RESUMO
PURPOSE: Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for 80%-90% of the cases. In Brazil, between 2018 and 2019, lung cancer was ranked as the second most frequent cancer among men and the fourth among women. The primary objectives were to describe the journey and survival rates of patients with advanced NSCLC treated in the Brazilian private health care system (HCS). MATERIALS AND METHODS: A retrospective cohort study was based on the search in administrative databases to analyze the Brazilian private HCS. Patients with advanced NSCLC diagnosed between 2011 and 2016 were included. The data on demographics, cancer-related information, treatment-related information, and resources used were collected. Survival analyses were performed using the semiparametric Kaplan-Meier method to assess mortality by NSCLC stage, with NSCLC diagnosis as the index date. RESULTS: A total of 5,016 patients were included. Most patients were between 60 and 69 years old (33.6%) and had completed elementary school (52.2%). There was a greater proportion of men (58.1% v 41.9%), and the majority of patients had stage IV NSCLC (67%). It took an average of 31 days, from the first consultation, to have diagnosis. In 44% of the cases, a clinical oncologist was the first specialist in the HCS that the patient was referred to. After the diagnosis, the median time to start of treatment was 35 days. Chemotherapy alone was the most common treatment regimen (32%). The median overall survival was 11.5 months and 6 months for stage II and IV NSCLC, respectively. CONCLUSION: This study provides contemporary data on stage III and IV NSCLC in private health care in Brazil, which has shown a high rate of metastatic disease diagnoses, high health care-related costs, and low survival rates.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Brasil/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Abstract Multi-drug resistant Gram-negative bacilli (GNB) have been reported as cause of serious hospital-acquired infections worldwide. The aim of this study was to investigate the in vitro activity of ceftolozane-tazobactam compared to other agents against GNB isolated from patients admitted to Brazilian medical centers between the years 2016 and 2017. Presence of β-lactamase encoding genes was also evaluated. Methods Antimicrobial susceptibility testing of GNB isolated from intra-abdominal (IAI), respiratory (RTI), and urinary tract infections (UTI) was performed according to ISO 227-1 guidelines and interpreted following CLSI and BrCAST/EUCAST guidelines. Qualifying Enterobacteriaceae isolates were screened for the presence of β-lactamase genes by PCR followed by DNA sequencing. Results 1748 GNB collected from UTI (45.2%), IAI (25.7%) and RTI (29.1%) were evaluated. Ceftolozane-tazobactam remained highly active (94.7%) against E. coli isolates. Among K. pneumoniae, susceptibility rates were 85.9% and 85.4% for amikacin and colistin, whereas ceftolozane-tazobactam (44.1% susceptible) and carbapenems (55.2-62.2% susceptible) showed poor activity due to bla KPC-2. Against E. cloacae amikacin, imipenem, and meropenem retained good activity (>90%). Ceftolozane-tazobactam was the most potent β-lactam agent tested against P. aeruginosa (90.9% susceptible), including ceftazidime and imipenem resistant isolates. β-lactamase encoding genes testing was carried out in 433 isolates. bla CTX-M variants were predominant in E. coli, P. mirabilis and E. cloacae. Among the K. pneumoniae molecularly tested, most carried bla KPC (68.5%), with all harboring bla KPC-2, except two isolates carrying bla KPC-3 or bla KPC-30. ESBL encoding genes, mainly CTX-M family, were frequently detected in K. pneumoniae, plasmid-mediated AmpC were rare. A variety of PDC encoding genes were detected in P. aeruginosa isolates with five isolates harboring MBL and one KPC encoding genes. Conclusion Ceftolozane-tazobactam was very active against E. coli, P. mirabilis and P. aeruginosa isolates and could constitute an excellent therapeutic option including for those isolates resistant to extended-spectrum cephalosporins and carbapenems but not producers of carbapenemases.
Assuntos
Humanos , Infecções por Pseudomonas , Cefalosporinas/farmacologia , Farmacorresistência Bacteriana , Infecções por Enterobacteriaceae , Antibacterianos/farmacologia , Pseudomonas aeruginosa , Brasil , Testes de Sensibilidade Microbiana , Escherichia coli , TazobactamRESUMO
ABSTRACT Background: The emergence of antibiotic resistance is increasing and there are few effective antibiotics to treat infections caused by resistant and multidrug resistant bacterial pathogens. This study aimed to evaluate the in vitro activity of ceftolozane-tazobactam against clinical bacterial isolates from Brazil. Methods: A total of 673 Gram-negative bacterial isolates including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and other Enterobacterales collected from 2016 to 2017 were tested, most of them isolated from patients in intensive care units. Minimum inhibitory concentrations (MIC50/90) were determined by broth microdilution for amikacin, aztreonam, cefepime, cefotaxime, cefoxitin, ceftolozane-tazobactam, ceftazidime, ceftriaxone, ciprofloxacin, colistin, ertapenem, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam using dried panels. Antimicrobial susceptibility results were interpreted according to Clinical and Laboratory Standards Institute criteria. Results: Susceptibility rates to ceftolozane-tazobactam ranged from 40.4% to 94.9%. P. aeruginosa susceptibility rate to ceftolozane-tazobactam was 84.9% (MIC50/90, 1/16 µg/mL) and 99.2% to colistin. For E. coli, ceftolozane-tazobactam inhibited 94.9% (MIC50/90, 0.25/1 µg/mL) of the microorganisms. The susceptibility rate of K. pneumoniae to ceftolozane-tazobactam was 40.4% (MIC50/90, 16/>32 µg/mL). Other Enterobacterales have shown susceptibility rates of 81.1% (MIC50/90, 0.5/16 µg/mL) to ceftolozane-tazobactam, 93.9% to meropenem, 90.9% to amikacin (90.9%), and 88.6% to ertapenem. In non-carbapenemase producing isolates, AmpC mutations were found three isolates. Conclusions: Ceftolozane-tazobactam has shown relevant activity against a large variety of the analyzed microorganisms collected from multiple centers in Brazil, showing promising results even in multidrug resistant strains.