Standard Regiment Research Articles

Mechanisms of Primaquine Induced Hemolysis in a Novel Humanized Murine Model of Mediterranean G6PD Deficiency

Background: Approximately half a billion individuals are genetically deficient in glucose 6-phosphate dehydrogenase (G6PD) due to amino acid variants generally thought to decrease enzyme half-life. Decreased G6PD activity limits the antioxidant capacity of red blood cells (RBCs). As such, certain drugs that induce oxidative stress can cause life-threatening hemolysis in G6PD deficient (G6DPd) individuals. Standard regiments of the only approved drugs that can cure liver phase Plasmodium vivax ( p. vivax) (i.e. primaquine and tafenoquine) are contraindicated in G6PDd patients due to risks of hemolysis. Effective treatment of G6PDd individuals infected with p. vivax requires a prolonged course of primaquine (8 weeks), leading to non-adherence, and subsequent reduced efficacy and increased risk of transmission. Despite decades of research and large drug screening programs, no non-hemolytic compound has been identified that can eradicate p. vivax. Lack of progress in this area has likely been hampered by an incomplete mechanistic understanding of primaquine induced hemolysis, in part due to the lack of an animal model that recapitulates G6PD instability. Methods: Recombinant non-deficient human hG6PD(ND) or the deficient Mediterranean variant (hG6PD(MED)) were expressed, purified, and subjected to thermal proteome profiling in combination with TMT10-assisted quantitative cross-linking proteomics. Mice were generated in which murine genomic G6PD is replaced with either genomic human hG6PD(ND) or hG6PD(MED). Hemolysis in humans is caused by primaquine metabolites (e.g. primaquine-5,6-orthoquinone (5,6-POQ)) and not primaquine itself. As such, RBCs from both strains were exposed to 5,6-POQ and then analyzed by 1) high resolution metabolomics and proteomics, 2) electron paramagnetic resonance (EPR) to measure superoxide, 3) methemoglobin (MetHb) formation, 4) light and electron microscopy, 5) in vitro hemolysis, and 6) in vivo hemolysis (clearance) after infusion into animals. In vivo pulse chase biotinylation allowed visualization and identification of younger (1-6 days) RBCs vs. older (7-55 day) RBCs. Results: Recombinant hG6PD(MED) enzyme had a 2.6-fold lower specific activity compared to hG6PD(ND). Thermal gradient crosslinking proteomics identified specific amino acid spacing (less than 26 angstroms) that was higher in hG6PD(ND) [82-95 and 91-432] vs. higher in hG6PD(MED) [89-205, 97-429, and 429-497]. Analysis of mice demonstrated that hG6PD(MED) RBCs had 5% of G6PD activity as compared to hG6PD(ND) RBCs, with an RBC age dependent decrease in G6PD activity in hG6PD(MED) RBCs. Exposure to 5,6-POQ caused increased superoxide generation, increased MetHb formation, alterations to morphology, in vitro hemolysis, and in vivo hemolysis of hG6PD(MED) RBCs compared to hG6PD(ND) RBCs. However, younger hG6PD(MED) RBCs with higher G6PD activity were highly resistant to 5,6-POQ induced hemolysis (both in vivo and in vitro). All experiments were carried out a minimum of 3 times and all stated findings were statistically significant (p<0.05). Proteomic and metabolomic analysis (with combined samples from multiple experiments) demonstrated oxidation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), resulting in a block in glycolysis that increases dihydroxyacetone phosphate (DHAP) leading to cytotoxic methylglyoxal that broadly oxidizes protein lysines to carboxymethyllysine (CML) - the first step in advanced glycation end products (AGEs) known to facilitate RBC clearance. Discussion: We identify specific conformational changes caused by the hG6PD(MED) variant resulting in decreased specific activity and half-life, and confirm that G6PD activity decreases with RBC age, in a humanized mouse model. The resistance of young hG6PD(MED) RBCs to 5,6-POQ has immediate practical ramifications, in that it supports the rationale of clinical studies currently proposing new dose escalation primaquine regimens to induce low level early hemolysis, leading to reticulocytosis, and decreasing the mean age of circulating RBCs such that increased parricidal doses of primaquine can then be tolerated in G6PDd patients. The elucidation of the metabolic and proteomic lesion (under conditions confirmed to cause 5,6-POQ induced hemolysis of hG6PD(MED) but not hG6PD(ND) RBCs) provides a mechanistic landscape to guide development of non-hemolytic drugs to treat p. vivax.

Efficacy of Intravitreal Anti Vascular Endothelial Growth Factor Injection Compared to Focal Therapy in Pediatric Patients with Coats Disease

Introduction: Coats disease is a retinal vascular disorder that may lead to progressive exudative retinal detachment. The standard regiment of treatment is focal therapy. However, its effectiveness may decrease when more than two quadrants of the retina exhibit vascular abnormalities. Thus, recent studies tried to use anti vascular endothelial growth factor (anti-VEGF) as therapy for the vascular problems. Aims: Comparing the efficacy between anti-VEGF injection and standard therapy regiment such as focal laser therapy. Methods: Literature searching was conducted through PubMed, ScienceDirect, Google Scholar, ProQuest, and SpringerLink. Search terms included "Coats’ Disease" and mesh terms of “Anti- VEGF". The efficacy is assessed based on Best-Corrected Visual Acuity (BCVA) and improvement in fundus manifestations. Results: All of the studies that conducted primary intravitreal anti-VEGF treatment were followed by necessary ablative treatment. These studies, such as by Yang Q and Zheng XX, et al. showed remarkable improvements in both visual acuity and anatomical outcomes. Laser therapy also gained satisfactory result in upgrading clinical stages, even though some complications including subretinal fibrosis, cataract, and vitreous hemorrhage were reported. A comparative study by Ray R, et al. noted that group undergoing anti-VEGF might require longer treatment sessions despite possible benefits. Conclusion: Anti-VEGF agents can be used as neoadjuvant in standard therapy. It did not reduce the time for full treatment, but the resolution of disease was seen in the most severe cases treated with combination therapy.

Combination of the natural product mensacarcin with vemurafenib (Zelboraf) combats BRAF mutant and chemo-resistant melanoma in vitro by affecting cell metabolism and cellular migration

Melanoma is the most prevalent and aggressive form of skin cancer, often with a low survival rate due to rapid metastasis and a high occurrence of multi-drug resistance (MDR). In this study, we examine the combination treatment of the recently discovered cytotoxic bacterial metabolite mensacarcin and FDA approved therapeutic vemurafenib (Zelboraf). Vemurafenib is the standard regiment for BRAF V600E mutation positive patients with unresectable or metastatic malignant melanoma. On its own, menscarcin induces mitochondrial dysfunction in selected BRAF-mutant melanoma cell lines. In combination treatment, mensacarcin enhances vemurafenib's cytotoxicity via metabolic impairment. Specifically, it lowers cellular glucose uptake, decreases the oxygen consumption rate, reduces the abundance of glycolytic enzymes, and halts wound healing. Mensacarcin alone retains strong cytotoxic effects in three vemurafenib resistant cell lines SK-Mel-28PLXr, A375PLXr, and A2058PLXr with an average IC50 of 1 μM, inducing apoptosis via the caspase-3/7 pathway. We also find that mensacarcin lowers metastatic migration in a wound healing assay and it alters the morphology of migrating cells on a nanofiber scaffold. Using extracellular matrix (ECM) mimicking fibers, mensacarcin treated cells exhibit a decrease in single cell maximum coil width and an increase in the protrusion length limiting cellular coiling behavior which may limit metastatic migration. In summary, the bacterial metabolite mensacarcin shows great promise as a melanoma drug lead in vitro: in combination with vemurafenib, the cytotoxic activity is enhanced, and alone, mensacarcin retains activity in BRAF inhibitor chemo-resistant melanoma cell lines, and features a unique, migratory limited single cell phenotype.

Autoimmune Hepatitis

Autoimmune hepatitis (AIH) is a condition caused by self-perpetuating immune response towards hepatocytes in liver. In children, AIH may progressed more rapidly compared to adults. Thus, early diagnosis and prompt treatment are the key for successful management of AIH. Five main characteristics of AIH include female predominance, increased IgG or hypergammaglobulinemia, circulatory autoantibody seropositivity, and hepatitis interface from the histological finding. Liver biopsy is needed to evaluate the degree of damage and to confirm the diagnosis. The standard regiment for AIH include prednisone (or prednisolone) and azathioprine. Other alternative treatments available for non-responder, such as mycophenolate mofetil, tacrolimus, cyclosporine, budesonide, rituximab, and infliximab. AIH treatment is recommended to be taken minimally for 2-3 years before attempting treatment termination.

A Comparative Study of Early Response Rate between Patient Given Standard Chemotherapy with Patient Given Combination Targeted Therapy in Non-Hodgkin Lymphoma Patients

Background: Treatment for non-Hodgin Lymphoma (NHL) with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been standard chemotherapy regimens for treatment of patients with diffuse large B cell lymphoma and follicular lymphoma. Rituximab, a chimeric monoclonal antibody against the CD20 B-cell antigen. Rituximab in combination with CHOP (RCHOP) increases better response rate without any significant increase in toxicity. The standard definition of treatment responseis based on changes in lesion dimensions with time. We conducted a comparative study to compare early response rate between CHOP andCHOP in NHL patients. Method: This study was using cohort prospective analysis and conducted at Wahidin Sudirohusodo Hospital from September 2018 until June 2019. The response rate was measured with the longest diameter of tumor and compared after 2 observational cycle periods of chemotherapy. Analysis to compare responserate was carried out using Independent T-test analysis. Results: Seventy patients enroll this study consisting of 38 subjects in CHOP group and 32 subjects in RCHOP group. Analysis to compare early responserate between CHOP and RCHOP was significant with p-value 0.001 (46.6% vs 67.0%;). Conclusions: Early response rate in patient given combination targeted therapy have better response rate than patient given standard regiment chemotherapy.

V7-07 ROBOTIC BLADDER NECK RECONSTRUCTION WITH SLING AND SPLIT APPENDIX TECHNIQUE FOR APPENDICOVESICOSTOMY AND MACE

You have accessJournal of UrologyPediatrics1 Apr 2017V7-07 ROBOTIC BLADDER NECK RECONSTRUCTION WITH SLING AND SPLIT APPENDIX TECHNIQUE FOR APPENDICOVESICOSTOMY AND MACE Molly Fuchs, Christina Ching, Christopher Brown, Richard Wood, Mark Levitt, Rama Jayanthi, and Daniel DaJusta Molly FuchsMolly Fuchs More articles by this author , Christina ChingChristina Ching More articles by this author , Christopher BrownChristopher Brown More articles by this author , Richard WoodRichard Wood More articles by this author , Mark LevittMark Levitt More articles by this author , Rama JayanthiRama Jayanthi More articles by this author , and Daniel DaJustaDaniel DaJusta More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1925AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Robotic surgical techniques have been adopted for procedures in pediatric urology even in reconstruction for neurogenic bladder. Our aim was to expand on the previously described bladder neck reconstruction with sling and Appendicovesicostomy (APV), by showing that the well described open split appendix technique can also be perform robotically, allowing for the creation of both APV and MACE. This video is to our knowledge, the first to demonstrate the use of robotic split appendix technique. METHODS A 6 year-old male with myelomeningocele, neurogenic bladder and bowel was not able to achieve urinary continence on a standard regiment of IC and anticholinergic. Urodynamic showed adequate bladder capacity at 300 ml with low storage pressure and adequate compliance. Unfortunately he had a low leak point pressure indicating poor outlet resistance. Thus indication for a bladder neck reconstruction with APV was made. There was also a need for implementing a good bowel regiment and after evaluation at our Center for Colorectal and pelvic Reconstruction by the colorectal surgeon, indication for a MACE was also made. We selected to utilize the Intuitive Surgical DaVinci® Si robotic surgery system for the operation. Prior to port placement, we performed cystoscopy and injected 300 units of Botox into the detrusor muscle, we placed ureteral catheter for easy ureteral orifice identification during bladder neck reconstruction and an 8 French Foley catheter. We used a 12mm camera port just superior to the umbilicus and three 8mm robotic ports. A 12mm accessory port was also placed for additional assistance. RESULTS The patient was admitted the day prior to the procedure for mechanical bowel prep. The next morning he was taken to the operating room for the procedure. Total operative time was 7 hours. Total console time was 6 hours. A 10 French Foley catheter was placed through the APV channel and an 8 French feeding tube was placed through the MACE. A 5 French feeding tube was left stenting the urethra and was removed prior to discharge. He was started on a clear liquid diet on post-operative day #2 and advanced as tolerated. The patient was discharged home on post-operative day #4. CONCLUSIONS Robotic assisted bladder neck reconstruction with split appendix technique to create both APV and MACE is technically feasible in the pediatric population. As experience increases with such techniques, these authors expect that robotic surgery will continue to be utilized in more complex reconstruction and patients can experience the benefits that minimally invasive techniques offer. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e825 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Molly Fuchs More articles by this author Christina Ching More articles by this author Christopher Brown More articles by this author Richard Wood More articles by this author Mark Levitt More articles by this author Rama Jayanthi More articles by this author Daniel DaJusta More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Echocardiography and cardiac biomarkers in patients with lung cancer treated with platinum-based chemotherapy

E-mail: daniel.omersa@klinika-golnik.si Objective: Platinum-based chemotherapy is a standard regiment for advanced lung cancer and adjuvant therapy in an early stage. It is ototoxic, nephrotoxic and induces oxidative stress whilst the data regarding cardiotoxicity remain scarce. Our aim was to assess cardiotoxicity of the platinum-based chemotherapy in patients with lung cancer. Patients and Methods: Patients with lung cancer referred for the first-line platinum-based chemotherapy were included in the study. Ultra-sensitive troponin T (usTnT), N-terminal pro-BNP (NT-proBNP) and echocardiography were performed at baseline, at the end of chemotherapy (visit two) and at the follow-up (visit three). We report mean ± standard deviation and the number (percentage) for numeric and categorical variables, respectively. Elevated usTnT and NTproBNP was defined as ≥30% increase from the baseline. Significant left ventricular ejection fraction (LVEF) was defined as a decrease of LVEF ≥10% to value ≤55% whereas diastolic dysfunction was defined using the European Society of Cardiology guidelines. Proπireni saaeetak / Extended abstract

A scanning electron microscope study on the effect of an experimental irrigation solution on smear layer removal.

The aim of this in vitro study was to evaluate the effect of an experimental irrigation solution, containing two different concentrations of papain, Tween 80, 2% chlorhexidine and EDTA, on removal of the smear layer. Thirty-six single-rooted teeth were divided into two experimental groups (n=12) and two positive and negative control groups of six. The canals were prepared with BioRaCe instruments up to BR7 (60/0.02). In group 1, canals were irrigated with a combination of 1% papain, 17% EDTA, Tween 80 and 2% CHX; in group 2, canals were irrigated with a combination of 0.1% papain, 17% EDTA, Tween 80 and 2% CHX. In group 3 (the negative control), the canal was irrigated with 2.5% NaOCl during instrumentation and at the end of preparation with 1 mL of 17% EDTA was used; in group 4 (positive control), normal saline was used for irrigation. The amount of the remaining smear layer was quantified according to Hulsmann method using scanning electron microscopy (SEM). Data was analyzed by the Kruskal-Wallis and Mann-Whitney tests. Two-by-two comparisons of the groups revealed no significant differences in terms of smear layer removal at different canal sections between the negative control group (standard regiment for smear layer removal) and 1% papain groups (P<0.05). Under the limitations of the present study, combination of 1% papain, EDTA, 2% chlorhexidine and Tween 80 can effectively remove smear layer from canal walls.

PTH-057 A Twin-Centre Randomized Trial of Increasing Clear Fluid Intake to Standard Moviprep Regimen in Adult Out-Patient Colonoscopy Improves Left Sided Bowel Cleansing & Polyp Detection Rates

IntroductionInadequate bowel preparation for colonoscopy is associated with increased complication rates and a reduction in diagnostic yield. Low volume 2L polyethylene glycol and ascorbic acid (Moviprep, Norgine Pharmaceuticals) has been...

The retrospective analysis of different therapies on 150 elderly patients with advanced non-small cell lung cancer.

There is still no standard regiment for the treatment of advanced elderly patients with non-small cell lung cancer (NSCLC). The aim of this study is to explore the best method for the advanced elderly NSCLC patients by analyzing the efficacy and toxicity of cisplatin combined chemotherapy, docetaxel chemotherapy and the best support care (BSC). One hundred and fifty elderly NSCLC patients (>=65 years) with different treatments from March 2003 to March 2007 in our hospital were retrospectively analyzed. The objective response rate (ORR) was 41.2% in cisplatin combined chemotherapy, which was significantly higher than 20.0% in docetaxel chemotherapy (P <0.05). Median survival time (MST) was 10.7 months, 9.2 months and 6.3 months, and one year survival rate was 39.7%, 36.7% and 17.3%, respectively in cisplatin combined chemotherapy, docetaxel chemotherapy and the best support care. MST was significantly longer (P <0.05) and one year survival rate was significantly higher (P <0.05) in the patients with chemotherapy than that with best support care. There was no significant difference of MST and one year survival between cisplatin combined chemotherapy and docetaxel chemotherapy (P >0.05). Grade 3-4 toxicity was more serious in cisplatin combined group than that in docetaxel group (P <0.05). Chemotherapy can prolong the survival time in elderly NSCLC patients. Even though the ORR is higher in cisplatin combined chemotherapy than that in docetaxel chemotherapy, there was no significant difference of MST and one year survival between cisplatin combined chemotherapy and docetaxel chemotherapy (P >0.05), which may due to the more serious toxicity. Docetaxel chemotherapy should be one of the standard regiment for the elderly NSCLC patients.

A Pilot Study of Mycophenolate Mofetil for the Prophylaxis and Treatment of Graft-Versus-Host Disease.

Graft-versus-host disease (GVHD) is a serious complication of allogeneic peripheral blood stem cell transplantation (PBSCT), which contribute to morbidity and mortality after transplantation. Approximately half of the patients that undergo allogeneic stem cell transplantation develop severe acute or chronic graft-versus-host disease [Shulman HM et al. Am J Med, 1980], which varies with the degree of histoincompatibility, the recipient and donor ages, the source and quality of donor T lymphocytes, the incidence of cytomegalovirus infection,and type of GVHD prophylaxis strategy. The combination of immunosuppressive drugs, CsA and short-course MTX is a standard regiment for prevention of GVHD after BMT [Nademanee A et al. Blood, 1995], and have been shown in randomize trials to be superior to either drug alone in preventing severe GVHD [Storb R N Engl J Med.1986]. Although the efficacy of the regimens in preventing GVHD, the incidence reported for GVHD after transplantation is 38–68%. Each of these agents is also associated with significant organ toxicity. MMF is an new immunosuppressive drug, which selectively inhibits proliferation of T and B lymphocytes, formation of antibodies, and glycosylation of adhesion molecules by inhibition purine nucleotide synthesis and depleting the lymphocytes and monocytes of guanosine triphosphate. In patients undergoing renal and heart transplantation, it has been successfully used to prevent graft rejection [Lang P et al.Transplantation, 2005]. We compared the effects of MMF+ CsA+ MTX as GVHD prophylaxis vs CsA + MTX in patients undergoing allogeneic peripheral blood stem cell transplantation. In all, 33 patients were enrolled in this study. The first group, of 16 patients, received CsA at 3mg/kg i.v. from day −1 to +30 day and MTX was on 15mg/m2 day +1 and 10mg/m2 day +3, +6, +11. The other group, of 17 patients received MMF 1g/d day −7 until day 0 and CsA + MTX. Here we used flow cytometric analysis technique to measure the changes of T cell subsets before and after treatment of MMF and CsA. Our study showed the incident of aGVHD is 25% when we combined standard GVHD proplylaxis with MMF after PBSCT, Which significantly reduce the risk of aGVHD than the combination of CsA and MTX (58.8%). Therefore, MMF is an effective drug in prophylaxis of aGVHD. Chronic GVHD is a late complication of PBSCT, Which develops approximately 30% in related donor HLA-matched allografts, and 60–70% in HLA-unmatched. The incident is not reduce with the development of aGVHD prophylaxis, Our result showed that the incident of cGVHD in research group (25%) is the same as the control group (23.5%). It seems that MMF is not reduce the incident of cGVHD, which may be different frome aGVHD. Our conclude that the number of CD3+ CD4+T cells decreased after the treatment of MMF, and those of CD3+ CD8+T cells increased,with reduction of the CD4+/CD8+ ratio. the number of CD25+ CD4+ and CD69+ CD8+ T cells were all increase. It seems that MMF may preferably effect on the CD3+CD4+T cells and the combination of MMF with CSA and MTX can significantly reduce the incidence of acute graft-vost-host diease, It appears to have a synergic action with CSA for the treatment of aGVHD.

Helicobacter Pylori Eradication with Beta Carotene, Ascorbic Acid and Allicin

In this study, in vivo effectiveness of ascorbic acid (AA), beta carotene (BC) and allicin in HP eradication were evaluated. 210 patients who are HP positive in biopsy were involved in this study. The patients randomised to seven treatment groups (each group consisting of 30 patients). The first group was given standard eradication treatment (lansaprasol 30 mg bid, clarithromycin 500 mg bid, amoxicillin 1 g bid for 14 days). Second group received AA 1000 mg/day in addition to the standard treatment. Third group received only AA 1000 mg/day for 14 days. Fourth group was treated with standard regiment plus 120 mg/day BC. Fifth group was given only BC 120 mg/day for 14 days. Sixth group was given standard regiment and allicin 4200 micrograms/day. Seventh group received only Allicin 1200 micrograms/day for 14 days. The eradication was achieved in 20 (66.6%) in group I, 15 (50%) in group II, 3 (10%) in group III, 15 (50%) in group IV, 0 (0%) in group V, 27 (90%) in group VI and 7 (23.3%) in group VII. Allicin seemed to be potentially effective agent for HP eradication but ascorbic acid, beta caroten was found to be ineffective.

Multicenter, randomized trial of ciprofloxacin plus azlocillin versus ceftrazidime plus amikacin for empiric treatment of febrile neutropenic patients

In a multicenter, randomized clinical trial, the efficacy of ciprofloxacin plus azlocillin was compared with that of a standard regiment of cerftazidime plus amikacin for the initial empiric treatment of fever in neutropenic cancer patients. In addition, the efficacy of early conversin from intravenous therapy to orally administered ciprofloxacin was compared with that of continued ceftrazidime plus amikacin. Seventy-one oncology patients with 79 episodes of fever and neutropenia were randomly assigned to receive initial empiric antibiotic therapy with either intravenously administered ciprofloxacin and azlocillin followed by orally administered ciprofloxacin (regimen 1, 25 episodes); ceftazidime and amikacin (regimen 2, 30 episodes), or ceftazidime and amikacin followed by oral ciprofloxacin (regimen 3, 24 episodes). Microbiologically documented infections were the cause of fever in 10 (40 percent), seven (23 percent), and nine (38 percent) episodes in regimens 1,2 and 3, respectively, including six, five, and four episodes of bacteremia. Patient survival was 90 to 92 percent in each regimen; however, some modification of antimicrobial therapy occurred in 65, 44 and 41 percent of surviving patients in regimens 1,2, and 3, respectively. The rate of clearance of initial bacteremia was 67 percent (four of six) in regimen 1, 100 percent (five of five) in regimen 2 and 50 percent (two of four) in regimen 3. Patients in regimens 1 and 3 were able to convert to orally administered ciprofloxacin in 32 (65 percent) of 49 episodes after a mean of six days of intravenous therapy. Superinfections occurred in 24, 10, and 12 percent of patients receiving regimens 1,2 and 3, respectively, and occurred similarly for patients receiving orally administered ciprofloxacin, 12 percent (four of 32), and intravenous therapy, 17 percent (eight of 47). Parenteral ciprofloxacin was generally well tolerated. One (4 percent) of 25 patients receiving regimen 1 experienced oto- or nephrotoxicity, compared with eight (15 percent) of 54 patients receiving regimens 1,2 and 3 (p = 0.15), including three patients who required premature termination of aminoglycosides therapy. Our data suggest that the combination of ciprofloxacin and azlocillin is an effective alternative to ceftazidime and amikacin for the initial empiric therapy of febrile neutropenic patients, is generally well tolerated, and avoids the oto- and nephrotoxicity associated with aminoglycoside use. In addition, a majority of patients could change to orally administered ciprofloxacin alone after sic days of parenteral therapy.