Pulsatile Delivery of Clarithromycin Alone or in Combination with Amoxicillin against Streptococcus pneumoniae

ABSTRACT We evaluated pulsatile dosing of clarithromycin and amoxicillin alone or combined against Streptococcus pneumoniae with various susceptibilities. When combined, pulsatile amoxicillin with clarithromycin was superior to either 8- or 12-h dosing against the intermediate strain and was identical for the susceptible strain. Pulse dosing of antimicrobials warrants further investigation.

Download Full-text

Genetic Characterization of Fluoroquinolone-Resistant Streptococcus pneumoniae Strains Isolated during Ciprofloxacin Therapy from a Patient with Bronchiectasis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.4.1419-1422.2003 ◽

2003 ◽

Vol 47 (4) ◽

pp. 1419-1422 ◽

Cited By ~ 16

Author(s):

Adela G. de la Campa ◽

María-José Ferrandiz ◽

Fe Tubau ◽

Román Pallarés ◽

Federico Manresa ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Genetic Characterization ◽

Susceptible Strain ◽

Low Level ◽

Resistant Strains ◽

Resistant Mutants ◽

High Level ◽

Level Resistance

ABSTRACT Five Spain9V-3 Streptococcus pneumoniae strains were isolated from a patient with bronchiectasis who had received long-term ciprofloxacin therapy. One ciprofloxacin-susceptible strain was isolated before treatment, and four ciprofloxacin-resistant strains were isolated during treatment. The resistant strains were derived from the susceptible strain either by a parC mutation (low-level resistance) or by parC and gyrA mutations (high-level resistance). This study shows that ciprofloxacin therapy in a patient colonized by susceptible S. pneumoniae may select fluoroquinolone-resistant mutants.

Download Full-text

ParC and GyrA May Be Interchangeable Initial Targets of Some Fluoroquinolones in Streptococcus pneumoniae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.2.302 ◽

1999 ◽

Vol 43 (2) ◽

pp. 302-306 ◽

Cited By ~ 55

Author(s):

Emmanuelle Varon ◽

Claire Janoir ◽

Marie-Dominique Kitzis ◽

Laurent Gutmann

Keyword(s):

Streptococcus Pneumoniae ◽

Susceptible Strain ◽

Quinolone Resistance ◽

Topoisomerase Iv ◽

Double Mutation ◽

Active Efflux ◽

Single Target ◽

Resistant Mutants ◽

The Individual

ABSTRACT To evaluate the role of known topoisomerase IV and gyrase mutations in the fluoroquinolone (FQ) resistance of Streptococcus pneumoniae, we transformed susceptible strain R6 with PCR-generated fragments encompassing the quinolone resistance-determining regions (QRDRs) of parC orgyrA from different recently characterized FQ-resistant mutants. Considering the MICs of FQs and the GyrA and/or ParC mutations of the individual transformants, we found three levels of resistance. The first level was obtained when a single target, ParC or GyrA, depending on the FQ, was modified. An additional mutation(s) in a second target, GyrA or ParC, led to the second level. The highest increases in resistance levels were seen for Bay y3118 and moxifloxacin with the transformant harboring a double mutation in both ParC and GyrA. When a single modified target was considered, only the ParC mutation(s) led to an increase in the MICs of pefloxacin and trovafloxacin. In contrast, the GyrA or ParC mutation(s) could lead to increases in the MICs of ciprofloxacin, sparfloxacin, grepafloxacin, Bay y3118, and moxifloxacin. These results suggest that the preferential target of trovafloxacin and pefloxacin is ParC, whereas either ParC or GyrA may both be initial targets for the remaining FQs tested. The contribution of the ParC and GyrA mutations to efflux-mediated FQ resistance was also examined. Active efflux was responsible for two- to fourfold increases in the MICs of ciprofloxacin for the transformants, regardless of the initial FQ resistance levels of the recipients.

Download Full-text

In Vitro Activity of Sanfetrinem and Affinity for the Penicillin-Binding Proteins of Streptococcus pneumoniae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.1.173 ◽

1998 ◽

Vol 42 (1) ◽

pp. 173-175 ◽

Cited By ~ 6

Author(s):

Farid Sifaoui ◽

Emmanuelle Varon ◽

Marie-Dominique Kitzis ◽

Laurent Gutmann

Keyword(s):

Streptococcus Pneumoniae ◽

Binding Proteins ◽

Susceptible Strain ◽

Vitro Activity ◽

In Vitro Activity ◽

Penicillin Binding Proteins ◽

Resistant Strains

ABSTRACT Against penicillin-susceptible pneumococci, the activity of sanfetrinem was similar to those of penicillin, amoxicillin, cefotaxime, imipenem, and meropenem, while against penicillin-resistant strains, sanfetrinem and the carbapenems exhibited superior activity (MICs at which 90% of strains are inhibited, ≤1 μg/ml). PBP 1a in the penicillin-susceptible strain and PBP 1a and PBP 2b in the more resistant isolates seemed to be the essential penicillin-binding proteins for imipenem and sanfetrinem.

Download Full-text

Single-Step Capsular Transformation and Acquisition of Penicillin Resistance in Streptococcus pneumoniae

Journal of Bacteriology ◽

10.1128/jb.186.11.3447-3452.2004 ◽

2004 ◽

Vol 186 (11) ◽

pp. 3447-3452 ◽

Cited By ~ 34

Author(s):

Krzysztof Trzciński ◽

Claudette M. Thompson ◽

Marc Lipsitch

Keyword(s):

Streptococcus Pneumoniae ◽

Multidrug Resistant ◽

Single Step ◽

Susceptible Strain ◽

Polymorphism Analysis ◽

Capsule Locus ◽

Elevated Rate ◽

Quellung Reaction ◽

Natural Settings ◽

Flanking Regions

ABSTRACT The capsule (cps) locus of Streptococcus pneumoniae is flanked by the pbp2x and pbp1a genes, coding for penicillin-binding proteins, enzymes involved in cell wall synthesis that are targets for β-lactams. This linkage suggested to us that selection for β-lactam resistance might coselect for capsular transformants. The recombination event would then involve PBP genes, as well as the cps operon, and would change both the serotype and the resistance profile of the strain. We transformed β-lactam-susceptible strain TIGR4 by using whole genomic DNA extracted from multidrug-resistant strain GA71, a serotype 19F variant of pneumococcal clone Spain23F-1, and selected β-lactam-resistant transformants. Smooth colonies appearing on selective plates were subcultured, serotyped by the Quellung reaction, and genotyped to confirm the presence of the GA71 pbp2x-cps19-pbp1a locus in the TIGR4 genetic background by restriction fragment length polymorphism analysis of the whole locus and its flanking regions. The results showed that a new serotype, combined with resistance to β-lactams, could emerge in a susceptible strain via a single transformation event. Quantitative analysis showed that transfer of the cps locus had occurred at an elevated rate in β-lactam-selected transformants. This suggests that in natural settings selection by host immunity and selection by antibiotics may be interrelated because of “hitchhiking” effects due to linkage of resistance determinants and the capsule locus.

Download Full-text

Novel Mechanism of Resistance to Oxazolidinones, Macrolides, and Chloramphenicol in Ribosomal Protein L4 of the Pneumococcus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.8.3554-3557.2005 ◽

2005 ◽

Vol 49 (8) ◽

pp. 3554-3557 ◽

Cited By ~ 101

Author(s):

Nicole Wolter ◽

Anthony M. Smith ◽

David J. Farrell ◽

William Schaffner ◽

Matthew Moore ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Ribosomal Protein ◽

Fitness Cost ◽

Susceptible Strain ◽

Gene Encoding ◽

Mechanism Of Resistance

ABSTRACT Two clinical Streptococcus pneumoniae isolates, identified as resistant to macrolides and chloramphenicol and nonsusceptible to linezolid, were found to contain 6-bp deletions in the gene encoding riboprotein L4. The gene transformed susceptible strain R6 so that it exhibited such resistance, with the transformants also showing a fitness cost. We demonstrate a novel bacterial mechanism of resistance to chloramphenicol and nonsusceptibility to linezolid.

Download Full-text