Search

This study aimed to conduct a retrospective Middle East systematic review and meta-analysis on the prevalence and antibiotic susceptibility pattern for this microorganism isolated from cystic fibrosis patients. We searched MEDLINE, the Cochrane Library, SCOPUS, and Web of Science (ISI) to identify studies that reported the prevalence of Pseudomonas aeruginosa isolated from cystic fibrosis (CF) patients, and antibiotic resistance patterns. To assess the quality of publications was used of a checklist provided by the Joanna Briggs Institute. Finally, the data was analyzed by comprehensive meta-analysis software. The studied populations comprised children and young, and adult CF patients. Patients were aged between 3 months-65 years. A higher percentage of CF patients were males. Pseudomonas aeruginosa frequency varied between 5.9 and 76.2% in the studies included. The combined prevalence of P aeruginosa was reported 34.3%. The lowest level resistance of P aeruginosa was toward colistin (0%-l3.3%) and ticarcillin (3.9%-24%). Our study showed the prevalence of P aeruginosa and antibiotic resistance are almost high, while colistin and ticarcillin are the best antibiotics to decrease postantibiotic effects (PAEs) in CF patients from the Middle East. Therefore, physicians should pay more attention to therapeutic protocols to prevent further resistance. [ABSTRACT FROM AUTHOR]

The indiscriminate use of antibiotics in agriculture has raised concerns about antibiotic residues in food products, necessitating robust analytical methods for detection and quantification. In this study, our primary aim was to develop a robust and advanced liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology specifically designed for the accurate quantification of ticarcillin degradation products in tomato leaves. The choice of ticarcillin as the target analyte stems from its frequent use in agriculture and the potential formation of degradation products, which can pose a threat to food safety. The use of tomatoes as the target sample matrix in this study is justified by their significance in human diets, their widespread cultivation, and their suitability as a model for assessing antibiotic residue dynamics in diverse agricultural environments. By optimizing the MS/MS parameters, the study successfully demonstrates the practicality and reliability of the employed LC-MS/MS method in accurately assessing ticarcillin degradation product (Thiophene-2-Acetic acid and Thiophene-3-Acetic acid) levels. The chromatographic separation was achieved using a specialized column, ensuring high resolution and sensitivity in detecting analytes. Multiple reaction monitoring (MRM) data acquisition was employed to enhance the selectivity and accuracy of the analysis. The developed method exhibited excellent linearity and precision, meeting the stringent requirements for antibiotic residue analysis in complex matrices. Key outcomes of this study include the successful identification and quantification of ticarcillin and its degradation products in tomato leaves, providing crucial insights into the fate of this antibiotic in agricultural settings. The methodology's applicability was further demonstrated by analyzing real-world samples, highlighting its potential for routine monitoring and ensuring food safety compliance. In summary, our study constitutes a noteworthy advancement in the domain of antibiotic residue analysis, offering a reliable method for quantifying ticarcillin degradation products in tomato leaves. The optimized parameters and MRM-based LC-MS/MS approach enhance the precision and sensitivity of the analysis, opening up opportunities for further studies in the assessment of antibiotic residues in agricultural ecosystems. [ABSTRACT FROM AUTHOR]

Efficient regeneration of transgenic plants from expiants after transformation is one of the crucial steps in developing genetically modified plants with desirable traits. Identification of novel plant growth regulators and developmental regulators will assist to enhance organogenesis in culture. In this study, we observed enhanced shoot regeneration from tomato cotyledon explants in culture media containing timentin, an antibiotic frequently used to prevent Agrobacterium overgrowth after transformation. Comparative transcriptome analysis of explants grown in the presence and absence of timentin revealed several genes previously reported to play important roles in plant growth and development, including Auxin Response Factors (ARFs), GRF Interacting Factors (GIFs), Flowering Locus T (SP5G), Small auxin up-regulated RNAs (SAUR) etc. Some of the differentially expressed genes were validated by quantitative real-time PCR. We showed that ticarcillin, the main component of timentin, degrades into thiophene acetic acid (TAA) over time. TAA was detected in plant tissue grown in media containing timentin. Our results showed that TAA is indeed a plant growth regulator that promotes root organogenesis from tomato cotyledons in a manner similar to the well-known auxins, indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA). In combination with the cytokinin 6-benzylaminopurine (BAP), TAA was shown to promote shoot organogenesis from tomato cotyledon in a concentration-dependent manner. To the best of our knowledge, the present study reports for the first time demonstrating the function of TAA as a growth regulator in a plant species. Our work will pave the way for future studies involving different combinations of TAA with other plant hormones which may play an important role in in vitro organogenesis of recalcitrant species. Moreover, the differentially expressed genes and long noncoding RNAs identified in our transcriptome studies may serve as contender genes for studying molecular mechanisms of shoot organogenesis. [ABSTRACT FROM AUTHOR]

Efficient regeneration of transgenic plants from explants after transformation is one of the crucial steps in developing genetically modified plants with desirable traits. Identification of novel plant growth regulators and developmental regulators will assist to enhance organogenesis in culture. In this study, we observed enhanced shoot regeneration from tomato cotyledon explants in culture media containing timentin, an antibiotic frequently used to prevent Agrobacterium overgrowth after transformation. Comparative transcriptome analysis of explants grown in the presence and absence of timentin revealed several genes previously reported to play important roles in plant growth and development, including Auxin Response Factors (ARFs), GRF Interacting Factors (GIFs), Flowering Locus T (SP5G), Small auxin up-regulated RNAs (SAUR) etc. Some of the differentially expressed genes were validated by quantitative real-time PCR. We showed that ticarcillin, the main component of timentin, degrades into thiophene acetic acid (TAA) over time. TAA was detected in plant tissue grown in media containing timentin. Our results showed that TAA is indeed a plant growth regulator that promotes root organogenesis from tomato cotyledons in a manner similar to the well-known auxins, indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA). In combination with the cytokinin 6-benzylaminopurine (BAP), TAA was shown to promote shoot organogenesis from tomato cotyledon in a concentration-dependent manner. To the best of our knowledge, the present study reports for the first time demonstrating the function of TAA as a growth regulator in a plant species. Our work will pave the way for future studies involving different combinations of TAA with other plant hormones which may play an important role in in vitro organogenesis of recalcitrant species. Moreover, the differentially expressed genes and long noncoding RNAs identified in our transcriptome studies may serve as contender genes for studying molecular mechanisms of shoot organogenesis.

The indiscriminate use of antibiotics in agriculture has raised concerns about antibiotic residues in food products, necessitating robust analytical methods for detection and quantification. In this study, our primary aim was to develop a robust and advanced liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology specifically designed for the accurate quantification of ticarcillin degradation products in tomato leaves. The choice of ticarcillin as the target analyte stems from its frequent use in agriculture and the potential formation of degradation products, which can pose a threat to food safety. The use of tomatoes as the target sample matrix in this study is justified by their significance in human diets, their widespread cultivation, and their suitability as a model for assessing antibiotic residue dynamics in diverse agricultural environments. By optimizing the MS/MS parameters, the study successfully demonstrates the practicality and reliability of the employed LC-MS/MS method in accurately assessing ticarcillin degradation product (Thiophene-2-Acetic acid and Thiophene-3-Acetic acid) levels. The chromatographic separation was achieved using a specialized column, ensuring high resolution and sensitivity in detecting analytes. Multiple reaction monitoring (MRM) data acquisition was employed to enhance the selectivity and accuracy of the analysis. The developed method exhibited excellent linearity and precision, meeting the stringent requirements for antibiotic residue analysis in complex matrices. Key outcomes of this study include the successful identification and quantification of ticarcillin and its degradation products in tomato leaves, providing crucial insights into the fate of this antibiotic in agricultural settings. The methodology’s applicability was further demonstrated by analyzing real-world samples, highlighting its potential for routine monitoring and ensuring food safety compliance. In summary, our study constitutes a noteworthy advancement in the domain of antibiotic residue analysis, offering a reliable method for quantifying ticarcillin degradation products in tomato leaves. The optimized parameters and MRM-based LC-MS/MS approach enhance the precision and sensitivity of the analysis, opening up opportunities for further studies in the assessment of antibiotic residues in agricultural ecosystems.

With the rapid and continuous emergence of antimicrobial resistance, bacterial infections became a significant global healthcare concern. One of the proposed strategies to combat multidrug-resistant pathogens is to use additional compounds, such as natural biologically active substances, as adjuvants for existing antibiotics. In this study, we investigated the potential of caffeine, the widely consumed alkaloid, to modulate the antibacterial effects of antibiotics commonly used in clinical practice. We used disc diffusion assay to evaluate the effects of caffeine on 40 antibiotics in two Staphylococcus aureus strains (methicillin-resistant and methicillin-sensitive). Based on the results of this step, we selected five antibiotics for which the greatest caffeine-induced improvements in antibacterial activity were observed, and further analyzed their interactions with caffeine using a checkerboard approach. Caffeine at concentrations of 250 µg/mL or higher halved the MIC values of ticarcillin, cefepime, gentamycin, azithromycin, and novobiocin for all gram-negative species investigated (Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii). At the highest caffeine concentrations tested (up to 16 mg/mL), decreases in MIC values were 8- to 16-fold. The obtained results prove that caffeine modulates the activity of structurally diverse antibiotics, with the most promising synergistic effects observed for cefepime and azithromycin toward gram-negative pathogens. [ABSTRACT FROM AUTHOR]

Infectious diseases account for 25% of the causes of death worldwide and this rate is expected to increase due to antibiotic resistance. Among the bacteria associated with healthcare infections, Staphylococcus aureus is a prevalent pathogen and about 50% of the isolates are found to be methicillin-resistant. Here we describe the identification of ticarcillin as a weak binder of the S. aureus UDP- N -acetylglucosamine 2-epimerase. After a docking screening, ticarcillin was identified as a ligand in using the recently proposed isothermal analysis of differential scanning fluorimetry data. Finally, an equilibrium MD simulation confirmed the docking binding mode as a stable pose, with large contributions to the binding energy coming from interactions between Arg206 and Arg207 and the carboxylate groups in ticarcillin. • S. aureus N-acetylglucosamine 2-epimerase (MnaA) interconverts GlcNac and ManNac with relevance in antibiotic resistance. • We screened existing drugs for S. aureus MnaA using a structure-based approach and identified 17 potential ligands. • Further analysis using isothermal analysis with DSF data confirmed ticarcillin as a SaMnaA ligand. • This finding allows the optimization of existing drugs for this new target and provides new mechanisms of action. [ABSTRACT FROM AUTHOR]

The aim of this narrative review was to discuss the literature on β-lactam antibiotic-associated hypokalemia, a potentially life-threatening electrolyte disorder. The PubMed, Web of Science, Cochrane Library, and Scopus databases were searched for articles published between 1965 and 2023, using the following terms: 'hypokalemia' OR 'potassium loss' OR 'potassium deficiency' AND 'beta-lactams' OR 'penicillin' OR 'penicillin G' OR 'cephalosporins' OR 'ceftazidime' OR 'ceftriaxone' OR 'flucloxacillin' OR 'carbapenems' OR 'meropenem' OR 'imipenem' OR 'cefiderocol' OR 'azlocillin' OR 'ticarcillin'. Additional search terms were 'hypokalemia' AND 'epidemiology' AND 'ICU' OR 'intensive care unit' OR 'ER' OR 'emergency department' OR 'ambulatory' OR 'old' OR 'ageing population', and experimental (animal-based) studies were excluded. A total of eight studies were selected and discussed, in addition to nine case reports and case series. Both older and currently used β-lactam antibiotics (e.g., ticarcillin and flucloxacillin, respectively) have been associated with therapy-related hypokalemia. The incidence of β-lactam antibiotic-associated hypokalemia may be as high as 40%, thus, the issue of β-lactam-associated hypokalemia remains clinically relevant. Although other causes of hypokalemia are likely to be diagnosed more frequently (e.g., due to diuretic therapy or diarrhea), the possibility of β-lactam-induced renal potassium loss should always be considered in individuals with so-called 'unexplained hypokalemia'., Competing Interests: Declaration of conflicting interestThe Authors declare that there is no conflict of interest.

Klebsiella pneumoniae is a major cause of hospital-acquired infections, mainly responsible for urinary, respiratory, and bloodstream infections, as well as infections in intensive care unit (ICU) patients. The emergence of [...]

Carbapenem-resistant Klebsiella pneumoniae has emerged as one of the major multidrug-resistant bacterial pathogens worldwide. The international spread of this pathogen has been linked to a few high-risk clone group (CG) [...]

Non-clinical antibiotic development relies on in vitro susceptibility and infection model studies. Validating the achievement of the targeted drug concentrations is essential to avoid under-estimation of drug effects and over-estimation of resistance emergence. While certain β-lactams (e.g., imipenem) and β-lactamase inhibitors (BLIs; clavulanic acid) are believed to be relatively unstable, limited tangible data on their stability in commonly used in vitro media are known. We aimed to determine the thermal stability of 10 β-lactams and 3 BLIs via LC-MS/MS in cation-adjusted Mueller Hinton broth at 25 and 36°C as well as agar at 4 and 37°C, and in water at -20, 4, and 25°C. Supplement dosing algorithms were developed to achieve broth concentrations close to their target over 24 h. During incubation in broth (pH 7.25)/agar, degradation half-lives were 16.9/21.8 h for imipenem, 20.7/31.6 h for biapenem, 29.0 h for clavulanic acid (studied in broth only), 23.1/71.6 h for cefsulodin, 40.6/57.9 h for doripenem, 46.5/64.6 h for meropenem, 50.8/97.7 h for cefepime, 61.5/99.5 h for piperacillin, and >120 h for all other compounds. Broth stability decreased at higher pH. All drugs were ≥90% stable for 72 h in agar at 4°C. Degradation half-lives in water at 25°C were >200 h for all drugs except imipenem (14.7 h, at 1,000 mg/L) and doripenem (59.5 h). One imipenem supplement dose allowed concentrations to stay within ±31% of their target concentration. This study provides comprehensive stability data on β-lactams and BLIs in relevant in vitro media using LC-MS/MS. Future studies are warranted applying these data to antimicrobial susceptibility testing and assessing the impact of β-lactamase-related degradation., Competing Interests: The authors declare no conflict of interest.

Aims: Determine the prevalence of "P. aeruginosa" among clinical samples demonstrated from Azadi Teaching Hospital in Kirkuk, Iraq and to study the antibiogram profile of the isolates. Duration of Study: from July-December 2016. Methodology: The clinical isolates were characterized by standard methods of culturing, biochemical tests then they were tested for their sensitivity toward various antimicrobial. Results: A total of 185 swab samples (50 urine samples, 50 vagina swabs, 50 wound swabs and 35 samples from burn patients) were demonstrated to detect on P. aeruginosa. After culturing 40 (21.6%) were positive for bacterial growth, out of 40 isolates of "Pseudomonas aeruginosa"; 5 (10%) were from urine, 10 (20%) from vagina swabs, 11 (22%) from wound samples and 14 (40%) from burn patient. The results showed the high prevalence among the female than male (52.5 and 47.5% respectively) and the high average of isolates were recorded among the old group 15 to 30 years (45%) and the low prevalence was <45 years (20%) among old group. Antibiotics susceptibility tests of "P. aeruginosa" towards 15 different types of antibiotics. The resistance against (Augmentin, Amoxicillin, Ampicillin and Cefixime) were 38 isolates 95%, 37 isolates 92.5%, 38 isolates 95% and38 isolates 95% respectively, Except (Ticarcillin, Ceftazidime and Imipenem) the isolates showed low resistance against them 11 isolates 27.5%, 7 isolates 17.5% and 2 isolates 5% respectively. (Azithromycin, Gentamycin, Ciprofloxacin, and Amikacin) were7 isolates 17.5%, 12 isolates 30%, 7 isolates 17.5%, and 10 isolates 25% respectively. Whereas, the results showed high resistance (39 isolates 97.5%, 35 isolates 87.5%, 39 isolates 97.5% and 40 isolates 100% against Trimethoprim- Sulfamethaxazole, Doxycycline, Chloramphenicol and Rifampicin respectively. Conclusion: The dissemination of bacterial resistant strains towards the antibiotics causes losing of drug efficacy cause of the lack of awareness, patient's noncompliance, indiscriminate use of antimicrobial agents and unhygienic condition. [ABSTRACT FROM AUTHOR]

Raw cow-milk has essentially role inbacteria transferring, causing diseases like Escherichia coli (E. coli).The presentstudy has aimed to delineate E. coli virulence gene heat labile (LT) and heat stable (ST) by using Polymerase Chain Reaction (PCR). In terms of methodology, 125 raw cow-milk samples from four suburbs distinct of karbala as Al-Hussainiya, Al-Zebeliya, Al-hindiya and Al-hurr have been gathered and examined from December 2018 to March 2019.Accordingly, E. colihas been distinguished in 51 samples(40.8%), also the study has shown that the E. coli isolated from raw cow-milk is resistant to Ticarcillin (%92.1) followed by TicarcillinClavulanicacid (90.1%), Topramycin (25.4%),Aztreonam (25.4%) and sensitive to Meropenem (100%),Imepenem (100%) and Colistin (%100). It also sensitive to Ciprofloxacin (94.1%) followed byPipracillin / Tazobactam (88.2%) Pipracillin(%82.3), Trimethoprim / Sulfamethoxazole(80.3%),Pefloxacin (78.4%),Cefepime (76.4%), Gentamicin (76.4%), Minocycline (74.5%) and Amicacin (%72.5).As a result, the molecular features of isolatedE. colihas beenperformed by PCR through the use of proper primers. Virulence profile of genes reveals that 2/51(4%)isolates of E. coli harbored LT genes and 7/51 (14%)isolates of E. coliharbored ST genes. The results have also highlighted poor hygienic practices in the study regions, bringing microbiological risks from raw cow-milk, therefore, the study has proposed an improved hygienic practices on processing, production and distribution to ensure the safety of dairy products, safeguarding public health and to emphasis veterinarians or stakeholders’ role in production and distribution. [ABSTRACT FROM AUTHOR]

There are very limited data on ticarcillin-clavulanate elimination by haemofiltration. We measured in vitro ticarcillin-clavulanate adsorption to polyacrylonitrile (PAN) filters and the sieving coefficient using a well-described bench model of haemofiltration. The dose of ticarcillin-clavulanate was 60/2 mg or 180/3 mg, and 0 or 12 g albumin was added to the 1 L of circulating blood-crystalloid mixture to produce four different experimental conditions. The experiment was repeated four times under each condition. Median (interquartile range [IQR]) ticarcillin adsorption varied from 28 (27-30) mg to 85 (78-90) mg. Adsorption was increased when the dose of ticarcillin was higher (P <0.001), but was not affected by the addition of albumin. Median (IQR) adsorption of clavulanate ranged from 0.67 (0.55-0.75) mg to 1.8 (0.33-3.5) mg and was neither dose dependent (P = 0.505) nor significantly affected by the addition of albumin. Median (IQR) ticarcillin sieving coefficient ranged from 0.73 (0.67-0.75) to 0.99 (0.97-1.03). It was significantly higher with a higher dose of ticarcillin (P = 0.021) and without addition of albumin (P = 0.015). Median (IQR) clavulanate sieving coefficient ranged from 1.03 (1.00-2.24) to 2.0 (1.98-2.47). Clavulanate sieving coefficient was not significantly affected by dose or the addition of albumin. These data indicate that significant adsorption of both ticarcillin and clavulanate occurs in vitro; however, this requires confirmation by clinical pharmacokinetic studies. The sieving coefficient data may help guide appropriate dosing of critically ill patients receiving haemofiltration until more extensive clinical pharmacokinetic data are available. [ABSTRACT FROM AUTHOR]

Ticarcillin–clavulanate covers a broad spectrum of pathogens that are common in premature infants. In infants <30 weeks gestational age, pharmacokinetic data to guide ticarcillin–clavulanate dosing are lacking. We enrolled 15 premature infants <30 weeks gestational age, determined pharmacokinetic parameters, and performed dosing simulations to determine optimal dosing for ticarcillin–clavulanate. The infants had a median (range) postnatal age (PNA) of 18 days (6–44 days) and gestational age of 25 weeks (23–28 weeks). Clearance was lower in infants with a PNA <14 days (0.050 L/kg/h [range 0.043–0.075]) compared with a PNA ≥14–45 days (0.078 L/kg/h [0.047–0.100]), consistent with maturation of renal function. Dosing simulations determined that ticarcillin 75 mg/kg q12h (PNA <14 days) or q8h (PNA ≥ 14–45 days) achieved the target exposure for organisms with a minimum inhibitory concentration ≤16 μ/mL in >90% of simulated infants. For highly resistant organisms (minimum inhibitory concentration 32 μg/mL), increased dosing frequency or extended infusion are necessary. [ABSTRACT FROM AUTHOR]

Objective: Recommended combination for the treatment of serious Stenotrophomonas maltophilia infections is ticarcillinclavulanate and co-trimoxazole (SXT). However, first agent is not available in our country, and the second component may be a matter of antimicrobial resistance or intolerance. Therefore, we aimed to evaluate antimicrobial susceptibility testing results of S. maltophilia and in vitro activity of ceftazidime and moxifloxacin as a potential therapeutic alternative. Methods: S. maltophilia strains isolated from clinical samples in Infectious Diseases and Clinical Microbiology Laboratory between 1 October 2007-23 November 2017 were included in the study. Disk diffusion antimicrobial susceptibility test results of the strains were evaluated retrospectively. The in vitro activity of combination of ceftazidime and moxifloxacin against 24 of these strains was investigated by Etest®. Results: During the study period, 649 S. maltophilia strains were isolated from 649 different patients, and 94%, 93%, 92%, 81%, 60%, 55%, 45%, 41%, 38% of the strains were susceptible to tigecycline, moxifloxacin, SXT, ciprofloxacin, cefoperazonesulbactam, ceftazidime, netilmicin, gentamicin and amikacin, respectively. For the 24 strains included in the combination study, the moxifloxacin minimal inhibitory concentration (MIC)50/MIC90 values were defined as 0.064/0.125 µg/mL (MIC range 0.023-4 µg/mL) and ceftazidime MIC50/MIC90 values were defined as 32/256 µg/mL (MIC range 1.5-256 µg/mL). According to the results of fractional inhibitor concentration (FIC) index; ceftazidime and moxifloxacin combination displayed synergism, additivity and indifference for 1 (4%), 18 (75%) and 5 (21%) strains, respectively and there was no antagonism. The FIC50/ FIC90 value is calculated as 0.75/1.01 (FIC range 0.5-1.01). Conclusions: SXT resistance in S. maltophilia strains is below 10%, but it should be closely monitored because of the limited treatment options. Tigecycline and moxifloxacin can be among the treatment alternatives because of their high sensitivity rates similar to SXT. The combination of moxifloxacin plus ceftazidime demonstrated in vitro synergism or additivity against majority of the strains. So, this combination may be used as an alternative for the treatment of patients with S. maltophilia infections if there is resistance or side effects to the antibiotics used as the first option. [ABSTRACT FROM AUTHOR]