scholarly journals Bactericidal activity of levofloxacin, gatifloxacin, penicillin, meropenem and rokitamycin against Bacillus anthracis clinical isolates

2002 ◽  
Vol 50 (6) ◽  
pp. 1059-1063 ◽  
Author(s):  
L. Drago
2004 ◽  
Vol 48 (3) ◽  
pp. 1055-1057 ◽  
Author(s):  
Rose Jung ◽  
Maroof Husain ◽  
Michael K. Choi ◽  
Douglas N. Fish

ABSTRACT The bactericidal activity of moxifloxacin alone and in combination with cefepime or piperacillin-tazobactam against clinical isolates of Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter baumannii was evaluated by using time-kill methods and antimicrobial concentrations of one-half and one times the MIC. Synergy was observed in 58 to 88% of the strains and resulted in bactericidal activity against 60 to 100% of the strains. Combinations including moxifloxacin demonstrated enhanced bactericidal activity compared with that of either agent tested alone.


2017 ◽  
Vol 85 (12) ◽  
Author(s):  
Shun Xin Wang-Lin ◽  
Ruth Olson ◽  
Janet M. Beanan ◽  
Ulrike MacDonald ◽  
Joseph P. Balthasar ◽  
...  

ABSTRACT Acinetobacter baumannii has become an important concern for human health due to rapid development and wide spread of antimicrobial-resistant strains and high mortality associated with the infection. Passive immunizations with antisera targeting outer membrane proteins (OMPs) have shown encouraging results in protecting mice from A. baumannii infection, but monoclonal anti-OMP antibodies have not been developed, and their potential therapeutic properties have not been explored. The goal of this report is to evaluate the antibacterial activity of monoclonal antibodies (MAbs) targeting outer membrane protein A (OmpA) of A. baumannii. Five anti-OmpA MAbs were developed using hybridoma technology and showed strong binding to strain ATCC 19606. However, low antibody binding was observed when they were tested against six clinical isolates, which included extensively drug-resistant strains. In contrast, high binding to an isogenic K1 capsule-negative mutant (AB307.30) was shown, suggesting that capsular polysaccharide mediated the inhibition of MAb binding to OmpA. Anti-OmpA MAbs increased the macrophage-mediated bactericidal activity of AB307.30 but failed to increase phagocytic killing of capsule-positive strains. Capsular polysaccharide was also protective against complement-mediated bactericidal activity in human ascites in the presence and absence of opsonization. Lastly, passive immunization with anti-OmpA MAbs did not confer protection against challenge with AB307-0294, the encapsulated parent strain of AB307.30, in a mouse sepsis infection model. These results reveal the important role of capsule polysaccharide in shielding OmpA and thereby inhibiting anti-OmpA MAb binding to clinical isolates. This property of capsule hindered the therapeutic utility of anti-OmpA MAbs, and it may apply to other conserved epitopes in A. baumannii.


2009 ◽  
Vol 53 (5) ◽  
pp. 2133-2135 ◽  
Author(s):  
Maria Souli ◽  
Panagiota Danai Rekatsina ◽  
Zoi Chryssouli ◽  
Irene Galani ◽  
Helen Giamarellou ◽  
...  

ABSTRACT Using time-kill methodology, we investigated the interactions of an imipenem-colistin combination against 42 genetically distinct Klebsiella pneumoniae clinical isolates carrying a bla VIM-1-type gene. Irrespective of the imipenem MIC, the combination was synergistic (50%) or indifferent (50%) against colistin-susceptible strains, while it was antagonistic (55.6%) and rarely synergistic (11%) against non-colistin-susceptible strains (with synergy being observed only against strains with colistin MICs of 3 to 4 μg/ml). The combination showed improved bactericidal activity against isolates susceptible either to both agents or to colistin.


mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Karine Loth ◽  
Agnès Vergnes ◽  
Cairé Barreto ◽  
Sébastien N. Voisin ◽  
Hervé Meudal ◽  
...  

ABSTRACT Big defensins, ancestors of β-defensins, are composed of a β-defensin-like C-terminal domain and a globular hydrophobic ancestral N-terminal domain. This unique structure is found in a limited number of phylogenetically distant species, including mollusks, ancestral chelicerates, and early-branching cephalochordates, mostly living in marine environments. One puzzling evolutionary issue concerns the advantage for these species of having maintained a hydrophobic domain lost during evolution toward β-defensins. Using native ligation chemistry, we produced the oyster Crassostrea gigas BigDef1 (Cg-BigDef1) and its separate domains. Cg-BigDef1 showed salt-stable and broad-range bactericidal activity, including against multidrug-resistant human clinical isolates of Staphylococcus aureus. We found that the ancestral N-terminal domain confers salt-stable antimicrobial activity to the β-defensin-like domain, which is otherwise inactive. Moreover, upon contact with bacteria, the N-terminal domain drives Cg-BigDef1 assembly into nanonets that entrap and kill bacteria. We speculate that the hydrophobic N-terminal domain of big defensins has been retained in marine phyla to confer salt-stable interactions with bacterial membranes in environments where electrostatic interactions are impaired. Those remarkable properties open the way to future drug developments when physiological salt concentrations inhibit the antimicrobial activity of vertebrate β-defensins. IMPORTANCE β-Defensins are host defense peptides controlling infections in species ranging from humans to invertebrates. However, the antimicrobial activity of most human β-defensins is impaired at physiological salt concentrations. We explored the properties of big defensins, the β-defensin ancestors, which have been conserved in a number of marine organisms, mainly mollusks. By focusing on a big defensin from oyster (Cg-BigDef1), we showed that the N-terminal domain lost during evolution toward β-defensins confers bactericidal activity to Cg-BigDef1, even at high salt concentrations. Cg-BigDef1 killed multidrug-resistant human clinical isolates of Staphylococcus aureus. Moreover, the ancestral N-terminal domain drove the assembly of the big defensin into nanonets in which bacteria are entrapped and killed. This discovery may explain why the ancestral N-terminal domain has been maintained in diverse marine phyla and creates a new path of discovery to design β-defensin derivatives active at physiological and high salt concentrations.


2012 ◽  
Vol 56 (11) ◽  
pp. 5990-5993 ◽  
Author(s):  
Lisa M. Avery ◽  
Molly E. Steed ◽  
Ashley E. Woodruff ◽  
Muhammad Hasan ◽  
Michael J. Rybak

ABSTRACTWe report two cases of daptomycin (DAP)-nonsusceptible (DNS) vancomycin-intermediateStaphylococcus aureus(VISA) vertebral osteomyelitis cases complicated by bacteremia treated with high-dose daptomycin and trimethoprim-sulfamethoxazole. Both patients responded rapidly and favorably to this combination. The clinical isolates from the two patients were testedpost hocin anin vitropharmacokinetic/pharmacodynamic (PK/PD) model to confirm the bactericidal activity and enhancement of daptomycin and trimethoprim-sulfamethoxazole. The combination of high-dose daptomycin and trimethoprim-sulfamethoxazole should be explored further for the treatment of DNS VISA strains.


2020 ◽  
Vol 9 (5-6) ◽  
pp. 671-679
Author(s):  
D. V. Tapalski ◽  
O. I. Savchenko ◽  
N. A. Bonda

Here, we characterized in public health organizations prevalence of carbapenemase-producing Klebsiella pneumoniae, sensitivity to antimicrobial agents (AMAs), combined antimicrobial agents, and decontaminants. For this, there were selected 58 clinical isolates of K. pneumoniae resistant to carbapenems and/or polymyxins and examined within the microbiological monitoring program. Genes encoding KPC, OXA-48, VIM, IMP, NDM carbapenemases were detected by real-time multiplex PCR. Sensitivity to antimicrobial agents was determined by an automated method on a microbiological VITEK-2 Compact analyzer (bioMérieux, France) and by serial broth microdilution method. Sensitivity to 11 dual antimicrobial agent combinations was determined by a modified method of multiple combination bactericidal antibiotic testing. As a part of combinations, AMAs at pharmacokinetic/pharmacodynamics (PK/PD) threshold concentrations (meropenem — 8 μg/ml, amikacin — 16 μg/ml, levofloxacin — 1 μg/ml, tigecycline — 0.5 μg/ml, phosphomycin — 32 μg/ml, colistin — 2 μg/ml) were tested. Susceptibility to 7 combined decontaminants of different composition was determined by the suspension method. Carbapenemase genes were detected in 22 K. pneumoniae clinical isolates, of which 19 isolates contained a blaOXA-48 gene and 3 isolates — gene blaNDM. Carbapenemase producing K. pneumoniae were identified in 10 Gomel public health organizations and five regional centers of the Gomel region. The majority of such strains were isolated from patients in ICU (63.6%) and surgical departments (27.3%). Tigecycline (100% of the sensitive isolates, МIC50 — 1 μg/ml, MIC90 — 1 μg/ml) and colistin (86.4% of the sensitive isolates, МIC50 — 0.5 μg/ml, MIC90 — 4 μg/ml) exhibited the highest activity against carbapenemase-producing K. pneumoniae, whereas aminopenicillins, cephalosporins, aztreonam, aminoglycosides, fluoroquinolones, chloramphenicol (no sensitive isolates) had exhibited the lowest efficacy. Bactericidal activity of all antibiotic combinations containing colistin was shown against 86.4–95.5% of K. pneumoniae isolates. At least 3 distinct combinations of antimicrobial agents with bactericidal activity were efficient against 21 K. pneumoniae isolates (95.5%). Only 1 bactericidal combination (meropenem–amikacin) was unveiled for one isolate (producer of NDM MBL with MIC of colistin 32 μg/ml). Geksadekon, duacid, oksidez, hlorocid and diajsid exerted a bactericidal effect at 1/4 work dose against all isolates. Duacid, oksidez, hlorocid and diajsid showed bactericidal effect at 1/16 work dose against 95.5–100% isolates. Thus, several decontaminant groups (oxidizing agents, chlorine-containing preparations) were characterized by bactericidal activity against multidrug-resistant and extremely drug-resistant of K. pneumoniae even at 4–16 times lower than recommended concentration.


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