Cephamycin B

Objectives: To develop a rapid and reliable tool to detect by multiplex PCR assays the most frequently widespread beta-lactamase genes encoding the OXA-1-like broad-spectrum beta-lactamases, extended-spectrum beta-lactamases (ESBLs), plasmid-mediated AmpC beta-lactamases and class A, B and D carbapenemases. Methods: Following the design of a specific group of primers and optimization using control strains, a set of six multiplex PCRs and one simplex PCR was created. An evaluation of the set was performed using a collection of 31 Enterobacteriaceae strains isolated from clinical specimens showing a resistance phenotype towards broad-spectrum cephalosporins and/or cephamycins and/or carbapenems. Direct sequencing from PCR products was subsequently carried out to identify beta-lactamase genes. Results: Under optimized conditions, all positive controls confirmed the specificity of group-specific PCR primers. Except for the detection of carbapenemase genes, multiplex and simplex PCR assays were carried out using the same PCR conditions, allowing assays to be performed in a single run. Out of 31 isolates selected, 22 strains produced an ESBL, mostly CTX-M-15 but also CTX-M-1 and CTX-M-9, SHV-12, SHV-5, SHV-2, TEM-21, TEM-52 and a VEB-type ESBL, 6 strains produced a plasmid-mediated AmpC beta-lactamase (five DHA-1 and one CMY-2) and 3 strains produced both an ESBL (two SHV-12, one CTX-M-15) and a plasmid-mediated AmpC beta-lactamase (DHA-1). Conclusions: We report here the development of a useful method composed of a set of six multiplex PCRs and one simplex PCR for the rapid screening of the most frequently encountered beta-lactamases. This method allowed direct sequencing from the PCR products.

Objective: To report two cases of hypertension related to amphotericin B infusion. Case summary: A 63-year-old woman with Candida albicans bacteremia and an 84-year-old man with Aspergillus fumigatus pneumonia developed hypertension within minutes of amphotericin B administration. Both patients' blood pressure returned to baseline soon after the infusion of amphotericin B was stopped. Neither patient was rechallenged. Discussion: A causal relationship may exist between the administration of amphotericin B and these hypertensive episodes. Blood pressure in both patients normalized without treatment on discontinuation of the infusion. The mechanism of amphotericin B-associated hypertension is unclear but could include vasoconstricting properties of the drug or the administration of intravenous NaCl 0.9% prior to amphotericin B infusion. We recommend that intravenous NaCl 0.9% be administered following amphotericin B infusion and that the infusion be stopped if hypertensive episodes arise. Conclusions: Both acute hypertension and hypotension can occur in patients receiving amphotericin B for systemic fungal infections.

The discovery of penicillin was announced over 60 years ago. It was the first beta-lactam antibiotic and the importance of this group is greater today than it has ever been. It is clear that even at 60 years of age, beta-lactams are going strong and no one contemplates their early retirement. Currently, sales of beta-lactam compounds form the largest share by far of the world's antibiotic market. The beta-lactam antibiotics include penicillins such as penicillin G, penicillin V, ampicillin, cloxacillin, and piperacillin; cephalosporins such as cephalothin, cephaloridine, cephalexin, and cefaclor; and cephamycins such as cefoxitin. In addition, beta-lactam antibiotics include the more recently developed nonclassical structures such as monobactams, including aztreonam; clavulanic acid, which is a component of the combination drug augmentin; and thienamycin, which is chemically transformed into imipenem, a component of the combination drug known as primaxin (or tienam). The classical beta-lactam antibiotics can be divided into hydrophobic and hydrophilic fermentation products. The hydrophobic members, e.g. benzylpenicillin (penicillin G) and phenoxymethylpenicillin (penicillin V), contain non-polar side chains, e.g. phenylacetate and phenoxyacetate, respectively, and are made only by filamentous fungi; the best known of these is Penicillium chrysogenum. The antibacterial spectrum of the hydrophobic penicillins is essentially Gram-positive. The hydrophilic types are penicillin N, cephalosporins and 7-alpha-methoxycephalosporins (cephamycins) which are made by fungi, actinomycetes and unicellular bacteria. They all contain the polar side chain, D-alpha-aminoadipate. We can draw a sequence of reactions which describes the biosynthesis of all penicillins and cephalosporins, however the total sequence exists in no one microorganism. All penicillin and cephalosporin biosynthetic pathways possess the first three steps in common and all cephalosporin pathways go through deacetylcephalosporin C. However, there are many subsequent biosynthetic reactions which vary in the different producing organisms. Production of beta-lactam antibiotics occurs best under conditions of nutrient imbalance and at low growth rates. Nutrient imbalance can be brought about by limitation of the carbon, nitrogen or phosphorus source. In addition to these factors, amino acids such as lysine and methionine exert marked effects on production of penicillins and/or cephalosporins by some microorganisms. Induction of some of the synthetases, especially the first enzyme, ACV synthetase, by methionine is the basis of the methionine stimulation of cephalosporin C synthesis in C. acremonium. Inhibition of homocitrate synthase is the mechanism involved in lysine inhibition of penicillin synthesis in Penicillium chrysogenum.