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

Histoplasmosis-related healthcare use, diagnosis, and treatment in a commercially insured population, United States.

Clinical Infectious Diseases April 30, 2019  

Benedict K1, Beer KD1, Jackson BR1.



Infections with Histoplasma can range from asymptomatic to life-threatening acute pulmonary or disseminated disease. Histoplasmosis can be challenging to diagnose and is widely under-recognized. We analyzed insurance claims data to better characterize histoplasmosis testing and treatment practices and its burden on patients.


We used the IBM® MarketScan® Research Databases to identify patients with histoplasmosis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 115.00-115.99) during 2012-2014. We analyzed claims in the 3 months before to the 1 year after diagnosis and examined differences between probable (hospitalized or >1 outpatient visit) and suspect (1 outpatient visit) patients.


Among 1,935 patients (943 probable, 922 suspect), 54% had codes for symptoms or findings consistent with histoplasmosis and 35% had ≥2 healthcare visits in the 3 months before diagnosis. Overall, 646 (33%) had any fungal-specific laboratory test: histoplasmosis antibody test (n= 349, 18%), Histoplasma antigen test (n=349, 18%), fungal smear (n=294, 15%), or fungal culture (n=223, 12%); 464 (24%) had a biopsy. Forty-nine percent of probable patients and 10% of suspect patients were prescribed antifungal medication in the outpatient setting. Total, 19% were hospitalized. Patients’ last histoplasmosis-associated healthcare visits occurred a median of 6 months after diagnosis.


Some histoplasmosis patients experienced severe disease, apparent diagnostic delays, and prolonged illness, whereas other patients lacked symptoms and were likely diagnosed incidentally (e.g., via biopsy). Low rates of histoplasmosis-specific testing also suggest incidental diagnoses and low provider suspicion, highlighting the need for improved awareness about this disease.



May 23, 2019 at 8:16 am

Mortality due to Cryptococcus neoformans and Cryptococcus gattiiin low-income settings: an autopsy study

Scientific Reports May 2019       

Cryptococcosis is a major opportunistic infection and is one of the leading causes of death in adults living with HIV in sub-Saharan Africa. Recent estimates indicate that more than 130,000 people may die annually of cryptococcal meningitis in this region.

Although complete diagnostic autopsy (CDA) is considered the gold standard for determining the cause of death, it is seldom performed in low income settings.

In this study, a CDA was performed in 284 deceased patients from Mozambique (n = 223) and Brazil (n = 61). In depth histopathological and microbiological analyses were carried out in all cases dying of cryptococcosis. We determined the cryptococcal species, the molecular and sero-mating types and antifungal susceptibility.

We also described the organs affected and reviewed the clinical presentation and patient management. Among the 284 cases included, 17 fatal cryptococcal infections were diagnosed. Cryptococcus was responsible for 16 deaths among the 163 HIV-positive patients (10%; 95%CI: 6–15%), including four maternal deaths.

One third of the cases corresponded to C. gattii (VGI and VGIV molecular types, Bα and Cα strains) and the remaining infections typed were caused by C. neoformans var. Grubii (all VNI and Aα strains). The level of pre-mortem clinical suspicion was low (7/17, 41%), and 7/17 patients (41%) died within the first 72 hours of admission.

Cryptococcosis was responsible for a significant proportion of AIDS-related mortality. The clinical diagnosis and patient management were inadequate, supporting the need for cryptococcal screening for early detection of the disease.

This is the first report of the presence of C. gattii infection in Mozambique…


May 22, 2019 at 7:53 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

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