In vitro susceptibility of ceftolozane/tazobactam against typhoidal, non-typhoidal and extended spectrum β-lactamase-producing Salmonella

2021 ◽  
Author(s):  
Jade L. L. Teng ◽  
Elaine Chan ◽  
Asher C. H. Dai ◽  
Gillian Ng ◽  
Tsz Tuen Li ◽  
...  
Keyword(s):  
United States ◽  
Antimicrobial Agents ◽  
The United States ◽  
Drug Resistant ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Extended Spectrum ◽  
Control And Prevention ◽  
Esbl Producers

Both typhoidal and non-typhoidal salmonellae are included in the top 15 drug-resistant threats described by the Center for Disease Control and Prevention of the United States. There is an urgent need to look for alternative antibiotics for the treatment of Salmonella infections. We examined the in vitro susceptibilities of ceftolozane/tazobactam and six other antibiotics on typhoidal and non-typhoidal salmonellae, including isolates that are extended-spectrum β-lactamase (ESBL)-positive, using the broth microdilution test. Of the 313 (52 typhoidal and 261 non-typhoidal) Salmonella isolates tested, 98.7% were susceptible to ceftolozane/tazobactam. Based on the overall MIC 50/90 values, Salmonella isolates were more susceptible to ceftolozane/tazobactam (0.25/0.5 mg/L) compared to all other comparator agents: ampicillin (≥64/≥64 mg/L), levofloxacin (0.25/1 mg/L), azithromycin (4/16 mg/L), ceftriaxone (≤0.25/4 mg/L), chloramphenicol (8/≥64 mg/L) and trimethoprim/sulfamethoxazole (1/≥8 mg/L). When comparing the activity of the antimicrobial agents against non-typhoidal Salmonella isolates according to their serogroup, ceftolozane/tazobactam had the highest activity (100%) against Salmonella serogroups D, G, I and Q isolates, whereas the lowest activity (85.7%) was observed against serogroup E isolates. All the 10 ESBL-producing Salmonella (all non-typhoidal) isolates, of which 8 were CTX-M-55-producers and 2 were CTX-M-65-producers, were sensitive to ceftolozane/tazobactam albeit with a higher MIC 50/90 value (1/2 mg/L) than non-ESBL-producers (0.25/0.5 mg/L). In summary, our data indicate that ceftolozane/tazobactam is active against most strains of both typhoidal and non-typhoidal salmonellae and also active against ESBL-producing salmonellae.

Assessment of Laboratory Performance With Streptococcus pneumoniae Antimicrobial Susceptibility Testing in the United States

1999 ◽  
Vol 123 (4) ◽  
pp. 285-289 ◽  
Author(s):  
Gary V. Doern ◽  
Angela B. Brueggemann ◽  
Michael A. Pfaller ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Streptococcus Pneumoniae ◽  
Antimicrobial Agents ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
The United States ◽  
National Committee ◽  
In Vitro Susceptibility ◽  
Susceptibility Tests

Abstract Objective.—To assess the performance of clinical microbiology laboratories in the United States when conducting in vitro susceptibility tests with Streptococcus pneumoniae. Methods.—The results of a nationwide College of American Pathologists Proficiency Survey test sample, in which susceptibility testing of an isolate of S pneumoniae was performed, were assessed with respect to precision and accuracy. Results.—Wide variability was noted among participating laboratories with both minimum inhibitory concentration procedures and disk diffusion susceptibility tests when both methods were applied to S pneumoniae. Despite this high degree of variation, categorical interpretive errors were uncommon. Numerous laboratories reported results for antimicrobial agents that are not recommended by the National Committee for Clinical Laboratory Standards for tests with S pneumoniae. Conclusions.—Current susceptibility testing practices with S pneumoniae in the United States indicate limited precision and a tendency for laboratories to test and report results obtained with antimicrobial agents of questionable therapeutic value against this organism. Continued efforts to standardize susceptibility testing of S pneumoniae in the United States are warranted. In addition, modifications of existing interpretive criteria may be necessary.

scholarly journals Activity of Ceftolozane-Tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae Isolates Collected from Respiratory Tract Specimens of Hospitalized Patients in the United States during 2013 to 2015

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Mariana Castanheira ◽  
Leonard R. Duncan ◽  
Rodrigo E. Mendes ◽  
Helio S. Sader ◽  
Dee Shortridge
Keyword(s):  
United States ◽  
Pseudomonas Aeruginosa ◽  
The United States ◽  
Drug Resistant ◽  
Broth Microdilution ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Encoding Genes ◽  
M 14

ABSTRACT The activities of ceftolozane-tazobactam and comparator agents against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States during 2013 to 2015 were evaluated. Organisms included 1,576 Pseudomonas aeruginosa and 2,362 Enterobacteriaceae isolates susceptibility tested using reference broth microdilution methods. Ceftolozane-tazobactam, cefepime, ceftazidime, meropenem, and piperacillin-tazobactam inhibited 96.3%, 84.8%, 83.5%, 80.0%, and 78.6%, respectively, of the P. aeruginosa isolates. Ceftolozane-tazobactam inhibited 77.5 to 85.1% of isolates nonsusceptible to antipseudomonal β-lactams and 86.6% and 71.0% of the 372 (23.6% overall) multidrug- and 155 (9.8%) extensively drug-resistant isolates tested. The activity of this combination was greater than those of other β-lactams evaluated against P. aeruginosa groups across all U.S. census divisions. Ceftolozane-tazobactam was active against 90.6% of the Enterobacteriaceae , being less active than only meropenem (95.6% susceptible) among the β-lactams evaluated. Against 145 Escherichia coli and Klebsiella pneumoniae isolates carrying extended-spectrum-β-lactamase (ESBL)-encoding genes without carbapenemases, ceftolozane-tazobactam inhibited 82.8% of these isolates and was more active than cefepime and piperacillin-tazobactam (15.2% and 74.3% susceptible, respectively). ESBL genes included in this analysis were mainly bla CTX-M-15 -like (89 isolates) and bla CTX-M-14 -like (22) genes but also bla SHV (31) and bla TEM (3). Ceftolozane-tazobactam also displayed activity (84.6% susceptible) against 13 isolates harboring acquired AmpC genes. All β-lactams displayed limited activity against bla KPC -carrying isolates. Ceftolozane-tazobactam was the most active β-lactam tested against P. aeruginosa isolates from isolates that were the probable cause of pneumonia and displayed in vitro activity against Enterobacteriaceae , including isolates resistant to cephalosporins and carrying ESBL genes.

scholarly journals 1593. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Against OXA-48 β-lactamase–Producing Enterobacterales Collected in International Medical Centers, Including the United States, in 2017–2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S793-S793
Author(s):  
Lynn-Yao Lin ◽  
Dmitri Debabov ◽  
William Chang
Keyword(s):  
Antimicrobial Agents ◽  
The United States ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Surveillance Program ◽  
Multiple Resistance ◽  
In Vitro Susceptibility ◽  
Medical Centers ◽  
Custom Made

Abstract Background OXA-48 is a carbapenemase with low-level hydrolytic activity toward cephalosporins. This study evaluated in vitro activities of ceftazidime-avibactam (CAZ-AVI), meropenem (MEM), meropenem-vaborbactam (MVB), ceftolozane-tazobactam (C/T), and other antimicrobial agents against 113 OXA-48-producing Enterobacterales with multiple resistance mechanisms collected in a 2017–2018 global surveillance program. Methods Nonduplicate clinical isolates of 113 Enterobacterales were collected from medical centers in 25 countries in 2017–2018. In vitro susceptibility tests were performed by broth microdilution with a custom-made panel consisting of CAZ-AVI, ceftazidime (CAZ), MEM, MVB, C/T, colistin (COL), gentamicin (GEN), levofloxacin (LEV), and amikacin (AMK). Whole genome sequencing or quantitative PCR data were used to analyze resistance mechanisms, such as OXA-48, extended-spectrum β-lactamase (ESBL), original-spectrum β-lactamase (OSBL), and AmpC β-lactamase. Clinical and Laboratory Standards Institute breakpoints were applied for susceptibility interpretations. Results Of 113 OXA-48–producing clinical isolates, 20 carried OXA-48 alone. The remaining 93 isolates carried additional β-lactamases, including 63 with ESBL (CTX-M-15) + OSBL (SHV, TEM), 15 with AmpC (DHA, AAC, CMY) + ESBL (CTX-M-15), and 15 with OSBL (SHV, TEM). 99.1% (all but 1) of all isolates tested were susceptible to CAZ-AVI, whereas 71.7%, 17.7%, and 14.2% were susceptible to MVB, MEM, and C/T, respectively. Among isolates harboring multiple resistance mechanisms (OXA-48 + ESBL + OSBL; n=63), 98.4%, 69.8%, 11.1%, and 7.9% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively. Among isolates carrying OXA-48 + AmpC + ESBL + OSBL (n=15), 100%, 66.7%, 13.3%, and 13.3% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively (Table). Aminoglycosides (AMK and GEN) and other β-lactams (eg, CAZ) were 20%–90% active against these isolates. COL was the second most effective comparator, inhibiting 83.2% of these isolates. Table Conclusion CAZ-AVI was the most effective agent in this study compared with other antibiotics, including β-lactams, β-lactam–β-lactamase inhibitor combinations, aminoglycosides, and COL, against OXA-48-producing Enterobacterales carrying multiple β-lactamases. Disclosures Lynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee)

scholarly journals In vitro susceptibility studies and detection of vancomycin resistance genes in clinical isolates of enterococci in Nagasaki, Japan

1997 ◽  
Vol 119 (2) ◽  
pp. 175-181 ◽  
Author(s):  
Y. HIRAKATA ◽  
T. YAMAGUCHI ◽  
K. IZUMIKAWA ◽  
J. MATSUDA ◽  
K. TOMONO ◽  
...  
Keyword(s):  
Resistance Genes ◽  
Antimicrobial Agents ◽  
The United States ◽  
Vancomycin Resistance ◽  
Single Step ◽  
Clinical Isolates ◽  
Glycopeptide Resistance ◽  
In Vitro Susceptibility ◽  
Enterococcus Gallinarum

Glycopeptide resistance in enterococci is now a cause of clinical concern in the United States and Europe. However, details of vancomycin resistance in enterococci in Japan have been unknown. We measured minimum inhibitory concentrations (MICs) of various antimicrobial agents for a total of 218 clinical strains of enterococci isolated in our hospital in 1995–6 in addition to 15 strains with known genotypic markers of resistance. We also screened vancomycin resistance genes using a single step multiplex-PCR.In clinical isolates, only two strains of Enterococcus gallinarum were of intermediate resistance to vancomycin (MIC, 8 μg/ml), while the others were all susceptible. Glycopeptides (vancomycin and teicoplanin) and streptogramins (RP 58500 and RPR 106972) showed potent antimicrobial effects for the isolates. In addition, ampicillin was also potent for Enterococcus faecalis, while ampicillin, minocycline and gentamicin were potent for Enterococcus avium. No vanA or vanB genes were detected, while vanC1 and vanC23 genes were detected from two and four strains, respectively. Our results suggest that incidence of VRE in Japan may be estimated as still very low at this time.

scholarly journals 129. Antimicrobial Activity of Ceftazidime–avibactam and Comparator Agents Tested against Gram-Negative Organisms Isolated from Patients with Bloodstream Infections in United States Medical Centers (2017–2018)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S93-S94
Author(s):  
Cecilia G Carvalhaes ◽  
Mariana Castanheira ◽  
Rodrigo E Mendes ◽  
Helio S Sader
Keyword(s):  
United States ◽  
New York ◽  
Bloodstream Infections ◽  
The United States ◽  
Multidrug Resistant ◽  
Medical Centers ◽  
Carbapenem Resistant ◽  
Gram Negative Organisms ◽  
Esbl Producers

Abstract Background We evaluated the antimicrobial susceptibility of Enterobacterales (ENT) and P. aeruginosa (PSA) causing bloodstream infections (BSIs) in the United States (US) hospitals. Methods A total of 3,317 ENT and 331 PSA isolates were consecutively collected (1/patient) from patients with BSI in 68 US medical centers in 2017–2018 and tested for susceptibility (S) by reference broth microdilution methods in a central laboratory as part of the International Network for Optimal Resistance Monitoring (INFORM) Program. β-Lactamase screening was performed by whole-genome sequencing on ENT with decreased S to broad-spectrum cephalosporins (ESBL phenotype). Results The most common ENT species isolated from BSI were E. coli (EC; 41.9% of ENT), K. pneumoniae (KPN; 24.4%), and E. cloacae (ECL; 8.7%), and the most active agents against ENT were ceftazidime–avibactam (CAZ-AVI; 99.9%S), amikacin (AMK; 99.6%S) and meropenem (MEM; 99.3%S). CAZ-AVI was active against all EC and KPN isolates (100.0%S). Only 2 ENT isolates (0.06%) were CAZ-AVI resistant, 2 NDM-1-producing ECL isolated in the New York City area. Ceftolozane–tazobactam (C-T) and piperacillin–tazobactam (PIP-TAZ) showed good activity against EC and KPN (92.2–98.9%S; Table), with limited activity against ECL (81.9–83.7%S). The most common ESBLs were CTX-M-type, which was observed in 93% of ESBL producers (mainly CTX-M-15 [64% of ESBL producers] and CTX-M-27 [13%]), and OXA-1/OXA-30 (42%); 42% of ESBL producers (n = 333, excluding carbapenemase producers) displayed ≥2 ESBL genes, mainly CTX-M-15 and OXA-1/OXA-30 (40% of ESBL producers). The most active agents against ESBL producers were CAZ-AVI (100.0%S), imipenem (99.4%S), and colistin (COL; 99.1%S). Only CAZ-AVI (99.4%S), AMK (96.2%S) and MEM (92.8%S) were active against >90% of multidrug-resistant (MDR) ENT. Among 19 carbapenem-resistant ENT (CRE; 0.6% of ENT), 9 produced a KPC-like, 2 an NDM-1, and 2 an NMC-A; carbapenemase genes were not found in 6 CRE isolates. COL (100.0%S), CAZ-AVI (98.5%S), AMK (98.5%S), C-T (98.1%S), and tobramycin (97.0%S) were very active against PSA. Conclusion CAZ-AVI exhibited potent in vitro activity and great spectrum against ENT (99.9%S) and PSA (98.5%) isolated from patients with BSI from US hospitals. Disclosures All authors: No reported disclosures.

scholarly journals Extensively Drug-Resistant Pseudomonas aeruginosa ST309 Harboring Tandem Guiana Extended Spectrum β-Lactamase Enzymes: A Newly Emerging Threat in the United States

2019 ◽  
Vol 6 (7) ◽  
Author(s):  
Ayesha Khan ◽  
Truc T Tran ◽  
Rafael Rios ◽  
Blake Hanson ◽  
William C Shropshire ◽  
...  
Keyword(s):  
United States ◽  
Pseudomonas Aeruginosa ◽  
Phylogenetic Analysis ◽  
The United States ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Class 1 Integron ◽  
E Coli ◽  
Extensively Drug Resistant ◽  
Extended Spectrum

Abstract Background Treatment of serious infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa remains a challenge, despite the introduction of novel therapeutics. In this study, we report 2 extensively drug-resistant clinical isolates of sequence type (ST) 309 P aeruginosa resistant to all β-lactams, including the novel combinations ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam. Methods Isolates were sequenced using both short-read (Illumina) and long-read technology to identify resistance determinants, polymorphisms (compared with P aeruginosa PAO1), and reconstruct a phylogenetic tree. A pair of β-lactamases, Guiana extended spectrum β-lactamase (GES)-19 and GES-26, were cloned and expressed in a laboratory strain of Escherichia coli to examine their relative impact on resistance. Using cell lysates from E coli expressing the GES genes individually and in tandem, we determined relative rates of hydrolysis for nitrocefin and ceftazidime. Results Two ST309 P aeruginosa clinical isolates were found to harbor the extended spectrum β-lactamases GES-19 and GES-26 clustered in tandem on a chromosomal class 1 integron. The presence of both enzymes in E coli was associated with significantly elevated minimum inhibitory concentrations to aztreonam, cefepime, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam, compared with those expressed individually. The combination of ceftazidime/avibactam plus aztreonam was active in vitro and used to achieve cure in one patient. Phylogenetic analysis revealed ST309 P aeruginosa are closely related to MDR strains from Mexico also carrying tandem GES. Conclusions The presence of tandem GES-19 and GES-26 is associated with resistance to all β-lactams, including ceftolozane/tazobactam. Phylogenetic analysis suggests that ST309 P aeruginosa may be an emerging threat in the United States.

scholarly journals 165. Emergence of Extensively Drug-Resistant Salmonella enterica Serotype Typhi Infections—United States, 2008–2020

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S99-S100
Author(s):  
Felicita Medalla ◽  
Louise Francois Watkins ◽  
Michael Hughes ◽  
Meseret Birhane ◽  
Layne Dorough ◽  
...  
Keyword(s):  
United States ◽  
Typhoid Fever ◽  
The United States ◽  
Empiric Therapy ◽  
Salmonella Typhi ◽  
International Travel ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Large Outbreak ◽  
Control And Prevention

Abstract Background Typhoid fever, caused by Salmonella Typhi, is fatal in 12%–30% of patients not treated with appropriate antibiotics. In 2016, a large outbreak of extensively drug-resistant (XDR) Typhi infections began in Pakistan with cases reported globally, including the United States. In 2021, the Centers for Disease Control and Prevention (CDC) issued a health advisory on XDR infections among U.S. residents without international travel. We describe resistance of Typhi infections diagnosed in the United States to help guide treatment decisions. Methods Typhoid fever is a nationally notifiable disease. Health departments report cases to CDC through the National Typhoid and Paratyphoid Fever Surveillance system. Isolates are submitted to the National Antimicrobial Resistance Monitoring System for antimicrobial susceptibility testing (AST) using broth microdilution. AST results are categorized by Clinical and Laboratory Standards Institute criteria. We defined XDR as resistant to ceftriaxone, ampicillin, chloramphenicol, and co-trimoxazole, and nonsusceptible to ciprofloxacin. Results During 2008–2019, of 4,637 Typhi isolates, 52 (1%) were ceftriaxone resistant (axo-R); 71% were ciprofloxacin nonsusceptible, 1 azithromycin resistant (azm-R), and none meropenem resistant. XDR was first detected in 2018, in 2% of 474 isolates and increased to 7% of 535 in 2019. Of the 52 axo-R isolates, 46 were XDR, of which 45 were from travelers to Pakistan, and one from a non-traveler; 6 were not XDR, of which 4 were linked to travel to Iraq. In preliminary 2020 reports, 23 isolates were XDR; 14 were from travelers to Pakistan, 8 from non-travelers, and 1 from someone with unknown travel status. Among those with XDR infection, median age was 11 years (range 1–62), 54% were female, and 62% were from 6 states. Conclusion Ceftriaxone-resistant Typhi infections, mostly XDR, are increasing. Clinicians should ask patients with suspected Typhi infections about travel and adjust treatment based on susceptibility results. Carbapenem, azithromycin, or both may be considered for empiric therapy of typhoid fever among travelers to Pakistan or Iraq and in uncommon instances when persons report no international travel. Ceftriaxone is an empiric therapy option for travelers to countries other than Pakistan and Iraq. Disclosures All Authors: No reported disclosures

scholarly journals Antimicrobial Resistance among Clinical Isolates ofStreptococcus pneumoniae in the United States during 1999–2000, Including a Comparison of Resistance Rates since 1994–1995

2001 ◽  
Vol 45 (6) ◽  
pp. 1721-1729 ◽  
Author(s):  
Gary V. Doern ◽  
Kristopher P. Heilmann ◽  
Holly K. Huynh ◽  
Paul R. Rhomberg ◽  
Stacy L. Coffman ◽  
...  
Keyword(s):  
United States ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Rank Order ◽  
The United States ◽  
Clinical Isolates ◽  
Beta Lactam ◽  
High Level ◽  
Resistance Rates

ABSTRACT A total of 1,531 recent clinical isolates of Streptococcus pneumoniae were collected from 33 medical centers nationwide during the winter of 1999–2000 and characterized at a central laboratory. Of these isolates, 34.2% were penicillin nonsusceptible (MIC ≥ 0.12 μg/ml) and 21.5% were high-level resistant (MIC ≥ 2 μg/ml). MICs to all beta-lactam antimicrobials increased as penicillin MICs increased. Resistance rates among non-beta-lactam agents were the following: macrolides, 25.2 to 25.7%; clindamycin, 8.9%; tetracycline, 16.3%; chloramphenicol, 8.3%; and trimethoprim-sulfamethoxazole (TMP-SMX), 30.3%. Resistance to non-beta-lactam agents was higher among penicillin-resistant strains than penicillin-susceptible strains; 22.4% of S. pneumoniae were multiresistant. Resistance to vancomycin and quinupristin-dalfopristin was not detected. Resistance to rifampin was 0.1%. Testing of seven fluoroquinolones resulted in the following rank order of in vitro activity: gemifloxacin > sitafloxacin > moxifloxacin > gatifloxacin > levofloxacin = ciprofloxacin > ofloxacin. For 1.4% of strains, ciprofloxacin MICs were ≥4 μg/ml. The MIC90s (MICs at which 90% of isolates were inhibited) of two ketolides were 0.06 μg/ml (ABT773) and 0.12 μg/ml (telithromycin). The MIC90 of linezolid was 2 μg/ml. Overall, antimicrobial resistance was highest among middle ear fluid and sinus isolates of S. pneumoniae; lowest resistance rates were noted with isolates from cerebrospinal fluid and blood. Resistant isolates were most often recovered from children 0 to 5 years of age and from patients in the southeastern United States. This study represents a continuation of two previous national studies, one in 1994–1995 and the other in 1997–1998. Resistance rates with S. pneumoniae have increased markedly in the United States during the past 5 years. Increases in resistance from 1994–1995 to 1999–2000 for selected antimicrobial agents were as follows: penicillin, 10.6%; erythromycin, 16.1%; tetracycline, 9.0%; TMP-SMX, 9.1%; and chloramphenicol, 4.0%, the increase in multiresistance was 13.3%. Despite awareness and prevention efforts, antimicrobial resistance with S. pneumoniae continues to increase in the United States.

scholarly journals Baseline Study To Determine In Vitro Activities of Daptomycin against Gram-Positive Pathogens Isolated in the United States in 2000-2001

2003 ◽  
Vol 47 (5) ◽  
pp. 1689-1693 ◽  
Author(s):  
Ian A. Critchley ◽  
Renée S. Blosser-Middleton ◽  
Mark E. Jones ◽  
Clyde Thornsberry ◽  
Daniel F. Sahm ◽  
...  
Keyword(s):  
United States ◽  
Outpatient Care ◽  
Antimicrobial Agents ◽  
The United States ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Oxacillin Resistance ◽  
Positive Spectrum

ABSTRACT The activity of daptomycin was assessed by using 6,973 gram-positive bacteria isolated at 50 United States hospitals in 2000 and 2001. Among the isolates of Streptococcus pneumoniae (n = 1,163) collected, the rate of penicillin resistance was 16.1%; rates of oxacillin resistance among Staphylococcus aureus isolates (n = 1,018) and vancomycin resistance among Enterococcus faecium isolates (n = 368) were 30.0 and 59.5%, respectively. Multidrug-resistant (MDR) phenotypes (isolates resistant to three or more different chemical classes of antimicrobial agents) accounted for 14.2% of S. pneumoniae isolates, 27.1% of S. aureus isolates, and 58.4% of E. faecium isolates. For all gram-positive species tested, MICs at which 90% of the isolates tested were inhibited (MIC90s) and MIC ranges for directed-spectrum agents (daptomycin, quinupristin-dalfopristin, and linezolid) were identical or highly similar for isolates susceptible or resistant to other agents or MDR. Daptomycin had a MIC90 of 0.12 μg/ml for both penicillin-susceptible and -resistant isolates of S. pneumoniae. Against oxacillin-resistant S. aureus daptomycin had a MIC90 of 0.5 μg/ml, and it had a MIC90 of 4 μg/ml against both vancomycin-susceptible and -resistant E. faecium. The MIC90s for daptomycin and other directed-spectrum agents were unaffected by the regional or anatomical origin of isolates or patient demographic parameters (patient age, gender, and inpatient or outpatient care). Our results confirm the gram-positive spectrum of activity of daptomycin and that its activity is independent of susceptibility or resistance to commonly prescribed and tested antimicrobial agents. This study may serve as a baseline to monitor future changes in the susceptibility of gram-positive species to daptomycin following its introduction into clinical use.

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