Posts filed under ‘Bacterias’

Antibiotics for operative vaginal delivery –  practice-changing data

LANCET June 15, 2019 V.393 N.10189 P.2361-2362


Antibiotics for operative vaginal delivery –  practice-changing data

The large randomised controlled trial on the effect of antibiotics to prevent infection after operative vaginal delivery by Marian Knight and colleagues1 in The Lancet is practice changing. Operative vaginal deliveries include either vacuum or forceps, and are used in about 2–15% of births.2 Even if one conservatively estimates 2% of babies are born by operative vaginal delivery globally, about 2 700 000 of the world’s 135 million annual births are operative vaginal deliveries. Up to 16% of these births can be associated with infection without antibiotics prophylaxis,3 representing about 432 000 annual infections associated with operative vaginal delivery worldwide……




LANCET June 15, 2019 V.393 N.10189 P.2395-2403


Prophylactic antibiotics in the prevention of infection after operative vaginal delivery (ANODE): a multicentre randomised controlled trial


Risk factors for maternal infection are clearly recognised, including caesarean section and operative vaginal birth. Antibiotic prophylaxis at caesarean section is widely recommended because there is clear systematic review evidence that it reduces incidence of maternal infection. Current WHO guidelines do not recommend routine antibiotic prophylaxis for women undergoing operative vaginal birth because of insufficient evidence of effectiveness. We aimed to investigate whether antibiotic prophylaxis prevented maternal infection after operative vaginal birth.


In a blinded, randomised controlled trial done at 27 UK obstetric units, women (aged ≥16 years) were allocated to receive a single dose of intravenous amoxicillin and clavulanic acid or placebo (saline) following operative vaginal birth at 36 weeks gestation or later. The primary outcome was confirmed or suspected maternal infection within 6 weeks of delivery defined by a new prescription of antibiotics for specific indications, confirmed systemic infection on culture, or endometritis. We did an intention-to-treat analysis. This trial is registered with ISRCTN, number 11166984, and is closed to accrual.


Between March 13, 2016, and June 13, 2018, 3427 women were randomly assigned to treatment: 1719 to amoxicillin and clavulanic acid, and 1708 to placebo. Seven women withdrew, leaving 1715 in the amoxicillin and clavulanic acid group and 1705 in the placebo groups. Primary outcome data were missing for 195 (6%) women. Significantly fewer women allocated to amoxicillin and clavulanic acid had a confirmed or suspected infection (180 [11%] of 1619) than women allocated to placebo (306 [19%] of 1606; risk ratio 0·58, 95% CI 0·49–0·69; p<0·0001). One woman in the placebo group reported a skin rash and two women in the amoxicillin and clavulanic acid reported other allergic reactions, one of which was reported as a serious adverse event. Two other serious adverse events were reported, neither was considered causally related to the treatment.


This trial shows benefit of a single dose of prophylactic antibiotic after operative vaginal birth and guidance from WHO and other national organisations should be changed to reflect this.


NIHR Health Technology Assessment programme.




June 14, 2019 at 3:54 pm

Reduced rate of intensive care unit acquired gram-negative bacilli after removal of sinks and introduction of ‘water-free’ patient care.

Antimicrob Resist Infect Control. June 2017 V.6 P.59.

Hopman J#1, Tostmann A#1, Wertheim H1, Bos M1, Kolwijck E1, Akkermans R2, Sturm P1,3, Voss A1,4, Pickkers P5, Vd Hoeven H5.



Sinks in patient rooms are associated with hospital-acquired infections. The aim of this study was to evaluate the effect of removal of sinks from the Intensive Care Unit (ICU) patient rooms and the introduction of ‘water-free’ patient care on gram-negative bacilli colonization rates.


We conducted a 2-year pre/post quasi-experimental study that compared monthly gram-negative bacilli colonization rates pre- and post-intervention using segmented regression analysis of interrupted time series data. Five ICUs of a tertiary care medical center were included. Participants were all patients of 18 years and older admitted to our ICUs for at least 48 h who also received selective digestive tract decontamination during the twelve month pre-intervention or the twelve month post-intervention period. The effect of sink removal and the introduction of ‘water-free’ patient care on colonization rates with gram-negative bacilli was evaluated. The main outcome of this study was the monthly colonization rate with gram-negative bacilli (GNB). Yeast colonization rates were used as a ‘negative control’. In addition, colonization rates were calculated for first positive culture results from cultures taken ≥3, ≥5, ≥7, ≥10 and ≥14 days after ICU-admission, rate ratios (RR) were calculated and differences tested with chi-squared tests.


In the pre-intervention period, 1496 patients (9153 admission days) and in the post-intervention period 1444 patients (9044 admission days) were included. Segmented regression analysis showed that the intervention was followed by a statistically significant immediate reduction in GNB colonization in absence of a pre or post intervention trend in GNB colonization. The overall GNB colonization rate dropped from 26.3 to 21.6 GNB/1000 ICU admission days (colonization rate ratio 0.82; 95%CI 0.67-0.99; P = 0.02). The reduction in GNB colonization rate became more pronounced in patients with a longer ICU-Length of Stay (LOS): from a 1.22-fold reduction (≥2 days), to a 1.6-fold (≥5 days; P = 0.002), 2.5-fold (for ≥10 days; P < 0.001) to a 3.6-fold (≥14 days; P < 0.001) reduction.


Removal of sinks from patient rooms and introduction of a method of ‘water-free’ patient care is associated with a significant reduction of patient colonization with GNB, especially in patients with a longer ICU length of stay.


June 3, 2019 at 6:20 pm

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

Older Posts


June 2019
« May    

Posts by Month

Posts by Category