Archive for November, 2016

Disseminated Mycobacterium abscessus Infection Following Septic Arthritis: A Case Report and Review of the Literature.

Medicine (Baltimore). 2015 May;94(21):e861.

Fukui S1, Sekiya N, Takizawa Y, Morioka H, Kato H, Aono A, Chikamatsu K, Mitarai S, Kobayashi S, Kamei S, Setoguchi K.

Author information

1From the Department of Rheumatology (SF, YT, S Kobayashi, S Kamei, KS); Clinical Laboratory (NS, HM, HK), Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo; and Department of Mycobacterium Reference and Research (AA, KC, SM), The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Kiyose, Japan.

Abstract

Mycobacterium abscessus is a rapidly growing mycobacterium found mainly in patients with respiratory or cutaneous infections, but it rarely causes disseminated infections.

Little is known about the clinical characteristics, treatment, and prognosis of disseminated M abscessus infection.

A 75-year-old Japanese woman who had been treated for 17 years with a corticosteroid for antisynthetase syndrome with antithreonyl-tRNA synthetase antibody developed swelling of her right elbow.

X-ray of her right elbow joint showed osteolysis, and magnetic resonance imaging revealed fluid in her right elbow joint.

M abscessus grew in joint fluid and blood cultures. She was diagnosed with a disseminated M abscessus infection following septic arthritis.

Antimicrobial treatment by clarithromycin, amikacin, and imipenem/cilastatin combined with surgical debridement was administered.

Although blood and joint fluid cultures became negative 1 week later, the patient died at 6 weeks from starting antimicrobial treatment.

We reviewed 34 cases of disseminated M abscessus infections from the literature. Most of the patients had immunosuppressive backgrounds such as transplantation, use of immunosuppressive agents, hematological malignancy, and end stage renal disease.

The duration from onset of symptoms to diagnosis was over 3 months in half of the cases. All fatal cases had positive blood cultures or use of immunosuppressive agents.

Clinicians should bear in mind that mycobacterial infections including M abscessus are one of the differential diagnoses in patients with subacute arthritis and soft tissue infections.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616402/pdf/medi-94-e861.pdf

November 30, 2016 at 1:42 pm

Update on pulmonary disease due to non-tuberculous mycobacteria.

Int J Infect Dis. 2016 Apr;45:123-34.

Stout JE1, Koh WJ2, Yew WW3.

Author information

1Division of Infectious Diseases and International Health, Department of Medicine, Duke University Medical Center, Box 102359-DUMC, Durham, NC 27710, USA. Electronic address: jason.stout@dm.duke.edu

2Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

3Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China.

Abstract

Non-tuberculous mycobacteria (NTM) are emerging worldwide as significant causes of chronic pulmonary infection, posing a number of challenges for both clinicians and researchers.

While a number of studies worldwide have described an increasing prevalence of NTM pulmonary disease over time, population-based data are relatively sparse and subject to ascertainment bias. Furthermore, the disease is geographically heterogeneous.

While some species are commonly implicated worldwide (Mycobacterium avium complex, Mycobacterium abscessus), others (e.g., Mycobacterium malmoense, Mycobacterium xenopi) are regionally important.

Thoracic computed tomography, microbiological testing with identification to the species level, and local epidemiology must all be taken into account to accurately diagnose NTM pulmonary disease.

A diagnosis of NTM pulmonary disease does not necessarily imply that treatment is required; a patient-centered approach is essential.

When treatment is required, multidrug therapy based on appropriate susceptibility testing for the species in question should be used. New diagnostic and therapeutic modalities are needed to optimize the management of these complicated infections.

PDF

http://www.ijidonline.com/article/S1201-9712(16)30993-6/pdf

November 30, 2016 at 1:39 pm

Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease.

J Korean Med Sci. 2016 May;31(5):649-59.

Kwon YS1, Koh WJ2.

Author information

1Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea .

2Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea .

Abstract

Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease.

The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms.

Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms.

For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates.

Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion.

For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy.

Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease.

Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835588/pdf/jkms-31-649.pdf

November 30, 2016 at 1:37 pm

Clinical efficacy and safety of multidrug therapy including thrice weekly intravenous amikacin administration for Mycobacterium abscessus pulmonary disease in outpatient settings: a case series.

BMC Infect Dis. 2016 Aug 9;16:396.

Namkoong H1,2,3, Morimoto K4, Nishimura T5, Tanaka H1, Sugiura H6, Yamada Y6, Kurosaki A7, Asakura T1, Suzuki S1, Fujiwara H8, Yagi K1, Ishii M1, Tasaka S1, Betsuyaku T1, Hoshino Y9, Kurashima A4, Hasegawa N10.

Author information

1Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

2Japan Society for the Promotion of Science, Tokyo, Japan.

3Department of Pulmonary Medicine, Eiju General Hospital, Tokyo, Japan.

4Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan.

5Keio University Health Center, Tokyo, Japan.

6Department of Diagnostic Radiology, Keio University School of Medicine, Tokyo, Japan.

7Department of Diagnostic Radiology, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan.

8Center for Infectious Diseases and Infection Control, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

9Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan.

10Center for Infectious Diseases and Infection Control, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. n-hasegawa@z8.keio.jp

Abstract

BACKGROUND:

Mycobacterium abscessus (M. abscessus) pulmonary disease is a refractory chronic infectious disease. Options for treating M. abscessus pulmonary disease are limited, especially in outpatient settings. Among parenteral antibiotics against M. abscessus, intravenous amikacin (AMK) is expected to be an effective outpatient antimicrobial therapy. This study evaluated the clinical efficacy and safety of intravenous AMK therapy in outpatients with M. abscessus pulmonary disease.

METHODS:

This retrospective chart review of cases of M. abscessus pulmonary disease evaluated patient background data, AMK dosage and duration, sputum conversion, clinical symptoms radiological findings, and adverse events. M. massiliense was excluded on the basis of multiplex PCR assay.

RESULTS:

Thirteen patients (2 men and 11 women) with M. abscessus pulmonary disease were enrolled at 2 hospitals. The median age at the initiation of intravenous AMK treatment was 65 years (range: 50-86 years). Patients received a median AMK dose of 12.5 mg/kg (range: 8.3-16.2 mg/kg) for a median duration of 4 months (range: 3-9 months). The addition of intravenous AMK led to sputum conversion in 10 of 13 patients, and 8 patients continued to have negative sputum status 1 year after treatment. Approximately half of the patients showed improvement on chest high-resolution computed tomography. There were no severe adverse events such as ototoxicity, vestibular toxicity, and renal toxicity.

CONCLUSIONS:

Thrice weekly intravenous AMK administration in outpatient settings is effective and safe for patients with M. abscessus pulmonary disease

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977760/pdf/12879_2016_Article_1689.pdf

November 30, 2016 at 1:35 pm

The C-Reactive Protein May Not Detect Infections Caused by Less-Virulent Organisms

Journal of Arthroplasty September 2016 V.31 N.9 P.152–155

Carl A. Deirmengian, Patrick A. Citrano, Simmi Gulati, Erick R. Kazarian, James W. Stave, Keith W. Kardo

Background

The aim of the present study was to evaluate the influence of organism type on the performance of the synovial fluid C-reactive protein (CRP) test.

Methods

We retrospectively reviewed the results of 21,422 synovial fluid samples sent to one common laboratory for the purpose of diagnostic testing for periprosthetic joint infection. Both a synovial fluid CRP result and a positive culture were present for 1789 submitted samples. The cultured organisms were grouped by species, virulence, and gram type; and the median CRP level was determined for each group.

Results

The median synovial fluid CRP level was significantly lower for less-virulent organisms, when compared to those organisms classified as virulent (15.10 mg/L vs 32.70 mg/L; P < .0001). Some less-virulent species such as yeast and Staphylococcus epidermidis were associated with a 4-10 times lower CRP response than those of virulent organisms such as Streptococcus agalactiae and Staphylococcus aureus (P < .0001). Bacterial gram type had no influence on the median CRP result. The rate of false-negative CRP values was 50.9% for yeast, 29.4% for S. epidermidis, 28.5% for all less-virulent organisms, and 11.6% for all virulent organisms.

Conclusion

The CRP response appears to be highly dependent on the infecting organism and is more likely to provide false-negative results in the setting of less-virulent organisms. Although the use of a CRP level is an important part of the workup for periprosthetic joint infection, surgeons must be aware that this protein may yield a false-negative result in the setting of less-virulent organisms.

 

PDF

http://www.arthroplastyjournal.org/article/S0883-5403(16)00259-X/pdf

November 29, 2016 at 1:30 pm

Coexisting cytomegalovirus infection in immunocompetent patients with Clostridium difficile colitis.

J Microbiol Immunol Infect. 2016 Jan 12.

Chan KS1, Lee WY2, Yu WL3.

Author information

1Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan City, Taiwan.

2Department of Pathology, Chi Mei Medical Center, Tainan City, Taiwan; Department of Pathology, Taipei Medical University, Taipei City, Taiwan.

3Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan City, Taiwan; Department of Medicine, Taipei Medical University, Taipei City, Taiwan. Electronic address: yuleon_md@yahoo.com.tw

Abstract

Cytomegalovirus (CMV) colitis usually occurs in immunocompromised patients with human immunodeficiency virus infection, organ transplantation, and malignancy receiving chemotherapy or ulcerative colitis receiving immunosuppressive agents.

However, CMV colitis is increasingly recognized in immunocompetent hosts.

Notably, CMV colitis coexisting with Clostridium difficile infection (CDI) in apparently healthy individuals has been published in recent years, which could result in high morbidity and mortality.

CMV colitis is a rare but possible differential diagnosis in immunocompetent patients with abdominal pain, watery, or especially bloody diarrhea, which could be refractory to standard treatment for CDI. As a characteristic of CDI, however, pseudomembranous colitis may be only caused by CMV infection.

Real-time CMV-polymerase chain reaction (PCR) for blood and stool samples may be a useful and noninvasive diagnostic strategy to identify CMV infection when treatment of CDI eventually fails to show significant benefits. Quantitative CMV-PCR in mucosal biopsies may increase the diagnostic yield of traditional histopathology.

CMV colitis is potentially life-threatening if severe complications occur, such as sepsis secondary to colitis, massive colorectal bleeding, toxic megacolon, and colonic perforation, so that may necessitate pre-emptive antiviral treatment for those who are positive for CMV-PCR in blood and/or stool samples while pending histological diagnosis

PDF

http://www.e-jmii.com/article/S1684-1182(16)00008-6/pdf

November 29, 2016 at 7:54 am

Cytomegalovirus related fatal duodenal diverticular bleeding: Case report and literature review.

World J Gastroenterol. 2016 Aug 21;22(31):7166-74.

Makker J1, Bajantri B1, Sakam S1, Chilimuri S1.

Author information

1Jasbir Makker, Sridhar Chilimuri, Division of Gastroenterology, Department of Medicine, Bronx Lebanon Hospital Center, Bronx, NY 10457, United States.

Abstract

Involvement of gastrointestinal tract by cytomegalovirus (CMV) is common. CMV infections mainly run their course without any clinical signs in immunocompetent hosts.

In contrast, CMV can cause severe infections with serious consequences in a immunocompromised state typically associated with organ transplants, highly immunosuppressive cancer chemotherapy, advanced HIV infection or treatment with corticosteroids.

The incidence and severity of these manifestations of CMV is directly proportional with the degree of cellular immune dysfunction, i.e., CD8+ Cytotoxic T-cell response.

Clinical manifestations of CMV can become apparent in different situations including reactivation of CMV from latency, primary infection in a seronegative host, or exposure of a seropositive host to a new strain of CMV.

As the clinical signs of CMV in immunodeficient patients are usually sparse, physicians should be highly vigilant about CMV infection, a treatable condition that otherwise is associated with significant mortality.

Here we report a rare case of severe gastrointestinal CMV infection with sustained immunodeficiency secondary to treatment with steroids manifesting as fatal duodenal diverticular bleeding.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988300/pdf/WJG-22-7166.pdf

November 29, 2016 at 7:51 am

PANCREATIC TOXICITY AS AN ADVERSE EFFECT INDUCED BY MEGLUMINE ANTIMONIATE THERAPY IN A CLINICAL TRIAL FOR CUTANEOUS LEISHMANIASIS.

Rev Inst Med Trop Sao Paulo. 2016 Sep 22;58:68.

Lyra MR1, Passos SR2,3, Pimentel MI1, Bedoya-Pacheco SJ1, Valete-Rosalino CM1,4,3, Vasconcellos EC1, Antonio LF1, Saheki MN1, Salgueiro MM1, Santos GP1, Ribeiro MN1, Conceição-Silva F5, Madeira MF1,3, Silva JL1, Fagundes A1, Schubach AO1,6,7.

Author information

1Fundação Oswaldo Cruz (FIOCRUZ), Instituto Nacional de Infectologia Evandro Chagas (INI), Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses. Rio de Janeiro, RJ, Brazil. E-mails: marcelo.lyra@ini.fiocruz.br; maria.pimentel@ini.fiocruz.br; sandro.bedoya@ensp.fiocruz.br; claudia.valete@ini.fiocruz.br; erimedi@hotmail.com; lilianedefatima@gmail.com; mauricio.saheki@ini.fiocruz.br; marizasalgueiro@hotmail.com; ginelza.santos@ini.fiocruz.br;  madelon.novato@ini.fiocruz.br; fatima.madeira@ini.fiocruz.br; jorge.silva@ini.fiocruz.br;  aline.fagundes@ini.fiocruz.br; armando.schubach@ini.fiocruz.br

2Fundação Oswaldo Cruz (FIOCRUZ) Instituto Nacional de Infectologia Evandro Chagas (INI), Laboratório de Pesquisa Clínica em Epidemiologia. Rio de Janeiro, RJ, Brazil. E-mail: sonialambert@gmail.com

3Fellow researcher (“Jovem Cientista do Nosso Estado”) of Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ). Rio de Janeiro, RJ, Brazil. E-mails: sonialambert@gmail.com; claudia.valete@ini.fiocruz.br; fatima.madeira@ini.fiocruz.br

4Universidade Federal do Rio de Janeiro (UFRJ). Rio de Janeiro, RJ, Brazil. E-mail: claudia.valete@ini.fiocruz.br

5Fundação Oswaldo Cruz (FIOCRUZ), Instituto Oswaldo Cruz (IOC), Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brazil. E-mail: fconei@ioc.fiocruz.br

6Fellow researcher of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Rio de Janeiro, RJ, Brazil. E-mail: armando.schubach@ini.fiocruz.br

7Fellow researcher (“Cientista do Nosso Estado”) of Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Rio de Janeiro, RJ, Brazil. E-mail: armando.schubach@ini.fiocruz.br

Abstract

American tegumentary leishmaniasis is an infectious disease caused by a protozoan of the genus Leishmania. Pentavalent antimonials are the first choice drugs for cutaneous leishmaniasis (CL), although doses are controversial.

In a clinical trial for CL we investigated the occurrence of pancreatic toxicity with different schedules of treatment with meglumine antimoniate (MA).

Seventy-two patients were allocated in two different therapeutic groups: 20 or 5 mg of pentavalent antimony (Sb5+)/kg/day for 20 or 30 days, respectively. Looking for adverse effects, patients were asked about abdominal pain, nausea, vomiting or anorexia in each medical visit.

We performed physical examinations and collected blood to evaluate serum amylase and lipase in the pre-treatment period, and every 10 days during treatment and one month post-treatment. Hyperlipasemia occurred in 54.8% and hyperamylasemia in 19.4% patients.

Patients treated with MA 20 mg Sb5+ presented a higher risk of hyperlipasemia (p = 0.023). Besides, higher MA doses were associated with a 2.05 higher risk ratio (p = 0.003) of developing more serious (moderate to severe) hyperlipasemia. The attributable fraction was 51% in this group.

Thirty-six patients presented abdominal pain, nausea, vomiting or anorexia but only 47.2% of those had hyperlipasemia and/ or hyperamylasemia. These findings suggest the importance of the search for less toxic therapeutic regimens for the treatment of CL.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048639/pdf/1678-9946-rimtsp-58-00068.pdf

November 28, 2016 at 8:39 pm

Clinical, laboratory, and therapeutic characteristics of American tegumentary leishmaniasis in the 15 th State Health Division, Northwest Paraná State, Southern Brazil.

Rev Soc Bras Med Trop. 2016 Sep-Oct;49(5):593-601.

Nassif PW1, Castilho-Peres M2, Rosa AP3, Silva AL4, Aristides SM5, Lonardoni MV5, Teixeira JJ5, Silveira TG5.

Author information

1Programa de Pós-Graduação Stricto Sensu em Ciências da Saúde, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.

215a Regional de Saúde de Maringá, Maringá, Paraná, Brazil.

3Faculdade Ingá, Maringá, Paraná, Brazil.

4Consórcio Público Intermunicipal de Saúde do Setentrião Paranaense (CISAMUSEP), Maringá, Paraná, Brazil.

5Departamento de Análises Clínicas e Biomedicina, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.

Abstract

INTRODUCTION:

American tegumentary leishmaniasis (ATL) is an endemic disease in many regions of Brazil; however, only few reports on the actual epidemiological conditions are available. Here, we aimed to assess the clinical, epidemiological, and laboratory characteristics of ATL patients and their treatment in the 15th Regional Health Division of Paraná State, Maringá, Brazil.

METHODS:

This epidemiological study included patients diagnosed with ATL from January 2010 to September 2014, from the 15th Regional Health Division database.

RESULTS:

A total of 220 cases aged 3-84 years (85% male and 60.9% with up to 8 years of schooling) were included. The cases were classified as having the cutaneous form (n=183; 83.2%), mucosal form (n=26; 11.8%), mucocutaneous form (n=11; 5%), and relapses (n=21; 9.6%). Diagnosis was made via laboratory test results in 197 (89.5%) patients, and 172 (78.2%) completed the treatment within the study period. With regard to patients with the cutaneous form, 134 (95%) were cured, 131 (97.8%) were treated with Glucantime(r), and 47 (36.7%) received dosage of >15 and <20mg Sb5+/kg/day. Among the cases with mucosal involvement, 87.1% were cured and most were treated with <20mg Sb5+/kg/day. Thus, the cure rate was 93.6%.

CONCLUSIONS:

During the study period in the 15th Regional Health Division of Paraná State, ATL cases had a good response to treatment with a low rate of relapse or treatment failure, although a high percentage of mucosal or mucocutaneous form cases was also noted.

PDF

http://www.scielo.br/pdf/rsbmt/v49n5/0037-8682-rsbmt-49-05-00593.pdf

November 28, 2016 at 8:37 pm

Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals

Science Translational Medicine

Andrew M. Bellinger1,2,3,*, Mousa Jafari1,*, Tyler M. Grant1,3,*, Shiyi Zhang1,*,†, Hannah C. Slater4, Edward A. Wenger5, Stacy Mo1, Young-Ah Lucy Lee1, Hormoz Mazdiyasni1, Lawrence Kogan1, Ross Barman1, Cody Cleveland1,6, Lucas Booth1, Taylor Bensel1, Daniel Minahan1, Haley M. Hurowitz1, Tammy Tai1, Johanna Daily7, Boris Nikolic8, Lowell Wood5, Philip A. Eckhoff5, Robert Langer1,9,10,‡ and Giovanni Traverso1,6,11,‡

1Department of Chemical Engineering and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

2Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

3Lyndra Inc., Watertown, MA 02472, USA.

4Department of Infectious Disease Epidemiology, MRC (Medical Research Council) Centre for Outbreak Analysis and Modelling, Imperial College London, London, U.K.

5Institute for Disease Modeling, Bellevue, WA 98005, USA.

6Division of Gastroenterology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

7Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

8Biomatics Capital, 1107 1st Avenue, Apartment 1305, Seattle, WA 98101, USA.

9Media Lab, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

10 Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

11Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Toward malaria eradication

Although we know how to prevent malaria, we have failed to eliminate this damaging disease. To help the millions of individuals still affected around the world, Bellinger et al. have designed an easy-to-administer device that provides long-lasting delivery of an antimalarial drug. A star-shaped, drug-containing material is packaged into a capsule. When swallowed, the capsule dissolves in the stomach, and the star unfolds, assuming a shape that cannot pass further down the intestine. The star delivers a drug toxic to malaria-carrying mosquitoes for weeks but eventually falls apart and passes harmlessly out of the body. Modeling studies show that long-term delivery of this drug may move us closer to the elimination of this problematic disease by improving patient adherence to treatment.

Abstract

Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra–long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra–long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy.

FULL TEXT

http://stm.sciencemag.org/content/8/365/365ra157.full

November 28, 2016 at 10:27 am

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