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Abstract: The emergence and rapid dissemination of extended-spectrum β-lactamase (ESBL)-producing isolates among Enterobacteriaceae coupled with increasing prevalence of stably derepressed and plasmid-borne AmpC producers have rendered broad-spectrum cephalosporins and β-lactam/β-lactamase inhibitor combinations less effective. This scenario has required the use of carbapenems for treatment of infections caused by such organisms. In this study, the in vitro activities of doripenem and comparator agents against Enterobacteriaceae, including ESBL- and AmpC-producing strains, were evaluated. A total of 36 614 isolates collected from more than 60 medical centers (2000–2007) were included and tested for susceptibility using reference methods and interpretive criteria, except for doripenem (product package insert). Overall, doripenem inhibited 98.7% of all Enterobacteriaceae tested at ≤0.5 μg/mL. ESBL rates were higher among Klebsiella pneumoniae (from 7.7% to 44.0%, varied by geographic region), followed by Escherichia coli (3.6–14.0%) and Proteus mirabilis (0.8–34.8%). Derepressed AmpC production-mediated resistance rates were highest among Enterobacter cloacae (26.6–38.7%) compared with other species and generally higher for strains isolated in the Asia-Pacific and Latin American regions. Doripenem inhibited 94.3% and 93.7% of the ESBL phenotype and derepressed AmpC isolates, respectively, and these resistances had little adverse influence on doripenem MIC50 values (nil to 2-fold increases). The observed increase in AmpC- and ESBL-producing Enterobacteriaceae necessitates a greater confidence on carbapenem empiric therapy. Doripenem could represent a valuable choice for broad-spectrum coverage of contemporary Enterobacteriaceae isolates with widespread resistance mechanisms. [Copyright &y& Elsevier]

• Staphylococcus aureus and Streptococcus pneumoniae causing pneumonia worldwide were tested. • 100% of S. aureus were susceptible to tedizolid, linezolid and vancomycin. • 100% of S. pneumoniae were susceptible to tedizolid at ≤0.5 mg/L. • S. aureus resistance rates varied between regions and were higher in the Asia-Pacific region. • Tedizolid was among the most active compounds in vitro. The antimicrobial activity of tedizolid and comparators was evaluated against a large worldwide collection of Staphylococcus aureus and Streptococcus pneumoniae isolates recovered from patients with pneumonia. Clinical isolates were collected from patients in 96 medical centres in the Asia-Pacific region, Europe, Latin America and the USA between 2017 and 2019, and tested for susceptibility by reference broth microdilution. The most active agents against S. aureus (n = 4667) were tedizolid (100.0% susceptible), linezolid (100.0% susceptible), ceftaroline (96.2% susceptible) and vancomycin (100.0% susceptible), but only tedizolid, linezolid and vancomycin retained activity against >95% of meticillin-resistant S. aureus isolates from all regions. In general, linezolid, ceftriaxone, ceftaroline, levofloxacin, penicillin and vancomycin showed susceptibility rates >95% against S. pneumoniae (n = 3008). However, only linezolid, ceftaroline, levofloxacin and vancomycin remained active (>95% susceptibility) against isolates displaying penicillin-non-susceptible or multidrug-resistant phenotypes. Penicillin-non-susceptible S. pneumoniae isolates were recovered less frequently from patients aged <5 years compared with other age groups. The in-vitro data presented here confirm the high potency of tedizolid against S. aureus and S. pneumoniae causing pneumonia worldwide. There is a need for further clinical evaluations of tedizolid for treating pneumonia caused by these pathogens. [ABSTRACT FROM AUTHOR]

Abstract: We evaluated the susceptibility rates for piperacillin/tazobactam tested against Pseudomonas aeruginosa isolates from the Asia-Pacific (APAC), Europe (EU), Latin America (LA), and North America (NA) for 1997 to 2007. A total of 25 460 isolates were tested originating from APAC (4441), EU (7695), LA (4277), and NA (9047). All testing was performed by reference broth microdilution methods. The samples were collected from >110 medical centers and samples averaging >30 nations/year. For this analysis, results from 1997 to 2007, 1997 to 1999, 2005 to 2007, APAC, EU, LA, and NA were assessed against several broad-spectrum β-lactams, including cefepime, ceftazidime, imipenem, meropenem, and piperacillin alone, for a total of 12 agents overall. Using P. aeruginosa breakpoints (≤64 μg/mL), piperacillin/tazobactam had the broadest coverage (% susceptible) in 2 regions (EU, LA) and, overall, at 83.6% followed by meropenem (83.0%) > imipenem (79.7%) > piperacillin (79.5%) > cefepime (77.5%) > ceftazidime (75.8%). Other non–β-lactam activity results were ciprofloxacin at only 71.5% susceptible, but tobramycin and polymyxin B had higher susceptibility rates (81.0% and 99.5%, respectively). Trends toward piperacillin/tazobactam resistance were noted between 1997 to 1999 and 2000 to 2007 in APAC (−11.6% susceptibility), NA (−4.0%), and EU (−2.3%). LA susceptibility rates were lowest overall but actually increased recently by +2.9% (current rate, 79.4% susceptible). For β-lactamase inhibitor combinations, susceptibility rates were higher for piperacillin/tazobactam when compared in all regions with piperacillin alone (+2.6–7.1%) and greatest for LA isolates. In contrast, ticarcillin/clavulanate susceptibility rates were lower than ticarcillin tested alone in NA (−1.5%, antagonism), and this agent only inhibited 70.3% of isolates worldwide. In conclusion, piperacillin/tazobactam remained a very active β-lactam when tested in vitro against clinical isolates of P. aeruginosa found in the SENTRY Program (1997–2007). Trends toward slightly decreased susceptibility were noted in all regions over the last decade (except LA); only polymyxins had susceptibility rates at >90%. Resistance surveillance programs should be sustained to document emerging resistance patterns of old and newer agents for difficult-to-treat pathogens such as P. aeruginosa. [Copyright &y& Elsevier]