OBJECTIVE

To determine the prevalence of rectal colonization with carbapenem-resistant organisms (CRO) among PGH neonatal intensive care unit (NICU) patients.

A prospective single-center observational study conducted over a 1-month period included all NICU 3 and cohort area patients admitted on April 24, 2024. Rectal swabs were collected for multidrug-resistant organism (MDRO) screening and repeated weekly for 1 month while admitted. Swabs were inoculated on chromogenic media, and isolates were identified and tested for antimicrobial sensitivity by disk diffusion. Clinical characteristics and outcomes were collected for 30 days from initial MDRO screening. Descriptive statistics were used to summarize the data.

The point prevalence of CRO colonization was 37% (14 of 38) at initial screening. There were 14 incident colonizations, hence the 4-week period prevalence of CRO colonization was 72.5% (29 of 40). The patients were mostly very preterm, very low birth weight neonates, majority were tested within the first 2 weeks of life, and half were exposed to meropenem at initial screening. Nosocomial infection developed in 29% and 64%, and 30-day mortality rate was 8% and 21% among initially non-CRO-colonized and CRO-colonized patients respectively. Despite high CRO colonization, no culture-proven CRO infection was observed. Surveillance screening documented persistent CRO colonization in 37%, but no decolonization. Escherichia coli, Klebsiella spp. and Serratia spp. were the most common colonizers.

The high prevalence of rectal CRO colonization in the NICU emphasizes the burden of antimicrobial resistance, but despite the high CRO colonization, no CRO infection was documented from the limited sample and study period.

BACKGROUND AND OBJECTIVE

Antimicrobial resistance (AMR) is a leading global public health concern as it resulted in more difficult-to-treat infections and fatalities. In the Philippines, drug-resistant E. coli, including multidrug-resistant (MDR), extended-spectrum beta-lactamase (ESBL)-producing, carbapenemase-producing carbapenem-resistant (CP-CR) E. coli, have been isolated from common food animals, increasing the risk of cross-contamination between humans, animals, and the environment. However, there is a lack of data on the distribution of E. coli in chicken meat in public wet markets. This study aims to describe the AMR profile of E. coli in raw chicken meat from retail stalls in a selected wet market in Manila City.

This quantitative descriptive study characterized the AMR profile of E. coli isolated from 25 raw chicken meat samples from a wet market in Manila City. Antimicrobial susceptibility was determined through disk diffusion method against 23 antimicrobial agents in 16 antimicrobial classes. MDR E. coli were identified based on the resistance patterns. ESBL- and carbapenemase-producing capacities of the bacteria were tested through double disk synergy test and modified carbapenem inactivation method, respectively.

Twenty-four out of 25 (96%) chicken samples contained E. coli isolates. Of these, 23 (96%) were classified as MDR. High resistance rates were observed against ampicillin (92%), tetracycline (88%), trimethoprim-sulfamethoxazole (83%), chloramphenicol (79%), ampicillin-sulbactam (75%), amoxicillin-clavulanic acid (67%), fosfomycin (67%), and streptomycin (54%). The majority of the E. coli isolates were still susceptible to a wide range of selected antimicrobial agents, including carbapenems (100%), ceftriaxone (100%), cefepime (100%), cefuroxime (96%), cefotaxime (96%), ceftazidime (96%), piperacillin-tazobactam (96%), aztreonam (96%), cefoxitin (92%), and nitrofurantoin (83%), among others. Meanwhile, none of the 24 isolated E. coli samples were classified as ESBL- and CP-CR E. coli.

Among the 25 chicken samples, 24 E. coli colonies were isolated that exhibited 0% to 92% resistance rates against selected antimicrobial agents. Most isolates were classified as MDR, but none were considered ESBLand CP-CR E. coli. This study suggests that chickens in wet markets can potentially serve as reservoir hosts for drugresistance genes, which could transfer to other bacteria and contaminate humans, animals, and the environment within the food production and supply chain. These findings emphasize the need for AMR surveillance and strategies to combat AMR in the Philippines through the One Health approach.

Five novel nor-eremophilane-type sesquiterpenoids, peniroqueforins E-H and J (1-4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), along with four known compounds (6 and 10-12), were isolated and characterized from fungus Penicillium roqueforti (P. roqueforti). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC₅₀) value of paclitaxel (PTX) combined with 1 in SW620/Ad300 cells was 50.36 nmol·L^-1, which was 65-fold more potent than PTX alone (IC₅₀ 3.26 μmol·L^-1). Subsequent molecular docking studies revealed an affinity between compound 1 and P-glycoprotein (P-gp), suggesting that this nor-eremophilane-type sesquiterpenoid (1) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.
Penicillium/chemistry* ; Humans ; Sesquiterpenes/isolation & purification* ; Cell Line, Tumor ; Molecular Structure ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/pharmacology* ; Drug Resistance, Multiple/drug effects* ; Molecular Docking Simulation

Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
Animals ; Panax/chemistry* ; Ginsenosides/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Mice ; Male ; Alkaloids/pharmacology* ; Coptis/chemistry* ; Drug Synergism ; Insulin Resistance ; Mice, Inbred C57BL ; Humans ; Transcriptome/drug effects* ; Blood Glucose/metabolism* ; Hypoglycemic Agents/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Hepatocytes/metabolism*

Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation

Helicobacter pylori is a bacterium that can cause chronic gastritis, peptic ulcers, and other gastrointestinal diseases. The World Health Organization has classified H. pylori as a group Ⅰ carcinogen. Antibiotics are the primary clinical approach for eradicating H. pylori. However, incomplete eradication of H. pylori by antibiotics can lead to persistent infection, which is a major risk factor for the high incidence of gastric cancer. The widespread use of antibiotics has led to the emergence of multidrug resistance in H. pylori, contributing to treatment failures of chronic gastric diseases and increasing the risk of spreading resistant strains. Multidrug-resistant H. pylori has become a serious challenge in the diagnosis and treatment of gastrointestinal diseases. This paper reviews the global trends in the development of multidrug resistance in H. pylori, the underlying mechanisms, the challenges it poses to clinical diagnosis, and its impact on drug development, drawing on relevant literature and the research findings from our group. It proposes using cgt expression as a novel method for determining viable bacteria, identifying intracellularization as a new form of resistance in H. pylori, and exploring the potential of O-glycans as a therapeutic approach against H. pylori to address multidrug resistance. It provides new insights into understanding the mechanisms of H. pylori multidrug resistance and its prevention strategies, offering promising directions for future clinical treatments and antimicrobial drug development.
Helicobacter pylori/genetics* ; Humans ; Drug Resistance, Multiple, Bacterial ; Helicobacter Infections/microbiology* ; Anti-Bacterial Agents/therapeutic use* ; Gastrointestinal Diseases/drug therapy*

Due to the wide application of silver-containing dressings and silver-coated medical devices in clinical treatment; the extensive use of antibacterial agents and heavy metal agents in feed factories, Escherichia coli has formed the tolerance to silver ions. To systematically understand the known silver ion resistance mechanisms of E. coli, this article reviews the complex regulatory network and various physiological mechanisms of silver ion tolerance in E. coli, including the regulation of outer membrane porins, energy metabolism modulation, the role of efflux systems, motility regulation, and silver ion reduction. E. coli reduces the influx of silver ions by missing or mutating outer membrane porins such as OmpR, OmpC, and OmpF. It adapts to high concentrations of silver ions by altering the expression of ArcA/B and enhances the efflux capacity of silver ions under high-concentration silver stress via the endogenous Cus system and exogenous Sil system. Furthermore, the motility of bacteria is related to silver tolerance. E. coli has the ability to reduce silver ions, thereby alleviating the oxidative stress induced by silver ions. These findings provide a new perspective for understanding the formation and spread of bacterial tolerance and provide directions for the development of next-generation silver-based antimicrobials and therapies.
Escherichia coli/genetics* ; Silver/pharmacology* ; Drug Resistance, Bacterial ; Anti-Bacterial Agents/pharmacology* ; Porins/metabolism*

Acinetobacter baumannii is a Gram-negative opportunistic pathogen widely distributed in hospital settings. It can survive for a long time and cause a variety of infections, including pneumonia, septicemia, urinary tract infections, and meningitis. The bacterium demonstrates extensive resistance, particularly to critical antibiotics like carbapenems and polymyxins, posing a serious threat to the recovery of severely ill patients. Carbapenem-resistant A. baumannii has been designated as a pathogen of critical priority on the World Health Organization (WHO) Bacterial Pathogen Priority List, requiring urgent development of new therapeutic agents. Phages, as a novel biological control approach, exhibit substantial potential in combating A. baumannii infections due to their specific ability to infect and lyse bacteria. This review highlights the application and potential of phages and phage-derived enzymes against multidrug-resistant A. baumannii, considering the epidemiological trends of A. baumannii in China, with the aim of providing innovative insights and strategies for phage therapy of drug-resistant bacterial infections.
Acinetobacter baumannii/drug effects* ; Drug Resistance, Multiple, Bacterial ; Phage Therapy/methods* ; Acinetobacter Infections/microbiology* ; Humans ; Bacteriophages/physiology* ; Anti-Bacterial Agents/pharmacology*

Germ cell tumors typically occur in the gonadal regions,characterized by high malignancy and rapid progression.Due to their high sensitivity to chemotherapy,the cure rate is generally high.However,a portion of patients still succumb to chemotherapy resistance and disease progression.The use of immune checkpoint inhibitors has significantly improved the prognosis for various solid tumors,while the immune mechanisms and efficacy of immunotherapy in germ cell tumors remain understudied.Whether relapsed and refractory germ cell tumors can benefit from immune checkpoint inhibitors remains to be investigated.In this review,we summarize the immune-related mechanisms,case reports,and clinical trials of immunotherapy in germ cell tumors to assess the effectiveness of this therapy,providing a reference for future basic research and clinical practice.
Humans ; Neoplasms, Germ Cell and Embryonal/therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Immunotherapy ; Testicular Neoplasms/drug therapy* ; Neoplasm Recurrence, Local ; Drug Resistance, Neoplasm