Structures of existing and new quinolones and relationship to bactericidal activity against Streptococcus pneumoniae

1999 ◽  
Vol 44 (2) ◽  
pp. 201-207 ◽  
Author(s):  
Junichi Mitsuyama
1999 ◽  
Vol 5 (2) ◽  
pp. 101-103
Author(s):  
Juan Carlos Rodríguez ◽  
Montserrat Ruiz ◽  
Fernando García ◽  
Gloria Royo

Chemotherapy ◽  
2001 ◽  
Vol 47 (6) ◽  
pp. 409-414 ◽  
Author(s):  
P. Joyanes ◽  
A. Pascual ◽  
M.J. Giménez ◽  
I. García ◽  
L. Aguilar ◽  
...  

2000 ◽  
Vol 44 (5) ◽  
pp. 1352-1355 ◽  
Author(s):  
Andrej Trampuz ◽  
Markus Wenk ◽  
Zarko Rajacic ◽  
Werner Zimmerli

ABSTRACT The pharmacokinetics of levofloxacin in serum and in skin blister fluid (SBF) was determined for 20 volunteers after a single 500-mg oral dose of levofloxacin. In addition, ex vivo bactericidal activity of SBF against Streptococcus pneumoniae and Staphylococcus aureus was studied. SBF containing levofloxacin and granulocytes killed 5.2 log of Streptococcus pneumoniae bacteria and 2.0 log of Staphylococcus aureus bacteria during a 6-h incubation.


1997 ◽  
Vol 41 (9) ◽  
pp. 2050-2052 ◽  
Author(s):  
C Doit ◽  
J Barre ◽  
R Cohen ◽  
S Bonacorsi ◽  
A Bourrillon ◽  
...  

Cerebrospinal fluid (CSF) was taken from 19 children with bacterial meningitis treated with cefotaxime (300 mg/kg of body weight/day) and vancomycin (60 mg/kg/day). Median levels of drugs in CSF were smaller than expected, as follows: 4.4 microg/ml for cefotaxime, 3.2 microg/ml for desacetylcefotaxime, and 1.7 microg/ml for vancomycin. The median CSF bactericidal titer against an intermediately cefotaxime-resistant pneumococcus was 1:4. Our data suggest at least an additive interaction between the drugs used in this study.


2003 ◽  
Vol 47 (4) ◽  
pp. 1308-1312 ◽  
Author(s):  
Gary E. Stein ◽  
Sharon Schooley ◽  
Kerin L. Tyrrell ◽  
Diane M. Citron ◽  
Ellie J. C. Goldstein

ABSTRACT Gatifloxacin (Bristol-Myers Squibb) and moxifloxacin (Bayer) are new methoxyfluoroquinolones with broad-spectrum activity against aerobic and anaerobic pathogens of the respiratory tract. In this investigation, we analyzed the bactericidal activity in serum over time of these antimicrobials against three aerobic (Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus) and four anaerobic (Peptostreptococcus micros, Peptostreptococcus magnus, Fusobacterium nucleatum, and Prevotella melaninogenica) bacteria associated with respiratory tract infections. Serum samples were obtained from 11 healthy male subjects following a single 400-mg oral dose of gatifloxacin and moxifloxacin. These samples were collected prior to and at 2, 6, 12, and 24 h after the dose of each drug. Gatifloxacin exhibited bactericidal activity for a median of 12 h against Streptococcus pneumoniae (MIC = 0.5 μg/ml), Peptostreptococcus micros (MIC = 0.25 μg/ml), and F. nucleatum (MIC = 0.5 μg/ml) and 24 h against H. influenzae (MIC = 0.03 μg/ml), Staphylococcus aureus (MIC = 0.125 μg/ml), Peptostreptococcus magnus (MIC = 0.125 μg/ml), and Prevotella melaninogenica (MIC = 0.5 μg/ml). Moxifloxacin exhibited bactericidal activity for a median of 24 h against Streptococcus pneumoniae (MIC = 0.125 μg/ml), H. influenzae (MIC = 0.015 μg/ml), Staphylococcus aureus (MIC = 0.06 μg/ml), F. nucleatum (MIC = 0.5 μg/ml), Prevotella melaninogenica (MIC =0.5 μg/ml), Peptostreptococcus magnus (MIC = 0.125 μg/ml), and Peptostreptococcus micros (MIC = 0.25 μg/ml). The results from this pharmacodynamic study suggest that these fluoroquinolones would have prolonged killing activity against these organisms in vivo and may have clinical utility in the treatment of mixed aerobic-anaerobic respiratory tract infections.


2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Dehua Luo ◽  
Li Huang ◽  
Vijay Singh Gondil ◽  
Wanli Zhou ◽  
Wan Yang ◽  
...  

ABSTRACT Streptococcus pneumoniae is a leading pathogen for bacterial pneumonia, which can be treated with bacteriophage lysins harboring a conserved choline binding module (CBM). Such lysins regularly function as choline-recognizing dimers. Previously, we reported a pneumococcus-specific lysin ClyJ comprising the binding domain from the putative endolysin gp20 from the Streptococcus phage SPSL1 and the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) catalytic domain from the PlyC lysin. A variant of ClyJ with a shortened linker, i.e., ClyJ-3, shows improved activity and reduced cytotoxicity. Resembling typical CBM-containing lysins, ClyJ-3 dimerized upon binding with choline. Herein, we further report a choline-recognizing variant of ClyJ-3, i.e., ClyJ-3m, constructed by deleting its C-terminal tail. Biochemical characterization showed that ClyJ-3m remains a monomer after it binds to choline yet exhibits improved bactericidal activity against multiple pneumococcal strains with different serotypes. In an S. pneumoniae-infected bacteremia model, a single intraperitoneal administration of 2.32 μg/mouse of ClyJ-3m showed 70% protection, while only 20% of mice survived in the group receiving an equal dose of ClyJ-3 (P < 0.05). A pharmacokinetic analysis following single intravenously doses of 0.29 and 1.16 mg/kg of ClyJ-3 or ClyJ-3m in BALB/c mice revealed that ClyJ-3m shows a similar half-life but less clearance and a greater area under curve than ClyJ-3. Taken together, the choline-recognizing monomer ClyJ-3m exhibited enhanced bactericidal activity and improved pharmacokinetic proprieties compared to those of its parental ClyJ-3 lysin. Our study also provides a new way for rational design and programmed engineering of lysins targeting S. pneumoniae.


Author(s):  
R. Diez-Martinez ◽  
H. D. De Paz ◽  
E. Garcia-Fernandez ◽  
N. Bustamante ◽  
C. W. Euler ◽  
...  

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