Posts filed under ‘Infecciones intraabdominales’

Carbapenem-Resistant Enterobacteriaceae Infections: Results From a Retrospective Series and Implications for the Design of Prospective Clinical Trials

Open Forum Infectious Diseases April 2017 V.4 N.2

Elizabeth L. Alexander; Jeffery Loutit; Mario Tumbarello; Richard Wunderink; Tim Felton …

Background.

The increasing incidence of multidrug-resistant Gram negatives, such as carbapenem-resistant Enterobacteriaceae (CRE), has resulted in a critical need for new antimicrobials. Most studies of new antimicrobials have been performed in patients with nondrug-resistant pathogens. We performed a retrospective analysis of patients with CRE infections to inform the design of phase 3 clinical trials.

Methods.

This was a retrospective study at 22 centers in 4 countries. Baseline data, treatment, and outcomes were collected in patients with complicated urinary tract infection (cUTI)/acute pyelonephritis (AP), hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), and bacteremia due to CRE.

Results.

Two hundred fifty-six cases of CRE infection were identified: 75 cUTI/AP, 21 HABP, 20 VABP, and 140 bacteremia. The patient population had significant comorbidities: 32.8% had chronic renal insufficiency, and 26.2% were immunocompromised. Illness severity at presentation was high: 29.3% presented with septic shock. Treatment regimens varied widely; however, a majority of patients received combination therapy. Outcomes were universally poor (28-day mortality was 28.1%) across all sites of infection, particularly in dialysis patients and those with sepsis.

Conclusions.

The CRE infections occured in patients with substantial comorbidities and were associated with high mortality and low rates of clinical cure with available antibiotics. Patients with these comorbidities are often excluded from enrollment in clinical trials for registration of new drugs. These results led to changes in the inclusion/exclusion criteria of a phase 3 trial to better represent the patient population with CRE infections and enable enrollment. Observational studies may become increasingly important to guide clinical trial design, inform on the existing standard of care, and provide an external control for subsequent trials.

PDF

https://watermark.silverchair.com/api/watermark?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAdkwggHVBgkqhkiG9w0BBwagggHGMIIBwgIBADCCAbsGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMZn7w0r8kx37PhNraAgEQgIIBjLKt0DouuWV11sRc8O-B6xxvAIOOUu170cfToimWAarK3pS8vgvRxMV2TmD9D5uxdT4RMRGUCy1jGrb7r7xt1tk71qTQlb-FDjXMkJR7SLpBdM24mW0SwQm1hUTgypdBxUZ9yNwoPvwE76KstP4DSUN6NKj0ioTM22Um7TOftKff3_cOlDS1O9Ex2sX89wsxgZFWOJieIgRj-Hts05GPoJG2DopwY2yBh6SsGZWREU4Fb9yAn3uSvHcWpeO_ORV8tsCuIrC1zprKAnL-KIrEmK6QR-1GNhnkvecyUt-PPDChwRylfyLGBpt797EaSyK8BbijeZwUQmGB28bd9Rms12-pZc2-eoheKmI_TpcTXr4A5cBh9LT3h0Bw1wOhsK9zhFLj7i1k90L3rpUEMcaDbIiqV8PfmaIFD6jGp2tVjiHIlHElyxymezBMy04QssCemVf29hUNX02GEbMnV2kQEmfdSzEq_0hp4v7t5mBroxc7TR3M7GRaWXp4pN4i1STLXYYg5QQGBPS5IFboGw

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September 3, 2017 at 6:51 pm

From Expert Protocols to Standardized Management of Infectious Diseases

Clinical Infectious Diseases  15 August 2017  V.65 N.suppl 1 S12–S19

Jean-Christophe Lagier; Camille Aubry; Marion Delord; Pierre Michelet; Hervé Tissot-Dupont …

We report here 4 examples of management of infectious diseases (IDs) at the University Hospital Institute Méditerranée Infection in Marseille, France, to illustrate the value of expert protocols feeding standardized management of IDs.

First, we describe our experience on Q fever and Tropheryma whipplei infection management based on in vitro data and clinical outcome.

Second, we describe our management-based approach for the treatment of infective endocarditis, leading to a strong reduction of mortality rate.

Third, we report our use of fecal microbiota transplantation to face severe Clostridium difficile infections and to perform decolonization of patients colonized by emerging highly resistant bacteria.

Finally, we present the standardized management of the main acute infections in patients admitted in the emergency department, promoting antibiotics by oral route, checking compliance with the protocol, and avoiding the unnecessary use of intravenous and urinary tract catheters.

Overall, the standardization of the management is the keystone to reduce both mortality and morbidity related to IDs.

PDF

https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cid/65/suppl_1/10.1093_cid_cix403/3/cix403.pdf?Expires=1502372492&Signature=LVAbXU3YuwNx~UkUFnKvXaFmayq1aLSWpor6xnVqc2jGiKuNc69M1UqI4xbuqSgRoOKoPhupwLOXRmDGZRMNfu1ydEj9NXbJnqvpBSeWUzfnWw~jYh2w3Y37B92GZwGPSe4XelatYtvhE7i8mqlvzzKKpL2cpkgYhApfvdGjdPIJ-cWZCHuU8dzEdHMOzmEjV-sJI1rBrwSqK4XlRyFojeLEKx5yBZxDukcIP2GQbPvbL1BYugZA~MAyA8mGR2GpExfsI14HZhD4mnTkj9UwjfA63wbptXdFn8jPuhfRCDI6Q52VtmEonPn~V4RR88mRqcV~l63vhtFfzysOXOk83A__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

August 9, 2017 at 8:50 am

Moraxella osloensis peritonitis : Case report and review.

Rev Esp Quimioter. 2016 Jun;29(3):161-3.

[Article in Spanish]

Hernández-Egido S1, Puerta-Mateo A, Cores-Calvo O, Ruiz-Ferraras E.

Author information

1 Sara Hernández Egido, Complejo Asistencial Universitario de Salamanca Paseo de San Vicente nº 58-182 C.P. 37007 Salamanca, Spain. sathassa@hotmail.com.

PDF

http://seq.es/seq/0214-3429/29/3/hernandez26mar2016.pdf

August 2, 2017 at 4:20 pm

Vancomycin-resistant enterococcal infections: epidemiology, clinical manifestations, and optimal management.

Infect Drug Resist. 2015 Jul 24;8:217-30.

O’Driscoll T1, Crank CW2.

Author information

1 Department of Pharmacy Practice, Chicago College of Pharmacy, Downers Grove, IL, USA.

2 Pharmacy Services, Rush-Copley Medical Center, Aurora, IL, USA.

Abstract

Since its discovery in England and France in 1986, vancomycin-resistant Enterococcus has increasingly become a major nosocomial pathogen worldwide.

Enterococci are prolific colonizers, with tremendous genome plasticity and a propensity for persistence in hospital environments, allowing for increased transmission and the dissemination of resistance elements.

Infections typically present in immunosuppressed patients who have received multiple courses of antibiotics in the past.

Virulence is variable, and typical clinical manifestations include bacteremia, endocarditis, intra-abdominal and pelvic infections, urinary tract infections, skin and skin structure infections, and, rarely, central nervous system infections.

As enterococci are common colonizers, careful consideration is needed before initiating targeted therapy, and source control is first priority.

Current treatment options including linezolid, daptomycin, quinupristin/dalfopristin, and tigecycline have shown favorable activity against various vancomycin-resistant Enterococcus infections, but there is a lack of randomized controlled trials assessing their efficacy.

Clearer distinctions in preferred therapies can be made based on adverse effects, drug interactions, and pharmacokinetic profiles.

Although combination therapies and newer agents such as tedizolid, telavancin, dalbavancin, and oritavancin hold promise for the future treatment of vancomycin-resistant Enterococcus infections, further studies are needed to assess their possible clinical impact, especially in the treatment of serious infections.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521680/pdf/idr-8-217.pdf

August 1, 2017 at 9:06 pm

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

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