A comparison of strategies for identifying patients at risk for carbapenem-resistant or extended ß-lactam-resistant Pseudomonas aeruginosa.

OBJECTIVES: To assess risk factors for carbapenem-resistant Pseudomonas aeruginosa (CR) and extended-ß-lactam-resistant P. aeruginosa (EBR) infection/colonization, and to develop and compare tools for predicting isolation of CR and EBR from clinical cultures. METHODS: This retrospective study analysed hospitalized patients with positive P. aeruginosa cultures between 2015 and 2021. Two case-control analyses were performed to identify risk factors and develop scoring tools for distinguishing patients with CR versus carbapenem-susceptible (CS) P. aeruginosa and EBR versus CS P. aeruginosa. The performance of institutionally derived scores, externally derived scores and the presence/absence of key risk factors to predict CR and EBR were then compared. RESULTS: A total of 2379 patients were included. Of these, 8.3% had a positive culture for CR, 5.0% for EBR and 86.7% for CS P. aeruginosa. There was substantial overlap in risk factors for CR and EBR. Institutional risk scores demonstrated modestly higher area under the ROC curve values than external scores for predicting CR (0.67 versus 0.58) and EBR (0.76 versus 0.70). Assessing the presence/absence of ≥1 of the two strongest predictors (prior carbapenem use or CR isolation within 90 days) was slightly inferior to scoring tools for predicting CR, and comparable for predicting EBR. CONCLUSIONS: Clinicians concerned about CR in P. aeruginosa should consider the likelihood of EBR when making treatment decisions. A simple approach of assessing recent history of CR isolation or carbapenem usage performed similarly to more complex scoring tools and offers a more pragmatic way of identifying patients who require coverage for resistant P. aeruginosa.

Prescribing of Outpatient Antibiotics Commonly Used for Respiratory Infections Among Adults Before and During the Coronavirus Disease 2019 Pandemic in Brazil.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic may have impacted outpatient antibiotic prescribing in low- and middle-income countries such as Brazil. However, outpatient antibiotic prescribing in Brazil, particularly at the prescription level, is not well-described. METHODS: We used the IQVIA MIDAS database to characterize changes in prescribing rates of antibiotics commonly prescribed for respiratory infections (azithromycin, amoxicillin-clavulanate, levofloxacin/moxifloxacin, cephalexin, and ceftriaxone) among adults in Brazil overall and stratified by age and sex, comparing prepandemic (January 2019-March 2020) and pandemic periods (April 2020-December 2021) using uni- and multivariate Poisson regression models. The most common prescribing provider specialties for these antibiotics were also identified. RESULTS: In the pandemic period compared to the prepandemic period, outpatient azithromycin prescribing rates increased across all age-sex groups (incidence rate ratio [IRR] range, 1.474-3.619), with the greatest increase observed in males aged 65-74 years; meanwhile, prescribing rates for amoxicillin-clavulanate and respiratory fluoroquinolones mostly decreased, and changes in cephalosporin prescribing rates varied across age-sex groups (IRR range, 0.134-1.910). For all antibiotics, the interaction of age and sex with the pandemic in multivariable models was an independent predictor of prescribing changes comparing the pandemic versus prepandemic periods. General practitioners and gynecologists accounted for the majority of increases in azithromycin and ceftriaxone prescribing during the pandemic period. CONCLUSIONS: Substantial increases in outpatient prescribing rates for azithromycin and ceftriaxone were observed in Brazil during the pandemic with prescribing rates being disproportionally different by age and sex. General practitioners and gynecologists were the most common prescribers of azithromycin and ceftriaxone during the pandemic, identifying them as potential specialties for antimicrobial stewardship interventions.

Trends in Inpatient Antibiotic Use Among Adults Hospitalized During the Coronavirus Disease 2019 Pandemic in Argentina, Brazil, and Chile, 2018-2021.

BACKGROUND: High rates of antibiotic use (AU) among inpatients with coronavirus disease 2019 (COVID-19) despite low rates of bacterial coinfection and secondary infection have been reported. We evaluated the impact of the COVID-19 pandemic on AU in healthcare facilities (HCFs) in South America. METHODS: We conducted an ecologic evaluation of AU in inpatient adult acute care wards in 2 HCFs each in Argentina, Brazil, and Chile. The AU rates for intravenous antibiotics were calculated as the defined daily dose per 1000 patient-days, using pharmacy dispensing records and hospitalization data from March 2018-February 2020 (prepandemic) and March 2020-February 2021 (pandemic). Differences in median AU were compared between the prepandemic and pandemic periods, using the Wilcoxon rank sum test to determine significance. Interrupted time series analysis was used to analyze changes in AU during the COVID-19 pandemic. RESULTS: Compared with the prepandemic period, the median difference in AU rates for all antibiotics combined increased in 4 of 6 HCFs (percentage change, 6.7%-35.1%; P < .05). In the interrupted time series models, 5 of 6 HCFs had significant increases in use of all antibiotics combined immediately at the onset of the pandemic (immediate effect estimate range, 15.4-268), but only 1 of these 5 HCFs experienced a sustained increase over time (change in slope, +8.13; P < .01). The effect of the pandemic onset varied by antibiotic group and HCF. CONCLUSIONS: Substantial increases in AU were observed at the beginning of the COVID-19 pandemic, suggesting the need to maintain or strengthen antibiotic stewardship activities as part of pandemic or emergency HCF responses.

Antibiotic Consumption During the Coronavirus Disease 2019 Pandemic and Emergence of Carbapenemase-Producing Klebsiella pneumoniae Lineages Among Inpatients in a Chilean Hospital: A Time-Series Study and Phylogenomic Analysis.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) on antimicrobial use (AU) and resistance has not been well evaluated in South America. These data are critical to inform national policies and clinical care. METHODS: At a tertiary hospital in Santiago, Chile, between 2018 and 2022, subdivided into pre- (3/2018-2/2020) and post-COVID-19 onset (3/2020-2/2022), we evaluated intravenous AU and frequency of carbapenem-resistant Enterobacterales (CRE). We grouped monthly AU (defined daily doses [DDD]/1000 patient-days) into broad-spectrum ß-lactams, carbapenems, and colistin and used interrupted time-series analysis to compare AU during pre- and post-pandemic onset. We studied the frequency of carbapenemase-producing (CP) CRE and performed whole-genome sequencing analyses of all carbapenem-resistant (CR) Klebsiella pneumoniae (CRKpn) isolates collected during the study period. RESULTS: Compared with pre-pandemic, AU (DDD/1000 patient-days) significantly increased after the pandemic onset, from 78.1 to 142.5 (P < .001), 50.9 to 110.1 (P < .001), and 4.1 to 13.3 (P < .001) for broad-spectrum ß-lactams, carbapenems, and colistin, respectively. The frequency of CP-CRE increased from 12.8% pre-COVID-19 to 51.9% after pandemic onset (P < .001). The most frequent CRE species in both periods was CRKpn (79.5% and 76.5%, respectively). The expansion of CP-CRE harboring blaNDM was particularly noticeable, increasing from 40% (n = 4/10) before to 73.6% (n = 39/53) after pandemic onset (P < .001). Our phylogenomic analyses revealed the emergence of two distinct genomic lineages of CP-CRKpn: ST45, harboring blaNDM, and ST1161, which carried blaKPC. CONCLUSIONS: AU and the frequency of CP-CRE increased after COVID-19 onset. The increase in CP-CRKpn was driven by the emergence of novel genomic lineages. Our observations highlight the need to strengthen infection prevention and control and antimicrobial stewardship efforts.

Deep Dive Into Gaps and Barriers to Implementation of Antimicrobial Stewardship Programs in Hospitals in Latin America.

BACKGROUND: Antimicrobial resistance has worsened in Latin America. There is an urgent need to understand the development of antimicrobial stewardship programs (ASPs) and the barriers to implementing effective ASPs in light of limited national action plans or policies to promote ASPs in the region. METHODS: We performed a descriptive mixed-methods study of ASPs in 5 Latin American countries in March-July 2022. An electronic questionnaire with an associated scoring system (hospital ASP self-assessment) was used, and ASP development was classified based on the scores (inadequate, 0-25; basic, 26-50; intermediate, 51-75; or advanced, 76-100). Interviews among healthcare workers (HCWs) involved in antimicrobial stewardship (AS) inquired about behavioral and organizational factors that influence AS activities. Interview data were coded into themes. Results from the ASP self-assessment and interviews were integrated to create an explanatory framework. RESULTS: Twenty hospitals completed the self-assessment, and 46 AS stakeholders from these hospitals were interviewed. ASP development was inadequate/basic in 35% of hospitals, intermediate in 50%, and advanced in 15%. For-profit hospitals had higher scores than not-for-profit hospitals. Interview data validated the self-assessment findings and provided further insight into ASP implementation challenges, which included limited formal hospital leadership support, inadequate staffing and tools to perform AS work more efficiently, limited awareness of AS principles by HCWs, and limited training opportunities. CONCLUSIONS: We identified several barriers to ASP development in Latin America, suggesting the need to create accurate business cases for ASPs to obtain the necessary funding for their effective implementation and sustainability.

Acute kidney injury in cystic fibrosis patients treated with intravenous colistimethate sodium or tobramycin.

OBJECTIVES: Colistimethate sodium and tobramycin are important systemic antibiotics for treatment of cystic fibrosis (CF) pulmonary exacerbations but can induce acute kidney injury (AKI). We characterize the rate of AKI in CF patients treated with systemic colistimethate sodium compared with tobramycin. METHODS: This single-centre, retrospective cohort study included hospitalized CF patients treated with IV colistimethate sodium or tobramycin. The primary outcome was AKI defined using the RIFLE criteria. Multivariate logistic regression using a mixed model was performed to identify variables that were independently associated with AKI. RESULTS: Overall, 156 patients representing 507 care encounters were included. The OR of AKI was not increased with IV colistimethate sodium relative to IV tobramycin after adjusting for other potential predictor variables (aOR 1.00; 95% CI 0.16-6.03). The frequency of AKI was 9.5% across all encounters, 6.9% with IV colistimethate sodium and 9.9% with IV tobramycin, with RIFLE category R (risk) being the most common stage, accounting for 4.2% of encounters with IV colistimethate sodium and 9.2% with IV tobramycin. The concomitant use of another nephrotoxin (aOR 2.51; 95% CI 1.27-4.95) or the combination of vancomycin and piperacillin/tazobactam (aOR 5.95; 95% CI 2.05-17.3) were both associated with increased odds of AKI. CONCLUSIONS: Systemic treatment with colistimethate sodium or tobramycin in the CF patient population is associated with a similar rate of nephrotoxicity. However, clinicians should be mindful of the increased risk for AKI in patients treated with either IV colistimethate sodium or IV tobramycin when used concurrently with other nephrotoxic agents, particularly the combination of vancomycin and piperacillin/tazobactam.

Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment. METHODS: We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW). RESULTS: 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33-.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36-.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia. CONCLUSIONS: In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.

Evaluation of targeted versus universal prophylaxis for the prevention of invasive fungal infections following lung transplantation.

BACKGROUND: Antifungal prophylaxis to prevent invasive fungal infections (IFI) is widely used following lung transplantation, but the optimal strategy remains unclear. We compared universal with targeted antifungal prophylaxis for effectiveness in preventing IFI. METHODS: Adult patients who underwent lung transplantation at the University of Michigan from /1 July 2014-31 December 2017 were studied for 18 months post-transplant. Universal prophylaxis consisted of itraconazole with or without inhaled liposomal amphotericin B. Using specific criteria, targeted prophylaxis was given with voriconazole for patients at risk for invasive pulmonary aspergillosis (IPA) and with fluconazole or micafungin for patients at risk for invasive candidiasis. Risk factors, occurrence of proven/probable IFI, and mortality were analyzed for the two prophylaxis cohorts. RESULTS: Of 105 lung transplant recipients, 84 (80%) received a double lung transplant, and 38 (36%) of patients underwent transplant for pulmonary fibrosis. Fifty-nine (56%) patients received universal antifungal prophylaxis, and 46 (44%), targeted antifungal prophylaxis. Among 20 proven/probable IFI, there were 14 IPA, 4 invasive candidiasis, 1 cryptococcosis, and 1 deep sternal mold infection. Six (10%) IFI occurred in the universal prophylaxis cohort and 14 (30%) in the targeted prophylaxis cohort. Five of 6 (83%) IFI in the universal prophylaxis cohort, compared with 9/14 (64%) in the targeted prophylaxis cohort, were IPA Candida infections occurred only in the targeted prophylaxis cohort. The development of IFI was more likely in the targeted prophylaxis cohort than the universal prophylaxis cohort, HR = 4.32 (1.51-12.38), P = .0064. CONCLUSIONS: Universal antifungal prophylaxis appears to be more effective than targeted antifungal prophylaxis for prevention of IFI after lung transplant.

Utility of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening in patients with acute myeloid leukemia (AML).

BACKGROUND: Current literature has demonstrated the utility of the MRSA nasal screen as a de-escalation tool to decrease unnecessary anti-MRSA antibiotic therapy. However, data on the applicability of this test in patients with hematologic malignancy is lacking. METHODS: This is a single-center, retrospective cohort study of patients with acute myeloid leukemia (AML) with or without a history of hematopoietic cell transplant (HCT), with pneumonia and MRSA nasal screening with respiratory cultures obtained. The primary outcome was to determine the negative predictive value (NPV) of the MRSA nasal screen for MRSA pneumonia. Secondary outcomes included sensitivity, specificity, positive predictive value (PPV) of the MRSA nasal screen and prevalence of MRSA pneumonia. RESULTS: Of 98 patients with AML and pneumonia, the prevalence of MRSA pneumonia was 4.1% with confirmed positive MRSA respiratory cultures observed in 4 patient cases. In patients with confirmed MRSA pneumonia, 3 had positive MRSA nasal screens while 1 had a false negative result, possibly due to a long lag time (21 days) between MRSA nasal screen and pneumonia diagnosis. Overall, the MRSA nasal screen demonstrated 75% sensitivity and 100% specificity, with a PPV of 100% and a NPV of 98.9%. CONCLUSIONS: Given the low prevalence, empiric use of anti-MRSA therapy in those AML and HCT patients with pneumonia may not be warranted in clinically stable patients. For patients in whom empiric anti-MRSA antibiotics are initiated, nasal screening for MRSA may be utilized to de-escalate anti-MRSA antibiotics in patients with AML with or without HCT.

Clinical Implications of Microbiologic Treatment Failure in the Setting of Clinical Cure of Bacterial Pneumonia.

BACKGROUND: Microbiologic cure is a common outcome in pneumonia clinical trials, but its clinical significance is incompletely understood. METHODS: We conducted a retrospective cohort study of adult patients hospitalized with bacterial pneumonia who achieved clinical cure. Rates of recurrent pneumonia and death were compared between patients with persistent growth of the index pathogen at the time of clinical cure (microbiologic failure) and those with pathogen eradication (microbiologic cure). RESULTS: Among 441 patients, 237 experienced microbiologic cure and 204 experienced microbiologic failure. Prevalences of comorbidities, ventilator dependence, and severity of acute illness were similar between groups. Patients with microbiologic failure experienced significantly higher rates of recurrent pneumonia or death following clinical cure than patients with microbiologic cure, controlling for comorbid conditions, severity of acute illness, appropriateness of empiric antibiotics, intensive care unit placement, tracheostomy dependence, and immunocompromised status (90-day multivariable adjusted odds ratio [OR], 1.56; 95% confidence interval [CI], 1.04-2.35). This association was observed among patients with pneumonias caused by Staphylococcus aureus (90-day multivariable adjusted OR, 3.69; 95% CI, 1.73-7.90). A trend was observed among pneumonias caused by nonfermenting gram-negative bacilli, but not Enterobacteriaceae or other pathogens. CONCLUSIONS: Microbiologic treatment failure was independently associated with recurrent pneumonia or death among patients with bacterial pneumonia following clinical cure. Microbiologic cure merits further study as a metric to guide therapeutic interventions for patients with bacterial pneumonia.

Ceftolozane/Tazobactam vs Polymyxin or Aminoglycoside-based Regimens for the Treatment of Drug-resistant Pseudomonas aeruginosa.

BACKGROUND: Ceftolozane/tazobactam is a novel cephalosporin/beta-lactamase inhibitor combination that often retains activity against resistant Pseudomonas aeruginosa. The comparative safety and efficacy vs polymyxins or aminoglycosides in this setting remains unknown. METHODS: A retrospective, multicenter, observational cohort study was performed. Patients who received ceftolozane/tazobactam were compared with those treated with either polymyxin or aminoglycoside-based regimens for infections due to drug-resistant P. aeruginosa. Multivariate logistic regression was performed controlling for factors associated with treatment to assess the independent impact of ceftolozane/tazobactam on clinical cure, acute kidney injury (AKI), and in-hospital mortality. RESULTS: A total of 200 patients were included (100 in each treatment arm). The cohort represented an ill population with 69% in the intensive care unit, 63% mechanically ventilated, and 42% in severe sepsis or septic shock at infection onset. The most common infection type was ventilator-associated pneumonia (52%); 7% of patients were bacteremic. Combination therapy was more commonly used in polymyxin/aminoglycoside patients than those who received ceftolozane/tazobactam (72% vs 15%, P < .001). After adjusting for differences between groups, receipt of ceftolozane/tazobactam was independently associated with clinical cure (adjusted odds ratio [aOR], 2.63; 95% confidence interval [CI], 1.31-5.30) and protective against AKI (aOR, 0.08; 95% CI, 0.03-0.22). There was no difference in in-hospital mortality. The number needed to treat for a clinical cure with ceftolozane/tazobactam was 5, and the number needed to harm with AKI with a polymyxin/aminoglycoside was 4. CONCLUSIONS: These data support the preferential use of ceftolozane/tazobactam over polymyxins or aminoglycosides for drug-resistant P. aeruginosa infections.

Impact of an Antimicrobial Stewardship Intervention on Within- and Between-Patient Daptomycin Resistance Evolution in Vancomycin-Resistant Enterococcus faecium.

Vancomycin-resistant Enterococcus (VRE) is a leading cause of hospital-acquired infection, with limited treatment options. Resistance to one of the few remaining drugs, daptomycin, is a growing clinical problem and has previously been described in this hospital. In response to increasing resistance, an antimicrobial stewardship intervention was implemented to reduce hospital-wide use of daptomycin. To assess the impact of the intervention, daptomycin prescribing patterns and clinically reported culture results from vancomycin-resistant Enterococcus faecium (VREfm) bloodstream infections (BSIs) from 2011 through 2017 were retrospectively extracted and the impact of the intervention was estimated using interrupted time series analysis (ITS). We corrected for a change in MIC determination methodology by retesting 262 isolates using Etest and broth microdilution. Hospital-wide and within-patient resistance patterns of corrected daptomycin MICs are reported. Our data show that daptomycin prescriptions decreased from an average of 287 days of therapy/month preintervention to 151 days of therapy/month postintervention. Concurrently, the proportion of patients experiencing an increase in daptomycin MIC during an infection declined from 14.6% (7/48 patients) in 2014 to 1.9% (1/54 patients) in 2017. Hospital-wide resistance to daptomycin also decreased in the postintervention period, but this was not maintained. This study shows that an antimicrobial stewardship-guided intervention reduced daptomycin use and improved individual level outcomes but had only transient impact on the hospital-level trend.

Survival in Patients with Candida glabrata Bloodstream Infection Is Associated with Fluconazole Dose.

Robust pharmacodynamic indices that align fluconazole dose or exposure with outcomes in invasive candidiasis due to Candida glabrata remain elusive. The purpose of this retrospective multicenter study was to evaluate a cohort of 127 patients with C. glabrata fungemia treated with fluconazole, using adjusted analyses to identify risk factors for 28-day death. No significant correlations were found between fluconazole area under the curve (AUC), AUC/MIC ratio, or MIC and survival. In multivariate logistic regression analyses, however, higher average fluconazole dose (odds ratio [OR], 1.006 [95% confidence interval [CI], 1.001 to 1.010]; P = 0.008), average fluconazole dose of ≥400 mg (OR, 3.965 [95% CI, 1.509 to 10.418]; P = 0.005), and higher fluconazole dose on day 1 of therapy (OR, 1.007 [95% CI, 1.002 to 1.011]; P = 0.002) were found to be independent predictors of 28-day survival. Additionally, the presence of a central venous catheter at the time of infection was found to be a significant risk factor for death. In conclusion, we found fluconazole dose to be an independent predictor of 28-day survival for patients with C. glabrata fungemia, with doses of ≥400 mg/day being associated with 28-day survival rates approaching 90%. These data indicate the use and efficacy of fluconazole in the treatment of this serious infection. Aggressive dosing appears to be necessary when fluconazole is used for the treatment of C. glabrata fungemia, irrespective of MIC.

Are In Vitro Susceptibilities to Azole Antifungals Predictive of Clinical Outcome in the Treatment of Candidemia?

The purpose of this review is to critically analyze published data evaluating the impact of azole pharmacokinetic and pharmacodynamic parameters, MICs, and Candida species on clinical outcomes in patients with candidemia. Clinical breakpoints (CBPs) for fluconazole and voriconazole, which are used to determine susceptibility, have been defined by the Clinical and Laboratory Standards Institute (CLSI) for Candida species. Studies evaluating the relationship between treatment efficacy and in vitro susceptibility, as well as the pharmacodynamic targets, have been conducted in patients treated with fluconazole for candidemia; however, for species other than Candida albicans and Candida glabrata, and for other forms of invasive candidiasis, data remain limited and randomized trials are not available. Limited data evaluating these relationships with voriconazole are available. While pharmacodynamic targets for posaconazole and isavuconazole have been proposed based upon studies conducted in murine models, CBPs have not been established by CLSI. Fluconazole remains an important antifungal agent for the treatment of candidemia, and data supporting its use based on in vitro susceptibility are growing, particularly for C. albicans and C. glabrata Further investigation is needed to establish the roles of voriconazole, posaconazole, and isavuconazole in the treatment of candidemia and for all agents in the treatment of other forms of invasive candidiasis.

A multicentre stewardship initiative to decrease excessive duration of antibiotic therapy for the treatment of community-acquired pneumonia.

Background: The increased emphasis on pneumonia-related performance measures and patient outcomes has led hospitals to implement multifaceted approaches to quickly identify patients with community-acquired pneumonia (CAP), start timely therapy and reduce readmission. However, there has been minimal focus on duration of therapy (DOT) and patients often receive prolonged antibiotic courses. The IDSA and American Thoracic Society (IDSA/ATS) CAP guidelines recommend 5 days of therapy for clinically stable patients that quickly defervesce and stewardship teams are well positioned to influence prescribing practices. Objectives: Determine the impact of a prospective stewardship intervention on total antibiotic DOT and associated clinical outcomes in hospitalized patients with CAP. Methods: This multicentre, quasi-experimental study evaluated three concurrent interventions over a 6 month period to promote appropriate DOT. All centres updated institutional CAP guidelines to promote IDSA/ATS-concordant DOT, provided education and conducted daily audit and feedback with intervention to provide patient-specific DOT recommendations. Results: A total of 600 patients with CAP were included (307 in the historical control group and 293 in the stewardship intervention group). The stewardship intervention increased compliance with DOT recommendations (42% versus 5.6%, P < 0.001) and reduced the median DOT per patient (6 versus 9 days, P < 0.001). Clinical outcomes, including mortality, readmission with pneumonia, presentation to the emergency centre/clinic with pneumonia and incidence of Clostridium difficile infection within 30 days of discharge, were not different between groups. Conclusions: This multicentre evaluation of a stewardship intervention in hospitalized CAP patients reduced the total antibiotic DOT and increased guideline-concordant DOT without adversely affecting patient outcomes.

Cost Analysis of Implementing Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Plus Real-Time Antimicrobial Stewardship Intervention for Bloodstream Infections.

Studies evaluating rapid diagnostic testing plus stewardship intervention have consistently demonstrated improved clinical outcomes for patients with bloodstream infections. However, the cost of implementing new rapid diagnostic testing can be significant, and such testing usually does not generate additional revenue. There are minimal data evaluating the impact of adding matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for rapid organism identification and dedicating pharmacy stewardship personnel time on the total hospital costs. A cost analysis was performed utilizing patient data generated from the hospital cost accounting system and included additional costs of MALDI-TOF equipment, supplies and personnel, and dedicated pharmacist time for blood culture review and of making interventions to antimicrobial therapy. The cost analysis was performed from a hospital perspective for 3-month blocks before and after implementation of MALDI-TOF plus stewardship intervention. A total of 480 patients with bloodstream infections were included in the analysis: 247 in the preintervention group and 233 in the intervention group. Thirty-day mortality was significantly improved in the intervention group (12% versus 21%, P < 0.01), and the mean length of stay was reduced, although the difference was not statistically significant (13.0 ± 16.5 days versus 14.2 ± 16.7 days, P = 0.44). The total hospital cost per bloodstream infection was lower in the intervention group ($42,580 versus $45,019). Intensive care unit cost per bloodstream infection accounted for the largest share of the total costs in each group and was also lower in the intervention group ($10,833 versus $13,727). Implementing MALDI-TOF plus stewardship review and intervention decreased mortality for patients with bloodstream infections. Despite the additional costs of implementing MALDI-TOF and of dedicating pharmacy stewardship personnel time to interventions, the total hospital costs decreased by $2,439 per bloodstream infection, for an approximate annual cost savings of $2.34 million.

Disease-based antimicrobial stewardship: a review of active and passive approaches to patient management.

Although new antimicrobial stewardship programmes (ASPs) often begin by targeting the reduction of antimicrobial use, an increasing focus of ASPs is to improve the management of specific infectious diseases. Disease-based antimicrobial stewardship emphasizes improving patient outcomes by optimizing antimicrobial use and increasing compliance with performance measures. Directing efforts towards the comprehensive management of specific infections allows ASPs to promote the shift in healthcare towards improving quality, safety and patient outcome metrics for specific diseases. This review evaluates published active and passive disease-based antimicrobial stewardship interventions and their impact on antimicrobial use and associated patient outcomes for patients with pneumonia, acute bacterial skin and skin structure infections, bloodstream infections, urinary tract infections, asymptomatic bacteriuria, Clostridium difficile infection and intra-abdominal infections. Current literature suggests that disease-based antimicrobial stewardship effects on medical management and patient outcomes vary based on infectious disease syndrome, resource availability and intervention type.

Clinical outcomes of Enterobacteriaceae infections stratified by carbapenem MICs.

The Clinical and Laboratory Standards Institute (CLSI) lowered the MIC breakpoints for meropenem and imipenem from 4 mg/liter to 1 mg/liter for Enterobacteriaceae in 2010. The breakpoint change improves the probability of pharmacodynamic target attainment and eliminates the need for microbiology labs to perform confirmatory testing for Klebsiella pneumoniae carbapenemase (KPC) production or other beta-lactamases that hydrolyze carbapenems. However, there are limited data evaluating clinical outcomes of the affected breakpoints, and it is unknown if patients infected with Enterobacteriaceae with reduced susceptibility are more likely to have poor outcomes when treated with a carbapenem. We conducted a single-center retrospective matched-cohort analysis in adult patients with Enterobacteriaceae infections treated with meropenem, imipenem, or doripenem. Patients with Enterobacteriaceae infection with a carbapenem MIC of 2 to 8 mg/liter were matched based on pathogen, source of infection, comorbidities, and disease severity (1:1 ratio) to those with a carbapenem MIC of ≤1 mg/liter. A total of 36 patients were included in the study. The group with carbapenem MICs of 2 to 8 mg/liter had a significantly higher 30-day mortality than the group with carbapenem MICs of ≤1 mg/liter (38.9% compared to 5.6%, P = 0.04). Total hospital length of stay (LOS) and intensive care unit (ICU) LOS were longer in the group with MICs of 2 to 8 mg/liter than in the group with MICs of ≤1 mg/liter (57.6 days compared to 34.4 days [P = 0.06] and 56.6 days compared to 21.7 days [P < 0.01], respectively). Patients infected with Enterobacteriaceae with a carbapenem MIC of 2, 4, or 8 mg/liter had higher mortality rates and longer ICU LOS than matched cohorts with carbapenem MICs of ≤1 mg/liter, which supports CLSI's recommendation to lower susceptibility breakpoints for carbapenems.

Defining access without excess: expanding appropriate use of antibiotics targeting multidrug-resistant organisms.

Antimicrobial resistance remains a significant global public health threat. Although development of novel antibiotics can be challenging, several new antibiotics with improved activity against multidrug-resistant Gram-negative organisms have recently been commercialised. Expanding access to these antibiotics is a global public health priority that should be coupled with improving access to quality diagnostics, health care with adequately trained professionals, and functional antimicrobial stewardship programmes. This comprehensive approach is essential to ensure responsible use of these new antibiotics.

Knowledge, attitudes and perceptions of Latin American healthcare workers relating to antibiotic stewardship and antibiotic use: a cross-sectional multi-country study.

BACKGROUND: The burden of antimicrobial resistance (AMR) in Latin America is high. Little is known about healthcare workers' (HCWs) knowledge, attitudes, and perceptions of antimicrobial stewardship (AS), AMR, and antibiotic use (AU) in the region. METHODS: HCWs from 42 hospitals from 5 Latin American countries were invited to take an electronic, voluntary, anonymous survey regarding knowledge, attitudes, and perceptions of AS, AMR, and AU between March-April 2023. FINDINGS: Overall, 996 HCWs completed the survey (52% physicians, 32% nurses, 11% pharmacists, 3% microbiologists, and 2% "other"). More than 90% of respondents indicated optimizing AU was a priority at their healthcare facility (HCF), 69% stated the importance of AS was communicated at their HCF, and 23% were unfamiliar with the term "antibiotic stewardship". Most (> 95%) respondents acknowledged that appropriate AU can reduce AMR; however, few thought AU (< 30%) or AMR (< 50%) were a problem in their HCF. Lack of access to antibiogram and to locally endorsed guidelines was reported by 51% and 34% of HCWs, respectively. Among prescribers, 53% did not consider non-physicians' opinions to make antibiotic-related decisions, 22% reported not receiving education on how to select antibiotics based on culture results and 60% stated patients and families influence their antibiotic decisions. CONCLUSIONS: Although HCWs perceived improving AU as a priority, they did not perceive AU or AMR as a problem in their HCF. AS opportunities include improved access to guidelines, access to AMR/AU data, teamwork, and education on AS for HCWs and patients and families.