Enhancement of Acinetobacter baumannii biofilm growth by cephem antibiotics via enrichment of protein and extracellular DNA in the biofilm matrices.

AIMS: The aims were to determine the effects of subinhibitory concentrations of eight cephem and carbapenem antibiotics on the biofilm formation of Acinetobacter baumannii cells and examine their effects on pre-established biofilms. METHODS AND RESULTS: Effects of antibiotics on biofilm formation were assayed using microtitre plates with polystyrene peg-lids. Cefmetazole, ceftriaxone, ceftazidime and cefpirome increased the biomass of pre-established biofilms on pegs in the range of their sub-minimum inhibitory concentrations (MICs), whereas none increased biofilm formation by planktonic cells. Carbapenems had a negative effect. The constituents of antibiotic-induced biofilms were analysed. Ceftriaxone or ceftazidime treatment markedly increased the matrix constituent amounts in the biofilms (carbohydrate, 2.7-fold; protein, 8.9-12.7-fold; lipid, 3.3-3.6-fold; DNA, 9.1-12.2-fold; outer membrane vesicles, 2.7-3.8-fold and viable cells, 6.8-10.1-fold). The antibiotic-enhanced biofilms had increased outer membrane protein A and were resistant to the anti-biofilm effect of azithromycin. CONCLUSIONS: Some cephems increased the biomass of pre-established biofilms in the ranges of their sub-MICs. The antibiotic-enhanced biofilms possessed more virulent characteristics than normal biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: Incomplete administration of certain cephems following biofilm-related Ac. baumannii infections could adversely cause exacerbated and chronic clinical results.

Assessment of Prophylactic Carbapenem Antibiotics Administration for Severe Acute Pancreatitis: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness of prophylactic antibiotics in severe acute pancreatitis (SAP) remains a debatable issue. This meta-analysis aimed to determine the efficacy of prophylactic carbapenem antibiotics in SAP. METHODS: This meta-analysis of prophylactic carbapenem antibiotics for SAP was conducted in PubMed, EMBASE, Web of Science, MEDLINE, and Cochrane Library up to February 2021. The related bibliographies were manually searched. The primary outcomes involved infected pancreatic or peripancreatic necrosis, mortality, complications, infections, and organ failure. RESULTS: Seven articles comprised 5 randomized controlled trials and 2 retrospective observational studies, including 3,864 SAP participants. Prophylactic carbapenem antibiotics in SAP were associated with a statistically significant reduction in the incidence of infections (odds ratio [OR]: 0.27; p = 0.03) and complications (OR: 0.48; p = 0.009). Nevertheless, no statistically significant difference was demonstrated in the incidence of infected pancreatic or peripancreatic necrosis (OR: 0.74; p = 0.24), mortality (OR: 0.69; p = 0.17), extrapancreatic infection (OR: 0.64, p = 0.54), pulmonary infection (OR: 1.23; p = 0.69), blood infection (OR: 0.60; p = 0.35), urinary tract infection (OR: 0.97; p = 0.97), pancreatic pseudocyst (OR: 0.59; p = 0.28), fluid collection (OR: 0.91; p = 0.76), organ failure (OR: 0.63; p = 0.19), acute respiratory distress syndrome (OR: 0.80; p = 0.61), surgical intervention (OR: 0.97; p = 0.93), dialysis (OR: 2.34; p = 0.57), use of respirator or ventilator (OR: 1.90; p = 0.40), intensive care unit treatment (OR: 2.97; p = 0.18), and additional antibiotics (OR: 0.59; p = 0.28) between the experimental and control groups. CONCLUSIONS: It is not recommended to administer routine prophylactic carbapenem antibiotics in SAP.

[Molecular epidemiology of carbapenem resistant Klebsiella pneumoniae in a hospital in Beijing].

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.

Strategically reducing carbapenem-resistant Acinetobacter baumannii through PDCA cycle-driven antibiotic management.

PURPOSE: With the escalating global challenge of antibiotic resistance, particularly the resistance rate of Acinetobacter baumannii, the need to rationalize carbapenem antibiotic use in clinical settings has become paramount. Our study tapped into a fishbone diagram to uncover the irrationalities in applying these antibiotics and highlight potential influencing factors. METHODS: Based on these analyses, we initiated targeted intervention strategies. A PDCA cycle-based scientific management approach was implemented through the combined efforts of our antimicrobial stewardship team and relevant departments. RESULTS: Our study showed a significant post-intervention increase in the rational use of carbapenem antibiotics (P < 0.01) and a concurrent decrease in the detection of carbapenem-resistant Acinetobacter baumannii. CONCLUSION: Our findings underscore that carbapenem usage can be effectively minimized with the continuous refinements offered by the PDCA cycle, leading to a reduction in multidrug-resistant bacteria, thus fostering rational drug use in healthcare.

Carbapenems versus ß-lactam and ß-lactamase inhibitors for treatment of nosocomial pneumonia: A systematic review and meta-analysis.

Background: Carbapenems and ß-lactam and ß-lactamase inhibitors (BLBLIs) have been used empirically in nosocomial pneumonia, but their efficacy and safety are controversial. Objective: We carried out a systematic review with meta-analysis to evaluate the efficacy and safety of carbapenems versus BLBLIs against nosocomial pneumonia. Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, CNKI, Wangfang, VIP and Sinomed were searched systematically through April 29, 2023 for clinical trials comparing carbapenems with BLBLIs for treatment of nosocomial pneumonia. Random-effects models were used to evaluate the impact of treatment on the risk ratio (RR) of all-cause mortality, clinical response, microbiologic response, resistance by Pseudomonas aeruginosa, adverse effects (AEs), and serious adverse effects. The quality of the evidence was assessed with the Cochrane risk of bias tool. The review was registerted in the INPLASY (INPLASY202340113). Results: Seven randomized controlled trials containing 3306 patients met our inclusion criteria Our meta-analysis showed no significant difference in all-cause mortality (RR = 0.88, 95% confidence interval [CI] = 0.75-1.03, I2 = 0%) or clinical cure (1.02, 0.96-1.09, 30%) or clinical failure (1.19, 0.97-1.47, 0%) or microbiologic clinical cure (0.98, 0.89-1.06, 40%) or Pseudomonas aeruginosa resistance (RR 2.43, CI 0.86-6.81, 49%, P = 0.09) or adverse events (0.98, 0.93-1.02, 0%) between carbapenems groups versus BLBLIs groups, but a significant difference was found for severe adverse events (RR 0.83, CI 0.73-0.94, 0%). Conclusion: Differences in the prevalence of mortality, clinical cure, or clinical failure were not observed between carbapenems groups versus BLBLIs groups in terms of nosocomial pneumonia. The use of carbapenems was linked to a tendency towards the emergence of P. aeruginosa resistance, however, no statistically significant difference was observed.

Clinical pharmacists' involvement in carbapenem antibiotics management at Wenzhou Integrated Hospital.

BACKGROUND: Carbapenem antibiotics are a pivotal solution for severe infections, particularly in hospital settings. The emergence of carbapenem-resistant bacteria owing to the irrational and extensive use of carbapenems underscores the need for meticulous management and rational use. Clinical pharmacists, with their specialized training and extensive knowledge, play a substantial role in ensuring the judicious use of carbapenem. This study aimed to elucidate the patterns of carbapenem use and shed light on the integral role played by clinical pharmacists in managing and promoting the rational use of carbapenem antibiotics at Wenzhou Integrated Traditional Chinese and Western Medicine Hospital. AIM: To analyze carbapenem use patterns in our hospital and role of clinical pharmacists in managing and promoting their rational use. METHODS: We performed a retrospective analysis of carbapenem use at our hospital between January 2019 and December 2021. Several key indicators, including the drug utilization index, defined daily doses (DDDs), proportion of antimicrobial drug costs to total hospitalization expenses, antibiotic utilization density, and utilization rates in different clinical departments were comprehensively analyzed. RESULTS: Between 2019 and 2021, there was a consistent decline in the consumption and sales of imipenem-cilastatin sodium, meropenem (0.3 g), and meropenem (0.5 g). Conversely, the DDDs of imipenem-cilastatin sodium for injection increased in 2020 and 2021 vs 2019, with a B/A value of 0.67, indicating a relatively higher drug cost. The DDDs of meropenem for injection (0.3 g) exhibited an overall upward trend, indicating an increasing clinical preference. However, the B/A values for 2020 and 2021 were both > 1, suggesting a relatively lower drug cost. The DDDs of meropenem for injection (0.5 g) demonstrated a progressive increase annually and consistently ranked first, indicating a high clinical preference with a B/A value of 1, signifying good alignment between economic and social benefits. CONCLUSION: Carbapenem use in our hospital was generally reasonable with a downward trend in consumption and sales over time. Clinical pharmacists play a pivotal role in promoting appropriate use of carbapenems.

Interprofessional Collaboration between ICU Physicians, Staff Nurses, and Hospital Pharmacists Optimizes Antimicrobial Treatment and Improves Quality of Care and Economic Outcome.

(1) Background: Antibiotic resistance is a worldwide health threat. The WHO published a global strategic plan in 2001 to contain antimicrobial resistance. In the following year, a workshop identified crucial barriers to the implementation of the strategy, e.g., underdeveloped health infrastructures and the scarcity of valid data as well as a lack of implementation of antibiotic stewardship (ABS) programs in medical curricula. Here, we show that interprofessional learning and education can contribute to the optimization of antibiotic use and preserving antibiotic effectiveness. We have initiated interprofessional rounds on a medical intensive care unit (MICU) with a focus on gastroenterology, hepatology, infectious diseases, endocrinology, and liver transplantation. We integrated ICU physicians, hospital pharmacists, nursing staff, and medical students as well as students of pharmacy to broaden the rather technical concept of ABS with an interprofessional approach to conceptualize awareness and behavioral change in antibiotic prescription and use. Methods: Clinical performance data and consumption figures for antibiotics were analyzed over a 10-year period from 2012 to 2021. The control period covered the years 2012-2014. The intervention period comprised the years 2015-2021, following the implementation of an interprofessional approach to ABS at a MICU of a German university hospital. Data from the hospital pharmacy, hospital administration, and hospital information system were included in the analyses. A specific electronic platform was developed for the optimization of documentation, interprofessional learning, education, and sustainability. The years 2020 and 2021 were analyzed independently due to the SARS-CoV-2 pandemic and the care of numerous COVID-19 patients at the MICU. Results: Implementation of an interprofessional ABS program resulted in the optimization of antibiotic management at the MICU. The suggestions of the hospital pharmacist for optimization can be divided into the following categories (i) indication for and selection of therapy (43.6%), (ii) optimization of dosing (27.6%), (iii) drug interactions (9.4%), (iv) side effects (4.1%), and (v) other pharmacokinetic, pharmacodynamic, and pharmacoeconomic topics (15.3%). These suggestions were discussed among the interprofessional team at the MICU; 86.1% were consequently implemented and the prescription of antibiotics was changed. In addition, further analysis of the intensive care German Diagnosis Related Groups (G-DRGs) showed that the case mix points increased significantly by 31.6% during the period under review. Accordingly, the severity of illness of the patients treated at the ICU as measured by the Simplified Acute Physiology Score (SAPS) II increased by 21.4% and the proportion of mechanically ventilated patients exceeded 50%. Antibiotic spending per case mix point was calculated. While spending was EUR 60.22 per case mix point in 2015, this was reduced by 42.9% to EUR 34.37 per case mix point by 2019, following the implementation of the interprofessional ABS program on the MICU. Through close interprofessional collaboration between physicians, hospital pharmacists, and staff nurses, the consumption of broad-spectrum antibiotics, e.g., carbapenems, was significantly reduced, thus improving patient care. In parallel, the case mix and case mix index increased. Thus, the responsible use of resources and high-performance medicine are not contradictory. In our view, close interprofessional and interdisciplinary collaboration between physicians, pharmacists, and nursing staff will be of outstanding importance in the future to prepare health care professionals for global health care to ensure that the effectiveness of our antibiotics is preserved.

Inhibitory effects of indoxyl sulfate and creatinine on the renal transport of meropenem and biapenem in rats.

Carbapenem antibiotics are excreted preferentially in the urine after intravenous administration, with organic anion transporters (OATs) known to be involved in the renal tubular secretion of carbapenem antibiotics. Various uremic toxins (UTs) accumulate in the blood of patients with end-stage renal failure, and some UTs such as indoxyl sulfate (IS) and creatinine (Cr) are excreted in the urine via OATs. However, information about the possible interactions between these UTs and carbapenems in the renal secretion remains limited. In this study, we investigated the effects of IS and Cr on the renal transport of anionic meropenem and zwitterionic biapenem by using rat renal cortical slices. The uptake of meropenem and biapenem in the renal cortical slices was significantly decreased in the presence of 0.1 mM IS or 1 mM Cr. When biapenem and Cr were co-administered to rats intravenously, biapenem clearance from the plasma was clearly retarded, reflecting the current in vitro results. However, IS and Cr exerted no inhibitory effect on the uptake of metformin, a substrate of renal organic cation transporter (OCT) 2, in the renal cortical slices. Thus, our findings indicate that IS and Cr interfere with the renal secretion of carbapenem antibiotics by preferentially inhibiting OATs.

Determination of synergistic effects of antibiotics and Zno NPs against isolated E. Coli and A. Baumannii bacterial strains from clinical samples.

The mortality rates has been increased globally due to multidrug resistant (MDR) E.coli and A.baumanii bacterial strains and also there is an emerging resistance of the Enterobacteriaceae family of bacteria to Carbapenem antibiotics (CRE) in Saudi Arabia. The main aim of our research study is to isolate E.coli and A. baumannii bacterial species from various collected clinical samples and to evaluate the MIC and FICI of Colistin, Ciprofloxacin, Meropenem and ZnO NPs and in combination of Colistin, Ciprofloxacin, Meropenem with ZnO NPs. The clinical isolated strains of A. baumannii (MRO-17-13) and A. baumannii (MRO-17-25) was found to be sensitive towards colistin with 0.5 µg/mL concentration, whereas, all the isolated A. baumannii strains showed similar MIC value 2 mg/mL when tested with ZnO NPs, the MIC value for the ZnO NPs was found to be similar for all the E.coli strains 0.25 mg/mL. The effects of all Ciprofloxacin concentrations used in the study were bacteriostatic against E. coli (01UR19006568-01) strain but 1 mg/mL concentration of ZnO NPs alone is showed bactericidal activity, ZnO NPs effect was found to be concentration dependent, as highest concentration of ZnO NPs showed strongest antibacterial effect. In conclusion, more investigation is required to evaluate the acceptable concentration of Zno NPs and antibiotics selected to avoid toxicity and must be tested against more clinically isolated gram-negative bacterial strains.

Establishment of UPLC-MS/MS method for the determination of plasma concentration of three common carbapenem antibiotics / 中国药房

OBJECTIVE To establish a UPLC-MS/MS method for the determination of plasma concentration of three carbapenem antibiotics， i.e. ertapenem （ETP）， imipenem （IPM） and meropenem （MEM）. METHODS After protein precipitation with methanol， the plasma samples were separated by ACQUITY UPLC BEH C18 column （2.1 mm×50 mm， 1.7 μm） using stable isotopes of three antibiotics （ETP-D4， IPM-D4， MEM-D6） as the internal standard. The mobile phases were 98% acetonitrile +2% water +0.1% formic acid and 98% water +2% acetonitrile +0.1% formic acid， by gradient elution. The flow rate was 0.3 mL/min and the column temperature was 40 ℃. Scanning analysis was performed in the positive ion and multiple reaction monitoring mode. RESULTS The method had good specificity， good linearity （r2≥0.993） in the range of 0.2-200， 0.1-100 and 0.1-100 μg/mL of ETP， IPM and MEM， and good intra-batch and inter-batch precision and accuracy （all RE≤5.14%， all RSD≤11.15%）， the matrix effect and extraction recovery were consistent （RSD≤12.99%）. CONCLUSIONS This study establishes the UPLC-MS/MS method to simultaneously quantify the plasma concentration of ETP， IPM and MEM. The method has the advantages of simple pretreatment， short detection time and small sample quantity to meet clinical requirement.

Photochemical degradation of the carbapenem antibiotics imipenem and meropenem in aqueous solutions under solar radiation.

This paper deals with the photochemical fate of two representative carbapenem antibiotics, namely imipenem and meropenem, in aqueous solutions under solar radiation. The analytical method employed for the determination of the target compounds in various aqueous matrices, such as ultrapure water, municipal wastewater treatment plant effluents, and river water, at environmentally relevant concentrations, was liquid chromatography coupled with hybrid triple quadrupole-linear ion trap-mass spectrometry. The absorption spectra of both compounds were measured in aqueous solutions at pH values from 6 to 8, and both compounds showed a rather strong absorption band centered at about 300 nm, while their molar absorption coefficient was in the order from 9 × 103-104 L mol-1 cm-1. The kinetics of the photochemical degradation of the target compounds was studied in aqueous solutions under natural solar radiation in a solar reactor with compound parabolic collectors. It was found that the photochemical degradation of both compounds at environmentally relevant concentrations follows first order kinetics and the quantum yield was in the order of 10-3 mol einsten-1. Several parameters were studied, such as solution pH, the presence of nitrate ions and humic acids, and the effect of water matrix. In all cases, it was found that the presence of various organic and inorganic constituents in the aqueous matrices do not contribute significantly, either positively or negatively, to the photochemical degradation of both compounds under natural solar radiation. In a final set of photolysis experiments, the effect of the level of irradiance was studied under simulated solar radiation and it was found that the quantum yield for the direct photodegradation of both compounds remained practically constant by changing the incident solar irradiance from 28 to 50 W m-2.

Identifying Risk Factors for Healthcare-Associated Infections Caused by Carbapenem-Resistant Acinetobacter baumannii in a Neonatal Intensive Care Unit.

OBJECTIVES: Acinetobacter baumannii is a causative pathogen of various healthcare-associated infections (HAIs) and is particularly prevalent in high-risk hospital settings. This study aimed to determine risk factors associated with HAIs caused by carbapenem-resistant A. baumannii (CRAB) in a neonatal intensive care unit (NICU). METHODS: This prospective study was performed between January 2013 and June 2014 among NICU patients at the Mansoura University Children's Hospital, Mansoura, Egypt. Neonates who developed HAIs due to CRAB were assigned to a case group, while those infected with carbapenem-sensitive A. baumannii (CSAB) were assigned to a control group. RESULTS: Among the 124 neonates who developed A. baumannii-caused HAIs during the study period, 91 (73.4%) were caused by CRAB and 33 (26.6%) were caused by CSAB. Prematurity, premature rupture of the membranes (PROM), a previous stay in another hospital, prolonged NICU stay, the presence of invasive devices, previous exposure to carbapenems or aminoglycosides and prolonged antibiotic therapy before infection were significantly associated with CRAB-caused HAIs. A multivariate logistic regression analysis identified prematurity (adjusted odds ratio [aOR] = 25.3; P <0.01), mechanical ventilation (aOR = 18.9; P <0.01) and the previous use of carbapenems (aOR = 124.7; P <0.01) or aminoglycosides (aOR = 22.6; P = 0.04) to be independent risk factors for CRAB infections. CONCLUSION: Various risk factors were significantly associated with CRAB-caused HAIs among the studied NICU patients.

Exposure to ertapenem is possibly associated with Pseudomonas aeruginosa antibiotic resistance.

The role of antibiotic exposure in the evolution and emergence of resistance is challenging to assess. We used carbapenem-resistant Pseudomonas aeruginosa (PA) phenotypes to assess possible factors that are associated with the occurrence and prognosis of such a phenotype and to examine the possible contribution of antibiotic exposure to the evolution of antimicrobial resistance. We conducted a nested case-control study. Cases were defined as patients from whom carbapenem-resistant ureidopenicillin-sensitive PA (CRUS-PA) was isolated; matched controls were PA patients who did not have isolation of CRUS-PA. We analysed potential predictors of CRUS-PA isolation and assessed their clinical significance (mortality and eventual isolation of pan-resistant PA), taking into account antibiotic exposures. We matched 800 case-control pairs. Case patients were more likely to have been exposed to anti-PA carbapenems (OR = 6.9; 95% CI, 2.5-18.6). This finding did not apply to the administration of other antibiotics. The mortality among CRUS-PA patients was similar to that of the controls (HR, 0.8 95%; CI, 0.6-1.1). Subsequent isolation of pan-resistant PA was more frequent among case patients compared with non-pan-resistant controls (p-value <0.05). Among cases, the risk of eventual pan-resistant PA isolation was increased in ertapenem recipients, only after and not prior to the index specimen date (HR, 1.9, 95%; CI, 1.01-3.4). Therefore we suggest that the CRUS-PA phenotype may represent pan beta-lactam resistance and that antibiotic exposure is associated with evolution of PA resistance phenotypes. We demonstrate a novel association of ertapenem with sequentially appearing PA resistance patterns.

Synthesis of related substances of tebipenem pivoxil / 中国药科大学学报

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.

Synthesis of carbapenem skeleton / 国际药学研究杂志

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.

Clinical characteristics and antimicrobial resistance of the bloodstream infections due to NDM-1 producing Klebsiella pneumoniae in children / 中国感染与化疗杂志

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.

Molecular epidemiology of carbapenem resistant Klebsiella pneumoniae in a hospital in Beijing / 中华预防医学杂志

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.

The role of the genetic elements bla oxa and IS Aba 1 in the Acinetobacter calcoaceticus-Acinetobacter baumannii complex in carbapenem resistance in the hospital setting

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.

Analysis of 73 Cases of Adverse Drug Reactions Caused by Carbapenem Antibiotics / 中国药师

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.