Activity of ACHN-490 against meticillin-resistant Staphylococcus aureus (MRSA) isolates from patients in US hospitals

Tenover, Fred C.; Tickler, Isabella A.; Armstrong, Eliana S.; Kubo, Aya; López, Sara; Persing, David H.; Miller, George H.

doi:10.1016/j.ijantimicag.2011.05.016

Cited by 26 publications

(19 citation statements)

References 16 publications

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“…The strains in the McDougal study reflected both the accumulation of chromosomal mutations (for fluoroquinolones) and plasmid-mediated resistance genes [including ermA and aph(2Љ)-Ia/aac(6=)-Ie]. The rise in tobramycin resistance observed among isolates from this study has been attributed to the widespread dissemination of the ant(4=)-Ia determinant in the United States (48). Taken together, these changes in susceptibility may have implications for the management of MRSA cases, especially in areas where USA300 isolates are common.…”

Section: Discussionmentioning

confidence: 68%

“…After inoculation, MIC trays were incubated at 35°C in ambient air for 18 to 24 h. Antimicrobial agent powders were obtained from Sigma-Aldrich (St. Louis, MO) or directly from the antimicrobial agent manufacturers. Microdilution wells containing daptomycin were supplemented with calcium to a final concentration of 50 g/ml as described by CLSI, and wells containing oxacillin were supplemented with NaCl to a final concentration of 2% (9,48). Selected isolates with borderline-susceptible results to linezolid and daptomycin were tested using Etest strips (bioMérieux, Durham, NC) as described by the manufacturer.…”

Section: Bacterial Isolatesmentioning

confidence: 99%

“…Quality control strains included S. aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 (10). Mueller-Hinton plates with Etest strips were incubated in ambient air at 35°C for 24 h. A subset of the combined MIC results for nasal and blood isolates, along with data on mechanisms of aminoglycoside resistance (not discussed here), have been published previously (48).…”

Section: Bacterial Isolatesmentioning

confidence: 99%

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Characterization of Nasal and Blood Culture Isolates of Methicillin-Resistant Staphylococcus aureus from Patients in United States Hospitals

Tenover¹,

Tickler²,

Goering

et al. 2012

Antimicrob Agents Chemother

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105

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A total of 299 nares and 194 blood isolates of methicillin-resistant Staphylococcus aureus (MRSA), each recovered from a unique patient, were collected from 23 U.S. hospitals from May 2009 to March 2010. All isolates underwent spa and staphylococcal cassette chromosome mec element (SCCmec) typing and antimicrobial susceptibility testing; a subset of 84 isolates was typed by pulsed-field gel electrophoresis (PFGE) using SmaI. Seventy-six spa types were observed among the isolates. Overall, for nasal isolates, spa type t002-SCCmec type II (USA100) was the most common strain type (37% of isolates), while among blood isolates, spa type t008-SCCmec type IV (USA300) was the most common (39%). However, the proportion of all USA100 and USA300 isolates varied by United States census region. Nasal isolates were more resistant to tobramycin and clindamycin than blood isolates (55.9% and 48.8% of isolates versus 36.6% and 39.7%, respectively; for both, P < 0.05). The USA300 isolates were largely resistant to fluoroquinolones. High-level mupirocin resistance was low among all spa types (<5%). SCCmec types III and VIII, which are rare in the United States, were observed along with several unusual PFGE types, including CMRSA9, EMRSA15, and the PFGE profile associated with sequence type 239 (ST239) isolates. Typing data from this convenience sample suggest that in U.S. hospitalized patients, USA100 isolates of multiple spa types, while still common in the nares, have been replaced by USA300 isolates as the predominant MRSA strain type in positive blood cultures.

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Section: Discussionmentioning

confidence: 68%

Section: Bacterial Isolatesmentioning

confidence: 99%

Section: Bacterial Isolatesmentioning

confidence: 99%

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Characterization of Nasal and Blood Culture Isolates of Methicillin-Resistant Staphylococcus aureus from Patients in United States Hospitals

Tenover¹,

Tickler²,

Goering

et al. 2012

Antimicrob Agents Chemother

Self Cite

105

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“…Plazomicin, a semisynthetic derivative of sisomycin, had MIC 90 values of Ͻ2 g/ml against E. coli, serine carbapenemase-producing K. pneumoniae, MDR Enterobacteriaceae with metallo-␤-lactamases, S. aureus (including MRSA), and Acinetobacter spp. that bore a variety of aminoglycoside resistance determinants (50)(51)(52)(53)(54). All known transferable aminoglycoside-modifying enzymes were unable to inactive plazomicin, although plasmid-carried armA and rmtC encoding ribosomal methyltransferases, such as those found in NDM-1 metallo-␤-lactamase (MBL)-producing pathogens, conferred resistance to plazomicin with MICs ranging from 64 to Ͼ256 g/ml (53).…”

Section: Aminoglycosidesmentioning

confidence: 99%

Investigational Antimicrobial Agents of 2013

Pucci

Bush

2013

Clin Microbiol Rev

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SUMMARY New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting.

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“…Furthermore, because combination therapy is of-ten used for severe nosocomial infections, we examined the activity of plazomicin in combination with other Gram-negative agents against a selection of carbapenem-resistant strains (8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

Can Plazomicin Alone or in Combination Be a Therapeutic Option against Carbapenem-Resistant Acinetobacter baumannii?

García-Salguero

Rodríguez-Avial

Picazo

et al. 2015

Antimicrob Agents Chemother

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Nosocomial pathogens can be associated with a variety of infections, particularly in intensive care units (ICUs) and in immunocompromised patients. Usually these pathogens are resistant to multiple drugs and pose therapeutic challenges. Among these organisms, Acinetobacter baumannii is one of the most frequent being encountered in the clinical setting. Carbapenems are very useful to treat infections caused by these drug-resistant Gram-negative bacilli, but carbapenem resistance is increasing globally. Combination therapy is frequently given empirically for hospital-acquired infections in critically ill patients and is usually composed of an adequate beta-lactam and an aminoglycoside. The purpose of this study was to evaluate the in vitro activity of plazomicin against carbapenem-resistant Acinetobacter baumannii. Amikacin was used as a comparator. The activity of plazomicin in combination with several different antibiotics was tested by disk diffusion, the checkerboard method, and time-kill studies. Synergy was consistently observed with carbapenems (meropenem and/or imipenem) along with plazomicin or amikacin. When the aminoglycosides were combined with other classes of antibiotics, synergy was observed in some cases, depending on the strain and the antibiotic combination; importantly, there was no antagonism observed in any case. These findings indicate the potential utility of plazomicin in combination with other antibiotics (mainly carbapenems) for the treatment of A. baumannii infections, including those caused by carbapenem-resistant isolates.

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Activity of ACHN-490 against meticillin-resistant Staphylococcus aureus (MRSA) isolates from patients in US hospitals

Cited by 26 publications

References 16 publications

Characterization of Nasal and Blood Culture Isolates of Methicillin-Resistant Staphylococcus aureus from Patients in United States Hospitals

Characterization of Nasal and Blood Culture Isolates of Methicillin-Resistant Staphylococcus aureus from Patients in United States Hospitals

Investigational Antimicrobial Agents of 2013

Can Plazomicin Alone or in Combination Be a Therapeutic Option against Carbapenem-Resistant Acinetobacter baumannii?

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