Posts filed under ‘Infecciones urinarias’

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

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September 3, 2017 at 6:51 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

“Urinary Tract Infection”—Requiem for a Heavyweight

The Journal of the American Geriatrics Society  May 19, 2017

Thomas E. Finucane MD

Johns Hopkins Bayview Medical Center, Baltimore, Maryland

Abstract

“Urinary tract infection” (“UTI”) is an ambiguous, expansive, overused diagnosis that can lead to marked, harmful antibiotic overtreatment. “Significant bacteriuria,” central to most definitions of “UTI,” has little significance in identifying individuals who will benefit from treatment. “Urinary symptoms” are similarly uninformative. Neither criterion is well defined. Bacteriuria and symptoms remit and recur spontaneously. Treatment is standard for acute uncomplicated cystitis and common for asymptomatic bacteriuria, but definite benefits are few. Treatment for “UTI” in older adults with delirium and bacteriuria is widespread but no evidence supports the practice, and expert opinion opposes it.

Sensitive diagnostic tests now demonstrate that healthy urinary tracts host a ubiquitous, complex microbial community. Recognition of this microbiome, largely undetectable using standard agar-based cultures, offers a new perspective on “UTI.” Everyone is bacteriuric. From this perspective, most people who are treated for a “UTI” would probably be better off without treatment. Elderly adults, little studied in this regard, face particular risk. Invasive bacterial diseases such as pyelonephritis and bacteremic bacteriuria are also “UTIs.”

Mindful decisions about antibiotic use will require a far better understanding of how pathogenicity arises within microbial communities. It is likely that public education and meaningful informed-consent discussions about antibiotic treatment of bacteriuria, emphasizing potential harms and uncertain benefits, would reduce overtreatment. Emphasizing the microbiome’s significance and using the term “urinary tract dysbiosis” instead of “UTI” might also help and might encourage mindful study of the relationships among host, aging, microbiome, disease, and antibiotic treatment…..

FULL TEXT

http://onlinelibrary.wiley.com/doi/10.1111/jgs.14907/full

PDF

http://onlinelibrary.wiley.com/doi/10.1111/jgs.14907/epdf

July 20, 2017 at 8:24 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

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May 7, 2017 at 8:00 pm

Intravenous fosfomycin-back to the future. Systematic review and meta-analysis of the clinical literature.

Clin Microbiol Infect. 2016 Dec 9. pii: S1198-743X(16)30610-3

Grabein B1, Graninger W2, Rodríguez Baño J3, Dinh A4, Liesenfeld DB5.

Author information

1 Department of Clinical Microbiology and Hospital Hygiene, Munich University Hospital, Munich, Germany.

2 Institute for Infectiology, Karl Landsteiner Society, Vienna, Austria.

3 Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitarios Virgen Macarena y Virgen del Rocío, Departamento de Medicina, Universidad de Sevilla-IBIS, Sevilla, Spain; Spanish Network for Research in Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain.

4 Infectious Disease Unit, R. Poincaré University Hospital, Garches, AP-HP, Versailles Saint Quentin University, Garches, France.

5 InfectoPharm Arzneimittel und Consilium GmbH, Heppenheim, Germany. Electronic address: david.liesenfeld@infectopharm.de

Abstract

OBJECTIVES:

We conducted a systematic review and meta-analysis to summarize the clinical evidence and usage patterns of intravenous fosfomycin from its development to the present time.

METHODS:

PubMed, the Cochrane Library and local journals were searched for relevant studies reporting aggregated data of intravenous fosfomycin use in adults and children, with no restrictions regarding study design. Single case reports were excluded. Data were systematically abstracted for all included studies. Clinical and microbiological efficacy from randomized controlled and comparative observational studies were synthesized using meta-analysis to calculate pooled effect sizes.

RESULTS:

In all, 128 studies on intravenous fosfomycin in 5527 patients were evaluated. Fosfomycin was predominantly used for sepsis/bacteraemia, urinary tract, respiratory tract, bone and joint, and central nervous system infections. No difference in clinical (OR 1.44, 95% CI 0.96-2.15) or microbiological (OR 1.28, 95% CI 0.82-2.01) efficacy between fosfomycin and other antibiotics was observed in comparative trials. The pooled estimate for resistance development during fosfomycin monotherapy was 3.4% (95% CI 1.8%-5.1%). Fosfomycin showed a favourable safety profile, with generally mild adverse events not requiring discontinuation of treatment. Included studies explored intravenous fosfomycin as an anti-staphylococcal agent in monotherapy and combination therapy, whereas studies from 1990 focused on combination therapy (fosfoymcin + β-lactams or aminoglycosides) for challenging infections frequently caused by multidrug-resistant organisms.

CONCLUSION:

Intravenous fosfomycin can play a vital role in the antibiotic armamentarium, given its long history of effective and safe use. However, well-designed randomized controlled trials are still desired.

PDF

http://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(16)30610-3/pdf

May 7, 2017 at 2:55 pm

Is asymptomatic bacteriuria a risk factor for prosthetic joint infection?

Clin Infect Dis. 2014 Jul 1;59(1):41-7.

Sousa R1, Muñoz-Mahamud E2, Quayle J3, Dias da Costa L1, Casals C2, Scott P3, Leite P1, Vilanova P2, Garcia S2, Ramos MH4, Dias J5, Soriano A6, Guyot A7.

Author information

Departments of Orthopaedics.

1 Department of Orthopaedics

2 Department of Orthopaedics, Bone and Joint Infection Unit.

3 Department of Orthopaedics.

4 Microbiology, Centro Hospitalar do Porto-Hospital de Santo António.

5 Department of Biostatistics, Administração Regional de Saúde do Norte, Porto, Portugal.

6 Department of Infectious Diseases, Hospital Clínic of Barcelona, Spain.

7 Department of Microbiology, Frimley Park Hospital, Frimley, United Kingdom.

Abstract

BACKGROUND:

Infection is a major complication after total joint arthroplasty. The urinary tract is a possible source of surgical site contamination, but the role of asymptomatic bacteriuria (ASB) before elective surgery and the subsequent risk of infection is poorly understood.

METHODS:

Candidates for total hip or total knee arthroplasty were reviewed in a multicenter cohort study. A urine sample was cultured in all patients, and those with ASB were identified. Preoperative antibiotic treatment was decided on an individual basis, and it was not mandatory or randomized. The primary outcome was prosthetic joint infection (PJI) in the first postoperative year.

RESULTS:

A total of 2497 patients were enrolled. The prevalence of ASB was 12.1% (303 of 2497), 16.3% in women and 5.0% in men (odds ratio, 3.67; 95% confidence interval, 2.65-5.09; P < .001). The overall PJI rate was 1.7%. The infection rate was significantly higher in the ASB group than in the non-ASB group (4.3% vs 1.4%; odds ratio, 3.23; 95% confidence interval, 1.67-6.27; P = .001). In the ASB group, there was no significant difference in PJI rate between treated (3.9%) and untreated (4.7%) patients. The ASB group had a significantly higher proportion of PJI due to gram-negative microorganisms than the non-ASB group, but these did not correlate to isolates from urine cultures.

CONCLUSIONS:

ASB was an independent risk factor for PJI, particularly that due to gram-negative microorganisms. Preoperative antibiotic treatment did not show any benefit and cannot be recommended.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305141/pdf/ciu235.pdf

April 6, 2017 at 8:30 am

Infectious Complications Following Transrectal Ultrasound–Guided Prostate Biopsy: New Challenges in the Era of Multidrug-Resistant Escherichia coli

Clinical Infectious Diseases July 15, 2013 V.57 N.2 P.267-274

CLINICAL PRACTICE

Deborah A. Williamson, Lucinda K. Barrett, Benjamin A. Rogers, Joshua T. Freeman, Paul Hadway, and David L. Paterson

1Faculty of Medical and Health Sciences, University of Auckland

2Department of Clinical Microbiology, Auckland District Health Board, New Zealand

3The University of Queensland, UQ Centre for Clinical Research, Brisbane

4Department of Urology, Royal Brisbane and Women’s Hospital, Herston, Queensland, Australia

Transrectal ultrasound (TRUS)–guided prostate biopsy is currently considered the standard technique for obtaining tissue to make a histological diagnosis of prostatic carcinoma. Infectious complications following TRUS-guided prostate biopsy are well described, and are reportedly increasing in incidence.

The role of antibiotic prophylaxis in reducing post–TRUS biopsy infections is now established, and many guidelines suggest that fluoroquinolone antimicrobials are the prophylactic agents of choice.

Of note, however, recent reports suggest an emerging association between TRUS biopsy and subsequent infection with fluoroquinolone-resistant Escherichia coli.

Against this background, we provide an overview of the epidemiology, prevention, and treatment of infectious complications following TRUS biopsy, in the wider context of increasing global antimicrobial resistance.

 

We provide an overview of the published literature relating to the epidemiology, prevention, and treatment of infections following transrectal ultrasound–guided prostate biopsy in the wider context of increasing antimicrobial resistance.

PDF

http://cid.oxfordjournals.org/content/57/2/267.full.pdf

February 20, 2017 at 3:21 pm

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