New Method Produces Precise Polymeric Nanoparticles for Clinical Applicability

While there are many types of drug ferrying nanoparticles already in existence and more under development, in order for them to be safe and effective in clinical practice they have to be uniformly manufacturable. Different sizes and shapes of nanoparticles can lead to inconsistent results. This can muddy studies and clinical results. Now researchers at Johannes Gutenberg University Mainz in Germany and University of Tokyo in Japan are reporting in the venerable journal Angewandte Chemie on a new method of producing nanoparticles uniformly, while giving scientists and engineers the ability to carefully control nano shape and function.

The investigators used reactive polypept(o)ides (polysarcosine-block-polypeptide copolymers) as the main ingredient to create carefully realized nanoparticles. This unusual material is resistant to reactions with proteins, exhibits high water-solubilty of polysarcosine, responds to external stimuli, and can be shaped in different ways.

Some details according to Johannes Gutenberg University Mainz:

In this cooperative work, the researchers could show for the first time that the formation of β-sheets by the synthetic polypeptide segment can be exploited to deliberately manipulate the morphology of polymeric micelles, which enables the synthesis of either spherical or worm-like micelles from the same block copolymer. By employing reactive groups in the polypeptide segment of the block copolymer, micelles can be core cross-linked by dithiols, resulting in bio-reversible disulfide bonds. Due a difference in redox potential, disulfides are considered stable extracellularly, while they are rapidly reduced to free dithiols intracellularly, which leads to a disintegration of the carrier system and release of the cargo.

“In this way, a variety of different nanocarriers with different functions becomes readily accessible from one single block copolymer and a very selective post-polymerization step. This modular approach to nanoparticles with different function and morphology bears the advantage to address important questions with good comparability, such as the influence of size and shape on in vivo circulation times, biodistribution, tumor accumulation, cell uptake and therapeutic response since the same starting material is used” comments Matthias Barz, [a leader of the research team].

Study in journal Angewandte Chemie: Secondary-Structure-Driven Self-Assembly of Reactive Polypept(o)ides: Controlling Size, Shape, and Function of Core Cross-Linked Nanostructures…

Via: Johannes Gutenberg University Mainz…

Summer School 2017: gli infermieri e la comunicazione

Esercitazioni pratiche per i medici alla Summer Simeu

Ormai è entrata nel vivo la settimana di formazione estiva Simeu per giovani medici e infermieri. Mentre per gli specializzandi è stata una giornata di esercitazioni pratiche, dalla Niv con Paolo Groff e Roberto Cosentini, all’ecografia toracica e cardiaca con Andrea Magnacavallo, all’utilizzo dei ventilatori, gli infermieri, al loro debutto questa mattina, sono partiti con la teoria: anche per loro Ecografia ed Elettrocardiografia in urgenza e principi di Crisis resource management.

Un manipolo di veri duri ha iniziato la giornata alle 6.30 con una corsa energizzante per affrontare la giornata impegnativa. E pare che l’esperimento sia riuscito e sarà ripetuto nei prossimi giorni, con un gruppo più numeroso e anche forse con ospiti eccellenti… 

Intanto questa sera ci sarà la prima attività formativa congiunta per medici e infermieri insieme sul tema attualissimo della responsabilità professionale, attività guidata da Annamaria Ferrari per il versante medico e da Luca Gelati per gli aspetti infermieristici.

“Gli infermieri presenti alla Summer quest’anno – racconta Matteo Cosi, responsabile area Nursing nazionale – sono tutti altamente specializzati perchè arrivano con un master già nel proprio bagaglio di conoscenze. Per loro, il valore aggiunto di questa esperienza non è quindi tanto la specializzazione ma soprattutto la possibilità di confronto tecnico e organizzativo con colleghi di altre regioni e anche di altre aree della medicina di emergenza urgenza. Il profilo professionale dell’infermiere di questa nostra disciplina è particolarmente mobile fra ruoli diversi, tutti ben rappresentati qui a Bertinoro”.

La riflessione sull’importanza della comunicazione nella professione dell’infermie d’emergenza

L’avvio vero delle attività per i giovani infermieri in realtà si è tenuto già ieri sera con una riflessione articolata sulla comunicazione, partendo dal racconto delle esperienze personali che hanno condotto alla scelta della professione, per arrivare all’importanza della cura della comunicazione con i colleghi in ogni gruppo di lavoro e con il paziente e i suoi familiari.

E insieme alla comunicazione la novità nei corsi nursing di quest’anno è la maxiemergenza, tema a cui sarà dedicato uno degli ultimi appuntamenti in calendario, previsto lunedì mattina. Un argomento sempre più sentito da medici e infermieri dell’emergenza sia per la recente ferita arrecata da catastrofi naturali che hanno colpito la penisola, e che hanno visto in prima linea i professionisti sanitari, sia per emergenze sociali che si riversano in prima istanza sul pronto soccorso.

UTI Empiric Antibiotics

Originally published at Pediatric EM Morsels on April 15, 2016. Updated on April 14, 2017. Reposted with permission.

Follow Dr. Sean M. Fox on twitter @PedEMMorsels

UTI Antibiotics

Last week we discussed making the diagnosis of an urinary tract infection.  Essentially, we reinforced the fact that we can only make a presumptive diagnosis of UTI in the ED.  In some situations, you may prefer to await the urine culture for more definitive answers; however, there will be many occasions when it is deemed appropriate to initiate empiric antibiotics.  When that is the case, what should you choose? Let’s look at some options for Empiric Antibiotics for UTI.

 

UTI: The Bugs

  • Worldwide, over the past several decades, antibiotic resistance has continued to evolve and increase. [Mishra, 2015; Echeverri, 2014; Mirsoleymani, 2014; Edlin, 2013]
  • E. coli is responsible for majority of UTIs (~80%). [Edlin, 2013; Bhat, 2011]
  • Other encountered uropathogens:
    • Klebsiella
    • Proteus
    • Group B Strep – consider in neonates and young infants.
    • Enterococcus – consider in neonates and young infants.
    • Staph saprophyticus
    • Pseudomonas
    • Fungi – seen in immunocompromised or diabetic patients or those with indwelling catheters or on long-term antbiotics.
  • Common contaminants:
    • Cornebacterium species
    • Coag-negative staph
    • Lactobacillus species
    • Alpha-hemolytic strep

 

UTI: Management

  • Local antimicrobial susceptibility patterns are the most important tool to help determine initial therapy. [Edlin, 2013; Jerardi, 2012; Subcommittee AAP, 2011]
  • Duration of therapy:
    • Short course (5 days) is as effective as 7-14 days for uncomplicated cystitis in children
    • Consider short courses for older children.
  • PO vs IV:
    • PO and IV therapies are equally efficacious. [Kowalsky, 2013; Subcommittee AAP, 2011]
    • Children with severe disease (ex, pyelonephritis) or medical complications (ex, immunocompromised) need to be treated with IV therapy until afebrile for 24 hours. Can be converted to oral afterwards.
    • Neonates require full sepsis evaluation and IV antibiotics!
    • >2 month olds:
      • Well appearing >2 month olds have low risk of UTI and concomitant meningitis[Tebruegge, 2011]
      • If considering outpatient management:
        • Kid has to look awesome!
        • Kid has to have excellent access to care.
        • Discuss with Primary Care Provider to ensure that everyone is on the same management page!

 

UTI: The Bugs

  • NO initial empiric choice is perfect.
    • Send the Culture!
    • Ensure follow-up!
  • Cephalosporins [Subcommittee AAP, 2011]
    • Have become a commonly selected 1st choice for UTI. [Bhat, 2011]
    • Some evidence that Nitrite-Negative U/A results may indicate increased risk for resistance to 1st and 2ndgeneration (Enterocococcus do not convert Nitrate to Nitrite). [Weisz, 2010]
    • Cefaclor
      • 50-100 mg/kg/Day divided in 3 doses
    • Cefixime
      • 8 mg/kg once a day
    • Cephalexin
      • Useful first generation cephalosporin.
      • Will NOT cover enterococcus.
      • 50-100 mg/kg/D divided in four doses.
    • Ceftriaxone
      • IM dosing can be used in those who won’t tolerate oral meds.
      • 50-100 mg/kg every 24 hours.
  • Amoxicillin / Ampicillin [Subcommittee AAP, 2011]
    • A large percentage of E. coli are resistant to ampicillin. [Gaspari, 2006]
    • Does attain high levels in the urine and is effective against E. coli. [Betrosian, 2009]
    • Recommendation is to use Amoxicillin with Clavulanate (20-40 mg/kg/D divded TID).
  • Trimehoprim-Sulfamethoxazole (TMP-SMZ) [Subcommittee AAP, 2011]
    • Ever increasing resistance, plus not an innocuous medicine. [Edlin, 2013]
    • Bacteria that are resistant to ampicillin are commonly also resistant to TMP-SMZ. [Gaspari, 2006]
    • The high resistance makes this a poor choice for empiric therapy of UTI. [Gaspari, 2006]
  • Nitrofurantoin
    • Attains good levels in urine, but not serum.
    • Good for nitrite-negative UTIs. [Weisz, 2010]
    • Should not be used to treat pyelonephritis or febrile infants. [Bhat, 2011; Subcommittee AAP, 2011]
  • Ciprofloxacin
    • Often avoided due to concern for cartilage injury, but this is not supported in the literature.
    • Reserved for resistant organisms. [Bhat, 2011]
    • Can use if need in special cases (ie, cystic fibrosis).

 

The Moral of the Morsel

  • Know your local antibiotic resistance patterns.
  • Avoid using TMP-SMZ empirically for UTI!
  • Ensure the Urine Culture gets sent (it is crucial for the diagnosis and for tailoring therapy).
  • Not every child needs empiric therapy for an abnormal urinalysis. Discuss with the Primary Care Physician when not clearly requiring empiric antibiotics.

 

References

Becknell B1, Schober M, Korbel L, Spencer JD. The diagnosis, evaluation and treatment of acute and recurrent pediatric urinary tract infections. Expert Rev Anti Infect Ther. 2015 Jan;13(1):81-90. PMID: 25421102. [PubMed] [Read by QxMD]

Dev Period Med. 2014 Oct-Dec;18(4):470-6. PMID: 25874786. [PubMed] [Read by QxMD]

Mirsoleymani SR1, Salimi M2, Shareghi Brojeni M3, Ranjbar M3, Mehtarpoor M4. Bacterial pathogens and antimicrobial resistance patterns in pediatric urinary tract infections: a four-year surveillance study (2009-2012). Int J Pediatr. 2014;2014:126142. PMID: 24959183. [PubMed] [Read by QxMD]

Vélez Echeverri C1, Serna-Higuita LM1, Serrano AK2, Ochoa-García C2, Rojas Rosas L2, María Bedoya A3, Suárez M4, Hincapié C4, Henao A4, Ortiz D4, Vanegas JJ1, Zuleta JJ5, Espinal D4. Resistance profile for pathogens causing urinary tract infection in a pediatric population, and antibiotic treatment response at a university hospital, 2010-2011. Colomb Med (Cali). 2014 Mar 30;45(1):39-44. PMID: 24970958. [PubMed] [Read by QxMD]

Mikrobiyol Bul. 2013 Oct;47(4):603-18. PMID: 24237429. [PubMed] [Read by QxMD]

Edlin RS1, Shapiro DJ, Hersh AL, Copp HL. Antibiotic resistance patterns of outpatient pediatric urinary tract infections. J Urol. 2013 Jul;190(1):222-7. PMID: 23369720. [PubMed] [Read by QxMD]

Kowalsky RH1, Shah NB. Update on urinary tract infections in the emergency department. Curr Opin Pediatr. 2013 Jun;25(3):317-22. PMID: 23652682. [PubMed] [Read by QxMD]

Jerardi KE1, Auger KA, Shah SS, Hall M, Hain PD, Myers AL, Williams DJ, Tieder JS. Discordant antibiotic therapy and length of stay in children hospitalized for urinary tract infection. J Hosp Med. 2012 Oct;7(8):622-7. PMID: 22833498. [PubMed] [Read by QxMD]

Tebruegge M1, Pantazidou A, Clifford V, Gonis G, Ritz N, Connell T, Curtis N. The age-related risk of co-existing meningitis in children with urinary tract infection. PLoS One. 2011;6(11):e26576. PMID: 22096488. [PubMed] [Read by QxMD]

Bhat RG1, Katy TA, Place FC. Pediatric urinary tract infections.Emerg Med Clin North Am. 2011 Aug;29(3):637-53. PMID: 21782079. [PubMed] [Read by QxMD]

Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management, Roberts KB. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011 Sep;128(3):595-610. PMID: 21873693. [PubMed] [Read by QxMD]

Betrosian AP1, Douzinas EE. Ampicillin-sulbactam: an update on the use of parenteral and oral forms in bacterial infections. Expert Opin Drug Metab Toxicol. 2009 Sep;5(9):1099-112. PMID: 19621991. [PubMed] [Read by QxMD]

Arredondo-García JL1, Soriano-Becerril D2, Solórzano-Santos F3, Arbo-Sosa A4, Coria-Jiménez R1, Arzate-Barbosa P1. Resistance of uropathogenic bacteria to first-line antibiotics in mexico city: A multicenter susceptibility analysis. Curr Ther Res Clin Exp. 2007 Mar;68(2):120-6. PMID: 24678125. [PubMed] [Read by QxMD]

Gaspari RJ1, Dickson E, Karlowsky J, Doern G. Multidrug resistance in pediatric urinary tract infections. Microb Drug Resist. 2006 Summer;12(2):126-9. PMID: 16922629. [PubMed] [Read by QxMD]

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