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The emergence of antimicrobial resistance is a significant public health issue worldwide, particularly for healthcare-associated infections caused by carbapenem-resistant gram-negative pathogens. Cefiderocol is a novel siderophore cephalosporin targeting gram-negative bacteria, including strains with carbapenem resistance. The structural characteristics of cefiderocol show similarity to both ceftazidime and cefepime, which enable cefiderocol to withstand hydrolysis by β-lactamases. The unique chemical component is the addition of a catechol moiety on the C-3 side chain, which chelates iron and mimics naturally occurring siderophore molecules. Following the chelation of iron, cefiderocol is actively transported across the outer membrane of the bacterial cell to the periplasmic space via specialized iron transporter channels. Furthermore, cefiderocol has demonstrated structural stability against hydrolysis by both serine- and metallo-β-lactamases, including clinically relevant carbapenemases such as Klebsiella pneumoniae carbapenemase, oxacillin carbapenemase-48, and New Delhi metallo-β-lactamase. Cefiderocol has demonstrated promising in vitro antibacterial and bactericidal activity, which correlates with its in vivo efficacy in several animal models. This article reviews the discovery and chemistry of cefiderocol, as well as some of the key microbiological and in vivo findings on cefiderocol from recently conducted investigations. [ABSTRACT FROM AUTHOR]

Cephalosporins are the key drugs for the treatment of salmonellosis. Resistance to cephalosporins in Salmonella spp. has become a serious public health concern worldwide. Although the sales of cephalosporins have increased by five times from 2008 to 2016 in Korea, limited information is available on cephalosporin resistance in Korea. Therefore, we aimed to investigate the trends in prevalence and characteristics of cephalosporin-resistant Salmonella isolates from poultry in Korea in the period between 2010 and 2017. A total of 141 Salmonella isolates were collected from various poultry industry sources, and 38 (27.0%) among them showed resistance to cephalosporins. In particular, resistance to the following cephalosporins increased significantly over the seven-year period cephalothin (from 5.0% to 29.2%), cephalexin, cefuroxime, cefotaxime, and ceftazidime (from 0% to 25.0%), and cefepime (from 0% to 12.5%). In addition, 12 isolates carried a β-lactamase gene. A non-extended-spectrum β-lactamase (ESBL) and plasmid-mediated AmpC β-lactamase (pAmpC) gene, bla TEM-1, was found in three isolates in the periods of 2010 to 2011 and 2012 to 2013, respectively. The bla CTX-M-79 (n = 4) and bla CTX-M-15 (n = 1) for ESBL genes and bla CMY-2 (n = 1) for pAmpC genes were only present in the 2016–2017 period. All ESBL/pAmpC-positive isolates had high minimum inhibitory concentrations for most cephalosporins and showed multi-drug resistance. In a conjugation experiment, the transfer of bla CTX-M-79 and bla CMY-2 genes was confirmed in transconjugants, which showed similar pattern of antibiotic resistance. This demonstrates that ESBL/pAmpC-producing Salmonella isolates might be transmitted to humans through contaminated poultry products. These findings suggest the need for the development of monitoring program and the guidelines for prudent use of antimicrobial agents in the poultry industry in Korea. [ABSTRACT FROM AUTHOR]

Cephalosporins are beta-lactam antibiotics that are widely used in China. Five generations of cephalosporins have been introduced in clinical practice to date; moreover, some new candidates are also undergoing clinical evaluations. To improve the success rates of new drug development, we need to have a comprehensive understanding about the relationship between the structure of cephalosporins and the toxicity that it induces at an early stage. In the cephalosporins toxicity study using zebrafish, the drug absorption is a key point. In this study, we determined the absorption of cephalosporins in zebrafish during toxicity test. The internal concentrations of 19 cephalosporins in zebrafish were determined using a developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Furthermore, a quantitative structure-activity relationship (QSAR) model was established by multilinear regression; moreover, it was used to predict the absorption of cephalosporins in zebrafish. During leave-one-out cross-validation, a satisfactory performance was obtained with a predictive ability (q 2) of 0.839. The prediction ability of the model was further confirmed when the predictive ability (q 2) was 0.859 in external prediction. The best QSAR model, which was based on five molecular descriptors, exhibited a promising predictive performance and robustness. In experiments involving drug toxicity, the developed QSAR model was used to estimate internal concentrations of cephalosporins. Thus, the toxicity results were correlated with the internal concentration of the drug within the larvae. The developed model served as a new powerful tool in zebrafish toxicity tests. [ABSTRACT FROM AUTHOR]

Background The epidemiology of antibiotic-resistant Enterobacteriaceae intestinal carriage in healthy US children has not been well characterized. Methods Children between 14 days and 14 years of age were enrolled during well-child visits in Oakland, California, Kansas City, Kansas, and Nashville, Tennessee, between December 2013 and March 2015. Data on recent antibiotic use by the child and travel and hospitalization history of all members of each child’s household were obtained with a risk-factor survey. Stool specimens collected from the subjects were screened for extended-spectrum β-lactamase-producing (ESBL-P) bacteria using CHROMagar ESBL medium. Putative ESBL-P Escherichia coli and Klebsiella colonies underwent phenotypic confirmation by double-disk synergy testing; confirmed third-generation cephalosporin-resistant (3GCR) isolates underwent additional antibiotic-susceptibility testing. Results In 519 subjects, the overall 3GCR Enterobacteriaceae carriage rate was 4.4% (n = 23) and ranged from 3.4% to 5.1% among the study sites. The ESBL-P Enterobacteriaceae carriage rate was 3.5% (n = 18). The rates of 3GCR Enterobacteriaceae carriage was highest in 1 to <2 year olds at 6.5%, and was 5.2% in <5 year-olds vs 1.7% in ≥5-year-olds (P =.11). 3GCR and ESBL-P Enterobacteriaceae carriage was associated with international travel within the previous year; 11.1% of ESBL-P Enterobacteriaceae carriers reported this history compared with 1.6% of noncarriers (P =.004). No other queried factor was found to increase risk. Of the 24 analyzed 3GCR isolates, 58% were multidrug resistant. Conclusions The 3GCR Enterobacteriaceae carriage rate exceeds 5% in healthy US children <5 years of age. International travel within the previous year increased the risk of 3GCR and ESBL-P Enterobacteriaceae carriage. In contrast, we found no differences in the rates of hospitalization or recent antibiotic exposure between carriers and noncarriers. Young children, who have the highest prevalence of colonization, might be a sentinel population to study to gain a better understanding of community sources of antibiotic-resistant Enterobacteriaceae. [ABSTRACT FROM AUTHOR]

Background: Kiebsieiia pneumoniae is an important and increasing cause of life-threatening disease in hospitalized neonates. Third generation cephalosporin resistance (3GC-R) is frequently a marker of multi-drug resistance, and can complicate management of infections. 3GC-R K. pneumoniae is hyper-endemic in many developing country settings, but its epidemiology is poorly understood and prospective studies of endemic transmission are lacking. We aimed to determine the transmission dynamics of 3GC-R K. pneumoniae in a newly opened neonatal unit (NU) in Cambodia and to address the following questions: what is the diversity of 3GC-R K. pneumoniae both within-and between-host; to what extent is high carriage prevalence driven by ward-based transmission; and to what extent can environmental contamination explain patterns of patient acquisition. Methods: We performed a prospective longitudinal study between September and November 2013. Rectal swabs from consented patients were collected upon NU admission and every 3 days thereafter. Morphologically different colonies from swabs growing cefpodoxime-resistant K. pneumoniae were selected for whole-genome sequencing (WGS). Results: One hundred and fifty-eight samples from 37 patients and 7 environmental sites were collected. 32/37 (86%) patients screened positive for 3GC-R K. pneumoniae and 93 colonies from 119 swabs were successfully sequenced. Isolates were resistant to a median of six (range 3-9) antimicrobials. WGS revealed high diversity; pairwise distances between isolates from the same patient were either 0-1 SNV or > 1,000 SNVs; 19/32 colonized patients harbored K. pneumoniae colonies differing by >1000 SNVs. Diverse lineages accounted for 18 probable importations to the NU and nine probable transmission clusters involving 19/37 (51%) of screened patients. Median cluster size was five patients (range 3-9). Seven out of 46 environmental swabs (15%) were positive for 3GC-R K. pneumoniae. Environmental sources were plausible sources for acquisitions in 2/9 transmission clusters, though in both cases other patients were also plausible sources. Conclusion: The epidemiology of 3GC-R K. pneumoniae was characterized by multiple introductions, high within- and between host diversity and a dense network of crossinfection, with half of screened neonates part of a transmission cluster. We found no evidence to suggest that environmental contamination was playing a dominant role in transmission. [ABSTRACT FROM AUTHOR]

To evaluate the relationship between the pharmacokinetic/pharmacodynamic (PK/PD) parameters and the antibacterial effect of cefquinome against Actinobacillus pleuropneumoniae , a tissue cage infection model was established in piglets. In this model, an initial count of A. pleuropneumoniae of approximately 10 6 CFU/mL was exposed to different concentrations of cefquinome after multiple administration at dosages of 0.2, 0.4, 0.8, 1, 2, 4 mg/kg body weight once a day for 3 days. Concentration of cefquinome and bacterial numbers of A. pleuropneumoniae in the tissue-cage fluid (TCF) were monitered. An inhibitory form of sigmoid maximum effect (E max ) model was used to estimate the relationship between the antibacterial effect and PK/PD indices of cefquinome against A. pleuropneumoniae . The minimum inhibitory concentration of cefquinome against A. pleuropneumoniae was 0.016 μg/mL in TCF. The total maximum antibacterial effect was a 3.96 log 10 (CFU/mL) reduction. In addition, the cumulative percentage of time over a 24 h period that the drug concentration exceeds the MIC ( %T  > MIC) was the pharmacokinetic-pharmacodynamic (PK-PD) index that best correlated with the antibacterial efficacy ( R 2  = 0.967). The estimated %T  > MIC values were 11.59, 27.49, and 59.81% for a 1/3-log 10 (CFU/mL) reduction, a 2/3-log 10 (CFU/mL) reduction, and a 1-log 10 (CFU/mL) reduction, respectively, during the 24h administration period of cefquinome. In conclusion, cefquinome exhibits excellent antibacterial activity and time-dependent characteristics against A. pleuropneumoniae in vivo . Furthermore, these data provide meaningful guidance to optimize regimens of cefquinome to treat respiratory tract infections caused by A. pleuropneumoniae . [ABSTRACT FROM AUTHOR]

Background Practice variation regarding perioperative antimicrobial prophylaxis in total artificial heart transplantations (TAH-t) across institutions is unknown. The aim of our survey was to assess the current practices for prevention of infection in TAH-t recipients among different programs. Methods An electronic survey was sent to programs that implant Syncardia TAH (Syncardia Systems, Tuscon, Ariz, USA). Proportions were analyzed for categorical variables; means and SDs were analyzed for continuous variables. Results The majority of centers (80.8%) had a formal surgical infection prophylaxis protocol. For non–penicillin-allergic patients, five (20.1%) institutions reported using a 4-drug regimen, seven (29.2%) used a 3-drug regimen, five (20.1%) used a 2-drug regimen, and seven (29.2%) used a cephalosporin alone. Similar data was seen in the penicillin-allergic patients. Infections were reported to occur postoperatively in 52.2% centers. During the first month after TAH-t, bacteremia represented 27.3%, driveline infections 27.2%, pulmonary infections 9%, and mediastinal infections 18.2%. The most common organisms seen within the first month were Candida spp. , Escherichia coli , and Pseudomonas aeruginosa (21.4%). In 65% of centers, the mean rate of death post–TAH-t due to infection was 14.5% (SD, 22.3%). The mean rate of patients surviving until orthotopic heart transplantation was 58.6% (SD, 27.7%). Conclusions Preventing infections post–TAH-t is key to decreasing morbidity and mortality. All institutions administered perioperative prophylaxis for TAH-t with significant variation among the centers. The majority of the centers have a formal perioperative prophylactic protocol. [ABSTRACT FROM AUTHOR]

A reversed-phase HPLC method (RP-HPLC) with UV detection was developed and validated for the quantitative determination of cefprozil, a second-generation cephalosporin. Due to β-lactam ring instability under alkaline conditions, this RP-HPLC method was applied for the determination of cefprozil in the presence of its possible degradation product. The interactions that govern the separation process with stationary phase were investigated at both molecular and quantum mechanical levels. Moreover, electrostatic potential maps were generated to determine the sites of interaction with mobile phase. The suggested method was validated in compliance with International Conference on Harmonization guidelines and successfully applied for the determination of cefprozil in its commercial pharmaceutical formulation. [ABSTRACT FROM AUTHOR]

In this report, redesigning cephalosporin C acylase from the Pseudomonas strain N176 revealed that the loss of stability owing to the introduced mutations at the active site can be recovered by repacking the nearby hydrophobic core regions. Starting from a quadruple mutant M31βF/H57βS/V68βA/H70βS, whose decrease in stability is largely owing to the mutation V68βA at the active site, we employed a computational enzyme design strategy that integrated design both at hydrophobic core regions for stability enhancement and at the active site for activity improvement. Single-point mutations L154βF, Y167βF, L180βF and their combinations L154βF/L180βF and L154βF/Y167βF/L180βF were found to display improved stability and activity. The two-point mutant L154βF/L180βF increased the protein melting temperature ( T ) by 11.7 °C and the catalytic efficiency V / K by 57 % compared with the values of the starting quadruple mutant. The catalytic efficiency of the resulting sixfold mutant M31βF/H57βS/V68βA/H70βS/L154βF/L180βF is recovered to become comparable to that of the triple mutant M31βF/H57βS/H70βS, but with a higher T . Further experiments showed that single-point mutations L154βF, L180βF, and their combination contribute no stability enhancement to the triple mutant M31βF/H57βS/H70βS. These results verify that the lost stability because of mutation V68βA at the active site was recovered by introducing mutations L154βF and L180βF at hydrophobic core regions. Importantly, mutation V68βA in the six-residue mutant provides more space to accommodate the bulky side chain of cephalosporin C, which could help in designing cephalosporin C acylase mutants with higher activities and the practical one-step enzymatic route to prepare 7-aminocephalosporanic acid at industrial-scale levels. [ABSTRACT FROM AUTHOR]

Cephalosporins are the β-lactam antibiotics for the treatment of infection diseases caused by gram-positive and gram-negative bacteria. Fungus Cephalosporium acremonium produces cephalosporin C (CPC) that is not potent for clinical use. Its molecule can be transformed to 7-amino cephalosporanic acid (7-ACA) as the intermediate compound for making semi-synthetic cephalosporin derivatives. The first method for production of 7-aminocephalosporanic acid involves the chemical reaction using toxic reagents and laborious procedures. The second method uses two-step and one-step enzymatic transformation. In two-step method, the first step involves the conversion of Ceph-C to Glutaryl-7-amino cephalosporanic acid (GL-7-ACA) by D-amino acid oxidase (DAAO) and the second step, GL-7-ACA acylase (GA) hydrolyzes GL-7-ACA to produce 7-ACA. The two-step enzymatic transformation was used widely because of its safety and environmental friendship. The one-step enzymatic transformation is developed because of process simplification and cost reduction. This method uses cephalosporin C acylase for transformation CPC to 7-ACA. Same microbes can produce cephalosporin C acylase such as Achromobacter xylosoxidans, Aeromonas sp., Arthrobacter viscosus, Bacillus laterosporus, Flavobacterium sp., Paecilomyces sp., and Pseudomonas sp. The natural of cephalosporin C acylase catalyzed the CPC to 7-ACA directly in a very low efficiency and the protein engineering of cephalosporin C acylase was used to increase activity. [ABSTRACT FROM AUTHOR]

Purpose: Infections caused by AmpC-positive bacteria results in high patient morbidity and mortality making their detection clinically important as they cannot be detected in routine susceptibility testing. This study aim to determine the prevalence of AmpC β-lactamase among Gram negative bacteria recovered from clinical specimens in Benin City, Nigeria. Methods: A total of 256 consecutive and non-repetitive Gram negative bacteria were recovered from various clinical specimens. The prevalence of AmpC β-lactamase was determined using a combination of disc antagonism test and cefoxitin-cloxacillin inhibition test. Disc susceptibility test was performed on all isolates using standard techniques. Results: Cefoxitin-cloxacillin inhibition test detected more AmpC β-lactamase than other tests. The prevalence of AmpC β-lactamase did not differ significantly between both genders and between inpatients and out-patients (p>0.05). Isolates recovered from sputum had significantly higher prevalence of AmpC β-lactamase producers compared with isolates from other clinical specimens (p=0.0484). The prevalence of AmpC production was significantly higher among isolates of Pseudomonas aeruginosa than other isolates (p = 0.0085). Isolates that produced AmpC β-lactamase were more susceptible to the test cephalosoprins. Conclusion: An overall prevalence of AmpC β-lactamase (15.23 %) was observed in this study. Pseudomonas aeruginosa was the most prevalent producer of AmpC enzymes. Prudent use of antibiotics is advocated. [ABSTRACT FROM AUTHOR]

Water-soluble fluorescent CdS quantum dots (QDs) capped with thioglycolic acid (TGA) were prepared. The resulting QDs have characteristic emission maximum at 514 nm after excitation at 370 nm. Fluorescent QDs were used for the quantification of cefixime based on its quenching effect on the fluorescence intensity of the QDs. Maximum fluorescence quenching was observed when 0.3 mM of QDs were mixed with cefixime and allowed to stand for 5 min. At optimum experimental conditions, the Stern-Volmer calibration plot of F/F against concentration of cefixime was linear in the range of 2-40 μg/mL. The limit of detection (3.3SD/b) and limit of quantification (10SD/b) were found to be 1.3 and 3.9 μg/mL respectively with RSD ≤ 1.56%. The proposed method was successfully applied to commercial formulations with % recovery in the range of 97.17 ± 1.16-100.15 ± 0.61.The results were compared with reference methods and evaluated statistically using student t-test and variance ratio F-test. [ABSTRACT FROM AUTHOR]

A simple, accurate and sensitive spectrophotometric method has been developed for the analysis of four cephalosporins, ceftriaxone (CEFT), cefatoxime (CEFX), ceftazidime (CEZD) and cefepime (CEPM) in bulk and in pharmaceutical formulations. The method is based on the diazotization of cephalosporins in acidic medium, followed by coupling with 3-amino phenol (AP), to give orange red colored product having a λmaxof 500 nm. The calibration graphs are rectilinear in the concentration ranges 20 -160 μg mL for CEFT, 20–140 μg mL-1for CEFX & CEPM and 24 - 168 μg mL-1for CEZD respectively in the final measured solution. All the optimum conditions are established and other analytical parameters are evaluated. Commonly associated excipients did not interfere with the determinations. Statistical analysis of results indicates that the method is precise and accurate. [ABSTRACT FROM PUBLISHER]

Background: The aim of the study was to provide detailed herd level cost information about an outbreak of interdigital phlegmon (IP), which has been an emerging problem with enlarged loose house barns in Finland in recent years. During enlargement, the farmer's financial situation is sensitive because of the large investments to the farm business and unexpected costs can risk the farm's survival. Results: The University of Helsinki research herd and three commercial herds having outbreaks of IP in 2012 or 2013 were visited to collect detailed information about the costs and economic impact of the outbreaks. The majority of the costs came from the discarded milk due to the antibiotic treatments. In Finland IP is usually treated with parental benzylpenicillin for 5 days which result in discarded milk for a total of 11 days. Third generation cephalosporins, widely used in other countries, have no milk withdrawal time. However, the use of these antibiotics is not recommended in Finland since these antimicrobials are critically important for human health. Herd-level costs varied between 4560 and 28,386 € depending on the herd size, the frequency of the infected cows, the antibiotics used and other costs involved. The average cost per infected cow was 489 €. Conclusions: The outbreaks of IP cause severe economic losses to dairy farms and the costs are lower if cows are treated with antibiotics with no withdrawal time. However, other costs, such as involuntary culling, reduced production and fertility also produce substantial costs to the farms. Early detection of sick animals, rapid treatment and control measures to limit the outbreak of IP can lower the costs. Because of the high costs farms should concentrate on preventing the disease. [ABSTRACT FROM AUTHOR]

Background: Extended spectrum β-lactamases (ESBLs), a group of enzymes conferring resistance to third generation cephalosporins have rapidly increased in Enterobacteriacae and pose a major challenge to human health care. Resistant isolates are common in domestic animals and clinical settings, but prevalence and genotype distribution varies on a geographical scale. Although ESBL genes are frequently detected in bacteria isolated from wildlife samples, ESBL dissemination of resistant bacteria to the environment is largely unknown. To address this, we used three closely related gull species as a model system and collected more than 3000 faecal samples during breeding times in nine European countries. Samples were screened for ESBL-producing bacteria, which were characterized to the level of ESBL genotype groups (SHV, TEM), or specific genotypes (CTX-M). Results: ESBL-producing bacteria were frequently detected in gulls (906 of 3158 samples, 28.7 %), with significant variation in prevalence rates between countries. Highest levels were found in Spain (74.8 %), The Netherlands (37.8 %) and England (27.1 %). Denmark and Poland represented the other extreme with no, or very few positive samples. Genotyping of CTX-M isolates identified 13 different variants, with blaCTX-M-1 and blaCTX-M-14 as the most frequently detected. In samples from England, Spain and Portugal, blaCTX-M-14 dominated, while in the rest of the sampled countries blaCTX-M-1 (except Sweden where blaCTX-M-15 was dominant) was the most frequently detected genotype, a pattern similar to what is known from studies of human materials. Conclusions: CTX-M type ESBLs are common in the faecal microbiota from gulls across Europe. The gull ESBL genotype distribution was in large similar to published datasets from human and food-production animals in Europe. The data suggests that the environmental dissemination of ESBL is high from anthropogenic sources, and widespread occurrence of resistant bacteria in common migratory bird species utilizing urban and agricultural areas suggests that antibiotic resistance genes may also be spread through birds. [ABSTRACT FROM AUTHOR]

A simple and specific liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) assay method has been developed and fully validated for the simultaneous quantification of cefixime (CX) and clavulanic acid (CA) in human plasma. Analytes and internal standard were extracted from human plasma by a solid phase extraction technique using a Sam prep (3 mL, 100 mg) extraction cartridge. The extracted samples were chromatographed on a reverse phase C18 column using a mixture of methanol : acetonitrile : 2 mM ammonium acetate (pH 3.5) (25 : 25 : 50, v/v/v) as the mobile phase at a flow rate of 0.8 mL/min. Quantification of the analytes were carried out using single quadrupole LC-APCI-MS through selected ion monitoring at m/z 452 and 198, respectively, for CX and CA. The assay was linear over the concentration range of 0.05-10.0 and 0.1-10.0 μg/mL, respectively, for CX and CA. The mean plasma extraction recoveries of the CX and CA were found to be 95.20-96.27% and 94.67-95.58%, respectively. The method was successfully applied for the determination of pharmacokinetics of CX and CA after oral administration of single dosage CX/CA (200/125 mg) pill to the humans (n = 12). [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study is the evaluation of the actual resistance to second, third, and fourth generation cephalosporins over bacterial strains isolated from respiratory infections. The main causes for cephalosporin resistance of pathogenic and conditioned pathogen bacteria are: widespread usage, and impair immune response. Materials and methods: The analyzed specimens were throat swabs and sputum, from adult patients. The tests were performed using disk diffusion technique. We tested the following cephalosporin: From second generation: cefuroxime axetil; from third generation: cefotaxime, ceftazidime, cefpodoxime; Combinations of cephalosporins and beta-lactamase inhibitors: cefotaxime + clavulanic acid; ceftazidim + clavulanic acid; From fourth generation: cefepime; and association cefepime and clavulanic acid. Results: The following bacterial strains were isolated: Staphylococcus aureus, Streptococcus pneumoniae, Group C β-hemolytic Streptococcus, E. coli, Klebsiella pneumoniae and Proteus sp. The Group A. β-hemolytic Streptococcus isolated strains were not tested. For Staphylococcus aureus, E. coli, K. pneumoniae and Proteus, we found a high frequency resistance tocefuroxim, approximately 47%. Highest resistance to third generation cephalosporin was identified to E.coli and Klebsiella pneumoniae, especially resistant to cefotaxime, cefotaxime + clavulanic acid and ceftazidime. Conclusions: Cefpodoxime can be considered as a first election antibiotic in treating upper and lower respiratory tract infections, due to the lowest level of bacterial strain resistance, approximately 10% of the third generation cephalosporines tested. Also, cefepime may be proper in treating severe respiratory tract infections, with resistant broad-spectrum antibiotics bacterial strains. In our trial, resistance to cefepime was to a minimum low, approximately 4%, represented by the E.coli strains. [ABSTRACT FROM AUTHOR]

There is no consensus on optimal screening procedures for multidrug-resistant Enterobacteriaceae ( MDRE) in intensive care units ( ICUs). Therefore, we assessed five strategies for the detection of extended-spectrum beta-lactamase ( ESBL) and high-level expressed AmpC cephalosporinase ( HL- CASE) producers. During a 3-month period, a rectal screening swab sample was collected daily from every ICU patient, from the first 24 h to the last day of ICU stay. Samples were plated on MDRE-selective media. Bacteria were identified using MALDI- TOF mass spectrometry and antibiograms were performed using disk diffusion. MDREs were isolated from 682/2348 (29.0%) screening samples collected from 93/269 (34.6%) patients. Incidences of patients with ESBL and HL- CASE producers were 17.8 and 19.3 per 100 admissions, respectively. In 48/93 patients, MDRE carriage was intermittent. Compared with systematic screening at admission, systematic screening at discharge did not significantly increase the rate of MDRE detection among the 93 patients (62% vs. 70%). In contrast, screening at admission and discharge, screening at admission and weekly thereafter, and screening at admission and weekly thereafter and at discharge significantly increased MDRE detection (77%, p 0.02; 76%, p 0.01; 86%, p <0.001, respectively). The difference in MDRE detection between these strategies relies essentially on the levels of detection of patients with HL- CASE producers. The most reasonable strategy would be to collect two samples, one at admission and one at discharge, which would detect 87.5% of the ESBL strains, 67.3% of the HL- CASE strains and 77.4% of all MDRE strains. This study should facilitate decision-making concerning the most suitable screening policy for MDRE detection in a given ICU setting. [ABSTRACT FROM AUTHOR]

The emergence of Klebsiella pneumoniae producing carbapenemase (KPC) has now become a global concern. As a part of a nationwide multicentre surveillance study in Cuba, three K. pneumoniae clinical isolates resistant to carbapenems were detected for a 1-month period (September to October 2011). PCR and sequence analysis revealed that the three strains harboured blaKPC-2. They showed resistance or intermediate susceptibility to expanded-spectrum cephalosporins, other β-lactams, a β-lactam/β-lactamase inhibitor combination, and gentamicin. Two strains were susceptible only to colistin, whereas the other strain showing colistin resistance was susceptible to fluoroquinolones. These blaKPC-2-positive K. pneumoniae strains were classified into ST1271 (CC29), a novel clone harbouring blaKPC-2, and were revealed to be genetically identical by PCR-basedDNAfingerprinting. The three patients infected with the KPC-producing K. pneumoniae had common risk factors, and had no overseas travel experience outside Cuba, suggesting local acquisition of the resistant pathogen. This is the first report of a KPC-producing K. pneumoniae in Cuba. Although detection of KPC in Enterobacteriaceae is still rare in Cuba, our finding indicated that KPC-producing bacteria are a global concern and highlighted the need to identify these microorganisms in clinical laboratories. [ABSTRACT FROM AUTHOR]

Highlights: [•] A cephalosporins enrichment technique based on C18-Fe3O4@mSiO2 was developed. [•] The mesopores on the surface of the microspheres exclude proteins. [•] The strong magnetic behaviors of the microspheres ensure a fast separation. [ABSTRACT FROM AUTHOR]

Highlights: [•] A LC–MS/MS method was developed for 10 cephalosporins in milk. [•] A simple pretreatment procedure based on SPE has been established. [•] Selectivity, linearity, trueness, precision, CCα and CCβ had been validated. [•] The whole method was fast, reliable, convenient and sensitive. [Copyright &y& Elsevier]

A sensitive and selective confirmatory method for milk-residue analysis of ten quinolones and eight cephalosporins by LC- MS/ MS has been developed herein. For the chromatographic separation of target analytes, a Perfectsil ODS-2 (250 × 4 mm, 5 μm) analytical column was used and gradient elution was applied, using a mobile phase of 0.1% w/w TFA in water and 0.1% w/w TFA in ACN. Ultrasound-assisted matrix solid-phase dispersion procedure was applied for the extraction and clean-up procedure of antimicrobials agents from milk matrix using a mixture of Bond Elut Plexa sorbent and Qu ECh ERS. The method was validated meeting the European Legislation determining selectivity, linearity response, trueness, precision (repeatability and between-day reproducibility), decision limit, detection capability, and ruggedness following the Youden approach. Recoveries of all antibiotics ranged from 81.7 to 117.9%, while RSD values were lower than 13.7%. Limits of quantification for all examined compounds ranged from 2.4 to 15.0 μg/kg, substantially lower than the maximum residue limits established by the European Union (30-100 μg/kg). [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of different hybrid inorganic-organic micro- and nanomaterials (Fe3O4/PEG600, Fe3O4/C12, ZSM-5) on the antibacterial activity of different cephalosporins against Gram-positive and Gram-negative bacterial strains. The synergic effect of the studied materials was demonstrated by the increase in the growth inhibition zones diameter. All tested hybrid micro- and nanomaterials increased the activity of cefotaxime against Staphylococcus aureus. ZSM-5 increased the activity of cefotaxime and ceftriaxone and Fe3O4/C12 that of ceftriaxone against Pseudomonas aeruginosa and S. aureus. The anti-Pseudomonas, anti-Klebsiella pneumoniae and anti-Bacillus subtilis activity of cefoperazone was increased by Fe3O4/C12 nanoparticles, while the ZSM-5 improved its anti-Escherichia coli, K. pneumoniae, S. aureus and B. subtilis activity, whereas Fe3O4/PEG600 against K. pneumoniae. The anti-K. pneumoniae activity of cefepime was increased by all tested nanoparticles, whereas its anti-B. subtilis and anti-E. coli activity was improved by Fe3O4/C12 and Fe3O4/PEG600 nanoparticles. In conclusion, both magnetic Fe3O4 nanoparticles, charged outside as extra-shell with the antibiotic as well as ZSM-5 microparticles carrying the antibiotic inside the pores, significantly and specifically improved cephalosporin efficacy. A probable explanation for the increase in the antibiotic efficiency is the better penetration through the cellular wall of the antibiotic charged nanoparticles. [ABSTRACT FROM AUTHOR]

Abstract: The phenomenon of CPC decomposition occurs in Escherichia coli JM105/pMKC-sCPCacy during the one-step enzymatic conversion of cephalosporin C (CPC) into 7-aminocephalosporanic acid (7-ACA) by CPC acylase (sCPCAcy) for synthesis of cephalosporin antibiotics. E. coli JM105/pMKC-sCPCacy can constitutively produce sCPCacy as a fusion protein with maltose binding protein (MBP). Control experiments verified that the cell lysis solution from the host E. coli JM105 resulted in CPC decomposition by approximately 15%. Two miscellaneous enzymes, β-lactamase (AmpC) and cephalosporin acetyl esterase (Aes), are believed to play a major role in the degradation of CPC. Using the Red recombination system, the genes ampC, aes or both ampC and aes were knocked out from the chromosome of E. coli JM105 to generate the engineers: E. coli JM105(ΔampC), E. coli JM105(Δaes) and E. coli JM105(ΔampC, Δaes). The CPC decomposition was reduced to 12.2% in E. coli JM105(Δaes), 1.3% in E. coli JM105(ΔampC), and even undetectable in ampC-aes double knockout cells of E. coli JM105(ΔampC, Δaes). When catalyzed by crude MBP-sCPCAcy isolated from E. coli JM105(ΔampC, Δaes)/pMKC-sCPCacy (3377U·l−1), the CPC utilization efficiency increased to 98.4% from the original 88.7%. Similar results were obtained for the ampC-aes double knockout host derived from E. coli JM109(DE3) and the CPC utilization efficiency enhanced to 99.3% in the catalysis of crude sCPCAcy harvested from E. coli JM109(DE3, ΔampC, Δaes)/pET28-sCPCacy. [Copyright &y& Elsevier]

Clin Microbiol Infect 2012; 18: E95-E98 Abstract We report here on the first identification of Shigella flexneri subserotype 1c in China. We also report the emergence of resistance to ciprofloxacin and third-generation cephalosporins in this subserotype 1c for the first time. Isolates of seven strains circulating in China yielded three new sequence types and seven pulsed-field gel electrophoresis patterns, thus demonstrating the existence of high genetic diversity within the isolates. Overall, the seven isolates showed reduced susceptibility to ciprofloxacin; one isolate was ciprofloxacin resistant, whilst another developed resistance to ciprofloxacin, norfloxacin, cefotaxime and ceftriaxone. [ABSTRACT FROM AUTHOR]

Abstract: Glutathione is a ubiquitous thiol in eukaryotic cells, and its high intracellular ratio of reduced form (GSH) to oxidized form (GSSG) is largely maintained by glutathione reductase (GR) using NADPH as electron donor. glrA, a glutathione reductase encoding gene, was found and cloned from Acremonium chrysogenum by searching its genomic sequence based on similarity. Its deduced protein exhibits high similarity to GRs of other eukaryotic organisms. Disruption of glrA resulted in lack of GR activity and accumulation of a high level of GSSG in A. chrysogenum. Overexpression of glrA dramatically enhanced GR activity and the ratio of GSH/GSSG in this fungus. The spore germination and hyphal growth of glrA disruption mutant was strongly reduced in chemical defined medium. Meanwhile, the mutant was more sensitive to hydrogen peroxide than the wild-type strain. We found that the glrA mutant recovered normal germination and growth by adding exogenous methionine (Met). Exogenous Met also enhanced the antioxidative ability of both the mutant and wild-type strain. GSH determination indicated that the total GSH and ratio of GSH/GSSG in the mutant or wild-type strain were significantly increased when addition of Met into the medium. The glrA mutant grew poorly and could not produce detectable cephalosporin in the fermentation medium without Met. However, its growth and cephalosporin production was restored with addition of exogenous Met. These results indicate that glrA is required for the normal growth and protection against oxidative damage in A. chrysogenum, and its absence can be complemented by exogenous Met. [Copyright &y& Elsevier]

Noncontrast computed tomography (CT) has great advantage with higher sensitivity and more clear modalities in detecting urinary tract radiolucent calculi in patients with acute renal insufficiency (ARI) compared to other image diagnosis approaches. We report two cases (female, 28 years old; male, 39 years old) with persistent flank pain and acute anuria after the administration of ceftriaxone (4.0 g daily) for 2 days intravenously. No abnormality was found in the kidney-ureter- bladder (KUB) areas with plain abdomen X-rays. A diagnosis of bilateral hydronephrosis was made by ultrasound examination in both cases. Serum creatinine levels reached up to 257 and 810 μ mol/L (normal serum creatinine level is 40-130 μ mol/L), respectively. Vague density spots were noticed in the pelvis with noncontrast multidetector-row CT (MDCT) scanning. However, distinguishable clusters of high-density shadows were seen in pelvic areas with maximum intensity projections (MIP, CT values in 30-128 HU). Ceftriaxone crystal calculi were found on both sides of distal ureters under endoscopy. Renal function recovered in both patients after double-J ureteral stents were installed. Out results demonstrated that noncontrast MDCT scanning and MIP reconstruction as an effective diagnostic tool could provide clear images in detection of radiolucent calculi in urinary tract when conventional X-rays image are not suitable in the patients with obstructive anuria and ARI of unknown origin. [ABSTRACT FROM AUTHOR]

Background: The study aimed to assess the prevalence of Enterococcus faecalis infections among patients with hospital-acquired surgical wound sepsis and bacteremia in surgical wards and identify the antimicrobial susceptibility in these pathogens. Genetic role of erythromycin, vancomycin, and cephalosporin resistance in these pathogens was also examined. Methods: Two hundred samples were collected from surgical wound infections and 100 blood cultures from patients with suggested bacteremia to identify E faecalis by phenotypic and genotypic methods. Antimicrobial susceptibility to 12 antimicrobial agents was tested. The presence of resistance genes was examined by polymerase chain reaction (PCR) assay. Results: E faecalis was isolated with a frequency of 24/200 (12%) from surgical wound samples and 2/100 (2%) from blood cultures. All isolates were completely resistant to cefepime, ampicillin, and tetracycline, 96% of isolates were resistant to erythromycin, 53.8% to vancomycin, and 23.1% to linezolid. Multidrug resistance (MDR) was found in 100% of isolates. ere(B) and erm(B) genes were present in 20/25 (80%) and 17/25 (68%) of erythromycin-resistant isolates, respectively, 15 (60%) isolates carry both ere(B) and erm(B) genes. Van A gene was detected in 71.4% of vancomycin-resistant isolates. All isolates were negative for mef(A/E), blaSHV, and blaTEM genes. Conclusion: MDR in all isolates (100%) and high-level resistance to gentamicin, erythromycin, and vancomycin were reported in E Faecalis isolates. In the studied isolates, erythromycin resistance mainly related to the presence of ere(B) and erm(B) genes and vancomycin resistance was mainly related to the presence of vanA gene. [ABSTRACT FROM AUTHOR]

The oxidation of cefalexin (CFX), a commonly used cephalosporin antibiotic, was investigated by permanganate (PM) in water. Apparent second-order rate constant of the reaction between CFX and PM was determined to be 12.71 ± (1.62) M−1·s−1 at neutral pH. Lower pH was favorable for the oxidation of CFX by PM. The presence of Cl− and HCO3− could enhance PM-induced oxidation of CFX, whereas HA had negligible effect on CFX oxidation by PM. PM-induced oxidation of CFX was also significant in the real wastewater matrix. After addition of bisulfite (BS), PM-induced oxidation was significantly accelerated owing to the generation of Mn(III) reactive species. Product analysis indicated oxidation of CFX to three products, with two stereoisomeric sulfoxide products and one di-ketone product. The thioether sulfur and double bond on the six-membered ring were the reactive sites towards PM oxidation. Antibacterial activity assessment indicated that the activity of CFX solution was significantly reduced after PM oxidation. [ABSTRACT FROM AUTHOR]

The article presents a brief analysis of Cefditoren Pivoxil, a third generation cephalosporin antibiotic medication, focusing on its effectiveness in clinical trials and its relatively low price compared to similar medications. Other topics mentioned include penicillin-resistant isolates, dosage interval, and Cefditoren's rate of protein binding.