Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Monobactams”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed1987

Cephalosporin, carbapenem, and monobactam antibiotics.

Cephalosporin and related antibiotics are highly effective bactericidal agents of relatively low toxicity. The spectrum of activity varies with the drug but is usually broad. The first-generation cephalosporins, and especially cefazolin, are most active against sensitive staphylococci and streptococci. Most second-generation (except cefoxitin) and third-generation cephalosporins show substantial activity against Haemophilus influenzae. All cephalosporins (except cefsulodin) are active against Klebsiella, Escherichia coli, and Proteus mirabilis, whereas only the third-generation agents have pronounced activity against the other Enterobacteriaceae. Imipenem (a carbapenem) is active against essentially all pathogenic organisms, but aztreonam (a monobactam) is active against only aerobic gram-negative bacilli. Advantages associated with some of the new cephalosporins are once-daily administration and high cerebrospinal fluid levels. With the development of new cephalosporins, however, new toxicities have become apparent, and superinfections and induction of resistance have become greater problems. The cephalosporins are among the most expensive antibiotics in use today; thus, use of these expensive agents must be justified by lower toxicity, greater efficacy, or both in comparison with drugs of more reasonable cost.

Bacteria↗
PubMed1999

Synthesis and antiviral activity of monobactams inhibiting the human cytomegalovirus protease.

A series of monobactam inhibitors of HCMV (N(o)) protease bearing a heterocycle linked by a methylene group at C-4 is described. Inhibitors containing a heterocycle such as a 2-furyl, 2-thiophenyl, 4-methyl-2-tetrazole and 2-benzothiazole were found to be active in a plaque reduction assay. Furthermore, 2-benzothiazole derivatives were shown to inhibit the HCMV protease activity inside cells by using a cell transfection assay, indicating that their antiviral activity in the plaque reduction assay could be attributed to protease inhibition.

Animals↗
PubMed1993

A class-A beta-lactamase from Pseudomonas stutzeri that is highly active against monobactams and cefotaxime.

A beta-lactamase produced by Pseudomonas stutzeri was purified to protein homogeneity, and its physicochemical and catalytic properties were determined. Its profile was unusual since, in addition to penicillins, the enzyme hydrolysed second- and third-generation 'beta-lactamase-stable' cephalosporins and monobactams with similar efficiencies. On the basis of the characteristics of the interaction with beta-iodopenicillanic acid, the enzyme could be classified as a class-A beta-lactamase. However, when compared with most class-A beta-lactamases, it exhibited significantly lower kcat./Km values for the compounds usually considered to be the best substrates of these enzymes.

Cefotaxime↗
PubMed1986

The in-vitro activity of SQ 82,291, a new monobactam, in comparison with aztreonam.

The in-vitro activity of a new monobactam antibiotic, SQ 82,291, was compared with that of aztreonam against 529 strains of aerobic and facultatively anaerobic bacteria. SQ 82,291, which is absorbed orally when administered as an ester, has shown good activity against different bacteria of the family Enterobacteriaceae and Haemophilus influenzae. The susceptibility of SQ 82,291 is lower than that to aztreonam in the species that were sensitive and SQ 82,291 showed no activity at all against staphylococci and strict anaerobes (like aztreonam); unlike aztreonam SQ 82,291 was not effective against Pseudomonas aeruginosa.

Aztreonam↗
PubMed1988

Comparative in-vitro activity of tigemonam, a new monobactam.

The in-vitro activity against Gram-negative aerobic bacterial pathogens of a new oral monobactam, tigemonam, was compared with those of amoxycillin/clavulanic acid, aztreonam, cefaclor, ceftazidime, cefuroxime, ciprofloxacin, co-trimoxazole and gentamicin, by an agar-dilution method. Tigemonam inhibited 90% of strains tested of Escherichia coli, Klebsiella spp., Proteus spp., Salmonella spp., Haemophilus influenzae and Branhamella catarrhalis at concentrations of 0.25 mg/l or below. The MIC90 for Enterobacter spp. was 16 mg/l and for Citrobacter 4 mg/l. Pseudomonas aeruginosa was resistant to tigemonam but susceptible to aztreonam. In comparison with the other oral antibiotics tested, tigemonam was generally more active. Tigemonam showed minimal inoculum dependence, between 10(2) and 10(6) cfu per spot. It is concluded that tigemonam is a candidate for clinical trials in patients with infections caused by Gram-negative aerobes other than pseudomonas and acinetobacter.

Anti-Bacterial Agents↗
PubMed1997

Potentiation of beta-lactams against Pseudomonas aeruginosa strains by Ro 48-1256, a bridged monobactam inhibitor of AmpC beta-lactamases.

Ro 48-1256 is a bridged monobactam inhibitor of Class C beta-lactamases, without significant antibacterial activity of its own. It was tested in combination with imipenem, meropenem, piperacillin and ceftazidime against Pseudomonas aeruginosa isolates, mutants and transconjugants. Imipenem was potentiated against all strains where the AmpC enzyme was inducible or derepressed, with its MICs being reduced from 1-2 mg/L to 0.25-0.5 mg/L for most isolates and from 8-16 mg/L to 1-2 mg/L for those lacking OprD (D2 porin). Ro 48-1256 also abolished in-vitro selection of OprD-deficient mutants by imipenem. Ceftazidime and piperacillin were potentiated against strains derepressed for AmpC enzyme, but not against those where the enzyme remained inducible. For over 90% of AmpC-derepressed organisms, the MICs of ceftazidime were reduced to < or = 8 mg/L by Ro 48-1256 (4 mg/L) and those of piperacillin were reduced to < or = 16 mg/L. Meropenem, which is very stable to AmpC, was not potentiated. Ro 48-1256 did not potentiate piperacillin, ceftazidime or carbapenems when resistance was mediated by Class A, B or D enzymes. Tazobactam, tested as control, had opposite behaviour to Ro 48-1256, potentiating beta-lactams when resistance was due to Class A beta-lactamases but failing to reverse resistance mediated by AmpC. Ro 48-1256 could be used with imipenem to overcome resistance mediated by loss of OprD, or with ceftazidime or piperacillin to overcome derepression of AmpC.

Anti-Bacterial Agents↗
PubMed2000

Effect of conalbumin on the activity of Syn 2190, a 1,5 dihydroxy-4-pyridon monobactam inhibitor of AmpC beta-lactamases.

Syn 2190, a 1,5 dihydroxy-4-pyridon monobactam inhibitor of AmpC enzymes, was tested against beta-lactamase-producing bacteria with piperacillin, piperacillin-tazobactam and ceftazidime as partner drugs. In the presence of conalbumin as an iron chelator, Syn 2190 potentiated these drugs against most AmpC producers, although Klebsiella spp. with plasmidic AmpC enzymes were an exception. Potentiation was much weaker without conalbumin, suggesting that Syn 2190 exploits a ferric uptake pathway, as do catecholic cephalosporins. Syn 2190 had little ability to potentiate partner drugs against strains with other beta-lactamase types but, with conalbumin, increased the activity of piperacillin-tazobactam against Escherichia coli transconjugants producing various class A or D enzymes.

Bacterial Proteins↗
PubMed1987

In vitro evaluation of tigemonam, a novel oral monobactam.

Tigemonam, a novel, orally administered monobactam, exhibited potent and specific activity in vitro against members of the family Enterobacteriaceae, Haemophilus influenzae, and Neisseria gonorrhoeae. Its activity was variable to poor against gram-positive bacteria, Acinetobacter spp., Pseudomonas aeruginosa, and anaerobes. Within its spectrum of activity, tigemonam was far superior to oral antibiotics currently available, including amoxicillin-clavulanic acid, cefaclor, and trimethoprim-sulfamethoxazole. In addition, tigemonam was superior to cefuroxime, which is under development as an oral pro-drug, and more active than cefixime against several genera of the Enterobacteriaceae. The activity of tigemonam against the enteric bacteria, Haemophilus species, and Neisseria species was, in general, comparable to that of the quinolone norfloxacin. The excellent activity of tigemonam against beta-lactamase-producing bacteria reflected its marked stability to hydrolysis by isolated enzymes. The expanded spectrum of activity against gram-negative bacteria observed with tigemonam thus extends oral beta-lactam coverage to include members of the Enterobacteriaceae that are intrinsically or enzymatically resistant to broad-spectrum penicillins and cephalosporins.

Acinetobacter↗
PubMed1987

In vivo evaluation of tigemonam, a novel oral monobactam.

Tigemonam, a new monobactam with excellent activity against gram-negative bacteria, was evaluated for in vivo efficacy and absorption after oral administration to laboratory animals. Tigemonam is absorbed when administered orally to mice and dogs. In a variety of gram-negative systemic infections in mice, orally administered tigemonam was efficacious in all infections studied. Comparison drugs such as amoxicillin, cephalexin, and cefaclor were less efficacious, especially in infections caused by beta-lactamase-producing organisms. In localized infections, tigemonam also demonstrated excellent in vivo activity. In acute pyelonephritis in mice caused by Escherichia coli or Proteus sp., tigemonam was very effective. In a rat lung model with Klebsiella pneumoniae, tigemonam was active with a median effective dose of 46 mg/kg compared with 160 mg/kg for cefaclor and over 200 mg/kg for amoxicillin. Tigemonam was well absorbed in laboratory animals and with its excellent gram-negative spectrum of activity should prove of value in oral antibiotic therapy in humans.

Acute Disease↗
PubMed1988

Tigemonam, an oral monobactam.

Tigemonam is an orally administered monobactam. At less than or equal to 1 microgram/ml it inhibited the majority of strains of Escherichia coli, Klebsiella spp., Enterobacter aerogenes, Citrobacter diversus, Proteus spp., Providencia spp., Aeromonas hydrophila, Salmonella spp., Shigella spp., Serratia marcescens, and Yersinia enterocolitica. At less than or equal to 0.25 microgram/ml it inhibited Haemophilus spp., Neisseria spp., and Branhamella catarrhalis. It did not inhibit Pseudomonas spp. or Acinetobacter spp. Tigemonam was more active than cephalexin and amoxicillin-clavulanate and inhibited many members of the family Enterobacteriaceae resistant to trimethoprim-sulfamethoxazole and gentamicin. Some Enterobacter cloacae and Citrobacter freundii strains resistant to aminothiazole iminomethoxy cephalosporins and aztreonam were resistant to tigemonam. The MIC for 90% of hemolytic streptococci of groups A, B, and C and for Streptococcus pneumoniae was 16 micrograms/ml, but the MIC for 90% of enterococci, Listeria spp., Bacteroides spp., and viridans group streptococci was greater than 64 micrograms/ml. Tigemonam was not hydrolyzed by the common plasmid beta-lactamases such as TEM-1 and SHV-1 or by the chromosomal beta-lactamases of Enterobacter, Morganella, Pseudomonas, and Bacteroides spp. Tigemonam inhibited beta-lactamases of E. cloacae and Pseudomonas aeruginosa but did not induce beta-lactamases. The growth medium had a minimal effect on the in vitro activity of tigemonam, and there was a close agreement between the MICs and MBCs.

Administration, Oral↗
PubMed1989

SHV-5, a novel SHV-type beta-lactamase that hydrolyzes broad-spectrum cephalosporins and monobactams.

SHV-5 (pI 8.2), a novel broad-spectrum beta-lactamase encoded by a ca. 150-kilobase plasmid, was found in Klebsiella pneumoniae 160. SHV-5 beta-lactamase caused decreased susceptibility to most penicillins, cephalosporins, and monobactams, except imipenem and compounds which have a C6 or C7 alpha-methoxy substituent. beta-Lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) inhibited its activity and showed a synergistic effect when associated with different hydrolyzable beta-lactam compounds. Hybridization studies suggested that this enzyme may be related to, or derived from, the SHV enzyme. Increased MICs of cephamycins and temocillin associated with a decreased synergistic effect of the inhibitors on K. pneumoniae 160 might be linked to a decrease in two outer membrane proteins.

Anti-Bacterial Agents↗
PubMed1997

Antibacterial activity of BMS-180680, a new catechol-containing monobactam.

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 < or = 0.5 microg/ml for Escherichia coli, Klebsiella spp., Citrobacter diversus, Enterobacter aerogenes, Serratia marcescens, Proteus spp., and Providencia spp. BMS-180680 had moderate activities (MIC90s of 2 to 8 microg/ml) against Citrobacter freundii, Morganella morganii, Shigella spp., and non-E. aerogenes Enterobacter spp. BMS-180680 was the only antibiotic evaluated that was active against >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.

Anti-Bacterial Agents↗
PubMed2004

Beta-lactams in the new millennium. Part-I: monobactams and carbapenems.

Beta-lactam ring-containing compounds such as penicillins, ampicillin, amoxicillin, cephalosporins and carbapenem are among the most famous antibiotics. This article reviews the recent developments in the study of such compounds. The introductory paragraph, which highlights the significance of the subject and cites most of the leading references of the previous century, is followed by an overview of beta-lactams and some novel methodologies for the synthesis of bi-, tri- and polycyclic derivatives. The rest of the sections deal with design, synthesis and biological activity of monobactams and carbapenems. Many of them have potential antibacterial activity, even against some resistant strains, and enzyme inhibitory activity.

Anti-Bacterial Agents↗
PubMed1999

Carbapenems and monobactams: imipenem, meropenem, and aztreonam.

Imipenem and meropenem, members of the carbapenem class of beta-lactam antibiotics, are among the most broadly active antibiotics available for systemic use in humans. They are active against streptococci, methicillin-sensitive staphylococci, Neisseria, Haemophilus, anaerobes, and the common aerobic gram-negative nosocomial pathogens including Pseudomonas. Resistance to imipenem and meropenem may emerge during treatment of P. aeruginosa infections, as has occurred with other beta-lactam agents; Stenotrophomonas maltophilia is typically resistant to both imipenem and meropenem. Like the penicillins, the carbapenems have inhibitory activity against enterococci. In general, the in vitro activity of imipenem against aerobic gram-positive cocci is somewhat greater than that of meropenem, whereas the in vitro activity of meropenem against aerobic gram-negative bacilli is somewhat greater than that of imipenem. Daily dosages may range from 0.5 to 1 g every 6 to 8 hours in patients with normal renal function; the daily dose of meropenem, however, can be safely increased to 6 g. Infusion-related nausea and vomiting, as well as seizures, which have been the main toxic effects of imipenem, occur no more frequently during treatment with meropenem than during treatment with other beta-lactam antibiotics. The carbapenems should be considered for treatment of mixed bacterial infections and aerobic gram-negative bacteria that are not susceptible to other beta-lactam agents. Indiscriminate use of these drugs will promote resistance to them. Aztreonam, the first marketed monobactam, has activity against most aerobic gram-negative bacilli including P. aeruginosa. The drug is not nephrotoxic, is weakly immunogenic, and has not been associated with disorders of coagulation. Aztreonam may be administered intramuscularly or intravenously; the primary route of elimination is urinary excretion. In patients with normal renal function, the recommended dosing interval is every 8 hours. Patients with renal impairment require dosage adjustment. Aztreonam is used primarily as an alternative to aminoglycosides and for the treatment of aerobic gram-negative infections. It is often used in combination therapy for mixed aerobic and anaerobic infections. Approved indications for its use include infections of the urinary tract or lower respiratory tract, intra-abdominal and gynecologic infections, septicemia, and cutaneous infections caused by susceptible organisms. Concurrent initial therapy with other antimicrobial agents is recommended before the causative organism has been determined in patients who are seriously ill or at risk for gram-positive or anaerobic infection.

Aztreonam↗
PubMed1983

Two new monobactam antibiotics produced by a Flexibacter sp. I. Taxonomy, fermentation, isolation and biological properties.

Two new beta-lactam antibiotics, namely SQ 28,502 and SQ 28,503, have been isolated from fermentations of a Flexibacter sp. They are demethoxy monobactams with oligopeptide side chains and have molecular weights of 1,462 and 1,446, respectively. These beta-lactams show a high degree of stability to a variety of beta-lactamases and act as potent irreversible inactivators of P99 beta-lactamase from Enterobacter cloacae. They exhibit weak antibacterial activity.

Anti-Bacterial Agents↗
PubMed1987

PB-5266 A, B and C, new monobactams. I. Taxonomy, fermentation and isolation.

New monobactams, PB-5266 A, B and C were isolated from the culture filtrate of Cytophaga johnsonae PB-5266 by various types of column chromatography and preparative reverse phase HPLC. PB-5266 A, B and C exhibited weak antibacterial activity against a sensitive mutant of Escherichia coli to beta-lactam antibiotics.

Anti-Bacterial Agents↗