Compassionate Use of Cefiderocol in the Treatment of an Intraabdominal Infection Due to Multidrug-Resistant Pseudomonas aeruginosa: A Case Report.

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections often represent a therapeutic challenge requiring utilization of older, more toxic antibiotics, or new agents with limited data. Once susceptibility to ß-lactam and fluoroquinolone antibiotics has been lost, other therapeutic options such as aminoglycoside or polymyxin antibiotics carry significant adverse effects such as nephrotoxicity, neurotoxicity, and ototoxicity. A novel cephalosporin, cefiderocol, lacks gram-positive and anaerobic activity but offers broad coverage of gram-negative bacteria, including P. aeruginosa. A unique catechol side chain gives it activity as a siderophore, thereby increasing bacterial uptake and decreasing efflux. Additionally, cefiderocol is stable against a wide array of ß-lactamases. Despite these promising characteristics, there are minimal data currently available in the literature detailing the use of cefiderocol in the treatment of MDR P. aeruginosa infections. We present a case of a 46-year-old man who developed an MDR P. aeruginosa intraabdominal infection where serious and life-threatening toxicities to aminoglycosides and polymyxin antibiotics led to the utilization of cefiderocol on compassionate use approval. The isolate was susceptible to cefiderocol, and the patient was treated for 28 days of therapy. He demonstrated clinical and radiographic resolution of his infection and was discharged to home.

Disseminated cryptococcosis associated with administration of eculizumab.

PURPOSE: A case report of fatal disseminated cryptococcosis in a patient treated with eculizumab is presented along with a review of literature suggesting a possible etiologic mechanism. SUMMARY: A 23-year-old man with a history of minimal change nephrotic syndrome was hospitalized for acute kidney injury and abdominal pain and swelling. He was found to have disseminated pneumococcal disease, including peritonitis, bacteremia, and pulmonic endocarditis. The patient developed evidence of microangiopathic hemolytic anemia, leading to a diagnosis of atypical hemolytic uremic syndrome, and was started on eculizumab. The patient initially improved but developed septic shock 18 days after the first dose of eculizumab. All subsequent blood, respiratory, and intraabdominal cultures grew Cryptococcus neoformans. Twenty-eight days after the initial dose of eculizumab, the patient died. Autopsy findings demonstrated disseminated cryptococcosis, with infection noted in lung, myocardial, kidney, and liver tissues. Considering the complement-dependent nature of host defenses against Cryptococcus species and available evidence regarding C. neoformans pathogenicity from studies of murine models, it was hypothesized that the patient's cryptococcosis and death were secondary to administration of eculizumab and consequent blockage of the C5 component of the complement cascade. Eculizumab is known to predispose recipients to infections with encapsulated organisms; however, this was believed to be the first reported case of infection with an encapsulated yeast possibly due to eculizumab use. Patients receiving eculizumab should be monitored closely for invasive cryptococcal infections. CONCLUSION: A 23-year-old man developed fatal disseminated cryptococcosis after treatment with eculizumab.

Outcomes of Cognitive-Behavioral Treatment for Insomnia on Insomnia, Depression, and Fatigue for Individuals with Multiple Sclerosis: A Case Series.

BACKGROUND: This clinical case series examined outcomes of cognitive-behavioral therapy for insomnia (CBT-I) in individuals with multiple sclerosis (MS). Current literature links insomnia with higher rates of depression and fatigue in individuals with MS. However, no research to date evaluates a targeted psychotherapeutic intervention for insomnia in this population. PARTICIPANTS AND METHODS: Eleven individuals with a diagnosis of MS and insomnia participated in individual or group-based CBT-I sessions at the Cleveland Clinic Sleep Disorders Center between 2008 and 2013. A medical record review examined these individuals' self-reported experiences of insomnia, depression, and fatigue at the preintervention and postintervention levels using the Insomnia Severity Index, nine-item Patient Health Questionnaire, and Fatigue Severity Scale. Total sleep time was also reported at pretreatment and posttreatment intervals. RESULTS: Overall, participants reported improvements regarding insomnia, fatigue, and depression after CBT-I. Total sleep time also increased by an average of 1.5 hours. Despite overall improvement, symptoms of fatigue, insomnia, and depression persisted, at varying levels, for most participants. CONCLUSIONS: These results strongly suggest that CBT-I may serve as an effective clinical intervention for individuals with MS who report symptoms of insomnia. Given the considerable overlap of experiences of insomnia, depression, and fatigue in people with MS, CBT-I may also be helpful in identifying areas that may require additional clinical intervention for persistent symptoms of depression and fatigue. Further research is necessary.

Current Trends in Retirement: Implications for Career Counseling and Vocational Psychology.

This paper provides an overview of emerging trends in retirement, examines demographic trends in the labor force, and provides practical recommendations for working with older workers across cultures (e.g., women and racial/ethnic minorities, among others). Increasingly, older workers in the United States remain in the workforce for reasons related to financial security, healthcare, and personal fulfillment. Although retirement trends have become more complex, there is limited empirical literature addressing this issue and the research available does not attend to the needs of a diverse workforce. Therefore, implications for training, practice, advocacy, and research with regards to working with older workers across cultures (e.g., women and racial/ethnic minorities, among others) are provided.

Fatal outbreak of an emerging clone of extensively drug-resistant Acinetobacter baumannii with enhanced virulence.

BACKGROUND: Severe Acinetobacter baumannii infections in immunocompetent patients are uncommon, and the virulence mechanisms of this organism are not fully understood. METHODS: Following an outbreak of fatal A. baumannii infections in a cohort of relatively immunocompetent patients (low comorbidity and illness severity scores), isolates were investigated with comparative genomics and in animal models. RESULTS: Two unrelated A. baumannii clades were associated with the outbreak. The clone associated with the majority of patient deaths, clade B, is evolutionarily distinct from the 3 international clonal complexes, belongs to multilocus sequence type (MLST) 10, and is most closely related to strains isolated from the Czech Republic, California, and Germany in 1994, 1997, and 2003, respectively. In 2 different murine models, clade B isolates were more virulent than comparator strains, including the highly virulent reference strain AB5075. The most virulent clade B derivative, MRSN 16897, was isolated from the patient with the lowest combined comorbidity/illness severity score. Clade B isolates possess a unique combination of putative virulence genes involved in iron metabolism, protein secretion, and glycosylation, which was leveraged to develop a rapid and specific clinical assay to detect this clade that cannot be distinguished by MLST. CONCLUSIONS: Clade B warrants continued surveillance and investigation.

Active screening in high-risk units is an effective and cost-avoidant method to reduce the rate of methicillin-resistant Staphylococcus aureus infection in the hospital.

OBJECTIVE: To evaluate the impact of active screening for methicillin-resistant Staphylococcus aureus (MRSA) on MRSA infection rates and cost avoidance in units where the risk of MRSA transmission is high. METHODS: During a 15-month period, all patients admitted to our adult medical and surgical intensive care units (ICUs) were screened for MRSA nasal carriage on admission and weekly thereafter. The overall rates of all MRSA infections and of nosocomial MRSA infection in the 2 adult ICUs and the general wards were compared with rates during the 15-month period prior to the start of routine screening. The percentage of patients colonized or infected with MRSA on admission and the cost avoidance of the surveillance program were also assessed. RESULTS: The overall rate of MRSA infections for all 3 areas combined decreased from 6.1 infections per 1,000 census-days in the preintervention period to 4.1 infections per 1,000 census-days in the postintervention period (P = .01). The decrease remained statistically significant when only nosocomial MRSA infections were examined (4.5 vs 2.8 infections per 1,000 census-days; P < .01), despite a corresponding increase during the postintervention period in the percentage of patients with onset of MRSA infection in the first 72 hours after admission to the general wards (46% to 81%; P < .005). A total of 3.7% of ICU patients were colonized or infected with MRSA on admission; MRSA would not have been detected in 91% of these patients if screening had not been performed. At a cost of Dollars 3,475/month for the program, we averted a mean of 2.5 MRSA infections/month for the ICUs combined, avoiding Dollars 19,714/month in excess cost in the ICUs. CONCLUSIONS: Even in a setting of increasing community-associated MRSA, active MRSA screening as part of a multi-factorial intervention targeted to high-risk units may be an effective and cost-avoidant strategy for achieving a sustained decrease of MRSA infections throughout the hospital.

Widespread emergence of methicillin resistance in community-acquired Staphylococcus aureus infections in Denver.

BACKGROUND: Increasing rates of methicillin resistance among out-patient Staphylococcus aureus infections led us to assess the epidemiology and outcome of a local outbreak. METHODS: A retrospective cohort study of outpatient skin and soft tissue infections due to S aureus in 2003. RESULTS: From 2002 to mid-2004, the percentage of outpatient S aureus isolates resistant to methicillin increased from 6 to 45%. In multivariate analysis, only male sex and age greater than 18 years were associated with methicillin resistance. Methicillin resistance was common (>15%) among isolates from patients in nearly all subgroups evaluated. Pulsed field gel electrophoresis showed isolates related to USA 300, but methicillin-resistant strains had unusually high rates of quinolone resistance. CONCLUSIONS: A single strain of methicillin-resistant S aureus is responsible for the increase in skin infections in outpatients without traditional risk factors for infection with an antibiotic-resistant strain. In areas with high rates of methicillin-resistant S aureus outpatient infections, we recommend non-beta-lactam antibiotics for initial treatment of skin and soft tissue infections.