Posts filed under ‘Resistencia bacteriana’

Still fighting prosthetic joint infection after knee replacement

LANCET Infectous Diseases June 2019 V.19 N.6

COMMENT – Still fighting prosthetic joint infection after knee replacement

We congratulate Erik Lenguerrand and colleagues on the publication of their paper in The Lancet Infectious Diseases1 and respect that it is a well-conducted study. In their large-scale observational study, the authors collected data from the UK National Joint Registry including a total of 679 010 primary knee arthroplasty cases and evaluated associations between patient, surgical, and healthcare system factors and the risk of revision for prosthetic joint infection. To the best of our knowledge, this is the largest cohort study to date analysing the risk factors for periprosthetic joint infection following primary total knee replacement…





LANCET Infectous Diseases June 2019 V.19 N.6

Risk factors associated with revision for prosthetic joint infection following knee replacement: an observational cohort study from England and Wales


Prosthetic joint infection is a devastating complication of knee replacement. The risk of developing a prosthetic joint infection is affected by patient, surgical, and health-care system factors. Existing evidence is limited by heterogeneity in populations studied, short follow-up, inadequate power, and does not differentiate early prosthetic joint infection, most likely related to the intervention, from late infection, more likely to occur due to haematogenous bacterial spread. We aimed to assess the overall and time-specific associations of these factors with the risk of revision due to prosthetic joint infection following primary knee replacement.


In this cohort study, we analysed primary knee replacements done between 2003 and 2013 in England and Wales and the procedures subsequently revised for prosthetic joint infection between 2003 and 2014. Data were obtained from the National Joint Registry linked to the Hospital Episode Statistics data in England and the Patient Episode Database for Wales. Each primary replacement was followed for a minimum of 12 months until the end of the observation period (Dec 31, 2014) or until the date of revision for prosthetic joint infection, revision for another indication, or death (whichever occurred first). We analysed the data using Poisson and piecewise exponential multilevel models to assess the associations between patient, surgical, and health-care system factors and risk of revision for prosthetic joint infection.


Of 679 010 primary knee replacements done between 2003 and 2013 in England and Wales, 3659 were subsequently revised for an indication of prosthetic joint infection between 2003 and 2014, after a median follow-up of 4·6 years (IQR 2·6–6·9). Male sex (rate ratio [RR] for male vs female patients 1·8 [95% CI 1·7–2·0]), younger age (RR for age ≥80 years vs <60 years 0·5 [0·4–0·6]), higher American Society of Anaesthesiologists [ASA] grade (RR for ASA grade 3–5 vs 1, 1·8 [1·6–2·1]), elevated body-mass index (BMI; RR for BMI ≥30 kg/m2 vs <25 kg/m2 1·5 [1·3–1·6]), chronic pulmonary disease (RR 1·2 [1·1–1·3]), diabetes (RR 1·4 [1·2–1·5]), liver disease (RR 2·2 [1·6–2·9]), connective tissue and rheumatic diseases (RR 1·5 [1·3–1·7]), peripheral vascular disease (RR 1·4 [1·1–1·7]), surgery for trauma (RR 1·9 [1·4–2·6]), previous septic arthritis (RR 4·9 [2·7–7·6]) or inflammatory arthropathy (RR 1·4 [1·2–1·7]), operation under general anaesthesia (RR 1·1 [1·0–1·2]), requirement for tibial bone graft (RR 2·0 [1·3–2·7]), use of posterior stabilised fixed bearing prostheses (RR for posterior stabilised fixed bearing prostheses vs unconstrained fixed bearing prostheses 1·4 [1·3–1·5]) or constrained condylar prostheses (3·5 [2·5–4·7]) were associated with a higher risk of revision for prosthetic joint infection. However, uncemented total, patellofemoral, or unicondylar knee replacement (RR for uncemented vs cemented total knee replacement 0·7 [95% CI 0·6–0·8], RR for patellofemoral vs cemented total knee replacement 0·3 [0·2–0·5], and RR for unicondylar vs cemented total knee replacement 0·5 [0·5–0·6]) were associated with lower risk of revision for prosthetic joint infection. Most of these factors had time-specific effects, depending on the time period post-surgery.


We have identified several risk factors for revision for prosthetic joint infection following knee replacement. Some of these factors are modifiable, and the use of targeted interventions or strategies could lead to a reduced risk of revision for prosthetic joint infection. Non-modifiable factors and the time-specific nature of the effects we have observed will allow clinicians to appropriately counsel patients preoperatively and tailor follow-up regimens.


National Institute for Health Research.

FULL TEXT 2/fulltext?dgcid=raven_jbs_etoc_email



May 24, 2019 at 7:39 am

Clinical Data on Daptomycin plus Ceftaroline versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

Antimicrob. Agents Chemother. May 2019 V.63 N.5

Matthew Geriak, Fadi Haddad, Khulood Rizvi, Warren Rose, Ravina Kullar, Kerry LaPlante, Marie Yu, Logan Vasina, Krista Ouellette, Marcus Zervos, Victor Nizet and George Sakoulas

Vancomycin (VAN) and daptomycin (DAP) are approved as a monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A regimen of daptomycin plus ceftaroline (DAP+CPT) has shown promise in published case series of MRSA salvage therapy, but no comparative data exist to compare up-front DAP+CPT head-to-head therapy versus standard monotherapy as an initial treatment. In a pilot study, we evaluated 40 adult patients who were randomized to receive 6 to 8 mg/kg of body weight per day of DAP and 600 mg intravenous (i.v.) CPT every 8 h (q8h) (n = 17) or standard monotherapy (n = 23) with vancomycin (VAN; dosed to achieve serum trough concentrations of 15 to 20 mg/liter; n = 21) or 6 to 8 mg/kg/day DAP (n = 2). Serum drawn on the first day of bacteremia was sent to a reference laboratory post hoc for measurement of interleukin-10 (IL-10) concentrations and correlation to in-hospital mortality. Sources of bacteremia, median Pitt bacteremia scores, Charlson comorbidity indices, and median IL-10 serum concentrations were similar in both groups. Although the study was initially designed to examine bacteremia duration, we observed an unanticipated in-hospital mortality difference of 0% (0/17) for combination therapy and 26% (6/23) for monotherapy (P = 0.029), causing us to halt the study. Among patients with an IL-10 concentration of >5 pg/ml, 0% (0/14) died in the DAP+CPT group versus 26% (5/19) in the monotherapy group (P = 0.057). Here, we share the full results of this preliminary (but aborted) assessment of early DAP+CPT therapy versus standard monotherapy in MRSA bacteremia, hoping to encourage a more definitive clinical trial of its potential benefits against this leading cause of infection-associated mortality. (The clinical study discussed in this paper has been registered at under identifier NCT02660346.)


May 21, 2019 at 3:53 pm

Considerations for Dose Selection and Clinical Pharmacokinetics/Pharmacodynamics for the Development of Antibacterial Agents

Antimicrob. Agents Chemother. May 2019 V.63 N.5

In June 2017, The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled “Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial Pathogens” to discuss details and critical parameters of various PK/PD methods and identify approaches for linking human pharmacokinetic (PK) data and drug efficacy analyses. The workshop participants included individuals from academia, industry, and government.


May 21, 2019 at 3:52 pm

REVISION – Difusión de los antibióticos en el sistema nervioso central

Revista Española de Quimioterapia Febrero 2018 V.31 N.1 P.1–12.

José María Cabrera-Maqueda,corresponding author1 Luna Fuentes Rumí,1 Gabriel Valero López,1 Ana Esther Baidez Guerrero,1 Estefanía García Molina,1 José Díaz Pérez,1 and Elisa García-Vázquez2


Las infecciones del SNC causadas por patógenos mutiresistentes suponen un reto terapéutico. El paso de fluidos y de solutos al SNC está estrechamente regulado a través de la BHE.La penetración de cualquier fármaco, inclusive los ATB, en el LCR depende del tamaño molecular, la lipofilicidad, la unión a proteínas plasmáticas y su afinidad por transportadores de la BHE. La relación entre el área bajo la curva en el LCR y el suero AUCCSF (Area Bajo la Curva en LCR)/AUCS (Area Bajo la Curva en suero) de una sustancia es el parámetro más preciso para determinar su capacidad de difusión.

Linezolid, algunas quinolonas y metronidazol consiguen altas concentraciones en LCR y son útiles para tratar microorganismos sensibles. Algunos ATB cuya permeabilidad a través de la BHE es baja pueden ser administrados directamente en el ventrículo a la vez que se realiza infusión IV. El ATB ideal para tratar una infección del SNC es pequeño, no tiene alta tasa de unión a proteínas plasmáticas, es moderadamente lipofílico y no es un ligando de alta afinidad a bombas de expulsión de la BHE.

Conocer la farmacocinética de los ATB y su interacción con la BHE permitirá mejorar el tratamiento de los pacientes con infecciones del SNC. En este artículo se exponen las propiedades físico-químicas de los principales grupos de ATB para evaluar cuáles son más prometedores en el tratamiento de las infecciones del SNC y cómo usarlos en la práctica clínica habitual.


May 19, 2019 at 7:13 pm

The widely used antimicrobial triclosan induces high levels of antibiotic tolerance in vitro and reduces antibiotic efficacy up to 100-fold in vivo.

Antimicrob Agents Chemother May 2019 V.63 N.5     

Westfall C et al.

The antimicrobial triclosan is used in a wide range of consumer products ranging from toothpaste, cleansers, socks, and baby toys. A bacteriostatic inhibitor of fatty acid synthesis, triclosan is extremely stable and accumulates in the environment.

Approximately 75% of adults in the United States have detectable levels of the compound in their urine, with a sizeable fraction of individuals (>10%) having urine concentrations equal to or greater than the minimal inhibitory concentration for Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA).

Previous work has identified connections between defects in fatty acid synthesis and accumulation of the alarmone guanosine tetraphosphate (ppGpp), which has been repeatedly associated with antibiotic tolerance and persistence.

Based on these data, we hypothesized that triclosan exposure may inadvertently drive bacteria into a state in which they are able to tolerate normally lethal concentrations of antibiotics.

Here we report that clinically relevant concentrations of triclosan increased E. coli and MRSA tolerance to bactericidal antibiotics as much as 10,000-fold in vitro and reduced antibiotic efficacy up to 100-fold in a mouse urinary tract infection model.

Genetic analysis indicated that triclosan-mediated antibiotic tolerance requires ppGpp synthesis but is independent of growth.

These data highlight an unexpected and certainly unintended consequence of adding high concentrations of antimicrobials in consumer products, supporting an urgent need to reevaluate the costs and benefits of the prophylactic use of triclosan and other bacteriostatic compounds.



May 16, 2019 at 9:08 am

Clinical Infectious Diseases May 1, 2019 V.68 N.9 P.1456-1462


Incidence of Acute Kidney Injury Among Critically Ill Patients With Brief Empiric Use of Antipseudomonal ß-Lactams With Vancomycin

Findings suggest that nephrotoxicity occurs after 3–5 days of piperacillin-tazobactam/vancomycin therapy. We found in a large observational study of intensive care unit patients that brief (<72-hour) empiric use of this combination was no more nephrotoxic than other such combinations.


Nephrotoxins contribute to 20%–40% of acute kidney injury (AKI) cases in the intensive care unit (ICU). The combination of piperacillin-tazobactam (PTZ) and vancomycin (VAN) has been identified as nephrotoxic, but existing studies focus on extended durations of therapy rather than the brief empiric courses often used in the ICU. The current study was performed to compare the risk of AKI with a short course of PTZ/VAN to with the risk associated with other antipseudomonal ß-lactam/VAN combinations.


The study included a retrospective cohort of 3299 ICU patients who received =24 but =72 hours of an antipseudomonal ß-lactam/VAN combination: PTZ/VAN, cefepime (CEF)/VAN, or meropenem (MER)/VAN. The risk of developing stage 2 or 3 AKI was compared between antibiotic groups with multivariable logistic regression adjusted for relevant confounders. We also compared the risk of persistent kidney dysfunction, dialysis dependence, or death at 60 days between groups.


The overall incidence of stage 2 or 3 AKI was 9%. Brief exposure to PTZ/VAN did not confer a greater risk of stage 2 or 3 AKI after adjustment for relevant confounders (adjusted odds ratio [95% confidence interval] for PTZ/VAN vs CEF/VAN, 1.11 [.85–1.45]; PTZ/VAN vs MER/VAN, 1.04 [.71–1.42]). No significant differences were noted between groups at 60-day follow-up in the outcomes of persistent kidney dysfunction (P = .08), new dialysis dependence (P = .15), or death (P = .09).


Short courses of PTZ/VAN were not associated with a greater risk of short- or 60-day adverse renal outcomes than other empiric broad-spectrum combinations.



May 5, 2019 at 11:56 am

A Therapeutic Strategy for All Pneumonia Patients: A 3-Year Prospective Multicenter Cohort Study Using Risk Factors for Multidrug-resistant Pathogens to Select Initial Empiric Therapy

Clinical Infectious Diseases April 1, 2019 V.68 N.7 P.1080-1088 


We applied a single algorithm to all forms of pneumonia, which was followed in 82.5% of a cohort of 1089 patients. Only 4.3% received inappropriate therapy; in multivariate analysis, site of pneumonia acquisition was not predictive of 30-day mortality.


Empiric therapy of pneumonia is currently based on the site of acquisition (community or hospital), but could be chosen, based on risk factors for multidrug-resistant (MDR) pathogens, independent of site of acquisition.


We prospectively applied a therapeutic algorithm based on MDR risks, in a multicenter cohort study of  1089 patients with 656 community-acquired pneumonia (CAP), 238 healthcare-associated pneumonia (HCAP), 140 hospital-acquired pneumonia (HAP), or 55 ventilator-associated pneumonia (VAP).


Approximately 83% of patients were treated according to the algorithm, with 4.3% receiving inappropriate therapy. The frequency of MDR pathogens varied, respectively, with VAP (50.9%), HAP (27.9%), HCAP (10.9%), and CAP (5.2%). Those with ≥2 MDR risks had MDR pathogens more often than those with 0–1 MDR risk (25.8% vs 5.3%, P < .001). The 30-day mortality rates were as follows: VAP (18.2%), HAP (13.6%), HCAP (6.7%), and CAP (4.7%), and were lower in patients with 0–1 MDR risks than in those with ≥2 MDR risks (4.5% vs 12.5%, P < .001). In multivariate logistic regression analysis, 5 risk factors (advanced age, hematocrit <30%, malnutrition, dehydration, and chronic liver disease), as well as hypotension and inappropriate therapy were significantly correlated with 30-day mortality, whereas the classification of pneumonia type (VAP, HAP, HCAP, CAP) was not.


Individual MDR risk factors can be used in a unified algorithm to guide and simplify empiric therapy for all pneumonia patients, and were more important than the classification of site of pneumonia acquisition in determining 30-day mortality.



May 4, 2019 at 12:14 pm

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