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Proposed changes in interpretive criteria and potency of ampicillin and ampicillin-sulbactam disks for susceptibility tests.

The accuracy of disk susceptibility tests with ampicillin and ampicillin-sulbactam was not improved when the amount of ampicillin was increased from 10 to 20 or 30 micrograms per disk. For testing members of the family Enterobacteriaceae, ampicillin disk tests correlated better with broth microdilution tests when the zone size standards were altered from greater than or equal to 14 greater than or equal to 17 mm for susceptible and from less than or equal to 11 to less than or equal to 13 mm for resistant. The same zone size breakpoints apply to tests with ampicillin-sulbactam disks (10/10 micrograms). When Staphylococcus, Branhamella, and Haemophilus species are tested against ampicillin, interpretive breakpoints are those separating beta-lactamase-producing strains from nonproducing strains. However, when ampicillin-sulbactam is tested, beta-lactamase enzymes are efficiently inhibited by the sulbactam component, and thus zone size standards for ampicillin do not apply: zone size standards for the Enterobacteriaceae can be used for testing the combination against Staphylococcus, Branhamella, and Haemophilus species. For Streptococcus, Enterococcus, and Listeria species, only ampicillin disks need be tested, since ampicillin-sulbactam disks give essentially identical results.

Ampicillin↗

Steady-state pharmacokinetics of cefoperazone and sulbactam in patients with acute appendicitis.

OBJECTIVE: To determine the steady-state pharmacokinetics of intravenously administered cefoperazone and sulbactam when given in combination to patients with acute appendicitis. METHODS: Six patients with normal renal and hepatic function received cefoperazone 2 g with sulbactam 1 g prior to appendectomy and then every 12 hours. Serial blood samples were collected after each patient received at least three doses of cefoperazone/sulbactam. RESULTS: Cefoperazone and sulbactam could be best described by a two-compartment model. Mean +/- SD values for cefoperazone steady-state volume of distribution (Vssd), elimination half-life (t1/2 beta), clearance (Cl), and area under the curve (AUC0-t) were 19.8 +/- 8.0 L, 3.97 +/- 1.06 h, 62.6 +/- 16.3 mL/min, and 556.9 +/- 122.0 mg.h/L, respectively. Sulbactam Vssd, t1/2 beta, Cl, and AUC0-t were 34.7 +/- 13.9 L, 1.39 +/- 0.4 h, 288.6 +/- 68.2 mL/min, and 64.8 +/- 24.5 mg.h/L, respectively. CONCLUSIONS: Compared with data from healthy volunteers, cefoperazone exhibited a decreased Cl and increased Vssd and t1/2 beta in patients with acute appendicitis. An increased Vssd also was observed for sulbactam. The disposition of cefoperazone/sulbactam is altered in this group of patients; however, these changes are not likely to warrant a dosage reduction.

Acute Disease↗

Epidemiology, resistance, and outcomes of Acinetobacter baumannii bacteremia treated with imipenem-cilastatin or ampicillin-sulbactam.

STUDY OBJECTIVE: To evaluate epidemiology, resistance, and treatment outcomes of Acinetobacter baumannii bacteremia treated with imipenem-cilastatin or ampicillin-sulbactam for 72 hours or longer. DESIGN: Retrospective analysis. SETTING: University teaching hospital. PATIENTS: Forty-eight patients with A. baumannii bacteremia. INTERVENTION: Evaluation of susceptibility and clinical data from 48 patients treated with either ampicillin-sulbactam or imipenem-cilastatin from 1987-1999. MEASUREMENTS AND MAIN RESULTS: Comparing ampicillin-sulbactam and imipenem-cilastatin, there were no differences between days of bacteremia (4 vs 2 days, p=0.05), days to resolution of temperature or white blood cell count, success or failure during or at end of treatment, or intensive care unit total or antibiotic-related length of stay (13 vs 10 days, p=0.05). Patients treated with ampicillin-sulbactam had significantly decreased antibiotic treatment costs (1500 dollars vs 500 dollars, p=0.004). CONCLUSION: Ampicillin-sulbactam is at least as effective as imipenem-cilastatin based on clinical response at days 2, 7, and end of treatment and is a cost-effective alternative for treatment of A. baumannii infections.

Acinetobacter Infections↗

[The in vitro effect of a combination of sulbactam with cephalothin and cefazolin on strains of Escherichia coli and Proteus mirabilis which produce beta lactamase].

The effect of the combination of sulbactam, cephalothin, and cephazolin was studied in vitro on 88 strains of E. coli and 11 strains of P. mirabilis producing beta-lactamases. Quantitative susceptibility of the tested strains to cephalothin was examined by the disk dilution method and the effect of the combinations with sulbactam by the micromethod. The production of beta-lactamases was determined by the qualitative test with the chromogenic substrate PODAC. Of the total number of 160 E. coli strains beta-lactamases were established in 53.3% of the strains. Of the 47 P. mirabilis strains 23.4% were found to produce beta-lactamases. The effect of the combinations with sulbactam was assessed as synergistic, additive, indifferent or antagonistic. In the combination of sulbactam in the concentration of 16.0 mg/l with cephalothin and cephazolin a higher rate of synergistic and additive effect was recorded on both strains. In none of the combinations did sulbactam exert an antagonistic effect.

Cefazolin↗

Differences between clavulanic acid and sulbactam in induction and inhibition of cephalosporinases in enterobacteria.

The ability of clavulanic acid and sulbactam to induce and inhibit cephalosporinases was evaluated in 16 clinical isolates of enterobacteria. Using the quantitative induction assay, the checkerboard method and the disc approximation test, clavulanic acid was shown to act as inducer for all species, whereas sulbactam only induced strains of Providencia stuartii. Antagonism was achieved using a combination of clavulanic acid and cefotaxime but a combination of sulbactam and cefotaxime was either synergistic or indifferent. This variation in effect was probably due to the fact that sulbactam, but not clavulanic acid could inhibit cephalosporinases. The data revealed a significant difference between sulbactam and clavulanic acid, which may have relevance to their relative usefulness in combination with beta-lactam antibiotics for the treatment of infections due to enterobacteria that produce inducible cephalosporinase.

Cephalosporinase↗

Interaction of clavulanic acid, sulbactam and cephamycin antibiotics with beta-lactamases.

The inhibitory effects of clavulanic acid, sulbactam and cephamycin antibiotics on chromosomally-mediated or plasmid-mediated beta-lactamases were investigated. The inhibition constants were determined by a non-linear regression analysis. Clavulanic acid and sulbactam had high affinities for the purified plasmid-mediated beta-lactamases such as SHV-1, TEM-1 and PSE-4, and were potent inhibitors as shown by their low Ki values. Except for Bacteroides beta-lactamase, which is sensitive to inhibition by cephamycin antibiotics, clavulanic acid and sulbactam were found not to be as effective against chromosomally-mediated beta-lactamases. The cephamycin antibiotics were better inhibitors of chromosomally-mediated beta-lactamases than those that are plasmid mediated. Except for P99 beta-lactamase, against which sulbactam and clavulanic acid were inactive, the cephamycin antibiotics were less effective inhibitors than sulbactam and clavulanic acid.

Anti-Bacterial Agents↗

Activity of beta-lactamase inhibitor sulbactam plus ampicillin against animal isolates of Pasteurella, Haemophilus, and Staphylococcus.

Antibiotic susceptibilities of Pasteurella sp, Haemophilus pleuropneumoniae, and Staphylococcus aureus isolates were determined. The combination of sodium sulbactam, a beta-lactamase inhibitor, and ampicillin had a synergistic effect against all ampicillin-resistant pathogens, rendering them susceptible to ampicillin. Studies of cell-free beta-lactamase from Pasteurella and Haemophilus isolates confirmed the presence of a constitutive penicillinase. Inhibitory concentrations of sulbactam-ampicillin were bactericidal, as demonstrated by killing curves. Ampicillin-resistant Pasteurella and Haemophilus isolates did not develop resistance to sulbactam-ampicillin when passed as many as 8 times in the presence of sublethal concentrations of sulbactam-ampicillin. The in vitro synergistic activity of sulbactam-penicillin also was seen in an in vivo synergistic response in mice challenge exposed to an ampicillin-resistant P haemolytica.

Ampicillin↗

[In vitro comparison of the beta lactamase-inhibitory action of clavulanic acid and sulbactam in ampicillin-resistant enterobacteria].

Comparative in vitro Studies of the beta-Lactamase Inhibitory Effects of Clavulanic Acid and Sulbactam on Ampicillin-resistant Enterobacteria. Clavulanic acid and sulbactam alone are infective against Pseudomonas and enterococci. Staphylococci and enterobacteriaceae are inhibited by high concentrations not attainable under clinical conditions. Strains of Acinetobacter, especially A. lwoffii are susceptible to clavulanic acid and highly susceptible to sulbactam. The sulbactam-ampicillin combination is superior to clavulanic acid-ampicillin against C. freundii, Enterobacter spp. and M. morganii. The latter combination is superior against Klebsiella spp. and E. coli. Antagonistic effects are more frequent with the clavulanic acid combination (Enterobacter spp. and C. freundii) but are rarely observed with the sulbactam combination (Providencia spp. and P. rettgeri).

Ampicillin↗

Ampicillin-sulbactam versus cefoxitin for prophylaxis in high-risk patients undergoing abdominal surgery.

This double-blind study compared ampicillin-sulbactam 3 g versus cefoxitin 2 g in 136 adult patients at risk for developing an infection after abdominal surgery. Separate randomization schedules were used for colorectal, upper gastrointestinal/biliary, and other abdominal procedures. Study antibiotics were administered within 30 minutes before incision and repeated 6 hours later. Patients having colorectal surgery received a third dose of antibiotic 6 hours after the second. Efficacy evaluations were made on 123 patients, 62 in the ampicillin-sulbactam group and 61 in the cefoxitin group. The overall postoperative infection rates were 12.9% for ampicillin-sulbactam and 9.8% for cefoxitin (p > 0.05); one wound infection occurred in each group. Adverse events were experienced by 13.2% of the ampicillin-sulbactam and 19.1% of the cefoxitin recipients (p > 0.05). Cost-minimization analysis revealed that ampicillin-sulbactam was a cost-effective alternative to cefoxitin for the prevention of infection after abdominal surgery.

Abdomen↗

[Prophylactic use of ampicillin and sulbactam in colonic surgery].

UNLABELLED: The purpose of the work was an evaluation of the effectiveness of ampicillin and sulbactam administered parenterally in the prophylaxis of infections in patients after colonic surgery. The group of patients treated with ampicillin and sulbactam was compared with the control group in which penicillin, gentamicin and metronidazole were given prophylactically. Surgical wound infections were found in the group receiving ampicillin and sulbactam in 20% of cases, and in the control group in 13.3% of patients. This difference was not statistically significant (p > 0.05). In both groups infections of all perineal wounds were observed after abdominoperineal operations. No allergic reactions nor side effects were found in the group treated with ampicillin and sulbactam. CONCLUSION: Prophylactic administration of ampicillin and sulbactam in colonic surgery is similar in its effectiveness to prophylactic administration of penicillin, gentamicin and metronidazole.

Aged↗

[Errors of the agar diffusion method to predict Escherichia coli's susceptibility to ampicillin-sulbactam and amoxicillin-clavulanic acid].

BACKGROUND: To evaluate the in vitro activity of the ampicillin-sulbactam and amoxicillin-clavulanic acid against Escherichia coli isolations resistant to ampicillin and amoxicillin and the efficacy of the disks of ampicillin sulbactam 10/10 microgram and amoxicillin-clavulanic acid 20/10 micrograms to differentiate the susceptible (S) and resistant (R) isolates. METHODS: We evaluated the in vitro susceptibility of 100 consecutive clinical isolates of ampicillin and amoxicillin resistant E. coli by the broth macrodilution method and disk diffusion test against ampicillin-sulbactam and amoxicillin-clavulanic acid. RESULTS: For amoxicillin-clavulanic acid the 64% of the isolates were susceptible, 34% were moderately susceptible and 2% were resistant. In contrast, the in vitro activity of ampicillin-sulbactam was inferior since 13% of the isolates were susceptible, 24% moderately susceptible and 63% were resistant. By using the disk of ampicillin-sulbactam 10/10 microgram we found a 13% of very major errors and a 44% of minor errors when we consider the actual rules of NCCLS (R < or = 11 mm and S > or = 15 mm). The best results were achieved when we took into account zone size < or = 15 mm as R and > or = 20 mm as S; however, the level of errors was high too (25% minor errors). For the disk of amoxicillin-clavulanic acid 20/10 micrograms we found a 31% of minor errors when using the advised break points (R < or = 13 mm and S > or = 18 mm). CONCLUSIONS: We consider that the disk diffusion tests are not applicable to these combinations when E. coli isolates resistant to aminopenicillin are evaluated. We advise not to extrapolate the results of sensibility or resistance from one combination to the other because it presents a different in vitro activity.

Amoxicillin↗

The value of chemoprophylaxis against Enterococcus species in elective cholecystectomy: a randomized study of cefuroxime vs ampicillin-sulbactam.

HYPOTHESIS: Cephalosporins are widely used and considered to be effective as prophylaxis in biliary surgery. Nevertheless, they lack activity against enterococci. We conducted a study to compare the efficacy of ampicillin-sulbactam vs cefuroxime in preventing surgical site infections following elective cholecystectomy. DESIGN: A prospective randomized controlled trial. SETTING: A major tertiary care hospital. PATIENTS: Four hundred eighteen randomized patients (of 549 total), who from July 2002 to August 2004 underwent elective open or laparoscopic cholecystectomy with prospective assessment for development of surgical site infections for 1 month postoperatively. INTERVENTION: A single intravenous dose of 1.5 g of cefuroxime (group A, n = 207) or 3 g of ampicillin-sulbactam (group B, n = 211) was administered during induction of anesthesia. Bile and gallbladder mucosal cultures were taken intraoperatively from all patients. MAIN OUTCOME MEASURE: Number of postoperative surgical site infections. RESULTS: A postoperative surgical site infection was noted in 19 (4.5%) of 418 patients, 18 from group A and 1 from group B (P<.001). In the group that received cefuroxime, 15 (83.3%) of 18 surgical site infections were due to Enterococcus species. Intraoperative bactibilia as well as intraoperative gallbladder rupture were associated with surgical site infections (P<.001). CONCLUSIONS: A single dose of ampicillin-sulbactam favored better compared with cefuroxime for prevention of postoperative surgical site infections due to Enterococcus species after elective cholecystectomy. Ampicillin-sulbactam may be a better agent for antimicrobial prophylaxis in high-risk patients undergoing elective cholecystectomy, especially in a setting where the incidence of enterococcal infections is higher.

Ampicillin↗

Derivative spectroscopy as a nonperturbative tool to detect the state of liposome-entrapped sulbactam.

Sulbactam, a beta-lactam antibiotic, absorbs uv light at 273 nm when in alkaline media, whereas at neutral or acidic pH this peak disappears. Sulbactam-loaded liposomes, prepared by reverse-phase evaporation, were spectroscopically analyzed by the derivative mode measuring the peak-through amplitude between +258 and -285 nm, so that the spectral interference of the sample is eliminated. Taking advantage of this experimental approach, we could study the influence of different parameters on the dissociation state of the drug when entrapped in dipalmitoyl phosphatidylcholine liposomes. In particular, following the time course of sulbactam peak disappearance, we found that: (i) the effectiveness of protonating the sulbactam of the chosen buffers is acetate/acetic acid > succinate/succinic acid > citrate/citric acid; (ii) the rate of signal disappearance is influenced by the externally imposed pH and can be somewhat related to the dissociation state of the organic acids; (iii) as expected, the whole phenomenon is temperature dependent. The observations reported here might be the basis for quantitative permeation studies in synthetic and/or natural membranes using this methodology.

1,2-Dipalmitoylphosphatidylcholine↗

In vitro activity of sulbactam plus ampicillin against hospital isolates of coagulase-negative staphylococci and Acinetobacter species.

The antimicrobial susceptibility of 54 recent clinical isolates of coagulase-negative slime- and non-slime-producing staphylococci and 52 Acinetobacter spp. to sulbactam, ampicillin and the combination of both drugs with a 1:1 ratio was studied by means of an agar dilution test. The coagulase-negative staphylococci showed resistance against sulbactam alone, whereas ampicillin as a single agent was nearly as active as sulbactam plus ampicillin (mode of MIC and MBC 0.03 and 4 mg/l vs. 1 mg/l; geometric mean of MIC and MBC 0.38 and 0.56 vs. 0.26 and 0.38 mg/l, respectively). Among slime-producing or non-slime-producing strains, there was no difference in the susceptibility against ampicillin alone compared to the sulbactam/ampicillin combination, with the exception of the higher MBC (mode: 4 mg/l) for slime-producing strains. Both ampicillin and the sulbactam/ampicillin combination were more active against non-slime-producing than slime-producing strains with modes of MIC and MBC of 0.03 vs. 1 or 4 mg/l. Acinetobacter spp. were susceptible to sulbactam alone (mode of MIC and MBC 1 mg/l; geometric mean of MIC and MBC 1.51 and 2.98, respectively), but resistant to ampicillin. However, the sulbactam/ampicillin combination was highly active against Acinetobacter spp. (mode of MIC and MBC 0.5 and 2 mg/l; geometric mean of MIC and MBC 0.74 and 2.08 mg/l, respectively).

Acinetobacter↗

Comparative in vitro activities of amoxicillin-clavulanate, ampicillin-sulbactam and piperacillin-tazobactam against strains of Escherichia coli and proteus mirabilis harbouring known beta-lactamases.

Strains of Escherichia coli (N = 124) and Proteus mirabilis (N = 29) harboring known beta-lactamases were analyzed as to their susceptibility to ampicillin, amoxicillin, and piperacillin alone and in combination with sulbactam, clavulanate, and tazobactam. With TEM 1-producing E. coli, a correlation between specific beta-lactamase activity and the MIC of piperacillin and ampicillin-sulbactam was observed. These strains also showed significant differences in susceptibilities to the various combinations, suggesting that, at least in strains resistant to one combination, several beta-lactam/beta-lactamase inhibitor combinations should be tested in the laboratory. All combinations tested enhanced the activity of the beta-lactam towards TEM 1-producing E. coli, piperacillin-tazobactam being the most active. The drugs were less active to OXA 1 enzymes; solely with piperacillin-tazobactam 90% of strains were within the therapeutic range of the drug. Sulbactam acted synergistically to chromosomally encoded beta-lactamases, whereas amoxicillin-clavulanate was inactive. Piperacillin and piperacillin-tazobactam inhibited all strains producing chromosomally encoded beta-lactamases at concentrations within the therapeutic range of the drugs. In contrast, TEM 2 of P. mirabilis was not sensitive to ampicillin-sulbactam, but to the other combinations; here again piperacillin-tazobactam was the most active.

Amoxicillin↗

Imipenem or cefoperazone-sulbactam combined with vancomycin for therapy of presumed or proven infection in neutropenic cancer patients.

The purpose of this prospective randomized study was to compare the efficacy and safety of imipenem and cefoperazone-sulbactam combined with vancomycin for the treatment of fever in neutropenic cancer patients. Patients were assigned to either imipenem 500 mg/m2 (500 mg for bone marrow transplant recipients) every 6 h or cefoperazone (2 g)-sulbactam (1 g) every 8 h All patients received vancomycin 1 g every 12 h. A total of 457 febrile or infectious episodes occurring in 407 patients were entered in the study. The response rate was 73% for imipenem plus vancomycin and 74% for cefoperazone-sulbactam plus vancomycin among the 369 episodes that could be evaluated. Response rates were comparable for the two regimens with regard to infecting organism, administration of antimicrobial prophylaxis, and neutrophil count and trend. The frequency of side-effects was significantly higher for imipenem plus vancomycin (11% vs.5%, p = 0.02), due to therapy-associated nausea and vomiting (5.3% vs. 0%, p = 0.0004). The overall frequency of superinfections was similar with both regimens, but Clostridium difficile colitis occurred significantly more often in patients receiving imipenem plus vancomycin (5 vs. 0, p = 0.02). In this study cefoperazone-sulbactam plus vancomycin was an effective alternative to imipenem plus vancomycin for initial therapy of fever in neutropenic patients.

Adolescent↗

Penetration of ampicillin and sulbactam into human epididymis and testis.

Urologic refertilization microsurgery such as vaso-vasostomy or vaso-epididymostomy benefits from perioperative antibiotic prophylaxis. The ability of ampicillin and sulbactam to penetrate sufficiently into mixed epididymis or testis tissue was investigated in nine patients (bodyweights ranged from 58 kg to 92 kg, mean 77.3 kg) undergoing orchiectomy for testicular cancer or advanced prostatic cancer. Each patient received a single infusion of 3 g ampicillin/sulbactam (ratio 2:1) preoperatively for antibiotic prophylaxis. The concentrations of both components were determined in serum and in epididymis/testis tissue samples taken 30 min to 65 min after infusion. Ampicillin was determined by bioassay and sulbactam was determined by gas chromatography/ mass spectrometry. Mean tissue concentrations of ampicillin were 38.5 +/- 15.9 mg/kg. Mean tissue concentrations of sulbactam at the same time were 19.8 +/- 5.2 mg/kg. Comparison of the tissue/serum ratios for both agents showed no significant difference. These values indicate that both compounds achieve high concentrations in the scrotal organs. The concentrations exceed the MIC (minimal inhibitory concentration) values of important bacterial pathogens such as Staphylococcus aureus involved in postoperative wound infections. The combination of ampicillin and sulbactam may be effective for perioperative prophylaxis in reconstructive scrotal urologic surgery.

Adult↗

Penetration of ampicillin and sulbactam into human costal cartilage.

The question of whether ampicillin and sulbactam are able to penetrate sufficiently into costal cartilage tissue was investigated in 21 children undergoing surgery for funnel chest malformations. The concentrations of both compounds were determined in the core and mantle pieces of samples taken 45 min or 120 min after infusion of ampicillin/sulbactam (33.3/16.7 mg/kg bodyweight) preoperatively for antibiotic prophylaxis. Ampicillin was determined by bioassay and sulbactam was determined by gas-chromatography/mass spectrometry. Mean concentrations of ampicillin were 23.3 mg/kg and 10.4 mg/kg at 45 min and at 27.4 mg/kg and 7.8 mg/kg 120 min in the mantle and core piece, respectively. Mean concentrations of sulbactam were at the same time 21.3 mg/kg and 9.7 mg/kg and 17.5 mg/kg and 11.9 mg/kg, respectively. These values indicate that both compounds achieve high concentrations even in bradytrophic tissue such as cartilage. The concentrations exceed the MIC values of important bacterial pathogens involved in postoperative wound infections. Therefore ampicillin protected by sulbactam appears to be a well-suited agent for perioperative prophylaxis in thoracic surgery.

Adolescent↗