A retrospective study on the outcome of children with extensively drug-resistant gram-negative infection treated with Colistin vs. other Antimicrobials

Introduction@#The increasing trend of extensively drug-resistant gram-negative infections led to the reconsideration of colistin as a valuable therapeutic option.@*Objectives@#To describe the clinical profile and treatment response of children with extensively drug resistant (XDR) Gram-negative infections given colistin versus other antimicrobials.@*Methods@#This retrospective descriptive study involved patients treated for XDR Gram-negative infections from January 2014 to June 2017 in a tertiary hospital in Metro Manila. Descriptive statistics were used to summarize clinical characteristics of subjects. Treatment response to colistin versus other antimicrobial agents were compared in terms of success, failure, and toxicity. The Fisher-exact and Mann Whitney U tests were used to assess statistical differences between the colistin and non-colistin groups. @*Results@#Majority of patients with XDR Gramnegative infections had previous antibiotic exposure. More patients in the colistin group received TPN 43.2% vs 23.7% (p=0.035), had a longer hospital stay prior to the onset of XDR Gram-negative infection, 27 days vs. 15.5 days (p=0.001), and had a longer total hospital stay with a median of 52 days vs 30 days (p < 0.001). Treatment success was significantly higher in the colistin group at 70.3%, as against 46.5% in the non-colistin group (p=0.014). There was no difference in the treatment duration of both groups. The colistin group had longer time to clinical response, with a mean of 6.27 (+ 3.57) days compared with those from the non-colistin group, with a mean of 4.36 (+ 1.77)(p=0.008). The colistin group had more fungal infections during the course of treatment (p=0.001).@*Conclusion@#Based on our institutional experience, colistin is considered relatively effective and safe in treating XDR Gram-negative infections in children.

Association of increased platelet-associated immunoglobulins with thrombocytopenia and the severity of disease in secondary dengue virus infections.

Severe thrombocytopenia and increased vascular permeability are two major characteristics of dengue haemorrhagic fever (DHF). To develop a better understanding of the roles of platelet-associated IgG (PAIgG) and IgM (PAIgM) in inducing thrombocytopenia and its severity of disease in patients with secondary dengue virus infection, the relationship between the PAIgG or PAIgM levels and disease severity as well as thrombocytopenia was examined in 78 patients with acute phase secondary infection in a prospective hospital-based study. The decrease in platelet count during the acute phase recovered significantly during the convalescent phase. In contrast, the increased levels of PAIgG or PAIgM that occurred during the acute phase of these patients decreased significantly during the convalescent phase. An inverse correlation between platelet count and PAIgG or PAIgM levels was found in these patients. Anti-dengue virus IgG and IgM activity was found in platelet eluates from 10 patients in an acute phase of secondary infection. Increased levels of PAIgG or PAIgM were significantly higher in DHF than those in dengue fever (DF). An increased level of PAIgM was associated independently with the development of DHF, representing a possible predictor of DHF with a high specificity. Our present data suggest that platelet-associated immunoglobulins involving antidengue virus activity play a pivotal role in the induction of thrombocytopenia and the severity of the disease in secondary dengue virus infections.

Age, temperature, and parasitaemia predict chloroquine treatment failure and anaemia in children with uncomplicated Plasmodium falciparum malaria.

The prevalence of chloroquine-resistant Plasmodium falciparum malaria has been increasing in sub-Saharan Africa and parts of South America over the last 2 decades, and has been associated with increased anaemia-associated morbidity and higher mortality rates. Prospectively collected clinical and parasitological data from a multicentre study of 788 children aged 6-59 months with uncomplicated P. falciparum malaria were analysed in order to identify risk factors for chloroquine treatment failure and to assess its impact on anaemia after therapy. The proportion of chloroquine treatment failures (combined early and late treatment failures) was higher in the central-eastern African countries (Tanzania, 53%; Uganda, 80%; Zambia, 57%) and Ecuador (54%) than in Ghana (36%). Using logistic regression, predictors of early treatment failure included younger age, higher baseline temperature, and greater levels of parasitaemia. We conclude that younger age, higher initial temperature, and higher baseline parasitaemia predict early treatment failure and a higher probability of worsening anaemia between admission and days 7 or 14 post-treatment.

The beneficial effects of weekly low-dose vitamin A supplementation on acute lower respiratory infections and diarrhea in Ecuadorian children.

BACKGROUND: Previous studies of large-dose vitamin A supplementation on respiratory morbidity have produced conflicting results in a variety of populations. The influence of malnutrition has not been examined in the majority of these trials. We hypothesized that weekly low-dose vitamin A supplementation would prevent respiratory and diarrheal disease morbidity and that malnutrition might influence the efficacy of vitamin A supplementation. METHODS: In a randomized, double-blind, placebo-controlled field trial of 400 children, 6 to 36 months of age in a high Andean urban slum, half of the children received 10 000 IU of vitamin A weekly and half received placebo for 40 weeks. Children were visited weekly at home by physicians and assessed for acute diarrheal disease and acute respiratory infections. RESULTS: Acute diarrheal disease and acute respiratory infection did not differ globally or by severity between supplement-treated and placebo groups. However, the incidence of acute lower respiratory infection (ALRI) was significantly lower in underweight (weight-for-age z score [WAZ] <-2 SD) supplement-treated children than in underweight children on placebo (8.5 vs 22.3 per 10(3) child-weeks; rate ratio: 0.38 [95% CI: 0.17-0.85]). ALRI incidence was significantly higher in normal-weight (WAZ >-2 SD) supplement-treated children than in normal-weight children on placebo (9.8 vs 4.4 per 10(3) child-weeks; rate ratio: 2.21 [95% CI: 1.24-3.93]). By logistic regression analysis the risk of ALRI was lower in underweight supplement-treated children than in underweight children on placebo (point estimate 0.148 [95% CI: 0.034-0.634]). In contrast, risk of ALRI was higher in normal-weight supplement-treated children (WAZ >-1 SD to mean) than in normal-weight children on placebo in the same WAZ stratum (point estimate: 2.51 [95% CI: 1.24-5.05]). The risk of severe diarrhea was lower in supplement-treated children 18 to 23 months of age than in children on placebo in this age group (point estimate: 0.26 [95% CI: 0.06-1.00]). CONCLUSIONS: Weekly low-dose (10 000 IU) vitamin A supplementation in a region of subclinical deficiency protected underweight children from ALRI and paradoxically increased ALRI in normal children with body weight over -1 SD. Protection from severe diarrhea was consistent with previous trials. Additional research is warranted to delineate potential beneficial and detrimental interactions between nutritional status and vitamin A supplementation regarding ALRI.

Effects of short-term zinc supplementation on cellular immunity, respiratory symptoms, and growth of malnourished Equadorian children.

OBJECTIVE: To assess the effect of zinc supplementation on respiratory tract disease, immunity and growth in malnourished children. DESIGN: A randomized double-blind placebo-controlled trial. SETTING: A day-care center in Quito, Ecuador. SUBJECTS: Fifty children (12-59 months old) recruited by height-for-age and weight-for-age deficit. INTERVENTIONS: Twenty-five children (supplemented, S group) received 10 mg/day of zinc as zinc sulfate, and 25 (nonsupplemented, NS group) received a placebo during 60 days. All were also observed during a 60-day postsupplementation period. Two children of the S group dropped out. Daily the clinical presence of cough, respiratory tract secretions, and fever, was recorded. On days 0,60 and 120, the cutaneous delayed-type hypersensitivity (DTH) to multiple antigens, and anthropometric parameters were assessed. On days 0 and 60 serum zinc levels were also measured. RESULTS: On day 60, DTH was significantly larger (20.8 +/- 7.1 vs 16.1 +/- 9.7 mm), and serum zinc levels were significantly higher (118.6 +/- 47.1 vs 83.1 +/- 24.5 micrograms/dl) in the S group than in the NS group (P <0.05 for each). The incidence of fever [relative risk (RR): 0.30, c.i. = 0.08- 0.95, P =0.02], cough (RR): 0.52, c.i. = 0.32-0.84, P = 0.004) and upper respiratory tract secretions (RR):0.72, c.i. = 0.59-0.88, P = 0.001) was lower in the S group than in the NS group at day 60. At the end of the postsupplementation observation period (day 120), the incidence of fever and upper respiratory tract secretions was the same in both the S and NS groups. The incidence of cough was higher at day 120 in the S group than in the NS group (RR): 2.28, c.i. = 1.37-3.83, P = 0.001). CONCLUSIONS: This study supports a role for zinc in immunity, and immunity to respiratory infections, while pointing out the need for larger studies.

Risk of diarrheal disease in Ecuadorian day-care centers.

To determine the risk for diarrheal disease (DD) in day-care centers (DCC) for children residing in a poor urban slum area of Quito, Ecuador, compared with that for children from the same environment but cared for in their own residential home (RH), a prospective age-, sex- and locale-controlled study of DD was conducted, including 115 children in DCC and 115 in RH, ages 12 to 42 months. The overall incidence of DD was 46/1000 child weeks. Diarrhea was more common in DCC than in RH (relative risk (RR), 1.75; 95% confidence interval (CI), 1.38 to 2.22; P < 0.001). Poor hygienic practices were more prevalent in DCC than in RH. The use of reused water for child handwashing before eating and for washing raw vegetables was associated with a higher risk of DD in DCC than in RH (RR = 4.08, CI 2.93 to 5.67, P < 0.001; RR = 3.90, CI 2.79 to 5.44, P < 0.001, respectively). These two practices were risk factors in the DCC (RR = 2.74, CI 2.08 to 3.68, P < 0.001; RR = 2.05, CI 1.55 to 2.71, P < 0.001, respectively) when compared with their absence in the same DCC. Shigella (RR = 3.58, CI 1.19 to 10.78, P < 0.02), Aeromonas (RR = 10.47, CI 1.35 to 81.05, P < 0.01), rotavirus (RR = 2.86, CI 1.87 to 4.39, P < 0.001) and Giardia (RR = 1.59, CI 1.00 to 2.59, P < 0.05) were more common in DCC than in RH. More than two-fifths of the Shigella and Aeromonas isolates were resistant to trimethoprim-sulfamethoxazole.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety, immunogenicity and protective effect of the SPf66 malaria synthetic vaccine against Plasmodium falciparum infection in a randomized double-blind placebo-controlled field trial in an endemic area of Ecuador.

A total of 537 subjects were randomized to receive either SPf66 malaria vaccine against Plasmodium falciparum or placebo in three doses (days 0, 30 and 180). Subjects completing the course of vaccination (230 in the vaccine and 238 in the placebo group) were followed up for a further 12 months. Case detection surveillance was implemented by parasitological cross-sectional surveys every 2 months and by monthly household visits to each participant. Symptomatic subjects were also diagnosed in a local health centre. Minor local side-effects were observed mainly after the second dose in about 19% of the vaccinated subjects and in 3.7% of the placebo group. Thirty days after the third dose the prevalence of anti-SPf66 antibodies was 57% in the vaccine and 8.8% in the placebo groups. The prevaccination prevalence of antibodies measured by indirect immunofluorescence assay increased with age and seemed to be inversely related to anti-SPf66 antibody production. Immune response to SPf66 was independent of age. Vaccine efficacy was calculated based on person-time of exposure. The protective effect considering any malaria episode was 66.8% (95% confidence interval = -2.7-89.3%) and considering only one episode per individual was 60.2% (95% confidence interval = -26-87.5%).