Sepsis resulting from Enterobacter aerogenes resistant to carbapenems after liver transplantation

BACKGROUND: Sepsis due to Enterobacter aerogenes (E. aerogenes) is rare after liver transplantation but is also a serious infection that may cause liver abscess. The purpose of this case report is to relate an unusual presentation of liver transplantation to show how successive treatment can be an appropriate option in septic patients after liver transplantation. METHOD: We report on a patient with liver transplantation who developed sepsis due to extended spectrum beta-lactamases and AmpC-producing E. aerogenes. RESULTS: A 39-year-old man had a biliary fistula and then was found to have multiple liver abscesses through abdominal ultrasound and an abdominal computed tomography scan, and carbapenem-sensitive E. aerogenes infection was confirmed. The patient was not successfully treated with conservative treatment consisting of intravenous carbapenems, percutaneous transhepatic cholangial drainage, and biliary stent placement by endoscopic retrograde cholangiopancreatography, so a second liver transplantation followed. Carbapenem-resistant E. aerogenes was detected in bile and blood after a five-week course of carbapenem therapy. The patient developed septic shock and multiple organ dysfunction syndrome. CONCLUSIONS: We first report an unusual case of sepsis caused by E. aerogenes after liver transplantation in China. Carbapenem-resistant E. aerogenes finally leads to uncontrolled sepsis with current antibiotics. We hypothesize that the infection developed as a result of biliary fistula and predisposing immunosuppressive agent therapy. Further research is progressing on the aspect of immunomodulation therapy. (Hepatobiliary Pancreat Dis Int 2009; 8: 320-322)

A comparative study on antimicrobial susceptibility of uroculturome of humans in health and urinary tract infections

Background:The uroculturome indicates the profile of culturable microbes inhabiting the urinary tract,and it is often required to do a urine culture to find an effective antimicrobial to treat urinary tract infections(UTIs).Methods:This study targeted to understand the profile of culturable pathogens in the urine of apparently healthy(128)and humans with clinical UTIs(161)and their antimicrobial susceptibility.All the urine samples were analyzed to quantify microbial load and determine the diversity and antimicrobial susceptibility of microbes following standard microbiological methods.Results:In urine samples from UTI cases,microbial counts were 1.2×10^(4)±6.02×10^(3) colony-forming units(cfu)/mL,while in urine samples from apparently healthy humans,the average count was 3.33±1.34×10^(3) cfu/mL.In eight samples(six from UTI cases and two from apparently healthy people,Candida(C.albicans 3,C.catenulata 1,C.krusei 1,C.tropicalis 1,C.parapsiplosis 1,C.gulliermondii 1)and Rhizopus species(1)were detected.Candida krusei was detected only in a single urine sample from a healthy person and C.albicans was detected both in urine of healthy and clinical UTI cases.Gram-positive(G+ve)bacteria were more commonly(Odds ratio,1.98;CI99,1.01-3.87)detected in urine samples of apparently healthy humans,and Gram-negative(G−ve)bacteria(Odds ratio,2.74;CI99,1.44-5.23)in urines of UTI cases.From urine samples of 161 UTI cases,a total of 90 different types of microbes were detected and,73 samples had only a single type of bacteria.In contrast,49,29,3,4,1,and 2 samples had 2,3,4,5,6 and 7 types of bacteria,respectively.The most common bacteria detected in urine of UTI cases was Escherichia coli(52 samples),in 20 cases as the single type of bacteria,other 34 types of bacteria were detected in pure form in 53 cases.From 128 urine samples of apparently healthy people,88 types of microbes were detected either singly or in association with others,from 64 urine samples only a single type of bacteria was detected while 34,13,3,11,2 and 1 sample yielded 2,3,4,5,6 and seven types of microbes,respectively.In the urine of apparently healthy humans too,E.coli was the most common bacteria,(10 samples)followed by Staphylococcus haemolyticus(9),S.intermedius(5),and S.aureus(5),and similar types of bacteria also dominated in cases of mixed occurrence,E.coli was detected in 26,S.aureus in 22 and S.haemolyticus in 19 urine samples,respectively.G+ve bacteria isolated from urine samples’irrespective of health status were more often(P<0.01)resistant than G−ve bacteria to ajowan oil,holy basil oil,cinnamaldehyde,and cinnamon oil,but more susceptible to sandalwood oil(P<0.01).However,for antibiotics,G+ve were more often susceptible than G−ve bacteria to cephalosporins,doxycycline,and nitrofurantoin.Conclusion:The study concludes that to understand the role of good and bad bacteria in the urinary tract microbiome more targeted studies are needed to discern the isolates at the pathotype level.Further,the study suggests the use of antibiotics by observing good antibiotic stewardship following antibiotic susceptibility testing only.

Risk Factors and Prevalence of Mother to New-Born Transmission of Carbapenemase Producing Enterobacteriaceae in Two Hospitals in Yaounde, Cameroon

Background: In African countries, where the burden of neonatal sepsis is the highest, the spread of Carbapenemases Producing Enterobacteriaceae (CPE) in the community, potentially contributing to neonatal mortality, is a public health concern. The transmission routes are not well defined, particularly the possible key role played by pregnant women. The aim of this study was to understand the neonatal acquisition of CPE in Yaounde, Cameroon. Methods: A transversal analytical study was conducted in an urban area. Maternal stool samples during delivery and the first stool from their new-born were collected and cultured to isolate Enterobacteria. After isolation, characterization using API20E identification system, and antibiotic susceptibility testing were performed according to the Antibiogram Committee of the French Society of Microbiology. Carbapenemases detection was done on each carbapenem-resistant strain using the Modified Hodge Test (MHT) and their classification using the synergy tests with different inhibitors. Results: Out of the 55 CPE isolates identified, Escherichia coli was the most encountered bacteria both in mothers (n = 18, 50.00%) and infants (n = 11, 57.89%). Class B and D carbapenemases were found both in mothers and infants. The estimated prevalence of vertical transmission in our study, was 10% (n = 12). Logistic regression showed that CPE carriage in mothers and CPE acquisition in their new-borns were independently associated with the presence of greenish amniotic fluid (OR = 7.33, p 0.0001 in mothers and OR = 4.09, p = 0.0086 in new-borns). Conclusion: Our results highlight the non-negligeable role played by pregnant women in the neonatal acquisition of CPE.

Newly Detected Transmission of bla_(KPC-2) by Outer Membrane Vesicles in Klebsiella Pneumoniae

Objective The prevalence of carbapenem-resistant Klebsiella pneumoniae(CR-KP)is a global public health problem.It is mainly caused by the plasmid-carried carbapenemase gene.Outer membrane vesicles(OMVs)contain toxins and other factors involved in various biological processes,includingβ-lactamase and antibiotic-resistance genes.This study aimed to reveal the transmission mechanism of OMV-mediated drug resistance of Klebsiella(K.)pneumoniae.Methods We selected CR-KP producing K.pneumoniae carbapenemase-2(KPC-2)to study whether they can transfer resistance genes through OMVs.The OMVs of CR-KP were obtained by ultracentrifugation,and incubated with carbapenem-sensitive K.pneumoniae for 4 h.Finally,the carbapenem-sensitive K.pneumoniae was tested for the presence of bla_(KPC-2)resistance gene and its sensitivity to carbapenem antibiotics.Results The existence of OMVs was observed by the electron microscopy.The extracted OMVs had bla_(KPC-2)resistance gene.After incubation with OMVs,bla_(KPC-2)resistance gene was detected in sensitive K.pneumoniae,and it became resistant to imipenem and meropenem.Conclusion This study demonstrated that OMVs isolated from KPC-2-producing CR-KP could deliver bla_(KPC-2)to sensitive K.pneumoniae,allowing the bacteria to produce carbapenemase,which may provide a novel target for innovative therapies in combination with conventional antibiotics for treating carbapenem-resistant Enterobacteriaceae.

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.

Risk Factors Associated with MDR and CR Acinetobacter baumannii Carriage among ICU Patients Hospitalized at MOI Teaching and Referral Hospital, Kenya

Background: Multi-drug resistant and Carbapenem-Resistant Acinetobacter baumannii (CRAB) infections present a significant challenge in hospital ICU settings worldwide and the threat posed is worse in developing countries including Kenya. Despite the limited treatment options, there is inadequate comprehensive data on factors associated with MDR and CR Acinetobacter baumannii carriage among ICU patients hospitalized at hospitals. This study therefore aimed to address this gap and determined risk factors associated with MDR and CR Acinetobacter baumannii carriage among ICU patients hospitalized at MOI Teaching and Referral Hospital, Kenya. Methods: Through cross-sectional study design, a total of 132 ICU admitted patients were purposively enrolled in this study between July 2019 and July 2020. Demographic and risk factors associated with MDR and CR Acinobacter baumannii were collected using structured questionnaire. Descriptive statistics and bivalent analysis were used for data analysis obtained. Level of statistical significance was 95% confidence interval (CI) for all analysis. Results: Bivariable analysis showed that employed participants were 3.4 times more likely to have A. baumannii compared to the unemployed (cOR = 3.38, 95%, CI: 1.09 - 10.43, p = 0.035). Patients who were having high BMI were likely to be infected by A. baumannii compared to those who had normal/low BMI (aOR = 11.2, 95%, CI: 3.57 - 21.11, p = 0.004). Those who were aged ≥ 50 years were 21 times more likely to be carbapenem-resistant Acinetobacter baumannii, COR = 21.0, 95% CI: 1.83 - 240.52, p = 0.011. Those who stayed in ICU for more than 30 days were 16 times more likely to be carbapenem-resistant Acinetobacter baumannii compared to those who had been admitted (COR = 16.0, 95% CI: 1.45 - 176.45, p = 0.019). Conclusion: Increased length of hospital stay, obesity and marital status were the factors found to be significantly associated with A. baumannii infections among ICU admitted patients. On the other hand, gender, age, level of education, occupation, referral status and presence of infection were found to have no significant association with A. baumannii infections among ICU admitted patients. All patients admitted to the intensive care units should be screened for colonization with A. baumannii, owing to the poor treatment outcomes associated with carriage of this multidrug resistant pathogen. Proper infection control in the ICU settings should be upheld to mitigate the spread of A. baumannii in the intensive care units.

Risk of transmission of carbapenem-resistant Enterobacteriaceae and related “superbugs” during gastrointestinal endoscopy

To evaluate the risk of transmission of carbapenem-resistant Enterobacteriaceae(CRE) and their related superbugs during gastrointestinal(GI) endoscopy. Reports of outbreaks linked to GI endoscopes contami-nated with different types of infectious agents, includ-ing CRE and their related superbugs, were reviewed. Published during the past 30 years, both prior to and since CRE's emergence, these reports were obtained by searching the peer-reviewed medical literature(via the United States National Library of Medicine's "MEDLINE" database); the Food and Drug Administration's Manu-facturer and User Facility Device Experience database, or "MAUDE"; and the Internet(via Google's search engine). This review focused on an outbreak of CRE in 2013 following the GI endoscopic procedure known as endoscopic retrograde cholangiopancreatography, or ERCP, performed at "Hospital X" located in the sub-urbs of Chicago(IL; United States). Part of the largest outbreak of CRE in United States history, the infection and colonization of 10 and 28 of this hospital's patients, respectively, received considerable media attention and was also investigated by the Centers for Disease Con-trol and Prevention(CDC), which published a report about this outbreak in Morbidity and Mortality WeeklyReport(MMWR), in 2014. This report, along with the results of an independent inspection of Hospital X's in-fection control practices following this CRE outbreak, were also reviewed. While this article focuses primar-ily on the prevention of transmissions of CRE and their related superbugs in the GI endoscopic setting, some of its discussion and recommendations may also apply to other healthcare settings, to other types of flexible endoscopes, and to other types of transmissible infec-tious agents. This review found that GI endoscopy is an important risk factor for the transmission of CRE and their related superbugs, having been recently as-sociated with patient morbidity and mortality following ERCP. The CDC reported in MMWR that the type of GI endoscope, known as an ERCP endoscope, that Hospi-tal X used to perform ERCP in 2013 on the 38 patients who became infected or colonized with CRE might be particularly challenging to clean and disinfect, because of the complexity of its physical design. If performed in strict accordance with the endoscope manufacturer's labeling, supplemented as needed with professional organizations' published guidelines, however, current practices for reprocessing GI endoscopes, which include high-level disinfection, are reportedly adequate for the prevention of transmission of CRE and their related superbugs. Several recommendations are provided to prevent CRE transmissions in the healthcare setting. CRE transmissions are not limited to contaminated GI endoscopes and also have been linked to other reusable flexible endoscopic instrumentation, including broncho-scopes and cystoscopes. In conclusion, contaminated GI endoscopes, particularly those used during ERCP, have been causally linked to outbreaks of CRE and their related superbugs, with associated patient morbidity and mortality. Thorough reprocessing of these complex reusable instruments is necessary to prevent disease transmission and ensure patient safety during GI endos-copy. Enhanced training and monitoring of reprocessing staffers to verify the proper cleaning and brushing of GI endoscopes, especially the area around, behind andnear the forceps elevator located at the distal end othe ERCP endoscope, are recommended. If the ERCPendoscope features a narrow and exposed channel thathouses a wire connecting the GI endoscope's controhead to this forceps elevator, then this channel's com-plete reprocessing, including its flushing with a deter-gent using a procedure validated for effectiveness, is also emphasized.

1β-Methyl Carbapenem 中间体的合成

综述了１β－ＭｅｔｈｙｌＣａｒｂａｐｅｎｅｍ中间体的合成方法，重点强调了如何构筑１位β构型的甲基。参考文献３７篇。

Relationship of multidrug-resistant gene and extended-spectrum carbapenem-resistance in Staphylococcus aureus

The aim of this study was to determine the relationship between phenotypic antimicrobial susceptibility patterns and extended-spectrum,carbapenem-resistance genes.A total of 109 clinical Staphilococcus aureus strains were subjected to 19 antimicrobial susceptibility tests.Resistance to methicillin(mecA),penicillin(blaTEM),and tetracycline(tetM)was detected.We compared the presence of the blaTEM genes with extended-spectrum,carbapenem-related genes and identified the types of SCCmec genes.Of 109 clinical S.aureus strains,62(56.88%)had methicillin resistance and 60 strains carried mecA.The prevalence of blaTEM and tetM genes was 81.65%and 37.61%,respectively.The most predominant SCCmec type was SCCmec type Ⅱ 28/60(46.67%),in 60 mecA-positive methicillin-resistant S.aureus(MRSA)isolates.The SCCmec prevalence rates were type ⅣA 30.00%(18/60),type Ⅳb 8.33%(5/60),type Ⅳd 6.67%(4/60),and non-typable 8.33%(5/60).Sixty of the 109(55.05%)MRSA isolates were positive for extended-spectrum carbapenems(31/60)(51.67%),cephalosporins 40/60(66.67%)and carbapenems 31/60(51.67%).The predominant SCCmec type II demonstrated more carbapenem-resistance than the ⅣA,Ⅳb and Ⅳd types.

Antimicrobial Resistance Profiles and Clonal Relatedness of <i>Pseudomonas aeruginosa</i>Strains Recovered from Wounds Infections of Outpatient Population Presenting in a Rural Hospital in Kenya

Pseudomonas aeruginosa is a leading cause of hospital infections and is intrinsically resistant to most antibiotics. Emergence of multidrug resistant (MDR) strains has been reported in the world and poses a great challenge in the management of infections associated with this species. While a substantial amount of research has been done on strains from most of other infection caused by this species in developed countries, little is known about the susceptibility profiles of strains recovered from African countries in general and Kenya in particular. Furthermore, there is paucity of data regarding strain, phenotype and genetic diversity of strains recoverable from wounds among patients in Kenya. The possible risk factors for acquisition of MDR strains and possible factors that could fuel clonal expansion in hospital and community settings remain undetermined. This cross-sectional study conducted in Tigoni Hospital, a rural area in Central Kenya sought to determine risk factors associated with carriage of MDR Pseudomonas aeruginosa in wounds among rural population. We also analyzed antimicrobial resistance profiles among these isolates. Prevalence of P. aeruginosa in wounds was 28% with 85 isolates recovered from wounds of 299 participants. Most antimicrobial resistance prevalence was recorded towards Ceftazidime (64%) and Cefepime (52%) while Piperacillin-tazobactam was the most effective antimicrobial agent with a resistance prevalence rate of 20%. Resistance towards new classes of aminoglycosides such as Gentamicin was at 45% while that towards Amikacin was at 40%. Compared to other related studies, relatively lower resistance towards Ciprofloxacin (25%) and Meropenem (40%) were recorded. Some of the risk factors identified for carriages of MDR strains were self-medication (p: 0.001, C.I: 3.01 - 8.86, O.R: 5.17) and non-completion of dosage (p: 0.12, C.I: 0.9 - 2.5, O.R: 1.5).

Phenotipic Prevalence of Antibiotic Resistance in Gabon

Background: The increasing phenomenon of bacterial resistance to antibiotics is a real public health problem. The main causes are poor management of hygiene and water quality, but also the use of antibiotics without precaution. The objective of this study was to isolate and determine the antibiotic resistance profile of the different bacteria found in the main hospitals and bacteriology laboratories in Gabon. Methods: 6034 samples were taken from hospitals in seven main cities of Gabon, and analyzed according to the usual techniques. The pathogenic strains were identified by Matrix-Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry. Antimicrobial susceptibility testing was performed by the agar disc diffusion method, according to the Antibiogram Committee of the French Society for Microbiology guidelines. Results: 974 pathogenic bacterial strains were found, including 890/974 (91.4%) Gram-negative bacilli. The systematic antimicrobial susceptibility testings identified 160/974 (16.4%) multi-resistant strains. Escherichia coli was the most represented species. 12.5% - 25% of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Citrobacter sedlakii strains were resistant to amoxicillin + clavulanic acid, third and fourth generation cephalosporins. Aminoglycoside resistance rates of 8.5% - 19% were also noted. 4.5% to 25% of the bacteria found were resistant to quinolones and cotrimoxazole. Resistance rates to carbapenems ranged from 1% to 10.5%. 16% of Staphylococcus aureus were methicillin-resistant (MRSA). Rates of extended spectrum beta-lactamase-producing enterobacteriaceae (ESBL-PE) ranged from 2.5% to 25%. Conclusion: This study showed an increasing evolution of bacterial resistance to antibiotics that are spreading throughout Gabon. This constitutes a threat to the health of Gabonese population.

Prevalence of Carbapenem-Resistant Klebsiella Pneumoniae （CRKP） and the Distribution of Class 1 Integron in Their Strains Isolated from a Hospital in Central China

Objective The aim of our study is to investigate the prevalence of Carbapenem-resistant Klebsiella pneumoniae （CRKP） and the genetic characteristics of the class 1 integron in CRKP on multi-drug resistance. Methods Clinical Klebsiella pneumoniae strains were collected from multiple departments of a hospital in central China. CRKP strains were identified among the isolates, and antibiotics susceptibility of CRKP strains was analyzed. The polymerase chain reaction （PCR） was adopted to amplify the class 1 integron variable area. The integron genetic structure was analyzed with enzyme digestion and DNA sequencing technology. The relation between class 1 integron and drug resistance was analyzed statistically. Results Totally 955 strains of Klebsiella pneumoniae were isolated from varied sites of the hospital, and 117（12.3%） of them were identified as CRKP, with a separation rate of 8.9% （26/292） in 2013, 11.3% （38/336） in 2014 and 16.2% （53/327） in 2015, which shows an increasing trend by year. 44.4% （52/117） of CRKP strains were separated from specimen of ICU, and 61.5% （72/117） were from sputum. Over 95% CRKP strains were resistant to ampicillin/sulbactam, aztreonam, imipenem, meropenem Ceftazidme,Cefotaxime,Cefepime,and Piperacillin, while relatively low resistant rates were found in Tigecycline （12.8%） and colistin （35.9%）. The class 1 integron was detected in 77.8% （91/117） of CRKP strains. Class 1 integron of CRKP was significantly correlated with the antibiotic resistance to the tobramycin, gentamicin and amikacin （all P〈0.01）. The gene cassette analysis of variable area of class 1 integron showed that aadA2 accounts for 64.8% （59/91）, aacA4-catB8-aadA1 23.1% （21/91）, and aadA2-dfrA25 12.1% （11/91）. Conclusions CRKP has an increasing trend in a clinical setting in China, and most of them were resistant to multiple antibiotics. Class 1 integron in CRKP has strong ability to capture the genes resistant to aminoglycosides antibiotics from environment, with the aadA2 gene as the most popular one.

Treatment of sepsis: What is the antibiotic choice in bacteremia due to carbapenem resistant Enterobacteriaceae?

Sepsis is one of the major challenges of today. Although gram-positive bacteria related infections are more prevalent in hospital setting, the highest mortality rate is associated with gram-negative microorganisms especially Enterobacteriaceae. Enterobacteriaceae, including Escherichia coli, Klebsiella spp., Proteus spp., Enterobacter spp. and Serratia spp. Resistance to β-lactams in Enterobacteriaceae is primarily attributed to the production of B-lactamase enzymes with subsequent antibiotic hydrolysis and to a lesser extent by alteration of efflux pump or porins expression. Carbapenem resistant Enterobacteriaceae(CRE) and Acinetobacter baumannii are the most notorious pathogens due to the high incidence of morbidity and mortality especially in the immunocompromised patients in the intensive care unit. The most appropriate antimicrobial therapy to treat CRE is still controversial. Combination therapy is preferred over monotherapy due to its broad-spectrum coverage of micro-organisms, due to its synergetic effect and to prevent development of further resistance. Current suggested therapies for CRE resistance as well as promising antibiotics that are currently under investigation for winning the war against the emerging CRE resistance are reviewed and discussed.

Ceftazidime resistance in Burkholderia pseudomallei:First report from India

Melioidosis,a disease of public health importance in Southeast Asia and Northern Australia,of late has shown an increasing trend in India,particularly Southern India.We describe a ease of a 39-year-old diabetic patient with left elbow septic arthritis,multiple liver,splenic abscesses, pneumonia,pleural effusion,followed by sepsis syndrome.Blood cultures and culture of the joint aspirate yielded pure growth of Burkholderia psettdomallei(B.pesudomallei),sensitive to carbapenem,co-trimoxazole and resistant to ceftazidime.The patient was successfully treated with imipenem- cilastin.He was discharged on co-trimoxazole to complete the 24 weeks course and follow-up has continued to date.The patient continues to remain asymptomatic.The case re-emphasizes the need to monitor the trend of B.pseudomallei in India,particularly the development of ceftazidime resistance,which incidentally is the drug of choice.

Study on the Stereoselective Synthesis of Carbapenem Sidechain (2S,4S)-4-Acetylsulphanyl-2-[(S)-1-phenylethylcarbamoyl]-pyrrolidine-1-carboxylic Acid 4-Nitrobenzyl Ester

A stereoselective and economic synthesis of the carbapenem sidechain (2S, 4S)-4-ace-tylsulphanyl-2-[(S)1-phenylethyl-carbamoyl] pyrrolidine-1-carboxylic acid 4-nitrobenzylester was developed. Due to the effect of spatial hindrance, only the (2S,4S) diastereomer 3 wasobtained by coupling 1 and the inexpensive racemic 2 catalyzed by EEDQ.

Insertion Sequence-Dependent <i>OmpK</i>36 Mutation Associated Ertapenem Resistance in Clinical <i>Klebsiella pneumoniae</i>

Extended-spectrum β-lactamases (ESBLs) and/or AmpC enzymes combined with deficiency of porins OmpK35 and OmpK36 are important for the development of carbapenem-resistant Klebsiella pneumoniae. We characterized the clinical K. pneumoniae human isolates and investigated the effect of meropenem induction on the ompK35 and ompK36 mutation to develop carbapenem resistance from six carbapenem-susceptible ESBL-producing K. pneumoniae strains. 163 clinical K. pneumoniae isolates were grouped mostly into the ESBL + AmpC (44.2%) and ESBL (42.9%) phenotypes. The resistance rate differed between cephalosporins (52.1% for cefepime - 97.5% for cefotaxime) and carbapenems (16% for meropenem - 28.2% for imipenem) (P blaTEM, blaSHV, blaCTX-M-3-like, and blaCTX-M-14-like of AmpA β-lactamase genes and blaDHA and blaCMY of AmpC β-lactamase genes. Compared to all 163 clinical isolates, the 56 carbapenem-resistant isolates carried less frequently of blaTEM, blaCTXM-14-like, and blaCTXM-3-like and more frequently of blaDHA-1 and blaCMY-2. The carbapenem-resistant isolates differed in prevalence against imipenem, ertapenem, and meropenem and lacked OmpK35 more frequently than OmpK36, but abnormal PCR amplicons were detected fewer in the Omp K35-deficient group than in the OmpK36-deficient group (32.5% vs. 68.4%, respectively). The carbapenem-resistant isolate mostly carried blaDHA (91.1%) and three isolates carried blaKPC-2. Following induction with meropenem insertion sequences in ompK36, not ompK36, were identified as IS5 for KP08, IS1 for KP15, and IS903 for KP16 isolates. OmpK36 deficiency increased resistance to ertapenem, but not imipenem and meropenem. Clinical isolates belonged mainly to ESBL + AmpC group and ESBL group with difference in resistance to cephalosporins and carbapenems, the bla genes. Carbapenem resistant isolates lacked OmpK35 expression, than the OmpK36 expression, Meropenem induction developed the carbapenem resistant isolates with insertion of different insertion sequences in ompK36, not ompK35.

Patient Demographics and Characteristics of Infection with Carbapenem-Resistant <i>Acinetobacter baumannii</i>in a Teaching Hospital from the United States

A characterization of the clinical demographic features of patients with infection caused Acinetobacter baumannii, and the antibiotyping of the isolates recovered from these patients was undertaken, with a special reference to carbapenem-resistant variants, and their risk factors. This study was conducted retrospectively from January 2010 to March 2011 at a 616-bed tertiary care university hospital. Sixty-four patients were identified. Clinical and microbiological data were analyzed for risk factors and demographic features to derive relative risk and odds ratio. We identified 100 A. baumannii from 64 patients during 15 months period. Significant risk factors were working age (18 - 60 years), male gender, hospital stay (>1 week but Pseudomonas aeruginosa, and Klebsiella pneumoniae were the significant co-infecting agents. The antibiogram demonstrated multidrug resistance in a majority of the isolates. Relative risk associated with ventilator, diabetes, and surgery was higher in repeat isolates than in first isolates and were multidrug resistant. Repeat isolates were more resistant that the first isolates to most anti-acinetobacter agents, but the overall crude mortality was not significant during this study period, and couldn’t correlated to the choice of treatment. In conclusion, a resistance against all clinically used carbapenems, and colistin is rapidly increasing in repeat isolates of A. baumannii;leaves narrow therapeutic options to treat multidrug-resistant and pandrug-resistant A. baumannii infection. For the first time we report rising incidence of colistin resistance by 20 percent in repeat isolates, and is worrisome for healthcare centers. A combination therapy should be adopted to treat such infection to avoid the emergence of colistin-resistant phenotypes in the United States.

Molecular Detection of Carbapenemase Genes in Extensive Drug Resistant Acinetobacter baumannii Clinical Isolates from ICU Patients, Khartoum

Background: The emergence of carbapenemase producing Acinetobacter baumannii is increasingly reported nowadays and constitutes a major problem to the intensive care unit (ICU) patients with notable extensive-drug resistance ability. The study investigates carbapenemase producing A. baumannii strains exhibiting an extensively drug-resistant (XDR) phenotype, isolated from ICU patients in Khartoum. Methods: A total of 100 nonduplicate Gram-negative coccobacilli strains were obtained from microbiology laboratory of ICU patients’ clinical isolates. Molecular identification of A. baumannii was performed by targeting 16S rRNA gene using specifically designed primers. Then, XDR strains were determined by susceptibility testing (disc diffusion). For detection of carbapenemase genes Polymerase chain reaction (PCR) was carried out. Result: Of 100 ICU clinical isolates, 38 (38.0%) was confirmed A. baumannii strains, those strains showed 100% carbapenem resistance and 60.5% extensive drug resistance to the antibiotics tested. The frequency of carbapenemase producer was 57.9% (22/38) of carbapenem resistance A. baumannii (CRAB). The most common carbapenemase associated with resistance was blaOXA gene followed by blaNDM and blaGES A. baumannii isolates. The co-occurrence of blaOXA-48-like and blaNDM, blaOXA-23-like and blaOXA-51, and blaNDM-1 and blaOXA-51 was detected in 22.7%, 18.2% strains and 4.5% respectively. A unique characteristic of our findings was the coharbouring of the genes blaNDM-1, blaOXA-23-like, blaOXA-51 and blaOXA-143 in 9.1% strains (2/22), and this was the first report in the Khartoum city, Sudan. Conclusion: We have demonstrated for the first time a high prevalence of XDR-carbapenemase producing A. baumannii clinical isolates from ICU patients in Khartoum. Also an emergent blaOXA-143 was reported as High-Risk Clones. This highlights the routine mentoring of XDR-carbapenemase producing A. baumannii to avoid clone dissemination in our region hospitals.

Solid-Phase Total Synthesis of 1-β-Methylcarbapenem

A 1-b-methylcarbapenem analogue 6 was synthesized on polystyrene-diethylsilane resin (PS-DES) using 2-azetidinone bearing with 2-oxazolidone chiral auxiliary as starting material.

Transmission of Carbapenem Resistance Between Human and Animal NDM-Positive Escherichia coli Strains

Although carbapenem use is prohibited in animals in China,carbapenem-resistant Escherichia coli(CREC),especially New Delhi metallo-β-lactamase(NDM)-producing strains,are widely prevalent in foodproducing animals.At present,the impact of livestock-associated CREC strains on human populations at the national level is unknown.Here,we conduct a retrospective cross-sectional study to investigate the prevalence of CREC from clinical settings across 22 Chinese provinces or municipalities and analyze anthropogenic factors associated with their presence.We also ascertain the blaNDMand blaKPCabundance among pig and chicken farms and present a detailed genomic framework for CREC of animal and human origin.Overall,631/29799(2.1%)clinical Escherichia coli(E.coli)isolates were identified as CREC.Multivariable analysis revealed that being male,an age below 1,an age between 13 and 18,provinces with greater chicken production,and provinces with higher pig production were associated with higher odds of CREC infection.In general,73.8%(n=45/61)of pig farms and 62.2%(n=28/45)of chicken farms had a blaNDMabundance of 1×10^(-5)to 1×10^(-3)and 1×10^(-3)to 1×10^(-2),respectively.Among all the Chinese NDM-positive E.coli(n=463)available at the National Center for Biotechnology Information(NCBI),the genomic analysis revealed that blaNDM-5and Inc X3 were the predominant carbapenemase gene-plasmid combination,while a highly homogeneous relationship between NDM-positive isolates from humans and animals was demonstrated at the plasmid and core genome levels.All the findings suggest frequent CREC transmission between humans and animals,indicating that further discussions on the use of antibiotics in animals and humans are needed,both in China and across the globe.