Serum Concentrations Of Ampicillin Research Articles

Dosing Optimization of Ampicillin-Sulbactam Based on Cystatin C in Elderly Patients with Pneumonia.

Ampicillin-sulbactam is a first-line therapy for pneumonia and is mainly excreted by the kidney. It is important to optimize the dose and dosing interval of ampicillin-sulbactam because in patients with decreased renal function and low skeletal muscle mass, such as the elderly, excess drug may burden renal function. In this study, we evaluated indices of renal function and optimized the dose and dosing interval of ampicillin-sulbactam based on pharmacokinetics (PK) and pharmacodynamics theory in elderly patients. The serum concentrations of ampicillin and sulbactam were measured by HPLC, and PK parameters were calculated. Correlations between the clearance of ampicillin or sulbactam and renal function were evaluated, and dosing optimization was calculated based on PK parameters. The PK parameters of ampicillin were CL = 6.5 ± 4.0 L/h, Vd = 19.3 ± 0.2 L, Ke = 0.4 ± 0.2, and t1/2 = 2.7 ± 1.6 h. The most correlated renal function index was estimated glomerular filtration rate (eGFRcys-c) calculated by serum cystatin-c (r = 0.7374, correlation formula; CL of ampicillin = 0.1937 × eGFRcys-c-0.6726). Based on this formula, we calculated the clearance of ampicillin and developed dosing regimens for the elderly. Serum cystatin-c concentration is an ideal index to optimize ampicillin-sulbactam antimicrobial therapy in elderly patients with pneumonia.

Intraperitoneal ampicillin treatment for peritoneal dialysis- related peritonitis with Listeria monocytogenes \u2013 a case report

BackgroundPeritoneal dialysis (PD)-related peritonitis is a rare but serious complication and is associated with increased morbidity and mortality rates. It is most commonly caused by Staphylococcus aureus or Staphylococcus epidermidis, but infection with Listeria monocytogenes may also occur. Recommendations for antibiotic treatment of a Listeria infection are currently based on a small number of case reports and suggest the administration of ampicillin. But unlike vancomycin or gentamicin, for ampicillin the route of application, the dosage, and the duration of treatment have not yet been established. We report a case in which PD-associated peritonitis due to Listeria infection was treated with ampicillin administered intravenously and intraperitoneally, separately and in combination.Case presentationA 72-year-old man with chronic kidney disease stage 5 dialysis (CKDG5D) secondary to hypertension and diabetes was hospitalised in April 2020 because of PD-related peritonitis caused by a Listeria infection. In accordance with the results of resistance tests, the patient was treated with intravenous ampicillin at a dosage of 6 g twice daily. After initial treatment the leukocyte count in the PD effluent had decreased substantially, but it was permanently reduced only with the addition of intraperitoneal ampicillin (4 g daily). Efficient serum concentrations of ampicillin were determined for both routes of administration, intravenous and intraperitoneal.ConclusionThis is the first case report demonstrating that PD-related peritonitis due to Listeria monocytogenes infection can be treated with intraperitoneal ampicillin and monitored by the determination of peripheral serum concentrations of ampicillin.

Infective Endocarditis Caused by <i>Enterococcus faecalis</i> treated with Continuous Infusion of Ampicillin without Adjunctive Aminoglycosides

Aminoglycosides are useful antimicrobial agents for treating infective endocarditis; however, they occasionally cause troublesome side effects, such as nephrotoxicity and ototoxicity. We herein report a case of infective endocarditis caused by Enterococcus faecalis that was treated successfully with continuous infusion of ampicillin without adjunctive aminoglycosides. The serum ampicillin concentrations were higher than the minimal inhibitory concentration for the target strain. Although the use of ampicillin monotherapy is currently avoided because double β-lactam therapy is reportedly more effective, continuous penicillin administration remains an effective therapeutic choice for treating infective endocarditis.

Optimal timing of ampicillin administration to pregnant women for establishing bactericidal levels in the prophylaxis of Group B Streptococcus

The purpose of this study was to determine the time necessary to achieve and maintain bactericidal concentrations of ampicillin in the cord blood. This was a prospective study in which women scheduled for an elective cesarean section were given intravenous ampicillin before the procedure. Cord and simultaneous maternal blood samples were collected at the time of delivery. Serum ampicillin levels were analyzed by high-performance liquid chromatography. The ratio of cord blood to maternal serum ampicillin concentration was found to increase over time in a linear fashion. There was no correlation between maternal body mass index (22.3 to 48.3 kg/m2) and ampicillin cord blood concentrations. All cord serum samples far exceeded minimal bactericidal concentrations reported for Group B Streptococcus (0.25 to 2.0 microg/mL), even at 338 minutes following administration. Bactericidal levels of ampicillin in the cord blood are rapidly achieved within 30 minutes of administration of ampicillin to the mother. The increase in the ratio of cord to maternal serum ampicillin levels is directly related to time, suggesting a decrease in the clearance of ampicillin in the newborns as compared to the mothers. The cord blood ampicillin concentration exceeds the maternal concentration and both continue to be above the minimal bactericidal concentrations at 5.6 hours after administration. No relationship was observed between the maternal body mass index and ratio of cord to maternal serum concentrations of ampicillin.

Multivariate meta-analysis of pharmacokinetic studies of ampicillin trihydrate in cattle

To investigate the feasibility of using multivariate cluster analysis to meta-analyze pharmacokinetic data obtained from studies of pharmacokinetics of ampicillin trihydrate in cattle and identify factors that could account for variability in pharmacokinetic parameters among studies. Data from original studies of the pharmacokinetics of ampicillin trihydrate in cattle in the database of the Food Animal Residue Avoidance Databank. Mean plasma or serum ampicillin concentration versus time data and potential factors that may have affected the pharmacokinetics of ampicillin trihydrate were obtained from each study. Noncompartmental pharmacokinetic analyses were performed, and values of pharmacokinetic parameters were clustered by use of multivariate cluster analysis. Practical importance of the clusters was evaluated by comparing the frequency of factors that may have affected the pharmacokinetics of ampicillin trihydrate among clusters. A single cluster with lower mean values for clearance and volume of distribution of ampicillin trihydrate administered PO, compared with other clusters, was identified. This cluster included studies that used preruminant calves in which feeding was withheld overnight and calves to which probenecid had been administered concurrently. Meta-analysis was successful in detecting a potential subpopulation of cattle for which factors that explained differences in pharmacokinetic parameters could be identified. Accurate estimates of pharmacokinetic parameters are important for the calculation of dosages and extended withdrawal intervals after extralabel drug administration.

Adequate serum concentrations of ampicillin and penicillin are maintained for > 40% of the interdose interval

Adequate serum concentrations of ampicillin and penicillin are maintained for > 40% of the interdose interval

Endometrial concentrations of ampicillin in mares after intrauterine infusion of the drug

SUMMARY Serum concentration of ampicillin, a semisynthetic penicillin, was measured in mares at various time intervals up to 24 hours after intrauterine infusion of 3 g of ampicillin. Blood samples were drawn immediately before infusion and at 1-, 4-, 10- and 24-hour intervals after infusion. At postinfusion hour 24, two endometrial biopsy specimens were obtained to measure endometrial concentrations of ampicillin. Blood was drawn twice as part of the 24-hour postinfusion sample collection, once before removal of the biopsy specimens and again 5 minutes after removal of the biopsy specimens. After drug infusion, more diestrous mares had detectable serum ampicillin concentration than did estrous mares for all samples, except the 24-hour prebiopsy sample. None of the 24-hour prebiopsy serum samples had detectable ampicillin concentration, but ampicillin was detected in the serum of 4 of 5 diestrous mares after endometrial biopsy. Endometrial concentrations of ampicillin were detectable at postinfusion hour 24 in estrous and diestrous mares, but were not different. All 24-hour biopsy specimens had ampicillin concentrations greater than the ampicillin minimal inhibitory concentration.

Concentrations of ampicillin in human serum and mixed saliva following a single oral administration of lenampicillin, and relationship between serum and mixed saliva concentrations.

The concentrations of ampicillin in serum and mixed saliva after a single oral administration of lenampicillin (500 mg) were determined by the paper disc method. The samples of serum and mixed saliva were obtained at 1, 2, 3 and 4 h after administration. The highest concentrations of ampicillin in serum and mixed saliva occurred 1 h after administration of lenampicillin, and were 11.55 and 0.060 micrograms/ml, respectively. A significant correlation coefficient between the concentrations of ampicillin in serum and mixed saliva, r = 0.71, P less than 0.001, was found.

The pharmacokinetics and sputum penetration of ampicillin and amoxycillin following simultaneous iv administration

Five patients with exacerbation of chronic bronchitis received as a single iv injection 500 mg of ampicillin and 500 mg of amoxycillin. Blood and sputum samples were collected at timed intervals following dosing and the concentrations of the two antibiotics present in the samples were determined by HPLC analysis. No statistically significant differences were observed between the serum concentrations of ampicillin and amoxycillin, and the pharmacokinetics of the two drugs were almost identical, with half lives of 93 min (amoxycillin) and 103 min (ampicillin). Sputum amoxycillin concentrations were significantly higher (Student's paired t-test; P less than 0.001) than those of ampicillin, with mean levels two hours after dosing of 2.9 mg/l (range 1.9-4.0) for amoxycillin and 1.4 mg/l (range 0.8-2.4) for ampicillin.

Effects of ampicillin on the elimination of enprofylline in man.

The effect of intravenously administered ampicillin on plasma levels and renal clearance of enprofylline was investigated in seven young and six elderly volunteers. On one occasion, each subject received 2 g of ampicillin intravenously, and serum concentrations of ampicillin were followed for 4 hours. On a separate occasion, a loading infusion of enprofylline was administered over 60 min., aiming at a plasma level of 2 micrograms/ml, and followed by a maintenance infusion. During this an infusion of 2 g of ampicillin was given for 10 min., and subsequently, renal clearance and plasma levels of enprofylline were followed for 4 hours. Plasma enprofylline levels increased significantly in the subjects after ampicillin infusion, but the effects on renal clearance of enprofylline were not statistically significant. The magnitude of the effects on enprofylline plasma levels and renal clearance from high doses of ampicillin do not suggest that interaction with beta-lactam antibiotics will be a serious problem for patients on enprofylline treatment.

Lenampicillin: is well absorbed after oral administration and produces high serum ampicillin concentrations

Lenampicillin: is well absorbed after oral administration and produces high serum ampicillin concentrations

Penicillin tolerant group a streptococci

A penicillin (PCN) tolerant [minimal inhibitory concentration (MIC) ⩽ 0.02, minimal bactericidal concentration (MBC) = 3.10 μg/ml] group A streptococcus (GAS) was recovered from the bone aspirate of a child with osteomyelitis. The penicillin therapy with 200,000 μm/kg · day, and subsequently ampicillin 360 mg/kg · day, resulting in a serum ampicillin concentration of 74 μg/ml, failed to achieve a serum bactericidal effect > 1:2. Ninety-nine additional isolates of GAS obtained from 99 infants and children with pharyngitis were randomly selected for study. Organisms were screened for tolerance by macrobroth dilution determination at 0.05 and 1.0 μg/ml of penicillin. Twenty-two of 100 organisms had MICs = 0.05 μg/ml and MBCs = 1.0 μg/ml; further tests were performed on these organisms. Twenty of the 22 strains (20% of all GAS) grown in Mueller-Hinton broth with 2% sheep blood were tolerant to penicillin at 24 hr, with MICs ⩽ 0.02 and MBCs = 0.39 μg/ml. When retested at 48 hr the MBCs of the 20 tolerant strains had decreased: three strains by twofold, three strains by fourfold, four strains by eight-fold, one strain by 16-fold, and nine strains by 40-fold or greater. Seven strains were not tolerant after 48 hr of incubation. The detection of tolerance was media dependent; only nine strains were tolerant when grown in Todd-Hewitt broth. Tolerance to GAS was more frequent than generally suspected. The phenomenon of tolerance, and potentially delayed killing may alter prophylaxis and therapy of GAS disease and merits further investigation.

Effects of ampicillin plus sulbactam on bowel flora in patients undergoing colorectal surgery.

The influence of a combination of ampicillin and a beta-lactamase inhibitor, sulbactam, on colonic bacterial flora was studied in patients undergoing colorectal surgery. Drug concentrations were determined in serum, intestinal mucosa, and feces. The results of the drug concentrations were correlated with changes in the numbers of aerobic and anaerobic bacterial bowel flora. Ampicillin and sulbactam were given intravenously to 21 patients in 500-mg doses of each drug every 8 h for 2 days. The first dose was given when anesthesia was begun. The concentrations of ampicillin in serum were significantly higher (0.01 greater than P greater than 0.001) than those of sulbactam. In contrast, at all time intervals, the concentrations of sulbactam in intestinal mucosa were significantly higher than those of ampicillin (0.05 greater than P greater than 0.01). The serum half-life of the two drugs was the same at 2.2 h. After one dose of the antibiotics, sulbactam was detectable in the feces of four patients, and ampicillin was detectable in the feces of 11 patients. During the 2 days of ampicillin and sulbactam prophylaxis, no measurable decrease occurred in the anaerobic flora of the bowel; a mean decrease of 3 logs occurred in the anaerobic bowel flora. The results of this study show that ampicillin and sulbactam prophylaxis had a greater effect on the anaerobic bowel flora than on the aerobic bowel flora. In light of the in vitro spectrum of ampicillin and sulbactam activity, it was surprising that bowel aerobic flora was unchanged.

Influence of the cupric ion on the ampicillin concentration in cervical mucus

The copper ion is known to inactivate the penicillin molecule in vitro . The possible fall in ampicillin concentration in cervical mucus, before and after insertion of a copper-IUD, was investigated. There was no significant change in the ampicillin concentration. Furthermore, no correlation was found between the concentrations of ampicillin in serum and cervical mucus.

Body fluid concentrations of ampicillin trihydrate in 6 horses after a single intramuscular dose.

Six adult mares were given a single dose of ampicillin trihydrate (250 mg/ml) intramuscularly at a dosage of 20 mg/kg body weight. Serum, synovial fluid, peritoneal fluid and urine ampicillin concentrations were measured serially over a 48 h period. The mean peak serum ampicillin concentration was 2.49 micrograms/ml at 6 h. Ampicillin was found in synovial fluid and peritoneal fluid, which obtained mean peak ampicillin concentrations of 1.65 micrograms/ml and 1.81 micrograms/ml at 6 h and 4 h respectively. These concentrations declined in parallel with serum concentrations and were still detectable at 48 h. Urine concentration of ampicillin was relatively high, with a mean peak concentration of 1364.9 micrograms/ml at 4 h.

Tissue distribution of ampicillin: assays in muscle tissue and subcutaneous tissue cage fluid from normal and nephrectomized rabbits.

Tissue distribution of ampicillin following a single intravenous injection was studied in normal and functionally nephrectomized rabbits. Serum concentrations of ampicillin were compared with those obtained in subcutaneous tissue cage fluid, muscle (measured by a direct agar diffusion method) and muscle tissue fluid (obtained from implanted cotton threads). Considerable differences were found. Penetration of ampicillin into rabbit muscle was rapid and the elimination half-life was similar to that of serum. Concentrations in tissue cage fluid were low as compared with muscle tissue fluid levels, and penetration and elimination was slower. Results from experiments in functionally nephrectomized rabbits showed that a steady state between serum and muscle seemed to be attained after 15-30 min. These results were used to estimate the degree of protein binding of ampicillin in muscle tissue fluid.

Ampicillin therapy of experimental enterococcal endocarditis.

In rabbits with experimental enterococcal endocarditis, subcutaneously implanted perforated polyethylene chambers were used for ampicillin administration by intra-chamber injection. A total of 21 days of intra-chamber ampicillin therapy sterilized vegetations of 14 out of 14 rabbits with experimental enterococcal endocarditis. In rabbits treated for less than 21 days, the duration of therapy and quantitative vegetation cultures were inversely related. Peak serum minimal bactericidal titers were greater than or equal to 1:8 in 94% of the determinations. Trough serum minimal bactericidal titers were less than or equal to 1:2. The mean trough serum ampicillin concentration (2.6 micrograms/ml) was greater than the minimal bactericidal concentration of ampicillin for the infecting enterococcus and less than the mean trough chamber fluid ampicillin concentration (3.7 micrograms/ml). Relatively prolonged therapy with intrachamber injections seemed to be well tolerated. Combination drug therapy of enterococcal endocarditis may not always be required. The maintenance of serum minimal bactericidal titers greater than or equal to 1:8 throughout the therapy of endocarditis, as is often recommended, may be unnecessary.

Factors affecting the absorption of ampicillin administered intramuscularly in dwarf goats

In nine healthy dwarf goats there were significantly higher serum concentrations of ampicillin after it was injected into the lateral neck muscles than after it was injected into the thigh. During fever, induced with Escherichia coli endotoxin, the rate of absorption of ampicillin from shivering muscles was faster, resulting in significantly higher serum concentrations of the antibiotic than in control non-febrile goats.

Differences in serum ampicillin concentrations among patients under constant-rate infusion.

Differences in serum ampicillin concentrations among patients under constant-rate infusion.

Effects of Probenecid on Blood Levels and Tissue Distribution of Ampicillin in Fowls and Turkeys

The effect of probenecid (a benzoic acid derivative which competitively inhibits active secretion of weak organic acids by the renal tubules) on serum ampicillin concentrations and the distribution of ampicillin in body organs was examined in fowls and turkeys. An aqueous solution of probenecid coadministered intramuscularly, at 200 mg/kg, with sodium ampicillin solution, at 25 mg/kg, resulted in peak serum antibiotic concentration of 16.5 microgram/ml. A similar dose of ampicillin administered alone produced a peak level of 4.6 microgram/ml. Subcutaneous injections of sodium ampicillin at 25 mg/kg with aqueous probenecid at 200 mg/kg resulted in a peak serum ampicillin concentration (12.8 microgram/ml) three times as high as the peak produced by the subcutaneous injection of ampicillin alone at 50 mg/kg (4.2 microgram/ml). The elimination half-life (t 1/2) of the drug (30 min) was increased to 1.5 hr by coadministration of probenecid parenterally, and serum antibiotic levels greater than or equal to 5.0 microgram/ml were maintained during 3 hours. Ampicillin seemed to be poorly absorbed from the gastrointestinal tract of fowls. A single oral bolus administration of ampicillin trihydrate aqueous suspension produced a peak of 0.6 microgram/ml, and coadministrations of aqueous probenecid suspension at 20, 50, and 100 mg/kg respectively produced peaks of 0.9, 1.25, and 1.5 microgram/ml. During 4 and 5 days, when ampicillin was added to the drinking water at rates of 200 and 50 mg/liter, serum ampicillin levels were rather low (peaks of 0.20 and 0.12 microgram/ml, respectively), and although these levels were increased by 50% with the coadministration of probenecid they were considered to be of limited clinical value for treating systemic bacterial infections. Probenecid did not change the distribution of ampicillin in the organs.