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PubMedDate not supplied

Bactericidal activity of low-dose ceftizoxime plus metronidazole compared with cefoxitin and ampicillin-sulbactam.

Eighteen volunteers received ceftizoxime 1 g plus metronidazole 500 mg intravenously every 12 hours, cefoxitin 2 g intravenously every 6 hours, and ampicillin-sulbactam 3 g every 6 hours in a triple-crossover, open-label study to compare serum bactericidal titers (SBTs) against two strains of Escherichia coli and Bacteroides fragilis. Serum was analyzed for drug concentration and bactericidal activity. Ceftizoxime-metronidazole exhibited a significantly greater (p < 0.05) area under the bactericidal curve and percentage of the dosing interval with SBTs of 1:2 or above against E. coli than cefoxitin or ampicillin-sulbactam. The respective values were equal to those of ampicillin-sulbactam for one strain of B. fragilis (both greater than cefoxitin) and greater than cefoxitin and ampicillin-sulbactam for the other strain. A 1-g dose of ceftizoxime given with metronidazole 500 mg every 12 hours should be an effective alternative to standard antibiotic treatment of mixed aerobic-anaerobic bacterial infections.

Adult↗

PubMed1996

[Bactericide activity of sulbactam before bacteria belonging to the Acinetobacter calcoaceticus-Acinetobacter baumannii complex].

BACKGROUND: To evaluate the bactericidal activity of colistin, imipenem and sulbactam against 24 Acinetobacter calcoaceticus-Acinetobacter baumannii complex isolations. METHODS: Bactericidal activity was estimated by using killing curves method. The concentrations employed were: colistin 4 mg/l, imipenem 8 mg/l and sulbactam 8 and 32 mg/l. RESULTS: Colistin was bactericidal in 24 isolations after 6 hours of incubation. When we used 8 mg/l of imipenem we detected bactericidal activity at the susceptible strains (MIC < or = 4 mg/l). We found bactericidal effect in 15 of 18 strains susceptible to sulbactam when we used 8 mg/l in killing curves after 24 hours of incubation. Using 32 mg/l we detected the same effect in 18 strains with MIC < or = 8 mg/l. CONCLUSIONS: Considering the high incidence of resistance in Acinetobacter spp. to several antibiotics including imipenem, we consider that sulbactam could be an excellent therapeutic alternative because it presents bactericidal activity in susceptible strains.

Acinetobacter↗

PubMed1992

Serum and blister fluid pharmacokinetics and bactericidal activities of ampicillin-sulbactam, cefotetan, cefoxitin, ceftizoxime, and ticarcillin-clavulanate.

Ampicillin-sulbactam, ticarcillin-clavulanate, cefoxitin, cefotetan, and ceftizoxime are promoted for the treatment of mixed aerobic-anaerobic bacterial infections. Their activities have been compared in vitro but not in vivo. In order to assess the in vivo activities of these agents in serum and interstitial fluid, we administered single, intravenous doses of these antimicrobial agents to healthy subjects. Concentrations of the antimicrobial agents in serum and suction-induced blister fluid and bactericidal activity were measured by high-pressure liquid chromatography and the standard methodology of the National Committee for Clinical Laboratory Standards, respectively. The organisms used for bactericidal activity tests were one isolate each of Staphylococcus aureus, Klebsiella pneumoniae, and Bacteroides fragilis. Pharmacokinetic parameters in serum and blister fluid were similar to those derived in other investigations. Of note were the high and prolonged concentrations of ticarcillin and cefotetan in blister fluid, despite high-level serum protein binding. The bactericidal activities in serum and blister fluid reflected the relative in vitro activities and kinetic dispositions of the various antimicrobial agents except for the bactericidal activity of cefotetan, which was substantially lower in blister fluid than serum, despite a blister fluid:serum area under the concentration-time curve ratio of 1.5. Similarly, the activity of ticarcillin-clavulanate in blister fluid was also substantially less than would have been predicted by the blister fluid:serum ratio of the area under the concentration-time curve of 1.1, possibly because of the low concentrations of clavulanate in blister fluid. The rankings of the in vivo bactericidal activities of the five drugs were as follows: for S. aureus, ampicillin-sulbactam > ticarcillin-clavulanate > ceftizoxime > cefoxitin > cefotetan; for K. pneumoniae, ceftizoxime > cefotetan > ampicillin-sulbactam = ticarcillin-clavulanate > cefoxitin; and for B.fragilis, ticarcillin-clavulanate > cefotetan > ceftizoxime > ampicillin-sulbactam = cefoxitin.

Adult↗

PubMed2004

Comparison in a rat thigh abscess model of imipenem, meropenem and cefoperazone-sulbactam against Acinetobacter baumannii strains in terms of bactericidal efficacy and resistance selection.

BACKGROUND: We compared imipenem, meropenem and cefoperazone-sulbactam against hospital originated A. baumannii strains in terms of bactericidal efficacy and selection of resistant mutants during treatment in a rat thigh abscess model. METHODS: A total of 18 strains were inoculated in 54 animals (one strain for three animals). Randomly selected 10 among these 18 strains were inoculated in another 10 rats as the control group. Imipenem, meropenem and cefoperazone-sulbactam were the antibiotics compared. After four days of treatment, Wistar albino rats (200 to 250 g) were sacrificed and the abscess materials were processed for mean colony counts and for the presence of resistant mutants. RESULTS: The mean CFUs per gram (mean +/- (std. deviation) [x10(4)]) of the abscess were: 9,14 (25,24), 2,11 (3,78), 1,20 (1,70) in the imipenem (n = 17), meropenem (n = 18) and cefoperazone-sulbactam (n = 17) groups, respectively. The differences were not significant. On the other hand, no resistant mutant was detected in abscess materials. CONCLUSION: This study indicated; first, cefoperazone-sulbactam is comparable to carbapenems in bactericidal efficacy in this particular abscess model and second, emergence of resistance due to spontaneous mutations is not at least a frequent phenomenon among A. baumannii.

Journal Article↗

PubMed1992

Ampicillin-sulbactam vs clindamycin in head and neck oncologic surgery. The need for gram-negative coverage.

This study was undertaken to assess whether gram-negative antimicrobial coverage is required in patients undergoing head and neck oncologic surgery. Ampicillin sodium-sulbactam sodium and clindamycin phosphate were compared in a prospective, randomized, parallel, double-blind trial of 212 patients undergoing head and neck procedures involving clean-contaminated wounds. Both antibiotics were given up to 1 hour before surgery and continued at 6-hour intervals after surgery for an additional eight doses. Fourteen infections occurred in the ampicillin-sulbactam-treated group (13.3%) and 29 infections in the clindamycin-treated group (27.1%). From patients receiving clindamycin, 29 gram-negative organisms were isolated, compared with six from those patients receiving ampicillin-sulbactam. This finding supports the need for gram-negative coverage in patients undergoing clean-contaminated head and neck oncologic surgery.

Adult↗

PubMed1998

A comparison of procaine penicillin with sulbactam-ampicillin in the treatment of peritonsillar abscesses.

The clinical efficacy of procaine penicillin and sulbactam-ampicillin was compared in patients with peritonsillar abscesses after peroral abscess drainage. Forty-two patients were randomly assigned to receive either procaine penicillin or sulbactam-ampicillin intramuscularly on an outpatient basis. The mean time required for clinical symptoms (throat pain, dysphagia and fever) to resolve was compared. No statistically significant difference was found between the clinical recoveries of patients using either antibiotic (P > 0.05). The authors conclude that intramuscular procaine penicillin can be safely prescribed on an outpatient basis to most patients with peritonsillar abscess after incision and drainage. In contrast, a broader spectrum and more expensive antibiotic, such as sulbactam-ampicillin, should be reserved for non-responders.

Adult↗

PubMedDate not supplied

In vitro activity of sulbactam in combination with various beta-lactam antibiotics.

Forty-three strains (beta-lactamase positive and negative) from the species of Haemophilus influenzae, Neisseria gonorrhoeae, Staphylococcus aureus, Escherichia coli, Serratia marcescens, Enterobacter cloacae, Acinetobacter baumanii, and Pseudomonas aeruginosa were studied for synergy between sulbactam and several beta-lactam antibiotics. Using a checkerboard method, synergy was observed with 10 to 55% of the beta-lactamase negative strains. Synergy was more frequent with the strains producing beta-lactamase. Using the killing curve method, synergy was also observed between sulbactam and beta-lactam antibiotics against some beta-lactamase negative strains. In addition, the regrowth of a resistant subpopulation was prevented by sulbactam.

Anti-Bacterial Agents↗

PubMed2004

Susceptibility of the Acinetobacter calcoaceticus-A. baumannii complex to imipenem, meropenem, sulbactam and colistin.

The Acinetobacter calcoaceticus-Acinetobacter baumannii complex includes some of the most clinically relevant species of the genus Acinetobacter due to their capacity to cause epidemic nosocomial outbreaks as well as their increasing resistance to antibiotics. Susceptibility of Acinetobacter strains varies greatly depending on origin, thus highlighting the importance of local analyses of susceptibility profiles. Two hundred twenty-one strains of the A. calcoaceticus-A. baumannii complex were identified using biochemical tests and were biotyped. Strain susceptibility to imipenem, meropenem, colistin and sulbactam was studied using agar dilution. Eight different biotypes were found, type 1 accounting for 69.2% of the strains. MIC(50) and MIC(90) to imipenem, meropenem, colistin and sulbactam were 4 and 8 mg/l, 16 and 32 mg/l, 0.5 and 1mg/l, and 8 and 16 mg/l, with susceptibility rates of 64.3, 22.6, 98.2 and 73.8%, respectively. Biotype 1 was the most resistant. A statistically significant difference was observed for the mean MIC of the four predominant biotypes to imipenem, meropenem and sulbactam but not to colistin.

Acinetobacter↗

PubMed1997

A prospective, double-blind, randomized, controlled clinical trial of ampicillin-sulbactam for preterm premature rupture of membranes in women receiving antenatal corticosteroid therapy.

OBJECTIVE: Our purpose was to test the efficacy of antibiotic prophylaxis in women with preterm premature rupture of the membranes who receive antenatal corticosteroids. STUDY DESIGN: A total of 112 women received one of three regimens in a double-blind randomized controlled trial: (1) ampicillin-sulbactam for 72 hours followed by amoxicillin-clavulanate, (2) ampicillin for 72 hours followed by amoxicillin, or (3) placebo. RESULTS: A total of 48.6% of neonates in the placebo group either died or had sepsis or respiratory distress syndrome versus 29.3% in the pooled antibiotic group (p < 0.05) and 26.3% in the ampicillin-sulbactam/amoxicillin-clavulanate subgroup (p < 0.05). All three neonatal deaths occurred in the placebo group (p = 0.03 versus pooled antibiotics). Mean birth weight was significantly greater in the pooled antibiotic group (1773 gm, p = 0.04) and in the ampicillin-sulbactam/amoxicillin-clavulanate subgroup (1870 gm, p = 0.02) than in the placebo group (1543 gm). Antibiotic prophylaxis reduced the need for prolonged ventilation (p = 0.05). CONCLUSIONS: Antibiotic prophylaxis in combination with corticosteroids in preterm premature rupture of membranes significantly lowered the total frequency of neonatal mortality, sepsis, and respiratory distress syndrome and significantly increased birth weight compared with corticosteroids alone.

Adrenal Cortex Hormones↗

PubMed2000

An efficient method for the synthesis of sulbactam pivoxil.

Sulbactam pivoxil, a prodrug of the beta-lactamase inhibitor sulbactam, was prepared in high yield by reacting the sodium salt of sulbactam with chloromethyl pivalate in a polar solvent, then diluting the reaction mixture with water and isolating the product by filtration. Dimethyl sulfoxide was found to be the solvent of choice among several aprotic organic solvents.

Enzyme Inhibitors↗

PubMed1985

Sulbactam kinetics and excretion into breast milk in postpartum women.

We gave intravenous infusions of sulbactam, a beta-lactamase inhibitor, in combination with ampicillin or cephalothin to women 2 days after cesarean section delivery. The elimination t1/2 was 1.0 hours, the volume of distribution at steady state was 268 ml/kg, and renal clearance was 295 ml/min. These values are similar to those in normal young men and in surgical patients and suggest that dose regimens of sulbactam will not need adjustment in the postpartum period. Sulbactam concentrations in breast milk averaged 0.5 micrograms/ml, a value similar to that of several beta-lactam antibiotics.

Ampicillin↗

PubMed2003

Comparative in vitro activity of piperacillin, piperacillin-sulbactam and piperacillin-tazobactam against nosocomial pathogens isolated from intensive care patients.

We investigated the antimicrobial activity of piperacillin-tazobactam versus piperacillin-sulbactam against common nosocomial pathogens (n = 565) isolated from intensive care patients. For Gram-positive bacteria, antimicrobial susceptibilities to the two piperacillin-beta-lactamase inhibitor combinations were almost identical. For Gram-negative bacteria, piperacillin-tazobactam exhibited greater activity against Escherichia coli and Proteus vulgaris than piperacillin-sulbactam. Both combinations, however, were equally effective against the other Enterobacteriaceae and Pseudomonas aeruginosa isolates. Piperacillin-sulbactam exhibited better antimicrobial activity against Acinetobacter baumannii. Our findings might prove important for the appropriate choice of antibiotic therapy with beta-lactam-beta-lactamase inhibitor combinations.

Anti-Bacterial Agents↗

PubMed1992

AIDS patients with bacterial lower respiratory tract infections: treatment with ofloxacin versus sulbactam-ampicillin.

In this open-label, randomized, parallel-groups study the Authors compare the parenteral administration of a beta-lactamase inhibitor associated with a semisynthetic penicillin (sulbactam-ampicillin) with the oral administration of a 3rd-generation quinolone (ofloxacin), in 20 HIV-infected subjects suffering from lower respiratory tract (LRT) infections. 12 patients were classified as AIDS, 6 as ARC (AIDS related complex) and 2 as asymptomatic seropositives. The risk of becoming HIV-infected and the work load for the health staff were also evaluated. The clinical and microbiological results indicate that oral ofloxacin is as effective as parenteral sulbactam-ampicillin for the treatment of LRT infections in HIV-positive individuals. In addition, the members of the health staff reported significantly less difficulty in administering ofloxacin in respect to sulbactam-ampicillin.

AIDS-Related Opportunistic Infections↗

PubMed2001

Randomized, double-blind, controlled study of cefoperazone-sulbactam plus cotrimoxazole versus ceftazidime plus cotrimoxazole for the treatment of severe melioidosis.

We conducted a prospective randomized, double-blind, controlled study of cefoperazone-sulbactam (ratio, 1:1; cefoperazone 25 mg/kg/day) plus cotrimoxazole (trimethoprim-sulfamethoxazole [TMP-SMZ] at a ratio of 80:400; TMP, 8 mg/kg/day) versus ceftazidime (100 mg/kg/day) plus cotrimoxazole (TMP, 8 mg/kg/day) for the treatment of severe melioidosis. Of 219 patients enrolled in the study, 102 (47%) had culture-proven melioidosis. These patients were assigned randomly to 2 treatment groups, each with 50 patients (2 patients were excluded). Mortality rates were not significantly different between the 2 groups: 18% in the cefoperazone-sulbactam group versus 14% in the ceftazidime group. The crude difference in the mortality rate was 4%, but when adjusted for type of infection the difference was 0.9% (95% confidence interval, -3.6% to 5.4%; P = .696). The duration of defervescence and the bacteriological response of successfully treated patients were similar in both groups, and both treatment regimens were well tolerated. Cefoperazone-sulbactam plus cotrimoxazole might be used as an alternative to ceftazidime plus cotrimoxazole as treatment for severe melioidosis.

Adult↗

PubMed1997

beta-Lactamase inhibition and in vitro activity of sulbactam and sulbactam/cefoperazone.

beta-Lactamase inhibitors such as sulbactam are beta-lactam compounds that have low antimicrobial activity but are able to inhibit enzymes (beta-lactamases) that destroy beta-lactam antibiotics like penicillins and cephalosporins. The main activity of beta-lactamase inhibitors is directed against plasmid-mediated transferable enzymes and various extended-spectrum enzymes. Sulbactam is also active against some of the fixed chromosomally mediated enzymes produced by gram-negative bacteria and is active against Bacteroides and Acinetobacter species. Cefoperazone, a third-generation cephalosporin, is active against a wide range of gram-positive and gram-negative bacteria, including Enterobacteriaceae and Pseudomonas species. However, transferable beta-lactamases are now produced by numerous gram-negative organisms, mitigating the effectiveness of therapy with this agent. Chromosomally mediated enzymes are less common but can be induced in some strains of Klebsiella, Enterobacter, and Serratia species. The full potential of cefoperazone against Enterobacteriaceae and Pseudomonas species is restored by the addition of sulbactam; this addition extends cefoperazone's spectrum of activity to include Bacteroides and Acinetobacter species.

Anti-Bacterial Agents↗

PubMedDate not supplied

Efficacy of sulbactam plus ampicillin in gynecologic infections.

The efficacy of sulbactam plus ampicillin in the treatment of various gynecologic infections was evaluated in 24 women (median age, 35 years). Ten women had pelvic cellulitis plus vaginal cuff abscess; six, pyeloperitonitis; three, vaginal cuff abscess; three, surgical wound sepsis; one, tubo-ovarian abscess; and one, endometritis. Surgical procedures preceding infection included abdominal hysterectomy, ovarian cyst removal, ectopic pregnancy, correction of cystocele, and uterine dilatation and curettage. Twenty patients received 1 g of sulbactam plus 1 g of ampicillin per dose; four received 0.5 g of sulbactam plus 1 g of ampicillin per dose. The combination was given iv every 6 hr for three to four days and then im every 8 hr for three to five days (mean treatment duration, seven days). Pus cultures yielded Enterobacteriaceae (21 cases), enterococci (two), Bacteroides fragilis (12), other Bacteroides species (five), Peptococcus species (nine), Peptostreptococcus species (seven), and other anaerobes (five). Six infections were purely anaerobic; 18 were mixed. All but two infections were cured by both clinical and bacteriologic criteria, with no adverse reactions. Parenteral sulbactam/ampicillin seems safe and effective in the treatment of gynecologic infections of moderate severity.

Adult↗

PubMedDate not supplied

An open, comparative study of sulbactam plus ampicillin vs. cefotaxime as initial therapy for serious soft tissue and bone and joint infections.

In an open, randomized, comparative study, patients with bone, joint, or soft-tissue infections were treated with sulbactam sodium plus ampicillin (sulbactam/ampicillin, 1 g of sulbactam and 2 g of ampicillin three times a day) or with cefotaxime (2 g three times a day) for two weeks as initial therapy. Thirteen patients were entered into the sulbactam/ampicillin group and nine into the cefotaxime group. Two weeks after the end of therapy, clinical cure or improvement was observed in all 13 patients treated with sulbactam/ampicillin and in seven of nine patients treated with cefotaxime. Staphylococcus aureus was not eliminated from one patient in each group. Recurrence of S. aureus infection occurred in two patients in the cefotaxime group within two weeks after the end of therapy. No adverse effects warranting discontinuation of antibiotic therapy were observed. The combination of sulbactam sodium plus ampicillin was at least equivalent to cefotaxime for the initial treatment of acute serious soft tissue and bone and joint infections.

Acute Disease↗

PubMedDate not supplied

Penetration of sulbactam into cerebrospinal fluid of patients with viral meningitis or without meningitis.

In a study designed to determine the penetration of sulbactam into the central nervous system, a single intramuscular dose of 0.5-1.0 g was given to 19 patients: nine with viral meningitis and 10 with normal cerebrospinal fluid (CSF). Drug levels in CSF were first detectable 2 hr after administration in patients with viral meningitis and 4 hr after administration in patients with normal CSF. The sulbactam levels were low (0-3.7 mg/ml), and no significant differences were found between levels in the two groups of patients. For the achievement of therapeutic concentrations of sulbactam in CSF, doses larger than those administered in this study should be used in conjunction with a beta-lactam antibiotic.

Adult↗