Clindamycin Protects Nonhuman Primates Against Inhalational Anthrax But Does Not Enhance Reduction of Circulating Toxin Levels When Combined With Ciprofloxacin.

BACKGROUND: Inhalational anthrax is rare and clinical experience limited. Expert guidelines recommend treatment with combination antibiotics including protein synthesis-inhibitors to decrease toxin production and increase survival, although evidence is lacking. METHODS: Rhesus macaques exposed to an aerosol of Bacillus anthracis spores were treated with ciprofloxacin, clindamycin, or ciprofloxacin + clindamycin after becoming bacteremic. Circulating anthrax lethal factor and protective antigen were quantitated pretreatment and 1.5 and 12 hours after beginning antibiotics. RESULTS: In the clindamycin group, 8 of 11 (73%) survived demonstrating its efficacy for the first time in inhalational anthrax, compared to 9 of 9 (100%) with ciprofloxacin, and 8 of 11 (73%) with ciprofloxacin + clindamycin. These differences were not statistically significant. There were no significant differences between groups in lethal factor or protective antigen levels from pretreatment to 12 hours after starting antibiotics. Animals that died after clindamycin had a greater incidence of meningitis compared to those given ciprofloxacin or ciprofloxacin + clindamycin, but numbers of animals were very low and no definitive conclusion could be reached. CONCLUSION: Treatment of inhalational anthrax with clindamycin was as effective as ciprofloxacin in the nonhuman primate. Addition of clindamycin to ciprofloxacin did not enhance reduction of circulating toxin levels.

Clinical characteristics and outcomes of patients with Escherichia coli in airway samples.

PURPOSES: Escherichia coli is one of the most common pathogens in nosocomial and community-acquired infections, but is an uncommon respiratory pathogen. However, this pathogen may at times be seen in respiratory secretions. The study aims to determine the clinical and prognostic value of E. coli in respiratory secretions. METHODS: Cultures of respiratory secretions from hospitalized and outpatients between 2009 and 2016 were screened for isolation of E. coli. We defined three groups of patients: "Sensitive (S)"-growth of E. coli sensitive to all antimicrobials tested; Intermediate (I)-resistant to 1-2 antimicrobial classes; and "Resistant (R)"-resistant to at least three antibiotic classes. We compared factors associated with resistant strains and outcomes between the groups. RESULTS: Eighty patients with E. coli isolates from respiratory secretions were identified while screening 177 712 (4.5: 10 000 samples). Of the E. Coli-positive cultures, 11 were from ambulatory patients, 31 patients were hospitalized and 37 were hospitalized and intubated. Ten people had bronchiectasis and 29 had COPD. Patients with resistant E. coli had significantly more hospitalization days prior to positive culture (S = 1.2 ± 1.89 days, I = 1.23 ± 1.5 days and R = 3.7 ± 5.4 days, respectively; P = 0.002). Mortality was higher in patients with a resistant strain (R) versus (I) or (S) (76.7%, 31.8% and 26.7%, respectively; P < 0.0001) and remained significantly elevated after correction for prior hospital days. CONCLUSIONS: Pulmonary infection due to E. coli is uncommon. Isolation of resistant E. coli is associated with length of previous hospitalization, elevated mortality and may be viewed as a nosocomial pathogen.

Timing, distribution, and microbiology of infectious complications after necrotizing pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a common acute abdominal disease worldwide, and its incidence rate has increased annually. Approximately 20% of AP patients develop into necrotizing pancreatitis (NP), and 40% to 70% of NP patients have infectious complications, which usually indicate a worse prognosis. Infection is an important sign of complications in NP patients. AIM: To investigate the difference in infection time, infection site, and infectious strain in NP patients with infectious complications. METHODS: The clinical data of AP patients visiting the Department of General Surgery of Xuanwu Hospital of Capital Medical University from January 1, 2014 to December 31, 2018 were collected retrospectively. Enhanced computerized tomography or magnetic resonance imaging findings in patients with NP were included in the study. Statistical analysis of infectious bacteria, infection site, and infection time in NP patients with infectious complications was performed, because knowledge about pathogens and their antibiotic susceptibility patterns is essential for selecting an appropriate antibiotic. In addition, the factors that might influence the prognosis of patients were analyzed. RESULTS: In this study, 539 strains of pathogenic bacteria were isolated from 162 patients with NP infection, including 212 strains from pancreatic infections and 327 strains from extrapancreatic infections. Gram-negative bacteria were the main infectious species, the most common of which were Escherichia coli and Pseudomonas aeruginosa. The extrapancreatic infection time (9.1 ± 8.8 d) was earlier than the pancreatic infection time (13.9 ± 12.3 d). Among NP patients with early extrapancreatic infection (< 14 d), bacteremia (25.12%) and respiratory tract infection (21.26%) were predominant. Among NP patients with late extrapancreatic infection (> 14 d), bacteremia (15.94%), respiratory tract infection (7.74%), and urinary tract infection (7.71%) were predominant. Drug sensitivity analysis showed that P. aeruginosa was sensitive to enzymatic penicillins, third- and fourth-generation cephalosporins, and carbapenems. Acinetobacter baumannii and Klebsiella pneumoniae were sensitive only to tigecycline; Staphylococcus epidermidis and Enterococcus faecium were highly sensitive to linezolid, tigecycline, and vancomycin. CONCLUSION: In this study, we identified the timing, the common species, and site of infection in patients with NP.

Antibiotic-resistant Pseudomonas aeruginosa infection in patients with bronchiectasis: prevalence, risk factors and prognostic implications.

Background and aims: Pseudomonas aeruginosa (PA) is the most common pathogen in bronchiectasis and frequently develops resistance to multiple classes of antibiotics, but little is known about the clinical impacts of PA-resistant (PA-R) isolates on bronchiectasis. We, therefore, investigated the prevalence, risk factors and prognostic implications of PA-R isolates in hospitalized bronchiectasis patients. Patients and methods: Between June 2011 and July 2016, data from adult bronchiectasis patients isolated with PA at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. PA was classified as PA-R in case antibiogram demonstrated resistance on at least one occasion. Results: Seven hundred forty-seven bronchiectasis patients were assessed. Of these, 147 (19.7%) had PA isolate in the sputum or bronchoscopic culture. PA-R and PA-sensitive accounted for 88 (59.9%) and 59 (31.1%) patients, respectively. In multivariate model, factors associated with PA-R isolate in bronchiectasis included prior exposure to antibiotics (odds ratio [OR] =6.18), three or more exacerbations in the previous year (OR =2.81), higher modified Medical Research Council dyspnea scores (OR =1.93) and greater radiologic severity (OR =1.15). During follow-up (median: 26 months; interquartile range: 6-59 months), 36 patients died, of whom 24 (66.7%) had PA-R isolate at baseline. However, PA-R isolate was not associated with greater all-cause mortality in bronchiectasis. Conclusion: PA-R infection is common among bronchiectasis patients, mainly determined by prior exposure to antibiotics, frequent exacerbations, more pronounced dyspnea and more severe radiologic involvement. However, PA-R isolate is not an independent risk factor for all-cause mortality in bronchiectasis.

Therapeutic effect of vitamin D in acute lower respiratory infection: A randomized controlled trial.

OBJECTIVES: To study the effect of vitamin D supplementation on the outcome of acute lower respiratory infection in hospitalized children. STUDY DESIGN: This is an open label parallel group randomized trial. Total of 154 children aged 2 mo-5 yrs (mean age 13 mo) admitted with acute lower respiratory infection (ALRI) were randomized to receive standard care therapy alone or standard care therapy for the respiratory infection along with a single oral dose of 100,000 IU of vitamin D3. Serum 25(OH)D levels were measured at admission in all the children and 72 h after administration of vitamin D in the supplemented group. Primary outcome measured was the duration of hospital stay. Secondary outcomes measured were mortality, incidence of complications, admission to PICU and recurrence of respiratory infections within 90 days of discharge. Primary outcome was compared using Mann Whitney U test and secondary outcomes were compared using chi-square or Fischer's exact test. RESULTS: Baseline characteristics were comparable between the two groups. There was no statistically significant difference in the primary outcome (Median duration of hospital stay in both the groups) and also in secondary outcomes (mortality, PICU admission, complications and recurrence of respiratory infections within 90 days of discharge). CONCLUSION: Single oral dose of 100,000 IU of vitamin D3 did not lead to reduction in duration of hospital stay, mortality, PICU admission or complications related to ALRI when compared to standard therapy alone in under five children hospitalized with ALRI but was able to achieve serum vitamin D sufficiency within 72 h of administration. Registered under clinical trial Registry of India Identifier no: CTRI/2014/09/005032.

The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Bacillus anthracis Infection in BALB/c Mice and Cynomolgus Macaques.

The fluorocycline TP-271 was evaluated in mouse and nonhuman primate (NHP) models of inhalational anthrax. BALB/c mice were exposed by nose-only aerosol to Bacillus anthracis Ames spores at a level of 18 to 88 lethal doses sufficient to kill 50% of exposed individuals (LD50). When 21 days of once-daily dosing was initiated at 24 h postchallenge (the postexposure prophylaxis [PEP] study), the rates of survival for the groups treated with TP-271 at 3, 6, 12, and 18 mg/kg of body weight were 90%, 95%, 95%, and 84%, respectively. When 21 days of dosing was initiated at 48 h postchallenge (the treatment [Tx] study), the rates of survival for the groups treated with TP-271 at 6, 12, and 18 mg/kg TP-271 were 100%, 91%, and 81%, respectively. No deaths of TP-271-treated mice occurred during the 39-day posttreatment observation period. In the NHP model, cynomolgus macaques received an average dose of 197 LD50 of B. anthracis Ames spore equivalents using a head-only inhalation exposure chamber, and once-daily treatment of 1 mg/kg TP-271 lasting for 14 or 21 days was initiated within 3 h of detection of protective antigen (PA) in the blood. No (0/8) animals in the vehicle control-treated group survived, whereas all 8 infected macaques treated for 21 days and 4 of 6 macaques in the 14-day treatment group survived to the end of the study (56 days postchallenge). All survivors developed toxin-neutralizing and anti-PA IgG antibodies, indicating an immunologic response. On the basis of the results obtained with the mouse and NHP models, TP-271 shows promise as a countermeasure for the treatment of inhalational anthrax.

Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age.

BACKGROUND: Vitamin A deficiency (VAD) is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to many adverse health consequences, including death. Based on prior evidence and a previous version of this review, the World Health Organization has continued to recommend vitamin A supplementation for children aged 6 to 59 months. There are new data available from recently published randomised trials since the previous publication of this review in 2010, and this update incorporates this information and reviews the evidence. OBJECTIVES: To assess the effects of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged six months to five years. SEARCH METHODS: In March 2016 we searched CENTRAL, Ovid MEDLINE, Embase, six other databases, and two trials registers. We also checked reference lists and contacted relevant organisations and researchers to identify additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster-RCTs evaluating the effect of synthetic VAS in children aged six months to five years living in the community. We excluded studies involving children in hospital and children with disease or infection. We also excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods, or beta-carotene supplementation. DATA COLLECTION AND ANALYSIS: For this update, two reviewers independently assessed studies for inclusion and abstracted data, resolving discrepancies by discussion. We performed meta-analyses for outcomes, including all-cause and cause-specific mortality, disease, vision, and side effects. We used the GRADE approach to assess the quality of the evidence. MAIN RESULTS: We identified 47 studies (4 of which are new to this review), involving approximately 1,223,856 children. Studies took place in 19 countries: 30 (63%) in Asia, 16 of these in India; 8 (17%) in Africa; 7 (15%) in Latin America, and 2 (4%) in Australia. About one-third of the studies were in urban/periurban settings, and half were in rural settings; the remaining studies did not clearly report settings. Most of the studies included equal numbers of girls and boys and lasted about a year. The included studies were at variable overall risk of bias; however, evidence for the primary outcome was at low risk of bias. A meta-analysis for all-cause mortality included 19 trials (1,202,382 children). At longest follow-up, there was a 12% observed reduction in the risk of all-cause mortality for vitamin A compared with control using a fixed-effect model (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.93; high-quality evidence). This result was sensitive to choice of model, and a random-effects meta-analysis showed a different summary estimate (24% reduction: RR 0.76, 95% CI 0.66 to 0.88); however, the confidence intervals overlapped with that of the fixed-effect model. Nine trials reported mortality due to diarrhoea and showed a 12% overall reduction for VAS (RR 0.88, 95% CI 0.79 to 0.98; 1,098,538 participants; high-quality evidence). There was no significant effect for VAS on mortality due to measles, respiratory disease, and meningitis. VAS reduced incidence of diarrhoea (RR 0.85, 95% CI 0.82 to 0.87; 15 studies; 77,946 participants; low-quality evidence) and measles (RR 0.50, 95% CI 0.37 to 0.67; 6 studies; 19,566 participants; moderate-quality evidence). However, there was no significant effect on incidence of respiratory disease or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR 1.97, 95% CI 1.44 to 2.69; 4 studies; 10,541 participants; moderate-quality evidence). AUTHORS' CONCLUSIONS: Vitamin A supplementation is associated with a clinically meaningful reduction in morbidity and mortality in children. Therefore, we suggest maintaining the policy of universal supplementation for children under five years of age in populations at risk of VAD. Further placebo-controlled trials of VAS in children between six months and five years of age would not change the conclusions of this review, although studies that compare different doses and delivery mechanisms are needed. In populations with documented vitamin A deficiency, it would be unethical to conduct placebo-controlled trials.

Persistence of antimicrobial resistance in respiratory streptococci.

OBJECTIVES: To assess whether persistence of antimicrobial resistance (i.e. non-susceptible resistance status) after treatment with penicillins or cephalosporins versus macrolides or tetracyclines differs and to compare the results obtained using routinely collected data with findings reported in prospective studies. METHODS: Routinely collected microbiological data from 14 voluntary participating laboratories (2005) containing information on resistance status and individual antimicrobial consumption patterns (mid 2004-2005) were analysed using a generalised estimating equation (GEE) approach. The link function was adjusted to acknowledge that the proportion of resistant isolates in the population not treated with antibiotics [baseline resistance (BR)] is not necessarily zero. To optimise the comparability of this study with prospective studies, the analysis was repeated after removal of 14 isolates from patients who did not survive 2005. RESULTS: BR estimates were unstable and their confidence intervals were wide, which called for a sensitivity analysis using an adjusted GEE model with three different BR estimates. All models indicated that the proportion of susceptible isolates differed by treatment group and increased significantly over time, with this increase being independent of treatment group. Persistence of resistance after exposure to macrolides or tetracyclines was approximately three times as long as after exposure to penicillins or cephalosporins. CONCLUSIONS: Resistance following treatment with macrolides or tetracyclines persists longer than following treatment with penicillins or cephalosporins, which confirms the findings from prospective studies and suggests the use of routinely collected data as a valuable alternative to determine such differences in persistence of resistance.

Obiltoxaximab Prevents Disseminated Bacillus anthracis Infection and Improves Survival during Pre- and Postexposure Prophylaxis in Animal Models of Inhalational Anthrax.

The Centers for Disease Control and Prevention recommend adjunctive antitoxins when systemic anthrax is suspected. Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. The impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indication are presented here. New Zealand White rabbits and cynomolgus macaques received obiltoxaximab as a single intramuscular or intravenous dose of 2 to 16 mg/kg of body weight at various times relative to Bacillus anthracis aerosol spore challenge. The primary endpoint was survival, and effect of treatment timing was explored. In rabbits, obiltoxaximab administration 9 h postchallenge singly or combined with a 5-day levofloxacin regimen protected 89% to 100% of animals compared to 33% with levofloxacin monotherapy. In cynomolgus macaques, a single intramuscular dose of 16 mg/kg obiltoxaximab led to 100% survival when given 1 to 3 days preexposure and 83% to 100% survival when given 18 to 24 h postexposure and prior to systemic bacteremia onset. Obiltoxaximab administration after bacteremia onset resulted in lower (25% to 50%) survival rates reflective of treatment setting. Prophylactic administration of obiltoxaximab before spore challenge or to spore-challenged animals before systemic bacterial dissemination is efficacious in promoting survival, ameliorating toxemia, and inhibiting bacterial spread to the periphery.

[Experience of using bacteriophages and bitsillin-5 to reduce the incidence of respiratory diseases of bacterial ethiology in military personnel].

The authors defined epidemiological efficacy and safety of the use of bacteriophages(streptococcal, staphylococcal, piobakferiophage multipartial) and bitsillin-5 to reduce tonsillitis morbidityand other respiratory diseases with bacterial etiology in groups of servicemen during their formationagainst increase of seasonal morbidity. The results of the use of these preventive agents were evaluatedby a comparative analysis of this disease in experimental and control groups. In total 510 healthy conscriptswere involved into the study. The effectiveness of prophylactic use of bacteriophages and bitsillin-5, whichprovided a reduction in the incidence of respiratory infections of bacterial ethiology, tonsillitis, and otherrespiratory diseases is showed. Recommendations on the choice of drugsfor the prevention of these infections,methods and organization of their application in organized groups are given.

Vitamin D supplementation for the prevention of childhood acute respiratory infections: a systematic review of randomised controlled trials.

Results from recent trials assessing the effect of vitamin D supplementation on the prevention of childhood acute respiratory infections (ARI) have been inconsistent. In the present study, we determined whether vitamin D supplementation prevents ARI in healthy children and repeated infections in children with previous ARI. We conducted a systematic literature search using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The search included only randomised controlled clinical trials (RCT) comparing vitamin D supplementation with either placebo or no intervention in children younger than 18 years of age. We identified seven RCT and found that the summary estimates were not statistically significantly associated with a reduction in the risk of ARI (relative risk (RR) 0·79, 95% CI 0·55, 1·13), all-cause mortality (RR 1·18, 95% CI 0·71, 1·94), or the rate of hospital admission due to respiratory infection in healthy children (RR 0·95, 95% CI 0·72, 1·26). However, in children previously diagnosed with asthma, vitamin D supplementation resulted in a 74% reduction in the risk of asthma exacerbation (RR 0·26, 95% CI 0·11, 0·59; test of heterogeneity, I 2= 0·0%). Our findings indicate a lack of evidence supporting the routine use of vitamin D supplementation for the prevention of ARI in healthy children; however, they suggest that such supplementation may benefit children previously diagnosed with asthma. Due to the heterogeneity of the included studies and possible publication biases related to this field, these results should be interpreted with caution.

Zinc supplementation in young children: A review of the literature focusing on diarrhoea prevention and treatment.

BACKGROUND & AIMS: It is estimated that zinc deficiency is responsible for 4.4% of childhood deaths in Africa, Asia, and Latin America. This review examines the impact of zinc supplementation, administered prophylactically or therapeutically, on diarrhoea. METHODS: Relevant published articles were identified through systematic searches of electronic databases. Bibliographies of retrieved articles were examined. RESULTS: A total of 38 studies were included in this review, 29 studies examined the effect of prophylactic zinc and nine studies examined the effects of therapeutic use of zinc for treatment of diarrhoea in children under five years. CONCLUSION: Prophylactic zinc has been shown to be effective in decreasing both prevalence and incidence of diarrhoea, reducing respiratory infections and improving growth in children with impaired nutritional status. There is less conclusive evidence of reduction in diarrhoea duration or diarrhoea severity. While prophylactic zinc decreases mortality due to diarrhoea and pneumonia, it has not been shown to affect overall mortality. Therapeutic use of zinc for the treatment of diarrhoea in children has been shown to reduce diarrhoea incidence, stool frequency and diarrhoea duration as well as respiratory infections in zinc deficient children. However, stool output is only reduced in children with cholera. Less conclusive evidence exists for therapeutic zinc reducing mortality due to diarrhoea and respiratory infections. Specific definitions of diarrhoea severity, respiratory infection in further studies as well as examination of prophylactic zinc effectiveness in diarrhoea duration and severity effectiveness of therapeutic zinc in reducing mortality due to diarrhoea and respiratory infections are warranted.

Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years of age.

BACKGROUND: Zinc deficiency is prevalent in low- and middle-income countries, and contributes to significant diarrhoea-, pneumonia-, and malaria-related morbidity and mortality among young children. Zinc deficiency also impairs growth. OBJECTIVES: To assess the effects of zinc supplementation for preventing mortality and morbidity, and for promoting growth, in children aged six months to 12 years of age. SEARCH METHODS: Between December 2012 and January 2013, we searched CENTRAL, MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, Embase, African Index Medicus, Conference Proceedings Citation Index, Dissertation Abstracts, Global Health, IndMED, LILACS, WHOLIS, metaRegister of Controlled Trials, and WHO ICTRP. SELECTION CRITERIA: Randomised controlled trials of preventive zinc supplementation in children aged six months to 12 years compared with no intervention, a placebo, or a waiting list control. We excluded hospitalised children and children with chronic diseases or conditions. We excluded food fortification or intake, sprinkles, and therapeutic interventions. DATA COLLECTION AND ANALYSIS: Two authors screened studies, extracted data, and assessed risk of bias. We contacted trial authors for missing information. MAIN RESULTS: We included 80 randomised controlled trials with 205,401 eligible participants. We did not consider that the evidence for the key analyses of morbidity and mortality outcomes were affected by risk of bias. The risk ratio (RR) for all-cause mortality was compatible with a reduction and a small increased risk of death with zinc supplementation (RR 0.95, 95% confidence interval (CI) 0.86 to 1.05, 14 studies, high-quality evidence), and also for cause-specific mortality due to diarrhoea (RR 0.95, 95% CI 0.69 to 1.31, four studies, moderate-quality evidence), lower respiratory tract infection (LRTI) (RR 0.86, 95% CI 0.64 to 1.15, three studies, moderate-quality evidence), or malaria (RR 0.90, 95% CI 0.77 to 1.06, two studies, moderate-quality evidence).Supplementation reduced diarrhoea morbidity, including the incidence of all-cause diarrhoea (RR 0.87, 95% CI 0.85 to 0.89, 26 studies, moderate-quality evidence), but the results for LRTI and malaria were imprecise: LRTI (RR 1, 95% CI 0.94 to 1.07, 12 studies, moderate-quality evidence); malaria (RR 1.05, 95% 0.95 to 1.15, four studies, moderate-quality evidence).There was moderate-quality evidence of a very small improvement in height with supplementation (standardised mean difference (SMD) -0.09, 95% CI -0.13 to -0.06; 50 studies), but the size of this effect might not be clinically important. There was a medium to large positive effect on zinc status.Supplementation was associated with an increase in the number of participants with at least one vomiting episode (RR 1.29, 95% CI 1.14 to 1.46, five studies, high-quality evidence). We found no clear evidence of benefit or harm of supplementation with regard to haemoglobin or iron status. Supplementation had a negative effect on copper status. AUTHORS' CONCLUSIONS: In our opinion, the benefits of preventive zinc supplementation outweigh the harms in areas where the risk of zinc deficiency is relatively high. Further research should determine optimal intervention characteristics such as supplement dose.

A multicenter case-case control study for risk factors and outcomes of extensively drug-resistant Acinetobacter baumannii bacteremia.

OBJECTIVE: Extensively drug resistant (XDR) Acinetobacter baumannii infections are increasing. Knowledge of risk factors can help to prevent these infections. METHODS: We designed a 1∶1∶1 case-case-control study to identify risk factors for XDR A. baumannii bacteremia in Singapore and Thailand. Case group 1 was defined as having infection due to XDR A. baumannii, and case group 2 was defined as having infection due to non-XDR A. baumannii. The control group comprised patients with blood cultures obtained to determine possible infection. RESULTS: There were 93 patients in each group. Pitt bacteremia score (adjusted odds ratio [aOR], 2.570 [95% confidence interval (CI), 1.528-4.322]), central venous catheters (CVCs; aOR, 12.644 [95% CI, 2.143-74.620]), use of carbapenems (aOR, 54.391 [95% CI, 3.869-764.674]), and piperacillin-tazobactam (aOR, 55.035 [95% CI, 4.803-630.613]) were independently associated with XDR A. baumannii bacteremia. In case group 2, Pitt bacteremia score (aOR, 1.667 [95% CI, 1.265-2.196]) and third-generation cephalosporins (aOR, 2.965 [95% CI, 1.224-7.182]) were independently associated with non-XDR A. baumannii bacteremia. Concurrent infections (aOR, 3.527 [95% CI, 1.479-8.411]), cancer (aOR, 3.172 [95% CI, 1.135-8.865]), and respiratory source (aOR, 2.690 [95% CI, 1.160-6.239]) were associated with an increased risk of 30-day mortality. Survivors received more active empirical therapy (16.7% vs 9.6%; P = .157), had fewer cases of XDR bacteremia (45.8% vs 52.6%; P = .452), and received higher median definitive polymyxin B doses (840,000 units vs 700,000 units; P = .339) CONCLUSIONS: Use of CVC and broad spectrum antibiotics were unique risk factors of XDR A. baumannii bacteremia. Effective antimicrobial stewardship together with use of a CVC bundle may reduce the incidence of these infections. Risk factors of acquisition and mortality may help identify patients for early initiation of polymyxin B therapy.

Use of adjuvant intralesional bevacizumab for aggressive respiratory papillomatosis in children.

IMPORTANCE: Juvenile recurrent respiratory papillomatosis (RRP) can be an aggressive disease process necessitating frequent trips to the operating room with multiple anesthetics for tumor debulking and airway preservation. Adjuvant therapy, such as that which is reported in this article, may help reduce the number of operative procedures affected children need each year and therefore may also affect their overall quality of life (QOL). OBJECTIVE: To describe our experience with intralesional bevacizumab (Avastin) treatment for children with severe RRP by comparing median number of surgical procedures per year, median duration of time between procedures, Derkay staging, and voice QOL before and after bevacizumab treatment. DESIGN: Prospective, consecutive case series. SETTING: Tertiary care aerodigestive center. PARTICIPANTS: Ten children, aged 18 months to 18 years, with severe RRP necessitating more than 4 operative interventions in 1 year whose parents (or legal guardians) consented to intralesional bevacizumab treatment. INTERVENTIONS: Intralesional bevacizumab administered at concentration of 2.5 mg/mL for 3 consecutive injections (with 532-nm pulsed KTP [potassium titanyl phosphate] laser when necessary) at intervals of 2 to 3 weeks. MAIN OUTCOME MEASURES: Time between surgical procedures, number of procedures per year, Derkay staging, total Pediatric Voice-Related Quality of Life (PVRQOL) score, Emotional PVRQOL score, and Physical PVRQOL score defined by comparing the year leading up to first of 3 bevacizumab injections with the year following the third bevacizumab injection. RESULTS: The median duration of time between surgical procedures increased by 5.9 weeks after bevacizumab (P = .002). The median number of procedures per year decreased by 4 (P = .002). Derkay staging decreased by 6 (P = .03). The median total PVRQOL score increased by 25.5 (P = .02), the median Emotional PVRQOL score increased by 11.3 (P = .047), and the median Physical PVRQOL score increased by 14.3 (P = .047). CONCLUSIONS AND RELEVANCE: Intralesional bevacizumab treatment may increase duration of time between surgical procedures and decrease number of procedures per year, while improving voice QOL.

Newborn calf welfare: a review focusing on mortality rates.

Calf mortality control is vitally important for farmers, not only to improve animal welfare, but also to increase productivity. High calf mortality rates can be related to larger numbers of calves in a herd, employee performance, severe weather, and the neonatal period covering the first 4 weeks of life. Although the basic premise of preventing newborn calf mortality is early detection and treatment of calves at risk for failure of passive transfer of immunoglobulins, calf mortality due to infectious diseases such as acute diarrhea increases in the presence of these physical and psychological stressors. This suggests that farmers should not ignore the effects of secondary environmental factors. For prevention rather than cure, the quality of the environment should be improved, which will improve not only animal welfare but also productivity. This paper presents a review of the literature on newborn calf mortality and discusses its productivity implications.

Doença respiratória aguda na criança: uma revisão integrativa / Acute respiratory disease in the child: an integrative review / Enfermedad respiratoria aguda en el niño: una revisión integradora

Este estudo teve por objetivo mapear as produções científicas nacionais e internacionais sobre a doença respiratória aguda na criança. A revisão ocorreu em julho de 2010, nas bases de dados LILACS, SciELO e MEDLINE, a partir da relação entre os descritores doenças respiratórias e criança. Foram selecionadas 53 publicações na íntegra, no período de 1988 a 2009, segundo critérios de inclusão/exclusão. Diante das lacunas encontradas, sugerimos a realização de estudos com ênfase no aspecto sociocultural e enfoque no cuidado, bem como uma abordagem qualitativa, pois foi constatado que grande parte dos estudos analisados encontra-se no nível de evidência 4, devido à sua natureza descritiva (estudos não experimentais). Além disso, torna-se imprescindível que essas produções estejam publicadas na íntegra, para estabelecer adequadamente a divulgação do conhecimento.

This study aimed to map Brazilian and international scientific papers on acute respiratory disease in children. The review was carried out in July 2010 in the LILACS, SciELO and MEDLINE databases through the relation between the descriptors respiratory tract diseases and child. Fifty-three full papers published from 1988 to 2009 were selected according to inclusion/exclusion criteria. Considering the gaps found, we suggest studies be conducted with an emphasis on sociocultural aspects and a focus on care, as well as a qualitative approach, because a large portion of the studies analyzed were found to be at Level of Evidence 4, due to their descriptive (non-experimental) design. It is also vital that these works be published in full text form, to assure proper dissemination of the knowledge.

Este estudio objetivó mapear las producciones científicas nacionales e internacionales acerca de la enfermedad respiratoria aguda en el niño. La revisión se llevó a cabo en julio de 2010, en las bases de datos LILACS, SciELO y MEDLINE, a partir de la relación entre los descriptores enfermedades respiratorias y niño. Fueron seleccionadas 53 publicaciones en su totalidad, en el periodo de 1988 hasta 2009, según criterios de inclusión/exclusión. Delante de las lagunas encontradas, sugerimos el desarrollo de estudios con énfasis en el aspecto sociocultural y enfoque en el cuidado, así como un abordaje cualitativo, pues se constató que una gran parte de los estudios analizados se encuentra en el nivel de evidencia 4, debido a su naturaleza descriptiva (estudios no experimentales). Además, se torna imprescindible que esas producciones sean publicadas en su totalidad, para establecer de modo adecuado la divulgación del conocimiento.

The effect of neoadjuvant chemoradiotherapy on airway colonization and postoperative respiratory complications in patients undergoing oesophagectomy for oesophageal cancer.

Respiratory complication is one of the important postoperative complications of oesophageal cancer. The aim of this study was to evaluate whether neoadjuvant chemotherapy before surgery is effective for postoperative respiratory complications. In this study, patients with oesophageal cancer were divided into two group: one with neoadjuvant therapy and the other without neoadjuvant therapy. Before surgery, they all underwent bronchoscopy and bronchoalveolar lavage. We evaluated respiratory complications and the effects of preoperative neoadjuvant therapy. Forty patients (M/F = 23/17 and mean age 61 years) were enrolled in this study. Twenty-two cases had cancer in the middle part and 18 in the lower part of the oesophagus. Significant correlation was observed between the number of positive micro-organism and difficulty in weaning and receiving neoadjuvant therapy. But no significant correlation was found between neoadjuvant therapy and respiratory complications.

Mortality following nursing home-acquired lower respiratory infection: LRI severity, antibiotic treatment, and water intake.

OBJECTIVE: In some nursing home populations, antibiotic treatment may not reduce mortality following lower respiratory infection (LRI). To better inform treatment decisions, we determined influences on mortality following LRI among antibiotic-treated and non-antibiotic-treated residents in 2 populations. DESIGN: Observational, prospective, cohort studies. SETTING: Ninety-seven nursing homes (36 US, 61 Netherlands). PARTICIPANTS: Residents (1044 US, 513 Netherlands) who met a standardized study definition for LRI. MEASUREMENTS: Demographics, symptoms and physical findings of LRI, functional status, major illness diagnoses, dementia status, treatments, and date of death within 6 months after diagnosis. METHODS: We estimated a 2-period (0-14/15-90 days) weighted proportional hazards model of mortality for antibiotic-treated (n = 1280) and non-antibiotic-treated (n = 277) residents; both weights and regressors provide "doubly robust" risk adjustment-for LRI (illness) severity using a prognostic score and for nonrandom receipt of antibiotic treatment using a propensity score. RESULTS: In both the United States and the Netherlands, 14-day mortality was associated with three factors-LRI severity, water intake at diagnosis, and antibiotic use (not directly by severe dementia)-that accounted for 82% or, sequentially, 39%, 42%, and 1% of the cross-national mortality difference. The LRI Severity Score (based only on at-diagnosis eating dependency, pulse rate, decreased alertness, and breathing difficulty, with adequate discrimination [c ≥ 0.74] and calibration, and cross-indexed to commonly used LRI mortality measures) was related to mortality through 90 days, regardless of treatment. With sufficient water intake at diagnosis, 14-day mortality was unrelated to not receiving antibiotic treatment (adjusted hazard ratio [AHR], 1.20; 95% confidence interval, 0.70-2.04); insufficient water intake was related to increased 14-day mortality with antibiotics (AHR, 1.90; 1.38-2.60) or without (AHR, 7.12; 4.83-10.5). After 14 days, relative mortality worsened for antibiotic-treated residents with insufficient water intake. Inadequate water intake was related to increased eating dependence at onset of the LRI (OR, 4.2; 3.0-5.8). CONCLUSION: LRI severity, water intake, and antibiotic use explain mortality in both studies and reconcile cross-study Dutch/US 14-day mortality differences. LRI severity, derived at 14 days, is related to mortality through 90 days, regardless of treatment, and is key to risk adjustment. With adequate hydration, the survival benefit from antibiotic use is nonsignificant. Conversely, hydration, even without antibiotic treatment, appears central to curative treatment. In LRI guidelines, treatment, and research, the relative benefits of antibiotics and hydration for curative treatment should be addressed.