Lactam Group Research Articles

Antibiotic Resistance and Growth of the Emergent Pathogen Escherichia albertii on Raw Ground Beef Stored under Refrigeration, Abuse, and Physiological Temperature

Escherichia albertii is an emerging gram-negative facultative rod that has been implicated in multiple cases of human diarrheal disease, particularly in young children. When biochemical and other typing methods have been used, this organism has often been misidentified due to similarities with other members of the family Enterobacteriaceae. Isolates have been reported to be capable of producing attachment and effacement lesions via the synthesis of intimin, cytolethal distending toxin, and a variant form of Shiga toxin. The purposes of this study were to characterize the antibiotic resistance characteristics and the growth of individual strains of E. albertii on raw ground beef at different storage temperatures. Nalidixic acid-resistant strains of E. albertii were inoculated onto raw ground beef to a target of 4.0 log CFU/g, and samples were then aerobically incubated at 5, 22, or 35°C for various time periods prior to microbiological enumeration of the pathogen on lactose-free MacConkey agar containing 50 mg of nalidixic acid per liter and 0.5% L-rhamnose. Antibiotic resistance was determined using a broth microdilution assay. E. albertii did not grow at 5°C, with populations declining slowly over 14 days of refrigerated storage. Strains of the organism grew well under abusive storage, increasing by 2.5 to 3.1 log CFU/g and 4.1 to 4.3 log CFU/g after 24 h at 22 and 35°C, respectively. All strains were resistant to tetracycline but were sensitive to tested cephalosporins and chloramphenicol. Resistance to penicillin was observed, but susceptibility to other members of the b -lactam group, including ampicillin, amoxicillin, and clavulanic acid, was recorded. E. albertii represents an emerging pathogen with a probable foodborne transmission route. Future research should focus on verifying food process measures able to inactivate the pathogen.

Evaluation of sensitivity of modified star protocol microbiological method for beta-lactame antibiotics detection in raw cow milk

Antibiotic residues when present in animal tissues, through food chain, can enter human body, causing allergic reactions or facilitating the development of resistant bacterial strains. In order to determine the presence of antibiotics in animal tissues, it is appropriate to use convenient, reliable and sensitive methods. Microbiological methods applied for the detection of antibiotic residues in primary products of animal origin are based on the sensitivity of specific bacterial strains to a particular group of antibiotics. Regulatives on the amount of pesticides, metals and metalloids and other toxic substances, chemotherapeutics, anabolics and other substances which can be found in food ("Off. Gazette", No. 5/92, 11/92 - corr. and 32/02), state that milk and milk products can be used in commercial purposes only if not contain antibiotics in quantities that can be detected by reference methods. The applied method is modified STAR (Screening test for detection of antibiotics) protocol, regulated by the CRL (Community Reference Laboratory) Fougeres, France, in which the initial validation of the method had been carried out. In accordance with the demands of Regulative Commission EC No657/2002, the sensitivity of modified STAR protocol for beta lactam antibiotics group was examined , that is, there was carried out a contracted validation of the method, which initial validation had been performed at CRL. In a couple of series of experiments, 20 blank samples of raw cow milk originating from animals not treated by antibiotics, had been examined. By the beginning of the experiment samples were stored in a freezer at -20?C. Samples of raw cow milk enriched by working solutions of seven beta-lactam antibiotics, in order to obtain concentrations at the level of 0.5, 1 and 1.5 MRL (Maximmum Residue Limit) for each given antibiotic (Commission Regulation EC No. 37/2010). For detection of beta-lactam antibiotics, there was used Kundrat agar test with previously inoculated G.stearothermophilus ATCC 10149 strain. Aliquots of 30 _l of working solution at 0.5, 1 and 1.5 MRL concentration level, for each antibiotic, were inflicted on two paper disks placed on inoculated Kundrat agar surface. Petri plates with Kundrat agar previously inoculated with G.stearothermophilus , on which the samples were deposited, were incubated for 12-15h at 55oC. The obtained width of microorganisms growth inhibition zone, that is supposed to be at least 2.0 mm, measured from the disc edge, demonstrated the capability to detect all the tested 7 antibiotics from the beta lactam group at a level below the MRLs. Consequently, this proves that use of this method it is possible to meet the demands of Regulative Commission EC No. 37/2010.

Myoclonic status epilepticus in six patients without epilepsy.

Myoclonic status epilepticus (MSE) is defined as prolonged period of myoclonic jerks that are correlated with epileptiform discharges on EEG. We here describe clinical features and video-EEG records of six adult patients with MSE who did not have a prior diagnosis of epilepsy. In four out of six patients, MSE was precipitated by drugs. Two out of four patients had chronic renal disease and received beta lactam group antibiotics. Two other patients, who described chronic pain, developed MSE while taking pregabalin. One patient who had dementia and family history of juvenile myoclonic epilepsy (JME) developed MSE one month after quetiapine was introduced. Another patient, who had a recent ischemic stroke, developed MSE due to an unknown reason. In these last two patients, an immediate triggering factor was not evident. Myoclonic status epilepticus ceased in five out of six patients after withdrawal of the drugs and/or intravenous antiepileptic treatment. Myoclonic status epilepticus is a rare event in patients without epilepsy. A correct diagnosis and prompt drug discontinuation may reverse this severe and life-threatening condition.

Three cases of oropharyngeal tularemia in Turkey

We aimed to attract our colleagues' attention to the oropharyngeal tularemia, which has been an infrequently diagnosed disease in otolaryngology clinics also becoming widespread in Turkey. A retrospective review of database of 3 patients was performed to find patients with Tularemia. The medical files, treatment charts, serological and PCR findings and radiological (magnetic resonance imaging), histopathological records of these patients were reviewed. The study group consisted of 3 oropharyngeal tularemia patients. All of them presented with tonsillopharyngitis and cervical lymphadenitis and all were resistant to beta lactam or cephalosporin group antibiotics. Two patients had magnetic resonance imaging findings. All patients had positive serological tests. Strongly positive serological tests led to the diagnosis of tularemia. All patients had positive PCR and direct fluorescent antibody (DFA) test. All patients responded to systemic streptomycin treatment. In the daily practice of an otolaryngologist, it is not usual to diagnose a patient with oropharyngeal tularemia. Tularemia should be considered in the differential diagnosis of massive adenotonsillar enlargement and extensive necrotic cervical lymphadenopathy not responding to beta lactam antibiotics as a result of the rising number of tularemia outbreaks outside the classic endemic areas.

Studies on bacterial infections of diabetic foot ulcer

Microbial study for aerobic organisms from 100 cases of diabetic foot ulcers was carried out to determine the etiological agents and their antibiogram. Polymicrobial infection was observed in all the cases. The most frequently isolated aerobic organisms were Staphylococcus aureus and Pseudomonas aeruginosa. Antimicrobial sensitivity pattern of the isolates were done in which imepenem was found to be effective. Imipenem belongs to the ß lactam group of new generation antibiotics.Key words: Diabetes, Imipenam, Foot ulcer.

The Biological Function of the Bacterial Isochorismatase-Like Hydrolase SttH

The streptothricin hydrolase (SttH), which is a member of the isochorismatase-like hydrolase (ILH) super-family, catalyzes the hydrolysis of the streptolidine lactam group in streptothricin (ST) antibiotics, thereby inactivating them. In this study we identified a novel homologous gene (sttH-sn) and sequenced the flanking regions of the sttH and sttH-sn genes. The organization of genes around the sttH, sttH-sn, and ILH genes revealed that a number of the genes were clustered with genes encoding oxidoreductases with molybdopterin binding subunits, suggesting that the true role of these gene products (SttHs and a number of ILHs) might have to do with the chemical modification of molybdopterin, rather than ST-resistance. In addition, mutant enzymes were constructed in which Ser was substituted for highly conserved Cys-176 and Cys-158 of SttH and SttH-sn respectively, and no enzyme activities were detected. Thus, biochemically, these ILHs were found to be "cysteine hydrolases."

Investigation on the flexibility of chiral tricyclic derivatives

In the perspective of generating libraries for broad screening purposes, the inversion barrier of enantiomeric conformers of various tricyclic compounds, characterized by a seven-membered ring featuring a lactam group with two aromatics condensed at its opposite sides, has been investigated by ab initio calculations and NMR spectroscopy. Solid-state structure characterizations by single-crystal X-ray diffraction have been also carried out. The aim was to assess if moving from ethers to sulfides and sulfones derivatives, causes the racemization barrier to vary. Investigation was also extended to thiolactam congeners. Structural and electronic effects were investigated on the energetics of the inversion process and structure-property relationships evidenced. Results suggest that the ring inversion of the oxo derivatives is easier with respect to the corresponding S/SO2 ones. Also amide molecules have, on the whole, smaller barriers with respect to the corresponding thioamide ones.

Microwave-Assisted Combinatorial Synthesis of Polysubstituent Imidazo[1,2-a]quinoline, Pyrimido[1,2-a]quinoline and Quinolino[1,2-a]quinazoline Derivatives

A series of unusual fused heterocyclic compound derivatives, consisting of a pyridine and a imidazole or pyrimidine core, with a bridgehead nitrogen, were successfully synthesized by a microwave-assisted, three-component domino reaction of aldehydes, enaminones, and malononnitrile. In this one-pot reaction, up to five new bonds were formed accompanied by generating the lactam group. This method has the advantages of short synthetic route, operational simplicity, increased safety for small-scale high-speed synthesis, and minimal environment impact.

Synthesis, physical properties, antimicrobial potentials of some antibiotics complexed with transition metals and their effects on alkaline phosphatase activities of selected rat tissues

Metal complexes of ampicillin trihydrate, chloramphenicol and oxytetracycline with Ni(II), Fe(III) and Co(II) chloride salts were prepared using standard methods. The geometry and the mode of binding of complexes have been proposed on the basis of chemical analysis, conductivity measurements, molec-ular weight determinations and spectroscopic studies. Ampicillin and oxytetracycline coordinated through the oxygen of the hydroxyl group and carbonyl group, and also through the nitrogen of the lactam group and amide group, respectively, in the complexes. Chloramphenicol coordinated through oxygen of the nitro group and carbonyl group and through nitrogen of the imines group in its mixed complexes. Thus, the three ligands used acted as terdentate ligands.Antimicrobial properties as well as the effect of administration of the metal complexes at the dose of 3.33 mg/kg body weight, thrice daily for 5 days on the alkaline phosphatase (ALP) activities of rat kidney, liver and serum were evaluated. Compared with their parent antibiotics, there was increase in the values of the physical properties of the metal complexes. The zone of inhibition for Escherichia coli, Staphylococcus aureus andKlebsiella pneumonia were significantly (P 0.05) in the serum enzyme. The results revealed more desirable physical properties and enhanced antimicrobial activities upon complexation with the metal ligands. The increased ALP activities in the tissues may have its consequential effect on the tissues. Key words: Metal complexes, complexation, antibiotics, antimicrobial properties, alkaline phosphatase.

Molecular mechanism of high pressure action on lupanine

High hydrostatic pressure (HHP) is an emerging tool for studying conformational changes in lipids, proteins and nucleic acids. Although many thermodynamic parameters describing those processes have been determined, a molecular mechanism of HHP action is poorly recognized. To get insight into that, we have studied quinolizidine alkaloid, lupanine. It consists of two quinolizidine moieties, one of which contains lactam group. Using Fourier-transform infrared (FT-IR) spectroscopy, we have showed that at 6 kbar, the intensity of amide band at 1589 cm −1 decreased and a new band at 1556 cm −1 appeared. These changes are due to the hydrolysis of lupanine to lupanic acid. That reaction was confirmed with 13C NMR spectra of lupanine exposed to HHP. The NMR signals at 176.6 and 184.3 ppm were assigned to lactam group of lupanine and carboxylic group of lupanic acid, respectively. The ring opening reaction of lupanine under HHP is reversible at ambient pressure, as evidenced by CD measurements. A slightly acidic condition induced by HHP causes protonation of lactam group and carbocation is formed, while on the other hand, water molecule as nucleophile attacks electrophilic carbon of lactam and electrons move towards oxonium ion. Finally, C N bond breaks down and carboxyl group is formed.

On the formation of 4-[ N,N-bis(2-chloroethyl)amino]phenyl acetic acid esters of hecogenin and aza-homo-hecogenin and their antileukemic activity

The p-[ N,N-bis(2-chloroethyl)amino]phenylacetic acid esters of hecogenin and aza-homo-hecogenin have been prepared and their antineoplastic activity was evaluated against two basic drug screening systems in rodents, P388 lymphocytic and L1210 lymphoid murine leukemias. Among the compounds tested, the p-[ N,N-bis(2-chloroethyl)amino]phenylacetic acid ester of aza-homo-hecogenin was appeared to possess a significant higher antileukemic effect. These results support that the alkylating esters of hecogenin produce important antitumor activity as well as, indicate that the aza-homo-hecogenin ester exhibits significantly higher activity due to lactam group (–NHCO–) modification.

V. Thioanalogues of sparteine lactams. (+)-2-Thiono-17-oxosparteine and (+)-2,17-dithionosparteine

The X-ray and spectroscopic results clearly indicate that the (+)-2-thiono-17-oxosparteine ( 1) and (+)-2,17-ditihionosparteine ( 2) are conformationally rigid. In order to analyze deviations of lactam/thiolactam groups from planarity induced by ring constraints, the Dunitz–Winkler approach has been used. The lactam and thiolactam groups are close to planarity, only the lactam group in one of the two independent molecules of 1 is markedly non-planar. The bond angles in the thiolactam and lactam groups are highly diverse. Rings A and C adopt a distorted sofa conformation in both compounds. The distortions in the molecules of 2 as compared with those in the related monothiolactams correspond to the unusual chemical shifts of H5(eq), H5(ax) and H11, as well as to the extremely low J 5ax-6 and extremely large J 5eq-6 coupling constants. Also chemical shifts show a similar regularity being extremely high and low for C2 and C17, respectively.

A comparative study of NMR chemical shifts of sparteine thiolactams and lactams

The 13C and 1H NMR spectra of the four possible thiolactams of sparteine ( 1 ) were recorded and the thiolactam group effects were determined. Most of the effects are greater than those of the lactam group in the oxo analogs. A good linear correlation between the 13C chemical shifts of CS and those of CO was found. The effects could help in assignment of the spectra and determination of conformation of thiolactams and related thiocarbonyl compounds.

A Simple Synthetic Protocol for the Protection of Amides, Lactams, Ureas, and Carbamates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Penicillin and semisynthetic penicillins in dermatology

Penicillins are one of most important antibiotics groups. They are extremely effective and still widely used. Moreover, they are the drugs of choice for a large number of infectious diseases. Penicillins belong to the -lactam group, which also include cephalosporins, monobactams, and carbapenems. -lactam antibiotics have four-membered ring structure. History The era of modern microbial chemotherapy stems from Paul Erlich’s work a century ago. In 1928, Alexander Fleming isolated penicillin from a sample of the mold Penicillinium notatum in his laboratory at St. Mary’s Hospital in London. This antibacterial substance was named penicillin by Fleming. It was not introduced into clinical practice until 1941, when Florey, Chain, and their colleagues had been successful in extracting enough penicillin. 1– 4 The first clinical trials were conducted in 1942 at Yale University and the Mayo Clinic with excellent results. Since 1957, after the 6-aminopenicillinic acid’s isolation, the development of numerous semisynthetic penicillins has continued. Chemistry

A simple synthetic protocol for the protection of amides, lactams, ureas, and carbamates

A new procedure for protecting the amide, lactam, urea, and carbamate NH group with a triphenylmethyl (Tr) group is described. The utility of this method is illustrated with molecules that contain other functional groups. A mild deprotection using trifluoroacetic acid makes this a useful method for attaching amide groups on resin for combinatorial synthesis.

Trace analysis of muramic acid in indoor air using an automated derivatization instrument and GC–MS 2 or GC–MS 3

An automated derivatization instrument has been developed for the preparation of alditol acetates from bacterial hydrolysates for analysis by gas chromatography–mass spectrometry (GC–MS). The current report demonstrates the utility of the automated instrument for the more demanding task of trace analysis of muramic acid (Mur) in airborne dust using gas chromatography-tandem mass spectrometry (GC–MS 2). Conditions for efficient derivatization of Mur, vital for trace analysis, are rigorous including lactam and imido group formation under anhydrous conditions. Furthermore, as the detection limit is lowered, possible contamination or carry-over of samples becomes an increasingly greater consideration and must not occur. The instrument meets these criteria and was successfully used for assaying the levels of Mur in laboratory air, which were found to be much lower than in the previous studies of heavily occupied schools and agricultural environments. The potential for GC–MS 3 in further lowering the detection limit was also demonstrated.

Intramolecular Diels–Alder reactions of N-alkenyl-2(1 H)-pyrazinones: generation of a novel type of cis-1,7-naphthyridine

The intramolecular Diels–Alder reaction of three 1-(ω-alkenyl)-2(1 H)-pyrazinones was investigated. Cycloaddition was shown to proceed for 1-(4-pentenyl)- and 1-(5-hexenyl)-2(1 H)-pyrazinone 5a and 5b to give the corresponding tricyclic hydrolysed adducts 7a and 7b , but not for the 1-(3-butenyl) derivative 5c . In contrast to 7b , the more strained 7a underwent selective acidic solvolysis of the tertiary lactam group to give methyl cis-8-oxo-6-phenyldecahydro[1,7]naphthyridine-6-carboxylate 8 . An NMR analysis of 8 is presented.

Copper(II) complexes of imidazolinone herbicides

The copper(II) complexes formed by the imidazolinone herbicide Imazapyr or (±)-2-4-isopropyl-(4-methyl-5-oxo-2-imidazolin-2-yl)-nicotinic acid (H 2imz) are described. The compounds isolated in the solid state confirm that Imazapyr is a versatile bipy-like ligand able to chelate the metal ion through two different donor sets. The pair of pyridine and imidazole nitrogen atoms is bound to copper in [Cu(Himz) 3] and [Cu(Himz) 2(H 2O)]. In these, a five-coordination at the metal ion and a geometry close to the trigonal bipyramid are favoured. The weak carboxylate group does not play a primary role in the complex formation properties of Imazapyr. However, its involvement yields the polymetallic compounds [Cu(Himz) 2] and [Cu 3(Himz) 4(H 2O) 4](NO 3) 2. The deprotonation of the lactam group provides Imazapyr with a stronger donor set, the lactam and the pyridine nitrogens, yielding 1:1 polymeric complexes [Cu(imz)(H 2O)] and [Cu(imz)(H 2O) 3] · H 2O. With the methyl ester of Imazapyr (HimzOMe), the different charge of the ligand deprotonated at the lactam group allows a bis-chelated complex [Cu(imzOMe) 2(H 2O)] · H 2O in which the metal ion adopts a five-coordination. Analogies have been established between the complexes of H 2imz, HimzOMe and 2,2′-bipyridine.

Laingolide, a novel 15-membered macrolide from Lyngbya bouillonii (cyanophyceae)

Laingolide ( 1), a novel 15-membered macrolide containing a lactam group was isolated from the blue-green alga Lyngbya bouillonii, collected on Laing Island (Papua-New Guinea). Its structure (without stereochemistry) was established by a detailed high-field 1D and 2D NMR study.