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Background: The combination aztreonam/avibactam is currently under Phase 3 trials for the treatment of serious infections caused by Gram-negative bacteria including those with MBLs.Objectives: To investigate the resistance mechanisms in Enterobacterales exhibiting aztreonam/avibactam MICs of ≥4 mg/L.Methods: Among 8787 Enterobacterales, 17 (0.2%) isolates exhibited an aztreonam/avibactam MIC of ≥4 mg/L. Isolates were sequenced and screened for β-lactamases. Sequences of porins, penicillin-binding protein 3 (PBP3) and expression levels of AmpC and AcrA were evaluated.Results: Eleven (11/4154 isolates; 0.26%) Escherichia coli, three (3/1981; 0.15%) Klebsiella pneumoniae and three (3/628; 0.5%) Enterobacter cloacae were identified. All E. coli showed either an 'YRIK' or 'YRIN' insertion in PBP3. In general, these isolates carried blaCMY and/or blaCTX-M variants, except for one isolate from Korea that also produced NDM-5 and one isolate from Turkey that produced OXA-48. Two DHA-1-producing K. pneumoniae overexpressed acrA and had a premature stop codon in either OmpK35 or OmpK36, whereas a third K. pneumoniae carried blaPER-2 and had a premature stop codon in OmpK35. All three E. cloacae expressed AmpC at levels ≥570-fold, but sequence analysis did not reveal known amino acid alterations associated with decreased avibactam binding or increased hydrolysis of β-lactams. Minor amino acid polymorphisms within OmpC, OmpF and PBP3 were noted among the E. cloacae.Conclusions: A small number of isolates (0.2%) met the inclusion criteria. E. coli showed altered PBP3 as the most relevant resistance mechanism, whereas K. pneumoniae had multiple resistance mechanisms. Further investigations are needed to clarify resistance in E. cloacae. [ABSTRACT FROM AUTHOR]

Background: POL7306 belongs to a new class of peptidomimetic outer-membrane-protein-targeting antibiotics with a novel mechanism of action. POL7306 is in development for the treatment of infections caused by antimicrobial-resistant Gram-negative bacteria and has demonstrated low cytotoxicity and nephrotoxicity.Methods: A total of 891 isolates were collected by the SENTRY Antimicrobial Surveillance Program from 134 medical centres in Europe (n = 424; 41 centres in 18 nations), the USA (n = 411 isolates from 67 centres), the Asia-Pacific region (n = 24; 15 centres in 6 nations) and Latin America (n = 32; 11 centres in 9 nations) and included 558 Enterobacterales, 310 non-fermenters and 23 fastidious organisms. Susceptibility testing was performed using the reference broth microdilution method and the medium was supplemented with 0.002% polysorbate-80 for testing POL7306. Resistant subsets were characterized by WGS.Results: POL7306 demonstrated potent in vitro activity against Enterobacterales [including carbapenem-resistant (MIC50/90, 0.06/0.25 mg/L), ESBL-producing (MIC50/90, 0.06/0.12 mg/L), KPC-producing (MIC50/90, 0.12/0.25 mg/L), MBL-producing (MIC50/90, 0.06/0.25 mg/L), colistin-non-susceptible, mcr-negative (MIC50/90, 0.5/2 mg/L) and mcr-positive (MIC50/90, 0.12/0.25 mg/L) Enterobacterales], Pseudomonas aeruginosa (MIC50/90, 0.25/0.25 mg/L), Acinetobacter baumannii (MIC50/90, 0.06/0.12 mg/L) and Stenotrophomonas maltophilia (MIC50/90, 0.06/0.25 mg/L).Conclusions: POL7306 demonstrated potent activity against a large collection of Gram-negative organisms collected worldwide that included colistin-resistant, XDR and ESBL- and carbapenemase-producing isolates for which there are currently limited treatment options. [ABSTRACT FROM AUTHOR]

• 19545 Gram-negative isolates were collected from medical centers located worldwide. • 82.0–94.4% of Enterobacterales (91.5% overall) were susceptible to cefoperazone-sulbactam at ≤16 mg/L. • 59.5–84.6% of P. aeruginosa (77.8% overall) were susceptible to cefoperazone-sulbactam at ≤16 mg/L. • Resistance rates varied widely and were generally higher in eastern Europe. • Cefoperazone-sulbactam was among the most active compounds in vitro. To evaluate the antimicrobial activities of cefoperazone-sulbactam and comparator agents tested against a large collection of clinical isolates of Gram-negative organisms. A total of 19 545 Gram-negative organisms were collected from medical centers located in western Europe (W-EUR; n = 10 626), eastern Europe and the Mediterranean region (E-EUR; n = 4029), the Asia-Pacific region (APAC; n = 2491), and Latin America (LATAM; n = 2399) in 2015–2016 and susceptibility tested by reference broth microdilution methods. Overall, 91.5% of Enterobacterales were susceptible (≤16 mg/L) to cefoperazone-sulbactam, with susceptibility rates ranging from 82.0% (E-EUR) to 94.4% (W-EUR); overall susceptibility to cefoperazone-sulbactam, piperacillin-tazobactam, imipenem, and ceftriaxone was 91.5%, 85.4%, 90.5%, and 72.1%, respectively. Among Pseudomonas aeruginosa isolates, cefoperazone-sulbactam susceptibility rates were higher in W-EUR, APAC, and LATAM (83.0–84.6%) compared to E-EUR (59.5%). Susceptibility to piperacillin-tazobactam, imipenem, and ceftazidime was 78.3%, 76.2%, and 82.0% in W-EUR; 52.3%, 43.5%, and 57.4% in E-EUR; 83.5%, 80.1%, and 84.5% in APAC; and 81.5%, 72.8%, and 83.0% in LATAM, respectively. Acinetobacter spp. susceptibility rates varied from 43.0% in E-EUR to 75.8% in LATAM (53.2% overall) for cefoperazone-sulbactam and from 19.8% in E-EUR to 40.2% in W-EUR (26.4% overall) for imipenem. Susceptibility rates varied widely among geographic regions and were generally lowest in E-EUR. Based on the potency and activity spectrum, cefoperazone-sulbactam remains among the most active compounds in vitro at published breakpoints. [ABSTRACT FROM AUTHOR]

Abstract: We report the results of the international daptomycin surveillance programs for Europe, Latin America, and selected Asia-Pacific nations. A total of 7948 consecutive Gram-positive organisms of clinical significance were collected in 2011 and susceptibility tested against daptomycin and various comparator agents by Clinical and Laboratory Standards Institute (Clinical and Laboratory Standards Institute. M07-A9. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard: ninth edition Wayne, PA: CLSI. 2012.; Cubicin Package Insert 2012. Cubist Pharmaceuticals, Inc, Lexington, MA. Available at http://www.cubicin.com/pdf/PrescribingInformation.pdf. Accessed January 1, 2012.) broth microdilution methods. The test medium was adjusted to contain physiological levels of calcium (50 mg/L) when testing daptomycin. Daptomycin exhibited potent activity against methicillin-susceptible and -resistant Staphylococcus aureus overall and for each region (MIC50/90, 0.25–0.5/0.5 μg/mL), with susceptibility rates at 100.0% in Latin America, Australia/New Zealand, and India, and at 99.9% in Europe. The daptomycin MIC50/90 for coagulase-negative staphylococci was also at 0.25–0.5/0.5 μg/mL, and only 1 isolate was considered nonsusceptible with a MIC value at 2 μg/mL. Daptomycin was also highly active against Enterococcus faecalis (MIC50/90, 1/1–2 μg/mL) and E. faecium (MIC50/90, 2/2 μg/mL for both vancomycin-susceptible and -resistant isolates). All enterococcal isolates were susceptible to daptomycin (MIC, ≤4 μg/mL) and tigecycline. Susceptibility to linezolid for E. faecalis was at 100.0%, while for E. faecium regional susceptibility rates were at 100.0% except in Europe (99.0%). Viridans group streptococci (MIC50/90, 0.25/1 μg/mL) and β-haemolytic streptococci (MIC50/90, ≤0.06/0.25 μg/mL) continue to be very susceptible to daptomycin. In summary, the results of this investigation document the high potency and wide spectrum of daptomycin when tested against a large resistance-surveillance collection of Gram-positive pathogens and indicate that daptomycin nonsusceptibility remains rare among indicated species after many years of clinical use worldwide. [Copyright &y& Elsevier]

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]

• Resistance to ceftazidime-avibactam (CAZ-AVI) in non-metallo-β-lactamase (MBL) producers is rare • This is caused by mutations on bla KPC or beta-lactamases production plus double porin alterations • CAZ-AVI inhibited 78.7% of the 286 carbapenem-resistant Enterobacterales (3.5% overall) and 100% of 226 non-MBL producers • OmpK36 alterations plus ceftazidime-hydrolysing enzymes lead to CAZ-AVI MICs > 4 mg/L • Most (9 of 15) isolates with these features were Klebsiella pneumoniae belonging to CC258 This study examined ceftazidime-avibactam activity against carbapenem-resistant Enterobacterales (CRE) clinical isolates and resistance mechanisms among non-metallo β-lactamase (MBL) producers displaying ceftazidime-avibactam MIC values at 4 mg/L. CRE isolates (286 of 8161 Enterobacterales) collected in Asia-Pacific, Europe and Latin America during 2016 were screened for carbapenemase genes. Selected isolates were susceptibility tested for ceftazidime-avibactam in the presence or absence of phenylalanine-arginyl β-naphthylamide (PAβN) and polymyxin B nonapeptide (PMBN). Genome sequences were investigated for the integrity of outer membrane protein (OMP) genes and multilocus sequence typing. qRT-PCR assays were conducted to determine expression of acrA, ampC , and OMP genes. Ceftazidime-avibactam inhibited 99.2% of the Enterobacterales , 22 (78.7%) of the 286 CRE and 226 (100%) non-MBL producers. Among carbapenemase producers (85.3%; 244 of 286), the most common gene was bla KPC (76 bla KPC-3 and 46 bla KPC-2), followed by bla OXA-48 -like (60 isolates) and bla NDM (37). Ceftazidime-avibactam MIC values at 4 mg/L were noted among 14 Klebsiella pneumoniae (13 carrying bla KPC and 1 bla CTX-M-15) mostly from Italy and Brazil and 1 Klebsiella aerogenes overexpressing ampC. PAβN did not significantly decrease ceftazidime-avibactam results, but adding PMBN did significantly decrease the MIC results for the combination. All K. pneumoniae isolates had a premature stop codon at OmpK35 and most isolates had L3 alterations of OmpK36, low expression of this gene, or OmpC disruption (K. aerogenes). Nine K. pneumoniae isolates belonged to clonal complex 258 and displayed intrahospital clonality. Ceftazidime-avibactam is an important addition to the armamentarium against multidrug-resistant organisms, and elevated MIC results for this combination seem to be associated with L3 OmpK36 alterations and β-lactamases able to hydrolyze ceftazidime. [ABSTRACT FROM AUTHOR]

Background: Aztreonam-avibactam is under clinical development for treatment of infections caused by carbapenem-resistant Enterobacterales (CRE), especially those resistant to recently approved β-lactamase inhibitor combinations (BLICs)., Objectives: To evaluate a large collection of CRE isolates, including those non-susceptible to ceftazidime-avibactam, meropenem-vaborbactam, and/or imipenem-relebactam., Methods: Overall, 24 580 Enterobacterales isolates were consecutively collected (1/patient) in 2020-2022 from 64 medical centres located in Western Europe (W-EU), Eastern Europe (E-EU), Latin America (LATAM), and the Asia-Pacific region (APAC). Of those, 1016 (4.1%) were CRE. Isolates were susceptibility tested by broth microdilution. CRE isolates were screened for carbapenemase genes by whole genome sequencing., Results: Aztreonam-avibactam inhibited 99.6% of CREs at ≤8 mg/L. Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam were active against 64.6%, 57.4%, and 50.7% of CRE isolates, respectively; most of the non-susceptible isolates carried metallo-beta-lactamases. Aztreonam-avibactam was active against ≥98.9% of isolates non-susceptible to these BLICs. The activity of these BLICs varied by region, with highest susceptibility rates observed in W-EU (76.9% for ceftazidime-avibactam, 72.5% for meropenem-vaborbactam, 63.8% for imipenem-relebactam) and the lowest susceptibility rates identified in the APAC region (39.9% for ceftazidime-avibactam, 37.8% for meropenem-vaborbactam, and 27.5% for imipenem-relebactam). The most common carbapenemase types overall were KPC (44.6% of CREs), NDM (29.9%), and OXA-48-like (16.0%). KPC predominated in LATAM (64.1% of CREs in the region) and W-EU (61.1%). MBL occurrence was highest in APAC (59.5% of CREs in the region), followed by LATAM (34.0%), E-EU (28.9%), and W-EU (23.6%)., Conclusions: Aztreonam-avibactam demonstrated potent activity against CRE isolates resistant to ceftazidime-avibactam, meropenem-vaborbactam, and/or imipenem-relebactam independent of the carbapenemase produced., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Aztreonam is a monobactam stable to hydrolysis by metallo-β-lactamases (MBLs) and avibactam is a non-β-lactam β-lactamase inhibitor that effectively inhibits serine carbapenemases (CPs). Aztreonam/avibactam is under clinical development for treatment of serious infections caused by Gram-negative bacteria, including MBL-producers., Objectives: To evaluate the in vitro activity of aztreonam/avibactam against clinical Enterobacterales isolates., Methods: 8787 Enterobacterales were collected consecutively from 64 medical centres located in Western Europe (W-EU; n = 4616; 26 centres in 10 nations), Eastern Europe (E-EU; n = 1554; 11 centres in 9 nations), the Asia-Pacific region (APAC; n = 1456; 17 centres in 9 nations), and Latin America (LATAM; n = 1161; 10 centres in 6 nations). Susceptibility tests were performed by reference broth microdilution methods and interpreted according to EUCAST criteria., Results: 99.9% of isolates were inhibited at aztreonam/avibactam MIC of ≤8 mg/L (MIC50/90, ≤0.03/0.12 mg/L), including 99.7% of carbapenem-resistant (CRE; n = 396; MIC50/90, 0.25/0.5 mg/L) and 99.7% of multidrug-resistant isolates (n = 1706; MIC50/90, 0.06/0.5 mg/L). CRE rates were 1.2%, 12.9%, 5.2%, and 5.8% in W-EU, E-EU, APAC, and LATAM, respectively (4.5% overall). A CP was identified in 90.2% of CRE isolates. The most common CPs were variants of KPC (35.9% of CRE), NDM (29.0%), and OXA-48 (26.8%). The highest aztreonam/avibactam MIC value among MBL-producers (n = 110; MIC50/90, 0.12/0.5 mg/L) was 2 mg/L. Susceptibility rates for ceftriaxone, meropenem, levofloxacin, and amikacin were highest in W-EU (80.9%, 99.0%, 80.7% and 97.9%, respectively) and lowest in E-EU (52.0%, 88.9%, 54.1%, and 84.2%, respectively)., Conclusions: Our results support clinical development of aztreonam/avibactam to treat infections caused by Enterobacterales, including MBL-producers., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To evaluate the antimicrobial activity of ceftaroline against Staphylococcus aureus isolated from patients with infective endocarditis (IE)., Methods: 23,833 S. aureus isolates were collected consecutively from patients with bloodstream infections (BSI) from 2010 to 2019, via the SENTRY Antimicrobial Surveillance Program, including 396 isolates from patients with a diagnosis of IE. Isolates were collected from 340 medical centers worldwide and susceptibility tested by reference broth microdilution in a monitoring laboratory., Results: The oxacillin resistance (MRSA) rate was 29.0% among IE isolates, and was higher in North America (40.3%) than in Europe (25.4%) or the Latin America/Asia-Pacific region (LATAM-APAC; 18.6%). Ceftaroline was active against 95.2% of IE isolates (MIC 50/90 , 0.25/1 mg/L), with ceftaroline susceptibility higher in North America (99.2%) and LATAM-APAC (98.3%) than in Europe (92.0%). Among MRSA isolates from IE (n = 115; MIC 50/90 , 1/2 mg/L), ceftaroline susceptibility was 98.0% in North America, 90.9% in LATAM-APAC, and 68.5% in Europe. Among BSI isolates, MRSA rates were 43.6% in North America and 25.6% in Europe, while ceftaroline susceptibility rates were 98.1% in North America and 95.4% in Europe., Conclusions: Ceftaroline demonstrated potent in vitro activity against a large collection of S. aureus isolates recovered from patients with BSI, including IE., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bloodstream infection (BSI) organisms were consecutively collected from >200 medical centers in 45 nations between 1997 and 2016. Species identification and susceptibility testing followed Clinical and Laboratory Standards Institute broth microdilution methods at a central laboratory. Clinical data and isolates from 264,901 BSI episodes were collected. The most common pathogen overall was Staphylococcus aureus (20.7%), followed by Escherichia coli (20.5%), Klebsiella pneumoniae (7.7%), Pseudomonas aeruginosa (5.3%), and Enterococcus faecalis (5.2%). S. aureus was the most frequently isolated pathogen overall in the 1997-to-2004 period, but E. coli was the most common after 2005. Pathogen frequency varied by geographic region, hospital-onset or community-onset status, and patient age. The prevalence of S. aureus isolates resistant to oxacillin (ORSA) increased until 2005 to 2008 and then declined among hospital-onset and community-acquired BSI in all regions. The prevalence of vancomycin-resistant enterococci (VRE) was stable after 2012 (16.4% overall). Daptomycin resistance among S. aureus and enterococci (DRE) remained rare (<0.1%). In contrast, the prevalence of multidrug-resistant (MDR) Enterobacteriaceae increased from 6.2% in 1997 to 2000 to 15.8% in 2013 to 2016. MDR rates were highest among nonfermentative Gram-negative bacilli (GNB), and colistin was the only agent with predictable activity against Acinetobacter baumannii-Acinetobacter calcoaceticus complex (97% susceptible). In conclusion, S. aureus and E. coli were the predominant causes of BSI worldwide during this 20-year surveillance period. Important resistant phenotypes among Gram-positive pathogens (MRSA, VRE, or DRE) were stable or declining, whereas the prevalence of MDR-GNB increased continuously during the monitored period. MDR-GNB represent the greatest therapeutic challenge among common bacterial BSI pathogens., (Copyright © 2019 Diekema et al.)

Objectives: Ceftaroline fosamil is approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs), including those caused by methicillin-resistant Staphylococcus aureus (MRSA). This study evaluated the frequency and antimicrobial susceptibility of organisms isolated from patients hospitalised with community-acquired (CA) SSSI in Europe, the Asia-Pacific region (APAC) and Latin America (LATAM)., Methods: Isolates (n=5120) were consecutively collected from patients hospitalised with CA-SSSI in 2014-2016 from 63 medical centres in 41 nations, stratified as Western Europe (20 centres/10 nations), Eastern Europe and the Mediterranean region (E-EUR; 16 centres/12 nations), APAC (16 centres/10 nations) and LATAM (11 centres/9 nations). Isolates obtained from outpatients or <48h after hospitalisation were considered CA. Organisms were tested for susceptibility by reference broth microdilution in a central laboratory., Results: S. aureus was the most common CA-SSSI organism in all regions, except LATAM, and represented 43.3% of the overall collection. MRSA rates varied from 15.8% (E-EUR) to 21.4% (APAC), being 18.5% overall. In general, 98.9% of S. aureus and 94.2% of MRSA isolates were susceptible to ceftaroline, with 99.5% of MRSA isolates inhibited at ≤2mg/L (0.5% resistant). Escherichia coli (14.2%) and β-haemolytic streptococci (BHS) (8.2%) ranked second and third overall, respectively, with wide regional variation. BHS isolates were highly susceptible to ceftaroline (highest MIC, 0.03mg/L), but exhibited decreased susceptibility to tetracycline and erythromycin., Conclusion: The frequency and antimicrobial susceptibility of CA-SSSI bacteria varied broadly by geographic region. Ceftaroline exhibited potent activity against S. aureus (including MRSA), BHS and ceftriaxone-susceptible Enterobacterales isolates., (Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the potency and spectrum of ceftaroline and comparator agents tested against contemporary bacteria isolated from patients with community-acquired bacterial pneumonia (CABP) in Europe (EUR), Asia-Pacific (APAC), and Latin America (LATAM)., Methods: A total of 4321 bacterial isolates were collected consecutively by the SENTRY Antimicrobial Surveillance Program in 2015-2017 from 65 medical centers located in Western Europe (W-EUR; 21 centers in 10 nations), Eastern Europe and the Mediterranean region (E-EUR; 15 centers in 11 nations), APAC (18 centers in nine nations), and LATAM (11 centers in nine nations). Isolates were collected from lower respiratory tract specimens, and an isolate obtained from an outpatient or earlier than 48h after hospitalization was considered community-acquired. Organisms were tested for susceptibility by reference broth microdilution methods in a central laboratory., Results: Among Streptococcus pneumoniae (n=1736), 99.9% of isolates were ceftaroline-susceptible (MIC 50/90 , 0.008/0.12mg/l), and ceftriaxone susceptibility (≤1mg/l) ranged from 97.4% in W-EUR to 85.3% in the APAC region. Ceftaroline was also active against Haemophilus influenzae (n=1172; MIC 50/90 , 0.008/0.03mg/l; 99.8%/93.9% susceptible per CLSI/EUCAST criteria) and Staphylococcus aureus (n=777; MIC 50/90 , 0.25/1mg/l; 97.4% susceptible). Oxacillin resistance ranged from 31.9% in the APAC region to 15.0% in E-EUR. Ceftaroline also demonstrated potent activity against Moraxella catarrhalis (n=613; MIC 50/90 , 0.06/0.25mg/l) and Haemophilus parainfluenzae (n=23; MIC 50/90 , 0.015/0.03mg/l)., Conclusions: Susceptibility rates varied widely by geographic region. Ceftaroline was active against the vast majority of bacterial organisms isolated from patients with CABP., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tigecycline and comparators were tested by the reference broth microdilution method against 33 348 non-duplicate bacterial isolates collected prospectively in 2016 from medical centres in the Asia-Pacific (3443 isolates), Europe (13 530 isolates), Latin America (3327 isolates) and the USA (13 048 isolates). Among 7098 Staphylococcus aureus isolates tested, >99.9% were inhibited by ≤0.5 mg/L tigecycline (MIC 50/90 , 0.06/0.12 mg/L), including >99.9% of methicillin-resistant S. aureus and 100.0% of methicillin-susceptible S. aureus. Tigecycline was slightly more active against Enterococcus faecium (MIC 50/90 , 0.03/0.06 mg/L) compared with Enterococcus faecalis (MIC 50/90 , 0.06/0.12 mg/L) and its activity was not adversely affected by vancomycin resistance when tested against these organisms. Tigecycline potency was comparable for Streptococcus pneumoniae (MIC 50/90 , 0.03/0.06 mg/L), viridans group streptococci (MIC 50/90 , 0.03/0.06 mg/L) and β-haemolytic streptococci (MIC 50/90 , 0.06/0.06 mg/L) regardless of species and penicillin susceptibility. Tigecycline was active against Enterobacteriaceae (MIC 50/90 , 0.25/1 mg/L; 97.8% inhibited at ≤2 mg/L) but was slightly less active against Enterobacteriaceae isolates expressing resistant phenotypes: carbapenem-resistant Enterobacteriaceae (MIC 50/90 , 0.5/2 mg/L; 98.0% susceptible); multidrug-resistant (MIC 50/90 , 0.5/2 mg/L; 93.1% susceptible); and extensively drug-resistant (MIC 50/90 , 0.5/4 mg/L; 87.8% susceptible). Tigecycline inhibited 74.4% of 888 Acinetobacter baumannii isolates at ≤2 mg/L (MIC 50/90 , 2/4 mg/L) and demonstrated good in vitro activity against Stenotrophomonas maltophilia (MIC 50/90 , 1/2 mg/L; 90.6% inhibited at ≤2 mg/L) Tigecycline was active against Haemophilus influenzae (MIC 50/90 , 0.12/0.25 mg/L) regardless of β-lactamase status. Tigecycline represents an important treatment option for resistant Gram-negative and Gram-positive bacterial infections., (Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

This study evaluated the in vitro activity of ceftolozane-tazobactam and comparator agents tested against Latin American isolates of Enterobacteriaceae and Pseudomonas aeruginosa from patients with health care-associated infections. Ceftolozane-tazobactam is an antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor. A total of 2415 Gram-negative organisms (537 P. aeruginosa and 1878 Enterobacteriaceae) were consecutively collected in 12 medical centers located in four Latin American countries. The organisms were tested for susceptibility by broth microdilution methods as described by the CLSI M07-A10 document and the results interpreted according to EUCAST and CLSI breakpoint criteria., Results: Ceftolozane-tazobactam (MIC 50/90 , 0.25/32μg/mL; 84.2% susceptible) and meropenem (MIC 50/90 , ≤0.06/0.12μg/mL; 92.6% susceptible) were the most active compounds tested against Enterobacteriaceae. Among the Enterobacteriaceae isolates tested, 6.6% were carbapenem-resistant Enterobacteriaceae and 26.4% exhibited an extended-spectrum β-lactamase non-carbapenem-resistant phenotype. Whereas ceftolozane-tazobactam showed good activity against extended-spectrum beta-lactamase, non-carbapenem-resistant phenotype strains of Enterobacteriaceae (MIC 50/90 , 0.5/>32μg/mL), it lacked useful activity against strains with a (MIC 50/90 , >32/>32μg/mL; 1.6% S) carbapenem-resistant phenotype. Ceftolozane-tazobactam was the most potent (MIC 50//90 , 0.5/16μg/mL) β-lactam agent tested against P. aeruginosa isolates, inhibiting 86.8% at an MIC of ≤4μg/mL. P. aeruginosa exhibited high rates of resistance to cefepime (16.0%), ceftazidime (23.6%), meropenem (28.3%), and piperacillin-tazobactam (16.4%)., Conclusions: Ceftolozane-tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than available cephalosporins and piperacillin-tazobactam when tested against Enterobacteriaceae., (Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

Solithromycin, a fourth-generation macrolide (a fluoroketolide with enhanced activity against macrolide-resistant bacteria due to interaction with three ribosomal sites) and the first fluoroketolide, was tested against a 2014 collection of 6,115 isolates, including Streptococcus pneumoniae (1,713 isolates), Haemophilus influenzae (1,308), Moraxella catarrhalis (577), Staphylococcus aureus (1,024), and beta-hemolytic streptococci (1,493), by reference broth microdilution methods. The geographic samples included 2,748 isolates from the United States, 2,536 from Europe, 386 from Latin America, and 445 from the Asia-Pacific region. Solithromycin was observed to be very active against S. pneumoniae (MIC50/90, 0.008/0.12 μg/ml), demonstrating 2-fold greater activity than telithromycin (MIC50/90, 0.015/0.25 μg/ml) and 16- to >256-fold greater activity than azithromycin (MIC50/90, 0.12/>32 μg/ml), with all strains being inhibited at a solithromycin MIC of ≤1 μg/ml. Against H. influenzae, solithromycin showed potency identical to that of telithromycin (MIC50/90, 1/2 μg/ml), and both of these compounds were 2-fold less active than azithromycin (MIC50/90, 0.5/1 μg/ml). All but one of the M. catarrhalis isolates were inhibited by solithromycin at ≤0.25 μg/ml. Solithromycin inhibited 85.3% of S. aureus isolates at ≤1 μg/ml, and its activity was lower against methicillin-resistant (MIC50/90, 0.06/>32 μg/ml) than against methicillin-susceptible (MIC50/90, 0.06/0.06 μg/ml) isolates. Little variation in solithromycin activity was observed by geographic region for the species tested. Solithromycin was very active against beta-hemolytic streptococci (MIC50/90, 0.015/0.03 μg/ml), and all isolates were inhibited at MIC values of ≤0.5 μg/ml. In conclusion, solithromycin demonstrated potent activity against global and contemporary (2014) pathogens that represent the major causes of community-acquired bacterial pneumonia. These data support the continued clinical development of solithromycin for the treatment of this important indication., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

A total of 2484 target bacterial pathogens were collected (one per patient episode) from patients in 16 Latin American medical centers located in seven nations during 2011. Isolate identity was confirmed at a coordinating laboratory and susceptibility testing was performed for ceftaroline and comparator agents according to reference broth microdilution methods. A total of 30.0% of isolates were from respiratory tract, 29.4% from skin and skin structure, 21.4% from blood stream, 7.9% from urinary tract and 11.3% from other sites. Ceftaroline was active against Staphylococcus aureus (42.8% MRSA) with 83.6% of the isolates at ≤ 1 mg/L and all isolates at ≤ 2 mg/L (MIC5090, 0.25/2mg/L). National MRSA rates ranged from a low of 28.8% in Colombia to a high of 68.1% in Chile. All Streptococcus pyogenes and Streptococcus agalactiae were susceptible to ceftaroline (MIC50/90 values were at ≤ 0.015/≤ 0.015 mg/L for both). All Streptococcus pneumoniae were susceptible to ceftaroline, linezolid, tigecycline and vancomycin. Susceptibility to ceftriaxone was at 88.4% (CLSI non-meningitis interpretive criteria) and 73.9% (CLSI meningitis interpretive criteria) for all S. pneumoniae. Ceftriaxone susceptibility was only at 33.3% (CLSI non-meningitis interpretive criteria) and 0.0% (CLSI meningitis interpretive criteria) for penicillin-intermediate (penicillin MIC, 4 mg/L) strains. All Haemophilus influenzae (29.4% β-lactamase-positive) isolates were susceptible to ceftaroline, amoxicillin-clavulanate, ceftriaxone, and levofloxacin. For the Latin American region, the ESBL-phenotype rate was 37.6% for Escherichia coli and 53.3% for Klebsiella pneumoniae. Ceftaroline was not active against ESBL-phenotype strains but was active against >90.0% of the non-ESBL-phenotype. The spectrum of activity of ceftaroline against pathogens from Latin America indicates that it merits further study for its potential use in the Latin American region., (Copyright © 2014. Published by Elsevier Editora Ltda.)

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with in vitro bactericidal activity against Gram-positive organisms, including methicillin-susceptible and -resistant Staphylococcus aureus, β-haemolytic and viridans group streptococci, and Streptococcus pneumoniae, as well as common Gram-negative organisms. In this study a total of 986 isolates collected in 2010 from patients in 15 medical centers in five Latin American countries from the Assessing Worldwide Antimicrobial Resistance Evaluation Program were identified as community-acquired respiratory tract or skin and soft tissue infection pathogens. Ceftaroline was the most potent agent tested against S. pneumoniae with a MIC90 value (0.12μg/mL) that was eight-fold lower than ceftriaxone, levofloxacin, and linezolid. Its spectrum of coverage (100.0% susceptible) was similar to tigecycline, linezolid, levofloxacin and vancomycin. Against Haemophilus influenzae and Moraxella catarrhalis, ceftaroline was the most active agent tested. The activity of ceftaroline against S. aureus (including MRSA) was similar to that of vancomycin and tetracycline (MIC90, 1μg/mL) and linezolid (MIC90, 2μg/mL). The β-haemolytic streptococci exhibited 100.0% susceptibility to ceftaroline. Ceftaroline activity against Escherichia coli, Klebsiella spp., and Enterobacter spp. was similar to that of ceftriaxone and ceftazidime. These parenteral cephalosporin agents have potent activity against non-extended-spectrum β-lactamase-phenotype strains, but are not active against extended-spectrum β-lactamase-phenotype strains. These results confirm the in vitro activity of ceftaroline against pathogens common in community-acquired respiratory tract and skin and soft tissue infection in Latin America, and suggest that ceftaroline fosamil could be an important therapeutic option for these infections., (Copyright © 2013 Elsevier Editora Ltda. All rights reserved.)

Tigecycline was approved by the United States Food and Drug Administration in 2005 and has generally retained activity against resistant Gram-positive and Gram-negative organisms. We monitored the in vitro activity of this glycylcycline in 2011 for continued potency worldwide. A total of 22,005 unique clinical isolates were consecutively collected in North America (NA; 9232 isolates), Europe (EU; 6776), Latin America (LA; 2016), and Asia-Pacific region (APAC, 3981) and tested for susceptibility according to the reference broth microdilution method recommendations against tigecycline and numerous comparators. Oxacillin (methicillin) resistance rates in methicillin-resistant Staphylococcus aureus (MRSA) were 49.3%, 30.2%, 42.9%, and 37.8%, and vancomycin resistance rates in enterococci (VRE) were 27.0%, 11.3%, 6.3%, and 4.0% in NA, EU, LA, and APAC, respectively. All MRSA (2839) and >99% of VRE were susceptible to tigecycline. Among Escherichia coli, extended-spectrum β-lactamase (ESBL) rates varied from 12.6% in the NA to 57.4% in APAC, and only one strain was nonsusceptible to tigecycline. Tigecycline was active against ESBL phenotype (96.5-98.4% susceptible) and meropenem-nonsusceptible Klebsiella spp. (94.3-100.0% susceptible). Only 4 of 213 (1.9%) meropenem-nonsusceptible Klebsiella spp. were tigecycline-nonsusceptible, all with tigecycline minimum inhibitory concentration (MIC) of 4 μg/mL (intermediate). Among ceftazidime-nonsusceptible Enterobacter spp., 94.7-98.2% were susceptible to tigecycline. Meropenem-nonsusceptible Acinetobacter spp. varied from 51.2% in NA to 80.9% in APAC; and 83.8% (LA) to 93.9% (APAC) of strains were inhibited at a tigecycline MIC of ≤2 μg/mL. Tigecycline showed potent activity against Stenotrophomonas maltophilia (89.3-98.3% inhibited at ≤2 μg/mL). In summary, tigecycline has sustained potent activity and a broad-spectrum against clinically important bacteria causing infections worldwide, including multidrug-resistant organism subsets., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The Zyvox® Annual Appraisal of Potency and Spectrum (ZAAPS) Program monitors the in vitro activities of linezolid and comparator agents for Gram-positive organisms in Latin America, Europe, Canada, and the Asia-Pacific. For the 2010 Program a total of 6305 Gram-positive strains were collected from 75 medical centres on five continents (24 countries). Reference broth microdilution susceptibility tests were performed on organisms from the following groups: Staphylococcus aureus (2875), coagulase negative staphylococci (CoNS) (855), enterococci (787), Streptococcus pneumoniae (926), viridans group and other streptococci (325), and beta-haemolytic streptococci (507). Linezolid demonstrated a 99.81% susceptibility rate among 6305 strains tested from 24 nations. Of the resistant isolates, four linezolid-resistant strains of enterococci (two each for Enterococcus faecalis and Enterococcus faecium) were found in four nations (China, Thailand, Germany, and Brazil). Eight CoNS (Staphylococcus epidermidis, Staphylococcus hominis) isolates were observed to be resistant to linezolid (MIC, ≥8 μg/ml). Two strains from Mexico were determined to be from an ongoing epidemic, and investigations showed that isolates from Italy and Brazil were also from circulating resistant clones discovered in earlier years. MRSA rates varied by region and between nations, as did resistances to other potential therapeutic agent options frequently listed for MRSA therapy such as clindamycin, fluoroquinolones and trimethoprim/sulfamethoxazole. In summary, the 2010 ZAAPS Program demonstrated that linezolid activity remains stable around the world with >99% susceptibility.

The activity of macrolides and other antimicrobials was evaluated by Clinical and Laboratory Standards Institute reference broth microdilution methods for Moraxella catarrhalis isolates collected during 2009-2011. In Europe, the United States, and Latin America, M. catarrhalis resistance to macrolides and tetracycline was <1%. However, in the Asia-Pacific region, clarithromycin and tetracycline resistance was 7.6% and 3.2%, respectively. The higher resistance rate in the Asia-Pacific region to clarithromycin and tetracycline was primarily due to isolates from multiple locations in China., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Dalbavancin, a long-acting lipoglycopeptide, was evaluated against 81,673 isolates of staphylococci, enterococci, and streptococci collected from 33 countries during worldwide resistance surveillance (2002 to 2007). Regardless of susceptibility to oxacillin, comparable potencies for dalbavancin against Staphylococcus aureus and coagulase-negative staphylococci from all countries were noted (MIC(90), 0.06 to 0.12 microg/ml). Vancomycin-susceptible Enterococcus spp. had dalbavancin MIC(90)s comparable to those for staphylococci, whereas vancomycin-resistant strains were more resistant (MIC(50), >4 microg/ml). beta-Hemolytic and viridians group streptococci were very susceptible to dalbavancin (MIC(90), or=16-fold more active than vancomycin against the monitored gram-positive species.

Ceftobiprole is a 1st-in-class anti-methicillin-resistant Staphylococcus aureus (MRSA) extended-spectrum cephalosporin currently in clinical trials for the treatment of complicated skin and skin structure infections (cSSSIs) and nosocomial pneumonia. This agent is also active against other prominent Gram-positive and Gram-negative pathogens, making it an attractive candidate for broad-spectrum therapy. We evaluated the in vitro potency of ceftobiprole tested against the most commonly occurring bacterial pathogens as part of a global surveillance study for the years 2005 to 2006 (>60 medical centers in North America, Latin America, and Europe). All isolates (40 675) were susceptibility tested using reference broth microdilution methods. Ceftobiprole inhibited 100% and >99% of tested S. aureus and coagulase-negative staphylococci at < or =4 and < or =8 microg/mL, respectively, although MIC90 values for oxacillin-resistant strains were 4-fold and 8-fold higher than oxacillin-susceptible isolates for the 2 groups. Ceftobiprole was also broadly active against Streptococcus pneumoniae, beta-hemolytic and viridans group streptococci, inhibiting >98% of isolates at < or =0.5 microg/mL. Although ceftobiprole was generally inactive against Enterococcus faecium, the majority of Enterococcus faecalis strains (95.7%) were inhibited at < or =4 microg/mL. This agent was similar in potency to the "3rd- and 4th-generation" cephems (MIC50 values, < or =0.06 microg/mL) for all tested Enterobacteriaceae. Although cefepime provided enhanced coverage against Klebsiella spp. (86.5% at < or =8 microg/mL versus 76.9-81.7% for ceftobiprole and ceftazidime), ceftobiprole and cefepime were superior to ceftazidime against Enterobacter spp. and Citrobacter spp. Against Pseudomonas aeruginosa, ceftobiprole was equal in potency to ceftazidime (MIC50, 2 microg/mL) and 2-fold more potent than cefepime. None of these agents inhibited >45% of Acinetobacter spp. at 8 mug/mL. Ceftobiprole is a new anti-MRSA beta-lactam with recognized activity against the most commonly occurring Enterobacteriaceae and P. aeruginosa, similar to that of extended-spectrum cephems. These characteristics warrant continued evaluation of the agent as empiric therapy for cSSSIs, and in pneumonia, especially in those institutions/regions where MRSA and P. aeruginosa may be prevalent.

The spectrum and potency of garenoxacin, a novel des-F(6)-quinolone, against a large international collection (11723 strains) of Gram-positive and Gram-negative bacterial pathogens that cause skin and soft tissue infections (SSTIs) were evaluated for the years 1999 to 2004. Consecutive nonduplicate bacterial isolates were collected from patients with documented community-acquired or nosocomial SSTI in >70 medical centers participating in the SENTRY Antimicrobial Surveillance Program in North America (37.4%), Europe (26.7%), Latin America (16.7%), and the Asia-Pacific region (19.2%). All isolates were tested using the reference broth microdilution methods against garenoxacin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and representative comparator agents used for the empiric or directed therapy for SSTI. Ranking pathogens producing SSTI during these years included Staphylococcus aureus (42.8%), Pseudomonas aeruginosa (11.1%), Escherichia coli (9.0%), Enterococcus spp. (7.3%), Klebsiella spp. (4.8%), Enterobacter spp. (4.7%), beta-hemolytic streptococci (4.3%), coagulase-negative staphylococci (4.0%), Proteus mirabilis (2.5%), and Acinetobacter spp. (2.1%). Garenoxacin was the most potent agent tested against S. aureus and was at least 2-fold more active than gatifloxacin (MIC(50), 0.06 mg/L) and 8-fold more active than levofloxacin (MIC(50), 0.25 mg/L). Furthermore, garenoxacin was 2- to 8-fold more potent than the fluoroquinolones against beta-hemolytic and viridans group streptococci, as well as up to 4-fold more active against enterococci. Garenoxacin was largely comparable with the comparator fluoroquinolones against E. coli, Klebsiella spp., and Acinetobacter spp., but it is less active than these agents against P. aeruginosa. In summary, garenoxacin was documented to be the most potent quinolone when tested against key Gram-positive pathogens (S. aureus, beta-hemolytic streptococci, viridans group streptococci, and enterococci) and was similar in activity to these agents against other species (Enterobacteriaceae and Acinetobacter spp.). These in vitro data suggest that garenoxacin warrants further clinical studies in SSTI, especially against staphylococci and streptococcal pathogens.

Garenoxacin is a novel des-F(6)-quinolone with a chemical structure that lacks the C6 position fluorine and has a unique difluoromethoxy substitution at position C8. This study evaluated the in vitro activity of garenoxacin tested against a large collection of Enterobacteriaceae collected worldwide. The bacterial isolates were consecutively collected from more than 70 medical centers from bloodstream, respiratory, urinary tract, and skin and soft tissue infections. The isolates were tested against garenoxacin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and many other oral and parenteral antimicrobial agents. All isolates were susceptibility tested by broth microdilution methods according to the Clinical and Laboratory Standards Institute (CLSI) guidelines and interpretative criteria. A garenoxacin-susceptible breakpoint of < or =2 microg/mL was applied for comparison purposes only. The fluoroquinolones were the most active oral compounds with overall susceptibility rates of 87.5% to 90.0%. Garenoxacin showed in vitro activity comparable with that of ciprofloxacin and the other fluoroquinolones against Escherichia coli (MIC(50), < or =0.03 microg/mL; 87.3% susceptible), Klebsiella spp. (MIC(50), 0.12 microg/mL; 90.4-94.5% susceptible), Enterobacter spp. (MIC(50), 0.12 microg/mL; 85.6-86.5% susceptible), Salmonella spp. (MIC(50), 0.06 microg/mL; 99.7% susceptible), and Shigella spp. (MIC(50), < or =0.03 microg/mL; 99.9% susceptible), which accounted for 87.0% of the Enterobacteriaceae strains tested. Garenoxacin was highly active against ciprofloxacin-susceptible strains (98.1% susceptibility), whereas ciprofloxacin-resistant strains were generally resistant to all other fluoroquinolones and also showed high rates of resistance to other orally administered antimicrobials. In conclusion, garenoxacin in vitro activity was similar to that of currently marketed fluoroquinolones and superior to other orally administered antimicrobial agents (cephalosporins, amoxicillin/clavulanate, and trimethoprim/sulfamethoxazole) when tested against more than 45,000 globally collected Enterobacteriaceae.

Emerging resistance phenotypes and antimicrobial resistance rates among pathogens recovered from community-acquired urinary tract infections (CA-UTI) is an increasing problem in specific regions, limiting therapeutic options. As part of the SENTRY Antimicrobial Surveillance Program, a total of 611 isolates were collected in 2003 from patients with CA-UTI presenting at Latin American medical centers. Each strain was tested in a central laboratory using Clinical Laboratory Standard Institute (CLSI) broth microdilution methods with appropriate controls. Escherichia coli was the leading pathogen (66%), followed by Klebsiella spp. (7%), Proteus mirabilis (6.4%), Enterococcus spp. (5.6%), and Pseudomonas aeruginosa (4.6%). Surprisingly high resistance rates were recorded for E. coli against first-line orally administered agents for CA-UTI, such as ampicillin (53.6%), TMP/SMX (40.4%), ciprofloxacin (21.6%), and gatifloxacin (17.1%). Decreased susceptibility rates to TMP/SMX and ciprofloxacin were also documented for Klebsiella spp. (79.1 and 81.4%, respectively), and P. mirabilis (71.8 and 84.6%, respectively). For Enterococcus spp., susceptibility rates to ampicillin, chloramphenicol, ciprofloxacin, and vancomycin were 88.2, 85.3, 55.9, and 97.1%, respectively. High-level resistance to gentamicin was detected in 24% of Enterococcus spp. Bacteria isolated from patients with CA-UTI in Latin America showed limited susceptibility to orally administered antimicrobials, especially for TMP/SMX and fluoroquinolones. Our results highlight the need for developing specific CA-UTI guidelines in geographic regions where elevated resistance to new and old compounds may influence prescribing decisions.

The antimicrobial susceptibility of 176 unusual non-fermentative gram-negative bacilli (NF-GNB) collected from Latin America region through the SENTRY Program between 1997 and 2002 was evaluated by broth microdilution according to the National Committee for Clinical Laboratory Standards (NCCLS) recommendations. Nearly 74% of the NF-BGN belonged to the following genera/species: Burkholderia spp. (83), Achromobacter spp. (25), Ralstonia pickettii (16), Alcaligenes spp. (12), and Cryseobacterium spp. (12). Generally, trimethoprim/sulfamethoxazole (MIC50, < 0.5 microg/ml) was the most potent drug followed by levofloxacin (MIC50, 0.5 microg/ml), and gatifloxacin (MIC50, 1 microg/ml). The highest susceptibility rates were observed for levofloxacin (78.3%), gatifloxacin (75.6%), and meropenem (72.6%). Ceftazidime (MIC50, 4 microg/ml; 83.1% susceptible) was the most active beta-lactam against B. cepacia. Against Achromobacter spp. isolates, meropenem (MIC50, 0.25 microg/ml; 88% susceptible) was more active than imipenem (MIC50, 2 microg/ml). Cefepime (MIC50, 2 microg/ml; 81.3% susceptible), and imipenem (MIC50, 2 microg/ml; 81.3% susceptible) were more active than ceftazidime (MIC50, >16 microg/ml; 18.8% susceptible) and meropenem (MIC50, 8 microg/ml; 50% susceptible) against Ralstonia pickettii. Since selection of the most appropriate antimicrobial agents for testing and reporting has not been established by the NCCLS for many of NF-GNB species, results from large multicenter studies may help to guide the best empiric therapy.

Oxazolidinones have become reliable clinical and candidate antimicrobial agents to be utilized for infections caused by multidrug-resistant Gram-positive cocci, especially vancomycin-resistant enterococci and methicillin-resistant staphylococci. However, mutational resistance of the ribosomal target has been described for several species. Longitudinal surveillance remains necessary to monitor for this evolving linezolid resistance pattern. A survey of linezolid and several comparison Gram-positive focused agents was initiated in 2002 (7971 strains, >99.0% compliance) for 54 participating sites in the United States, Canada, Europe (6 nations), Latin America (2 nations), and the Asia Pacific (2 nations). The 5 and 25 sites in Canada and the United States, respectively, submitted 200 strains each to a central laboratory for organism identification/confirmation and reference MIC processing. The 10 remaining nations had 200 strain samples from 1 to 4 separate institutions. Linezolid resistance (MIC >/= 8 microg/mL) was confirmed by alternative susceptibility testing methods (Etest, AB BIO Disk, Solna, Sweden; disk diffusion method) and target mutation characterization by PCR and sequence analysis. Linezolid activity against the 6 major organism groups did not vary between geographic areas. A total of 98.1% of linezolid MIC values were between 0.5 and 2 microg/mL, and only 0.5% of results were at 4 microg/mL, which included 32 Staphylococcus aureus (0.9%) and 5 (0.5%) enterococcal isolates. Linezolid resistance was detected in only 4 isolates (0.05%): 1 each Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium, and a viridans group Streptococcus. All 4 isolates had a G2576U mutation in the 23S rRNA target. Linezolid activity as outlined by these Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) Program results demonstrate sustained, near complete activity against contemporary Gram-positive isolates on 4 monitored continents and in centers utilizing oxazolidinones. Rare linezolid-resistant strains were identified in the United States only (0.05% resistance overall).

Carbapenem resistance among Pseudomonas aeruginosa and Acinetobacter spp. is becoming a critical therapeutic problem worldwide. The SENTRY Antimicrobial Surveillance Program monitors pathogen frequency and antimicrobial resistance patterns of nosocomial and community-acquired infections through sentinel hospitals on five continents. Pseudomonas spp. and Acinetobacter spp. strains resistant to imipenem (MIC, >/=16 mg/l), meropenem (MIC, >/=16 mg/l), and ceftazidime (MIC, >/=32 mg/l) collected from January 2001 to December 2003 were routinely screened for antimicrobial resistance genes. Resistant isolates were initially tested for metallo-beta-lactamase (MbetaL) production by phenotypic tests (disk approximation or MbetaL Etest strip) and then characterization of the MbetaL (hydrolysis assays, PCR for bla(IMP), bla(VIM), bla(SPM), gene sequencing). Eighty-nine isolates (33 Acinetobacter spp., 54 Pseudomonas aeruginosa, and 2 P. fluorescens) had positive phenotypic screening tests. Among those, 34 isolates producing MbetaL were identified, including 7 Acinetobacter spp., 25 P. aeruginosa and 2 P. fluorescens. The MbetaLs identified were IMP-1, VIM-2 and two newly described enzymes: SPM-1 and IMP-16. The greatest concentration of MbetaL strains was in Brazil, where imipenem-resistant P. aeruginosa increased significantly in the time period evaluated by the SENTRY Program. MbetaL-producing P. aeruginosa was detected in São Paulo (SPM-1) and Brasilia (SPM-1 and IMP-16), Brazil and Caracas, Venezuela (VIM-2); while MbetaL-producing Acinetobacter spp. isolates were detected in São Paulo, Brazil (IMP-1). P. fluorescens isolates producing IMP-1 and VIM-2 were detected in São Paulo, Brazil and Santiago, Chile, respectively. The emergence and dissemination of mobile MbetaL-producing isolates represent an alarming factor for increasing resistance to carbapenems in several medical centres evaluated by the SENTRY Program in Latin America.

The principal aim of this study was to evaluate the genomic diversity among the imipenem-nonsusceptible Acinetobacter spp. (INSA) collected from the Latin American medical centers within the SENTRY Antimicrobial Surveillance Program. The INSA isolates were collected from patients with bloodstream infections, who were hospitalized in seven Latin American countries between 1997 and 1999. For epidemiologic comparison, 20 carbapenem-susceptible Acinetobacter spp. (CSA) isolates were collected in the same period of time from the respective medical centers. A total of 23 Acinetobacter spp. isolates exhibiting imipenem MIC values of >/=8 microg/ml were typed by ribotyping, an automated molecular method. The isolates showing an identical ribogroup were also typed by pulsed-field gel electrophoresis (PFGE). The antimicrobial susceptibility to various antimicrobial agents was evaluated using a reference broth microdilution technique. Among the INSA isolates, 13 distinct ribogroups were observed, whereas 16 ribogroups were detected among the CSA. Nearly 57% of the INSA belonged to only four ribogroups. Identical ribogroups and PFGE patterns were observed among INSA and CSA isolates collected from medical centers located in different countries (Brazil and Argentina). Our results showed: (1) a higher genomic variability among the CSA; (2) presence of epidemic clones among INSA isolates encountered in Latin American medical centers; and (3) spread of INSA and CSA epidemic clones between Latin American countries.

Since January 2002 Pseudomonas sp. strains resistant to carbapenems and ceftazidime have been routinely screened as part of the SENTRY Antimicrobial Surveillance Program for metallo-beta-lactamase production, and their resistance determinants have been analyzed. Pseudomonas aeruginosa index strain 101-4704, which harbors a novel bla(IMP) variant, bla(IMP-16), was isolated in April 2002 from a 60-year-old man in Brasilia, Brazil. bla(IMP-16) was found on the chromosome of the P. aeruginosa index strain, and the deduced amino acid sequence (IMP-16) showed the greatest identities to IMP-11 (90.3%) and IMP-8 (89.5%). Sequence analysis revealed that bla(IMP-16) was associated with a class 1 integron, which also encoded aminoglycoside-modifying enzymes. Downstream of bla(IMP-16) resided an open reading frame, which consisted of a new aminoglycoside-modifying gene, namely, aac(6')-30, which was fused with aac(6')-Ib'. The amino acid sequence of the aac(6')-30 putative protein showed the most identity (52.7%) to the sequence of AAC(6')-29b described previously. The fourth gene cassette constituted aadA1. The steady-state kinetics of IMP-16 demonstrated that the enzyme preferred cephalosporins and carbapenems to penicillins. The main functional difference observed among the kinetic values for IMP-16 compared to those for other IMPs was a lack of cefoxitin hydrolysis and a lower kcat/Km value for imipenem (0.36 microM(-1) . s(-1)). This report further emphasizes the spread of metallo-beta-lactamase genes and their close association with various aminoglycoside resistance genes.

Objectives: This longitudinal study evaluated the in vitro activity of anidulafungin against 880 clinical yeast isolates and 68 mould isolates from 64 medical centres in North America, Latin America and Europe., Methods: MICs of anidulafungin, amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole and voriconazole were determined using reference method (M27-A2) guidelines. The M38-A reference method was used for the filamentous fungi, including determination of minimum effective concentrations (MECs) of anidulafungin., Results: Anidulafungin was more active when compared with fluconazole and itraconazole for Candida albicans (MIC(90), 0.06 mg/L), Candida tropicalis (MIC(90), 0.06 mg/L), Candida glabrata (MIC(90), 0.12 mg/L), Candida krusei (MIC(90), 0.06 mg/L) and Candida lusitaniae (MIC(90), 1 mg/L) as well as the less-often encountered yeast species. Anidulafungin was less active against Candida parapsilosis, Candida guilliermondii and Candida famata (MIC(50), 1-2 mg/L). Anidulafungin also exhibited excellent activity against all Aspergillus spp. (MEC(90), < or =0.03 mg/L). Anidulafungin was also evaluated comparing two end point reading criteria and two incubation intervals. Data indicate that longer incubation periods do not significantly influence overall MIC ranges. These international surveillance results for anidulafungin confirm the activity observed in studies of smaller numbers of isolates.

The alarming emergence and spread of antimicrobial resistance among common bacteria threatens the effectiveness of therapy for many infections. Surveillance of antimicrobial resistance is essential to identify the major problems and guide adequate control measures. Several resistance surveillance programs have been implemented in North America and Europe in the last decade; however, very few programs have assessed antimicrobial resistance in Latin American countries. The SENTRY Antimicrobial Surveillance Program was initiated in 1997 and represents the most comprehensive surveillance program in place at the present time worldwide. The SENTRY Program collects consecutive isolates from clinically documented infections in more than 80 medical centers worldwide (10 in Latin America). The isolates are collected according to the type of infection (objectives) and susceptibility tested in a central microbiology laboratory by reference broth microdilution methods according to NCCLS guidelines. The Program also incorporated molecular typing (ribotyping and PFGE) and resistance mechanism analysis of selected isolates. In this report we present a very broad analysis of the data generated by testing almost 20,000 bacterial isolates against more than 30 antimicrobial agents. The susceptibility results (MIC(50), MIC(90) and % susceptible) are presented in 11 tables according to the organism and site of infection. The data from Brazil, as well as the data from isolates collected in 2001, are analyzed separately. This report allows the evaluation of the activities numerous antimicrobial agents against clinical isolates collected in Latin American countries.

As part of the Latin American arm of the SENTRY Antimicrobial Surveillance Program, 7,207 bacterial isolates collected consecutively from bloodstream infections (BSI) during the period of January 1997 through December 2000 were analyzed. Ten Latin American laboratories located in six countries participated in the study during each year. Antimicrobial susceptibility testing was performed using the reference NCCLS broth microdilution method. The most frequently isolated species were (n/%): Staphylococcus aureus (1,532/21.3%), Escherichia coli (1,239/17.2%), coagulase-negative Staphylococcus (1,002/13.9%), Klebsiella pneumoniae (664/9.2%), and Pseudomonas aeruginosa (470/6.5%). The prevalence of S. aureus as a cause of BSI increased from 20.5% in 1997 to 23.3% in 2000 (p = 0.011), but oxacillin-resistance rates remained relatively stable during this period (around 30%). Enterococci (216 isolates) showed low rates of resistance to both vancomycin (2.4%) and ampicillin (7.9%) and 72.7% of 289 Streptococcus pneumoniae isolates evaluated were susceptible to penicillin (MIC

We report the results of pathogen frequency and antimicrobial susceptibility of isolates collected from skin and soft tissue infections (SSTIs) in Latin American medical centers during the first 4 years (1997-2000) of the SENTRY Antimicrobial Surveillance Program. Ten laboratories participated each year distributed among nine cities in six countries. A total of 1,789 bacterial isolates were susceptibility tested by reference broth microdilution at the coordinating central laboratory. Results from isolates collected during the year 2000 were compared with those from isolates collected during the prior three years. Selected carbapenem-resistant Pseudomonas aeruginosa were genotyped by automated ribotyping to evaluate the occurrence of clonal, epidemic dissemination. The five most frequently isolated species were (n/%): Staphylococcus aureus (584/32.8%), Escherichia coli (233/13.1%), P. aeruginosa (211/11.9%), Enterococcus spp. (137/7.7%), and Klebsiella spp. (127/5.8%). The most problematic antimicrobial resistances were related to the high prevalence of multi-drug resistant (MDR) Gram-negative bacilli. Carbapenem resistance among non-fermentative Gram-negative bacilli was much higher than that reported in other regions evaluated in the SENTRY Program. Only 74.9% of P. aeruginosa and 84.9% of Acinetobacter spp. were considered susceptible to imipenem. The antimicrobial susceptibility rates of P. aeruginosa decreased during the study period for most antimicrobial agents evaluated. More than 40% of K. pneumoniae and nearly 10% of E. coli showed an extended spectrum beta-lactamase phenotype. Only 73.4% of E. coli and 76.0% of Enterobacter spp. were susceptible to ciprofloxacin. The molecular typing of carbapenem-resistant P. aeruginosa demonstrated clonal dissemination in two institutions. These reported results indicate that rates of resistance among isolates causing SSTI continue to raise in Latin America, with specific concerns for the high prevalence of MDR Gram-negative bacilli. National and international surveillance programs as a guide to focusing intervention strategies should assist in the control of escalating antimicrobial resistance in this geographic area.

Urinary tract infections (UTI) are one of the most common infectious diseases diagnosed in outpatients as well as in hospitalized patients. The objective of this study was to report the frequency of occurrence and antimicrobial susceptibility of uropathogens collected in Latin America between 1997 to 2000 through the SENTRY Antimicrobial Surveillance Program. Antimicrobial susceptibility testing was performed and results interpreted using reference broth microdilution methods. In the 4 year period, a total of 1961 urine isolates from hospitalized patients were included. The patients' mean age was 51.3 years and most of the infections occurred among women (65.6%). Esherichia coli was the most frequent pathogen isolated followed by Klebsiella spp., Pseudomonas aeruginosa, and Proteus mirabilis. Among the E. coli isolates, piperacillin/tazobactam, aztreonam, extended-spectrum cephalosporins, carbapenems and amikacin constitute reasonable therapeutic options for treatment of serious UTI in Latin America (91.0-100.0% susceptible). High resistance rates to fluoroquinolones (17.5-18.9%) and trimethoprim/sulfamethoxazole (>45.0%) were observed among the E. coli. In contrast, nitrofurantoin displayed susceptibility rate of > 87.0%. Against Klebsiella spp. infections, the only effective therapeutic option would be the carbapenems due to the high number of isolates (>30.0%) producing extended-spectrum beta-lactamases (ESBL). Even the new fluoroquinolones showed limited activity against Klebsiella spp. (72.1-88.6% susceptible) and the P. aeruginosa isolates showed high resistance rates to most antimicrobial agents tested. The results of this survey endorse the importance of Enterobacteriaceae as cause of UTI in Latin America. Our results also demonstrate that the uropathogens isolated in the Latin American medical centers exhibit high resistance to various classes of antimicrobial agents. Carbapenem-resistant P. aeruginosa, ciprofloxacin-resistant E. coli, ESBL-producing K. pneumoniae constitute serious problem in this geographic region.

Recent years have seen a dramatic rise in the incidence and severity of cases of human salmonellosis. In addition, multidrug resistant strains have arisen. The objective of this study was to characterize the antimicrobial susceptibility profile of Salmonella spp. clinical isolates collected from Latin American medical centers as part of the SENTRY Antimicrobial Surveillance System. A total of 144 bloodstream Salmonella spp. isolates were collected between 1997 and 2000. The susceptibility to diverse antimicrobial agents was tested by broth microdilution techniques according to the NCCLS recommendations. The Salmonella spp. strains were more frequently collected from adult patients (67.0%; 21-60 years) and isolated from Chile (28.5%) > Brazil (25.0%) > Mexico (18.8%) > Colombia (11.8%). Ampicillin (MIC(50), 1 microg/ml) showed good in vitro activity (92.4% susceptibility). Meropenem (MIC(50), 0.06 microg/ml) and gatifloxacin (MIC(50), 0.03 microg/ml) were the most potent compounds against the Salmonella spp. isolates (100.0% susceptible) followed by piperacillin/tazobactam (99.3%), ceftazidime (98.6%), ceftriaxone (98.6%), and amoxicillin/clavulanic acid (94.4%). The lowest susceptibility rates were observed for tetracycline (87.5%) and trimethoprim/sulfamethoxazole (91.7%). Four of 144 (2.8%) Salmonella spp. isolates demonstrated an ESBL phenotype; however, only two (1.4%) were confirmed as an inhibitable ESBL producer. The results of this study show that multidrug resistance, especially fluoroquinolone resistance, does not represent a serious problem among Salmonella isolates collected from the Latin American medical centers as monitored by the SENTRY Program.