Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Mezlocillin”

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 19 recordsLinked to original sources
PubMed1986

Determination of mezlocillin and its penicilloate and penilloate by high-performance liquid chromatography and stability of mezlocillin at different temperatures.

A method is described for the determination of mezlocillin and its metabolites penicilloic acid and penilloic acid in biological fluids by high-performance liquid chromatography. The stability of mezlocillin in serum and buffer was studied at different temperatures (4, -20, -70, and -196 degrees C) over a period of 6 months. Mezlocillin remained stable at -70 and -196 degrees C, whereas degradation was observed at -20 and 4 degrees C in serum and buffer.

Chromatography, High Pressure Liquid↗
PubMed1989

[In vitro interaction of mezlocillin with fluorouracil and mitomycin].

The interaction of mezlocillin (Baypen) with either fluorouracil (5-fluorouracil, 5-FU) or mitomycin was tested in vitro by incubating colorectal carcinoma cell line HT 29 with varying concentrations of mezlocillin, 5-FU, mitomycin and the combinations of mezlocillin + 5-FU and mezlocillin + mitomycin. Inhibition of colony growth in soft agar of treated compared with untreated cells was used as an in vitro response parameter. Concentration ranges were representative for regional chemotherapy with mitomycin or 5-FU and perioperative antibiotic therapy with mezlocillin. Mezlocillin, 5-FU and mitomycin showed dose-dependent inhibition of colony growth. Mezlocillin produced a maximal toxicity of 16% at 1000 micrograms/ml. Toxicity of 5-FU was reduced by addition of mezlocillin. The increase of colony growth after coincubation of mezlocillin with 5-FU (compared to cells treated with 5-FU alone) at a mezlocillin concentration of 10 micrograms/ml was 47% to 116%, at 100 micrograms/ml 44% to 132%, depending on the 5-FU test concentrations. The 5-FU toxicity in some instances was nearly abolished. There was no interaction between mezlocillin and mitomycin. The interference of mezlocillin with 5-FU-toxicity should be respected in case of combined perioperative antitumor and antibiotic therapy with 5-FU mezlocillin. Similar interactions with related antibiotics cannot be excluded.

Cell Survival↗
PubMed1978

Mezlocillin: a new acyl ureidopenicillin. Antimicrobial activity and combination effects with four aminoglycoside antibiotics.

Mezlocillin (Baypen), carbenicillin and mezlocillin combined with gentamicin, sisomicin, tobramycin and amikacin, respectively, were tested in vitro against 325 fresh clinical isolates of pathogenic gram-negative bacteria using the tube dilution procedure. The new acyl ureidopenicillin has a greater antimicrobial activity than carbenicillin against nearly all species tested. The comparison of the effectiveness of the mezlocillin-aminoglycoside combinations demonstrates the superiority of mezlocillin-sisomicin against Escherichia coli, Klebsiella, Serratia and Proteus spp., whereas mezlocillin-tobramycin is most active against gentamicin-sensitive Pseudomonas aeruginosa, and mezlocillin-amikacin against Enterobacter and gentamicin-resistant P. aeruginosa. The combination effects achieved in the majority of strains were addition or synergism. The resistance rate and the bactericidal efficacy of mezlocillin were clearly improved when mezlocillin was combined with aminoglycoside antibiotics. Mezlocillin-amikacin showed the lowest resistance rate (10.2%) followed by mezlocillin-sisomicin (12.3%), mezlocillin-gentamicin (15.1%) and mezlocillin-tobramycin (18.5%). In most species, mezlocillin-sisomicin has proved to be the combination with the best bactericidal potency.

Amikacin↗
PubMed1984

Pharmacokinetics and bacteriological efficacy of mezlocillin in experimental Escherichia coli and Listeria monocytogenes meningitis.

The purpose of this study was to determine the pharmacokinetics and bacteriological effect of mezlocillin in experimental meningitis caused by Listeria monocytogenes and two Escherichia coli strains. The half-life of mezlocillin in cerebrospinal fluid (CSF) was approximately twice that in serum of experimentally infected animals, and the penetration of drug into CSF was 5 to 15% after a single dose and 5 to 20% after continuous-infusion experiments. The bactericidal titer in CSF for both susceptible E. coli and L. monocytogenes was 1:8, whereas for the resistant E. coli strain, titers were less than 1:2 after single doses of 50 or 100 mg of mezlocillin per kg and 1:4 with continuous infusion. After single-dose and continuous-infusion experiments, the bacteriological effect of mezlocillin in experimental L. monocytogenes infections was similar to that of ampicillin. Mezlocillin reduced the colony counts of of susceptible E. coli in CSF by 90% or more after a single dose or continuous infusion but had no appreciable effect on resistant E. coli after a single dose of 50 mg/kg. In contrast, a single dose of 100 mg of mezlocillin per kg eradicated the resistant strain from CSF, despite a bactericidal titer in CSF of less than 1:2. This unexpected finding prompted us to evaluate the effect of serum on the in vitro susceptibilities of selected coliforms to mezlocillin. The activity of mezlocillin against one susceptible and four resistant strains of gram-negative, enteric bacilli was enhanced manyfold by the addition of fresh rabbit serum; this effect was abolished by heating the serum at 56 degrees C for 30 min. This interaction of mezlocillin and serum against coliform bacteria should be examined in a larger number of experimentally infected animals and in specimens obtained from mezlocillin-treated infants.

Animals↗
PubMed1984

Comparative efficacies of mezlocillin and ampicillin alone or in combination with gentamicin in the treatment of Streptococcus faecalis endocarditis in rabbits.

The in vitro and in vivo activities of mezlocillin and ampicillin, alone and in combination with gentamicin, against Streptococcus faecalis were compared. In vitro, relative bactericidal and activities for 10 strains of S. faecalis were as follows: mezlocillin plus gentamicin greater than ampicillin plus gentamicin (P is not significant) greater than mezlocillin (P less than 0.01) greater than ampicillin (P less than 0.01) greater than gentamicin (P less than 0.01) greater than control (P less than 0.01). One of the strains was used to induce endocarditis in rabbits. Infected rabbits were treated by random selection with ampicillin, mezlocillin, ampicillin plus gentamicin, mezlocillin plus gentamicin, or saline (control) for 7 days. Among antibiotic-treated rabbits, survival rates were the same, but ampicillin was less effective than the other regimens in sterilizing both blood cultures (P less than 0.001 on day 4) and cardiac vegetations (P less than 0.05 on day 7). Differences in quantitative vegetation cultures among rabbits treated with mezlocillin, mezlocillin plus gentamicin, or ampicillin plus gentamicin and sacrificed on day 7 were not significantly different. Peak inhibitory and bactericidal antibacterial activity titers in serum determined during treatment were higher with mezlocillin (with or without gentamicin) than with ampicillin (with or without gentamicin) (P less than 0.01). Mezlocillin may be more effective than ampicillin in the treatment of S. faecalis infections in humans.

Ampicillin↗
PubMed1982

[Pharmacokinetics of mezlocillin. Comparison with ampicillin and influence of probenecid (author's transl)].

In a randomized cross-over study 10 healthy male volunteers received a single 1 g dose of 6-[R]-2-3-methylsulfonyl -2- oxo-imidazolisine -1- carboxamido) -2- phenyl-acetamido]-penicillanic acid sodium salt (mezlocillin) and of ampicillin, either intravenously or intramuscularly. Following the intravenous loading dose, mean peak serum levels of 101 micrograms/ml for mezlocillin and 91.5 micrograms/ml for ampicillin were recorded. The ultimate half-life t 1/2 of mezlocillin (46.4 min) was slightly shorter than that of ampicillin (52.4 min). Similarly, the total volume of distribution of mezlocillin (24.1 l) was slightly inferior to that of ampicillin (29.4 l). The proportions of the dose administered recovered in the urine of 24 hours were 50.4 % for mezlocillin and 69.9 % for ampicillin. The total clearances of the two antibiotics were not significantly different, but the renal clearance of mezlocillin (186.6 ml/min/1.73 m2) was significantly lower than that of ampicillin (309.5 ml/min/1.73 m2). Following intramuscular injection, the mean peak serum levels obtained were 15.6 microgram/ml with mezlocillin and 15.1 micrograms/ml with ampicillin. The half-lives of the antibiotics were 50.0 min and 57.2 min respectively. The bioavailable fractions of mezlocillin and ampicillin, as measured from the areas under the serum concentration curves wer 63 % and 75 % respectively of the values determined after intravenous injection. The oral administration of 1 g probenecid one hour before an intramuscular injection of mezlocillin increased the peak serum level and area under the curve by 65 % and decreased the total clearance, renal clearance and apparent volume of distribution by 38 %, 52 %, and 35 % respectively. However, the ultimate half-life was not significantly altered (50.5 min without, and 52.0 min with probenecid).

Adult↗
PubMed1993

A randomized study of cefepime versus the combination of gentamicin and mezlocillin as an adjunct to surgical treatment in patients with acute cholecystitis.

In patients with acute cholecystitis, antibiotics are used as an adjunct to cholecystectomy to reduce the incidence of postoperative septic complications thought to be related to bactibilia. Combinations of penicillins, or cephalosporins or aminoglycosides, or both, are often used. Cefepime is a fourth-generation cephalosporin with excellent activity against gram-positive and gram-negative bacteria, including Pseudomonas species. It has a prolonged serum half-life, allowing twice-daily dosing, and is not nephrotoxic. This study was undertaken to determine whether or not cefepime was as effective as the combination of gentamicin and mezlocillin in patients with acute cholecystitis. One hundred and forty-nine patients were randomized, two to one, to receive cefepime or gentamicin and mezlocillin. Cefepime was given intravenously at 2 grams every 12 hours; gentamicin, 1.0 to 1.5 milligrams per kilograms every eight hours, and mezlocillin, 3 to 4 grams every four to six hours. All patients underwent cholecystectomy. Bile cultures were obtained, and concentrations of cefepime in blood, bile, peritoneal fluid and gallbladder were determined in a subset of patients. There were 56 evaluable cefepime-treated and 34 evaluable gentamicin and mezlocillin-treated patients. Bactibilia was present in 17 of 56 cefepime-treated patients (30.4 percent) and ten of 34 gentamicin and mezlocillin-treated patients (29.4 percent). Enterococci were recovered in six cefepime-treated patients. Clinical and bacteriologic responses were similar for the cefepime-treated and gentamicin and mezlocillin-treated groups, with one failure in each group, a wound infection in a patient receiving cefepime and a subhepatic abscess in a patients receiving gentamicin and mezlocillin. Other measures of outcome, such as the number of days of fever, days nothing by mouth, days of hospitalization and days of antibiotic therapy were similar in both groups. Cefepime, with every 12 hour dosing, achieved extremely high concentrations in all tissues assayed at the time of the operation, a mean of eight hours after administration. Adverse clinical events were similar in both treatment groups. Cefepime is as effective as gentamicin and mezlocillin in preventing septic complications after cholecystectomy for acute cholecystitis. Cefepime requires fewer doses, does not require drug monitoring, is not associated with nephrotoxicity and may therefore prove to be a cost-effective alternative to combination therapy that uses an aminoglycoside.

Acute Disease↗
PubMed1986

Behaviour of TEM-1 beta-lactamase as a resistance mechanism to ampicillin, mezlocillin and azlocillin in Escherichia coli.

Escherichia coli isolates which synthesised the extremely common 'TEM-1' plasmid mediated beta-lactamase were more resistant to the alpha-aminopenicillins, ampicillin, mezlocillin and azlocillin, than were strains which lacked this enzyme. However, many TEM-1+ isolates remained sensitive to therapeutic concentrations of mezlocillin (less than 64 mg/l), whereas virtually none was susceptible to such levels of ampicillin or azlocillin. Transconjugants of E. coli K12 into which we introduced various TEM-1 coding plasmids similarly acquired lower levels of resistance to mezlocillin than to ampicillin and azlocillin. Those which expressed relatively small amounts of enzyme remained sensitive to 64 mg/l of mezlocillin, whereas they were substantially resistant (MIC greater than 64 mg/l) to the other alpha-aminopenicillins. These data suggested that the enzyme afforded weaker protection against mezlocillin than against azlocillin and ampicillin and we attempted to relate this finding to its hydrolytic activity. Extracted TEM-1 beta-lactamase hydrolysed high concentrations of mezlocillin more rapidly than ampicillin and azlocillin; however, mezlocillin was calculated to be the weakest substrate at the low concentrations which are likely to be obtainable in the bacterial cell. These data may partly account for the residual activity of mezlocillin against enzyme producers, but target and permeability factors probably also contribute.

Ampicillin↗
PubMed1984

Mezlocillin and ticarcillin alone and combined with gentamicin in the treatment of experimental Enterobacter aerogenes endocarditis.

The efficacies of mezlocillin and ticarcillin, each alone and in combination with gentamicin, in the therapy of experimental left-sided Enterobacter aerogenes endocarditis in rabbits were compared. Each beta-lactam was administered intramuscularly at a dose of 180 mg/kg every 6 h either alone or with gentamicin (1.7 mg/kg intramuscularly every 8 h). Bacterial populations at the start of therapy (7 days after initiation of infection) were 9 to 10 log10 CFU/g of vegetation. Ticarcillin produced concentrations in serum that were twice those produced by mezlocillin, but the therapeutic ratios of mezlocillin and ticarcillin (ratio of peak level in serum to MBC) were the same. All of the therapeutic regimens given for either 5 or 10 days were effective in reducing vegetation counts when compared with the untreated controls (P less than 0.01 for all comparisons), except mezlocillin alone and ticarcillin alone, which caused insignificant reductions in counts after 5 days of therapy (P greater than 0.05). After 10 days of therapy, the only regimen that was significantly different from another was that of mezlocillin plus gentamicin, which was significantly better than that of ticarcillin alone (P less than 0.01). These studies document that mezlocillin and ticarcillin were both effective in reducing the numbers of E. aerogenes CFU in vegetations in rabbits with experimental endocarditis when the drugs were given over a prolonged course. More rapid and extensive reduction in vegetation counts was achieved with combinations of an aminoglycoside plus mezlocillin or ticarcillin. Mortality was significantly less among rabbits treated with mezlocillin plus gentamicin.

Animals↗
PubMed1982

[Systemic mezlocillin prophylaxis in elective colon surgery].

A prospective randomized, controlled study comprising 100 patients was performed to evaluate the effect of mezlocillin given prophylactically in elective colon surgery. Fifty-two patients were treated and 48 served as controls. Both groups were well-matched for age, sex, disease and surgical procedure. 2 g of mezlocillin were given intravenously before surgery and then every eight hours until the fifth postoperative day. The concentrations of mezlocillin in serum and tissues were determined in 20 patients and related to the MICs of the contaminants and the bacteria isolated postoperatively. A significantly lower incidence of intra-abdominal complications, peritonitis, urinary tract infections and wound infections was found in the mezlocillin group (10%) than in the controls (46%). The average number of postoperative hospital days decreased significantly from 23 days in the control group to 19 days in the mezlocillin group. The analysis of the bacteriological results gave no indication of a selection of resistant strains due to the prophylactic use of mezlocillin. No side-effects were found in connection with mezlocillin prophylaxis.

Adult↗
PubMed1982

[Pharmacokinetics and dosage of mezlocillin administered by intravenous infusion].

Mezlocillin was administered to seven healthy adults by i. v. infusion at two different speeds. They received 1.6 g mezlocillin in five minutes with the initial loading infusion and 1.3 g mezlocillin in one hour with the following infusion. Our aim was to achieve a 100 mg/l steady state serum concentration. The mezlocillin concentrations in the serum averaged 118.7 (+/- 31.2) mg/l at the end of this infusion. Four hours later they were 2.79 (+/- 1.41) mg/l and after six hours 0.96 (+/- 0.93) mg/l. The urinary excretion during the six hours averaged 60.5% of the applied dose of 2.9 g mezlocillin. The pharmacokinetic parameters of mezlocillin were calculated automatically using a two-compartment model. The average values were the following: biological half-life (beta) 72.7 (+/- 26) minutes; total plasma clearance 2.447 (+/- 0.586) ml/s; distribution volume (Vd area) 15.30 (+/- 6.12) l, i. e. 0.21 l/kg. Deviations from the mezlocillin serum concentrations desired (100 mg/l) are explained by interindividual differences in the pharmacokinetic behaviour and by the use of a two-compartment model.

Adult↗
PubMed1988

Cefoperazone plus piperacillin versus mezlocillin plus tobramycin as empiric therapy for febrile episodes in neutropenic patients.

The double beta-lactam combination of cefoperazone plus piperacillin was compared with an aminoglycoside-containing regimen of mezlocillin plus tobramycin in a prospective, randomized trial of empiric therapy for febrile neutropenic patients (neutrophils no more than 1,000/mm3). Thirty febrile episodes were treated with cefoperazone plus piperacillin and mezlocillin plus tobramycin, respectively. There was no significant difference between the two groups with respect to age, sex, pretherapy neutrophil count, and mean duration of therapy. The majority of patients had neutrophil counts of no more than 200/mm3 at the initiation of therapy. Only microbiologically and clinically documented infections were evaluated for efficacy. The cefoperazone plus piperacillin regimen appeared to have a comparable response rate with the mezlocillin plus tobramycin regimen (20 of 24 patients [83 percent] versus 16 of 23 patients [70 percent]). Gram-positive micro-organisms were seen predominantly in this study, with the cefoperazone plus piperacillin regimen achieving a bacteriologic response in 84 percent, as opposed to 60 percent for those organisms treated with the mezlocillin plus tobramycin regimen. Neither regimen was totally effective against coagulase-negative staphylococci. Eight superinfections occurred in the cefoperazone plus piperacillin arm, whereas 11 superinfections occurred in the mezlocillin plus tobramycin arm. Although fungal superinfections were most common, the number of gram-positive superinfections in the mezlocillin plus tobramycin arm exceeded those seen in the cefoperazone plus piperacillin arm. The incidence of antibiotic-related side effects was similar in the two groups. Hypokalemia was most frequently seen. Both skin rashes and nephrotoxicity were more common with mezlocillin plus tobramycin. Cefoperazone plus piperacillin was found to be effective empiric therapy in febrile neutropenic patients. This double beta-lactam combination may be particularly useful for patients who have or are at high risk for the development of renal insufficiency.

Adolescent↗
PubMed1983

A prospective randomized trial to compare mezlocillin and metronidazole with cefuroxime and metronidazole as prophylaxis in elective colorectal operations.

A prospective randomized trial has compared a broad spectrum ureidopenicillin with a broad spectrum cephalosporin for prophylaxis against the aerobic organisms encountered during elective colonic surgery. Even though only two doses of antibiotics were administered the incidence of severe sepsis was low. Severe wound infection occurred in three of the patients receiving mezlocillin and metronidazole (6 per cent) compared with six in the group receiving cefuroxime and metronidazole (13 per cent). Minor wound sepsis was recorded in 24 per cent of patients receiving mezlocillin and metronidazole compared with only 11 per cent after cefuroxime and metronidazole. There were two episodes of septicaemia, one in each group, and three abscesses, all of which occurred in patients receiving metronidazole and mezlocillin. The total number of surgically related infections was, however, significantly less with cefuroxime and metronidazole (N = 13) compared with mezlocillin and metronidazole (N = 23; P less than 0.03). Escherichia coli was the principal organism responsible for surgically-related postoperative sepsis: (22 isolates: 14 mezlocillin and eight cefuroxime) all of which sensitive to the agents used. Pseudomonas aeruginosa was recovered from 10 patients (three mezlocillin and seven cefuroxime), all of the isolates were resistant to both antibiotics and were associated with severe morbidity. There were 11 isolates of Staphylococcus spp. (nine mezlocillin and two cefuroxime: P less than 0.03). Postoperative diarrhoea occurred in six patients, all were in the group receiving cefuroxime and metronidazole. (Clostridium difficile was recovered from the stool in three of which one was associated with Cl. difficile cytotoxin.)

Adolescent↗
PubMed1988

A trial of mezlocillin versus cefuroxime with or without metronidazole for the prevention of wound sepsis after biliary and gastrointestinal surgery.

A randomized controlled trial was undertaken to compare the role of mezlocillin, as the sole prophylactic agent, with a combination of cefuroxime and metronidazole in patients undergoing biliary and gastrointestinal surgery. No difference in wound infection rates was seen in patients following appendicectomy, biliary or gastro-oesophageal surgery. A significantly higher wound infection rate was seen in patients undergoing colorectal surgery who received mezlocillin alone (30.2%) compared with those receiving cefuroxime and metronidazole (11.5%): this rate was similar to that of historical placebo controls in other units. The wound infections seen in patients receiving mezlocillin alone were polymicrobial involving organisms of faecal origin, including non-sporing anaerobes which were predominantly sensitive to mezlocillin. Infections due to Staphylococcus aureus, resistant to mezlocillin, were more frequent in patients receiving mezlocillin and usually secondary in nature. We conclude that mezlocillin may be an effective sole prophylactic agent in appendicectomy but not in colorectal surgery; the possible reasons for failure to adequately prevent infection, following colorectal surgery, are discussed.

Biliary Tract Diseases↗
PubMed1990

In vitro comparison of mezlocillin and piperacillin plus tobramycin or gentamicin versus 100 gram-negative nosocomial bloodstream isolates.

We compared the in vitro activity of mezlocillin and piperacillin, alone and in combination with tobramycin or gentamicin, against clinical isolates of gram-negative bacilli from hospitalized patients with 100 distinct episodes of nosocomial bacteremia. The minimum inhibitory concentrations (MICs) necessary to inhibit 50% and 90% of isolates showed that piperacillin was most active against Pseudomonas aeruginosa. The MIC needed to inhibit 90% of isolates also showed that mezlocillin was more active against Enterobacter cloacae. Activities of the two acylaminopenicillins were comparable against the rest of the isolates. Combining the acylaminopenicillins with either gentamicin or tobramycin decreased the MICs fourfold or more for both combinations. Synergy occurred more frequently with mezlocillin-gentamicin (12%), followed by piperacillin-tobramycin (9%), mezlocillin-tobramycin (6%), and piperacillin-gentamicin (5%). Antagonism for Enterobacteriaceae isolates was observed most frequently with the combination of piperacillin plus tobramycin (20%), followed by mezlocillin plus tobramycin (17.6%), piperacillin plus gentamicin (12.9%), and mezlocillin plus gentamicin (8.2%). There are very few differences in the activities of mezlocillin and piperacillin combined with either gentamicin or tobramycin versus nosocomial gram-negative bloodstream isolates.

Drug Synergism↗
PubMed1984

Developmental pharmacokinetics of mezlocillin in newborn infants.

Single-dose pharmacokinetics of mezlocillin were studied in 53 newborn infants (72% less than or equal to 36 weeks' gestation) given ampicillin and an aminoglycoside for suspected or proved sepsis. Mezlocillin (75 mg/kg IV or IM) was substituted for ampicillin, serum was assayed microbiologically, and noncompartmental pharmacokinetic parameters were calculated. Analysis of covariance showed that dose/area under the serum concentration-time curve for mezlocillin was influenced by body weight, intramuscular administration, and treatment with gentamicin. A dual intravenous/intramuscular nonlinear regression model yielded an apparent intramuscular bioavailability of 84%. Clearance was proportional to body weight (WT) (r2 = 0.70). Mean CL/WT (0.078 L/hr/kg) was one-half adult values and influenced by gestational age. Steady-state volume of distribution varied linearly with weight (r2 = 0.80), the mean value (0.38 L/kg) being twice that in adults. Mezlocillin half-life (mean 3.71 hours) exceeded adult values and did not correlate with weight. Twenty-four newborn infants received 75 mg/kg mezlocillin every 6 or every 8 hours, along with gentamicin, during the first 7 to 10 days of life. Peak (1.5 hours) and trough (6 or 8 hours) concentrations were determined; the latter decreased from day 3 to days 7 to 10, suggesting a possible postnatal age-dependent change in mezlocillin elimination. Although mezlocillin disposition is affected by age and therapeutic factors, weight alone may adequately predict dosing requirements.

Adult↗
PubMed1980

Potential of mezlocillin as empiric single-agent therapy in febrile granulocytopenic cancer patients.

Mezlocillin was used as an initial empiric antibiotic therapy for febrile (> 101 degrees F, ca. 38.33 degrees C) granulocytopenic (< 1,000/microliter) cancer patients. Patients known to be colonized with an organism resistant to 100 micrograms of mezlocillin per mol were excluded. The initial 25 cases (23 patients) received intravenous mezlocillin, 260 mg per kg per day in six divided doses; the mean 1-h-postinfusion serum level was 69 micrograms/ml. Because of the low serum level, the next 25 cases (22 patients) received 450 mg/kg per day, also in six divided doses, resulting in a mean 1-h-postinfusion serum level of 161 micrograms/ml. Both dosage regimens provided similar efficacy. Combined results show that 11 of 21 microbiologically documented infections and 7 of 13 clinically documented infections improved. Instances of bacteremia (number of cases in parentheses) were caused by Pseudomonas aeruginosa (two), Staphylococcus epidermidis (two), Clostridia perfringens (one), and Bacillus species (one); only one case improved. A rise in granulocyte count to > 500/microliters, a serum bactericidal activity of greater than or equal to 1:8 against the infecting pathogen, or both were indicators of a good therapeutic response. Despite exclusion of patients known to be previously colonized with mezlocillin-resistant organisms, 7 of 23 pathogens required a minimal concentration of greater than or equal to 100 micrograms of mezlocillin per ml for inhibition. In addition, surveillance cultures from 18 cases showed resistant organisms colonizing the gingiva, rectum, or both. Side effects of mezlocillin were minimal and included pseudoproteinuria, asymptomatic transient rise in bilirubin, and easily reversible kypokalemia. Mezlocillin, a new semisynthetic penicillin with little toxicity, was found to be inadequate as a single-agent empiric antibiotic therapy for febrile, granulocytopenic cancer patients.

Adult↗
PubMed1983

Excretion of azlocillin and mezlocillin by the normal pancreas and in acute pancreatitis in dogs and rats.

Dogs and rats were studied to evaluate the excretion of two new acyl-ureidopenicillins, azlocillin and mezlocillin, in the pancreatic fluid. After intravenous administration of 55 mg X kg-1 of either drug, an extremely low concentration (less than 3.0 micrograms X ml-1) of both antibiotics was measured in pancreatic juice of conscious dogs. In rats, both azlocillin and mezlocillin were excreted by the pancreas in bactericidal concentrations (greater than 10 micrograms X ml-1) during the first 15 min following their injection. In anesthetized dogs and rats in which acute pancreatitis was induced by injection of sodium taurocholate into the main pancreatic duct, the tissue concentration of mezlocillin (55 mg X kg-1 i.v.) was significantly higher than in the pancreatic tissue of control animals. In both instances, bactericidal concentrations of mezlocillin were measured in the pancreatic tissue. During the first 30 min following its injection, the concentration of mezlocillin was about five times higher in inflammed pancreatic tissue than in the normal pancreas (dogs: 44 +/- 14 vs. 5 +/- 3 micrograms X g-1 tissue; rats: 67 +/- 10 vs. 13 +/- 2 micrograms X g-1). These data indicate that (1) azlocillin and mezlocillin are excreted in bactericidal concentrations by the normal pancreas only in rats but not in dogs, and (2) in both species, bactericidal concentrations of mezlocillin can be observed in the normal pancreatic tissue and in acute pancreatitis; its concentration being significantly higher in acute pancreatitis than in controls.

Acute Disease↗