Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021311 (Infection)
 38,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The therapeutic perspectives of flomoxef, SCE 2787, cefpirome, cefepime, latamoxef, cefotaxime and of piperacillin plus tazobactam were comparatively evaluated by their in vitro activity against 1119 clinical isolates of 83 bacterial species. Escherichia coli, Klebsiella spp. Enterobacter sakazakii, Proteus spp. and Shigella spp. were about equally susceptible to the cephalosporins (MIC90: 0.06 to 0.5 mg/l), while the MIC90 for piperacillin plus tazobactam was between 2 and 16 mg/l. Enterobacter cloacae, Enterobacter aerogenes and Serratia spp. were most susceptible to SCE 2787, cefpirome and cefepime (MIC90: 0.06 to 2 mg/l) followed by latamoxef, cefotaxime, flomoxef and piperacillin plus tazobactam. For Citrobacter spp., Providencia spp. and Yersinia enterocolitica MIC90 were between 0.06 and 0.5 mg/l. Flomoxef was between 2 to 4 log2 less active against these species but more active than piperacillin plus tazobactam (MIC90: 2 and 8 mg/l). Morganella morganii and Hafnia alvei were most susceptible to cefepime, cefpirome and latamoxef (MIC90: 0.13 to 0.5 mg/l) while cefotaxime (MIC90: 8 mg/l) and piperacillin plus tazobactam (MIC90: 8 and greater than 64 mg/l) were the least active compounds. SCE 2787, cefepime and cefpirome were the most potent beta-lactams against the majority of the 13 species of non-fermentative bacilli (NFB) investigated (MIC90: 0.5 to 16 mg/l). The oxacephems were the least active compounds against NFB. Cefepime was the most active of the compounds included against Pseudomonas aeruginosa (MIC90: 16 mg/l). Haemophilus spp., Neisseria gonorrhoeae and Bordetella pertussis were most susceptible to cefotaxime (MIC90: 0.03 to 0.06 mg/l). Latamoxef had the lowest activity of all compounds against gram-positive cocci. Flomoxef was the most active compound against penicillinase producing Staphylococcus aureus and about equally active as the other betalactams against methicillin susceptible staphylococci of other staphylococcal species.(ABSTRACT TRUNCATED AT 250 WORDS)
Infection 1991
PMID:In vitro activity and stability against novel beta-lactamases of investigational beta-lactams (cefepime, cefpirome, flomoxef, SCE2787 and piperacillin plus tazobactam) in comparison with established compounds (cefotaxime, latamoxef and piperacillin). 166 18

Forty-three clinical isolates of enterobacteria were selected for the production of the new plasmid-mediated expanded-spectrum beta-lactamase CTX-1. The geometric means of MICs were ranged as follows: ticarcillin, greater than 4096 mg/l; ticarcillin + clavulanic acid (2 mg/l), 64-87 mg/l; LY 163892, 8.0-69.1 mg/l; cefotaxime, 5.7-26.4 mg/l; temocillin, 8.0-21.8 mg/l; Ro 158074, 4.0-18.7 mg/l aztreonam, 1.0-14.4 mg/l and BMY 28142, 1.4-2.8 mg/l. Moxalactam, imipenem and CM 40876 were resistant to hydrolysis and MICs were lower than 2.0 mg/l. A high protective effect on cefotaxime (MIC less than or equal to 0.5 mg/l) was obtained by sulbactam (4 mg/l). Escherichia coli transconjugants from each species showed similar levels of MICs.
Infection
PMID:Susceptibility of new beta-lactams to the expanded-spectrum beta-lactamase CTX-1. 264 26

The recent literature was reviewed with regard to the risks of superinfection following beta-lactam chemotherapy. The summary publications for the pseudomonas-active penicillins (azlocillin, carbenicillin, mezlocillin, piperacillin and ticarcillin), cefoperazone, cefotaxime, ceftazidime, imipenem and moxalactam show marked variations. Moxalactam was most likely to produce both gram-negative (5-38%) and enterococcal (2.2-12%) superinfections. Ceftazidime or moxalactam therapy was more often associated with anaerobic superinfections, usually by Clostridium spp., than the other beta-lactams. Comparable and lower incidences of superinfections were cited for cefoperazone, ceftazidime, mezlocillin and imipenem. The most common pathogens for the above drugs were the fungi (Candida spp.), Pseudomonas spp. and some beta-lactamase-producing Enterobacteriaceae. Staphylococcal, Escherichia coli and Klebsiella spp. secondary infections were more common in patients receiving the newer penicillins. Cefotaxime had a very low incidence of superinfections (1.1%), especially caused by gram-positive organisms such as enterococci. The reasons for this favorable feature seem to be: excellent inhibitory activity and beta-lactamase stability against a wide variety of bacterial pathogens, synergistic interactions of cefotaxime and its desacetyl metabolite, enhanced anti-enterococcal activity of cefotaxime in the presence of a human serum factor and interactions of cefotaxime and desacetyl cefotaxime to suppress the development of antimicrobial resistance. The most common superinfections following cefotaxime treatment were with Pseudomonas spp., Enterobacter spp. and fungi. Cefotaxime appears to possess physical-chemical characteristics that react favorably with bacteria and the host to minimize gram-positive superinfections, especially with most enteric Streptococcus spp. (Streptococcus faecalis and Streptococcus faecium).
Infection 1985
PMID:Gram-positive superinfections following beta-lactam chemotherapy: the significance of the enterococcus. 390 52

We evaluated the microbiologic characteristics including MIC determinations, synergy plate assays and serum bactericidal activity for two regimens being examined as empiric antibiotic therapy for febrile granulocytopenic cancer patients. The regimens consisted of moxalactam (4 g.i.v. q12h) plus piperacillin (75 mg/kg i.v. q6h) or moxalactam (as above) plus amikacin (levels adjusted to one hour post-infusion levels of 25 mg/l and troughs of 6-8 mg/l). Detailed pharmacokinetics were ascertained for the beta lactams. All drugs were active against a panel of 11 strains each of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. The pharmacokinetic profile showed serum levels sufficient to provide good antimicrobial activity throughout the dosing interval. Both regimens displayed synergistic or partially synergistic activity in the main for the test organisms; moxalactam plus piperacillin produced good results against S. aureus and P. aeruginosa. In the serum bactericidal assays, the moxalactam-piperacillin combination produced significantly higher mean titers at both peak and trough when compared to the moxalactam-amikacin regimen. This may be because moxalactam acts as a beta lactamase inhibitor for both staphylococcal beta lactamase, as well as the Sabath-Abraham Id type beta lactamase carried by P. aeruginosa (among others). Moxalactam-piperacillin deserves extensive evaluation as empiric therapy for the febrile neutropenic cancer patients.
Infection
PMID:Moxalactam and piperacillin: a study of in vitro characteristics and pharmacokinetics in cancer patients. 398 51

Moxalactam (LY127935) is a new beta-lactam antibiotic which is chemically related to the cephalosporins. The agent is highly active against the Enterobacteriaceae, with most organisms sensitive to 0.1 mcg/ml or less. It is also active at low concentration against gentamicin-resistant strains of Providencia and Serratia. Minimal inhibitory concentrations of moxalactam for Pseudomonas aeruginosa are approximately four-fold lower than those of carbenicillin for the same isolates. It is highly active against Hemophilus influenzae, including ampicillin-resistant strains, with all strains tested sensitive to 0.1 mcg/ml or less. The majority of strains of Neisseria gonorrheae and Neisseria meningitidis are sensitive to 0.1 mcg/ml or less. Moxalactam is more active against Bacteroides fragilis than cefoxitin. However, activity of moxalactam against gram-positive cocci was uniformly less than cephalothin and other cephalosporins tested. Little effect of inoculum size was observed with moxalactam except for particular strains of gram-negative bacilli. The drug was found to be 40-43% bound to human serum proteins.
Infection 1980
PMID:In vitro studies of moxalactam (LY127935), a new beta-lactam antibiotic with significant activity against gram-negative bacteria. 644 71

The antibacterial activity of moxalactam was studied in vitro against 229 clinical isolates of gram-positive and gram-negative aerobic microorganisms using the agar dilution technique. Mueller-Hinton agar was used as growth medium. The results were compared to those obtained with cefamandole. All isolates of Staphylococcus aureus and Streptococcus pneumoniae were inhibited by moxalactam at a concentration of 8 microgram/ml or less. The concentrations of cefamandole with which the same effect was obtained were 0.5 microgram/ml and 2 microgram/ml respectively. Moxalactam was highly inhibitory against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Proteus morganii - 90% of the strains were inhibited by 0.125 microgram/ml. Moxalactam was highly superior against Proteus rettgeri and Pseudomonas aeruginosa, which are usually resistant to cefamandole: the MIC100 and MIC90 were 0.25 microgram/ml and 8 microgram/ml respectively. High sensitivity was found in strains of Salmonella species, nine of which were Salmonella typhi: the MIC90 was < 0.063 microgram/ml versus the eightfold higher concentration of cefamandole. The broad-spectrum activity and unusual MIC patterns of moxalactam - eight or manyfold higher concentrations of cefamandole were needed to inhibit 90% of most gram-negative strains studied - make moxalactam an unusual and promising antibiotic.
Infection 1980
PMID:In vitro antibacterial activity of moxalactam, a new broad-spectrum semisynthetic antibiotic. 644 72

Twenty-four patients were treated with moxalactam for 25 serious infections. Nineteen patients were septicemic and 18 presented severe underlying diseases considered to impair the normal response to bacterial pathogens. All of the pathogens had MICs of less than 12 mg/l except one Pseudomonas aeruginosa strain with an MIC of 32 mg/l. The dosage ranged from 3 to 12 g/day; the route of administration was either i.v. or i.m. The duration of treatment was six to 26 days. Six patients had urinary tract infections (three bacteremia), four had pulmonary abscesses (two bacteremia), five had septic thrombophlebitis (five bacteremia) and ten had miscellaneous infections (nine bacteremia). Twenty-two (92%) patients responded favourably. Four patients (16.6%) developed superinfections due to organisms highly resistant to moxalactam: three Streptococcus faecalis, one Bacteroides fragilis and one Aspergillus flavus. Tolerance was good. Nine moderate adverse reactions were observed: three cases of transient eosinophilia, two of phlebitis, three hepatic enzyme alterations and one rash. Moxalactam kinetics were measured in serum from 15 patients with normal renal function after receiving 1 g i.v. over 30 min. The mean peak level after the infusion was 82.8 +/- 12.1 (SE) mg/l; the mean trough level 8 h later was 6.2 +/- 1.7 (SE) mg/l. The serum half-life was 2.6 +/- 0.6 (SE) h for the beta phase. Plasma clearance was 76.8 +/- 8.2 ml/min. Moxalactam was found to be highly effective in the therapy of life-threatening infections.
Infection
PMID:Moxalactam therapy of serious infections. 661 77

Moxalactam was evaluated as the sole therapy of 45 episodes of infection in 41 patients due primarily to bacteria resistant to older antibiotics. Infections included bacteremias, pulmonary, skin and soft tissue infections, osteomyelitis, and meningitis. Clinical and bacteriological cure was achieved in 69% of infections. Cure was achieved with moxalactam in patients infected with cefazolin-resistant, carbenicillin-resistant, chloramphenicol and gentamicin-resistant organisms. Although adverse reactions were generally mild, diarrhea developed in five patients, a major increase in prothrombin time and bleeding in three patients and a disulfiram reaction in two patients.
Infection
PMID:The use of moxalactam in the treatment of serious infections due to multi-resistant organisms. 666 67