2.Recent progress in development of antibiotics against Gram-negative bacteria.
Acta Pharmaceutica Sinica 2013;48(7):993-1004
Multidrug-resistant (MDR) bacterial infections, especially those caused by Gram-negative pathogens, have emerged to be one of the world's greatest health threats. However, not only have recent decades shown a steady decline in the number of approved antimicrobial agents but a disappointing discovery also void. The development of novel antibiotics to treat MDR Gram-negative bacteria has been stagnated over the last half century. Though few compounds have shown activities in vitro, in animal models or even in clinical studies, the global antibiotic pipeline is not encouraging. There are a plethora of unexpected challenges that may arise and cannot always be solved to cause promising drugs to fail. This review intends to summarize recent research and development activities to meet the inevitable challenge in restricting the proliferation of MDR Gram-negative bacteria, with focus on compounds that have entered into clinical development stage. In addition to new analogues of existing antibiotic molecules, attention is also directed to alternative strategies to develop antibacterial agents with novel mechanisms of action.
Aminoglycosides
;
pharmacology
;
therapeutic use
;
Animals
;
Anti-Bacterial Agents
;
pharmacology
;
therapeutic use
;
Antibodies, Monoclonal
;
pharmacology
;
therapeutic use
;
Drug Discovery
;
Drug Resistance, Multiple, Bacterial
;
Enzyme Inhibitors
;
pharmacology
;
therapeutic use
;
Ferrous Compounds
;
pharmacology
;
therapeutic use
;
Gram-Negative Bacteria
;
drug effects
;
Gram-Negative Bacterial Infections
;
drug therapy
;
Humans
;
Peptides
;
pharmacology
;
therapeutic use
;
Peptidomimetics
;
pharmacology
;
therapeutic use
;
Tetracyclines
;
pharmacology
;
therapeutic use
;
beta-Lactamase Inhibitors
;
beta-Lactams
;
pharmacology
;
therapeutic use
3.Research progress about photothermal nanomaterials with targeted antibacterial properties and their applications in wound healing.
Xiangnan YUAN ; Shaojie TAN ; Jing GAO ; Lu WANG
Journal of Biomedical Engineering 2022;39(1):207-216
With the development of photothermal nanomaterials, photothermal therapy based on near-infrared light excitation shows great potential for the bacterial infected wound treatment. At the same time, in order to improve the photothermal antibacterial effect of wound infection and reduce the damage of high temperature and heat to healthy tissue, the targeted bacteria strategy has been gradually applied in wound photothermal therapy. In this paper, several commonly used photothermal nanomaterials as well as their targeted bacterial strategies were introduced, and then their applications in photothermal antibacterial therapy, especially in bacterial infected wounds were described. Besides, the challenges of targeted photothermal antibacterial therapy in the wound healing application were analyzed, and the development of photothermal materials with targeted antibacterial property has prospected in order to provide a new idea for wound photothermal therapy.
Anti-Bacterial Agents/pharmacology*
;
Humans
;
Nanostructures/therapeutic use*
;
Staphylococcus aureus
;
Wound Healing
;
Wound Infection/therapy*
4.New Therapeutic Strategies against Helicobacter pylori.
Bong Ku KANG ; Sung Min PARK ; Byung Wook KIM
The Korean Journal of Gastroenterology 2014;63(3):146-150
The standard therapy for Helicobacter pylori infection in Korea is a triple-drug regimen consisting of a proton pump inhibitor with two antibiotics such as clarithromycin, amoxicillin, and metronidazole. However, as the eradication rate of this regimen has declined over the past decade, this prompted the formulation of new therapeutic regimens. New therapeutic strategies against H. pylori infection that had been tried all over the world include sequential therapy, concomitant therapy, and tailored therapy This article will review the basic concepts and the results of previous clinical trials on the aforementioned new therapeutic regiments.
Amoxicillin/pharmacology/therapeutic use
;
Anti-Bacterial Agents/pharmacology/*therapeutic use
;
Clarithromycin/pharmacology/therapeutic use
;
Disease Eradication/trends
;
Drug Therapy, Combination
;
Helicobacter Infections/*drug therapy
;
*Helicobacter pylori/drug effects
;
Humans
;
Nitroimidazoles/pharmacology/therapeutic use
;
Proton Pump Inhibitors/pharmacology/therapeutic use
5.The combination of ciprofloxacin and indomethacin suppresses the level of inflammatory cytokines secreted by macrophages in vitro.
Ke LIU ; Jing YU ; Yu XIA ; Lei-Ting ZHANG ; Sui-Yan LI ; Jun YAN
Chinese Journal of Traumatology 2022;25(6):379-388
PURPOSE:
The combined use of antibiotics and anti-inflammatory medicine to manage bacterial endotoxin-induced inflammation following injuries or diseases is increasing. The cytokine level produced by macrophages plays an important role in this treatment course. Ciprofloxacin and indomethacin, two typical representatives of antibiotics and anti-inflammatory medicine, are cost-effective and has been reported to show satisfactory effect. The current study aims to investigate the effect of ciprofloxacin along with indomethacin on the secretion of inflammatory cytokines by macrophages in vitro.
METHODS:
Primary murine peritoneal macrophages and RAW 264.7 cells were administrated with lipopolysaccharide (LPS) for 24 h. The related optimal dose and time point of ciprofloxacin or indomethacin in response to macrophage inflammatory response inflammation were determined via macrophage secretion induced by LPS. Then, the effects of ciprofloxacin and indomethacin on the secretory functions and viability of various macrophages were determined by enzyme-linked immunosorbent assay and flow cytometry analysis, especially for the levels of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor (TNF)-α. The optimal dose and time course of ciprofloxacin affecting macrophage inflammatory response were determined by testing the maximum inhibitory effect of the drugs on pro-inflammatory factors at each concentration or time point.
RESULTS:
According to the levels of cytokines secreted by various macrophages (1.2 × 106 cells/well) after administration of 1 μg/mL LPS, the optimal dose and usage timing for ciprofloxacin alone were 80 μg/mL and 24 h, respectively, and the optimal dose for indomethacin alone was 10 μg/mL. Compared with the LPS-stimulated group, the combination of ciprofloxacin and indomethacin reduced the levels of IL-1β (p < 0.05), IL-6 (p < 0.05), IL-10 (p < 0.01)), and TNF-α (p < 0.01). Furthermore, there was greater stability in the reduction of inflammatory factor levels in the combination group compared with those in which only ciprofloxacin or indomethacin was used.
CONCLUSION
The combination of ciprofloxacin and indomethacin suppressed the levels of inflammatory cytokines secreted by macrophages in vitro. This study illustrates the regulatory mechanism of drug combinations on innate immune cells that cause inflammatory reactions. In addition, it provides a new potential antibacterial and anti-inflammatory treatment pattern to prevent and cure various complications in the future.
Humans
;
Mice
;
Animals
;
Cytokines
;
Lipopolysaccharides/pharmacology*
;
Interleukin-10
;
Indomethacin/therapeutic use*
;
Interleukin-6/therapeutic use*
;
Ciprofloxacin/therapeutic use*
;
Macrophages
;
Tumor Necrosis Factor-alpha
;
Inflammation/drug therapy*
;
Anti-Inflammatory Agents/therapeutic use*
;
Anti-Bacterial Agents/therapeutic use*
6.Practicability study on a group of vigilant chemical compounds including chlorheridine diacetate.
Xiao-Min FU ; Ai-Hua JIN ; Jian ZOU ; Qian-Li LI
National Journal of Andrology 2002;8(5):329-331
OBJECTIVESTo test in vitro the spermatozocidine drug which can also prevent sex transmitting diseases (STD) pathogens.
METHODSChlorheridine diacetate and other three chemical compounds were applied in vitro spermatozocidine and sperm inhibitting tests.
RESULTSThe lowest concentrations of chlorheridine diacetate and p-nitrophenol which can inhibit human sperm in 20 seconds were 1.25 mg/ml. The minimal inhibitory concentration and minimal bactericidal concentration of chlorheridine diacetate and p-nitrophenol on Streptococcus albus Stemberg were 0.125 to 0.50 mg/ml and 0.25 to 1.00 mg/ml.
CONCLUSIONSChlorheridine diacetate and p-uitrophenol have strong spermatozocidine and antibacteria effects.
Acetates ; pharmacology ; therapeutic use ; Anti-Bacterial Agents ; pharmacology ; therapeutic use ; Humans ; Male ; Microbial Sensitivity Tests ; Neisseria gonorrhoeae ; drug effects ; Nitrophenols ; pharmacology ; therapeutic use ; Sexually Transmitted Diseases ; prevention & control ; Spermatocidal Agents ; pharmacology ; therapeutic use ; Spermatozoa ; drug effects ; Streptococcus ; drug effects
7.Effects of cefdinir in pediatric infectious diseases.
Chinese Journal of Pediatrics 2005;43(3):233-235
8.Clinical Factors Associated with Acquisition of Resistance to Levofloxacin in Stenotrophomonas maltophilia.
Ji Hyeon BAEK ; Chang Oh KIM ; Su Jin JEONG ; Nam Soo KU ; Sang Hoon HAN ; Jun Yong CHOI ; Dongeun YONG ; Young Goo SONG ; Kyungwon LEE ; June Myung KIM
Yonsei Medical Journal 2014;55(4):987-993
PURPOSE: Fluoroquinolones, rapidly gaining prominence in treatment of Stenotrophomonas maltophilia (SMP), are noted for their potency and tolerability. However, SMP may rapidly acquire resistance to fluoroquinolones. We evaluated associations of clinical factors with acquisition of levofloxacin resistance (LFr) in SMP. MATERIALS AND METHODS: Our retrospective cohort study was based on patient data collected between January 2008 and June 2010. Through screening of 1275 patients, we identified 122 patients with data for SMP antibiotic susceptibility testing in > or =3 serial SMP isolates. RESULTS: We assigned the 122 patients to either the SS group (n=54) in which levofloxacin susceptibility was maintained or the SR group (n=31) in which susceptible SMP acquired resistance. In multivariate regression analysis, exposure to levofloxacin for more than 3 weeks [odds ratio (OR) 15.39, 95% confidential interval (CI) 3.08-76.93, p=0.001] and co-infection or co-colonization with Klebsiella pneumoniae resistant to levofloxacin (OR 4.85, 95% CI 1.16-20.24, p=0.030) were independently associated with LFr acquisition in SMP. CONCLUSION: Acquisition of LFr during serial sampling of SMP was related to the levofloxacin exposure.
Aged
;
Anti-Bacterial Agents/*pharmacology/*therapeutic use
;
Fluoroquinolones/pharmacology/therapeutic use
;
Gram-Negative Bacterial Infections/drug therapy
;
Humans
;
Levofloxacin/*pharmacology/*therapeutic use
;
Microbial Sensitivity Tests
;
Middle Aged
;
Retrospective Studies
;
Stenotrophomonas maltophilia/drug effects/*pathogenicity
9.Sequential Bilateral Lung Resection in a Patient with Mycobacterium Abscessus Lung Disease Refractory to Medical Treatment.
Seung Heon LEE ; Joo Won MIN ; Sang Won UM ; Seon Sook HAN ; Sung Koo HAN ; Young Soo SHIM ; Jae Joon YIM
Yonsei Medical Journal 2010;51(1):141-144
Mycobacterium abscessus (M. abscessus) is the second most common nontuberculous mycobacteria (NTM) in South Korea. Nevertheless, the diagnosis and treatment of M. abscessus lung disease can be problematic. Surgical resection has been tried for patients with localized M. abscessus lung disease refractory to medical treatment. Here, we report on a 25-year-old woman with M. abscessus lung disease who had been diagnosed and treated three times for pulmonary tuberculosis. She was initially diagnosed as having M. intracellulare lung disease; however, M. abscessus was isolated after several months of medication. She had multiple bronchiectatic and cavitary lesions bilaterally, and M. abscessus was repeatedly isolated from her sputa despite prolonged treatment with clarithromycin, ethambutol, moxifloxacin, and amikacin. She improved only after sequential bilateral lung resection. Based on the experience with this patient, we suggest that, if medical treatment fails, surgical resection of a diseased lung should be considered even in patients with bilateral lesions.
Adult
;
Anti-Bacterial Agents/pharmacology/*therapeutic use
;
Female
;
Humans
;
Lung Diseases/*drug therapy/*microbiology/surgery
;
Mycobacteria, Atypical/drug effects/*physiology
10.Risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children: a Meta analysis.
Bi-Yu LIN ; Jing-Ting LIU ; Feng-Ling JIN
Chinese Journal of Contemporary Pediatrics 2022;24(1):96-101
OBJECTIVES:
To systematically assess the risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children.
METHODS:
PubMed, Web of Science, China National Knowledge Infrastructure Database, Wanfang Data, China Biology Medicine disc were searched to obtain the articles on risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children published up to May 31, 2021. RevMan 5.3 software was used to perform the Meta analysis.
RESULTS:
A total of 13 articles were included, with 1 501 samples in total. The Meta analysis showed that indwelling gastric tube (OR=4.91), tracheal intubation (OR=5.03), central venous catheterization (OR=3.75), indwelling urinary catheterization (OR=4.11), mechanical ventilation (OR=3.09), history of hospitalization in the intensive care unit (OR=2.39), history of surgical operation (OR=3.22), previous use of third-generation cephalosporins (OR=2.62), previous use of carbapenem antibiotics (OR=3.82), previous use of glycopeptide antibiotics (OR=3.48), previous use of β-lactamase inhibitors (OR=2.87), previous use of antifungal drugs (OR=2.48), previous use of aminoglycoside antibiotics (OR=2.54), and Apgar score ≤7 at 1 minute after birth (OR=2.10) were risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children (P<0.05).
CONCLUSIONS
Invasive operations, history of hospitalization in the intensive care unit, previous use of antibiotics such as carbapenem antibiotics, and Apgar score ≤7 at 1 minute after birth are risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children.
Anti-Bacterial Agents/therapeutic use*
;
Carbapenem-Resistant Enterobacteriaceae
;
Carbapenems/pharmacology*
;
Child
;
Enterobacteriaceae Infections/microbiology*
;
Humans
;
Risk Factors