In-vitro and in-vivo potency of five new fluoroquinolones against anaerobic bacteria

1986 ◽  
Vol 18 (6) ◽  
pp. 693-701 ◽  
Author(s):  
Prabhavathi B. Fernandes ◽  
Nathan Shipkowitz ◽  
Robert R. Bower ◽  
Kenneth P. Jarvis ◽  
Jonina Weisz ◽  
...  
Keyword(s):  
1999 ◽  
Vol 43 (4) ◽  
pp. 738-744 ◽  
Author(s):  
P. J. Petersen ◽  
N. V. Jacobus ◽  
W. J. Weiss ◽  
P. E. Sum ◽  
R. T. Testa

ABSTRACT The 9-t-butylglycylamido derivative of minocycline (TBG-MINO) is a recently synthesized member of a novel group of antibiotics, the glycylcyclines. This new derivative, like the first glycylcyclines, theN,N-dimethylglycylamido derivative of minocycline and 6-demethyl-6-deoxytetracycline, possesses activity against bacterial isolates containing the two major determinants responsible for tetracycline resistance: ribosomal protection and active efflux. The in vitro activities of TBG-MINO and the comparative agents were evaluated against strains with characterized tetracycline resistance as well as a spectrum of recent clinical aerobic and anaerobic gram-positive and gram-negative bacteria. TBG-MINO, with an MIC range of 0.25 to 0.5 μg/ml, showed good activity against strains expressing tet(M) (ribosomal protection), tet(A), tet(B),tet(C), tet(D), and tet(K) (efflux resistance determinants). TBG-MINO exhibited similar activity against methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant streptococci, and vancomycin-resistant enterococci (MICs at which 90% of strains are inhibited, ≤0.5 μg/ml). TBG-MINO exhibited activity against a wide diversity of gram-negative aerobic and anaerobic bacteria, most of which were less susceptible to tetracycline and minocycline. The in vivo protective effects of TBG-MINO were examined against acute lethal infections in mice caused by Escherichia coli, S. aureus, andStreptococcus pneumoniae isolates. TBG-MINO, administered intravenously, demonstrated efficacy against infections caused byS. aureus including MRSA strains and strains containingtet(K) or tet(M) resistance determinants (median effective doses [ED50s], 0.79 to 2.3 mg/kg of body weight). TBG-MINO demonstrated efficacy against infections caused by tetracycline-sensitive E. coli strains as well asE. coli strains containing either tet(M) or the efflux determinant tet(A), tet(B), ortet(C) (ED50s, 1.5 to 3.5 mg/kg). Overall, TBG-MINO shows antibacterial activity against a wide spectrum of gram-positive and gram-negative aerobic and anaerobic bacteria including strains resistant to other chemotherapeutic agents. The in vivo protective effects, especially against infections caused by resistant bacteria, corresponded with the in vitro activity of TBG-MINO.


1995 ◽  
Vol 1 (5) ◽  
pp. 462-478 ◽  
Author(s):  
Waltraud Eggert-Kruse ◽  
Gerhard Rohr ◽  
Wolfram Ströck ◽  
Susanne Pohl ◽  
Beate Schwalbach ◽  
...  

Abstract The clinical significance of micro-organisms in semen samples of asymptomatic subfertile patients is a matter of constant debate. Usually little attention is paid to anaerobic bacteria as they are sensitive to transportation and culturing, and differentiation is difficult, costly and time-consuming. In the present study, special screening was carried out for anaerobes in ejaculates in addition to the routine microbial cultures of genital secretions of both partners. In addition to standard semen analysis and evaluation of sperm ability to penetrate cervical mucus (CM) in vivo (postcoital testing) and in vitro using a standardized test system, semen samples from 126 randomly chosen males of couples with a median duration of infertility of 4 years were examined for colonization with anaerobic bacteria. All couples were without clinical signs or symptoms of genital tract infection. The special care taken for anaerobic growth in semen samples gave a high rate of positive cultures and showed that nearly all ejaculates (99%) were colonized with anaerobic micro-organisms, and potentially pathogenic species were found in 71% of men. This rate was more than four times higher than that obtained with routine cultures and standard transportation (16%). Anaerobic bacterial growth of ≥106 colony forming units (CFU)/ml was seen in 42% (total range 103-108 CFU/ml). In addition, aerobic growth was found in 96%(≥106 CFU/ml in 21%), potentially pathogenic species in 61% of semen specimens. There were no marked differences in the prevalence of anaerobic micro-organisms in patients with reduced or normal sperm count, motility or morphology. Nor was there any significant difference in anaerobic colonization between samples with impaired or good ability to penetrate CM of female partners (in vivo or in vitro), or the CM of fertile donors in the in-vitro sperm-cervical mucus penetration test (SCMPT) in this asymptomatic group of patients. There was no clear association between microbial colonization and subsequent fertility in vivo within an observation period of 6 months. The results of this study suggest that anaerobic bacteria are often not detected when routine methods for microbial evaluation are used. This should be considered during assisted reproduction and in patients with symptoms of genital tract infection and should lead to further studies in infertile patients where subclinical infection or inflammation is indicated by specific markers in semen samples.


Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4519
Author(s):  
Marzena Kucia ◽  
Ewa Wietrak ◽  
Mateusz Szymczak ◽  
Paweł Kowalczyk

In this present study, the bacteriostatic effect of Salistat SGL03 and the Lactobacillus salivarius strain contained in it was investigated in adults in in vivo and in vitro tests on selected red complex bacteria living in the subgingival plaque, inducing a disease called periodontitis, i.e., chronic periodontitis. Untreated periodontitis can lead to the destruction of the gums, root cementum, periodontium, and alveolar bone. Anaerobic bacteria, called periopathogens or periodontopathogens, play a key role in the etiopathogenesis of periodontitis. The most important periopathogens of the oral microbiota are: Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and others. Our hypothesis was verified by taking swabs of scrapings from the surface of the teeth of female hygienists (volunteers) on full and selective growth media for L. salivarius. The sizes of the zones of growth inhibition of periopathogens on the media were measured before (in vitro) and after consumption (in vivo) of Salistat SGL03, based on the disk diffusion method, which is one of the methods of testing antibiotic resistance and drug susceptibility of pathogenic microorganisms. Additionally, each of the periopathogens analyzed by the reduction inoculation method, was treated with L. salivarius contained in the SGL03 preparation and incubated together in Petri dishes. The bacteriostatic activity of SGL03 preparation in selected periopathogens was also analyzed using the minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests. The obtained results suggest the possibility of using the Salistat SGL03 dietary supplement in the prophylaxis and support of the treatment of periodontitis—already treated as a civilization disease.


mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Jeffrey M. Flynn ◽  
Lydia C. Cameron ◽  
Talia D. Wiggen ◽  
Jordan M. Dunitz ◽  
William R. Harcombe ◽  
...  

ABSTRACT A critical limitation in the management of chronic polymicrobial infections is the lack of correlation between antibiotic susceptibility testing (AST) and patient responses to therapy. Underlying this disconnect is our inability to accurately recapitulate the in vivo environment and complex polymicrobial communities in vitro. However, emerging evidence suggests that, if modeled and tested accurately, interspecies relationships can be exploited by conventional antibiotics predicted to be ineffective by standard AST. As an example, under conditions where Pseudomonas aeruginosa relies on cocolonizing organisms for nutrients (i.e., cross-feeding), multidrug-resistant P. aeruginosa may be indirectly targeted by inhibiting the growth of its metabolic partners. While this has been shown in vitro using synthetic bacterial communities, the efficacy of a “weakest-link” approach to controlling host-associated polymicrobial infections has not yet been demonstrated. To test whether cross-feeding inhibition can be leveraged in clinically relevant contexts, we collected sputa from cystic fibrosis (CF) subjects and used enrichment culturing to isolate both P. aeruginosa and anaerobic bacteria from each sample. Predictably, both subpopulations showed various antibiotic susceptibilities when grown independently. However, when P. aeruginosa was cultured and treated under cooperative conditions in which it was dependent on anaerobic bacteria for nutrients, the growth of both the pathogen and the anaerobe was constrained despite their intrinsic antibiotic resistance profiles. These data demonstrate that the control of complex polymicrobial infections may be achieved by exploiting obligate or facultative interspecies relationships. Toward this end, in vitro susceptibility testing should evolve to more accurately reflect in vivo growth environments and microbial interactions found within them. IMPORTANCE Antibiotic efficacy achieved in vitro correlates poorly with clinical outcomes after treatment of chronic polymicrobial diseases; if a pathogen demonstrates susceptibility to a given antibiotic in the lab, that compound is often ineffective when administered clinically. Conversely, if a pathogen is resistant in vitro, patient treatment with that same compound can elicit a positive response. This discordance suggests that the in vivo growth environment impacts pathogen antibiotic susceptibility. Indeed, here we demonstrate that interspecies relationships among microbiotas in the sputa of cystic fibrosis patients can be targeted to indirectly inhibit the growth of Pseudomonas aeruginosa. The therapeutic implication is that control of chronic lung infections may be achieved by exploiting obligate or facultative relationships among airway bacterial community members. This strategy is particularly relevant for pathogens harboring intrinsic multidrug resistance and is broadly applicable to chronic polymicrobial airway, wound, and intra-abdominal infections.


2001 ◽  
Vol 45 (6) ◽  
pp. 1743-1745 ◽  
Author(s):  
Graham H. Coombs ◽  
Jeremy C. Mottram

ABSTRACT Methionine γ-lyase, the enzyme which catalyzes the single-step conversion of methionine to α-ketobutyrate, ammonia, and methanethiol, is highly active in many anaerobic pathogenic microorganisms but has no counterpart in mammals. This study tested the hypothesis that this pathogen-specific enzyme can be exploited as a drug target by prodrugs that are exclusively activated by it. Trifluoromethionine was confirmed as such a prodrug and shown to be highly toxic in vitro to the anaerobic protozoan parasiteTrichomonas vaginalis, to anaerobic bacteria containing methionine γ-lyase, and to Escherichia coli expressing the trichomonad gene. The compound also has exceptional activity against the parasite growing in vivo, with a single dose preventing lesion formation in five of the six mice challenged. These findings suggest that trifluoromethionine represents a lead compound for a novel class of anti-infective drugs with potential as chemotherapeutic agents against a range of prokaryotic and eukaryotic anaerobic pathogens.


2001 ◽  
Vol 2001 ◽  
pp. 100-100
Author(s):  
J. Periz ◽  
K. Hillman

Lactobacillus probiotics have consistently shown in vitro properties of key importance in the prevention of diarrhoea at weaning. However, these probiotics have shown variable results in pigs in vivo, and it is important to determine the reasons for this variability if the efficacy of the preparations is to be improved. Hillman et al. (1993) reported that there are significant oxygen levels along the piglet intestine. As Lactobacillus spp. are primarily anaerobic bacteria, and are isolated and examined in vitro under anaerobic conditions, it is possible that the presence of oxygen along the piglet intestine could be exerting a detrimental action on their probiotic effectiveness. This experiment was set up to examine the influence of oxygen on two porcine Lactobacillus spp which have been previously demonstrated to inhibit the growth of Escherichia coli K88 in vitro (Hillman and Fox, 1994).


2009 ◽  
Vol 43 (5) ◽  
pp. 928-938 ◽  
Author(s):  
Lisa Charneski ◽  
Priti N Patel ◽  
Donna Sym

Objective To review the pharmacology, antimicrobial activity, pharmacokinetics, clinical applications, and safety of telavancin, a new lipoglycopeptide antibiotic. Data Sources Literature was obtained from MEDLINE (1966–April 2009) and International Pharmaceutical Abstracts (1971–April 2009) using the search terms telavancin and TD-6424, and also from Theravance, Inc., and Astellas Pharma US, Inc. Study Selection And Data Extraction Available English-language articles were reviewed, as well as information obtained from Theravance, Inc., and Astellas Pharma US, Inc. Data Synthesis Telavancin has rapid bactericidal activity against gram-positive aerobic and anaerobic bacteria through multiple mechanisms of action. In vitro and Phase 2 in vivo data support the efficacy of telavancin against antibiotic-resistant gram-positive organisms. On March 4, 2008, the Food and Drug Administration (FDA) accepted as complete for review Theravance's response to the October 19, 2007, New Drug Application approvable letter for telavancin to be used as treatment for complicated skin and skin structure infections (cSSSIs) caused by gram-positive bacteria. QTc interval prolongation has been reported, although the clinical impact of this has not been determined. Drug interactions have not been identified as of yet. Conclusions Telavancin is currently under review by the FDA for the treatment of cSSSIs caused by gram-positive bacteria. The completion of Phase 3 trials will determine whether telavancin will have a role in the treatment of other infections caused by resistant gram-positive bacteria.


2001 ◽  
Vol 45 (9) ◽  
pp. 2455-2459 ◽  
Author(s):  
Tsuneo Kanamaru ◽  
Yoshitaka Nakano ◽  
Yukio Toyoda ◽  
Ken-Ichiro Miyagawa ◽  
Mayumi Tada ◽  
...  

ABSTRACT The antibacterial activity of TAK-083 was tested against 54 clinical isolates of Helicobacter pylori and was compared with those of amoxicillin, clarithromycin, and metronidazole. The growth-inhibitory activity of TAK-083 was more potent than that of amoxicillin, clarithromycin, or metronidazole (the MICs at which 90% of the strains are inhibited were 0.031, 0.125, 64, and 8 μg/ml, respectively). The antibacterial activity of TAK-083 was highly selective against H. pylori; there was a >30-fold difference between the concentration of TAK-083 required to inhibit the growth of H. pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure ofH. pylori strains to TAK-083 at the MIC or at a greater concentration resulted in an extensive loss of viability. When four H. pylori strains were successively subcultured in the medium containing subinhibitory concentrations of TAK-083, no significant change in the MICs of this compound was observed. TAK-083 strongly inhibited the formation of tryptophanyl-tRNA in H. pylori while exhibiting little effect on the same system in eukaryotes. TAK-083 was efficacious in the treatment of gastric infection caused by H. pylori in Mongolian gerbils. The results presented here indicate that TAK-083 is a promising candidate for the treatment of H. pylori infection.


2020 ◽  
Author(s):  
David Ranava ◽  
Cassandra Backes ◽  
Ganesan Karthikeyan ◽  
Olivier Ouari ◽  
Audrey Soric ◽  
...  

AbstractTo clarify the principles controlling inter-species interactions, we previously developed a co-culture model with two anaerobic bacteria, Clostridium acetobutylicum and Desulfovibrio vulgaris Hildenborough, in which nutritional stress for D. vulgaris induced tight cell-cell inter-species interaction. Here we show that exchange of metabolites produced by C. acetobutylicum allows D. vulgaris to duplicate its DNA, and to be energetically viable even without its substrates. Physical interaction between C. acetobutylicum and D. vulgaris (or Escherichia coli and D. vulgaris) is linked to the quorum-sensing molecule AI-2, produced by C. acetobutylicum and E. coli. With nutrients D. vulgaris produces a small molecule that inhibits in vitro the AI-2 activity, and could act as an antagonist in vivo. Sensing of AI-2 by D. vulgaris could induce formation of an intercellular structure that allows directly or indirectly metabolic exchange and energetic coupling between the two bacteria.


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