Aztreonam in the treatment of serious orthopedic infections

Pribyl, Charles R.; Salzer, R. H.; Beskin, James L.; Haddad, Ray J.; Pollock, Beatrice; Beville, R; Holmes, B; Mogabgab, William J.

doi:10.1016/0002-9343(85)90205-0

Cited by 40 publications

(14 citation statements)

References 5 publications

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“…Aztreonam has excellent activity against gram-negative microorganisms, beta-lactamase stability, activity in anaerobic and acidotic milieus, and good penetration into both synovial fluid and bone. These qualities are consistent with early reports of its efficacy in the treatment of gram-negative bone and joint infections (12,22). …”

supporting

confidence: 90%

Aztreonam penetration into synovial fluid and bone

MacLeod¹,

Bartley²,

Jo³

et al. 1986

Antimicrob Agents Chemother

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Eighteen patients with uncomplicated degenerative joint disease requiring joint replacement (hip or knee) were given a single 2-g intravenous dose of aztreonam over a 5-min period preoperatively. The mean concentration in synovial fluid of 83.0 9.2 >g/ml averaged 0.99 times the concomitant levels in serum. The mean concentration in cancellous bone of 16.0 4.3 Lg/g averaged 0.20 times the concomitant levels in serum.The increasing incidence of gram-negative bone and joint infections (14,19), particularly in patients with underlying diseases (13), combined with a higher incidence of poor therapeutic outcome in patients with such infections treated with available antimicrobial agents (10,29) (17), except that the samples were pulverized with a Spex freezer-mill prior to assay. The limit of detection of the assay was 0.1 ,ug/g of bone. The coefficient of variation and mean recovery from standards were 8.0 and 79.0%, respectively.Bone samples were prepared for high-pressure liquid chromatography by a procedure identical to that used for the bioassay and then filtered (Millex; 0.45 pum [pore size]; Millipore Corp., Bedford, Mass.). They were then analyzed with a high-pressure liquid chromatography system consisting of an Altex model 11OA pump set for 2 ml/min, a 37-to 50-,um silica gel precolumn, a 30-to 38-,um C18 guard column, a Waters Associates, Inc., 10-,um ,Bondpak analytical column (150 by 3.9 mm), and a UV detector set for 290 nm. The mobile phase was 85 parts 5 mM tetrabutylammonium sulfate, adjusted to pH 2.85 with 1 M KH2PO4, and 15 parts acetonitrile. Samples were introduced via a 20-,u precision loop injector. The limit of detection was 1 ,ug/g, the coefficient of variation was 8.1%, and the mean recovery from standards was 87.0%.The method used for microbiological assay of synovial fluid was identical to that previously reported for urine (20), except that samples were diluted 1:20 in 0.1 M phosphate buffer (pH 6) prior to assay. The limit of detection was 0.4 ,g/ml. The coefficient of variation and mean recovery were 3.5 and 98%, respectively. The high-pressure liquid chromatographic assay of synovial fluid was done by a method identical to that previously reported for serum (20). The limit of detection was 0.5 ,ug/ml. The coefficient of variation and recovery from standards were 8.5 and 98%, respectively.Assays of hemoglobin in blood, bone, and synovial fluid and correction of aztreonam concentrations for blood contamination were performed by previously described methods (17). Samples whose blood contents were 51% or more were excluded from analysis. No specimens suitable for assay could be obtained from patient 6.Results of the aztreonam assays are listed in Table 1. The mean concentration in serum at the time of bone and synovial fluid removal was 78 ,ug/ml. The mean concentration in bone was 16 ,ug/g. Concentrations of aztreonam in individual bone specimens were variable but showed a 710

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supporting

confidence: 90%

Aztreonam penetration into synovial fluid and bone

MacLeod¹,

Bartley²,

Jo³

et al. 1986

Antimicrob Agents Chemother

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“…In addition, the range of target microorganisms tested in this study was larger than that Cronobacter sakazakii (previously known as Enterobacter sakazakii) is a Gram-negative, peritrichously motile, nonspore-forming bacterium which has been the cause of many serious diseases in humans, including meningitis, hydrocephalus, necrotizing enterocolitis, septicemia, and brain abscesses (3,31,40). Infants, especially those who are immunocompromised or of low birth weight, are a major risk group for infection, whereas adults are rarely infected (7,14,24,33,35). There have been a total of 120 cases of C. sakazakii infection, with 27 deaths being reported for infants alone (9).…”

Section: Discussionmentioning

confidence: 99%

Altering the Composition of Caseicins A and B as a Means of Determining the Contribution of Specific Residues to Antimicrobial Activity

Norberg

O’Connor

Stanton

et al. 2011

Appl Environ Microbiol

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Caseicin A (IKHQGLPQE) and caseicin B (VLNENLLR) are antimicrobial peptides generated through the bacterial fermentation of sodium caseinate, and on the basis of this and previous studies, they are active against many Gram-negative pathogens (Cronobacter sakazakii, Cronobacter muytjensii, Salmonella enterica serovar Typhimurium, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas fluorescens) as well as the Gram-positive organism Staphylococcus aureus. Here we describe further studies with the aim of establishing the importance of specific (charged and nonpolar aliphatic) residues within the caseicin peptides and the effects that they have on the bacteria listed above. In order to achieve our objective, we created four derivatives of each caseicin (A1 to A4 and B1 to B4) in which specific residues were altered, and results obtained with these derivatives were compared to wild-type caseicin activity. Although conversion of cationic residues to alanine in caseicins B1 (R8A change), A1 (K2A), A2 (H3A), and A3 (K2A-H3A) generally resulted in their activity against microbial targets being reduced or unaltered, C. sakazakii DPC6440 was unusual in that it displayed enhanced sensitivity to three peptides (caseicins A1, A3, and B2) in which positively charged residues had been eliminated. While the replacement of leucine with alanine in selected variants (B3 and B4) resulted in reduced activity against a number of strains of Cronobacter and, in some cases, S. Typhimurium, these changes enhanced the activities of these peptides against DPC6440 and a number of S. aureus strains. It is thus apparent that the importance of specific residues within the caseicin peptides is dependent on the strain being targeted.In recent years, the milk protein casein has been identified as a rich source of antimicrobial peptides, many of which have been characterized extensively. The casein-derived caseicin A and B peptides, which are the subjects of this study, were originally identified following a bacterial fermentation of sodium caseinate and were previously shown to exhibit antibacterial activity against strains of Cronobacter sakazakii and Escherichia coli (15). These and a number of other casein-derived antimicrobials are primarily cationic in nature, and thus it was plausible that these functioned in a manner similar to that for classical cationic antimicrobial peptides (cAMPs). As well as being cationic, cAMPs are amphipathic and hydrophobic ␣-helical peptides which are active against a range of microbial targets as a consequence of permeabilization of the cytoplasmic membrane leading to loss of the proton gradient (6, 21, 25, 37). The importance of the charged residues within cAMPs is apparent from studies on peptide derivatives with reduced cationic charges, which were shown to exhibit reductions in antimicrobial activity (19). These observations prompted the initiation of corresponding investigations, described here, to assess the importance of a number of residues, including cationic amino acids, in caseicins A and B.The an...

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“…Enterobacter sakazakii is a food-borne pathogen capable of causing meningitis (4,13,38), sepsis (38), bacteremia (40), and necrotizing enterocolitis (55) in preterm neonates and immunocompromised adults (9,15,25,30,45). Its genetic and phenotypic diversity has been demonstrated (24,33), and certain clusters may substantially differ in thermal tolerance (8,58).…”

mentioning

confidence: 99%

Attachment of and Biofilm Formation by Enterobacter sakazakii on Stainless Steel and Enteral Feeding Tubes

Kim

Ryu

Beuchat

2006

Appl Environ Microbiol

152

103

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Enterobacter sakazakii has been reported to form biofilms, but environmental conditions affecting attachment to and biofilm formation on abiotic surfaces have not been described. We did a study to determine the effects of temperature and nutrient availability on attachment and biofilm formation by E. sakazakii on stainless steel and enteral feeding tubes. Five strains grown to stationary phase in tryptic soy broth (TSB), infant formula broth (IFB), or lettuce juice broth (LJB) at 12 and 25°C were examined for the extent to which they attach to these materials. Higher populations attached at 25°C than at 12°C. Stainless steel coupons and enteral feeding tubes were immersed for 24 h at 4°C in phosphate-buffered saline suspensions (7 log CFU/ml) to facilitate the attachment of 5.33 to 5.51 and 5.03 to 5.12 log CFU/cm 2 , respectively, before they were immersed in TSB, IFB, or LJB, followed by incubation at 12 or 25°C for up to 10 days. Biofilms were not produced at 12°C. The number of cells of test strains increased by 1.42 to 1.67 log CFU/cm 2 and 1.16 to 1.31 log CFU/cm 2 in biofilms formed on stainless steel and feeding tubes, respectively, immersed in IFB at 25°C; biofilms were not formed on TSB and LJB at 25°C, indicating that nutrient availability plays a major role in processes leading to biofilm formation on the surfaces of these inert materials. These observations emphasize the importance of temperature control in reconstituted infant formula preparation and storage areas in preventing attachment and biofilm formation by E. sakazakii.

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Aztreonam in the treatment of serious orthopedic infections

Cited by 40 publications

References 5 publications

Aztreonam penetration into synovial fluid and bone

Aztreonam penetration into synovial fluid and bone

Altering the Composition of Caseicins A and B as a Means of Determining the Contribution of Specific Residues to Antimicrobial Activity

Attachment of and Biofilm Formation by Enterobacter sakazakii on Stainless Steel and Enteral Feeding Tubes

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