Combination Of Antibiotics Research Articles

Antibacterial boosting effect of combined antibiotics and wild mushroom (Langermannia bicolor) reduces the survival of multidrug-resistant bacteria

This study set out to evaluate how effective the unexplored macrofungi Langermannia bicolor is in providing a biomolecular repertoire capable of optimizing the action of antibacterials available on the market. Extract and fractions (obtained by fractionation with acetone) of L. bicolor were quantified for the presence of proteases and hemagglutinin, and the composition of carbohydrates, proteins, and phenolic and flavonoid compounds; then, they were tested against multidrug-resistant gram-positive and gram-negative strains combined with conventional antibiotics from different classes. Fraction 2 (F2) stood out for its high proteolytic and hemagglutinating capacities, and could reduce the therapeutic dosage of all the antibiotics in the different pathogens tested. The samples – especially Fraction 2 – showed promising results in optimizing the action of antibiotics, thus potentially mitigating the escalation of resistance in bacteria. This project is the first to investigate the medicinal properties of L. bicolor, focusing on its major biomolecules, and potential as an antibiotics enhancer.

Silver and Titanium Oxides Coated on g-C3N4 Nanocomposite for Photocatalytic Degradation of Mixture of Brilliant Green-Congo Red Dyes and Ciprofloxacin Antibiotic Under Visible Light Irradiation

Silver and titanium oxides coated graphitic carbon nitride (Ag2O/TiO2/g-C3N4) nanocomposite was created by a single-step thermal polymerization. The Fourier Transform infrared (FT-IR), UV-visible absorption spectroscopy (UV-vis), X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET) methods, thermal gravimetric analysis (TGA), photoluminescence (PL), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were within the numerous techniques used to characterize this nanocomposite. Both the photoluminescence (PL) spectrum and the Tauc plot indicated that the Ag2O/TiO2/g-C3N4 nanocomposite had a lower electron-hole pair recombination rate and lower band gap energy. The coating of Ag2O and TiO2 on g-C3N4 was verified by TEM. The Ag2O/TiO2/g-C3N4 nanocomposite was used in the photocatalytic degradation of a Brilliant green (BG)-Congo red (CR) dye combination and ciprofloxacin (CIP) antibiotic under visible light irradiation. According to the research, under visible light irradiation, the Ag2O/TiO2/g-C3N4 nanocomposite photocatalytic activity simultaneously degraded a mixture of BG-CR dyes, with BG (93%) and CR (85%) degrading percentages in 70 min and CIP (82%) degrading in 120 min. Superoxide and hydroxyl radicals were primarily responsible for the degradation of BG and CR dyes under visible light irradiation, whereas holes and hydroxyl radicals were investigated as important oxidative species in the photocatalytic degradation of CIP utilizing the Ag2O/TiO2/g-C3N4 nanocomposite.Graphical

Improvement of IL-4, IL-6, IL-10, TNF-α and IFN-γ in children with mycoplasma pneumonia through the combination of video scenario-based breathing training and antibiotics.

This study aims to investigate the effects of video scenario-based breathing training on interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in children with Mycoplasma pneumonia. A total of 106 children with Mycoplasma pneumonia treated in our hospital from February 2022 to April 2024 were selected. According to different nursing methods, children receiving routine intervention were assigned to the control group, while those undergoing video scenario-based breathing training were assigned to the training group. The serum inflammatory indexes, improvement time of clinical symptoms and lung function recovery were compared between the two groups before training, and at 1 and 2 weeks after training. Before training, there was no statistically significant difference in serum inflammatory and lung function indexes between the two groups (p > 0.05). After 1 and 2 weeks of training, the forced expiratory volume in 1s (FEV1), peak expiratory flow rate (PEF), and the ratio of FEV1 to forced vital capacity (FEV1/FVC) in both groups increased, with higher values in the training group than in the control group, and the difference was statistically significant (p < 0.05). The time for cough disappearance, wheezing disappearance, lung rales disappearance and high fever abatement in the training group was lower than that in the control group, with statistically significant differences (p < 0.05). The levels of IL-4, IL-6, IL-10, TNF-α, and IFN-γ decreased in both groups, with lower levels in the training group than in the control group, and the difference was statistically significant (p < 0.05). Video scenario-based breathing training can improve lung function, alleviate clinical symptoms and signs, and reduce serum inflammatory levels of IL-4, IL-6, IL-10, TNF-α and IFN-γ in children with Mycoplasma pneumonia.

Analysis of antibiotic sensitivity of clinical strains of microorganisms with the Russian Mueller–Hinton broth

Introduction. One of the reasons for spreading antibiotic-resistant microorganisms is the uncontrolled use and inadequate empirical prescription of antibiotics which is not based on the results of the pathogen sensitivity testing. The broth dilution method and one of its implementation options, the reference microdilution method, in contrast to the disk diffusion method, allows testing virtually all pathogen-antibiotic combinations. To realize the method, a production technology of Russian Mueller–Hinton broth (MHB-Obolensk) has been developed under the import substitution program. The aim. To evaluate the quality of the developed domestic Mueller–Hinton broth in comparative tests with its imported analog BD BBL (MHB-BD) in testing clinical strains of microorganisms, including microorganism–antibiotic combinations pairs which cannot be reliably investigated by the disc diffusion method. Materials and methods. The study investigated the sensitivity of 47 clinical strains of Gram-positive and Gram-negative bacteria to antibiotics of various functional groups using the broth microdilution method with MHB-Obolensk and MHB-BD. Results. The MICs values of antibiotics for clinical strains obtained with the developed and control media did not practically differ from each other or differed by +/– one dilution. The difference by two two-fold dilutions was noted when testing Enterococcus faecium–ampicillin, Klebsiella pneumoniae–meropenem, Pseudomonas aeruginosa–levofloxacin and Staphylococcus aureus–ciprofloxacin combinations. For the first two combinations, the MIC values were lower in MHB-Obolensk, and for the last two, they were higher than in MHB-BD. The differences obtained did not affect the clinical categories of sensitivity. Conclusion. The antibiograms of clinical strains in developed Russian Mueller–Hinton broth was obtained, which did not differ from those for the comparison medium. MHB-Obolensk complies with the requirements of national and international standards and can be used to reliably test, among other things, current combinations of microorganism–antibiotic pairs that cannot be studied using the disk diffusion method.

ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro.

Despite ongoing antibiotic development, evolution of resistance may render candidate antibiotics ineffective. Here we studied in vitro emergence of resistance to 13 antibiotics introduced after 2017 or currently in development, compared with in-use antibiotics. Laboratory evolution showed that clinically relevant resistance arises within 60 days of antibiotic exposure in Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, priority Gram-negative ESKAPE pathogens. Resistance mutations are already present in natural populations of pathogens, indicating that resistance in nature can emerge through selection of pre-existing bacterial variants. Functional metagenomics showed that mobile resistance genes to antibiotic candidates are prevalent in clinical bacterial isolates, soil and human gut microbiomes. Overall, antibiotic candidates show similar susceptibility to resistance development as antibiotics currently in use, and the corresponding resistance mechanisms overlap. However, certain combinations of antibiotics and bacterial strains were less prone to developing resistance, revealing potential narrow-spectrum antibacterial therapies that could remain effective. Finally, we develop criteria to guide efforts in developing effective antibiotic candidates.

Antibiotic Resistance of Staphylococcus aureus Strains—Searching for New Antimicrobial Agents—Review

Inappropriate and excessive use of antibiotics is responsible for the rapid development of antimicrobial resistance, which is associated with increased patient morbidity and mortality. There is an urgent need to explore new antibiotics or alternative antimicrobial agents. S. aureus a commensal microorganism but is also responsible for numerous infections. In addition to innate resistance to β-lactam antibiotics, S. aureus strains resistant to methicillin (MRSA) often show resistance to other classes of antibiotics (multidrug resistance). The advancement of phage therapy against MRSA infections offers a promising alternative in the context of increasing antibiotic resistance. Therapeutic phages are easier to obtain and cheaper to produce than antibiotics. However, there is still a lack of standards to ensure the safe use of phages, including purification, dosage, means of administration, and the quantity of phages used. Some bacteria have developed defense mechanisms against phages. The use of phage cocktails or the combination of antibiotics and phages is preferred. For personalized therapy, it is essential to set up large collections to enable phage selection. In the future, the fight against MRSA strains using phages should be based on a multidisciplinary approach, including molecular biology and medicine. Other therapies in the fight against MRSA strains include the use of endolysin antimicrobial peptides (including defensins and cathelicidins). Researchers’ activities also focus on the potential use of plant extracts, honey, propolis, alkaloids, and essential oils. To date, no vaccine has been approved against S. aureus strains.

Spectrophotometric Detection of Beta-Lactamase Inhibition by Plant Extracts

Background: Antibiotic-resistant bacteria have been spreading with increasing frequency over the past several decades. The decreasing effectiveness of therapies in treating bacterial resistance, due to the production of beta-lactamase (EC.3.5.2.6), has led to combining beta-lactamase inhibitors with commonly used beta-lactam antibiotics. Phytochemical compounds produced by plants have varied biological properties such as antioxidant, antimicrobial, antidiabetic, anti-inflammatory, anticancer, antihypertensive and others. Polyphenolics, flavonoids, coumarins, alkaloids, tannins, steroids and terpenoids are the main phytochemicals found in plants extracts. This study aims to assess the inhibitory activity of Annona senegalensis Pers., Terminalia superba Engl. &amp; Diels, Ipomoea batatas Lam., and Psidium guajava L. against a Bacillus cereus beta-lactamase and four beta-lactamases extracted from clinical isolates of Escherichia coli. Methods: Beta-lactamase inhibition was measured using a spectrophotometric assay with benzylpenicillin as the substrate, by a modified acidimetric method. Clavulanic acid was used as the standard beta-lactamase inhibitor. Subsequently, the inhibition of the hydrolysis of other commonly used beta-lactam antibiotics was assessed using a UV spectrophotometric method. Results: Among the tested extracts, Ipomoea batatas showed no effect on the beta-lactamases, whereas Terminalia superba and Annona senegalensis exhibited inhibitory activity against all the beta-lactamases. Psidium guajava inhibited two of the five tested enzymes. The highest percentage of inhibition was observed with Terminalia superba on the beta-lactamase of Bacillus cereus, reaching 75.73%. Regarding the combination of beta-lactam antibiotics with plant extracts, the combination of Terminalia superba and ceftriaxone showed the highest inhibition, with a percentage of 64.90%. The combination of Annona senegalensis and ceftazidime was the least effective, with an inhibition rate of only 12.95%. Conclusion: Two of the tested ethanolic plant extracts showed interesting beta-lactamase inhibitory effects and could contribute to the development of more effective therapies against beta-lactamase-producing bacteria by combining natural inhibitors from plants with existing beta-lactam antibiotics.

Emerging Threats: Antimicrobial Resistance in Extended-Spectrum Beta-Lactamase and Carbapenem-Resistant Escherichia coli.

Antimicrobial resistance (AMR) in Escherichia coli strains, particularly those producing Extended-Spectrum Beta-Lactamase (ESBL) and Carbapenemase (CR-Ec), represents a serious global health threat. These resistant strains have been associated with increased morbidity, mortality, and healthcare costs, as they limit the effectiveness of standard antibiotic therapies. The prevalence of ESBL- and CR-Ec-producing strains continues to rise, driven by the overuse and misuse of antibiotics in healthcare and agricultural settings, and facilitated by global interconnectedness through international travel, trade, and food distribution. This review article examines the molecular mechanisms behind ESBL and CR resistance, focusing on the key genes involved in these processes, such as blaCTX-M, blaKPC, and blaNDM, and the clinical challenges posed by these strains. Additionally, the public health impact, including the spread of infections in hospital and community environments, is highlighted. The discussion emphasizes the urgent need for improved diagnostic tools, robust surveillance systems, and innovative therapeutic strategies. Emerging treatments, including phage therapy and novel antibiotic combinations, show promise in addressing these challenges and offer potential breakthroughs in combating resistant strains. Lastly, the review calls for stronger antimicrobial stewardship and policy reforms to mitigate the spread of resistant E. coli strains and protect global public health. Effective intervention at multiple levels, from diagnostics to policy, is critical to controlling the threat posed by AMR.

Editorial for Special Issue “Antibiotic Combination Therapy: A Strategy to Overcome Bacterial Resistance”

Editorial for Special Issue “Antibiotic Combination Therapy: A Strategy to Overcome Bacterial Resistance”

Unveiling the impact of traditional Chinese herbal medicines on cutaneous adverse drug reactions: A landmark 15-year nationwide study.

Traditional Chinese herbal medicines (TCMs) have become increasingly integrated into global healthcare systems, often used alongside conventional pharmaceuticals. While TCMs offer therapeutic benefits, their concomitant use with other medications raises concerns over cutaneous adverse drug reactions (CADRs). Despite the widespread use of TCMs, large-scale studies examining their safety in combination with antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) remain limited. This study aimed to analyze the frequency and severity of CADRs associated with TCMs, focusing on their interactions with antibiotics and NSAIDs in a comprehensive dataset spanning over 15 years in China. We retrospectively reviewed clinical data from over 1.8 million patient visits annually between 2007 and 2022. Both mild and severe CADRs (SCARs) associated with TCMs, antibiotics, and NSAIDs were evaluated. While used in combination with antibiotics or NSAIDs, TCMs did not significantly increase the incidence of SCARs, although TCMs, antibiotics, or NSAIDs accounted for a proportion of CADRs. In contrast, the combination of antibiotics with NSAIDs showed a higher frequency of SCARs compared to monotherapy. These results suggest that TCMs have a favorable safety profile in multi-drug regimens, but careful monitoring is essential, particularly in multi-drug therapies involving conventional medications. This groundbreaking study provides unprecedented insights into the role of TCMs in CADRs, highlighting their potential for safer integration into multi-drug regimens. Although TCMs did not exacerbate the risk of severe reactions when combined with antibiotics or NSAIDs, vigilance in drug safety protocols remains crucial. These findings support the cautious and well-regulated use of TCMs within broader healthcare frameworks, promoting their safe integration alongside conventional therapies.

Exploring in vitro efficacy of rCHAPk with antibiotic combinations, and promising findings of its therapeutic potential for clinical-originated MRSA wound infection.

The increasing threat of antimicrobial-resistant bacteria, particularly Staphylococcus aureus, which rapidly develops multidrug resistance and commonly colonizes wound surfaces, demands innovative strategies. Phage-encoded endolysins offer a dual-purpose approach as topical therapies for infectious skin wounds and synergistic agents to reduce high-dose antibiotic dependence. This study explores recombinant CHAPk (rCHAPk), efficiently synthesized within 3 h, displaying broad-spectrum antibacterial activity against 11 Gram-positive strains, including resistant variants, with rapid bactericidal kinetics. Application of 10 μg of rCHAPk reduced OD600 by 0.4 within 5 min against a clinical methicillin-resistant S. aureus (MRSA) strain. Combining rCHAPk (1.875 μg/mL) with oxacillin/vancomycin lowered their minimum bactericidal concentrations to 1 μg/mL from initial values over 64 μg/mL and 32 μg/mL, respectively, with a fractional inhibitory concentration index below 0.1. rCHAPk retained efficacy after one year of refrigerated storage. In in vivo experiments, rCHAPk outperformed commercial fucidin therapy in MRSA-induced murine wound models over two weeks, enhancing wound healing by modulating pro-inflammatory cytokine responses and the proliferative phase. This study, for the first time, investigates rCHAPk's in vitro combination with antibiotics and wound healing parameters, highlighting its potential as a potent antibacterial agent synergizing with antibiotics to address antibiotic-resistant bacterial wound infections.

How can traditional Chinese medicine enhance the efficacy of antibiotics in the treatment of MRSA-infected pneumonia: an experimental study on the combination of Reyanning mixture and linezolid.

The Reyanning Mixture (RYN) is a Chinese patent medicine widely used in the treatment of respiratory inflammatory diseases in China and has potential in the treatment of bacteria-infected pneumonia. The present study aimed to demonstrate the therapeutic potential of RYN in combination with linezolid for the treatment of MRSA-infected pneumonia and to explore the mechanisms of action and active components. The pharmacodynamics of RYN alone and in combination with linezolid was investigated in a rat model of MRSA-induced pneumonia. Transcriptomics, ELISA, western blot and qRT-PCR were used to explore and verify the pharmacological mechanism of the anti-inflammatory effect of RYN. UPLC-MS and molecular docking were used to explore the anti-inflammatory components of RYN for the treatment of MRSA-infected pneumonia. In vivo, RYN reduced lung injury and inflammation in patients with pneumonia. In particular, the combination of RYN and linezolid enhanced the therapeutic effect compared to that of either treatment alone. Further research suggests that the synergistic therapeutic effect of the combination may be related to the inhibition of the inflammatory response by RYN and the enhancement of linezolid inhibition and clearance of MRSA in lung tissues by RYN. RYN plays an anti-inflammatory role in MRSA-infected pneumonia by inhibiting the TLR2/NF-κB/NLRP3 pathway, with 7 active components that may play a dominant role. These results indicate that RYN may serve as an adjuvant drug to antibiotics for the treatment of MRSA-associated pneumonia. Exploration of its active components and mechanisms is conducive to the clinical application and quality improvement of RYN. More importantly, this study showed that the synergistic therapeutic effect of the combination of traditional Chinese medicine and antibiotics may be a valuable therapeutic strategy.

Epidemiology and Mechanism of Drug Resistance of Multidrug-Resistant Klebsiella Pneumoniae Isolated from Patients with Urinary Tract Infection in Beijing Teaching Hospital, China.

Klebsiella pneumoniae is an important pathogenic bacterium in causing urinary tract infection. With the overuse of antibiotics, bacteria resistant to quinolones combined with carbapenems are increasing. In this study, we investigated the epidemiology, molecular characteristics, drug resistance of multidrug-resistant Klebsiella pneumoniae (MDR-KPN) isolated from urine samples. It provides theoretical basis for the treatment of urinary tract infection by clinicians. Fifty-one strains of Klebsiella pneumonia were obtained from urine samples collected between 2012 and 2017 in total. All the strains are multi-drug resistant bacteria. This paper used multilocus sequence typing (MLST) to determine molecular epidemiological typing. We performed antimicrobial susceptibility testing and investigated quinolones and carbapenems resistance genes. The strains which we collected were resistant to ciprofloxacin and Levofloxacin. In an epidemiological analysis using MLST, 86.27% (44/51) of isolates were confirmed to be ST11. The main carbapenem resistance gene was KPC-19, 78.43(40/51). Among the quinolone resistance genes, the major resistance genes were aac(6')-Ib-cr, oqxA and oqxB. The main molecular epidemiological types we detected was ST11. The main resistance gene of carbapenems was KPC-19. The quinolone resistance genes are mainly aac(6')-Ib-cr, oqxA and oqxB. The experimental results can help control the use of quinolones and carbapenems, and we could provide rational drug use basis for clinicians to treat urinary tract infection. For MDR-KPN, a combination of multiple antibiotics is necessary.

Azo derivatives of monoterpenes as anti-Helicobacter pylori agents: from synthesis to structure-based target investigation.

Helicobacter pylori (Hp) infection affects nearly half of the global population. Current therapeutic options include the administration of a combination of antibiotics and proton pump inhibitors, although antimicrobial resistance rise remains a big concern. Phenolic monoterpenes, e.g., eugenol, vanillin, carvacrol, and thymol, have always attracted researchers for their multifaced biological activities and the possibility to be easily derivatized. Thereby, herein we present the functionalization of such compounds through the conventional aryl diazotization reaction, generating a series of mono- and bis-azo derivatives (1-28). Also, to continue previous studies, we investigated the role of the free phenolic moiety of thymol with eight compounds (29-36). The compounds were tested against four Hp strains including three clinical isolates, finding some potent and selective inhibitors of bacterial growth. Thus, the representative compounds underwent in vitro cytotoxicity evaluation on two normal cell lines and putative target investigation by performing a structure-based approach based on docking calculations on some of the most studied pharmacological targets for Hp, e.g., urease, β-hydroxyacyl-acyl carrier protein dehydratase, glucose 6-phosphate dehydrogenase, and inosine 5'-monophosphate dehydrogenase.

Therapy Pattern and Potential for Drug Interactions In COPD Patients at S.K. Lerik Regional Hospital Of Kupang City

Chronic Obstructive Pulmonary Disease (COPD) is a respiratory disease characterized by persistent airflow limitation and is associated with an increased chronic inflammatory response to certain irritants, gases, or particles. COPD management uses a combination of drugs to treat the disease's symptoms, which varies depending on the patient's condition. The combination of these drugs has the potential to cause drug interactions that result in Drug Related Problems (DRP). A DRP is defined as a change in the effect of a drug due to being given together with other drugs. This study aims to describe the pharmacological therapy given and the potential for drug interactions in COPD therapy at the S.K Lerik Regional General Hospital. This research is descriptive, non-experimental, and observational, using retrospective data. The sample in this study was the medical record data of COPD patients hospitalized at the S.K Lerik Regional General Hospital, with a total sampling technique. The study’s results revealed that the COPD patients’ treatment at the S.K Lerik Hospital mainly uses a combination of corticosteroid therapy (methylprednisolone), bronchodilators (salbutamol), and antibiotics (ceftriaxone). The highest potential for drug interactions was at the mild severity level with the interaction between methylprednisolone and salbutamol, which was given to all patients (12 patients). Due to the high potential for drug interactions of these two drugs, further monitoring is needed in COPD patients to determine the manifestations of these drug interactions in clinical conditions

Synergistic Potential of Antibiotics with Cancer Treatments.

Intratumoral microbiota, the diverse community of microorganisms residing within tumor tissues, represent an emerging and intriguing field in cancer biology. These microbial populations are distinct from the well-studied gut microbiota, offering novel insights into tumor biology, cancer progression, and potential therapeutic interventions. Recent studies have explored the use of certain antibiotics to modulate intratumoral microbiota and enhance the efficacy of cancer therapies, showing promising results. Antibiotics can alter intratumoral microbiota's composition, which may have a major role in promoting cancer progression and immune evasion. Certain bacteria within tumors can promote immunosuppression and resistance to therapies. By targeting these bacteria, antibiotics can help create a more favorable environment for chemotherapy, targeted therapy, and immunotherapy to act effectively. Some bacteria within the tumor microenvironment produce immunosuppressive molecules that inhibit the activity of immune cells. The combination of antibiotics and other cancer therapies holds significant promise for creating a synergistic effect and enhancing the immune response against cancer. In this review, we analyze several preclinical studies that have been conducted to demonstrate the synergy between antibiotics and other cancer therapies and discuss possible clinical implications.

Antibiotic use at the Centre Hospitalier Universitaire de Zone d'Abomey Calavi/Sô-Ava (CHUZ/AS) in Benin: a point prevalence survey.

Antimicrobial stewardship promotes the appropriate use of antibiotics to prevent the emergence and spread of antimicrobial resistance. This study evaluated the use of antibiotics using a point prevalence survey at the Centre Hospitalier Universitaire de Zone d'Abomey Calavi/Sô-Ava (CHUZ/AS) in Benin. This cross-sectional study utilized the WHO point prevalence survey methodology for monitoring antibiotic use among inpatients in hospitals. The survey was conducted from 11 January 2022 to 19 January 2022 among hospitalized patients before 8:00 a.m. on the day of the survey. Of the 111 inpatient medical files reviewed, the prevalence of antibiotic use was 82.9%. The number of antibiotics received per patient ranged from 1 to 5, with a mean of 2.45 ± 1.11 and a median of 2. The most commonly prescribed class of antibiotics was beta-lactams (46.7%), aminoglycosides (20.6%) and nitroimidazoles (19.7%). According to the WHO AWaRe classification, 30.4% of inpatients received the Access group of antibiotics and 44% received a combination of Access and Watch group antibiotics; treatment was empiric in 94.5% of encounters. Only 22.7% of patients were treated based on microbiological examination/culture and sensitivity testing. This study found a high prevalence of antibiotic use among inpatients at the CHUZ/AS Tertiary Care Hospital in Benin. The most prescribed antibiotics were ampicillin, metronidazole and ceftriaxone. Consequently, the study found a low use of culture and sensitivity testing to guide treatment, particularly in the paediatric and surgical population, and the preference for broad-spectrum antibiotics suggests that antibiotic use at the CHUZ/AS Tertiary Care is not optimal. Therefore, antimicrobial stewardship programmes, policies and guidelines must be instigated and strengthened to address these gaps and promote rational use of antibiotics.

Rapid and precise treatment selection for antimicrobial-resistant infection enabled by a nano-dilution SlipChip.

Antimicrobial resistance (AMR) has become an increasingly severe threat to global health, and AMR-associated infection is one of the leading causes of death around the world. Due to the long turnaround time and the limited flexibility and availability of current antimicrobial susceptibility testing (AST) methods, a large portion of patients with bacterial infections are still treated empirically, increasing the risk of mistreatment. To address the demand for precision treatment of bacterial infections, we developed a nano-dilution SlipChip (nd-SlipChip)-based systematic evaluation method, which facilitates rapid, logic feedback for the assessment of antibiotics, antibiotic combinations, and phage therapy. The nd-SlipChip can conveniently generate a microdroplet array with serially diluted antibiotics and determine the minimal inhibitory concentration (MIC) within 2h by monitoring bacterial growth profiles, facilitating timely treatment selection. We demonstrated this method for 24 clinical isolates, including gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii) and gram-positive bacteria (Staphylococcus aureus). Three clinical isolates performed the second-stage antibiotic combinations screening, and effective combination therapies were identified for two of them. The remaining isolate proceeded to third-stage phage screening, where suitable phages were successfully selected. The nd-SlipChip provides a rapid and systematic approach for the precise selection of therapies targeting bacterial infections.

The Combination of Phage Therapy and β-Lactam Antibiotics for the Effective Treatment of Enterococcus faecalis Infections

A phage–antibiotic synergy could be an alternative in urinary tract infection (UTI) therapy, as it leads to the elimination of bacteria and to the reduction in variants resistant to phages and antibiotics. The aims of the in vitro study were to determine whether phages vB_Efa29212_2e and vB_Efa29212_3e interact synergistically with selected antibiotics in the treatment of E. faecalis infections, to optimize antibiotic concentrations and phage titers for the most effective combinations, and to assess their impact on the number of spontaneous resistant variants and on the phages’ reproductive cycles. The modified double-layer disc diffusion method, checkboard, time–kill assays, one-step growth method and the double agar overlay plaque assay were implemented. Synergistic interactions were most often observed after the combined action of phages 2e or 3e and β-lactam antibiotics on E. faecalis strains. The beneficial effects depended on the bacterial strain, phage and antibiotic used. The lowest minimum inhibitory concentration (MIC50) values of the antibiotics were recorded, after the application of low titers of phage 2e, and high titers of phage 3e. The combined use of the tested agents resulted in a significant reduction in the number of resistant variants and had an impact on the reproductive cycle of the tested phages, e.g., a 50% increase in burst size, and a 5 min reduction in the latency period of 2e were observed. The study confirmed beneficial interactions between phages and β-lactam antibiotics against E. faecalis growth.

Fungal hepatic abscess formation postlaparoscopic cholecystectomy

Abstract Laparoscopic cholecystectomy is the preferred method for treating acute cholecystitis. Although the incidence of postoperative infections in laparoscopic cholecystectomy is low, serious postoperative surgical site infections are still reported. Hepatic abscesses, particularly fungal, can occur post-cholecystectomy leading to significant mortality and morbidity. We report a case of a 58-year-old female who underwent laparoscopic cholecystectomy and subsequently developed fever, jaundice, and right upper quadrant pain. Laboratory results showed deranged liver function tests with raised inflammatory markers. Radiographic investigations, including CT and MRI, revealed an irregular hilar lesion with periportal changes suggestive of an abscess with portal vein thrombosis. Histopathological examination of the biopsy obtained from the hilar lesion showed a fungal hepatic infection, and particularly conidiobolomycosis. To our best knowledge, this is the first case that reports this fungal infection as a complication of laparoscopic cholecystectomy. The patient was managed with a combination of intravenous antibiotics and antifungals, which yielded mild improvement. Unfortunately, the patient decided to leave the hospital against medical advice, limiting the information on the disease course.