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PubMed1983

The elimination of sulbactam alone and combined with ampicillin in patients with renal dysfunction.

Sulbactam, a beta-lactamase inhibitor, was given as a single agent to 12 subjects with varying degrees of renal dysfunction. The half-life in normal subjects was 1.1 h and increased to 21.3 h in those with terminal renal failure. Sulbactam together with ampicillin was given to a further five subjects. It was concluded that if the two agents are given together, the plasma ratio of one to the other will remain constant whatever the renal function.

Ampicillin↗
PubMed1986

A non-comparative study of parenteral ampicillin and sulbactam in intra-thoracic and intra-abdominal infections.

Fifty-four patients were treated with intravenous ampicillin and sulbactam in an open study of intra-thoracic and intra-abdominal infection. Thirty-one were treated with 500 mg each of the combination 6-hourly while 23 patients were given 1 g of ampicillin and 500 mg of sulbactam, 6-hourly. Thirteen of fourteen (93%) patients with severe respiratory tract infection and 22/26 (85%) patients in the intra-abdominal infection group responded clinically and bacteriologically. Seven patients with clinical sepsis (but not confirmed bacteriologically) improved on therapy. 50/55 (91%) clinical isolates from this study were eliminated. An increase in MIC was found in two cases. There were minimal side effects, pain at site of injection being the commonest complaint.

Abdomen↗
PubMed1993

An open trial of cefoperazone plus sulbactam for the treatment of fever in cancer patients.

Cancer patients received cefoperazone plus sulbactam for 673 febrile episodes presumed to be caused by infection. Overall, 415 (76%) of the 545 evaluable episodes responded. There were 213 responses (84%) amongst the 254 fevers of unknown origin and 202 responses (69%) amongst the 291 documented infections. Fifty-one (61%) of the 83 episodes pneumonia and 74 (64%) of the 115 episodes of bacteraemia responded. Only 39 (58%) of the 67 infections caused by Gram-positive bacteria responded compared with 55 (86%) of 64 Gram-negative infections which included seven of eight caused by Pseudomonas aeruginosa. Eighteen (67%) of 27 polymicrobial infections responded to the regimen. Response rates were significantly lower amongst the 125 patients whose neutrophil counts decreased during therapy than amongst the 158 patients whose neutrophil counts increased. Adverse events which were possibly or probably related to antibiotic therapy were observed during 73 of the episodes; the most commonly reported side-effects were diarrhoea and skin rash. Six patients developed a coagulopathy without haemorrhage and two experienced anaphylactic reactions. In this open trial cefoperazone plus sulbactam proved to be an effective regimen for initial therapy of fever in cancer patients. It should be combined with a glycopeptide in those institutions where infections caused by methicillin-resistant staphylococci are frequently encountered.

Adolescent↗
PubMed1984

Pharmacokinetics of parenteral sulbactam in patients with appendicitis.

The distribution and elimination of a new beta-lactamase inhibitor, sulbactam, were characterized in patients with gangrenous or perforated appendicitis. Using a two-compartment model, the distribution volumes for the central and total body were approximately 11 and 25 L, respectively. Sulbactam is rapidly distributed and eliminated with rate constants of about 3.7 and 0.7 h-1, respectively. Mean total body clearance was 311 ml/min. In contrast to previously reported data from normal subjects, surgical patients have more rapid total body clearance and larger steady-state distribution volumes.

Appendicitis↗
PubMed2006

Detection of bacterial strains producing sulbactam- or tazobactam-sensitive beta-lactamases by the use of disks containing the inhibitors alone instead of combining them with antibiotics.

The author demonstrated that disks containing beta-lactamase inhibitors sulbactam or tazobactam combined with ampicillin (SAM) and piperacillin (TZP) are not suitable for performing the double-disk synergy test (DDST) with the aim of determining the sensitivity of beta-lactamases to these inhibitors. The presence of antibiotics (especially of piperacillin) is so disturbing that the results of testing are not specific. In contrast, the use of disks containing sulbactam or tazobactam alone yields very specific results. The author suggested to the firms producing sensi-disks that they make these commercially available to laboratory workers.

Ampicillin↗
PubMed1982

Comparative pharmacokinetics and tissue penetration of sulbactam and ampicillin after concurrent intravenous administration.

A combination of 500 mg each of sulbactam and ampicillin was administered intravenously into six healthy male volunteers, and subsequent serum and blister fluid levels were measured. Both dogs had similar serum half-lives of about 1 h. The concentrations of sulbactam in serum and blister fluid were about 1.5 times those of ampicillin, and appeared to be pharmacokinetically well matched when administered in equal doses.

Adult↗
PubMed1982

Synergistic activity of mecillinam in combination with the beta-lactamase inhibitors clavulanic acid and sulbactam.

The beta-lactamase inhibitors clavulanic acid and sulbactam were combined with mecillinam. beta-Lactamase-containing Escherichia coli resistant to mecillinam was synergistically inhibited by both clavulanic acid and sulbactam. beta-Lactamase-containing Enterobacter was synergistically inhibited, but strains lacking beta-lactamases were not synergistically inhibited. Synergistic inhibition was noted for beta-lactamase-containing, mecillinam-resistant Klebsiella, Citrobacter, Serratia, and Salmonella isolates, but only 18% of beta-lactamase-containing Proteus mirabilis, Providencia rettgeri, Providencia stuartii, and Morganella morganii were synergistically inhibited by the combinations.

Amdinocillin↗
PubMed1984

Comparative activities of the beta-lactamase inhibitors YTR 830, sodium clavulanate, and sulbactam combined with amoxicillin or ampicillin.

YTR 830, a new beta-lactamase inhibitor, was compared with clavulanic acid and sulbactam against aminopenicillin-resistant clinical isolates. At a concentration of 8 micrograms/ml, YTR 830 was as effective as clavulanate or sulbactam in reducing the aminopenicillin MICs. Combined with amoxicillin, YTR 830 is a potentially useful agent for therapy of many bacterial infections.

Amoxicillin↗
PubMed1985

In vitro susceptibility of Campylobacter jejuni to 27 antimicrobial agents and various combinations of beta-lactams with clavulanic acid or sulbactam.

The in vitro susceptibility of human isolates of Campylobacter jejuni was investigated with 27 antibiotics and 8 combinations of beta-lactams with clavulanic acid or sulbactam. Ansamycin, the new quinolines, erythromycin, and cefpirome were the most active drugs against C. jejuni; amoxicillin, ampicillin, cefotaxime, and ceftazidime 90% of the isolates, greater than or equal to 50 mg/liter). The activity of various beta-lactams was unchanged by the addition of clavulanic acid or sulbactam.

Anti-Bacterial Agents↗
PubMed1986

High-pressure liquid chromatographic assay of sulbactam in plasma, urine, and tissue.

A reverse-phase high-pressure liquid chromatography method for the quantitation of sulbactam in plasma, urine, and tissue is described. The assay used the formation of an imidazole derivative followed by extraction with acetonitrile and dichloromethane and used UV absorbance for detection. The mobile phase consisted of acetonitrile, tetrabutylammonium hydroxide, and phosphate buffer. The assay was linear from 100 micrograms/ml (g of tissue) to 1 microgram/ml (g). Within- and between-batch recovery was greater than 90%. The coefficient of variation was generally less than 15%. There were no interfering peaks in the quantitation of sulbactam.

Cefoperazone↗
PubMed1988

Susceptibilities of Hong Kong isolates of multiply resistant Shigella spp. to 25 antimicrobial agents, including ampicillin plus sulbactam and new 4-quinolones.

Seventy-two percent of 129 shigella isolates from two Hong Kong hospitals were Shigella flexneri. Twenty-six percent were S. sonnei, and there was only one isolate each of S. dysenteriae and S. boydii. Ninety-six percent of the isolates were resistant to two or more antibiotics, and up to 11 resistances were seen in a single isolate. Fifty-seven percent or more of these isolates were resistant to ampicillin, streptomycin, tetracycline, chloramphenicol, and sulfamethoxazole; and up to twenty-three percent were resistant to kanamycin, trimethoprim, trimethoprim-sulfamethoxazole, and gentamicin. All the isolates were susceptible to amikacin, nalidixic acid, and the newer 4-quinolone agents; and all but one were susceptible to the cephalosporins tested. Only three isolates remained resistant to ampicillin in the presence of sulbactam. Ampicillin plus sulbactam or the newer 4-quinolone agents may be alternatives for the treatment of severe infections caused by multiply resistant shigellas.

Ampicillin↗
PubMed1989

Pseudomonas cepacia susceptibility to sulbactam.

For 25 of 32 Pseudomonas cepacia isolates, predominantly from sputum of adult patients, agar dilution MICs of sulbactam were 2.5 micrograms/ml, and for only one was the MIC more than 80 micrograms/ml. Susceptibility was reliably predicted by response to a commercial sulbactam-ampicillin disk.

Humans↗
PubMed1993

Characterization of a new TEM-type beta-lactamase resistant to clavulanate, sulbactam, and tazobactam in a clinical isolate of Escherichia coli.

A clinical Escherichia coli strain highly resistant to the combinations of amoxicillin-clavulanate, ampicillin-sulbactam, and piperacillin-tazobactam was isolated from a patient with a community-acquired urinary tract infection who was previously treated with amoxicillin-clavulanate. These resistances were carried by a 45-kb conjugative plasmid encoding for a single beta-lactamase with a pI of 5.4. Cloning and sequencing of the new beta-lactamase, IRT-3, revealed identity with the blaT1 gene encoding the TEM-1 beta-lactamase except for a replacement of the methionine residue at position 67 by isoleucine and of the methionine residue at position 180 by threonine. Both mutations were segregated by the construction of hybrid genes, and only the mutation at methionine at position 67 was related to resistance to the suicide inhibitors. The inhibitory effects of clavulanate, sulbactam, and tazobactam on the TEM-1 enzyme were substantially decreased in comparison with those on IRT-3, as indicated by the 50% inhibitory concentrations.

Clavulanic Acid↗
PubMed1994

Susceptibilities of 200 penicillin-susceptible and -resistant pneumococci to piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, ceftazidime, and ceftriaxone.

MICs of eight beta-lactams (piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, ceftazidime, and ceftriaxone) were determined by agar dilution against 64 penicillin-susceptible, 70 intermediately penicillin-resistant, and 66 fully penicillin-resistant pneumococci. The MICs of piperacillin with and without tazobactam for 90% of the susceptible, intermediately resistant, and resistant strains tested (MIC90s) were < or = 0.064, 2.0, and 4.0 micrograms/ml, respectively. By comparison, those of ampicillin with and without sulbactam were 0.125, 2.0, and 4.0 micrograms/ml and those of ceftriaxone were < or = 0.064, 1.0, and 2.0 micrograms/ml, respectively. Strains were less susceptible to ticarcillin with and without clavulanate (MIC90s, 2.0, 64.0, and 128.0 micrograms/ml) and ceftazidime (MIC90s, 1.0, 8.0, and 32.0 micrograms/ml).

Ampicillin↗
PubMed1997

Comparison of the bactericidal activities of piperacillin-tazobactam, ticarcillin-clavulanate, and ampicillin-sulbactam against clinical isolates of Bacteroides fragilis, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa.

Owing to the broad spectrum of activity afforded by beta-lactam-beta-lactamase inhibitor preparations, these agents are frequently selected as empiric therapy for the treatment of mixed infections such as intra-abdominal and diabetic foot infections, either alone or in combination with an aminoglycoside. Twelve healthy volunteers were enrolled in a randomized, open-label, four-way crossover trial comparing the bactericidal activities of piperacillin-tazobactam, ticarcillin-clavulanate, and ampicillin-sulbactam against microorganisms commonly isolated from mixed infections. Subjects received the following regimes: (i) 3.375 g of piperacillin-tazobactam intravenously (i.v.) every 6 h (q6h) (ii) 4.5 g of piperacillin-tazobactam i.v. q8h, (iii) 3.1 g of ticarcillin-clavulanate i.v. q6h, and (iv) 3.0 g of ampicillin-sulbactam i.v. q6h. Serum bactericidal titers were determined and used to calculate the duration of measurable bactericidal activity over the dosing interval of each of the regimens against two clinical isolates of Bacillus fragilis, Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa. The percentage of the dosing interval over which drug concentrations in serum remained above the MIC for each organism was determined and compared with the observed duration of bactericidal activity was noted (r = 0.78; P < 0.001). All of the regimens demonstrated good activity against B. fragilis and E. coli. Against E. faecalis and P. aeruginosa, however, all of the regimens provided bactericidal activity for less than 50% of the respective dosing intervals. These data suggest that use of shorter dosing intervals or continuous-infusion regimens should be considered in combination with an aminoglycoside to improve the bactericidal profiles of these agents for E. faecalis and P. aeruginosa.

Adult↗
PubMed1997

Importance of beta-lactamase inhibitor pharmacokinetics in the pharmacodynamics of inhibitor-drug combinations: studies with piperacillin-tazobactam and piperacillin-sulbactam.

An in vitro pharmacokinetic model was used to study the pharmacodynamics of piperacillin-tazobactam and piperacillin-sulbactam against gram-negative bacilli producing plasmid-encoded beta-lactamases. Logarithmic-phase cultures were exposed to peak antibiotic concentrations observed in human serum after the administration of intravenous doses of 3 g of piperacillin and 0.375 g of tazobactam or 0.5 g of sulbactam. Piperacillin and inhibitor were either dosed simultaneously or piperacillin was dosed sequentially 0.5 h after dosing with the inhibitor. In studies with all four test strains, the pharmacodynamics observed after simultaneous dosing were similar to those observed with the sequential regimen. Since the ratio between piperacillin and tazobactam was in constant fluctuation after sequential dosing, these data suggest that the pharmacodynamics of the piperacillin-inhibitor combinations were not dependent upon maintenance of a critical ratio between the components. Furthermore, when regrowth was observed, the time at which bacterial counts began to increase was similar between the simultaneous and sequential dosing regimens. Since the pharmacokinetics of the inhibitors were the same for all regimens, these data suggest that the length of time that the antibacterial activity was maintained over the dosing interval with these combinations was dictated by the pharmacokinetics of the beta-lactamase inhibitor in the combination. The antibacterial activity of the combination appeared to be lost when the amount of inhibitor available fell below some critical concentration. This critical concentration varied depending upon the type and amount of enzyme produced, as well as the specific inhibitor used. These results indicate that the antibacterial activity of drug-inhibitor combinations, when dosed at their currently recommended ratios, is more dependent on the pharmacokinetics of the inhibitor than on those of the beta-lactam drug.

Bacteria↗
PubMed1999

Evaluation of bactericidal activities of LY333328, vancomycin, teicoplanin, ampicillin-sulbactam, trovafloxacin, and RP59500 alone or in combination with rifampin or gentamicin against different strains of vancomycin-intermediate Staphylococcus aureus by time-kill curve methods.

This in vitro study evaluated the activities of vancomycin, LY333328, and teicoplanin alone and in combination with gentamicin, rifampin, and RP59500 against Staphylococcus aureus isolates with intermediate susceptibilities to vancomycin. Ampicillin-sulbactam and trovafloxacin were also evaluated. LY333328 and ampicillin-sulbactam resulted in bactericidal activity against all isolates. The combination of gentamicin with glycopeptides showed synergistic activity, while rifampin had no added benefit.

Ampicillin↗
PubMed1984

Interpretive standards and quality control limits for susceptibility tests with ampicillin-sulbactam combination disks.

In vitro studies were performed to evaluate susceptibility tests with disks containing 10 micrograms of ampicillin plus 10 micrograms of sulbactam. Interpretive zone standards of less than or equal to 11 mm (resistant), 12 to 13 mm (intermediate), and greater than or equal to 14 mm (susceptible) are proposed. A nine-laboratory coordinated study was performed to establish tentative zone size limits for quality control of ampicillin-sulbactam disks. This included data with a new control strain selected to monitor performance of such combination disks.

Acinetobacter↗