BACKGROUND: Aminoglycosides are useful for the treatment of aerobic gram-negative infections, and this is despite the narrow therapeutic index and the potential nephrotoxicity and ototoxicity. Once daily dosing of aminoglycosides has recently been suggested as an alternative method to multiple daily dosing. We compared the two dosing regimens of aminoglycosides for the development of nephrotoxicity. METHODS: This study was conducted as part of an ongoing quality improvement program. For the administration of aminoglycosides in adult patients with suspected or documented gram-negative infection, multiple daily dosing was used until April 2005 and thereafter once daily dosing was recommended. RESULTS: A total of 85 patients who received aminoglycoside for more than 3 days from March to August 2005 were available for analysis (40 in the once daily dosing group and 45 in the multiple daily dosing group). The mean duration of administration was 7.7 (range: 3-19) days in the once daily dosing group and 8.0 (range: 3-31) days in the multiple daily dosing group (p=0.83). Aminoglycoside-associated nephrotoxicity was observed in a patient in the once daily dosing group (2.5% vs 0%, respectively, p=0.48). CONCLUSIONS: No significant difference in the development of nephrotoxicity was found between the two dosing regimens for aminoglycosides, but this finding had low statistical power. This may be due to underdosing of aminoglycosides in the multiple daily dosing group.
Acute Kidney Injury ; Adult ; Aminoglycosides* ; Drug Administration Schedule ; Humans ; Quality Improvement

PURPOSE: Transrectal ultrasonography-guided prostate biopsy (TRUS-Bx) is an essential procedure for diagnosing prostate cancer. The American Urological Association (AUA) Guideline recommends fluoroquinolone alone for 1 day during TRUS-Bx. However, this recommendation may not be appropriate in regions where the prevalence of quinolone-resistant Escherichia coli is high. We investigated the real practice of antibiotic prophylaxis for TRUS-Bx in Korea. MATERIALS AND METHODS: A total of 77 hospitals performing TRUS-Bx were identified and an e-mail was sent to the Urology Department of those hospitals. The questions in the e-mail included the choice of antibiotics before and after the procedure and the duration of antibiotic therapy after TRUS-Bx. RESULTS: A total of 54 hospitals (70.0%) responded to the e-mail. Before TRUS-Bx, all hospitals administered intravenous antibiotic prophylaxis. The percentage of hospitals that used quinolone, cephalosporin, and aminoglycoside alone was 48.1%, 20.4%, and 9.3%, respectively. The percentage of hospitals that used two or more antibiotics was 22.2%. After biopsy, all 54 hospitals prescribed oral antibiotics. The percentage of hospitals that prescribed quinolone alone, cephalosporin alone, or a combination of two or more antibiotics was 77.8%, 20.4%, and 1.8%, respectively. The duration of antibiotic use was more than 3 days in most hospitals (79.6%). Only four hospitals (7.4%) followed the AUA recommendation of a 1-day regimen. CONCLUSIONS: The AUA recommendation was not followed by most hospitals in Korea. This clinical behavior might reflect the high quinolone resistance rate in Korea, and further studies on the most efficient prophylactic antibiotics after TRUS-Bx in Korea are warranted.
Aminoglycosides/*administration & dosage ; Anti-Bacterial Agents/*administration & dosage ; Antibiotic Prophylaxis/*methods ; Biopsy/adverse effects ; Cephalosporins/*administration & dosage ; Cross-Sectional Studies ; Drug Resistance, Bacterial ; Escherichia coli Infections/*prevention & control ; Humans ; Male ; Prostate/pathology ; Prostatic Neoplasms/pathology ; Quinolones/*administration & dosage ; Republic of Korea

PURPOSE: Transrectal ultrasonography-guided prostate biopsy (TRUS-Bx) is an essential procedure for diagnosing prostate cancer. The American Urological Association (AUA) Guideline recommends fluoroquinolone alone for 1 day during TRUS-Bx. However, this recommendation may not be appropriate in regions where the prevalence of quinolone-resistant Escherichia coli is high. We investigated the real practice of antibiotic prophylaxis for TRUS-Bx in Korea. MATERIALS AND METHODS: A total of 77 hospitals performing TRUS-Bx were identified and an e-mail was sent to the Urology Department of those hospitals. The questions in the e-mail included the choice of antibiotics before and after the procedure and the duration of antibiotic therapy after TRUS-Bx. RESULTS: A total of 54 hospitals (70.0%) responded to the e-mail. Before TRUS-Bx, all hospitals administered intravenous antibiotic prophylaxis. The percentage of hospitals that used quinolone, cephalosporin, and aminoglycoside alone was 48.1%, 20.4%, and 9.3%, respectively. The percentage of hospitals that used two or more antibiotics was 22.2%. After biopsy, all 54 hospitals prescribed oral antibiotics. The percentage of hospitals that prescribed quinolone alone, cephalosporin alone, or a combination of two or more antibiotics was 77.8%, 20.4%, and 1.8%, respectively. The duration of antibiotic use was more than 3 days in most hospitals (79.6%). Only four hospitals (7.4%) followed the AUA recommendation of a 1-day regimen. CONCLUSIONS: The AUA recommendation was not followed by most hospitals in Korea. This clinical behavior might reflect the high quinolone resistance rate in Korea, and further studies on the most efficient prophylactic antibiotics after TRUS-Bx in Korea are warranted.
Aminoglycosides/*administration & dosage ; Anti-Bacterial Agents/*administration & dosage ; Antibiotic Prophylaxis/*methods ; Biopsy/adverse effects ; Cephalosporins/*administration & dosage ; Cross-Sectional Studies ; Drug Resistance, Bacterial ; Escherichia coli Infections/*prevention & control ; Humans ; Male ; Prostate/pathology ; Prostatic Neoplasms/pathology ; Quinolones/*administration & dosage ; Republic of Korea

This study was undertaken to evaluate the in vitro activities of arbekacin-based combination regimens against vancomycin hetero-intermediate Staphylococcus aureus (hetero-VISA). Combinations of arbekacin with vancomycin, rifampin, ampicillin-sulbactam, teicoplanin, or quinipristin-dalfopristin against seven hetero-VISA strains and two methicillin-resistant S. aureus strains were evaluated by the time-kill assay. The combinations of arbekacin with vancomycin, teicoplanin, or ampicillinsulbactam showed the synergistic interaction against hetero-VISA strains. Data suggest that these arbekacin-based combination regimens may be useful candidates for treatment options of hetero-VISA infections.
Virginiamycin/administration & dosage ; Vancomycin/*administration & dosage ; Teicoplanin/administration & dosage ; Sulbactam/administration & dosage ; Staphylococcus aureus/*drug effects/isolation & purification ; Staphylococcal Infections/drug therapy/microbiology ; Microbial Sensitivity Tests ; Methicillin Resistance ; Humans ; Drug Synergism ; Drug Resistance, Bacterial ; Dibekacin/administration & dosage/*analogs & derivatives ; Anti-Bacterial Agents/*administration & dosage ; Ampicillin/administration & dosage ; Aminoglycosides/*administration & dosage

Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of myeloid precursors arrested in their maturation, creating a diverse disease entity with a wide range of responses to historically standard treatment approaches. While significant progress has been made in characterizing and individualizing the disease at diagnosis to optimally inform those affected, progress in treatment to reduce relapse and induce remission has been limited thus far. In addition to a brief summary of the factors that shape prognostication at diagnosis, this review attempts to expand on the current therapies under investigation that have shown promise in treating AML, including hypomethylating agents, gemtuzumab ozogamicin, FLT3 tyrosine kinase inhibitors, antisense oligonucleotides, and other novel therapies, including aurora kinases, mTOR and PI3 kinase inhibitors, PIM kinase inhibitors, HDAC inhibitors, and IDH targeted therapies. With these, and undoubtedly many others in the future, it is the hope that by combining more accurate prognostication with more effective therapies, patients will begin to have a different, and more complete, outlook on their disease that allows for safer and more successful treatment strategies.
Aminoglycosides ; administration & dosage ; Antibodies, Monoclonal, Humanized ; administration & dosage ; Elafin ; genetics ; Histone Deacetylase Inhibitors ; therapeutic use ; Humans ; Isocitrate Dehydrogenase ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; pathology ; Proto-Oncogene Proteins c-pim-1 ; metabolism ; TOR Serine-Threonine Kinases ; genetics

This study is to investigate the inhibitory effect of lidamycin (LDM) and its combination with methotrexate (MTX) on lung metastasis of fibrosarcoma by bioluminescence imaging in athymic mice. A stable luciferase transfected HT-1080 cell line was constructed and the capability to establish experimental lung metastasis in athymic mice was confirmed. The optical imaging system was applied to evaluate the formation of lung metastasis in vivo. In addition, metastatic nodules were counted for the evaluation of inhibition rates. As shown, the fluorescent intensity of luciferase-transfected HT-1080 cells was colinear with the cell population and the minimal detected cell population was 100 cells/well. Optical imaging showed that the fluorescent intensity of treated group was apparently lower than that of the control. The inhibition rates of lung metastasis by LDM alone at 0.025 mg x kg(-1) and 0.05 mg x kg(-1) were 53.9% and 75.9%, respectively, while that of MTX alone at 0.5 mg x kg(-1) was 70.2%. The combination of LDM at 0.025 mg x kg(-1) and MTX at 0.5 mg x kg(-1) showed an inhibition rate of 88.7%. The coefficient of drug interaction (CDI) was 0.82. The results herein demonstrated that LDM alone had strong anti-metastasis effect on human fibrosarcoma HT-1080 and the inhibition efficacy is strengthened when combined with MTX.
Aminoglycosides ; administration & dosage ; Animals ; Antibiotics, Antineoplastic ; administration & dosage ; Antimetabolites, Antineoplastic ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cell Line, Tumor ; Drug Synergism ; Enediynes ; administration & dosage ; Female ; Fibrosarcoma ; pathology ; Humans ; Luminescent Measurements ; Lung ; pathology ; Lung Neoplasms ; drug therapy ; pathology ; secondary ; Methotrexate ; administration & dosage ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Random Allocation ; Transfection ; Xenograft Model Antitumor Assays

Antibiotics are widely used in the treatment of premature low birth-weight babies, either as blind therapy before infection is confirmed or, more specifically against a pathogen of known antibiotic susceptibility. The requirements of an antibiotic for use in the newborn are different from those in older patients and in almost every respect there are differences in the pharmacology and pharmacokinetics of antibiotics in the very young. A wide range of bacteria are responsible for infection in the new born and the distribution of these organisms will vary not only from country to country, but also from hospital to hospital. Antibiotics in current use are less effective against bacteria infecting the newborn than they once were and the introduction of new antibiotics, notably the third generation cephalosporins, provides an opportunity to reassess current antibiotic practices. This paper outlines the general considerations for chemotherapy in small babies and attempts to identify those areas where a review of current antibiotic practice is required. It is essential that decisions regarding antibiotic policies for neonatal units should be made locally and that they reflect local experience and the range of pathogens most frequently encountered and their sensitivity patterns.
Aminoglycosides ; therapeutic use ; Anti-Bacterial Agents ; metabolism ; therapeutic use ; toxicity ; Bacterial Infections ; drug therapy ; Drug Administration Schedule ; Humans ; Infant, Newborn ; Infant, Premature, Diseases ; drug therapy ; Kinetics ; Microbial Sensitivity Tests ; Risk ; Time Factors

BACKGROUND: Acute pyelonephritis in women can be treated with trimethoprim-sulfamethoxazole (SXT), fluoroquinolone, aminoglycosides, second- and third- generation cephalosporins. The purpose of this study is to provide basic informations for the choice of the most effectve and economic first-line antibiotics among several agents to clinicians, who manage community- acquired acute pyelonephritis. METHODS: We investigated antibiotic sensitivities of 130 organisms isolated from urine culture of 165 patients, who admitted to Catholic University St. Vincent's Hospital due to community-acquired acute pyelonephritis from February 2001 to November 2002. All those patients had more than 105 cfu/mL on urine culture and we analyzed the usage of antibiotics and clinical course in those patients. RESULTS: Among 130 isolates, 120 isolates were E. coli, 6 K. pneumoniae, 1 K. oxytoca, 1 Enterobacter aerogenes and 2 Proteus mirabilis. Among 120 E. coli, the rates of resistance were 59.2% to piperacillin, 58.3% to cephalothin, 36.7% to sulfamethoxazole, 19.2 % to gentamicin, and 7.5% to ciprofloxacin in order. For 120 E. coli isolates, 100%, 99.2%, 99.2%, 99.2%, and 97.5% were susceptible to imipenem, cefotaxime, cefuroxime, amikacin, and piperacillin/tazobactam, respectively. Among 165 patients, 130 patients who had positive urine or blood culture, were divided into three groups according to the first-line antibiotics administered on the day of admission. Gentamicin (5 mg/kg q 24h) were infused to 90 patients, and 9 (10%) of 90 patients revealed clinical manifestations of therapeutic failure such as persistent fever and pyuria in group I. Cefuroxime were administered to 36 patients in group II and all 36 patients revealed evidences of clinical success such as defervescence and absence of pyuria. Intravenous antibiotics changed to oral administration of the first-, second-cephalosporin, and trimethoprim- sulfamethoxazole in all patients except one patient, who received oral fluoroquinolone according to the results of antibiotic sensitivities. CONCLUSION: Cefuroxime, amikacin, and the third- generation cephalosporins showed excellent antibacterial activity against isolated organisms from women with acute pyelonephritis in this study, and gentamicin could be used as initial empiric regimen with careful monitoring of clinical response and antibiotic sensitivities of isolated microorganisms. These findings would be useful informations to physicians, who are trying to use low-priced antibiotics with narrow spectrum antibacterial activity, sparing more expensive and broad spectrum antibiotics in managing urinary tract infections.
Administration, Oral ; Amikacin ; Aminoglycosides ; Anti-Bacterial Agents* ; Cefotaxime ; Cefuroxime ; Cephalosporins ; Cephalothin ; Ciprofloxacin ; Enterobacter aerogenes ; Female ; Fever ; Gentamicins ; Humans ; Imipenem ; Piperacillin ; Pneumonia ; Proteus mirabilis ; Pyelonephritis* ; Pyuria ; Sulfamethoxazole ; Trimethoprim, Sulfamethoxazole Drug Combination ; Urinary Tract Infections

This study is to investigate inhibitory effects of lidamycin (LDM) on the proliferation of HERG K+ channel highly expressing cancer cells and its synergy with anticancer drugs. MTT assay was used to examine the inhibitory effects of lidamycin combined with various anticancer drugs on the proliferation of human lung cancer A549 cells, human colon cancer HT-29 cells and herg-stably-transfected A549 cells. Using the xenograft model of subcutaneously transplanted HT-29 in nude mice, inhibitory effect was appraised in vivo. The coefficient of drug interaction (CDI) was used to evaluate the synergistic effect of drug combination. LDM significantly inhibited the proliferation ofA549 cells and HT-29 cells with IC50 values of 2.14 and 4.64 ng mL(-1), respectively. The efficacy in HT-29 cells with high HERG potassium expression level is less potent than that in A549 cells with low expression level. In terms of IC50 values, LDM suppressed the growth of herg-stably-transfected A549 cells less potently than pCDNA3.1-stably-transfected A549 cells. There existed synergistic effects in the combinations of fluorouracil (5-FU) and LDM, doxorubicin (DOX) and LDM, or hydroxycamptothecine (HCPT) and LDM. CDI values of the combinations of 5-FU and LDM were more than 0.75. CDI values of LDM and DOX were more than 0.70, but some CDI values of LDM and HCPT were less than 0.70. As for the CDI values, synergistic effects of the combination of LDM and HCPT were the most potent of the three groups. There is no relationship between the inhibitory effect of the growth of cancer cells by 5-FU and HERG potassium expression level. HERG expression level negatively correlated with inhibitory effect on the proliferation of cancer cells by DOX. HERG expression levels and chemosensitivity were positively correlated for HCPT. In the model of subcutaneously xenograft transplanted HT-29 in vivo, LDM and/or HCPT effectively inhibited the growth of HT-29 in nude mice, and the optimum CDI of the combination of LDM and HCPT was less than 1. HERG expression level negatively correlates the chemosensitivity of cancer cells to LDM. There exist synergistic effects in vitro and in vivo in the combination of LDM and HCPT, which inhibitory effects of the proliferation of cancer cells positively modulated by HERG potassium expression level. HERG K+ channel may become a target of combined therapy for choosing anticancer drugs.
Aminoglycosides ; administration & dosage ; pharmacology ; Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Antineoplastic Agents, Phytogenic ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Camptothecin ; administration & dosage ; analogs & derivatives ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Doxorubicin ; administration & dosage ; Drug Synergism ; ERG1 Potassium Channel ; Enediynes ; administration & dosage ; pharmacology ; Ether-A-Go-Go Potassium Channels ; metabolism ; Fluorouracil ; administration & dosage ; HT29 Cells ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays

OBJECTIVELidamycin (LDM) can be dissociated to an apoprotein (LDP) and an active enediyne chromophore (AE). The detached AE can reassemble with its LDP-containing fusion protein to endow the latter with potent antitumor activity. However, the reassembly of AE with LDP is affected by several factors. Our aim was to optimize the assembly efficiency of the AE with a LDP-containing fusion protein and investigate the influence of several factors on the assembly efficacy.

METHODSA method based on RP-HPLC was developed to analyze the assembly rate, and an orthogonal experimental design L(9) (3(4)) was used to investigate the effects of temperature, assembly time, pH and molecular ratio of LDP-containing fusion protein to AE on the assembly rate. Furthermore, the determined optimum conditions for the assembly rate of the LDP-containing fusion protein with AE were applied and evaluated.

RESULTSA calibration curve based on the LDM micromolar concentration against the peak-area of AE by HPLC was obtained. The order in which individual factors in the orthogonal experiment affected the assembly rate were temperature>time>pH>molar ratio of AE to protein and all were statistically significant (P<0.01). The optimal assembly conditions were temperature at 10°C, time of 12 h, pH 7.0, and the molar ratio of AE: protein of 5:1. The assembly rate of AE with a LDP-containing fusion protein was improved by 23% after condition optimization.

CONCLUSIONThe assembly rate of chromophore of lidamycin with its LDP-containing fusion protein was improved after condition optimization by orthogonal design, and the optimal conditions described herein should prove useful for the development of this type of LDP-containing fusion protein.

Aminoglycosides ; administration & dosage ; chemical synthesis ; chemistry ; pharmacology ; Antibiotics, Antineoplastic ; administration & dosage ; chemical synthesis ; chemistry ; pharmacology ; Apoproteins ; chemistry ; Cell Line, Tumor ; Cell Survival ; Chromatography, High Pressure Liquid ; Drug Design ; Enediynes ; administration & dosage ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Recombinant Fusion Proteins ; chemistry ; Single-Chain Antibodies ; chemistry