scholarly journals Comparison of the postantibiotic and postantibiotic sub-MIC effects of levofloxacin and ciprofloxacin on Staphylococcus aureus and Streptococcus pneumoniae.

1997 ◽  
Vol 41 (5) ◽  
pp. 950-955 ◽  
Author(s):  
L Licata ◽  
C E Smith ◽  
R M Goldschmidt ◽  
J F Barrett ◽  
M Frosco
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Resistant Strain ◽  
Drug Exposure ◽  
Inhibitory Concentration ◽  
Resistant Isolate ◽  
Postantibiotic Effect ◽  
Methicillin Resistant ◽  
Susceptible Isolate

The postantibiotic subminimum inhibitory concentration effect (PA SME) may simulate in vivo drug exposure more accurately than the postantibiotic effect (PAE) since subinhibitory concentrations of drug persist between antibiotic dosings. In this study, we compared the PAEs and PA SMEs of levofloxacin and ciprofloxacin for clinical isolates of fluoroquinolone-susceptible Staphylococcus aureus and Streptococcus pneumoniae. At two times the MIC, PAEs of levofloxacin were an average of 0.6 h longer than the PAEs obtained for ciprofloxacin for methicillin-susceptible and methicillin-resistant S. aureus strains. The PAEs of levofloxacin and ciprofloxacin ranged from 1.8 to 3.1 and 1.1 to 2.4 h, respectively. Continued exposure of the methicillin-resistant strain to 1/16, 1/8, and 1/4 the MIC resulted in PA SMEs of 6.5, 15.3, and >22.3 h, respectively, for levofloxacin and 3.8, 8.0, and 12.3 h, respectively, for ciprofloxacin. For isolates of S. pneumoniae, at two times the MIC of both fluoroquinolones, the average PAEs of levofloxacin and ciprofloxacin were equivalent: 1.3 h for the penicillin-susceptible isolate and 0.6 h for the penicillin-resistant isolate. Continued exposure of the penicillin-susceptible S. pneumoniae strain to 1/16, 1/8, and 1/4 the MIC resulted in average PA SMEs of 1.0, 1.4, and 2.8 h, respectively, for levofloxacin and 1.8, 2.0, and 2.5 h, respectively, for ciprofloxacin. Continued exposure of penicillin-resistant S. pneumoniae to 1/16, 1/8, and 1/4 the MIC of the same fluoroquinolones resulted in average PA SMEs of 0.6, 1.1, and 2.9 h, respectively, for levofloxacin and 0.6, 1.1, and 1.5 h, respectively, for ciprofloxacin. The PA SMEs observed demonstrate the superior activity of levofloxacin against methicillin-susceptible or methicillin-resistant S. aureus. Although PAEs were similar for the penicillin-susceptible and penicillin-resistant S. pneumoniae strains, the PA SME of levofloxacin at one-fourth the MIC was longer for penicillin-resistant S. pneumoniae.

scholarly journals In Vitro and In Vivo Activities of DA-7867, a New Oxazolidinone, against Aerobic Gram-Positive Bacteria

2005 ◽  
Vol 49 (6) ◽  
pp. 2498-2500 ◽  
Author(s):  
Eun Jeong Yoon ◽  
Yeong Woo Jo ◽  
Sung Hak Choi ◽  
Tae Ho Lee ◽  
Jae Keol Rhee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Infection Models ◽  
Vancomycin Resistant

ABSTRACT In vitro and in vivo activities of DA-7867 were assessed against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. All isolates were inhibited by DA-7867 at ≤0.78 μg/ml, a four-times-lower concentration than that of inhibition by linezolid. For murine infection models, DA-7867 also exhibited greater efficacy than linezolid against all isolates tested.

scholarly journals In VivoAntibacterial Activity of MRX-I, a New Oxazolidinone

2014 ◽  
Vol 58 (4) ◽  
pp. 2418-2421 ◽  
Author(s):  
Cong-Ran Li ◽  
Qian-Qian Zhai ◽  
Xiu-Kun Wang ◽  
Xin-Xin Hu ◽  
Guo-Qing Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Local Infection ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Content Type ◽  
Vancomycin Resistant Enterococci ◽  
Infection Models ◽  
Vancomycin Resistant

ABSTRACTMRX-I is a potent oxazolidinone antibiotic against Gram-positive pathogens, including methicillin-resistantStaphylococcus aureus(MRSA), penicillin-resistantStreptococcus pneumoniae(PRSP), penicillin-intermediateS. pneumoniae(PISP), and vancomycin-resistant enterococci (VRE). In this study, thein vivoefficacy of orally administered MRX-I was evaluated using linezolid as a comparator. MRX-I showed the same or better efficacy than linezolid in both systemic and local infection models against the tested strains.

scholarly journals Antimicrobial activity of SM-17466, a novel carbapenem antibiotic with potent activity against methicillin-resistant Staphylococcus aureus.

1995 ◽  
Vol 39 (4) ◽  
pp. 910-916 ◽  
Author(s):  
Y Sumita ◽  
H Nouda ◽  
K Kanazawa ◽  
M Fukasawa
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Antibacterial Activities ◽  
Infection Model ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Wide Range

The in vitro and in vivo antibacterial activities of SM-17466, a new 1 beta-methyl carbapenem, were evaluated against a wide range of clinical bacterial isoaltes and compared with the activities of meropenem, imipenem, vancomycin, and arbekacin. SM-17466 had a broad spectrum of action against gram-positive bacteria, showing especially potent activity against methicillin-resistant staphylococci. The MICs of SM-17466, meropenem, imipenem, vancomycin, and arbekacin at which 90% of clinical isolates of methicillin-resistant Staphylococcus aureus were inhibited were 3.13, 50, 100, 1.56, and 3.13 micrograms/ml, respectively. This activity of SM-17466 was almost equivalent to those of the antibiotics used for the treatment of infections caused by this organism. SM-17466 also showed bactericidal activity against methicillin-resistant S. aureus. In contrast, SM-17466 was less active against gram-negative bacteria, especially against Pseudomonas aeruginosa, compared with the other carbapenems; however, of the carbapenems, SM-17466 exhibited the highest activity against Haemophilus influenzae and Bacteriodes fragilis. SM-17466, at a 50% inhibitory concentration of less than 1 microgram/ml, bound to penicillin-binding proteins 1 to 4 in methicillin-susceptible S. aureus and also had good binding to penicillin-binding protein 2' in a methicillin-resistant strain (50% inhibitory concentration, 5.9 micrograms/ml). This high affinity, which was 10 and 20 times greater than those for meropenem and imipenem, respectively, was reflected in the potent activity of SM-17466 against methicillin-resistant S. aureus. SM-17466 demonstrated excellent in vivo efficacy against methicillin-susceptible and -resistant S. aureus strains in a mouse peritoneal infection model: the efficacy of SM-17466 against methicillin-resistant strains was equal to or one-third that of vancomycin. This activity was comparable to the in vitro activity of SM-17466. The subcutaneous injection of SM-17466 in mice revealed that the half-life of SM-17466 in serum was about 18 min, intermediate between those of vancomycin and arbekacin and 1.5-fold that of imipenem-cilastatin. SM-17466 was resistant to hydrolysis by swine renal dehydropeptidase I, to an extent comparable to the resistance shown by meropenem.

scholarly journals 596. Distinct, Segregated Daptomycin-Susceptible and Daptomycin-Nonsusceptible Staphylococcus aureus Populations Associated with Tricuspid-Valve Infective Endocarditis

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S280-S281
Author(s):  
Christopher R Miller ◽  
Somrita Dey ◽  
Paula Smolenski ◽  
Pushkar S Kulkarni ◽  
George Sakoulas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Tricuspid Valve ◽  
Population Analysis ◽  
Resistant Isolate ◽  
Pharmacodynamic Modeling ◽  
Anatomical Site ◽  
Accessory Gene ◽  
Host Defense Peptides ◽  
Susceptible Isolate

Abstract Background Loss of daptomycin susceptibility in Staphylococcus aureus is often associated with sequestered foci of infection, driven by selection pressure from both administered antibiotics and host defense peptides. Susceptibility testing of the organism cultured from blood is assumed to parallel that of the infectious foci, such as heart valves. We studied a case of tricuspid valve endocarditis where one leaflet yielded exclusively daptomycin-nonsusceptible S. aureus and another leaflet yielded purely daptomycin-susceptible S. aureus. We examined the responses of the two populations to different anti-staphylococcal therapies to identify regimens effective against both isolates. Methods Both isolates were whole-genome-sequenced using Illumina technologies. The presence of heterogeneous daptomycin-resistant subpopulations was assessed by dilution plating and population analysis profiling. One compartment pharmacokinetic/pharmacodynamic modeling was used to simulate different potential antistaphylococcal pharmacotherapies against each isolate. Hemolysin activity was evaluated as a surrogate for accessory gene regulator function. Results The daptomycin-susceptible isolate did not demonstrate heteroresistance while the daptomycin-resistant population was uniformly daptomycin nonsusceptible. The daptomycin non-susceptible isolate demonstrated regrowth by 72 hours of simulated treatment with vancomycin (2 g Q12H) or daptomycin (10 mg/kg daily). Adding cefazolin (2 g Q8H) to vancomycin or daptomycin prevented regrowth at 72 hours. The daptomycin-resistant isolate was deficient in hemolysin production suggesting agr dysfunction. Comparative sequencing identified daptomycin-resistant isolate mutations in mprF, purR and agrA. Conclusion This case underscores the complex dynamics of the emergence of S. aureus resistance to daptomycin in vivo. Our pharmacokinetic modeling supports combination therapy in the treatment of endovascular MRSA infection. Reduced hemolytic activity supports the hypothesis that agr modulation is associated with persistent infection and/or treatment failure. Ongoing studies will identify features of distinct bacterial populations that promote ecological succession during infection at a sequestered anatomical site. Disclosures All authors: No reported disclosures.

scholarly journals Efficacy of Ceftaroline Fosamil against Penicillin-Sensitive and -Resistant Streptococcus pneumoniae in an Experimental Rabbit Meningitis Model

2013 ◽  
Vol 57 (10) ◽  
pp. 4653-4655 ◽  
Author(s):  
P. Cottagnoud ◽  
M. Cottagnoud ◽  
F. Acosta ◽  
A. Stucki
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Bactericidal Activity ◽  
Resistant Strain ◽  
Gram Positive ◽  
Ceftaroline Fosamil ◽  
Gram Negative ◽  
Methicillin Resistant ◽  
Content Type ◽  
Gram Negative Organisms

ABSTRACTCeftaroline is a new cephalosporin with bactericidal activity against resistant Gram-positive organisms, including methicillin-resistantStaphylococcus aureus(MRSA) and penicillin-resistantStreptococcus pneumoniae, as well as common Gram-negative organisms. This study tested the prodrug, ceftaroline fosamil, against a penicillin-sensitive and a penicillin-resistant strain ofS. pneumoniaein an experimental rabbit meningitis model. The penetration of ceftaroline into inflamed meninges was approximately 14%. Ceftaroline fosamil was slightly superior to ceftriaxone against the penicillin-sensitive strain and significantly superior to the combination of ceftriaxone and vancomycin against the penicillin-resistant strain.

scholarly journals Causes and Implications of the Disappearance of Rifampin Resistance in a Rat Model of Methicillin-Resistant Staphylococcus aureus Foreign Body Osteomyelitis

2015 ◽  
Vol 59 (8) ◽  
pp. 4481-4488 ◽  
Author(s):  
Cassandra L. Brinkman ◽  
Harmony L. Tyner ◽  
Suzannah M. Schmidt-Malan ◽  
Jayawant N. Mandrekar ◽  
Robin Patel
Keyword(s):  
Staphylococcus Aureus ◽  
Foreign Body ◽  
Treatment Completion ◽  
Resistant Bacteria ◽  
Methicillin Resistant ◽  
Content Type ◽  
Susceptible Isolate ◽  
Rifampin Resistance

ABSTRACTOrthopedic foreign body-associated infections are often treated with rifampin-based combination antimicrobial therapy. We previously observed that rifampin-resistant and methicillin-resistantStaphylococcus aureus(MRSA) isolates were present 2 days after cessation of rifampin therapy in experimental foreign body osteomyelitis. Unexpectedly, only rifampin-susceptible isolates were detected 14 days after the completion of treatment. We studied two rifampin-resistant isolates recovered 2 days after treatment and one rifampin-susceptible isolate recovered 14 days after treatment. Growing these isolates alonein vitroorin vivodemonstrated no fitness defects; however, in mixed culture, rifampin-susceptible bacteria outcompeted rifampin-resistant bacteria.In vivo, two courses of rifampin treatment (25 mg/kg of body weight every 12 h for 21 days) yielded a greater decrease in bacterial quantity in the bones of treated animals 14 days following treatment than that in animals receiving a single course of treatment (P= 0.0398). In infections established with equal numbers of rifampin-resistant and rifampin-susceptible bacteria, one course of rifampin treatment did not affect bacterial quantities. Rifampin-resistant and rifampin-susceptible isolates were recovered both 2 days and 14 days following treatment completion; however, the proportion of animals with rifampin-resistant isolates was lower at 14 days than that at 2 days following treatment completion (P= 0.024). In untreated animals infected with equal numbers of rifampin-resistant and rifampin-susceptible bacteria for 4 weeks, rifampin-susceptible isolates were exclusively recovered, indicating the outcompetition of rifampin-resistant by rifampin-susceptible isolates. The data presented imply that although there is no apparent fitness defect in rifampin-resistant bacteria when grown alone, they are outcompeted by rifampin-susceptible bacteria when the two are present together. The findings also suggest that selected rifampin resistance may not persist in initially rifampin-susceptible infections following the discontinuation of rifampin.

scholarly journals Efficacy of Levofloxacin for Experimental Aortic-Valve Endocarditis in Rabbits Infected with Viridans Group Streptococcus or Staphylococcus aureus

1999 ◽  
Vol 43 (11) ◽  
pp. 2742-2746 ◽  
Author(s):  
Henry F. Chambers ◽  
Qing Xiang ◽  
Liu ◽  
Lucian Liuxin Chow ◽  
Corinne Hackbarth
Keyword(s):  
Staphylococcus Aureus ◽  
Aortic Valve ◽  
Resistant Strain ◽  
Single Agent ◽  
Rabbit Model ◽  
Susceptible Strain ◽  
Methicillin Resistant ◽  
Days Of Therapy

ABSTRACT Levofloxacin is among the more active fluoroquinolones against streptococci and staphylococci. It is effective against moderately severe infections caused by these organisms, but its efficacy in the treatment of bacteremia and serious infections such as endocarditis is not well defined. We compared the efficacy of levofloxacin to those of standard agents in the rabbit model of aortic-valve endocarditis caused by fluoroquinolone-susceptible strains including a penicillin-susceptible strain of Streptococcus sanguis, a penicillin-resistant strain of Streptococcus mitis, a methicillin-resistant strain of Staphylococcus aureus, and a methicillin-susceptible strain of S. aureus. Levofloxacin administered intramuscularly at dosages of 20 to 40 mg/kg of body weight twice daily (b.i.d.) was completely ineffective against the penicillin-susceptible strain, with mean vegetation titers after 3 days of therapy not statistically significantly different from those for controls. Levofloxacin was no more effective than penicillin against the penicillin-resistant strain. Levofloxacin administered for 4 days at a dosage of 20 mg/kg b.i.d. was at least as effective as vancomycin administered intravenously at a dosage of 25 mg/kg b.i.d. against the methicillin-resistant S. aureus strain and was as effective as nafcillin administered intramuscularly at 100 mg three times daily against the methicillin-susceptible strain. Emergence of resistance to levofloxacin in vitro was less likely to occur than resistance to ciprofloxacin, and resistance to levofloxacin was not observed in vivo. Levofloxacin-rifampin combinations were antagonistic in vitro and in vivo. Levofloxacin was highly effective as a single agent against experimental staphylococcal endocarditis but was surprisingly ineffective against streptococcal endocarditis, suggesting that it has a potential role as treatment for serious S. aureus but not viridans group streptococcal infections in humans.

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