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PubMed1996

Efficacy of ampicillin-sulbactam is not dependent upon maintenance of a critical ratio between components: sulbactam pharmacokinetics in pharmacodynamic interactions.

An in vitro pharmacokinetic model (IVPM) and a mouse model of lethal bacteremia were used to compare the pharmacodynamics of ampicillin-sulbactam when the two components were dosed simultaneously and in sequence against TEM-1-producing Escherichia coli. The challenge isolates included three strains of E. coli producing various levels of beta-lactamase. Human pharmacokinetics of ampicillin-sulbactam (1.5- and 3.0-g intravenous doses) were simulated in each model, and pharmacodynamic interactions were evaluated over one 6-h dosing interval. Against all three strains, the sequential dosing of sulbactam prior to ampicillin did not alter the pharmacodynamics of these combinations from comparison with results obtained with the simultaneous administration of the two components. Similar pharmacodynamics were observed for the two dosing regimens regardless of the ampicillin-sulbactam dose used or whether the bacteria were treated in an immunocompetent mouse or in the absence of immune defenses in the IVPM. When antibacterial activity was lost and regrowth of the inoculum was observed, viable bacterial counts increased in both the simultaneous and sequential regimens at a point when sulbactam levels fell below a critical concentration. These data suggest that the efficacy of ampicillin-sulbactam is not dependent upon the maintenance of a constant 2:1 ratio for the two components. Rather, the efficacy of ampicillin-sulbactam appears to be dependent upon the maintenance of one or both components above a critical concentration. Furthermore, the pharmacokinetics of sulbactam, specifically, how long sulbactam levels remain above a minimum critical concentration, appears to dictate how long antibacterial activity is maintained with the combination.

Ampicillin↗
PubMed1991

In vitro inactivation of aminoglycosides by sulbactam, other beta-lactams, and sulbactam-beta-lactam combinations.

At clinically achievable levels (e.g., 25 micrograms/ml), sulbactam exerted no effect on aminoglycoside concentrations when incubated together in pooled serum at 37 degrees C for up to 24 h. Sulbactam alone and in combination with ampicillin or cefoperazone inactivated tobramycin, gentamicin, netilmicin, and amikacin in vitro when the sulbactam concentration was 200 to 225 micrograms/ml. At 75 micrograms/ml, sulbactam inactivated only tobramycin. Inactivation of tobramycin by high concentrations of sulbactam occurred even at -20 degrees C, but not at -70 degrees C, and was influenced by the serum matrix.

Amikacin↗
PubMed1997

Tazobactam-piperacillin compared with sulbactam-ampicillin, clavulanic acid-ticarcillin, sulbactam-cefoperazone, and piperacillin for activity against beta-lactamase-producing bacteria isolated from patients with complicated urinary tract infections.

The antibacterial activity of tazobactam-piperacillin was compared with that of sulbactam-ampicillin, clavulanic acid-ticarcillin, sulbactam-cefoperazone and piperacillin against beta-lactamase-producing bacteria isolated from patients with complicated urinary tract infections. Tazobactam-piperacillin showed a broad antibacterial spectrum against gram-negative and gram-positive bacteria. The minimum inhibitory concentrations (MIC90) of tazobactam-piperacillin were 6.25 micrograms/ml against Escherichia coli, 1.56 micrograms/ml against Proteus mirabilis, 3.13 micrograms/ml against Proteus vulgaris, 6.25 micrograms/ml against methicillin-susceptible Staphylococcus aureus, and 6.25 micrograms/ml coagulase-negative methicillin-susceptible staphylococci. Against all beta-lactamase-producing bacteria tested the antibacterial activity of tazobactam-piperacillin was at least 4- to 64-fold stronger than that of piperacillin, clavulanic acid-ticarcillin, and sulbactam-ampicillin, and similar to or greater than that of sulbactam-cefoperazone except for E. coli.

Ampicillin↗
PubMed1989

Inactivation of beta-lactamases by sulbactam and enhanced clinical activity due to target-site binding of the combination of sulbactam and ampicillin.

In addition to the beta-lactamase-inactivation activity of sulbactam, a stronger bactericidal activity has been confirmed with sulbactam/ampicillin than with either antibiotic alone. To clarify this latter mechanism, binding affinities of the combination drug were compared with those of ampicillin and sulbactam alone against the PBPs of E. coli, S. aureus, P. vulgaris and H. influenzae. Ampicillin showed the highest binding activity to the PBP fraction essential for septum formation such as PBP3 of E. coli, whereas sulbactam manifested the strongest affinity for the PBP fraction necessary for cell elongation such as PBP1a of E. coli. Sulbactam/ampicillin bound strongly to both PBP fractions. Light microscopy and scanning electronmicroscopy of these bacteria grown in the presence of the antibiotics revealed that more rapid formation of bulge or spheroplast forms of the cells are seen in the presence of small amounts of sulbactam/ampicillin compared to larger amounts of each drug alone. It is concluded that sulbactam/ampicillin, by synergistic inhibition of PBP fractions essential for bacterial cell division, can manifest a stronger bactericidal effect on Gram-positive and Gram-negative bacteria than each drug alone, not only in beta-lactamase-producing strains but also in ampicillin-sensitive strains.

Ampicillin↗
PubMed1990

In vitro activities of ampicillin-sulbactam and cefoperazone-sulbactam against oxacillin-susceptible and oxacillin-resistant staphylococci.

Ampicillin-sulbactam and cefoperazone-sulbactam were tested against staphylococci that were collected from 40 different medical centers throughout the United States. Oxacillin-resistant strains were resistant to both drug combinations, but oxacillin-susceptible strains were uniformly susceptible. The latter included strains with borderline susceptibility to oxacillin and methicillin.

Ampicillin↗
PubMed1991

[Physiological model of sulbactam pharmacokinetics in rats and humans. Distribution of sulbactam in the tissues after intravenous and intramuscular administration].

A 10-compartment physiological model of sulbactam pharmacokinetics is described. The model provides simulation of the pharmacokinetic profiles of the drug observed after its intra-muscular and intravenous administration in rats and humans. The adequate description of the drug distribution in human blood suggested that the model was applicable in designing rational schemes of sulbactam use.

Animals↗
PubMed2001

[Escherichia coli eradication from the blader urine by amoxicillin-sulbactam. Intrinsic activity of the inhibitor].

RATIONALE: At urine concentrations obtained after the oral administration of amoxicillin-sulbactam (500/500 mg) this combination inhibits roughly 90% of Escherichia coli and Proteus mirabilis strains. AIMS: To administer amoxicilin-sulbactam 875/125 mg and to determine: a) minimum inhibitory concentration (MIC) of sulbactam for E. coli and P. mirabilis; b) urine inhibitory titres power (UIT) against amoxicillin-resistant E. coli or P. mirabilis; c) urine concentrations of sulbactam; and to verify whether sulbactam 125 mg as single drug, attains a high enough UIT to support the intrinsic action of the inhibitor; and to compare the activity of amoxicillin-sulbactam and amoxicillin-clavulanate and that of sulbactam and clavulanate. METHODS: Twelve healthy volunteers received a single oral dose of amoxicillin-sulbactam 875/125 mg or amoxicillin-clavulanate 875/125 mg, according to a randomized cross-over design. Urine samples were drawn at: 0 (basal), 2, 4, and 6 hours after dosing. Urine pH, specific gravidity and UIP were assessed. Thirty nine strains isolated from urine samples were used: 30 TEM-1 producing E. coli strains and 3 extended spectrum CTX-M-2 betalactamase-producing E. coli; and 6 P. mirabilis resistant to both combinations. In 6 healthy volunteers, sulbactam 125 mg was administered orally and UIT against E. coli (MIC amoxicillin > 2048 mg/l) was assessed. RESULTS AND DISCUSSION: MIC-90 for amoxicillin plus sulbactam or clavulanate were similar to those for sulbactam or clavulanate alone, without any difference attributable to the chemical composition of the urine. The activity of amoxicillin plus the inhibitors could be due, not only to the inhibition of betalactamase but also to the intrinsic effect of the inhibitor. Both combinations showed an equivalent inhibitory activity. Two-hour UIT remained high for the entire 6-h evaluation period. Sulbactam concentration far exceed sulbactam MIC for the 6h-period, inhibiting urine E. coli. We disagree with the cut-off limit proposed for intermediate values of NCCLS, which, for these antimicrobial are 16/8, a value lower than those obtained in urine samples after the administration of betalactamase inhibitors. This may be an explanation for the beneficial effect of amoxicillin-sulbactam in the recovery of uncomplicated lower urinary tract infections in women when the involved strains were considered resistant by diffusional methods.

Adult↗
PubMed1985

The cefoperazone-sulbactam combination. In vitro qualities including beta-lactamase stability, antimicrobial activity, and interpretive criteria for disk diffusion tests.

Three concentrations of the penicillanic acid sulfone, sulbactam were tested in combination with cefoperazone against 632 recent clinical bacterial isolates. Cefoperazone was effective alone (less than or equal to 16 micrograms/mL) against 95% of Enterobacteriaceae and combined with 4 micrograms/mL sulbactam inhibited 99.5% of strains. This coverage of enteric bacilli was superior to timentin (99.1%), ceftazidime (98.2%), and tobramycin (90.9%). The minimum inhibitory concentrations (MICs) of cefoperazone-susceptible strains also were markedly decreased by sulbactam (overall MIC90s, 8.0 micrograms/mL for cefoperazone and 1.0 microgram/mL for cefoperazone and 4.0 micrograms/mL for sulbactam). Sulbactam also expanded the spectrum of cefoperazone against Acinetobacter species, some rare Pseudomonas species, and Bacteroides fragilis group species. Sulbactam had direct antimicrobial activity against the acinetobacters and Pseudomonas acidovorans, but the increased activity of cefoperazone-sulbactam against some other Pseudomonas species and anaerobes was attributed to beta-lactamase inhibition. The cefoperazone MICs against beta-lactamase producing Staphylococcus species also were lowered to the level of enzyme-deficient strains. Cefoperazone bactericidal activity was improved by 4.0 micrograms/mL sulbactam, and no antagonism was observed. beta-lactamase hydrolysis studies confirmed a slow hydrolysis of cefoperazone only by TEM beta-lactamases and a high-grade resistance to enzyme breakdown by sulbactam. Differential beta-lactamase affinity studies for cefoperazone and sulbactam showed potential efficacy and applications to plasmid-mediated TEM and OXA enzymes and only marginal effective sulbactam inhibition of Pseudomonas and Klebsiella species enzymes. Disk diffusion studies on 556 strains confirmed the applicability of the cefoperazone 75-micrograms disk to testing routine isolates other than enterococci and methicillin-resistant Staphylococcus aureus. The addition of 4.0 micrograms sulbactam/mL in a fixed concentration to dilution test systems and 15 micrograms sulbactam to the 75 micrograms cefoperazone disk were recommended for in vitro tests. Susceptibility and resistant interpretive criteria for the disk and dilution tests can be applied with confidence. Only 0.4% false-susceptibility errors and a 97.5% absolute interpretive agreement were achieved using the 75 micrograms cefoperazone/15 micrograms sulbactam disk.

Anti-Bacterial Agents↗
PubMed1989

Single-dose pharmacokinetics of intravenous ampicillin plus sulbactam in healthy elderly and young adult subjects.

The pharmacokinetics of intravenous ampicillin and sulbactam, a beta-lactamase inhibitor, were evaluated in two different age groups. Twelve healthy elderly subjects (age 65-93 years) and 12 healthy young adult subjects (age 20-35 years) received both a dose of ampicillin 1 g plus sulbactam 0.5 g and a higher dose of ampicillin 2 g plus sulbactam 1 g after a one-week period between doses. A reverse-phase high-pressure liquid chromatography method was used for the quantitation of ampicillin and sulbactam in serum and urine. The pharmacokinetic parameters for both ampicillin and sulbactam were calculated by computer-based two-compartment nonlinear model. After a 30-min infusion, serum concentrations of both drugs declined in a biexponential manner for both doses. Elderly subjects demonstrated significantly lower total clearances (Clt) than young adult subjects of ampicillin 1 g (220.0 +/- 104.2 vs 360.0 +/- 95.8 ml/min/1.73 m2), ampicillin 2 g (72.6 +/- 36.6 vs 306.8 +/- 109.77 ml/min/1.73 m2), sulbactam 0.5 g (122.3 +/- 47.8 vs 263.9 +/- 93.7 ml/min/1.73 m2), and sulbactam 1 g (171.2 +/- 85.8 vs 391.7 +/- 70.8 ml/min/1.73 m2), respectively. Significance was defined as P less than 0.05. Renal clearance was also significantly reduced in the elderly subjects. Area under the curve was found to be significantly increased in the elderly subjects compared to the young subjects for both ampicillin and sulbactam as were the beta elimination half-lives. No significant difference in the apparent volume of distribution, when adjusted for body weight, was found for either sulbactam (P greater than 0.95) or ampicillin (P greater than 0.95) between the two groups. Linear regression analysis revealed that age was significantly correlated with the Clt of ampicillin 1 g (r = 0.85, P less than 0.001), ampicillin 2 g (r = 0.90, P less than 0.001), sulbactam 0.5 g (r = 0.80, P less than 0.001), and sulbactam 1 g (r = 0.93, P less than 0.001). A multivariate analysis showed a slight improvement in correlation when creatinine clearance was added to age and compared with Clt. Urinary recovery of both ampicillin and sulbactam was approximately 60% after 14 h.

Adult↗
PubMed1998

Comparison of concentrations of sulbactam-ampicillin administered by bolus injections or bolus plus continuous infusion in tissues of patients undergoing colorectal surgery.

The concentrations of sulbactam and ampicillin were determined in sera and different abdominal tissues of 16 patients who underwent elective colorectal surgery. Patients were randomly allocated to two groups. At the time of induction of anesthesia, patients in group 1 (eight patients) were given 1,000 mg of sulbactam with 2,000 mg of ampicillin by intravenous bolus injection (3 min). This dose was administered again after 2 h by bolus injection by the same route. Patients in group 2 (eight patients) were given the same initial dose of sulbactam-ampicillin by bolus injection (3 min). Then, a continuous infusion of 1,000 mg of sulbactam with 2,000 mg of ampicillin in normal saline was immediately started and was administered over a 4-h period. Blood samples were collected to determine peak (10 min) and trough (end of surgery) antibiotic levels. Serial blood samples were also collected at predetermined periods (at the time of opening and closing of the abdominal cavity and at the time of surgical anastomosis). Abdominal wall fat, epiploic fat, and colonic wall tissue samples were collected simultaneously. Antibiotic concentrations were determined by high-performance liquid chromatography. Similar levels of the drugs in serum were observed for the two regimens of administration, with trough sulbactam levels of 33 +/- 16 and 37 +/- 22 microg/ml in groups 1 and 2, respectively, and trough ampicillin levels of 72 +/- 55 and 79 +/- 47 microg/ml in groups 1 and 2, respectively. Similar sulbactam concentrations were observed in abdominal tissues whichever regimen of administration was used; in fatty tissues the sulbactam concentrations ranged from 2.7 to 3.8 microg/g for group 1 and from 1.7 to 4.0 microg/g for group 2, and sulbactam concentrations in the colonic wall were 5.6 +/- 7.7 and 6.8 +/- 3.2 microg/g in groups 1 and 2, respectively (not significant). Again, no influence of the regimen of administration was observed on tissue ampicillin concentrations; in fatty tissues ampicillin concentrations ranged from 4.1 to 5.4 microg/g for group 1 and from 3.2 to 5.8 microg/g for group 2, and sulbactam concentrations in the colonic wall were 7.0 +/- 2.8 and 11.0 +/- 4.7 microg/g for groups 1 and 2, respectively (not significant). In most patients, the concentrations of ampicillin-sulbactam were greater than the MIC at which 50% of isolates are inhibited (MIC50) for Bacteroides fragilis in the fatty tissues. In the colonic wall, for most patients the concentrations of ampicillin-sulbactam were greater than the MIC90 for B. fragilis. No influence of the regimen of administration was observed on the ratio of the two components in the tissues investigated and in sera. In conclusion, a second intraoperative bolus injection or a continuous infusion were equally effective in maintaining sulbactam-ampicillin concentrations in abdominal tissues. The first method of administration can be recommended since it is easier to handle.

Ampicillin↗
PubMed1988

Sulbactam: a beta-lactamase inhibitor.

The chemistry, pharmacology, microbiology, pharmacokinetics, clinical efficacy, and adverse effects of sulbactam are reviewed. Sulbactam is a competitive, irreversible beta-lactamase inhibitor. Its binding to penicillin-binding proteins imparts weak intrinsic antibacterial activity. Synergy of sulbactam with beta-lactam antibiotics is most marked in bacterial species in which beta lactamase is a major mechanism of resistance. Sulbactam sodium is available in combination with ampicillin sodium for injection in a 1:2 ratio of sulbactam to ampicillin. Sultamicillin, an oral prodrug that is hydrolyzed to equimolar amounts of ampicillin and sulbactam, is in clinical trials. Ampicillin and sulbactam have similar pharmacokinetic properties. Sulbactam-ampicillin appears to be most useful for the treatment of polymicrobial aerobic or anaerobic infections and uncomplicated gonorrhea. Persistence, relapse, and superinfections have been reported after sulbactam-ampicillin treatment of urinary-tract and respiratory-tract infections. The combination is not effective against pseudomonal infections. Sulbactam-ampicillin is generally well tolerated. By restoring or expanding the activity of older, well-established beta-lactam antibiotics, sulbactam offers a new approach to the management of bacterial infections; the minimal toxicity of sulbactam-ampicillin makes the combination appealing for the treatment of gram-negative nonpseudomonal and anaerobic infections.

Chemical Phenomena↗
PubMed1989

Pharmacokinetics of ampicillin (2.0 grams) and sulbactam (1.0 gram) coadministered to subjects with normal and abnormal renal function and with end-stage renal disease on hemodialysis.

The single-dose pharmacokinetics of intravenously administered ampicillin (2.0 g) and sulbactam (1.0 g) were studied in normal subjects and in patients with various degrees of creatinine clearance (CLCR). Six normal subjects (CLCR, greater than 60 ml/min), six patients with mild renal failure (CLCR, 31 to 60 ml/min), four patients with severe renal failure (CLCR, 7 to 30 ml/min), and four patients requiring maintenance hemodialysis (CLCR, less than 7 ml/min) were studied. The terminal half-lives for ampicillin and sulbactam more than doubled in patients with severe renal failure compared with subjects with normal renal function and mild renal insufficiency. CLCR significantly correlated with ampicillin (r = 0.88) and sulbactam (r = 0.54) total body clearance. Mean steady-state volume of distribution and nonrenal clearance for ampicillin and sulbactam were not affected by renal function. Hemodialysis approximately doubled the ampicillin and sulbactam total body clearance. Mean totals of 34.8 +/- 4.0% of the ampicillin dose and 44.7 +/- 3.2% of the sulbactam dose were removed during a 4-h hemodialysis treatment. A slight rebound in concentrations in serum after hemodialysis was observed for both drugs in all four subjects. In hemodialysis patients, the ampicillin half-life was 17.4 +/- 8.0 h and the sulbactam half-life was 13.4 +/- 7.4 h. The ampicillin and sulbactam half-lives were appreciably altered during the hemodialysis period (means of 2.2 and 2.3 h, respectively). The nearly parallel decrease in total body clearance, with volume of distribution and nonrenal clearance remaining relatively constant, suggests that the same ratio of ampicillin to sulbactam is appropriate regardless of renal function. An adjustment of the ampicillin (2.0 g) and sulbactam (1.0 g) dose to twice daily would be appropriate in patients with a CLCR between 7 and 30 ml/min. Doses should be given every 24 h for those undergoing maintenance hemodialysis. On hemodialysis days, doses should be given after hemodialysis.

Adult↗
PubMed1990

Activity of sulbactam in combination with ceftriaxone in vitro and in experimental endocarditis caused by Escherichia coli producing SHV-2-like beta-lactamase.

We studied the efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ceftriaxone in vitro and in experimental endocarditis due to an Escherichia coli strain producing an extended-spectrum beta-lactamase most similar to SHV-2, a new mechanism of resistance to broad-spectrum cephalosporins among members of the family Enterobacteriaceae. In vitro, ceftriaxone demonstrated an important inoculum effect (MICs were 2 and 256 micrograms/ml with 5 X 10(5) and 5 X 10(7) CFU of inoculum per ml, respectively). Sulbactam inhibited the beta-lactamase degradation of ceftriaxone and enhanced the killing by ceftriaxone with both inocula tested. In vivo, sulbactam (100 mg/kg every 8 h) or ceftriaxone (15 or 30 mg/kg every 24 h) alone were ineffective after a 4-day therapy. The addition of sulbactam to ceftriaxone (15 mg/kg) or to the ceftriaxone (15 mg/kg)-netilmicin (6 mg/kg every 24 h) combination produced a reduction of 2 log10 CFU/g of vegetation greater than that produced by therapy without sulbactam. The sulbactam-ceftriaxone (30 mg/kg) combination produced a reduction of almost 5 log10 CFU/g of vegetation greater than that produced by single-drug therapy (P less than 0.01), sterilized five of eight vegetations (versus none of seven for ceftriaxone [30 mg/kg] alone; P less than 0.05), and was as effective as the ceftriaxone (15 mg/kg)-sulbactam-netilmicin combination. We concluded that (i) SHV-2 production was responsible for ceftriaxone failure in vivo, probably because of the high inoculum present in vegetations; (ii) sulbactam used in a regimen which provided levels in serum constantly above 4 micrograms/ml and a vegetation/serum peak ratio of approximately 1:3 enhanced the activity of a broad-spectrum cephalosporin in a severe experimental infection; and (iii) the highest dose of ceftriaxone in combination with sulbactam was as effective as the lowest dose of ceftriaxone plus sulbactam plus an aminoglycoside.

Animals↗
PubMed2000

Risk factors for recovery of ampicillin-sulbactam-resistant Escherichia coli in hospitalized patients.

Ampicillin-sulbactam resistance in Escherichia coli is an emerging problem. This study determined risk factors for the recovery of ampicillin-sulbactam-resistant E. coli in hospitalized patients. A case-control design was used to compare two groups of case patients with control patients. The first group of case patients consisted of patients from whom nosocomially acquired ampicillin-sulbactam-resistant E. coli strains were isolated, and the second group of case patients consisted of patients from whom ampicillin-sulbactam-susceptible E. coli strains were isolated. Control patients were a random selection among 5% of all patients admitted during the same time period. Risk factors analyzed included antimicrobial drug exposure, comorbid conditions, and demographics. Univariate and multivariate analyses were performed. Ampicillin-sulbactam-resistant E. coli strains were isolated from 175 patients, and ampicillin-sulbactam-susceptible E. coli strains were isolated from 577 patients. Nine hundred thirty-four control patients were selected. Exposure to penicillin antibiotics as a class and to ampicillin and ampicillin-sulbactam individually were the only significant, independent risk factors associated with the isolation of ampicillin-sulbactam-resistant E. coli (odds ratio [OR] = 2.32 [P < 0.001], OR = 3.04 [P = 0.02], and OR = 1.72 [P = 0.04], respectively), but they were not associated with the isolation of ampicillin-sulbactam-susceptible E. coli. Interestingly, exposure to piperacillin-tazobactam tended to protect against the isolation of E. coli strains resistant to ampicillin-sulbactam, but this did not reach statistical significance (OR = 0.13; P = 0.11).

Aged↗
PubMed2005

Pharmacokinetics of an ampicillin-sulbactam combination after intravenous and intramuscular administration to neonatal calves.

The pharmacokinetics of a 2:1 ampicillin-sulbactam combination after intravenous (i.v.) and intramuscular (i.m.) injection at a single dose rate of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam) were studied in 10-day-old neonatal calves (n = 10). The plasma concentration-time data of both antibiotics were best fitted to an open two-compartment model after i.v. administration. After i.m. administration, an open two-compartment model demonstrated first order absorption. The apparent volumes of distribution of ampicillin and sulbactam, calculated by the area method, were 0.20+/-0.01 and 0.18+/-0.01 L/kg, respectively, and the total body clearances were 0.51+/-0.03 and 0.21+/-0.01 L/kg h. The elimination half-lives of ampicillin after i.v. and i.m. administration were 0.99+/-0.03 and 1.01+/-0.02 h, respectively, whereas for sulbactam the half-lives were 2.24+/-0.02 and 3.44+/-0.94 h. The bioavailability after i.m. injection was high and similar for both drugs (70.31+/-0.2% for ampicillin and 68.62+/-4.44% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.47+/-0.02 and 0.72+/-0.01 h, respectively) and peak concentrations were also similar but not proportional to the dose administered (17.88+/-0.91 mg/L of ampicillin and 12.92+/-0.79 mg/L of sulbactam). Both drugs had similar pharmacokinetic behaviour after i.m. administration. Since the plasma concentrations of sulbactam were consistently higher during the elimination phase of their disposition, consideration could be given to formulating the ampicillin-sulbactam combination in a ratio higher than 2:1.

Ampicillin↗
PubMed1998

Efficacy of sulbactam alone and in combination with ampicillin in nosocomial infections caused by multiresistant Acinetobacter baumannii.

From March 1995 to March 1997, sulbactam was prospectively evaluated in patients with non-life-threatening multiresistant Acinetobacter baumannii infections. During this period, 47 patients were treated with sulbactam; of them, five were excluded because they had received < or =48 h of sulbactam therapy. A total of 42 patients, 27 males and 15 females with a mean age of 60+/-15 years, were finally evaluated. Infections were as follows: surgical wound, 19; tracheobronchitis, 12; urinary tract, 7; catheter-related bacteraemia, 2; and pneumonia, 2. Eighteen patients received intravenous sulbactam alone (1 g every 8 h) and 24 patients received intravenous sulbactam/ampicillin (1 g:2 g every 8 h) with no major adverse effects. Of the 42 patients, 39 improved or were cured and showed A. baumannii eradication and one patient had persistence of wound infection after 8 days of sulbactam/ampicillin requiring surgical debridement. Two patients died after 3 days of therapy (one of the deaths was attributable to A. baumannii infection). The in-vitro activity of the sulbactam/ampicillin combination was by virtue of the antimicrobial activity exhibited by sulbactam. Killing curves showed that sulbactam was bacteriostatic; no synergy was observed between ampicillin and sulbactam. Our results indicate that sulbactam may prove effective for non-life-threatening A. baumannii infections. Its role in the treatment of severe infections is unknown. However, the current formulation of sulbactam alone may allow its use at higher doses and provide new potential synergic combinations, particularly for those infections by A. baumannii resistant to imipenem.

Acinetobacter↗
PubMed1994

Randomized comparison of ampicillin-sulbactam to cefoxitin and doxycycline or clindamycin and gentamicin in the treatment of pelvic inflammatory disease or endometritis.

OBJECTIVE: To evaluate the efficacy and safety of ampicillin-sulbactam (3 g every 6 hours) in patients with pelvic inflammatory disease or postpartum endometritis using a randomized, comparative, multicenter study of parallel design. METHODS: Eligible patients with pelvic inflammatory disease were randomized to receive either ampicillin-sulbactam or cefoxitin (2 g every 6 hours) plus doxycycline (100 mg every 12 hours). Those with endometritis were randomized to ampicillin-sulbactam or clindamycin (900 mg every 8 hours) plus gentamicin (1.5 mg/kg every 8 hours). In the ampicillin-sulbactam group, chlamydia-positive patients also received oral doxycycline. RESULTS: For pelvic inflammatory disease, the clinical response rates (cure or improvement) were 85.5% (47 of 55) and 89.6% (43 of 48) in the ampicillin-sulbactam and cefoxitin and doxycycline groups, respectively (chi 2 = 0.10, P = .76). For endometritis, the clinical response rates were 88.7% (141 of 159) and 90.8% (139 of 153) in the ampicillin-sulbactam and clindamycin and gentamicin groups, respectively (chi 2 = 0.15, P = .70). The percentages of patients with pelvic inflammatory disease who had adverse experiences were not significantly different in the cefoxitin and doxycycline group (47% [29 of 62]) than in those receiving ampicillin-sulbactam (33% [22 of 66]) (P = .12). These adverse effects were mostly mild or moderate. In the endometritis subjects, the incidence of adverse experiences in the ampicillin-sulbactam group (11% [20 of 179]) was comparable to that during treatment with clindamycin and gentamicin (12% [22 of 180]). These adverse experiences were also mostly mild to moderate. CONCLUSION: Ampicillin-sulbactam is as effective and well tolerated as combination regimens using cefoxitin plus doxycycline and clindamycin plus-gentamicin for the treatment of pelvic inflammatory disease or endometritis, respectively.

Adult↗