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The emergence of Klebsiella pneumoniae carbapenemases (KPCs) producing bacteria has become a significant global public health challenge while the optimal treatment remains undefined. We performed a systematic review of published studies and reports of treatment outcomes of KPC infections using MEDLINE (2001–2011). Articles or cases were excluded if one of the following was fulfilled: no individual patient data provided, no treatment regimen specified, no treatment outcome specified, report of colonization, or greater than three antibiotics were used to treat the KPC infection. Data extracted included patient demographics, site of infection, organism, KPC subtype, antimicrobial therapy directed at KPC-infection, and treatment outcome. Statistical analysis was performed in an exploratory manner. A total of 38 articles comprising 105 cases were included in the analysis. The majority of infections were due to K. pneumoniae (89%). The most common site of infection was blood (52%), followed by respiratory (30%), and urine (10%). Forty-nine (47%) cases received monotherapy and 56 (53%) cases received combination therapy directed at the KPC-infection. Significantly more treatment failures were seen in cases that received monotherapy compared to cases who received combination therapy (49% vs 25%; p= 0.01). Respiratory infections were associated with higher rates of treatment failure with monotherapy compared to combination therapy (67% vs 29% p = 0.03). Polymyxin monotherapy was associated with higher treatment failure rates compared to polymyxin-based combination therapy (73% vs 29%; p = 0.02 ) ; similarly, higher treatment failure rates were seen with carbapenem monotherapy compared to carbapenem-based combination therapy (60% vs 26%; p = 0.03). Overall treatment failure rates were not significantly different in the three most common antibiotic-class combinations: polymyxin plus carbapenem, polymyxin plus tigecycline, polymyxin plus aminoglycoside (30%, 29%, and 25% respectively; p=0.6). In conclusion, combination therapy is recommended for the treatment of KPC infections; however, which combination of antimicrobial agents needs to be established in future prospective clinical trials.

Objective: To review the mechanism of action, mechanisms of resistance, in vitro activity, pharmacokinetics, pharmacodynamics, and clinical data for a novel aminoglycoside. Data sources: A PubMed search was performed from January 2006 to August 2019 using the following search terms: plazomicin and ACHN-490. Another search was conducted on clinicaltrials.gov for published clinical data. References from selected studies were also used to find additional literature. Study selection and data extraction: All English-language studies presenting original research (in vitro, in vivo, pharmacokinetic, and clinical) were evaluated. Data synthesis: Plazomicin has in vitro activity against several multi-drug-resistant organisms, including carbapenem-resistant Enterobacteriaceae. It was Food and Drug Administration (FDA) approved to treat complicated urinary tract infections (cUTIs), including acute pyelonephritis, following phase II and III trials compared with levofloxacin and meropenem, respectively. Despite the FDA Black Box Warning for aminoglycoside class effects (nephrotoxicity, ototoxicity, neuromuscular blockade, and pregnancy risk), it exhibited a favorable safety profile with the most common adverse effects being decreased renal function (3.7%), diarrhea (2.3%), hypertension (2.3%), headache (1.3%), nausea (1.3%), vomiting (1.3%), and hypotension (1.0%) in the largest in-human trial. Relevance to patient care and clinical practice: Plazomicin will likely be used in the treatment of multi-drug-resistant cUTIs or in combination to treat serious carbapenem-resistant Enterobacteriaceae infections. Conclusions: Plazomicin appears poised to help fill the need for new agents to treat infections caused by multi-drug-resistant Enterobacteriaceae.

We sought to compare patient outcomes between carbapenem-resistant (CRE) and carbapenem-susceptible (CSE) infections at our academic medical center. We conducted a retrospective cohort study of adult patients with a positive culture of E. coli, E. cloacae, K. aerogenes, K. oxytoca, and/or K. pneumoniae admitted at UK HealthCare (January 1, 2010-December 31, 2019). Based on the type of pathogen on the date of the first culture (index date), patients were included in the CRE (i.e., exposed) group, or the CSE (comparator) group. Exclusion criteria were age < 18 years old, pregnancy, endocarditis, osteomyelitis, necrotizing fasciitis, or cystic fibrosis. We evaluated the impact of CRE vs CSE on a composite outcome of 30-day of all-cause mortality or discharge to hospice using Kaplan-Meier survival curves and Cox proportional hazard regression with inverse probability of treatment weights (IPTW). Of 17,839 hospitalized patients, 128 and 6,953 patients were included in the CRE and CSE groups, respectively. Baseline differences existed in sex-assigned-at-birth, admission source, time-to-index culture, and infection type/severity. Most CRE index cultures observed (76%) only exhibited resistance to ertapenem. IPTW-adjusted HR [95% CI] of composite outcome was 0.99 [0.65, 1.51] after 30 days. Follow-up analysis in patients with carbapenem-non-susceptible bloodstream infections on index yielded an HR of 1.38 [0.85, 2.24]. Risk of composite outcome was not estimated to differ between patients with CRE and CSE in the overall analysis. Although follow-up analysis identified an increased risk, we cannot statistically distinguish this from a null effect.

Currently, the Infectious Diseases Society of America (IDSA) Guidelines for Uncomplicated Urinary Tract Infections (UTIs) recommend a 3 to 7-day antibiotic course of oral beta-lactam agents when other recommended agents are not feasible. In recent years, studies have demonstrated efficacy in shorter courses of antimicrobial therapy for acute uncomplicated cystitis compared with longer courses, but there is limited data regarding intravenous beta-lactams for acute uncomplicated cystitis. This single-center, retrospective, non-inferiority cohort study included adult patients admitted to University of Kentucky Albert B. Chandler Medical Center or Good Samaritan Hospital with acute uncomplicated cystitis. The primary outcome assessed was treatment failure, defined as the need for retreatment with additional antibiotic therapy within 30 days of antibiotic completion. Secondary outcomes include incidence of C. difficile infection within 30 days of antibiotic therapy, hospital readmission, and outpatient telephone encounters within 30 days of discharge. Patients were divided into the short course (those receiving three days or less of beta-lactam antibiotics and at least 1 day was IV) or the long course (those receiving four or more days of beta lactam antibiotics). Overall, 52 patients met the criteria to be included in the final study, with 33 in the short course beta-lactam group and 19 in the long-course beta-lactam group. Failure rates between short and long course were 15.2% and 15.8% respectively (p=1.000). Ceftriaxone was the most commonly utilized antibiotic in both groups. The median total antibiotic duration between the long and short groups was 3 and 6 days respectively (p<0.001). In hospitalized patients warranting initial IV therapy for acute uncomplicated cystitis, a 3-day total of beta-lactam therapy, with transition to oral, should be considered.

Background: Asymptomatic bacteriuria (ASB) is often overtreated, risking patient harm through unnecessary antimicrobial use and fostering antimicrobial resistance. Despite this, patients continue to be treated for ASB requiring targeted intervention for antimicrobial stewardship teams across health systems. Objectives: This study assessed the impact of a multistep urinary tract infection (UTI)-focused stewardship initiative by comparing the incidence of asymptomatic urinary presentation (AUP) treatment before and after implementation. Design: Retrospective cohort study. Methods: Patients ⩾18 years at University of Kentucky HealthCare who received antimicrobial therapy with a urinalysis (UA) and/or urine culture (UCx) collected for a presumed UTI between January 2023 and March 2023 (pre-implementation) and January 2024 and March 2024 (post-implementation) were included in the study. Our primary outcome was to compare the frequency of AUP treatment between groups. Results: Overall, 288 patients were included in the study, with 144 patients in both the pre- and post-implementation groups. Treatment of AUPs significantly decreased by 12% after initiative implementation (47% pre-implementation vs 35% post-implementation, p = 0.042). Additionally, we observed a significant difference in guideline-adherent management between the two groups (29% pre-implementation vs 44% post-implementation, p = 0.007). Patients were more likely to receive guideline-adherent UTI treatment durations (38% vs 53%, p = 0.009) and guideline-adherent definitive antibiotics (18% vs 35%, p < 0.001) post-implementation compared to pre-implementation. Conclusion: Our stewardship initiative resulted in reduced treatment of AUPs and improved adherence to UTI management guidelines. Overall, a multifaceted stewardship initiative is a successful intervention to decrease the treatment of AUPs and unnecessary antibiotic utilization. However, additional frontline stewardship initiatives are likely warranted to decrease the unnecessary ordering of UAs.

We assessed breakpoint changes of 13,101 Enterobacterales and Pseudomonas aeruginosa isolates from the past decade. All β-lactams and fluoroquinolones demonstrated decreased susceptibilities following breakpoint changes. Enterobacter cloacae experienced the largest average decrease in susceptibility amongst the Enterobacterales at 5.3% and P. aeruginosa experienced an average decrease in susceptibility of 9.3%.

Vancomycin therapy is associated with an increased risk of acute kidney injury (AKI). Previous studies suggest that area under the curve (AUC) monitoring reduces the risk of AKI, but literature is lacking to support this in patients receiving longer durations of vancomycin therapy. Retrospective cohort study. Patients ≥18 years old, admitted between August 2015 and July 2017 or October 2017 and September 2019, and received at least 14 days of intravenous (IV) vancomycin therapy were included in the study. Our primary outcome was the incidence of AKI between trough monitoring and AUC monitoring groups using Kidney Disease Improving Global Outcomes criteria. Secondary outcomes included inpatient mortality, median inpatient length of stay, and median intensive care unit length of stay. Overall, 582 patients were included in the study, with 318 patients included in the trough monitoring group and 264 included in the AUC monitoring group. The median duration of vancomycin therapy was 23 days (interquartile range, 16-39). Patients within the trough monitoring group had a higher incidence of AKI compared to the AUC monitoring group (45.6% vs 28.4%, < 0.001). Furthermore, logistic regression analysis showed that AUC monitoring was associated with a 54% lower incidence of AKI (OR 0.46, 95% CI [0.31-0.69]). All-cause inpatient mortality was numerically higher in the trough monitoring group (12.9% vs 8.3%, = 0.078). In patients who received at least 14 days of IV vancomycin therapy, AUC monitoring was associated with a lower incidence of AKI.

The objective of this study was to determine antibiotic appropriateness based on Loeb minimum criteria (LMC) in patients with and without altered mental status (AMS). Retrospective, quasi-experimental study assessing pooled data from 3 periods pertaining to the implementation of a UTI management guideline. Academic medical center in Lexington, Kentucky. Adult patients aged ≥18 years with a collected urinalysis receiving antimicrobial therapy for a UTI indication. Appropriateness of UTI management was assessed in patients prior to an institutional UTI guideline, after guideline introduction and education, and after implementation of a prospective audit-and-feedback stewardship intervention from September to November 2017-2019. Patient data were pooled and compared between patients noted to have AMS versus those with classic UTI symptoms. Loeb minimum criteria were used to determine whether UTI diagnosis and treatment was warranted. In total, 600 patients were included in the study. AMS was one of the most common indications for testing across the 3 periods (19%-30.5%). Among those with AMS, 25 patients (16.7%) met LMC, significantly less than the 151 points (33.6%) without AMS ( < .001). Patients with AMS are prescribed antibiotic therapy without symptoms indicative of UTI at a higher rate than those without AMS, according to LMC. Further antimicrobial stewardship efforts should focus on prescriber education and development of clearly defined criteria for patients with and without AMS.

Objective: This study evaluated the survival benefit of US community-acquired pneumonia (CAP) practice guidelines in the intensive care unit (ICU) setting. Methods: We conducted a retrospective cohort study of adult patients with CAP who were admitted to 5 community hospital ICUs between November 1, 1999, and April 30, 2000. The guidelines for antibiotic prescriptions were the 2007 Infectious Diseases Society of America/American Thoracic Society guidelines. Guideline-concordant antimicrobial therapy was defined as a β-lactam plus fluoroquinolone or macrolide, antipseudomonal β-lactam plus fluoroquinolone, or antipseudomonal β-lactam plus aminoglycoside plus fluoroquinolone or macrolide. Patients with a documented β-lactam allergy were considered to have received guideline-concordant therapy if they received a fluoroquinolone with or without clindamycin, or aztreonam plus fluoroquinolone with or without aminoglycoside. All other antibiotic regimens were considered to be guideline discordant. Time to clinical stability, time to oral antibiotics, length of hospital stay, and in-hospital mortality were evaluated with regression models that included the outcome as the dependent variable, guidelineconcordant antibiotic therapy as the independent variable, and the Pneumonia Severity Index (PSI) score and facility as covariates. Results: The median age of the 129 patients included in the study was 71 years (interquartile range, 60–79 years). Sixty-two of 129 patients (48%) were male. Comorbidities included liver dysfunction (7 patients [5%]), heart failure (62 [48%]), renal dysfunction (39 [30%]), cerebrovascular disease (21 [16%]), and cancer (14 [11%]). The median (25th–75th percentile) PSI score was 119 (98–142), and overall mortality was 19% (25 patients). Patient demographics were similar between groups. Fifty-three patients (41%) received guideline-endorsed therapies. Guideline-discordant therapy was associated with an increase in inpatient mortality (25% vs 11%; odds ratio = 2.99 [95% CI, 1.08–9.54]). Receipt of guideline-concordant antibiotics was not associated with reductions in time to clinical stability, time to oral antibiotics, or length of hospital stay when patients who died were excluded from the analysis. Conclusion: Guideline-concordant empiric antibiotic therapy was associated with improved survival among these patients with CAP who were admitted to 5 ICUs.