Risk factors and epidemiologic predictors of blood stream infections with New Delhi Metallo-b-lactamase (NDM-1) producing Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae conferred by New Delhi metallo-b-lactamase (NDM-1) resistance mechanism are endemic in India and Southeast Asia. An understanding of risk factors for NDM-1 infections is necessary to guide prevention strategies. We performed a retrospective case-control study of patients admitted at Christian Medical College Hospital, Vellore, India between May 2010 and August 2014 with Klebsiella pneumoniae blood stream infection (BSI). We compared patients with BSI caused by NDM-1 producing strains to two control groups: BSI with other multidrug resistant (MDR) strains and BSI with pan-susceptible strains. The study groups were assessed for risk factors for the outcomes: (1) infection with any MDR strain compared to pan-susceptible; and, (2) infection with NDM-1 strain as compared with other MDR and (3) Mortality. A total of 101 patients with BSI with NDM-1 producing Klebsiella pneumoniae were matched to two groups of controls: 112 with non-NDM-1 MDR strains and 101 with pan-susceptible strains. Medical (OR 10.4) and neonatal (OR 0.7) ICU admission, central venous catheter placement (CVC, OR 7.4) predicted MDR BSI. Prior carbapenem use (OR 8.4) and CVC (OR 4.8) predicted acquisition of an NDM-1 strain. Significant predictors for mortality included ICU stay (OR 3.0), mechanical ventilation (OR 3.2), female gender (OR 2.2), diabetes (OR 0.4). CVC placement, prior carbapenem use and ICU admission were significantly associated with BSI with NDM-1 producing and other MDR strains.

Sunshine, rainfall, humidity and child pneumonia in the tropics: time-series analyses.

Few studies have formally examined the relationship between meteorological factors and the incidence of child pneumonia in the tropics, despite the fact that most child pneumonia deaths occur there. We examined the association between four meteorological exposures (rainy days, sunshine, relative humidity, temperature) and the incidence of clinical pneumonia in young children in the Philippines using three time-series methods: correlation of seasonal patterns, distributed lag regression, and case-crossover. Lack of sunshine was most strongly associated with pneumonia in both lagged regression [overall relative risk over the following 60 days for a 1-h increase in sunshine per day was 0·67 (95% confidence interval (CI) 0·51-0·87)] and case-crossover analysis [odds ratio for a 1-h increase in mean daily sunshine 8-14 days earlier was 0·95 (95% CI 0·91-1·00)]. This association is well known in temperate settings but has not been noted previously in the tropics. Further research to assess causality is needed.

Serious community-acquired neonatal infections in rural Southeast Asia (Bohol Island, Philippines).

OBJECTIVE: To determine the bacterial etiology, clinical presentation and risk factors for outcome of serious community-acquired infections in young infants. STUDY DESIGN: Infants younger than 60 days, admitted for severe pneumonia or suspected sepsis/meningitis were prospectively evaluated using complete blood count, blood culture, chest radiograph, cerebrospinal fluid (CSF) culture in suspected meningitis. chi2 or Fisher's exact test and stepwise logistic regression were used for analysis. RESULTS: Thirty-four of 767 enrolled infants had a positive blood or CSF culture. Gram-negative bacteria were more frequent than Gram positive: overall (P=0.004), in those below 7 days of age (P=0.002) and among home deliveries (P=0.012). Case fatality rates were higher among infants below 1 week old (OR 4.14, P<0.001), those with dense (OR 2.92, P<0.001) or diffuse radiographic infiltrates (OR 2.79, P=0.003). CONCLUSIONS: Gram-negative enteric bacteria are the predominant causes of community-acquired infections in Filipino infants below 2 months old. Age below 7 days and radiographic pneumonia predicted death.

The initial detection of human immunodeficiency virus 1 and its subsequent spread in prostitutes in Tamil Nadu, India.

To determine the prevalence of HIV-1 antibody and risk factors associated with a positive test in a heterosexually promiscuous female population, we initially screened 412 prostitutes in remand homes in three cites and three towns in Tamil Nadu state (southern India) and then tested all new entrants to one home in Vellore from 1986 to 1990. The proportion of women infected (10 of 102) from the port city of Madras was greater than from all other cities or towns combined (four of 310, p = 0.0002). The only significant risk factor for development of HIV-1 antibody was exposure to foreigners (odds ratio: 7.71; 95% confidence interval 4.2-11.2; p = 0.0004), after correcting for the influence of city. In Vellore the prevalence of HIV-1 antibody increased from 1.8% in 1986 to 28.6% in 1990, with a doubling time of 0.95 years. We hypothesize that HIV-1 infection has been introduced into India relatively recently into the heterosexually promiscuous population, where there has been some spread. Preventive measures should be urgently directed toward this population to prevent spread in the general population.

Respiratory syncytial virus (RSV) infection in preterm infants and the protective effects of RSV immune globulin (RSVIG). Respiratory Syncytial Virus Immune Globulin Study Group.

OBJECTIVE: To evaluate the safety and efficacy of respiratory syncytial virus immune globulin (RSVIG) in the prevention of severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in infants born prematurely with or without bronchopulmonary dysplasia (BPD). METHODS: Data from a prospective, blinded, randomized, multicenter trial during three consecutive RSV seasons involving 249 children. This analysis comprises 162 preterm children, of whom 102 had BPD. The 87 children with congenital heart disease (CHD) were excluded from this analysis. Children were randomized to receive monthly infusions of RSVIG 750 mg/kg (high dose), RSVIG 150 mg/kg (low dose), or no RSVIG: Results from the preterm infants with and without BPD who received RSVIG 750 mg/kg are contrasted with control infants who did not receive RSVIG: RESULTS: As compared with controls, high-dose RSVIG administration significantly reduced the incidences of RSV LRTI (P = .01) and moderate-to-severe LRTI (P = .006). RSV-associated hospitalization also was decreased (P = .06) as well as were total RSV-associated days in the intensive care unit (P = .05). Significantly fewer preterm infants developed severe RSV LRTI in the RSVIG group compared with controls (4/58 [7%] vs 14/58 [24%], respectively; P = .01). Adverse reactions occurred in 5% of RSVIG infusions. These were generally mild and included reversible fluid overload, transient fever, and decreases in oxygen saturation. There was one death unrelated to either RSV or RSVIG administration. CONCLUSIONS: Prophylaxis with RSVIG is safe and is currently the only effective means to prevent severe RSV LRTI in high-risk preterm infants.

Clinical signs of acute lower respiratory tract infections in malnourished infants and children.

OBJECTIVES: To determine the reliability of respiratory rate and subcostal retractions in diagnosing acute lower respiratory infection (ALRI) in undernourished children. METHODS: Three hundred twelve children with ALRI and 446 with upper respiratory infection were classified according to weight and height as normal, stunted, wasted or stunted and wasted and also as normal, underweight or marasmus. The sensitivity and specificity of tachypnea, subcostal retractions and the presence of either sign in identifying children with a clinical diagnosis of ALRI or radiologic pneumonia in each of the nutritional categories were determined and compared. RESULTS: Among children with ALRI the mean respiratory rate in those with normal nutrition (61.5 +/- 16.1, n = 160) was not significantly different from those who were stunted (57.5 +/- 16.5, n = 59), wasted (61.3 +/- 14, n = 66) or stunted and wasted (55.4 +/- 12.8, n = 27) (P > 0.05) or from those classified as underweight (60 +/- 15.9, n = 150) or marasmus (62.5 +/- 14.5, n = 27) (P > 0.4). The sensitivity and specificity of tachypnea, subcostal retraction or the presence of either sign in detecting ALRI was also not statistically significantly different among the children in the different nutritional categories (P > 0.05). The sensitivity of tachypnea or subcostal retraction in identifying children with radiologic pneumonia was also not significantly different among children in the different nutritional categories; the sensitivity of either sign was higher in under-weight children than in children with normal nutrition (P = 0.028). CONCLUSIONS: The data suggest that the current WHO algorithm is suitable for diagnosis of ALRI in undernourished children.

Standardized diagnosis of pneumonia in developing countries.

The World Health Organization recommends the use of raised respiratory rate and chest wall indrawing to enable health workers in developing countries to diagnose pneumonia. We evaluated the current World Health Organization guidelines for management of the child with cough or difficult breathing in Manila, Philippines and Mbabane, Swaziland using an identical protocol in both countries. Raised respiratory rate was defined as greater than or equal to 50/minute for children ages 2 to 12 months and greater than or equal to 40/minute for children 12 months to 5 years. Chest wall indrawing was defined as inward movement of the bony structures of the lower chest wall with inspiration. In the Philippines raised respiratory rate or chest wall indrawing, when applied by a pediatrician, was found to have a sensitivity of 0.81 and specificity of 0.77 for predicting pneumonia as determined by a pediatrician with the aid of a chest roentgenogram. In Swaziland the sensitivity was 0.77 and the specificity was 0.80. When applied by health workers the sensitivity was similar but the specificity was lower. The current World Health Organization ARI case management guidelines predicted pneumonia with similar sensitivity and specificity in two very different developing countries, the Philippines and Swaziland.

Immunoprophylaxis and immunotherapy: role in the prevention and treatment of repiratory syncytial virus.

It is now apparent that neutralizing antibody may play an important role in ameliorating RSV lower repiratory tract illness. At the present time immunoprophylaxis and immunotherapy with polyclonal antibodies show the most promise in the prevention and treatment of RSV illness. Several questions remained to be answered. These include the practical application of IGIV in prevention and treatment of RSV illness. Intravenous lines are often difficult to place and maintain. With the further development of polyclonal or monoclonal antibodies it may be possible to immunize prospective donors and boost their anti RSV titers to the degree that a hyper-immune IGIV with sufficient antibody to be given intramuscularly could be produced. The role for RSV-specific monoclonal antibodies for disease prevention or treatment must be defined as well as the appropriatee viral epitopes to target. In the absence of a safe and effective vaccine, it is clear that, despite these questions passive immunotherapy and immunoprophylaxis offers the greatest hope for the prevention and treatment of RSV disease in high risk infants and children.

Respiratory syncytial virus prophylaxis--the story so far.

Respiratory syncytial virus (RSV) is a common and highly contagious pathogen that infects nearly all children by the age of 2 years. It is responsible for significant morbidity and mortality worldwide among certain high-risk paediatric populations. Therapy is sub-optimal for RSV, thus treatment focuses on ameliorating symptoms. Since discovery of the virus in the 1950s, efforts have been ongoing to develop a safe and effective vaccine. These efforts have met with serious obstacles. Passive immunoprophylaxis presents a viable alternative to active immunization. In 1998, the genetically engineered humanized monoclonal antibody (palivizumab) was granted FDA (Food and Drug Administration) approval for prophylaxis of high-risk children in the United States; EMEA (European Agency for the Evaluation of Medicinal Products) approval followed in 1999 for Europe. It is now approved in over 45 countries worldwide. Palivizumab was shown to significantly reduce RSV-related hospitalizations in North America and Europe with few adverse effects. Clinical trial and outcomes data documenting experience with palivizumab to date continue to extend the initial safety and efficacy observations.

An update on respiratory syncytial virus epidemiology: a developed country perspective.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and young children worldwide, and an important cause of morbidity, hospitalization, and mortality. The infections caused by RSV are seasonal, peaking predictably in the winter months in temperate climates, and in the hottest months and the rainy season in tropical climates. The involvement of the lower respiratory tract, manifest clinically as bronchiolitis or pneumonia, is the hallmark of severe RSV disease. Other indicators of severe disease include requirement for, and duration of, hospitalization, supplemental oxygen, management in an intensive care setting, and mechanical ventilation. Host-related risk factors for severe RSV disease include preterm birth, infection before 6 months of age, chronic lung disease, and congenital heart disease. Environmental risk factors for severe RSV infection include poverty, crowding, exposure to tobacco smoke, and malnutrition. Factors that increase frequency of the infection include young age, multiple gestation, family history of atopy, lack of parental education, household crowding, older school-age siblings, lack of breast feeding, day-care attendance, passive smoke exposure, and discharge from a neonatal intensive care unit between September and December. Recent studies in Europe, North America and Japan have evaluated the number of children affected as well as the medical resources necessary to care for these children. Continuing surveillance is the key to tracking the seasonality, risk factors, morbidity and mortality associated with RSV infection. Epidemiological studies are also the basis for development of appropriate local prevention strategies.

Evidence for HTLV-III infection in prostitutes in Tamil Nadu (India).

PIP: Blood samples were collected from 102 female prostitutes housed in a custodial care institution in Tamil Nadu, India, to determine the presence of antibodies to human T-lymphotropic virus type III (HTLV-III). Both social and sexual histories were taken from 101 of the 102 women. Commercial test kits were used to test sera for antibody to HTLV-III. Reactive sera were tested for a 2nd time by the enzyme-linked immunoabsorbent assay (ELISA). Those repeatedly reactive sera were transported to the US, the National Institutes of Health, for western blot analysis. The sera from 11 of the study subjects were found to be repeatedly reactive in ELISA, and 10 were confirmed to have specific antibody to the virus by western blot analysis. Both infected and uninfected women were similar in age and of low socioeconomic status. The risk ratio for HTLV-III antibody was 8.2 in those women who had had sexual exposure to foreigners. None of the women were intravenous drug abusers, and all denied oral or rectal intercourse. On the basis of the stringent criteria used in the western blot analysis, it is believed that the 10 women have HTLV-III antibody. This emerges as the 1st report of evidence for HTLV-III infection in India. 10-40% of prostitutes in North America and Europe have HTLV-III antibody; the risk factors for infection appear to be intravenous drug use and penis-rectal intercourse. 54-88% of prostitutes in Central Africa have HTLV-III antibody, and the frequency of sexual contact with different partners is more important here as a risk-factor than the type of intercourse. As the prostitutes in this study in Indian did not use intravenous drugs and did not practice penis-rectal or penis-oral intercourse and had been prostitutes for shorter periods of time than the noninfected women and had fewer contacts, it is believed that HTLV-III infection has been introduced only recently into prostitutes in India. Sexual exposure to foreigners was a significant factor in the infected women.^ieng

Room air challenge: prediction for successful weaning of oxygen-dependent infants.

OBJECTIVE: The objective of this study was to determine the time required for equilibration of oxygen saturation (SpO2) and the oxygen flow rate that might predict readiness for oxygen weaning to room air in preterm infants with improving bronchopulmonary dysplasia (BPD). STUDY DESIGN: This was a prospective longitudinal cohort study, conducted in the neonatal care unit and the neonatal high risk follow-up clinic. Seventeen preterm children with BPD (mean postconceptual age 39.9 [range 31.5 to 43.5] weeks) were enrolled. With the infants breathing room air, the SpO2 pulse and respiratory rates, and clinical status were monitored for 120 minutes. Factors that predicted a successful room air challenge were determined. Children successfully weaned were followed up for 6 months after discontinuation of oxygen therapy. RESULTS: A total of 20 room air challenges were done in 17 study infants. In most infants the lowest SpO2 value (mean 89.7%) was reached within the first 40 minutes. Infants with an SpO2 > or = 92% at 40 minutes continued to have values > or = 92% at 120 minutes (specificity, 100%; sensitivity, 42%). In all infants receiving oxygen flow rates < or = 20 ml/kg per minute an SpO2 > or = 92% was maintained after 40 and 120 minutes. Infants who were successfully weaned to room air showed maintenance of weight and height percentiles 6 months after discontinuation of oxygen therapy. One child was rehospitalized and oxygen support reinstituted because of viral pneumonia. CONCLUSIONS: An SpO2 value > or = 92% at 40 minutes best predicts readiness for oxygen weaning to room air in infants with improving BPD. Infants requiring oxygen flow rates < or = 20 ml/kg per minute are also likely to be weaned off oxygen support.

Clinical practice guidelines for the management of chronic sinusitis in children.

Chronic sinusitis in children is a common and vexing disease for clinicians and the public. There are insufficient data in the literature to develop an evidence-based clinical guideline. Experience in managing pediatric chronic sinusitis has been gained through a multidisciplinary clinic at our institution during the past 3 years. A panel of experts was formed, and with the guidance of a guideline methodologist, the development of a rigorous outcome-based guideline was undertaken. Symptom-improvement and recurrence estimates for a variety of medical and surgical treatments were assessed. Wide probability estimates were made by the panelists in most cases. Although we refrained from making specific recommendations, we developed a ranked series of practical treatment options taking into account side effects and costs.

A primate model of respiratory syncytial virus infection.

To determine whether bonnet monkeys are susceptible to infection and disease due to respiratory syncytial virus (RSV), 4 juvenile bonnet monkeys (Macaca radiata) were inoculated with RSV intratracheally and sacrificed at 3, 5, 7 and 9 days post infection. RSV was cultured from pre-autopsy broncheoalveolar lavage fluid from all 4 animals with a peak titre of virus on day 9. Serum RSV neutralizing antibody was present by day 7. Animals developed tachypnoea and chest retractions by 5th day post infection and 2 animals had lobular pneumonia on chest radiography. The pathological changes were of a bronchovascular inflammation, interstitial pneumonia and alveolitis, akin to that seen in humans. These findings show that bonnet monkeys can be infected with RSV, and can develop immune response and clinical and pathological changes similar to those seen in human infants with RSV disease. Thus intractracheal RSV inoculation of juvenile bonnet monkeys appears to be a good model to study pathogenesis of RSV disease.

Comparing the performance of rat lungs preserved for 6 or 12 hours after perfusion with low-potassium dextran or histidine-tryptophan-ketoglutarate.

INTRODUCTION: In lung transplantation, graft dysfunction is a frequent cause of mortality; the etiopathogenesis is related to ischemia-reperfusion injury. We sought to compare the lung performance of rats after reperfusion after presentation with 3 solutions at 2 ischemia times. METHODS: We randomized 60 male Wistar rats to undergo anterograde perfusion via the pulmonary artery with low-potassium dextran (LPD), histidine-tryptophan ketoglutarate (HTK), or saline. After extraction, the heart-lung blocks were preserved in a solution at hypothermia for 6 or 12 hours before perfusion with homologous blood for 60 minutes using ex vivo system Isolated Perfused Rat or Guinea Pig Lung System (Harvard Apparatus). Respiratory mechanics, pulmonary weight, pulmonary artery pressure (PAP), and relative lung oxygenation capacity (ROC) measurements were obtained every 10 minutes. RESULTS: Comparing tidal volume (TV), compliance, resistance, ROC, PAP, and pulmonary weight the LPD, HTK, and saline group did not differ at 6 and 12 hours. The TV was higher in the lungs with 6-hour ischemia in the LPD, HTK, and saline groups. Compliance was higher in the lungs with 6-hour ischemia in the LPD and saline groups. There were no differences in ROC values comparing lungs with 6- versus 12-hour ischemia in the LPD group. A significant difference was observed between lungs in the HTK and saline groups. Resistance was higher in the lungs with 12-hour ischemia among the LPD, HTK, and saline groups. There was a gradual weight increase in the lungs, particularly those undergoing 12-hour ischemia, despite the absence of a significant difference between groups. CONCLUSION: Rat lungs perfused with LPD and HTK preservation solutions showed similar reperfusion performances in this ex-vivo perfusion model.