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Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) can cause serious nosocomial infections. The reported misidentification of Bcc as P. aeruginosa , besides the contrasting susceptibility patterns between these two pathogens, underscores the importance of accurate identification and the need to explore therapeutic approaches that could eradicate them both. Our study aimed to evaluate the susceptibilities of both pathogens to different antibiotics and test the effectiveness of different antimicrobial combinations. In addition, we compared conventional phenotypic and automated identification methods using the VITEK 2 system with PCR amplification and sequencing of recA gene to differentiate between P. aeruginosa and Bcc. Amplification by PCR of the recA gene showed high specificity in the identification of Bcc in comparison with conventional and automated phenotypic methods. Significant differences in susceptibility were observed with P. aeruginosa isolates having more susceptibility to colistin and ceftazidime, while Burkholderia isolates were more susceptible to cotrimoxazole and minocycline. Both P. aeruginosa and Burkholderia isolates tested were more susceptible to N-Acetyl-L-Cysteine (NALC) plus meropenem or levofloxacin, followed by gentamicin plus piperacillin/tazobactam. Synergistic effect of NALC plus meropenem or levofloxacin may help in the eradication of both pathogens to overcome the diagnostic challenges posed by the possible misidentification using conventional identification methods.

Background: Carbapenemase-producing Gram-negative (CPGN) bacteria impose life-threatening infections with limited treatment options. Rigor and rapid detection of CPGN-associated infections is usually associated with proper treatment and better disease prognosis. Accordingly, this study aimed at evaluating the phenotypic methods versus genotypic methods used for the detection of such pathogens and determining their sensitivity/specificity values. Methods: A total of 71 CPGN bacilli (30 Enterobacterales and 41 non-glucose-fermenting bacilli) were tested for the carbapenemase production by the major phenotypic approaches including, the modified Hodge test (MHT), modified carbapenem inactivation method (mCIM), combined disk test by EDTA (CDT) and blue-carba test (BCT). The obtained results were statistically analyzed and correlated to the obtained resistant genotypes that were determined by using polymerase chain reactions (PCR) for the detection of the major carbapenemase-encoding genes covering the three classes (Class A, B, and D) of carbapenemases. Results: In comparison to PCR, the overall sensitivity/specificity values for detection of carbapenemase-producing organism were 65.62%/100% for MHT, 68.65%/100% for mCIM, 55.22%/100% for CDT and 89.55%/75% for BCT. The sensitivity/specificity values for carbapenemase-producing Enterobacterales were, 74%100% for MHT, 51.72%/ 100% for mCIM, 62.07%/100% for CDT and 82.75%/100% for BCT. The sensitivity/specificity values for carbapenemase-producing non-glucose fermenting bacilli were, 62.16%/100% for MHT, 81.57%/100% for mCIM, 50/100% for CDT and 94.74%/66.66% for BCT. Considering these findings, BCT possess a relatively high performance for the efficient and rapid detection of carbapenemase producing isolates. Statistical analysis showed significant association ( p <  0.05) between bla NDM and/or bla VIM genotypes with MHT/CDT; bla KPC / bla GIM genotypes with CDT and bla GIM genotype with BCT. Conclusion: The current study provides an update on the performance of the phenotypic tests which are varied depending on the tested bacterial genera and the type of the carbapenemase. The overall sensitivity/specificity values for detection of CPO were 65.62%/100% for MHT, 68.65%/100% for mCIM, 55.22%/100% for CDT and 89.55%/75% for BCT. Based on its respective diagnostic efficiency and rapid turnaround time, BCT is more likely to be recommended in a resource-limited settings particularly, when molecular tests are not available.

Background Micromonospora purpureochromogenes NRRL B-16094, a natural producer of gentamicin (GEN), a 5,6-diglycosylated 2-dexoystreptamine-aminoglycoside antibiotic (2DOS-AGA) broad-spectrum bactericidal activity. In literature, limited studies are concerned with the biosynthetic route and various cultural conditions influencing GEN production. Methods Therefore, this study aimed to explore the GEN biosynthesis pathway and compare it to that of fortimicin and kanamycin. In addition, four key environmental conditions influencing GEN production were statistically optimized using response surface D-optimal design (DOD). Herein, the biosynthetic pathway of GEN was proposed based on the biochemistry of the identified genes/proteins within the gene cluster. Comparing the GEN-biosynthetic gene cluster to that of kanamycin and fortimicin suggested that gentamicin biosynthesis could have originated from a combination of biosynthetic pathways of both antibiotics. Results For the optimization experiments, culture media 4 (CM4) and 6 (CM6) gave the highest specific productivity at 6.36 and 3.80 µg/mg, respectively. A DOD quadratic model was successfully generated to optimize four key environmental factors. Predicted and experimentally confirmed optimized factors were an initial pH of 7, an incubation temperature of 30˚C, and an agitation of 300 rpm for 10 days. This resulted in a 13.5-fold increase (289.5 µg/mL) over that produced by the basic CM1 production medium (21.4 µg/mL) and 2.4 times (over that obtained by CM4 (123.7 µg/mL) as verified by HPLC analysis. Conclusion DOD is an efficient tool for optimizing GEN. Accordingly, the optimized conditions are highly advisable during the scaling up of GEN production by M. purpureochromogenes NRRL B-16094.

The Lamiaceae plants are recognized in folk medicine for their antibacterial and anti-inflammatory properties. This study reports the first MS-based metabolomics analysis, integrating with chemometrics to explore metabolome heterogeneity in Salvia rosmarinus Spenn. (rosemary) and Origanum vulgare L. (oregano), and to pinpoint the key metabolites driving their antibacterial, antioxidant, and anti-inflammatory activities. UPLC–QTOF–MS/MS facilitated the identification of 164 metabolites, including flavonoids and hydroxycinnamic acids, which were reported for the first time in these species. For instance, salvianolic acid D and quercetin coumaroylhexoside were detected in rosemary, while salvianolic acid K, cleroden J, and flavonoids like nepitrin were newly reported in oregano. In biological evaluation, rosemary strongly inhibited methicillin-resistant Staphylococcus aureus and Escherichia coli , exhibited the highest radical scavenging capacity in DPPH assay, and showed superior anti-inflammatory effects through COX-II inhibition and TNF-α and NF-κB suppression. In contrast, oregano displayed the strongest reducing power in FRAP assay. Chemometric analyses revealed that flavonoids, hydroxycinnamic acids, and terpenes were the principal discriminating classes. Partial least squares analysis correlated rosemary’s antibacterial and radical scavenging activity with hydroxycinnamic acids, flavonoids, and terpenes, while its anti-inflammatory effects were linked to flavonoids and diterpenes. In oregano, FRAP reducing power correlated with benzyl derivatives, organic acids, and hydroxycinnamic acids.

Background Macrolide-resistant and methicillin-resistant Staphylococcus aureus , particularly those exhibiting pristinamycin resistance, impose significant medical health consequences with limited therapeutic options. This study is designed to determine their prevalence in a major tertiary care hospital in Egypt, antimicrobial susceptibility and evaluate various pristinamycin (PST)-antibiotic combinations. Methods Standard procedures were employed for isolation, identification, antimicrobial susceptibility, and molecular analysis of key macrolide- and methicillin-resistant genes. Phenotypic relatedness and antibiotic combinations of pristinamycin with other antimicrobial agents were done using the heatmap analysis and checkerboard assay. Results Out of 154 positive cultures of S. aureus were collected from different types of skin infections. The lowest resistance was shown for linezolid (5.2%), followed by vancomycin (9.1%), teicoplanin (9.1%), chloramphenicol (12.3%), and doxycycline (14.9%). The MDR isolates (43%, n  = 67) showed diverse phenotypic relatedness. They showed multiple antibiotic resistance (MAR) index range from 0.31–1.0, exhibiting 100% non-susceptibility to cefoxitin (MRSA), erythromycin, and clarithromycin known as macrolide resistant S. aureus (McRSA), followed by 80%, 74.6%, and 46.2% for clindamycin, azithromycin, and PST, respectively. All the MDR isolates gave positive nuc , mec A and confirmed MRSA. The erm C, erm A, and msr A, genes were detected in 49.25%, 26.8%, and 23.8% of the MDR isolates, respectively. The PST-doxycycline and PST-levofloxacin combinations were mostly synergistic in 82.13% and 70.14%, while PST-linezolid showed mostly additive effects in 67% of the MDR S. aureus isolates. Conclusion This study highlights the high prevalence of MRSA isolates recovered from various skin infections. Linezolid, vancomycin, teicoplanin, pristinamycin, chloramphenicol, and doxycycline remain effective therapeutic options. Macrolide and methicillin resistance are increasingly developing among S. aureus clinical isolates. The pristinamycin combination with doxycycline or levofloxacin was mostly synergistic and recommended for clinical evaluation.

Background Multidrug-resistant (MDR) P. aeruginosa is a rising public health concern, challenging the treatment of such a ubiquitous pathogen with monotherapeutic anti-pseudomonal agents. Worryingly, its genome plasticity contributes to the emergence of P. aeruginosa expressing different resistant phenotypes and is now responsible for notable epidemics within hospital settings. Considering this, we aimed to evaluate the synergistic combination of fortimicin with other traditional anti-pseudomonal agents and to analyze the resistome of pan-drug resistant (PDR) isolate. Methods Standard methods were used for analyzing the antimicrobial susceptibility tests. The checkerboard technique was used for the in vitro assessment of fortimicin antibiotic combinations against 51 MDR P. aeruginosa and whole genome sequencing was used to determine the resistome of PDR isolate. Results Out of 51 MDR P. aeruginosa, the highest synergistic effect was recorded for a combination of fortimicin with β-lactam group as meropenem, ceftazidime, and aztreonam at 71%, 59% and 43%, respectively. Of note, 56.8%, 39.2%, and 37.2% of the tested MDR isolates that had synergistic effects were also resistant to meropenem, ceftazidime, and aztreonam, respectively. The highest additive effects were recorded for combining fortimicin with amikacin (69%) and cefepime (44%) against MDR P. aeruginosa. Resistome analysis of the PDR isolate reflected its association with the antibiotic resistance phenotype. It ensured the presence of a wide variety of antibiotic-resistant genes (β-lactamases, aminoglycosides modifying enzymes, and efflux pump), rendering the isolate resistant to all clinically relevant anti-pseudomonal agents. Conclusion Fortimicin in combination with classical anti-pseudomonal agents had shown promising synergistic activity against MDR P. aeruginosa. Resistome profiling of PDR P. aeruginosa enhanced the rapid identification of antibiotic resistance genes that are likely linked to the appearance of this resistant phenotype and may pave the way to tackle antimicrobial resistance issues shortly.

Aflatoxin contamination of milk is a serious health concern. When animals ingested food contaminated with aflatoxin B1 (AFB1), it would be converted into aflatoxin M1 (AFM1) and secreted in the milk. This carcinogenic and hepatotoxic toxin could be overcome by biological methods. Therefore, this study aimed to assess the anti-aflatoxigenic effect of the probiotic Lactobacillus rhamnosus ( L. rhamnosus ) ATCC 7469, as well as its synbiotic combination with chitosan ZnO nanocomposite using ELISA. This is carried out by measuring AFM1 concentration in 90 milk samples, including 73 raw and 27 powdered milk samples. The average AFM1 concentration was 11.22 ± 11.31 and 10.62 ± 8.08 µg/kg, which exceeded the international regulatory limits for raw and powdered milk, respectively. All milk samples were treated with L. rhamnosus ATCC 7469 and a synbiotic combination of chitosan/ZnO nanocomposite and L. rhamnosus ATCC 7469 . The results showed that the probiotic L. rhamnosus ATCC 7469 , and the synbiotic combination significantly reduced the AFM1 concentration in milk ( p value  ≤ 0.05). The used probiotic bacteria showed binding to AFM1 from 10 to 83.8%, while the binding range increased to 34–92% after treating milk with the synbiotic combination. In conclusion, the biological treatment of milk using the probiotic, L. rhamnosus ATCC 7469 , alone or in combination with chitosan/ZnO nanocomposite, is an efficient method for reducing the AFM1 concentration in milk. This study highlights the use of both metal nanoparticles (as a prebiotic) and probiotics, forming a synbiotic approach to control milk contamination with aflatoxins in the laboratory.

Bloodstream infections with multidrug-resistant (MDR) Gram-negative bacteria (GNB) are among the most frequent complications in immunocompromised cancer patients because of their considerable morbidity and mortality. Several guidelines on antimicrobial therapy have addressed empirical treatment for such serious infections; however, the emergence of microbial resistance has become a significant problem worldwide. In this study, starting from November 2015 to October 2016, a total of 529 blood specimens were collected from febrile neutropenic cancer patients at a tertiary care cancer hospital in Egypt. On examination for positive bacterial growth, it was found that 334 specimens showed no growth, while 195 were positive. Out of the 195 positive culture specimens, 102 (102/195, 52.3%) were Gram-negative and 93 (93/195, 47.7%) were Gram-positive. Out of the 102 GNB, 70 (70/102, 68.6%) were MDR, including (27/70, 38.6%), (24/70, 34.3%), (9/70, 12.8%), (4/70, 5.7%), (2/70, 2.8%), (2/70, 2.8%), and (2/70, 2.8%). All MDR GNB showed high resistance to ampicillin, cefepime, ceftriaxone, and cephradine (minimum inhibitory concentration at which 50% of the isolates were inhibited [MIC ] >512 μg/mL for each). However, they showed good susceptibility to colistin (MIC <1 μg/mL). The most common extended-spectrum β-lactamases (ESBLs) genes detected were (39/70, 55.7%), (31/70, 44.3%), and (22/70, 31.4%). The most common aminoglycoside-resistant gene detected was ' (42/70, 60%) followed by the plasmid-mediated quinolone resistance determinants; (2/70, 2.8%), (9/70, 12.8%), and (19/70, 27.1%). ESBL determinants were significantly associated with resistance to ciprofloxacin, levofloxacin, amikacin, and carbapenems ( -value <0.005). The fractional inhibitory concentration index for ampicillin/sulbactam plus ceftriaxone, ampicillin/sulbactam plus amikacin, and amikacin plus levofloxacin showed synergism against 29 (29/70, 41.4%), 19 (19/70, 27.1%), and 11 (11/70, 15.7%) isolates of the tested MDR GNB isolates, respectively. Accordingly, new empirical antibiotics should be administered including the use of colistin or meropenem alone or both against the MDR GNB in neutropenic cancer patients.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting the substantia nigra where functions controlling body movement take place. Manganese (Mn) overexposure is linked to a neurologic syndrome resembling PD. Sesamol, thymol, wheat grass (WG), and coenzyme Q10 (CoQ10) are potent antioxidants, anti-inflammatory, and anti-apoptotic nutraceuticals. We investigated the potential protective effects of these nutraceuticals alone or in combinations against MnCl2-induced PD in rats. Seven groups of adult male Sprague Dawley rats were categorized as follows: group (I) was the control, while groups 2–7 received MnCl2 either alone (Group II) or in conjunction with oral doses of sesamol (Group III), thymol (Group IV), CoQ10 (Group V), WG (Group VI), or their combination (Group VII). All rats were subjected to four behavioral tests (open-field, swimming, Y-maze, and catalepsy tests). Biochemical changes in brain levels of monoamines, ACHE, BDNF, GSK-3β, GABA/glutamate, as well as oxidative stress, and apoptotic and neuroinflammatory biomarkers were evaluated, together with histopathological examinations of different brain regions. Mn increased catalepsy scores, while decreasing neuromuscular co-ordination, and locomotor and exploratory activity. It also impaired vigilance, spatial memory, and decision making. Most behavioral impairments induced by Mn were improved by sesamol, thymol, WG, or CoQ10, with prominent effect by sesamol and thymol. Notably, the combination group showed more pronounced improvements, which were confirmed by biochemical, molecular, as well as histopathological findings. Sesamol or thymol showed better protection against neuronal degeneration and some behavioral impairments induced by Mn than WG or CoQ10, partly via interplay between Nrf2/HO-1, TLR4/NLRP3/NF-κB, GSK-3β and Bax/Bcl2 pathways.

Milk contaminated with aflatoxin can lead to liver cancer. Aflatoxin B1 (AFB1), a serious animal feed contaminant, is transformed into Aflatoxin M1 (AFM1) and secreted in milk. In this study, a biological method using probiotic bacteria, Lactobacillus rhamnosus (L. rhamnosus) in combination with Saccharomyces cerevisiae (S. cerevisiae), was used to assess their antiaflatoxigenic effect in animal milk. A Box–Behnken design was used to establish the optimal ratio of L. rhamnosus and S. cerevisiae, incubation time, and temperature for efficient AFM1 detoxification from milk. To achieve this, the primary, interaction, and quadratic effects of the chosen factors were investigated. To investigate the quadratic response surfaces, a second-order polynomial model was built using a three-factor, three-level Box–Behnken design. The quantity of AFM1 was detected by the ELISA technique. The results of these experiments obtained an optimum condition in AFM1 detoxification of the three tested factors in order to maximize their effect on AFM1 detoxification in milk. The model was tested in three highly contaminated milk samples to assure the efficacy of the model. AFM1 detoxification was up to 98.4% in contaminated milk samples. These promising results provide a safe, low-cost, and low-time-consuming solution to get rid of the problem of milk contamination with AFM1.