Ceftazidime-Avibactam in the Treatment of Patients with Bacteremia or Nosocomial Pneumonia: A Systematic Review and Meta-analysis.

INTRODUCTION: Ceftazidime-avibactam (CAZ-AVI) is a combination of the third-generation cephalosporin ceftazidime and the novel, non-ß-lactam ß-lactamase inhibitor avibactam that is approved for the treatment of pediatric (≥ 3 months) and adult patients with complicated infections including hospital-acquired and ventilator-associated pneumonia (HAP/VAP), and bacteremia. This systematic literature review and meta-analysis (PROSPERO registration: CRD42022362856) aimed to provide a quantitative and qualitative synthesis to evaluate the effectiveness of CAZ-AVI in treating adult patients with bacteremia or nosocomial pneumonia caused by carbapenem-resistant Enterobacterales (non metallo-ß-lactamase-producing strains) and multi-drug resistant (MDR) Pseudomonas aeruginosa infections. METHODS: The databases included in the search, until November 7, 2022, were Embase and PubMed. A total of 24 studies (retrospective: 22, prospective: 2) with separate outcomes for patients with bacteremia or pneumonia were included. RESULTS: The outcomes assessed were all-cause mortality, clinical cure, and microbiological cure. Qualitative (24 studies) and quantitative (8/24 studies) syntheses were performed. The quality of the studies was assessed using the MINORS checklist and the overall risk of bias was moderate to high. CONCLUSIONS: In studies included in the meta-analysis, lower all-cause mortality for patients with bacteremia (OR = 0.30, 95% CI 0.19-0.46) and improved rates of clinical cure for patients with bacteremia (OR = 4.90, 95% CI 2.60-9.23) and nosocomial pneumonia (OR = 3.20, 95% CI 1.55-6.60) was observed in the CAZ-AVI group compared with the comparator group. Data provided here may be considered while using CAZ-AVI for the treatment of patients with difficult-to-treat infections. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022362856.

Global trends in carbapenem- and difficult-to-treat-resistance among World Health Organization priority bacterial pathogens: ATLAS surveillance program 2018-2022.

OBJECTIVES: To report trends in carbapenem resistance and difficult-to-treat resistance (DTR) among clinical isolates of Gram-negative priority pathogens collected by the ATLAS global surveillance program from 2018 to 2022. METHODS: Reference broth microdilution testing was performed in a central laboratory for 79,214 Enterobacterales, 30,504 Pseudomonas aeruginosa, and 13,500 Acinetobacter baumannii-calcoaceticus complex isolates collected by a constant set of 157 medical centres in 49 countries in Asia Pacific (APAC), Europe (EUR), Latin America (LATAM), Middle East-Africa (MEA), and North America (NA) regions. MICs were interpreted by 2023 CLSI M100 breakpoints. ß-lactamase genes were identified for meropenem-nonsusceptible (MIC ≥2 mg/L) Enterobacterales isolates. RESULTS: Carbapenem-resistant Enterobacterales (CRE) detection increased (P < 0.05) in APAC, EUR, LATAM, and MEA regions and decreased in NA, while annual DTR percentages increased in all five regions. Carbapenem-resistant P. aeruginosa (CRPA; decreased in MEA region) and carbapenem-resistant A. baumannii-calcoaceticus complex (CRAB; decreased in MEA region and increased in EUR) remained relatively stable over time in all regions, although notably, annual percentages of CRAB and DTR A. baumannii-calcoaceticus complex isolates were consistently >25 percentage points lower in NA than in other regions. For all regions except NA, the majority of changes in CRE percentages could be attributed to hospital-acquired infections. Among meropenem-nonsusceptible Enterobacterales, KPC was the most frequent carbapenemase in NA and EUR each year. NDM was the most prevalent carbapenemase detected in 2022 in other global regions. CONCLUSION: CRE, CRPA, CRAB, and DTR rates vary among global regions over time highlighting the need for continuing surveillance to inform treatment strategies and antimicrobial stewardship.

Rhode Island (RI) Women's Breast Cancer Mammography Use Prior to and After Cancer Diagnosis: Linkage of RI Cancer Registry Data With RI All-Payer Claims Database.

OBJECTIVE: A limitation of the central cancer registries to examine associations between mammography use and cancer diagnosis is their lack of cancer screening history. To fill this measurement gap, Rhode Island Cancer Registry (RICR) breast cancer (BC) records were linked to Rhode Island-all-payer claims database (RI-APCD) to study Rhode Island (RI) women's regular mammography use and identify its predictors. METHODS: From the linked 2011-2019 data, we identified 4 study cohorts: (1) women who ever received mammography by Women's Cancer Screening Program (WCSP) and were diagnosed with BC ("WCSP-BC" cohort: n = 149), (2) women diagnosed with BC outside of WCSP (BC-control cohort: n = 4304), (3) women with a history of mammography use at WCSP but no BC diagnosis (n = 6513), and (4) general RI women with no BC diagnosis (n = 15 121). Logistic regressions were conducted to identify predictors of regular mammography use. RESULTS: The linkage for RI-APCD and RICR for our study had a high matching rate of 82%. Mammography use prior to BC diagnosis was not different between the WCSP-BC cohort and the BC-control cohort (58% vs 57%). Women in the BC-control cohort who had mammography in 2 years prior to their cancer diagnosis were more likely of being diagnosed at an early-stage disease. Among BC-control group, women with no anxiety/depression or with no preventive examinations were less likely of regular mammography use. Among women with no BC, a lower proportion of women with a history of screening at WCSP had regular mammography use, compared with the general RI women (38% vs 66%). CONCLUSION: RI-APCD data linkage with RICR provides excellent opportunities to examine regular mammography use among RI women and compare their outcomes to the general women population in the state. We identified opportunities for improving their mammography use. A measurement gap in the central cancer registries can be effectively reduced by utilizing statewide claims database.

Association of guideline-concordant care with survival, health care utilization, and costs among older women with advanced epithelial ovarian cancer.

OBJECTIVES: To examine guideline-concordant care (GCC) for ovarian cancer, identify its predictors, and evaluate the associations between GCC and survival, health care expenditures, and utilization. STUDY DESIGN: A retrospective cohort study using Surveillance, Epidemiology, and End Results-Medicare data. METHODS: Women aged 66 to 90 years who received a diagnosis of stage II or higher epithelial ovarian cancer during 2011-2015 were included (N = 3237). The National Comprehensive Cancer Network clinical practice guidelines were used to identify GCC. Logistic regression was conducted to identify predictors of GCC, a Cox proportional hazards model was used to examine mortality, and generalized linear models were used to examine mean monthly Medicare expenditures and health care utilization. RESULTS: Approximately 57% of women received GCC and 11.6% of women did not receive any cancer-specific treatment. Women who were relatively older (adjusted odds ratio [AOR], 0.272; 95% CI, 0.210-0.351), had Census tract income of $50,000 or less (AOR, 0.709; 95% CI, 0.551-0.913), had a psychiatric condition (AOR, 0.655; 95% CI, 0.464-0.923), and had adenocarcinoma histology (AOR, 0.564; 95% CI, 0.441-0.721) were significantly less likely to receive GCC. Race/ethnicity was not found to be a significant predictor of GCC. Women who received surgery only or chemotherapy only had a significant higher hazard of all-cause mortality and ovarian cancer-specific mortality compared with those who received GCC (surgery only: adjusted HR [AHR], 2.307; chemotherapy only: AHR, 1.802). Receiving chemotherapy only was associated with 45% (P < .0001) higher mean monthly expenditures compared with those who received GCC. CONCLUSIONS: Non-GCC was associated with worsened survival, higher health care utilization, and increased expenditures. It is important to highlight that women who received GCC were associated with better survival likely due to favorable prognostic clinical factors.

Antimicrobial Susceptibility Among Gram-Negative Isolates in Pediatric Patients in Latin America, Africa-Middle East, and Asia From 2016-2020 Compared to 2011-2015: Results From the ATLAS Surveillance Study.

BACKGROUND: Antimicrobial resistance (AMR) data in the pediatric population are limited, particularly in developing countries. This study assessed the AMR profile and key resistance phenotypes and genotypes for Gram-negative bacteria (GNB) isolates collected as part of the Antimicrobial Testing Leadership and Surveillance program from pediatric patients in Latin America, Africa-Middle East, and Asia in 2016-2020 versus 2011-2015. METHODS: Minimum inhibitory concentrations by broth microdilution methodology were interpreted per the Clinical and Laboratory Standards Institute. European Committee on Antimicrobial Susceptibility Testing breakpoints were used for interpreting colistin activity. ß-lactamase genes were screened by polymerase chain reaction and sequencing. RESULTS: For Acinetobacter baumannii, low susceptibility (<60.0%) was observed for all antimicrobials, except colistin (≥92.9%), across regions and year periods. Ceftazidime-avibactam, amikacin, colistin, and meropenem were mostly active (78.6%-100.0%) against Enterobacter cloacae, Escherichia coli, and Klebsiella pneumoniae. For Pseudomonas aeruginosa, susceptibility to ceftazidime-avibactam, amikacin, and colistin was ≥85.9%. Among resistance phenotypes, carbapenem-resistant (CR, ≥44.8%) and difficult-to-treat resistant (DTR, ≥37.1%) rates were the highest in A. baumannii. A consistent increase in CR and DTR K. pneumoniae was noted across regions over time. Extended-spectrum ß-lactamases (ESBL)-producing K. pneumoniae (32.6%-55.6%) were more frequent than ESBL-producing E. coli (25.3%-37.1%). CTX-M was the dominant ESBL among Enterobacterales. NDM-positive Enterobacterales species and VIM-positive P. aeruginosa were identified across regions. CONCLUSIONS: This study identified high susceptibility to few agents for key GNB in pediatric patients. Continued surveillance of resistance phenotypes and genotypes at regional levels may help to guide appropriate treatment decisions.

In vitro activity of aztreonam-avibactam against Enterobacterales isolates collected in Latin America, Africa/Middle East, Asia, and Eurasia for the ATLAS Global Surveillance Program in 2019-2021.

This study aimed to report reference method antimicrobial susceptibility results for 24,937 recent (2019-2021) clinical isolates of Enterobacterales from 27 countries in Latin America, Eurasia, Africa/Middle East, and Asia with a focus on the investigational combination aztreonam-avibactam against metallo-ß-lactamase (MBL) isolates. Antimicrobial susceptibility testing was performed by the CLSI broth microdilution methodology. Minimum inhibitory concentrations (MICs) were interpreted using the CLSI (2022) breakpoints for all agents except aztreonam-avibactam (provisional pharmacokinetic/pharmacodynamic susceptible breakpoint, ≤ 8 mg/L) and tigecycline (US-FDA). Molecular testing for ß-lactamase genes was performed on isolates with meropenem MICs ≥ 2 mg/L, ceftazidime-avibactam MICs ≥ 16 mg/L, and/or aztreonam-avibactam MICs ≥ 16 mg/L, and 50% of isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella variicola, and Proteus mirabilis testing with ceftazidime and/or aztreonam MICs ≥ 2 mg/L. Aztreonam-avibactam inhibited 99.8% of all Enterobacterales at ≤ 8 mg/L (MIC90, 0.25 mg/L) and maintained activity against phenotypically resistant subsets of multidrug-resistant (MDR) (99.5% susceptible), extensively drug-resistant (XDR) (98.7%), and carbapenem-resistant Enterobacterales (CRE) (99.1%) isolates. At ≤ 8 mg/L, aztreonam-avibactam inhibited 100%, 99.6%, 99.6%, and 98.8% of KPC-, OXA-48-like-, ESBL-, and MBL-carrying isolates, respectively. MBL-positive isolates were most prevalent in India (20.5%), Guatemala (13.8%), and Jordan (13.2%). No differences in the activity of aztreonam-avibactam were observed across the global regions evaluated. At a concentration of ≤ 8 mg/L, aztreonam-avibactam inhibited almost all Enterobacterales collected from developing countries, including MBL-producing isolates. The widespread dissemination of MBLs among Enterobacterales highlights the unmet need for new agents such as aztreonam-avibactam for the treatment of CRE infections.

Real-World Outcomes Associated With Letermovir Use for Cytomegalovirus Primary Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients: A Systematic Review and Meta-analysis of Observational Studies.

Background: A systematic review and meta-analysis of real-world observational studies was conducted to summarize the impact of letermovir cytomegalovirus (CMV) primary prophylaxis (PP) among adult allogeneic hematopoietic cell transplant (allo-HCT) recipients. Methods: Systematic searches in Medline/PubMed, Embase, and conferences (from database inception to October 2021) were conducted to identify studies for inclusion. Random-effects models were used to derive pooled estimates on the relative effectiveness of letermovir PP compared to controls. Results: Forty-eight unique studies (N = 7104 patients) were included, most of which were comparative, single-center, and conducted in the United States. Letermovir PP was associated with statistically significant reduction in odds of CMV reactivation (pooled odds ratio [pOR], 0.13 and 0.24; P < .05), clinically significant CMV infection (pOR, 0.09 and 0.19; P < .05), and CMV disease (pOR, 0.31 and 0.35; P < .05) by day +100 and day +200 after allo-HCT, respectively. Letermovir PP was associated with significantly lower odds of all-cause (pOR, 0.73; P < .01) and nonrelapse mortality (pOR, 0.65; P = .01) beyond day 200 after allo-HCT. Conclusions: Letermovir for CMV PP was effective in reducing the risk of CMV-related complications overall and mortality beyond day 200 among adult allo-HCT recipients.

Evaluation of the association between health insurance status and healthcare utilization and expenditures among adult cancer survivors in the United States.

BACKGROUND: Health care expenditures for cancer care has increased significantly over the past decade and is further projected to rise. This study examined the associations between health insurance status and total direct health care expenditures and health care utilization among cancer survivors living in the United States. METHODS: A cross-sectional study of cancer survivors aged ≥18 years, identified from the Medical Expenditures Panel Survey (MEPS) during 2017 using International Classification of Diseases, Tenth Revision codes specific for cancer. Health insurance was categorized into Private, Medicare, Medicaid, and uninsured. Multivariable ordinary least squares regression was used to examine the association between log expenditures and health insurance. Negative binomial regression with log link was used to obtain adjusted incident rate ratios (AIRR) for health care utilization. Survey weights were used to produce nationally representative estimates of the US population. RESULTS: A total of 1140 (weighted = 13.9 million) cancer survivors were identified. Compared to the adjusted mean annual health care expenditures for the private group ($14,265; 95% confidence interval (CI): $12,645 to $16,092), the adjusted mean annual health care expenditures for the Medicare group were higher ($15,112; 95%CI: $13,361 to $17,092). As compared to the private group, the average annual expenditures for uninsured cancer survivors ($2315; 95%CI:1038 to $3501) was significantly lower and so was their health care utilization. Adjusted rates of ER visits for Medicaid were twice (AIRR:2.04; SE:0.28; p = 0.001) as compared to privately insured. CONCLUSIONS: A difference in the average total direct expenditures between uninsured and privately insured patients was found. Uninsured had the lowest health care utilization while Medicaid reported significantly higher number of ER visits. Despite differences in program structures, health care expenditures across insurance types were similar. Lower utilization of health care services among uninsured suggests cost maybe a barrier to accessing care.

Adverse Events Induced by Nivolumab Plus Ipilimumab vs. Nivolumab Monotherapy among Cancer Patients: A Systematic Review and Meta-Analysis.

A systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to examine treatment-related adverse events (TRAEs) for combination of nivolumab (NIVO) and ipilimumab (IPI) compared to NIVO monotherapy among cancer patients. We searched several databases to identify relevant RCTs. Meta-analysis was performed using random-effects model. In fourteen RCTs included in the study, we found that compared to NIVO monotherapy, combination NIVO + IPI increased the risk of any grade (Risk Ratio (RR) = 1.11), and grade 3 or 4 (RR = 1.95) TRAEs. Compared to NIVO, NIVO + IPI had higher risk for any grade colitis (RR = 4.52), pneumonitis (RR = 3.06), and diarrhea (RR = 1.68).