scholarly journals Antibiofilm efficacy of focused high-energy extracorporeal shockwaves and antibiotics in vitro

2021 ◽  
Vol 10 (1) ◽  
pp. 77-84
Author(s):  
Alexander Milstrey ◽  
Steffen Rosslenbroich ◽  
Jens Everding ◽  
Michael J. Raschke ◽  
Robert Geoff Richards ◽  
...  
Keyword(s):  
Bacterial Count ◽  
High Energy ◽  
Antibiotic Administration ◽  
Bacterial Counts ◽  
Shockwave Therapy ◽  
Combined Application ◽  
Fold Reduction ◽  
Fracture Nonunions ◽  
Viable Bacteria

Aims Biofilm formation is one of the primary reasons for the difficulty in treating implant-related infections (IRIs). Focused high-energy extracorporeal shockwave therapy (fhESWT), which is a treatment modality for fracture nonunions, has been shown to have a direct antibacterial effect on planktonic bacteria. The goal of the present study was to investigate the effect of fhESWT on Staphylococcus aureus biofilms in vitro in the presence and absence of antibiotic agents. Methods S. aureus biofilms were grown on titanium discs (13 mm × 4 mm) in a bioreactor for 48 hours. Shockwaves were applied with either 250, 500, or 1,000 impulses onto the discs surrounded by either phosphate-buffered saline or antibiotic (rifampin alone or in combination with nafcillin). The number of viable bacteria was determined by quantitative culture after sonication. Representative samples were taken for scanning electron microscopy. Results The application of fhESWT led to a ten-fold reduction in bacterial counts on the metal discs for all impulse numbers compared to the control (p < 0.001). Increasing the number of impulses did not further reduce bacterial counts in the absence of antibiotics (all p > 0.289). Antibiotics alone reduced the number of bacteria on the discs; however, the combined application of the fhESWT and antibiotic administration further reduced the bacterial count compared to the antibiotic treatment only (p = 0.032). Conclusion The use of fhESWT significantly reduced the colony-forming unit (CFU) count of a S. aureus biofilm in our model independently, and in combination with antibiotics. Therefore, the supplementary application of fhESWT could be a helpful tool in the treatment of IFIs in certain cases, including infected nonunions. Cite this article: Bone Joint Res 2021;10(1):77–84.

scholarly journals In Vitro and In Vivo Activities of Novel Fluoroquinolones Alone and in Combination with Clarithromycin against Clinically Isolated Mycobacterium avium Complex Strains in Japan

2007 ◽  
Vol 51 (11) ◽  
pp. 4071-4076 ◽  
Author(s):  
Yoshihisa Kohno ◽  
Hideaki Ohno ◽  
Yoshitsugu Miyazaki ◽  
Yasuhito Higashiyama ◽  
Katsunori Yanagihara ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Mycobacterium Avium ◽  
Antimicrobial Agents ◽  
Histopathological Examination ◽  
Bacterial Counts ◽  
Viable Bacteria ◽  
The Individual ◽  
Combination Regimens

ABSTRACT The recommended treatments for Mycobacterium avium complex (MAC) infectious disease are combination regimens of clarithromycin (CLR) or azithromycin with ethambutol and rifamycin. However, these chemotherapy regimens are sometimes unsuccessful. Recently developed antimicrobial agents, such as newer fluoroquinolones (FQs) containing C-8 methoxy quinolone (moxifloxacin [MXF] and gatifloxacin [GAT]), are expected to be novel antimycobacterial agents. Here, we evaluated the in vitro and in vivo antimycobacterial activities of three FQs (MXF, GAT, and levofloxacin) and CLR against clinically isolated MAC strains. Subsequently, the in vitro and in vivo synergic activities of FQ-CLR combinations against MAC strains were investigated. CLR and the individual FQs alone showed promising activity against MAC strains in vitro, and the bacterial counts in organs (lungs, liver, and spleen) of MAC-infected mice treated with single agents were significantly reduced compared to control mice. CLR showed the best anti-MAC effect in vivo. When the three FQs were individually combined with CLR in vitro, mild antagonism was observed for 53 to 57% of the tested isolates. Moreover, mice were infected with MAC strains showing mild antagonism for FQ-CLR combinations in vitro, and the anti-MAC effects of the FQ-CLR combinations were evaluated by counting the viable bacteria in their organs and by histopathological examination after 28 days of treatment. Several FQ-CLR combinations exhibited bacterial counts in organs significantly higher than those in mice treated with CLR alone. Our results indicate that the activity of CLR is occasionally attenuated by combination with an FQ both in vitro and in vivo and that this effect seems to be MAC strain dependent. Careful combination chemotherapy using these agents against MAC infectious disease may be required.

scholarly journals In VitroAntibacterial and Antibiofilm Activities of Chlorogenic Acid against Clinical Isolates ofStenotrophomonas maltophiliaincluding the Trimethoprim/Sulfamethoxazole Resistant Strain

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Arunkumar Karunanidhi ◽  
Renjan Thomas ◽  
Alex van Belkum ◽  
Vasanthakumari Neela
Keyword(s):  
Chlorogenic Acid ◽  
Inhibition Zone ◽  
Clinical Isolates ◽  
Antibiofilm Activity ◽  
Log Reduction ◽  
Fold Reduction ◽  
Viable Bacteria ◽  
Study Support ◽  
Time Kill

Thein vitroantibacterial and antibiofilm activity of chlorogenic acid against clinical isolates ofStenotrophomonas maltophiliawas investigated through disk diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill and biofilm assays. A total of 9 clinicalS. maltophiliaisolates including one isolate resistant to trimethoprim/sulfamethoxazole (TMP/SMX) were tested. The inhibition zone sizes for the isolates ranged from 17 to 29 mm, while the MIC and MBC values ranged from 8 to 16 μg mL−1and 16 to 32 μg mL−1. Chlorogenic acid appeared to be strongly bactericidal at 4x MIC, with a 2-log reduction in viable bacteria at 10 h.In vitroantibiofilm testing showed a 4-fold reduction in biofilm viability at 4x MIC compared to 1x MIC values (0.085<0.397A 490 nm) of chlorogenic acid. The data from this study support the notion that the chlorogenic acid has promisingin vitroantibacterial and antibiofilm activities againstS. maltophilia.

scholarly journals In vivo monitoring of viable bacteria by SPECT using 99mTc-HYNIC(GH)2-UBI 29-41 and 99mTc-HYNIC(Tricine)2-UBI 29-41

2021 ◽  
Author(s):  
Yuri Nishiyama ◽  
Tomoya Uehara ◽  
Kenichi Okazaki ◽  
Hideki Maki ◽  
Kohji Abe ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Radiochemical Purity ◽  
Bacterial Count ◽  
Infection Site ◽  
Cell Infection ◽  
Peptide Labeling ◽  
Viable Bacteria ◽  
Over Time

Abstract Background: The number of bacterial infections that—for various reasons—are challenging to cure continues to increase. One such reason is persister cell infection. To investigate persister formation and persister infections, viable bacteria must be evaluated in the same animal over time. In this study, the feasibility of monitoring viable bacteria by SPECT using two labeled peptides was evaluated. Results: Two types of ubiquicidin (UBI) 29-41 labeled with technetium-99m, 99mTc-HYNIC(GH)2-UBI 29-41 and 99mTc-HYNIC(Tricine)2-UBI 29-41, were synthesized. The in vitro binding of these labeled peptides to Staphylococcus aureus was measured. For the in vivo study, each labeled peptide was injected into S. aureus infected mouse thigh after treatment with various doses of ciprofloxacin (CPFX). Two hours after injection, the accumulation of each labeled peptide at the infection site was assessed by SPECT, and then the number of viable bacteria was determined from the accumulation detected. The peptide labeling was successful, and the radiochemical purity was 91±9% (GH, n=8) and 100% (Tricine, n=8). The in vitro binding of the labeled peptides to S. aureus (5×108 cfu) without serum was 78.9% (GH) and 85.5% (Tricine) of the total 99mTc activity. With serum, the binding rate was 67.5% (GH) and 13.3% (Tricine). The accumulation of labeled peptide was calculated from the SPECT images, and that in the bacterial infection site (left thigh) was higher than that in the non-infection site (right thigh) for both peptides. Good correlation was found between the target-to-non-target (T/NT) ratios of each labeled peptide and the viable bacterial count at the infection site, and 99mTc-HYNIC(Tricine)2-UBI 29-41 had a wider range than 99mTc-HYNIC(GH)2-UBI 29-41.Conclusion: Using the SPECT/labeled peptide method, it was possible to monitor viable bacterial count in the range 103–108 cfu, which is appropriate for tracking viable bacterial counts in the same animal over time.

scholarly journals Efficacy of Daptomycin in Experimental Endocarditis Due to Methicillin-Resistant Staphylococcusaureus

2003 ◽  
Vol 47 (5) ◽  
pp. 1714-1718 ◽  
Author(s):  
George Sakoulas ◽  
George M. Eliopoulos ◽  
Jeff Alder ◽  
Claudie Thauvin- Eliopoulos
Keyword(s):  
Subcutaneous Administration ◽  
Phase Iii ◽  
Methicillin Resistant ◽  
Bacterial Counts ◽  
Phase Iii Clinical Trials ◽  
Viable Bacteria ◽  
The Mean ◽  
The Difference ◽  
Lipopeptide Antibiotic

ABSTRACT Methicillin-resistant Staphylococcus aureus is becoming increasingly prevalent as both a nosocomial and a community-acquired pathogen. Daptomycin, a lipopeptide antibiotic now in phase III clinical trials, is rapidly bactericidal in vitro against a range of gram-positive organisms, including methicillin-resistant S. aureus (MRSA). In this study, we compared the efficacy of daptomycin with that of vancomycin, each with or without rifampin, in a model of experimental aortic valve endocarditis due to MRSA. The infecting strain (MRSA strain 32) was susceptible to daptomycin (MIC = 1 μg/ml), vancomycin (MIC = 0.5 μg/ml), and rifampin (MIC = 0.5 μg/ml). Daptomycin was administered at 25 or 40 mg/kg q24h (q24h) by subcutaneous injection in an attempt to simulate human doses of 4 and 6 mg/kg q24h, respectively. Vancomycin was given at 150 mg/kg q24h by continuous intravenous infusion. Rifampin was given at 25 mg/kg by intramuscular injection q24h. Treatment was started 6 h postinoculation and continued for 4.5 days. Outcome was assessed by counting the residual viable bacteria in vegetations. The mean peak daptomycin levels in serum at 2 h after subcutaneous administration of 25 and 40 mg/kg were 64 and 91 μg/ml, respectively. Daptomycin was undetectable in serum at 24 h. The total exposure was comparable to that achieved clinically in humans receiving the drug. Bacterial counts (mean log10 number of CFU per gram ± the standard deviation) in untreated controls reached 10.6 ± 0.8. In treated rats, bacterial counts were as follows: vancomycin, 7.1 ± 2.5; daptomycin at 25 mg/kg, 5.5 ± 1.7; daptomycin at 40 mg/kg, 4.2 ± 1.5. The difference between daptomycin at 40 mg/kg and vancomycin at 150 mg/kg was statistically significant (P = 0.004). In the study of combination therapy, vegetation bacterial counts were as follows: daptomycin at 40 mg/kg, 4.6 ± 1.6; rifampin, 3.6 ± 1.3; vancomycin plus rifampin, 3.3 ± 1.1; daptomycin plus rifampin, 2.9 ± 0.8. The difference between daptomycin and daptomycin plus rifampin was statistically significant (P = 0.006). These results support the continued evaluation of daptomycin for serious MRSA infections, including infective endocarditis.

scholarly journals Net effect of inoculum size on antimicrobial action of ampicillin-sulbactam: studies using an in vitro dynamic model.

1997 ◽  
Vol 41 (1) ◽  
pp. 7-12 ◽  
Author(s):  
A A Firsov ◽  
M Ruble ◽  
D Gilbert ◽  
D Saverino ◽  
D Savarino ◽  
...  
Keyword(s):  
Dynamic Model ◽  
Approximate Equation ◽  
Bacterial Count ◽  
Inoculum Size ◽  
Antimicrobial Action ◽  
Time Curve ◽  
Bacterial Counts ◽  
The Difference ◽  
Different Strains

To examine the predictable effect of inoculum size on the kinetics of the antimicrobial action of ampicillin-sulbactam, five TEM-1 beta-lactamase-producing Escherichia coli strains were studied in an in vitro dynamic model at two different initial inocula (N0S). All bacteria were exposed to ampicillin-sulbactam in a simulated system reflecting the pharmacokinetic profiles in human tissue after the administration of a single intravenous dose of ampicillin (2 g) plus sulbactam (1 g). Each strain was studied at low (4.0 to 5.2 log CFU/ml) and high (5.0 to 7.1 log CFU/ml) N0S. Despite pronounced differences in susceptibilities, the patterns of the killing curves observed with a given strain at different N0S were similar. As expected, viable bacterial counts increased with inoculum size. Striking visual contrasts in the respective curves for each organism were reflected by the area under the bacterial count-time curve (AUBC) but not by the difference between the N0 and the lowest bacterial counts (Nmin) at the nadir of the killing curve: the N0-associated changes in the AUBC on average were 75%, versus 2.5% for log N0--logNmin. To examine qualitative differences in antimicrobial effects at different N0S (i.e., the net effect of the inoculum), the difference in the high and low N0S was subtracted from each point on the killing curve obtained at the higher N0 for each strain. These adjusted curves were virtually superimposable on the observed killing curves obtained at the lower N0. Moreover, by using adjusted data, the AUBC values were similar at the two inocula, although slight (average, 11%) but systematic increases in the AUBC occurred at high N0S. Thus, there was only a weak net effect of inoculum size on the antibacterial effect of ampicillin-sulbactam. Due to similar slopes of the AUBC-log N0 plots, the antibacterial action at different N0S may be easily predicted by an approximate equation; the predicted AUBCs were unbiased and well correlated with the observed AUBCs (r = 0.997). Compiled data obtained with normalized AUBCs for different strains at different N0S yielded a positive correlation (r = 0.963) between the N0-normalized AUBC and the MIC of ampicillin-sulbactam. The adjustment and normalization procedure described might be a useful tool for revealing the net effect of the inoculum and to predict the inoculum effect if there are no qualitative differences in antimicrobial action at different inocula.

scholarly journals Relationships between antimicrobial effect and area under the concentration-time curve as a basis for comparison of modes of antibiotic administration: meropenem bolus injections versus continuous infusions.

1997 ◽  
Vol 41 (2) ◽  
pp. 352-356 ◽  
Author(s):  
A A Firsov ◽  
H Mattie
Keyword(s):  
Comparative Studies ◽  
Dynamic Models ◽  
Antimicrobial Effect ◽  
Bacterial Count ◽  
Antibiotic Administration ◽  
Time Curve ◽  
Wide Range ◽  
Accurate Comparison ◽  
Time Courses

In comparative studies of different modes of administration (MAs) simulated in in vitro dynamic models, only one dose of antibiotic is usually mimicked. Such an experimental design can provide a prediction of the antimicrobial effect (AME) of a given combination of drug, clinical isolate, and infection site, but may be inappropriate for accurate comparison of MAs. An alternative design providing comparison of different MAs with various antibiotic doses in a wide range and with evaluation of the respective relationships between AME and the AUC was proposed and examined. Two series of meropenem pharmacokinetic profiles, i.e., monoexponentially decreasing concentrations (bolus doses) and constant concentrations (6-h continuous infusion), were in vitro simulated. The simulated initial concentrations (Co[from 0.62 to 48 micrograms/ml]) and steady-state concentrations (Css[from 0.016 to 8 micrograms/ml]) were chosen to provide similar AUC for 0 to 6 h (AUC0-6) ranges for both MAs (from 0.070 to 50.0 micrograms.h/ml and from 0.09 to 48.0 micrograms.h/ml, respectively). The AME of meropenem on Staphylococcus aureus ATCC 25923 (MIC, 0.06 micrograms/ml) was determined at each time (t) point as a difference (E) between the logarithms of viable counts (N) in the control cultures without antibiotic (NC) and in cultures exposed to antibiotics (NA). Time courses of E observed at different Co of Css levels were compared in terms of the areas under the E-t curves (ABBCt). The finite values of the ABBCt observed by the end of the 6 -h observation period, which are equivalent to the area between bacterial count-time curves observed in the absence and presence of antibiotic (ABBC), were plotted versus the respective AUCs produced by each of the MAs. The ABBC versus AUC curves had a similar pattern: a plateau achieved at high AUCs followed by a steep rise in ABBC at relatively low AUCs was inherent in both of the MAs. The superiority of bolus dosing over the infusions could be documented only for meropenem concentrations below the MIC. At higher Co or Css (i.e., at an AUC of > or = 0.4 micrograms.h/ml), the ABBC versus AUC curves plotted for each of the MAs could practically be superimposed. On the whole, both MAs appeared to be equiefficient in terms of the ABBC. These results suggest that AUC analysis of the AME may be a useful tool for comparing different MAs. Such comparative studies should be designed in a manner that provides the use of similar AUC ranges, since the AUC may be considered as a common pharmacokinetic denominator in comparing one MA or dosing regimen to another.

scholarly journals Efficacy of Removal of Sucrose-Supplemented Interproximal Plaque by Electric Toothbrushes in an In Vitro Model

2005 ◽  
Vol 71 (2) ◽  
pp. 1114-1116 ◽  
Author(s):  
C. K. Hope ◽  
A. Petrie ◽  
M. Wilson
Keyword(s):  
In Vitro Model ◽  
High Energy ◽  
Low Energy ◽  
Fluid Shear ◽  
Shear Forces ◽  
Plaque Removal ◽  
Plaque Development ◽  
Viable Bacteria ◽  
Vitro Model

ABSTRACT Electric toothbrushes were evaluated using a model of plaque removal by fluid shear forces. Sucrose supplementation during plaque development did not affect the removal of bacteria from biofilm exposed to low-energy shear but did increase their resistance to high-energy shear. The toothbrush supplying high-energy shear forces removed significantly more viable bacteria.

COVID-19: Opinion in Prevention and dietary based management hypothesis

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Ashraf Talaat Youssef
Keyword(s):  
Fatty Acids ◽  
Saturated Fatty Acids ◽  
Lung Damage ◽  
Gastric Aspirate ◽  
Enveloped Viruses ◽  
Multiple Organs ◽  
Fold Reduction ◽  
Antiviral Activities

The pandemic of COVID-19 had started in Wuhan city china in late 2019 with a subsequent worldwide spread. The viral infection can seriousely affect multiple organs mainly lungs, kidneys, heart, liver and brain and may lead to respiratory, renal, cardiac or hepatic failure.Vascular thrombosis of unexplained mechanism that may lead to widespread blood clots in multiple organs and cytokine storms that result of overstimulation of the immune system subsequent of lung damage may lead to sudden decompensation due to hypotension and more damage to liver, kidney, brain or lungs.Until now no drug had proved efficient in getting rid of the problem and controlling the pandemic mainly depends on preventive measures.Many preventive measures can be considered to prevent the worldwide spread of viral transmission. Polyunsaturated long chain fatty acids (PUFAs) and the medium chain saturated fatty acids (MCSFAs) and their corresponding monoglycerides had high antiviral activities against the enveloped viruses which reach to more than 10,000 -fold reduction in the viral titres in vitro and in vivo after testing of its gastric aspirate, and can contribute to the systemic immunity against the enveloped viruses.

scholarly journals Introducing intrauterine antibiotic infusion as a novel approach in effectively treating chronic endometritis and restoring reproductive dynamics: a randomized pilot study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Konstantinos Pantos ◽  
Mara Simopoulou ◽  
Evangelos Maziotis ◽  
Anna Rapani ◽  
Sokratis Grigoriadis ◽  
...  
Keyword(s):  
Fertility Restoration ◽  
Statistical Significance ◽  
Antibiotic Administration ◽  
Oral Antibiotic ◽  
Treatment Rate ◽  
Chronic Endometritis ◽  
Vitro Fertilization ◽  
Significant Difference ◽  
Antibiotic Infusion

AbstractThe chronic nature of Chronic Endometritis (CE) along with the challenging management and infertility entailed, call for cutting-edge therapeutic approaches. This study introduces the novel treatment of intrauterine antibiotic infusion (IAI) combined with oral antibiotic administration (OAA), and it assesses respective performance against the gold standard treatment of OAA. Data sourced herein reports on treatment efficiency and fertility restoration for both patients aiming to conceive naturally or via In Vitro fertilization. Eighty CE patients, 40 presenting with recurrent implantation failure, and 40 with recurrent pregnancy loss, were enrolled in the IVF and the natural conception arm respectively. Treatment was subjected to randomization. Effectively treated patients proceeded with either a single IVF cycle or were invited to conceive naturally over a 6-month period. Combination of IAI and OAA provided a statistically significant enhanced effectiveness treatment rate (RR 1.40; 95%CI 1.07–1.82; p = 0.01). No statistically significant difference was observed regarding the side-effects rate (RR 1.33; 95%CI 0.80–2.22; p = 0.52). No statistically significant difference was observed for either arm regarding live-birth rate. Following an intention-to-treat analysis, employment of IAI corresponds to improved clinical pregnancy rate-albeit not reaching statistical significance. In conclusion, complimentary implementation of IAI could provide a statistically significant enhanced clinical treatment outcome.

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