Activity of ceftolozane-tazobactam and comparators against gram-negative bacilli: Results from the study for monitoring antimicrobial resistance trends (SMART - Brazil; 2016-2017)

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.

Activity of ceftolozane-tazobactam and comparators against gram-negative bacilli: Results from the study for monitoring antimicrobial resistance trends (SMART - Brazil; 2016-2017).

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 ß-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 ß-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 blaKPC-2. Against E. cloacae amikacin, imipenem, and meropenem retained good activity (>90%). Ceftolozane-tazobactam was the most potent ß-lactam agent tested against P. aeruginosa (90.9% susceptible), including ceftazidime and imipenem resistant isolates. ß-lactamase encoding genes testing was carried out in 433 isolates. blaCTX-M variants were predominant in E. coli, P. mirabilis and E. cloacae. Among the K. pneumoniae molecularly tested, most carried blaKPC (68.5%), with all harboring blaKPC-2, except two isolates carrying blaKPC-3 or blaKPC-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.

DISSEMINATED FUNGAL INFECTION WITH ADRENAL INVOLVEMENT: REPORT OF TWO HIV NEGATIVE BRAZILIAN PATIENTS / Infecções fúngicas disseminadas com acometimento das supra-renais: descrição de dois pacientes brasileiros HIV-negativos

Paracoccidioidomycosis and histoplasmosis are systemic fungal infections endemic in Brazil. Disseminated clinical forms are uncommon in immunocompetent individuals. We describe two HIV-negative patients with disseminated fungal infections, paracoccidioidomycosis and histoplasmosis, who were diagnosed by biopsies of suprarenal lesions. Both were treated for a prolonged period with oral antifungal agents, and both showed favorable outcomes.

A paracoccidioidomicose e a histoplasmose são infecções fúngicas sistêmicas endêmicas no Brasil. As formas clínicas disseminadas são incomuns em pacientes imunocompetentes. Nós descrevemos dois pacientes HIV-negativos com infecções fúngicas disseminadas, paracoccidioidomicose e histoplasmose, que foram diagnosticadas por biópsias de lesões de supra-renal. Ambos foram tratados por períodos prolongados com antifúngicos orais, evoluindo com boa resposta terapêutica.

DISSEMINATED FUNGAL INFECTION WITH ADRENAL INVOLVEMENT: REPORT OF TWO HIV NEGATIVE BRAZILIAN PATIENTS.

Paracoccidioidomycosis and histoplasmosis are systemic fungal infections endemic in Brazil. Disseminated clinical forms are uncommon in immunocompetent individuals. We describe two HIV-negative patients with disseminated fungal infections, paracoccidioidomycosis and histoplasmosis, who were diagnosed by biopsies of suprarenal lesions. Both were treated for a prolonged period with oral antifungal agents, and both showed favorable outcomes.

Clinical and microbiological characterization of KPC-producing Klebsiella pneumoniae infections in Brazil.

In 2008 isolates of KPC-producing Klebsiella pneumoniae (KPC-KPN) were detected for the first time at Hospital Heliópolis, São Paulo, Brazil. The aim of this study was to characterize the clinical and microbiological outcomes of infections caused by KPC-KPN. A historical cohort of patients from whom KPC-KPN strains were isolated was performed. Isolates were identified as resistant to ertapenem by automated broth microdilution system and screened as carbapenemase producers by the modified Hodge test. The beta-lactamase resistance gene blaKPC was detected by PCR. The genetic relatedness of isolates was determined by PFGE. The study provides early clinical experience in treating KPC-KPN infections in a Brazilian tertiary center.

Clinical and microbiological characterization of KPC-producing Klebsiella pneumoniae infections in Brazil

In 2008 isolates of KPC-producing Klebsiella pneumoniae (KPC-KPN) were detected for the first time at Hospital Heliópolis, São Paulo, Brazil. The aim of this study was to characterize the clinical and microbiological outcomes of infections caused by KPC-KPN. A historical cohort of patients from whom KPC-KPN strains were isolated was performed. Isolates were identified as resistant to ertapenem by automated broth microdilution system and screened as carbapenemase producers by the modified Hodge test. The beta-lactamase resistance gene blaKPC was detected by PCR. The genetic relatedness of isolates was determined by PFGE. The study provides early clinical experience in treating KPC-KPN infections in a Brazilian tertiary center.