2019 update of the WSES guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients.

In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.

WSES guidelines for management of Clostridium difficile infection in surgical patients.

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.

Fidaxomicin Use and Clinical Outcomes for Clostridium difficile-Associated Diarrhea.

BACKGROUND: Fidaxomicin has been scrutinized because of its high acquisition cost. Real-world experience is needed to determine whether fidaxomicin has value in patients with Clostridium difficile-associated diarrhea (CDAD) and certain risk factors. METHODS: In this single-center, retrospective cohort study, patients 18 years or older with diarrheal symptoms and positive polymerase chain reaction assay for C. difficile toxin B gene or pseudomembranes were administered fidaxomicin between August 2011 and March 2013. Clinical success was defined as the resolution of signs and symptoms of disease and no further therapy required for CDAD as of the second day after cessation of fidaxomicin therapy. The recurrence of CDAD was defined by the reappearance of signs and symptoms of disease after the cessation of therapy, a new positive C. difficile polymerase chain reaction result, and the need for CDAD retreatment. Readmissions were tracked for 90 days after hospital discharge. RESULTS: Of the 60 patients who received fidaxomicin, 58 (96.7%) achieved clinical success. Twenty-six (43.3%) of the 60 patients were being treated for a second or greater episode. Six (10.3%) of the 58 patients had recurrence within 90 days after the initial treatment course, and 4 (6.9%) were readmitted within 30 days after hospital discharge. CONCLUSIONS: In this real-world setting, fidaxomicin resulted in a high rate of clinical success, a low rate of recurrence, and a low readmission rate.

Demonstrating the value of antimicrobial stewardship programs to hospital administrators.

The movement away from fee-for-service models to those that emphasize quality of care and patient outcomes affords a unique opportunity for antimicrobial stewardship programs to expand their value for hospital administration. Antimicrobial stewardship participants must collaborate with administrators and key stakeholders to position themselves to improve economic, process, and outcomes measures. This will allow the establishment of antimicrobial stewardship programs as essential components of the present and future healthcare quality journey.

Assessing appropriateness of antimicrobial therapy: in the eye of the interpreter.

To address the increase of drug-resistant bacteria and widespread inappropriate use of antimicrobials, many healthcare institutions have implemented antimicrobial stewardship programs to promote appropriate use of antimicrobials and optimize patient outcomes. However, a consensus definition of appropriate use is lacking. We conducted a multicenter observational study to compare 4 definitions of appropriateness--a study site-specific definition, use supported by susceptibility data, use supported by electronic drug information resources (Clinical Pharmacology/Micromedex), or study site principal investigator (PI) opinion-among patients receiving 1 or more of 13 identified antimicrobials. Data were collected for 262 patients. Overall, appropriateness with the 4 definitions ranged from 79% based on PI opinion to 94% based on susceptibility data. No single definition resulted in consistently high appropriate use for all target antimicrobials. For individual antimicrobials, the definitions with the highest rate of appropriate use were Clinical Pharmacology/Micromedex support (6 of 7 antimicrobials) and susceptibility data (5 of 7 antimicrobials). For specific indications, support from susceptibility data resulted in the highest rate of appropriate use (4 of 7 indications). Overall comparisons showed that appropriateness assessed by PI opinion differed significantly compared with other definitions when stratified by either target antimicrobial or indication. The significant variability in the rate of appropriate use highlights the difficulty in developing a standardized definition that can be used to benchmark judicious antimicrobial use.

Breaking down the barriers: challenges with development and implementation of an industry-sponsored antimicrobial stewardship data collection and analysis tool.

Partnership between clinicians and the pharmaceutical industry with a focus on antimicrobial stewardship research initiatives is a necessary step toward meeting the shared goals of combating inappropriate antimicrobial use, improving patient outcomes, and minimizing resistance development. Achieving these goals requires outcomes-focused data collection and monitoring tools for antimicrobial stewardship programs (ASP) that consider real-world data about how antimicrobials are used to treat patients. Here we highlight the experiences and challenges associated with the development and implementation of an industry-sponsored electronic antimicrobial stewardship data collection and analysis tool (AS-DCAT). The benefits and risks of the industry-sponsored AS-DCAT from the perspectives of the sponsoring company and participating sites are discussed. Barriers encountered as well as general considerations and recommendations for preventing or overcoming those barriers for future studies and tool development are provided.

Linezolid-induced lactic acidosis corrected with sustained low-efficiency dialysis: a case report.

Linezolid, an oxazolidinone antibiotic, has been reported to increase the risk of lactic acidosis and peripheral neuropathy because it disrupts mitochondrial function. This case report describes the development of lactic acidosis in a 63-year-old man who had received 3 months of treatment with intravenous linezolid for pulmonary nocardiasis, and correction of the acidotic state with sustained low-efficiency dialysis. This case demonstrates that renal replacement therapy can be an alternative to discontinuation alone for rapid reversal of linezolid-induced lactic acidosis.

Augmentation with atypical antipsychotics for depression: a review of evidence-based support from the medical literature.

Major depressive disorder (MDD) is a chronic mental illness that affects an estimated 5-26% of adults at some time in their lives. Treatment is often started as pharmacotherapy using a single drug such as a selective serotonin reuptake inhibitor. If a patient fails to respond adequately to the initial antidepressant, typically three pharmacotherapy options are available to the practitioner. The dose of the current therapy can be maximized, a change can be made to a different drug, or the current regimen can be augmented with another drug. Atypical antipsychotics have recently become a major focus for augmentation of traditional antidepressant therapy. This review summarizes the evidence for efficacy and safety of augmenting treatment-refractory or treatment-resistant depression with atypical antipsychotics. The National Library of Medicine's MEDLINE database was searched for all English-language articles published from January 1966-December 2011 describing the use of atypical antipsychotics in treatment-resistant depression. The literature retrieved was limited to case series, open-label trials, and randomized controlled trials (RCT). Studies of bipolar depression, psychotic depression, or studies conducted in children and adolescents were excluded. Thirty-five studies using atypical antipsychotics for augmentation treatment of depression were included in this analysis. Trials were identified for aripiprazole (six open-label; three RCT), clozapine (one case series), olanzapine (three open-label, including two case series; four RCT), quetiapine (four open-label; five RCT), risperidone (two open-label; five RCT), and ziprasidone (two open-label). The atypical antipsychotics may be effective as adjunctive therapy in MDD; however, their adverse effect profile may be unfavorable to some patients. Trying at least one alternative treatment strategy after an initial antidepressant is indicated before augmentation is implemented with these agents. If atypical antipsychotics are used, safety and efficacy should be frequently reassessed and dosage should be individualized.

Assessment of vancomycin dosing and subsequent serum concentrations in pediatric patients.

BACKGROUND: Because of concerns regarding increasing microbial resistance to vancomycin, adult treatment guidelines recommend higher trough concentrations based on the type of infectious process. Although these recommendations are not specific to pediatrics, the principles can be extrapolated. Desired higher trough serum concentrations will require escalated dosages of vancomycin in children. OBJECTIVE: To evaluate current dosing regimens and subsequent trough serum concentrations of vancomycin in children, compare these to reference recommended dosages and guidelines, and predict a dosing equation to achieve desired serum concentrations. METHODS: Pharmacokinetic parameters of children in a community teaching hospital who were prescribed vancomycin from January 2005 to May 2010 were evaluated in this retrospective chart review. Vancomycin dosing and subsequent serum concentrations were analyzed. Therapeutic serum concentrations were evaluated and compared to vancomycin prescribing and monitoring guidelines by year. RESULTS: Four hundred thirty-five trough serum concentrations determined in 295 patients were analyzed. The average dosages, when evaluated by year, were 48 mg/kg/day (2005-2008) and 59 mg/kg/day (2009-2010). Using trough concentration recommendations of 5-15 mg/L, vancomycin regimens provided therapeutic trough concentrations 78% of the time from 2005 to 2008. Using 10-20 mg/L as the trough recommendations in 2009-2010, only 49% of serum concentrations reached a therapeutic level. Based on our predictive equation for children aged 1 month-18 years with normal renal function, a vancomycin dosage of 70 mg/kg/day is required to provide trough serum concentrations of 10 mg/L; a dosage of 85 mg/kg/day is required to provide trough serum concentrations of 15 mg/L. CONCLUSIONS: Our institution was primarily using vancomycin dosing regimens that were recommended in pediatric references (40-60 mg/kg/day), which resulted in subtherapeutic serum concentrations in our population based on new monitoring recommendations. Considering that the currently desired therapeutic trough concentrations of vancomycin are 10-20 mg/L, the total daily dosage should be increased.

Retrospective Analysis of Clinical and Cost Outcomes Associated with Methicillin-Resistant Staphylococcus aureus Complicated Skin and Skin Structure Infections Treated with Daptomycin, Vancomycin, or Linezolid.

Objective. The objective of this analysis was to compare clinical and cost outcomes associated with patients who had suspected or documented methicillin-resistant Staphylococcus aureus (MRSA) infections treated with daptomycin, vancomycin, or linezolid in complicated skin and skin structure infections (cSSSIs). Design. This was a retrospective analysis conducted from February to June of 2007. Appropriate data was collected, collated, and subsequently evaluated with the purpose of quantifying length of stay, antibiotic therapy duration, clinical cure rates, adverse drug events, and cost of hospitalization. Results. All 82 patients included in the analysis experienced clinical cure. The duration of antibiotic therapy was similar among the three groups yet the length of hospitalization was slightly shorter in the daptomycin group. Conclusions. The incidence of resistant staphylococcal infections is increasing; therefore, judicious use of MRSA active agents is paramount. Future studies are necessary to determine if MRSA treatment options can be stratified based on the severity of the infectious process.

Zanamivir for the prevention of influenza in adults and children age 5 years and older.

On a yearly basis there are 3-5 million severe cases and 250,000-500,000 deaths worldwide attributed to influenza. Four antiviral medications are currently available on the market; however, resistance has resulted in the armamentarium being shrunk to two remaining active treatment options for influenza. These two neuraminidase inhibitors, oseltamivir and zanamivir, are recommended for the treatment and prophylaxis of influenza A and B in children and adults. Zanamivir, which is the focus of this review, is an inhaled antiviral that has shown benefit in the community, household, and nursing home population for post-exposure prophylaxis. Zanamivir protection rates range from 67%-84% in clinical trials of adults and children. Although the influenza vaccine remains the best modality to combat the disease, zanamivir may also assist in decreasing morbidity associated with influenza A and B.

Analysis of adherence to national nosocomial pneumonia treatment guidelines.

BACKGROUND: Guidelines for the management of adults with hospital-acquired (HAP), ventilator-associated (VAP), and healthcare-associated (HCAP) pneumonia were recently updated. These evidence-based guidelines emphasize early, appropriate antimicrobials, as well as, de-escalation of initial therapy based upon microbiologic cultures and clinical response of the patient, and to shorten duration of therapy to a minimum effective period. OBJECTIVE: To evaluate adherence to the nosocomial pneumonia guidelines before and after a multifaceted educational intervention in conjunction with the implementation of an adult pneumonia order set. METHODS: A three phase, retrospective, observational analysis was performed among patients with nosocomial pneumonia in a tertiary care facility. The phases consisted of an analysis of medical charts to identify empiric antimicrobial therapy for patients with nosocomial pneumonia; education of physicians on the guidelines; and repeat review of medical charts of patients with nosocomial pneumonia to observe for guideline adherence. An adult pneumonia order set was introduced to the medical staff prior to the initiation of the observational analysis and provided a modality for prescribers to be most compliant with the current recommendations for treating pneumonia. Order set utilization was tracked throughout the observational analysis to determine if various educational interventions increased compliance. RESULTS: Thirty-three patients were evaluated pre-education: 5 transferred, 16 discharged, and 12 died. Thirty-one patients were evaluated post-education: 6 transferred, 21 discharged, and 4 died. The combined sixty-seven patients received two hundred forty-eight orders for forty-four unique antimicrobial agents from five different services. Appropriateness of antimicrobial prescribing, designated by adherence to the clinical practice guidelines, did not improve following an educational intervention. However, the adult pneumonia order set was utilized in forty-eight percent of the post-education group while only being implemented in nine percent of the pre-education group. The prescribing of single or additional antimicrobials, while utilizing the adult pneumonia order set, commonly resulted in overall noncompliance with the consensus guidelines. CONCLUSION: This analysis showed that educational efforts alone were not effective in improving the appropriateness of prescribing empiric antimicrobial therapy in accordance with the guidelines. Prescribing compliance with pre-printed orders, in addition to periodic interactive educational interventions, should be addressed when introducing and maintaining adherence to new clinical practice guidelines.

Comparison of the modification of diet in renal disease and Cockcroft-Gault equations for antimicrobial dosage adjustments.

BACKGROUND: Direct measurement of glomerular filtration rate (GFR) is considered to be the most accurate method of assessing kidney function, albeit difficult and costly. With the derivation of the Modification of Diet in Renal Disease (MDRD) equation to estimate GFR in patients with chronic kidney disease, questions exist as to whether this method should be preferred over the Cockcroft-Gault (CG) equation when making dosage adjustments for renally eliminated antimicrobials. OBJECTIVE: To determine whether a difference exists when making antimicrobial dosage adjustments in patients with chronic kidney disease based on estimation of GFR using the MDRD and CG equations. METHODS: We conducted an observational analysis of 409 patients with chronic kidney disease who were admitted to a tertiary care facility with an inpatient dialysis center and nephrology unit. GFR was calculated using both the 4- or 6-variable MDRD equation and the CG equation and compared using correlation and Bland-Altman methodology. Dosage discordance rates of the selected antimicrobials were determined on the basis of manufacturer renal dose recommendations. RESULTS: Average +/- SD GFR for all patients using the CG equation was 34.8 +/- 12 mL/min and, using the MDRD equation, was 40.2 +/- 12 mL/min (absolute mean difference 5.40; 95% CI 4.66 to 6.15; p < 0.001). The correlation coefficient between the 2 estimations, among all patients, was excellent (r = 0.80). The Bland-Altman plot yielded limits of agreement of -9.8 and 20.6; thus, the MDRD estimation may range from 9.8 mL/min below to 20.6 mL/min above the CG estimation for 95% of the cases. A discordance rate of 21-37% (p < 0.001) existed among the recommended dosing adjustments of the selected antimicrobials. CONCLUSIONS: This analysis demonstrated statistically significant differences between the CG and MDRD equations, resulting in different dosing recommendations in 21-37% of patients. The clinical significance of these differences is uncertain in the absence of data regarding clinical outcomes that would result from the use of the discordant doses.