Ceftolozane/tazobactam for the treatment of bacteremia: a systematic literature review (SLR).

BACKGROUND: Bloodstream infections (BSIs), or bacteremia, are responsible for considerable disease burden. Increasing rates of antibiotic resistance and delays in selection of appropriate treatment lead to increased morbidity, mortality, and costs. Due to limitations of current standard treatments, especially for bacteremia caused by resistant pathogens, a systematic literature review (SLR) was conducted to understand the utilization of ceftolozane/tazobactam (C/T) in bacteremia. METHODS: Electronic database searches of EMBASE®, MEDLINE®, CCTR and Northern Lights, as well as hand searches of conference proceedings from the last two annual meetings (i.e., 2018, 2019) of the European Congress of Clinical Microbiological and Infectious Diseases (ECCMID) and the Infectious Diseases Society of America's annual meeting (IDWeek) were conducted. A total of 23 studies reporting on patients with bacteremia receiving C/T were included in the review. RESULTS: Most studies were observational (k = 20 studies), though few interventional studies were also identified (k = 3). Heterogeneity was ubiquitous with respect to source of bacteremia (i.e., primary or secondary), source of infection (for secondary bacteremia), pathogen type, antibiotic resistance, C/T dose, and outcome definitions. This heterogeneity, along with limited data, and small sample sizes (n = 1 to 31) made it difficult to draw any substantial conclusions, though overall results were favorable to C/T with respect to the outcomes of interest. Nineteen studies reported clinical cure or success (primary bacteremia: k = 6, reported range: 33.3% to 100%; secondary bacteremia: k = 8, 60% to 100%; mixed/unspecified bacteremia: k = 10, 50% to 91.7%). Eight studies reported microbiological cure or eradication rates (primary: k = 3, all reporting 100%; secondary: k = 4, 68% to 80%; mixed/unspecified: k = 5, 60% to 80%). Thirteen studies reported mortality (primary: k = 4, 0% to 14%; secondary: k = 7, 0% to 100%; or mixed/unspecified bacteremia: k = 7, 0% to 51.6%). One study each also reported composite clinical response, relapse, hospital re-admission, and hospital length of stay. CONCLUSIONS: Although the available evidence and observed trends for C/T in bacteremia should be interpreted with caution, the direction of effect would support the utilization of C/T for these difficult to treat infections. Future research should supplement the existing evidence by considering the impact of key treatment effect modifiers without contributing to the observed heterogeneity.

Incremental clinical and economic burden of suspected respiratory infections due to multi-drug-resistant Pseudomonas aeruginosa in the United States.

BACKGROUND: Multi-drug resistant (MDR) Pseudomonas aeruginosa can negatively affect patients and hospitals. AIM: To evaluate excess mortality and cost burden among patients hospitalized with suspected respiratory infections due to MDR P. aeruginosa vs patients with non-MDR P. aeruginosa in 78 United States (US) hospitals. METHODS: This study analyzed electronically captured microbiological and outcomes data of patients hospitalized with non-duplicate P. aeruginosa isolates from respiratory sources collected ≥3 days after admission to identify hospital-onset MDR or non-MDR P. aeruginosa per the Centers for Disease Control and Prevention definition. The risk of multi-drug resistance was estimated on mortality, length of stay (LOS), cost, operation gain/loss, and 30-day readmission. A sensitivity analysis was conducted utilizing a cohort with pharmacy data available. FINDINGS: Of 523 MDR and 1381 non-MDR P. aeruginosa cases, unadjusted mortality was 23.7% vs 18.0% and multi-variable-adjusted mortality was 20.0% (95% confidence interval (CI): 14.3-27.2%) vs 15.5% (95% CI: 11.2-20.9%; P=0.026), the average adjusted excess LOS was 6.7 days (P<0.001); excess cost per case was US$22,370 higher (P=0.002) and operational loss per case was US$10,661 (P=0.024) greater, and the multi-variable adjusted readmission rate was 16.2% (95% CI: 11.2-22.9%) vs 11.1% (95% CI: 7.8-15.6%; P=0.006). The sensitivity analysis yielded similar results. CONCLUSIONS: Compared with suspected infections due to non-MDR P. aeruginosa, patients with MDR P. aeruginosa had higher risk of mortality, readmission, and longer LOS, as well as US$20,000 incremental cost and >US$10,000 incremental net loss per case after controlling for patient and hospital characteristics.

Echinocandins: are they all the same?

The discovery of echinocandins, and their development and approval, was hailed as a significant addition to our antifungal armamentarium, previously predominated by polyenes and azoles. To date, three echinocandins (anidulafungin, caspofungin, and micafungin) have been approved by the U.S. Food and Drug Administration for the treatment of fungal infections. Since all three echinocandins target the fungal cell wall and share a similar structural chemical backbone, they are perceived to be identical. However, a scientific literature review shows distinct differences among the echinocandins in terms of in vitro activity, fungicidal activity, post-antifungal effect, paradoxical effect, and activity on biofilms. More investigation is warranted to determine if the observed differences among the echinocandins can translate to clinical advantages.

Acquisition of vancomycin-resistant enterococci during scheduled antimicrobial rotation in an intensive care unit.

Scheduled rotation of treatment of gram-negative antimicrobial agents has been associated with reduction of serious gram-negative infections. The impact of this practice on other nosocomial infections has not been assessed. The purpose of this study was to determine if scheduled antimicrobial rotation reduced rates of acquisition of enteric vancomycin-resistant enterococci (VRE) among 740 patients admitted to an intensive care unit (ICU). The preferred gram-negative agent was ceftazidime during rotation 1 and ciprofloxacin during rotation 2. Unadjusted VRE acquisition rates were 8.5 cases per 1000 ICU days and 11.7 cases per 1000 ICU days during rotations 1 and 2, respectively (P<.01). However, scheduled antimicrobial rotation of ceftazidime with ciprofloxacin had no effect on the risk of acquiring VRE in the ICU after adjustment for known risk factors. Independent predictors of acquisition of VRE were enteral feedings, higher colonization pressure, and increased duration of anaerobic therapy. Our findings can confirm no additional beneficial or adverse effect on VRE acquisition among ICU patients as a result of this practice.