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Pharmacokinetic/Pharmacodynamic Modeling of Antibiotics
Published in Hartmut Derendorf, Günther Hochhaus, Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Arno Nolting, Hartmut Derendorf
Sturm57 investigated single (S) versus multiple (M) doses of netilmicin in the treatment of Gram-negative bacteremia. Seventy patients were randomly treated with either a single dose of netilmicin (6 mg/kg IV) or with the conventional multiple dose (2 mg/kg q8h). There was completely favorable outcome (defined as clinical cure with bacteriological elimination) in 25 (71%) of the S patients and in 27 (77%) of the M patients. Since only one S patient showed nephrotoxicity the authors suggested that the single-dose treatment is preferred. Hollender and co-workers58 investigated the efficacy of netilmicin given once a day vs. three times a day (given alone or in combination with metronidazole in patients with gangrenous appendicitis and intra-abdominal infections). All but 1 of 56 patients were cured with the once-daily treatment, whereas 54 out of 55 were cured with the three times a day treatment. The authors concluded that both treatments were equally safe. Mailer and colleagues59 compared once-daily (11 mg/kg q24h) administration of amikacin with twice-daily (5 to 6 mg/kg q12h) administration. Patients were treated for 3 to 14 d. All patients responded with clinical improvement or cure. Neither treatment appeared to be superior.
Sisomicin and Netilmicin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Netilmicin, either alone or in combination with a beta-lactam antibiotic, has been used to treat severe infections such as pyelonephritis, biliary tract infections, peritonitis, pleuropulmonary infections, and septicemia caused by gentamicin-susceptible Gram-negative bacilli. Results of treatment have usually been satisfactory and similar to those that would be expected from a similar gentamicin regimen (Klastersky et al., 1977; Panwalker et al., 1978; Snydman et al., 1979; Brandenhoff et al., 1980; Aroney et al., 1981; Perera et al., 1982; Lerner et al., 1983; Lane, 1984; Prins et al., 1994). However, the same concerns for gentamicin monotherapy in other than urinary tract infections also apply to netilmicin (Vidal et al., 2007). Most clinicians prefer to use the more familiar and usually less expensive gentamicin for the treatment of these infections, but some may prefer netilmicin because of its lower potential to cause ototoxicity (Jackson, 1984). Netilmicin also appears as effective as amikacin for the treatment of complicated urinary tract infections caused by Gram-negative bacilli susceptible to both antibiotics (Maigaard et al., 1978). The drug is about as efficacious clinically as tobramycin when serious infections due to organisms susceptible to both antibiotics are treated (Bernstein et al., 1986; Gorse et al., 1992).
Critical Appraisal of Animal Models for Antibiotic Toxicity
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Patricia D. Williams, Girard H. Hottendorf
Comparative assessments of aminoglycoside nephrotoxicity using the rat have not only substantiated clinical findings of nephrotoxicity associated with these drugs but have provided information on relative toxicities when human studies have been lacking or inadequate. Comparisons have been reported in which extensive dose-response data well into the human therapeutic range have been generated [75,78]. Figures 3 and 4 illustrate several such comparisons. Note that the linear and parallel dose-response curves in Figure 3 provide a means for establishing the relative toxic potencies of gentamicin, tobramycin, and amikacin. Figure 4, on the other hand, reveals a dose-response curve for netilmicin that is not parallel to that of gentamicin and amikacin, thus precluding statistical comparisons involving netilmicin. It is also interesting to note the flatness of the netilmicin curve compared with those of the other aminoglycosides. The relative flat dose-response for netilmicin has been reported in other studies utilizing high multiples of the human netilmicin dose [93–95]. High-dose comparisons predicted a low nephrotoxic potential of netilmicin relative to other aminoglycosides. However, from the data depicted in Figure 2, the flatness of the dose-response curve for netilmicin appears to extrapolate into a comparable or higher nephrotoxic risk at the lower doses approaching clinical relevance. The clinical use of netilmicin has been associated with appreciable nephrotoxicity despite the hopes provided by the early high-dose experimentation in rats [96–99]. Thus, the utilization of dose-response analyses employing sufficient dose levels inclusive of anticipated human doses can provide valuable insights into comparative toxic potentials and the risks of human exposure.
Systematic review on activity of liposomal encapsulated antioxidant, antibiotics, and antiviral agents
Published in Journal of Liposome Research, 2022
Reshna K. R, Preetha Balakrishnan, Sreerag Gopi
Gortzi et al. (2006) demonstrated the potential antioxidant and antimicrobial food preservative ability of four Thymus spp. (boissieri, longicaulis, leucospermus, and ocheus), (Figure 8). The diffusion technique of Bauer–Kirby (disc method), by measuring the zone of inhibition against four Gram-positive bacteria, four Gram-negative bacteria, including three human pathogenic fungi and against the food-pathogen bacteria Listeria monocytogenes. Standard antibiotics netilmicin and 5-flucytocine were used in order to control the sensitivity of the tested bacteria and fungi, respectively. The methanolic as well as the dichloromethane extracts of the Thymus spp. have also been studied for their antimicrobial activities, before and after encapsulation in liposomes. The methanolic extracts of T. longicaulis and T. ocheus appeared as the most active ones against most of the studied microorganisms (8- to 11-mm zones of inhibition). In general, the Gram-negative bacteria appeared as the most resistant ones as well as Candida Albicans among the tested fungi. After the encapsulation, the exhibited antimicrobial activities appeared much stronger (significant at p =.05), mostly against the Gram-positive bacteria as well as against the foodborne pathogen L. monocytogenes (10- to 15-mm zones of inhibition) (Gortzi et al.2006).
The Short-Term Efficacy of Biweekly Subconjunctival Bevacizumab in Diabetic Macular Edema
Published in Current Eye Research, 2020
Volkan Yeter, Özlem Eşki Yücel, Hakkı Birinci
All injections were performed using topical proparacaine drops (Alcaine 0.5%, Alcon Pharm. Ltd., Switzerland) in office. One minute after topical anesthesia, 5 mg (0.2cc) bevacizumab (Altuzan; Roche Ltd., Basel, Switzerland) was injected into subconjunctival space at inferio-temporal area of the eye by 26-gauge needle when the patient was looking nasally and upward. After injection, just one drop of netilmicin (Netira eye drop, S.I.F.I., San Antonio, Italy) was administrated to the eye and no medication was prescribed. We recommended all the patients to avoid pressure over his/her eye for 8 hours in order to prevent the reflux of the medicine. Patients were also examined next day and at first week after first SB injection for evaluating any ocular or systemic adverse effects in addition to the biweekly visits of the study. Three consecutive injections were performed—in biweekly intervals—at baseline, two weeks after first injection (at second week), two weeks after second injection (at the end of the first month).
Efficacy of Sunitinib, Sunitinib-Hesperetin, and Sunitinib-Doxycycline Combinations on Experimentally-Induced Corneal Neovascularization
Published in Current Eye Research, 2019
Yeliz Ekim, Selcuk Kara, Baran Gencer, Turan Karaca
The study included a total of 32 male Wistar albino rats weighing 250–300 g. Rats were anesthetized with 20 mg/kg ketamine hydrochloride (Ketalar, Eczacıbaşı, Turkey) + 4 mg/kg xylazine (Alfazyne, EgeVet, Turkey) with additional topical anesthesia of 0.5% proparacaine (Alcaine, Alcon, Turkey). One eye of each subject was included in the study. After anesthesia, the eyes were cauterized using the silver nitrate technique described by Mahoney et al. 34 Corneal cauterization was performed in a width of 2–3 mm in the center of the right cornea using a stick covered in 75% silver nitrate and 25% potassium nitrate, which was applied for 10 seconds. After the procedure, the eye was washed with 10 ml of 0.09% saline. A topical antibiotic (netilmicin) treatment was applied twice daily for 2 days. Before the cauterization procedure, the rats were randomly distributed into 4 groups of 8 rats each. All cauterization procedures were carefully performed by the same researcher. From the 3rd through the 15th day, the planned treatment agents were applied topically twice a day as follows: Group 1 (n = 8): artificial tears, Group 2 (n = 8): sunitinib (0.5 mg/ml), Group 3 (n = 8): sunitinib (0.5 mg/ml) and hesperetin (0.2 mg/ml) combination, and Group 4 (n = 8): sunitinib (0.5 mg/ml) and doxycycline (20 mg/ml) combination. In the groups that received combination treatments, care was taken to leave at least 5 minutes between the topical administration of each agent.