Acanthamoeba keratitis in Mexico: Report of a clinical case and importance of sensitivity assays for a better outcome.

Acanthamoeba keratitis (AK) is a sight-threatening corneal infection. The early symptoms include redness, pain, photophobia and intense tearing. Chronic infection usually progresses to stromal inflammation, ring ulcers, corneal opacification and hypopyon. Here we document an AK case in a high myopic 38-year-old woman from Mexico City, with a history of wearing contact lenses while swimming. Corneal scrapes cultures were positive only for amoebae, consequently a treatment including netilmicin 0.3% and oral itraconazole 100 mg/12 h was prescribed. The infection was resolved after 8 months, leaving a slight leucoma outside the visual axis, with a visual acuity of 20/150. In the laboratory, the amoebic isolate was axenized in PYG medium, with an optimal growth at 30 °C, and was identified morphologically as Acanthamoeba polyphaga according to the taxonomic criteria of Page (1988) and placed in the T4 group by genotyping. The virulence of this strain (40%) was determined by intranasal inoculation of 1 × 106/20 µl trophozoites in BALB/c mice recovering from brain, proving their invasion ability and by the interaction with monolayers of epithelial cells of the established MDCK line of canine kidney origin (1:2 ratio of interaction), at 1, 3, 6, 8 and 24 h; trophozoites migrated to cell junctions inducing few lytic zones. In addition to the biological characterization, in vitro drug sensitivity tests were performed using chlorhexidine, itraconazole, netilmicin and voriconazole. Results revealed that voriconazole was the most effective compound. A. polyphaga remains as one of the most frequently isolated species producing AK. The treatment of AK case using netilmicin and oral itraconazole solved the disease, but the healing process was wide-ranging (8 months). The use of voriconazole and chlorhexidine may be an alternative treatment of future AK cases in Mexico.

Vulvo-vaginitis in prepubertal girls: new ways of administering old drugs.

STUDY OBJECTIVE: To evaluate the effectiveness and safety of local vs systemic antibiotic treatment in the management of recurrent vulvovaginitis in children. DESIGN: Randomized treatment and follow-up of 90 cases of persistent vulvovaginitis. SETTING: The Department of Medicine and Health Sciences, Institute of Gynecology and Obstetrics, University of Molise, Italy. METHODS: Between January 2009 and December 2012, 90 prepubertal girls (Tanner Stage I) aged 6-12 years, with recurrent discharge not responding to common hygienic measures and not suspected of being sexually abused, were treated, 45 patients with oral antibiotic treatment (group 1) and 45 patients with a local antibiotic treatment (group 2). Vaginal cultures were prepared before treatment and follow-ups were made after 3 months. RESULTS: Bacterial pathogens were isolated in vaginal secretions of 84/90 (93%) girls. There were 6 girls receiving antibiotic treatment who had persistent discharge and repetitive isolations of Escherichia coli. Administration type was selected at random. Symptoms and signs were resolved in all girls, but we observed 1 recurrence (2.22%) in group 2 vs 6 recurrences (13.33%) in group 1 (P = .049). In group 1 we observed 3 cases (6.67%) of gastro-intestinal side effects vs no cases in group 2 (P = .079). CONCLUSION: Topical medication based on netilmicin, associated with Benzalkonium-Chloride, showed a clinical and microbiological effectiveness in first-line treatment of bacterial vulvovaginitis in children, comparable to conventional drugs; so local treatment may be a good alternative to systemic treatment decreasing the use of oral antibiotics in young people and related risks of bacterial resistances.

'Leptotrichia amnionii', a newly reported cause of early onset neonatal meningitis.

'Leptotrichia amnionii' is an underestimated fastidious inhabitant of the vaginal flora that can cause upper genital tract infections when predisposing factors are present. We describe here what is believed to be the first reported case of early onset meningitis due to 'L. amnionii' in a neonate with intrauterine growth retardation. The outcome was favourable after cefotaxime treatment.

The optimal aminoglycoside and its dosage for the treatment of severe Enterococcus faecalis infection. An experimental study in the rabbit endocarditis model.

Aminoglycosides are recommended for the treatment of Enterococcus faecalis infections, especially in severe and bacteremic infection. However, the optimal aminoglycoside or the optimal dosage remains uncertain. This study aimed to compare the activity of four aminoglycosides against E. faecalis (gentamicin, netilmicin, tobramycin, and amikacin) and two dosages of gentamicin. One clinical strain of E. faecalis was used to induce aortic endocarditis in the study rabbits. Each aminoglycoside was infused daily over 3 days with a computer-regulated flow simulating human pharmacokinetics of 15 mg/kg/day for amikacin, 6 mg/kg/day for netilmicin, and 3 mg/kg/day for gentamicin and tobramycin. Additionally, two dosages of gentamicin (simulating 3 or 6 mg/kg/day) were compared over 1 or 3 days of treatment. The in vivo efficacy was assessed according to the bacterial count in vegetations, in comparison with a control group. Of the four aminoglycosides tested, only gentamicin and netilmicin showed significant antibacterial efficacy after 3 days of treatment. After only 1 day of treatment, the high dosage of gentamicin (6 mg/kg/day) was more effective than the standard dosage (3 mg/kg/day). Among the tested aminoglycosides, gentamicin showed the best efficacy, with the best results after 24 h of treatment for the highest dosage.

Bilateral methicillin-resistant Staphylococcus aureus keratitis following hyperopic photorefractive surgery.

To report clinical manifestations of a female patient with bilateral bacterial keratitis following photorefractive keratectomy (PRK). Bilateral PRK was performed for moderate hyperopia. Bandage contact lenses were fitted at the conclusion of the surgery. Bilateral infectious keratitis with hypopion was diagnosed within 4 days after surgery. Smear and culture were obtained and showed the presence of methicillin-resistant Staphylococcus aureus (MRSA). The patient was treated with systemic prednisone and topical antibiotics (vancomycin, tobramycin and netylmicin) and betamethasone. After 1 month corneal leukoma was still present and remained unchanged during the following 7 months. Infectious keratitis is a rare complication of PRK that appears early in the postoperative period. MRSA keratitis may determine long-term visual impairment despite prompt therapeutic intervention.

Efficacy and safety of netilmycin/dexamethasone preservative-free and tobramycin/dexamethasone-preserved fixed combination in patients after cataract surgery.

PURPOSE: To compare the efficacy and safety of preservative-free Netilmycin/Dexamethasone with that of preserved Tobramycin/Dexamethasone, postcataract surgery. METHODS: Prospective, randomized, single-blind study on patients submitted to phacoemulsification. During preoperatory visits, at 7 and 21 days conjunctival hyperemia, corneal edema, Tyndall, Shirmer I, corneal and conjunctival lissamine green and fluorescein staining, and intraocular pressure (IOP) were recorded. Postoperative pain (at day 7) and the subjective tolerability (at day 21) were investigated. RESULTS: Eighty patients completed the study and the data collected were analyzed (44 on Netilmycin/Dexamethasone). Regarding the primary efficacy variable, intraocular inflammation, no microbial events were recorded, but aqueous flare was significantly lower with Tobramycin/Dexamethasone at 1 week (P = 0.002). Regarding secondary efficacy variables, conjunctival hyperemia was lower in patients under Tobramycin/Dexamethasone (P < 0.001), but corneal edema and ocular pain were similar. Regarding safety, no significant differences on ocular surface status were recorded. Both formulations were well tolerated, but Tobramycin/Dexamethasone caused an increased IOP at 1 week (P < 0.0001). CONCLUSIONS: Both the studied fixed combinations are safe and effective in controlling postoperative inflammation and preventing postoperative ocular infections. Tobramycin/Dexamethasone has a quicker anti-inflammatory effect but needs IOP monitoring. Further studies on more patients using a sounder scientific design are needed to confirm our findings.

Bacillus cereus meningitis in a term neonate.

A case of Bacillus cereus meningitis in a term neonate without identifiable risk factors or source of the organism is presented. Prompt identification of the organism and treatment resulted in a favourable outcome.

Polyhydroxyethylaspartamide-based micelles for ocular drug delivery.

In this paper three copolymers of polyhydroxyethylaspartamide (PHEA), bearing in the side chains polyethylene glycol (PEG) and/or hexadecylamine (C(16)) (PHEA-PEG, PHEA-PEG-C(16) and PHEA-C(16) respectively) have been studied as potential colloidal drug carriers for ocular drug delivery. The physical characterization of all three PHEA derivatives, using the Langmuir trough (LT) and micellar affinity capillary electrophoresis (MACE) techniques allowed to assume that whereas alone PHEA backbone is an inert polymer with respect to the interactions with lipid membranes and drug complexation, when PHEA chains are grafted with long alkyl chains like C(16) or in combination C(16) chains and hydrophilic chains like PEG, copolymers with lipid membrane interaction ability and drug complexation capability are obtained. In vitro permeability studies performed on primary cultured rabbit conjunctival and corneal epithelia cells, using PHEA-C(16) and PHEA-PEG-C(16) as micelle carriers for netilmicin sulphate, dexamethasone alcohol and dexamethasone phosphate, demonstrated that in all cases drug loaded PHEA-C(16) and PHEA-PEG-C(16) micelles provide a drug permeation across ocular epithelia greater than simple drug solutions or suspensions. In particular PHEA-PEG-C(16) acts as the best permeability enhancer in our experimental model. In vivo bioavailability studies conducted with PHEA-PEG-C(16) micelles loaded with dexamethasone alcohol, confirmed that this system also provides a drug bioavailability greater in comparison with that obtained with water suspension of the same drug after ocular administration to rabbits.

[Optimalisation of netilmicin dosage based on therapeutic drug monitoring during the first days of life in very preterm neonates (gestational age 23-32 weeks)]. / Optymalizacja dawkowania netylmycyny w oparciu o terapie monitorowana stezeniem antybiotyku w pierwszych dniach zycia u noworodków bardzo niedojrzalych (23-32 tygodnie ciazy).

AIM: The aim of this study was to optimalise netilmicin dosage in low and very low birthweight premature neonates, based on drug serum concentrations obtained during therapeutic drug monitoring (TDM). PATIENTS AND METHODS: Prospective study of 55 neonates born at gestational age 23-32 (GA) and birthweight between 480 g to 1780 g, with suspected intrauterine infection, in whom netilmicin serum concentration was monitored. Initially the antibiotic was administered every 24 hours (group I: n=16; mean GA=28+/-3 weeks). Peak level was measured 30 minutes after completion of infusion after the 2(nd) dose of the drug, and trough level was measured immediately before administration of the 3(rd) dose of the drug. Due to excessive trough levels, the dosing regimen was modified, prolonging the interval between doses to 48 hours. Such dosing regimen was used in neonates, enrolled in group II (n=39; mean GA=28+/-2 weeks). Pharmacokinetic parameters were evaluated in order to find correlations between them and neonatal maturity, birthweight and creatinine serum concentration. Serum netilmicin concentration was measured by fluorescence polarization immunoassay (FPIA), using TDx/FLx (Abbott Laboratories). Creatinine concentration was measured on the 3(rd) day of life using Cobas Integra 400. All children in the study underwent the first hearing examinations under 3 months of age. After excluding changes which could affect hearing ability, behavioural examination was conducted. If its result was inconclusive or abnormal, the child was referred for ABR (auditory brain stem response) examination. The children were followed-up until they were 2 years old. RESULTS: Netilmicin peak levels in both groups were within the recommended range (11.33+/-3.27 microg/mL in group I; 13.35+/-5.67 microg/mL in group II). Safe trough level was exceeded in 81.2% neonates in group I and 28.2% in group II. This was observed in the most immature neonates: born 23-27(th) GA, with mean birthweight 805+/-293 g, in whom trough level was on average 2.93 microg/mL and t(0.5) was 20.8 hours. Negative correlation was found between trough level and gestational age (r=-0.524; p<0.001) and birthweight (r= -0.293; p=0.030). Negative correlations was also found between t(0.5) and gestational age (r= -0.489; p<0.001) and birthweight (r=-0.320; p=0.016). No child was diagnosed with hearing impairment in group II and one case in group I. CONCLUSIONS: The results indicate that netilmicin dosage of 6 mg/kg every 48 h can ensure the desired trough and peak levels in premature neonates without the necessity of routine monitoring of antibiotic concentration. However, in very premature neonates (

Individualising netilmicin dosing in neonates.

PURPOSE: The aim of this study was develop an optimal dosing regimen for netilmicin in neonates. METHODS: This was a population pharmacokinetic study in 97 neonates aged from 2 to 28 days after the due date who were being treated with netilmicin for suspected sepsis. The model was used to simulate dosing regimens. RESULTS: The principle factors influencing netilmicin clearance (CL) were postmenstrual age (PMA) and current body weight (CWT), and the principal determinant of volume of distribution (V) was CWT. The final covariate model was CL = 0.192 x (CWT/2)(1.35) x (PMA/40)(1.03), V = 1.5 x (CWT/2)(0.3). The optimal dosing was 5 mg/kg ever 36 h, 5 mg/kg every 24 h, 6 mg/kg every 24 h and 7 mg/kg every 24 h for neonates < or =27, 28-30, 31-33 and > or =34 weeks PMA, respectively. CONCLUSION: Individualisation of netilmicin dosing in neonates requires adjustment of dose by body weight, and dosing interval by both PMA and CWT.

Use of netilmicin once or twice daily in preterm newborns: evaluation of nephrotoxicity by urinary alpha1-microglobulin and retinol binding protein.

Since aminoglycoside efficacy is proportional to serum peak/MIC ratio and linked to post antibiotic effect, use of netilmicin once rather than twice a day has been proposed. On the other hand netilmicin might play a role in drug-induced nephrotoxicity, mainly on proximal tubule. Urinary retinol binding protein (RBP) and alpha1 microglobulin (alpha1m) are early and specific indicators of tubular damage and dysfunction. 21 preterm neonates (GA < 37 weeks) were divided in two groups on the basis of netilmicin administration modality (1: once a day, 2: twice a day, both for 7 days, at 5 mg/kg/die) and differences in netilmicin tolerability were assessed by evaluation of alpha1m and RBP levels by immunonephelometric method. No significant differences were found between the two groups either considering levels at time 1 and at time 2, or considering the difference between time 1 and 2 (Delta1/2). In our study once-daily dosing schedule shows similar low rates of nephrotoxicity, compared with multiple daily dosing schedule: this result may support the general adoption of once-daily dosing of netilmicin in clinical practice.

Impact of aminoglycoside cycling in six tertiary intensive care units: prospective longitudinal interventional study.

AIM: To determine the effect of aminoglycoside cycling in six tertiary intensive care units (ICU) on the rates of sepsis, aminoglycoside resistance patterns, antibiotic consumption, and costs. METHODS: This was a prospective longitudinal interventional study that measured the effect of change from first-line gentamicin usage (February 2002-February 2003) to amikacin usage (February 2003-February 2004) on the aminoglycoside resistance patterns, number of patients with gram-negative bacteremia, consumption of antibiotics, and the cost of antimicrobial drugs in 6 tertiary care ICUs in Zagreb, Croatia. RESULTS: The change from first-line gentamicin to amikacin usage led to a decrease in the overall gentamicin resistance of gram-negative bacteria (GNB) from 42% to 26% (P<0.001; z-test of proportions) and netilmicin resistance from 33% to 20% (P<0.001), but amikacin resistance did not change significantly (P=0.462), except for Acinetobacter baumanni (P=0.014). Sepsis rate in ICUs was reduced from 3.6% to 2.2% (P<0.001; chi(2) test), with a decline in the number of nosocomial bloodstream infections from 55/100 patient-days to 26/100 patient-days (P=0.001, chi(2) test). Furthermore, amikacin use led to a 16% decrease in the overall antibiotic consumption and 0.1 euro/patient/d cost reduction. CONCLUSION: Exclusive use of amikacin significantly reduced the resistance of GNB isolates to gentamicin and netilmicin, the number of GNB nosocomial bacteremias, and the cost of total antibiotic usage in ICUs.

Prospective, randomized trial comparing short and long intravenous antibiotic treatment of acute pyelonephritis in children: dimercaptosuccinic acid scintigraphic evaluation at 9 months.

OBJECTIVE: We report a prospective, randomized, multicenter trial that compared the effect of 3 vs 8 days of intravenous ceftriaxone treatment on the incidence of renal scarring at 6 to 9 months of follow-up in 383 children with a first episode of acute pyelonephritis. METHODS: After initial treatment with intravenous netilmicin and ceftriaxone, patients were randomly assigned to either 5 days of oral antibiotics (short intravenous treatment) or 5 days of intravenous ceftriaxone (long intravenous treatment). Inclusion criteria were age 3 months to 16 years and first acute pyelonephritis episode, defined by fever of >38.5 degrees C, C-reactive protein level of >20 mg/L, and bacteriuria at >10(5)/mL. All patients underwent 99m technetium-dimercaptosuccinic acid scintigraphy 6 to 9 months after inclusion. A total of 548 children were included, 48 of whom were secondarily excluded and 117 of whom were lost to follow-up or had incomplete data; therefore, 383 children were eligible, 205 of them in the short intravenous treatment group and 178 in the long intravenous treatment group. RESULTS: At inclusion, median age was 15 months, median duration of fever was 43 hours, and median C-reactive protein level was 122 mg/L. A total of 37% (143 of 383) of patients had a vesicoureteral reflux grades 1 to 3. Patient characteristics at inclusion were similar in both groups, except for a significantly higher proportion of girls in the short intravenous treatment group. The frequency of renal scars at scintigraphy was similar in both groups. Multivariate analysis demonstrated that renal scars were significantly associated with increased renal height at initial ultrasound and with the presence of grade 3 vesicoureteric reflux. CONCLUSIONS: The incidence of renal scars was similar in patients who received 3 days compared 8 days of intravenous ceftriaxone. Increased renal height at initial ultrasound examination and grade 3 vesicoureteric reflux were significant risk factors for renal scars.

[Sudden cardiorespiratory arrest in adults with acute epiglottitis. Report of 2 cases]. / Parada cardiorrespiratoria súbita en adultos con epiglotitis aguda presentación de dos casos.

We report two adult cases of sudden cardiorespiratory arrest because an acute epiglottitis that ocurred in our hospital. Although it is an uncommon pathology nowdays with good prognosis generally, we try to call the attention about this complication which can happen of unforseeable way even in previous absence of respiratory obstruction. One of the patients required coniotomy in ICU due to impossibility of orotracheal intubation (OI) and the other died in spite of an urgent performance.

[Pseudomonas and acute external otitis. Results of a microbiological study in patients without previous antibiotic treatment]. / Pseudomonas y otitis externa aguda. Resultados de un estudio microbiológico en pacentes sin tratamiento antibiótico previo.

We report the results of a microbiological clinic study that was performed by our ENT Department between years 2000 and 2001 whose main objective was to determine, in Badajoz Area of Health, which bacteria were involved in the acute diffuse external otitis of patients without previous antibiotic treatment (two weeks before obtaining the samples). Of 79 isolated microorganisms in 62 patients that fulfilled the requirements established Pseudomonas, mainly P. Aeruginosa, represented a 46.83% altogether followed by Staphylococcus (18.98%). In almost one fourth part of the cases strains of associated fungi were identified.

Pharmacokinetics of a netilmicin loading dose on the first postnatal day in preterm neonates with very low gestational age.

OBJECTIVE: Pharmacokinetic parameters are important for dose adjustment of aminoglycosides, but they are highly variable in neonates. In this study the pharmacokinetics of a netilmicin loading dose was investigated on the first postnatal day in preterm neonates with very low gestational age (GA). METHODS: In an open prospective study, 20 neonates with GA between 22.9 and 32.0 weeks and suspected postnatal bacterial infection received an intravenous loading dose of 5 mg/kg netilmicin over 1 h during the first postnatal day. Netilmicin serum concentrations were determined by an enzyme multiplied immunoassay. RESULTS: The systemic clearance of netilmicin normalized to body weight (BW) was not significantly different in three GA subgroups (0.59+/- 0.02 ml/min/kg for GA <24 weeks, 0.72+/-0.14 ml/min/kg for GA 24-27 weeks, and 0.62+/-0.19 ml/min/kg for GA 27-32 weeks, P=0.123). Similar results were also obtained for serum elimination half-time and for the distribution volume normalized to BW. Multiple regression analysis showed that systemic clearance and volume of distribution (both not normalized to BW) significantly correlated with BW (P<0.0001) but not with GA. In the entire group, 20% of peak concentrations were below the target of 6 mg/l, and 63% of trough concentrations were above the target of 2 mg/l. CONCLUSION: In neonates with very low GA, the pharmacokinetic parameters of netilmicin determined after an intravenous loading dose were not dependent on GA when normalized to BW. A number of neonates did not reach targeted peak and trough netilmicin serum concentrations, suggesting that a higher loading dose and a prolonged dosing interval might enhance the effectiveness and safety of netilmicin in preterm neonates immediately after birth.