Comparative in vitro activity of meropenem versus other extended-spectrum antimicrobials against randomly chosen and selected resistant clinical isolates tested in 26 North American centers.

The in vitro antibacterial activity of meropenem and up to nine other antimicrobials was compared in studies at 26 North American centers from 1989 to 1992 with use of standardized and controlled procedures for determining minimal inhibitory concentrations (MICs) against 12,483 recent clinical isolates and additional drug-resistant strains. Overall, carbapenems were the most active drugs. The antibacterial activity of meropenem was consistent against random isolates in all centers; however, inclusion of large proportions of multidrug-resistant gram-negative aerobes by some centers did increase MICs of meropenem and the comparators.

Comparison of antibacterial activities of meropenem and six other antimicrobials against Pseudomonas aeruginosa isolates from North American studies and clinical trials.

The in vitro activity of meropenem was compared with those of six other antimicrobials against up to 1,182 clinical isolates of Pseudomonas aeruginosa from 16 North American centers by means of standardized controlled methods. Meropenem was the most active drug. These isolates were less frequently resistant to meropenem (4.

Penetration of meropenem in plasma and abdominal tissues from patients undergoing intraabdominal surgery.

We assessed the penetration of a new carbapenem antibiotic, meropenem, into abdominal tissues. A single 1,000-mg intravenous dose was administered to 66 patients undergoing elective intraabdominal surgery. Plasma, body fluid (peritoneal fluid and bile), and tissue samples (colon, gallbladder, omentum, stomach, fascia, muscle, and skin) were taken at various times up to 8 hours after administration of the dose.

Tissue penetration of Meropenem in patients undergoing gynecologic surgery.

The purpose of this study was to assess the tissue-penetrating ability of a new beta-lactam antibiotic, meropenem, in 64 patients undergoing elective gynecologic surgery. Patients received a single 500-mg dose intravenously before surgery. Plasma and tissue concentrations of meropenem were highest at approximately 1 hour, and good tissue penetration was seen in the variety of specimens evaluated.

A compilation of meropenem tissue distribution data.

Meropenem body fluid and tissue concentration data from both published studies and samples obtained during efficacy evaluation have been compiled and presented according to a consistent format to facilitate comparison. The concentration data have been compared with the mode MIC data available for the pathogens isolated during the clinical evaluation of meropenem. These data support the widespread and rapid penetration of meropenem into the interstitial fluid of those tissues not protected by a tight epithelial barrier.

Comparison of the activity of meropenem with that of other agents in the treatment of intraabdominal, obstetric/gynecologic, and skin and soft tissue.

Meropenem, a new carbapenem with improved stability in the presence of human dehydropeptidase-I[1], was evaluated in three prospective, multicenter, randomized, controlled clinical trials in North America. We compared the in vitro activity of meropenem and conventional antimicrobial agents for the treatment of intraabdominal, obstetric/gynecologic, and skin or soft tissue infections as well as the responses of pathogens to all of these agents. The trials of the drug for intraabdominal infection were double blind, and those for the obstetric/gynecologic and soft tissue infections were open labeled.

Antibacterial activity of meropenem and selected comparative agents against anaerobic bacteria at seven North American centers.

The antibacterial activity of meropenem and comparative agents against approximately 1,000 anaerobes was determined using the disk dilution methods recommended by the National Committee for Clinical Laboratory Standards (NCCLS). The organisms represented 27 species of six genera and included the most common pathogens. Meropenem and imipenem were the most active drugs and were comparable in overall activity, generally exhibiting an MIC90 of < or = 1 micrograms/mL.

Quality control criteria for testing the susceptibility of anaerobic bacteria to meropenem.

Reference values for quality control of in vitro susceptibility tests with meropenem against anaerobic bacteria were determined in a multilaboratory study by the approved National Committee for Clinical Laboratory Standards agar dilution method for the four quality control strains. The study protocol also included the evaluation of microdilution testing, medium additives, and multiple lots of media. The recommended MIC control ranges for three of the control organisms are as follows: Bacteroides fragilis ATCC 25285, 0.

Development of a meropenem susceptibility disc: drug content, preliminary interpretive and quality control criteria and potency bioassay.

Laboratory studies were conducted to develop an appropriate susceptibility disc for meropenem. Laboratory-prepared paper discs containing 5, 10, and 20 micrograms of meropenem were investigated. Agar dilution MICs and agar disc diffusion tests were performed with 367 rapidly growing clinical isolates by methods recommended by the National Committee for Clinical Laboratory Standards (NCCLS).

The postantibiotic effect of meropenem and imipenem on selected bacteria.

Controlled experiments were conducted to determine the in-vitro postantibiotic effect (PAE) of meropenem and imipenem on ten selected bacteria representative of medically important species: Staphylococcus aureus (2). Pseudomonas aeruginosa (4), Escherichia coli (1), Serratia marcescens (1), Morganella morganii (1), and Providencia stuartii (1). The PAE was determined by comparing serial colony counts of cultures recovering from exposure to drug concentrations at 4 x MIC for 1.

Kibdelins, novel glycopeptide antibiotics. I. Discovery, production, and biological evaluation.

A new subspecies of Kibdelosporangium aridum subsp. largum (SK&F AAD-609), was isolated and shown to produce novel glycopeptides related to aridicins, but containing a homologous series of glycolipids based on N-acylglucosamine. These compounds showed improvements over the aridicins in in vitro activity and were effective in mouse protection studies against a range of Gram-positive bacteria, including methicillin resistant staphylococci.

Charge and lipophilicity govern the pharmacokinetics of glycopeptide antibiotics.

The pharmacokinetics and urinary excretion of nine glycopeptide antibiotics with diverse pIs (3.8 to 8.5) and lipophilicities were studied.

Comparative laboratory studies on alpha-methoxyimino furyl- and phenylacetamido cephalosporins: structure-activity relationships.

Eleven new cephalosporins (three phenylacetamido and eight furylacetamido) containing a methoxyimino group on the 7 beta-acyl side chain and having various substituents at their 3-positions, exhibited similar qualitative, but differing quantitative in vitro antibacterial spectra compared to that of cefuroxime, the first therapeutically used alpha-methoxyimino cephalosporin. The syn-isomers and the alpha-acyl substituted compounds are more active than either the anti-isomer or the beta-acyl substituted compounds. Compounds containing substituted tetrazole rings at the 3-position are likewise more active than those containing other types of substituents in this position.

Antimicrobial activity of aridicins, novel glycopeptide antibiotics with high and prolonged levels in blood.

Three new glycopeptide antibiotics, aridicins A, B, and C, produced by Kibdelosporangium aridum have a spectrum of antimicrobial activity in vitro which is similar to that of vancomycin. The antimicrobial activities of these glycopeptides against clinical bacterial isolates were compared with those of vancomycin and other related glycopeptide antibiotics in vitro by agar dilution and microtiter broth dilution tests and in vivo in mouse protection studies. In vitro they were somewhat less effective than vancomycin against strains of Staphylococcus aureus and less active against coagulase-negative Staphylococcus spp.

Penetration of cefonicid into human breast milk and various body fluids and tissues.

A new cephalosporin, cefonicid (1 g), was given intramuscularly to 49 patients 1 hr before they were to undergo surgery and to 10 healthy lactating women. The concentration of cefonicid was assayed by disk agar diffusion with the use of Bacillus subtilis as the test organism. Concentrations of cefonicid in tissue and fluid specimens were obtained.

Antimicrobial activity of SK&F 88070, an expanded-spectrum cephalosporin with high and prolonged levels in blood.

SK&F 88070 (7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-3- [[[1-(2-sulfaminoethyl)-1H-tetrazol-5-yl]thio] methyl]-3-cephem-4-carboxylic acid) is a new parenteral cephalosporin with an expanded-spectrum profile of antibacterial activity, including activity against Pseudomonas aeruginosa, and with high and prolonged levels in sera of experimental animals. The activity of SK&F 88070 was compared with those of cefotaxime and other cephalosporins against more than 500 clinical isolates in vitro by microtiter twofold dilution tests in Mueller-Hinton broth. SK&F 88070 was extremely potent against all of the members of the family Enterobacteriaceae that were tested, including beta-lactamase-producing strains.

Five cephalosporins: pharmacokinetics and their relation to antibacterial potency.

In a group of adult volunteers, pharmacokinetic profiles of five cephalosporins were correlated with their minimal inhibitory concentrations (MICs90) against Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter aerogenes. Subjects received the following intravenous regimens in a randomized, crossover fashion: (1) 0.5 gm, 1 gm, or 2 gm of cefazolin; (2) 2 gm of cephalothin; (3) 1 gm of cephapirin; (4) 1 gm of cefoxitin; or (5) 0.

Ceftizoxime kinetics and renal handling.

The kinetics and renal handling of ceftizoxime were examined after intravenous and intramuscular injection and the effect of probenecid on its excretion was investigated. Peak serum level after 1000 mg IV was 60.5 microgram/ml and half-life (t 1/2) was 1.

Kinetics and renal handling of cefonicid.

Cefonicid kinetics were determined after intravenous and intramuscular injection and the renal handling of the drug was examined, including the effect of probenecid on its excretion. Peak serum levels after 1000 and 500 mg intravenously was 221 and 91 micrograms/ml. The half-life (t1/2) was the same for both regimens (3.

Serum protein binding alterations of selected cephalosporin antibiotics by fatty acids and their derivatives.

Saturated fatty acids containing 10--14 carbon atoms were more potent inhibitors of serum protein binding than those containing shorter or longer carbon chains. Introduction of unsaturation into chains containing 16 or 18 carbons increased their inhibitory potency. Triglycerides and fatty acid esters, chlorides, thiols, and amides had no inhibitory activity.

In vitro and in vivo laboratory studies on three hydroxyiminophenylacetyl cephalosporins with particular reference to SK&F 80303, an unusually long-acting cephalosporin.

Three cephalosporins with 7-(2-hydroxyiminophenylacetamido) side chains (SK&F 79433, 80000 and 80303), differing in their 3-substituents, exhibited similar broad-spectrum antibacterial activity in vitro against strains of Staphylococcus aureus, Streptococcus faecalis and various Gram-negative bacilli. All three were active in vivo (s.c.

SK&F 75073, new parenteral broad-spectrum cephalosporin with high and prolonged serum levels.

SK&F 75073, a new parenteral cephalosporin, was found to have broad in vitro and in vivo antibacterial activity including isolates usually resistant to cephalothin and cefazolin. This activity included indole-positive Proteus and Enterobacter species and some Serratia isolates. Proteus mirabilis strains were particularly susceptible, as were Haemophilus influenzae and Neisseria species.

Semiautomated turbidimetric microbiological assay for cefazaflur.

A quantitative semi-automated turbidimetric bioassay for cefazaflur, using Streptococcus faecium as the indicator, is described. Assays were run at pH 6.5 approximately 7 for 3.

Biological and chemotherapeutic studies on three semisynthetic cephamycins.

Three semisynthetic cephamycin antibiotics (7alpha-methoxy-cephalosporins), SK&F 73678, SK&F 83088 (CS-1170) and cefoxitin, have been found to possess favorable biological and chemotherapeutic properties. All three cephamycins are active in vitro against strains of Staphylococcus aureus and a variety of gram-negative bacilli. Beta-lactamase producing organisms including indole-producing Proteus spp.