J Pharm Biomed Anal, 2005 Jan 4, 36(5), 969 - 74 Chemiluminescence determination of amikacin based on the inhibition of the luminol reaction catalyzed by copper; Ramos Fernandez JM et al.; A simple and sensitive method has been proposed for the amikacin sulphate determination . It is based on the inhibition of the chemiluminescence (CL) emission generated from the oxidation of luminol in alkaline medium by H(2)O(2) catalyzed by Cu(II), due to the interaction caused by amikacin, which forms a robust complex with the catalyst . The optimization of the experimental and instrumental variables affecting this CL inhibition effect has been carried out using statistical models, based on the application of two-level full factorial and Box-Behnken designs . The performance characteristics of the proposed method have been established, showing that the method is efficient to determine amikacin sulphate in the linear range of 9.89-20mg/L with a detection limit of 2.97mg/L . It has been successfully applied to the amikacin sulphate determination in pharmaceutical formulations. Eur J Clin Microbiol Infect Dis . 2004 Dec 15; {Epub ahead of print} Pneumonia involving Aspergillus and Rhizopus spp . after a near-drowning incident with subsequent Nocardia cyriacigeorgici and N . farcinica coinfection as a late complication; van Dam AP et al.; Reported here is the case of a 22-year-old man who developed pneumonia with unusual pathogens after a near-drowning incident . On day 7 following admission, Rhizopus spp . and Aspergillus fumigatus were cultured from the patient's bronchoalveolar lavage fluid . One week later, sputum cultures revealed N . cyriacigeorgici as well as N . farcinica . The patient recovered fully after prolonged therapy with liposomal amphotericin B, amikacin, meropenem and cotrimoxazole. Support Care Cancer . 2004 Dec 15; {Epub ahead of print} A randomized clinical trial of ceftriaxone and amikacin versus piperacillin tazobactam and amikacin in febrile patients with hematological neoplasia and severe neutropenia; Rossini F et al.; GOAL OF WORK: We compared the efficacy of ceftriaxone (CA regimen) and piperacillin-tazobactam (PTA regimen) in association with amikacin in the treatment of febrile episodes in severely neutropenic hematological patients . PATIENTS AND METHODS: A total of 252 febrile episodes in 224 patients were randomized . MAIN RESULTS: The CA regimen was effective in 62/122 evaluable episodes (50.8%), and the PTA regimen was effective in 64/121 (52.9%; P>0.2) . Median time to failure was 4 and 5 days (P>0.1) . Further infections developed in 21/122 episodes (17.2%) with the CA regimen and in 12/121 (9.9%) with the PTA regimen (P=0.06) . The overall mortality at the end of the febrile episode was 11/243 (4.5%); seven deaths were considered to be related to infection . CONCLUSIONS: Patients treated with piperacillin-tazobactam and amikacin tended to become afebrile sooner and to suffer a lower rate of further infections, even though our data did not show any statistically significant differences between the two groups. J Chromatogr A, 2004 Nov 26, 1058(1-2), 197 - 201 Hydrophilic interaction chromatography combined with tandem-mass spectrometry to determine six aminoglycosides in serum; Oertel R et al.; A specific and automated method was developed to quantitate the aminoglycosides amikacin, gentamicin, kanamycin, neomycin, paromomycin, and tobramycin simultaneously in human serum . Samples were prepared with an automated solid phase extraction (SPE) . The hydrophilic interaction chromatography (HILIC) was used for separation of analytes from endogenous compounds and baseline separation . The aminoglycosides were detected with electrospray ionisation tandem mass spectrometry (ESI-MS-MS) . Using a volume of 500 microl biological sample the lower limits of quantification were 100 ng/ml or better . The described HILIC-MS-MS method is suitable for therapeutic drug monitoring and for clinical and pharmcokinetical investigations of the aminoglycosides. Int J Syst Evol Microbiol, 2004 Nov, 54(Pt 6), 2385 - 91 Mycobacterium cosmeticum sp . nov., a novel rapidly growing species isolated from a cosmetic infection and from a nail salon; Cooksey RC et al.; Four isolates of a rapidly growing Mycobacterium species had a mycolic acid pattern similar to that of Mycobacterium smegmatis, as determined by HPLC analyses . Three of the isolates were from footbath drains and a sink at a nail salon located in Atlanta, GA, USA; the fourth was obtained from a granulomatous subdermal lesion of a female patient in Venezuela who was undergoing mesotherapy . By random amplified polymorphic DNA electrophoresis and PFGE of large restriction fragments, the three isolates from the nail salon were shown to be the same strain but different from the strain from the patient in Venezuela . Polymorphisms in regions of the rpoB, hsp65 and 16S rRNA genes that were shown to be useful for species identification matched for the two strains but were different from those of other Mycobacterium species . The 16S rRNA gene sequence placed the strains in a taxonomic group along with Mycobacterium frederiksbergense, Mycobacterium hodleri, Mycobacterium diernhoferi and Mycobacterium neoaurum . The strains produced a pale-yellow pigment when grown in the dark at the optimal temperature of 35 degrees C . Biochemical testing showed that the strains were positive for iron uptake, nitrate reduction and utilization of d-mannitol, d-xylose, iso-myo-inositol, l-arabinose, citrate and d-trehalose . The strains were negative for d-sorbitol utilization and production of niacin and 3-day arylsulfatase, although arylsulfatase activity was observed after 14 days . The isolates grew on MacConkey agar without crystal violet but not on media containing 5 % (w/v) NaCl or at 45 degrees C . They were susceptible to ciprofloxacin, amikacin, tobramycin, cefoxitin, clarithromycin, doxycycline, sulfamethoxazole and imipenem . The name Mycobacterium cosmeticum sp . nov . is proposed for this novel species; two strains, LTA-388(T) (=ATCC BAA-878(T)=CIP 108170(T)) (the type strain) and 2003-11-06 (=ATCC BAA-879=CIP 108169) have been designated, respectively, for the strains of the patient in Venezuela and from the nail salon in Atlanta, GA, USA. Vet Res Commun, 2004 Jul, 28(5), 429 - 35 Pharmacokinetics of amikacin in lactating sheep; Haritova A et al.; The pharmacokinetics of amikacin (AMK) were investigated after intravenous (i.v.) and intramuscular (i.m.) administration of 7.5 mg/kg bw in 6 healthy lactating sheep . After i.v . AMK injection (as a bolus), the elimination half-life (t1/2beta), the volume of distribution (Vd,area), the total body clearance (ClB) and the area under the concentration-time curve (AUC) were 1.64 +/- 0.06 h, 0.19 +/- 0.02 L/kg, 1.36 +/- 0.1 ml/min per kg and 94.09 +/- 6.95 (microg.h)/ml, respectively . The maximum milk concentration of AMK (Cmax), the area under the milk concentration-time curve (AUCmilk) and the ratio AUCmilk/AUCserum were 1.18 +/- 0.22 microg/ml, 22.45 +/- 3.21 (micro.h)/ml and 0.24 +/- 0.02, respectively . After i.m . administration of AMK the t1/2beta, Cmax, time of Cmax (tmax) and absolute bioavailability (Fabs) were 1.29 +/- 0.1 h, 16.97 +/- 1.54 microg/ml, 1.0 +/- 0 h and 64.88% +/- 6.16%, respectively . The Cmax, AUCmilk and the ratio AUCmilk/AUCserum were 0.33 microg/ml, 1.67 (microg.h)/ml and 0.036, respectively. J Coll Physicians Surg Pak, 2004 Sep, 14(9), 522 - 6 Allogeneic peripheral blood stem cell transplantation in patients with haematological malignancies; Shamsi TS et al.; OBJECTIVE: To report the initial data on allogeneic peripheral blood stem cell transplantation for haematological malignancies in Pakistan . DESIGN: A single centre descriptive study . PLACE AND DURATION OF STUDY: Bismillah Taqee Institute of Health Sciences and Blood Diseases Centre from September 1999 to June 2004 . PATIENTS AND METHODS: Patients with haematological malignancies were included who had received allogeneic PBSC transplantation of Filgrastim (rhG-CSF) mobilized peripheral blood stem cells from HLA-identical siblings (except one 5/6 antigen sibling) with Busulphan and Cyclophosphamide standard conditioning therapy in all patients . No patient received antibiotics for gut decontamination . Empirical antibiotics included Ceftriaxone and Amikacin for febrile neutropenia, oral Itraconazole for antifungal prophylaxis while oral acyclovir was used for antiviral prophylaxis . All donors and recipients were CMV IgG positive Cyclosporin A / Methotrexate were given for graft versus host disease (GvHD) prophylaxis . Stem cells were harvested using Haemonetics MCS+ cell separator . All patients received G-CSF starting from day +4 until their neutrophil count rose to normal . RESULTS: There were 21 patients with age range of 8-38 years and male to female ratio of 2:1 . Engraftment was achieved in all patients; median time to absolute neutrophil count of > 0.5 x 10(9)/l was 10 days (range 8 - 12 days) and platelet count of > 20 x 10(9)/l was 14 days (12-17 days) . Acute graft versus host disease ( aGvHD) was seen in 7 patients; one patient had grade IV skin and hepatic GvHD; another patient had grade III gut GvHD, grade II GvHD was seen in 3 patients while grade I skin aGvHD was seen in 2 patients . Median hospital stay was 34 days . Treatment related mortality was seen in 3 patients (18%) . Chronic GvHD was seen in 5 patients . Four more patients died during the follow-up period . Malaria was seen in 2 while tuberculosis developed in one case . Relapse was seen in 2 patients . The estimated probability of survival at one hundred day, at one year and five years was 82, 47 and 40 percent respectively . CONCLUSION: Haematopoietic stem cell transplant programme can be developed in a developed country setting . Post transplant complications are similar to what have been reported in the developed countries . In endemic areas malaria could prove to be fatal if not recognised and treated early. ANZ J Surg, 2004 Aug, 74(8), 662 - 6 Mycobacterium fortuitum: an iatrogenic cause of soft tissue infection in surgery; Muthusami JC et al.; BACKGROUND: Mycobacterium fortuitum is an uncommon cause of soft tissue infections . Treatment is often inadequate with persistence of infection unless the aetiological agent and its antibiotic sensitivity are accurately established . METHODS: Medical records of 23 patients with chronic soft tissue infection caused by M . fortuitum over a 12-year period from 1991 to 2002 were studied . RESULTS: In 20 patients the cause was iatrogenic, following intramuscular injections (12), laparoscopy (5) and other surgical procedures (3) and in three patients discharging sinuses developed spontaneously . Patients presented with recurrent abscesses or chronic discharging sinuses that did not respond to conventional surgical drainage . The diagnosis was established by isolating M . fortuitum from the tissues in all cases . The treatment consisted of a more aggressive surgical intervention in form of excision, debridement and extensive lay open with curettage and prolonged administration of appropriate antibiotics . The organism showed maximum sensitivity to amikacin and ciprofloxacin . Healing occurred in all cases . Three patients suffered recurrences: two responded to further debridement and antibiotics and are well at 2 and 5 years, respectively . CONCLUSION: A high index of suspicion based on clinical presentation is essential to diagnose M . fortuitum as a cause of soft tissue infection . Treatment involves aggressive surgical debridement and administration of combination antibiotics based on sensitivity, which should be continued for a period that will ensure complete healing and prevent recurrence. J Comp Neurol, 2004 Sep 13, 477(2), 149 - 60 Calpain activity in the amikacin-damaged rat cochlea; Ladrech S et al.; The principal aim of this study was to investigate the involvement of calpain in the degeneration of hair cells and ganglion neurons in the amikacin-poisoned rat cochlea . An antibody designed against fodrin-breakdown products (FBDP), which result exclusively from cleavage by calpain, was used . In addition, the involvement of both caspases and protein kinase C (PKC) was studied using, respectively, antibodies against activated caspase 3 and PKCgamma . The results demonstrate the accumulation of FBDP in the degenerating hair cells, in some supporting cells such as Deiters cells, and, later, in the affected ganglion neurons that had been deprived of their sensory targets . Activated caspase 3 was evidenced in a few dying hair cells and ganglion neurons . PKCgamma was highly expressed in all ganglion neurons, sometimes after the loss of hair cells . We conclude that calpain plays a role in the degradation of both the sensory cells and neurons after amikacin ototoxicity . In the poisoned hair cells, calpain and caspase 3 may have synergistic effects in the process of apoptosis . In the ganglion neurons deprived of their sensory elements, calpain may have a prominent role in cell degradation . By contrast, in these ganglion neurons PKCgamma may be implicated in a survival process . Finally, we suggest that calpain is involved in the remodeling of Deiters cells during the scarring process that follows hair cell loss. J Clin Pathol, 2004 Aug, 57(8), 807 - 12 Secular trends of nocardia infection over 15 years in a tertiary care hospital; Matulionyte R et al.; AIMS: To assess the incidence of nocardia infection over 15 years in a tertiary care hospital . METHODS: Over a 15 year period, Nocardia spp were isolated from 20 patients hospitalised at the Geneva University Hospitals, Switzerland . RESULTS: Sixteen patients had one or more underlying conditions . The median time between symptom onset and diagnosis was 30 days . The most common initial unconfirmed diagnosis was pulmonary tuberculosis (four) . The lung was involved in 16 cases, followed by the central nervous system (two) and skin (two); one patient had disseminated infection . The most common species identified was N asteroides . In vitro susceptibility testing was performed on 14 of 20 strains . All strains were susceptible to imipenem and amikacin . Initial treatment with trimethoprim/sulfamethoxazole (TMP/SMX) was started in 14 patients, although five patients had to be switched to another treatment because of side effects or lack of efficacy . A cure was observed in 15 patients, death in three, and relapse or complications in two . CONCLUSIONS: Nocardiosis can become a severe infection and mainly affects profoundly immunocompromised patients . Differential diagnosis often delays the time to diagnosis, which worsens the outcome . New diagnostic tools, such as the polymerase chain reaction, could provide more rapid and reliable results . TMT/SMX was the most commonly prescribed treatment, but needed to be changed for another treatment because of side effects or lack of efficacy in a considerable proportion of patients . Imipenem should be used as an alternative treatment for severely ill patients, and the sulfa combination for less severe infections. Clin Infect Dis, 2004 Jul 15, 39 Suppl 1, S56 - 8 Monotherapy versus dual therapy based on risk categorization of febrile neutropenic patients; Ohyashiki K; Cefepime monotherapy was compared with cefepime-plus-amikacin dual therapy for treatment of febrile neutropenic patients . Response rates were significantly lower for patients receiving monotherapy who had neutrophil counts of <500 cells/mm3 but did not differ significantly between patients receiving dual therapy who had neutrophil counts of > or =500 cells/mm3 or <500 cells/mm3 . Dual therapy is recommended for the initial treatment of patients with neutropenia with <500 cells/mm3 . Dual therapy was significantly more effective in patients with neutropenia lasting <5 days . The response rates to monotherapy or dual therapy did not differ significantly when neutropenia persisted for > or =6 days, indicating that sustained neutropenia is a risk factor for failure of initial empirical therapy . The rate of response to monotherapy was lower in leukemic patients, whereas the rate of response to dual therapy did not differ between leukemic and nonleukemic groups . The rate of response to either monotherapy or dual therapy did not differ for patients with temperatures of > or =38 degrees C or 37.5 degrees C-38 degrees C . Overall, defervescence occurred in >80% of patients with mild infections, whereas only 32% of those with moderate to severe infection responded by day 3 and 69.8% by day 7. Biol Neonate, 2004, 86(3), 207 - 11 Epub 2004 Jul 07. Effects of co-administration of ibuprofen-lysine on the pharmacokinetics of amikacin in preterm infants during the first days of life; Allegaert K et al.; The aim of this study was to assess the effects of intravenous co-administration of ibuprofen-lysine on the pharmacokinetics of amikacin during the first days of life in preterm infants . The pharmacokinetics of amikacin were retrospectively calculated in a cohort of 73 neonates (gestational age <31 weeks) who received either ibuprofen-lysine or placebo following inclusion in the multicentre ibuprofen prophylaxis study . Assuming a one-compartment model with instantaneous input and first-order output, there was no significant difference in the median distribution volume (0.63 vs . 0.59 liters/kg), but the median serum half-life (16.4 vs . 12.4 h) of amikacin was significantly longer (p <0.02), and the clearance (0.36 vs . 0.6 ml/kg/min; p <0.005) of amikacin was significantly lower in infants who received ibuprofen-lysine . We conclude that the time interval between consecutive amikacin administrations should be prolonged, if ibuprofen-lysine is co-administered. Zhonghua Jie He He Hu Xi Za Zhi, 2004 May, 27(5), 328 - 31 {Treatment and a follow-up study on wound infection by Mycobacterium chelonae: report of 168 cases}; Weng KR et al.; OBJECTIVE: To summarize the experience of treatment on wound infection by non-tuberculous Mycobacterium (NTM) after operations . METHODS: A hundred and sixty-eight patients with NTM incision infection were retrospectively reviewed in terms of diagnosis, treatment and follow-up in a period of 4.5 years . On the basis of the results of in vitro drug sensitivity test, the main antibiotics used were clarithromycin and amikacin . The course of therapy was 4 - 8 months . An extirpative excision was performed in 104 cases following one month treatment by antibiotics and then followed by antibiotic therapy for 3 - 5 months after excision . RESULTS: Primary closure was achieved in 98 of the 104 cases . Fifty patients were cured by the use of antibiotics with dressing change . Eight patients were cured by dressing change without antibiotics . Five children with wound infection by NTM after circumcision were cured by antibiotics with local laser therapy . One patient with infection after hernia operation was cured by amikacin blocking of the area surrounding the lesion . There was no relapse after follow-up for four and half years . CONCLUSION: The study demonstrates that sensitive antibiotics combined with surgery extirpative excision is effective for wound infection by NTM. Eur Arch Otorhinolaryngol . 2004 May 28; {Epub ahead of print} Dose-dependent dual effect of melatonin on ototoxicity induced by amikacin in adult rats; Erdem T et al.; ABTRACTThe aim of this animal study was to reveal the dose-dependent effects of melatonin on aminoglycoside ototoxicity by utilizing distortion product otoacoustic emissions (DPOAEs) . Forty-four adult (aged 12 months) rats were divided into five groups . Rats of the control group (group C) were injected with vehicle, while the melatonin group (group M) received melatonin (4 mg/kg per day); there were four rats in each of these groups . The study groups consisted of 12 rats per group, and they were treated as follows: 600 mg/kg per day amikacin (group A), amikacin plus a low dose (0.4 mg/kg per day) melatonin (group AML) and amikacin plus high dose (4 mg/kg per day) melatonin (group AMH) for 14 days . During the serial measurements on days 0, 5, 10 and 15, the DPOAE results of groups C,M and AML were not significantly changed . Amikacin ototoxicity findings for input/output (I/O) functions were detected on the 3rd measurement of the study in group A . High-dose melatonin clearly enhanced and accelerated amikacin-induced ototoxicity . The DP-gram amplitudes and I/O amplitudes were reduced, and I/O thresholds were increased in group AMH . Group AMH was the group that was affected the most and earliest by amikacin . Our study results showed that while low-dose melatonin protected the inner ear from ototoxicity, high dose melatonin facilitated amikacin-induced ototoxicity, possibly via the vasodilatory effect, leading to an increased accumulation of amikacin in the inner ear . Probably, the protective effect of the melatonin at a dose of 0.4 mg/kg per day is related to its antioxidant properties . Apparently, the vasodilatory effect of melatonin seems to be more prominent than its antioxidant effect in high doses. J Infect Chemother, 2004 Apr, 10(2), 101 - 4 Subcutaneous tissue release of amikacin from a fibrin glue/polyurethane graft; Nishimoto K et al.; We investigated whether fibrin glue (FG) might be useful as a carrier of amikacin (AMK) for prevention of local graft infection . After AMK (4.0 mg)-treated FG (AMK-FG) polyurethane grafts were implanted subcutaneously in the anterior abdominal region of Sprague-Dawley rats, AMK concentrations in tissues surrounding the implantation sites were compared over time with concentrations at the same sites in rats given an intravenous injection of AMK (4.0 mg) . In the injection group, AMK concentrations in serum were detectable only for 4 h, whereas AMK released from AMK-FG grafts remained detectable over 24 h . Until 4 h after implantation, AMK concentrations in tissues near implantation sites were significantly higher in the AMK-FG graft group than in the injection group; peak local concentrations during that time were 210 times higher for the AMK-FG graft group than for the injection group . Areas under the tissue concentration-time curve (AUC) for AMK were 171 microg x h/g and 1.35 microg x h/g in the AMK-FG graft and injection groups, respectively . FG therefore was considered to control release of AMK and to maintain a high AMK concentration in tissues surrounding the implantation site . Thus, AMK-FG polyurethane graft delivery may be useful in preventing local infection by local delivery of AMK. Clin Infect Dis, 2004 Jun 1, 38(11), 1538 - 44 Epub 2004 May 05. Aminoglycoside toxicity: daily versus thrice-weekly dosing for treatment of mycobacterial diseases; Peloquin CA et al.; Aminoglycoside use is limited by ototoxicity and nephrotoxicity . This study compared the incidences of toxicities associated with 2 recommended dosing regimens . Eighty-seven patients with tuberculosis or nontuberculous mycobacterial infections were prospectively randomized by drug to receive 15 mg/kg per day or 25 mg/kg 3 times per week of intravenous streptomycin, kanamycin, or amikacin . Doses were adjusted to achieve target serum concentrations . The size of the dosage and the frequency of administration were not associated with the incidences of ototoxicity (hearing loss determined by audiogram), vestibular toxicity (determined by the findings of a physical examination), or nephrotoxicity (determined by elevated serum creatinine levels) . Risk of ototoxicity (found in 32 {37%} of the patients) was associated with older age and with a larger cumulative dose received . Vestibular toxicity (found in 8 {9%} of the patients) usually resolved, and nephrotoxicity (found in 13 {15%} of the patients) was mild and reversible in all cases . Subjective changes in hearing or balance did not correlate with objective findings . Streptomycin, kanamycin, and amikacin can be administered either daily or 3 times weekly without affecting the likelihood of toxicity. Acta Paediatr, 2004 Mar, 93(3), 356 - 60 Evaluation of an amikacin loading dose for nosocomial infections in very low birthweight infants; Berger A et al.; AIM: To develop a simplified amikacin dosage regimen for nosocomial infections in preterm infants including a loading dose in order to achieve therapeutic Maximum Serum Concentrations early in the course of therapy . METHODS: Open, non-comparative study during November 2000 to April 2001 . The modified amikacin dosing and monitoring protocol included a loading dose of 10 mg/kg in the first week of life, followed by a maintenance regimen of 7.5 mg/kg every 24 h . After the first week of life the corresponding doses were 17 mg/kg (loading) and 15 mg/kg (maintenance) . A peak level was measured 30 min after the second dose, a trough level immediately before the third dose . RESULTS: Twenty-five very low birthweight infants (median birthweight 739 g, median gestational age 25 wk) who had 34 episodes of amikacin treatment were included in the analysis . Median amikacin peak and trough values were 37.1 micromol/l and 6.3 micromol/l, respectively . Twenty-nine of all peak levels (85%) and 30 of all trough levels (88%) were within the targeted range of >35 micromol/l and <8.5 micromol/l, respectively . All patients with elevated trough levels were of extremely low birthweight and were born in the 24th week of gestation . Hearing evaluations were performed in 17 of 19 surviving infants at discharge home, all of which gave normal results . CONCLUSION: The new amikacin dosing protocol yielded targeted peak and trough concentrations in a high percentage of very low birthweight infants with nosocomial infection after the first week of life . Our simplified dosage regimen achieved acceptable serum concentrations in all birthweight and gestational age groups, with the exception of extremely low birthweight infants weighing less than 700 g and/or with a gestational age of 24 wk or less . Only limited information can be gained from our data regarding the use of amikacin during the first week of life. Mycoses, 2004 Apr, 47(3-4), 156 - 8 Protothecosis successfully treated with amikacin combined with tetracyclines; Zhao J et al.; Summary We report a case of protothecosis in an 18-year-old female student caused by Prototheca zopfii successfully treated with amikacin combined with tetracyclines . Zusammenfassung Es wird uber eine Protothecose, verursacht durch Prototheca zopfii, bei einer 18-jahrigen Studentin berichtet, die erfolgreich mit Amikacin in Kombination mit Tetracyclinen behandelt wurde. Z Geburtshilfe Neonatol, 2004 Feb, 208(1), 32 - 5 {Complicating neonatal Escherichia coli meningitis}; Sonntag J et al.; Neonatal Escherichia coli meningitis is a serious disease with high mortality and poor outcome . Ventriculitis, brain abscess and subdural empyema are frequent, with no homogeneous recommendations available for these complications . The case of a newborn infant who developed sepsis and meningitis caused by E . coli is presented . During intravenous treatment with ampicillin, cefotaxime and gentamycin in recommended doses, the patient developed severe subdural abscesses detected on MRI . After consequent antibiotic therapy over 2 months with fosfomycin, amikacin and meropenem the patient improved clinically and the abscesses regressed and disappeared without neurosurgical intervention . At the age of 6.5 months the infant is healthy and well developed . The conservative treatment of subdural abscesses complicating neonatal Escherichia coli meningitis without neurosurgical intervention is possible . The treatment of the individual case should be discussed between pediatrician and neurosurgeon. J Pharm Biomed Anal, 2004 Mar 10, 34(5), 1021 - 7 Selective kinetic determination of amikacin in serum using long-wavelength fluorimetry; Sanchez-Martinez ML et al.; A simple and rapid method for the determination of the antibiotic amikacin, involving the use of a long-wavelength fluorophor, namely indocyanine green, (ICG) is presented . The dye is oxidised by cerium(IV) in acidic medium, resulting in a sharp decrease of the fluorescence, but this fluorescence quenching is inhibited in the presence of amikacin, which can be ascribed to the formation of an ion pair between the fluorophor and the analyte . The initial rate of the system is monitored at lambda(ex): 765 nm and lambda(em): 812 nm as excitation and emission wavelengths, respectively, using the stopped-flow mixing technique, which makes the method applicable to automatic routine analysis . Each measurement is obtained in only 2-3s . The method presents a detection limit of 0.02 microg m1(-1) in standard solutions, which corresponds to 2.5 microg ml(-1) in serum samples . The precision is in the range 4.8-6% . The good selectivity of the method allows amikacin to be determined in the presence of other antibiotics, including other aminoglycoside antibiotics, in serum . The recoveries obtained from the analysis of different samples were in the range 89.4-104.7%. Ann Neurol, 2004 Mar, 55(3), 422 - 6 Readthrough of dystrophin stop codon mutations induced by aminoglycosides; Howard MT et al.; We report the translational readthrough levels induced by the aminoglycosides gentamicin, amikacin, tobramycin, and paromomycin for eight premature stop codon mutations identified in Duchenne's and Becker's muscular dystrophy patients . In a transient transfection reporter assay, aminoglycoside treatment results show that one stop codon mutation is suppressed significantly better (up to 10% stop codon readthrough) than the others; five show lower but statistically significant suppression (< 2% stop codon readthrough); and two appear refractory to aminoglycoside treatment . Readthrough levels do not substantially vary between different sources of gentamicin, and, for this set of mutations, the efficiency of termination at the premature stop codon mutation does not appear to correlate with disease severity. J Formos Med Assoc, 2003 Nov, 102(11), 805 - 7 Therapeutic keratectomy for Mycobacterium abscessus keratitis after LASIK; Sun YC et al.; We report successful treatment of a case of Mycobacterium abscessus keratitis after laser in situ keratomileusis (LASIK) with therapeutic lamellar keratectomy . A 34-year-old woman developed a 2 x 2 mm feathery infiltration within the interface inferior to the pupil margin with mild inflammation of the conjunctiva in her left eye 40 days after LASIK surgery . Bacterial culture from the infiltrates of the interface of the stromal bed revealed Mycobacterium abscessus . After combination antibiotic therapy including amikacin and ciprofoxacin was given for 6 weeks, infiltration persisted despite the development of necrosis in the flap tissue . Therapeutic lamellar keratectomy combined with flap removal was performed . No recurrence was found 1 year after the surgery . Therapeutic lamellar keratectomy with flap removal can provide an effective treatment modality for the management of post-LASIK Mycobacterium abscessus keratitis that is unresponsive to medical treatment. J Dermatol, 2003 Oct, 30(10), 742 - 7 Pulse therapy with amikacin and dapsone for the treatment of actinomycotic foot: a case report; Sharma N et al.; Actinomycetoma is a chronic disease caused by aerobic actinomycetes and affecting the skin, subcutaneous tissue, and bones . It causes significant morbidity and clinically manifests as abscesses and sinus/fistulae with or without granules . Early diagnosis is based on the color, size, histopathology of the granules; culture and metabolic studies are used for further species differentiation . Although sulfamethoxazole-trimethoprim alone or in combination with dapsone for a variable period of time are used as first line agents for treatment, slow response to the therapy and high relapse rates have led to increasing usage of alternative agents like gentamycin, amikacin and cefotaxime . We report a case of actinomycetoma foot who had complete treatment failure with a sulfamethoxazole-trimethoprim-dapsone combination and was successfully treated with combination therapy of amikacin and dapsone without any side effects. Arch Otolaryngol Head Neck Surg, 2003 Dec, 129(12), 1331 - 3 Reversible anosmia after amikacin therapy; Welge-Luessen A et al.; Olfactory disorders are among the rare adverse effects of antibiotic therapy . To date, olfactory losses or distortions have been reported after the use of doxycycline, amoxicillin, clarithromycin, roxithromycin, kanamycin sulfate, and streptomycin sulfate . We describe what we believe to be the first case of transient anosmia associated with the use of intravenous amikacin sulfate . The appearance of the disorder and its subsequent resolution were demonstrated by psychometric testing as well as by chemosensory evoked potentials . Based on the well-documented temporal course of the anosmia, there is a probable causal correlation between the administration of amikacin and the appearance of the olfactory disturbance . However, the exact pathogenesis of the anosmia is still a matter of conjecture. Shanghai Kou Qiang Yi Xue, 2003 Apr, 12(2), 96 - 8 {Analysis of parotid sialography and intervention in 78 cases of chronic pyogenic parotitis}; Mu BQ et al.; OBJECTIVE: To study the value of parotid sialography and intervention in the diagnosis and treatment of chronic pyogenic parotitis . METHODS: Undertake the technique of parotid sialography with 48% Lipiodol ultra-fluide (France) under X-ray upon 78 patients who were given systemic anti-infections and supporting treatments only with non-obvious-results, and classify all the cases into chronic obstructive (21 cases) and nonobstructive parotitis (57 cases) according to the results of sialography through microcatheter, then go on with bacterial culture and drug sensitivity test . Filling treatments were carried out on obstructive parotitis cases through the duct with mixed liquor consisting of 2% lidocanine, 1% methylviolet . In the same way, alpha-chymotrypsin, amikacin, lidocaine was used in nonobstructive cases . RESULTS: The cure rate of chronic obstructive parotitis was 80.95%, the cure rate of chronic nonobstructive parotitis was 87.72% . CONCLUSION: The method of parotid sialography and intervention in the diagnosis and treatment of chronic pyogenic parotitis is an effective way to treat chronic pyogenic parotitis. J Clin Pharm Ther, 2003 Oct, 28(5), 425 - 32 Application of artificial neural network modelling to identify severely ill patients whose aminoglycoside concentrations are likely to fall below therapeutic concentrations; Yamamura S et al.; OBJECTIVE: Identification of ICU patients whose concentrations are likely to fall below therapeutic concentrations using artificial neural network (ANN) modelling and individual patient physiologic data . METHOD: Data on indicators of disease severity and some physiologic data were collected from 89 ICU patients who received arbekacin (ABK) and 61 who received amikacin (AMK) . Three-layer ANN modelling and multivariate logistic regression analysis were used to predict the plasma concentrations of the aminoglycosides (ABK and AMK) in the severely ill patients . RESULTS: Predictive performance analysis showed that the sensitivity and specificity of ANN modelling was superior to multivariate logistic regression analysis . For accurate modelling, a predictable range should be inferred from the data structure before the analysis . Restriction of the predictable region, based on the data structure, increased predictive performance . CONCLUSION: ANN analysis was superior to multivariate logistic regression analysis in predicting which patients would have plasma concentrations lower than the minimum therapeutic concentration . To improve predictive performance, the predictable range should be inferred from the data structure before prediction . When applying ANN modelling in clinical settings, the predictive performance and predictable region should be investigated in detail to avoid the risk of harm to severely ill patients. J Am Vet Med Assoc, 2003 Nov 15, 223(10), 1469 - 74 Injection of corticosteroids, hyaluronate, and amikacin into the navicular bursa in horses with signs of navicular area pain unresponsive to other treatments: 25 cases (1999-2002); Dabareiner RM et al.; OBJECTIVE: To determine history, clinical and radiographic abnormalities, and outcome in horses with signs of navicular area pain unresponsive to corrective shoeing and systemic nonsteroidal anti-inflammatory drug administration that were treated with an injection of corticosteroids, sodium hyaluronate, and amikacin into the navicular bursa . DESIGN: Retrospective study . ANIMALS: 25 horses . PROCEDURE: Data collected from the medical records included signalment, history, horse use, severity and duration of lameness, shoeing regimen, results of diagnostic anesthesia, radiographic abnormalities, and outcome . RESULTS: 17 horses had bilateral forelimb lameness, 7 had unilateral forelimb lameness, and 1 had unilateral hind limb lameness . Mean duration of lameness was 9.2 months . All horses had been treated with corrective shoeing and nonsteroidal anti-inflammatory drugs for at least 6 months; 18 had previously been treated by injection of corticosteroids and sodium hyaluronate into the distal interphalangeal joint . Fourteen horses had mismatched front feet, and 21 horses had signs of pain in response to application of pressure over the central aspect of the frog . Palmar digital nerve anesthesia resulted in substantial improvement in or resolution of the lameness in all horses . Twenty horses (80%) were sound and returned to intended activities 2 weeks after navicular bursa treatment; mean duration of soundness was 4.6 months . Two horses that received numerous navicular bursa injections had a rupture of the deep digital flexor tendon at the level of the pastern region . CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that navicular bursa treatment may provide temporary improvement in horses with signs of chronic navicular area pain that fail to respond to other treatments. Indian J Ophthalmol, 2003 Sep, 51(3), 263 - 5 Interface keratitis due to Mycobacterium fortuitum following laser in situ keratomileusis; Fogla R et al.; A case of unilateral interface keratitis due to Mycobacterium fortuitum following simultaneous bilateral LASIK procedure for low myopia is reported . Excimer phototherapeutic keratectomy was performed to the stromal bed to reduce the infective load . Intensive topical therapy with topical amikacin and ciprofloxacin resulted in resolution of the keratitis. Antimicrob Agents Chemother, 2003 Oct, 47(10), 3296 - 304 Inhibition of aminoglycoside 6'-N-acetyltransferase type Ib-mediated amikacin resistance by antisense oligodeoxynucleotides; Sarno R et al.; Amikacin has been very useful in the treatment of infections caused by multiresistant bacteria because it is refractory to the actions of most modifying enzymes . However, the spread of AAC(6')-I-type acetyltransferases, enzymes capable of catalyzing inactivation of amikacin, has rendered this antibiotic all but useless in some parts of the world . The aminoglycoside 6'-N-acetyltransferase type Ib, which is coded for by the aac(6')-Ib gene, mediates resistance to amikacin and other aminoglycosides . RNase H mapping and computer prediction of the secondary structure led to the identification of five regions accessible for interaction with antisense oligodeoxynucleotides in the aac(6')-Ib mRNA . Oligodeoxynucleotides targeting these regions could bind to native mRNA with different efficiencies and mediated RNase H digestion . Selected oligodeoxynucleotides inhibited AAC(6')-Ib synthesis in cell-free coupled transcription-translation assays . After their introduction into an Escherichia coli strain harboring aac(6')-Ib by electroporation, some of these oligodeoxynucleotides decreased the level of resistance to amikacin . Our results indicate that use of antisense compounds could be a viable strategy to preserve the efficacies of existing antibiotics to which bacteria are becoming increasingly resistant. Eur J Drug Metab Pharmacokinet, 2003 Jan-Mar, 28(1), 1 - 6 Relative pharmacokinetics of three amikacin brands in onco-hemotologic pediatric patients experiencing febrile neutropeina; Jamshaid M et al.; Three commercially available brands of amikacin were investigated in a parallel study design for the assessment of comparative pharmacokinetics in pediatric oncology patients with chemotherapy-induced neutropenic febrile episode . Amikacin concentration in serum samples was determined by fluorescence polarization immunoassay method using Abbott TDx system . Computer software, PK II was used for computation of pharmacokinetic parameters of amikacin . The serum concentration of all brands nonsignificantly (p > 0.05) varied at all time points, except at 1 and 2 hrs post dosing . At 1 hr post dosing, the serum concentration of brand II varied from rest of two brands . Whereas at 2 hr following I/V infusion, brands II and I were statistically different . Highest serum concentration of 38.69 +/- 1.45 microg/ml was observed in case of brand III while brands I and II showed lower but not significantly different serum concentration values, i.e., 36.30 +/- 1.65 and 37.89 +/- 1.32 microg/ml, respectively when compared with brand I . The other pharmacokinetic parameters of 3 brands found to have non-significant difference (P < 0.05) except, t(1/2)alpha and Cl of brands I and II that deviated statistically significant (p < 0.01) . The relative bioavailability of brand II and III as compared with brand I, considered as standard 86.17 and 96.86%, respectively falls within the accepted limits of +/- 20% required for the bioequivalence of any two brands . Based upon findings of the present study, all these brands may be used interchangeably in oncology patients . Further studies, however are needed to determine whether the statistically elevated Cl value in brand II is of any clinical significance. Braz J Infect Dis, 2003 Apr, 7(2), 111 - 20 Evaluation of ticarcillin/clavulanic acid versus ceftriaxone plus amikacin for fever and neutropenia in pediatric patients with leukemia and lymphoma; Petrilli AS et al.; BACKGROUND: The empirical use of antibiotic treatments is widely accepted as a means to treat cancer patients in chemotherapy who have fever and neutropenia . Intravenous monotherapy, with broad spectrum antibiotics, of patients with a high risk of complications is a possible alternative . METHODS: We conducted a prospective open-label, randomized study of patients with lymphoma or leukemia who had fever and neutropenia during chemotherapy . Patients received either monotherapy with ticarcillin/clavulanic acid (T) or ceftriaxone plus amikacin (C+A) . RESULTS: Seventy patients who presented 136 episodes were evaluated, 68 in each arm of the study . The mean neutrophil counts at admission were 217cells/mm(3) (T) and 201cells/mm(3) (C+A) . The mean duration of neutropenia was 8.7 days (T) and 7.6 days (C+A) . Treatment was successful without the need for modifications in 71% of the episodes in the T group and 81% in the C+A group (p=0.23) . Treatment was considered to have failed because of death in two episodes (3%) in the T group and three episodes (4%) in the C+A group, and because of a change in the drug applied in one episode in the T group and two episodes in the C+A group . Overall success was 96% (T) and 93% (C+A) . Adverse events that occurred in group T were not related to the drugs used in this study . CONCLUSION: In pediatric and adolescent patients with leukemia or lymphoma, who presented with fever and neutropenia, during chemotherapy, ticarcillin/clavulanic acid was as successful as the combination of ceftriaxone plus amikacin . It should be considered an appropriate option for this group of patients at high risk for infections. Adv Drug Deliv Rev, 2003 Sep 12, 55(9), 1233 - 51 Clinical application of artificial neural network (ANN) modeling to predict pharmacokinetic parameters of severely ill patients; Yamamura S; Artificial neural network (ANN) modeling was used to evaluate the pharmacokinetics of aminoglycosides (arbekacin sulfate and amikacin sulfate) in severely ill patients . The plasma level was predicted by ANN modeling using parameters related to the severity of the patient's condition and the predictive performance was shown to be better than could be achieved using multiple regression analysis . These results indicate that there is a non-linear relationship between the pharmacokinetics of aminoglycosides and the severity of the patient's condition, and this should be taken into account when determining the dose for severely ill patients . Patients whose plasma levels are likely to fall below the effective level can be identified by ANN modeling with a predictive sensitivity and specificity superior to multivariate logistic regression analysis . The predictable range should be inferred from the data structure before the modeling in order to improve the predictive performance . The volume of distribution (Vd) in the normal range was weakly predicted by ANN modeling from the patients' data . Prediction of clearance by ANN modeling was poorer than that obtained from serum creatinine concentration by linear regression analysis . These results suggest that the input-output relationship (linear or non-linear) should be taken into account in selecting the modeling method . Linear modeling can give better predictive performance for linear systems and non-linear modeling can give better predictive performance for non-linear systems . In general, the performance of ANN modeling was superior to linear modeling for PK/PD prediction . For accurate modeling, a predictable range should be inferred from the data structure before the analysis . Restriction of the predictable region, as determined from the data structure, produced an increase in prediction performance . When applying ANN modeling in clinical settings, the predictive performance and predictable region should be investigated in detail to avoid the risk of harm to severely ill patients. J Pediatr Nurs, 2003 Aug, 18(4), 287 - 92 Life span of peripheral intravenous cannula in a neonatal intensive care unit of a developing country; Gupta P et al.; The use of peripheral intravenous cannulas (IVCs) in the care of sick newborns is a common practice . IVCs, priced five times higher than conventional steel needles, can be more cost effective if insight is available on the variables affecting their life span in situ . The present report summarizes the efforts made to ascertain these factors in a neonatal intensive care unit (NICU) of a developing country . A total of 186 peripheral IVCs (24-gauge teflon) were used in 78 newborns amounting to 7,583 hours of IV therapy (mean, 40.8 hr per cannula; range, 1-136 hr) . Of these, 25 cannulas were removed selectively and 84, 50, 17, and 10 were removed for swelling, dislodgement/leakage, blockage, and local erythema, respectively . The median survival time of IVC as expressed by Kaplan-Meir survival analysis was 40 hours (SE, 2.49; 95% confidence interval, 35.12-44.88) . Birth weight, gestation, application of splint, fluid and glucose infusion rate, site of cannulation, and administration of ampicillin, gentamicin, amikacin, vancomycin, phenobarbitone, blood products, or calcium gluconate did not influence the median life span of IVCs . Children receiving cefotaxime had a significantly lower median survival time as compared with those not receiving it (36 vs 47 hours, p =.007) . Median survival time of IVCs in our set-up was comparable with those in developed countries and was not governed by the cannula or patient variables . Cefotaxime use led to decreased survival of IVCs; though this effect appeared to be related to the mode of administration rather than to the drug per se. Ophthalmologe, 2003 Jul, 100(7), 550 - 3 Epub 2003 Jun 26. {Diagnosis and treatment of mycobacterial keratitis following LASIK . Case report and review of the literature}; Holzer MP et al.; BACKGROUND: Mycobacterial keratitis is a rare complication following LASIK but can lead to an extremely unfavourable outcome . The diagnosis and treatment is often delayed due to confusion with other entities including diffuse lamellar keratitis and poor clinical outcomes with flap amputation and/or keratoplasty are often the case . PATIENT AND METHODS: We report the results of LASIK in a 51-year-old woman with subsequent early-diagnosed mycobacterial keratitis and compared this case to treatments and outcomes reported in the literature . RESULTS: The patient presented 10 days following LASIK with a white focal infiltrate in the stromal interface . The flap was lifted and cultures from the stromal bed and the reverse of the flap were obtained and the interface irrigated . The patient was treated with topical antibiotics (ciprofloxacin 0.3%, amikacin 2.5%, clarithromycin 40 mg/ml and tobramycin 15 mg/ml) for 8 weeks and at the most recent follow-up she had a visual acuity of 1.25 . CONCLUSION: In a large number of published cases in the literature the flap had to be amputated and/or corneal transplants were necessary . Early diagnosis and treatment however, are essential to successfully treat post-LASIK keratitis . Therefore the patients should be followed up carefully in the early postoperative period. Int J Pediatr Otorhinolaryngol, 2003 Sep, 67(9), 1019 - 21 Otogenic cerebral venous infarction: a rare complication of acute otitis media; Ozer E et al.; A case of cerebral venous infarction (CVI) as a complication of acute otitis media (AOM) was presented in a 16-month-old male patient . The patient admitted with AOM in the right ear, ipsilateral facial paralysis and contralateral hemiplegia . Computerized tomography of the brain showed low density areas involving both the cortex and subcortical white matter in the right frontoparietal region, and there were patchy and multifocal enhancing areas with intravenous contrast enhancement . These findings disclosed the diagnosis of venous infarctions involving the superficial cortical veins on the right side . Complete recovery was achieved with 2 weeks of sulbactam-ampicilline, amikacin and prednisolone treatment . Although it is rather rare, CVI should also be remembered among the otogenic intracranial complications. J Pineal Res, 2003 Sep, 35(2), 85 - 90 Amikacin-induced acute renal injury in rats: protective role of melatonin; Parlakpinar H et al.; It is well established that some agents such as aminoglycosides generate free oxygen radicals, leading to an increased oxireductase production, which in turn increases tissue toxicity . The aim of this study is to test whether melatonin, the chief secretory product of the pineal gland and a highly effective antioxidant and free radical scavenger, reduces the nephrotoxicity caused by amikacin (AK) . Herein, we investigated the physiologic and pharmacological role of melatonin in influencing AK-induced nephrotoxicity . For this, pinealectomized (Px) and sham operated (non-Px) rats were used . Both AK and melatonin were administered to all groups . We investigated the effects of melatonin on AK-induced changes in levels of malondialdehyde (MDA), a lipid peroxidation product, glutathione (GSH), an antioxidant whose levels are influenced by oxidative stress, and blood urea nitrogen (BUN) and serum creatine (Cr) levels . Morphologic changes in the kidney were also examined by using light microscopy . MDA levels were found to be higher in Px than in non-Px AK-treated animals . Melatonin administration to Px rats reduced MDA levels . In relative to non-Px rats, Px animals treated with AK had significantly lower GSH concentrations while melatonin administration elevated GSH levels in the kidney; however, this stimulatory effect of melatonin was not observed in non-Px AK-treated rats . Treatment with AK alone resulted in significantly higher plasma Cr and BUN levels . Repeated administration of melatonin prevented the AK-induced elevation of plasma Cr and BUN levels . Morphologic damage to renal tubules as a result of AK was more severe in the renal cortex than in the medulla . The damage to the kidney induced by AK was reversed by melatonin in the Px rats . In conclusion, these results show that physiologic melatonin concentrations are important in reducing AK-induced renal damage, while pharmacologic concentrations of melatonin did not add to the beneficial effect. J Chemother, 2003 Jun, 15(3), 253 - 9 Ticarcillin-clavulanic acid plus amikacin versus ceftazidime plus amikacin in the empirical treatment of fever in acute leukemia: a prospective randomized trial; Fanci R et al.; We evaluated the efficacy of ticarcillin-clavulanic acid plus amikacin (TCA) with ceftazidime plus amikacin (CFA) as empiric therapy of fever in acute leukemia in a total of 127 episodes . The overall success rate of the therapy (survival) was 93% in TCA group and 92% in CFA group . Success without therapy modifications (afebrile at 72 hours) was 39% for TCA, 31% for CFA; success with modifications was 55% and 61% respectively . Failure (death due to documented or presumed infection) was 6% for TCA and 8% for CFA . Differences were not statistically significant . The success without modifications was higher in the group of patients with fever of unknown origin (FUO) than in documented infections (DI), mainly with CFA . No differences were documented in the resistance rate and in clinical outcome during severe neutropenia (ANC <100 microl) . In our experience TCA is as effective as CFA as first-line treatment in severe neutropenic patients with acute leukemia, although in both regimens patients with DI are likely to require modifications in treatment. J Am Acad Audiol, 2003 Apr, 14(3), 134 - 43 Antioxidant enzyme levels inversely covary with hearing loss after amikacin treatment; Klemens JJ et al.; This study's purpose was to determine if a correlation exists between cochlear antioxidant activity changes and auditory function after induction of amino-glycoside (AG) ototoxicity . Two groups of five 250-350 g albino guinea pigs served as subjects . For 28 days, albino guinea pigs were administered either 200 mg/kg/day amikacin, or saline subcutaneously . Auditory brainstem response testing was performed prior to the first injection and again before sacrifice, 28 days later . Cochleae were harvested and superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase activities and malondialdehyde levels were measured . All antioxidant enzymes had significantly lower activity in the amikacin group (p < or = 0.05) than in the control group . The difference in cochlear antioxidant enzyme activity between groups inversely correlated significantly with the change in ABR thresholds . The greatest correlation was for the high frequencies, which are most affected by aminoglycosides . This study demonstrates that antioxidant enzyme activity and amikacin-induced hearing loss significantly covary. J Indian Med Assoc, 2003 Jan, 101(1), 16 - 7, 23 Treating tuberculous lymphadenitis--ifs and buts; Mukherjee S et al.; Treatment of tuberculous (TB) lymphadenitis is virtually a specialist's job due to multiple aetiopathological factors . Diagnosis is difficult often requiring biopsy for several times . Treatment monitoring is more complex due to peculiar behaviour of TB lymph nodes . Situation has become worse due to sharp increase in the incidence of atypical mycobacteria . Due to profound improvement in antibiotic action, life-expectancy of immuno-compromised patients has also increased along with increased incidence of atypical mycobacteria in them . Clarithromycin, ethambutol, rifabutin and amikacin seem to act best on atypical mycobacteria-induced lymphadenitis . Along with rise of multi-drug resistance (MDR), drug-resistant TB lymphadenitis cases are also on the rise. Yonsei Med J, 2003 Jun 30, 44(3), 517 - 22 Comparative vestibulotoxicity of different aminoglycosides in the Guinea pigs; Selimoglu E et al.; The histopathological alterations in the vestibule due to aminoglycosides are well defined . Although there are reports comparing the vestibulotoxic effects of the many aminoglycosides, this is the first study to compare the effects of the most commonly used aminoglycosides i.e., streptomycin, gentamicin, amikacin and netilmicin administered both transtympanically and systemically . The transtympanic and systemic administration of each aminoglycoside caused similar histopathological alterations in the vestibule . The most severe degeneration in the cristae ampullaris, utriculus and sacculus was observed after streptomycine administration . The severity of the vestibular damage in terms of magnitude was in the order of streptomycine, gentamicin, amikacin, and netilmicin. J Perinat Med, 2003, 31(3), 237 - 41 Amikacin alters auditory brainstem conduction time in newborns; Poblano A et al.; The purpose of this paper was to describe whether there are some relationships between amikacin serum levels and central conduction time in brainstem auditory evoked potentials (BAEP) within therapeutic range levels in newborns as index of drug toxicity in brainstem auditory centers in neonatally exposed infants . We performed a cross-sectional study to compare BAEP from 35 infants under amikacin administration and 24 control infants; both examinations were blinded to investigators . Bivariate and partial correlations were calculated between amikacin and BAEP measurements in treated infants . Amikacin determinations were within therapeutic levels . No clinical alterations in BAEP were found and no differences between amikacin-treated and control infants were found . Significant positive Pearson correlation between latency of I-III interwaves interval and amikacin Cmin serum levels was found and was present when calculations were controlled by partial correlations for gestational age at birth and Apgar score at 5 min . The findings suggest that increased amikacin levels in newborns are related to increased latencies in I-III interwave interval in infants, which may be an early index of brainstem effects of subclinical neurotoxicity of amikacin. J Antimicrob Chemother, 2003 Jul, 52(1), 78 - 82 Epub 2003 Jun 12. Evaluation of commercial assays for vancomycin and aminoglycosides in serum: a comparison of accuracy and precision based on external quality assessment; Wilson JF et al.; OBJECTIVE: To compare the accuracy and precision of commercial assay techniques in the measurement of gentamicin, tobramycin, amikacin, netilmicin and vancomycin in serum . METHODS: Data from the measurement of 40 external quality assessment samples from 358 laboratories providing a therapeutic drug monitoring service were analysed . RESULTS: Significant differences between techniques in accuracy and precision were observed for all drugs . Coefficients of variation ranged from 4.1% to 9.8% for the aminoglycosides and from 6.7% to 11.7% for vancomycin . The percentage difference in measurements from the weighed-in drug concentration ranged from -10.1% to +4.0% for the aminoglycosides and from -3.5% to +5.7% for vancomycin . The Dade Behring Emit immunoassay was notable in producing significantly more outliers (>4 S.D . from the weighed-in concentration) than other techniques in the measurement of gentamicin, amikacin and vancomycin . CONCLUSIONS: All assays performed to a satisfactory standard for measurement in non-renal patients, but none met the more stringent standards desirable for monitoring patients with renal impairment. Graefes Arch Clin Exp Ophthalmol, 2003 Jun, 241(6), 478 - 83 Epub 2003 May 14. Pars plana vitrectomy with or without silicone oil endotamponade in post-traumatic endophthalmitis; Azad R et al.; BACKGROUND: Results of core vitrectomy in post-traumatic endophthalmitis are poor . Our initial results of complete vitrectomy with primary silicone oil endotamponade were promising . A comparative study of this procedure with conventional core vitrectomy was therefore carried out . METHODS: A prospective randomized controlled study of 24 consecutive cases of post-traumatic endophthalmitis was conducted . Patients were randomized into two groups in the absence of clinical improvement after primary tap and treatment with intravitreal vancomycin and amikacin: group 1 consisted of patients who underwent core vitrectomy alone, group 2 of patients who underwent complete vitrectomy with silicone oil endotamponade . All patients included in the study received intravenous antibiotics and underwent lensectomy . Patients were followed up 1, 2, 4 and 12 weeks postoperatively . In all patients of group 2, silicone oil was removed 6 weeks after primary surgery . The mean duration of follow-up was 112+/-55 days . RESULTS: Vision of 20/400 or better was obtained in 58.33% of cases (14/24) . Visual acuity of only one patient in group 1 was >or=20/200, compared with that of 58.3% of patients (7/12) in group 2 ( P=0.02) . Intra-operative retinal breaks were found in 50% (6/12) of the patients belonging to group 1, but did not affect the final visual outcome . In group 1, 33.33% (4/12) developed rhegmatogenous retinal detachment in the immediate post-operative period . Only one of these patients had useful final visual outcome after resurgery . CONCLUSION: Complete vitrectomy with primary silicone oil endotamponade is a useful treatment modality which improves the anatomical and functional results in post-traumatic endophthalmitis. Clin Pharmacokinet, 2003, 42(5), 493 - 500 Aminoglycoside dosages and nephrotoxicity: quantitative relationships; Rougier F et al.; OBJECTIVE: To develop a model that relates the probability of occurrence of nephrotoxicity to the cumulative area under the curve (AUC) of amikacin serum concentration . DESIGN AND PATIENTS: This was a retrospective study of two groups of patients in whom nephrotoxicity was observed after administration of amikacin . The first group consisted of patients treated with once-daily administration (ODA) {n = 13} . The second group consisted of patients treated with twice-daily administration (TDA) {n = 22} . MAIN OUTCOME MEASURES: The probability of nephrotoxicity occurrence . RESULTS: The model is a powerful tool to represent and describe the influence of the dosage regimen on aminoglycoside nephrotoxicity . The onset of nephrotoxicity is delayed in the ODA group (p = 0.01) for the same total daily dose among the two groups . The cumulative serum AUC values at onset of nephrotoxicity were greater for the ODA group (p = 0.029) . In addition, for the same probability of nephrotoxicity occurrence (50%), the cumulative AUC for the ODA dosage regimen is 2 613 mg . h/L versus only 1 521 mg . h/L for the TDA dosage regimen . The difference in nephrotoxicity between ODA and TDA is greatest for a cumulative AUC of 2 495 mg . h/L, which corresponds to standard therapy with amikacin 900 mg/day during a 7-day period, i.e . 15 mg/kg/day for a 60kg patient with normal renal function (initial creatinine clearance >80 mL/min) . For an AUC above 2 495 mg . h/L, the difference in nephrotoxicity decreases slowly to zero . This result means that ODA is especially justified when the treatment is administered over a short duration, i.e . less than 7 days . CONCLUSIONS: The utility of selecting ODA in order to obtain less nephrotoxicity in comparison with TDA is therefore not established when the treatment is prolonged . In clinical use, the choice of the dosage regimen is not clear-cut, and both expected efficacy and expected toxicity must be taken into account in order to obtain an overall optimisation of each patient's therapy. Rev Lat Am Enfermagem, 2003 Jan-Feb, 11(1), 88 - 95 {Drug therapy orphans: the administration of intravenous drugs in hospitalized children}; Peterlini MA et al.; Descriptive study, developed at a general university hospital that aimed at verifying the number and types of i.v . drugs administered to children, the adequacy of their pharmacological presentation for pediatric use and the estimated costs of some drugs administration . In a period of 30 days, 8,245 drug doses were administered, with an average of 274.83 doses a day, and a yearly estimation of 98.940 . The most used drugs were methylprednisolone, vancomycin, furosemide, ranitidine, penicillin, amikacin, midazolam, fentanyl, ceftriaxone, cephalothin, oxacillin, ampicillin and metronidazole . None of the 41 different drugs had a pediatric presentation, what caused, in some cases, more manipulation during the preparation, increasing the contamination risks and the loss of stability . Authors observed that the lack of pediatric presentation generated an increase in care costs; as an example, considering the prescription of a child in the period after surgery, with an estimated time of hospitalization of 5 days, the daily therapy costs were of U$6.71, and U$39.52 of drugs were thrown away as they exceeded the children therapeutic needs. Lupus, 2003, 12(4), 312 - 6 Mycobacterium avium complex-associated hemophagocytic syndrome in systemic lupus erythematosus patient: report of one case; Yang WK et al.; Hemophagocytic syndrome (HPS) in systemic lupus erythematosus(SLE) patients has not commonly been reported . In this case study, we report the first case of Mycobacterium avium complex (MAC)-associated hemophagocytic syndrome in a patient with systemic lupus erythematosus (SLE) . This SLE patient, a 15-year-old girl, had been on a high dose of prednisolone (> 0.5mg/kg/day) for more than 3 years . She presented with a spiking fever, hepatosplenomegaly, pancytopenia, hyperferritinemia and adult respiratory distress syndrome . Bone marrow examination revealed hemophagocytosis as well as non-caseating granulomatosis . There was no indication of SLE fare-up . She responded poorly to initial treatment with methyl-prednisolone, intravenous immumoglobulin, etoposide, and drugs for Mycobacterium tuberculosis including rifampin, ethambutol, isoniazid and pyramide . However, gastric lavage culture revealed MAC . Following treatment with clarithromycin, ciprofloxacin and amikacin, her condition gradually improved and she was discharged 3 months after admission . In SLE patients with pancytopenia and hyperferritinemia, MAC-associated HPS should be considered in the differential diagnosis. Chemotherapy, 2003 May, 49(1-2), 24 - 6 In vitro activity of azithromycin in combination with amikacin, ceftazidime, ciprofloxacin or imipenem against clinical isolates of Acinobacter baumannii; Fernandez-Cuenca F et al.; The in vitro activity of the two-drug combinations of azithromycin with amikacin, ceftazidime, ciprofloxacin or imipenem against five clonally unrelated strains of Acinobacter baumannii were evaluated . Synergy studies were performed by the checkerboard microtiter method . The fractional inhibitory concentration (FIC) index was calculated for each drug combination . None of the four combinations tested was antagonistic . The combination of azithromycin and ceftazidime was synergistic (FIC index <or=0.5) for one strain and partially synergistic (FIC index 0.75) for another strain . An additive effect (FIC index = 1) was observed for the combinations of azithromycin with imipenem (two strains) or ceftazidime (one strain) . The activities of the other combinations were indifferent (FIC index range from 1.5 to 2.5) . It is concluded that azithromycin combined with ceftazidime has moderate synergistic activity against some multiresistant A . baumannii . Infection, 2003 Mar, 31(2), 112 - 4 Disseminated Nocardia asteroides infection in an immunocompetent woman following an arm injury; Benes J et al.; A case of disseminated infection with Nocardia asteroides in a 55-year-old immunocompetent woman after mild trauma to the arm is reported . Secondary dissemination was identified in the skin, right kidney, liver, peritoneal cavity, lungs and thigh . The patient was successfully treated with surgical drainage and a 9-week course of antibiotics including cefotaxime, amikacin, chloramphenicol, trimethoprim/sulfamethoxazole (TMP/SMX) and doxycycline . The administration of TMP/SMX in combination with doxycycline was clinically beneficial despite in vitro resistance. J Clin Microbiol, 2003 Apr, 41(4), 1705 - 9 Nocardia veterana, a new emerging pathogen; Pottumarthy S et al.; Nocardia veterana is a newly described species named after the veteran's hospital where it was first isolated . This initial type strain was not thought to be clinically significant . We describe three cases of pulmonary disease attributable to N . veterana: two cases in patients presenting with multiple pulmonary nodules in a setting of immunocompromise and one case of exacerbation of chronic pulmonary disease . The isolates were susceptible to ampicillin, imipenem, gentamicin, amikacin, and trimethoprim-sulfamethoxazole and had reduced susceptibilities to ceftriaxone, cefotaxime, minocycline, and ciprofloxacin . The MICs of amoxicillin-clavulanate were higher than that of ampicillin alone, and the bacteria produced a beta-lactamase detectable only after induction with clavulanic acid . Phenotypically, the isolates could not be characterized beyond the Nocardia genus level . All three isolates were definitively identified as N . veterana by PCR and sequencing of the 16S rRNA gene . On the basis of their susceptibility and restriction enzyme analysis profiles, our findings indicate that they could potentially be misidentified as N . nova . These cases illustrate the pathogenic potential of this newly described species and emphasize the importance of accurate identification of Nocardia isolates to the species level by integrated use of phenotypic and genotypic methods. Klin Monatsbl Augenheilkd, 2003 Mar, 220(3), 204 - 6 Endogenous pneumococcal endophthalmitis followed by pneumococcal-induced uveitis; Nessi F et al.; BACKGROUND: We describe the case of a fulminant bilateral endophthalmitis occurring in a patient, who had 9 years earlier a splenectomy for an idiopathic thrombocytopenic purpura . HISTORY AND SIGNS: A 40-year-old woman, back from a trip to Morocco, presented with high fever, rapid decrease in visual acuity and loss of consciousness . Medical examination revealed a pneumococcal meningitis and bilateral endophthalmitis . THERAPY AND OUTCOME: Endophthalmitis was treated with local and intravitreal antibiotics injections (vancomycin and amikacin) . Repeated parabulbar betamethasone injections were performed . Intravenous (iv) methylprednisolone pulses were followed by oral steroid therapy while systemic antibiotics were given (ceftriaxone and vancomycin) . In spite of this therapy, fundus examination was impossible because the anterior chamber was filled with fibrin . A cataract developed with severe vitritis and we could observe a progressive narrowing of the anterior chamber . The patient underwent a bilateral vitrectomy and lensectomy . The retina had no lesion . No bacteria were found in the vitreous culture . Evolution was characterized by an increased ocular pressure due to anterior synechiae . Visual acuity remained under 1/10 . The severe ocular inflammation could be the result of a mixed mechanism including an infectious followed by a severe immune response against bacterial components . CONCLUSIONS: This case report is rare . To our knowledge, only 3 similar cases have been reported in the literature. J Fr Ophtalmol, 2003 Feb, 26(2), 175 - 81 {Nontuberculous mycobacterial keratitis: report of two cases causing infectious crystalline keratopathy}; Labalette P et al.; We report two cases of nontuberculous mycobacterial keratitis, occurring after corneal trauma with superficial foreign body and after perforating keratoplasty for alkali burn, respectively . Patients initially presented with indolent white corneal infiltrates, which did not respond to topical treatment . Both secondarily developed infectious crystalline keratopathy with unequal intensity . In the first case, the excised flap of lamellar keratectomy was cultured, allowing identification of Mycobacterium abscessus . Mycobacterium chelonae was isolated from a corneal biopsy in the second case . The clinical course showed poor response to antibiotic therapy consisting of ciprofloxacin and amikacin drops in conjunction with a new-generation oral macrolide . Corneal infection recurred after lamellar keratectomy in the first patient . Topical corticosteroid interruption burst corneal inflammation and induced stromal necrosis in the other patient . These intractable mycobacterial infections were finally controlled with penetrating keratoplasty . Our data suggest that a rapidly growing mycobacteria culture is required when clinical presentation consists of chronic bacterial keratitis or infectious crystalline keratopathy. J Antimicrob Chemother, 2003 Apr, 51(4), 803 - 11 Epub 2003 Mar 13. Role of the acetyltransferase AAC(6')-Iz modifying enzyme in aminoglycoside resistance in Stenotrophomonas maltophilia; Li XZ et al.; Stenotrophomonas maltophilia is an emerging nosocomial pathogen that displays high-level intrinsic resistance to multiple antibiotics including aminoglycosides . A gene {aac(6')-Iz} encoding an aminoglycoside-modifying enzyme, AAC(6')-Iz acetyltransferase, was recently cloned and sequenced in S . maltophilia, but its importance with respect to aminoglycoside resistance in this organism was not determined . Using a homologous gene replacement approach, mutants carrying unmarked chromosomal deletions of the aac(6')-Iz gene were constructed in wild-type and in vitro-selected aminoglycoside-resistant S . maltophilia . AAC(6')-Iz-deficient mutants derived from both wild-type and aminoglycoside-resistant strains displayed an increase in susceptibility to amikacin, netilmicin, sisomicin and tobramycin (4- to 32-fold decrease in MICs), known substrates for AAC(6')-I enzymes . The cloned aac(6')-Iz gene restored the aminoglycoside resistance of the aac(6')-Iz mutants, and could also confer aminoglycoside resistance upon Escherichia coli . To assess the significance of the aac(6')-Iz gene with respect to the aminoglycoside resistance of clinical strains, its distribution was assessed in 65 clinical isolates from two hospitals . Using PCR, Southern hybridization, RT-PCR and/or nucleotide sequencing, the aac(6')-Iz gene was identified in 57% of the isolates . Susceptibility tests indicated a good correlation between the presence of the aac(6')-Iz gene and the resistance to tobramycin, netilmicin and sisomicin in these strains . These results indicate that the aac(6')-Iz gene is an important contributor to aminoglycoside resistance in clinical strains of S . maltophilia, particularly to tobramycin. Ann Trop Paediatr, 2003 Mar, 23(1), 75 - 8 Disseminated nocardiosis in an immunocompetent child; Singh NP et al.; We report a 2-month-old child with a disseminated Nocardia farcinica infection that presented with suppurative lymphatic abscess . The child did not have any predisposing factors and responded to treatment with co-trimoxazole and amikacin . This is first case report of disseminated nocardiosis caused by Nocardia farcinica in an immunocompetent child. Bioorg Med Chem Lett, 2003 Mar 24, 13(6), 993 - 6 Inhibition of bacterial IF2 binding to fMet-tRNA((fMet)) by aminoglycosides; Evans JM et al.; Screening for inhibitors of bacterial protein synthesis Initiation Factor 2 (IF2) binding to N-formyl-Methionyl-transfer RNA (fMet-tRNA((fMet))) identified a series of aminoglycosides, that included amikacin and kanamycin A1, as inhibitors of this interaction . Subsequent testing revealed that aminoglycosides displayed a wide range of inhibitory activity . However, the failure of these compounds to completely inhibit binding of IF2 to fMet-tRNA((fMet)), the known ability of aminoglycosides to bind RNA, and the ability of the aminoglycosides to displace PicoGreen bound to fMet-tRNA((fMet)) suggest these compounds act by binding fMet-tRNA((fMet)) . This hypothesis is further supported by isothermal denaturation experiments that failed to show any interaction between the IF2 protein and the aminoglycosides. Fa Yi Xue Za Zhi, 2002 Aug, 18(3), 132 - 4, 136 {Tryptase and fatal anaphylaxic reaction}; Shen YW et al.; OBJECTIVE: To investigate the relationship between tryptase in serum and anaphylaxis . METHODS: The concentrations of tryptase in the sera of heart blood in three persons died from anaphylaxis shock were detected by ELISA . The first sample was obtained from a man, aged 38, died of injecting Amikacin . The second sample was obtained from a man, aged 42, died of injecting Cephradine . The third sample was from a woman, aged 39, died of injecting Lincomycin . All samples were stored in -20 degrees C . RESULTS: The concentrations of tryptase in sera were 52 ng/ml, 121 ng/ml and 0.73 ng/ml . It was unknown why the concentration of tryptase in the third sample was normal . CONCLUTION: In fetal anaphylaxia reaction tryptase measurement is a useful indicator, but the diagnosis is not to be based on the test alone. Yan Ke Xue Bao, 1998 Sep, 14(3), 156 - 63 Mycobacterium chelonei keratitis: report of a case and review of the literature; Wong AK et al.; BACKGROUND: Mycobacterium (M) chelonei keratitis is a rare opportunistic eye infection that can cause significant morbidity when not being treated properly . The first case was documented by Gangadharam et al in 1978 and since then, a total of 49 cases were reported in the literature . One alarming fact is that more than 50% of cases were found in the Chinese population and mostly reported in recent years . The key to successful management of M . chelonei keratitis is early diagnosis by high index of suspicion . In order to alert ophthalmologists of this condition, we report a typical case of M . chelonei keratitis and review the literature of all the reported cases with special reference to its risk factors, treatments and outcome . METHODS: The cases reported in the literature and a case of our own were reviewed and analyzed . RESULTS: Our case was a 42-year-old gentleman who developed M . chelonei keratitis following pterygium surgery . He had typical clinical features of irregular infiltrates with radiating projections, indistinct fluffy lesion margins, satellite lesions and associated epithelial defect . Penetrating keratoplasty was performed after failed medical treatments . He recovered fully with a best corrected visual acuity (BCVA) of 20/30 at 24 months after the corneal transplant . A total of 49 cases were reported in the literature . The major risk factor was corneal injury, including surgical trauma . Corneal foreign bodies (24 cases, 48%) were found to be highly correlated, especially metallic foreign bodies (16 cases, 32%) . Diagnosis was usually delayed for weeks or months and medical treatment alone often failed . Amikacin is usually the treatment of choice but its efficacy is just sub-optimal . Multi-resistance to the commonly used board spectrum antibiotics is not uncommon . The drug sensitivity test against atypical mycobacterium is technically difficult to perform and in vitro results are well known to be poorly related to clinical response . Combined extirpative keratectomy and topical antibiotics had been tried and was shown to be effective . Penetrating keratoplasty appeared to be a good definitive treatment for drug-resistance and advanced cases . CONCLUSION: M . chelonei keratitis is a rare opportunistic infection . The major risk factor is eye injury, with foreign bodies or surgical trauma . Diagnosis is often missed and delayed as a result of its scarcity and variable presentations . High index of clinical suspicion with early diagnosis and prompt combined medical and surgical intervention seem to be the best measure to decrease ocular morbidity . Good alertness and knowledge of this condition would help our patients in the Far East as the literature review has shown a recent trend of increase in frequency and more than 50% of the reported cases come from the Chinese patients. J Ocul Pharmacol Ther, 2002 Dec, 18(6), 549 - 58 In vivo transscleral iontophoresis of amikacin to rabbit eyes; Vollmer DL et al.; The objectives of these studies were to determine the amount and distribution of the aminoglycoside antibiotic amikacin delivered to rabbit eyes following transscleral iontophoresis and to determine the inter-study reproducibility of delivery over three identical studies . New Zealand White rabbits (N = 6 per dose group) were treated with a 200-mg/mL amikacin solution at 0, 2, 3 or 4 mA of (+) DC current for 20 minutes . Amikacin concentrations in eye tissues were highest with the 4-mA treatment . Concentrations for all three studies at this current were approximately 5.4, 40, 41, 343, and 92 mcg/g in the vitreous humor, anterior segment, non-treated hemisphere of the sclera, treated hemisphere of the sclera, and retina/choroid, respectively . These values were approximately 27, 50, 40, 10, and 13 fold greater than in the 0-mA control group and are well above the in vitro minimum inhibitory concentrations (MICs) for this drug . Inter-study reproducibility (measured as %CV) depended on the tissue type and treatment group and ranged from 8% for the retina/choroid to 51% for the anterior segment in the 4-mA group . Pretreatment with topical proparacaine hydrochloride local anesthetic did not affect amikacin delivery and total drug delivered was not affected by delivery time for the same total charge administered . Therapeutically relevant amounts of amikacin were delivered into eye tissues in a reproducible and controllable manner. Infection, 2002 Dec, 30(6), 338 - 40 Infection with Nocardia species: clinical spectrum of disease and species distribution in Madrid, Spain, 1978-2001; Pintado V et al.; BACKGROUND: Clinical experience with nocardiosis is very limited in European countries . We describe 34 cases of nocardial infection seen at one Spanish teaching hospital . PATIENTS AND METHODS: A retrospective review of the clinical features and outcome of nocardial infections was conducted during a 24-year period (1978-2001) . All cases were confirmed by culture . RESULTS: Predisposing factors included immunosuppression and/or pulmonary disease in 85% of patients; eight cases were related to HIV infection . Most isolates were initially identified as Nocardia asteroides complex (97%) . The most common clinical form was pulmonary disease (41%), followed by disseminated (15%), cutaneous (12%), cerebral (9%) and articular disease (3%) . A high proportion of patients (20%) had pulmonary colonization . Therapy with sulfonamides, imipenem or amikacin was given to 26 patients and a clinical response was observed in 65%.Overall mortality among patients with nocardial disease was 48% (13/27) but only seven patients (26%) died from nocardiosis . CONCLUSION: Nocardiosis remains a rare opportunistic infection that appears in immunosuppressed patients . HIV infection has become a common predisposing condition . The species distribution and disease spectrum are similar to those described in other European countries . Although most patients develop active disease, pulmonary colonization might not be as rare as has generally been assumed.Treatment with sulfonamides is usually effective and many patients may remain free of nocardial disease for a prolonged period. J Pediatr Hematol Oncol, 2002 Dec, 24(9), 714 - 6 Continuous infusion of ceftazidime in the empiric treatment of febrile neutropenic children with cancer; Dalle JH et al.; PURPOSE: Infection remains one of the most important complications in cancer therapy . The choice of antibiotics and the method of administration can affect results . Beta-lactam antibiotics can be administered by several short injections per day or by continuous infusion . The latter modality may provide superior pharmacokinetics . PATIENTS AND METHODS: The authors studied the pharmacokinetics of ceftazidime in children treated for malignancy and in febrile aplasia after chemotherapy . They received a continuous infusion of ceftazidime (200 mg/kg/day) after a loading dose (65 mg/kg/day) administered with amikacin (25 mg/kg/day) and vancomycin (50 mg/kg/day).RESULTS Twenty-three pharmacokinetic studies were performed . Mean ceftazidime serum levels were 31.1 +/- 11.9, 31.2 +/- 10, 32.4 +/- 11.6, 33 +/- 11.6, and 30.4 +/- 12.1 mg/L at 25, 27, 30, 36, and 43 hours, respectively . Treatment was tolerated well . There were no toxic or infectious deaths . CONCLUSIONS: Ceftazidime's time-dependent pharmacokinetics shows the advantage of continuous infusion . This study confirmed the feasibility and safety of this administration schedule in the empiric treatment of febrile neutropenic children with cancer. J Zoo Wildl Med, 2002 Sep, 33(3), 193 - 203 Population pharmacokinetics of antituberculous drugs and treatment of Mycobacterium bovis infection in bongo antelope (Tragelaphus eurycerus isaaci); Auclair B et al.; After clinical illness, treatment, and death of a captive male bongo antelope (Tragelaphus eurycerus isaaci) caused by tuberculosis involving Mycobacterium bovis, four tuberculin test reactive captive bongos were treated for 6 mo with isoniazid (INH) and rifampin (RIF) and intermittent single doses of other medications before being euthanized . In all cases, postmortem examination indicated no evidence of active disease and cultures of multiple organs were negative . We present detailed pharmacokinetic (PK) data for amikacin (AMK), ethambutol (EMB), INH, pyrazinamide (PZA), RIF, and levofloxacin in four female bongos . Adequate absorption and serum levels were obtained after parenteral administration of AMK, EMB, and INH and after oral administration of INH and PZA . Parenterally administered drugs were well described by a one-compartment PK model with first-order absorption and elimination processes . Treatment with INH and RIF over a 6-mo period did not result in demonstrable adverse effects . Starting doses of 10-15 mg/kg, i.m., or 30 mg/kg, p.o., of INH, 50 mg/kg, p.o., of EMB, and 25 mg/kg, i.m., s.i.d., of AMK are recommended . The treatment is continued with at least two drugs to which the organism is susceptible for a total treatment length of 6-12 mo . Treatment may be an option to eradicate M . bovis from suspect animals, with carefully administered and monitored drug treatment. Ther Drug Monit, 2002 Dec, 24(6), 696 - 700 Effect of analytical inaccuracy on dose adjustment for vancomycin, amikacin, and tobramycin using the Abbottbase Pharmacokinetic Systems; Zaera S et al.; The authors studied the inaccuracy effect in the determination of C(min) and C(1h) post-infusion serum concentrations of vancomycin, amikacin, and tobramycin on the recommended dose regimen (RDR) using the Abbottbase Pharmacokinetic Systems (PKS) program (Abbott; Abbott Park, IL) . According to previously established criteria, the clinically acceptable error (CAE) was defined as 1/8 of the therapeutic range . For a total of 647 simulations, in most cases (94.3%) an inaccuracy of up to three times the CAE did not lead to changes in the RDR . However, and particularly for amikacin and tobramycin, in some cases an inaccuracy in the order of the CAE in C(min) lead to important differences in the RDR, which could have important consequences in clinical practice . For therapeutic monitoring of these antibiotics, it is suggested that a serum concentration from a previous moment in time, which may be determined with greater precision and accuracy, could be used instead of C(min). Ann Biol Clin (Paris), 2002 Nov-Dec, 60(6), 723 - 30 {Evaluation of Emit netilmicin and amikacin assays on Dimension RXL HM (Dade Behring) open channels}; Vetele F et al.; The aim of this study was to evaluate and to validate an enzyme immunoassay in homogeneous phase for netilmicin and amikacin, adapted on the Dimension RXL HM (Dade Behring) machine . The results were compared with those obtained with automated polarization of fluorescence immunoassay using TDx FLx (Abbott) . The protocol of the study and the analytical criteria were inspired by the protocol Valtec version 2002 recommended by the French Society of Clinical Biology (SFBC) . The validation of this technique as adapted to the Dimension RXL HM has allowed its use for routine dosage adjustment of amikacin and netilmicin . The practicability is however the weak point of the adaptation of these techniques, even limiting as for their implementation. Eur J Biochem, 2002 Nov, 269(22), 5547 - 56 DNA and RNA damage by Cu(II)-amikacin complex; Jezowska-Bojczuk M et al.; The oxidation-promoting reactivity of copper(II) complex of aminoglycosidic antibiotic amikacin {Cu(II)-Ami} in the presence of hydrogen peroxide, was studied at pH 7.4, using 2'-deoxyguanosine (dG), pBR322 plasmid DNA and yeast tRNAPhe as target molecules . The mixtures of complex with H2O2 were found to be efficient oxidants, converting dG to its 8-oxo derivative, generating strand breaks in plasmid DNA and multiple cleavages in tRNAPhe . The complex underwent autooxidation as well, with amikacin hydroperoxides as likely major products . This reactivity pattern was found to be due to a combination of metal-bound and free hydroxyl radicals. Ophthalmology, 2002 Nov, 109(11), 2144 - 8 Massive mycobacterial choroiditis during highly active antiretroviral therapy: another immune-recovery uveitis? Zamir E, Hudson H, Ober RR, Kumar SK, Wang RC, Read RW, Rao NA. PURPOSE: To describe the ocular presentation of disseminated mycobacterial disease occurring during immune-recovery in a patient with acquired immune deficiency syndrome (AIDS) . STUDY DESIGN: Case report and literature review . PARTICIPANTS: A 41-year-old AIDS patient with a prior diagnosis of cytomegalovirus retinitis . METHODS: The patient developed progressive, bilateral multifocal choroiditis with panuveitis 2 months after beginning and responding to highly active antiretroviral therapy . His left eye became blind and painful and was enucleated . Pathologic examination revealed massive choroiditis with well-formed, discrete granulomas and multiple intracellular and extracellular acid-fast organisms within the choroidal granulomas . Culture and polymerase chain reaction of vitreous specimens revealed Mycobacterium avium complex (MAC) . RESULTS: Empiric, and later sensitivity-guided, local and systemic antibiotic therapy was used to treat the remaining right eye, but it continued to deteriorate . Despite medical therapy, three vitrectomies and repeated intravitreal injections of amikacin, a total retinal detachment ensued . One week after the third vitrectomy, the patient died from mesenteric artery thrombosis in the setting of disseminated mycobacterial disease . CONCLUSIONS: This is the first report of ocular inflammation as the presenting finding in the recently recognized syndrome of immune-recovery MAC disease . Pathogenesis of this entity is related to an enhanced immune response to a prior, subclinical, disseminated infection . The formation of discrete granulomas, normally absent in MAC infections in AIDS, reflects this mechanism. Pol J Pharmacol, 2002 May-Jun, 54(3), 275 - 80 Effects of some drugs on rat erythrocyte 6-phosphogluconate dehydrogenase: an in vitro and in vivo study; Ciftci M et al.; The in vitro and in vivo effects of some drugs on rat erythrocytes 6-phosphogluconate dehydrogenase were investigated in this study . Rat erythrocyte 6-phosphogluconate dehydrogenase was partially purified with ammonium sulfate precipitation . The enzyme activity was determined by Beutler's method . Some drugs such as ampicillin, amikacin sulfate, and netilmicin sulfate inhibited the enzyme activity in in vitro conditions, while metamizole activated it . The I50 values of the inhibiting drugs were 66.2, 5.836, and 0.963 mM, respectively . For the drugs having low I50 values (drug concentrations which produce 50% inhibition) (amikacin sulfate and netilmicin sulfate), in vivo studies were performed in rats (Sprague-Dawley) . Amikacin sulfate at 64 mg/kg inhibited the enzyme activity significantly (p < 0.05) 2 h after dosing . Netilmicin sulfate at 6.4 mg/kg also inhibited the enzyme significantly (p < 0.05) 4 h after dosing . Amikacin sulfate and netilmicin sulfate inhibited rat erythrocyte 6-phospogluconate dehydrogenase both in vivo and in vitro . The enzyme was inhibited in vitro by ampicillin and activated in vitro by metamizole. CLAO J, 2002 Oct, 28(4), 228 - 30 Mycobacterium chelonae keratitis associated with soft contact lens wear; Malecha MA et al.; PURPOSE: To report a case of Mycobacterium chelonae keratitis associated with soft contact lens wear . METHODS: A 17-year-old boy who wore frequent replacement soft contact lenses developed keratitis in the right eye . There was no history of trauma to the right eye . The patient was treated initially with topical ciprofloxacin but without improvement . On presentation, visual acuity in his right eye was 20/40 . A Gram-stained scraping of the corneal infiltrate revealed beaded filamentous rods, and the organisms were acid-fast positive . The patient's right eye was treated with intensive topical amikacin, 20 mg/mL, and 10 % sulfacetamide . Eventually, Mycobacterium chelonae was cultured on Sabourard's agar, topical sulfacetamide was stopped, and amikacin was continued . RESULTS: The patient's keratitis responded well to amikacin and resolved over a period of 4 weeks . Visual acuity in the right eye improved to 20/25 . CONCLUSIONS: Mycobacterium chelonae is a rare cause of keratitis in soft contact lens wearers . We have identified fewer than five cases of Mycobacterium chelonae keratitis associated with soft contact lenses in the literature . Prompt and accurate diagnosis of the organism using comeal scraping can lead to appropriate therapy and resolution of the keratitis. Asian J Androl, 2002 Sep, 4(3), 163 - 7 Treatment of chronic bacterial prostatitis with amikacin through anal submucosal injection; Hu WL et al.; AIM: To assess the efficacy and safety of anal submucosal injection (ASI) of amikacin in chronic bacterial prostatitis (CBP) . METHODS: Fifty male outpatients with CBP were randomly divided into two groups . Thirty cases of ASI group were given amikacin 400 mg daily by ASI for ten times and the other twenty cases of intramuscular injection (IM) group were given the same drug daily by IM . All patients were evaluated with NIH-Chronic prostatitis symptom index (NIH-CPSI), the bacteria culture of the expressed prostate secretion (EPS), proctoscopic examination, rectal biopsy and the clinical manifestation were checked at pretreatment and on day 7 and 90 after cessation of therapy . RESULTS: The cure rate, apparent effective rate and effective rate of ASI group and IM group were 33.3% vs 5% (P<0.05), 43.3% vs 10% (P<0.05) and 16.7% vs 20% (P>0.05), respectively . The score of NIH-CPSI in both of ASI group and IM group decreased significantly 7 days after cessation of therapy, both ASI and IM of amikacin could relieve symptoms within a short time . However, 3 months after cessation of therapy the score of NIH-CPSI in ASI group continued down in spite of no significant differences compared with 7 days after cessation of therapy, but the score of IM group was rebound nearly closed to level of pretreatment at 23.8 8.5 and significantly higher than that of ASI group . The amount of white blood cell (WBC) of EPS in ASI group increased slightly at 7 days after cessation of therapy without significant difference with pretreatment (P>0.05), but it significantly decreased at 3 months after cessation of therapy, the amount of WBC of EPS in ASI group was lower than that of IM group at 3 months after cessation of therapy (P<0.05) . Proctoscopic examination of anal canal were normal after ASI therapy and the rectum biopsy showed no obvious histopathologic abnormality at the site of injection except mild focal submucosal infiltration of lymphocytes and plasma cells at 7 days after cessation of therapy which disappeared on 3 months after cessation of therapy . All patients had no evident complications . CONCLUSION: ASI could be recommended as a new safe, effective, painless method of antibiotics administration in the treatment of CBP. Infection, 2002 Aug, 30(4), 243 - 5 Pulmonary nocardiosis in a non-Hodgkin's lymphoma patient; Hizel K et al.; Nocardiosis is an opportunistic infection especially in immunocompromised patients . Lungs are the most common infection sites and therapy poses some difficulties . We describe a case of pulmonary infection with Nocardia asteroides in a non-Hodgkin's lymphoma patient . Although the mortality from pulmonary nocardiosis is high in immunocompromised patients, our patient was successfully treated with trimethoprim-sulfamethoxazole (TMP/SMZ) and amikacin . Maintenance therapy with TMP/SMZ was continued for 1 year . This case supports the importance of the long-term maintenance treatment after the initial combination therapy. J Int Med Res, 2002 Jul-Aug, 30(4), 406 - 12 Comparative cochlear toxicities of streptomycin, gentamicin, amikacin and netilmicin in guinea-pigs; Kalkandelen S et al.; All the aminoglycoside antibiotics now in clinical use are ototoxic . This study was designed to compare the toxic effects of four aminoglycoside antibiotics, streptomycin, gentamicin, amikacin and netilmicin, administered to guinea-pigs systemically (at respective doses of 125 mg/kg, 50 mg/kg, 150 mg/kg or 37.5 mg/kg, twice daily for 1 week) or topically via the transtympanic route (0.25 ml/kg in 4% saline, twice daily for 1 week) . Chosen doses were 10-20 times higher than the recommended human dosage . Cochlear damage was observed in all animals that were given systemic and local aminoglycosides . The severity of the cochlear damage was in the order gentamicin, amikacin, streptomycin, netilmicin, with gentamicin being the most toxic . No statistically significant difference between the severity of cochlear damage resulting from the systemic and topical applications was detected. J Clin Microbiol, 2002 Aug, 40(8), 2930 - 5 Clinical and laboratory features of Mycobacterium mageritense; Wallace RJ Jr et al.; Six clinical isolates of the nonpigmented, rapidly growing species Mycobacterium mageritense were recovered from sputum, bronchial wash, blood, sinus drainage, and two surgical wound infections from separate patients in Texas, New York, Louisiana, and Florida . The isolates matched the ATCC type strain by PCR restriction enzyme analysis of the 65-kDa hsp gene sequence of Telenti, high-performance liquid chromatography, biochemical reactions, and partial 16S rRNA gene sequencing . These are the first isolates of this species to be described in the United States and the first isolates to be associated with clinical disease . Susceptibility testing of all known isolates of the species revealed all isolates to be susceptible or intermediate to amikacin, cefoxitin, imipenem, and the fluoroquinolones and sulfonamides but resistant to clarithromycin . Because of their phenotypic and clinical similarity to isolates of the Mycobacterium fortuitum third biovariant complex (sorbitol positive), isolates of M . mageritense are likely to go undetected unless selected carbohydrate utilization or molecular identification methods are used. Anesthesiology, 2002 Jul, 97(1), 199 - 206 Influence of lung aeration on pulmonary concentrations of nebulized and intravenous amikacin in ventilated piglets with severe bronchopneumonia; Elman M et al.; BACKGROUND: Pulmonary concentrations of aminoglycosides administered intravenously are usually low in the infected lung parenchyma . Nebulization represents an alternative to increase pulmonary concentrations, although the obstruction of bronchioles by purulent plugs may impair lung deposition by decreasing lung aeration . METHODS: An experimental bronchopneumonia was induced in anesthetized piglets by inoculating lower lobes with a suspension of 10(6) cfu/ml Escherichia coli . After 24 h of mechanical ventilation, 7 animals received two intravenous injections of 15 mg/kg amikacin, and 11 animals received two nebulizations of 40 mg/kg amikacin at 24-h intervals . One hour following the second administration, animals were killed, and multiple lung specimens were sampled for assessing amikacin pulmonary concentrations and quantifying lung aeration on histologic sections . RESULTS: Thirty-eight percent of the nebulized amikacin (15 mg/kg) reached the tracheobronchial tree . Amikacin pulmonary concentrations were always higher after nebulization than after intravenous administration, decreased with the extension of parenchymal infection, and were significantly influenced by lung aeration: 197 +/- 165 versus 6 +/- 5 microg/g in lung segments with focal bronchopneumonia (P = 0.03), 40 +/- 62 versus 5 +/- 3 microg/g in lung segments with confluent bronchopneumonia (P = 0.001), 18 +/- 7 versus 7 +/- 4 microg/g in lung segments with lung aeration of 30% or less, and 65 +/- 9 versus 2 +/- 3 microg/g in lung segments with lung aeration of 50% or more . CONCLUSIONS: In a porcine model of severe bronchopneumonia, the nebulization of amikacin provided 3-30 times higher pulmonary concentrations than the intravenous administration of an equivalent dose . The greater the lung aeration, the higher were the amikacin pulmonary concentrations found in the infected lung segments. Hear Res, 2002 Jul, 169(1-2), 121 - 9 Amikacin ototoxicity enhanced by Ginkgo biloba extract (EGb 761); Miman MC et al.; An animal study was realized to investigate the possible beneficial effect of EGb 761 as an antioxidant agent on amikacin ototoxicity by measuring distortion product otoacoustic emissions (DPOAEs) . Twenty-eight adult rats were grouped equally as follows . GROUP AMIKACIN: rats received amikacin 600 mg/kg/day intramuscularly between postnatal days (PND) 30 and PND44 . Group amikacin/EGb 761: rats received amikacin 600 mg/kg/day intramuscularly between PND30 and PND44 and EGb 761 100 mg/kg/day orally between PND30 and PND50 . Group EGb 761: rats received equivolume saline intramuscularly between PND30 and PND44 and EGb 761 100 mg/kg/day orally between PND30 and PND50 . NO TREATMENT GROUP: rats received nothing . Group amikacin was found to be affected only on the last measurement day of study (PND57) . The frequencies greater than 2002 Hz were significantly reduced compared with the amplitudes of PND30 (P<0.05) . Group amikacin/EGb 761 was most and earliest affected by amikacin-induced ototoxicity . DPOAE amplitudes were found in this group to be decreased at 2-6 kHz starting on PND50 . The results of Group EGb 761 and No treatment group were not significantly changed . For the DPOAE input/output amplitude thresholds, Group amikacin (P<0.05) and Group amikacin/EGb 761 (P<0.01) had significantly elevated thresholds on PND57, except at 5 kHz for Group amikacin (P=0,06) . According to the results of the study, EGb 761 may be regarded as a facilitating drug for the development of amikacin ototoxicity . The results of the present study may warn against concomitant use of aminoglycosides, specifically amikacin, with EGb 761. Hematol Oncol, 2002 Jun, 20(2), 51 - 62 Tuberculosis in blood and marrow transplant recipients; Yuen KY et al.; Although one third of the world's population is infected with tuberculosis (TB), TB in blood and marrow transplant (BMT) recipients is relatively less well studied, as the incidence of TB is relatively low in developed countries with BMT units . Since the report of the first two cases in 1983, 52 cases of TB complicating BMT have been reported in the English literature from BMT centers in ten different countries . Not unexpectedly, the two largest series were reported from areas with a high incidence of TB in the general population, with about 45 cases per 10(5) inhabitants per year in Spain and about 100 cases per 10(5) inhabitants per year in Hong Kong respectively . The overall frequency of occurrence of TB in BMT recipients was 0.4% (52 cases among 13 881 BMT recipients), with a male:female ratio of 11:9 and median age of 33 (range 7-57) . The incidence of TB in the general population is a major predictor of a higher frequency of occurrence in BMT recipients . Moreover, allogeneic transplantation, graft-versus-host disease, and total body irradiation were found to be risk factors associated with TB . Among the 48 cases in whom the time of manifestation were reported, only one case manifested during the neutropenic period (day 11) . On the other hand, 11 cases (23%) manifest after engraftment but before day 100, and 36 (75%) manifest after day 100 . The most important aspect towards making the diagnosis is a high index of suspicion, as TB occurred in relatively low frequencies especially in developed countries, and the clinical patterns usually mimic other more common infectious and non-infectious complications after BMT . As the incidence of drug resistant TB is increasing, we prefer to treat our patients for at least one year (as compared with six months in immunocompetent hosts) with four drugs in the first six months and two or three drugs for another six months . In those patients who could not tolerate oral medication, we used an intravenous regimen of rifampicin, ciprofloxacin, and amikacin until oral therapy could be instituted . The absence of relapse after termination of treatment in our patients suggested that secondary prophylaxis would not be necessary as long as immune function has been restored . With the rising incidence of TB in countries that previously enjoyed a very low prevalence of TB, attributed to the growing population of HIV-infected subjects with TB, and the changing patterns of population migration, it is important to bear a high index of suspicion of Mycobacterium tuberculosis as a pathogen in BMT recipients . Antibiot Khimioter, 2001, 46(12), 42 - 52 {Efficacy of monotherapy by meropenem in ventilator-associated pneumonia}; Alvarez Lerma F; Serious Infections Study Group; We performed a prospective, open label, randomized study in intensive care unit patients with ventilator-associated pneumonia (VAP) to determine the efficacy and safety of empiric intravenous (i.v.) meropenem monotherapy compared with the combination of ceftazidime plus amikacin . A total of 140 patients receiving mechanical ventilation and diagnosed with pneumonia were included in the study . Patients were randomized to receive either 1 g meropenem i.v . every 8 hours or 2 g ceftazidime i.v . every 8 hours plus 15 mg/kg amikacin daily, administered to patients with normal renal function as two daily doses . Satisfactory clinical responses (cure or improvement) were achieved at the end of treatment in 68.1% of meropenem-treated patients and 54.9% in the ceftazidime/amikacin treated group (relative risk 1.25; 95% confidence interval > 1.00, 1.55) . When non-evaluable patients were excluded from the analysis, the satisfactory clinical response was 82.5% and 66.1% for the meropenem and ceftazidime/amikacin patients, respectively (p = 0.044) . Logistic regression demonstrated that treatment with meropenem and both the basic traumatic and medical pathologies were significantly associated with a satisfactory response . Adverse events judged to be possible or probably related to treatment were reported by seven (10.1%) patients in the meropenem group and by eight patients (11.3%) in the ceftazidime/amikacin group . The results of this study confirm that monotherapy with meropenem is well tolerated and provides superior efficacy to the conventional combination of ceftazidime and amikacin in combating VAP. Int J Tuberc Lung Dis, 2002 Jul, 6(7), 622 - 7 Hearing loss and nephrotoxicity in long-term aminoglycoside treatment in patients with tuberculosis; de Jager P et al.; OBJECTIVE: To investigate the ototoxic and nephrotoxic effects of long-term use of aminoglycosides . DESIGN: Patients treated for tuberculosis with aminoglycosides were evaluated for hearing loss and nephrotoxicity for a minimum of 14 days . RESULTS: Hearing loss of 15 decibels (dB) at two or more frequencies, or at least 20 dB hearing loss at at least one frequency, was found in 18% of our total population treated with aminoglycosides (amikacin, kanamycin and/or streptomycin) . In the group treated with kanamycin this percentage was 15.6 . None of the factors sex, age, treatment duration, total aminoglycoside doses or first serum creatinine concentration, was found to be associated with hearing loss . Nephrotoxicity percentages at the end of treatment with aminoglycoside or kanamycin are 7.5% (1.9%) and 4.5% (2.3%) respectively, using the definition increase of serum creatinine > or = 27 micromol/l (> or = 44 micromol/l) . Patients developing nephrotoxicity had a longer duration of treatment and received larger total doses . CONCLUSIONS: Patients developing nephrotoxicity had a significantly longer duration of treatment with aminoglycosides, and received a larger total dose . We did not find any factor significantly associated with the development of hearing loss . In the long-term treatment of tuberculosis with aminoglycosides, ototoxicity seems to be a greater problem than nephrotoxicity. Br J Dermatol, 2002 Jul, 147(1), 170 - 3 Cutaneous Mycobacterium fortuitum infection mimicking lupus vulgaris; Lin YC et al.; We report a woman with a lupus vulgaris-like skin eruption caused by Mycobacterium fortuitum . The presence of mycobacteria was confirmed with tissue culture and also the detection of mycobacterial heat shock protein 65 (hsp65) DNA in the biopsy specimen . The eruption resolved after treatment with amikacin and clarithromycin . Lupus vulgaris-like lesions might be included in the clinical spectrum of infections caused by rapidly growing mycobacteria. Pathol B