scholarly journals A Study of the Disruptive Effect of the Acetate Fraction of Punica granatum Extract on Cryptococcus Biofilms

2021 ◽  
Vol 11 ◽  
Author(s):  
Paulo C. M. Villis ◽  
Alessandra T. de Macedo ◽  
Haryne L. A. Furtado ◽  
Pedro H. C. Fontenelle ◽  
Ingrid S. Gonçalves ◽  
...  
Keyword(s):  
Treatment Options ◽  
Folk Medicine ◽  
Antimicrobial Effect ◽  
Punica Granatum ◽  
Cryptococcus Laurentii ◽  
Disruptive Effect ◽  
Worldwide Distribution ◽  
Kill Curve ◽  
Therapeutic Alternatives ◽  
Time Kill

Cryptococcosis, caused by yeasts of the genus Cryptococcus, is an infectious disease with a worldwide distribution. Cryptococcus neoformans and Cryptococcus gattii are the species that commonly cause this disease in humans; however, infections caused by Cryptococcus laurentii, especially in immunocompromised patients, are increasingly being reported. Owing to the increase in the resistance of fungi to antifungals, and a lack of treatment options, it is important to seek new therapeutic alternatives such as natural products. Among these are plant species such as Punica granatum, which is used in folk medicine to treat various diseases. This study aimed to evaluate the activity of the acetate fraction of P. granatum leaf extract against environmental and clinical isolates of Cryptococcus. Three environmental isolates of C. laurentii, PMN, PMA, and PJL II, isolated from soils of different municipalities in the state of Maranhão, a clinical isolate, C. gattii, from a patient with neurocryptococcosis, and a standard strain of C. gattii (ATCC 32068) were used. The minimum and fractional inhibitory concentrations (MIC and FIC, respectively) and time-kill curve of the extract and fluconazole were determined to assess the susceptibility profile of the fungal isolates. Larvae of Tenebrio molitor were infected with Cryptococcus strains, and the effects of acetate fraction of P. granatum extract and fluconazole on the survival and fungal burden were determined. The extract activity was tested against pre-formed biofilms. The acetate fraction of P. granatum extract showed promising antifungal activity against all the species of Cryptococcus evaluated in this study, with an MIC value lower than that of fluconazole. The indices obtained in the FIC test indicated that the antimicrobial effect of the combination of the extract and antifungal was indifferent for 80% of the isolates. The P. granatum acetate fraction reduced the pre-formed biofilm of some isolates, showing better activity than fluconazole, which is consistent with results from fluorescence microscopy. This is the first study on the use of P. granatum and its ability to inhibit Cryptococcus biofilms; therefore, further studies and tests are needed to investigate the components and mechanism of action of P. granatum against cryptococcosis agents.

scholarly journals Relationships of the Area under the Curve/MIC Ratio to Different Integral Endpoints of the Antimicrobial Effect: Gemifloxacin Pharmacodynamics in an In Vitro Dynamic Model

2001 ◽  
Vol 45 (3) ◽  
pp. 927-931 ◽  
Author(s):  
Alexander A. Firsov ◽  
Irene Y. Lubenko ◽  
Yury A. Portnoy ◽  
Stephen H. Zinner ◽  
Sergey N. Vostrov
Keyword(s):  
Area Under The Curve ◽  
Antimicrobial Effect ◽  
Time Curve ◽  
Marginal Value ◽  
Actual Effect ◽  
Control Growth ◽  
Effect Duration ◽  
Kill Curve ◽  
Time Kill

ABSTRACT Most integral endpoints of the antimicrobial effect are determined over an arbitrarily chosen time period, such as the dosing interval (τ), regardless of the actual effect duration. Unlike the τ-related endpoints, the intensity of the antimicrobial effect (I E) does consider its duration—from time zero to the time when bacterial counts on the regrowth curve achieve the same maximal numbers as in the absence of the antimicrobial. To examine the possible impact of this fundamental difference on the relationships of the antimicrobial effect to the ratio of the area under the concentration-time curve (AUC) to the MIC, a clinical isolate ofStaphylococcus aureus was exposed to simulated gemifloxacin pharmacokinetics over a 40-fold range of AUC/MIC ratios, from 11 to 466 h. In each run, I E and four τ-related endpoints, including the area under the time-kill curve (AUBC), the area above the curve (AAC), the area between the control growth and time-kill curves (ABBC), and the ABBC related to the area under the control growth curve (AUGC), were calculated for τ = 24 h. Unlike the I E, which displayed pseudolinear relationships with the AUC/MIC ratio; each τ-related endpoint showed a distinct saturation at potentially therapeutic AUC/MIC ratios (116 to 466 h) when the antimicrobial effect persisted longer than τ. This saturation results from the underestimation of the true effect and may be eliminated if ABBC, AAC, and AUBC (but not AUGC) are modified and determined in the same manner as the I E to consider the actual effect duration. These data suggest a marginal value of the τ-related endpoints as indices of the total antimicrobial effect. Since all of them respond to AUC/MIC ratio changes less than theI E, the latter is preferable in comparative pharmacodynamic studies.

scholarly journals Twenty-four-hour area under the concentration-time curve/MIC ratio as a generic predictor of fluoroquinolone antimicrobial effect by using three strains of Pseudomonas aeruginosa and an in vitro pharmacodynamic model.

1996 ◽  
Vol 40 (3) ◽  
pp. 627-632 ◽  
Author(s):  
K J Madaras-Kelly ◽  
B E Ostergaard ◽  
L B Hovde ◽  
J C Rotschafer
Keyword(s):  
Antibacterial Effect ◽  
Antimicrobial Effect ◽  
Time Curve ◽  
Emax Model ◽  
Concentration Time ◽  
Mueller Hinton ◽  
Kill Curve ◽  
Time Kill ◽  
Mueller Hinton Broth

Several investigators have suggested that the 24-h area under the concentration-time curve (AUC)/MIC ratio (AUC/MIC24 or AUIC24) can be used to make comparisons of antimicrobial activity between fluoroquinolone antibiotics. Limited data exist regarding the generic predictive ability of AUC/MIC24 for the antimicrobial effects of fluoroquinolones. The purposes of the present investigation were to determine if the AUC/MIC24 can be used as a generic outcome predictor of fluoroquinolone antibacterial activity and to determine if a similar AUC/MIC24 breakpoint can be established for different fluoroquinolones. Using an in vitro pharmacodynamic model, 29 duplicate concentration time-kill curve experiments simulated AUC/MIC24s ranging from 52 to 508 SIT-1.h (inverse serum inhibitory titer integrated over time) with ciprofloxacin or ofloxacin against three strains of Pseudomonas aeruginosa. Each 24-h experiment was performed in cation-supplemented Mueller-Hinton broth with a starting inoculum of 10(6) CFU/ml. At timed intervals cation-supplemented Mueller-Hinton broth samples were collected for CFU and fluoroquinolone concentration determinations. Transformation of bacterial counts into the cumulative bacterial effect parameter of the 24-h area under the effect curve (AUEC24) was performed for each concentration time-kill curve. Multivariate regression analysis was used to compare pharmacodynamic predictors (AUC/MIC24, 24-h AUC, peak concentration [Cmax] to MIC ratios [Cmax:MIC], etc.) with ln AUEC24. To identify threshold breakpoint AUC/MIC24s, AUEC24s were stratified by the magnitude of AUC/MIC24 into subgroups, which were analyzed for differences in antibacterial effect. The Kruskal-Wallis test and subsequent Tukey's multiple comparison test were used to determine which AUC/MIC subgroups were significantly different. Multiple regression analysis revealed that only AUC/MIC24 (r2 = 0.65) and MIC (r2 = 0.03) were significantly correlated with antibacterial effect. At similar AUC/MIC24s, yet different MICs, Cmaxs, or elimination half-lives, the AUEC24s were similar for both fluoroquinolones. The relationship between AUC/MIC24 and ln AUEC24 was best described by a sigmoidal maximal antimicrobial effect (Emax) model (r2 = 0.72; Emax = 9.1; AUC/MIC50 = 119 SIT-1.h; S = 2.01 [S is an exponent that reflects the degree of sigmoidicity]). Ciprofloxacin-bacteria AUC/MIC24 values of < 100 SIT-1.h were significantly different (P < 0.05) from the AUC/MIC24 values of > 100 SIT-1.h. An ofloxacin AUC/MIC24 of > 100 SIT-1.h and an AUC/MIC24 of < 100 SIT-1.h exhibited a trend toward a significant difference (P > 0.05 but < 0.1). The inverse relationship between drug exposure and MIC increase postexposure was described by a sigmoidal fixed Emax model (AUC/MIC24, r2 = 0.40; AUC/MIC50 = 95 SIT-1.h; S = 1.97; Cmax:MIC, r2 = 0.41; Cmax:MIC50 = 7.3; S = 2.01). These data suggest that AUC/MIC24 may be the most descriptive measurement of fluoroquinolone antimicrobial activity against P. aeruginosa, that ofloxacin and ciprofloxacin have similar AUC/MIC24 threshold breakpoints at approximately 100 SIT-1.h, that the concentration-dependent selection of resistant organisms may parallel the threshold breakpoint of the antimicrobial effect, and that AUC/MIC24 generically describes the antibacterial effects of different fluoroquinolones.

scholarly journals Trans-Cinnamaldehyde Exhibits Synergy with Conventional Antibiotic against Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Vol 22 (5) ◽  
pp. 2752
Author(s):  
Shu Wang ◽  
Ok-Hwa Kang ◽  
Dong-Yeul Kwon
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Synergistic Effects ◽  
Regulatory Gene ◽  
Western Blot Assay ◽  
Methicillin Resistant ◽  
Wide Range ◽  
Kill Curve ◽  
Conventional Antibiotics ◽  
Time Kill

Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen worldwide and has acquired multiple resistance to a wide range of antibiotics. Hence, there is a pressing need to explore novel strategies to overcome the increase in antimicrobial resistance. The present study aims to investigate the efficacy and mechanism of plant-derived antimicrobials, trans-cinnamaldehyde (TCA) in decreasing MRSA’s resistance to eight conventional antibiotics. A checkerboard dilution test and time–kill curve assay are used to determine the synergistic effects of TCA combined with the antibiotics. The results indicated that TCA increased the antibacterial activity of the antibiotics by 2-16-fold. To study the mechanism of the synergism, we analyzed the mecA transcription gene and the penicillin-binding protein 2a level of MRSA treated with TCA by quantitative RT-PCR or Western blot assay. The gene transcription and the protein level were significantly inhibited. Additionally, it was verified that TCA can significantly inhibit the biofilm, which is highly resistant to antibiotics. The expression of the biofilm regulatory gene hld of MRSA after TCA treatment was also significantly downregulated. These findings suggest that TCA maybe is an exceptionally potent modulator of antibiotics.

scholarly journals Antimicrobial Activity of Roselle-capped​ Silver​ Nanochip on Aggregatibacter actinomycetemcomitans

2021 ◽  
Author(s):  
Sirorat Wacharanad ◽  
Puncharee Thatree ◽  
Punchaya Yiemwattana ◽  
Penpitcha Paoprajak ◽  
Pimchanok Ngamsangiam ◽  
...  
Keyword(s):  
Nitrate Solution ◽  
Synthesis Method ◽  
Antimicrobial Effect ◽  
Silver Nitrate Solution ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Microwave Assisted Synthesis ◽  
Alginate Gel ◽  
Diffusion Technique ◽  
Inhibition Zones ◽  
Time Kill

Abstract Objectives This article aimed to study the effects of the​ roselle-capped​ silver​ nanochip​ ​(SNP-Ro​ chip)​ against Aggregatibacter actinomycetemcomitans, and the toxicity of this film on fibroblast cells to develop this SNP-Ro chip into a local chemical for the treatment of periodontitis in the future. Materials and Methods Using a microwave-assisted synthesis method, silver​ nanoparticles (SNPs) were prepared from a silver nitrate solution and roselle extract as a reducing and capping agent. Then, SNP-Ro chips were fabricated by mixing a solution of SNP-Ro with alginate gel. The antimicrobial effect of the synthesized SNP-Ro chips was performed by the disc diffusion technique and time kill assay. The cytotoxic effect was also determined by the MTS assay. Statistical Analysis One-way analysis of variance (ANOVA) and Scheffe’s method were used to analyze the data for this experiment. Results All three ratios of the SNP-Ro chip produced inhibition zones ranging between 18.75 ± 2.08 and 19.03 ± 2.25 mm. In studying the killing time, the three groups of the SNP-Ro chips completely eradicated A. actinomycetemcomitans within 180 minutes. The percentage of the viable SNP-Ro chip-treated human gingival fibroblasts (HGFs) were significantly increased when compared with the alginate chip-treated cells (p < 0.05). Conclusion This study developed a new method for the deposition of SNPs in alginate gel to make a thin small chip for the sustained release of the SNPs in a periodontal lesion. Therefore, the SNP-Ro chip has the potential to be developed as an adjunctive locally delivered antimicrobial agent in periodontal therapy.

scholarly journals Emergent Polymyxin Resistance: End of an Era?

2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Zekun Li ◽  
Yuping Cao ◽  
Lingxian Yi ◽  
Jian-Hua Liu ◽  
Qiwen Yang
Keyword(s):  
Susceptibility Testing ◽  
Treatment Options ◽  
Effective Control ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Poor Clinical Outcome ◽  
Ventilator Support ◽  
Multiple Risk Factors ◽  
Chromogenic Agar ◽  
Therapeutic Alternatives

Abstract Until recently, the polymyxin antibiotics were used sparingly due to dose limiting toxicities. However, the lack of therapeutic alternatives for infections caused by highly resistant Gram-negative bacteria has led to the increased use of the polymyxins. Unfortunately, the world has witnessed increased rates of polymyxin resistance in the last decade, which is likely in part due to its irrational use in human and veterinary medicine. The spread of polymyxin resistance has been aided by the dissemination of the transferable polymyxin-resistance gene, mcr, in humans and the environment. The mortality of colistin-resistant bacteria (CoRB) infections varies in different reports. However, poor clinical outcome was associated with prior colistin treatment, illness severity, complications, and multidrug resistance. Detection of polymyxin resistance in the clinic is possible through multiple robust and practical tests, including broth microdilution susceptibility testing, chromogenic agar testing, and molecular biology assays. There are multiple risk factors that increase a person’s risk for infection with a polymyxin-resistant bacteria, including age, prior colistin treatment, hospitalization, and ventilator support. For patients that are determined to be infected by polymyxin-resistant bacteria, various antibiotic treatment options currently exist. The rising trend of polymyxin resistance threatens patient care and warrants effective control.

scholarly journals Antibacterial Inhibitory Effects of Punica Granatum Gel on Cariogenic Bacteria: An in vitro Study

2017 ◽  
Vol 10 (2) ◽  
pp. 152-157 ◽  
Author(s):  
Grazielle Millo ◽  
Apa Juntavee ◽  
Ariya Ratanathongkam ◽  
Natsajee Nualkaew ◽  
Peerapattana, Jomjai ◽  
...  
Keyword(s):  
High Performance ◽  
In Vitro Study ◽  
Punica Granatum ◽  
Antibacterial Activities ◽  
Diffusion Method ◽  
Inhibitory Effects ◽  
Cariogenic Bacteria ◽  
Zones Of Inhibition ◽  
Time Kill

ABSTRACT Aim This study evaluated the in vitro antibacterial effects of the formulated Punica granatum (PG) gel against Streptococcus mutans, Streptococcus sanguinis, and Lactobacillus casei. Materials and methods The PG extract was dissolved in water at 500 mg/mL. High performance liquid chromatography (HPLC) was used for identification and quantification of chemical marker punicalagin. Minimum bactericidal concentration (MBC) and time-kill assay (TKA) were investigated. Antibacterial activities of the formulated PG gel, 2% chlorhexidine (CHX) gel and blank gel were tested by measuring the zones of inhibition through agar well diffusion method. Results The HPLC results showed presence of punicalagin at 2023.58 ± 25.29 μg/mL in the aqueous PG extract and at 0.234% (w/w) in the formulated PG gel. The MBC for S. mutans, S. Sanguinis, and L. casei were 250, 125, and 500 mg/mL respectively. The TKA of 500 mg/mL aqueous PG extract showed total inhibition of S. mutans, S. Sanguinis, and L. casei at 6, 1, and 24 hours contact time respectively. Agar well diffusion revealed that for S. mutans, CHX gel > PG gel > blank gel; for S. sanguinis, CHX gel = PG gel > blank gel; for L. casei, CHX gel > PG gel = blank gel. Comparison of the PG gel potency showed that S. sanguinis = S. mutans > L. casei. Conclusion The PG gel equivalent to 0.234% punicalagin (w/w) inhibited S. mutans and S. sanguinis but not L. casei within 24 hours incubation period and has the potential to be used for caries prevention. How to cite this article Millo G, Juntavee A, Ratanathongkam A, Nualkaew N, Peerapattana J, Chatchiwiwattana S. Antibacterial Inhibitory Effects of Punica Granatum Gel on Cariogenic Bacteria: An in vitro Study. Int J Clin Pediatr Dent 2017;10(2):152-157.

scholarly journals Antimicrobial Properties of 8-Hydroxyserrulat-14-en-19-oic Acid for Treatment of Implant-Associated Infections

2012 ◽  
Vol 57 (1) ◽  
pp. 333-342 ◽  
Author(s):  
Justyna Nowakowska ◽  
Hans J. Griesser ◽  
Marcus Textor ◽  
Regine Landmann ◽  
Nina Khanna
Keyword(s):  
Structural Changes ◽  
Treatment Options ◽  
Antimicrobial Properties ◽  
Bactericidal Effect ◽  
Mouse Tissue ◽  
Logarithmic Phase ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Time Kill

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.

scholarly journals Effect of Achyranthes aspera, 0.2% Aqueous Chlorhexidine Gluconate and Punica granatum Oral Rinse on the Levels of Salivary Streptococcus mutans in 8 to 12 Years Old Children

2015 ◽  
Vol 16 (11) ◽  
pp. 903-909
Author(s):  
Deepak Goel ◽  
Aayushi Bansal ◽  
Anant Gopal Nigam
Keyword(s):  
Streptococcus Mutans ◽  
Antimicrobial Effect ◽  
Punica Granatum ◽  
Chlorhexidine Gluconate ◽  
Plaque Index ◽  
Plaque Score ◽  
Achyranthes Aspera ◽  
Oral Rinse ◽  
Group B ◽  
Mouth Rinsing

ABSTRACT Background and objectives To study the effect Achyranthes aspera, 0.2% aqueous chlorhexidine gluconate and Punica granatum oral rinse on salivary Streptococcus mutans count in children. Materials and methods A total of 60 children of 8 to 12 years of age were randomly allocated into 3 groups. Group A was given 0.2% chlorhexidine mouthwash, group B was given 10% A. aspera mouthwash and group C was given 15% P. granatum mouthwash. The day 1 saliva samples were collected from the subjects and innoculated onto mitis salivarius bacitracin (MSB) agar. The colony counts were obtained by a clinical microbiologist who was blinded to the subject allocation. Plaque scores were then recorded by the investigator with the help of a volunteer. Following this, they received a thorough scaling and polishing. Subjects in each group were then provided with 140 ml of the respective mouthwash, as a daily supervised rinse after breakfast and before sleeping as per instructions. Following mouth rinsing, the children were instructed not to eat or drink for 15 minutes. At the 7th day, unstimulated saliva was again collected from the subjects of all 3 groups, inoculated onto MSB agar and colony count was obtained. Modified Quigley- Hein plaque index was also evaluated for the refreshed score at this stage. Colony counting was done using loop method and statistical analysis was done using Statistical Package for the Social Science (SPSS) software version 21. Results All the three mouthwashes showed statistically significant reduction of S. mutans count and plaque index after 7 days, i.e. chlorhexidine (p < 0.001 for reduction in S. mutans count and p < 0.05 for plaque score reduction), A. aspera (p < 0.01 for reduction in S. mutans count and p < 0.05 for plaque score reduction) and P. granatum (p < 0.01 for reduction in S. mutans count and p < 0.05 for plaque score reduction). Chlorhexidine had marginally better results in reducing S. mutans count. Conclusion • Efficacy of chlorhexidine, A. aspera and P. granatum was statistically significant with respect to reduction of S. mutans count with chlorhexidine being marginally better than the other two, • All the three mouthwashes were found to be at par when plaque index values from baseline and after interception of 7 days was calculated, • Punica granatum has better antimicrobial effect than A. aspera. How to cite this article Bansal A, Marwah N, Nigam AG, Goenka P, Goel D. Effect of Achyranthes aspera, 0.2% Aqueous Chlorhexidine Gluconate and Punica granatum Oral Rinse on the Levels of Salivary Streptococcus mutans in 8 to 12 Years Old Children. J Contemp Dent Pract 2015;16(11):903-909.

scholarly journals Semimechanistic Pharmacokinetic/Pharmacodynamic Modeling of Fosfomycin and Sulbactam Combination against Carbapenem-Resistant Acinetobacter baumannii

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Sazlyna Mohd Sazlly Lim ◽  
Aaron J. Heffernan ◽  
Jason A. Roberts ◽  
Fekade B. Sime
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Pharmacodynamic Modeling ◽  
Synergistic Activity ◽  
Bacterial Burden ◽  
Target Attainment ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Time Kill

ABSTRACT Due to limited treatment options for carbapenem-resistant Acinetobacter baumannii (CR-AB) infections, antibiotic combinations are now considered potential treatments for CR-AB. This study aimed to explore the utility of fosfomycin-sulbactam combination (FOS/SUL) therapy against CR-AB isolates. Synergism of FOS/SUL against 50 clinical CR-AB isolates was screened using the checkerboard method. Thereafter, time-kill studies against two CR-AB isolates were performed. The time-kill data were described using a semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Monte Carlo simulations were then performed to estimate the probability of stasis, 1-log kill, and 2-log kill after 24 h of combination therapy. The FOS/SUL combination demonstrated a synergistic effect against 74% of isolates. No antagonism was observed. The MIC50 and MIC90 of FOS/SUL were decreased 4- to 8-fold, compared to the monotherapy MIC50 and MIC90. In the time-kill studies, the combination displayed bactericidal activity against both isolates and synergistic activity against one isolate at the highest clinically achievable concentrations. Our PK/PD model was able to describe the interaction between fosfomycin and sulbactam in vitro. Bacterial kill was mainly driven by sulbactam, with fosfomycin augmentation. FOS/SUL regimens that included sulbactam at 4 g every 8 h demonstrated a probability of target attainment of 1-log10 kill at 24 h of ∼69 to 76%, compared to ∼15 to 30% with monotherapy regimens at the highest doses. The reduction in the MIC values and the achievement of a moderate PTA of a 2-log10 reduction in bacterial burden demonstrated that FOS/SUL may potentially be effective against some CR-AB infections.

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