the pH, PaO2, Na, Cl and significant increases in PaCO2 and K over time in both groups. The changes were greater and faster at room temperature. The significant decrease in pH over time was not found until 30 minutes at room temperature and 45 minutes on ice. There were significant decreases in PaO2, concurrent with significant increases in PaCO2 from 15 minutes onwards in both groups. Both Na and K exhibited a significant change at 60 minutes in the room temperature group. Significant decreases of Cl over time were not found until 15 minutes at room temperature, and 30 minutes on ice. CONCLUSION: For ABG and electrolytes analysis, the blood sample should be analyzed within 15 minutes and be stored at either room temperature or on ice.

Clinical presentations of pandemic 2009 influenza A (H1N1) virus infection in hospitalized Thai children.

BACKGROUND: A novel influenza A (H1N1) virus of swine origin caused human infection and acute respiratory illness in Mexico during the spring of 2009. After that, the virus spread globally, resulting in the influenza pandemic. OBJECTIVE: To observe the clinical manifestations of the 2009 pandemic influenza A (H1N1) and the epidemic waves of hospitalized children for a period of one year. MATERIAL AND METHOD: A prospective observational study of children under eighteen years old, confirmed having the 2009 pandemic influenza (H1N1) infection by real-time reverse-transcription-polymerase-chain-reaction (RT-PCR), admitted at Queen Sirikit National Institute of Child Health, Bangkok, Thailand during one year, from 1st June 2009 to 31st May 2010. RESULTS: A total of 83 pandemic influenza infected children were admitted during a one-year period. There were two waves of epidemic outbreak, the first wave from June to August 2009 and the second wave from January to February 2010. There were 47 cases of males (56.6%), with the highest attack rates among children 1-5 years of age (48.2%). The youngest case was a 29-day old girl. The correct provisional diagnosis of pandemic influenza infection are 39.5%, the other initial diagnosis are pneumonia, bronchiolitis, tonsillitis, encephalitis, and dengue infection. Most patients coming for care had typical, influenza-like symptoms with fever (98.8%), cough (92.6%) and rhinorrhea (74.1%). Systemic symptoms are frequent. Gastrointestinal symptoms (including vomiting (46.9%) and diarrhea (24.7%)) occur more commonly than seasonal influenza. Pneumonia is the most common complication (43.2%); other complications include bronchiolitis, hemoptysis, acute respiratory distress syndrome (ARDS) and encephalitis. In one case, a seven year old girl suffered from ARDS, sepsis, multi-organ dysfunction syndrome and ventilator associated pneumonia, but survived with some neurological sequelae. Radiographic findings included diffuse interstitial, alveolar infiltrates and some in lobar distributions. Apart from oseltamivir the other antibiotics included ceftriaxone, cefotaxime, amplicillin and azithromycin, were added for pneumonia. All patients in the present study survived. CONCLUSION: The burden and character of pandemic influenza infection in developing countries are still incompletely understood. Early therapy with oseltamivir in severely ill patients, without waiting for laboratory confirmation for diagnosis, will save patients from severe complications.

Development of triplex SYBR green real-time PCR for detecting Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella spp. without extraction of DNA.

Although Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella spp. are prevalent causes of community-acquired pneumonia, rapid and sensitive diagnosis is difficult. Real-time PCR provides rapid and sensitive diagnosis, however, DNA extraction is still required, which is time-consuming, costly and includes a risk of contamination. Therefore, we aimed to develop triplex real-time PCR without DNA extraction. AmpDirect(R) Plus which inhibits PCR inhibitors was used as the PCR buffer. Melting temperatures of the PCR products for the three bacteria were analyzed by SYBR green triplex real-time PCR and were found to be significantly different. Detection limits of bacteria cells diluted in nasopharyngeal aspirates (NPAs) were comparable with the detection limits of previously reported real-time PCR. Our PCR without DNA extraction and probe real-time PCR with DNA extraction showed identical results for the detection of the three bacteria from 38 respiratory specimens (sputum, endotracheal aspirates, and NPAs) collected from patients with pneumonia. No cross-reaction with other bacteria was observed. Our triplex real-time PCR successfully detected and differentiated the three bacteria. Although further field tests are required, our assay is a promising method for the rapid and cost-effective detection of the three bacteria.

Are we adequately managing children with wheeze using the standard case management guidelines?

INTRODUCTION: Prevalence of wheezing is increasing, bronchodilators are sub-optimally utilized and antibiotics are over-prescribed. In Thailand, current case management guidelines based on WHO guidelines, recommend two doses of rapid-acting bronchodilator for children with audible wheeze and fast breathing (FB) and/or lower chest indrawing (LCI). OBJECTIVE: To document the response of children with wheeze with FB and/or LCI to up to three doses of bronchodilator therapy and followed children whose FB and LCI disappeared for 7 days. MATERIAL AND METHOD: We documented response to up to three dose of inhaled salbutamol in consecutively assessed eligible children 1-59 months of age presenting with auscultatory/audible wheeze and FB [WHO defined non-severe pneumonia (NSP)] and/or LCI [WHO defined severe pneumonia (SP)] at the outpatient department of a referral hospital. Data were collected for up to 7 days in responders to bronchodilator therapy. RESULTS: Of 534 children were screened from November 2001 to February 2003, 263 (49.3%) had wheeze and NSP and 271 (50.7%) had wheeze and SP Forty-eight children (9%) had audible wheeze. At screening, 224/263 (85.2%) children in the NSP group and 195/271 (72.0%) in the SP group responded to inhaled salbutamol. 86/419 (20.5%) responded to the third dose of bronchodilator Four hundred and nineteen responders were enrolled and followed up. On follow-up, 14/217 (6.5%) responders among the NSP group and 24/190 (12.6%) among the SP group showed deterioration. Age 1-11 months at screening was identified as an independent predictor of subsequent deterioration. Two seasonal peaks from December to March and from August to October were documented. CONCLUSION: A third dose of bronchodilator therapy at screening will improve the specificity of case management guidelines and reduce antibiotic use. Physicians should use auscultation for management of wheeze.

Mycoplasma pneumonia in young children, 2-5 years of age.

BACKGROUND: Mycoplasma pneumoniae is one of the most common causes of childhood community-acquired pneumonia (CAP), particularly in school-age children. Information regarding this infection in pre-school age children is lacking. OBJECTIVE: To determine the prevalence of M. pneumoniae in young children aged under 5 years with CAP. MATERIAL AND METHOD: This prospective study was conducted at Queen Sirikit National Institute of Child Health (QSNICH), Bangkok, Thailand between December 2001 and November 2002. We enrolled children aged 2 to 5 years with a clinical and radiological diagnosis of CAP. Acute and convalescent sera were collected and measured by using a particle agglutination test. Polymerase chain reaction (PCR) assay for M. pneumoniae was detected from nasopharyngeal secretions. Criteria for diagnosis were defined as > or = 4-found rising of mycoplasma antibody or titer > or = 1:160 with positive PCR. RESULTS: Thirteen out of 113 CAP patients were diagnosed as mycoplasma pneumonia. Three of them were diagnosed by > or = 4-fold rising of mycoplasma antibody while another 10 patients were diagnosed by mycoplasma titer > or = 1:160 with positive PCR for M. pneumoniae. Clinical symptoms and signs of these 13 mycoplasma pneumonia in young patients were fever (85%), cough (92%), dyspnea (85%), diarrhea (15%), rales (85%), wheezing or rhonchi (46%), and skin rash (15%). Leucocytosis (wbc > 15,000/cumm) was found in 46%. Chest x-rays revealed interstitial infiltration (71%), patchy infiltration (29%) and no pleural effusion was detected. Choices of antibiotic were erythromycin (31%), beta lactam antibiotics (61%), and antibiotic was not prescribed in one patient (8%). Sixty-nine percent of the patients improved, while 31% did not, possibly due to the use of beta lactam antibiotics, or non use of antibiotics. CONCLUSION: Mycopalsma pneumonia is not uncommon in children aged 2-5 years with CAP. Clinical signs, symptoms and radiological findings are non-specific and cannot be differentiated from other causes of CAP.

Prevalence and clinical presentations of atypical pathogens infection in community acquired pneumonia in Thailand.

OBJECTIVES: To determine the prevalence of atypical pneumonia and clinical presentations in patients with community acquired pneumonia (CAP). MATERIAL AND METHOD: A prospective multi-centered study was performed in patients aged > or = 2 years with the diagnosis of CAP who were treated at seven governmental hospitals in Bangkok from December 2001 to November 2002. The diagnosis of current infection was based on > or = 4 fold rise in antibody sera or persistently high antibody titers together with the presence of DNA of M. pneumoniae or C. pneumoniae in respiratory secretion or antigen of L. pneumophila in the urine. Clinical presentations were compared between patients with atypical pneumonia and unspecified pneumonia. RESULTS: Of 292 patients, 18.8% had current infection with atypical respiratory pathogens (M. pneumoniae 14.0%, C. pneumoniae 3.4%, L. pneumophila 0.4% and mixed infection 1.0%). Only age at presentation was significantly associated with atypical pneumonia in adults, while absence of dyspnea, lobar consolidation, and age > or = 5 years were significant findings for atypical pneumonia in children. CONCLUSION: The present study confirms the significance of atypical pathogens in adults and children. Moreover lobar consolidation is likely to predict atypical pneumonia in childhood CAP.

Prevalence and clinical features of mycoplasma pneumoniae in Thai children.

OBJECTIVE: To determine the prevalence and clinical features of mycoplasma pneumoniae in Thai children with community acquired pneumonia (CAP). MATERIAL AND METHOD: Diagnosis of current infection was based on > or = 4 fold rise in antibody sera or persistently high antibody titers together with the presence of mycoplasma DNA in respiratory secretion. The clinical features were compared between children who tested positive for M pneumoniae, and those whose results were negative. RESULTS: Current infection due to M. pneumoniae was diagnosed in 36 (15%) of 245 children with paired sera. The sensitivity and specificity of polymerase chain reaction (PCR) in diagnosing current infection in the present study were 78% and 98% respectively. The mean age of children with mycoplasma pneumoniae was higher than CAP with unspecified etiology. The presenting manifestations and initial laboratory finding were insufficient to predict mycoplasma pneumoniae precisely, the presence of chest pain and lobar consolidation on chest X-ray, however, were significant findings in children with mycoplasma pneumoniae. CONCLUSION: The present study confirms that M. pneumoniae plays a significant role in CAP in children of all ages. Children with this infection should be identified in order to administer the appropriate antibiotic treatment.

Human disease from influenza A (H5N1), Thailand, 2004.

Influenza A (H5N1) is endemic in poultry across much of Southeast Asia, but limited information exists on the distinctive features of the few human cases. In Thailand, we instituted nationwide surveillance and tested respiratory specimens by polymerase chain reaction and viral isolation. From January 1 to March 31, 2004, we reviewed 610 reports and identified 12 confirmed and 21 suspected cases. All 12 confirmed case-patients resided in villages that experienced abnormal chicken deaths, 9 lived in households whose backyard chickens died, and 8 reported direct contact with dead chickens. Seven were children <14 years of age. Fever preceded dyspnea by a median of 5 days, and lymphopenia significantly predicted acute respiratory distress syndrome development and death. Among hundreds of thousands of potential human cases of influenza A (H5N1) in Asia, a history of direct contact with sick poultry, young age, pneumonia and lymphopenia, and progression to acute respiratory distress syndrome should prompt specific laboratory testing for H5 influenza.

Factors effecting the outcome of acute respiratory distress syndrome in pediatric patients treated with high frequency oscillatory ventilation.

OBJECTIVES: To evaluate the survival rate and factors affecting the outcome of pediatric patients treated with high-frequency oscillatory ventilation (HFOV) for diffuse alveolar disease (DAD) compatible with acute respiratory distress syndrome (ARDS). METHOD: A cohort study was conducted at the pediatric intensive care unit of Queen Siritkit National Institute of Child Health from 1st January 1999 to 31st December 2001. Children who suffered from DAD compatible with ARDS were enrolled. Inclusion criteria were PaO2/FiO2 < 200 and oxygenation index (OI) > 10. High-frequency oscillatory ventilator (3100A Sensor Medics Corp, Yorba Linda, Calif) was used applying high volume strategy of treatment. Patients were weaned to conventional ventilation (CV) once clinical improvement occurred. Demographic data, duration of CV mode before changing to HFOV, duration of HFOV, ventilator parameters and gas exchange variables from beginning and during the course of HFOV were recorded, so patient data could be compared between surviving and non-surviving groups. RESULTS: A total of 21 children were enrolled during the 3 year period. There were 4 patients with simultaneous air leak syndrome and a total of 10 male patients. The average age was 3.58 +/- 3.9 years. There were 11 surviving patients (52.4%). Data of ventilator parameters and gas exchange variables after changing to HFOV for 4-6 hours for the two groups, FiO2 was higher (0.99 +/- 0.32 vs 0.84 +/- 0.18; p = 0.02) and alveolar arterial oxygen gradient [P(A-a)O2] was lower (448.5 +/- 140.8 vs 562.7 +/- 99.9 mmHg; p = 0.047) in the surviving group than in the non-surviving group. Concerning mean airway pressure (Paw), oxygenation index (OI), P(A-a)O2 and PaO2/FiO2 at initiation and during the course of HFOV with comparison of the surviving and non-surviving groups: Paw and OI decreased in the surviving group and was significantly different at 36 and 24 hours respectively. P(A-a)O2 was statistically significantly lower at 6 hours after HFOV initiation in the surviving group. PaO2/FiO2 was statistically significantly increased at 24 hours in the surviving group. CONCLUSION: Implement of HFOV is useful in patients with DAD, ARDS and air leak syndrome from the initial phase of illness which fulfill criteria for decreasing ventilator induced lung injury and thus decrease the mortality rate from ARDS. Predisposing survival factor showing statistically significant differences was lower Paw during CV before changing to HFOV, lower Paw at 36 hours, lower OI at 24 hours, lower P(A-a)O2 at 6 hours and higher PaO2/FiO2 at 24 hours. These parameters are good indicators for the prognosis of ARDS for patients responding or not responding to HFOV.