Neonatal sepsis is the third leading cause of neonatal mortality and a major public health problem, especially in developing countries. Although recent medical advances have improved neonatal care, ...many challenges remain in the diagnosis and management of neonatal infections. The diagnosis of neonatal sepsis is complicated by the frequent presence of noninfectious conditions that resemble sepsis, especially in preterm infants, and by the absence of optimal diagnostic tests. Since neonatal sepsis is a high-risk disease, especially in preterm infants, clinicians are compelled to empirically administer antibiotics to infants with risk factors and/or signs of suspected sepsis. Unfortunately, both broad-spectrum antibiotics and prolonged treatment with empirical antibiotics are associated with adverse outcomes and increase antimicrobial resistance rates. Given the high incidence and mortality of sepsis in preterm infants and its long-term consequences on growth and development, efforts to reduce the rates of infection in this vulnerable population are one of the most important interventions in neonatal care. In this review, we discuss the most common questions and challenges in the diagnosis and management of neonatal sepsis, with a focus on developing countries.
Enteropathogenic Escherichia coli (EPEC) is an important diarrheal pathogen of young children. As the diagnosis of EPEC is now based mainly on molecular criteria, there has been an important change ...in its prevalence. The purpose of this study is to review the current epidemiology of EPEC infection and the new insights into its physiopathology.
Recent epidemiological studies indicate that atypical EPEC (aEPEC) is more prevalent than typical EPEC (tEPEC) in both developed and developing countries, and that aEPEC is important in both pediatric endemic diarrhea and diarrhea outbreaks. Therefore, it is important to further characterize the pathogenicity of these emerging strains. The virulence mechanisms and physiopathology of the attaching and effacing lesion (A/E) and the type three secretion-system (T3SS) are complex but well studied. A/E strains use their pool of locus of enterocyte effacement (LEE)-encoded and non-LEE-encoded effector proteins to subvert and modulate cellular and barrier properties of the host. However, the exact mechanisms of diarrhea in EPEC infection are not completely understood.
Remarkable progress has been made to identify virulence determinants required to mediate the pathogenesis of EPEC. However, fast, easy, and inexpensive diagnostic methods are needed in order to define optimal treatment and prevention for children in endemic areas.
Despite azithromycin being used in some countries to treat infections caused by Gram-negative pathogens, no resistance breakpoint for Escherichia coli exists. The aim of this study was to analyse the ...levels and mechanisms of azithromycin resistance in E. coli. The presence of chromosomal (rplD, rplV and 23S rRNA) mutations, 10 macrolide resistance genes (MRGs) and efflux pump overexpression was determined in 343 E. coli isolates. Overall, 89 (25.9%) isolates had MICs ≥ 32 mg/L to azithromycin, decreasing to 42 (12.2%) when assayed in the presence of Phe-Arg-β-Napthylamide, with 35 of these 42 possessing at least one MRG. Efflux pumps played a role in azithromycin resistance affecting the Minimal Inhibitory Concentration (MIC) levels of 91.2% isolates whereas chromosomal alterations seem to have a minimal role. At least one MRG was found in 22.7% of the isolates with mph(A) being the most commonly found gene. The mph(A) gene plays the main role in the development of azithromycin resistance and 93% of the mph(A)-carrying isolates showed a MIC of 32 mg/L. In the absence of a specific resistance breakpoint our results suggest a MIC of 32 mg/L to be considered in order to detect isolates carrying mechanisms able to confer azithromycin resistance.
Class 1 and Class 2 integrons are mobilizable elements able to carry a variety of antibiotic resistance determinants. In the present study, Class 1 and 2 integrons present in 355 pathogenic ...Escherichia coli (285 diarrheagenic, of these 129 were enteropathogenic, 90 enteroaggregative, 66 enterotoxigenic, and 70 bacteremic) isolated from healthy and ill children under age 5 from periurban areas of Lima, Peru, were characterized. The presence of integrase 1 and 2 was established by polymerase chain reaction (PCR), and variable regions were grouped by PCR-restriction fragment length polymorphism and subsequent sequencing. Antimicrobial resistance was established by disk diffusion. Ninety-seven isolates (27.3%) presented integrase 1, and 16 (4.5%) presented integrase 2 (P < 0.0001); in addition, seven (2.0%) isolates, six diarrheagenic and one bacteremic, presented both integrase genes. The presence of integrase 1 was more frequent among bacteremic isolates (P = 0.0004). Variable regions were amplified in 76/120 (63.3%) isolates with up to 14 gene arrangements. The most prevalent gene cassettes were those encoding dihydrofolate reductases as well as aminoglycoside modifying enzymes. Of note, Class 1 integrons tended to be associated with the presence of extended-spectrum β-lactamases (ESBLs). A variety of Class 1 and 2 integrons were detected in diarrheagenic and bacteremic E. coli, demonstrating the heterogeneity of variable regions circulating in the area. The association of integrons with ESBLs is worrisome and has an impact on the development of multidrug resistance.
The inappropriate use of antibiotics significantly contributes to the development of antibiotic resistance. There is limited information about the use of antibiotics among parents from rural areas in ...Peru. This study aimed to describe the knowledge, attitudes and practices towards antibiotics among parents of children < 5 years of age from rural communities in Peru; to explore the association between knowledge and attitudes towards antibiotics and to explore determinants of low knowledge and self-medicating his/her child with antibiotics.
Cross-sectional study in six rural primary health centres in Peru using a self-administered survey. Crude and adjusted Prevalence Ratios (PR), and 95% Confidence Intervals (95% CI) were calculated to explore determinants of low knowledge and of having self-medicated his/her child with antibiotics. Linear regression was used to explore the association between knowledge and attitudes.
A total of 231 parents were included. The largest gap in knowledge was among 183 parents (79%) who did not know that antibiotics cannot cure viral infections. The largest gap in attitudes was among 185 participants (80%) that did not disagree with "If I want my child to receive antibiotics, I would not be satisfied if the doctor refuses to prescribe them". More than half of parents (n = 120, 52%) reported having self-medicated his/her child with antibiotics. A positive correlation was found between knowledge and attitudes (Coefficient 0.53, 95% CI 0.38-0.68) after adjusting for the age and the education of the parent. Parents who were < 20 years old were more likely to have low knowledge about antibiotics (crude PR 2.39, 95% CI 1.32-4.34) compared to those aged > 40 years. Parents who had self-medicated his/her child with antibiotics (n = 120, 52%) were more likely to have purchased antibiotics without prescription (aPR 2.70, 95% CI 1.74-4.19) and to have received antibiotics after the recommendation of a pharmacist (aPR 1.79, 95% CI 1.13-2.82).
Knowledge about antibiotics among parents from rural settings in Peru is limited and highlights the need for educational interventions. Public health policies to limit the acquisition of antibiotics without prescription should be implemented.
To determine the effect of bovine lactoferrin on prevention of late-onset sepsis (LOS) and neurodevelopment delay.
Randomized, double-blind, controlled trial in neonates with a birth weight of ...500-2000 g in 3 neonatal units in Lima, Peru, comparing bovine lactoferrin 200 mg/kg/day with placebo administered for 8 weeks. The primary outcome was the first episode of culture-proven LOS or sepsis-associated death. Neurodevelopment delay was assessed by the Mullen Scales at 24 months corrected age.
Of the 414 infants enrolled, 209 received bovine lactoferrin and 205 received placebo. LOS or sepsis-associated death occurred in 22 infants (10.5%) in the bovine lactoferrin group vs 30 (14.6%) in the placebo group; there was no difference after adjusting for hospital and birth weight; hazard ratio 0.73 (95% CI, 0.42-1.26). For infants with birth weights of <1500 g the hazard ratio was 0.69 (95% CI, 0.39-1.25). The mean age-adjusted normalized Mullen composite score at 24 months was 83.3 ± 13.6 in the bovine lactoferrin group vs 82.6 ± 13.1 in the placebo group. Growth outcomes and rehospitalization rates during the 2-year follow-up were similar in both groups, except for significantly less bronchiolitis in the bovine lactoferrin group (rate ratio, 0.34; 95% CI, 0.14-0.86).
Supplementation with bovine lactoferrin did not decrease the incidence of sepsis in infants with birth weights of <2000 g. Growth and neurodevelopment outcomes at 24 months of age were similar. Neonatal bovine lactoferrin supplementation had no adverse effects.
ClinicalTrials.gov: NCT01525316.
The objective of the present study was to characterize Salmonella enterica serovar Infantis isolated from chicken meat determining their clonal relationships with S. Infantis isolated from children ...with diarrhea. Fifteen meat-recovered S. Infantis were analyzed. Susceptibility levels to 14 antibacterial agents, the presence of ESBL and that of inducible plasmid-mediated AmpC (i-pAmpC) were determined by phenotypical methods. The presence of ESBL and pAmpC was confirmed by PCR, and detected ESBL-encoding genes were sequenced and their transferability tested by conjugation. The presence of gyrA mutations as well as Class 1 integrons was determined by PCR. Clonal relationships were established by REP-PCR and RAPD. In addition, 25 clinical isolates of S. Infantis were included in clonality studies. All meat-recovered S. Infantis were MDR, showing resistance to ampicillin, nitrofurans and quinolones, while none was resistant to azithromycin, ceftazidime or imipenem. ESBL (blaCTX-M-65) and i-pAmpC (blaDHA) were detected in 2 and 5 isolates respectively (in one case concomitantly), with blaCTX-M-65 being transferable through conjugation. In addition, 1 isolate presented a blaSHV gene. All isolates presented D87Y at GyrA, nalidixic acid active efflux pump and a Class 1 integron of ~1000 bp (aadA1). Clonal analysis showed that all isolates were related. Further they were identical to MDR blaCTX-M-65-producing S. Infantis isolates causing children diarrhea in Lima. The dissemination of MDR blaCTX-M-65-producing S. Infantis between marketed meat and children highlights a public health problem which needs be controlled at livestock level.
•Multidrug resistant S. Infantis were recovered from food samples.•Presence of CTX-M-65 was detected in 2 food-recovered S. Infantis.•Clonal relations between food and human S. Infantis isolates are shown.
Much has been learned in recent years about the mechanisms by which breastfeeding improves child health and survival. However, there has been little progress in using these insights to improve ...pediatric care. Factors that are important for protecting the breast fed infant might be expected to decrease the adverse effects of weaning on diarrhea, growth, and development. Lactoferrin, an iron-binding protein with multiple physiological functions (anti-microbial, anti-inflammatory, and immunomodulatory), is one of the most important proteins present in mammalian milk. Protection against gastroenteritis is the most likely biologically relevant activity of lactoferrin. Multiple
in vitro and animal studies have shown a protective effect of lactoferrin on infections with enteric microorganisms, including rotavirus,
Giardia,
Shigella,
Salmonella and the diarrheagenic
Escherichia coli. Lactoferrin has two major effects on enteric pathogens: it inhibits growth and it impairs function of surface expressed virulence factors thereby decreasing their ability to adhere or to invade mammalian cells. Thus, lactoferrin may protect infants from gastrointestinal infection by preventing the attachment by enteropathogens in the gut. Recently several clinical trials in children have started to address this issue. Whether lactoferrin can prevent a significant portion of diarrheal disease remains to be determined.
Enterotoxigenic Escherichia coli (ETEC) ranks among the most relevant diarrheagenic pathogens. Efforts to design vaccines to fight ETEC have been focused on colonizing factors (CFs) and atypical ...virulence factors (AVF). An effective vaccine must account for differences in the regional prevalence of these CFs and AVFs to be truly effective in a given area. In the present study, the presence of 16 CFs and 9 AVFs, as well as the heat-stable (ST) variants (STh or STp), was established by polymerase chain reaction in 205 Peruvian ETEC isolates (120 from diarrhea cases and 85 from healthy controls). Ninety-nine (48.3%) isolates were heat-labile, 63 (30.7%) ST, and 43 (21.0%) presented both toxins. Of ST isolates, 59 (28.8%) possessed STh, 30 (14.6%) STp, five (2.4%) both STh and STp, and 12 (5.8%) were not amplified for any variant tested. The presence of CFs was associated with diarrhea (P < 0.0001). The presence of eatA as well as concomitant presence of CSI, CS3, and CS21 and of C5 and C6 was statistically related to diarrhea cases. The present results suggests that, if effective, a vaccine considering CS6, CS20, and CS21, together with EtpA, would provide protection against 64.4% of the isolates analyzed, whereas the addition of CS12 and EAST1 would lead to 83.9% coverage. Large studies are needed to establish both the ideal candidates to be considered to develop a vaccine effective in the area, and continuous surveillance is needed to detect displacement of circulating isolates that may compromise future vaccines.
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