Methicillin-resistant Research Articles

Multidrug resistance in urinary E. coli higher in males compared to females

Multidrug resistance in urinary E. coli higher in males compared to females

Retrospective analysis of antimicrobial susceptibility profiles of non- diphtheriae Corynebacterium species from a tertiary hospital and reference laboratory, 2012–2023

ABSTRACT A total of 1,925 Corynebacterium isolates were tested for antimicrobial susceptibility at the Mayo Clinic Microbiology laboratory (Rochester, Minnesota) from January 2012 to March 2023, with C. striatum (35.6%) and C. amycolatum (24.4%) identified as the predominant species. Species known to potentially carry diphtheria toxin were excluded. Common sources of isolation included skin and soft tissue (56.8%), bone and/or native joint synovial fluid (14.2%), urine (13.1%), sputum (6.1%), and blood (5.9%). For penicillin, susceptibility decreased from 47.5% (58 of 122) in 2012 to 20.6% (14 of 68) in 2023. Isolates also showed a decrease in susceptibility to erythromycin from 22.4% (26 of 116) in 2012 to 13.2% (9 of 68) in 2023. Susceptibility to trimethoprim-sulfamethoxazole averaged around 50% throughout the period. Notably, linezolid and vancomycin were universally effective in vitro against all species. The highest susceptibility rates among tested oral agents were to linezolid and doxycycline for non- C . striatum species. Daptomycin minimal inhibitory concentrations (MICs) of >256 µg/mL were observed for one C. amycolatum isolate, one C. tuberculostearicum isolate, and for seven C. striatum isolates, all from patients with prior daptomycin exposure. Daptomycin MICs of 2 µg/mL (nonsusceptible) were observed in one C. striatum isolate recovered from a daptomycin-naïve patient and in six C. jeikeium isolates, from both daptomycin-exposed and non-exposed patients. Significant variation in susceptibility profiles across different Corynebacterium species underscores the importance of performing antimicrobial susceptibility testing to guide effective treatment. Moreover, multidrug resistance observed in C. striatum poses substantial therapeutic challenges especially in patients requiring prolonged or chronic antibiotic suppression.

Microalgae-Assisted Treatment of Wastewater Originating from Varied Sources, Particularly in the Context of Heavy Metals and Antibiotic-Resistant Bacteria

The increasing prevalence of heavy metals and antibiotic-resistant bacteria in wastewater (WW) raises serious environmental and public health concerns. This study investigates the efficiency of the microalgal strain Chlorella vulgaris EV-465 in treating wastewater and evaluates the antibiotic resistance profile of bacterial strains obtained from WW samples. Chlorella vulgaris EV-465 was used to treat four types of wastewater—domestic, municipal, hospital, and industrial wastewater—through 21 days of incubation. The findings demonstrated pH stabilization and significant decreases in nutrients (total nitrogen—TN, total phosphorus—TP), biological oxygen demand (BOD), chemical oxygen demand (COD), heavy metal (HM) concentrations, and bacterial count. Copper (Cu) showed the highest reduction, decreasing by 80% in industrial wastewater within 14 days, while lead (Pb) proved more resistant to removal, with only a 50% decrease by day 21. Additionally, the algae decreased bacterial counts, lowering colony-forming units (Log CFU/mL) from 9.04 to 4.65 in municipal wastewater over the 21-day period. Antibiotic susceptibility tests for isolated bacterial strains revealed high levels of resistance, with seven out of nine bacterial strains exhibiting multidrug resistance. Notably, Enterococcus faecium (PBI08), Acinetobacter baumannii (YBH19), and Pseudomonas aeruginosa (NBH16) displayed resistance to all nine antibiotics tested. Among the tested antibiotics, Ciprofloxacin showed the highest efficacy, with 66% susceptibility of tested bacterial strains. Cluster and phylogenetic analyses showed that the majority of the isolated bacterial strains belonged to the genera Pseudomonas and Escherichia, highlighting their genetic diversity and varied resistance mechanisms.

A novel shiga toxigenic E. coli sequence type harbouring multidrug resistance isolated from raw milk

Abstract The objective was to examine the prevalence of extended-spectrum β-lactam (ESBL) resistance among Shiga toxigenic Escherichia coli (STEC) isolated from raw milk. The findings from disc diffusion analysis and polymerase chain reaction revealed a high occurrence of ESBL resistance, specifically to penicillins, cephalosporins, and carbapenems, in isolated STEC strains. Additionally, a distinct sequence type of STEC was also identified in milk through comparative analysis.

Etiology, risk factors and outcomes of bacteremia in patients with hematologic malignancies and febrile neutropenia in Uganda

Abstract Background We determined the etiology, risk factors and outcomes associated with bacteremia in patients with hematologic malignancies and febrile neutropenia (FN) at the Uganda Cancer Institute (UCI). Methods UCI adult and pediatric inpatients with hematologic malignancies and FN were prospectively enrolled and followed up to determine 30-day mortality. Blood drawn from participants with FN was cultured in the BACTEC 9120 blood culture system. Antimicrobial susceptibility testing was performed with the disk diffusion method on identified bacteria. Logistic regression and Cox proportional hazards regression were applied to estimate associations between participant characteristics and FN, bacteremia, and mortality. Results Of 495 participants, majority (N=306, 62%) were male. Median age was 23 years (IQR:11-42 years). Of the 132 participants who experienced FN, 43 (33%) had bacteremia. Participants with younger age (OR:0.98, p=0.05), severe neutropenia (OR: 2.9, p=0.01), hypotension (OR: 2.46, p=0.04), mucositis (OR: 2.77, p=0.01) and receiving chemotherapy (OR:2.25, p=0.03) were more likely to have bacteremia. Fifty (78%) bacteria isolated were Gram negative. E. coli (n=25, 50%) was predominant. Thirty-seven (86%) out of 43 episodes were caused by multidrug resistant (MDR) bacteria. 30-day overall survival for participants with bacteremia was significantly lower than that for participants with no bacteremia (p=0.05). MDR bacteremia (HR=1.84, p=0.05) was associated with increased risk of death. Conclusion Bacteremia was frequent in patients with hematologic cancer and FN and was associated with poor survival. MDR bacteria were the main cause of bacteremia and mortality. There is a need for robust infection control and antimicrobial stewardship programs in cancer centers in sub-Saharan Africa.

Comparative Study of Staphylococcus aureus Biofilm Formation among Clinical Isolates and Nasal Colonisers

Staphylococcus aureus (S. aureus) a noted versatile facultative commensal with pathogenic potential. This facultatively anaerobic cocci lives a commensal lifestyle in about a quarter of the world’s population awaiting a breach in the immune barrier to establish as a debilitating pathogen. This bacterium produces biofilms which acts as adhesive molecule enhancing the bacterial virulence and gives it an ability to withstand antibiotics, thereby causing tremendous burden on the healthcare community in terms of patient mortality and morbidity. This study assesses the biofilm producing ability among clinical isolates of staphylococci in comparison to colonizing staphylococci isolated from anterior nares of healthcare personnel. The present cross-sectional observational study was conducted in a tertiary care hospital in Mysore, India. In this study, 50 pathogenic isolates of S. aureus were assessed for phenotypic biofilm production. Additionally, 100 healthcare personnel were screened for nasal colonisation with S. aureus and the colonizing isolates were also screened for phenotypic biofilm formation. Phenotypic biofilm formation was evident among 22% of the pathogenic isolates. 23% of clinical S. aureus isolates demonstrated methicillin resistance (MRSA). There was no significant association of MRSA status with biofilm production (p > 0.05). Out of the 100 healthcare professionals screened for nasal carriage of S. aureus, 30% were colonized with S. aureus. Biofilm production among colonizing S. aureus isolates was found to be 26.6%. Methicillin resistance was a whopping 40% among the colonising strains. MRSA carriage was found to be highest among those healthcare personnel who had worked for an average of 20-30 years in the hospital environment. The Present study showed no significant association of biofilm production with the pathogenic potential of the S. aureus isolates (p > 0.05). Additionally, there was no significant association of methicillin resistance with the pathogenicity of the isolate. In conclusion, the interplay of virulence genes, biofilm forming ability, drug resistance of the isolate in coordination with the host immune status dictate the fate of the colonising as well as clinical isolates of S. aureus.

The Hidden Threat of Antimicrobial Resistance: A Case Study from A Private Hospital in Jordan

Antibiotic resistance is considered a widespread problem with global health implications, leading to increased patient morbidity and impacting the selection of effective antibiotics, consequently influencing patient recovery. This study aimed to assess antibiogram resistance patterns of bacterial records at the Islamic Hospital in Jordan using a retrospective study during the period 2020-2022. A total of 9369 samples obtained from different patients were cultured. Data were processed and analyzed with SPSS v.23.0. The results showed that 2841 (30.3%) samples were positive for bacterial infections. Microbial profiles of positive samples indicated the highest proportion for Escherichia coli, 39%, followed by Klebsiella pneumoniae 12% were the most frequent Gram-negative bacterial isolates, whereas Staphylococcus aureus 13% and Streptococcus pneumoniae 4% were the most common Gram-positive bacterial isolates. Interestingly, multidrug-resistant bacteria comprised 61.7% of the isolates. The percentage of multi-drug resistance in isolates of Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae was 68.7%, 73.1%, and 72%, respectively. Escherichia coli was most resistant to ampicillin (89%) and most sensitive to imipenem (100%). Klebsiella pneumoniae showed a 100% sensitivity to meropenem but 49% resistance to ceftriaxone. Pseudomonas aeruginosa was the most sensitive to amikacin and colistin (86% and 100%, respectively). Staphylococcus aureus isolates have resistance rates of 78% for ciprofloxacin, 35.6% for clindamycin and an overall resistance rate of 68.7%. These findings indicate multiple resistance for isolated bacteria. Therefore, antimicrobial resistance should be monitored continuously, and patients should be treated based on anti-microbial susceptibility tests.

PLLA Porous Scaffold as a 3D Breast Cancer Model to Investigate Drug Resistance.

Multidrug resistance remains one of the major challenges in breast cancer research, often leading to treatment failure. To better understand this mechanism, sophisticated three-dimensional (3D) tumor models are necessary, as they offer several advantages over traditional bidimensional (2D) cultures. In this study, poly-l-lactic-acid porous scaffolds were produced using a thermally induced phase separation technique and employed as 3D models for breast cancer cell lines: MDA-MB-231, MCF-7, and its multidrug-resistant variant, MCF-7R. The MTS assay was used to compare growth inhibition following doxorubicin treatment in 2D and 3D. Remarkably, the IC50 values increased in 3D cultures compared to 2D: MDA-MB-231 (445 vs. 54.5 ng/mL), MCF-7 (7.45 vs. 0.75 μg/mL), and MCF-7R (165 vs. 39 μg/mL). MCF-7R, which usually shows greater resistance in 2D, demonstrated even higher resistance in 3D. In fact, IC50 was not reached within 3 days as with the other models, but only after 6 days. Cellular morphology also played a crucial role. When treated with concentrations higher than the IC50, MDA-MB-231 cells lost their physiological 3D clustered structure, while MCF-7 and its resistant variant exhibited disrupted layers. All cell lines in 3D showed higher chemoresistance, suggesting a more biomimetic spatial architecture. Our work bridges the gap between monolayer and animal models, highlighting the potential of polymeric 3D scaffolds in breast cancer research.

Exploring the Antibacterial Properties and Chemical Profiles of Essential Oils from Syzygium aromaticum and Nigella sativa Against MDR Bacteria

For centuries, plants have been studied for their healing properties. Recently, the rise of antibiotic resistance in bacteria has prompted scientists to explore herbal remedies. Syzygium aromaticum, from the Myrtaceae family, has been utilized as a histological clearing agent. In contrast, Nigella sativa (black cumin), a member of the Ranunculaceae family, has long been utilized in traditional medicine dating back to ancient times. The current study investigates the chemical composition and antibacterial activity of essential oils from Syzygium aromaticum (clove) and Nigella sativa (black cumin) against multidrug-resistant (MDR) bacteria. Using the agar well diffusion method, Syzygium aromaticum exhibited significant antibacterial activity, particularly against Salmonella typhi (30.66 mm inhibition zone), while Nigella sativa was effective only against Staphylococcus aureus (19 mm). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values for Syzygium aromaticum ranged from 3.53 to 7.06 mg/mL, indicating stronger antibacterial properties than Nigella sativa (MIC: 12.7 mg/mL, MBC: 22.5 mg/mL). GC-MS analysis revealed that Syzygium aromaticum contained bioactive compounds like Diglycolic acid (76.59%) and Eugenol (2.06%), while Nigella sativa was dominated by Heptasiloxane (80.83%) and Thymoquinone (2.66%). These findings suggest that Syzygium aromaticum essential oil could serve as a potent natural antimicrobial agent against MDR pathogens.

Structure of a dimeric full-length ABC transporter.

Activities of ATP binding cassette (ABC) proteins are regulated by multiple mechanisms, including protein interactions, phosphorylation, proteolytic processing, and/or oligomerization of the ABC protein itself. Here we present the structure of yeast cadmium factor 1 (Ycf1p) in its mature form following cleavage by Pep4p protease. Ycf1p, a C subfamily ABC protein (ABCC), is homologue of human multidrug resistance protein 1. Remarkably, a portion of cleaved Ycf1p forms a well-ordered dimer, alongside monomeric particles also present in solution. While numerous other ABC proteins have been proposed to dimerize, no high-resolution structures have been reported. Both phosphorylation of the regulatory (R) region and ATPase activity are lower in the Ycf1p dimer compared to the monomer, indicating that dimerization affects Ycf1p function. The interface between Ycf1p protomers features protein-protein interactions and contains bound lipids, suggesting that lipids stabilize the dimer. The Ycf1p dimer structure may inform the dimerization interfaces of other ABCC dimers.

Molecular mechanism and application of emerging technologies in study of bacterial persisters.

Since the discovery of antibiotics, they have served as a potent weapon against bacterial infections; however, natural evolution has allowed bacteria to adapt and develop coping mechanisms, ultimately leading to the concerning escalation of multidrug resistance. Bacterial persisters are a subpopulation that can survive briefly under high concentrations of antibiotic treatment and resume growth after lethal stress. Importantly, bacterial persisters are thought to be a significant cause of ineffective antibiotic therapy and recurrent infections in clinical practice and are thought to contribute to the development of antibiotic resistance. Therefore, it is essential to elucidate the molecular mechanisms of persister formation and to develop precise medical strategies to combat persistent infections. However, there are many difficulties in studying persisters due to their small proportion in the microbiota and their non-heritable nature. In this review, we discuss the similarities and differences of antibiotic resistance, tolerance, persistence, and viable but non-culturable cells, summarize the molecular mechanisms that affect the formation of persisters, and outline the emerging technologies in the study of persisters.

Evaluation of the Antibacterial and Antibiofilm Activity of Erythrina senegalensis Leaf Extract Against Multidrug-Resistant Bacteria

Biofilms are bacterial communities on surfaces within an extracellular matrix. Targeting biofilm-specific bacteria is crucial, and natural compounds with reported antibiofilm activity have garnered significant interest. The study evaluated the antibacterial and antibiofilm activity of Erythrina senegalensis leaf extract against multidrug-resistant (MDR) Gram-negative bacteria, including Salmonella typhimurium, Salmonella typhi, Salmonella enteritidis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The leaf extract was prepared using aqueous and ethanol solvents, and qualitative phytochemical screening revealed the presence of various bioactive compounds such as tannins, saponins, cardiac glycosides, flavonoids, terpenoids, alkaloids, anthraquinone, reducing sugar, and ketones. A Kirby–Bauer disc diffusion assay was performed to test the susceptibility of antibiotics, and the antibacterial efficacy of the aqueous and ethanol extracts of E. senegalensis was determined using the cup-plate method, while the antibiofilm activities were determined using the crystal violet titer-plate method. The aqueous and ethanol extracts of Erythrina senegalensis revealed the presence of tannins, saponins, cardiac glycosides, flavonoids, terpenoids, alkaloids, anthraquinone, reducing sugar, and ketones. The study found that the Gram-negative bacteria isolates that were MDR were S. typhimurium, S. enteritidis, and P. aeruginosa, while K. pneumoniae was resistant to beta-lactam and fluoroquinolones, and S. typhi was sensitive to all antibiotics tested. Statistically, susceptibility to antibiotics had an inverse, weak, and significant relationship with biofilm production (r = −0.453, −0.106, −0.124, −0.106, −0.018, n = 10, p < 0.05). The aqueous extract showed good biofilm inhibition against K. pneumoniae and P. aeruginosa, and poor biofilm inhibition against S. enteritidis, while S. typhimurium and Salmonella typhi exhibited no biofilm inhibition. The ethanol extract did not demonstrate any antibiofilm activity against the tested Gram-negative pathogens. The study suggests that the Gram-negative bacteria’s capacity to form biofilms is negatively associated with their antibiotic resistance phenotypes, and the aqueous extract of E. senegalensis exhibited moderate antibiofilm activity against K. pneumoniae, P. aeruginosa, and S. enteritidis.

Antimicrobial Resistance in Lactococcus spp. Isolated from Native Brazilian Fish Species: A Growing Challenge for Aquaculture

Lactococcus spp. has emerged as a pathogen that is affecting global aquaculture, with L. garvieae, L. petauri, and L. formosensis causing piscine lactococcosis. While antimicrobials are commonly used to treat diseases in aquaculture, reports of antimicrobial resistance in fish isolates are increasing. However, little is known about the susceptibility patterns of Lactococcus spp. strains isolated from native fish species in Brazil. This study aimed to assess the antimicrobial susceptibility of these strains and establish a provisional epidemiological cutoff value for L. garvieae using the normalized resistance interpretation approach. A total of 47 isolates were tested: 17 L. garvieae, 24 L. petauri, and 6 L. formosensis. The isolates were classified as wild-type (WT) or non-wild-type (NWT) based on inhibition zone diameters. Isolates classified as NWT for three or more antimicrobial classes were considered multidrug-resistant, and the multiple antibiotic resistance (MAR) index was calculated. The results revealed heterogeneity in antimicrobial resistance profiles, with higher resistance to trimethoprim/sulfamethoxazole and norfloxacin. Resistance to other antimicrobials, including florfenicol and oxytetracycline (approved for use in Brazil), varied according to the bacterial species. Lactococcus petauri (87.5%) and L. formosensis (66.7%) showed the highest multidrug resistance, compared to L. garvieae (11.7%), along with higher MAR index values. These findings suggest that multidrug-resistant strains could pose future challenges in the production of native species, underscoring the need for ongoing monitoring of antimicrobial resistance and responsible use of antimicrobials in aquaculture.

Genomic characterisation of an extended-spectrum β-Lactamase-producing Klebsiella pneumoniae isolate assigned to a novel sequence type (6914).

Cow milk, which is sometimes consumed raw, hosts a plethora of microorganisms, some of which are beneficial, while others raise food safety concerns. In this study, the draft genome of an extended-spectrum β-lactamase-producing Klebsiella pneumoniae subsp. pneumoniae strain Cow102, isolated from raw cow milk used to produce traditional foods in Nigeria, is reported. The genome has a total length of 5,359,907bp, with 70 contigs and a GC content of 57.35%. A total of 5,244 protein coding sequences were detected with 31% mapped to a subsystem, and genes coding for amino acids and derivatives being the most prevalent. Multilocus sequence typing revealed that the strain had new allelic profile assigned to the novel 6914 sequence type possessing capsular and lipopolysaccharide antigen K locus 122 with an unknown K type (KL122) and O locus O1/O2v2 with type O2afg, respectively. A total of 28 resistance-related genes, 98 virulence-related genes, two plasmids and five phages were identified in the genome. The resistance genes oqxA, oqxB and an IS3 belonging to cluster 204 were traced to bacteriophage Escher 500,465. Comparative analysis predicted one strain specific orthologous group comprising three genes. This report of a novel sequence type (ST6914) in K. pneumoniae presents a new allelic profile, indicating ongoing evolution and diversification within the species. Its uniqueness suggests it may represent a locally evolved lineage, although further sampling would be necessary to confirm this hypothesis. The strain's multidrug resistance, virulence gene repertoire, and isolation from animal milk render it a potentially significant public health concern, underscoring the importance of genomic surveillance in non-clinical settings to detect emerging strains. Further research is required to fully characterise the capsular K type of ST6914.

“Unmasking the Uncommon”: A case series of multi-drug resistant Elizabethkingia meningoseptica causing late-onset sepsis and meningitis in preterm neonates

Elizabethkingia meningoseptica is an uncommon nosocomial pathogen that causes meningitis, pneumonia, and sepsis in neonates and in immunocompromised individuals. It exhibits resistance to many commonly employed first-line antibiotics used to treat gram-negative pathogens. Herein, we present three cases of late-onset sepsis with multi-drug resistant (MDR) Elizabethkingia meningoseptica in high-risk neonates. Case 1 was a one-day-old preterm low-birth-weight infant who presented with respiratory distress syndrome and septic shock. The patient was intubated and administered empirical broad-spectrum antibiotics and antifungal agents. Blood culture grew Candida krusei, hence Amphotericin B was initiated. Repeat blood culture on day 27 showed gram-negative bacilli, identified as Elizabethkingia meningoseptica by MALDI-TOF . Antibiotic susceptibility testing (AST) revealed resistance to Piperacillin/Tazobactam, but sensitivity to Vancomycin, Levofloxacin, and Minocycline. IV Vancomycin was administered, which resulted in clinical improvement and negative blood culture results. Case 2 was an eleven-day-old preterm, low-birth-weight baby who presented with fever. Initial investigations revealed normal complete blood counts (CBC) parameters and elevated CRP levels. Blood and CSF cultures isolated Elizabethkingia meningoseptica with a similar AST pattern. Intravenous Ciprofloxacin was initiated with clinical improvement and negative follow-up blood cultures. Case 3 was a one-day-old preterm baby, appropriate-to-gestational age, presenting with respiratory distress syndrome. The infant was intubated and started on inotropic support and intravenous antibiotics. Blood cultures on day 4 showed Elizabethkingia meningoseptica and Vancomycin was started. Follow-up cultures on days 6 and 14 grew Acinetobacter baumannii. A combination of Levofloxacin and Colistin was added, and blood cultures were negative after seven days, with clinical improvement. Elizabethkingia meningoseptica is a significant cause of hospital-acquired infections, especially in Neonatal Intensive Care Unit (NICU), leading to outbreaks. Clinicians must have a high degree of suspicion of E. meningoseptica for gram-negative bacilli causing sepsis and meningitis in high-risk patients. Recent technological advances have enabled accurate speciation to guide therapy and reduce morbidity and mortality rates.

The antimicrobial and antibiofilm effects of gentamicin, imipenem, and fucoidan combinations against dual-species biofilms of Staphylococcus aureus and Acinetobacter baumannii isolated from diabetic foot ulcers.

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia due to impaired insulin production or utilization, leading to severe health complications. Diabetic foot ulcers (DFUs) represent a major complication, often exacerbated by polymicrobial infections involving Staphylococcus aureus and Acinetobacter baumannii. These pathogens, notorious for their resistance to antibiotics, complicate treatment efforts, especially due to biofilm formation, which enhances bacterial survival and resistance. This study explores the synergistic effects of combining gentamicin, imipenem, and fucoidan, a sulfated polysaccharide with antimicrobial properties, against both planktonic and biofilm forms of S. aureus and A. baumannii. Isolates of S. aureus and A. baumannii were collected from DFUs and genetically confirmed. Methicillin resistance in S. aureus was identified through disk diffusion and PCR. Biofilm formation, including dual-species biofilms, was analyzed using the microtiter plate method. The antimicrobial efficacy of gentamicin, imipenem, and fucoidan was assessed by determining the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), and minimum biofilm eradication concentration (MBEC). Synergistic interactions were evaluated using the fractional inhibitory concentration index (FICi) and fractional bactericidal concentration index (FBCi). The expression of biofilm-associated genes (icaA in S. aureus and bap in A. baumannii) was analyzed, and the cytotoxicity of fucoidan was assessed. The study revealed that 77.4% of S. aureus and all A. baumannii isolates showed multidrug resistance. Among 837 tested conditions for dual-species biofilm formation, 72 resulted in strong biofilm formation and 67 in moderate biofilm formation. The geometric mean MIC values for gentamicin were 12.2µg/mL for S. aureus, 22.62µg/mL for A. baumannii, and 5.87µg/mL for their co-culture; for imipenem, they were 19.84, 9.18, and 3.70µg/mL, respectively, and for fucoidan, 48.50, 31.20, and 19.65µg/mL, respectively. The MBC values for gentamicin were 119.42, 128, and 11.75µg/mL; for imipenem, they were 48.50, 14.92, and 8µg/mL; and for fucoidan, they were 88.37, 62.62, and 42.48µg/mL. The MBIC values were 55.71, 119.42, and 18.66µg/mL for gentamicin; 68.59, 48.50, and 25.39µg/mL for imipenem; and 153.89, 101.49, and 53.53µg/mL for fucoidan. The MBEC values were 315.17, 362.03, and 59.25µg/mL for gentamicin; 207.93, 157.58, and 74.65µg/mL for imipenem; and 353.55, 189.46, and 99.19µg/mL for fucoidan. When cultured in planktonic form, the geometric mean FICi and FBCi values indicated additive effects, while co-culture showed FICi values of ≤ 0.5, suggesting a synergistic interaction. Treatment with gentamicin and fucoidan led to significant downregulation of the icaA and bap genes in both single-species and dual-species biofilms of S. aureus and A. baumannii. The reductions in gene expression were more pronounced in dual-species biofilms compared to single-species biofilms. Additionally, treatment with imipenem and fucoidan also resulted in significant downregulation of these genes in both biofilm types. Cytotoxicity assessments indicated that higher concentrations of fucoidan were toxic, yet no harmful effects were noted at the optimal synergistic concentrations used with antibiotics. In our investigation, we found that combining gentamicin, imipenem, and fucoidan had a synergistic effect on dual-species biofilms of S. aureus and A. baumannii, suggesting potential benefits for treating such infections effectively. This underscores the importance of understanding microbial interactions, antibiotic susceptibility, and biofilm formation in DFUs.

Phage therapeutic delivery methods and clinical trials for combating clinically relevant pathogens.

The ongoing global health crisis caused by multidrug-resistant (MDR) bacteria necessitates quick interventions to introduce new management strategies for MDR-associated infections and antimicrobial agents' resistance. Phage therapy emerges as an antibiotic substitute for its high specificity, efficacy, and safety profiles in treating MDR-associated infections. Various in vitro and in vivo studies denoted their eminent bactericidal and anti-biofilm potential. This review addresses the latest developments in phage therapy regarding their attack strategies, formulations, and administration routes. It additionally discusses and elaborates on the status of phage therapy undergoing clinical trials, and the challenges encountered in their usage, and explores prospects in phage therapy research and application.

Integrated virtual screening and MD simulation study to discover potential inhibitors of mycobacterial electron transfer flavoprotein oxidoreductase.

Tuberculosis (TB) continues to be a major global health burden, with high incidence and mortality rates, compounded by the emergence and spread of drug-resistant strains. The limitations of current TB medications and the urgent need for new drugs targeting drug-resistant strains, particularly multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB, underscore the pressing demand for innovative anti-TB drugs that can shorten treatment duration. This has led to a focus on targeting energy metabolism of Mycobacterium tuberculosis (Mtb) as a promising approach for drug discovery. This study focused on repurposing drugs against the crucial mycobacterial protein, electron transfer flavoprotein oxidoreductase (EtfD), integral to utilizing fatty acids and cholesterol as a carbon source during infection. The research adopted an integrative approach, starting with virtual screening of approved drugs from the ZINC20 database against EtfD, followed by molecular docking, and concluding with molecular dynamics (MD) simulations. Diacerein, levonadifloxacin, and gatifloxacin were identified as promising candidates for repurposing against TB based on their strong binding affinity, stability, and interactions with EtfD. ADMET analysis and anti-TB sensitivity predictions assessed their pharmacokinetic and therapeutic potential. Diacerein and levonadifloxacin, previously unexplored in anti-tuberculous therapy, along with gatifloxacin, known for its efficacy in drug-resistant TB, have broad-spectrum antimicrobial properties and favorable pharmacokinetic profiles, suggesting potential as alternatives to current TB treatments, especially against resistant strains. This study underscores the efficacy of computational drug repurposing, highlighting bacterial energy metabolism and lipid catabolism as fruitful targets. Further research is necessary to validate the clinical suitability and efficacy of diacerein, levonadifloxacin, and gatifloxacin, potentially enhancing the arsenal against global TB.

Back Cover

In this picture, the Chinese classical mythic figure Red Boy, holding a red tasseled gun (adriamycin), is attacking a lots of monster (live balls, multidrug resistance cancer cells) with the help of the Samadhi fire (polycyclic polyprenylated acylphloroglucinols, PPAPs). This indicates that PPAPs along with adriamycin show good cytotoxic activity on multidrug resistance cancer cells. More details are discussed in the article by Yuan et al. on pages 3293—3307. image

Time to Cure and Predictive Factors Among Patients with Multi-Drug Resistance Tuberculosis in Puntland, Somalia: A Retrospective Cohort Study

Background: Multi-drug-resistant tuberculosis, also known as MDR-TB, is caused by bacteria that are resistant to the most effective first-line anti-tuberculosis medications, which are rifampicin and isoniazid. MDR-TB is an increasing global concern, and its spread has varying cure times for patients affected. Thus, this study was intended to investigate the median time to cure and identify predictive factors for patients with MDR-TB in Puntland, Somalia. Methods: A retrospective cohort study was carried out at the MDR-TB center in Galkayo, Puntland, Somalia between the years of July 2017 and August 2023. The study utilized data that were collected from the inquiry form and monitoring cards of a randomly selected sample of 130 patients over a 6-year period. The data were entered into Epi-Data version 4.3 and analyzed using R Programming version 4.4.0. Non-parametric methods were used to estimate the median time to cure for patients with MDR-TB. Semi-parametric and parametric models were employed to determine predictive factors that influence the time to cure for MDR-TB patients. The Akaike Information Criteria (AIC) and Bayesian Information Criteria (BIC) of different survival models were compared to select the model that offers the best fit. Results: Out of the total of MDR-TB patients, 109(83.85%) were cured and 21(16.15%) were censored during the follow-up period. The median time to cure from MDR-TB was found to be 619 days which is approximately 20 months. In accordance with the AIC and BIC, the Log-logistic accelerated failure time model was the best fit for the data as compared to the other AFT models. The result of the Log-logistic AFT model revealed that age, sex, disease site, and comorbidities significantly affect the time to cure for MDR-TB. According to this study, older age with MDR-TB patients, male MDR-TB patients, MDR-TB patients with comorbid conditions, and extrapulmonary MDR-TB patients had a longer time to cure than their reference categories. Conclusion: Based on the findings of the study, the median time to cure for patients with MDR-TB in Puntland was found to be 20 months. Sex, disease site, comorbidities and age were predictive factors of time to cure from MDR-TB.