Wednesday, October 18, 2017

Neurotoxicity of cefepime in relation to plasma concentration


In this single-centre retrospective cohort study, we enrolled all adult hospitalized patients receiving cefepime and undergoing TDM from January 2013 through July 2016. The primary outcome was the incidence of clinical toxicity; a secondary outcome was clinical failure. Plasma samples were analysed via high-performance liquid chromatography with ultraviolet detection.


A total of 161 cefepime concentrations were drawn from 93 patients. Roughly half (82/161, 51%) and one-third (49/161, 30%) were trough and steady-state levels from patients receiving intermittent and continuous infusions, respectively; median concentrations were 17.6 mg/L (IQR 9.7-35.2) and 29.2 mg/L (IQR 18.9-45.9). Ten patients (11%) experienced a neurologic event considered at least possibly related to cefepime; neurotoxicity was associated with poorer renal function (median creatinine clearance 54 (IQR 39-97) vs. 75 mL/min/1.732 (IQR 44-104)) and longer cefepime durations (mean 8.3 (SD±6.7) vs. 13.3 days (± 14.2), p = 0.071). Patients with trough levels greater than 20 mg/L had a fivefold higher risk for neurologic events (OR 5.05, 95% CI 1.3-19.8).


Neurotoxicity potentially related to cefepime occurred at plasma concentrations greater than 35 mg/L. For those receiving intermittent infusions, trough concentrations greater than 20 mg/L should be avoided until further information is available from prospective studies.

Tuesday, October 17, 2017

Which of the two popular regimens for community acquired pneumonia is best?


The best treatment option for hospitalized patients with community-acquired pneumonia (CAP) has not been defined. The effectiveness of β-lactam/fluoroquinolone (BLFQ) versus β-lactam/macrolide (BLM) combinations for the treatment of patients with CAP was evaluated.


PubMed, Scopus and the Cochrane Library were searched for observational cohort studies, non-randomized and randomized controlled trials providing data for patients with CAP receiving BLM or BLFQ. Mortality was the primary outcome. A meta-analysis was performed. MINORS and GRADE were used for data quality assessment.


Seventeen studies (16 684 patients) were included. Randomized trials were not identified. A variety of β-lactams, fluoroquinolones and macrolides were used within and between the studies. Mortality was reported at different time points. The available body of evidence had very low quality. In the analysis of unadjusted data, mortality with BLFQ was higher than with BLM (risk ratio 1.33, 95% CI 1.15–1.54, I2 28%). BLFQ was associated with higher mortality regardless of the study design, mortality recording time, study period and study BLM group mortality. BLFQ was associated with higher mortality in American but not European studies. No difference was observed in patients with bacteraemia and septic shock. In the meta-analysis of adjusted mortality data, a non-significant difference between the two regimens was observed (eight studies, adjusted risk ratio 1.26, 95% CI 0.95–1.67, I2 43%).


In the absence of data from randomized controlled trials recommendations cannot be made for or against either of the studied regimens in this group of hospitalized patients with CAP. Well designed randomized controlled trials comparing the two regimens are warranted.

Of interest, they didn’t compare fluoroquinolone monotherapy which is also popular and endorsed by CAP guidelines.

Monday, October 16, 2017

Sunday, October 15, 2017

The coming microbial apocalypse: Staph aureus in retreat?

Twenty years ago the post antibiotic era was predicted for gram positive infections. Five years or so later CA-MRSA began to overtake HA-MRSA. The takeover is complete, with the result that today’s MRSA, though resistant to most beta lactam antibiotics, is sensitive to several older antimicrobial agents besides vancomycin, in contrast to the older traditional MRSA (HA-MRSA). In a new development, a goodly number of MSSA  infections show susceptibility to plain penicillin.

Friday, October 13, 2017

Inappropriate IVC filter use continues apace

This is despite mounting evidence supporting restricted use as recommended in guidelines. This was the topic of several articles of interest in the May issue of Thrombosis Research.

Methods and results

We analyzed hospital discharge records of all patients with active cancer who were admitted to a California hospital specifically for acute DVT or PE between 2005 through 2009. Propensity and competing risk methodology were used to determine if IVCF-use lowered either 30-day mortality or the risk of recurrent PE, DVT, and major bleeding within 180 days. Among 14,000 patients, an IVCF was placed in 2747 (19.6%), but only 577 (21%) of these IVCF patients had an apparent indication for filter use because of acute bleeding or undergoing major surgery. Data on anticoagulation use was not available. Filter-use provided no reduction in either 30-day mortality (HR = 1.12, 95% CI: 0.99–1.26, p = 0.08) or the adjusted 180-day risk of subsequent PE (±DVT) (HR = 0.81, 95% CI: 0.52–1.27, p = 0.36). Filter use was, however, associated with an increase in the adjusted180-day risk of recurrent DVT (HR = 2.10, 95% CI: 1.53–2.89, p less than 0.0001).


We conclude that in this population-based study, approximately 20% of cancer patients with acute VTE received an IVCF, but only 21% of these had an indication for IVCF use. Overall, IVCF use provided neither a short-term survival benefit nor a reduction in risk of recurrent PE, but IVCF use was associated with a higher risk of recurrent DVT.


Inferior vena cava filters are used to prevent embolization of a lower extremity deep vein thrombosis when the risk of pulmonary embolism is thought to be high. However, evidence is lacking for their benefit and guidelines differ on the recommended indications for filter insertion. The study aim was to determine the reasons for inferior vena cava filter placement and subsequent complication rate.

Materials and methods

A retrospective cohort of patients receiving inferior vena cava filters in Edmonton, Alberta, Canada from 2007 to 2011. Main outcome was the indication of inferior vena cava filter insertion. Other measures include baseline demographic and medical history of patients, clinical outcomes and filter retrieval rates.


464 patients received inferior vena cava filters. An acute deep vein thrombosis with a contraindication to anticoagulation was the indication for 206 (44.4%) filter insertions. No contraindication to anticoagulation could be identified in 20.7% of filter placements. 30.6% were placed in those with active cancer, in which mortality was significantly higher. Only 38.9% of retrievable filters were successfully retrieved.


Inferior vena cava filters were placed frequently in patients with weak or no guideline-supported indications for filter placement and in up to 20% of patients with no contraindication to anticoagulation. The high rates of cancer and the high mortality rate of the cohort raise the possibility that some filters are placed inappropriately in end of life settings.

Here are a couple of related editorials: [1] [2]

Thursday, October 12, 2017

Inappropriate anaerobic coverage for patients with pneumonia in the ICU

This practice was common in this study. Anaerobic coverage is often provided as a knee jerk response to “suspected aspiration” without careful assessment of the risk factors for anaerobic infection.