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Antimicrobial Agents and Chemotherapy Sep 1984We compared ceftazidime with moxalactam, a commonly utilized, currently available drug. The microbiological activities of ceftazidime and moxalactam were studied. In... (Comparative Study)
Comparative Study
We compared ceftazidime with moxalactam, a commonly utilized, currently available drug. The microbiological activities of ceftazidime and moxalactam were studied. In addition, single-dose pharmacokinetics and serum bactericidal activity 1 and 6 h after a 2.0-g, 30-min infusion of each drug were determined in a crossover study in human volunteers. In vitro, both drugs had MICs for 90% of the isolates of less than 1.0 microgram/ml against the common members of the family Enterobacteriaceae and of 8.0 micrograms/ml against Staphylococcus aureus. Against Pseudomonas aeruginosa ceftazidime was more active than moxalactam, the respective MICs for 90% of the isolates being 8 and 128 micrograms/ml. Mean half-lives were 1.75 (+/- 0.21) h for ceftazidime and 2.5 (+/- 0.38) h for moxalactam. The serum bactericidal titers for both compounds against Escherichia coli and Klebsiella pneumoniae were high. Titers against S. aureus 6 h after infusion were negative. The mean (geometric) serum bactericidal titer of ceftazidime against 31 strains of P. aeruginosa (1:44) was higher than that of moxalactam (1:3.4).
Topics: Adolescent; Adult; Bacteria; Blood Bactericidal Activity; Ceftazidime; Humans; Kinetics; Male; Microbial Sensitivity Tests; Moxalactam; Protein Binding
PubMed: 6391372
DOI: 10.1128/AAC.26.3.388 -
Antimicrobial Agents and Chemotherapy Nov 1981The pharmacokinetics of cefotaxime, moxalactam, and ceftazidime were investigated in six human volunteers who received in a crossover fashion doses of 0.5, 1.0, and 2.0... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The pharmacokinetics of cefotaxime, moxalactam, and ceftazidime were investigated in six human volunteers who received in a crossover fashion doses of 0.5, 1.0, and 2.0 g of each drug by a 5-min infusion. Doses of 1.0 g were repeated after the administration of probenecid. Serum and urine concentrations were assayed with an agar diffusion method. Serum concentrations of moxalactam exceeded those of ceftazidime at all times and were distinctly higher than those of cefotaxime. The normalized area under the concentration time curve (defined as the ratio of the area under the curve per dose) reflects this relationship: compared with cefotaxime the normalized area under the curve of moxalactam was 3 to 4 times higher, and that of ceftazidime was 2 to 3 times higher. By intra-individual comparisons, the area under the curve of moxalactam was 44% larger than that of ceftazidime. With increasing doses, cefotaxime exhibited a nonlinear increase of the area under the curve. The half-lives of moxalactam, ceftazidime, and cefotaxime were 2.34, 1.95, and 1.16 h, respectively. The volume of distribution averaged 0.20 +/- 0.03, 0.23 +/- 0.02, and 0.25 +/- 0.04 liters per kg, and the mean total body clearance was 84, 131, and 328 ml/min for moxalactam, ceftazidime, and cefotaxime, respectively. The 24-h urinary recovery was highest for moxalactam (75 +/- 4%) followed by ceftazidime (68 +/- 11%) and cefotaxime (53 +/- 6%). The influence of probenecid on serum concentrations, half-life, area under the curve, and clearance was most apparent with cefotaxime, whereas the pharmacokinetics of moxalactam and ceftazidime were only slightly affected. After the 0.5- and 2.0- g doses of cefotaxime, desacetyl-cefotaxime activity (determined by high-pressure liquid chromatography) reached a peak of 2.7 and 9.9 mug/ml and declined with a half-life of 1.9 and 1.4 h. The ratio of the R(-) and S(-) epimers of moxalactam, which could be differentiated by high-pressure liquid chromatography, fell rapidly from 0.81 at 0.17 h to 0.5 at 5 h, indicating the presence of twice as much of the microbiologically less active S(-) epimer. From a pharmacokinetic standpoint it appears reasonable to conclude that moxalactam and possibly ceftazidime could be administered twice daily and that cefotaxime could be administered three or even four times daily.
Topics: Cefotaxime; Ceftazidime; Cephalosporins; Cephamycins; Chromatography, High Pressure Liquid; Humans; Kinetics; Male; Moxalactam; Stereoisomerism; Time Factors
PubMed: 6275776
DOI: 10.1128/AAC.20.5.567 -
Antimicrobial Agents and Chemotherapy Mar 1983The pharmacokinetics of cefoperazone, cefotaxime, and moxalactam were compared in a cross-over randomized study in 10 healthy volunteers. Each subject received 1.0 g of... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The pharmacokinetics of cefoperazone, cefotaxime, and moxalactam were compared in a cross-over randomized study in 10 healthy volunteers. Each subject received 1.0 g of the three drugs by bolus intravenous injection over 3 min. Serum and urine concentrations were assayed by a microbiological method and in addition by high-pressure liquid chromatography (HPLC) for cefotaxime in five subjects. Maximal concentrations in serum 5 min after the injection were 163 +/- 40.3 mg/liter for cefoperazone, 86.1 +/- 19.0 mg/liter for cefotaxime, and 95.5 +/- 21.1 mg/liter for moxalactam. After 12 h, 1.2 +/- 1.4 mg of cefoperazone per liter and 1.8 +/- 0.9 mg of moxalactam per liter could still be measured. Eight hours after the administration of cefotaxime, serum concentrations were below the detection limit of 0.3 mg/liter in most subjects. By HPLC analysis, the mean maximal concentration of desacetyl cefotaxime was 16.6 +/- 10.5 mg/liter 5 min after application; the metabolite exceeded the serum concentration of the parent compound after 1 to 2 h. Relevant pharmacokinetic parameters were calculated, using two- and three-compartment models. The terminal half-life was 144.1 +/- 37.3 min for cefoperazone, 76.1 +/- 32.0 min for cefotaxime, and 272.4 +/- 114.1 min for moxalactam. The apparent volume of distribution corresponded to the extracellular volume. Only 25.1 +/- 8% of cefoperazone could be detected in urine compared with 53.3 +/- 8.1% of cefotaxime and 61.0 +/- 9.2% of moxalactam in 24 h. A total of 89.6 +/- 11.4% of the cefotaxime dose could be recovered by HPLC in urine, 60.6 +/- 7.7% as cefotaxime and 29.1 +/- 7.0% as desacetyl cefotaxime.
Topics: Adult; Anti-Bacterial Agents; Cefoperazone; Cefotaxime; Cephalosporins; Cephamycins; Chromatography, High Pressure Liquid; Female; Half-Life; Humans; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Moxalactam
PubMed: 6303213
DOI: 10.1128/AAC.23.3.429 -
Infection and Drug Resistance 2019Monte Carlo simulation (MCS) was used to evaluate optimal dosage for cefepime (FEP), moxalactam (MOX), and cefperazone/sulbactam (CFZ/SBT) against extended-spectrum...
Monte Carlo simulation (MCS) was used to evaluate optimal dosage for cefepime (FEP), moxalactam (MOX), and cefperazone/sulbactam (CFZ/SBT) against extended-spectrum β-lactamase (ESBL) producers isolated from the Blood Bacterial Resistant Investigation Collaborative System. : Minimum inhibitory concentration (MIC) was tested by agar dilution, and ESBL producers were identified by modified Clinical and Laboratory Standards Institute tests. Pharmacokinetic parameters were derived from data on healthy individuals, and probability of target attainment (PTA) and cumulative fraction of response (CFR) %fT >MIC values were estimated by MCS. A total of 2032 (875 ESBL-producing) and (157 ESBL-producing) strains, and 371 other strains, were isolated from patients with bloodstream infections (BSIs). MIC values for FEP, MOX, and CFZ/SBT against ESBL-producing and were 64/64 mg/L, 2/32 mg/L, and 64/128 mg/L, respectively. Conventional MOX and CFZ/SBT doses failed to reach 90% PTA against isolates with MICs ≥8 mg/L and ≥4 mg/L, respectively. Against ESBL producers, neither FEP nor CFZ/SBT achieved ≥90% CFR, while CFRs for MOX (1 g iv q6h, 2 g iv q12h, and 2 g iv q8h) exceeded 90% against ESBL-producing . Simulated CFRs for FEP and MOX were similar (>90%) against non-ESBL-producing , and higher than CFRs for CFZ/SBT. ESBL producers from BSIs were highly susceptible to MOX, and PTA values were generally higher for MOX than FEP or CFZ/SBT for conventional dosing regimens. This large MCS analysis shows that MOX but not FEP or CFZ/SBT can be used empirically to treat BSIs caused by ESBL-producing strains.
PubMed: 31190908
DOI: 10.2147/IDR.S193712 -
Journal of Clinical Microbiology Aug 2002Very-low-level methicillin-resistant Staphylococcus aureus (MRSA), or class 1 MRSA, is often misdiagnosed as methicillin-susceptible S. aureus (MSSA). We evaluated the...
Evaluation of three techniques for detection of low-level methicillin-resistant Staphylococcus aureus (MRSA): a disk diffusion method with cefoxitin and moxalactam, the Vitek 2 system, and the MRSA-screen latex agglutination test.
Very-low-level methicillin-resistant Staphylococcus aureus (MRSA), or class 1 MRSA, is often misdiagnosed as methicillin-susceptible S. aureus (MSSA). We evaluated the performances of three methods for detection of low-level methicillin resistance: the disk diffusion method using the cephamycin antibiotics cefoxitin and moxalactam, the Vitek 2 system (bioMérieux), and the MRSA-screen test (Denka). Detection of the mecA gene by PCR was considered to be the "gold standard." We also determined the sensitivity of the oxacillin disk diffusion method with 5- and 1-microg disks and that of the Oxascreen agar assay with 6 mg of oxacillin liter(-1) for detection of MRSA. We compared the distributions of MICs of oxacillin and cefoxitin by the E-test (AB Biodisk), and those of moxalactam by dilutions in agar, for MRSA and MSSA isolates. The 152 clinical isolates of S. aureus studied were divided into 69 MSSA (mecA-negative) and 83 MRSA (mecA-positive) isolates, including 63 heterogeneous isolates and 26 class 1 isolates (low-level resistance). The cefoxitin and moxalactam disk diffusion tests detected 100% of all the MRSA classes: cefoxitin inhibition zone diameters were <27 mm, and moxalactam inhibition zone diameters were <24 mm. The Vitek 2 system and the MRSA-screen test detected 94 and 97.6% of all MRSA isolates, respectively. The sensitivities of the 5- and 1-microg oxacillin disks were 95.2 and 96.4%, respectively, whereas that of the Oxascreen agar screen assay was 94%. All of the tests except the 1-microg oxacillin disk test were 100% specific. For the class 1 MRSA isolates, the sensitivity of the Vitek 2 test was 92.3%, whereas those of the MRSA-screen test and the disk diffusion method with cefoxitin and moxalactam were 100%. Therefore, the cefoxitin and moxalactam disk diffusion methods were the best-performing tests for routine detection of all classes of MRSA.
Topics: Bacterial Proteins; Carrier Proteins; Cefoxitin; Gene Expression Regulation, Bacterial; Hexosyltransferases; Hospitalization; Humans; Lactams; Latex Fixation Tests; Methicillin; Methicillin Resistance; Microbial Sensitivity Tests; Moxalactam; Muramoylpentapeptide Carboxypeptidase; Oxacillin; Penicillin-Binding Proteins; Peptidyl Transferases; Staphylococcal Infections; Staphylococcus aureus
PubMed: 12149327
DOI: 10.1128/JCM.40.8.2766-2771.2002 -
PloS One 2020β-Lactam antibiotic detection has significant implications in food safety control, environmental monitoring and pharmacokinetics study. Here, we report the development...
β-Lactam antibiotic detection has significant implications in food safety control, environmental monitoring and pharmacokinetics study. Here, we report the development of two BADAN-conjugated β-lactamases, E166Cb and E166Cb/N170Q, as sensitive biosensors for β-lactam antibiotic detection. These biosensors were constructed by coupling an environment-sensitive BADAN probe onto location 166 at the active site of the PenP β-lactamase E166C and E166C/N170Q mutants. They gave fluorescence turn-on signals in response to β-lactam antibiotics. Molecular dynamics simulation of E166Cb suggested that the turn-on signal might be attributed to a polarity change of the microenvironment of BADAN and the removal of the fluorescence quenching effect on BADAN exerted by a nearby Tyr-105 upon the antibiotic binding. In the detection of four β-lactams (penicillin G, penicillin V, cefotaxime and moxalactam), both E166Cb and E166Cb/N170Q delivered signal outputs in an antibiotic-concentration dependent manner with a dynamic range spanning from 10 nM to 1 μM. Compared to E166Cb, E166Cb/N170Q generally exhibited more stable signals owing to its higher deficiency in hydrolyzing the antibiotic analyte. The overall biosensor performance of E166Cb and E166Cb/N170Q was comparable to that of their respective fluorescein-modified counterparts, E166Cf and E166Cf/N170Q. But comparatively, the BADAN-conjugated enzymes showed a higher sensitivity, displayed a faster response in detecting moxalactam and a more stable fluorescence signals towards penicillin G. This study illustrates the potential of BADAN-conjugated β-lactamases as biosensing devices for β-lactam antibiotics.
Topics: 2-Naphthylamine; Anti-Bacterial Agents; Biosensing Techniques; Enzymes, Immobilized; Molecular Dynamics Simulation; beta-Lactamases; beta-Lactams
PubMed: 33125437
DOI: 10.1371/journal.pone.0241594 -
Antimicrobial Agents and Chemotherapy Aug 1987The disposition of moxalactam (MOX) and N-methyltetrazolethiol (NMTT) in rats and monkeys after intravenous injection was investigated, focusing on the in vivo... (Comparative Study)
Comparative Study
The disposition of moxalactam (MOX) and N-methyltetrazolethiol (NMTT) in rats and monkeys after intravenous injection was investigated, focusing on the in vivo liberation of NMTT, by using [NMTT-14C]MOX and [14C]NMTT. After [NMTT-14C]MOX injection, MOX levels in plasma quickly became high in both rats and monkeys and then declined, with half-lives at the beta phase of 18.8 and 67.1 min, respectively. The levels of NMTT liberated from MOX were much lower than those of MOX, but the apparent elimination was significantly slow. The levels of MOX and NMTT in rat liver were almost comparable but lower than those in plasma. With [14C]NMTT administration, the level of NMTT in plasma declined, with half-lives at the beta phase of 21.5 min in rats and 54.0 min in monkeys. After [NMTT-14C]MOX injection, most of the radioactivity was excreted in urine as MOX, with 11% of the dose in rats and 8% of the dose in monkeys eliminated as NMTT until 24 h. Total biliary excretion was 26% of the injected radioactivity in rats, and most of it was due to MOX. In one monkey, the total biliary excretion was only 0.2% of the injected radioactivity. With [14C]NMTT administration, most radioactivity was excreted in the urine as unchanged NMTT in both animals. Oral administration in rats showed that part of the biliary-excreted MOX was degraded to NMTT in the intestine and then absorbed. Repeated administration of [NMTT-14C]MOX to rats did not change the levels of MOX and NMTT in plasma or liver nor did it change the excretion profiles. Thus, accumulation of MOX and NMTT did not occur.
Topics: Animals; Azoles; Bile; Feces; Female; Injections, Intravenous; Kinetics; Liver; Macaca fascicularis; Male; Moxalactam; Rats; Rats, Inbred Strains; Species Specificity; Subcellular Fractions; Tetrazoles; Tissue Distribution
PubMed: 3631941
DOI: 10.1128/AAC.31.8.1169 -
Antimicrobial Agents and Chemotherapy Feb 1982The pharmacokinetics and bacteriological efficacy of cefoperazone, cefuroxime, ceftriaxone, and moxalactam were evaluated in the experimental rabbit meningitis model of...
The pharmacokinetics and bacteriological efficacy of cefoperazone, cefuroxime, ceftriaxone, and moxalactam were evaluated in the experimental rabbit meningitis model of Haemophilus influenzae type b or Streptococcus pneumoniae infection. The cerebrospinal fluid penetration of these beta-lactam antibiotics was from 3 to 14% and was greater in Haemophilus-infected that in pneumococcus-infected animals. With the exception of moxalactam, the antibacterial activity in cerebrospinal fluid and change in concentration of bacteria during therapy with the test drugs were comparable to those of penicillin G in pneumococcal infection. In animals infected with H. influenzae, cefoperazone, moxalactam, and ceftriaxone were as effective as chloramphenicol in reducing the bacterial counts in cerebrospinal fluid. Moxalactam and ceftriaxone produced the largest cerebrospinal fluid bactericidal titers against this beta-lactamase-producing strain of Haemophilus. On the basis of these data, it was concluded that ceftriaxone and cefoperazone were effective against both pathogens in this meningitis model, whereas moxalactam was effective against only Haemophilus, and cefuroxime was effective against only S. pneumoniae.
Topics: Animals; Cefoperazone; Cefotaxime; Ceftriaxone; Cefuroxime; Cephalosporins; Cephamycins; Dose-Response Relationship, Drug; Infusions, Parenteral; Kinetics; Male; Meningitis, Haemophilus; Meningitis, Pneumococcal; Moxalactam; Rabbits; Streptococcus pneumoniae
PubMed: 6280599
DOI: 10.1128/AAC.21.2.262 -
Antimicrobial Agents and Chemotherapy Feb 2016Class C β-lactamases poorly hydrolyze cephamycins (e.g., cefoxitin, cefotetan, and moxalactam). In the past 2 decades, a new family of plasmid-based AmpC β-lactamases...
Class C β-lactamases poorly hydrolyze cephamycins (e.g., cefoxitin, cefotetan, and moxalactam). In the past 2 decades, a new family of plasmid-based AmpC β-lactamases conferring resistance to cefoxitin, the FOX family, has grown to include nine unique members descended from the Aeromonas caviae chromosomal AmpC. To understand the basis for the unique cephamycinase activity in the FOX family, we determined the first X-ray crystal structures of FOX-4, apo enzyme and the acyl-enzyme with its namesake compound, cefoxitin, using the Y150F deacylation-deficient variant. Notably, recombinant expression of N-terminally tagged FOX-4 also yielded an inactive adenylylated enzyme form not previously observed in β-lactamases. The posttranslational modification (PTM), which occurs on the active site Ser64, would not seem to provide a selective advantage, yet might present an opportunity for the design of novel antibacterial drugs. Substantial ligand-induced changes in the enzyme are seen in the acyl-enzyme complex, particularly the R2 loop and helix H10 (P289 to N297), with movement of F293 by 10.3 Å. Taken together, this study provides the first picture of this highly proficient class C cephamycinase, uncovers a novel PTM, and suggests a possible cephamycin resistance mechanism involving repositioning of the substrate due to the presence of S153P, N289P, and N346I substitutions in the ligand binding pocket.
Topics: Aeromonas caviae; Amino Acid Sequence; Anti-Bacterial Agents; Bacterial Proteins; Cefoxitin; Crystallography, X-Ray; Drug Resistance, Multiple, Bacterial; Escherichia coli Proteins; Microbial Sensitivity Tests; Models, Molecular; Molecular Sequence Data; Protein Isoforms; Protein Processing, Post-Translational; Sequence Alignment; Tandem Mass Spectrometry; beta-Lactamases
PubMed: 26525784
DOI: 10.1128/AAC.01887-15 -
Antimicrobial Agents and Chemotherapy May 1981The activities of moxalactam and cefotaxime, alone and combined with ampicillin or penicillin, against 40 isolates of group B streptococci were assessed by using the... (Comparative Study)
Comparative Study
The activities of moxalactam and cefotaxime, alone and combined with ampicillin or penicillin, against 40 isolates of group B streptococci were assessed by using the microtiter broth dilution, checkerboard, and time-kill techniques. Penicillin and cefotaxime were bactericidal for all isolates at concentrations of 0.06 micrograms/ml or less. Ampicillin was slightly less active. Moxalactam was bactericidal for all strains at concentrations of 4 to 8 micrograms/ml. The ampicillin- moxalactam combination was partially synergistic for 60% of the isolates tested; the ampicillin-cefotaxime combination was partially synergistic for 35% of these isolates. No instances of antagonism were observed. In time-kill evaluations, ampicillin (3.0 micrograms/ml) and penicillin (0.75 micrograms/ml) effected 2.5 to 3.5 log10 reductions in numbers of colony-forming units. The addition of 4 micrograms of cefotaxime per ml or 8 to 16 micrograms of moxalactam per ml to penicillin or ampicillin did not alter killing kinetics. Moxalactam and cefotaxime neither enhanced nor decreased the activity of ampicillin or penicillin against group B streptococci.
Topics: Ampicillin; Cefotaxime; Cephalosporins; Cephamycins; Drug Synergism; Humans; Moxalactam; Penicillin G; Penicillin Resistance; Streptococcal Infections; Streptococcus agalactiae
PubMed: 6271048
DOI: 10.1128/AAC.19.5.794