Russell J. Benefield

An international, multicentre survey of β-lactam antibiotic therapeutic drug monitoring practice in intensive care units

OBJECTIVES Emerging evidence supports the use of therapeutic drug monitoring (TDM) of β-lactams for intensive care unit (ICU) patients to optimize drug exposure, although limited detail is available on how sites run this service in practice. This multicentre survey study was performed to describe the various approaches used for β-lactam TDM in ICUs. METHODS A questionnaire survey was developed to describe various aspects relating to the conduct of β-lactam TDM in an ICU setting. Data sought included: β-lactams chosen for TDM, inclusion criteria for selecting patients, blood sampling strategy, analytical methods, pharmacokinetic (PK)/pharmacodynamic (PD) targets and dose adjustment strategies. RESULTS Nine ICUs were included in this survey. Respondents were either ICU or infectious disease physicians, pharmacists or clinical pharmacologists. Piperacillin (co-formulated with tazobactam) and meropenem (100% of units surveyed) were the β-lactams most commonly subject to TDM, followed by ceftazidime (78%), ceftriaxone (43%) and cefazolin (43%). Different chromatographic and microbiological methods were used for assay of β-lactam concentrations in blood and other biological fluids (e.g. CSF). There was significant variation in the PK/PD targets (100% fT>MIC up to 100% fT>4×MIC) and dose adjustment strategies used by each of the sites. CONCLUSIONS Large variations were found in the type of β-lactams tested, the patients selected for TDM and drug assay methods. Significant variation observed in the PK/PD targets and dose adjustment strategies used supports the need for further studies that robustly define PK/PD targets for ICU patients to ensure a greater consistency of practice for dose adjustment strategies for optimizing β-lactam dosing with TDM.

Risk of Fungal Endophthalmitis Associated with Cataract Surgery: A Mini-Review

Fungal endophthalmitis is a rare complication after cataract surgery and is associated with significant morbidity including vision loss. The common causative fungal pathogens implicated in fungal endophthalmitis after cataract surgery include Candida species (spp.) and molds such as Aspergillus spp. and Fusarium spp. Early diagnosis and effective antifungal treatment after a high index of clinical suspicion are required to reduce unfavorable complications and to preserve eye function. This review discusses epidemiology, pathogenesis, clinical features, diagnosis, management, and outcomes associated with fungal endophthalmitis after cataract surgery.

A multicenter evaluation of the safety of drotrecogin alfa (activated) in patients with baseline bleeding precautions.

PURPOSE We recently reported an increased incidence of serious bleeding events and mortality in patients with baseline bleeding precautions treated with drotrecogin alfa (activated) compared to patients without such precautions. Whether these observations were specific to our single medical campus is unclear. METHODS All patients who received drotrecogin alfa (activated) for the treatment of severe sepsis from January 2006 through September 2009 within the South Central Veterans Affairs Health Care Network were retrospectively reviewed using a regional clinical database. Demographic information, bleeding precautions that were exclusion criteria of the PROWESS trial, and 30-day post-discharge incidences of serious bleeding events and mortality were collected. RESULTS Seventy-nine patients from 5 medical centers were included. Serious bleeding events occurred in 4 of 24 patients (16.7%) with any bleeding precaution vs 1 of 55 patients (1.8%) without a bleeding precaution (P=0.03). All patients (5) who experienced a serious bleeding event died compared to 39 of 74 patients (52.7%) who did not (P=0.06). Seventeen of 24 patients (70.8%) with bleeding precautions died vs 27 of 55 patients (49.1%) without bleeding precautions (P=0.07). The number of serious bleeding events did not allow meaningful multivariate analyses. The mean number of failing organs was an independent predictor of 30-day post-discharge mortality (OR 1.63 for each organ failed, 95% CI 1.05- 2.6). CONCLUSIONS The findings of this study were consistent with our prior observations and suggest the risk for serious bleeding events with drotrecogin alfa (activated) may outweigh any potential benefit in patients with baseline bleeding precautions.

Patient Variables Associated with Nafcillin Plasma Concentrations and Toxicity.

Primary objective: To retrospectively review nafcillin plasma concentrations (CNAF) and determine nafcillin clearance (CLNAF) in a diverse sample of patients treated with nafcillin administered as a continuous infusion. Secondary objective: To identify clinical variables associated with CLNAF and nafcillin‐related adverse drug reactions (ADRs).

Utilization of posaconazole oral suspension or delayed-released tablet salvage treatment for invasive fungal infection.

Posaconazole may be useful for salvage treatment (ST) for invasive fungal infections (IFIs). The aim of this study was to evaluate the efficacy of posaconazole ST with either posaconazole oral suspension (SUS) or delayed‐released tablet (TAB) in patients with IFI. A retrospective review of patients who received posaconazole ST for IFI at the University of Utah Health Sciences Center between December 2007 and March 2014 was conducted. A total of 14 episodes of posaconazole ST for proven (9 episodes) and probable (5 episodes) IFI were identified in 14 patients. The median age was 54 years and the majority of patients (64.3%) had underlying haematological diseases. Posaconazole SUS and TAB were used in 11 episodes and 3 episodes respectively. The duration of posaconazole ST ranged from 28 to 370 days with a median of 65 days. Posaconazole ST with TAB achieved favourable serum posaconazole trough concentrations (median 1.4 μg mL−1) compared to posaconazole SUS (median 1.0 μg mL−1). The overall clinical success rate with posaconazole ST was 71.4% (10 of 14 episodes). One patient died of progression of IFI. Adverse events were noted in two patients. Posaconazole SUS or TAB may be used effectively for IFI ST.

Potentially serious drug interactions resulting from the pre-travel health encounter

Abstract Travelers seen for pretravel health encounters are frequently prescribed new travel-related medications, which may interact with their previously prescribed medications. In a cohort of 76 324 travelers seen at 23 US clinics, we found that 2650 (3.5%) travelers were prescribed travel-related medications with potential for serious drug interactions.

Impact of a Multiplex PCR Assay for Bloodstream Infections With and Without Antimicrobial Stewardship Intervention at a Cancer Hospital

Abstract Implementation of Biofire FilmArray Blood Culture Identification Multiplex PCR panel (BCID) at a cancer hospital was associated with reduced time to appropriate antimicrobial therapy. Additional reductions were not observed when BCID was coupled with antimicrobial stewardship intervention.

622: PHARMACOKINETIC MODELING OF VANCOMYCIN SERUM AND CSF CONCENTRATIONS IN ICU PATIENTS

Critical Care Medicine • Volume 46 • Number 1 (Supplement) www.ccmjournal.org Learning Objectives: Neurological involvement is seen infrequently in leptospirosis. Cerebellar syndromes and cranial nerve palsies are seen very rarely in this disease and often lead to delayed diagnosis. Methods: A 50-year-old Indian male farmer presented with unsteady gait and abnormal facial expressions since one day. On examination, he had stable vital signs except for an elevated temperature. Neurological examination revealed dysarthria, left-sided gaze preference, horizontal nystagmus, left-sided facial palsy with left-sided ptosis. Pan-cerebellar dysfunction noted gait ataxia, dysdiadochokinesia and impaired finger-nose test. Blood counts and serum chemistries were within normal limits. Imaging of the brain and cerebral vasculature was unrevealing for any acute pathology. Cerebrospinal fluid showed normal parameters and negative microbiology including cryptococcus and mycobacterium. The patient was started on supportive therapy for cerebellitis. Additional infectious work up for herpes, rubella, enterovirus, varicella and viral encephalitis was negative. Leptospira serology showed high IgM titers and microscopic agglutination test was > 1:800; suggestive of acute Leptospira infection. The patient was started on intravenous ceftriaxone and doxycycline for primary neuroleptospirosis. He showed dramatic recovery with normal gait and coordination within 10 days. He was discharged with full functional and neurological recovery. Results: Leptospirosis is a common zoonotic disease in tropical climates and is associated with breeding of livestock, workplace exposure, heavy rainfall and inadequate sanitation. Neurological leptospirosis typically manifests as aseptic meningitis. Cerebellar involvement is seen in < 3% of the patients and neuropathies (mono and poly) are seen in < 1%. These rare presentations of a common disease are often a cause for delayed diagnosis, thereby delaying prompt treatment.

Pharmacokinetics of acyclovir in a morbidly obese patient with renal impairment

Cmax 43.0 mg/L C8h 16.1 mg/L AUC0–8h 217 mg h/L AUC0–24h a 650 mg h/L Vd 34.2 L Vd normalised to TBW 0.32 L/kgTBW Vd normalised to IBW 0.63 L/kgIBW Vd normalised to AdjBW 0.45 L/kgAdjBW Vd normalised to BSA 28.2 L/1.73 m2 CL 4.62 L/h CL normalised to TBW 0.043 L/h/kgTBW CL normalised to IBW 0.084 L/h/kgIBW CL normalised to AdjBW 0.061 L/h/kgAdjBW CL normalised to BSA 3.81 L/h/1.73 m2 ke 0.14 h−1 t1/2 5.13 h Measured CLCr 19.4 mL/min