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To enhance the quality control of tebipenem pivoxil and establish its quality criteria,the synthetic route of tebipenem pivoxil was analyzed and five related substances (P1,P2,P6,P8 and P9)were synthesized and characterized by 1H NMR and MS.The purities of the related substances were over 95% via HPLC detec-tion.The target compounds can be used as the reference of the related substances in the quality control of tebi-penem pivoxil.The starting materials were cheap and easy to obtain;the reaction conditions were mild.
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Objective To investigete a new synthetic route for carbapenem skeleton(1)for industrial production. Methods (3S,4R)-4-acetoxy-3-[(1R)-(tert-butyldimethylsilyloxy)ethyl]azetidin-2-one(4-AA)was used as raw material,and 1 was obtained from it through a homemade chiral auxiliary zinc powder catalyzed Reformatsky reaction,hydrolysis,the introduction of β-carboxyl es?ter structure,deprotection,cyclization,and activation by diphenyl chlorophosphate. The each key process was optimized,and the structures of intermediate and target compounds were confirmed by MS,GC-MS and 1H NMR.Results and Conclusion The total yield was 19.9%.The improved process conditions are mild,easy to operate,and suitable for industrial production.
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Objective To investigate the clinical characteristics and antibiotic resistance of the bloodstream infections due to NDM-1 producing Klebsiella pneumoniae in children.Methods The nonduplicate carbapenem-resistant Klebsiella pneumoniae (CRKp) strains isolated from blood samples were collected in Beijing Children's Hospital from January 2011 to August 2014.Antimicrobial susceptibility was tested with broth microdilution method.PCR amplification and DNA sequencing were conducted targeting blaNDM-1 genes.Medical records were reviewed and analyzed.Results Of the 52 CRKp strains,blaNDM-1 gene was detected in 28 strains.All NDM-l-producing strains were multidrug-resistant.All the 28 isolates were resistant to penicillin,cephalosporins,piperacillin-tazobactam,and imipenem.More than 75.0％ of these NDM-1-producing strains were resistant to aztreonam,trimethoprim-sulfamethoxazole,gentamicin,and meropenem (92.9％,26/28).NDM-1-producing isolates had higher carbapenem MICs than non-NDM-1-producing isolates.Most (82.1％,23/28) of the NDM-1-producing isolates were isolated from hematology-oncology ward.The most common underlying disease was hematologic malignancy (78.6％,22/28).Febrile neutropenia was found in 20 (71.4％) patients.No difference was found between NDM-1-producing and non-NDM-1-producing CRKp infection in terms of repeated hospitalization (P=0.202),prior antibiotic use (P=0.615),underlying diseases (P=0.856),and deep venous catheter (P=0.099).After the susceptibility results were available,37 patients received carbapenembased combination regimen.The mortality did not show difference between NDM-1 producing CRKp infections and non-NDM-1-producing CRKp infections,7.1％ (2/28) vs.12.5％ (3/24),P=0.625.Conclusions The NDM-1 carbapenemase producing Klebsiella pneumoniae is emerging in this hospital.NDM-1-producing strains are resistant to multiple antimicrobial agents,associated with higher carbapenem MIC value.However,no difference was found in the clinical features between the bloodstream infections due to NDM-1-producing strain and those due to non-NDM-1-producing strains.
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Objective@#To reveal the molecular epidemiological characteristics of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) isolated from a three level teaching hospital in Beijing.@*Methods@#Pulsed field gel electrophoresis (PFGE) was carried out to subtyping 375 CRKP isolated in that hospital between May 2010 and October 2015. Fifteen strains were chose based on the PFGE patterns to be analyzed by multi-locus sequence typing (MLST) and detection of carbapenem-resistance genes. One strain (A1502) was selected for whole genome sequencing and analyzing.@*Results@#The 375 CRKP were divided into 140 PFGE types, among which five types contained more than five strains. The dominant types were distributed in different time periods and wards. Among the 15 strains tested by MLST and carbapenem-resistance genes detection, 13 were ST11 strains carrying KPC-2 gene. By genome-based typing, A1502 was clustered together with strains from other hospitals of Beijing but far from the strains from Shanghai and Hangzhou.@*Conclusion@#The CRKP epidemic clone (ST11 clone carrying KPC-2) has been spreading within single hospital and across different hospitals in Beijing.
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Abstract: INTRODUCTION: Members of the Acinetobacter genus are key pathogens that cause healthcare-associated infections, and they tend to spread and develop new antibiotic resistance mechanisms. Oxacillinases are primarily responsible for resistance to carbapenem antibiotics. Higher rates of carbapenem hydrolysis might be ascribed to insertion sequences, such as the ISAba1 sequence, near bla OXA genes. The present study examined the occurrence of the genetic elements bla OXA and ISAba1 and their relationship with susceptibility to carbapenems in clinical isolates of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex. METHODS: Isolates identified over 6 consecutive years in a general hospital in Joinville, Southern Brazil, were evaluated. The investigation of 5 families of genes encoding oxacillinases and the ISAba1 sequence location relative to bla OXA genes was conducted using polymerase chain reaction. RESULTS: All isolates presented the bla OXA-51-like gene (n = 78), and 91% tested positive for the bla OXA-23-like gene (n = 71). The presence of ISAba1 was exclusively detected in isolates carrying the bla OXA-23-like gene. All isolates in which ISAba1 was found upstream of the bla OXA-23-like gene (n = 69) showed resistance to carbapenems, whereas the only isolate in which ISAba1 was not located near the bla OXA-23-like gene was susceptible to carbapenems. The ISAba1 sequence position of another bla OXA-23-like-positive isolate was inconclusive. The isolates exclusively carrying the bla OXA-51-like gene (n = 7) showed susceptibility to carbapenems. CONCLUSIONS: The presence of the ISAba1 sequence upstream of the bla OXA-23-like gene was strongly associated with carbapenem resistance in isolates of the A. calcoaceticus-A. baumannii complex in the hospital center studied.
Subject(s)
Humans , Bacterial Proteins/genetics , DNA, Bacterial/genetics , Carbapenems/pharmacology , Acinetobacter calcoaceticus/drug effects , beta-Lactam Resistance/genetics , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology , Phenotype , Bacterial Proteins/metabolism , Brazil , Acinetobacter Infections/microbiology , Polymerase Chain Reaction , Electrophoresis, Gel, Pulsed-Field , Acinetobacter calcoaceticus/isolation & purification , Acinetobacter calcoaceticus/genetics , Acinetobacter baumannii/isolation & purification , Acinetobacter baumannii/genetics , GenotypeABSTRACT
Objective:To investigate the adverse drug reactions ( ADR) caused by carbapenem antibiotics and discuss the influen-cing factors to provide reference for the rational use of carbapenems in clinics. Methods:The ADR caused by carbapenems from March 1, 2008 to August 1, 2014 in our hospital were statistically analyzed. Results:Totally 73 cases of ADR were caused by carbapenems. The number of ADR for men and women was similar. The ADR occurred in 80-year-old people with more frequency. The incidence of ADR on the first day of administration was relative high. The ADR were mainly manifested as skin and appendages disorders and nerve system damage. Conclusion: Great attention should be paid to the ADR of carbapenems and the state of patients. The medication should be adjusted in the patients with declined renal function and nerve system basic diseases in order to reduce the damage of ADR.
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Klebsiella pneumoniae is well known as a causative agent of both community and nosocomial infections and is generally believed to be the cause of 10% of the nosocomial infection. Recently, with the widespread using of carbapenem, the isolation of carbapenem-resistant strains has been greatly increased, which bring great dififculties and challenges in clinical treat-ment. In this article, the progresses in the mechanisms of carbapenem, resistance inKlebsiella pneumoniae such as the acquisition of carbapenemases, hyperproduction of AmpC cephalosporinases or extended spectrum beta-lactamases (ESBLs) in combination with loss of the outer membrane protein, eflfux pump system, and bioiflm were reviewed.
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To critically evaluate the mechanisms of the interaction between valproic acid and carbapenem antibiotics. Research about the interaction between valproic acid and carbapenem antibiotics related case reports those were indexed from the Pubmed database. Studies to explain the decrease were carried out using rats and monkeys by the following mechanism; absorption, distribution, metabolism, and excretion of valproic acid. Carbapenem antibiotics induced a decrease of plasma concentration of valproic acid in epileptic patients during valproic acid therapy, resulting in the recurrence of epileptic seizures. Therefore, therapy with valproic acid and carbapenem antibibiotics should be avoided.