Faculty Bibliography

Fidaxomicin was given to treat proven Clostridium difficile infection (CDI) in 20 patients receiving care in critical care units (CCUs) and compared with 30 patients on general medical floors. At baseline, CCU patients had more initial CDI episodes, severe and complicated disease, and concurrent broad-spectrum antibiotic coverage. On multivariate analysis, response of fidaxomicin therapy among critically ill patients was comparable to that among patients in the general medical wards.

BACKGROUND: Recent studies described an increase in acute kidney injury when high dose gentamicin was included in perioperative prophylaxis for orthopedic surgeries. To this effect, we compared the rate of nephrotoxicity for selected orthopedic surgeries where gentamicin was included (Gentamicin Group) to those where it was not included (Control Group) for perioperative prophylaxis and evaluated risk factors for nephrotoxicity. METHODS: Spine, hip and knee surgeries performed between April 2011 and December 2013 were reviewed retrospectively. Gentamicin was given to eligible patients based on age, weight and Creatinine Clearance. Nephrotoxicity was assessed using Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) criteria. RESULTS: Among selected surgeries (N = 1590 in Gentamicin Group: hip = 926, spine = 600, knee = 64; N = 2587 in CONTROL GROUP: hip = 980, spine = 902, knee = 705), patients' body weight, serum creatinine, comorbidities and surgery duration were similar in Gentamicin Group and CONTROL GROUP. Gentamicin median dose was 4.5 mg/kg of dosing weight. Nephrotoxicity rate was 2.5% in Gentamicin Group and 1.8% in CONTROL GROUP, p = 0.17. Most cases of nephrotoxicity were Risk category by RIFLE criteria (67% in Gentamicin Group and 72% in CONTROL GROUP, p = 0.49). In logistic regression, risk factors for nephrotoxicity were hospital stay >1 day prior to surgery (odds ratio = 8.1; 95% confidence interval = 2.25-28.97, p = 0.001), knee or hip surgery (odds ratio = 4.7; 95% confidence interval = 2.9-9.48, p = 0.0005) and diabetes (odds ratio = 1.95; 95% confidence interval = 1.13-3.35, p = 0.016). Receipt of gentamicin was not an independent predictor of nephrotoxicity (odds ratio = 1.5; 95% confidence interval = 0.97-2.35, p = 0.07). CONCLUSION: In this cohort, rate of nephrotoxicity was similar between Gentamicin Group and Control Group. Single high dose gentamicin is a safe and acceptable option for perioperative prophylaxis in eligible patients undergoing orthopedic surgeries.

OBJECTIVES: Polymyxin B is an active agent against many MDR Gram-negative bacteria, but nephrotoxicity is a major hindrance to its widespread use. To guide its optimal use, we determined the risk factors for nephrotoxicity onset associated with polymyxin B. METHODS: In a multicentre, retrospective, cohort study, we evaluated adult patients with normal renal function who received >/=72 h of polymyxin B therapy. Pertinent information was retrieved from medical records; patients were followed for up to 30 days after therapy was started. The primary endpoint of this study was the onset of nephrotoxicity. A Cox proportional hazards model was used for analysis. RESULTS: A total of 192 patients (52.1% male, 67.7% Caucasian) were evaluated. The mean +/- SD age, actual body weight (ABW) and daily dose by ABW were 68.3 +/- 17.2 years, 71.5 +/- 20.4 kg and 1.5 +/- 0.5 mg/kg, respectively. The median duration of therapy was 9.5 days. The overall prevalence rate of nephrotoxicity was 45.8% and the median onset of nephrotoxicity was 9 days. Independent risk factors for the onset of nephrotoxicity included daily dose by ABW (HR = 1.73; P = 0.022), concurrent use of vancomycin (HR = 1.89; P = 0.005) and contrast media (HR = 1.79; P = 0.009). Nephrotoxicity was seen earlier in the high-risk group (P = 0.003). CONCLUSIONS: Risk factors for nephrotoxicity onset associated with polymyxin B were identified. In conjunction with susceptibility and other pharmacokinetic/pharmacodynamic data, our results can be used to optimize treatment for MDR Gram-negative infections.

Piperacillin-tazobactam (PTZ) is frequently used as empirical and targeted therapy for Gram-negative sepsis. Time-dependent killing properties of PTZ support the use of extended-infusion (EI) dosing; however, studies have shown inconsistent benefits of EI PTZ treatment on clinical outcomes. We performed a retrospective cohort study of adult patients who received EI PTZ treatment and historical controls who received standard-infusion (SI) PTZ treatment for presumed sepsis syndromes. Data on mortality rates, clinical outcomes, length of stay (LOS), and disease severity were obtained. A total of 843 patients (662 with EI treatment and 181 with SI treatment) were available for analysis. Baseline characteristics of the two groups were similar, except for fewer female patients receiving EI treatment. No significant differences between the EI and SI groups in inpatient mortality rates (10.9% versus 13.8%; P = 0.282), overall LOS (10 versus 12 days; P = 0.171), intensive care unit (ICU) LOS (7 versus 6 days; P = 0.061), or clinical failure rates (18.4% versus 19.9%; P = 0.756) were observed. However, the duration of PTZ therapy was shorter in the EI group (5 versus 6 days; P < 0.001). Among ICU patients, no significant differences in outcomes between the EI and SI groups were observed. Patients with urinary or intra-abdominal infections had lower mortality and clinical failure rates when receiving EI PTZ treatment. We did not observe significant differences in inpatient mortality rates, overall LOS, ICU LOS, or clinical failure rates between patients receiving EI PTZ treatment and patients receiving SI PTZ treatment. Patients receiving EI PTZ treatment had a shorter duration of PTZ therapy than did patients receiving SI treatment, and EI dosing may provide cost savings to hospitals.

Objectives: Accurate diagnosis of infections in transplant recipients remains a daunting task. To address the diagnoses dilemma, we assessed feasibility of procalcitonin (PCT), a recently approved biomarker in patients at a major University Medical Center in New York. Methods: All data was retrieved retrospectively after approval from Institutional Review Board. Transplant recipients were compared with general medicine patients, and patients with hematologic neoplasia and those being cared for in medical and surgical intensive care units between April 2012 and February 2013. Chi-square and Mann Whitney U test were used for statistical analysis. PCT (ng/ml) and other values are given as median [range]. Results: Among 342 patients studied, transplant recipients (n=26) were younger (60 vs. 69 years; p<0.01), had fewer cardiovascular diseases (19.2% vs. 44.3%; P<0.05), whereas diabetes was more common compared with other patients (53.8% vs. 21.8%; P<0.05). APACHE II scores was not different in either group (15 vs. 17; p=0.06). Similarly, there were no differences for corticosteroid use, chemotherapy and surgeries (P>0.05). PCT values were higher in transplant recipients with bacteremia, Gram-negative infections, and pneumonia (Table 1). There were no significant differences in PCT values among recipients of SOT vs. HSCT (1.62 [0.05-197] vs. 0.28 [0.05-13.1], respectively; P=0.3) during early (<1 month) or later transplant period (1.9 [0.05-13.10] vs. 1.15 [0.015-197], respectively; P=0.8). Conclusions: PCT appears as a promising diagnostic tool for transplant recipients with bacteremia, Gram-negative infections and pneumonia. Further validation studies are underway. TABLE 1. Comparison of PCT in transplant and other patients. (Table Presented)

Data that can be used to guide perioperative antibiotic prophylaxis in our era of emerging antibiotic resistance are limited. We reviewed orthopedic surgeries complicated by surgical site infections (SSIs). Eighty percent of 69 arthroplasty and 80 spine fusion SSIs were infected with Gram-positive bacteria; most were staphylococcal species; and more than 25% of Staphylococcus aureus and more than 65% of coagulase-negative staphylococci were methicillin-resistant. Gram-negative bacteria were isolated from 30% of arthroplasty SSIs and 25% of spine fusion SSIs. Resistance to cefazolin was higher than 40%. A significant proportion of SSIs were caused by resistant organisms, and antibiotic guidelines were altered to provide more adequate surgical prophylaxis.

INTRODUCTION: The indications for vancomycin prophylaxis to prevent Methicillin-resistant Staphylococcus aureus (MRSA) surgical site infections are increasing. The recommended dose of vancomycin has traditionally been 1 gram intravenous. However, the increasing prevalence of obesity in our population coupled with increasing resistance of MRSA to vancomycin has resulted in recent recommendations for weight-based dosing of vancomycin at 15mg/kg. We hypothesize that the standard one gram dose of vancomycin is inadequate to meet the recently recommended dosage of 15mg/kg. METHODS: We performed a retrospective chart review on 216 patients who were screened positive for MRSA prior to undergoing elective total joint or spine surgeries between January 2009 to January 2012. All patients were given 1 gram of vancomycin within an hour prior to surgical incision as prophylaxis. Using the revised dosing protocol of 15mg/kg of body weight for vancomycin, proper dosage was calculated for each patient. These values were then compared to the 1 gram dose given to the patients at time of surgery. Patients were assessed as either underdosed (a calculated weight-based dose >1 gram) or overdosed (a calculated weight-based dose <1 gram). Additionally, we used actual case times and pharmacokinetic equations to determine the vancomycin (VAN) levels at the end of the procedures. RESULTS: Out of 216 patients who tested positive for MRSA, 149 patients (69%) were determined to be underdosed and 22 patients (10%) patients were determined to be overdosed. The predicted VAN level at the end of procedure was <15 mg/L in 60% of patients with 1 gram dose compared to 12% (p=0.0005) with weight base dose. Six patients developed post-operative MRSA surgical site infections (SSI). Of these six patients; four had strains of MRSA with vancomycin minimum inhibitory concentration of >1.0mg/L. Based on 1g dosing, 5/6 patients with MRSA positive SSIs had wound closure levels of <15 mg/L and all six were <20 mg/L. CONCLUSION: In settings such as hospitals, where the risk for resistant bacteria, especially MRSA, is high, it is becoming increasingly important to accurately dose patients who require vancomycin. In order to avoid incorrect dosing of vancomycin health care providers must use weight-based dosing.

The treatment of choice for Stenotrophomonas maltophilia is trimethoprim-sulfamethoxazole (SXT). Fluoroquinolones (FQs) have in vitro activity against S. maltophilia; however, there is limited published information on their effectiveness. The purpose of this study is to compare the effectiveness of FQs and SXT for the treatment of S. maltophilia. A retrospective review of 98 patients with S. maltophilia infections who received SXT or FQ monotherapy was conducted. Patients >/=18 years old with a positive culture for S. maltophilia and clinical signs of infection who received treatment for >/=48 h were included. Microbiological cure and clinical response were evaluated at the end of therapy (EOT). In-hospital mortality and isolation of nonsusceptible isolates were also evaluated. Thirty-five patients received SXT, and 63 patients received FQ; 48 patients received levofloxacin, and 15 patients received ciprofloxacin. The most common infection was pulmonary. The overall microbiological cure rate at EOT was 63%. Thirteen of 20 patients (65%) who received SXT and 23 of 37 patients (62%) who received FQ had microbiological cure at EOT (P = 0.832). The overall clinical success rate was 55%, 52% for those who received FQ and 61% for those who received SXT (P = 0.451). In-hospital mortality was 24%, with similar rates in the two groups (25% for FQ versus 22% for SXT; P = 0.546). Development of resistance on repeat culture was 30% for FQ and 20% for SXT (P = 0.426). Fluoroquinolone and SXT monotherapies may be equally effective for the treatment of S. maltophilia infections. Resistance was documented in subsequent isolates of S. maltophilia in both groups.

Polymyxins are reserved for salvage therapy of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Though synergy has been demonstrated for the combination of polymyxins with carbapenems or tigecycline, in vitro synergy tests are nonstandardized, and the clinical effect of synergy remains unclear. This study describes outcomes for patients with CRKP infections who were treated with polymyxin B monotherapy. We retrospectively reviewed the medical records of patients with CRKP infections who received polymyxin B monotherapy from 2007 to 2011. Clinical, microbiology, and antimicrobial treatment data were collected. Risk factors for treatment failure were identified by logistic regression. Forty patients were included in the analysis. Twenty-nine of 40 (73%) patients achieved clinical cure as defined by clinician-documented improvement in signs and symptoms of infections, and 17/32 (53%) patients with follow-up culture data achieved microbiological cure. End-of-treatment mortality was 10%, and 30-day mortality was 28%. In a multivariate analysis, baseline renal insufficiency was associated with a 6.0-fold increase in clinical failure after adjusting for septic shock (odds ratio [OR] = 6.0; 95% confidence interval [CI] = 1.22 to 29.59). Breakthrough infections with organisms intrinsically resistant to polymyxins occurred in 3 patients during the treatment. Eighteen of 40 (45%) patients developed a new CRKP infection a median of 23 days after initial polymyxin B treatment, and 3 of these 18 infections were polymyxin resistant. The clinical cure rate achieved in this retrospective study was 73% of patients with CRKP infections treated with polymyxin B monotherapy. Baseline renal insufficiency was a risk factor for treatment failure after adjusting for septic shock. Breakthrough infections with organisms intrinsically resistant to polymyxin B and development of resistance to polymyxin B in subsequent CRKP isolates are of concern.

The feasibility of fidaxomicin versus vancomycin and metronidazole (conventional therapy) was assessed in 59 transplant recipients with 61 episodes of Clostridium difficile-associated diarrhea (CDAD). Overall clinical cure was achieved in 86% of episodes, and in 7% of episodes, infection recurred. Fidaxomicin was well tolerated. Clinical cures were not significantly different compared with conventional therapy (67% versus 89%, respectively; P = 0.06). Univariate analysis of predictors for lack of clinical cure included continued use of broad-spectrum systemic antibiotics (P = 0.026) and prior diagnosis of CDAD (95% confidence interval, 1.113 to 19.569; odds ratio, 4.667; P = 0.041). New-onset vancomycin-resistant Enterococcus (VRE) colonization was not noted after fidaxomicin therapy alone. However, this occurred in 10 of 28 patients (36%) following conventional therapy, and 2 of 3 patients with subsequent bacteremia died.