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At least 19 recordsLinked to original sources
PubMed2000

Modified antibiotics-methylated ampicillin and ethylated ampicillin-inhibit growth of ampicillin-resistant strain of bacteria.

Bacterial resistance to antibiotics is a significant problem in health facilities and results in higher costs for health care and increased fatalities due to infection. The work presented here suggests that antibiotic molecular structure can be altered in a selected manner, which will revive the bacterial growth inhibiting capability. A bacterial strain PKK3535(DH1), which is resistant to the antibiotic ampicillin, was found to be highly growth inhibited by these altered forms of ampicillin when tested in tissue culture. The level of growth inhibition of bacterial strain PKK3535(DHI) was greater than 50%, for both molecular variants of ampicillin that were investigated. The bacteria strain used for testing was a clinical isolate obtained from the University Hospital of the University of Nebraska, Omaha. These two antibiotic variants were methylated ampicillin and ethylated ampicillin. The synthetic procedure for generating these variants is presented as well as the molecular structure. The methylated and ethylated ampicillin were found to be stable at 0 degrees C for many weeks, were somewhat less soluble than normal ampicillin, but dissolved in LB plate media. The resistant bacteria strain was plated onto LB media with altered ampicillin and profound inhibition of bacteria growth was seen within the first 24 hours of incubation. These molecular variants of ampicillin provide evidence of a means to combat the proliferation of resistant bacterial strains. The molecular alteration of antibiotics may provide a suitable means to study and combat the appearance of antibiotic-resistant bacteria.

Ampicillin↗
PubMed1987

The efficacy of sulbactam-ampicillin in the therapy of respiratory disease associated with ampicillin resistant Pasteurella species in housed calves.

Sulbactam-ampicillin is a combination of sulbactam, a beta-lactamase inhibitor, and ampicillin, a broad spectrum beta-lactam antibiotic. The efficacy of sulbactam-ampicillin was evaluated in the treatment of calf respiratory disease associated with ampicillin-sensitive and ampicillin-resistant strains of Pasteurella haemolytica and Pasteurella multocida. Treatment with sulbactam-ampicillin was compared with treatment with ampicillin alone in 123 Friesian calves, between three and five weeks old, exhibiting clinical signs of respiratory disease. Seven of the 59 calves treated with ampicillin died whereas only one death occurred in the 64 calves treated with sulbactam-ampicillin. In the calves which survived, treatment with sulbactam-ampicillin resulted in a significantly better clinical response, as measured by the reduction in severity of clinical signs. The results of bacteriological examinations indicated that there was a marked increase in the proportion of ampicillin-resistant isolates of P haemolytica subsequent to treatment with ampicillin, whereas the proportion of ampicillin-resistant isolates of P. haemolytica recovered from calves treated with sulbactam-ampicillin had declined. The superior efficacy of sulbactam-ampicillin observed in this study is explained by the inhibitory effect of sulbactam on beta-lactamases produced by resistant bacteria, thus rendering them susceptible to the ampicillin.

Ampicillin↗
PubMed2004

Genetic and molecular characterization of beta-lactamase-negative ampicillin-resistant Haemophilus influenzae with unusually high resistance to ampicillin.

Previous studies with beta-lactamase-negative, ampicillin-resistant (BLNAR) Haemophilus influenzae from Japan, France, and North America indicate that mutations in ftsI encoding PBP3 confer ampicillin MICs of 1 to 4 micro g/ml. Several BLNAR strains with ampicillin MICs of 4 to 16 micro g/ml recently isolated from North America were studied. Pulsed-field gel electrophoresis identified 12 unique BLNAR strains; sequencing of their ftsI transpeptidase domains identified 1 group I and 11 group II mutants, as designated previously (K. Ubukata, Y. Shibasaki, K. Yamamoto, N. Chiba, K. Hasegawa, Y. Takeuchi, K. Sunakawa, M. Inoue, and M. Konno, Antimicrob. Agents Chemother. 45:1693-1699, 2001). Geometric mean ampicillin MICs for several clinical isolates were 8 to 10.56 micro g/ml. Replacement of the ftsI gene in H. influenzae Rd with the intact ftsI from several clinical isolates resulted in integrants with typical BLNAR geometric mean ampicillin MICs of 1.7 to 2.2 micro g/ml. Cloning and purification of His-tagged PBP3 from three clinical BLNAR strains showed significantly reduced Bocillin binding compared to that of PBP3 from strain Rd. Based on these data, changes in PBP3 alone could not account for the high ampicillin MICs observed for these BLNAR isolates. In an effort to determine the presence of additional mechanism(s) of ampicillin resistance, sequencing of the transpeptidase regions of pbp1a, -1b, and -2 was performed. While numerous changes were observed compared to the sequences from Rd, no consistent pattern correlating with high-level ampicillin resistance was apparent. Additional analysis of the resistant BLNAR strains revealed frame shift insertions in acrR for all four high-level, ampicillin-resistant isolates. acrR was intact for all eight low-level ampicillin-resistant and four ampicillin-susceptible strains tested. A knockout of acrB made in one clinical isolate (initial mean ampicillin MIC of 10.3 micro g/ml) lowered the ampicillin MIC to 3.67 micro g/ml, typical for BLNAR strains. These studies illustrate that BLNAR strains with high ampicillin MICs exist that have combined resistance mechanisms in PBP3 and in the AcrAB efflux pump.

Ampicillin↗
PubMed1984

A comparison of ampicillin-cefotaxime and ampicillin-chloramphenicol in childhood bacterial meningitis: an experience in 55 patients.

Ampicillin-cefotaxime was tested as initial therapy of presumptive bacterial meningitis in 55 children greater than or equal to 2 months of age at our hospital. During the first year of this ongoing trial, 11 patients, 10 whose CSF yielded ampicillin-resistant Haemophilus influenzae type b (MIC greater than 16 mg/l, beta-lactamase +) and one, indole-negative proteus (MIC 4 mg/l), were begun on ampicillin-cefotaxime and then continued on cefotaxime alone. All did well clinically except one who convulsed briefly but recovered without sequelae. The cefotaxime MICs/MBCs of the beta-lactamase-positive H. influenzae isolates (less than or equal to 0.007 to 0.03/less than or equal to 0.007 to 0.12) and the proteus isolate (0.03/0.12) were significantly lower than chloramphenicol MICs/MBCs (0.25 to 1.0/0.5 to 1.0 and 8/greater than 16). We followed 44 other children with meningitis due to ampicillin-sensitive organisms who were treated with ampicillin or penicillin after 1 or 2 days of ampicillin-cefotaxime. Aetiological agents included ampicillin-sensitive H. influenzae (25), pneumococci (9), meningococci (8), Strept. MG (1) and Listeria monocytogenes (1). 40/44 recovered uneventfully. There were 4 neurological complications: the streptococcal meningitis sustained a brain abscess and the three others were motor incoordination (sensitive haemophilus), hearing loss and subdural effusion (2 pneumococci). There were no deaths. 18/48 children managed initially with ampicillin-chloramphenicol during the same 12-month period one year earlier had significant neurological complications and/or sequelae and there was one death; aetiological agents included sensitive H. influenzae (30), pneumococci (9), ampicillin-resistant haemophilus (5), meningococci (3) and pneumococci plus strept. MG (1). The two groups were comparable except for the number of resistant haemophilus and meningococcal strains and underlying disease more frequent in the ampicillin-cefotaxime group. A significant reduction of neurological morbidity (5/55 or 9.1% vs. 18/48 or 37.5%:P less than 0.001) was therefore associated with the ampicillin-cefotaxime schedule in the initial treatment of proven bacterial meningitis. A prolonged hospitalization (greater than 15 days) was less frequent (P less than 0.01) in the ampicillin-cefotaxime group (3/55 or 5.5% vs. 13/48 or 27.1%). The results of the trial to date are considered to be very promising.

Adolescent↗
PubMed1983

Comparison of in vitro and in vivo ampicillin susceptibility of Escherichia coli pretreated with low concentrations of mecillinam and ampicillin.

The ampicillin susceptibility of Escherichia coli showing morphological changes after pretreatment with low concentrations of mecillinam (spherical forms) or ampicillin (filaments) was compared in vitro and in vivo in short term experiments. Normal non-pretreated bacteria and mecillinam- or ampicillin-pretreated bacteria were cultured in vitro in the presence and absence of ampicillin. The growth curves were mathematically described as quadratic functions of time and these functions provided parameters characterizing the growth kinetics. The mecillinam pretreatment did not affect the growth rate relative to that of normal non-pretreated bacteria. The ampicillin susceptibility of these mecillinam-pretreated forms was, however, strongly increased. The ampicillin pretreatment resulted in an increased initial growth rate of the bacteria which normalized after about 1 1/2 h. The ampicillin susceptibility of these bacteria was unchanged. The growth and the ampicillin susceptibility of these ampicillin- or mecillinam-pretreated bacteria in an intramuscular infection in irradiated granulopenic mice were comparable with those seen in vitro. This outcome in vivo was influenced by the granulocytes when growth and ampicillin susceptibility were determined in non-irradiated mice. The mecillinam-pretreated bacteria were slightly more affected by both granulocytes and ampicillin than normal bacteria were. The ampicillin-pretreated bacteria were affected by both these factors to the same extent as normal bacteria.

Amdinocillin↗
PubMed1996

Treatment of experimental endocarditis due to ampicillin-susceptible or ampicillin-resistant Salmonella enteritidis.

Using two strains of Salmonella enteritidis, one susceptible and one resistant to ampicillin, we studied the efficacies of ampicillin, gentamicin, ampicillin plus gentamicin, ofloxacin, and cefotaxime for the treatment of experimental salmonella endocarditis. Rabbits were treated for 3 days with dosages of antibiotic selected to achieve concentrations in serum equivalent to those obtained in humans during therapy. Aortic salmonella endocarditis seemed to be very difficult to treat, and all antimicrobial regimens failed to achieve the complete sterilization of cardiac vegetations. In vitro studies did not accurately predict the in vivo response to therapy, and no correlations regarding the synergistic activity of the combination of ampicillin plus gentamicin were observed. For the ampicillin-susceptible S. enteritidis isolate, ampicillin and cefotaxime produced the greatest reduction in the number of organisms in vegetations, with no significant differences between them. For the ampicillin-resistant strain, the combination of ampicillin with gentamicin produced a synergistic effect that was not anticipated by the in vitro studies. Both cefotaxime and ofloxacin were effective in reducing the number of microorganisms in the vegetations, although the reduction produced by cefotaxime was less that that produced against the ampicillin-susceptible strain. Monotherapy with gentamicin exhibited only modest activity against the ampicillin-susceptible S. enteritidis strain.

Ampicillin↗
PubMed1988

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↗
PubMed1998

Microbiological assay of ampicillin in serum and aqueous humor of patients given ampicillin-sulbactam injection.

The aim of this study was to determine the bacterial growth inhibitory activities of ampicillin in aqueous humor and serum of patients administered ampicillin-sulbactam combination intramuscularly prior to cataract surgery. 43 patients received a combination of both antibiotics intramuscularly at varying periods (60-140 minutes) prior to surgery. Aqueous humor and venous blood were collected at the beginning of the surgery. For microbiological assay, spores of Bacillus subtilis were incorporated in the agar. The test sample and the standard solutions (calibrators) of ampicillin and ampicillin-sulbactam combination were placed in 3 mm wells in the agar. The diameter zones of growth inhibitory activities of ampicillin of the calibrators and the test samples measured in mm were extrapolated to the standard curve and were recorded as ampicillin activity in micrograms/ml. The results of the assay were placed in 5 groups according to the time intervals between injection and collection of serum and aqueous humor (< or = 70, 75, 80, 90, > 90 minutes). Ampicillin activities in sera and aqueous humor of group 5 (> 90 minutes) were significantly higher than the others (p < 0.001). The ratio of ampicillin activities of sera and aqueous humor in group 5 patients was significantly lower indicating higher concentration of ampicillin activity in aqueous humor during this period. Bacterial growth inhibitory activities of ampicillin-sulbactam combination were adequate in aqueous humor of all patients with highest activity being 90 minutes after intramuscular administration indicating the potential usefulness of this antibiotic combination as chemoprophylaxis prior to cataract surgery.

Adult↗
PubMed1986

In vitro comparison of ampicillin-chloramphenicol and ampicillin-cefotaxime against 284 Haemophilus isolates.

Since November 1982 at the Sainte-Justine Hospital in Montreal, ampicillin and cefotaxime were used in association as initial treatment (greater than or equal to 48 h) for childhood bacterial meningitis. In this report is described the in vitro interaction of the new regimen in comparison with that of the previous ampicillin-chloramphenicol combination against 284 Haemophilus isolates. Among the 156 ampicillin-susceptible, beta-lactamase-negative isolates, synergy was detected in 13 with ampicillin-cefotaxime, and antagonism was detected in only 1; in contrast, synergy was found in only 2 strains with ampicillin-chloramphenicol, and antagonism was found in 15. These differences were statistically significant (P less than 0.01). Such significant differences were not observed among the 128 ampicillin-resistant, beta-lactamase-positive Haemophilus isolates. The synergy of ampicillin-cefotaxime did not contribute to a decrease of the MIC of cefotaxime for 90% of isolates tested, whereas the antagonism of ampicillin-chloramphenicol did not contribute to increase the MIC of ampicillin for 90% of isolates tested.

Ampicillin↗
PubMedDate not supplied

The bactericidal activity of ampicillin, daptomycin, and vancomycin against ampicillin-resistant Enterococcus faecium.

Ampicillin, daptomycin, and vancomycin, alone and in combination with gentamicin, were examined for bactericidal effects on ampicillin-resistant Enterococcus faecium using broth dilution minimum inhibitory concentrations (MICs) and time-kill studies. We tested 12 ampicillin-resistant isolates and demonstrated the following MICs and MBCs, respectively: ampicillin, greater than or equal to 32 micrograms/ml and greater than 256 micrograms/ml; daptomycin, less than or equal to 4 micrograms/ml and less than or equal to 16 micrograms/ml; and vancomycin, less than or equal to 4 micrograms/ml and greater than 64 micrograms/ml. Time-kill studies demonstrated that daptomycin alone had marked activity against the ampicillin-resistant E. faecium and that the addition of gentamicin resulted in synergistic killing. In addition, ampicillin and vancomycin were not bactericidal for the ampicillin-resistant isolates without the addition of gentamicin. The present study supports the consideration of daptomycin alone or in combination with an aminoglycoside as an alternative therapy for ampicillin-resistant enterococci, although additional clinical experience is now necessary.

Ampicillin↗
PubMed1987

In vitro activity of ampicillin plus sulbactam against anaerobes compared to ampicillin and cefoxitin.

The antimicrobial susceptibility of 195 recent clinical isolates of anaerobic bacteria was studied to ampicillin alone, ampicillin + 1 mg/l sulbactam, ampicillin + 5 mg/l sulbactam, and cefoxitin by means of agar dilution tests. The ampicillin-sulbactam combinations were the most effective drugs against species of the Bacteroides fragilis group, the MIC90 of ampicillin + 5 mg/l sulbactam for B. fragilis being less than 1 mg/l, compared to 256 mg/l of ampicillin, 4 mg/l of ampicillin + 1 mg/l sulbactam, and 8 mg/l of cefoxitin. No significant difference between ampicillin alone and in combination with sulbactam was observed against gram-positive anaerobic rods, Peptococcus spp. and Peptostreptococcus spp. with MIC's less than 2 mg/l.

Ampicillin↗
PubMed1982

Comparative plasma ampicillin levels and bioavailability of five parenteral ampicillin formulations in ruminant calves.

Plasma ampicillin concentrations were determined in an eight-ways crossover trial involving six ruminant calves, which were treated intravenously (i.v.) with sodium ampicillin at 15.5 mg/kg and intramuscularly (i.m.) with five different ampicillin trihydrate or ampicillin anhydrate formulations at 7.7 mg/kg. The mean plasma concentration-time curve (Cp) after intravenous ampicillin sodium administration was described biexponentially, as: Cp = 38.8 e -0.0268t + 0.45 e -0.0058t. Intramuscular injection, into the lateral neck, of Ampikel-20 and Polyflex resulted in 100 per cent bioavailabilities within 12 h post injection (p.i.), but the biological half-lives (t1/2) were different, being 2.1 and 3.8 h, respectively. Ampikel-20 produced the highest peak plasma drug concentrations (mean C max :4.8 microgram ampicillin/ml). After intramuscular injection of Penbritin the mean bioavailability for the first 12 h p.i. was 63 per cent, the mean t1/2 was 5.9 h, and the mean Cmax was 1.8 microgram/ml. Treatment with Albipen and Duphacillin resulted in low plasma ampicillin levels, which were maintained for 3 to 6 days p.i., limited bioavailability during the first 12 h p.i., and a mean t1/2 of 22.2 and 11.9 h, respectively. Plasma concentrations of ampicillin from four hours onwards after i.m. and s.c. administration of Ampikel-20 at a dose level of 15.5 mg/kg were similar. The duration of potentially therapeutic plasma ampicillin concentrations after administration of each formulation is presented. Pre-slaughter withdrawal times for diseased calves are suggested for the different formulations studied.

Ampicillin↗
PubMed1975

Serum concentrations of ampicillin and probenecid and ampicillin excretion after repeated oral administration of a pivampicillin-probenecid salt (MK-356).

Twenty male volunteers received oral doses (2100, 1050, and 525 mg) of a pivampicillin-probenecid salt in a 1 to 1 molar ratio (MK-356) at 12 hour intervals. After each dose peak serum concentrations of probenecid were observed 2 hours later than peak concentrations of ampicillin. Following the first dose of MK-356 the apparent elimination rate of ampicillin was dose-dependent and did not follow first order kinetics, as it showed a longer apparent half life after a higher dose. An equal dose of MK-356 administered 12 hours later caused an increase in the peak serum ampicillin level greater than expected from the concentration of ampicillin after the preceding dose. In twelve male volunteers who received at random 525 mg of MK-356 or 350 mg of pivampicillin, each three times daily for 4 days, the areas under the ampicillin concentration curve were the same after the first or last dose of either drug. When 2100 or 1050 mg of MK-356 was taken as an initial dose, 30 to 40 per cent of the ampicillin was recovered from urine in the ensuing 12 hours. The results indicate that when at least 400 mg probenecid was coadministered twice daily with 700 mg pivampicillin (MK-356), the peak serum concentrations of ampicillin were increased and its elimination rate slowed following successive doses.

Administration, Oral↗
PubMed1978

Plasma levels of ampicillin in pregnant women following administration of ampicillin and pivampicillin.

A single dose of ampicillin as been reported to produce lower plasma levels in pregnant than in nonpregnant women. In the present study plasma and urine levels oa ampicillin were studied in pregnant women following administration of multiple oral doses as well as single doses of 0.35 Gm. of pivampicillin and 0.5, 1.0, and 2.0 Gm. of ampicillin. Assays for levels of ampicillin were performed by means of a disc-agar-diffusion method. Multiple doses of ampicillin resulted in plasma levels and recovery in urine similar to those after a single dose. Mean plasma levels were low. A dose of 1.0 Gm. of ampicillin resulted in plasma levels in pregnant women comparable to those reported earlier by us in nonpregnant women following a dose of 0.5 Gm. A dose of 0.35 Gm. of pivampicillin resulted in plasma levels considerably lower than those reported by others in nonpregnant subjects, but plasma levels and recovery in urine were as high as those produced in pregnant women by 0.5 Gm. of ampicillin.

Ampicillin↗