Antimicrobial peptides (AMPs) are short proteins with antimicrobial activity. A large portion of known AMPs originate from insects, and the number and diversity of these molecules in different ...species varies considerably. Insect AMPs represent a potential source of alternative antibiotics to address the limitation of current antibiotics, which has been caused by the emergence and spread of multidrug-resistant pathogens. To get more insight into AMPs, we investigated the diversity and evolution of insect AMPs by mapping their phylogenetic distribution, allowing us to predict the evolutionary origins of selected AMP families and to identify evolutionarily conserved and taxon-specific families. Furthermore, we highlight the use of the nematode Caenorhabditis elegans as a whole-animal model in high-throughput screening methods to identify AMPs with efficacy against human pathogens, including Acinetobacter baumanii and methicillin-resistant Staphylococcus aureus. We also discuss the potential medical applications of AMPs, including their use as alternatives for conventional antibiotics in ectopic therapies, their combined use with antibiotics to restore the susceptibility of multidrug-resistant pathogens, and their use as templates for the rational design of peptidomimetic drugs that overcome the disadvantages of therapeutic peptides.
The article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’.
The implementation of antimicrobial stewardship programs (ASPs) is a promising strategy to help address the problem of antimicrobial resistance. We sought to determine the efficacy of ASPs and their ...effect on clinical and economic parameters. We searched PubMed, EMBASE, and Google Scholar looking for studies on the efficacy of ASPs in hospitals. Based on 26 studies (extracted from 24,917 citations) with pre- and postimplementation periods from 6 months to 3 years, the pooled percentage change of total antimicrobial consumption after the implementation of ASPs was -19.1% (95% confidence interval CI = -30.1 to -7.5), and the use of restricted antimicrobial agents decreased by -26.6% (95% CI = -52.3 to -0.8). Interestingly, in intensive care units, the decrease in antimicrobial consumption was -39.5% (95% CI = -72.5 to -6.4). The use of broad-spectrum antibiotics (-18.5% 95% CI = -32 to -5.0 for carbapenems and -14.7% 95% CI = -27.7 to -1.7 for glycopeptides), the overall antimicrobial cost (-33.9% 95% CI = -42.0 to -25.9), and the hospital length of stay (-8.9% 95% CI = -12.8 to -5) decreased. Among hospital pathogens, the implementation of ASPs was associated with a decrease in infections due to methicillin-resistant Staphylococcus aureus (risk difference RD = -0.017 95% CI = -0.029 to -0.005), imipenem-resistant Pseudomonas aeruginosa (RD = -0.079 95% CI = -0.114 to -0.040), and extended-spectrum beta-lactamase Klebsiella spp. (RD = -0.104 95% CI = -0.153 to -0.055). Notably, these improvements were not associated with adverse outcomes, since the all-cause, infection-related 30-day mortality and infection rates were not significantly different after implementation of an ASP (RD = -0.001 95% CI = -0.009 to 0.006, RD = -0.005 95% CI = -0.016 to 0.007, and RD = -0.045% 95% CI = -0.241 to 0.150, respectively). Hospital ASPs result in significant decreases in antimicrobial consumption and cost, and the benefit is higher in the critical care setting. Infections due to specific antimicrobial-resistant pathogens and the overall hospital length of stay are improved as well. Future studies should focus on the sustainability of these outcomes and evaluate potential beneficial long-term effects of ASPs in mortality and infection rates.
Adjusting to a continuously changing environment is a key feature of life. For metazoans, environmental changes include alterations in the gut microbiota, which can affect both memory and behavior. ...The bacteriovorous nematode Caenorhabditis elegans discriminates between pathogenic and non-pathogenic food sources, avoiding the consumption of pathogens. Here, we demonstrate the role of the intestine in regulating C. elegans avoidance to Pseudomonas aeruginosa by an insulin-like neuropeptide encoded by ins-11. The transcriptional expression of ins-11 is controlled through transcription factor hlh-30 and the p38 mitogen-activated protein kinase (MAPK) pathway. ins-11 negatively controls signal pathways in neurons that regulate aversive learning behavior. Attenuation of ins-11 increased avoidance behavior and survival on pathogenic bacteria but decreased opportunities to find a food source as well as lowered energy storage and the number of viable progeny. Our findings support a role for the intestine in avoidance and identify an advantageous role for negative feedback that allows C. elegans to actively balance noxious and favorable environments.
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•A neuropeptide, encoded by ins-11, negatively regulates aversive learning behavior•hlh-30 and the p38 MAPK pathway control ins-11 expression in the intestine•ins-11 inhibits abnormal expression of serotonin and the insulin pathway in neurons•Increased avoidance extends survival but reduces fat storage and progeny
Lee and Mylonakis describe the inhibitory role of a neuropeptide that is encoded by ins-11 and is expressed in intestine. The neuropeptide prevents abnormal activation of neurons that stimulate aversive learning behavior in C. elegans. ins-11 allows nematodes to adjust when they move between pathogenic and non-pathogenic microbes.
Background. Screening of high-risk patients for invasive aspergillosis (IA) has the potential to decrease the use of empiric antifungal agents. However, the performance of different screening methods ...has not been studied. Methods. We performed a meta-analysis of published studies to assess the diagnostic performance of galactomannan (GM) and polymerase chain reaction (PCR) as weekly screening tests in high-risk populations. The sensitivity and specificity of 6 approaches combining GM and PCR were estimated using the bivariate model. Results. Thirteen studies with 1670 patients met our inclusion criteria. Single positive test results had modest sensitivity and specificity for screening (respectively, 92% and 90% for GM; 84% and 76% for PCR). The screening approach with the highest sensitivity was the one that used at least 1 GM- or PCR-positive result to define a positive episode, achieving a sensitivity of 99%, significantly higher than any single test (P = .0018 compared with GM and P < .0001 compared with PCR). Meanwhile, when both GM and PCR were positive for the same patient, the specificity increased to 98%, which was not significantly different compared to the specificity of at least 2 positive GM (95%, P = .56 for the comparison) or PCR results (93%, P = .07 for the comparison). Conclusions. When screening high-risk patients for IA with GM and PCR tests, the absence of any positive test can obviate the need for antifungal agents with a negative predictive value of 100%, whereas the presence of at least 2 positive results is highly suggestive of an active infection with a positive predictive value of 88%.
Invasive fungal infections constitute a serious threat to an ever-growing population of immunocompromised individuals and other individuals at risk. Traditional diagnostic methods, such as ...histopathology and culture, which are still considered the gold standards, have low sensitivity, which underscores the need for the development of new means of detecting fungal infectious agents. Indeed, novel serologic and molecular techniques have been developed and are currently under clinical evaluation. Tests like the galactomannan antigen test for aspergillosis and the β-glucan test for invasive Candida spp. and molds, as well as other antigen and antibody tests, for Cryptococcus spp., Pneumocystis spp., and dimorphic fungi, have already been established as important diagnostic approaches and are implemented in routine clinical practice. On the other hand, PCR and other molecular approaches, such as matrix-assisted laser desorption ionization (MALDI) and fluorescence in situ hybridization (FISH), have proved promising in clinical trials but still need to undergo standardization before their clinical use can become widespread. The purpose of this review is to highlight the different diagnostic approaches that are currently utilized or under development for invasive fungal infections and to identify their performance characteristics and the challenges associated with their use.
Background. Previous reports on molecular rapid diagnostic testing (mRDT) do not consistently demonstrate improved clinical outcomes in bloodstream infections (BSIs). This meta-analysis seeks to ...evaluate the impact of mRDT in improving clinical outcomes in BSIs. Methods. We searched PubMed, CINAHL, Web of Science, and EMBASE through May 2016 for BSI studies comparing clinical outcomes between mRDT and conventional microbiology methods. Results. Thirty-one studies were included with 5920 patients. The mortality risk was significantly lower with mRDT than with conventional microbiology methods (odds ratio OR, 0.66; 95% confidence interval CI, .54–.80), yielding a number needed to treat of 20. The mortality risk was slightly lower with mRDT in studies with antimicrobial stewardship programs (ASPs) (OR, 0.64; 95% CI, .51–.79), and non-ASP studies failed to demonstrate a significant decrease in mortality risk (0.72; .46–1.12). Significant decreases in mortality risk were observed with both gram-positive (OR, 0.73; 95% CI, .55–.97) and gram-negative organisms (0.51; .33–.78) but not yeast (0.90; .49–1.67). Time to effective therapy decreased by a weighted mean difference of −5.03 hours (95% CI, −8.60 to −1.45 hours), and length of stay decreased by −2.48 days (−3.90 to −1.06 days). Conclusions. For BSIs, mRDT was associated with significant decreases in mortality risk in the presence of a ASP, but not in its absence. mRDT also decreased the time to effective therapy and the length of stay. mRDT should be considered as part of the standard of care in patients with BSIs.
Pediatric bloodstream infections (BSIs) with Extended-Spectrum Beta-Lactamase- producing Enterobacteriaceae (ESBL-PE) are associated with worse clinical outcomes. We aimed to estimate the prevalence ...of and the mortality associated with ESBL-PE in this patient population.
A systematic review and meta-analysis using PubMed and EMBASE and included studies reporting the prevalence of ESBL-PE among confirmed BSIs in patients <19 years old.
Twenty three (out of 1,718 non-duplicate reports) studies that provided data on 3,381 pediatric BSIs from 1996 to 2013 were included. The prevalence of ESBL-PE was 9% 95%CI (6, 13) with an annual increase of 3.2% (P = 0.04). The prevalence was 11% 95%CI (6, 17) among neonates, compared to 5% 95%CI (0, 14) among children older than 28 days. The pooled prevalence was 15% in Africa 95%CI (8, 23), 12% in South America 95%CI (5, 23), 11% in India 95%CI (7, 17), 7% in the rest of Asia 95%CI (0, 22), 4% in Europe 95%CI (1, 7) and 0% in Oceania 95%CI (0, 3). Importantly, the mortality in neonates with BSI due to ESBL-PE was 36% 95%CI (22, 51), compared to 18% 95%CI (15, 22) among all other neonates with BSI and this difference was statistically significant (P = 0.01).
In the pediatric population, the prevalence of BSI due to ESBL-PE is significant and is associated with increased mortality in neonates. Further studies are warranted to establish a high-risk group and the evaluation of preventive measures, such as antibiotic stewardship programs and infection control measures, in this population is urgently needed.
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