scholarly journals Comparison of the In Vitro Efficacies of Moxifloxacin and Amoxicillin against Listeria monocytogenes

2008 ◽  
Vol 52 (5) ◽  
pp. 1697-1702 ◽  
Author(s):  
S. Grayo ◽  
O. Join-Lambert ◽  
M. C. Desroches ◽  
A. Le Monnier

ABSTRACT Listeria monocytogenes is a facultative intracellular bacterium that causes severe infections associated with a high mortality rate. Moxifloxacin presents extended activity against gram-positive bacteria and has recently been suggested to be a potential alternative in the treatment of listeriosis. We evaluated the in vitro efficacy of moxifloxacin against L. monocytogenes using a combination of epidemiological and experimental approaches. The median MIC of moxifloxacin for a large collection of L. monocytogenes strains of various origins (human, food, and environment) was 0.5 μg/ml (MIC range, 0.064 to 1 μg/ml). No differences were observed, irrespective of the origin of the strains. Moreover, no cross-resistance with fluoroquinolones was detected in strains that have been reported to be resistant to ciprofloxacin. The in vitro activities of moxifloxacin and amoxicillin were compared by time-kill curve and inhibition of intracellular growth experiments by using a model of bone marrow-derived mouse macrophages infected by L. monocytogenes EGDe. Both moxifloxacin and amoxicillin were bactericidal in broth against extracellular forms of L. monocytogenes. However, moxifloxacin acted much more rapidly, beginning to exert its effects in the first 3 h and achieving complete broth sterilization within 24 h of incubation. Moxifloxacin has a rapid bactericidal effect against intracellular reservoirs of bacteria, whereas amoxicillin is only bacteriostatic and appears to prevent cellular lysis and the subsequent bacterial spreading to adjacent cells. No resistant bacteria were selected during the in vitro experiments. Taken together, our results suggest that moxifloxacin is an interesting alternative to the reference treatment, combining rapid and bactericidal activity, even against intracellular bacteria.

2012 ◽  
Vol 57 (1) ◽  
pp. 333-342 ◽  
Author(s):  
Justyna Nowakowska ◽  
Hans J. Griesser ◽  
Marcus Textor ◽  
Regine Landmann ◽  
Nina Khanna

ABSTRACTTreatment options are limited for implant-associated infections (IAI) that are mainly caused by biofilm-forming staphylococci. We report here on the activity of the serrulatane compound 8-hydroxyserrulat-14-en-19-oic acid (EN4), a diterpene isolated from the Australian plantEremophila neglecta. EN4 elicited antimicrobial activity toward various Gram-positive bacteria but not to Gram-negative bacteria. It showed a similar bactericidal effect against logarithmic-phase, stationary-phase, and adherentStaphylococcus epidermidis, as well as against methicillin-susceptible and methicillin-resistantS. aureuswith MICs of 25 to 50 μg/ml and MBCs of 50 to 100 μg/ml. The bactericidal activity of EN4 was similar againstS. epidermidisand its Δicamutant, which is unable to produce polysaccharide intercellular adhesin-mediated biofilm. In time-kill studies, EN4 exhibited a rapid and concentration-dependent killing of staphylococci, reducing bacterial counts by >3 log10CFU/ml within 5 min at concentrations of >50 μg/ml. Investigation of the mode of action of EN4 revealed membranolytic properties and a general inhibition of macromolecular biosynthesis, suggesting a multitarget activity.In vitro-tested cytotoxicity on eukaryotic cells was time and concentration dependent in the range of the MBCs. EN4 was then tested in a mouse tissue cage model, where it showed neither bactericidal nor cytotoxic effects, indicating an inhibition of its activity. Inhibition assays revealed that this was caused by interactions with albumin. Overall, these findings suggest that, upon structural changes, EN4 might be a promising pharmacophore for the development of new antimicrobials to treat IAI.


2015 ◽  
Author(s):  
Sunniva Foerster ◽  
Magnus Unemo ◽  
Lucy J Hathaway ◽  
Nicola Low ◽  
Christian L Althaus

Gonorrhea is a sexually transmitted infection caused by the Gram-negative bacteriumNeisseria gonorrhoeae. Resistance to first-line empirical monotherapy has emerged, so robust methods are needed to appropriately evaluate the activity of existing and novel antimicrobials against the bacterium. Pharmacodynamic functions, which describe the relationship between the concentration of antimicrobials and the bacterial net growth rate, provide more detailed information than the MIC only. In this study, a novel standardized in vitro time-kill curve assay was developed. The assay was validated using five World Health OrganizationN. gonorrhoeaereference strains and various concentrations of ciprofloxacin, and then the activity of nine antimicrobials with different target mechanisms were examined against a highly susceptible clinical wild type isolate (cultured in 1964). From the time-kill curves, the bacterial net growth rates at each antimicrobial concentration were estimated. Finally, a pharmacodynamic function was fitted to the data, resulting in four parameters that describe the pharmacodynamic properties of each antimicrobial. Ciprofloxacin resistance determinants shifted the pharmacodynamic MIC (zMIC) and attenuated the bactericidal effect at antimicrobial concentrations above the zMIC. Ciprofloxacin, spectinomycin and gentamicin had the strongest bactericidal effect during the first six hours of the assay. Only tetracycline and chloramphenicol showed a purely bacteriostatic effect. The pharmacodynamic functions differed between antimicrobials, showing that the effect of the drugs at concentrations below and above the MIC vary widely. In conclusion,N. gonorrhoeaetime-kill curve experiments analyzed with pharmacodynamic functions have potential for in vitro evaluation of new and existing antimicrobials and dosing strategies to treat gonorrhea.


2021 ◽  
Vol 8 (1) ◽  
pp. 160-165
Author(s):  
Masaaki Minami ◽  
Takafumi Ando ◽  
Hidemi Goto ◽  
Michio Ohta

Mupirocin (MUP) is an effective antibiotic against MRSA. Its bactericidal effect is stable under acid condition. By validating its antibacterial effect of Helicobacter pylori, we try to clarify MUP effect on H. pylori. The present study was conducted to investigate the effect of MUP on clarithromycin (CLR) / metronidazole (MNZ) -resistant and -susceptible strains of H. pylori, the time-kill effect of MUP, and the post antibiotic effect (PAE). We investigated the minimal inhibitory concentration (MIC) and the minimal bactericidal effect (MBC) of MUP against 140 H. pylori, which include clinical strains, ATCC43504, 26695 and J99. Ten of them were CLR -resistant strains and 3 were MNZ-resistant strains. The MIC90 and MBC of MUP on all 140 strains is 0.064 μg / ml, and 0.1 μg / ml, respectively. There were no differences of MUP effect between susceptible and resistant strains either for CLR or MNZ. Time-kill curve test and PAE test of MUP on ATCC43504 were performed. By adding MUP, time-kill curve showed that bacterial quantities decreased in dose and time-dependent manner. No viable colony was found after 12-hour culture with 0.1 μg / ml MUP. The value of PAE is 12. MUP is a potential effective antibiotic for H. pylori even those for CLR / MNZ -resistant strains.


Author(s):  
Wei Yu ◽  
Yicheng Huang ◽  
Chaoqun Ying ◽  
Yanzi Zhou ◽  
Li Zhang ◽  
...  

Abstract Background The aim of this study was to investigate the mechanism of Listeria monocytogenes (Lm) pathogenicity and resistance. In addition, the effect of existing treatment options against Lm were systematically evaluated. Methods Six Lm isolates were collected and antimicrobial susceptibility testing of 15 antibiotics were done. Subsequently, whole genome sequencing and bioinformatics analysis were performed. Biofilm formation was evaluated by crystal violet staining. Furthermore, the effect of meropenem, linezolid, penicillin, vancomycin, trimethoprim/sulfamethoxazole were determined using the time-kill assay. Results Four sequence types (STs) were identified (ST1, ST3, ST87, ST451). Multi-virulence-locus sequence typing (MVLST) results classified ST87 isolates into cluster. All isolates were resistant to fosfomycin and daptomycin with fosX and mprF. In addition, a total of 80 virulence genes were detected and 72 genes were found in all six isolates. Seven genes associated with haemolysin were found in 26530 and 115423. However, due to lack of one genomic island including virulence genes related to flagellar synthesis, isolate 115423 produced less biofilm than five other isolates. Even all isolates were susceptible to vancomycin, the in vitro time-kill assay showed vancomycin monotherapy resulted in less than 2 log10 CFU/mL compared with the initial count. Trimethoprim/sulfamethoxazole at serum or cerebrospinal fluid concentrations had bactericidal effect against tested Lm strains at 24 h. Conclusions ST87 clone was a typical prevalent ST in clinical Lm isolates in China. Trimethoprim/sulfamethoxazole might be greater potential therapeutic option against Lm infections.


1997 ◽  
Vol 41 (6) ◽  
pp. 1260-1268 ◽  
Author(s):  
M Tanaka ◽  
M Hohmura ◽  
T Nishi ◽  
K Sato ◽  
I Hayakawa

The in vitro antibacterial activity of DU-6681a, a parent compound of DZ-2640, against gram-positive and -negative bacteria was compared with those of penems and cephalosporins currently available. MICs at which 90% of the isolates are inhibited (MIC90s) of the compound for clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis, including methicillin-susceptible and -resistant strains, were 0.10, 25, and 12.5 microg/ml, respectively. DU-6681a inhibited the growth of all strains of Streptococcus pyogenes and of penicillin-susceptible and -insusceptible Streptococcus pneumoniae at 0.006, 0.025, and 0.20 microg/ml, respectively, and MIC90s of the compound were 6.25 and >100 microg/ml for Enterococcus faecalis and Enterococcus faecium, respectively. MIC90s of DU-6681a were 0.20, 0.10, and 0.025 microg/ml for Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae, respectively. For Pseudomonas aeruginosa, the MIC50 and MIC90 of DU-6681a were 25 and 50 microg/ml, respectively. DU-6681a activity was not affected by different media, varied inoculum size (10(4) to 10(7) CFU), or the addition of human serum but was decreased under acidic conditions against gram-negative bacteria, under alkaline conditions against gram-positive bacteria, and in human urine, as was the activity of the other antibiotics tested. The frequency of spontaneous resistance to DU-6681a was less than or equal to those of the reference compounds. Time-kill curve studies demonstrated the bactericidal action of DU-6681a against S. aureus, S. pneumoniae, Escherichia coli, and H. influenzae.


Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 130 ◽  
Author(s):  
Berna Ozbek-Celik ◽  
Damla Damar-Celik ◽  
Emel Mataraci-Kara ◽  
Cagla Bozkurt-Guzel ◽  
Paul B. Savage

Objectives: The ceragenins, or CSAs, were designed to mimic the activities of antimicrobial peptides and represent a new class of antimicrobial agent. The aim of this study was to comparatively investigate the antimicrobial activities of first/second generation ceragenins and various antibiotics against multidrug-resistant (MDR) Klebsiella pneumoniae, including colistin-resistant bacteria. Also, the synergistic effects of two ceragenins with colistin or meropenem were investigated with six K. pneumoniae strains presenting different resistant patterns. Methods: Minimal inhibition concentrations (MICs) were determined by the microdilution method according to the CLSI. Antibiotic combination studies were evaluated by the time–kill curve method. Results: MIC50 and MIC90 values of tested ceragenins ranged from 8 to 32 mg/L and 16 to 128 mg/L. Overall, among the ceragenins tested, CSA-131 showed the lowest MIC50 and MIC90 values against all microorganisms. The MICs of the ceragenins were similar or better than tested antibiotics, except for colistin. Synergistic activities of CSA-131 in combination with colistin was found for strains both at 1× MIC and 4× MIC. No antagonism was observed with any combination. Conclusions: First-generation ceragenins CSA-13 and CSA-44 and second-generation ceragenins CSA-131, CSA-138 and CSA-142 have significant antimicrobial effects on MDR K. pneumoniae. Mechanisms allowing resistance to clinical comparator antibiotics like colistin did not impact the activity of ceragenins. These results suggest that ceragenins may play a role in treating infections that are resistant to known antibiotics.


2008 ◽  
Vol 52 (11) ◽  
pp. 3875-3882 ◽  
Author(s):  
Cong-Ran Li ◽  
Xin-Yi Yang ◽  
Ren-Hui Lou ◽  
Wei-Xin Zhang ◽  
Yue-Ming Wang ◽  
...  

ABSTRACT Vertilmicin is a new semisynthetic aminoglycoside with a structure similar to that of netilmicin except for a methyl group at the C-6′ position. In the present study, the in vitro antibacterial activity of vertilmicin was studied, and its susceptibility to modifications by the recombinant aminoglycoside bifunctional modifying enzyme AAC(6′)-APH(2″) was compared with those of verdamicin and netilmicin. A total of 1,185 clinical isolates collected from hospitals in Beijing between 2000 and 2001 were subjected to the in vitro antibacterial activity evaluations, including MIC, minimum bactericidal concentration (MBC), and time-kill curve tests. The MICs were evaluated in non-gentamicin-resistant (gentamicin-susceptible and gentamicin-intermediate) strains and gentamicin-resistant strains, respectively. For most of the non-gentamicin-resistant bacteria (except for the isolates of Pseudomonas spp.), the MIC90s of vertilmicin were in the range of 0.5 to 8 μg/ml, comparable to those of the reference aminoglycosides. For the gentamicin-resistant isolates, the three semisynthetic aminoglycosides (vertilmicin, netilmicin, and amikacin) demonstrated low MIC50s and/or MIC90s, as well as high percent susceptibility values. Among the study drugs, vertilmicin showed the lowest MIC90s, 16 μg/ml, for the gram-positive gentamicin-resistant isolates of Staphylococcus aureus and Staphylococcus epidermidis. Meanwhile, vertilmicin was a potent bactericidal agent, with MBC/MIC ratios in the range of 1 to 2 for Escherichia coli, Klebsiella pneumoniae, and S. aureus and 1 to 4 for S. epidermidis. The time-kill curve determination further demonstrated that this effect was rapid and concentration dependent. In evaluations of susceptibility to modifications by the recombinant AAC(6′)-APH(2″) with maximum rate of metabolism/Km measurements, vertilmicin exhibited susceptibilities to both acetylation and phosphorylation lower than those of netilmicin and verdamicin.


1998 ◽  
Vol 42 (8) ◽  
pp. 1973-1979 ◽  
Author(s):  
Christine E. Thorburn ◽  
Sarah J. Knott ◽  
David I. Edwards

ABSTRACT The β-lactam susceptibilities of 65 strains ofStreptococcus pneumoniae for which penicillin MICs covered a broad range were assessed. The order of potency was amoxicillin (AMX) = amoxicillin-clavulanate (AMC) > penicillin G > cefpodoxime (CPO) > cefuroxime (CXM) > cefprozil > cefaclor > loracarbef > cefixime. No decrease in susceptibility was seen following repeated subculture of two penicillin-susceptible strains of S. pneumoniae in AMX, AMC, cefaclor, or loracarbef, whereas repeated exposure to CPO and CXM resulted in 4- to 32-fold decreases in susceptibility for both strains. When one of these strains was exposed to concentrations of CPO, CXM, AMX, and AMC achieved in the serum of humans following the administration of an oral dose, all agents were rapidly bactericidal, with no decrease in susceptibility up to 72 h. This was consistent with antibiotic concentrations exceeding the MICs for 100% of the dosing interval. For a penicillin-resistant strain, MICs were exceeded for 29% of the 12-h dosing interval for 500 mg of AMX, 42% of the interval for AMC with 875 mg of AMX and 125 mg of clavulanate (875/125 mg of AMC) 21% of the interval for 500 mg of CXM, and 0% of the interval for 200 mg of CPO. Consequently, only 875/125 mg of AMC produced a sustained bactericidal effect. A four- to eightfold reduction in susceptibility to CPO and CXM and cross-resistance with cefotaxime, but not penicillin or AMC, were selected following exposure to simulated serum CPO and CXM concentrations. In addition, AMX and AMC were the only agents which consistently produced a >99% reduction in bacterial numbers in time-kill studies using concentrations of antibiotic achieved in middle ear fluid for all three strains of penicillin-resistant S. pneumoniae tested.


2000 ◽  
Vol 44 (4) ◽  
pp. 1062-1066 ◽  
Author(s):  
Michael J. Rybak ◽  
Ellie Hershberger ◽  
Tabitha Moldovan ◽  
Richard G. Grucz

ABSTRACT The in vitro activity of daptomycin was compared with those of vancomycin, linezolid, and quinupristin-dalfopristin against a variety (n = 203) of gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and S. epidermidis (MRSA and MRSE, respectively), vancomycin-resistant enterococci (VRE), and vancomycin-intermediate S. aureus(VISA). Overall, daptomycin was more active against all organisms tested, except Enterococcus faecium and VISA, against which its activity was similar to that of quinupristin-dalfopristin. In time-kill studies with MRSA, MRSE, VRE, and VISA, daptomycin demonstrated greater bactericidal activity than all other drugs tested, killing ≥3 log CFU/ml by 8 h. Daptomycin may be a potential alternative drug therapy for multidrug-resistant gram-positive organisms and warrants further investigation.


2020 ◽  
Author(s):  
Wei Yu ◽  
Yicheng Huang ◽  
Lihua Guo ◽  
Jiajie Zhang ◽  
Yaqiong Zhan ◽  
...  

Abstract Background: Invasive Listeria monocytogenes (Lm) carry a high mortality despite antibiotic treatment. The aim of this study was to investigate the mechanism of pathogenicity and resistance. In addition, the effect of existing treatment options against Lm were systematically evaluated as well. Methods: Three Lm isolates were collected and 15 antibiotics susceptibility tests were done. Subsequently, whole genome sequencing and bioinformatics analysis were performed. Furthermore, the effect of meropenem, linezolid, benzylpenicillin, vancomycin, trimethoprim/sulfamethoxazole were determined using the time-kill assay.Results: Two sequence types (STs) were identified for isolate 23949 (ST87), 26530 (ST3), 34096 (ST87), respectively. All isolates were resistant to fosfomycin and daptomycin. The resistant genes fosX, mprF, norB and vgaALC were identified in all isolates. Furthermore, 80 virulence genes were detected and 72 genes were found in all three isolates. There were 26 virulent genes associated with the structure, biosynthesis, motor switch of flagellum. And other virulent genes were involved in chemotaxis, protease, internalin and metabolism. It is of note that 8 genes (inlJ, llsB, llsD, llsG, llsH, llsP, llsX, llsY) were only found in 26530 isolated from cerebrospinal fluid (CSF), 7 of which were associated with haemolysin. Further in vitro time-kill assay found trimethoprim/sulfamethoxazole at serum or CSF concentrations had bactericidal effect (>3.5 log10 CFU/ml) against three tested Lm strains at 24 h. Conclusions: The involved virulence factors were mainly associated with bacterial pathogenicity. Notably, trimethoprim/sulfamethoxazole might be greater potential therapeutic option against Lm bloodstream infection or intracranial infection.


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