scholarly journals In Vitro Synergism of Colistin and N-acetylcysteine against Stenotrophomonas maltophilia

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 101 ◽  
Author(s):  
Nagaia Ciacci ◽  
Selene Boncompagni ◽  
Felice Valzano ◽  
Lisa Cariani ◽  
Stefano Aliberti ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Respiratory Infections ◽  
Topical Administration ◽  
Opportunistic Pathogen ◽  
Wide Range ◽  
Tract Infections ◽  
Human Infections ◽  
Time Kill ◽  
Dose Dependent

Stenotrophomonas maltophilia is an emerging global opportunistic pathogen, responsible for a wide range of human infections, including respiratory tract infections. Intrinsic multidrug resistance and propensity to form biofilms make S. maltophilia infections recalcitrant to treatment. Colistin is among the second-line options in case of difficult-to-treat S. maltophilia infections, with the advantage of being also administrable by nebulization. We investigated the potential synergism of colistin in combination with N-acetylcysteine (NAC) (a mucolytic agent with antioxidant and anti-inflammatory properties) against S. maltophilia grown in planktonic phase and biofilm. Eighteen S. maltophilia clinical isolates (comprising three isolates from cystic fibrosis (CF) and two trimethoprim-sulfamethoxazole (SXT)-resistant strains) were included. Checkerboard assays showed a synergism of colistin/NAC combinations against the strains with colistin Minimum Inhibitory Concentration (MIC) >2 µg/mL (n = 13), suggesting that NAC could antagonize the mechanisms involved in colistin resistance. Nonetheless, time–kill assays revealed that NAC might potentiate colistin activity also in case of lower colistin MICs. A dose-dependent potentiation of colistin activity by NAC was also clearly observed against S. maltophilia biofilms, also at sub-MIC concentrations. Colistin/NAC combinations, at concentrations likely achievable by topical administration, might represent a valid option for the treatment of S. maltophilia respiratory infections and should be examined further.

scholarly journals Synergistic Activity of Capsaicin and Colistin Against Colistin-Resistant Acinetobacter baumannii: In Vitro/Vivo Efficacy and Mode of Action

2021 ◽  
Vol 12 ◽  
Author(s):  
Tingting Guo ◽  
Mengying Li ◽  
Xiaoli Sun ◽  
Yuhang Wang ◽  
Liying Yang ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Opportunistic Pathogen ◽  
Antibacterial Activities ◽  
Synergistic Activity ◽  
Alternative Medicines ◽  
New Treatment ◽  
Time Kill ◽  
Dose Dependent

Acinetobacter baumannii is an opportunistic pathogen predominantly associated with nosocomial infections. With emerging resistance against polymyxins, synergistic combinations of drugs are being investigated as a new therapeutic approach. Capsaicin is a common constituent of the human diet and is widely used in traditional alternative medicines. The present study evaluated the antibacterial activities of capsaicin in combination with colistin against three unrelated colistin-resistant Acinetobacter baumannii strains in vitro and in vivo, and then further studied their synergistic mechanisms. Using the checkerboard technique and time-kill assays, capsaicin and colistin showed a synergistic effect on colistin-resistant A. baumannii. A mouse bacteremia model confirmed the in vivo effects of capsaicin and colistin. Mechanistic studies shown that capsaicin can inhibit the biofilm formation of both colistin-resistant and non-resistant A. baumannii. In addition, capsaicin decreased the production of intracellular ATP and disrupted the outer membrane of A. baumannii. In summary, the synergy between these drugs may enable a lower concentration of colistin to be used to treat A. baumannii infection, thereby reducing the dose-dependent side effects. Hence, capsaicin–colistin combination therapy may offer a new treatment option for the control of A. baumannii infection.

Efficacy of Pexiganan Combination with Tigecycline in a Mouse Model of Pseudomonas aeruginosa Sepsis

2019 ◽  
Vol 18 (24) ◽  
pp. 2127-2132 ◽  
Author(s):  
Oscar Cirioni ◽  
Oriana Simonetti ◽  
Gianluca Morroni ◽  
Lucia Brescini ◽  
Wojciech Kamysz ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Respiratory Tract Infections ◽  
Resistance Mechanisms ◽  
Skin Infections ◽  
In Vivo Experiment ◽  
Wide Range ◽  
Tract Infections ◽  
Time Kill

Background: Pseudomonas aeruginosa is a gram-negative pathogen, associated with a severe mortality rate. It is also difficult to treat due to numerous resistance mechanisms to a wide range of antibiotics. Objective: Evaluate the activity of pexiganan, an antimicrobial peptide, in combination with two clinical antibiotics (azithromycin and tigecycline) that are not active against P. aeruginosa. Methods: Ten clinical P. aeruginosa were isolated from urinary tract infections, blood culture, skin infections and respiratory tract infections. Minimum inhibitory concentrations (MICs) and synergies were evaluated by broth microdilution, checkerboard assays and time-kill studies. In vitro synergy was confirmed with an in vivo experiment using a murine model of sepsis. Results: Pexiganan MICs were included between 2 and 16 mg/L. Tigecycline and azithromycin MICs were high as expected (4-64 mg/L and 32-256 mg/L, respectively). Pexiganan and azithromycin combination resulted to be additive or indifferent while tigecycline and pexiganan combination was synergic against seven out of ten P. aeruginosa and additive against the other strains. In vivo experiment confirmed the in vitro synergy, denoting a significative reduction of bacteria in mice treated with pexiganan and tigecycline combination. Conclusion: Antimicrobial peptides are molecules that could be useful in the fight against infections and pexiganan seems to be one of the most promising. Our results demonstrated that, in association with tigecycline, pexiganan administration could overcome antibiotic resistance and increase the effectiveness of treatment against P. aeruginosa sepsis.

Relationship between clinical site of isolation and ability to form biofilms in vitro in nontypeable Haemophilus influenzae

2015 ◽  
Vol 61 (3) ◽  
pp. 243-245 ◽  
Author(s):  
Najla A. Obaid ◽  
Glenn A. Jacobson ◽  
Stephen Tristram
Keyword(s):  
Cystic Fibrosis ◽  
Haemophilus Influenzae ◽  
Otitis Media ◽  
Respiratory Infections ◽  
Infection Type ◽  
Opportunistic Pathogen ◽  
Nontypeable Haemophilus Influenzae ◽  
Clinical Source ◽  
Tract Infections

Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen associated with a range of infections, including various lower respiratory infections, otitis media, and conjunctivitis. There is some debate as to whether or not NTHi produces biofilms and, if so, whether or not this is relevant to pathogenesis. Although many studies have examined the association between in vitro biofilm formation and isolates from a specific infection type, few have made comparisons from isolates from a broad range of isolates grouped by clinical source. In our study 50 NTHi from different clinical sources, otitis media, conjunctivitis, lower respiratory tract infections in both cystic fibrosis and non-cystic fibrosis patients, and nasopharyngeal carriage, plus 10 nasopharyngeal isolates of the commensal Haemophilus haemolyticus were tested for the ability to form biofilm by using a static microtitre plate crystal violet assay. A high degree of variation in biofilm forming ability was observed across all isolates, with no statistically significant differences observed between the groups, with the exception of the isolates from conjunctivitis. These isolates had uniformly lower biofilm forming ability compared with isolates from the other groups (p < 0.005).

scholarly journals In Vitro Synergistic Interactions of Isavuconazole and Echinocandins against Candida auris

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 355
Author(s):  
Unai Caballero ◽  
Sarah Kim ◽  
Elena Eraso ◽  
Guillermo Quindós ◽  
Valvanera Vozmediano ◽  
...  
Keyword(s):  
Interaction Model ◽  
Antifungal Drugs ◽  
Health Concern ◽  
Candida Auris ◽  
Fungistatic Activity ◽  
Drug Concentrations ◽  
Low Concentrations ◽  
Wide Range ◽  
Time Kill

Candida auris is an emergent fungal pathogen that causes severe infectious outbreaks globally. The public health concern when dealing with this pathogen is mainly due to reduced susceptibility to current antifungal drugs. A valuable alternative to overcome this problem is to investigate the efficacy of combination therapy. The aim of this study was to determine the in vitro interactions of isavuconazole with echinocandins against C. auris. Interactions were determined using a checkerboard method, and absorbance data were analyzed with different approaches: the fractional inhibitory concentration index (FICI), Greco universal response surface approach, and Bliss interaction model. All models were in accordance and showed that combinations of isavuconazole with echinocandins resulted in an overall synergistic interaction. A wide range of concentrations within the therapeutic range were selected to perform time-kill curves. These confirmed that isavuconazole–echinocandin combinations were more effective than monotherapy regimens. Synergism and fungistatic activity were achieved with combinations that included isavuconazole in low concentrations (≥0.125 mg/L) and ≥1 mg/L of echinocandin. Time-kill curves revealed that once synergy was achieved, combinations of higher drug concentrations did not improve the antifungal activity. This work launches promising results regarding the combination of isavuconazole with echinocandins for the treatment of C. auris infections.

scholarly journals Urinary Excretion and Bactericidal Activities of a Single Oral Dose of 400 Milligrams of Fleroxacin versus a Single Oral Dose of 800 Milligrams of Pefloxacin in Healthy Volunteers

1998 ◽  
Vol 42 (7) ◽  
pp. 1659-1665 ◽  
Author(s):  
Kurt G. Naber ◽  
Ursula Theuretzbacher ◽  
Martina Kinzig ◽  
Orlin Savov ◽  
Fritz Sörgel
Keyword(s):  
Oral Dose ◽  
Healthy Volunteers ◽  
Single Oral Dose ◽  
E Coli ◽  
Wide Range ◽  
The Mean ◽  
Bactericidal Activities ◽  
Tract Infections ◽  
Time Kill ◽  
Randomized Crossover Study

ABSTRACT Twelve healthy volunteers participated in this randomized crossover study to compare the concentrations and recovery levels of fleroxacin and pefloxacin in urine and to assess their bactericidal activities against 12 strains of urinary pathogens with different susceptibilities over a wide range of MICs. The volunteers received a single oral dose of 400 mg of fleroxacin or 800 mg of pefloxacin. The mean cumulative renal excretion of unchanged fleroxacin,N-demethyl-fleroxacin, and N-oxide-fleroxacin accounted for 67, 7, and 6% of the total dose, respectively. The total urinary recovery of pefloxacin and the active metabolite norfloxacin was 34%. In the time-kill and the urinary bactericidal titer (UBT) studies, only the subjects’ urine not supplemented with broth was used. With most tested organisms and both quinolones it took more than 8 h to achieve a reduction in CFU of 99.9% (3 log units). Overall, there was a good correlation between UBTs and MICs for the strains. Against Escherichia coli ATCC 25922 the median UBTs were similar for both antibiotics and at least 1:8 for 96 h; against the E. coli strain for which the MIC was 0.5 μg/ml the UBT was at least 1:4 for 48 h. The UBTs of both drugs against Klebsiella pneumoniae were at least 1:16 for 72 h. The UBTs for Staphylococcus aureus (the MIC for which was 16 μg/ml) of both antibiotics were low, and in some of the samples, no bactericidal titers were observed. UBTs for Proteus mirabilis of pefloxacin are significantly higher than those of fleroxacin. For Pseudomonas aeruginosa the median UBTs were present for the 24-to-48-h interval. The same is true forEnterococcus faecalis. Against Staphylococcus saprophyticus, UBTs were present for at least 48 h with both quinolones. Overall, a single oral dose of 400 mg of fleroxacin exhibits UBTs comparable to those of 800 mg of pefloxacin. Therefore, it may be expected that half of the dose of fleroxacin gives comparable results in the treatment of urinary tract infections; this should be substantiated in comparative clinical trials.

In Vitro Activity of Cefixime and Six Other Agents Against Nosocomial Pathogens of the Enterobacteriaceae Family

1987 ◽  
Vol 8 (6) ◽  
pp. 241-244 ◽  
Author(s):  
Maury E. Mulligan ◽  
Y.Y. Kwok
Keyword(s):  
Respiratory Infections ◽  
Nosocomial Pathogens ◽  
The Family ◽  
Vascular Infections ◽  
Resistant Strains ◽  
Providencia Stuartii ◽  
Tract Infections ◽  
Abdominal Infections ◽  
Orally Active

AbstractCefixime, a broad-spectrum, orally active cephalosporin, was more active in vitro than ampicillin, cefaclor, cephalothin, and trimethoprim/sulfamethoxazole against 194 nosocomial pathogens of the family Enterobacteriaceae. Activity was especially good against Klebsiella spp, Proteus spp, Serratia spp, and Providencia stuartii. Although gentamicin had equivalent or better activity against Citrobacter spp, Enterobacter spp, Escherichia coli, and Morganella morganii, all 23 of the gentamicin-resistant strains studied were susceptible to Cefixime. Isolates tested were from urinary tract infections, abdominal infections, wounds, vascular infections, and respiratory infections; they were sequentially collected nosocomial pathogens from a single institution. This orally active cephalosporin should be considered for therapy of a variety of nosocomial infections involving gram-negative bacillary pathogens.

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.

Reservoirs of resistance: polymyxin resistance in veterinary-associated companion animal isolates of Pseudomonas aeruginosa

2019 ◽  
Vol 185 (7) ◽  
pp. 206-206 ◽  
Author(s):  
Andrea Scott ◽  
Sian Pottenger ◽  
Dorina Timofte ◽  
Matthew Moore ◽  
Laura Wright ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Pathogenic Bacteria ◽  
Inhibitory Concentration ◽  
Respiratory Infections ◽  
Companion Animals ◽  
Opportunistic Pathogen ◽  
Polymyxin B ◽  
Potential Reservoir ◽  
Human Infections ◽  
Animal Isolates

BackgroundPseudomonas aeruginosa is an opportunistic pathogen and a major cause of infections. Widespread resistance in human infections are increasing the use of last resort antimicrobials such as polymyxins. However, these have been used for decades in veterinary medicine. Companion animals are an understudied source of antimicrobial resistant P. aeruginosa isolates. This study evaluated the susceptibility of P. aeruginosa veterinary isolates to polymyxins to determine whether the veterinary niche represents a potential reservoir of resistance genes for pathogenic bacteria in both animals and humans.Methods and resultsClinical P. aeruginosa isolates (n=24) from UK companion animals were compared for antimicrobial susceptibility to a panel of human-associated isolates (n=37). Minimum inhibitory concentration (MIC) values for polymyxin B and colistin in the companion animals was significantly higher than in human isolates (P=0.033 and P=0.013, respectively). Genotyping revealed that the veterinary isolates were spread throughout the P. aeruginosa population, with shared array types from human infections such as keratitis and respiratory infections, suggesting the potential for zoonotic transmission. Whole genome sequencing revealed mutations in genes associated with polymyxin resistance and other antimicrobial resistance-related genes.ConclusionThe high levels of resistance to polymyxin shown here, along with genetic similarities between some human and animal isolates, together suggest a need for sustained surveillance of this veterinary niche as a potential reservoir for resistant, clinically relevant bacteria in both animals and humans.

scholarly journals In vitro Insecticidal and Time-Kill Profile of Ethyl Acetate Extract of Marine Streptomyces sp. Isolated from Sundarbans, Bangladesh

2015 ◽  
Vol 17 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Md Anwarul Haque ◽  
Ashish Kumar Sarker ◽  
Mohammad Sayful Islam ◽  
Md Ajijur Rahman ◽  
Md Akter Uzzaman Chouduri ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Mangrove Forest ◽  
Bacterial Strains ◽  
Streptomyces Species ◽  
Streptomyces Sp ◽  
Cell Counts ◽  
Wide Range ◽  
Marine Streptomyces ◽  
Time Kill

The marine soil and sediment samples were collected from different locations of mangrove forest Sundarbans, Bangladesh the largest tidal halophytic mangrove forest in the world. A total of twenty nine Actinomycete strains (AIAH-1 to AIAH-29) were isolated by serial dilution method using isolation media. Among twenty nine strains, AIAH-10 was selected for further study due to its potent antibacterial activity against a wide range of pathogenic bacterial strains. On the basis of morphological, cultural and biochemical studies, the strain AIAH-10 was assigned to Streptomyces sp. The present study was designed to investigate the in vitro insecticidal and time-kill profile of ethyl acetate extracts of marine Streptomyces sp. A dose dependent mortality was observed against the larvae of Sitophilus oryzae. The larval mortality was recorded as 100% in the concentration of 80 mg/ml and higher concentrations, LC50 was found as 11.48 mg/ml. The minimum inhibitory concentration was recorded as 8 to 32 mg/ml against six different pathogenic bacterial strains. Average Log10 reductions in viable cell counts for the extracts ranged from 1.91 Log10 and 2.86 Log10 cfu/mL after 3 h interaction and 2.10 Log10 and 2.93 Log10 after 6 h interaction at MIC, 2 × MIC, 3 × MIC and 4 × MIC concentrations. This investigation reveals that the Streptomyces species isolated from Sundarbans, Bangladesh may be interesting source for the isolation of potent bioactive compounds. DOI: http://dx.doi.org/10.3329/bpj.v17i2.22332 Bangladesh Pharmaceutical Journal 17(2): 151-156, 2014

scholarly journals Nitrofurantoin Combined With Amikacin: A Promising Alternative Strategy for Combating MDR Uropathogenic Escherichia coli

2020 ◽  
Vol 10 ◽  
Author(s):  
Zi-Xing Zhong ◽  
Ze-Hua Cui ◽  
Xiao-Jie Li ◽  
Tian Tang ◽  
Zi-Jian Zheng ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Resistance ◽  
Galleria Mellonella ◽  
Synergistic Effects ◽  
Promising Alternative ◽  
Poor Patient Compliance ◽  
Life Threatening ◽  
Tract Infections ◽  
Time Kill

Urinary tract infections (UTI) are common infections that can be mild to life threatening. However, increased bacterial resistance and poor patient compliance rates have limited the effectiveness of conventional antibiotic therapies. Here, we investigated the relationship between nitrofurantoin and amikacin against 12 clinical MDR uropathogenic Escherichia coli (UPEC) strains both in vitro and in an experimental Galleria mellonella model. In vitro synergistic effects were observed in all 12 test strains by standard checkerboard and time-kill assays. Importantly, amikacin or nitrofurantoin at half of the clinical doses were not effective in the treatment of UPEC infections in the G. mellonella model but the combination therapy significantly increased G. mellonella survival from infections caused by all 12 study UPEC strains. Taken together, these results demonstrated synergy effects between nitrofurantoin and amikacin against MDR UPEC.

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