Vancomycin therapy in critically ill patients on continuous renal replacement therapy; are we doing enough?

BACKGROUND: Recommendations regarding vancomycin dosing and monitoring in critically ill patients on continuous renal replacement therapy (CRRT) are limited. This is a retrospective study to assess the adequacy of current vancomycin dosing and monitoring practice for patients on CRRT in a tertiary hospital in Riyadh, Saudi Arabia. METHODS: A retrospective chart review of adult patients admitted between 1 April 2011 and 30 March 2013 to critical care and received intravenous vancomycin therapy whilst on CRRT was performed. RESULTS: A total of 68 patients received intravenous vancomycin therapy whilst on CRRT, of which 32 met the inclusion criteria. Fifty-one percent were males and median (range) age was 62.5 (19 - 90) years. Median APACHE II score was 33.5 (22-43) and median Charlson Comorbidity Score was 4 (0-8). The mean (± standard deviation) dose of vancomycin was 879.9 mg (± 281.2 mg) for an average duration of 5.9 days (± 3.7 days). All patients received continuous veno-venous haemofiltration (CVVH). A total of 55 vancomycin level readings were available from the study population, ranging from 6.6 to 41.3, with wide variations within the same sampling time frames. Vancomycin levels of > 15 mg/L or were achieved at least once in 24 patients (75.0%), but only 11 patients (34.3%) had 2 or more serum vancomycin level readings of 15 mg/L or more. CONCLUSION: Therapeutic vancomycin levels are difficult to maintain in critically ill patients who are receiving IV vancomycin therapy whilst on CRRT. Aggressive dosing schedules and frequent monitoring are required to ensure adequate vancomycin therapy in this setting.

Physicians' knowledge, perceptions, and attitudes toward antimicrobial prescribing in Riyadh, Saudi Arabia.

OBJECTIVES: To assess knowledge, perceptions, and attitudes toward antimicrobial prescribing among physicians practicing in Riyadh, Saudi Arabia. METHODS: A questionnaire was developed and distributed to physicians working in hospitals in Riyadh, Saudi Arabia between June and August 2013. The results were analyzed using Stata 12 software. RESULTS: Two hundred and twelve (84.8%) full responses were returned. Most respondents perceived antimicrobial resistance as a significant problem in their daily practice (119, 56.1%) and at a national level (148, 69.8%). Inappropriate empirical therapy (101, 47.6%) and excessive use of antimicrobials in healthcare settings (66, 31.1%) were believed to be the main contributors to increasing bacterial resistance. Respondents favor treating infection rather than colonization (98, 46.2%), and physician education (74, 34.9%) as the most effective interventions to reduce antimicrobial resistance. Many respondents (95, 44.8%) do not feel confident in their knowledge of antimicrobial prescribing. Two-thirds of the respondents (135, 63.7%) have local antimicrobial guidelines, of which 90 (66.7%) felt were useful. Most respondents (160, 75.5%) considered their local infectious diseases service to be very helpful. CONCLUSION: There are considerable unmet training and education need for physicians in the area of antimicrobial prescribing. Local antimicrobial guidelines need revision to ensure they are more relevant and helpful for medical practitioners.

High dose intravenous colistin methanesulfonate therapy is associated with high rates of nephrotoxicity; a prospective cohort study from Saudi Arabia.

BACKGROUND: Nephrotoxicity is an important adverse effect of colistin methanesulfonate (CMS) therapy. No data exist on rates and risk factors for colistin-related nephrotoxicity in Saudi Arabia (SA). We conducted a prospective cohort study to identify rates and risk factors for CMS nephrotoxicity in our patient population. METHODS: We prospectively included adult patients who received ≥48 hours of intravenous CMS therapy. Pregnant patients and those on renal replacement were excluded. Patients received 9 million units (mU) loading dose followed by 3 mU 8 hourly. In renal impairment, CMS dosing was adjusted according to calculated creatinine clearance (CrCl). Nephrotoxicity was defined as per RIFLE criteria (Risk, Injury, Failure, Loss and End-stage renal disease). Statistical analysis was performed using SPSS version 20.0 (IBM, Armonk, New York, USA). The study was approved by the institution's Research Ethics Committee. RESULTS: A total of 67 patients were included in the study. Mean (±standard deviation) age was 57.5 (±24.0) years, Charlson Co-morbidity Score 2.88 (±2.39), CrCl 133.60 (±92.54) mL/min and serum albumin 28.65 (±4.45) g/L. Mean CMS dose was 0.11 (±0.04) mU/kg/day and mean total CMS dose received was 101.21 (±47.37) mU. Fifty-one (76.1%) patients developed RIFLE-defined nephrotoxicity. Mean total CMS dose and duration of therapy before onset of nephrotoxicity were 66.71 (±43.45) mU and 8.70 (±6.70) days, respectively. In bivariate analysis, patients with nephrotoxicity were significantly older (P 0.013) and had lower baseline serum albumin (P 0.008). Multivariate logistic regression identified serum albumin [odds ratio (OR) 0.72; 95% confidence interval (CI) 0.57-0.93; P 0.010] and intensive care admission (OR 16.38; 95% CI 1.37-195.55; P 0.027) as independent risk factors for CMS nephrotoxicity. CONCLUSIONS: High dose intravenous CMS therapy is associated with high rates of nephrotoxicity in SA. Independent risk factors for colistin nephrotoxicity were baseline hypoalbuminemia and intensive care admission.

Update on colistin in clinical practice.

Considerable progress has been made in the last decade towards better understanding of the optimal clinical use of colistin. It has become evident that higher intravenous (iv) colistin methanesulfonate (CMS) doses are important, probably with the addition of a loading dose in critically ill patients. Higher CMS doses lead to increased risk of nephrotoxicity, which seems reversible in most cases. Intravenous colistin is reasonably efficacious, but should continue to be considered only in the absence of safer alternatives. Although theoretically appealing, there is insufficient evidence to support inhaled colistin mono-therapy in non-cystic fibrosis patients. Moreover, the balance of evidence available at present is not in favor of adjunctive inhaled colistin therapy. Intrathecal or intra-ventricular colistin administration are appropriate options for neurosurgical meningitis caused by colistin-susceptible, multidrug resistant gram-negative bacteria. Ongoing randomized, controlled trials will hopefully help decide if combining colistin with a carbapenem, fosfomycin, or rifampicin is of clinical advantage.