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PubMed1993

Ampicillin-sulbactam susceptibility testing criteria.

In vitro studies in five different medical centers documented the susceptibility of 2,440 consecutive isolates of the Enterobacteriaceae against ampicillin-sulbactam disks of different potencies. For determination of MICs, both 2:1 or 1:1 ratios were used as long as the concentrations of sulbactam at the breakpoints remained the same, i.e. MIC < or = 16/8.0 micrograms/ml or < or = 8.0/8.0 micrograms/ml for the susceptible category. Disks containing 10 micrograms of ampicillin and 10 micrograms of sulbactam are still to be preferred with interpretive criteria of > or = 15 mm for susceptible and < or = 11 mm for resistant (MIC > or = 64/32 micrograms/ml or > or = 32/32 micrograms/ml). The reliability of the disk test actually diminished when the amount of sulbactam in the disk was increased.

Ampicillin↗
PubMed1983

Pharmacokinetics of sulbactam and ampicillin following oral administration of sultamicillin with probenecid.

Eight volunteers each received lg of probenecid followed immediately by 1.5 g sultamicillin, both given by the oral route. Plasma concentrations of ampicillin and sulbactam were measured using a differential bioassay method. An ampicillin mean peak plasma concentration of 23.1 mg/l was found typically 1.5 h after dosing; the mean peak plasma concentration of sulbactam (10.0 mg/l) occurred at the same time. The mean plasma half-life of ampicillin was 1.45 h and that of sulbactam 1.3 h. The mean urinary recovery of ampicillin was 65% and that of sulbactam 62%. Five of the volunteers reported minor changes in bowel habits.

Administration, Oral↗
PubMed1991

A rabbit model for bacterially induced preterm pregnancy loss: intervention studies with ampicillin-sulbactam.

We conducted experiments with a previously described rabbit model of Escherichia coli-induced preterm pregnancy loss. Does at 70% gestation were inoculated hysteroscopically with 0.2 ml of Escherichia coli (10(5) colony-forming units per milliliter) or saline solution. Animals were randomly assigned to either receive treatment with ampicillin-sulbactam (begun 1 to 2 hours before inoculation and continued for up to 7 days) or to receive no therapy. Animals were killed after delivery or after 7 days. Saline solution-inoculated animals had no pregnancy loss. Of the Escherichia coli-inoculated animals, those treated with ampicillin-sulbactam had significantly fewer deliveries, fewer positive cultures, and more live fetuses than the untreated animals (p less than or equal to 0.001). Cultures from multiple sites, amniotic fluid prostaglandin levels, and maternal progesterone levels were obtained, and the placenta, uterus, and fetal lung were histologically evaluated. In the second phase of the study, the Escherichia coli-inoculated animals were treated with ampicillin-sulbactam at one of three times: at inoculation or 2 or 4 hours after inoculation. The Escherichia coli-inoculated does treated with ampicillin-sulbactam at or before inoculation had significantly fewer deliveries, fewer positive cultures, and more live fetuses than the Escherichia coli-inoculated does in which treatment was delayed 4 hours (p less than or equal to 0.01).

Ampicillin↗
PubMed1993

Pharmacokinetics of ampicillin and sulbactam in pregnancy.

OBJECTIVE: This study evaluated the effects pregnancy had on pharmacokinetic parameters of ampicillin and sulbactam. STUDY DESIGN: Twenty-two women undergoing cesarean section for obstetric indications were randomly assigned to receive a single intraoperative dose of either 1 gm of ampicillin intravenously or 1 gm of ampicillin plus 0.5 gm of sulbactam intravenously after umbilical cord clamping. Blood was drawn from an indwelling intravenous catheter at 15, 30, 45, 60, 120, 240, and 360 minutes after infusion of the antibiotic for determination of serum ampicillin and/or sulbactam levels. Pharmacokinetic parameters were determined by fitting data (serum concentrations versus time) to a single-compartment model that provided elimination rate constants, beta-intercept (calculated concentration at 0 minutes), area under the time-versus-concentration curve, half-life of the drug, total body clearance, and volume of distribution. After the examination 6 weeks post partum, each subject was given an additional dose of the drug she had received during cesarean section, and a second pharmacokinetic study was performed and compared with the previous results. RESULTS: Pregnancy significantly increased the elimination rate constant, decreased the area under the drug-versus-time curve, shortened the serum half-life, and increased the total body clearance in comparison with these parameters in the nonpregnant state for ampicillin. Sulbactam kinetics were similarly affected, although these changes failed to attain statistical significance. CONCLUSION: Because pregnancy is associated with more rapid elimination of beta-lactam drugs, physicians treating infections in pregnant or newly parturient women should consider using shorter intervals between antibiotic doses when a range of dosage intervals is under consideration.

Ampicillin↗
PubMed1993

A rabbit model for ascending infection in pregnancy: intervention with indomethacin and delayed ampicillin-sulbactam therapy.

OBJECTIVE: In a modified pregnant rabbit model using intracervical inoculation of Escherichia coli we investigated the effects of administration of delayed antibiotics and indomethacin on outcomes. STUDY DESIGN: We inoculated 10(5) colony-forming units of Escherichia coli or saline solution bilaterally in the cervix of New Zealand White rabbits at 70% of gestation and assigned animals to ampicillin-sulbactam therapy beginning at 0, 4, 8, 12, and 16 hours after inoculation with Escherichia coli or to no antibiotic therapy. We alternated indomethacin pretreatment in rabbits receiving no antibiotic therapy and rabbits starting ampicillin-sulbactam 4 hours after inoculation. RESULTS: Compared with saline solution inoculated control animals, those inoculated with Escherichia coli (and given no antibiotic therapy) had significant increases in fetal loss, fever, bleeding at 24 hours, and positive cultures (100%, 92%, 76%, 98% versus 0%, respectively, all p < 0.01). In Escherichia coli-inoculated animals receiving no antibiotic therapy pretreatment with indomethacin significantly decreased bleeding and delivery within first 24 hours compared with those not treated with indomethacin (p < 0.05) but did not significantly improve fetal survival. Ampicillin-sulbactam treatment stated at 0, 4, 8, and 12 hours after inoculation resulted in improved fetal survival compared with the untreated group (100%, 56%, 50%, 50% versus 0%, respectively, all p < 0.05). Treatment initiated at 16 hours resulted in outcomes similar to Escherichia coli-inoculated animals receiving no antibiotic therapy. CONCLUSION: Intracervical Escherichia coli inoculation produced infection in the uterus and uniform pregnancy loss. Pretreatment with indomethacin did not result in improved fetal survival. Ampicillin-sulbactam therapy, initiated as long as 12 hours after Escherichia coli inoculation, resulted in significant improvement in fetal survival compared with antibiotic therapy. We believe this model mimics ascending infection in pregnancy more closely than do previous animal models.

Ampicillin↗
PubMed1996

Meconium-stained amniotic fluid-associated infectious morbidity: a randomized, double-blind trial of ampicillin-sulbactam prophylaxis.

OBJECTIVE: To evaluate the efficacy of intrapartum prophylactic administration of ampicillin-sulbactam in reducing intraamniotic infection and postpartum endometritis in patients with meconium-stained amniotic fluid (AF). METHODS: Patients with intrapartum meconium-stained AF were randomized to receive either ampicillin-sulbactam or normal saline (placebo) intravenously at the time of diagnosis of meconium and every 6 hours until delivery. The outcomes of the two groups were compared with respect to intra-amniotic infection and postpartum endometritis. RESULTS: During the study period, 332 patients with meconium-stained AF were approached for participation, and 120 patients met inclusion criteria and were enrolled. Patient demographics, labor, and delivery characteristics were similar. Ampicillin-sulbactam reduced the incidence of intra-amniotic infection from 23.3 to 6.7%, (P = .02; relative risk [RR] 0.48, 95% confidence interval [CI] 0.22-0.98). The incidence of postpartum endometritis was also reduced, but the difference was statistically nonsignificant (8.3 versus 16.7%, P = .16; RR 0.64, 95% CI 0.30-1.33). CONCLUSION: Prophylactic intravenous ampicillin-sulbactam significantly reduces intra-amniotic infection in patients with meconium-stained AF.

Adult↗
PubMed1994

First and second derivative spectrophotometric determination of cefoperazone and sulbactam in injections.

A simple, spectrophotometric assay to measure the concentrations of cefoperazone and sulbactam in injectable formulations is described. Since zero-order spectra are subject to interference, derivative spectrophotometry was used to enhance the spectral details. A linear relationship between derivative amplitudes and the concentrations of the compounds was found. Beer's law is obeyed up to 75 and 80 micrograms ml-1 of cefoperazone in the first and second derivative modes, respectively, and up to 75 micrograms ml-1 of sulbactam in the second derivative mode. Detection limits were 0.64 and 0.88 microgram ml-1, respectively for cefoperazone in the first and second derivative modes and 0.30 micrograms ml-1 for sulbactam in the second derivative mode. The method is rapid, simple, does not require a separation step and has successfully been applied to the assay of commercial injections containing cefoperazone and sulbactam.

Anti-Infective Agents, Urinary↗
PubMedDate not supplied

Antimicrobial susceptibility of clinical isolates of Haemophilus influenzae to ampicillin-sulbactam.

A total of 1092 clinical isolates of Haemophilus influenzae (306 type b; 786 non-type-b), from five medical centers were obtained during 1987 and 1988. Disk diffusion antimicrobial susceptibilities were obtained for all isolates, and broth microdilution susceptibilities were obtained for 502 isolates. Beta-lactamase was produced by 34.3% of type-b and 22.1% of non-type-b isolates, with some geographic variations. Using disk diffusion antimicrobial susceptibility testing, all isolates were susceptible to ampicillin-sulbactam, ceftriaxone, cefuroxime, and rifampin; two isolates were resistant to chloramphenicol. Whether tested using a fixed ratio of ampicillin to sulbactam of 2:1 or a fixed concentration of sulbactam, the ampicillin-sulbactam combination demonstrated good activity against clinical isolates of H. influenzae. Only 8 of the 1092 isolates did not produce beta-lactamase but demonstrated MICs of greater than or equal to 2 micrograms/ml for ampicillin.

Ampicillin↗
PubMed2005

In vitro synergy test of meropenem and sulbactam against clinical isolates of Acinetobacter baumannii.

Meropenem and imipenem are often the drugs of choice for the treatment of infections due to multidrug-resistant Acinetobacter baumannii. The present study aimed at evaluating the interaction between meropenem and sulbactam through microdilution and checkerboard methods against 48 clinical isolates of A. baumannii collected from Brazilian hospitals. All the isolates presented elevated minimum inhibitory concentration (>or=2 microg/mL) to either meropenem or sulbactam. The checkerboard method with the combination of meropenem and sulbactam demonstrated 29.2% (14/48) synergism, 47.9% (23/48) partial synergism, 10.5% (5/48) additive, 6.2% (3/48) indifference, and 6.2% (3/48) antagonism (SigmaFIC(min)=0.09 and SigmaFIC(max)=8). Thus, combinations of meropenem and sulbactam may show synergism or partial synergism for most A. baumannii isolates. Further studies may help identify treatment options for patients with infections caused by these organisms, particularly with this combination, where both drugs have time-dependent activities and might be suitable for therapy optimization studies.

Acinetobacter baumannii↗
PubMed2006

In vitro activity of cefepime combined with sulbactam against clinical isolates of carbapenem-resistant Acinetobacter spp.

The aim of this study was to assess the in vitro activity of cefepime combined with sulbactam against carbapenem-resistant clinical isolates of Acinetobacter spp. The checkerboard method was used to determine whether combinations act synergistically against these strains. Twenty-three Acinetobacter baumannii and one Acinetobacter junii found to be carbapenem resistant were included in the study. The susceptibility results for cefepime and sulbactam were interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922 were used as quality control strains. The combination of cefepime and sulbactam demonstrated the following interactions: 33.3% (8/24) synergism; 58.3% (14/24) partial synergism; 4.2% (1/24) additive; 4.2% (1/24) indifference; and no antagonism (minimum and maximum fractional inhibitory concentration index 0.25 and 1.5, respectively). According to our in vitro study results, combinations of cefepime with sulbactam have moderate synergistic activity against some carbapenem-resistant strains of Acinetobacter spp., which could be beneficial for the treatment of infections due to multidrug-resistant strains of Acinetobacter spp.

Acinetobacter↗
PubMed1997

Inhibition of biliary endoprostheses occlusion by ampicillin-sulbactam in an in vitro model.

An important first step in stent occlusion is the formation of a bacterial biofilm. This is followed by deposition of granules similar to that found in brown pigment stones. Previous in vitro models for studying occlusion have used synthetic biles without bilirubin or pooled human bile, which is limited in supply. Our aim was to develop a new in vitro model of stent occlusion with porcine gallbladder bile and then, with the model, assess whether ampicillin-sulbactam can prevent biofilm formation and thus occlusion. Sterile porcine gallbladder bile was contaminated with Escherichia coli then divided into eight reservoirs, four of which then received ampicillin-sulbactam. The bile was then circulated through 10F polyethylene stents. Bile was changed weekly for 8 weeks. In the stents that were untreated, biofilm and sludge were seen in all four, whereas the four ampicillin-sulbactam-treated stents had no biofilm when viewed by electron microscopy. Furthermore, the levels of calcium, cholesterol, and bilirubin in the reservoirs decreased significantly in the untreated bile as compared with the treated bile (p < 0.05). In this in vitro model, the losses of calcium, cholesterol, and bilirubin are likely caused by deposition of granules into the biofilm matrix. Ampicillin-sulbactam can prevent biofilm formation if used continuously.

Ampicillin↗
PubMed1998

UV-spectrophotometric determination of ampicillin sodium and sulbactam sodium in two-component mixtures.

A simple spectrophotometric method is used for the resolution of the binary mixtures of ampicillin sodium and sulbactam sodium. In aqueous solution, zero-order spectra are subject to interference, so first-derivative spectrophotometry was used to enhance the spectral details allowing the determination of ampicillin sodium from the signal at the zero-crossing point for sulbactam sodium at 268 nm. In 0.1 N sodium hydroxide, sulbactam sodium was determined from the absorbance at 260 nm with negligible contribution from ampicillin sodium. Also, sulbactam sodium was determined without interference using first- and second-derivative spectra in 0.1 N sodium hydroxide at 276 nm (peak-height) and 262-284 nm (peak-to-peak), respectively. The method is rapid, simple, does not require a separation step and allows the determination of each drug without interference from the other. The proposed method has been applied successfully to the assay of these drugs in mixtures and in commercial injections.

Ampicillin↗
PubMed2001

The in vitro activity of sulbactam combined with third generation cephalosporins against third generation cephalosporin-resistant bacteria.

The in vitro activity of the beta-lactamase inhibitor sulbactam combined with cefuroxime, cefotaxime or ceftazidime in the ratio of 1:1 was studied against ceftazidime- or cefuroxime-resistant Gram-negative rods and Staphylococcus aureus. Sulbactam enhanced the antibacterial activities of cefuroxime, cefotaxime and ceftazidime against Gram-negative rods. The MIC(90) of ceftazidime against Escherichia coli, Enterobacter cloacae, Citrobacter freundii, Acinetobacter spp. and Pseudomonas aeruginosa was reduced 4-fold and that of cefotaxime against E. coli, E. cloacae, C. freundii and Acinetobacter spp. reduced by 2-4-fold. However, sulbactam did not enhance the activities of cefuroxime, cefotaxime or ceftazidime against S. aureus, enterococci and Stenotrophomonas maltophilia. With the combination of sulbactam and ceftazidime at the ratio of 1:1, 38.4% of E. coli, 45.3% of E. cloacae, 66.6% of C. freundii and 60% of Acinetobacter spp. initially resistant to ceftazidime became susceptible.

Cephalosporin Resistance↗
PubMed1990

Orally effective acid prodrugs of the beta-lactamase inhibitor sulbactam.

Sulbactam (1) is a beta-lactamase inhibitor with limited oral bioavailability. Lipophilic double-ester prodrug sulbactam pivoxil (2) significantly improves the oral absorption of sulbactam, as does the mutual prodrug double ester sultamicillin (3). We have found that double-ester prodrugs of sulbactam terminating in a carboxyl group (8) also were effective oral-delivery vehicles in rats. Carboxyl-terminated double esters have several potential advantages over their nonionizable lipophilic counterparts, including water solubility, crystallinity, choice of salts for dosage forms, and formation of innocuous byproducts on hydrolysis.

Animals↗
PubMed1993

Effect of sulbactam on infections caused by imipenem-resistant Acinetobacter calcoaceticus biotype anitratus.

A recent outbreak of multiresistant strains of Acinetobacter calcoaceticus biotype anitratus was observed mostly, but not exclusively, in the surgical intensive care unit in our hospital. Disk diffusion and microdilution susceptibility studies demonstrated resistance to imipenem, all aminoglycosides, and all individual beta-lactam antibiotics. Only ampicillin plus sulbactam, cefoperazone plus sulbactam, and polymyxin produced zone sizes and MICs in the susceptible ranges. Determination of MICs and MBCs demonstrated that sulbactam was the antimicrobial agent responsible for the killing of these organisms. Nine of 10 patients who were infected with imipenem-resistant Acinetobacter strains and received ampicillin plus sulbactam for > 3 days improved clinically, and in many cases organisms were eradicated from the site of isolation.

Acinetobacter Infections↗
PubMed1997

Evaluation of the resistance induction in enteric flora in children caused by oral ampicillin plus sulbactam.

To evaluate the effect on bacterial resistance of a beta-lactamase inhibitor, resistance patterns of predominant bacteria in enteric flora were evaluated before and after a 7-day course of oral ampicillin (100 mg/kg/days, qid, in 16 patients) and ampicillin-sulbactam (50 mg/kg/day of ampicillin, bd, in 32 patients) therapy. Ampicillin and ampicillin-sulbactam MICs for Escherichia coli, the predominant bacteria in all cases, and resistance rates of E. coli species to both antibiotics were 51.20 +/- 13.80 mg/L, 87.5% and 4.84 +/- 2.11 mg/L, 21% before the treatment respectively. Post-treatment MICs and resistance rates were 106.51 +/- 14.05 mg/L, 100% and 15.89 +/- 5.76 mg/L, 37.5% respectively, indicating a significant increase in MICs of both antibiotics (P < 0.05), being more prominent in the case of ampicillin-sulbactam (about four-fold). We concluded that oral ampicillin-sulbactam could also decrease the susceptibility of the enteric flora to ampicillin.

Ampicillin↗
PubMed2004

Post-antibiotic and post-beta-lactamase inhibitor effects of ceftazidime plus sulbactam on extended-spectrum beta-lactamase-producing Gram-negative bacteria.

OBJECTIVES: To measure the in vitro post-antibiotic effect (PAE) and post-beta-lactamase inhibitor effect (PLIE) of a ceftazidime-sulbactam combination on bacteria producing extended-spectrum beta-lactamases (ESBLs). METHODS: PAE and PLIE were studied for ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae. Two ATCC beta-lactamase-negative strains of E. coli and K. pneumoniae were used as controls. The MICs of a ceftazidime-sulbactam combination were determined with a fixed concentration of sulbactam (8 mg/L). The organisms were exposed to the antibiotics at twice the MIC for 2 h before removal of the antibiotics by filtration of the culture. Bacteria on the filter were resuspended in drug-free medium to determine the PAE and in medium containing ceftazidime, at the same concentration as originally present, to determine the PLIE. RESULTS: The PAE of ceftazidime was similar for bacteria producing the same ESBL except for E. coli producing CTX-M-1. PLIE values varied according to the type of beta-lactamase but similar results were observed for the strains producing the same ESBLs. PLIEs were longer than PAEs and were longer when the MICs of ceftazidime were lower. CONCLUSIONS: To the best of our knowledge, we describe here for the first time an in vitro PLIE for a ceftazidime-sulbactam combination on different bacteria producing different ESBLs. These findings indicate that suicide inhibitors may be used in combination with third-generation cephalosporins.

Anti-Bacterial Agents↗
PubMed2006

Prevention of rifampicin resistance in Acinetobacter baumannii in an experimental pneumonia murine model, using rifampicin associated with imipenem or sulbactam.

OBJECTIVES: To examine the development of rifampicin resistance in multidrug-resistant Acinetobacter baumannii exposed to rifampicin and the prevention of the appearance of rifampicin-resistant mutants when rifampicin is used in association with imipenem or sulbactam. METHODS: A clinical strain of multidrug-resistant A. baumannii was used to examine the frequency of resistance to rifampicin in vivo, in a pneumonia model in immunocompetent C57BL/6 mice. The in vitro and in vivo prevention of the development of resistance to rifampicin was analysed using rifampicin alone or in association with imipenem or sulbactam, in time-kill studies and in the experimental murine pneumonia, respectively. RESULTS: Rifampicin-resistant mutants were found at 48 and 72 h, both in vitro and in vivo, when rifampicin was used alone, with the MIC increasing from 4 to > or =128 mg/L. The in vivo frequency of rifampicin-resistant mutants was 3 x 10(-6). On the contrary, no resistant mutants appeared after 72 h, in vitro or in vivo, when rifampicin was employed in association with imipenem or sulbactam. After six daily passages in rifampicin-free agar plates the resistant mutants maintained the high resistance to rifampicin (> or =128 mg/L). CONCLUSIONS: These results suggest that rifampicin must not be used alone in the treatment of infections caused by multidrug-resistant A. baumannii. In these cases, rifampicin may be used in combination with imipenem or sulbactam, which prevent the development of resistance to rifampicin.

Acinetobacter Infections↗