Laura Aragon

Successful Treatment of Carbapenemase-Producing Pandrug-Resistant Klebsiella pneumoniae Bacteremia

ABSTRACT New antibiotic options are urgently needed for the treatment of carbapenem-resistant Enterobacteriaceae infections. We report a 64-year-old female with prolonged hospitalization following an intestinal transplant who developed refractory bacteremia due to a serine carbapenemase-producing pandrug-resistant isolate of Klebsiella pneumoniae. After failing multiple antimicrobial regimens, the patient was successfully treated.

Clinical infectious diseases pharmacists in the United States: a problem of both supply and demand

TO THE EDITOR—The importance of antimicrobial stewardship (AS) to the future of healthcare is emphasized by recent statements of the US government calling for widespread implementation of robust AS programs, which applies to >5700 US hospitals [1]. The Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance AS identify a clinical pharmacist with infectious diseases (ID) training as 1 of 2 core AS team members [2]. The Society of Infectious Diseases Pharmacists (SIDP) and Infectious Diseases Practice Research Network of the American College of Clinical Pharmacy (ACCP) recommend that future pharmacists seeking a clinical ID position complete a postgraduate year 1 (PGY-1) pharmacy practice residency and postgraduate year 2 (PGY-2) ID specialty residency [3]. Today, concern exists over the shortages of adequately trained ID pharmacists [4, 5], and as such, the future supply of clinical ID pharmacists is dependent on the availability of postgraduate ID training opportunities. The purpose of this correspondence is to objectively describe the current state of (1) postgraduate training opportunities for pharmacists looking to specialize in ID and (2) demand for clinical ID pharmacists. To quantify and characterize postgraduate training opportunities, we accessed pharmacy residency and fellowship directories of SIDP, American Society of Health-System Pharmacists (ASHP), and ACCP. Site information was crossreferenced to account for duplication, and available data points were collected for analysis. To assess the demand for clinical ID pharmacists, we utilized Web-based searches (eg, www.monster. com, www.usajobs.gov) and accessed employment postings provided by relevant pharmacy organizations (eg, ASHP, SIDP). These were compiled using Microsoft Excel software and evaluated individually to prevent duplication. We performed this snapshot assessment in October 2014, identifying 89 postgraduate ID training programs and 32 clinical ID pharmacist employment listings. Collected data are presented in Table 1. For training programs, none focused specifically on AS, although by nature AS concepts are incorporated into training and accreditation standards for PGY-2 ID residencies mentions AS briefly [7]. For employment, 23 (72%) mentioned AS within the job description and 29 (91%) were inpatient positions. In addition to the 32 clinical ID pharmacist positions, 5 academic and 10 industrybased (eg, medical science liaison) ID pharmacist jobs were found. If AS programs are destined to become part of the healthcare landscape and clinical ID pharmacists are essential for such a transition, the data presented here represent cause for substantial concern. Quantitatively and geographically, current opportunities for training and employment are considerably inadequate to fulfill the anticipated future needs for thousands of US institutions. Indeed, alternative educational programs such as certificate programs [8, 9] may assist in filling some existing gaps, but are limited in their scope. As healthcare continues to evolve and the role of AS grows, early recognition of existing barriers by stakeholders is essential to future success. The impact of the current clinical ID pharmacist supply and demand deficiencies within the United States noted here requires consideration during this AS program implementation and expansion period.

Intravenous Fosfomycin Treatment for Carbapenem-Resistant Klebsiella pneumoniae in the United States

We read with interest the report by Kyle et al on the use of an oral fosfomycin-containing antibiotic regimen for the treatment of refractory carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteremia. They reported a stem cell transplant recipient with septic shock caused by CRKP, in whom sterilization of blood cultures was only achieved after addition of high-dose oral fosfomycin (9 g orally, every 8 hours), with a successful outcome. Nonetheless, oral administration of antibiotics for the treatment of bacteremia is suboptimal in critically ill patients and should only be considered as a desperate measure. Although not available in the United States, intravenous (IV) fosfomycin has been used in Europe for CRKP with promising results. We would like to expand the observations from Kyle et al by reporting a patient with refractory CRKP bacteremia in whom sterilization of blood cultures was rapidly achieved after addition of IV fosfomycin. A 45-year-old woman underwent orthotopic liver transplant for cirrhosis secondary to nonalcoholic steatohepatitis. The posttransplant course was complicated by graft failure and prolonged stay in the intensive care unit; during this time, she was exposed to cefepime, piperacillin/tazobactam, meropenem, colistin, and tigecycline. On posttransplant day 149, she developed bowel ischemia and septic shock. Peritoneal fluid and blood cultures were positive for CRKP resistant to colistin (minimum inhibitory concentration [MIC] = 12 μg/mL) and tigecycline. She was initially treated with extended-infusion meropenem (1 g IV every 8 hours) and amikacin (7.5 mg/kg IV every 24 hours) without resolution of bacteremia. Because of hemodynamic instability, she was not considered a surgical candidate and efforts were made to maximize her medical therapy. One week later, colistin (2.5 mg/kg IV every 12 hours) and rifampin (600 mg IV every 24 hours) were added. Her cultures cleared on this regimen, but she had recurrent bacteremia 96 hours later. The CRKP isolate was fosfomycin susceptible (MIC = 16 μg/mL). IV fosfomycin was purchased from Europe and arrived at our institution 10 days later (after a 3-day delay in customs). On posttransplant day 173, fosfomycin (8 g IV every 8 hours) was started. Blood cultures became negative within 24 hours. Although hypokalemia is a potential side effect of fosfomycin, her lowest potassium level was 3.5 mmol/L (normal: 3.6-5 mmol/L) while on fosfomycin therapy. Unfortunately, on posttransplant day 179, the patient succumbed to Candida parapsilosis fungemia and multiorgan failure. This case, along with previous reports, suggests that fosfomycin is a safe and potentially useful antibiotic option for the treatment of serious infections caused by multidrug-resistant CRKP. After more than 40 years of its discovery, only the oral form of fosfomycin—approved by the Food and Drugs Administration (FDA) for uncomplicated urinary tract infections—is widely used in the United States. The poor bioavailability of oral fosfomycin (approximately 37%) limits its use in critically ill patients, particularly those with abdominal sepsis. When needed, IV fosfomycin has to be imported from Europe (from pharmaceutical companies such as Nordic Pharma in the United Kingdom and InfectoPharm in Germany) after an emergency investigational new drug application is approved by the FDA. This imposes significant delays that jeopardize the timely initiation of effective antibiotic therapy. Until newer and more effective antibiotics become available for the treatment of CRKP, we strongly feel that the availability of IV fosfomycin is urgently needed in the United States.

Mycobacterium abscessus complex infections: A retrospective cohort study

Abstract Background Infections caused by Mycobacterium abscessus group strains are usually resistant to multiple antimicrobials and challenging to treat worldwide. We describe the risk factors, treatment, and clinical outcomes of patients in 2 large academic medical centers in the United States. Methods A retrospective cohort study of hospitalized adults with a positive culture for M. abscessus in Miami, Florida (January 1, 2011, to December 31, 2014). Demographics, comorbidities, the source of infection, antimicrobial susceptibilities, and clinical outcomes were analyzed. Early treatment failure was defined as death and/or infection relapse characterized either by persistent positive culture for M. abscessus within 12 weeks of treatment initiation and/or lack of radiographic improvement. Results One hundred eight patients were analyzed. The mean age was 50.81 ± 21.03 years, 57 (52.8%) were females, and 41 (38%) Hispanics. Eleven (10.2%) had end-stage renal disease, 34 (31.5%) were on immunosuppressive therapy, and 40% had chronic lung disease. Fifty-nine organisms (54.6%) were isolated in respiratory sources, 21 (19.4%) in blood, 10 (9.2%) skin and soft tissue, and 9 (8.3%) intra-abdominal. Antimicrobial susceptibility reports were available for 64 (59.3%) of the patients. Most of the isolates were susceptible to clarithromycin, amikacin, and tigecycline (93.8%, 93.8%, and 89.1%, respectively). None of the isolates were susceptible to trimethoprim/sulfamethoxazole, and only 1 (1.6%) was susceptible to ciprofloxacin. Thirty-six (33.3%) patients early failed treatment; of those, 17 (15.7%) died while hospitalized. On multivariate analysis, risk factors significantly associated with early treatment failure were disseminated infection (odds ratio [OR], 11.79; 95% confidence interval [CI], 1.53–81.69; P = .04), acute kidney injury (OR, 6.55; 95% CI, 2.4–31.25; P = .018), organ transplantation (OR, 2.37; 95% CI, 2.7–23.1; P = .005), immunosuppressive therapy (OR, 2.81; 95% CI, 1.6–21.4; P = .002), intravenous amikacin treatment (OR, 4.1; 95% CI, 0.9–21; P = .04), clarithromycin resistance (OR,79.5; 95% CI, 6.2–3717.1, P < .001), and presence of prosthetic device (OR, 5.43; 95% CI, 1.57–18.81; P = .008). Receiving macrolide treatment was found to be protective against early treatment failure (OR, 0.13; 95% CI, 0.002–1.8; P = .04). Conclusions Our cohort of 108 M. abscessus complex isolates in Miami, Florida, showed an in-hospital mortality of 15.7%. Most infections were respiratory. Clarithromycin and amikacin were the most likely agents to be susceptible in vitro. Resistance to fluoroquinolone and trimethoprim/sulfamethoxazole was highly common. Macrolide resistance, immunosuppression, and renal disease were significantly associated with early treatment failure.

Cost Reduction of Inhaled Tobramycin by Use of Preservative-Free Intravenous Tobramycin Given via Inhalation.

This study evaluates drug cost outcomes related to automatic therapeutic substitution of branded tobramycin solution for inhalation (TOBI®) with inhaled generic preservative-free intravenous tobramycin (PFIT). A retrospective single-center evaluation of inhaled tobramycin use from 2008 through 2012 was performed. Number of doses dispensed and acquisition costs were obtained. Hourly wage data was acquired, pharmacy production costs were estimated and total cost-savings calculated. Days of therapy (DOTs) were determined for each year. Quality assurance and safety data was collected. In 2008, TOBI® drug costs and doses dispensed were

Characteristics of primary literature in the field of antimicrobial stewardship, 2000-2013.

118,665 and 1769, respectively. Following implementation of the interchange in May 2009, TOBI® utilization ceased. PFIT costs in 2010 through 2012 averaged

Working Together to Define Antibiotic Appropriateness: Point Prevalence Survey in 47 Intensive Care Units from 12 US Hospitals, Partnership for Quality Care, March 2017

34,775 annually and TOBI® cost-avoidance exceeded

Obtaining i.v. fosfomycin through an expanded-access protocol

94,000 annually when accounting for pharmacy production costs, which were determined to be at most

Recognition of Advanced Pharmacy Practice Experience Student Participation Within Antimicrobial Stewardship Activities

5.28 per dose. The maximum estimated pharmacy production cost ranged from

Application of Precision Medicine Through the Molecular Characterization of Extensively Drug Resistant (XDR) Klebsiella pneumoniae in a Multivisceral Transplant Candidate

8812 to