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Objectives: To investigate the pattern of antibiotic use in the hospital over a 3-year period according to individual drugs and hospital departments., Setting: 335 adult beds of a tertiary hospital in Northern Israel during the years 1998-2000. An antibiotic control policy restricts the use of the most expensive antibiotics and those with broad spectrum of activity and a major impact on bacterial resistance., Methods: The ATC/DDD and DU 90% methodologies were used. The use of antibiotics was expressed as the number of defined daily doses (DDD) per 100 bed-days., Results: The total antibiotic use varied during the study period from 93.7-101.0 DDD/100 bed-days (p < 0.1). Thirteen drugs accounted for 90% of the total volume. The use of broad spectrum penicillins was the highest of all drugs followed by cephalosporins and oral quinolones. The highest rates of antibiotic use were found in the departments of ENT, urology, gynecology and orthopedics and in the intensive care unit (ICU). The total restricted antibiotics use was 7.2 DDD/100 bed-days and was the highest in the ICU., Conclusions: The ATC/DDD methodology provided delineation and interpretation of antibiotic usage patterns in the hospital. Although the overall use is higher then that found in several reports from European hospitals, stratification by individual drugs and by hospital department yielded similar trends.

Ramsay Hunt syndrome is an herpetic disease with ominous prognosis regarding the facial nerve. Treatment with acyclovir, a well-known virostatic agent, has been given in a small number of patients in recent years with excellent results. We report on the administration of acyclovir intravenously for 7 days in 31 patients with Ramsay Hunt syndrome, with overall recovery rate of 82.6%. There were no side effects regarding this treatment.

The emergency room (ER) is an important focal point for the initiation of antimicrobial therapy but there are few data on antimicrobial prescribing in the ER. The objective of the study was to describe antimicrobial prescribing in Israeli ERs and to compare patterns of prescribing between four different ERs in Northern Israel. The medical records of all patients who attended the ERs during February 2001 were examined. Those patients who were discharged home with a prescription for an antibiotic formed the sample. Paediatric data were only available for two of the four ERs. A total of 970 adults and 470 children attended the four ERs during 1 month and were discharged home with an antibiotic prescription representing 14.6 and 19.9%, respectively, of the total number of patients who visited the ERs. The most common diagnosis leading to an antibiotic prescription was respiratory tract infections (64 in adults and 90% in children). In adults, cefuroxime-axetil and amoxycillin-clavulanate (both second-line antibiotics) were the most frequently prescribed antibiotics, together accounting for 50% of all antibiotic prescriptions, while in children amoxycillin-clavulanate was favoured (58.9%). 'Viral infections' accounted for 22.5% of all prescriptions in adults, but only 2.3% in children. Otitis media accounted for almost half of all prescriptions in children. For some diagnoses, such as pneumonia in adults and tonsillitis in children, there was uniformity of prescribing among the different ERs, while for other diagnoses, there were large discrepancies. The ER represents an important source of inappropriate antibiotic prescribing, and measures to curb inappropriate prescribing are urgently needed.

The pharmacokinetics and pharmacodynamics of meropenem were investigated in 14 critically ill patients with sepsis. Patients with creatinine clearance (CrCl) higher than 50 ml/min received 1 g meropenem three times daily (Group I) and patients with CrCl lower than 50 ml/min received 1 g meropenem twice daily (Group II). Meropenum concentrations in plasma were determined by high performance liquid chromatography with UV detection. The pharmacokinetic parameters differed between the two groups as follows, Group I, maximal concentration 56.3 +/- 19.1 microg/ml; trough concentration 3.3 +/- 2.5 microg/ml; elimination half life 2.5 +/- 1.2 h; clearance (Cl) 155.8 +/- 40.6 ml/min; MRT 2.2 +/- 0.4 h; steady state volume of distribution (V(ss)) 21.7 +/- 5.7 l, and AUC(-8) 119.4 +/- 32.6 microg/ml h. Group II, maximal concentration 71.1 +/- 5.1 microg/ml; trough concentration 3.4 +/- 1.8 microg/ml; elimination half life 3.9 +/- 1.6 h; Cl 77.7 +/- 15.8 ml/min; MRT 3.5 +/- 0.6 h; V(ss), 17.1 +/- 2.1 l, and AUC(0-12) 230.2 +/- 43.3 microg/ml h. The most frequently isolated bacteria from blood and wound infections were Acinetobacter baumanii, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli; their meropenem minimal inhibitory concentrations (MICs) ranged from 0.064 to 3.0 mg/l. In most cases the pharmacodynamic parameters, measured as T>MIC index, were higher than 75%. In both groups, patients with susceptible pathogens (MIC<1 mg/l) had meropenem plasma levels which exceeded the MIC for the whole dosing interval. When pathogens were highly resistant (A. baumanii or P. aeruginosa) the T>MIC indices were lower.

Vancomycin concentrations in serum, tissues, and sternum, administered as prophylaxis to patients during coronary artery bypass surgery, were measured. Vancomycin (15 mg/kg) was administered to 15 patients 1 hour before skin incision. Blood, tissue, and sternum samples were collected before, during, and after bypass. The concentration in serum at the end of infusion was 55.1 +/- 22.8 microg/mL, the mean elimination half-life was 9 +/- 4 hours, the areas under the concentration-time curve (AUC) from 0 to 12 hours and from 0 to infinity were 90.6 +/- 25.1 and 289.7 +/- 86.5 microg/h per mL, respectively, the mean residence time (MRT) was 11.9 +/- 5.0 hours, the mean volume of distribution was 51.1 +/- 12.2 L, and the total clearance was 78.3 +/- 32.6 mL/min. Vancomycin concentrations in serum, tissues, and sternum during the operation were greater than the MIC90 for most staphylococci and ranged from 16 to 55 microg/mL in serum and from 4 to 39 microg/g in sternum and tissues.

A modified high performance liquid chromatography (HPLC) method for the quantification of vancomycin levels in plasma and tissues is described. The method uses solid phase extraction (SPE) of vancomycin from the samples and reversed phase HPLC with UV detection. The method was fully validated in terms of recovery, linearity, selectivity and various stability conditions. Vancomycin was determined in plasma samples obtained from 15 patients undergoing cardiopulmonary bypass, before and repeatedly during 12 h after drug administration. The vancomycin levels in plasma were measured by HPLC and by fluorescence polarization immunoassay (FPIA) (TDX). The following correlation was found: TDX = 0.84 HPLC + 1.04. The mean vancomycin levels in skin, fat, atrium, pericardium and sternum, before and after bypass, are reported.

Herpes zoster oticus produces facial paralysis with a low recovery rate. Acyclovir, a specific virostatic drug, was given intravenously in five herpes zoster oticus patients, and in three of them was followed by oral therapy. In follow-ups of 1 to 24 months, one patient had grade I recovery, three patients grade II, and one grade III. These good results encourage the use of acyclovir in herpes zoster oticus patients.

To evaluate the penetration of ciprofloxacin, a new wide-spectrum oral antibiotic, into the vitreous, ciprofloxacin was administered orally to 21 patients who were scheduled to undergo vitreal surgery. Seven patients received 750 mg ciprofloxacin 4 hr before surgery (group I), seven patients received this dose 8 hr before surgery (group II), and seven patients received two 750-mg doses of oral ciprofloxacin every 12 hr. The last dose was administered 12 hr before surgery (group III). Vitreous and blood samples were collected simultaneously and assayed for ciprofloxacin concentrations by bioassay and high-performance liquid chromatography.

Twenty-three consecutive patients with malignant external otitis (MEO) were treated with oral ciprofloxacin, 1.5-2.25 g/day for 6 weeks. Treatment was combined with local surgical debridement. Patients were discharged early for ambulatory follow-up. Few minor side effects were reported, and full compliance with the study drug was observed. In 21 patients cure was achieved; in 2 the response was not adequate. Oral ciprofloxacin is an effective, convenient, nontoxic, economically justified alternative to the combination intravenous therapy previously advocated.

The Ear, Nose, and Throat department of the Meir Hospital treated 91 patients with malignant external otitis during the past 16 years. The last 23 patients with malignant external otitis were treated with ciprofloxacin 750 mg twice daily, combined with local excision of the aural lesion. The records of 61 of our previous 68 patients who underwent surgery and were hospitalized and treated with an intravenous extended-spectrum penicillin and gentamicin for six to eight weeks, were analyzed. Twenty-one of 23 patients treated with ciprofloxacin were cured; therapy failed in two patients. Treatment averaged 16.8 days of hospitalization, and bacteriologic eradication was achieved after an average of 7.04 days, as compared with 49 and 15.3 days, respectively, in the group of patients with the intravenous treatment. The mean peak concentrations of ciprofloxacin in serum varied between 2.5 and 3.7 micrograms/ml, and the drug concentrations in different ear tissues were 0.2 to 13 micrograms/g. The treatment with ciprofloxacin was well tolerated with no significant side effects, whereas serious side effects were noted in 45.9 percent of the previous intravenously treated group. The concentrations of the drug in serum and ear tissues were higher than the average minimal inhibitory concentration for Pseudomonas aeruginosa. Use of ciprofloxacin treatment, combined with local excision of the aural lesion, will bring about healing of malignant external otitis in the majority of cases. Ciprofloxacin can be given on an ambulatory basis after a relatively short period of hospitalization.