scholarly journals In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium Chloride

2021 ◽  
Vol 14 (6) ◽  
pp. 517
Author(s):  
Joseph Blondeau ◽  
Heleen DeCory
Keyword(s):  
Staphylococcus Epidermidis ◽  
Benzalkonium Chloride ◽  
Bacterial Species ◽  
Drug Resistant ◽  
Resistance Development ◽  
Aureus Isolate ◽  
Killing Activity ◽  
Time Kill ◽  
Variable Impact

Background: Besifloxacin ophthalmic suspension 0.6% (w/v%) contains benzalkonium chloride (BAK) as a preservative. We evaluated the in vitro time-kill activity of besifloxacin, alone and in combination with BAK, against common bacteria implicated in ophthalmic infections. Methods: The activity of besifloxacin (100 µg/mL), BAK (10, 15, 20, and 100 µg/mL), and combinations of besifloxacin and BAK were evaluated against isolates of Staphylococcus epidermidis (n = 4), Staphylococcus aureus (n = 3), Haemophilus influenzae (n = 2), and Pseudomonas aeruginosa (n = 2) in time-kill experiments of 180 min duration. With the exception of one S. aureus isolate, all of the staphylococcal isolates were methicillin- and/or ciprofloxacin-resistant; one P. aeruginosa isolate was ciprofloxacin-resistant. The reductions in the viable colony counts (log10 CFU/mL) were plotted against time, and the differences among the time–kill curves were evaluated using an analysis of variance. Areas-under-the-killing-curve (AUKCs) were also computed. Results: Besifloxacin alone demonstrated ≥3-log killing of P. aeruginosa (<5 min) and H. influenzae (<120 min), and approached 3-log kills of S. aureus. BAK alone demonstrated concentration-dependent killing of S. epidermidis, S. aureus and H. influenzae, and at 100 µg/mL produced ≥3-log kills in <5 min against these species. The addition of BAK (10, 15, and 20 µg/mL) to besifloxacin increased the rate of killing compared to besifloxacin alone, with earlier 3-log kills of all species except P. aeruginosa and a variable impact on S. aureus. The greatest reductions in AUKC were observed among H. influenzae (8-fold) and S. epidermidis (≥5-fold). Similar results were found when the isolates were evaluated individually by their resistance phenotype. Conclusions: In addition to confirming the activity of 100 µg/mL BAK as a preservative in the bottle, these data suggest that BAK may help besifloxacin to achieve faster time-kills on-eye in the immediate timeframe post-instillation before extensive dilution against bacterial species implicated in ophthalmic infections, including drug-resistant S. epidermidis. Greater killing activity may help prevent resistance development and/or help treat resistant organisms.

scholarly journals Pseudomonas aeruginosa PAO 1 In Vitro Time–Kill Kinetics Using Single Phages and Phage Formulations—Modulating Death, Adaptation, and Resistance

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 877
Author(s):  
Ana Mafalda Pinto ◽  
Alberta Faustino ◽  
Lorenzo M. Pastrana ◽  
Manuel Bañobre-López ◽  
Sanna Sillankorva
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Chronic Infections ◽  
Swarming Motility ◽  
Resistance Development ◽  
Healthcare Settings ◽  
Time Kill

Pseudomonas aeruginosa is responsible for nosocomial and chronic infections in healthcare settings. The major challenge in treating P. aeruginosa-related diseases is its remarkable capacity for antibiotic resistance development. Bacteriophage (phage) therapy is regarded as a possible alternative that has, for years, attracted attention for fighting multidrug-resistant infections. In this work, we characterized five phages showing different lytic spectrums towards clinical isolates. Two of these phages were isolated from the Russian Microgen Sextaphage formulation and belong to the Phikmvviruses, while three Pbunaviruses were isolated from sewage. Different phage formulations for the treatment of P. aeruginosa PAO1 resulted in diversified time–kill outcomes. The best result was obtained with a formulation with all phages, prompting a lower frequency of resistant variants and considerable alterations in cell motility, resulting in a loss of 73.7% in swimming motility and a 79% change in swarming motility. These alterations diminished the virulence of the phage-resisting phenotypes but promoted their growth since most became insensitive to a single or even all phages. However, not all combinations drove to enhanced cell killings due to the competition and loss of receptors. This study highlights that more caution is needed when developing cocktail formulations to maximize phage therapy efficacy. Selecting phages for formulations should consider the emergence of phage-resistant bacteria and whether the formulations are intended for short-term or extended antibacterial application.

scholarly journals Correlation of Checkerboard Synergy Testing with Time-Kill Analysis and Clinical Outcomes of Extensively Drug-Resistant Acinetobacter baumannii Respiratory Infections

2016 ◽  
Vol 60 (11) ◽  
pp. 6892-6895 ◽  
Author(s):  
Derek N. Bremmer ◽  
Karri A. Bauer ◽  
Stephanie M. Pouch ◽  
Keelie Thomas ◽  
Debra Smith ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Clinical Outcomes ◽  
Clinical Utility ◽  
Respiratory Infections ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Time Kill ◽  
Synergy Testing

ABSTRACTWe tested 76 extensively drug-resistant (XDR)Acinetobacter baumanniiisolates by the checkerboard method using only wells containing serum-achievable concentrations (SACs) of drugs. Checkerboard results were correlated by time-kill assay and clinical outcomes. Minocycline-colistin was the best combinationin vitro, as it inhibited growth in one or more SAC wells in all isolates. Patients who received a combination that inhibited growth in one or more SAC wells demonstrated better microbiological clearance than those who did not (88% versus 30%;P= 0.025). The checkerboard platform may have clinical utility for XDRA. baumanniiinfections.

scholarly journals In vitro activities of oxazolidinone compounds U100592 and U100766 against Staphylococcus aureus and Staphylococcus epidermidis.

1996 ◽  
Vol 40 (3) ◽  
pp. 799-801 ◽  
Author(s):  
G W Kaatz ◽  
S M Seo
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Inhibitory Activity ◽  
Antimicrobial Agents ◽  
Methicillin Resistant ◽  
Clinical Strains ◽  
Time Kill

The new oxazolidinone antimicrobial agents U100592 and U100766 demonstrated good in vitro inhibitory activity against clinical strains of Staphylococcus aureus and Staphylococcus epidermidis regardless of methicillin susceptibility. Both agents appeared bacteriostatic by time-kill analysis. Stable resistance to low multiples of the MIC of either drug could be produced only in methicillin-resistant S. aureus.

scholarly journals Cross-class metallo-β-lactamase inhibition by bisthiazolidines reveals multiple binding modes

2016 ◽  
Vol 113 (26) ◽  
pp. E3745-E3754 ◽  
Author(s):  
Philip Hinchliffe ◽  
Mariano M. González ◽  
Maria F. Mojica ◽  
Javier M. González ◽  
Valerie Castillo ◽  
...  
Keyword(s):  
Full Range ◽  
Drug Resistant ◽  
Binding Modes ◽  
X Ray ◽  
Free Thiol ◽  
Extensively Drug Resistant ◽  
Multiple Binding ◽  
Almost All ◽  
Time Kill

Metallo-β-lactamases (MBLs) hydrolyze almost all β-lactam antibiotics and are unaffected by clinically available β-lactamase inhibitors (βLIs). Active-site architecture divides MBLs into three classes (B1, B2, and B3), complicating development of βLIs effective against all enzymes. Bisthiazolidines (BTZs) are carboxylate-containing, bicyclic compounds, considered as penicillin analogs with an additional free thiol. Here, we show both l- and d-BTZ enantiomers are micromolar competitive βLIs of all MBL classes in vitro, with Kis of 6–15 µM or 36–84 µM for subclass B1 MBLs (IMP-1 and BcII, respectively), and 10–12 µM for the B3 enzyme L1. Against the B2 MBL Sfh-I, the l-BTZ enantiomers exhibit 100-fold lower Kis (0.26–0.36 µM) than d-BTZs (26–29 µM). Importantly, cell-based time-kill assays show BTZs restore β-lactam susceptibility of Escherichia coli-producing MBLs (IMP-1, Sfh-1, BcII, and GOB-18) and, significantly, an extensively drug-resistant Stenotrophomonas maltophilia clinical isolate expressing L1. BTZs therefore inhibit the full range of MBLs and potentiate β-lactam activity against producer pathogens. X-ray crystal structures reveal insights into diverse BTZ binding modes, varying with orientation of the carboxylate and thiol moieties. BTZs bind the di-zinc centers of B1 (IMP-1; BcII) and B3 (L1) MBLs via the free thiol, but orient differently depending upon stereochemistry. In contrast, the l-BTZ carboxylate dominates interactions with the monozinc B2 MBL Sfh-I, with the thiol uninvolved. d-BTZ complexes most closely resemble β-lactam binding to B1 MBLs, but feature an unprecedented disruption of the D120–zinc interaction. Cross-class MBL inhibition therefore arises from the unexpected versatility of BTZ binding.

Vancomycin and rifampin therapy for Staphylococcus epidermidis meningitis associated with CSF shunts

1981 ◽  
Vol 55 (4) ◽  
pp. 633-636 ◽  
Author(s):  
Myles E. Gombert ◽  
Sheldon H. Landesman ◽  
Michael L. Corrado ◽  
Sherman C. Stein ◽  
Ellen T. Melvin ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Susceptibility Testing ◽  
Csf Shunt ◽  
Csf Shunts ◽  
Methicillin Resistant ◽  
Content Type ◽  
Favorable Clinical Response ◽  
Time Kill ◽  
Fine Print

✓ Three patients with Staphylococcus epidermidis meningitis associated with cerebrospinal fluid (CSF) shunt devices were treated with a combination of intravenous vancomycin and oral rifampin. Two of the isolates were methicillin-resistant. All patients had a favorable clinical response. Time-kill curves showed that the addition of rifampin to vancomycin resulted in enhanced bactericidal activity against all isolates when compared to either antibiotic alone. This finding suggests that the combination of oral rifampin and intravenous vancomycin may be useful in the treatment of methicillin-resistant and recalcitrant methicillin-sensitive S. epidermidis meningitis associated with CSF shunts. In vitro susceptibility testing should be performed.

scholarly journals In VitroAntifungal Activity of Naftifine Hydrochloride against Dermatophytes

2013 ◽  
Vol 57 (9) ◽  
pp. 4369-4372 ◽  
Author(s):  
M. Ghannoum ◽  
N. Isham ◽  
A. Verma ◽  
S. Plaum ◽  
A. Fleischer ◽  
...  
Keyword(s):  
Developed Countries ◽  
Microsporum Canis ◽  
Test Panel ◽  
Resistance Development ◽  
Epidermophyton Floccosum ◽  
Content Type ◽  
Development Of Resistance ◽  
Time Kill ◽  
Dose Dependent

ABSTRACTThe incidence of superficial dermatophytoses is high in developed countries, and there remains a need for effective topical antifungals. In this study, we evaluated thein vitroantifungal activity of naftifine hydrochloride, the active ingredient in naftifine hydrochloride cream and gel 1% and 2%, against dermatophytes. The MICs and minimum fungicidal concentrations (MFCs) of naftifine hydrochloride against 350 clinical strains, includingTrichophyton rubrum,T. mentagrophytes,T. tonsurans,Epidermophyton floccosum, andMicrosporum canis, were determined using the CLSI methodology. Subsets from this test panel were subsequently tested in a time-kill assay at 0.125×, 0.25×, 0.5×, and 1× the MFC for each isolate. CFU counts were performed over a period of 48 h of incubation. Additionally, in order to determine the potential for resistance development, six strains were subjected to 15 serial passages in concentrations higher than the MIC for each strain. MICs were determined following each passage. The MIC range against the dermatophyte isolates tested was 0.015 to 1.0 μg/ml, with naftifine hydrochloride being fungicidal against 85% of theTrichophytonspecies. The time-kill assay showed dose-dependent activity, with the greatest reduction in the numbers of CFU corresponding to the highest drug concentration. There was no increase in MIC for any strains following repeated exposure to naftifine hydrochloride. Naftifine hydrochloride demonstrated potent activity against all dermatophytes tested, and none of the isolates within this test panel demonstrated the potential for the development of resistance. Thus, future clinical studies of naftifine hydrochloride against dermatophytes may be warranted for the treatment of superficial dermatophytoses.

scholarly journals Susceptibility of Vascular Implants to Colonization in vitro by Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Pseudomonas aeruginosa

2017 ◽  
Vol 66 (1) ◽  
pp. 125-129
Author(s):  
Witold Woźniak ◽  
Aleksandra Kozińska ◽  
Piotr Ciostek ◽  
Izabela Sitkiewicz
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Enterococcus Faecalis ◽  
Staphylococcus Epidermidis ◽  
Bacterial Species ◽  
Silver Ions ◽  
Pericardial Patch ◽  
Associated Bacteria ◽  
Omniflow Ii

We compared association of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Enterococcus faecalis with nine vascular implants after co-culture. Vascular implants were composed of various materials such as warp knitted polyester (with or without gelatin and silver ions), expanded polytetrafluoroethylene and biological materials – surface treated porcine pericardial patch and Omniflow II. The lowest overall number of associated bacteria was detected for polytetrafluoroethylene implants and porcine pericardial patch. The highest overall number of associated bacteria was detected for Omniflow II implant. The major source of variation, i.e. primary factor influencing colonization, is the implant type (56.22%), bacterial species is responsible for only 1.81%, and interaction of those two factors – 13.09% of variation.

scholarly journals Phytochemicals from Citrus Limon Juice as Potential Antibacterial Agents

2020 ◽  
Vol 8 (1) ◽  
pp. 1-6
Author(s):  
Nitika Singh ◽  
Jyotsna Jaiswal ◽  
Priyanka Tiwari ◽  
Bechan Sharma
Keyword(s):  
Staphylococcus Epidermidis ◽  
Shigella Flexneri ◽  
Bacterial Species ◽  
Herbal Medicines ◽  
Cost Effective ◽  
Salmonella Typhi ◽  
Citrus Limon ◽  
Drug Resistant ◽  
Potential Activity ◽  
Novel Drug

Background: Citrus limon (lemon) belongs to the Rutaceae family and has great therapeutic applications. The chemical ingredients of C. limon have been used in the formulation of several ethnic herbal medicines. The application of antibiotics has shown the development of drug resistance in antibacterial drugs. Due to the drug-resistant nature of microorganisms, there is an urgent need to develop a novel drug active against wildtype and MDR resistant strains of pathogens. Aim: The present study is an endeavor to characterize the juice of C. limon towards its total antioxidants potential activity (FRAP), DPPH and antibacterial efficacy. Methods and Materials: The antimicrobial activity was evaluated using different bacterial species such as Salmonella typhi, Neisseria gonorrhoeae, Citrobacter species, Shigella flexneri and Staphylococcus epidermidis. Results: The results of the present study indicated the antibacterial potential of C. limon fruit juice. Among the tested bacterial species, Shigella flexneri displayed maximum inhibition followed by the other microbes such as Staphylococcus epidermidis, Citrobacter species and Salmonella typhi. Conclusion: These findings may be utilized in the development of cost effective, safe and efficient novel drugs active against several pathogenic multi drug-resistant microorganisms.

scholarly journals In Vitro Activities of Colistin and Sitafloxacin Combinations against Multidrug-, Carbapenem-, and Colistin-Resistant Acinetobacter baumannii Using the Broth Microdilution Checkerboard and Time-Kill Methods

Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 516
Author(s):  
Vipavee Rodjun ◽  
Jantana Houngsaitong ◽  
Preecha Montakantikul ◽  
Taniya Paiboonvong ◽  
Piyatip Khuntayaporn ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Clinical Studies ◽  
Tertiary Care ◽  
Resistant Isolate ◽  
Drug Resistant ◽  
Broth Microdilution ◽  
Time Kill ◽  
Tertiary Care Hospitals

Drug-resistant Acinetobacter baumannii (A. baumannii) infections are a critical global problem, with limited treatment choices. This study aims to determine the in vitro activities of colistin–sitafloxacin combinations against multidrug-, carbapenem- and colistin-resistant A. baumannii (MDR-AB, CRAB, CoR-AB, respectively) clinical isolates from tertiary care hospitals. We used the broth microdilution checkerboard and time-kill methods in this study. Synergy was found using both methods. The colistin–sitafloxacin combination showed synergy in MDR-AB, CRAB, and CoR-AB isolates (3.4%, 3.1%, and 20.9%, respectively). No antagonism was found in any type of drug-resistant isolate. The majority of CoR-AB isolates became susceptible to colistin (95.4%). The time-kill method also showed that this combination could suppress regrowth back to the initial inocula of all representative isolates. Our results demonstrated that the colistin–sitafloxacin combination might be an interesting option for the treatment of drug-resistant A. baumannii. However, further in vivo and clinical studies are required.

scholarly journals MIC-Based Interspecies Prediction of the Antimicrobial Effects of Ciprofloxacin on Bacteria of Different Susceptibilities in an In Vitro Dynamic Model

1998 ◽  
Vol 42 (11) ◽  
pp. 2848-2852 ◽  
Author(s):  
Alexander A. Firsov ◽  
Sergey N. Vostrov ◽  
Alexander A. Shevchenko ◽  
Stephen H. Zinner ◽  
Giuseppe Cornaglia ◽  
...  
Keyword(s):  
Dynamic Model ◽  
Bacterial Species ◽  
Maximal Effect ◽  
Bacterial Strains ◽  
Time Curve ◽  
Antimicrobial Effects ◽  
E Coli ◽  
Kill Curve ◽  
Time Kill

ABSTRACT Multiple predictors of fluoroquinolone antimicrobial effects (AMEs) are not usually examined simultaneously in most studies. To compare the predictive potentials of the area under the concentration-time curve (AUC)-to-MIC ratio (AUC/MIC), the AUC above MIC (AUCeff), and the time above MIC (T eff), the kinetics of killing and regrowth of four bacterial strains exposed to monoexponentially decreasing concentrations of ciprofloxacin were studied in an in vitro dynamic model. The MICs of ciprofloxacin for clinical isolates ofStaphylococcus aureus, Escherichia coli11775 (I) and 204 (II), and Pseudomonas aeruginosa were 0.6, 0.013, 0.08, and 0.15 μg/ml, respectively. The simulated values of AUC were designed to provide similar 1,000-fold (S. aureus, E. coli I, and P. aeruginosa) or 2,000-fold (E. coli II) ranges of the AUC/MIC. In each case except for the highest AUC/MIC ratio, the observation periods included complete regrowth in the time-kill curve studies. The AME was expressed by its intensity,I E (the area between the control growth and time-kill and regrowth curves up to the point where the viable counts of regrowing bacteria are close to the maximum values observed without drug). For most AUC ranges the I E-AUC curves were fitted by an E max (maximal effect) model, whereas the effects observed at very high AUCs were greater than those predicted by the model. The AUCs that produced 50% of maximal AME were proportional to the MICs for the strains studied, but maximal AMEs (I E max ) and the extent of sigmoidicity (s) were not related to the MIC. BothT eff and log AUC/MIC correlated well withI E (r 2 = 0.98 in both cases) in a species-independent fashion. UnlikeT eff or log AUC/MIC, a specific relationship between I E and log AUCeff was inherent in each strain. Although each I E and log AUCeff plot was fitted by linear regression (r 2 = 0.97 to 0.99), these plots were not superimposed and therefore are bacterial species dependent. Thus, AUC/MIC and T eff were better predictors of ciprofloxacin’s AME than AUCeff. This study suggests that optimal predictors of the AME produced by a given quinolone (intraquinolone predictors) may be established by examining its AMEs against bacteria of different susceptibilities.T eff was shown previously also to be the best interquinolone predictor, but unlike AUC/MIC, it cannot be used to compare different quinolones. AUC/MIC might be the best predictor of the AME in comparisons of different quinolones.

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