Review of Medical Therapies for the Management of Pulmonary Embolism.

Traditionally, the management of patients with pulmonary embolism has been accomplished with anticoagulant treatment with parenteral heparins and oral vitamin K antagonists. Although the administration of heparins and oral vitamin K antagonists still plays a role in pulmonary embolism management, the use of these therapies are limited due to other options now available. This is due to their toxicity profile, clearance limitations, and many interactions with other medications and nutrients. The emergence of direct oral anticoagulation therapies has led to more options now being available to manage pulmonary embolism in inpatient and outpatient settings conveniently. These oral therapeutic options have opened up opportunities for safe and effective pulmonary embolism management, as more evidence and research is now available about reversal agents and monitoring parameters. The evolution of the pharmacological management of pulmonary embolism has provided us with better understanding regarding the selection of anticoagulants. There is also a better understanding and employment of anticoagulants in pulmonary embolism in special populations, such as patients with liver failure, renal failure, malignancy, and COVID-19.

State of the Art: Extracorporeal Cardiopulmonary Resuscitation for In-Hospital Arrest.

Extracorporeal membrane oxygenation has been used since the 1970s and recently has seen increased use for in-hospital arrest requiring extracorporeal cardiopulmonary resuscitation (ECPR). This paper provides an updated review of the ECPR literature and practical recommendations for implementation of an ECPR program.

Pharmacist-driven antimicrobial optimization in the emergency department.

PURPOSE: A pharmacist-driven antimicrobial optimization service in the non-trauma emergency department (ED) of an 864-bed non-profit tertiary care teaching hospital was reviewed to assess its value. Local antimicrobial resistance patterns of urine, wound, stool, and blood cultures were also studied to determine whether or not empiric prescribing practices should be modified. METHODS: A retrospective electronic chart review was performed for ED patients with positive cultures during two different three-month periods. During Period 1, ED nursing management performed positive culture follow-up. During Period 2, ED clinical pharmacists performed this role. The primary objective was to determine the value of the pharmacist-driven antimicrobial optimization service as measured by the number of clinical interventions made when indicated. The secondary objective was to examine resistance patterns of urine and wound isolates in order to determine if empiric prescribing patterns in the ED should be modified. RESULTS: During Period 1, there were 499 patient visits with subsequent positive cultures. Of those, 76 patients (15%) were discharged home. Nursing management intervened on 21 of 42 (50%) positive cultures that required an intervention; in Period 2, there were 473 patient visits with subsequent positive cultures, and 64 (14%) were discharged home. Pharmacists intervened on 24 of 30 (80%) cultures where an intervention was indicated resulting in a 30% increase in interventions for inappropriate therapy (p = 0.01). A review of the secondary objective revealed a 38% fluoroquinolone resistance rate of E. coli, the most frequently isolated urinary organism. CONCLUSION: Pharmacist-driven antimicrobial stewardship program resulted in a 30% absolute increase in interventions for inappropriate therapy as compared to the nursing-driven model. This stewardship program has further demonstrated the value of ED pharmacists. Pharmacist interventions should help to ensure that infections are resolved through modification of antimicrobial therapies for patients with bug-drug mismatches. The fluoroquinolone resistance rate indicates a need to consider alternative therapies for uncomplicated urinary tract infections. Nitrofurantoin remains with good coverage against E. coli and Enterococcus species but should be used in uncomplicated patients with normal renal function.

Applying the Beers and STOPP Criteria to Care of the Critically Ill Older Adult.

Potentially inappropriate medications impact pharmacotherapy for the older adult in critical care settings. Critical care teams must be aware of the Beers and Screening Tool of Older Person's Prescriptions criteria as resources to identify medications that may cause adverse drug events in the elderly. Although criteria should not replace clinical judgment, awareness of these guidelines may direct critical care teams to minimize dosing and duration of potentially inappropriate medications to improve outcomes in the intensive care unit.

Evaluation of a daptomycin dose-optimization protocol.

PURPOSE: The impact of an institutional protocol intended to improve daptomycin dosing for vancomycin-resistant enterococci (VRE) infections was investigated. SUMMARY: Daptomycin has been reported to have optimal activity against VRE at weight-based doses of ≥8 mg/kg. As part of an initiative to optimize daptomycin dosing for all indications and regimens, a large medical center implemented a protocol restricting daptomycin prescribing to infectious-diseases specialists and a nomogram recommending elevated daptomycin dosing for all VRE infections, with baseline and weekly creatinine phosphokinase (CPK) determinations during daptomycin therapy. Protocol implementation was preceded by educational efforts targeting medical and pharmacy staff. A retrospective study was conducted to compare prescribing behavior and safety monitoring rates during the 12 months before and 16 months after protocol implementation; the baseline characteristics of the preimplementation cohort (n = 95) and postimplementation cohort (n = 72) were similar. The mean daptomycin doses before and after the protocol was implemented were 453 mg (6.1 mg/kg) and 576 mg (7.6 mg/kg), respectively. After protocol implementation, there were significant increases in the proportion of patients who received doses of ≥8 mg/kg (52% in the postimplementation period versus 4% in the preimplementation period, p < 0.05) and in the rate of baseline CPK assessment (64% versus 43%, p < 0.05). CONCLUSION: Implementation of a daptomycin dosing protocol by a multidisciplinary antimicrobial stewardship team optimized treatment by increasing the mean dose of daptomycin administered to hospitalized adults with non-urinary VRE infections and improved the rate of safety monitoring.

Impact of prior inappropriate fluconazole dosing on isolation of fluconazole-nonsusceptible Candida species in hospitalized patients with candidemia.

Prior use of fluconazole is a modifiable risk factor for the isolation of fluconazole-nonsusceptible Candida species. Optimization of the use of fluconazole by appropriate dose or duration may be able to minimize the risk of resistance. The objective of this study was to evaluate the effects of prior fluconazole therapy, including the dose and duration, on fluconazole susceptibility among Candida species isolated from hospitalized patients with candidemia. A retrospective cohort study of hospitalized patients with a first occurrence of nosocomial candidemia, from 2006 to 2009, was carried out. The relationships between the initial dose and duration of prior fluconazole therapy and the isolation of fluconazole-nonsusceptible Candida species were assessed. An initial fluconazole dose greater than 2 mg/kg and less than 6 mg/kg of body weight was considered suboptimal. A total of 177 patients were identified, of whom 133 patients aged 61 ± 16 years (56% male, 51% Caucasian, 51% with an APACHE II score of ≥ 15) had candidemia more than 2 days after the hospital admission day. Nine of 107 (8%) patients with fluconazole-susceptible Candida species and 9 of 26 (35%) patients with fluconazole-nonsusceptible Candida species had prior fluconazole exposure (risk ratio [RR], 3.03; 95% confidence interval [95% CI], 1.57 to 5.86; P, 0.0022). Preexposure with an initial dose of fluconazole greater than 2 mg/kg and less than 6 mg/kg occurred in 3 of 9 (33%) and 8 of 9 (89%) patients with fluconazole-susceptible and fluconazole-nonsusceptible Candida species, respectively (P, 0.0498). We conclude that patients with candidemia due to fluconazole-nonsusceptible Candida species were more likely to have received prior fluconazole therapy. Suboptimal initial dosing of prior fluconazole therapy was associated with candidemia with fluconazole-nonsusceptible Candida species.

Improving patient care through implementation of an antimicrobial stewardship program.

PURPOSE: The implementation of an antimicrobial stewardship program at a health system is described. SUMMARY: In 2008, the Center for Antimicrobial Stewardship and Epidemiology (CASE) was formed at St. Luke's Episcopal Hospital (SLEH) to improve the quality of care for patients as it related to antimicrobial therapy. The charter of CASE contained specific aims for improving patient care, furthering clinical research, and training the next generation of clinical infectious diseases pharmacists. The CASE team consists of at least two infectious diseases pharmacists and one physician (the medical director) who provide direct oversight for antimicrobial utilization within the hospital. The CASE medical director, an infectious diseases physician, is responsible for overseeing the activities of the center. With the oversight of the CASE advisory board, the medical director develops and implements the antimicrobial stewardship and management policies for SLEH. Another key innovative feature of CASE is its extensive involvement in training new infectious diseases pharmacists and conducting research. CASE uses a model in which a clinical scenario or problem is identified, a research project is undertaken to further elucidate the problem, and policy changes are made to improve patient outcomes. The CASE team is supported by a CASE advisory board, a CASE research collaborative including university faculty, and a dedicated training program for pharmacy fellows, residents, and students. CONCLUSION: Implementation of an antimicrobial stewardship program at a health system helped decrease the inappropriate use of antibiotics, improve patient care and outcomes, further clinical research, and increase training opportunities for future clinical infectious diseases pharmacists.

Impact of multidrug-resistant Pseudomonas aeruginosa bacteremia on patient outcomes.

Trends of rising rates of resistance in Pseudomonas aeruginosa make selection of appropriate empirical therapy increasingly difficult, but whether multidrug-resistant (MDR) P. aeruginosa is associated with worse clinical outcomes is not well established. The objective of this study was to determine the impact of MDR (resistance to three or more classes of antipseudomonal agents) P. aeruginosa bacteremia on patient outcomes. We performed a retrospective cohort study of adult patients with P. aeruginosa bacteremia from 2005 to 2008. Patients were identified by the microbiology laboratory database, and pertinent clinical data were collected. Logistic regression was used to explore independent risk factors for 30-day mortality. Classification and regression tree analysis was used to determine threshold breakpoints for continuous variables. Kaplan-Meier survival analysis was used to compare time to mortality, after normalization of the patients' underlying risks by propensity scoring. A total of 109 bacteremia episodes were identified; 25 episodes (22.9%) were caused by MDR P. aeruginosa. Patients with MDR P. aeruginosa bacteremia were more likely to receive inappropriate empirical therapy (44.0% and 6.0%, respectively; P < 0.001) and had longer prior hospital stays (32.6 +/- 37.3 and 14.4 +/- 43.6 days, respectively; P = 0.046). Multivariate regression revealed that 30-day mortality was associated with multidrug resistance (odds ratio [OR], 6.8; 95% confidence interval [CI], 1.9 to 24.0), immunosuppression (OR, 5.0; 95% CI, 1.4 to 17.5), and an APACHE II score of > or = 22 (OR, 29.0; 95% CI, 5.0 to 168.2). Time to mortality was also shorter in the MDR cohort (P = 0.011). Multidrug resistance is a significant risk factor for 30-day mortality in patients with P. aeruginosa bacteremia; efforts to curb the spread of MDR P. aeruginosa could be beneficial.

Prevalence, resistance mechanisms, and susceptibility of multidrug-resistant bloodstream isolates of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an important pathogen commonly implicated in nosocomial infections. The occurrence of multidrug-resistant (MDR) P. aeruginosa strains is increasing worldwide and limiting our therapeutic options. The MDR phenotype can be mediated by a variety of resistance mechanisms, and the corresponding relative biofitness is not well established. We examined the prevalence, resistance mechanisms, and susceptibility of MDR P. aeruginosa isolates (resistant to > or =3 classes of antipseudomonal agents [penicillins/cephalosporins, carbapenems, quinolones, and aminoglycosides]) obtained from a large, university-affiliated hospital. Among 235 nonrepeat bloodstream isolates screened between 2005 and 2007, 33 isolates (from 20 unique patients) were found to be MDR (crude prevalence rate, 14%). All isolates were resistant to carbapenems and quinolones, 91% were resistant to penicillins/cephalosporins, and 21% were resistant to the aminoglycosides. By using the first available isolate for each bacteremia episode (n = 18), 13 distinct clones were revealed by repetitive-element-based PCR. Western blotting revealed eight isolates (44%) to have MexB overexpression. Production of a carbapenemase (VIM-2) was found in one isolate, and mutations in gyrA (T83I) and parC (S87L) were commonly found. Growth rates of most MDR isolates were similar to that of the wild type, and two isolates (11%) were found to be hypermutable. All available isolates were susceptible to polymyxin B, and only one isolate was nonsusceptible to colistin (MIC, 3 mg/liter), but all isolates were nonsusceptible to doripenem (MIC, >2 mg/liter). Understanding and continuous monitoring of the prevalence and resistance mechanisms of MDR P. aeruginosa would enable us to formulate rational treatment strategies to combat nosocomial infections.

Outcomes of bacteremia due to Pseudomonas aeruginosa with reduced susceptibility to piperacillin-tazobactam: implications on the appropriateness of the resistance breakpoint.

BACKGROUND: Bacteremia due to Pseudomonas aeruginosa is associated with grave clinical outcomes. Recent studies have emphasized the importance of appropriate empirical therapy, but controversy arises when piperacillin-tazobactam is used against isolates with reduced susceptibility. METHODS: We performed a retrospective cohort study of pseudomonal bacteremia from 2002 to 2006. Patients were identified by the microbiology laboratory database, and pertinent clinical data (demographic characteristics, baseline Acute Physiology and Chronic Health Evaluation [APACHE] II scores, source of bacteremia, and therapy) were retrieved from the electronic medical records. All patients received appropriate empirical therapy within 24 h of positive culture results. Patients receiving piperacillin-tazobactam were compared with those receiving other agents (control subjects). The primary outcome was 30-day mortality from the first day of bacteremia. RESULTS: A total of 34 bacteremia episodes were identified involving isolates with reduced susceptibility to piperacillin-tazobactam (minimum inhibitory concentration, 32 or 64 mg/L, reported as susceptible); piperacillin-tazobactam was empirically given in 7 episodes. There was no significant difference in baseline characteristics between the 2 groups. Thirty-day mortality was found to be 85.7% in the piperacillin-tazobactam group and 22.2% in the control group (P = .004). Time to hospital mortality was also found to be shorter in the piperacillin-tazobactam group (P < .001). In the multivariate analysis, 30-day mortality was found to be associated with empirical piperacillin-tazobactam therapy (odds ratio, 220.5; 95% confidence interval, 3.8-12707.4; P = .009), after adjustment for differences in age and APACHE II score. CONCLUSIONS: In P. aeruginosa bacteremia due to isolates with reduced piperacillin-tazobactam susceptibility, empirical piperacillin-tazobactam therapy was associated with increased mortality. Additional studies are warranted to examine the appropriateness of the current Clinical Laboratory Standards Institute resistance breakpoint of piperacillin-tazobactam.

Erythromycin reduces delayed gastric emptying in critically ill trauma patients: a randomized, controlled trial.

BACKGROUND: Early enteral feeding has been shown to be beneficial in improving outcome in critically injured trauma patients. Delayed gastric emptying occurs frequently in trauma patients, increasing the time to achieve nutritional goals, and limiting the benefit of early enteral feedings. Intravenous erythromycin is an effective agent for improving gastric motility in diabetics and postgastrectomy patients. The purpose of this study is to determine the effectiveness of erythromycin for improving gastric motility in critically injured trauma patients. METHODS: All critically injured patients who received gastric feedings within 72 hours of admission were candidates for the study. Those patients who failed to tolerate feedings at 48 hours (gastric residual > 150 mL) were eligible for enrollment. Patients were prospectively assigned to two treatment groups by randomization to receive either erythromycin (ERY) or placebo (PLA). Treatment was continued in patients who tolerated gastric feedings until the feedings were no longer required. Patients with continued intolerance for 48 hours after randomization were considered failures of therapy and given metoclopramide. RESULTS: Sixty-eight patients were enrolled and were well matched for age, sex, and Injury Severity Score. Mortality, intensive care unit length of stay, hospital length of stay, number of ventilator days, and rate of nosocomial infections were similar in each group. There was a significant difference between the ERY group and the PLA group in the amount of feedings tolerated at 48 hours (58% vs. 44%, p = 0.001). There was no difference in the amount of feedings tolerated (as a percentage of target goal volume) throughout the entire duration of the study (ERY [65% of target] vs. PLA [59%], p = 0.061). Overall success of therapy at 48 hours was 56% in the ERY group versus 39% in the PLA group, but this also did not reach statistical significance (p = 0.22). CONCLUSION: Intravenous erythromycin improves gastric motility and enhances early nutritional intake in critically injured patients.

Treatment of gram-positive infections: past, present, and future.

The need for strategic planning for antimicrobial use has reached a critical point. The rise in resistant nosocomial and community gram-positive bacteria mandates appropriate antibiotic selection and dosing. The development of new compounds is not the answer, because many are based off existing structures to which bacteria have already developed resistance. New antimicrobial agents are falling to the resistant mechanisms developed by the bacteria, after only limited clinical exposure. Judicious use of antimicrobial agents and applying pharmacokinetic principles when dosing can help slow the rate of resistance.