Multidrug-resistant Bacteria Research Articles

Development of membrane-targeting chalcone derivatives as antibacterial agents against multidrug-resistant bacteria

The striking rise of infections caused by multidrug-resistant pathogens has evolved as a serious threat to public health worldwide. To develop new antibacterials to combat multidrug-resistant bacteria, a novel class of amphiphilic chalcone derivatives serving as antimicrobial peptidomimetics was designed and synthesized. Among them, the most promising compound 14b displayed broad-spectrum antimicrobial activity against both Gram-positive bacteria (MICs = 0.5-1 μg/mL) and Gram-negative bacteria (MICs = 1-32 μg/mL), low hemolytic activity, and good membrane selectivity. Moreover, compound 14b exhibited rapid bactericidal action, a low probability of developing resistance, high proteolytic stability, and strong capabilities of inhibiting and destroying bacterial biofilms. Further mechanism investigations revealed that compound 14b possessed strong membrane-disrupting abilities and could disintegrate the integrity of bacterial cell membranes by destroying transmembrane potential and enhancing membrane permeability, and causing the generation of intracellular ROS and the leakage of DNA and proteins, ultimately leading to bacterial death. More importantly, compound 14b also showed excellent in vivo therapeutic potency in a mouse septicemia model infected by both Gram-positive and Gram-negative bacteria, indicating its potential to be an antibacterial agent to confront bacterial infections.

The application value of bacteriophage in patients with severe drug-resistant bacterial infections

The emergence of antimicrobial resistance (AMR) represents one of the most significant global public health threats, imposing substantial economic burdens. To address this critical issue of resistance, one of the most promising alternative strategies for treating antimicrobial resistant bacterial infections is bacteriophage therapy. Bacteriophages exhibit high specificity towards bacteria, capable of lysing and killing specific bacterial strains. Phage cocktails can broaden the spectrum of activity, contribute to target multiple types of bacteria. Personalized bacteriophage therapy, tailored to individual patients, enhances precise targeting of pathogens. Increasing evidence supports the feasibility of phage-antibiotic combinations in treating multidrug-resistant bacteria. Furthermore, genetic engineering, including technologies like clustered regularly interspaced short palindromic repeats (CRISPR)-Cas, has advanced the development of engineering phages, providing novel ways to kill bacterial hosts. This review discusses the research progress of bacteriophage for refractory infections caused by multidrug-resistant bacteria, the advantages and limitations of phage therapy, and highlights clinical studies and case reports of various phage treatment modalities.

Colistin-niclosamide effervescent dry suspension combats colistin-resistant Salmonella in vitro and in vivo

The increasing incidence of bacterial infections caused by multidrug-resistant (MDR) Gram-negative bacteria has deepened the need for new effective treatments. It has been reported that niclosamide (NIC) can restore the sensitivity of Gram-negative bacteria to colistin (COL). However, NIC is practically insoluble in water and sparingly soluble in organic solvents, leading to limited therapeutic applications. This study aims to prepare a COL-NIC effervescent dry suspension (CNEDS) and evaluate its antibacterial effect against COL-resistant Salmonella both in vitro and in broiler chickens. With the sedimentation volume ratio as an index, suitable suspending agent, wetting agent, filler and effervescent agent were screened through a single-factor method. The preparation conditions were optimized using the Box-Behnken response surface method to obtain the formulation for CNEDS. The quality evaluation results showed that the successfully prepared CNEDS had a sedimentation volume ratio of 0.99, a drying weight loss of 1.3%, and a re-dispersion capability of 1-2 times, all of which met pharmacopoeial requirements. In terms of pharmacological evaluation, we first demonstrated that CNEDS substantially restored COL sensitivity against COL-resistant bacteria. Subsequently, time-killing analysis, scanning electron microscopy (SEM) and live/dead assays confirmed the antibacterial activity of CNEDS against COL-resistant bacteria. Finally, a Salmonella infection model in broiler chickens was established to further assess the therapeutic effect of CNEDS in vivo. CNEDS improved the survival rate of broiler chickens, reduced the bacterial burden on organs. These findings suggest that CNEDS effectively overcome COL resistance, indicating its potential for the treatment of COL-resistant bacterial infections in broiler chickens.

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.

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.

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.

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.

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.

Performance evaluation of the Specific Reveal system for rapid antibiotic susceptibility testing from positive blood cultures containing Gram-negative pathogens.

Rapid antimicrobial drug administration is crucial for the efficient treatment of sepsis or septic shock, but empirical therapy is limited by the increasing prevalence of multidrug-resistant bacteria. Thus, rapid and reliable antimicrobial susceptibility testing (AST) is needed to start appropriate antimicrobial drug administration as quickly as possible. In the present study, we evaluated the performance of the Reveal rapid AST system. From February to April 2021, 102 positive blood culture bottles (BCBs) from hospitalized patients with bacteremia caused by Gram-negative bacteria were included in the study. All isolates were tested by the Reveal system directly from the positive BCBs in comparison to the DxM MicroScan WalkAway. Essential agreement (EA) and category agreement (CA) were high with 98.5% and 97.1%, respectively. We also determined the susceptibility of 10 highly resistant CDC & FDA AR strains in duplicate. Here, EA was 99.6% and CA 97.9%. The average time to result by Reveal was 5.4 h ± 1.2 h compared to an average of 16 h by DxM MicroScan WalkAway for clinical strains and 3.8 h ± 1.2 h for more resistant CDC & FDA AR strains. Susceptibility determination with the Reveal rapid AST system directly from positive BCBs is for the frequently represented bug-drug combinations a reliable and accurate approach, meeting the European ISO guideline for the performance of AST systems. Moreover, AST directly from blood cultures performed with the Reveal system saves time when compared to the conventional AST, as no subculturing is needed and time to result is very short.

Risk Factors for Invasive Surgical Site Infections Among Adult Single Liver Transplant Recipients at Duke University Hospital in the Period 2015–2020

Background. Invasive primary surgical site infections (IP-SSI) are a severe complication of liver transplant surgery. Identification of risk factors for IP-SSI is critical to IP-SSI prevention. Methods. All adult single liver transplants performed at Duke University Hospital in the period 2015–2020 were reviewed for IP-SSI occurring within 90 d of transplant. Risks for IP-SSI were identified using least absolute shrinkage and selection operator variable selection procedure. A 2-sided P value of <0.05 was considered statistically significant. Results. IP-SSI were identified in 34/470 (7.2%) adult single liver transplants. Repeat transplantation, spilt liver, Roux-en-Y biliary anastomosis, anastomotic leak, and post-transplant renal replacement therapy were positively associated with IP-SSI. IP-SSI were associated with increased length of index transplant hospitalization (24.5 versus 10.0 d, P < 0.01) and 1-y all-cause mortality (14.7% versus 4.1%, P = 0.02). Gram positive bacteria were the main pathogens (51.7%), followed by Gram negative bacteria (24.1%) and Candida (24.1%). Multidrug resistance bacteria increased over time (27.3% in 2015 versus 66.7% in 2020, P = 0.17). Conclusions. In the setting of routine antimicrobial prophylaxis and an overall low rate of IP-SSI, surgical factors were the main determinants of IP-SSI among adult liver transplant recipients. IP-SSI had a negative impact on the length of index transplant hospitalization and 1-y mortality. While the surgical factors associated with an increased risk of IP-SSI are not easily modifiable, their impact may be best contained by close clinical monitoring and tailored antimicrobial therapy.

Antibiotic efficacy and resistance patterns of urinary tract infection-causing bacteria in dogs and resistome of multidrug-resistant Klebsiella pneumoniae via whole genome sequencing in South Korea

Bacterial urinary tract infections (UTIs) are prevalent in dogs and necessitate antibiotic intervention. However, the emergence of multidrug-resistant (MDR) bacteria poses significant challenges to antibiotic therapy. Although fosfomycin has been demonstrated to achieve and maintain high concentrations in urine, suggesting its potential for treating UTIs in dogs, its efficacy and the resistance profiles of urinary pathogens from canine UTIs remain elusive. Therefore, this study was conducted to investigate the antibiotic susceptibility of bacterial pathogens isolated from companion dogs with UTIs, with a particular focus on their susceptibility and resistance to fosfomycin. A total of 70 isolates from urine samples were analyzed, of which Escherichia coli (n = 18), Proteus mirabilis (n = 9), Klebsiella pneumoniae (n = 5), and Staphylococcus pseudintermedius (n = 5) were predominant. Resistance to erythromycin was most prevalent (94.59%), followed by clindamycin (91.89%) and ampicillin (78.37%), whereas the lowest resistance rate was observed for amikacin (5.40%). Resistance to fosfomycin was observed in 15 out of the 37 predominant isolates (40.54%), including all K. pneumoniae isolates (100%). All isolates, except 4 E. coli strains, were categorized as MDR (33 out of 37; 89.18%). The resistance rates for amoxicillin/clavulanic acid and trimethoprim-sulfamethoxazole, which are common first-line antibiotics for canine UTIs, were 48.64 and 56.75%, respectively. Whole-genome sequencing of K. pneumoniae isolates, which exhibited high resistance to fosfomycin, revealed multiple antibiotic resistance genes, with chromosomal fosA present in all isolates. Among the 27 dogs with recurrent infection included in this study, 2 were administered fosfomycin, resulting in clinical remission, as evidenced by negative urine culture tests. Overall, this study is the first to demonstrate the importance of assessing fosfomycin resistance profile for optimal treatment of canine UTIs, particularly in cases involving MDR strains.

Synthetic indole derivatives as an antibacterial agent inhibiting respiratory metabolism of multidrug-resistant gram-positive bacteria.

The survival of modern medicine depends heavily on the effective prevention and treatment of bacterial infections, are threatened by antibacterial resistance. The increasing use of antibiotics and lack of stewardship have led to an increase in antibiotic-resistant pathogens, so the growing issue of resistance can be resolved by emphasizing chemically synthesized antibiotics. This study discovered SMJ-2, a synthetic indole derivative, is effective against all multidrug-resistant gram-positive bacteria. SMJ-2 has multiple targets of action, but the primary mechanism inhibits respiratory metabolism and membrane potential disruption. SMJ-2 was discovered to interfere with the mevalonate pathway, ultimately preventing the synthesis of farnesyl diphosphate, a precursor to the antioxidant staphyloxanthin, eventually releasing reactive oxygen species, and leading phagocytic cells to destroy pathogens. Additionally, no discernible biochemical and histopathological alterations were found in the mouse acute toxicity model. This study emphasizes mechanistic insights into SMJ-2 as a potential antibacterial with an unusual method of action.

Nucleus-Targeting Photosensitizers Enhance Neutrophil Extracellular Traps for Efficient Eradication of Multidrug-Resistant Bacterial Infections.

Neutrophil extracellular traps (NETs) are web-like complexes of DNA and proteins that are extruded by activated neutrophils and play critical roles as major components of the innate immune response against pathogen invasion. However, some microbes have developed strategies to evade NET attacks, leading to impaired immune defenses and persistent infections. In this study, an engineered neutrophil strategy for enhancing the antibacterial activity of NETs is developed. A nucleus-targeting photosensitizer (NCP) with strong reactive oxygen species production and a strong DNA-binding capacity is synthesized. NCP-loaded neutrophils are subsequently constructed via direct incubation of NCP with neutrophils, and the NCP is closely inserted into the nucleus DNA. Upon activation by bacteria-related toxins, NCP-coupled NETs can be released rapidly, actively trapping bacteria and providing a high local concentration of NCP around them. Both in vitro and in vivo results revealed that NCP-coupled NETs can effectively eradicate various multidrug-resistant bacteria and biofilms through photodynamic therapy, overcome bacterial immune evasion, and promote tissue recovery from severe wound infections. This design can significantly strengthen NET function, providing a non-antibiotic alternative platform for treating bacterial infectious diseases.

Antimicrobial Peptides: A Promising Alternative to Conventional Antimicrobials for Combating Polymicrobial Biofilms.

Polymicrobial biofilms adhere to surfaces and enhance pathogen resistance to conventional treatments, significantly contributing to chronic infections in the respiratory tract, oral cavity, chronic wounds, and on medical devices. This review examines antimicrobial peptides (AMPs) as a promising alternative to traditional antibiotics for treating biofilm-associated infections. AMPs, which can be produced as part of the innate immune response or synthesized therapeutically, have broad-spectrum antimicrobial activity, often disrupting microbial cell membranes and causing cell death. Many specifically target negatively charged bacterial membranes, unlike host cell membranes. Research shows AMPs effectively inhibit and disrupt polymicrobial biofilms and can enhance conventional antibiotics' efficacy. Preclinical and clinical research is advancing, with animal studies and clinical trials showing promise against multidrug-resistant bacteria and fungi. Numerous patents indicate increasing interest in AMPs. However, challenges such as peptide stability, potential cytotoxicity, and high production costs must be addressed. Ongoing research focuses on optimizing AMP structures, enhancing stability, and developing cost-effective production methods. In summary, AMPs offer a novel approach to combating biofilm-associated infections, with their unique mechanisms and synergistic potential with existing antibiotics positioning them as promising candidates for future treatments.

Meropenem-vaborbactam as intrathecal-sparing therapy for the treatment of carbapenem-resistant K. pneumoniae shunt-related ventriculitis: two case reports and review of the literature.

Recently, an increase in cases of multidrug-resistant Gram-negative bacteria post-neurosurgical ventriculitis and meningitis is reported. Treating these infections has become challenging due to the limited availability of antibiotics and the need to select those with optimal pharmacodynamic and pharmacokinetic profiles. There is limited evidence regarding the use of meropenem-vaborbactam in treating carbapenem-resistant Enterobacterales infections of the central nervous system. We report two new cases of shunt-related ventriculitis due to carbapenem-resistant K.pneumoniae with a favorable microbiological evolution after IV only combination therapy with meropenem-vaborbactam.

Prevalence of multidrug-, extensively drug-, and pandrug-resistant bacteria in clinical isolates from King Khaled Hospital, Najran, Saudi Arabia

Abstract Background Saudi Arabia faces a growing antimicrobial resistance (AMR) problem, exacerbated by the widespread use of antibiotics in clinical and agricultural settings. Despite this, AMR surveillance has been limited, particularly in regions like Najran, making this study critical for informing local and national public health strategies. Aim This study explored the prevalence of multidrug-resistant, extensively drug-resistant, and Pandrug-resistant bacteria in Najran, Saudi Arabia. Study design This is a cross-sectional study. Methods This study included 559 diverse clinical samples (urine, wound, etc.) collected from various departments in King Khaled Hospital, Saudi Arabia. The Phoenix BD instrument was used for complete bacterial identification and antibiotic sensitivity testing. Demographic and clinical data were analyzed statistically. Results Of the 559 samples, the culture positivity rates were as follows: 51% for Escherichia coli, 22% for Staphylococcus aureus, 14% for Klebsiella pneumoniae, 6% for Acinetobacter baumannii, 6% for Pseudomonas aeruginosa, and 1% for Enterococcus faecium. Majority of the cases were from male (57%), and age 50+ (59%) recorded highest cases. Participants from outpatient department (OPD) ward recorded the highest (56%) cases, while urine sample recorded the highest (49%) cases. About 84% of the isolates were multidrug‑resistance (MDR), 10% were extensively drug‑resistance (XDR), and 6% pandrug‑resistance (PDR). Our analysis showed high sensitivity to Oxazolidonone, Tetracycline, carbapenems, Lipopeptide, Aminoglycopeptide classes of antibiotics. Conclusions The study revealed a high prevalence of drug resistance, highlighting the critical importance of continued surveillance and research to mitigate the spread of antimicrobial resistance and preserve the effectiveness of existing therapies.

Investigation of the Mechanism of Action of AMPs from Amphibians to Identify Bacterial Protein Targets for Therapeutic Applications

Antimicrobial peptides (AMPs) from amphibians represent a promising source of novel antibacterial agents due to their potent and broad-spectrum antimicrobial activity, which positions them as valid alternatives to conventional antibiotics. This review provides a comprehensive analysis of the mechanisms through which amphibian-derived AMPs exert their effects against bacterial pathogens. We focus on the identification of bacterial protein targets implicated in the action of these peptides and on biological processes altered by the effect of AMPs. By examining recent advances in countering multidrug-resistant bacteria through multi-omics approaches, we elucidate how AMPs interact with bacterial membranes, enter bacterial cells, and target a specific protein. We discuss the implications of these interactions in developing targeted therapies and overcoming antibiotic resistance (ABR). This review aims to integrate the current knowledge on AMPs’ mechanisms, identify gaps in our understanding, and propose future directions for research to harness amphibian AMPs in clinical applications.

Interferon signalling and non-canonical inflammasome activation promote host protection against multidrug-resistant Acinetobacter baumannii.

Multidrug-resistant (MDR) Acinetobacter baumannii are of major concern worldwide due to their resistance to last resort carbapenem and polymyxin antibiotics. To develop an effective treatment strategy, it is critical to better understand how an A. baumannii MDR bacterium interacts with its mammalian host. Pattern-recognition receptors sense microbes, and activate the inflammasome pathway, leading to pro-inflammatory cytokine production and programmed cell death. Here, we examined the effects of a systemic MDR A. baumannii infection and found that MDR A. baumannii activate the NLRP3 inflammasome complex predominantly via the non-canonical caspase-11-dependent pathway. We show that caspase-1 and caspase-11-deficient mice are protected from a virulent MDR A. baumannii strain by maintaining a balance between protective and deleterious inflammation. Caspase-11-deficient mice also compromise between effector cell recruitment, phagocytosis, and programmed cell death in the lung during infection. Importantly, we found that cytosolic immunity - mediated by guanylate-binding protein 1 (GBP1) and type I interferon signalling - orchestrates caspase-11-dependent inflammasome activation. Together, our results suggest that non-canonical inflammasome activation via the (Interferon) IFN pathway plays a critical role in the host response against MDR A. baumannii infection.

Extended-Spectrum Beta-Lactamase-Producing and Multidrug-Resistant Escherichia coli and Klebsiella spp. from the Human–Animal–Environment Interface on Cattle Farms in Burkina Faso

Extended-spectrum beta-lactamase (ESBL)-producing and multidrug-resistant Enterobacterales pose a major threat to both human and animal health. This study assessed the prevalence of ESBL-producing Escherichia coli (ESBL-Ec) and Klebsiella spp. (ESBL-K) on cattle farms in Ouagadougou, Burkina Faso, using a One Health approach. From May 2021 to September 2022, cattle faeces, farmers’ stools, their drinking water and farm soil samples were collected from semi-intensive and traditional farms. An ESBL-selective medium was used to obtain resistant isolates, which were further characterised using biochemical tests. Antimicrobial susceptibility testing was performed using the Kirby–Bauer disc diffusion method. ESBL-Ec and/or ESBL-K were detected in 188 of 322 samples (58.0%). The prevalence of ESBL-Ec isolates was 42.2% (136/322) and that of ESBL-K isolates was 24.5% (79/322). Notably, 156 of the 188 ESBL isolates (83.0%) exhibited multidrug resistance. The highest resistance rates were observed against tetracycline and cotrimoxazole. Importantly, no isolates showed resistance to meropenem, which was used to test for carbapenem resistance. This study highlights the presence of ESBL-Ec and ESBL-K among the humans, animals and environment of the cattle farms. Good hygiene and biosafety practices are essential to limit the potential spread of multidrug-resistant bacteria between different interfaces on farms.

Bacteria carrying mobile colistin resistance genes and their control measures, an updated review.

The plasmid encoded mobile colistin resistance (MCRs) enzyme poses a significant challenge to the clinical efficacy of colistin, which is frequently employed as a last resort antibiotic for treating infections caused by multidrug resistant bacteria. This transferase catalyzes the addition of positively charged phosphoethanolamine to lipid A of the outer membrane of gram-negative bacteria, thereby facilitating the acquired colistin resistance. This review aims to summarize and critically discuss recent advancements in the distribution and pathogenesis of mcr-positive bacteria, as well as the various control measures available for treating these infections. In addition, the ecology of mcr genes, colistin-resistance mechanism, co-existence with other antibiotic resistant genes, and their impact on clinical treatment are also analyzed to address the colistin resistance crisis. These insights provide a comprehensive perspective on MCRs and serve as a valuable reference for future therapeutic approaches to effectively combat mcr-positive bacterial infections.