Antimicrobial Susceptibility of Acinetobacter calcoaceticus-Acinetobacter baumannii Complex and Stenotrophomonas maltophilia Clinical Isolates: Results From the SENTRY Antimicrobial Surveillance Program (1997-2016).

BACKGROUND: Acinetobacter calcoaceticus-A. baumannii (Acb) complex and Stenotrophomonas maltophilia represent frequent causes of hospital-acquired infections. We evaluated the frequency and resistance rates of Acb complex and S. maltophilia isolates from medical centers enrolled in the SENTRY Program. METHODS: A total of 13 752 Acb complex and 6467 S. maltophilia isolates were forwarded to a monitoring laboratory by 259 participating sites from the Asia-Pacific region, Latin America, Europe, and North America between 1997 and 2016. Confirmation of species identification and antimicrobial susceptibility testing were performed using conventional methods and/or matrix-assisted laser desorption ionization-time of flight mass spectrometry and the broth microdilution method, respectively. Antimicrobial susceptibility results were interpreted by CLSI and EUCAST 2018 criteria. RESULTS: Acb complex and S. maltophilia were most frequently isolated from patients hospitalized with pneumonia (42.9% and 55.8%, respectively) and bloodstream infections (37.3% and 33.8%, respectively). Colistin and minocycline were the most active agents against Acb complex (colistin MIC50/90, ≤0.5/2 mg/L; 95.9% susceptible) and S. maltophilia (minocycline MIC50/90, ≤1/2 mg/L; 99.5% susceptible) isolates, respectively. Important temporal decreases in susceptibility rates among Acb complex isolates were observed for all antimicrobial agents in all regions. Rates of extensively drug-resistant Acb complex rates were highest in Europe (66.4%), followed by Latin America (61.5%), Asia-Pacific (56.9%), and North America (38.8%). Among S. maltophilia isolates, overall trimethoprim-sulfamethoxazole (TMP-SMX) susceptibility rates decreased from 97.2% in 2001-2004 to 95.7% in 2013-2016, but varied according to the geographic region. CONCLUSIONS: We observed important reductions of susceptibility rates to all antimicrobial agents among Acb complex isolates obtained from all geographic regions. In contrast, resistance rates to TMP-SMX among S. maltophilia isolates remained low and relatively stable during the study period.

Ceftolozane-tazobactam activity against drug-resistant Enterobacteriaceae and Pseudomonas aeruginosa causing healthcare-associated infections in Latin America: report from an antimicrobial surveillance program (2013-2015)

ABSTRACT 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 (MIC50/90, 0.25/32 µg/mL; 84.2% susceptible) and meropenem (MIC50/90, ≤0.06/0.12 µg/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 (MIC50/90, 0.5/>32 µg/mL), it lacked useful activity against strains with a (MIC50/90, >32/>32 µg/mL; 1.6% S) carbapenem-resistant phenotype. Ceftolozane-tazobactam was the most potent (MIC50//90, 0.5/16 µg/mL) β-lactam agent tested against P. aeruginosa isolates, inhibiting 86.8% at an MIC of ≤4 µg/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.

Ceftolozane-tazobactam activity against drug-resistant Enterobacteriaceae and Pseudomonas aeruginosa causing healthcare-associated infections in Latin America: report from an antimicrobial surveillance program (2013-2015).

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 ß-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 (MIC50/90, 0.25/32µg/mL; 84.2% susceptible) and meropenem (MIC50/90, ≤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 ß-lactamase non-carbapenem-resistant phenotype. Whereas ceftolozane-tazobactam showed good activity against extended-spectrum beta-lactamase, non-carbapenem-resistant phenotype strains of Enterobacteriaceae (MIC50/90, 0.5/>32µg/mL), it lacked useful activity against strains with a (MIC50/90, >32/>32µg/mL; 1.6% S) carbapenem-resistant phenotype. Ceftolozane-tazobactam was the most potent (MIC50//90, 0.5/16µg/mL) ß-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 ß-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than available cephalosporins and piperacillin-tazobactam when tested against Enterobacteriaceae.

Ceftaroline activity tested against contemporary Latin American bacterial pathogens (2011)

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 againstStaphylococcus aureus (42.8% MRSA) with 83.6% of the isolates at <1mg/L and all isolates at <2mg/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/<0.015mg/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, 4mg/L) strains. AllHaemophilus 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.

Ceftaroline activity tested against contemporary Latin American bacterial pathogens (2011).

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% ß-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.

Spectrum and potency of ceftaroline against leading pathogens causing community-acquired respiratory tract and skin and soft tissue infections in Latin America, 2010

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with in vitro bactericidal activity against Gram-positive organisms, including methicillinsusceptible 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 (0.12 µg/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 (MIC90,1 µg/mL) and linezolid (MIC90,2 Jg/mL). The 1-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 These parenteral cephalosporin agents have potent activity against non-extended-spectrum-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 communityacquired 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.

Spectrum and potency of ceftaroline against leading pathogens causing community-acquired respiratory tract and skin and soft tissue infections in Latin America, 2010.

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, ß-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 ß-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 ß-lactamase-phenotype strains, but are not active against extended-spectrum ß-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.

An international activity and spectrum analysis of linezolid: ZAAPS Program results for 2011.

Through a continuing resistance surveillance monitoring program, linezolid was shown to maintain its spectrum and potency against a collection of 8059 clinically relevant Gram-positive strains collected from patients at 79 medical centers in 33 countries and Hong Kong. Linezolid MIC90 values were 2 µg/mL for methicillin-resistant and -susceptible Staphylococcus aureus and enterococci, and the MIC90 value was 1 µg/mL for coagulase-negative staphylococci (CoNS), ß-hemolytic streptococci, Streptococcus pneumoniae, and viridans group streptococci. Reference broth microdilution susceptibility testing for linezolid demonstrated a 99.83% susceptibility rate for all organisms. All S. aureus were inhibited by ≤2 µg/mL. Three (0.3%) of 928 strains of CoNS had a linezolid MIC of 4 µg/mL and contained the cfr resistance gene; 1 also had a mutation in L3. There were 14 linezolid-resistant strains detected from 7 countries (Brazil [5], France [1], Germany [2] Greece [2], Italy [2], Ireland [1], and Spain [1]) representing 5 species (E. faecium, S. capitis, S. epidermidis, S. hominis, S. lugdenensis). A mobile cfr gene was noted in 2 species having elevated linezolid MIC values; one was a S. haemolyticus isolate with a MIC at 4 µg/mL. Resistance rates were as follows for the 6 groups of organisms sampled in the 2011 ZAAPS Program: CoNS, 1.2%; enterococci, 0.39%; among S aureus, S. pneumoniae, viridans group streptococci, and ß-hemolytic streptococci, no resistance was detected. As the activities of commonly used antimicrobials continue to be compromised by evolving resistance mechanisms in Gram-positive pathogens, linezolid-resistant strains remain uncommon and without increasing occurrence.

Antimicrobial resistance among Gram-negative bacilli isolated from Latin America: results from SENTRY Antimicrobial Surveillance Program (Latin America, 2008-2010).

This study updates the frequency and resistance rates of Gram-negative bacilli isolated from Latin American medical centers enrolled in the SENTRY Antimicrobial Surveillance Program. A total of 12,811 bacterial organisms, including 5704 Gram-negative bacilli (44.5%), were consecutively collected (1 per patient) between January 2008 and December 2010 from 10 Latin American medical centers located in Argentina, Brazil, Chile, and Mexico. Antimicrobial susceptibility testing was performed and interpreted by the Clinical and Laboratory Standards Institute broth microdilution method at a central laboratory. All Gram-negative organisms with reduced susceptibility to imipenem or meropenem (MIC, ≥ 2 µg/mL) were screened for carbapenemase production by the modified Hodge test and by polymerase chain reaction. ESBL rates were 18.1%, 12.8%, 23.8%, and 48.4% among Escherichia coli and 60.4%, 49.9%, 59.2%, and 33.3% among Klebsiella spp. from Argentina, Brazil, Chile, and Mexico, respectively. Meropenem-nonsusceptible Klebsiella spp. rate was highest in Brazil (11.1%), followed by Argentina (8.2%), Chile (5.0%), and Mexico (0.8%). Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae was not detected in 2008, but emerged in 2009 (10 strains) and increased significantly in 2010 (44; P < 0.0001). bla(KPC-2) was detected in 54 (65.9%) of 85 carbapenem-nonsusceptible K. pneumoniae. Meropenem-nonsusceptible P. aeruginosa was observed in 53.8%, 46.7%, 33.3%, and 28.8% of strains from Argentina, Brazil, Chile, and Mexico, respectively. Imipenem-resistant Acinetobacter spp. rates increased from 6.4%, 12.6%, and 0.0% in the 1997-1999 period to 84.9%, 71.4%, and 50.0% in 2008-2010 in Argentina, Brazil, and Chile, respectively. Oxacillinase (OXA)-producing Acinetobacter spp. was documented in Argentina (OXA-23 and -24), Brazil (OXA-23), Chile (OXA-58), and Mexico (OXA-24). Only colistin showed >77% overall coverage against the 5 most frequently isolated Gram-negative bacilli from Latin American Medical centers participating in the SENTRY Program.

Resistance trends in gram-negative bacteria: surveillance results from two Mexican hospitals, 2005-2010.

BACKGROUND: Hospital-acquired infections caused by multiresistant gram-negative bacteria are difficult to treat and cause high rates of morbidity and mortality. The analysis of antimicrobial resistance trends of gram-negative pathogens isolated from hospital-acquired infections is important for the development of antimicrobial stewardship programs. The information obtained from antimicrobial resistant programs from two hospitals from Mexico will be helpful in the selection of empiric therapy for hospital-acquired gram-negative infections. FINDINGS: Two thousand one hundred thirty two gram-negative bacteria collected between January 2005 and December 2010 from hospital-acquired infections occurring in two teaching hospitals in Mexico were evaluated. Escherichia coli was the most frequently isolated gram-negative bacteria, with >50% of strains resistant to ciprofloxacin and levofloxacin. Klebsiella spp. showed resistance rates similar to Escherichia coli for ceftazidime (33.1% vs 33.2%), but exhibited lower rates for levofloxacin (18.2% vs 56%). Of the samples collected for the third most common gram-negative bacteria, Pseudomonas aeruginosa, >12.8% were resistant to the carbapenems, imipenem and meropenem. The highest overall resistance was found in Acinetobacter spp. Enterobacter spp. showed high susceptibility to carbapenems. CONCLUSIONS: E. coli was the most common nosocomial gram-negative bacilli isolated in this study and was found to have the second-highest resistance to fluoroquinolones (>57.9%, after Acinetobacter spp. 81.2%). This finding represents a disturbing development in a common nosocomial and community pathogen.

Contemporary activity of colistin and polymyxin B against a worldwide collection of Gram-negative pathogens: results from the SENTRY Antimicrobial Surveillance Program (2006-09).

OBJECTIVES: To comparatively evaluate the antimicrobial activities of colistin and polymyxin B with those of other antimicrobials against a worldwide collection of 40 625 Gram-negative bacilli. METHODS: Antimicrobial susceptibility testing was performed and interpreted using the CLSI broth microdilution method except for colistin against Enterobacteriaceae. RESULTS: The polymyxins showed potent in vitro activities (MIC90, ≤ 0.5-1 mg/L) against this large collection of clinical isolates, with very low resistance rates (< 0.1%-1.5%). Resistance to the polymyxins remained stable among organisms tested except for Klebsiella spp. isolates collected from the Asia-Pacific and Latin American regions, where a trend towards greater resistance was observed (P  ≤  0.05). In addition, an important reduction in imipenem susceptibility among Acinetobacter spp. and Klebsiella spp. was demonstrated in most geographical regions. CONCLUSIONS: Although the polymyxins showed excellent in vitro activity against the vast majority of Gram-negative bacilli evaluated, a trend to greater resistance was observed in the Asia-Pacific and Latin American regions. Therefore, the clinical use of polymyxins must be cautious and surveillance monitored.

Antimicrobial susceptibility patterns of KPC-producing or CTX-M-producing Enterobacteriaceae.

Enterobacteriaceae clinical isolates harboring KPC-(178 strains) or CTX-M-encoding (67 strains) genes were collected during surveillance programs in the 2000-2007 period; and susceptibility was tested by broth microdilution methods. Organisms were dominantly collected in U.S. hospitals (93%). CTX-M-15 and -14 were the most prevalent CTX-M types (97%), all collected from the United States. KPC producers were isolated in the United States (160/178), Israel, China, and Argentina. bla(CTX-M)-carrying isolates were 95.5 and 98.5%, susceptible to Imipenem and meropenem respectively, and were all susceptible to tigecycline, whereas KPC-producing isolates were highly resistant to all antimicrobials tested except polymyxin B and tigecycline (90.6% and 99.4% susceptibility, respectively). The occurrence of KPC-producing and CTX-M-producing isolates has rapidly increased especially in U.S. hospitals, and expanded therapeutic options are needed to treat infections caused by these emerging organisms.

Antimicrobial susceptibility of gram-positive bacteria isolated in brazilian hospitals participating in the SENTRY Program (2005-2008)

We report the antimicrobial susceptibility patterns of the most frequently isolated Gram-positive bacteria in the Brazilian hospitals participating in the SENTRYAntimicrobial Surveillance Program. The strains were consecutively collected (one per patient) between January 2005 and September 2008 and susceptibility tested by reference broth microdilution methods at the JMI Laboratories (North Liberty, Iowa, USA). A total of 3,907 Gram-positive cocci were analyzed. The Gram-positive organisms most frequently isolated from bloodstream infections were Staphylococcus aureus (2,218 strains; 20.2 percent of total), coagulase-negative staphylococci (CoNS; 812 strains [14.7 percent]), and Enterococcus spp. (754 strains; 5.0 percent). S. aureus ranked first (28.1 percent) and Enterococcus faecalis ranked 7th (4.5 percent) among cases of skin and soft tissue infections. S. aureus was also the second most frequently isolated pathogen from patients with lower respiratory tract infections (24.9 percent of cases) after Pseudomonas aeruginosa (30.5 percent). Resistance to oxacillin was observed in 31.0 percent of S. aureus and the vast majority of oxacillin-resistant (MRSA) strains were also resistant to clindamycin, ciprofloxacin and levofloxacin. Vancomycin, linezolid and daptomycin were all very active against S. aureus strains tested (>99.9-100.0 percent susceptible), but daptomycin (MIC50, 0.25 g/mL and MIC90, 0.5 g/mL) was four- to eight-fold more potent than vancomycin (MIC50 and MIC90 of 1 g/mL) and linezolid (MIC50, 1 g/mL and MIC90, 2 g/mL). Vancomycin resistance increased significantly among enterococci during the study period, but it was restrict to only one medical center until 2007 and emerged in a second medical center in 2008. Daptomycin was the most active antimicrobial tested against enterococci in general (100.0 percent susceptible), followed by linezolid (99.9 percent susceptible), ampicillin (87.4 percent) and vancomycin (84.6 percent)...

Dissemination of a bla(VIM-2)-carrying integron among Enterobacteriaceae species in Mexico: report from the SENTRY Antimicrobial Surveillance Program.

Three VIM-2-producing Enterobacteriaceae (two Enterobacter cloacae and one Klebsiella oxytoca) isolates recovered from patients in a Mexican hospital were characterized during the SENTRY Antimicrobial Surveillance Program (2005-2007). These strains carried identical bla(VIM-2) integrons in a 450-kb plasmid. The interspecies dissemination of this bla(VIM-2)-harboring element emphasizes the potential for spread of genetic structures carrying metallo-beta-lactamases that could limit therapeutic options in this geographic region.

TR-700 in vitro activity against and resistance mutation frequencies among Gram-positive pathogens.

BACKGROUND: TR-700, the active component of the oxazolidinone prodrug TR-701, has demonstrated potent activity against numerous Gram-positive species. In this study, single-step mutation frequencies, passaging and the activity of TR-700 were tested against a worldwide collection of linezolid-non-susceptible organisms and matched controls. METHODS: One hundred and twenty linezolid-non-susceptible and 120 controls matched by genus/species, geographic origin, site of infection and time were susceptibility tested by reference broth microdilution methods. Species of isolates were: Enterococcus faecalis (16 linezolid non-susceptible/16 wild-type strains); Enterococcus faecium (55/55), Staphylococcus aureus (8/8); coagulase-negative staphylococci (at least 7 spp., 40/40) and viridans group streptococci (2 spp., 1/1). 23S rRNA target mutations or cfr genes were detected by PCR and sequencing. RESULTS: Among linezolid-non-susceptible strains, the resistance mechanisms were G2576T (109), cfr (4) and unknown (7), with strains originating from Europe, Far East and North and South America. Most strains were multidrug-resistant and cfr isolates exhibited co-resistance to phenicols, clindamycin, linezolid, pleuromutilins and streptogramin B. TR-700 MIC values, regardless of species, were 4-32-fold lower than those of linezolid. TR-700 MIC results were < or = 4, < or = 8 or < or = 16 mg/L for 88%, 96% and > 99% of linezolid-non-susceptible strains, respectively. Spontaneous single-step mutations were undetected (<1.1 x 10(-9)) and 14 day passaging studies produced modest TR-700 MIC elevations compared with linezolid controls. CONCLUSIONS: TR-700 exhibited enhanced activity against linezolid-non-susceptible and wild-type control strains of Gram-positive cocci. A significant number (nearly 90%) of linezolid-non-susceptible strains were inhibited by potentially achievable levels (< or = 4 mg/L) of TR-700. All strains with the emerging cfr-mediated resistance determinant had TR-700 MIC results at < or = 8 mg/L.

Antimicrobial susceptibility of gram-positive bacteria isolated in Brazilian hospitals participating in the SENTRY Program (2005-2008).

We report the antimicrobial susceptibility patterns of the most frequently isolated Gram-positive bacteria in the Brazilian hospitals participating in the SENTRY Antimicrobial Surveillance Program. The strains were consecutively collected (one per patient) between January 2005 and September 2008 and susceptibility tested by reference broth microdilution methods at the JMI Laboratories (North Liberty, Iowa, USA). A total of 3,907 Gram-positive cocci were analyzed. The Gram-positive organisms most frequently isolated from bloodstream infections were Staphylococcus aureus (2,218 strains; 20.2% of total), coagulase-negative staphylococci (CoNS; 812 strains [14.7%]), and Enterococcus spp. (754 strains; 5.0%). S. aureus ranked first (28.1%) and Enterococcus faecalis ranked 7th (4.5%) among cases of skin and soft tissue infections. S. aureus was also the second most frequently isolated pathogen from patients with lower respiratory tract infections (24.9% of cases) after Pseudomonas aeruginosa (30.5%). Resistance to oxacillin was observed in 31.0% of S. aureus and the vast majority of oxacillin-resistant (MRSA) strains were also resistant to clindamycin, ciprofloxacin and levofloxacin. Vancomycin, linezolid and daptomycin were all very active against S. aureus strains tested (>99.9-100.0% susceptible), but daptomycin (MIC(50), 0.25 g/mL and MIC(90), 0.5 g/mL) was four- to eight-fold more potent than vancomycin (MIC(50) and MIC(90) of 1 g/mL) and linezolid (MIC(50), 1 g/mL and MIC(90), 2 g/mL). Vancomycin resistance increased significantly among enterococci during the study period, but it was restrict to only one medical center until 2007 and emerged in a second medical center in 2008. Daptomycin was the most active antimicrobial tested against enterococci in general (100.0% susceptible), followed by linezolid (99.9% susceptible), ampicillin (87.4%) and vancomycin (84.6%). In conclusion, daptomycin and linezolid showed excellent in vitro activity against contemporary Gram-positive organisms (3,907) collected in Brazilian hospitals monitored by the SENTRY Program, including MRSA, vancomycin-resistant enterococci (VRE) and other multi-drug-resistant organisms. Although vancomycin resistance rates in Brazil appears to be relatively low compared to those reported in the USA, VRE has emerged and rapidly disseminated in some Brazilian medical centers.

Tigecycline activity tested against 11808 bacterial pathogens recently collected from US medical centers.

Tigecycline activity was evaluated against 11808 pathogens isolated from 30 US medical centers. Susceptibility testing was performed by reference broth microdilution methods. Tigecycline (MIC(50/90), 0.12/0.25 microg/mL) was highly active against Staphylococcus aureus and coagulase-negative staphylococci, regardless of oxacillin resistance. This glycylcycline (MIC(50), 0.12 microg/mL) was 8- and 16-fold more potent than penicillin and linezolid against enterococci and was the most potent agent tested versus Streptococcus pneumoniae. Against Enterobacteriaceae, tigecycline (MIC(90), 1 microg/mL; 98.9% susceptible) was as active as imipenem. This study demonstrated the sustained potency of tigecycline against contemporary clinically relevant Gram-positive and Gram-negative pathogens; tigecycline resistance was rare (0.3%).

Evaluation of the susceptibility profiles, genetic similarity and presence of qnr gene in Escherichia coli resistant to ciprofloxacin isolated in Brazilian hospitals.

Increasing quinolone resistance has been reported worldwide, mainly among clinical isolates of Escherichia coli. The objectives of this study were to determine the susceptibility profile, the genetic relatedness, and the prevalence of the qnr gene among ciprofloxacin-resistant Escherichia coli isolated from distinct Brazilian hospitals. A total of 144 ciprofloxacin-resistant Escherichia coli were isolated from 17 Brazilian hospitals between January/2002 and June/2003. The antimicrobial susceptibility testing was performed by microdilution according to NCCLS. The presence of the qnr gene was initially screened by colony blotting, and then confirmed by PCR followed by DNA sequencing. Ninety-five urinary ciprofloxacin-resistant Escherichia coli were further selected for molecular typing by pulsed-field gel electrophoresis (PFGE). Imipenem and meropenem showed the highest susceptibility rates (100.0% for both compounds) followed by amikacin (91.0%) and piperacillin/tazobactan (84.8%). A single ciprofloxacin-resistant Escherichia coli isolate was positive for qnr among the 144 ciprofloxacin-resistant Escherichia coli. Forty-six PFGE patterns were observed among the 95 ciprofloxacin-resistant Escherichia coli type. This study shows that therapeutic options are limited for treatment of ciprofloxacin-resistant Escherichia coli due to the presence of additional mechanisms of antimicrobial resistance, such as ESBL production. The qnr gene was uncommon among ciprofloxacin-resistant Escherichia coli clinical isolates, but its identification might indicate the emergence of this mechanism of quinolone resistance in Brazil. The great genomic variability found among the ciprofloxacin-resistant Escherichia coli highlights the importance of the appropriate use of quinolone to restrict the selection of resistant isolates.