Showing papers on "Aztreonam published in 1997"
TL;DR: This collection of blood isolates from the same patient appears to represent the in vivo evolution of resistance under selective pressure of treatment with various cephalosporins.
Abstract: Nine isolates of Escherichia coli were recovered from seven blood cultures over a period of 3 months from a 19-month-old female with aplastic anemia. Initial isolates were susceptible to extended-spectrum cephalosporins, including ceftazidime (MIC, or = 128 micrograms/ml) and other cephalosporins and the monobactam aztreonam. Molecular typing methods, including plasmid profile analysis, pulsed-field gel electrophoresis, and arbitrarily primed PCR, indicated that the nine isolates were derived from a common ancestor. Dot blot hybridization and PCR analysis of total bacterial DNA using blaSHV- and blaTEM-specific DNA probes and primers identified the presence of a blaTEM beta-lactamase gene in all of the isolates and a blaSHV gene in the isolates with elevated ceftazidime MICs. Isoelectric focusing analysis of crude lysates showed that all nine isolates contained an enzyme with a pI of 5.4 corresponding to the TEM-1 beta-lactamase, and those isolates containing an SHV-type beta-lactamase demonstrated an additional band with a pI of 7.6. The first of the ceftazidime-resistant isolates appeared to hyperproduce the SHV enzyme compared to the other resistant isolates. DNA sequencing revealed a blaSHV-1 gene in the first ceftazidime-resistant isolate and a novel blaSHV gene, blaSHV-8, with an Asp-to-Asn substitution at amino acid position 179 in the remaining four isolates. Three of the ceftazidime-resistant isolates also showed a change in porin profile. The patient had received multiple courses of antimicrobial agents during her illness, including multiple courses of ceftazidime. This collection of blood isolates from the same patient appears to represent the in vivo evolution of resistance under selective pressure of treatment with various cephalosporins.
268 citations
TL;DR: OXA-18 is peculiar since it is a class D beta-lactamase which confers high resistance to extended-spectrum cephalosporins and seems to have unique hydrolytic properties among non-class A enzymes.
Abstract: Clinical isolate Pseudomonas aeruginosa Mus showed resistance both to extended-spectrum cephalosporins and to aztreonam. We detected a typical double-disk synergy image when ceftazidime or aztreonam was placed next to a clavulanic acid disk on an agar plate. This resistance phenotype suggested the presence of an extended-spectrum beta-lactamase. Isoelectric focusing revealed that this strain produced three beta-lactamases, of pI 5.5, 7.4, and 8.2. A 2.6-kb Sau3A fragment encoding the extended-spectrum beta-lactamase of pI 5.5 was cloned from P. aeruginosa Mus genomic DNA. This enzyme, named OXA-18, had a relative molecular mass of 30.6 kDa. OXA-18 has a broad substrate profile, hydrolyzing amoxicillin, ticarcillin, cephalothin, ceftazidime, cefotaxime, and aztreonam, but not imipenem or cephamycins. Its activity was totally inhibited by clavulanic acid at 2 microg/ml. Hydrolysis constants of OXA-18 (Vmax, Km) confirmed the MIC results. Cloxacillin and oxacillin hydrolysis was noticeable with the partially purified OXA-18. The blaOXA-18 gene encodes a 275-amino-acid protein which has weak identity with all class D beta-lactamases except OXA-9 and OXA-12 (45 and 42% amino acid identity, respectively). OXA-18 is likely to be chromosomally encoded since no plasmid was found in the strain and because attempts to transfer the resistance marker failed. OXA-18 is peculiar since it is a class D beta-lactamase which confers high resistance to extended-spectrum cephalosporins and seems to have unique hydrolytic properties among non-class A enzymes.
210 citations
TL;DR: The data indicate that ESBLs occur in several species of Enterobacteriaceae and at a relatively high incidence at this institution and that the standard disk diffusion method with cefpodoxime and the DD method with several beta-lactams are practical and cost-effective methods for detecting ESBL-producing isolates of the family Enterobacteria.
Abstract: A total of 907 consecutive isolates of members of the family Enterobacteriaceae recovered during a 20-week period were tested for production of extended-spectrum beta-lactamases (ESBLs) by the double-disk (DD) potentiation method. Of 84 DD-positive isolates, 83 (9.2%) produced ESBLs based on isoelectric focusing. SHV-derived ESBLs and several TEM-derived ESBLs were present in nine species, including the first isolate of Citrobacter koserii and Morganella morganii known to harbor an SHV-derived ESBL. Results of testing 58 nonrepeat isolates for ESBL production by several recommended methods were as follows (percent detected in parentheses): DD method with aztreonam (95), ceftazidime (79), ceftriaxone (88), or cefpodoxime (90); broth microdilution method with ceftazidime (86) or cefotaxime (91) alone or in combination with clavulanate; and the standard disk diffusion method with new breakpoints and standard concentrations of aztreonam (78), ceftazidime (79), ceftriaxone (83), or cefpodoxime (98) or a novel concentration (5 microg) of ceftazidime (88). In three instances during an extended part of the study, an ESBL-producing isolate and a non-ESBL-producing isolate of the same species were recovered from a single blood culture bottle. These data indicate that ESBLs occur in several species of Enterobacteriaceae and at a relatively high incidence at our institution and that the standard disk diffusion method with cefpodoxime and the DD method with several beta-lactams are practical and cost-effective methods for detecting ESBL-producing isolates of Enterobacteriaceae.
184 citations
TL;DR: Pseudomonas aeruginosa AH, isolated in Ankara, Turkey, was highly resistant to ceftazidime and produced a beta-lactamase that gave a doublet of bands at pIs 8.7 and 8.9, and a minor sequence change in OXA-2 gave a major extension of cephalosporinase activity and contingent resistance.
Abstract: Pseudomonas aeruginosa AH, isolated in Ankara, Turkey, was highly resistant to ceftazidime (MIC, 128 microg/ml) and produced a beta-lactamase that gave a doublet of bands at pIs 8.7 and 8.9. beta-Lactamase production was transferable to P. aeruginosa PU21 by conjugation and was determined by a ca. 450-kb plasmid, pMLH54. The transconjugant and Escherichia coli transformed with the cloned gene showed increased resistance to ceftazidime (especially) and to cefpirome, ceftazidime, ceftriaxone, moxalactam, and aztreonam, but not to carbapenems. Resistance was not reversed by clavulanic acid or tazobactam. Sequencing revealed that the beta-lactamase responsible for this resistance was identical to OXA-2 except that glycine replaced aspartate at position 150. Compared to OXA-2, the new enzyme, named OXA-15, had greater cephalosporinase activity, with increased relative hydrolysis rates for cephaloridine and cephalothin and, most dramatically, for ceftazidime. Cefotaxime and carbapenems remained stable to hydrolysis. Thus, as in the TEM, SHV, and OXA-10 (PSE-2) beta-lactamase families, a minor sequence change in OXA-2 gave a major extension of cephalosporinase activity and contingent resistance. The gene encoding the new beta-lactamase, bla(OXA-15), lay close to the highly conserved 3' end of an integron and had flanking sequences typical of an integron-associated gene cassette. Restriction mapping and partial sequence data indicated that pMLH54 carries an integron with three putative gene cassettes: bla(OXA-15) itself, aadB [coding aminoglycoside nucleotidyltransferase (2")-1a], and an uncharacterized cassette.
94 citations
TL;DR: The ease with which highly resistant bacteria can be imported into the UK and spread within hospitals is demonstrated, particularly amongst patients on the liver transplant unit.
Abstract: Sixteen strains of Escherichia coli with high-level resistance to extended-spectrum cephalosporins and other classes of antibiotic have been isolated at St James' University Hospital, Leeds. They produce up to three separate beta-lactamases: TEM-1, SHV-5 and, in five isolates, a plasmid-mediated AmpC-type enzyme. With the exception of carbapenems, the isolates reported in this study were resistant to all beta-lactam antibiotics including extended-spectrum cephalosporins and the monobactam aztreonam. There was evidence of the spread of a plasmid encoding SHV-5, particularly amongst patients on the liver transplant unit. Sensitivity to beta-lactam antibiotics in five isolates expressing the AmpC-type beta-lactamase was not restored by the beta-lactamase inhibitor clavulanic acid. These bacteria also carried blaSHV-5 on a large plasmid. PCR-amplification of the structural gene and digestion with restriction endonucleases demonstrated that the plasmid-mediated blaAmpC probably identified as BIL-1 using the criteria available. Four of the five patients carrying isolates that carried the plasmid-located blaAmpC gene had recently visited the Indian subcontinent and we presume that they returned carrying these bacteria. Restriction fragment length polymorphism analysis using pulsed field gel electrophoresis (PFGE) suggests that at least four distinct strains existed amongst these five isolates. The two isolates that had very similar PFGE patterns had different plasmid profiles and were isolated from different locations in the hospital and at different times. This study demonstrates the ease with which highly resistant bacteria can be imported into the UK and spread within hospitals.
79 citations
TL;DR: The resistance of E. coli P37 to mechanism-based inactivators results from a higher level of production of the TEM-derived enzyme due to the G-to-T substitution at position 162 (G-162-->T) in the promoter region of blaTEM and from the structural modifications resulting from the Met-69-->Leu and Arg-275-->Gln substitutions that characterize IRT-14 beta-lactamase.
Abstract: IRT-14 (TEM-45) is a new mutant TEM-type beta-lactamase that was isolated from clinical Escherichia coli P37 and that confers resistance to broad-spectrum penicillins with reduced sensitivity to beta-lactamase inhibitors. The MICs of amoxicillin alone and of amoxicillin combined with 2 micrograms of clavulanic acid or 2 micrograms of tazobactam per ml were 4,096, 2,048, and 1,024 micrograms/ml, respectively. The strain was susceptible to cephalosporins, aztreonam, moxalactam, and imipenem. The enzyme was purified to homogeneity, and values of the kinetic parameters Kcat, Km, and Kcat/Km were determined for different substrates. This enzyme, with a pI of 5.2, was found to have reduced affinity for broad-spectrum penicillins and cephalosporins. The values of 50% inhibitory concentrations of clavulanic acid, sulbactam, tazobactam, and brobactam are correlated with the higher KmS for substrates. The resistance of E. coli P37 to mechanism-based inactivators results from a higher level of production of the TEM-derived enzyme due to the G-to-T substitution at position 162 (G-162-->T) in the promoter region of blaTEM and from the structural modifications resulting from the Met-69-->Leu and Arg-275-->Gln substitutions that characterize IRT-14 beta-lactamase.
44 citations
TL;DR: BMS-180680 was the only antibiotic evaluated that was active against >90% of the Pseudomonas aeruginosa, Burkholderia cepacia, and Stenotrophomonas maltophilia strains tested.
Abstract: The in vitro activities of a new catechol-containing monobactam, BMS-180680 (SQ 84,100), were compared to those of aztreonam, ceftazidime, imipenem, piperacillin-tazobactam, ciprofloxacin, amikacin, and trimethoprim-sulfamethoxazole. BMS-180680 was often the most active compound against many species of the family Enterobacteriaceae, with MICs at which 90% of the isolates were inhibited (MIC90s) of 90% of the Pseudomonas aeruginosa (MIC90, 0.25 microg/ml), Burkholderia cepacia, and Stenotrophomonas maltophilia (MIC90s, 1 microg/ml) strains tested. BMS-180680 was inactive against most strains of Pseudomonas fluorescens, Pseudomonas stutzeri, Pseudomonas diminuta, and Burkholderia pickettii. BMS-180680 was moderately active (MIC90s of 4 to 8 microg/ml) against Alcaligenes spp. and Acinetobacter lwoffii and less active (MIC90, 16 microg/ml) against Acinetobacter calcoaceticus-Acinetobacter baumanii complex. BMS-180680 lacked activity against gram-positive bacteria and anaerobic bacteria. Both tonB and cir fiu double mutants of E. coli had greatly decreased susceptibility to BMS-180680. Of the TEM, PSE, and chromosomal-encoded beta-lactamases tested, only the K1 enzyme hydrolyzed BMS-180680 to any measurable extent. Like aztreonam, BMS-180680 bound preferentially to penicillin-binding protein 3. The MICs of BMS-180680 were not influenced by the presence of hematin or 5% sheep blood in the test medium or with incubation in an atmosphere containing 5% CO2. BMS-180680 MICs obtained under strict anaerobic conditions were significantly higher than those obtained in ambient air.
37 citations
TL;DR: Erythromycin and azithromycin have value primarily for treatment of endocervical chlamydial infections and mycoplasma pneumonia in obstetric patients and for intrapartum prophylaxis against group B streptococcal infection in patients who are allergic to beta-lactam antibiotics.
32 citations
TL;DR: Data from a multilaboratory Colombia surveillance project was initiated in early 1997 to monitor the potency and spectrum of six broad-spectrum antimicrobial agents to provide a resistance statistical baseline to which future studies in this nation can be compared.
32 citations
TL;DR: Data from broad-host-range vector studies are consistent with the conclusion that PBP3 has to achieve a certain level of saturation, with beta-lactams targeted to this protein, to result in cell inhibition or death.
Abstract: By using a broad-host-range vector, pUCP27, the Pseudomonas aeruginosa and Escherichia coli pbpB genes, which encode penicillin-binding protein 3 (PBP3), were separately overexpressed in a P. aeruginosa strain, PAO4089, that is deficient in producing chromosomal beta-lactamase. Susceptibility studies indicated that overproduction of the P. aeruginosa PBP3 in PAO4089 resulted in twofold-increased resistance to aztreonam, fourfold-increased resistance to cefepime and cefsulodin, and eightfold-increased resistance to ceftazidime, whereas overproduction of the P. aeruginosa PBP3 in PAO4089 did not affect susceptibility to PBP1-targeted cephaloridine or PBP2-targeted imipenem. Similar results were obtained with PAO4089 overproducing E. coli PBP3, with the exception that there was no influence on the MICs or minimal bactericidal concentrations of cefsulodin and cefepime, which have very low affinities for E. coli PBP3. These data are consistent with the conclusion that PBP3 has to achieve a certain level of saturation, with beta-lactams targeted to this protein, to result in cell inhibition or death.
31 citations
TL;DR: Cefoxitin merits clinical evaluation in infections caused by bacteria that produce ESBLs, and ceftibuten MICs increased with higher inocula when tested against strains producing SHV-4 orSHV-5 and, to a lesser extent, strains producing multiple beta-lactamases.
Abstract: Background. Infections caused by Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) are a growing clinical problem. However, there is wide variation in the level of resistance to third generation beta-lactams conferred by these enzymes. Methods. We studied 33 Klebsiella pneumoniae and 4 Escherichia coli isolates producing ESBLs obtained from outbreaks in 14 different hospitals and a nursing home in the United States. Microdilution testing with standard (10 4-5 colony-forming units/ml) and large (10 6-7 colony-forming units/ml) inocula, was used to compare the minimum inhibitory concentrations (MICs) of ceftibuten, a novel oral oxyimino beta-lactam, with those of other third generation beta-lactams (cefotaxime, ceftazidime, aztreonam, cefixime, cefpodoxime and cefoxitin). Results. Twenty-seven of the clinical isolates had well-characterized ESBLs of 10 different types, 7 of which produced TEM-1; 1 isolate also produced LXA-1. Two strains produced more than 1 ESBL. The remaining 10 strains produced 8 as yet uncharacterized types of ESBL. With large inocula 73% tested susceptible to ceftibuten, whereas 8 to 22% tested susceptible to the other third generation beta-lactam antibiotics. Ceftibuten MICs increased with higher inocula when tested against strains producing SHV-4 or SHV-5 and, to a lesser extent, strains producing multiple beta-lactamases. Only cefoxitin showed a smaller inoculum effect. Conclusion. Ceftibuten merits clinical evaluation in infections caused by bacteria that produce ESBLs.
TL;DR: Most strains tested were susceptible to minocycline, ceftazidime, ciprofloxacin, and trimethoprim-sulfamethoxazole, and all strains were resistant to aminoglycosides, and only some strains wereresistant to imipenem.
TL;DR: The activity of some third generation cephalosporins, aztreonam, imipenem, ciprofloxacin, and amikacin against isolates of Acinetobacter baumannii of various biotypes has been studied and isolates, independently of the biotype, exhibited a broad multiresistance.
TL;DR: The Etest seems to render accurate results for these seven antimicrobial agents evaluated, and quality control results conformed to published MIC ranges.
TL;DR: Different antimicrobial agents appear to exert different effects in vitro on the TNF response of macrophages to bacterial stimulation, as seen in New Zealand white rabbits.
Abstract: Alveolar macrophages from New Zealand white rabbits were incubated with twice the MIC of amikacin, ciprofloxacin, aztreonam, ceftazidime and imipenem and exposed to either 10 4 , 10 5 or 10 6 cfu/mL live Pseudomonas aeruginosa ATCC 27853 or 0.1, 1 or 10 mg/L purified lipopolysaccharide (LPS) derived from P. aeruginosa to determine the effects of different classes of antimicrobial agent on production of tumour necrosis factor (TNF). Incubation of macrophages with ciprofloxacin and amikacin resulted in less TNF activity after exposure to live P. aeruginosa than was found for saline, aztreonam, ceftazidime or imipenem (P < 0.05). However, no significant differences were found between any of the agents after macrophages had been exposed to purifi ed LPS. Different antimicrobial agents therefore appear to exert different effects in vitro on the TNF response of macrophages to bacterial stimulation.
TL;DR: The role of the monobactam aztreonam in burn wound infections and compared it to the aminoglycosides amikacin and gentamicin as well as piperacillin for the Enterobacteriacae and Pseudomonas aeruginosa were evaluated.
TL;DR: Analysis of beta-lactam susceptibility patterns suggested that cephalosporinase derepression and intrinsic resistance were the predominant underlying mechanisms in Pseudomonas aeruginosa isolates.
TL;DR: Two seriously neutropenic patients with severe infections caused by Stenotrophomonas maltophilia were treated with aztreonam/clavulanic acid (2:1) combination and both patients evolved favorably.
Abstract: Two seriously neutropenic patients (a 23-year-old man with a promyelocytic acute myeloid leukemia [AML-M3] and a 77-year old male with an immature acute myeloid leukemia [AML-M1] diagnosis) with severe infections caused by Stenotrophomonas maltophilia were treated with aztreonam/clavulanic acid (2:1) combination. In the first patient the infection was caused by a multiresistant strain and in the second, by a strain with poor response to trimethoprim-sulfamethoxazole and other antimicrobial agents. After treatment with aztreonam/clavulanic acid both patients evolved favorably.
TL;DR: The variability in the resistance of these K. oxytoca strains would seem to be due to variation in the level of production of the beta-lactamases rather than to structural alteration of the enzymes.
Abstract: Klebsiella oxytoca strain HB60 is highly resistant to cefoperazone and aztreonam (MICs = 128 mg/L). It produces a chromosomally encoded beta-lactamase of pI 5.7 which was highly efficient against penicillins, first-generation cephalosporins and cefoperazone, a non-oxyimino third-generation cephalosporin. Aztreonam and oxyimino broad-spectrum cephalosporins were less good substrates. The beta-lactamase activity was susceptible to inhibition by clavulanic acid (IC50 = 1 microM). The enzyme purified to homogeneity had a specific activity towards benzylpenicillin of 3670 U/mg. The 263 amino acid residues of the protein were sequenced by Edman degradation of proteolytic peptides. The beta-lactamase was shown to belong to the OXY-2 group as it had only one amino acid substitution (Asn for Asp at ABL position 197) compared with the beta-lactamase (pI 5.2) from the aztreonam-susceptible K. oxytoca strain SL911 and two substitutions (Ala223 for Val and Asp255 for Asn) compared with the beta-lactamase (pI 6.4) from the aztreonam-resistant K. oxytoca strain D488. These three OXY-2-group enzymes behave in the same way towards beta-lactam antibiotics. The variability in the resistance of these K. oxytoca strains would thus seem to be due to variation in the level of production of the beta-lactamases rather than to structural alteration of the enzymes.
TL;DR: Despite observations of markedly increased and highly variable V in critically ill surgical patients, a standard dosage of aztreonam was usually sufficient to maintain adequate serum drug levels.
Abstract: The pharmacokinetics of aztreonam in critically ill surgical patients with serious gram-negative infections were studied. Blood samples were taken before and at 30 minutes, 2.5 hours, and 5 hours after a dose of aztreonam 2 g i.v. every six hours. All patients had received at least two aztreonam doses before the dosage interval being studied. Aztreonam concentrations were measured by high-performance liquid chromatography. Aztreonam's pharmacokinetics, the severity of illness, and patient outcomes were examined. A total of 28 patients with 111 serum aztreonam concentrations were included in the analysis. The patients were young (mean age, 35 years) and predominantly male. The mean APACHE II score was 19.3, and 22 patients had sepsis. Four patients died. The mean volume of distribution (V) of 0.35 L/ kg was nearly twice the previously reported steady-state value for healthy volunteers (0.18 L/kg) and was highly variable. A slightly higher than normal mean V, 0.22 L/ kg, was seen in a subset of six patients whose infection occurred earlier in their intensive care and who had lower APACHE II scores. While with some antibiotics the elevated V would imply difficulty in achieving therapeutic drug levels, 99 (89%) of the 111 concentrations were at or above the in vitro susceptibility breakpoint of 8 micrograms/mL. Despite observations of markedly increased and highly variable V in critically ill surgical patients, a standard dosage of aztreonam was usually sufficient to maintain adequate serum drug levels.
TL;DR: Cefepime, a new parenteral cephalosporin, was evaluated for its in vitro antibacterial activity in comparison with other broad-spectrum antibiotics against a total of 445 recently isolated microorganisms of nosocomial origin and imipenem was the most active compound.
Abstract: Cefepime, a new parenteral cephalosporin, was evaluated for its In Vitro antibacterial activity in comparison with other broad-spectrum antibiotics against a total of 445 recently isolated microorganisms of nosocomial origin. Cefepime was highly active against all species of Enterobacteriaceae with minimum inhibitory concentrations (MIC90s) ranging from 0.25-8 μ/ml. Cefepime showed moderate activity against Acinetobacter spp (MIC50 and MIC90, 16 μ/ml) but its activity was superior to that of any drug tested, except imipenem. Against Pseudomonas aeruginosa its activity was comparable to that of ceftazidime and was greater than that of cefotaxime, aztreonam, ciprofloxacin and aminoglycosides. Of all the agents tested, imipenem was the most active compound. Cefepime was active against Staphylococcus aureus and coagulase-negative methicillin-susceptible staphylococci but it had no activity against methicillin-resistant staphylococci and enterococci.
TL;DR: Among 48 clinical strains of Klebsiella pneumoniae isolated in a university hospital in Northern Greece, 29 exhibited resistance to third generation cephalosporins (3GC) and aztreonam, which record a diversity of β-lactamases and explain the variousβ - lactam resistance patterns observed in the sample.
Abstract: Among 48 clinical strains of Klebsiella pneumoniae isolated in a university hospital in Northern Greece, 29 (60.4%) exhibited resistance to third generation cephalosporins (3GC) and aztreonam. Thirty-two (66.7%) of the isolates were found resistant to the combination of ampicillin/sulbactam and six (12.5%) exhibited resistance to all the above antibiotics plus cefoxitin. Resistance to 3GC was related mostly with the presence of a β-lactamase exhibiting pI 8.2 and substrate profile of an SHV-5 type enzyme and rarely (in two of the cefoxitin resistant strains) with the presence of plasmid-mediated class C cephalosporinases. Resistance to the ampicillin/sulbactam combination was associated with the presence of a β-lactamase with pI 5.4, presumably representing a TEM-1 β-lactamase. These findings record a diversity of β-lactamases and explain, at least partly, the variousβ -lactam resistance patterns observed in our K. pneumoniae sample.
TL;DR: The high rates of PTZ resistance in E. coli and K. pneumoniae and the extensive cross-resistance to other beta-lactams suggest that PTZ should be used with caution in the clinical setting.
TL;DR: Stenotrophomonas maltophilia strain 298/85 was isolated from the extensively inflamed conjunctiva of a neonate in a regional hospital in Ostrava, Czech Republic and was resistant to all available antibiotics except cefepime and trimethoprim.
TL;DR: Though both agents selectively affect PBP 3, as manifested by elongated bacteria, they induce in the peripheries of the clots thickening, breaks, and detachment in bacterial cell walls, alterations which are generally associated with antibiotics affecting PBP 1a and 1b.
Abstract: The differential tissue distributions of aztreonam and ceftazidime within fibrin clots infected with Pseudomonas aeruginosa, Enterobacter cloacae, and Serratia marcescens, their efficacies, and the in vivo bacterial morphological changes induced by these drugs were evaluated. Rabbits were given intravenously a single dose of 100 mg of either agents/kg of body weight. In the cores of the clots, the peak levels of both drugs were much lower than those observed in the peripheries and in serum. Aztreonam's half-lives within the peripheries and in the cores of the fibrin clots were up to six times higher than observed in serum, while ceftazidime's half-lives in clots were twice that observed in serum. This resulted in a much greater penetration ratio for aztreonam than for ceftazidime. Both drugs controlled the growth of P. aeruginosa in vivo, but E. cloacae and S. marcescens responded better to ceftazidime. Morphological changes were more abundant in the peripheries than in the cores of the clots. In the control group, P. aeruginosa's morphology in the cores was different than that in the peripheries of the clots. Against P. aeruginosa, aztreonam did induce morphological changes in the cores while ceftazidime did not. Electron microscopic studies revealed that morphological changes associated with aztreonam seemed different than those of ceftazidime. Along with elongation of bacteria, more bow tie and herniated bacteria were observed with aztreonam. Though both agents selectively affect PBP 3, as manifested by elongated bacteria, they induce in the peripheries of the clots thickening, breaks, and detachment in bacterial cell walls, alterations which are generally associated with antibiotics affecting PBP 1a and 1b.
TL;DR: Simple, rapid, sensitive, precise, and reproducible assay methods have been developed for the quantification of BMS-180680 in dog and rat plasma using aztreonam as the internal standard.
Abstract: BMS-180680 is a monobactam antibiotic currently under development for the treatment of gram negative bacteria including Pseudomonas aeruginosa. Simple, rapid, sensitive, precise, and reproducible assay methods have been developed for the quantification of BMS-180680 in dog and rat plasma using aztreonam as the internal standard. The assay methods involve a single-step protein precipitation by addition of acetonitrile, followed immediately by centrifugation, after which the supernatant is evaporated to dryness (65°C) under a gentle stream of nitrogen. The residue is re-constituted in the mobile phase, transferred to a micro-WISP vial and injected on to a Zorbax It, C-18 HPLC column preceded by a guard column. Mobile phase comprised 17% acetonitrile and 83% of 40 mM dibasic ammonium phosphate and 6 mM tetrabutylammonium hydrogen sulfate. A small amount of tetrahydrofuran (20 mL/liter of mobile phase) was added and the apparent pH of the mobile phase was adjusted to 4.1 with 85% phosphoric acid. The...
01 Nov 1997-Zentralblatt Fur Bakteriologie-international Journal of Medical Microbiology Virology Parasitology and Infectious Diseases
TL;DR: Six Klebsiella pneumoniae strains collected from two hospitals in Ostrava, Czech republic indicated production of ESBLs by these strains, and two strains from patients of the ICU in the University Hospital were resistant to cephalothin, cefotaxime and ceftazidime.
Abstract: Summary Six Klebsiella pneumoniae strains were collected from two hospitals in Ostrava, Czech republic. Four strains (Nos. 209, 217, 218, 222) were isolated from sputa of critically ill patients from Municipal Hospital Vitkovice — Ostrava. They were resistant to cephalothin, cefotaxime, and ceftazidime (MIC > 100 mg × 1 -1 ). Strain No. 218 was intermediately resistant also to ofloxacin and aztreonam (MIC = 12.5 mg × 1 -1 ), strain No. 222 wa resistant to aztreonam (MIC = 50 mg × 1 -1 ). Determinants of resistance to cephalothin, cefotaxime, aztreonam and ceftazidime were transferred to re strains of P. mirabilis P-38 rif + and E. coli K-12 No. 3110 rif + by all four strains. Synergy between clavulanate-cefotaxime, clavulanate-ceftazidime and clavulanate-aztreonam indicated production of ESBLs by these strains. Two strains, No. 214 and 224, from patients of the ICU in the University Hospital were resistant to cephalothin, cefotaxime and ceftazidime (MIC > 100 × 1 -1 ). Strain No. 214 was intermediately resistant to aztreonam and ofloxacin (MIC = 12,5 mg × 1 -1 ) and strain No. 224 was highly resis aztreonam (MIC = 50 mg × 1 -1 ). Synergy between clavulanate and cefotaxime as well as between clavulanate and aztreonam, but not between clavulanate ceftazidime corresponds with non-transferable ceftazidime resistance in strains No. 214 and 224 and indicates different types of ESBL in strains from each of two hospitals.
Journal Article•
TL;DR: Resistance to imipenem and meropenem, reported sporadically in Enterobacteriaceae and more frequently in Pseudomonas aeruginosa, can be caused, among other mechanisms, by the combination of changes in permeability and hyperproduction of inducible chromosomal beta-lactamases.
Abstract: Resistance to imipenem and meropenem, reported sporadically in Enterobacteriaceae and more frequently in Pseudomonas aeruginosa, can be caused, among other mechanisms, by the combination of changes in permeability and hyperproduction of inducible chromosomal beta-lactamases. In this study, the in vitro activity of imipenem and meropenem was analysed by the agar dilution method against cefotaxime, ceftazidime, and aztreonam resistant clinical strains of Enterobacteriaceae (n = 202) and P. aeruginosa (n = 90). This phenotype is consistent with the hyperproduction of group 1 chromosomal beta-lactamases and was previously determined in stably derepressed mutants in the same species, obtained from strains with inducible beta-lactamase expression by selection with cefotaxime and ceftazidime. Likewise, the activity of imipenem and meropenem against the same number of clinical isolates susceptible to cefotaxime, ceftazidime, and aztreonam was evaluated. In general, imipenem and meropenem showed an excellent activity, which was intrinsically greater for meropenem against Enterobacteriaceae and P. aeruginosa organisms. Nevertheless, imipenem and meropenem activity was slightly affected on cefotaxime, ceftazidime, and aztreonam resistant isolates of E. cloacae (MIC90, 1 and 0.2 microgram/ml, respectively), E. aerogenes (1 and 0.2 microgram/ml), C. freundii (1 and 0.1 microgram/ml), M. morganii (1 and 0.5 microgram/ml), and S. marcescens (4 and 0.5 micrograms/ml). On the other hand, the activity of imipenem and meropenem against ceftazidime and aztreonam resistant isolates of P. aeruginosa was more significantly affected, with MIC90 values of 64 and 16 micrograms/ml, respectively.