Posts filed under ‘Infecciones intraabdominales’

SOMANZ guidelines for the investigation and management sepsis in pregnancy.

Aust N Z J Obstet Gynaecol. July 3, 2017    

Bowyer L1, Robinson HL2, Barrett H3, Crozier TM4, Giles M5,6, Idel I7, Lowe S8, Lust K9, Marnoch CA10, Morton MR11, Said J12,13, Wong M14, Makris A15,16.

Author information

1 Maternal Fetal Medicine, Royal Hospital for Women, Sydney, New South Wales, Australia.

2 Department of Medicine, Ipswich Hospital, Ipswich, Queensland, Australia.

3 Department of Obstetric Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia.

4 Intensive Care, Monash Medical Health, Melbourne, Victoria, Australia.

5 Department of Infectious Diseases, Alfred Health, Melbourne, Victoria, Australia.

6 Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia.

7 Department of Nephrology, Eastern Health, Melbourne, Victoria, Australia.

8 Royal Hospital for Women, Sydney, New South Wales, Australia.

9 Department of Obstetrics and Gynaecology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia.

10 Auckland District Health Board, Auckland, New Zealand.

11 Women’s and Babies Division, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia.

12 Department of Maternal Fetal Medicine, Sunshine Hospital, Melbourne, Victoria, Australia.

13 Maternal Fetal Medicine, Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia.

14 Department of Anaesthesia, Royal Women’s Hospital, Melbourne, Victoria, Australia.

15 Department of Nephrology, Liverpool Hospital, Liverpool, New South Wales, Australia.

16 Department of Medicine, Western Sydney University, Sydney, New South Wales, Australia.

Abstract

SOMANZ (Society of Obstetric Medicine Australia and New Zealand) has written a guideline to provide evidence-based guidance for the investigation and care of women with sepsis in pregnancy or the postpartum period.

The guideline is evidence-based and incorporates recent changes in the definition of sepsis. The etiology, investigation and treatment of bacterial, viral and non-infective causes of sepsis are discussed.

Obstetric considerations relevant to anaesthetic and intensive care treatment in sepsis are also addressed. A multi-disciplinary group of clinicians with experience in all aspects of the care of pregnant women have contributed to the development of the guidelines.

This is an executive summary of the guidelines.

abstract

http://onlinelibrary.wiley.com/doi/10.1111/ajo.12646/abstract

PDF

http://onlinelibrary.wiley.com/doi/10.1111/ajo.12646/epdf

July 11, 2017 at 3:42 pm

Efficacy and safety of ridinilazole compared with vancomycin for the treatment of Clostridium difficile infection: a phase 2, randomised, double-blind, active-controlled, non-inferiority study

Lancet Infectious Diseases July 2017 V.17 N.7

Dr Richard J Vickers, PhD’, Glenn S Tillotson, PhD, Richard Nathan, MD, Sabine Hazan, MD, John Pullman, MD, Christopher Lucasti, DO, Kenneth Deck, MD, Prof Bruce Yacyshyn, MD, Benedict Maliakkal, MD, Yves Pesant, MD, Bina Tejura, MD, Prof David Roblin, FRCP, Prof Dale N Gerding, MD, Prof Mark H Wilcox, MD for the show CoDIFy study group†

Background

Clostridium difficile infection is the most common health-care-associated infection in the USA. We assessed the safety and efficacy of ridinilazole versus vancomycin for treatment of C difficile infection.

Methods

We did a phase 2, randomised, double-blind, active-controlled, non-inferiority study. Participants with signs and symptoms of C difficile infection and a positive diagnostic test result were recruited from 33 centres in the USA and Canada and randomly assigned (1:1) to receive oral ridinilazole (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days. The primary endpoint was achievement of a sustained clinical response, defined as clinical cure at the end of treatment and no recurrence within 30 days, which was used to establish non-inferiority (15% margin) of ridinilazole versus vancomycin. The primary efficacy analysis was done on a modified intention-to-treat population comprising all individuals with C difficile infection confirmed by the presence of free toxin in stool who were randomly assigned to receive one or more doses of the study drug. The study is registered with ClinicalTrials.gov, number NCT02092935.

Findings

Between June 26, 2014, and August 31, 2015, 100 patients were recruited; 50 were randomly assigned to receive ridinilazole and 50 to vancomycin. 16 patients did not complete the study, and 11 discontinued treatment early. The primary efficacy analysis included 69 patients (n=36 in the ridinilazole group; n=33 in the vancomycin group). 24 of 36 (66·7%) patients in the ridinilazole group versus 14 of 33 (42·4%) of those in the vancomycin group had a sustained clinical response (treatment difference 21·1%, 90% CI 3·1–39·1, p=0·0004), establishing the non-inferiority of ridinilazole and also showing statistical superiority at the 10% level. Ridinilazole was well tolerated, with an adverse event profile similar to that of vancomycin: 82% (41 of 50) of participants reported adverse events in the ridinilazole group and 80% (40 of 50) in the vancomycin group. There were no adverse events related to ridinilazole that led to discontinuation.

Interpretation

Ridinilazole is a targeted-spectrum antimicrobial that shows potential in treatment of initial C difficile infection and in providing sustained benefit through reduction in disease recurrence. Further clinical development is warranted.

Funding

Wellcome Trust and Summit Therapeutics.

PDF

http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(17)30235-9.pdf

 

Lancet Infectious Diseases July 2017 V.17 N.7

COMMENT – Expanding the armamentarium for the treatment of Clostridium difficile infection 

Simon D Goldenberg

In The Lancet Infectious Diseases, Richard Vickers and colleagues1 report results of a phase 2 study of ridinilazole, a promising new drug for the treatment of Clostridium difficile infection. Although efforts to improve infection control practices and antimicrobial stewardship have led to significant reductions in some countries, C difficile infection remains a substantial problem worldwide.

All-cause 30-day mortality associated with C difficile infection has been reported to be in the region of 9–38%.3, 4 Furthermore, cases are associated with excess length of hospital stay of approximately 7 days (and 12 days in severe cases). C difficile infection usually occurs following disruption of the intestinal microbiota resulting from exposure to antibiotics. The risk of C difficile infection increases by up to six times during antibiotic therapy and in the month thereafter.

PDF

http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(17)30237-2.pdf

June 23, 2017 at 7:56 am

Ceftolozane/tazobactam activity against drug-resistant Enterobacteriaceae and Pseudomonas aeruginosa causing urinary tract and intraabdominal infections in Europe: report from an antimicrobial surveillance programme (2012–15)

Journal of Antimicrobial Chemotherapy May 2017 V.72 N.5

EDITOR’S CHOICE

Michael A. Pfaller; Matteo Bassetti; Leonard R. Duncan; Mariana Castanheira

Objectives:

To evaluate the in vitro activity of ceftolozane/tazobactam and comparators tested against European isolates of Enterobacteriaceae and Pseudomonas aeruginosa from hospitalized patients with urinary tract infection or intraabdominal infections.

Methods:

A total of 6553 Gram-negative organisms (603 P. aeruginosa and 5950 Enterobacteriaceae) were consecutively collected from 41 hospitals located in 17 European countries plus Israel and Turkey. The organisms were tested for susceptibility by broth microdilution methods and the results interpreted according to EUCAST and CLSI breakpoint criteria.

Results:

Ceftolozane/tazobactam [MIC50/90 0.25/1 mg/L; 93.5%/91.3% susceptible (S) (CLSI/EUCAST criteria)] and meropenem [MIC50/90 ≤0.06/≤0.06 mg/L; 98.1%/98.3% S (CLSI/EUCAST)] were the most active compounds tested against Enterobacteriaceae. Among the Enterobacteriaceae isolates, 1.9% were carbapenem resistant (CRE), 15.2% exhibited an ESBL non-CRE phenotype, 14.6% were MDR, 2.2% were XDR and <0.1% were pan-drug resistant (PDR). Whereas ceftolozane/tazobactam showed activity against ESBL non-CRE phenotype isolates (MIC50/90 0.5/8 mg/L), it lacked useful activity against strains with a CRE (MIC50/90 >32/>32 mg/L; 3.6% S) or PDR (MIC50 >32 mg/L; 0.0% S) phenotype. Ceftolozane/tazobactam was the most potent (MIC50/90 0.5/4 mg/L) β-lactam agent tested against P. aeruginosa isolates, inhibiting 91.7% at an MIC of ≤4 mg/L. P. aeruginosa exhibited high rates of resistance to cefepime (20.6%), ceftazidime (23.1%), meropenem (9.0%) and piperacillin/tazobactam (26.9%) (EUCAST criteria). Among these four P. aeruginosa resistant phenotypes, 61.3%–70.4% were susceptible to ceftolozane/tazobactam.

Conclusions:

Ceftolozane/tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than currently available cephalosporins and piperacillin/tazobactam when tested against Enterobacteriaceae.

PDF

https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jac/72/5/10.1093_jac_dkx009/1/dkx009.pdf?Expires=1494290906&Signature=PwSqO0ia77fjFIGKAD-W7rdRM5XjqvpROnT0K-LohId~LiUbAxo0px11Dxre1WTGBWhaMlZq5X6G180jhdj-NtSzi1Iu~6KARm~e8UGTBuVzV0X-Xb5iQrejbrdikp-krcYo967o99FoG~-XOpVwEuORM95fqKgqUQpG-0Afn-X6ceMYzUfT4A5sKJxR0uDL7Kghjz4KxfBo6FS8y-NsbwIblUMmNl-m35sUsB2hyztQnKcMDeCS3TCeo3djHeI07MIUOHBFKsheiiCmCN6EbOj1FnV0NJ1HuhNE1l7sr4Jggny0sNk90PitwHXRkrodP3JL-PwETe0Ywihi4qT0dQ__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

May 7, 2017 at 8:00 pm

Estimating the burden of invasive and serious fungal disease in the United Kingdom

Journal of Infection January 2017 V.74 N.1

Matthew Pegorie a, David W. Denning b,c,d, *, William Welfare a,d

a Public Health England North West Health Protection Team (Greater Manchester), UK

bNational Aspergillosis Centre, University Hospital of South Manchester, Manchester, UK

c The University of Manchester, Manchester, UK

d Manchester Academic Health Sciences Centre, University of Manchester, UK

Background: The burden of fungal disease in the UK is unknown. Only limited data are systematically collected. We have estimated the annual burden of invasive and serious fungal disease.

Methods: We used several estimation approaches. We searched and assessed published estimates of incidence, prevalence or burden of specific conditions in various high risk groups. Studies with adequate internal and external validity allowed extrapolation to estimate current UK burden. For conditions without adequate published estimates, we sought expert advice.

Results: The UK population in 2011 was 63,182,000 with 18% aged under 15 and 16% over 65. The following annual burden estimates were calculated: invasive candidiasis 5142; Candida peritonitis complicating chronic ambulatory peritoneal dialysis 88; Pneumocystis pneumonia 207e587 cases, invasive aspergillosis (IA), excluding critical care patients 2901e2912, and IA in critical care patients 387e1345 patients, <100 cryptococcal meningitis cases. We estimated 178,000 (50,000e250,000) allergic bronchopulmonary aspergillosis cases in people with asthma, and 873 adults and 278 children with cystic fibrosis. Chronic pulmonary aspergillosis is estimated to affect 3600 patients, based on burden estimates post tuberculosis and in sarcoidosis.

Conclusions: Uncertainty is intrinsic to most burden estimates due to diagnostic limitations, lack of national surveillance systems, few published studies and methodological limitations. The largest uncertainty surrounds IA in critical care patients. Further research is needed to produce a more robust estimate of total burden

PDF

http://www.journalofinfection.com/article/S0163-4453(16)30273-0/pdf

March 25, 2017 at 5:40 pm

Inhibition of Plasmodium Liver Infection by Ivermectin

Antimicrobial Agents & Chemotherapy February 2017 V.61 N.2 e02005-16

António M. Mendes, Inês S. Albuquerque, Marta Machado, Joana Pissarra, Patrícia Meireles, and Miguel Prudêncio

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal

Avermectins are powerful endectocides with an established potential to reduce the incidence of vector-borne diseases. Here, we show that several avermectins inhibit the hepatic stage of Plasmodium infection in vitro. Notably, ivermectin potently inhibits liver infection in vivo by impairing parasite development inside hepatocytes. This impairment has a clear impact on the ensuing blood stage parasitemia, reducing disease severity and enhancing host survival. Ivermectin has been proposed as a tool to control malaria transmission because of its effects on the mosquito vector. Our study extends the effect of ivermectin to the early stages of mammalian host infection and supports the inclusion of this multipurpose drug in malaria control strategies.

PDF

http://aac.asm.org/content/61/2/e02005-16.full.pdf+html

January 25, 2017 at 2:29 pm

Review – Role of cephalosporins in the era of Clostridium difficile infection

Journal of Antimicrobial Chemotherapy January 2017 V.72 N.1 P. 1-18

Mark H. Wilcox; James D. Chalmers; Carl E. Nord; Jane Freeman; Emilio Bouza

The incidence of Clostridium difficile infection (CDI) in Europe has increased markedly since 2000. Previous meta-analyses have suggested a strong association between cephalosporin use and CDI, and many national programmes on CDI control have focused on reducing cephalosporin usage. Despite reductions in cephalosporin use, however, rates of CDI have continued to rise. This review examines the potential association of CDI with cephalosporins, and considers other factors that influence CDI risk. EUCLID (the EUropean, multicentre, prospective biannual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhoea) reported an increase in the annual incidence of CDI from 6.6 to 7.3 cases per 10 000 patient bed-days from 2011–12 to 2012–13, respectively. While CDI incidence and cephalosporin usage varied widely across countries studied, there was no clear association between overall cephalosporin prescribing (or the use of any particular cephalosporin) and CDI incidence. Moreover, variations in the pharmacokinetic and pharmacodynamic properties of cephalosporins of the same generation make categorization by generation insufficient for predicting impact on gut microbiota. A multitude of additional factors can affect the risk of CDI. Antibiotic choice is an important consideration; however, CDI risk is associated with a range of antibiotic classes. Prescription of multiple antibiotics and a long duration of treatment are key risk factors for CDI, and risk also differs across patient populations. We propose that all of these are factors that should be taken into account when selecting an antibiotic, rather than focusing on the exclusion of individual drug classes.

FULL TEXT

https://academic.oup.com/jac/article/72/1/1/2643139/Role-of-cephalosporins-in-the-era-of-Clostridium

PDF

http://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jac/72/1/10.1093_jac_dkw385/3/dkw385.pdf?Expires=1485599756&Signature=SddUPWXGgMIOXumKQr~qwNbCCMxsK8SI2aZVv0uL-tQpcHQXAjZGqgaF-JwVD0zdothcR0oHpy7YxjIXxOHKBLyTs1AWogBxAKbIw~YoEBxpodh~dPhFEWIX4DQ21EgUHCpEL5RWCCEUgCc8OSWe5So2NuUc~TYUPuHbcKVkWII~FWDqAFTjhzQ4zHBQjynBNavwak6qKUDIsMt5ZVatILj2ojFwALSL0EMe14CdE5iD-hOrfocqBpltMzG3Nm1TqVyGfkeXJ5V7xhE6Gq-CWaMkN8nIApRi2-BeZ2cs9A7p6ILOCUkp2FUSf5BNw-0RCizaK2v8SA3zFJCdwoUqFw__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

January 24, 2017 at 8:09 am

Short- and long-term effects of oral vancomycin on the human intestinal microbiota

Journal of Antimicrobial & Chemotherapy January 1, 2017 V.72 N.1 P.128-136

Sandrine Isaac, Jose U. Scher, Ana Djukovic, Nuria Jiménez, Dan R. Littman, Steven B. Abramson, Eric G. Pamer, and Carles Ubeda

1Departamento de Genómica y Salud, Centro Superior de Investigación en Salud Pública – FISABIO, Valencia, Spain

2Department of Medicine, New York University School of Medicine and Hospital for Joint Diseases, New York, NY, USA

3Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY, USA

4Howard Hughes Medical Institute, New York University School of Medicine, New York, NY, USA

5Immunology Program and Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

6Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

7Centers of Biomedical Research Network (CIBER) in Epidemiology and Public Health, Madrid, Spain

Background

Oral vancomycin remains the mainstay of therapy for severe infections produced by Clostridium difficile, the most prevalent cause of healthcare-associated infectious diarrhoea in developed countries. However, its short- and long-term effects on the human intestinal microbiota remain largely unknown.

Methods

We utilized high-throughput sequencing to analyse the effects of vancomycin on the faecal human microbiota up to 22 weeks post-antibiotic cessation. The clinical relevance of the observed microbiota perturbations was studied in mice.

Results

During vancomycin therapy, most intestinal microbiota genera and operational taxonomic units (OTUs) were depleted in all analysed subjects, including all baseline OTUs from the phylum Bacteroidetes. This was accompanied by a vast expansion of genera associated with infections, including Klebsiella and Escherichia/Shigella. Following antibiotic cessation, marked differences in microbiota resilience were observed among subjects. While some individuals recovered a microbiota close to baseline composition, in others, up to 89% of abundant OTUs could no longer be detected. The clinical relevance of the observed microbiota changes was further demonstrated in mice, which developed analogous microbiota alterations. During vancomycin treatment, mice were highly susceptible to intestinal colonization by an antibiotic-resistant pathogen and, upon antibiotic cessation, a less-resilient microbiota allowed higher levels of pathogen colonization.

Conclusions

Oral vancomycin induces drastic and consistent changes in the human intestinal microbiota. Upon vancomycin cessation, the microbiota recovery rate varied considerably among subjects, which could influence, as validated in mice, the level of susceptibility to pathogen intestinal colonization. Our results demonstrate the negative long-term effects of vancomycin, which should be considered as a fundamental aspect of the cost–benefit equation for antibiotic prescription.

PDF

http://jac.oxfordjournals.org/content/72/1/128.full.pdf+html

January 6, 2017 at 7:34 am

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