Cefoperazone Research Articles

Mastitis: Havoc to dairy cattle in Mizoram

Mastitis is the widely prevalent malady of dairy cattle. The present study aimed at finding the prevalence of bovine mastitis in Mizoram and to explore the treatment options with different antibiotics after determining the etiology. Hundred animals from 18 different farms were screened using modified California Mastitis test and recorded as positive and negative based on appearance of precipitation. An overall incidence rate of mastitis was observed as 72%. The milk samples were collected from positive animals, and microbial etiology were determined using appropriate laboratory techniques. The different organisms isolated were Staphylococci, Streptococci and E. coli. Animals were grouped into three groups and treated with Ceftizoxime, Cefoperazone sodium, Cefquinome sulphate and Cefquinome sulphate. It is observed that the third group where, Cefquinome sulphate and Cefquinome sulphate used showed 100% cure. These observations necessitate the requirement of regular screening of cattle and application of preventive and control measures for mastitis.

A prospective observational study of drug prescription pattern of antibiotics in diabetic foot ulcer in tertiary care teaching hospital

Background: Our aim was to study a prescribing pattern of antibiotics used in diabetic foot ulcer (DFU).Methods: 50 patients were selected by inclusion and exclusion criteria basis. It was a prospective observational study conducted in Department of Surgery, Rajah Muthiah Medical College Hospital (RMMCH), Annamalai University.Results: This study reveals that male patients 60% are more prone to develop diabetic foot ulcer than the female patients 40%. Patients of 50 to 60 age group 32% has higher prevalence of DFU. The most commonly prescribed antibiotics are metronidazole 48% and cefotaxime 48% followed by piperacillin and tazobactam combination 30%, ciprofloxacin 20%, linezolid 18%, amoxicillin and clavulanic acid combination 12%, cefixime 6%, clindamycin 4%, amikacin 4%, faropenam 4%, ceftriaxone 2%, amoxicillin 2%, gentamicin 2%, cefoperazone sodium and sulbactam combination 2%.Conclusions: Lack of antibiotic sensitivity test leads to growth of organism, wrong antibiotic selection and irrational use of antibiotics. And also observed patient developed resistance to linezolid antibiotic when used as a first choice of drug to treat diabetic foot infection including methicillin-resistant Staphylococcus aureus (MRSA) infected patients.

The potential risk factors of nephrotoxicity during vancomycin therapy in Chinese adult patients

ObjectiveTo evaluate potential risk factors that may make patients susceptible to nephrotoxicity in those concomitantly receiving vancomycin in the hospital.MethodsThis was a single-centre retrospective analysis of patients treated with vancomycin...

Application of antibiotics in treatment of coronavirus disease 2019 in a designated hospital.

To explore the prescribing habits of doctors, and to provide basis for rational use of antibiotics in clinical practice via investigating and analyzing the applications of antibiotics in treatment of coronavirus disease 2019 (COVID-19) in the designated hospital. Specification, quantity, amount, defined daily dose system (DDDs), defined daily dose consumption (DDDc), antibiotics use density (AUD), composition, frequency of use, combined use of antibacterial drugs used in the hospital were analyzed between Feb. 2020 and Mar. 2020. A total of 25 antibiotic drugs in 12 categories were used. The total cost for antibiotic drugs was 1 million 238 thousand yuan, in which quinolone accounts for 48%, the third generation cephalosporin/lactamase inhibitors accounts for 15.86%, antifungals accounts for 14.17%, oxazolidone accounts for 13.46%, and carbapenms account for 12.73%. The top three drugs of DDDs and AUD were moxifloxacin hydrochloride tablets, moxifloxacin hydrochloride and sodium chloride injection, cefoperazone sodium and sulbactam sodium for injection. The proportion of patients who had been used more than two kinds of antibiotics was 22.36%. Broad-spectrum, high-potency antibiotics are used at the beginning of COVID-19 treatment. The varieties of antibiotics meet the requirements of the management of antibiotics, and the utilization rate of antibiotics and the cost proportion of antibiotics in COVID-19 patients are within a reasonable range.In the future, for the treatment of COVID-19, we should continue to summarize the experience, improve the strategies, and rationally apply antibiotics on the basis of guidelines.

Systematic research to overcome newly emerged multidrug-resistant bacteria.

In the 1980s, I found that the chromosomal β-lactamase of Klebsiella pneumoniae LEN-1 showed a very high similarity to the R-plasmid-mediated penicillinase TEM-1 on the amino acid sequence level, and this strongly suggested the origination of TEM-1 from the chromosomal penicillinases of K. pneumoniae or related bacteria. Moreover, the chromosomal K1 β-lactamase (KOXY) of Klebsiella oxytoca was found to belong to the class A β-lactamases that include LEN-1 and TEM-1, although KOXY can hydrolyze cefoperazone (CPZ) like the chromosomal AmpC-type cephalosporinases of various Enterobacteriaceae that can hydrolyze several cephalosporins including CPZ. Furthermore, my collaborators and I found plural novel serine-type β-lactamases, such as MOX-1, SHV-24, TEM-91, CTX-M-64, CMY-9, CMY-19, GES-3, GES-4, and TLA-3, mediated by plasmids. Besides these serine-type β-lactamases, we also first identified exogenously acquired metallo-β-lactamases (MBLs), IMP-1 and SMB-1, in imipenem-resistant Serratia marcescens, and the IMP-1-producing S. marcescens TN9106 became the index case for carbapenemase-producing Enterobacteriaceae. I developed the sodium mercaptoacetic acid (SMA)-disk test for the simple identification of MBL-producing bacteria. We were also the first to identify a variety of plasmid-mediated 16S ribosomal RNA methyltransferases, RmtA, RmtB, RmtC, and NpmA, from various Gram-negative bacteria that showed very high levels of resistance to a wide range of aminoglycosides. Furthermore, we first found plasmid-mediated quinolone efflux pump (QepA) and fosfomycin-inactivating enzymes (FosA3 and FosK). We also first characterized penicillin reduced susceptible Streptococcus agalactiae, macrolide-resistant Mycoplasma pneumoniae, as well as Campylobacter jejuni, and Helicobacter pylori, together with carbapenem-resistant Haemophilus influenzae. We constructed a PCR-based open reading frame typing method for rapid identification of Acinetobacter baumannii international clones.

Discovery of specific HDAC6 inhibitor with anti-metastatic effects in pancreatic cancer cells through virtual screening and biological evaluation.

Histone deacetylase 6 (HDAC6) has been demonstrated to play a major role in cell motility and aggresome formation, and HDAC6 inhibition is therefore considered as a promising epigenetic strategy for cancer treatment. At present, only a minority of compounds have been reported as HDAC6 inhibitors, so specific HDAC6 inhibitors with safety profile need to be discovered urgently. In this paper, HDAC6 inhibitors with diverse structures were used to generate the pharmacophore model by ligand-based method, which contained two hydrogen bond acceptors and two hydrophobic groups. A combined virtual screening based on pharmacophore model and molecular docking was adopted to screen potential HDAC6 inhibitors. Subsequently, the HDAC6 inhibitory activity of the hit compounds were evaluated using an in vitro enzyme binding inhibition assay. The experimental results illustrated that cefoperazone sodium had the strongest inhibitory effect on HDAC6 among the six screened compounds, and its IC50 value was 8.59±1.06μM. Cefoperazone sodium significantly catalyzed the hyperacetylation of α-tubulin but not histone H3, proving that cefoperazone sodium was a selective inhibitor of HDAC6. Since the expression of HDAC6 plays an important role in cancer metastasis, the effects of cefoperazone sodium on migration and invasion of human pancreatic cancer PANC-1 cells were further investigated by wound healing and transwell chamber assays. It was found that cefoperazone sodium could evidently inhibit the migration and invasion of PANC-1 cells. Furthermore, the binding pattern of inhibitor at the active site of the crystal structure was revealed by molecular docking, providing a reference value for the structural design and optimization of HDAC6 inhibitors. This study provides a systematic virtual screening approach for discovering HDAC6 active inhibitors, and by which the specific effect of cefoperazone sodium against HDAC6 was found, suggesting its potential application on cancer therapy.

The report of two cases infection with novel coronavirus (2019-ncov) after kidney transplantation and the association literature analyzation/ 中华器官移植杂志

Objective To investigate the clinical experience of patients with novel coronavirus (2019-ncov) infection after kidney transplantation. Method Clinical data of two patients with 2019-nCoV infection after renal transplantationin Jan 2020 Renmin Hospital of Wuhan Universiyt were retrospectively analyzed.Case 1 was a 48-year-old male with CMV pneumonia secondary to 2019-nCoV infection at 4 months after transplantation. CT imaging showed multiple patchy ground-glass images of both lungs. Case 2 was a 59-year-old male, who was screened positive for 2019-nCoV nucleic acid due to fever at 9 days after renal transplantation and showed no clinical manifestations of pneumonia. After diagnosis, case 1 was transferred to a designated hospital for isolation. Treatment regimens: cefoperazone sulbactam sodium + linezolid to resist infection, gamma globulin to enhance immunity function, methylprednisolone to control inflammatory response, antiviral regimens including arbidol tablets + lopina-velitonavir tablets. Case 2 was treated with isolated treatment in a single room. The treatment plan included anti-infection (cefoperazone sulbactam sodium), enhancing immunity function (gamma globulin), antivirus therapy with arbidol and other symptomatic treatment. Result Follow up with 3 weeks, case 1 recovered with renal dysfunction, nucleic acid test with nasopharyngeal swabs turned negative, and pulmonary imaging improved. Case 2 showed no obvious clinical symptoms, and the nucleic acid test of nasopharyngeal swabs turned negative for 3 times. Conclusion Renal transplant recipients should receive fine protection to avoid exposure to high-risk environments. Diagnosis should be defined with combination of clinical manifestations, nucleic acid test and pulmonary imaging. At present, there are no antiviral drugs and symptomatic treatment is the main choice. Key words: 2019-nCov; NCP; Kidney transplant; Level III Protection

Severe Coronavirus disease 2019 successfully treated with glucocorticoid and high-dose intravenous immunoglobulin: A case report and analysis of clinical experience

Objective To report a case of severe Coronavirus disease 2019 (COVID-19) that had been successfully treated with glucocorticoid and intravenous immunoglobulin therapy. Methods and results The patient was a healthcare provider in Wuhan City who was taking care of COVID-19 patients before the onset of the disease. He started to cough with a little white sticky sputum on January 16, 2020 and had a fever on January 22 (up to 38.5 ℃) before admission. CT results showed mild exudation in both lungs. Oral oseltamivir and intravenous moxifloxacin, cefoperazone and sulbactam sodium were given in addition to nutritional support. On January 26, the patient had chest tightness and shortness of breath. A swab test was positive for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) nucleic acid, and chest CT results showed moderate exudation in both lungs. On January 28, shortness of breath worsened and intravenous methylprednisolone (40 mg, qd) and immunoglobulin (10 g, qd) were given. On January 30, shortness of breath further worsened;he had a body temperature of 40.7 ℃, pulse oxygen saturation (SpO2) of 83% with oxygen inhalation at 10 L/min, and lymphocyte count of 0.5×109/L. The dose of methylprednisolone and immunoglobulin were adjusted to 40 mg, q12h and 20 g, qd, respectively. Subcutaneous injection of thymalfasin (1.6 mg, qd) was added. Then the body temperature returned to normal, and symptoms such as chest tightness and shortness of breath were gradually improved. On January 31, SpO2 was 88% with oxygen inhalation at 10 L/min and a chest CT results revealed large amount of exudation in both lungs. On February 2, SpO2 was 95% with oxygen inhalation at 5 L/min and the dose of methylprednisolone was then gradually reduced. A chest CT results on February 3 revealed improved lung inflammation, and a throat swab on February 4 and 9 was negative for SARS-CoV-2 nucleic acid. Conclusion Glucocorticoid should be used with caution in patients with early and mild COVID-19. However, appropriate dosage of glucocorticoid can be used to modulate lung inflammation in patients with decompensated respiratory failure. Additionally, large dose of immunoglobulin can be given if necessary.

Meta-analysis of randomized controlled trials on effect of Tanreqing Injection combined with Western medicine on acute exacerbation of chronic bronchitis

To systematically review the effectiveness and safety of Tanreqing Injection in treating acute exacerbation of chronic bronchitis( AECB). CNKI,Wan Fang,VIP,CBM,Medline,Cochrane Library,EMbase and Web of Science were retrieved,and randomized controlled trials for the effect of Tanreqing Injection in the treatment of acute exacerbation of chronic bronchitis were screened. The quality of the included studies was evaluated according to the Cochrane Handbook's evaluation criteria. The data was analyzed by RevMan 5.3. Totally 23 RCTs involving 1 901 patients were included,including 952 in the experimental group and 949 in the control group. The Meta-analysis demonstrated that in terms of the disappearance time of fever,the group of Tanreqing Injection combined with the conventional therapy was superior to conventional therapy group( RR =-1. 03,95%CI[-1. 45,-0. 62],P<0. 000 01); compared with the conventional therapy group,the group of Tanreqing Injection combined with conventional therapy had a higher cure rate for AECB( RR = 1. 17,95% CI[1. 13,1. 23],P < 0. 000 01). The group of Tanreqing Injection combined with levofloxacin had a higher cure rate for AECB than the levofloxacin group( RR = 1. 23,95% CI[1. 08,1. 41],P = 0. 002). The group of Tanreqing Injection combined with cefuroxime had a higher cure rate for AECB than the cefuroxime group( RR = 1. 22,95%CI[1. 05,1. 42],P = 0. 01).The group of Tanreqing Injection combined with cefoperazone sodium and sulbactam sodium had a higher cure rate for AECB than the group of cefoperazone sodium and sulbactam sodium( RR = 1. 22,95% CI[1. 04,1. 44],P = 0. 02). The outcomes of disappearance time of cough and expectoration had a huge heterogeneity,so were used for descriptive analysis. The adverse reactions mainly included skin rash,dizziness,gastrointestinal reactions. Based on the available data and the results of the analysis,the group of Tanreqing Injection combined with Western medicine has a higher cure rate for acute exacerbation of chronic bronchitis,and the effect in reducing symptoms disappearance time. In view of the limited number of included studies,small sample size and low methodological quality,the results of this study need to be confirmed with high-level clinical trials.

Clinical characteristics of elderly patients with disulfiram-like reaction: a retrospective analysis of 19 cases

Objective To analyze the clinical characteristics of elderly patients with disulfiram-like reaction, in order to raise awareness of this disease. Methods Clinical data of 19 elderly patients diagnosed as disulfiram-like reaction in the emergency department of Beijing Hospital from January 2012 to March 2017 were retrospectively analyzed.Disulfiram-like reaction was diagnosed by comprehensive data of the drugs-induced disulfiram-like reaction, related clinical manifestations, auxiliary examination, treatment response, and by differential diagnosis. Results All of 19 patients were male, with one or more chronic disease, mean ± SD age were 75.6±5.1 years.Of 19 patients, 16 patients were taking antibiotics, including ceftriaxone, cefoperazone sodium sulbactam, cefpropene, cefuroxime and moxifloxacin, and other patients received warfarin sodium, glimepiride and metformin before the onset of disulfiram-like reaction.Clinical manifestations of disulfiram-like reaction mainly involved the cardiovascular system such as palpitation, chest distress, angina, hypotension, etc., and might be accompanied by dizziness, facial flushing, awareness disorder, gastrointestinal hemorrhage, renal dysfunction, etc.The myocardial ischemia in ECG was observed in 13 patients, the elevated serum troponin in 3 patients, and a continuing organ dysfunction in 1 patient. Conclusions The elderly patients with disulfiram-like reaction are mainly male, with various pathogenic factors and dangerous prognosis.The symptoms of cardiovascular system are obvious, including arrhythmia, myocardial injury, heart failure, shock and other serious cardiovascular complications. Key words: Disulfiram; Alcoholism; Antibiotc

Complete Genome Sequence of Photobacterium damselae Subsp. damselae Strain SSPD1601 Isolated from Deep-Sea Cage-Cultured Sebastes schlegelii with Septic Skin Ulcer.

Photobacterium damselae subsp. damselae (PDD) is a Gram-negative bacterium that can infect a variety of aquatic organisms and humans. Based on an epidemiological investigation conducted over the past 3 years, PDD is one of the most important pathogens causing septic skin ulcer in deep-sea cage-cultured Sebastes schlegelii in the Huang-Bohai Sea area and present throughout the year with high abundance. To further understand the pathogenicity of this species, the pathogenic properties and genome of PDD strain SSPD1601 were analyzed. The results revealed that PDD strain SSPD1601 is a rod-shaped cell with a single polar flagellum, and the clinical symptoms were replicated during artificial infection. The SSPD1601 genome consists of two chromosomes and two plasmids, totaling 4,252,294 bp with 3,751 coding sequences (CDSs), 196 tRNA genes, and 47 rRNA genes. Common virulence factors including flagellin, Fur, RstB, hcpA, OMPs, htpB-Hsp60, VasK, and vgrG were found in strain SSPD1601. Furthermore, SSPD1601 is a pPHDD1-negative strain containing the hemolysin gene hlyAch and three putative hemolysins (emrA, yoaF, and VPA0226), which are likely responsible for the pathogenicity of SSPD1601. The phylogenetic analysis revealed SSPD1601 to be most closely related to Phdp Wu-1. In addition, the antibiotic resistance phenotype indicated that SSPD1601 was not sensitive to ceftazidime, pipemidic, streptomycin, cefalexin, bacitracin, cefoperazone sodium, acetylspiramycin, clarithromycin, amikacin, gentamycin, kanamycin, oxacillin, ampicillin, and trimethoprim-sulfamethoxazole, but only the bacitracin resistance gene bacA was detected based on Antibiotic Resistance Genes Database. These results expand our understanding of PDD, setting the stage for further studies of its pathogenesis and disease prevention.

Mineralization of cefoperazone in acid medium by the microwave discharge electrodeless lamp irradiated photoelectro-Fenton using a RuO2/Ti or boron-doped diamond anode.

The mineralization of 125 mL of 50-300 mg L-1 cefoperazone (CFPZ) has been comparatively studied by electrochemical advanced oxidation processes (EAOPs) like anodic oxidation (AO), electro-Fenton (EF) and photoelectro-Fenton (PEF) with a RuO2/Ti or boron-doped diamond (BDD) anode and an activated carbon fiber (ACF) cathode. A microwave discharge electrodeless lamp (MDEL) was used as the UV source in PEF process. CFPZ decays always followed pseudo-first-order kinetics and their constant rates increased in the order: AO < EF < MDEL-PEF, regardless of anode types. Higher mineralization was achieved in all methods using BDD instead of RuO2/Ti, while the most potent BDD-MDEL-PEF gave 88% mineralization under its optimum conditions of 0.36 A, pH 3.0 and 1.0 mmol L-1 Fe2+. The synergistic mechanisms were explored by quantifying the electrogenerated H2O2 and formed •OH, in which 2.27 and 2.58 mmol L-1 H2O2 were accumulated in AO-H2O2 with RuO2/Ti or BDD anode, respectively, while 92.0 and 263.5 μmol L-1 •OH were generated in EF with RuO2/Ti or BDD anode, respectively. The oxidation power of EAOPs with different anodes was also compared by measuring the evolutions of NO3- and NH4+ as well as four generated carboxylic acids including oxalic, oxamic, formic and fumaric acids.

Spectroscopic and Molecular Docking Investigations on the Effect of the Interaction Between Cefoperazone Sodium and Papain to Drug Efficacy

Under the experimental condition of pH=7.40, papain (PAPA) was used as the detection object, and the binding behavior of cefoperazone sodium (CFZ) and PAPA at three temperatures was studied by multi-spectroscopy and molecular docking. The results showed that CFZ can effectively quench the endogenous fluorescence of PAPA, form a 1:1 complex, and change the conformation of PAPA. At 293 K, the fluorescence intensity of the system had a good linear relationship with the CFZ concentration in the range of 4.0×10-6 ∼ 1.0×10-4 mol/L. The detection limit of the method was 2.43×10-6 mol/L (n=10), indicating that the reaction can be used to achieve rapid determination of CFZ content in the actual drug. Based on the experimental data, a mathematical model combining CFZ and PAPA was established. When the peak plasma concentration of CFZ was 106.0 mg/L after intravenous infusion of 1 g, the drug binding rate of CFZ-PAPA system was 2.70 %, indicating the combination of CFZ and PAPA did not affect the efficacy of CFZ, that is, when taking CFZ, it is safe to consume PAPA. Molecular simulation studies had showed that the interaction between CFZ and PAPA had not only electrostatic forces but also hydrogen bonding, which was consistent with the results of spectroscopy and thermodynamic studies.

Microbiological profile of urinary tract infection in a tertiary care hospital

Background: Urinary tract infections are amongst the most common infections encountered in clinical practice. Area specific monitoring studies aimed to gain knowledge about the type of pathogens responsible for UTIs and their resistance patterns may help the clinician to choose the correct empirical treatment. Objective: We aimed to study the antibiotic resistance pattern of the urinary pathogens isolated from patients in our tertiary care hospital. Methods: This observational study was conducted at N.H.L. Medical College and V.S. Hospital, Ahmedabad Gujarat, India from January to June 2016. The study included all the patients who were admitted or visited the outpatient department in the hospital with symptoms of UTI and had UTI confirmed by positive urine culture reports. Culture and antibiotic susceptibility was carried out as per standard microbiological procedures. Results: Significant bacteriuria was present in 24.26% of the samples, 64.58% were sterile and 11.16% showed insignificant bacteriuria. The most common pathogens isolated were Escherichia coli (61.42%), Klebsiella spp (14.22%) and Pseudomonas aeruginosa (8.02%). For enterobacteriaceae isolates the mean resistance was low for cefoperazone sulbactam (34.4%), amikacin (29.4%), nitrofurantoin (27.6%) and carbapenems (30%). Isolates of Pseudomonas aeruginosa and Acinetobacter baumannii were highly resistant to multiple antimicrobial agents. Conclusion: A high isolation rate of pathogens from urine samples of clinically suspected UTI shows a good correlation between clinical findings and microbiological methods. The antibiotics commonly used in UTIs are less effective. Regular monitoring is required to establish reliable information about resistance pattern of urinary pathogens for optimal empirical therapy of patients with UTIs. Key Words: Urinary Tract Infection, Antibiotic Resistance, Antibiogram.

A reductant colorimetric method for the rapid detection of certain cephalosporins via the production of gold and silver nanoparticles

A simple colorimetric method for the quantitative detection of two cephalosporins, cefoperazone (CFZ) and cefepime (CPM), has been developed and validated for the application in clinical and quality control laboratories. The method was based on exploiting the reducing properties of cephalosporins due to the 7-aminocephalosporanic acid dihydrothiazine and a β-lactam ring to produce gold (GNPs) or silver (AgNPs) nanoparticles from their corresponding metal solutions. The resulting nanoparticles exhibited surface plasmon resonance signals at 530–550 nm or 430 nm for GNPs or AgNPs, respectively, with an intensity dependent on drug concentration that permits the quantitative analysis. Furthermore, the resulting nanoparticles were characterised using a dynamic light scattering instrument and transmission electron microscopy. Factors influence the reaction, such as the reagents volume, pH, temperature and reaction time, have been studied and optimised. In addition, the study was validated according to the official guidelines and extended to evaluate the antimicrobial activity to assess potential drug degradation during the analysis. Overall, the method developed in this study can be used for the quantitative analysis of CFZ and CPM in pure forms and pharmaceutical preparations with relatively good sensitivity and selectivity as well as, acceptable accuracy and precision.

17 PERIPARTUM ANTIBIOTIC EXPOSURE INDUCES PERSISTENT GUT DYSBIOSIS, IMPAIRS THE DEVELOPMENT OF IMMUNE TOLERANCE, AND INCREASES RISK FOR INFLAMMATORY BOWEL DISEASE IN GENETICALLY SUSCEPTIBLE OFFSPRING

The prevalence and incidence of inflammatory bowel diseases (IBD) has rapidly increased over the past century. Although the etiology of IBD remains unclear, changes in societal norms, environment, diet, and lifestyles are likely contributory factors that promote IBD on a background of genetic susceptibility. The imbalance of intestinal microbiota (dysbiosis) is caused by various factors and it has been suggested that dysbiosis results in disturbances in host-microbe interactions leading to the skewed immune system and IBD onset. Epidemiological studies suggest an association between antibiotic exposure in early childhood and increased risk for IBD development. Although dysbiosis in early life may be particularly profound since it could be a critical developmental window for both intestinal microbiota and the immune system, no direct causal links or mechanistic insights have yet been established. In the present study, we employed the IL-10 deficient (IL-10 KO) genetically susceptible murine colitis model to examine a causal link between antibiotic-induced dysbiosis in early life with the onset of IBD later life. We investigated the impacts of the broad-spectrum antibiotic, cefoperazone (CPZ), on the incidence of spontaneous colitis and chemical (dextran sulfate sodium; DSS)-induced colitis in offspring when administered during the preterm and post-natal (peripartum) periods. CPZ is an FDA-approved third-generation cephalosporin antibiotic that is commonly used during pregnancy and the neonatal period, therefore our study was designed to recapitulate common clinical practices. The 16S rRNA gene amplicon sequencing analysis was performed to assess the gut bacterial compositions. Peripartum CPZ exposure caused gut microbial dysbiosis in dams. This dysbiosis was vertically transmitted to litters and persisted into their adulthood. Furthermore, the metagenomic shot-gun sequencing analysis showed that not only was persistent community membership but also functional alterations of intestinal microbiota as a whole were evident in offspring. Fecal microbiota transplantation from untreated and CPZ-exposed dams into germ-free IL-10 KO females demonstrated that CPZ-induced dysbiosis resulted in a skewed immune system in their subsequent offspring. Together, our findings show that early life exposure to maternal CPZ-induced dysbiosis leads to a persistent dysbiosis, impaired development of immune tolerance to commensal microbiota, and increases IBD risk in IL-10KO offspring. This study supports a potential role of maternal dysbiosis during the peripartum period as a risk factor for IBD in genetically susceptible offspring but also the idea that acquisition of specific microbes early in life is essential for maintaining health later in life.

17 PERIPARTUM ANTIBIOTIC EXPOSURE INDUCES PERSISTENT GUT DYSBIOSIS, IMPAIRS THE DEVELOPMENT OF IMMUNE TOLERANCE, AND INCREASES RISK FOR INFLAMMATORY BOWEL DISEASE IN GENETICALLY SUSCEPTIBLE OFFSPRING

The prevalence and incidence of inflammatory bowel diseases (IBD) has rapidly increased over the past century. Although the etiology of IBD remains unclear, changes in societal norms, environment, diet, and lifestyles are likely contributory factors that promote IBD on a background of genetic susceptibility. The imbalance of intestinal microbiota (dysbiosis) is caused by various factors and it has been suggested that dysbiosis results in disturbances in host-microbe interactions leading to the skewed immune system and IBD onset. Epidemiological studies suggest an association between antibiotic exposure in early childhood and increased risk for IBD development. Although dysbiosis in early life may be particularly profound since it could be a critical developmental window for both intestinal microbiota and the immune system, no direct causal links or mechanistic insights have yet been established. In the present study, we employed the IL-10 deficient (IL-10 KO) genetically susceptible murine colitis model to examine a causal link between antibiotic-induced dysbiosis in early life with the onset of IBD later life. We investigated the impacts of the broad-spectrum antibiotic, cefoperazone (CPZ), on the incidence of spontaneous colitis and chemical (dextran sulfate sodium; DSS)-induced colitis in offspring when administered during the preterm and post-natal (peripartum) periods. CPZ is an FDA-approved third-generation cephalosporin antibiotic that is commonly used during pregnancy and the neonatal period, therefore our study was designed to recapitulate common clinical practices. The 16S rRNA gene amplicon sequencing analysis was performed to assess the gut bacterial compositions. Peripartum CPZ exposure caused gut microbial dysbiosis in dams. This dysbiosis was vertically transmitted to litters and persisted into their adulthood. Furthermore, the metagenomic shot-gun sequencing analysis showed that not only was persistent community membership but also functional alterations of intestinal microbiota as a whole were evident in offspring. Fecal microbiota transplantation from untreated and CPZ-exposed dams into germ-free IL-10 KO females demonstrated that CPZ-induced dysbiosis resulted in a skewed immune system in their subsequent offspring. Together, our findings show that early life exposure to maternal CPZ-induced dysbiosis leads to a persistent dysbiosis, impaired development of immune tolerance to commensal microbiota, and increases IBD risk in IL-10KO offspring. This study supports a potential role of maternal dysbiosis during the peripartum period as a risk factor for IBD in genetically susceptible offspring but also the idea that acquisition of specific microbes early in life is essential for maintaining health later in life.

Clinical features and prognosis of children with hematological malignancies after chemotherapy with Stenotrophomonas maltophilia blood stream infection

Objective To investigate the clinical features and prognosis of children with hematological malignancies after chemotherapy accompanied with Stenotrophomonas maltophilia blood stream infection (BSI). Methods The clinical data and antimicrobial susceptibility test of 25 hospitalized children with hematological malignancies who were diagnosed as Stenotrophomonas maltophilia BSI in the Department Pediatric Hematology of Fujian Medical University Union Hospital from January 2013 to May 2018 were analyzed retrospectively. Results A total of 25 children, including 18 males and 7 females with the median age 4 (1-11) years old were diagnosed as hematological malignancies and all received chemotherapy. The frequent risk factors of Stenotrophomonas maltophilia BSI in children with hematological malignancies included prior carbapenem antibiotic for more than 1 week (80%, 20/25), and neutropenia for more than 1 week (68%,17/25) and indwelling central venous catheter (48%, 12/25). Clinically, the main manifestations included neutropenia with fever after chemotherapy; however, anti-pseudomonas cephalosporin/carbicillin antibiotic combined with vancomycin and anti-fungal therapies were ineffective. Drug susceptibility test showed that all strains were sensitive to compound sulfamethoxazole, levofloxacin and minocycline. Before blood culture report, 3 patients died of septic shock, pulmonary hemorrhage and respiratory failure; after blood culture report, the treatment regimens were adjusted to compound sulfamethoxazole combined with cefoperazone sodium and sulbactam sodium (200-260 mg·kg-1·d-1) or levofloxacin anti-infective. Finally, 18 patient was cured, 2 patients died of the bad efficacy of underlying diseases, and 2 patients died of pulmonary hemorrhage. The overall fatality rate was 28% (7/25) and the related mortality rate caused by Stenotrophomonas maltophilia BSI was 20% (5/25). Conclusion Stenotrophomonas maltophilia BSI in children with hematological malignancies after chemotherapy has a high fatality rate, and better basic disease control and appropriate antibacterial therapy are the key to improve the prognosis. Key words: Hematologic neoplasms; Hematologic diseases; Stenotrophomonas maltophilia; Blood stream infection; Child; Prognosis

Analysis of clinical distribution and drug resistance of pseudomonas aeruginosa in the Sixth Hospital of Ningbo

Objective To investigate the drug resistance of pseudomonas aeruginosa changes in the Sixth Hospital of Ningbo, Zhejiang province, in order to provide a basis for clinical rational use of antimicrobial drugs. Methods The clinical distribution and drug resistance to commonly used antimicrobial agents in 1970 strains of pseudomonas aeruginosa from the Sixth Hospital of Ningbo in 2014-2016 were retrospectively analyzed.The data were statistically analyzed using WHONET 5.6 software, excel software, SPSS17.0 software. Results Clinical specimens isolated 15 963 strains of pathogenic bacteria, including 1 970 strains pseudomonas aeruginosa, accounted for 12.34%.The detection rate of multi-drug resistance pseudomonas aeruginosa(MDRPA) reduced year by year, the detection rate in 2014 was 60.95%, which in 2015 was 58.00%, which in 2016 was 45.58%.Pseudomonas aeruginosa was mainly isolated from sputum(67.16%), followed by wound secretion(23.05%). The detection rate of pseudomonas aeruginosa in ICU and geriatric department was higher, accounted for 20.25% and 25.28% respectively.The resistance of pseudomonas aeruginosa to many kinds of antimicrobial agents was increased from 2014 to 2016, the resistance rates to cefoperazone/ sulbactam were>30% in 3 years, the resistance rate to imipenem was higher than meropenem.The drug resistance of pseudomonas aeruginosa isolated from sputum in ICU was higher than that in geriatric department(all P<0.05). Conclusion Pseudomonas aeruginosa nosocomial infection in the Sixth Hospital of Ningbo is severe, the infection rate and drug resistance monitoring should be strengthened, in order to reduce the infection rate and drug resistance. Key words: Pseudomonas aeruginosa; Drug resistance, bacterial; Infection; Anti-bacterial agents; Small-area analysis

Luminescent Lanthanide-Collagen Peptide Framework for pH-Controlled Drug Delivery.

Collagen mimetic scaffolds play a pivotal role in regenerative medicine and tissue engineering due to their extraordinary structural and biological features. We have herein, for the first time, reported the construction of luminescent lanthanide-collagen peptide hybrid three-dimensional nanofibrous scaffolds, which well mimic the characteristic architectural structure of native collagen. Three collagen mimetic peptides, composed of repetitive central (GPO)7 sequences and altered terminal amino acids, have been shown to consistently self-assemble to form biocompatible nanofibers under the trigger of a variety of lanthanide ions, which also functionalize the assembled materials with easily tunable photoluminescence. Furthermore, the collagen peptide-lanthanide hybrid scaffolds possess programmable pH-responsive features. The lanthanide ion-mediated assembly of all three collagen peptides are conveniently and reversibly regulated by pH, while their pH-dependent patterns are finely tuned by the identity of terminal amino acids. Using camptothecin and cefoperazone sodium as two model drugs, the drug-loading and releasing efficiency of the collagen peptide-lanthanide scaffolds are nicely modulated by pH, demonstrating the efficacy of these nanofibrous scaffolds as pH-responsive drug carriers. These novel luminescent collagen peptide-lanthanide scaffolds provide a facile system for pH-controlled drug delivery, suggesting promising applications in the development of therapies for many diseases.