Cefaclor concentrations in human serum, gingiva, mandibular bone, and dental follicle following a single oral administration.

1. Cefaclor concentrations in human serum (n = 59), gingiva (n = 46), mandibular bone (n = 39), and dental follicle (n = 42) following a single oral administration of cefaclor (500 mg) were measured by the paper disk method. 2. The peak times of serum, gingiva, mandibular bone, and dental follicle were 1.5, 2, 2, and 1.5 hr, respectively. 3. The mean peak concentrations of serum, gingiva, mandibular bone, and dental follicle were 7.58 micrograms/ml, 3.71, 1.59 and 2.42 micrograms/g, respectively. 4. The concentration ratios of gingiva/serum, mandibular bone/serum, and dental follicle/serum at peak times of the tissues were 0.49, 0.18, and 0.32, respectively. 5. Mean cefaclor concentrations in gingiva, mandibular bone, and dental follicle at peak times exceeded MIC for 90% for clinically isolated strains of alpha-hemolytic Streptococci.     

Ampicillin concentrations in radicular cysts following a single oral administration of bacampicillin

• 1.1. Ampicillin concentrations in cyst wall (wall) and cyst fluid (fluid) of radicular cyst and serum following a single oral administration of bacampicillin (equivalent to 500 mg of ampicillin) were measured by a paper disk method.
• 2.2. The mean peak concentrations of ampicillin in wall, fluid, and serum occurred at identical times, 1.5 hr, and were 2.39 μg/g, 0.77, and 10.24 μg/ml, respectively.
• 3.3. Mean ampicillin concentration ratios of wall/serum, fluid/serum, and fluid/wall at the peak time were 0.23, 0.07, and 0.40, respectively.
• 4.4. Mean ampicillin concentrations in wall and fluid at the peak time exceeded MIC (minimum inhibitory concentration) for 90% (0.5 μg/ml) for clinically isolated strains of α-hemolytic Streptococci.

     

Ampicillin concentrations in human serum, gingiva, the mandibular bone, and dental follicle following a single oral administration

Ampicillin (ABPC) concentrations in human serum, gingiva, the mandibular bone, and dental follicle after a single oral administration of ampicillin (500 mg) were assayed by the agar diffusion (paper disc) method. The peak times of all specimens were identical, being 120 min after administration. The peak concentrations of the respective specimens were 2.01 micrograms/ml, 1.03, 0.34, and 0.72 micrograms/g, respectively. The concentration ratios of gingiva, the mandibular bone, and dental follicle to their corresponding serum at the peak time were 0.51, 0.16, and 0.35, respectively.     

Cephalexin concentrations in human serum, gingiva, and mandibular bone following a single oral administration

1. Cephalexin concentrations in human serum, gingiva, and mandibular bone after a single oral administration of cephalexin (500 mg) were measured by the paper disc method. 2. The peak times of serum, gingiva, and mandibular bone were approximately 90, 120 and 120 min, respectively. 3. The peak concentrations of serum, gingiva, and mandibular bone were 10.58 micrograms/ml, 5.57 micrograms/g and 2.12 micrograms/g, respectively. 4. The concentration ratio of gingiva/serum and mandibular bone/serum peak time of serum were 0.47 and 0.18, respectively. 5. Cephalexin concentrations in gingiva and mandibular bond did not exceed the MIC80s for clinically isolated strains of Staphylococcus aureus spp., alpha-Streptococci and Peptostreptococcus spp.     

Effect of probenecid on the excretion of ampicillin in human bile

1. Ampicillin concentrations were determined in serum and bile after intravenous injection into patients with T-tube bile drainage of 1 gram ampicillin before and during probenecid medication. The concentrations were followed up to fifteen hours after injection.2. Probenecid increased the half-life of ampicillin in serum from 74 minutes to 137 minutes.3. Ampicillin concentrations in bile were higher following probenecid medication and a concentration over 5 mug/ml was obtained for 3 h longer than before probenecid.4. The ampicillin concentrations in bile were approximately the same as those in serum both before and during probenecid medication suggesting passive transport of ampicillin from blood to bile.5. A combined treatment of ampicillin and probenecid might be of clinical value in the therapy of cholangitis and typhoid carriers.     

Adjuvant arthritis-induced changes on ampicillin binding in serum and tissues under the influence of non-steroidal anti-inflammatory drugs in rats.

Adjuvant arthritis, as a model for investigating rheumatoid arthritis (RA), is characterized by reduced plasma albumin levels and interferes with drug binding in the plasma and tissues (liver and bone). Ampicillin interacts with non-steroidal anti-inflammatory drugs (NSAIDs) due to the acidic pk(a). The aim of this study was to investigate in vitro the concentrations of ampicillin in the serum, femur, mandible and liver proteins following the co-administration of ketoprofen, flurbiprofen, ibuprofen, oxyphenbutazone and ASA in adjuvant arthritis versus healthy control rats. Ampicillin binding was found to be reduced in the serum of arthritic rats, and ampicillin binding to serum proteins was also reduced under the influence of NSAIDs in the control animals. Differences in ampicillin binding were observed in the various tissues due to the effect of adjuvant arthritis as well as that due to the co-administration of NSAIDs. In conclusion, this in vitro study may provide a plausible explanation for the ampicillin-NSAIDs interaction and such a finding may be of therapeutic significance in the treatment of painful arthritic disease such as RA.     

Ampicillin in portal and peripheral blood and bile after oral administration of ampicillin and pivampicillin

Summary The concentration of ampicillin in serum and bile has been determined in 10 patients after oral administration of equivalent doses of ampicillin (500 mg) and pivampicillin (700 mg). Ampicillin produced maximum concentrations in bile twice as high as in serum, and, after pivampicillin, peak levels of ampicillin occurred earlier and were approximately four times greater than after ampicillin. In 11 other patients, ampicillin was determined simultaneously in peripheral and portal blood, collected from an umbilical vein catheter, following a dose of pivampicillin or an intravenous injection of ampicillin. The peak concentration of ampicillin after an oral dose was twice as high in portal blood as in peripheral blood. There appears to be passive transfer of ampicillin from blood to bile.     

Concentrations of ampicillin and cefadroxil in human serum and mixed saliva following a single oral administration of talampicillin and cefadroxil, and relationships between serum and mixed saliva concentrations

The concentrations of ampicillin (ABPC) from talampicillin (TAPC) and cefadroxil (CDX) in serum and mixed saliva were assayed by the thin layer disc plate method. Talampicillin and cefadroxil (500 mg) were given by a single oral administration. The relationships between serum and mixed saliva ampicillin and cefadroxil concentrations were evaluated in the paired specimens collected from 10 different persons, respectively. The means of concentration ratios of mixed saliva to serum ampicillin and cefadroxil were 0.006 +/- 0.003 and 0.025 +/- 0.010 (mean +/- SD), respectively. Significant correlation coefficients between mixed saliva and serum concentrations were found for both ampicillin and cefadroxil, which were r = 0.78, P less than 0.001, and r = 0.67, P less than 0.001, respectively.     

In vitro evaluation of teicoplanin and other antimicrobials against streptococci group D bacteria

In vitro activities of teicoplanin were compared with those of ampicillin, imipenem, rifampicin, coumermycin and vancomycin against clinical isolates of Streptococcus faecalis (n = 100) and Streptococcus faecium (n = 30). Against Str. faecalis, ampicillin and imipenem had an MIC90 and MBC90 of 3.9 micrograms/ml. Coumermycin and rifampicin had poor bactericidal activity with MBC90 values of 31.2 and 62.5 micrograms/ml. Teicoplanin was extremely active with an MIC90 of 0.95 microgram/ml and an MBC90 of 1.86 micrograms/ml.     

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

Summary 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.     

The effect of a combination of ampicillin and sulbactam against clinical anaerobic isolates

Effect of a Combination of Ampicillin and Sulbactam on Clinical Isolates of Anaerobic Bacteria. The antimicrobial susceptibility of 182 recent clinical isolates of anaerobic bacteria to ampicillin alone, ampicillin plus 1 mg/l sulbactam, ampicillin plus 5 mg/l sulbactam, and cefoxitin was studied by means of agar dilution tests. The ampicillin-sulbactam combination (Unacid) was most effective against species of the Bacteroides fragilis group, the MIC90 of ampicillin plus 5 mg/l sulbactam for B. fragilis being less than or equal to 1 mg/l, compared to 256 mg/l of ampicillin, 4 mg/l of ampicillin plus 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 or cocci.     

In vitro activity of inexpensive topical alternatives against Candida spp. isolated from the oral cavity of HIV-infected patients

The use of inexpensive topical alternatives, e.g. oil of melaleuca (tea tree oil (TTO)), chlorhexidine (CHX), povidone iodine (PI) and gentian violet (GV), to treat oral candidiasis in human immunodeficiency virus (HIV)-infected patients has been proposed in resource-poor countries. However, pre-clinical studies comparing the antifungal activity of these agents are lacking. This study compared the minimal inhibitory concentrations (MICs) of TTO, GV, PI, CHX and fluconazole (FLZ) against 91 clinical Candida strains using Clinical and Laboratory Standard Institute (CLSI) methodology. Isolates were obtained from the oral cavity of acquired immune deficiency syndrome (AIDS) patients. Among the topical agents examined, GV showed the most potent activity against all Candida isolates tested (MIC range, MIC for 50% of the organisms (MIC(50)) and MIC for 90% of the organisms (MIC(90)) of 0.03-0.25 microg/mL, 0.06 microg/mL and 0.1 2microg/mL, respectively). CHX was 64 times less active than GV (MIC range, MIC(50) and MIC(90) of 0.5-16 microg/mL, 4 microg/mL and 8 microg/mL, respectively). The lowest antifungal activity was seen for PI (MIC(90)=0.25%). Moreover, GV, unlike the other topical agents tested, was fungicidal (minimum fungicidal concentration=1 microg/mL) against Candida albicans isolates (n=83). In addition, GV showed activity against FLZ-resistant C. albicans (n=3). The combination of GV and FLZ was not antagonistic and there was no interaction between the two compounds. GV possesses potent antifungal activity against FLZ-susceptible and -resistant Candida strains and is not antagonistic when used in combination with FLZ. In vivo evaluation is warranted.     

Synthesis and in vitro-anticancer and antimicrobial evaluation of some novel quinoxalines derived from 3-phenylquinoxaline-2(1H)-thione

Two novel series derived from 3-phenylquinoxaline-2(1H)-thione 2 and 2-(hydrazinocarbonylmethylthio)-3-phenylquinoxaline 6 have been synthesized. Eight out of twenty six new compounds were selected at the National Cancer Institute for evaluation of their in vitro-anticancer activity. Among them, compounds 3b, 3c, 4b, and 4c displayed moderate to strong growth inhibition activity against most of the tested sub-panel tumor cell lines with GI(50) 10(-5) to 10(-6 )molar concentrations. Compound 4b exhibited a significant value of percent tumor growth inhibition against breast cancer at concentration < 10(-8) M. Compound 4c showed moderate selectivity towards leukemia cell lines with GI(50) of 1.8 to 3.8 microM (selectivity ratio = 5.7). Preliminary antimicrobial testing revealed that compounds 7a, 7b, 8a, 11a, and 11b were as active as ampicillin against B. subtilis (MIC = 12.5 microg/mL). Compounds 7b and 8a were also nearly as active as ampicillin against E. coli (MIC = 12.5 microg/mL). In addition, compounds 4a, 7b, 10b, and 11a were as active as ampicillin against P. aerugenosa (MIC = 50 microg/mL). However, compounds 7b, 8a, and 10b showed mild activity against C. albicans (MIC = 50 microg/mL). The values of minimum bactericidal concentrations indicated that compounds 4a and 7b were bactericidal against B. subtilis and P. aerugenosa, respectively, while compound 10b was bactericidal against both organisms. However, compound 11a was bactericidal against E. coli, P. aerugenosa, and S. aureus.     

Penetration of levofloxacin into paranasal sinuses mucosa of patients with chronic rhinosinusitis after a single 500 mg oral dose.

Respiratory fluoroquinolones are currently considered by several guidelines among the most effective antimicrobial agents for the treatment of acute bacterial rhinosinusitis. The aim of this study was to assess levofloxacin penetration into paranasal sinuses mucosa of 15 patients with chronic rhinosinusitis 1h (n = 4), 2 h (n = 5) and 3 h (n = 6) after a single 500 mg oral dose. Levofloxacin concentrations in plasma and tissue samples were assessed by means of HPLC. Median of mucosal concentrations were 0.96 mg l(-1) at 1 h, 2.50 mg l(-1) at 2 h, 5.84 mg l(-1) at 3 h. Average paranasal sinuses mucosa-to-plasma ratios raised from 1.46 at 1 h, to 1.81 at 2 h and to 2.56 at 3 h. These data are consistent with 500 mg oral levofloxacin ensuring appropriate therapeutic exposure in sinonasal tissue of patients with chronic rhinosinusitis, the concentrations between 1 and 3 h post-dosing being almost always higher than the MIC90 against the major bacterial pathogens responsible for upper respiratory tract infections.     

Transport of cefotetan into the otorhinolaryngeal tissues

The tissue specimens were taken to evaluate the efficacy of cefotetan (CTT), a new cephamycin antibiotic, for otorhinolaryngological infectious diseases. The concentrations of CTT in palatine tonsils, maxillary sinus mucosa, wall of maxillary sinus cysts, discharge from otitis media and saliva were studied. The serum level determined at 3 hours following intravenous injection of 1 g of the drug was 49.2 micrograms/ml (n = 4). The serum level at 12 hours following intravenous injection of 2 g of the drug was 14.4 micrograms/ml (n = 4). 15-25% of the serum levels of CTT were demonstrated in palatine tonsils, 20.7-35.7% in maxillary sinus mucosa. We detected high levels of CTT in the effusion of acute maxillary sinusitis, 24.0 micrograms/ml (2 g, i.v., 90 min.), 26.3 micrograms/ml (1 g, i.v., 120 min.). On the other hand, we detected only a few per cent of the serum level of CTT in the effusion of chronic maxillary sinusitis.     

Ampicillin concentrations in human serum and periodontal membrane following a single oral administration of bacampicillin

Ampicillin concentrations in human serum and periodontal membrane after a single oral administration of bacampicillin (500 mg) were assayed by the agar diffusion (paper disc) method. The peak times of serum and periodontal membrane were nearly identical, being approx. 90 min after administration. The peak concentrations of serum and periodontal membrane were 12.81 micrograms/ml and 6.97 micrograms/g, respectively. The concentration ratio of periodontal membrane to serum at the peak time was 0.56.     

Virulence and antimicrobial resistance in clinical Enterococcus faecium

The aim of the present study was to determine the occurrence of seven virulence determinants in Enterococcus faecium clinical blood culture isolates over a 6-year period and to investigate possible correlations between virulence and antibiotic resistance. Two hundred and sixty-three isolates were screened for the presence of genes coding for aggregation substance (asa1), cytolysin (cylA), collagen-binding protein (ace), Enterococcusfaecalis endocarditis antigen (efaA(fs)), enterococcal surface protein (esp(fm)), gelatinase (gelE) and hyaluronidase (hyl(fm)) by polymerase chain reaction. The minimum inhibitory concentrations (MICs) of ampicillin, ciprofloxacin, gentamicin, imipenem, linezolid and vancomycin were determined by the agar dilution method and the MIC of daptomycin was determined by Etest. The esp(fm) gene was found in 56% of the isolates, hyl(fm) in 4%, whilst the other virulence genes were detected only sporadically (< or = 1%). The level of antibiotic resistance was 77% to ampicillin, 90% to ciprofloxacin and 83% to imipenem; 5% of the isolates were resistant to vancomycin and 2% were resistant to gentamicin (high-level resistance, MIC > or = 500 mg/L). A significant correlation was found between the presence of esp(fm) and resistance to ampicillin, ciprofloxacin and imipenem (P<0.01). Twelve isolates were esp(fm)-positive and ampicillin-susceptible.     

Investigation of the concentration of cefmenoxime transferred to human serum and tissues in oral region

The concentration transferred to human serum and tissues in oral region after the administration of cefmenoxime (CMX) were investigated. The results were obtained as follows: The mean values of CMX-concentrations in serum at 15, 30, 60, 120 and 180 minutes after the intravenous administration of 20 ml of 5% glucose solution containing 1 g of CMX were 84.1, 52.7, 28.2, 12.7 and 8.81 micrograms/ml, respectively. The half-life times of serum concentration at T1/2 alpha and T1/2 beta were 0.55 and 1.05 hours, respectively. The mean concentrations transferred to gingiva at 15 (1 case), 30, 60 and 120 minutes after the intravenous administration of the same dose of CMX were 49.2, 14.1, 9.93 and 3.48 micrograms/g, respectively. Moreover, the ratios (tissue concentration to serum concentration) were also 67.50, 27.95, 38.46 and 32.28% at each time, respectively. CMX was administered intravenously for postoperative treatments of 13 patients, resulting in good effect from the laboratory data and clinical findings. No side effects were obtained.     

Intrarenal concentration-time profile of ampicillin after administration of bacampicillin to patients before nephrectomy

Nineteen patients with renal cancer who were to undergo nephrectomy received a single oral dose of bacampicillin 800 mg at approximately three (N = 5), six (N = 7), or nine (N = 7) hours before nephrectomy. Serum samples were taken at 30, 60, and 90 minutes after administration and at nephrectomy. Urine was collected immediately before operation. Samples of medulla and cortex tissues were immediately and carefully dissected from a healthy part of the removed kidney and homogenized with a buffer solution. All concentrations were determined by bioassay. Bacampicillin was well absorbed, with a mean +/- SD serum concentration of 16.0 +/- 11.4 mg/L at one hour. The concentrations in renal tissues were higher than the serum levels taken at the same time, and the highest concentrations were found in the urine. the mean ampicillin elimination half-life was approximately the same in the cortex, medulla, and urine, (2.7, 2.3, and 2.4 hr, respectively) but it was shorter in the serum (1.4 hr). Bacampicillin 800 mg produced concentrations in the renal tissues that were higher and more sustained than in the serum and were well above the minimum inhibitory concentrations for common urinary pathogens even ten hours after the dose.     

Ampicillin concentrations in human serum and periodontal membrane following a single oral administration of talampicillin

1. Ampicillin concentrations in human serum and periodontal membrane after a single oral administration of talampicillin (500 mg) were assayed by the agar diffusion (paper disc) method. 2. The peak times of serum and periodontal membrane were identical, being 150 min after administration. 3. The peak concentrations of serum and periodontal membrane were 7.81 micrograms/ml and 4.11 micrograms/g, respectively. 4. The mean ratio of periodontal membrane to serum concentration at the peak time was 0.53.