Linezolid for the Treatment of Urinary Tract Infections Caused by Vancomycin-Resistant Enterococci.

Vancomycin-resistant enterococci (VRE) account for a large proportion of hospital-acquired infections. Determining optimal treatment of VRE urinary tract infections (UTIs) is challenging. The purpose of this study was to determine if a difference in efficacy or safety exists between linezolid and non-linezolid treatments for VRE UTIs. This retrospective cohort evaluated patients admitted between 1 June 2012-30 November 2017 who were treated for VRE UTI. Patients must have had at least one sign, symptom, or laboratory confirmation of UTI to be included. The primary endpoint of this study was difference in clinical cure between linezolid and non-linezolid treatment options. Secondary endpoints included 30-day recurrence, 30-day infection-related readmission, inpatient mortality, infection-related hospital length of stay (LOS), and time to appropriate therapy. A total of 45 patients (33 linezolid and 12 non-linezolid) were included. Clinical cure occurred in 71.4% linezolid and 58.3% non-linezolid (p = 0.476). No patients had a 30-day infection-related readmission or 30-day recurrence. Of the 45 patients, 6 (13.3%) patients died during admission, and 5 of those deaths were in the linezolid group (p = 1.000). No significant difference was found for clinical cure between linezolid and non-linezolid treatment options for VRE UTIs.

Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to Enterobacter, Serratia, and Citrobacter Species.

OBJECTIVES: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. METHODS: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection. RESULTS: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51-1.72) in multivariable Cox proportional hazards regression analysis. CONCLUSIONS: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents.

Impact of an infectious diseases advanced pharmacy practice experience on student knowledge.

INTRODUCTION: The goal of this assessment was to determine knowledge acquisition by pharmacy students during an infectious diseases (ID) advanced pharmacy practice experience (APPE). METHODS: A 50-question knowledge-based examination was given to every student on a five-week ID APPE between July 1, 2013 and May 5, 2017. The examination was also given to control students (those who did not have an ID APPE) immediately prior to graduation. The primary outcome was difference in examination performance after completion of the ID APPE. Secondary outcomes included correlations between examination performance and number of previous inpatient clinical rotations (ICR), average score in therapeutic coursework (TC), and rotation block (RB). RESULTS: Forty students were included (control = 5, experimental = 35). Average pre-test scores were similar between experimental and control students [61.7 (10.9)% versus 62.0 (5.1)%, respectively], but experimental post-test scores [80.2 (7.9)%] were significantly better than pre-test scores for both experimental (p < .05) and control student (p < .05) examination scores. ICR [1.3 (1.0) rotations], TC [81.5 (3.9)%], and RB (median = 4) had a positive correlation with pre-examination performance (R = .5, .5, and .4, respectively). DISCUSSION: Improved ID pharmacotherapy knowledge is needed. Baseline scores of students taking an ID elective were similar to control students who completed the entire year of APPEs, and knowledge scores were higher in ID students after APPE completion. There was a positive, but not strong, correlation between pre-examination performance and number of previous rotations, therapeutic coursework, and rotation block. CONCLUSION: A five-week ID elective APPE improved student performance on a knowledge-based examination. Consideration should be given to more consistent integration of ID principles across all rotation types.

Newest lipoglycopeptides for the management of acute bacterial skin and skin structure infections.

Acute bacterial skin and skin structure infections (ABSSSIs) are some of the most commonly encountered infections worldwide. Hospitalizations as a result of ABSSSIs are associated with high mortality. This article discusses the role of oritavancin and dalbavancin, the two newest lipoglycopeptides, in the context of the other available I.V. infusion standard therapy options.

Rethinking urinary antibiotic breakpoints: analysis of urinary antibiotic concentrations to treat multidrug resistant organisms.

OBJECTIVE: The present study analyzed whether renally eliminated antibiotics achieve sufficient urinary concentrations based on their pharmacokinetic/pharmacodynamic principles to effectively eradicate organisms deemed resistant by automated susceptibility testing. RESULTS: Lower median minimum inhibitory concentrations against enterobacteriaceae were noted for ceftriaxone, cefepime, and doripenem when comparing Etest® to Vitek®. All Pseudomonas aeruginosa isolates were susceptible to cefepime, ciprofloxacin, and doripenem with both susceptibility methods, but higher median minimum inhibitory concentrations were observed with Etest®. Urine concentrations/time profiles were calculated for standard doses of ceftriaxone, cefepime, doripenem, and ciprofloxacin. The data presented in the current study suggests high urine concentrations of antibiotics may effectively eradicate bacteria which were determined to be resistant per in vitro susceptibility testing.

Systematic review of professional liability when prescribing ß-lactams for patients with a known penicillin allergy.

OBJECTIVE: To describe medical negligence and malpractice cases in which a patient with a known penicillin allergy received a ß-lactam and experienced an adverse reaction related to the ß-lactam. DATA SOURCES: Lexis-Nexus, Westlaw, and Google Scholar were searched. STUDY SELECTIONS: Medical negligence and malpractice cases were eligible for inclusion if they met the following criteria: the plaintiff had a known penicillin allergy, received a ß-lactam, and experienced an adverse event. All United States federal and state cases were eligible. RESULTS: Twenty-seven unique cases met the inclusion criteria. Eighteen cases involved the receipt of a penicillin-based antibiotic; of these cases with a known legal outcome, the plaintiff (patient or representative) prevailed or settled in 3 cases and defendants (providers) prevailed in 7 cases. Seven cases involved the receipt of a cephalosporin; of these cases with a known legal outcome, the plaintiff settled with physicians before trial in 1 case and defendants prevailed in 3 cases. Two cases involved the receipt of a carbapenem. Defendants prevailed in one case and the legal outcome of the other case is unknown. In cases in which the defense successfully moved for summary judgment, judges cited a lack of scientific evidence demonstrating a cephalosporin or carbapenem was contraindicated for a patient with a penicillin allergy. CONCLUSION: The cases with published legal outcomes found limited professional liability for clinicians who prescribed cephalosporins or carbapenems to a patient with a known penicillin allergy. These results may decrease the litigation fears of practitioners and risk managers within health care systems.

Risk Factors for Failure in Complicated Intraabdominal Infections.

OBJECTIVES: Approximately 20% of patients with complicated intraabdominal infections (cIAIs) fail therapy. The purpose of this study was to identify risk factors for clinical failure in patients with cIAIs. METHODS: International Classification of Diseases, Ninth Revision codes for cIAIs were obtained to identify patients. Adult patients who received at least 48 hours of intravenous antibiotics were included. Patients were chronologically matched for age, sex, and comorbidities. The primary outcome was clinical failure. Statistical analysis included bivariate tests and multivariable logistic regression. RESULTS: A total of 1405 patients were screened; 139 patients were included. The median (interquartile range) age and Charlson Comorbidity Index were 54 (37-62) years and 0 (0-1), respectively. Clinical failure was observed in 47 patients (34%), with 5 deaths (3.6%). Multivariate analysis of the unmatched population showed older age was protective (odds ratio [OR] 0.967, 95% confidence interval [CI] 0.944-0.991). In the matched population elevated serum creatinine (OR 2.2168, 95% CI 1.091-4.308) and increased time to source control (OR 1.015, 95% CI 1.000-1.030) were predictive of clinical failure. CONCLUSIONS: In a low comorbid cIAI population with and without surgical intervention, serum creatinine was an independent risk factor for clinical failure. In the matched case-control of patients, time to source-control procedure was an independent predictor of clinical failure.

Impact of an antifungal stewardship intervention on optimization of candidemia management.

BACKGROUND: Candidemia represents a leading cause of healthcare-associated bloodstream infections with significant morbidity and mortality. Previous studies have demonstrated that comprehensive care bundles improve candidemia management but are time-consuming. OBJECTIVE: To determine the impact of a one-time targeted candidemia intervention on time to initiation of adequate therapy compared to standard of care. METHODS: This Institutional Review Board (IRB)-approved, quasi-experiment evaluated a targeted candidemia intervention involving a single phone call to the primary team providing recommendations for care. Daily follow-up was provided by the infectious diseases (ID) consult service. Two time periods were evaluated: pre-intervention (01 August 2012 to 31 July 2014) and post-intervention (01 October 2014 to 30 September 2016). The primary endpoint was time to adequate antifungal therapy (TTx) in the business hours (6 a.m. to 6 p.m. Monday through Friday) population (BHP). Secondary endpoints were TTx in the total population as well as infection-related length of stay (IF-LOS) and compliance with quality indicators (composite endpoint: ophthalmology (OPH) consult, repeat cultures, and ⩾14 days of adequate therapy). RESULTS: In all, 117 patients were included (pre-intervention = 50, post-intervention = 67, BHP = 51). TTx decreased from 2 h 57 m to 2 h 12 m (p = 0.094) in the BHP and 3 h 30 m to 2 h 9 m (p = 0.021) in the total population. There was no difference in IF-LOS (p = 0.797), compliance with quality indicators (p = 0.343), or in-hospital mortality (p = 0.761). Post-intervention, there were more ID and OPH consults (p < 0.001). CONCLUSIONS: Our one-time candidemia intervention did not statistically decrease time to adequate therapy in the BHP, but did in the total population. No differences were found for other clinical outcomes, except increases in ID and OPH consults. Further studies are needed to examine whether a one-time intervention is non-inferior to a more comprehensive care bundle.

Time-Kill Analysis of Ceftolozane/Tazobactam Efficacy Against Mucoid Pseudomonas aeruginosa Strains from Cystic Fibrosis Patients.

INTRODUCTION: Mucoid Pseudomonas aeruginosa (MP) strains in cystic fibrosis (CF) patients are thought to initiate the chronic infection stage of CF and are associated with pulmonary function decline. OBJECTIVES: The purpose of this study was to assess the susceptibility of MP strains to ceftolozane/tazobactam and the efficacy of ceftolozane/tazobactam against MP strains compared with those for standard-of-care antipseudomonal antibiotics. METHODS: Ten clinical isolates of MP from CF patients were tested for susceptibility with Etest and time-kill analysis with ceftolozane/tazobactam compared with ceftazidime, cefepime, ciprofloxacin, meropenem, tobramycin, and polymyxin B. The physiologic free peak concentrations were used in the time-kill experiments. RESULTS: Ceftolozane/tazobactam minimum inhibitory concentrations ranged from 0.032 to 1.5 mg/L. In the time-kill analysis, the mean starting inoculum for the isolates was 6.29 ± 0.22 log10 colony forming units (CFU) per milliliter. On average, ceftolozane/tazobactam, cefepime, ciprofloxacin, meropenem, tobramycin, and polymyxin B all demonstrated bactericidal activity. With all isolates taken into account, polymyxin B, tobramycin, meropenem, and ceftolozane/tazobactam 3 g were the most potent, with reductions in inoculum of 5.07 ± 0.45, 4.58 ± 2.2, 4.76 ± 0.71, and 4.17 ± 0.94 log10 CFU/mL, respectively. Ceftolozane/tazobactam 1.5 g, cefepime, and ciprofloxacin reduced the starting inoculum by 3.74 ± 0.99, 3.42 ± 1.4, and 3.23 ± 2.0 log10 CFU/mL, respectively. Despite 90% susceptibility, ceftazidime was bactericidal against seven of ten strains, with an average reduction in starting inoculum of 2.91 ± 2.2 log10 CFU/mL. CONCLUSION: Ceftolozane/tazobactam activity against MP strains derived from CF patients was comparable to that of standard-of-care agents at both the 1.5-g dose and the 3-g dose. Further in vitro modeling and clinical trials are warranted.

Shifts in antimicrobial consumption and infection rates before and during a piperacillin/tazobactam shortage.

OBJECTIVES: Anti-infective shortages represent a growing threat to optimum management of infected patients and alter the institutional selective pressure against hospital-acquired infections (HAIs). The objective of this analysis was to assess the impact of a shortage of piperacillin/tazobactam (TZP) on overall antibacterial use and HAI rates at an academic institution. METHODS: Antimicrobial use and infection data were extracted from TheraDoc Clinical Surveillance Software (Premier, Inc.) for adult patients and were stratified as pre-shortage (October-December 2014) and post-shortage (February-April 2015). Paediatric and emergency department use were excluded. Antimicrobial use was reported as percent change and defined daily doses (DDD)/1000 patient-days (PD). Pre- and post-shortage vancomycin-resistant enterococci (VRE) and Clostridium difficile-associated diarrhoea (CDAD) rates were normalised to 1000 PD/month. RESULTS: Total use of target antimicrobials remained constant before and after TZP shortage (990.29 vs. 957.77). Total TZP use fell 95.2% (81.1 vs. 3.9). Total meropenem use rose 96.0% (42.3 vs. 82.9) after the shortage, driven by a 125.4% increase in use for non-ICU patients. Cefepime and ceftazidime use rose 97.9% (28.2 vs. 55.8) and 94.2% (1.6 vs 3.0), respectively. Cefepime use in non-ICU patients rose 223.2%. Fluoroquinolone consumption did not differ between periods. CDAD rates decreased (-21.8%), whilst VRE rates doubled during the shortage (0.6 vs. 1.3 infections/1000 PD/month). CONCLUSIONS: Whilst overall antimicrobial use appeared steady, the TZP shortage resulted in increased use of multiple other antimicrobials. The doubling of VRE rates is concerning and illustrates the need for increased antimicrobial stewardship vigilance and education in response to shifting prescribing patterns during shortages.

Mechanisms of fosfomycin resistance in carbapenem-resistant Enterobacter sp.

We report on fosfomycin susceptibility and mechanisms of resistance in clinical strains of blaKPC-positive Enterobacter sp. (n = 19). A total of 14 strains (74%) were susceptible to fosfomycin; 8 strains (42%) were positive for fosA and no strains were positive for FosA3 or FosC2. FosA presence does not appear to correlate with susceptibility.

Managing acute bacterial skin and skin structure infections: Focus on new lipoglycopeptides.

Acute bacterial skin and skin structure infections (ABSSSI) are some of the most commonly encountered infections worldwide. Hospitalizations as a result of ABSSSI are associated with high mortality. This article discusses the role of oritavancin and dalbavancin, two new lipoglycopeptides, in the context of the other I.V. available standard therapy options.

Comparison of susceptibility patterns using commercially available susceptibility testing methods performed on prevalent Candida spp.

The rising rates of invasive fungal infections caused by non-albicans Candida and the increasing emergence of antifungal resistance complicate the management of invasive candidiasis. Accurate and timely antifungal susceptibility testing is critical to targeting antifungal therapy. The purpose of this study was to compare commercially available susceptibility testing methods using prospectively collected Candida isolates. Susceptibility testing was performed on 74 Candida isolates collected from July 2014 to March 2015 using broth microdilution according to the Clinical and Laboratory Standards Institute method, Etest, Vitek 2 (YS-05) and Sensititre. Essential agreement and categorical agreement (CA) were assessed using the reference method. Of the 34 total blood isolates collected, Candida albicans comprised only 38 % (13) of the Candida spp. with Candidaglabrata being nearly as prevalent (29 %, 10). CA using Etest was 86 % for fluconazole, 72 % for caspofungin, 98 % for micafungin and 97 % for anidulafungin. Vitek 2 CA was 90 % for fluconazole and 98 % for caspofungin. Sensititre CA was 93 % for fluconazole, 98 % for caspofungin, 98 % for micafungin and 100 % for anidulafungin. Although our study tested a small population of Candida isolates, our results were variable by method. When implementing antifungal susceptibility testing, clinicians should be aware of the strengths and limitations of each testing method.

Therapeutic options for vancomycin-resistant enterococcal bacteremia.

Enterococcal infections are relatively common among hospitalized patients, likely because these organisms are commensals of human gastrointestinal and genitourinary tracts. With widespread usage of glycopeptides in both humans and livestock, vancomycin-resistant enterococci (VRE) quickly emerged. Bloodstream infections caused by these isolates are of significant concern with limited bactericidal options for treatment. Presently, daptomycin and linezolid serve as the mainstays of therapy, although resistance to both agents has been documented. Newer antimicrobials, specifically lipoglycopeptides and oxazolidinones, have been developed with in vitro activity against these organisms. However, no clinical data are available with their usage for VRE infections, let alone those in the bloodstream. This review focuses on the epidemiology, current and potential future therapeutic options for the treatment of VRE bacteremia.

Daptomycin-induced rhabdomyolysis and acute liver injury.

Daptomycin use is a known cause of rhabdomyolysis; its role in liver injury is less certain. We report a case of daptomycin-induced rhabdomyolysis with liver injury. This report indicates a role for liver function monitoring while receiving daptomycin, as well as the importance of promptly considering drug toxicities in acute and emergency care settings.

Cost-benefit and effectiveness analysis of rapid testing for MRSA carriage in a hospital setting.

A cost-effectiveness analysis was conducted comparing the polymerase chain reaction assay and traditional microbiological culture as screening tools for the identification of methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to the pediatric and surgical intensive care units (PICU and SICU) at a 722 bed academic medical center. In addition, the cost benefits of identification of colonized MRSA patients were determined. The cost-effectiveness analysis employed actual hospital and laboratory costs, not patient costs. The actual cost of the PCR assay was higher than the microbiological culture identification of MRSA ($602.95 versus $364.30 per positive carrier identified). However, this did not include the decreased turn-around time of PCR assays compared to traditional culture techniques. Patient costs were determined indirectly in the cost-benefit analysis of clinical outcome. There was a reduction in MRSA hospital-acquired infection (3.5 MRSA HAI/month without screening versus 0.6/month with screening by PCR). A cost-benefit analysis based on differences in length of stay suggests an associated savings in hospitalization costs: MRSA HAI with 29.5 day median LOS at $63,810 versus MRSA identified on admission with 6 day median LOS at $14,561, a difference of $49,249 per hospitalization. Although this pilot study was small and it is not possible to directly relate the cost-effectiveness and cost-benefit analysis due to confounding factors such as patient underlying morbidity and mortality, a reduction of 2.9 MRSA HAI/month associated with PCR screening suggests potential savings in hospitalization costs of $142,822 per month.

Artemether-lumefantrine: an option for malaria.

OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of artemether-lumefantrine for the treatment of Plasmodium falciparum malaria. DATA SOURCES: English-language articles indexed in PubMed (1947-November 2011) were identified, using the search terms artemether-lumefantrine, artemether-lumefantrine AND malaria, Coartem, and Coartem AND malaria. STUDY SELECTION AND DATA EXTRACTION: Available English-language articles were reviewed. In addition, the malaria treatment regimens recommended by region as provided by the World Health Organization and the treatment guidelines from the Centers for Disease Control and Prevention were reviewed. DATA SYNTHESIS: Artemether-lumefantrine is an artemisinin-derived combination antimalarial approved by the Food and Drug Administration in 2009 for the treatment of P. falciparum malaria. The dual mechanisms of action of artemether-lumefantrine provide rapid and sustained parasite clearance. In the reviewed studies, the polymerase chain reaction (PCR)-corrected 28-day cure rates of artemether-lumefantrine were noninferior to the most common comparators, including chloroquine, dapsone, and other artemisinin derivatives (86-100% vs 51-100%, respectively). PCR-corrected day-42 cure rates were 92-99.3% for artemether-lumefantrine versus 62-100% for the comparator groups. The major adverse effects (gastrointestinal and central nervous system) were mild to moderate in severity and did not require a change in therapy. Although adherence to artemether-lumefantrine has been described as a potential problem due to the complicated dosing schedule, studies have described clinical cure rates similar to those of other antimalarials. CONCLUSIONS: Artemether-lumefantrine is a safe and effective treatment for children and adults with P. falciparum malaria.