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1.
Activity of hypothiocyanite and lactoferrin (ALX-009) against respiratory cystic fibrosis pathogens in sputum.
Tunney, MM, Payne, JE, McGrath, SJ, Einarsson, GG, Ingram, RJ, Gilpin, DF, Juarez-Perez, V, Elborn, JS
The Journal of antimicrobial chemotherapy. 2018;(12):3391-3397
Abstract
OBJECTIVES To determine the antimicrobial activity of ALX-009, a combination of bovine lactoferrin and hypothiocyanite, in sputum against Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc), key pathogens causing infection in the lungs of cystic fibrosis (CF) patients. METHODS The antimicrobial activity of ALX-009 against clinical respiratory P. aeruginosa isolates was determined by time-kill assay. Sputum from CF patients was treated with ALX-009, either alone or in combination with tobramycin, and the effect on P. aeruginosa, Bcc and total sputum density was determined. RESULTS Time-kill assay indicated that ALX-009 was bactericidal at 24 h against 4/4 P. aeruginosa isolates under aerobic conditions, and against 3/4 isolates under anaerobic conditions. ALX-009 was also bactericidal against P. aeruginosa in sputum samples at 6 h (n = 22/24 samples) and 24 h (n = 14/24 samples), and demonstrated significantly greater activity than tobramycin at both timepoints. Activity against Bcc in sputum samples (n = 9) was also demonstrated, but the magnitude of change in Bcc density was less than for P. aeruginosa. To determine the effect of treating sputum with two doses of ALX-009, similar to current regimens for inhaled antibiotics, aliquots of a further 10 sputum samples positive for P. aeruginosa were treated with one (t = 0 h) or two doses (t = 0 h, t = 12 h) of ALX-009; treatment with two doses resulted in bactericidal activity in 7/10 samples at 34 h compared with only 3/10 samples when treatment was with one dose. CONCLUSIONS ALX-009 demonstrates promise as a novel antimicrobial that could be used to decrease P. aeruginosa density in the lungs of people with CF.
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2.
Vaginitis: Diagnosis and Treatment.
Paladine, HL, Desai, UA
American family physician. 2018;(5):321-329
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Abstract
Vaginitis is defined as any condition with symptoms of abnormal vaginal discharge, odor, irritation, itching, or burning. The most common causes of vaginitis are bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis. Bacterial vaginosis is implicated in 40% to 50% of cases when a cause is identified, with vulvovaginal candidiasis accounting for 20% to 25% and trichomoniasis for 15% to 20% of cases. Noninfectious causes, including atrophic, irritant, allergic, and inflammatory vaginitis, are less common and account for 5% to 10% of vaginitis cases. Diagnosis is made using a combination of symptoms, physical examination findings, and office-based or laboratory testing. Bacterial vaginosis is traditionally diagnosed with Amsel criteria, although Gram stain is the diagnostic standard. Newer laboratory tests that detect Gardnerella vaginalis DNA or vaginal fluid sialidase activity have similar sensitivity and specificity to Gram stain. Bacterial vaginosis is treated with oral metronidazole, intravaginal metronidazole, or intravaginal clindamycin. The diagnosis of vulvovaginal candidiasis is made using a combination of clinical signs and symptoms with potassium hydroxide microscopy; DNA probe testing is also available. Culture can be helpful for the diagnosis of complicated vulvovaginal candidiasis by identifying nonalbicans strains of Candida. Treatment of vulvovaginal candidiasis involves oral fluconazole or topical azoles, although only topical azoles are recommended during pregnancy. The Centers for Disease Control and Prevention recommends nucleic acid amplification testing for the diagnosis of trichomoniasis in symptomatic or high-risk women. Trichomoniasis is treated with oral metronidazole or tinidazole, and patients' sex partners should be treated as well. Treatment of noninfectious vaginitis should be directed at the underlying cause. Atrophic vaginitis is treated with hormonal and nonhormonal therapies. Inflammatory vaginitis may improve with topical clindamycin as well as steroid application.
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Challenges for Managing Candidatus Liberibacter spp. (Huanglongbing Disease Pathogen): Current Control Measures and Future Directions.
Blaustein, RA, Lorca, GL, Teplitski, M
Phytopathology. 2018;(4):424-435
Abstract
Huanglongbing (HLB; "citrus greening" disease) has caused significant damages to the global citrus industry as it has become well established in leading citrus-producing regions and continues to spread worldwide. Insecticidal control has been a critical component of HLB disease management, as there is a direct relationship between vector control and Candidatus Liberibacter spp. (i.e., the HLB pathogen) titer in HLB-infected citrus trees. In recent years, there have been substantial efforts to develop practical strategies for specifically managing Ca. Liberibacter spp.; however, a literature review on the outcomes of such attempts is still lacking. This work summarizes the greenhouse and field studies that have documented the effects and implications of chemical-based treatments (i.e., applications of broad-spectrum antibiotics, small molecule compounds) and nonchemical measures (i.e., applications of plant-beneficial compounds, applications of inorganic fertilizers, biological control, thermotherapy) for phytopathogen control. The ongoing challenges associated with mitigating Ca. Liberibacter spp. populations at the field-scale, such as the seasonality of the phytopathogen and associated HLB disease symptoms, limitations for therapeutics to contact the phytopathogen in planta, adverse impacts of broad-spectrum treatments on plant-beneficial microbiota, and potential implications on public and ecosystem health, are also discussed.
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Effect of Antimicrobial Treatment on the Resolution of Middle-Ear Effusion After Acute Otitis Media.
Ruohola, A, Laine, MK, Tähtinen, PA
Journal of the Pediatric Infectious Diseases Society. 2018;(1):64-70
Abstract
BACKGROUND Acute otitis media (AOM) induces middle-ear effusion (MEE), which affects hearing. The effect of antimicrobial treatment on the resolution of MEE is controversial, and the factors that affect resolution are unknown. METHODS We studied the effect of antimicrobial treatment on the time to the resolution of MEE as a secondary objective in our randomized double-blind placebo-controlled trial. Children aged 6 to 35 months with stringently diagnosed AOM were allocated to receive amoxicillin-clavulanate (161 patients) or placebo (158 patients) for 7 days and closely followed for 3 months. This study was registered at ClinicalTrials.gov (identifier NCT00299455). RESULTS The median times to resolution of MEE were 20 days (95% confidence interval [CI], 16-24 days) and 29 days (95% CI, 26-32 days) in the amoxicillin-clavulanate and placebo groups, respectively (P = .10). The resolution of MEE was confirmed in 138 (86%) of 161 and 132 (84%) of 158 patients in the amoxicillin-clavulanate and placebo groups, respectively (P = .59). In multivariable analysis, the resolution of MEE was prolonged most significantly by at least 1 recurrence of AOM during follow-up. MEE resolved in 65 (65%) of 100 patients with a recurrence of AOM during follow-up and in 205 (94%) of 219 of those without a recurrence (P < .001) (median times to resolution, 67 vs 15 days, respectively; P < .001). CONCLUSIONS Immediate antimicrobial treatment of AOM does not significantly affect the resolution of MEE in young children. Subsequent recurrences of AOM are a major reason for the persistence of MEE.
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Traditional Uses, Phytochemistry, and Antimicrobial Activities of Eugenia Species - A Review.
de Souza, AM, de Oliveira, CF, de Oliveira, VB, Betim, FCM, Miguel, OG, Miguel, MD
Planta medica. 2018;(17):1232-1248
Abstract
Antimicrobial resistance is a critical health problem, and pathogens responsible for common infections have developed resistance to antimicrobials, posing a threat to global health and placing a huge burden on health services. During the past two decades, the search for new bioactive agents in nature has become extremely important for promoting health and in the development of more efficient antimicrobials. The genus Eugenia is one of the largest in the Myrtaceae family, comprising approximately 1000 species from Mexico to Argentina, with a few species distributed in Australia and Africa. Eugenia species are used in folk medicine, with antidiabetic, antirheumatic, antipyretic, anti-inflammatory, antidiarrheal, antifungal, and antibacterial properties. This study systematically reviews the Eugenia species to compile the phytochemical composition and antimicrobial effects. In addition, we provide information regarding the traditional uses and cytotoxic activity of Eugenia species. We conducted a systematic literature search of specialized databases (Web of Science, Scielo, Lilacs, Pubmed, Science Direct, Scopus) and selected articles published between 1973 and 2015 using Eugenia and antimicrobial activity, Eugenia and toxicity, and Eugenia and chemical composition as key words. Ninety-three studies were included, and the phytochemical analyses from these studies show that Eugenia species are a rich source of flavonoids, tannins, triterpenes, and sesquiterpenes. Chemical constituents play an apparent role in the antimicrobial effects and reinforce the known antimicrobial potential of the Eugenia genus. It is worth mentioning that some Eugenia species cause significant cytotoxicity.
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Prophylactic lactoferrin for preventing late-onset sepsis and necrotizing enterocolitis in preterm infants: A PRISMA-compliant systematic review and meta-analysis.
He, Y, Cao, L, Yu, J
Medicine. 2018;(35):e11976
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Abstract
BACKGROUND Currently, prophylactic use of drugs to promote a healthy gut microbiota and immune system in preterm infants is hot debated, among which lactoferrin is a promising supplementation. However, the effect and safety of lactoferrin to prevent late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants remains controversial. METHODS Databases including Medline, Ovid-Embase, The Cochrane Library, CBM, CNKI, and VIP database of Chinese Journal were searched to collect randomized controlled trials (RCTs) about lactoferrin for preventing LOS and NEC in preterm infants. Languages of included RCTs were restricted to English and Chinese. Meta-analysis was conducted by Rev Man 5.3 software. The Mantel-Haenszel method with random-effects model was used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). RESULTS A total of 9 RCTs, involving 1834 patients, were included. Pooled analysis showed that prophylactic lactoferrin could significantly reduce the incidence all culture-proven LOS (41/629 [6.5%] vs 96/659 [15.3%]; RR 0.47; 95% CI 0.33-0.67; P < .01) and NEC (stage II or more) (9/448 [2.0%] vs 26/462 [5.6%]; RR 0.40; 95% CI 0.18-0.86; P < .01). Lactoferrin was also associated with a significantly decreased hospital-acquired infection (16/139 [11.5%] vs 35/140 [25%]; RR 0.47; 95% CI 0.27-0.80; P < .01); and infection-related mortality (4/474 [0.8%] vs 25/505 [4.9%]; RR 0.24; 95% CI 0.04-1.32; P < .01, I = 53%). Lactoferrin could shorten time to reach full enteral feeding (weighted mean difference [WMD] = -2.11, 95% CI -3.12 to -1.10; P < .01) and showed a decreasing trend of duration of hospitalization (WMD = -1.69, 95% CI -6.87 to 3.50; P < .01; I = 95%). Lactoferrin did not have a significant effect on all-cause mortality (22/625 [3.5%] vs 35/647 [5.4%]; RR 0.70; 95% CI 0.38-1.30; P = .16; I = 13%). None of the included trials reported any confirmed adverse effects caused by the supplemented lactoferrin or probiotics. CONCLUSION Current evidence indicates that lactoferrin could significantly reduce the incidence of NEC and LOS, and decrease the risk of hospital-acquired infection and infection-related mortality in premature infants without obvious adverse effects.
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Role of Lactoferrin in Neonates and Infants: An Update.
Manzoni, P, Dall'Agnola, A, Tomé, D, Kaufman, DA, Tavella, E, Pieretto, M, Messina, A, De Luca, D, Bellaiche, M, Mosca, A, et al
American journal of perinatology. 2018;(6):561-565
Abstract
Lactoferrin is one of the most represented and important bioactive proteins in human and mammal milk. In humans, lactoferrin is responsible for several actions targeting anti-infective, immunological, and gastrointestinal domains in neonates, infants, and young children. Evidence-based data vouch for the ability of supplemented lactoferrin to prevent sepsis and necrotizing enterocolitis in preterm infants and to reduce the burden of morbidity related to gastrointestinal and respiratory pathogens in young children. However, several issues remain pending regarding answers and clarification related to quality control, correct intakes, optimal schedules and schemes of supplementations, interactions with probiotics, and different types of milk and formulas. This review summarizes the current evidence regarding lactoferrin and discusses the areas in need of further guidance prior to the adoption of strategies that include a routine use of lactoferrin in neonates and young children.
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A Population-Based Cohort Study on the Drug-Specific Effect of Statins on Sepsis Outcome.
Lee, CC, Lee, MG, Hsu, TC, Porta, L, Chang, SS, Yo, CH, Tsai, KC, Lee, M
Chest. 2018;(4):805-815
Abstract
BACKGROUND Whether statin treatment, proved by recent experimental studies to have an antimicrobial activity, exerts a drug- or a class-specific effect in sepsis remains unknown. METHODS Short-term mortality in patients with sepsis was analyzed using data from the National Health Insurance Research Database. Use of statins was defined as the cumulative use of a specific statin (atorvastatin, simvastatin, or rosuvastatin) for > 30 days prior to the index sepsis admission. We determined the association between statin and sepsis outcome by multivariate-adjusted Cox models and propensity score (PS)-matched analysis, using a 1:1:1 PS matching technique. RESULTS A total of 52,737 patients with sepsis fulfilled the inclusion criteria, of which 1,855 were prescribed atorvastatin, 916 were prescribed simvastatin, and 732 were prescribed rosuvastatin. Compared with nonusers, simvastatin (hazard ratio [HR], 0.72; 95% CI, 0.58-0.90) and atorvastatin (HR, 0.78; 95% CI, 0.68-0.90) were associated with an improved 30-day survival, whereas rosuvastatin was not (HR, 0.87; 95% CI, 0.73-1.04). Using rosuvastatin as the reference, atorvastatin (HR, 0.79; 95% CI, 0.64-0.99) and simvastatin (HR, 0.77; 95% CI, 0.59-0.99) had superior effectiveness in preventing mortality. CONCLUSIONS Compatible with in vitro experimental findings, our results suggest that the drug-specific effect of statins on sepsis is not correlated to their lipid-lowering potency.
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Acne Vulgaris.
Zaenglein, AL
The New England journal of medicine. 2018;(14):1343-1352
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10.
Prevention of Prematurity: Advances and Opportunities.
Govindaswami, B, Jegatheesan, P, Nudelman, M, Narasimhan, SR
Clinics in perinatology. 2018;(3):579-595
Abstract
Preterm birth (PTB) rate varies widely and has significant racial and ethnic disparities. Although causal mechanisms are ill understood, socioenvironment, phenotype, and genotype provide insight into pathways for preventing PTB. Data suggest varied response to current medical interventions is explicable Approved by underlying pharmacogenomics. Currently, prevention focuses on minimizing iatrogenic PTB and risk reduction especially in those with prior PTB using proven medical and public health strategies. In the future, preventive approaches will be based on better understanding of sociodemography, nutrition, lifestyles, and underlying individual genetic and epigenetic variation. Statistical approaches and "big-data" models are critical in future study.