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At least 19 recordsLinked to original sources
PubMed1984

Moxalactam plus piperacillin versus moxalactam plus amikacin in febrile granulocytopenic patients.

In a prospective randomized trial, febrile granulocytopenic patients received either moxalactam plus piperacillin or moxalactam plus amikacin as initial empiric antimicrobial therapy. Most patients were also given prophylactic vitamin K. The overall response rates for the two regimens were similar (105 of 136, or 77 percent, for moxalactam plus piperacillin versus 107 of 136, or 79 percent, for moxalactam plus amikacin). For Pseudomonas aeruginosa infections, the response rate was better in patients receiving moxalactam plus amikacin (seven of nine versus one of five, p = 0.06); two patients treated with moxalactam plus piperacillin experienced relapse of P. aeruginosa bacteremia in association with the emergence of beta-lactam-resistant P. aeruginosa isolates. On the other hand, bacteremic enterococcal superinfections occurred in seven patients receiving moxalactam plus amikacin but in none given moxalactam plus piperacillin (p = 0.02). Serious side-effects were minimal with both regimens, and nephrotoxicity was less common in patients receiving moxalactam plus piperacillin (two of 136 versus six of 136, p = 0.28). There was no antibiotic-related hemorrhage. These results suggest that the overall efficacy and toxicity of moxalactam plus piperacillin and moxalactam plus amikacin are similar. Moxalactam/piperacillin therapy may be limited in certain patients by the emergence of beta-lactam-resistant P. aeruginosa, whereas enterococcal superinfections may complicate moxalactam/amikacin therapy.

Adolescent↗
PubMed1981

Penetration of moxalactam into its target proteins in Escherichia coli K-12: comparison of a highly moxalactam resistant mutant with its parent strain.

An eschericia coli K-12 mutant highly resistant to moxalactam but only slightly resistant to other beta-lactam antibiotics was obtained by mutagen treatment. The affinity of moxalactam for its target penicillin-binding proteins was unchanged, as was the level of beta-lactamase activity. The penetration of [14C] moxalactam, however, was markedly reduced in the mutant. Electrophoretic analysis revealed alterations of the outer membrane proteins. A reduction in the amount of one of the pore-forming proteins (porins) was especially noteworthy. These data suggest that moxalactam resistance is the result of an alteration in the outer membrane structure.

Bacterial Proteins↗
PubMed1983

Enterococcal liver abscess associated with moxalactam therapy. Review of literature on enterococcal superinfections in association with moxalactam therapy.

Moxalactam, a third-generation cephalosporin, has been demonstrated to have an ultrawide spectrum of antibacterial activity. One important gap in this impressive spectrum is the enterococcus. Superinfections and colonization with enterococci have been reported following moxalactam therapy. Sites involved have included the urinary tract, wounds, middle ear, and blood stream. To our knowledge, we report the first case of enterococcal liver abscess following moxalactam therapy. The abscess was localized by ultrasound examination and microbiologic diagnosis made by aspiration using a skinny needle. Without surgical drainage or therapeutic aspiration, institution of appropriate antibiotic therapy in optimum dosage resulted in complete resolution. The literature on enterococcal superinfections in association with moxalactam therapy and nonsurgical management of liver abscesses is reviewed.

Cephalosporins↗
PubMed1983

Comparison of moxalactam and gentamicin in the treatment of complicated urinary tract infections.

Moxalactam and gentamicin were compared in a prospective, randomized study of 49 hospitalized patients with complicated urinary tract infections. Patients received parenteral moxalactam, 250 mg every 12 h, or gentamicin, 1 mg/kg every 8 h. The average duration of therapy (moxalactam, 7.5 days; gentamicin, 8.6 days) was similar for both groups. Sixty-two percent of patients treated with moxalactam and 57% of those receiving gentamicin were cured of their infection, as defined by a negative culture after therapy. No side effects required discontinuation of either drug. An enterococcus caused two superinfections and three reinfections in patients treated with moxalactam. Moxalactam resistance developed in Pseudomonas aeruginosa isolates from three patients treated with moxalactam. Moreover, two of these isolates showed decreased susceptibility to gentamicin, tobramycin, and amikacin. An additional 10 patients with gentamicin-resistant but moxalactam-susceptible isolates were treated with moxalactam. Forty percent of these patients were cured of their infections. Moxalactam appears to be a safe, effective drug for complicated urinary tract infections caused by susceptible bacteria, including those resistant to gentamicin. However, patients receiving moxalactam should be carefully monitored to detect enterococcal superinfections or development of resistance to moxalactam in isolates of P. aeruginosa.

Adult↗
PubMed1984

Moxalactam plus ticarcillin or tobramycin for treatment of febrile episodes in neutropenic cancer patients.

Moxalactam disodium in combination with ticarcillin disodium or tobramycin sulfate was used to treat 445 episodes of suspected or confirmed infection in patients with cancer. The majority had leukemia and neutropenia. The rate of cures during the 231 confirmed infections was 65% for moxalactam and ticarcillin and 64% for moxalactam and tobramycin. Both regimens were comparable against aerobic gram-negative and polymicrobial infections. In gram-positive infections, the response rate for moxalactam and ticarcillin was 73% and for moxalactam and tobramycin, 53%. Only three of nine enterococcal infections responded to treatment. Thirteen percent of all organisms recovered were resistant to moxalactam. Side effects occurred infrequently; the most important was coagulopathy due to moxalactam. Nephrotoxic effects occurred in six patients receiving moxalactam and tobramycin and in none of those receiving moxalactam and ticarcillin. In 39 patients, a superinfection was confirmed. Fourteen were fungal, three were due to enterococcus, and one due to Klebsiella species. Eleven of the 14 fungal episodes occurred in the moxalactam-ticarcillin group. Moxalactam with ticarcillin and moxalactam with tobramycin are equally active for the initial treatment of presumed infection in patients with neutropenia.

Adolescent↗
PubMed1988

Moxalactam vs tobramycin-clindamycin. A randomized trial in secondary peritonitis.

One hundred five patients with peritonitis were randomized to receive either tobramycin sulfate plus clindamycin phosphate or moxalactam alone before surgical intervention. Fifty-nine patients were evaluable. A mean of 3.1 (moxalactam) and 3.5 (tobramycin-clindamycin) pathogens per patient were identified. Overall success rate was 85% (tobramycin-clindamycin, 24/30; moxalactam, 26/29). When patients with appendicitis were excluded, there was an observed but not statistically significant advantage of moxalactam over tobramycin-clindamycin (85% vs 67%). There were five deaths (tobramycin-clindamycin, four; moxalactam, one). Other complications included hypoprothrombinemia (tobramycin-clindamycin, five; moxalactam, five), renal dysfunction (tobramycin-clindamycin, three; moxalactam, one), and superinfection (tobramycin-clindamycin, nine; moxalactam, six). More wound infections were noted in the group given tobramycin-clindamycin. These data suggest that moxalactam is as safe and efficacious as tobramycin plus clindamycin. The observed benefits of this agent warrant study in a larger sample to verify advantages of moxalactam over combination therapy.

Abscess↗
PubMed1981

Comparative multiple-dose pharmacokinetics of cefotaxime, moxalactam, and ceftazidime.

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.

Cefotaxime↗
PubMed1986

A prospective randomized study of moxalactam versus gentamicin and clindamycin in penetrating abdominal trauma.

We conducted a randomized, prospective study of moxalactam versus gentamicin plus clindamycin in 42 patients with penetrating abdominal trauma. Patients were randomized to receive intravenously either 2 grams of moxalactam every 12 hours or 80 milligrams of gentamicin every eight hours and 600 milligrams of clindamycin every six hours. Antibiotics were administered preoperatively and continued for a minimum of five days if hollow viscus injury occurred. For those without hollow viscus injury, only those patients receiving a minimum of three days of antibiotics were evaluated. A single intramuscular dose of 10 milligrams of vitamin K was also administered to all patients in the moxalactam group. There were 39 males and three females with a mean age of 33 years. Twenty patients received moxalactam and 22 received gentamicin plus clindamycin. The mechanism of injury was gunshot wound in 32 patients and stab wounds in ten patients. Eight patients in each group sustained injuries to the small intestine or colon, or both. The mean injury severity score was 22.6 and 21.2 in the single and double antibiotic regimen, respectively. The mean duration of antibiotic therapy was 5.8 and 7.0 days in the single and double antibiotic group, respectively. No infectious complications occurred in the moxalactam group whereas five infections occurred in four patients in the gentamicin plus clindamycin group (p less than 0.05). These infections included one intra-abdominal abscess, two wound infections and two episodes of necrotizing fasciitis of the wound and abdominal wall. There were no complications attributable to moxalactam therapy. The over-all mortality rate was zero per cent. The total pharmacy cost of a five day course of moxalactam plus a single dose of vitamin K is $204.67 compared with $226.00 for a similar course of gentamicin plus clindamycin. We conclude that: moxalactam is at least, if not more, effective in preventing infectious complications after penetrating abdominal trauma compared with gentamicin plus clindamycin; moxalactam is safe in the doses used when combined with vitamin K, and 3, moxalactam is more cost-effective than gentamicin plus clindamycin dual antibiotic therapy.

Abdominal Injuries↗
PubMed1984

Empiric therapy with moxalactam alone in patients with bacteremia.

Moxalactam was administered (20 mg/kg intravenously every 8 hours) as single-drug empiric antimicrobial therapy to 63 patients with bacteremia who were neither neutropenic nor immunosuppressed. Six patients (10%) had microorganisms that were susceptible to moxalactam and resistant to all other antimicrobial agents tested; two patients (3%) had microorganisms that were resistant to moxalactam and other agents tested. Of these 63 patients, 47 (75%) were cured with moxalactam therapy. Nine patients (14%) had breakthrough bacteremia while receiving other antimicrobial therapy and were cured subsequently with moxalactam therapy alone. The two major risk factors for failure of moxalactam therapy were polymicrobial bacteremia and an extrahepatic intra-abdominal source of infection; these two conditions frequently coexisted. Six of nine patients with polymicrobial bacteremia died. Superinfection (one pseudomonal, five enterococcal) was responsible for 6 of the 16 treatment failures. Enterococcal superinfection occurred exclusively among patients who had received relatively prolonged therapy with moxalactam for extrahepatic intra-abdominal infection, especially intraabdominal abscess. These five patients died, and postmortem examination showed that enterococcal superinfection was the major cause of death in all. Mild, reversible adverse reactions associated with use of moxalactam occurred in 14 of the 63 patients (22%). None had clinically overt bleeding. The use of moxalactam alone seems to be safe and effective and a cost-effective alternative empiric antimicrobial therapy for most patients with bacteremia who are not immunosuppressed or neutropenic and who are not at high risk of having Pseudomonas or polymicrobial bacteremia.

Abdomen↗
PubMed1999

Epimerization of moxalactam by albumin and simulation of in vivo epimerization by a physiologically based pharmacokinetic model.

We investigated the mechanism of epimerization (R to S or S to R) of moxalactam in serum of rats, dogs, and humans. The epimerization of moxalactam occurred in the serum of these animals, but not in the serum filtrate. The albumin fraction of human serum purified by gel filtration catalysed the epimerization of moxalactam at an identical rate to serum, but other fractions (i.e., lipoproteins and globulins) showed slower epimerization. alpha 1-acid glycoprotein, which was eluted in the same fraction with albumin by G-200 gel filtration, did not epimerize moxalactam. The presence of 2 mM warfarin decreased the binding of R- and S-moxalactam and decreased the epimerization of moxalactam in human serum. These results demonstrate moxalactam was epimerized on the warfarin binding site on albumin in serum. Additionally, a physiologically based pharmacokinetic model shows that the epimerization of moxalactam after administration in dogs is simulated by the epimerization in serum.

Animals↗
PubMed1986

Pharmacokinetics of intravenous and intraperitoneal moxalactam in chronic ambulatory peritoneal dialysis.

The kinetics of moxalactam has been investigated in 10 subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). A single 1 g dose was injected i.v. and a 1 g dose was given intraperitoneally in the CAPD fluid during a 4 h dwell-time. Moxalactam was assayed by HPLC. After i.v. injection, the serum kinetics of moxalactam were: plasma t 1/2 = 17.9 h; volume of distribution at steady-state, 0.27 l/kg; total plasma clearance, 12.8 ml/min; peritoneal clearance, 2.1 ml/min. Dialysate moxalactam concentrations rose rapidly but only 20% of the dose was eliminated by the peritoneal route. After intraperitoneal instillation, moxalactam appeared in the serum rapidly and the peak serum concentration ranged from 21 to 49 micrograms/ml after between 4 and 5 h. The absorption of moxalactam from the peritoneal space was 57 +/- 16%. The data suggest that moxalactam has bidirectional exchange characteristics through the peritoneal membrane. Instillation of moxalactam in CAPD fluid may permit rapid absorption and the appearance of a therapeutic serum concentration.

Adult↗
PubMed1982

On the disulfiram-like activity of moxalactam.

A three-way crossover study was undertaken in 10 healthy subjects to characterize the reported disulfiram-like activity of moxalactam and to assess its influence on ethanol and acetaldehyde metabolism. On different occasions separated by at least 2 wk subjects were given in random order: 0.5 gm/kg ethanol orally, 0.5 gm/kg ethanol followed in 1 hr by 1.0 gm IV moxalactam, and 1.0 gm IV moxalactam every 8 hr for four doses followed by 0.5 gm/kg ethanol. Mean ethanol elimination rates of 13.1 +/- 0.76, 10.1 +/- 1.11, and 10.9 +/- 1.06 mg/dl/hr (mean +/- SEM) were observed in the three protocols, respectively. Corresponding mean estimated acetaldehyde clearance rates were 103.7 +/- 15.55, 92.8 +/- 13.79, and 97.3 +/- 10.41 l/min (mean +/- SEM). While no consistent moxalactam effect on ethanol or acetaldehyde elimination was observed, two subjects experienced mild disulfiram-like reactions to ethanol after moxalactam pretreatment. In one subject this reaction was associated with markedly elevated blood acetaldehyde concentrations. We conclude that moxalactam pretreatment may induce a disulfiram-like reaction after ethanol ingestion in some, probably due to inhibition of aldehyde dehydrogenase, and that alcoholic beverages are contraindicated in patients receiving moxalactam. We suggest, however, that such reactions will not occur when moxalactam is given after ethanol ingestion.

Acetaldehyde↗
PubMedDate not supplied

Effects of moxalactam on blood coagulation and platelet function.

Bleeding complications have occasionally been reported in clinical trials of moxalactam therapy for debilitated and/or malnourished patients. Complications that occur secondary to hypothrombinemia are readily corrected by administration of 5-10 mg of vitamin K. In a few instances, the bleeding complications occurred secondary to suppression of platelet function. The present studies aim at clarifying the mechanisms by which bleeding problems attributable to moxalactam and other beta-lactam antibiotics occur. Moxalactam in vitro did not inhibit blood coagulation or platelet aggregation at concentrations of 700 micrograms of moxalactam/ml. When administered to five normal male volunteers at a dosage of 3 g of moxalactam four times daily for seven days, the antibiotic did not affect the levels of vitamin K-dependent clotting factors II, VII, IX, and X or vitamin K-independent clotting factors V, VIII, and I. Consistently normal levels of the abnormal prothrombin precursor descarboxyprothrombin, as determined by immunochemical and functional assays, showed that moxalactam did not possess warfarin-like properties. Moxalactam induced a significant suppression of adenosine diphosphate (ADP)-induced platelet aggregation. It appears that moxalactam inhibits ADP-induced platelet aggregation in vivo by perturbing the platelet membrane, thus making ADP receptors unavailable to the agonist. Of 33 additional beta-lactam antibiotics tested, 27 were found to suppress ADP-induced aggregation at high concentrations in vitro. It is concluded that moxalactam, as well as many newer and older broad-spectrum antibiotics, causes bleeding complications in debilitated patients by elimination of vitamin K-producing gut microorganisms. However, the clinical implications of the observed suppression of platelet function by many beta-lactam antibiotics are unclear.

Biomarkers↗
PubMedDate not supplied

Ethanol-moxalactam interactions in vivo.

Adverse reactions similar to disulfiram reactions observed in volunteers given moxalactam prompted an investigation to determine whether moxalactam, like disulfiram, leads to an accumulation of acetaldehyde during ethanol metabolism. Concentrations of ethanol and acetaldehyde in blood of male Wistar rats given test compounds and ethanol were determined by gas chromatography. Moxalactam, like disulfiram, had no effect on concentrations of ethanol but increased the concentrations of acetaldehyde. However, the effect after treatment with moxalactam was less than after treatment with disulfiram. The interval between pretreatment with moxalactam and administration of ethanol that gave the maximal effect ranged from 3 to 24 hr. When ethanol was given before or at the same time as moxalactam, no effect was observed. Cefamandole and cefoperazone, which, like moxalactam, have a methyltetrazolethiol side chain, increased concentrations of acetaldehyde, but penicillin G, carbenicillin, cephalothin, cephradine, cefoxitin, cefazolin, and cefotaxime had no effect. For prevention of a disulfiram-like reaction, physicians should caution patients to avoid alcoholic beverages for several days after treatment with moxalactam, cefamandole, or cefoperazone.

Acetaldehyde↗
PubMedDate not supplied

Moxalactam--absorption, excretion, distribution, and metabolism.

Levels of moxalactam in serum of healthy volunteers after single intramuscular injection, slow bolus intravenous injection, or intravenous infusion were proportional to the dose given. After intravenous bolus injection of 1 g of moxalactam, the peak serum level was 201.0 micrograms/ml, the half-life (beta-phase) was 126 min, and the cumulative urinary excretion during a 10-hr period was 90.5% of the dose. The values for cefazolin in the same volunteers were similar to those for moxalactam. No accumulation of the drug in serum was found even after multiple intravenous injections of 1 g every 12 hr for five days. Probenecid administered orally did not significantly affect levels of moxalactam in serum or urinary recovery, an observation which suggests that renal excretion of moxalactam takes place mainly through glomerular filtration. The serum half-life (beta-phase) of moxalactam in subjects with a creatinine clearance rate of less than or equal to 10 ml/min was markedly prolonged. Concentrations of moxalactam in bile were higher than those of cefazolin in a crossover study. Concentrations in sputum were 1.84-2.11 micrograms/ml in individuals given 1 g by intravenous slow bolus injection. No active metabolite of moxalactam was detected in plasma or urine.

Adolescent↗
PubMedDate not supplied

Moxalactam therapy vs. standard antimicrobial therapy for selected serious infections.

Moxalactam was studied in a prospective randomized clinical trial in 97 hospitalized patients suspected of having infection caused by moxalactam-susceptible bacteria. Seventy-eight of the 97 patients had clinical and/or bacteriologic evidence of infection, including pneumonia, cellulitis, urinary tract infection, bacteremia, and fever in neutropenic patients. Patients in the control group received antibiotics deemed appropriate by the attending physicians, whereas the moxalactam-treated group received only the study drug. Successful treatment was defined as the resolution of illness sufficient to allow discontinuation of parenteral antibiotic therapy. No significant difference was seen in efficacy with 33 (86.8%) of 38 patients in the moxalactam-treated group and 32 (80%) of 40 in the control group treated successfully (P greater than 0.20). The mean number of febrile days was significantly less in the moxalactam-treated group than in the control group (P less than 0.05). Renal toxicity occurred more frequently in the control group (P = 0.036). Fungal superinfection developed in two patients in the control group and in one in the moxalactam-treated group. An enterococcal superinfection of the bloodstream developed in one patient treated with moxalactam. Thus moxalactam appears to be comparable in efficacy to combinations of antibiotics in the treatment of selected seriously ill patients and may have less renal toxicity.

Anti-Bacterial Agents↗
PubMed1981

Pharmacokinetics of moxalactam and cefazolin compared in normal volunteers.

The pharmacokinetics of moxalactam, a new beta-lactam antibiotic with an unusually broad spectrum of activity, were studied in normal volunteers and compared with the pharmacokinetics of cefazolin. After a 1,000-mg intramuscular injection of moxalactam, a mean peak serum level of 49 +/- 10 micrograms/ml was achieved at 30 to 60 min which was equivalent to the level achieved with 0.5 g of cefazolin. Serum levels of 4.57 +/- 0.63 micrograms/ml, above the inhibitory levels for most organisms, were present at 8 h. The half-life of moxalactam was 2.3 h. After a 30-min intravenous infusion of 1 g, the serum level of moxalactam was 60 +/- 18.8 micrograms/ml. This compares with a serum level of 70 micrograms/ml obtained with an infusion of 0.5 g of cefazolin. At 6 h, 3.59 +/- 0.68 microgram/ml of moxalactam was present. The half-life of moxalactam was 2.3 h, similar to that of cefazolin. By 1 h after administration, serum levels of moxalactam were higher after intramuscular administration than after intravenous delivery. Urinary recovery of the drug was 76% after intramuscular injection and 74% after intravenous infusion, with the majority of the drug having been excreted in the first 4 h after administration. Urinary recovery of cefazolin was 85%. The pharmacokinetics of moxalactam are similar to those of cefazolin.

Adult↗
PubMed1983

Renal disposition of moxalactam in experimental animals as revealed by stop-flow analysis.

The mechanisms of moxalactam excretion were studied by stop-flow analysis in dogs, monkeys, and rabbits. In dogs, the amount of moxalactam excreted in the urine was almost equal to that estimated by glomerular filtration. There was no specific moxalactam peak corresponding to the p-aminohippuric acid (PAH) peak in the stop-flow patterns of the dogs. The PAH peak disappeared with administration of probenecid, but the moxalactam stop-flow pattern showed no change. In monkeys, no specific moxalactam peak corresponding to the PAH peak could be detected. In the stop-flow pattern of the rabbit, the peak moxalactam concentration corresponded with that of PAH and disappeared with probenecid. These results suggest that in dogs and monkeys renal excretion of moxalactam takes place mostly through glomerular filtration. In rabbits, however, there is a small renal tubular secretory component added to the primary element, glomerular filtration. These observations point to differences in the mechanisms of moxalactam excretion in different animal species.

Animals↗