Med Pregl, 2002 Nov-Dec, 55(11-12), 506 - 12 {Use of antibiotics in otorhinolaryngologic practice}; Stefan-Mikic S et al.; INTRODUCTION: This study investigated utilization of antibacterial agents at the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad-Liman and at the Ear, Nose and Throat Clinic of the Clinical Center Novi Sad, in the period February-March 2001 . MATERIAL AND METHODS: All antibacterial agents were classified as group J, regarding Anatomic-Therapeutic-Chemical Classification . Data on drug utilization were presented in Defined Daily Doses (DDD) . Patients who were under observation were all treated with antibiotics . RESULTS: In regard to prescribed treatment in the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad-Liman, most outpatients were treated with macrolide antibiotics--in 26.21%; combination of penicillin and beta-lactamase inhibitors in 20.83% and pyranosides in 16.12% . At the Ear, Nose and Throat Clinic of the Clinical Center Novi Sad, macrolides and lincosamines were most frequently used--in 20.46%; cephalosporins in 19.87% and penicillins susceptible to beta-lactamase in 18.85% . It is extremely positive and in agreement with current pharmacotherapeutic principles that in both institutions peroral ampicillins have not been prescribed . Aminoglycosides have been prescribed in less than 1% of patients of the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad-Liman, whereas they were much more frequently prescribed at the Ear, Nose and Throat Clinic of the Clinical Center Novi Sad--in 11.25% . Although there is a positive postantibiotic effect in regard to these antibiotics and it is recommended to use them once a day, in both examined institutions aminoglycosides were given twice a day . In regard to bacterial identification it was done in 80.76% of patients of the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad-Liman, while in the Ear, Nose and Throat Clinic of the Clinical Center Novi Sad it was done only in 32.42% . CONCLUSIONS: Although treatment performed on empirical basis and clinical findings is usually correct, a greater percentage of antibiotic prescriptions should be confirmed by antibiograms providing optimal therapy and decreased degree of resistance. Zh Mikrobiol Epidemiol Immunobiol, 2000 Jul-Aug, (4 Suppl), 71 - 6 {Resistance of Escherichia coli to "Intercid", a leukocyte cation protein}; Gritsenko VA et al.; In vitro experiments on 120 E . coli strains isolated from different sources (43 from water, 22 from the feces of healthy persons, 55 from patients with extraintestinal E . coli infections) have demonstrated that some of E . coli isolated, mainly the causative agents of extraintestinal infections, are resistant to the antibacterial action of "intercid" and have anti-Intercid activity (AIA) and a high level of antilysozyme activity . The use of the correlation and two-factor analyses has made it possible to establish the relationship between these characteristics and to find out an even more important contribution of AIA to the determination of bacterial Intercid-resistance (fusion force h2 = 13.1-25.0%) . Experiments on E . coli isogenic variants with phenotypes AIA+ and AIA- have shown that AIA is an additional factor which determines the resistance of E . coli to "intercid". Biomaterials, 2003 Jul, 24(16), 2759 - 65 Biological efficacy of electroless-deposited silver on plasma activated polyurethane; Gray JE et al.; Silver coating of catheters has been shown to have inhibitory effects on bacterial growth and adhesion to catheter surfaces . In this study, plasma-modification was used to enhance the adhesion of an electroless silver coating on polyurethane . Both the antibacterial and antiadhesive properties of these coatings were investigated . Bacterial growth was inhibited in cultures exposed to silver-treated polyurethane compared to unmodified polyurethane . Higher growth inhibition was observed for polyurethane surfaces with lower silver coverage . Bacterial adhesion was completely inhibited on all silver-coated surfaces. Planta Med, 2003 Apr, 69(4), 371 - 4 Antibacterial alkaloids from Zanthoxylum rhoifolium; de A Gonzaga W et al.; Two new dihydrobenzophenanthridine-type alkaloids, 6-methoxy dioxolo{4',5':4,5}benzo{c} dioxolo{4,5- j}phenanthridine (1) and 2,3,13-trimethoxy-5,11a-dihydro dioxolo{4',5':4,5}benzo{c}phenanthridine (2) were isolated from the stem bark of Zanthoxylum rhoifolium, together with four other previously known benzophenanthridine alkaloids, 6-acetonyldihydronitidine (3) {= 8-acetonyldihydronitidine}, 6-acetonyldihydroavicine (4) {= 8-acetonyldihydroavicine}, 6-acetonyldihydrochelerythrine (5) and xanthoxyline (6) . The structures were elucidated mainly by spectroscopic methods, including 1D and 2D NMR spectroscopy . For alkaloids 1 and 2 we propose the trivial names rhoifolines A and B . The crude plant extracts and the alkaloids 3, 4 and 6 showed activity against Gram (+/-) bacteria, while the new alkaloids 1 and 2 were inactive. Eur J Biochem, 2003 May, 270(9), 1969 - 79 Solution structure of crotamine, a Na+ channel affecting toxin from Crotalus durissus terrificus venom; Nicastro G et al.; Crotamine is a component of the venom of the snake Crotalus durissus terrificus and it belongs to the myotoxin protein family . It is a 42 amino acid toxin cross-linked by three disulfide bridges and characterized by a mild toxicity (LD50 = 820 micro g per 25 g body weight, i.p . injection) when compared to other members of the same family . Nonetheless, it possesses a wide spectrum of biological functions . In fact, besides being able to specifically modify voltage-sensitive Na+ channel, it has been suggested to exhibit analgesic activity and to be myonecrotic . Here we report its solution structure determined by proton NMR spectroscopy . The secondary structure comprises a short N-terminal alpha-helix and a small antiparallel triple-stranded beta-sheet arranged in an alphabeta1beta2beta3 topology never found among toxins active on ion channels . Interestingly, some scorpion toxins characterized by a biological activity on Na+ channels similar to the one reported for crotamine, exhibit an alpha/beta fold, though with a beta1alphabeta2beta3 topology . In addition, as the antibacterial beta-defensins, crotamine interacts with lipid membranes . A comparison of crotamine with human beta-defensins shows a similar fold and a comparable net positive potential surface . To the best of our knowledge, this is the first report on the structure of a toxin from snake venom active on Na+ channel. Vestn Khir Im I I Grek, 2003, 162(1), 57 - 61 {Comparative clinical-economic analysis of antibiotic therapy in pyogenic inflammatory diseases of the lower extremities}; Shliapnikov SA et al.; A randomized comparative investigation was carried out in two equal groups of patients with pyo-inflammatory diseases of lower extremities (the total number 50 patients) in order to study effectiveness and tolerance to Netilmycin (1st group) and Gentamycin (2nd group) given in combination with Cefasolin . Clinical symptoms were estimated immediately after operation, in 3, 6 and 10-12 days after it . Bacteriological investigations were fulfilled immediately after operation, in 72 h and in 6-10 days after the beginning of antibacterial therapy . Clinical and biochemical investigations of blood were fulfilled before and in 10 days after the beginning of the treatment . Effectiveness of the treatment in the first group was 100%, in the second group--80% . In the second group the antibiotics were changed in 20% of cases and the average duration of hospitalization among the patients of this group was reliably longer that in the first group . The eradication rating of Netilmycin was higher than that of Gentamycin (25 strains from 25 and 20 from 25 respectively) . Gentamycin had a pronounced nephrotoxic effect (elevation of the level of creatinin and urea of blood in dynamics by 21% and 32%), as compared with Netilmycin (9% and 3%) . Total expenses to antibiotic therapy in the first group made up 97,650 rub, and in the second group 106,245 rub . Netilmycin in combination with Cefasolin was more effective for acute pyo-inflammatory diseases of lower extremities than a combination of Gentamycin with Cefasolin, it more rapidly resulted in reduction of clinical signs of inflammation, was better endured and more economical. Biochemistry, 2003 Apr 29, 42(16), 4669 - 80 NMR structure of the cathelin-like domain of the protegrin-3 precursor; Yang Y et al.; In mammals, numerous precursors of antibacterial peptides with unrelated sequences share a similar prosequence of 94-114 residues, termed the cathelin-like domain . The cathelin-like domain of protegrin-3 (ProS) was overexpressed in Escherichia coli and uniformly labeled with (15)N or (15)N and (13)C, and its three-dimensional structure was determined by heteronuclear NMR at pH 6.2 . Under these conditions and due to the cis-trans isomerization of the R(87)-P(88) and D(118)-P(119) amide bonds, the ProS structure was found to adopt four almost equally populated conformations in slow exchange on the NMR chemical shift time scale . The ProS structure consists of an N-terminal alpha-helix (Y(34)-N(48)) cradled by a four-stranded antiparallel beta-sheet (beta1, N(53)-L(60); beta2, K(74)-P(86); beta3, V(104)-V(111); and beta4, I(122)-C(124)) . The solution structure of ProS, which is monomeric, allowed us to determine the structure of the L1 and L2 loops, which are too mobile in the crystal structure . The regions common to the solution and X-ray structures were found to be very similar . Finally, since the overall fold of ProS is very similar to that of cystatins despite a low degree of sequence identity, the ProS solution structure was compared to the solution and X-ray structures of the chicken cystatin . This comparison revealed that the structures of the L1 and L2 loops as well as that of the appending domain are quite different in the two proteins . These differences are mainly due to the high proline residue content (10%) which disorganizes the hydrogen bond network of a part of the ProS beta-sheet in contrast to that of the chicken cystatin structure. Infez Med, 2002 Jun, 10(2), 61 - 72 {Present and future of cephalosporins}; Cornaglia G; The cephalosporins today, and particularly the third-generation cephalosporins, still possess an activity spectrum and microbiological potency such that several authors continue to regard them as the gold standard of beta-lactam antibiotic therapy . Comparison with the rapid onset of resistance to other extensively used drugs, such as the macrolides and quinolones, places the emphasis once again squarely on the great reliability of the antibacterial action of the cephalosporins and, particularly, on the validity of their targets at the bacterial cell level . The beneficial use of cephalosporins for a vast range of infectious diseases is amply confirmed by the most authoritative international guidelines and bears witness to the role of great importance that these drugs still play in all fields of antibiotic therapy, as a result of the variety of the compounds available, their broad spectrum of antibacterial activity, their multiple clinical potentialities and their excellent tolerability . The cephalosporins therefore continue to constitute a firm reference point in the overcrowded antibiotics scene and, if used appropriately, promise to conserve their leading role for a long time to come. J Antimicrob Chemother, 2003 May, 51 Suppl 1, 21 - 7 Adverse drug reactions: implications for the development of fluoroquinolones; Ball P; Quinolone antibacterials, originally derived from anti-malarial compounds, have been developed through side-chain and nuclear manipulation, notably by piperazine and other mono- or bi-cyclic substitutions at the 7 position (giving anti-pseudomonal activity and greater anti-Gram-negative activity) and fluorination at various sites (giving increased anti-Gram-positive activity) . The class has now been in clinical use for 40 years . Increased activity has not been without cost: for example, specific idiosyncratic reactions have consigned agents such as the 1-(2,4)-difluorophenyl compounds, such as temafloxacin (haemolytic uraemic syndrome) and trovafloxacin (hepatotoxic reactions), to restriction, suspension or withdrawal . Class adverse drug reactions (ADRs), variable in frequency and severity within the group, have significantly affected individual groups of compounds, such as the 8-chloro derivatives (Bay y 3118, clinafloxacin and sitafloxacin), which, whilst extremely potent, are also highly phototoxic and have largely been discarded. J Antimicrob Chemother, 2003 May, 51 Suppl 1, 1 - 11 Development of the quinolones; Andersson MI et al.; Since their discovery in the early 1960s, the quinolone group of antibacterials has generated considerable clinical and scientific interest . Nalidixic acid, the first quinolone to be developed, was obtained as an impurity during the manufacture of quinine . Since this time, many derivatives have been synthesized and evaluated for their antibacterial potency . Two major groups of compounds have been developed from the basic molecule: quinolones and naphthyridones . Manipulations of the basic molecule, including replacing hydrogen with fluorine at position 6, substituting a diamine residue at position 7 and adding new residues at position 1 of the quinolone ring, have led to enhanced antibacterial efficacy . In general these compounds are well tolerated . However, some of these structural changes have been found to correlate with specific adverse events: the addition of fluorine or chlorine at position 8 being associated with photo-reactivity, e.g . Bay y 3118 and sparfloxacin; and the substitution of an amine or a methyl group at position 5 having a potential role in QTc prolongation, e.g . sparfloxacin and grepafloxacin . Progressive modifications in molecular configuration have resulted in improved breadth and potency of in vitro activity and pharmacokinetics . One of the most significant developments has been the improved anti-Gram-positive activity of the newer compounds, such as moxifloxacin and garenoxacin . In the current millennium, these new agents may play an important role in the treatment of respiratory infections. BMJ, 2003 Apr 19, 326(7394), 850 - 2 Outbreak of severe acute respiratory syndrome in Hong Kong Special Administrative Region: case report; Chan-Yeung M et al.; OBJECTIVE: To describe the outbreak of severe acute respiratory syndrome in Hong Kong . DESIGN: Descriptive case series . SETTING: Hong Kong, Special Administrative Region, China RESULTS: The outbreak started with a visitor from southern China on 21 February . At the hospitals where the first cases were treated the disease spread quickly among healthcare workers, and then out into the community as family members became infected . By 1 April, 685 cases had been reported with 16 deaths . Symptoms include high fever and one or more respiratory symptoms (including cough, shortness of breath, and difficulty breathing) . Changes in lung tissue suggest that part of the lung damage is due to cytokines induced by the microbial agent, which has led to empirical treatment with corticosteroids, broad spectrum antiviral agent, and antibacterial cover . There is strong evidence that a novel coronavirus is the pathogen . Precautions for droplet infection should be instituted, including the wearing of masks and rigorous disinfection and hygiene procedures . On 27 March the Department of Health announced drastic measures, including vigorous contact tracing and examination, quarantine of contacts in their homes, and closure of all schools and universities . CONCLUSION: The rapidity of the spread of the disease and the morbidity indicate that the agent responsible is highly infectious and virulent . Strict infection control measures for droplet and contact transmission by healthcare workers, a vigilant healthcare profession, and public education are essential for disease prevention. Am J Respir Crit Care Med, 2003 Aug 1, 168(3), 281 - 6 Epub 2003 Apr 17. Reduced nitric oxide in sinus epithelium of patients with radiologic maxillary sinusitis and sepsis; Deja M et al.; Radiologic maxillary sinusitis is an important risk factor for development of bronchopneumonia in mechanically ventilated patients . Nitric oxide produced within the paranasal sinuses is considered to provide an antibacterial environment and to modulate mucociliary clearance function . We hypothesized that a reduced formation of nitric oxide might contribute to the compromised local host defense in radiologic maxillary sinusitis and measured nitric oxide levels directly within maxillary sinuses of septic patients with radiologic maxillary sinusitis (n = 11), whose sinuses were fenestrated to eliminate a possible septic focus . Data were compared with those of patients without airway inflammation (n = 11, control subjects) . Despite local inflammation and infection, we found considerably lower maxillary nitric oxide levels than in control subjects (31 +/- 10 versus 2554 +/- 385 parts per billion, mean +/- standard error of the mean, p < 0.001) . Consistently, immunohistochemical and in situ hybridization investigations revealed strongly reduced expression of inducible nitric oxide synthase . By applying ultrastructural immunolocalization, we identified cilia and microvilli of the maxillary sinus epithelium as the major nitric oxide production site in control subjects . Our findings provide evidence of markedly reduced nitric oxide production in maxillary sinuses of patients with radiologic maxillary sinusitis and sepsis, implicating impaired local host defense and an increased risk for secondary infections. Parassitologia, 2002 Dec, 44(3-4), 153 - 6 Antifungal activity of essential oils from leaves and flowers of Inula viscosa (Asteraceae) by Apulian region; Cafarchia C et al.; Some essential oils from several plants (Artemisia verlotorum, Lavandula augustifolia, Ocimum gratissimum) have proved to have acaricidal, antifungal and antibacterial activity . Inula viscosa Ait . (Asteraceae), a plant growing spontaneously in the Mediterranean area, is currently used by popular medicine for its therapeutic effects . Flavonoids, azulenes, sesquiterpenes, and essential oils have been isolated and identified from its leaves . This paper reports the results of the composition and antifungal activity in vitro against dermatophytes and Candida spp . of the four essential oils obtained by steam distillation of the leaves, flowers, whole plant and whole plants without flower extracts of I . viscosa . All the extracts proved to have a significant antifungal activity against dermatophytes even at low concentrations (0.01 mg/ml) . The leaf extracts exhibited the greatest antifungal efficacy . The high concentration of the sesquiterpene (carboxyeudesmadiene), occurring in the leaf extracts, may explain its greater antifungal activity. Int J Food Sci Nutr, 2003 Jan, 54(1), 89 - 95 Black tea extract and dental caries formation in hamsters; Linke HA et al.; Several studies have suggested that green tea and Oolong tea extracts have antibacterial and anticariogenic properties in vitro and in vivo . The aim of the present study was to determine the effect of a standardized black tea extract (BTE) on caries formation in inbred hamsters on a regular and a cariogenic diet . Eighty hamsters were divided into four groups of 20 animals each . Two groups received a pelleted regular diet (LabChow) with water or BTE ad libitum . The other two groups received a powdered cariogenic diet (Diet 2000, containing 56% sucrose) with water or BTE ad libitum . The animals were kept for 3 months on their respective diets and then were sacrificed . The heads were retained, the jaws were prepared and stained using alizarin mordant red II, and were then scored for dental caries according to the Keyes method . This is the first study indicating that BTE, as compared with water, significantly decreased caries formation by 56.6% in hamsters on a regular diet and by 63.7% in hamsters on a cariogenic diet (P < 0.05) . In the cariogenic diet group BTE, reduced the mandibular caries score of the hamsters slightly more than the maxillary caries score . The fluoride content of the standardized BTE solution was frequently monitored during the experiment; the mean fluoride concentration was found to be 4.22 ppm . A frequent intake of black tea can significantly decrease caries formation, even in the presence of sugars in the diet. Protein Expr Purif, 2003 Apr, 28(2), 350 - 6 Expression of the recombinant antibacterial peptide sarcotoxin IA in Escherichia coli cells; Skosyrev VS et al.; Sarcotoxin IA is an antibacterial peptide that is secreted by a meat-fly Sarcophaga peregrina larva in response to a hypodermic injury or bacterial infection . This peptide is highly toxic against a broad spectrum of both Gram-positive and Gram-negative bacteria and lethal to microbes even at nanomolar concentrations . However, research needs as well as its potential use in medicine require substantial amounts of highly purified sarcotoxin . Because heterologous expression systems proved to be inefficient due to sarcotoxin sensitivity to intracellular proteases, here we propose the biosynthesis of sarcotoxin precursors in Escherichia coli cells that are highly sensitive to the mature peptide . To optimize its biosynthesis, sarcotoxin was translationally fused with proteins highly expressed in E . coli . A fusion partner and the position of sarcotoxin in the chimeric polypeptide were crucial for protecting the sarcotoxin portion of the fusion protein from proteolysis . Released after chemical cleavage of the fusion protein and purified to homogeneity, sarcotoxin displayed antibacterial activity comparable to that previously reported for the natural peptide. J Med Chem, 2003 Apr 24, 46(9), 1567 - 70 The pharmacophore of short cationic antibacterial peptides; Strom MB et al.; Cationic antibacterial peptides have been proclaimed as new drugs against multiresistant bacteria . Their limited success so far is partially due to the size of the peptides, which gives rise to unresolved issues regarding administration, bioavailability, metabolic stability, and immunogenicity . We have systematically investigated the minimum antibacterial motif of cationic antibacterial peptides regarding charge and lipophilicity/bulk and found that the pharmacophore was surprisingly small, opening the opportunity for development of short antibacterial peptides for systemic use. Klin Med (Mosk), 2003, 81(3), 51 - 4 {Comparative effectiveness of antibacterial drugs in the treatment of reactive arthritis}; Glazunov AV et al.; The authors have studied efficacy of various antibacterial drugs in reactive arthritis (RA) . A comparative randomized trial was made of efficacy of doxocycline (DC) in a dose 200 mg/day, erythromycin (EM) in a dose 2 g/day, co-trimoxazole (CT) in a dose 1920 mg/day, cyprofloxacin (CF) in a dose 1 g/day in 79 RA patients . Each of the drug was given as two three-week courses with a 3-week interval . The patients were followed up for 12 months . The assessment of the drugs effect on the articular syndrome and the symptoms of the infectious focus was made with the use of computer questionnaire . 3-month remission was achieved in 9 DC patients (43%), 5 EM patients (24%), 6 CF patients (32%) and only in one CT patient (6%) . Suppression of the infectious foci was similar for all the drugs tested during the follow-up period . Within the first three months of the trial DC had significant advantages over the other antibiotics in management of the articular syndrome . CF was highly effective (p < 0.001) in patients with RA running up to one year . The conclusion is made that suppression of the symptoms of the focal infection is not sufficient for RA effective treatment, antibiotics vary significantly by their effect on the course of the articular process. Eur J Clin Pharmacol, 2003 Apr, 58(12), 843 - 9 Epub 2003 Mar 18. Problems in collecting comparable national drug use data in Europe: the example of antibacterials; Ronning M et al.; OBJECTIVE: To describe the methodological problems in collecting retrospectively comparable data on drug use and to compare the use of antibacterials in some European countries . METHODS: A spreadsheet was distributed in 2000 through the European Drug Utilisation Research Group (EuroDURG) network, requesting 1994-1999 data on use of antibacterials for systemic use (ATC group J01), from ambulatory, hospital, or total care, aggregated at ATC 4th level, and presented in defined daily doses per 1000 inhabitants per day (in the 1999 ATC/DDD version or specified other version) . RESULTS: The network was able to provide national utilization data for two or more years in the requested period from 16 countries (4 only from primary care, 3 both from primary care and total use, and 9 only total use data) . The main methodological problems identified were: use of divergent ATC/DDD versions, divergent assignment of DDDs for combination products and the use of unofficial or national DDDs . It was possible to correct for the different ATC/DDD versions to some extent, except for the cephalosporin group (not included in the analysis), as the collection of data at the ATC 4th level precluded recalculation of DDDs . In the seven countries with primary care data the total J01 antibacterials use varied by a factor of 2.5 (Belgium 23.4 and The Netherlands 9.5 DDDs per 1000inhabitants per day) . The use of J01A tetracyclines varied fourfold, and the use of J01C penicillins and J01F macrolides and lincosamides approximately threefold . Significant reduction over time was seen in J01A and an increase in J01F . CONCLUSIONS: In the scientific and regulatory community it is still difficult to perform a valid and comprehensive cross-national collection of utilization data on antibacterials . White spots on the European map persist for ambulatory care data, and data are missing for the hospital sector in most countries . For a thorough explanation of the considerable intercountry variability (especially in antibacterial subgroups and time trends analysis) a sustained and concerted effort is necessary to implement a validation process of the ATC/DDD use in the various countries and to adopt a common methodological approach to the collection of utilization data at the substance level (ATC 5th level). J Antimicrob Chemother, 2003 May, 51(5), 1159 - 65 Epub 2003 Apr 14. Enhancement of antibacterial and lipopolysaccharide binding activities of a human lactoferrin peptide fragment by the addition of acyl chain; Majerle A et al.; Cationic antibacterial peptides are potentially therapeutic in the treatment of sepsis, because of their amalgamated antibacterial and lipopolysaccharide-binding activities . We prepared acyl analogues of the peptide fragment of human lactoferrin, which originally had weak antibacterial activity . It was found that 12 carbon units constitute the optimal acyl chain length, enhancing the antibacterial activity and binding of lipopolysaccharide by up to two orders of magnitude . Lactoferrin-based lipopeptides approached the activity of polymyxin B, a lipopeptide of natural origin, but were also active against Gram-positive bacteria. J Antimicrob Chemother, 2003 May, 51(5), 1109 - 17 Epub 2003 Apr 14. Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protection; Ruiz J; Quinolones are broad-spectrum antibacterial agents, commonly used in both clinical and veterinary medicine . Their extensive use has resulted in bacteria rapidly developing resistance to these agents . Two mechanisms of quinolone resistance have been established to date: alterations in the targets of quinolones, and decreased accumulation due to impermeability of the membrane and/or an overexpression of efflux pump systems . Recently, mobile elements have also been described, carrying the qnr gene, which confers resistance to quinolones. Dev Comp Immunol, 2003 Jun-Jul, 27(6-7), 513 - 20 Mass spectrometric analyses of CL(39), CL(41) and H(1), H(2), H(3) confirm identity with fetidin and lysenin produced by earthworm leukocytes; Koenig S et al.; Antibacterial proteins realize effective immunological mechanisms against invading pathogens . Some of them exert hemolytic and agglutinating properties . Here, we analyzed two hemolysins isolated from cell lysate (CL(39) and CL(41)) and three hemolytic proteins isolated from coelomic fluid (H(1), H(2) and H(3)) of the annelid Eisenia fetida using mass spectrometry and bioinformatics . We demonstrated the identity of CL(39,41) with fetidin and lysenin; these have been described earlier . H(1-3) share sequence components with fetidin but they seem to be glycosylated as shown for H(1) . The results help to resolve a long debate concerning nomenclature and identity of these hemolytic proteins . They support: (1) . the concept that the hemolytic proteins originate from chloragocytes; (2) . their origin to some extent from large coelomocytes; and (3) . the view that they are secreted into CF. Vet Rec, 2003 Mar 29, 152(13), 392 - 4 Clinical efficacy of flunixin, carprofen and ketoprofen as adjuncts to the antibacterial treatment of bovine respiratory disease; Lockwood PW et al.; Three non-steroidal anti-inflammatory drugs (NSAIDs), flunixin, ketoprofen and carprofen, were used in conjunction with ceftiofur, in the treatment of naturally occurring bovine respiratory disease . Sixty-six mixed-breed beef cattle weighing on average 197 kg met the inclusion criteria of pyrexia of at least 40 degrees C, an illness score indicating at least moderate illness and at least moderate dyspnoea . They were allocated randomly to four treatment groups . All the groups received ceftiofur for three days at a dose rate of 1.1 mg/kg by intramuscular injection, and three groups received, in addition, a single dose of either flunixin (2.2 mg/kg by intravenous injection) or ketoprofen (3 mg/kg by intravenous injection) or carprofen (1.4 mg/kg by subcutaneous injection) . During the first 24 hours of the study, the pyrexia of the three groups treated with a NSAID was reduced significantly more than the pyrexia of the group treated with ceftiofur alone, and two and four hours after treatment the reduction in pyrexia was significantly greater in the groups treated with flunixin and ketoprofen than in the group treated with carprofen . There were no statistically significant differences between the four groups with respect to depression, illness scores, dyspnoea or coughing . There was less lung consolidation in the three groups treated with a NSAID than in the animals treated with ceftiofur alone, but the difference was significant only in the group treated with flunixin. Medicina (Kaunas), 2003, 39(3), 260 - 5 {The influence of the initial antibacterial treatment effectiveness, clinical and etiological factors on non-resolvent severe pneumonia and outcome}; Dudzevicius V et al.; AIM: To evaluate the influence of the initial pneumonia treatment effectiveness, clinical and etiological factors, local innate immune response intensity on pneumonia non-resolution and mortality . MATERIALS AND METHODS: One hundred one bronchoscopy and bronchoalveolar lavage performed to 68 severe community (CAP) or hospital-acquired pneumonia patients survived during initial 5-7-day treatment period . Initial treatment effectiveness, age, pneumonia type, presence of mechanical ventilation, comorbidities, coma, antibacterial treatment, pathogen isolation and treatment changes were assessed . Logistic regression analysis was performed to detect factors associated with non-resolving pneumonia and mortality . RESULTS: Etiotropical treatment was administered to 30.9% of patients . Initial antibacterial treatment was corrected in 64.7% of all cases . After 21-30 days from the pneumonia onset survived 66.2% of patients (n=43) . Pneumonia course could be evaluated in 52 cases . Delayed resolution of the pneumonia was stated in 32.7% of cases (n=17) . Pneumonia was cured or condition improved in 64.3% of the CAP patients (n=9) and 68.4% of the hospital-acquired pneumonia patients (n=26) . Only ineffective initial pneumonia treatment significantly increased probability of non-resolving pneumonia on multivariate analysis (OR 16.92, 95% CI 2.02-141.72, p<0.05) . Influence of etiotropic treatment was not significant . Isolation of two or more pathogens from bronchoalveolar lavage fluid after the initial treatment was significantly associated with mortality on multivariate analysis (OR 6.25, CI 1.06-36.74, p<0.05) . The other analyzed variables had no significant influence on pneumonia resolution and outcome . In conclusion, the initial pneumonia treatment failure increases probability of the non-resolving pneumonia . Etiotropical treatment has no impact on pneumonia outcome when adequate empirical antibacterial treatment is administered, however, it allows to reduce unnecessary use of the broad-spectrum antibacterials . Mortality is associated with the presence of the polymicrobial infection after the initial pneumonia treatment. Eur J Pharm Sci, 2003 Apr, 18(5), 323 - 8 Electrochemical reduction of desmycosin, structure investigation and antibacterial evaluation of the resulting products; Ivekovic D et al.; Electrochemical reduction of desmycosin at the mercury electrode in aqueous medium was investigated by cyclic voltammetry and preparative scale electrolysis was carried out for the isolation and identification of products . Structure analyses of the resulting products were accomplished by MS, 1D and 2D NMR spectroscopy . The results obtained show that dimerization and two electron reduction of desmycosin occur in parallel yielding a symmetric dimer at position C13 and 10,11-dihydrodesmycosin as the end products . 10,11-dihydrodesmycosin shows decreased antibacterial activity in vitro in comparison with desmycosin, while the dimer is inactive. Biochemistry, 2003 Apr 22, 42(15), 4406 - 13 Structure-activity studies of the inhibition of FabI, the enoyl reductase from Escherichia coli, by triclosan: kinetic analysis of mutant FabIs; Sivaraman S et al.; Triclosan, a common antibacterial additive used in consumer products, is an inhibitor of FabI, the enoyl reductase enzyme from type II bacterial fatty acid biosynthesis . In agreement with previous studies {Ward, W . H., Holdgate, G . A., Rowsell, S., McLean, E . G., Pauptit, R . A., Clayton, E., Nichols, W . W., Colls, J . G., Minshull, C . A., Jude, D . A., Mistry, A., Timms, D., Camble, R., Hales, N . J., Britton, C . J., and Taylor, I . W . (1999) Biochemistry 38, 12514-12525}, we report here that triclosan is a slow, reversible, tight binding inhibitor of the FabI from Escherichia coli . Triclosan binds preferentially to the E.NAD(+) form of the wild-type enzyme with a K(1) value of 23 pM . In agreement with genetic selection experiments {McMurry, L . M., Oethinger, M., and Levy, S . B . (1998) Nature 394, 531-532}, the affinity of triclosan for the FabI mutants G93V, M159T, and F203L is substantially reduced, binding preferentially to the E.NAD(+) forms of G93V, M159T, and F203L with K(1) values of 0.2 microM, 4 nM, and 0.9 nM, respectively . Triclosan binding to the E.NADH form of F203L can also be detected and is defined by a K(2) value of 51 nM . We have also characterized the Y156F and A197M mutants to compare and contrast the binding of triclosan to InhA, the homologous enoyl reductase from Mycobacterium tuberculosis . As observed for InhA, Y156F FabI has a decreased affinity for triclosan and the inhibitor binds to both E.NAD(+) and E.NADH forms of the enzyme with K(1) and K(2) values of 3 and 30 nM, respectively . The replacement of A197 with Met has no impact on triclosan affinity, indicating that differences in the sequence of the conserved active site loop cannot explain the 10000-fold difference in affinities of FabI and InhA for triclosan. Vet Surg, 2003 Mar-Apr, 32(2), 128 - 33 In vitro elution of gentamicin from Plaster of Paris beads; Santschi EM et al.; OBJECTIVE: To determine the in vitro elution characteristics of gentamicin from Plaster of Paris-gentamicin (POP-gent) beads . STUDY DESIGN: In vitro, controlled, experimental study . METHODS: The POP-gent beads were made using a bead mold from 20 g calcium sulfate hemihydrate, 5 mL (500 mg) gentamicin solution, and 3 mL of phosphate buffered saline (PBS) . Control beads were made similarly, using 30 g of dried powder and 8 mL of PBS . Beads were left in the mold overnight, gas-sterilized with ethylene oxide, and stored at room temperature for 5 months before testing . Bead chains were placed in sterile tubes containing porcine serum, and tubes were placed in a 37 degrees C incubator on a rocker . Serum was removed at intervals over 14 days and the concentration of gentamicin determined by fluorescent polarization immunoassay . Serum antibacterial activity was determined against an equine origin Escherichia coli . RESULTS: POP-gent beads released gentamicin for the 14-day sampling period . Eighty percent of the gentamicin incorporated in the beads was released over the first 48 hours . Eluent from POP-gent beads inhibited the growth of E coli at all time periods . No gentamicin was eluted from control beads and control eluent did not inhibit growth of E coli . CONCLUSIONS: In this experimental model, POP-gent beads released bactericidal drug for 14 days . Eighty percent of the gentamicin incorporated into the beads was released during the first 48 hours . The drug retains its bactericidal activity after ethylene oxide sterilization and storage at room temperature for up to 5 months . CLINICAL RELEVANCE: Pop-gent beads may be a useful repository device to deliver gentamicin locally in tissues . Clin Microbiol Rev, 2003 Apr, 16(2), 189 - 208 Potential impact of increased use of biocides in consumer products on prevalence of antibiotic resistance; Gilbert P et al.; There has recently been much controversy surrounding the increased use of antibacterial substances in a wide range of consumer products and the possibility that, as with antibiotics, indiscriminate use of biocides might contribute to the overall pattern of susceptibility in the general environment and in the clinic . Such speculation, based on the isolation of resistant mutants from in vitro monoculture experiments, is not reflected by an emergence of biocide-resistant strains in vivo . This review provides a broad coverage of the biocide and resistance literature and evaluates the potential risks, perceived from such laboratory monoculture experiments, against evidence gathered over 50 years of field studies . An explanation for the continued effectiveness of broad-spectrum biocidal agents against the decline in efficacy of therapeutic agents is provided based on the fitness costs of resistance and the ubiquity of naturally occurring substances that possess antibacterial effect . While we conclude from this review of the literature that the incorporation of antibacterial agents into a widening sphere of personal products has had little or no impact on the patterns of microbial susceptibility observed in the environment, the associated risks remain finite . The use of such products should therefore be associated with a clear demonstration of added value either to consumer health or to the product life . Hygienic products should therefore be targeted to applications for which the risks have been established. Support Care Cancer, 2003 Jun, 11(6), 362 - 70 Epub 2003 Apr 11. Piperacillin-tazobactam is more effective than ceftriaxone plus gentamicin in febrile neutropenic patients with hematological malignancies: a randomized comparison; Gorschluter M et al.; GOALS: Efficacy and costs of empirical antibacterial therapy in febrile neutropenic patients are important issues . Several strategies have been reported to be similarly effective: monotherapy with cefepime, ceftazidime or a carbapenem or duotherapy with an antipseudomonal beta-lactam antibiotic or ceftriaxone in combination with an aminoglycoside . Piperacillin-tazobactam monotherapy is promising, but its role in this setting still has to be defined . PATIENTS AND METHODS: Of 212 consecutive febrile episodes in 130 neutropenic patients with hematological malignancies randomized to receive either piperacillin-tazobactam (4.5 g every 8 h; group A) or ceftriaxone (2 g once daily plus gentamicin 5 mg/kg once daily; group B), 183 episodes (98 group A, 85 group B) were evaluable for response . RESULTS: Defervescence within 72 h without modification of the antibiotic therapy was achieved in 56/98 episodes (57.1%) in group A and in 30/85 (35.3%) in group B (P=0.0047) . If fever persisted, teicoplanin plus gentamicin (group A) or teicoplanin plus ciprofloxacin (group B) were added . All patients still febrile then received meropenem, teicoplanin and amphotericin B . With these modifications of antibiotic therapy, 89.8% of patients in group A had responded at 21 days but only 71.8% in group B (P=0.005) . The mean total antibiotic drug cost in group A was only 39.4% of that in group B (euro 445 versus euro 1129; P=0.010) . CONCLUSION: Piperacillin-tazobactam monotherapy is significantly more effective and cost-efficient than ceftriaxone plus gentamicin as first-line therapy in febrile neutropenic patients with hematological malignancies. Biometals, 2003 Sep, 16(3), 411 - 8 Platinum(II) and palladium(II) complexes with 2-acetyl pyridine 4N-ethyl thiosemicarbazone able to overcome the cis-platin resistance . Structure, antibacterial activity and DNA strand breakage; Kovala-Demertzi D et al.; The reactions of Pd(II) and Pt(II) with 2-Acetyl Pyridine N(4)-Ethyl-Thiosemicarbazones, HAc4Et and 2-Acetyl Pyridine N(4)-1-(2-pyridyl)-piperazinyl Thiosemicarbazone, HAc4PiPiz and 2-Formyl Pyridine N(4)-1-(2-pyridyl)-piperazinyl Thiosemicarbazone, HFo4PiPiz afforded the complexes, {Pd(Ac4Et)}, 1, {Pd(HAc4Et)2}Cl2, 2 and {Pd(Ac4Et)2}, 3 {Pt(Ac4Et)}, 4, {Pt(HAc4Et)2}Cl2, 5, {Pt(Ac4Et)2}, 6 and {Pd(Fo4PipePiz)Cl}, 7, {Pd(Fo4PipePiz)2}, 8, {Pd(Ac4PipePiz)Cl}, 9 and {Pd(Ac4PipePiz)2}, 10 . The crystal structure of the complex {Pt(Ac4Et)2}, 6 has been solved . The platinum(II) atom is in a square planar environment surrounded by two cis nitrogen atoms and two cis sulfur atoms . The ligands are not equivalent, one being tridentate with (N,N,S) donation, the other being monodentate using only the sulfur atom to coordinate to the metal . The tridentate ligand shows a Z, E, Z configuration while the monodentate ligand shows an E, E, Z . Inter-molecular hydrogen bonds stabilize the structure, while the crystal packing is determined by pi-pi, and Pt-C interactions . The antibacterial effect of Pd(II) and Pt(II) complexes were studied in vitro . The complexes were found to have effect on Gram(+) bacteria, while the same complexes showed no bactericidal effect on Gram(-) bacteria . The effect of the Pd(II) and Pt(II) complexes on the in vitro DNA strand breakage was studied by agarose gel electrophoresis . The complexes 1-6 were found to exhibit a cytotoxic potency in a very low micromolar range and to be able to overcome the cisplatin resistance of A2780/Cp8 cells. Schweiz Monatsschr Zahnmed, 2003, 113(2), 136 - 42 {Delmopinol--an alternative to chlorhexidine?}; Arweiler NB et al.; The prevention of caries and gingivitis is mainly based upon modalities aiming to reduce supra- and subgingival dental plaque . Certain antibacterial agents may compensate for non-adequately self-performed mechanical plaque removal . While such prophylactic agents exhibit an antibacterial effect against oral microorganisms, the new agent delmopinol possesses the property of inhibiting the adhesion of oral microorganisms to the tooth surface . In numerous studies, delmopinol showed a plaque inhibitory potential . However, due to the lower efficacy and side effects similar to those of chlorhexidine, at present, delmopinol cannot be considered as an alternative to chlorhexidine . A long-term utilization of delmopinol in addition to the regular mechanical plaque control might be possible . For the time being there is a lack of studies comparing the efficacy of delmopinol to that of other antibacterial substances such as amine fluoride/stannous fluoride, triclosan/copolymer or cetylpyridinium chloride. Anticancer Res, 2003 Jan-Feb, 23(1A), 355 - 62 Luteolin induces N-acetylation and DNA adduct of 2-aminofluorene accompanying N-acetyltransferase activity and gene expression in human bladder cancer T24 cell line; Su CC et al.; Arylamine N-acetyltransferase (NAT) plays an important role in the first step of arylamines metabolism . Luteolin has shown antibacterial, antioxidant and antineoplastic activity . To glean insights into the mechanism of action of luteolin, we assessed the effects of luteolin on NAT activity and gene expression and DNA-2-aminofluorene (AF) adduct formation in human bladder cancer T24 cells . By using high performance liquid chromatography, the amounts of N-acetylation of AF and DNA adducts were determined and quantitated . Gene expression was performed by using polymerase chain reaction and gel electrophoresis . The results indicated: 1) luteolin displayed a dose-dependent inhibition of NAT activity and gene expression (NAT1 mRNA) in T24 cells; 2) time-course experiments showed that N-acetylation of AF measured from intact T24 cells was inhibited by luteolin for up to 48 hours; 3) using standard steady-state kinetic analysis, it was demonstrated that luteolin was a possible uncompetitive inhibitor of NAT activity in T24 cells; and 4) the DNA-AF adduct formation in T24 cells was inhibited by luteolin . This report is the first finding which has shown luteolin to affect human T24 cell NAT activity and gene expression (NAT1 mRNA) and DNA-AF adduct formation. Russ J Immunol, 1998 Jul, 3(2), 159 - 166 Immunocorrection Therapy in Complex Treatment of Prostatitis; Guskov AR et al.; Previously, we had shown that patients with chronic prostatitis exhibited impassability of the prostate excretory ducts leading to the microabscesses formation in the prostate tissue . The main reasons of low efficacy of traditional antibacterial therapy were elucidated . The antibacterial therapy was shown to induce secondary immunodeficiency . Proceeding from the above, we elaborated new strategy for treating chronic prostatitis that included two main components: surgical recovery of draining from the prostate lobules (using vacuum aspiration); and complex prostatitis treatment containing obligatory immunocorrection . Ninety four patients with chronic prostatitis aged 20-55 years were examined and treated . The immunocorrection comprised three steps: (i) antioxidant therapy and initial immunocorrection accompanying surgical draining recovery; (ii) antibiotic therapy and immunocorrection; and (iii) post-treatment recovery therapy that was selected individually for each patient . The latter enabled to reveal and to treat successfully individual immune system disturbances . As a result, 97% of patients exhibited complete recovery of the prostate function and sexual activity. J Ethnopharmacol, 2003 May, 86(1), 59 - 61 Antibacterial activity of two plant extracts on eight burn pathogens; Gnanamani A et al.; Antibacterial activity of crude alcoholic extract of Datura alba and Celosia argentea leaves were studied against pathogens isolated from infected burn patients . The disc-diffusion method showed significant zone of lysis against all the pathogens studied and the results are comparable to the conventional antibiotic cream namely Silver Sulphadiazine (SSD) . On comparing the efficiency of the two extracts, extract of D . alba exhibited more than 50% increase in antibacterial activity compared to C . argentea. J Chromatogr A, 2003 Mar 21, 990(1-2), 247 - 58 Development and validation of a capillary zone electrophoresis method for the quantitative determination of anthocyanins in wine; Saenz-Lopez R et al.; A capillary zone electrophoresis (CZE) method is proposed for the quantitative determination of anthocyanins in wine as an alternative to high-performance liquid chromatography . The CZE separation was carried out using a 46 cm (effective length) x 75 microm I.D . fused-silica capillary at 10 degrees C and a 50 mM sodium tetraborate buffer at pH 8.4 with 15% of methanol as modifier . A voltage of 25 kV and a hydrodynamic injection of 300 mbar s were used . The electropherograms were recorded at 599 nm . It was found that SO2 (antibacterial and antioxidant agent added to wine during its production) increased the absorbance of anthocyanins at 599 nm in a basic medium . Therefore, a concentration of 250 mg/l of SO2 was added to the samples and the calibration solution before the analysis in order to avoid errors by this matrix effect . The analytical response was linear (R=0.998) between 10 and 700 microg/ml of malvidin-3-O-glucoside . The limit of detection and the reproducibility (as a relative standard deviation, n=11) were 1 microg/ml and 1.5%, respectively . Finally, the CZE method was validated by the analysis of synthetic wine samples (errors less than 8%) and by the comparison of the results obtained in the analysis of different monovarietal wines by CZE with those obtained by the standard HPLC method . In this comparison, a good correlation (R=0.998) with a slope of 1.005+/-0.044 and an intercept of -0.752+/-6.690 was obtained for malvidin-3-O-glucoside. Vet Clin North Am Food Anim Pract, 2003 Mar, 19(1), 109 - 38, vi Mastitis therapy and pharmacology; Erskine RJ et al.; Mastitis remains the most frequent cause of antibacterial use on dairy farms and contributes to a substantial portion of total drug and veterinary costs incurred by the dairy industry . Ultimately, the best outcome of mastitis therapy is a positive effect on the amount of marketed milk harvested and long-term survival of the cow . This article describes the strategies of therapy for bovine mastitis, with an emphasis on antibacterial and anti-inflammatory therapy. Clin Infect Dis, 2003 Apr 15, 36(Suppl 3), S117 - 22 Forum report: issues in clinical trials of empirical antifungal therapy in treating febrile neutropenic patients; Bennett JE et al.; There is inferential evidence that some patients with prolonged neutropenia and fever not responding to antibacterial agents are at sufficient risk of deep mycoses to warrant empirical therapy, although superiority of an antifungal agent over placebo has not been conclusively demonstrated . Amphotericin B deoxycholate, liposomal amphotericin B, and intravenous itraconazole followed by oral itraconazole solution are licensed in the United States for this indication . Fluconazole and voriconazole have given favorable results in clinical trials of patients with low and high risk of deep mold infections, respectively . Design features that can profoundly influence outcome of empirical trials are (1) inclusion of low-risk patients, (2) failure to blind the study, (3) obscuration of antifungal effects by changing antibacterial antibiotics, (4) failure to balance both arms of the study in terms of patients with prior antifungal prophylaxis or with severe comorbidities, (5) the merging of end points evaluating safety with those of efficacy, and (6) choice of different criteria for resolution of fever. Curr Pharm Des, 2003, 9(11), 857 - 66 Structure-based design approaches to cell wall biosynthesis inhibitors; Katz AH et al.; This review summarizes some of the published attempts to incorporate protein and NMR structures in the design of new antibiotics that specifically target Cell Wall biosynthesis . Most of the steps involved in peptidglycan synthesis have been investigated as potential strategies against cell wall inhibition . Structural information has been most useful in the design of molecules in the Mur enzyme pathway, penicillin binding proteins and lactamases, as well as proteins that are part of the final steps of transglycosylation - in particular, d-Ala-d-Ala ligase . Several unique issues exist in the design of effective antibacterials, such as the significant differences in protein structure between organisms, such as the case of MurB in which a large amino acid loop that occupies the active site of the E . Coli is gone in the Staph aureus enzyme . Additionally, bacterial resistance is an important issue, and in some cases, structural information can be used to understand the source of this resistance . For example, mutations within the d-Ala-d-Ala ligases lead to the inability of Vancomycin antibiotics to bind. Curr Pharm Des, 2003, 9(12), 983 - 8 Separating fact from fiction: the data behind allergies and side effects caused by penicillins, cephalosporins, and carbapenem antibiotics; Leviton I; Antibiotics developed over the past quarter century have greatly improved toxic to therapeutic ratios compared to older agents . This is due to both a wider spectrum of in vitro antibacterial activity and less frequent side effects . In combination with once daily dosing and nearly complete bioavailability of some newer agents, the better risk to benefit ratios have led to empiric antibiotic use in many situations even when bacterial infections are not likely . Many newer antibiotics are not often considered toxic, although their side effects have been documented in medical literature, and several antibiotics that were considered very safe have been removed from the market or their use severely restricted within a relatively short time after their introduction . An understanding of the frequency and mechanism of unintended effects helps physicians minimize them, treat them quickly and effectively when they occur, and even avoid them . Drug interactions and potential adverse effects of beta-lactam antibiotics, penicillins, cephalosporins, and carbapenems, are presented. Curr Top Med Chem, 2003, 3(9), 1021 - 42 Oxazolidinone antibacterial agents: a critical review; Hutchinson DK; This review covers recent developments in several important aspects of research on oxazolidinone antibacterial agents . Structure-activity relationships are first discussed, emphasizing bioisosteric replacements for the both the oxazolidinone ring and the N-acetylaminomethyl group at C-5 . The oxazolidinones have a mechanism of action that is distinct from other antibacterial agents, whereby protein synthesis is inhibited prior to initiation . Studies aimed at determining how the oxazolidinones bind to the bacterial ribosome and interfere with peptidyl transferase activity are described in detail, and are then related to the nature of the changes in the ribosomal RNA leading to resistance . Toxicity of the oxazolidinones remains a critical issue, in that early lead compounds exhibited lethal toxicity in animal studies . Preclinical and clinical safety studies of both eperezolid and linezolid are summarized, giving emphasis to histopathological effects observed in early animal studies . These studies are then related to thrombocytopenia and pancytopenia observed in patients treated with linezolid for extended time periods . Finally, studies to determine the nature and potential severity of drug-drug interactions in patients undergoing linezolid therapy are discussed. Mini Rev Med Chem, 2003 Jun, 3(4), 305 - 13 Biological activity of some monocyclic- and bicyclic beta-lactams with specified functional groups; Hwu JR et al.; This Review contains our recent studies on evaluation of biological activities associated with monocyclic beta-lactams and bicyclic beta-lactam antibiotics containing various heteroatoms . A series of bicyclic beta-lactams was synthesized, which possessed electron-withdrawing groups, such as an ester, mesylate, and triflate functionality . These beta-lactams exhibited enhanced antibacterial activity. Curr Med Chem, 2003 Jun, 10(11), 925 - 53 Anticancer and antiviral sulfonamides; Scozzafava A et al.; The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anti- carbonic anhydrase, diuretic, hypoglycemic and antithyroid activity among others . A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial antitumor activity in vitro and in vivo . Although they have a common chemical motif of aromatic/heterocyclic or amino acid sulfonamide, there are a variety of mechanisms of their antitumor action, such as carbonic anhydrase inhibition, cell cycle perturbation in the G1 phase, disruption of microtubule assembly, functional suppression of the transcriptional activator NF-Y, and angiogenesis (matrix metalloproteinase, MMP) inhibition among others . Some of these compounds selected via elaborate preclinical screenings or obtained through computer-based drug design, are currently being evaluated in clinical trials . The review summarizes recent classes of sulfonamides and related sulfonyl derivatives disclosed as effective tumor cell growth inhibitors, or for the treatment of different types of cancer . Another research line that progressed much in the last time regards different sulfonamides with remarkable antiviral activity . Thus, at least two clinically used HIV protease inhibitors possess sulfonamide moieties in their molecules, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with less toxicity or activity against drug-resistant viruses . Several non nucleoside HIV reverse transcriptase or HIV integrase inhibitors containing sulfonamido groups were also reported . Another approach to inhibit the growth of retroviruses, including HIV, targets the ejection of zinc ions from critical zinc finger viral proteins, which has as a consequence the inhibition of viral replication in the absence of mutations leading to drug resistance phenotypes . Most compounds with antiviral activity possessing this mechanism of action incorporate in their molecules primary sulfonamide groups . Some small molecule chemokine antagonists acting as HIV entry inhibitors also possess sulfonamide functionalities in their scaffold. J Chemother, 2003 Feb, 15(1), 53 - 9 Recurrent respiratory tract infections in pediatric age: a population-based survey of the therapeutic role of macrolides; Principi N et al.; In order to evaluate the efficacy of macrolides in pediatric patients with recurrent respiratory tract infections (RRTIs), we enrolled 1,706 children (783 females) aged between 6 months and 14 years (median: 4 years) with an acute respiratory infection and a history of RRTIs (> or = 8 episodes per year if aged < 3 years; > or = 6 episodes per year if aged > or = 3 years) . The therapies were chosen by the primary care pediatricians and their effects on respiratory relapses were blindly analyzed . Regardless of age and clinical diagnosis, the children treated with macrolides showed a significantly higher rate of short- and long-term clinical success than those receiving beta-lactams (p<0.0001) or symptomatics alone (p<0.0001) . These data show that macrolide therapy of acute respiratory infections influences the natural history of RRTIs, probably because of their elective activity on atypical bacteria . They also suggest the possible importance of these pathogens in causing recurrences of respiratory infections in children and show that the infections they cause may have a more complicated course unless treated with adequate antibacterial drugs. J Chemother, 2003 Feb, 15(1), 27 - 30 Bacterial susceptibilities to piperacillin/tazobactam in a tertiary care hospital: 5-year review; Platsouka E et al.; Several factors influence the speed of development of antibacterial resistance, among which is the amount of antibiotic consumption . During the 3-year period 1998-2000, the consumption of piperacillin/tazobactam (pip/tazo) increased by 85% in our hospital . Five years ago we conducted a comparative in vitro study to evaluate susceptibilities of microorganisms to pip/tazo . The objective of the present study was to re-evaluate in vitro susceptibilities to pip/tazo, compared to other beta-lactams, and the potential impact its increased consumption might have on its susceptibility patterns . The study was performed between November 2000 and April 2001 . As in 1996, of the beta-lactams studied, pip/tazo and imipenem had the highest susceptibility rates against selected pathogens (>90% susceptibility rates) . P . aeruginosa susceptibilities to both imipenem and pip/tazo were high (97% for both) . P . aeruginosa susceptibilities to cefepime were lower . Despite its increased use, pip/tazo retained its initially observed high susceptibility rates for the study pathogens. J Environ Pathol Toxicol Oncol, 2003, 22(1), 41 - 8 Antibacterial medicinal plants Equiseti herba and Ononidis radix modulate micronucleus formation in human lymphocytes in vitro; Joksic G et al.; We assessed the in vitro cytogenetic effects of extracts of the commonly used medicinal plants Equiseti herba, Ononidis radix, and Uvae ursi on irradiated human blood lymphocytes . We examined the acquired micronucleus formation in unirradiated and irradiated samples of cultured blood lymphocytes using the cytochalasin block micronucleus test (CBMN) . Centromere-positive micronuclei were identified by fluorescence in situ hybridization using a DNA probe labeled with alpha-satellite digogsigenin . Equiseti herba had weak clastogenic properties, increasing the yield of micronuclei in unirradiated samples and reducing the level of radiation-induced micronuclei in a concentration-dependent manner . In the control, unirradiated samples, 36.8% of micronuclei were centromere-positive (MNC+), while in the irradiated ones the percentage of MNC+ ranged from 10.8-15.3%, indicating a clastogenic mechanism for the micronuclei formation . Ononidis radix was a strong clastogen and radiosensitizer, rapidly increasing the yield of micronuclei in unirradiated samples up to 5-fold and potentiating the yield of radiation-induced micronuclei up to 1.7-fold . In cultures treated with Ononidis radix, the percentage of MNC+ micronuclei ranged from 18.8 to 23.8%, indicating that micronuclei originated by a clastogenic mechanism . Uvae ursi did not affect the yield of micronuclei either in unirradiated or in irradiated samples . The micronucleus formation assay is a reliable screen for plant extracts and purified compounds, for the identification of compounds that might either inhibit clastogenesis or potentiate radiotherapy for malignancy. J Wound Care, 2003 Mar, 12(3), 113 - 8 A reappraisal of the role of cerium in burn wound management; Lansdown AB et al.; A rare earth element, cerium, was introduced as an antibacterial agent in 1976 but has rarely been used due to the emphasis on wound excision . Used in combination with silver sulphadiazine, it may improve patient survival when excision is not possible. J Wound Care, 2003 Mar, 12(3), 93 - 8 Management of chronic leg ulcers by nurses working in the community in Sweden and the UK; Hjelm K et al.; OBJECTIVE: This study compared the management of chronic leg ulcers by nurses in community, primary health care and nursing home settings in Kronoberg, Sweden, and East Riding, UK . METHOD: A questionnaire was sent to all nurses in the two areas enquiring about their occupational background, leg ulcer management, resource utilisation and education and training . It also asked about their preferred treatment choices for four types of chronic leg ulcers described in case studies . Response rates of 50% (UK) and 54% (Sweden) were achieved . RESULTS: Nurses in the UK undertook diagnostic investigations of non-healing leg ulcers as part of the initial assessment, whereas in Sweden these were undertaken by physicians . In Sweden daily dressing changes were more frequent and often involved nurse auxiliaries . Patients and relatives almost never participated in dressing changes in the two countries . Sodium chloride was the most commonly used cleansing agent in the UK, as opposed to warm water in Sweden . The use of antibacterial/antiseptic dressings and antibiotics was more frequent in the UK . Nurses there also used scientific and professional literature more frequently . Swedish nurses experienced more problems in obtaining new information . CONCLUSION: Differences exist between the two countries in leg ulcer management . These may be related to differences in the health-care systems, staff training and attitudes to evidence-based practice. Recenti Prog Med, 2003 Apr, 94(4), 177 - 85 {Bartonellosis}; Mansueto P et al.; In the last years the number of Bartonella species significantly raised, often with an epidemiological profile of emergent disease . B . bacilliformis is the etiological agent of Carrion's disease . B . clarridgeiae has been associated, together with B . henselae, to Cat-Scratch Disease (CSD), whereas B . elizabethae to endocarditis and B . grahamii to neuroretinitis . B . henselae has been associated to CSD and, in patients with immunodeficiency, together with B . quintana, to bacillary angiomatosis, to peliosis and to endocarditis . B . quintana is the etiological agent of "trench fever", in its "classical" and "urban" form . B . vinsonii subsp . arupensis and subsp . berkhoffii have been associated to bacteremia and endocarditis . The diagnosis foresees pathological examination of the lesions, germ isolation and use of specific serological test and of polymerase chain reaction . Prognosis is, generally, favourable . Therapy foresees the use of numerous antibacterial agents, like: penicillins, cephalosporins, aminoglycosides, tetracyclines, macrolides, quinolones, trimethoprim-sulfomethoxazole and rifampicin. Planta Med, 2003 Mar, 69(3), 282 - 4 Composition and antibacterial activity of the essential oil of Satureja parnassica subsp parnassica; Tzakou O et al.; The essential oils of Satureja parnassica subsp . parnassica (samples A and B), were analyzed by means of GC/MS . From the fifty-seven identified constituents representing 98.5 % and 99.35 % of the oils respectively, ( E)-caryophyllene, carvacrol and caryophyllene oxide were the major components of sample A (flowering stage), whereas in sample B (vegetative stage) major components were spathulenol, p-cymene and linalool . The oils were tested against Helicobacter pylori (HP), as well as against six aerobically growing bacteria . Both samples showed a moderate activity against Gram-positive bacteria; sample A oil showed greater anti-HP activity than sample B. Planta Med, 2003 Mar, 69(3), 277 - 81 Antibacterial evaluation of cnicin and some natural and semisynthetic analogues; Bruno M et al.; Some ester derivatives of salonitenolide have been prepared from cnicin, a germacranolide sesquiterpenoid . The compounds were tested for their antibacterial activity . The 8,15-diesters showed a good activity, comparable with that of cnicin . The 15-monoester compounds were not very active showing that esterification at the C-8 position is an important structural feature for antibacterial properties. Planta Med, 2003 Mar, 69(3), 274 - 7 Antibacterial activity and chemical composition of essential oil of Chrysanthemum boreale; Kim KJ et al.; The essential oil of Chrysanthemum boreale Makino was analyzed by means of GC and GC-MS . Eighty-seven constituents were identified, representing 94.13 % of the total oil and the major components were camphor, alpha-thujone, cis-chrysanthenol, 1,8-cineole, alpha-pinene, and beta-caryophyllene . Furthermore, the essential oil exhibited antibacterial activity (MIC, more than 800 microg/mL versus 0.125 microg/mL for ampicillin) after it was tested against 6 Gram(+) bacteria and 8 Gram(-) bacteria. Planta Med, 2003 Mar, 69(3), 212 - 7 Calcaelin, a new protein with translation-inhibiting, antiproliferative and antimitogenic activities from the mosaic puffball mushroom Calvatia caelata; Ng TB et al.; Fresh fruiting bodies of the mushroom Calvatia caelata, commonly known as the mosaic puffball, were extracted with 10 mM Tris-HCl buffer (pH 7.2) . The extract was subjected to a chromatographic procedure which has been successfully used to isolate ribosome-inactivating proteins from plants . It was first applied to an Affi-gel blue gel column previously equilibrated and eluted with 10 mM Tris-HCl buffer . The adsorbed fraction eluted with 1.5 M NaCl in the buffer was then purified by chromatography on DEAE-cellulose in the same buffer . The unadsorbed fraction yielded essentially a single peak when it was chromatographed on a column of Mono S . When the peak was then gel filtered on Superdex 75, it yielded a homogeneous peak with a molecular mass of 39 kDa . The protein, which was designated calcaelin, was dissociated into two subunits with a molecular mass of 19 kDa and 20 kDa, respectively, in SDS-polyacrylamide gel electrophoresis . The two bands exhibited the same N-terminal amino acid sequence which was somewhat similar to those of plant ribosome-inactivating proteins . A lesser degree of sequence homology to the fungal ribosome inactivating proteins alpha-sarcin and restrictocin was detected . Calcaelin inhibited translation in rabbit reticulocyte lysate with an IC 50 value of 4 nM and displayed a heat-labile RNase activity of 1.58 U/mg toward yeast tRNA . It exhibited an antimitogenic activity toward mouse splenocytes, and it reduced the viability of breast cancer cells . There was no hemagglutinating, antibacterial or antifungal activity. Drug News Perspect, 2002 Mar, 15(2), 121 - 127 The Therapeutic Role of Macrolides and Ketolides: Not Just Antibacterials; Hunter PA; The 6th International Conference on Macrolides, Azalides, Streptogramins, Oxazolidinones and Ketolides was held this year in Bologna, Italy, January 24-25, 2002 . While oxazolidinones were featured in only one presentation, there were many presentations on the azalide azithromycin . There were also presentations on other macrolides (clarithromycin) and ketolides (telithromycin and ABT-773), and a few presentations on streptogramins . Several stimulating and well-attended workshops, as well as special symposia, made it an interesting and worthwhile meeting . (c) 2002 Prous Science . All rights reserved. Allerg Immunol (Paris), 2003 Feb, 35(2), 61 - 3 Anaphylactic reaction to cinoxacin: report of one case associated with inferior acute myocardial infarction; Quercia O et al.; Cinoxacin is an oral synthetic antibacterial agent, of the second generation quinolones group, with excellent efficacy in respiratory, intra-abdominal, pelvic, and skin and soft tissue infections . Overall, quinolones are well tolerated drugs, although phototoxicity and photoallergenicity is well demonstrated experimentally . In this report we show you a case of a man who presented a anaphylactic reaction associated with myocardial infarction, after taking a capsule of cinoxacin . We suppose that there is a direct participation of the heart in anaphylactic reactions, because acttivated mast-cells mediators can determine cardiovascular effects . Then performed double-blind placebo controlled challenge test with an alternative drug . We did not observe any adverse immediate or late adverse reaction to this drug. J Infect Chemother, 2003 Mar, 9(1), 12 - 5 In-vitro activity of sitafloxacin (DU-6859a), either singly or in combination with rifampin analogs, against Mycobacterium leprae; Dhople AM et al.; The in-vitro antibacterial activity of sitafloxacin (DU-6859a) against Mycobacterium leprae was evaluated and compared with those of ofloxacin, levofloxacin, and ciprofloxacin . Two biochemical indicators (intracellular ATP and uptake of {(3)H}-thymidine) were used to measure the in-vitro growth of M . leprae in Dhople-Hanks (DH) medium . Sitafloxacin was found to be more potent than the other three commonly used fluoroquinolones, with the minimum inhibitory concentration (MIC) against M . leprae being 0.1875 microg/ml and the action being bactericidal . The MICs of ofloxacin, levofloxacin, and ciprofloxacin were 1.5, 0.75, and 3.0 microg/ml, respectively . Similar to ofloxacin and levofloxacin, sitafloxacin also exhibited synergistic activity when combined with either rifabutin or KRM-1648, but not with rifampin . Thus, further studies on the incorporation of sitafloxacin in multidrug therapy regimens in treating leprosy patients are suggested. Chem Pharm Bull (Tokyo), 2003 Apr, 51(4), 435 - 9 Four new saponins from the starfish Certonardoa semiregularis; Wang W et al.; Four new saponins, designated as certonardosides K-N (1-3, 5), were isolated, along with culcitoside C(6) (4), from the brine shrimp active fraction of the starfish Certonardoa semiregularis . The structures were determined on the basis of spectral analysis and chemical derivatization . These compounds were evaluated for cytotoxicity and antibacterial activity. Phytother Res, 2003 Mar, 17(3), 282 - 4 In vitro cytotoxicity activity of Diosquinone, a naphthoquinone epoxide; Adeniyi BA et al.; Diosquinone {1}, a naphthoquinone epoxide previously isolated from the root bark of Diospyros mespiliformis (Hostch) and D . tricolor {Ebenaceae} is been assessed for cytotoxicity activity against ten cancer cell lines by standard NIH method . The ethno-pharmacological claim of this plant and the previously observed good antibacterial activity of this compound among the others isolated from this plant suggest its probable cytotoxicity activity . Diosquinone was observed to be very active against most of the cancer cell lines . It shows very good activity against all the cell lines tested with ED50 value ranging between 0.18 microg/ml . against Human Glioblastoma (U373) to 4.5 microg/ml . against Hormone dependent human prostrate cancer( LNCaP) . Phytother Res, 2003 Mar, 17(3), 217 - 21 In vitro susceptibility of Helicobacter pylori to isoquinoline alkaloids from Sanguinaria canadensis and Hydrastis canadensis; Mahady GB et al.; Methanol extracts of the rhizomes of Sanguinaria canadensis, and the roots and rhizomes of Hydrastis canadensis, two plants used traditionally for the treatment of gastrointestinal ailments, were screened for in vitro antibacterial activity against 15 strains of Helicobacter pylori . The rhizome extracts, as well as a methanol extract of S . canadensis suspension-cell cultures inhibited the growth of H . pylori in vitro, with a MIC50 range of 12.5-50.0 microg/ml . Three isoquinoline alkaloids were identified in the active fraction . Sanguinarine and chelerythrine, two benzophenanthridine alkaloids, inhibited the growth of the bacterium, with an MIC50 of 50.0 and 100.0 microg/ml, respectively . Protopine, a protopine alkaloid, also inhibited the growth of the bacterium, with a MIC50 of 100 microg/ml . The crude methanol extract of H . canadensis rhizomes was very active, with an MIC50 of 12.5 microg/ml . Two isoquinoline alkaloids, berberine and beta-hydrastine, were identified as the active constituents, and having an MIC50 of 12.5 and 100.0 microg/ml, respectively . FASEB J, 2003 May, 17(8), 958 - 60 Epub 2003 Mar 28. Influence of the macrophage bacterial resistance gene, Nramp1 (Slc11a1), on the induction of allergic asthma in the mouse; Smit JJ et al.; Based on the hygiene hypothesis that lack of early childhood bacterial infections would favor development of allergic disease, we hypothesize that genes controlling antibacterial resistance may be important as well . We, therefore, studied whether Nramp1 alleles that determine resistance (Nramp1r) or susceptibility (Nramp1s) to intracellular bacteria at the macrophage level affect sensitivity to induction of allergic asthma . Nramp1s and congenic Nramp1r mice were sensitized with ovalbumin/alum on days 0 and 14 and challenged with ovalbumin or saline aerosols on days 42, 45, and 48 . On day 49, airway responsiveness was assessed, blood was withdrawn, and lung lavage was performed . We demonstrated that ovalbumin sensitization and challenge of Nramp1s and Nramp1r mice caused comparable airway hyperreactivity and airway eosinophilia and a similar increase in serum levels of ovalbumin-specific IgG1 and IgG2a . Ovalbumin challenge, however, induced significantly lower serum levels of total and ovalbumin-specific IgE and significantly lower mast cell degranulation in Nramp1r mice as compared with Nramp1s mice . In addition, ovalbumin challenge of Nramp1r mice led to significantly less release of Th2 cytokines into the airways . Results show that Nramp1 can affect the development of allergy but not the development of airway hyperresponsiveness in the mouse. Bioorg Med Chem, 2003 May 1, 11(9), 1957 - 67 Synthesis of (3,4) beta-methylenecepham and (3,4) beta-methylene-carbacepham via intramolecular carbene addition to double bond; Korda A et al.; A series of new (3,4) beta-methylenecepham and carbacepham analogues were synthesised as potential antibacterial agents . The key step of the synthesis included presumed generation of the carbene species from the oxalimide substrate effected by triethylphosphite and its intramolecular addition to the double bond . The stereochemistry of the tricyclic system has been elucidated by NMR and X-ray crystallography . In preliminary screening, two of the synthesised compounds exhibited modest antibacterial activity at 1.5-2.0 mg/mL against a number of bacterial strains. Chem Biol, 2003 Mar, 10(3), 279 - 88 Clorobiocin biosynthesis in Streptomyces: identification of the halogenase and generation of structural analogs; Eustaquio AS et al.; Clorobiocin (clo) and novobiocin (nov) are potent inhibitors of bacterial DNA gyrase . The two substances differ in the substitution pattern at C-8' of the aminocoumarin ring, carrying a chlorine atom or a methyl group, respectively . By gene inactivation, clo-hal was identified as the gene of the halogenase responsible for the introduction of the chlorine atom of clorobiocin . Inactivation of cloZ did not affect clorobiocin formation, showing that this ORF is not essential for clorobiocin biosynthesis . Expression of the methyltransferase gene novO in the clo-hal(-) mutant led to the very efficient formation of a hybrid antibiotic containing a methyl group instead of a chlorine atom at C-8' . Comparison of the antibacterial activity of clorobiocin analogs with -Cl, -H, or -CH(3) at C-8' showed that chlorine leads to 8-fold higher activity than hydrogen and to 2-fold higher activity than a methyl group. Carbohydr Res, 2003 Mar 14, 338(6), 571 - 5 Effect of chlorhexidine on molecular weight distribution of fructans produced by fructosyltransferase in solution and immobilized on surface; Rozen R et al.; The effect of chlorhexidine (CHX), a potent antibacterial agent, was tested on the molecular weight distribution (MWD) of fructans synthesized by cell-free fructosyltransferase (FTF) in solution in comparison to FTF immobilized onto hydroxyapatite (HA) . Size-exclusion chromatography (SEC) analysis has shown that cell-free FTF, both in solution and immobilized on HA, produces both low MW (1.9-2.2 kDa) and high MW (913-1047 kDa) fructans . CHX at a concentration of 0.02% altered the MWD of the fructans by reducing the polydispersity ratio and changing the MWD of the fructans synthesized both by immobilized FTF and by FTF in solution . These changes of the fructans in the presence of CHX adds a new prospective to the anticaries effect of CHX in addition to its antibacterial properties. J Inorg Biochem, 2003 Apr 1, 94(4), 355 - 64 In vitro oxidative activity of cupric complexes of kanamycin A in comparison to in vivo bactericidal efficacy; Szczepanik W et al.; The interactions of copper(II) complexes of kanamycin A with oxidation-susceptible biomolecules: 2'-deoxyguanosine, plasmid DNA and yeast tRNA(Phe) were studied in both the presence and absence of hydrogen peroxide . The mixture of complex with H(2)O(2) was found to be an efficient oxidant, converting dG to its 8-oxo derivative, generating strand breaks in plasmid DNA and multiple cleavages in tRNA(Phe) . Some of these reactions may play a role in toxic effects of aminoglycoside antibiotics . These complexes were screened for their antibacterial activity . The microbiological studies undertaken to compare the bactericidal action of kanamycin A alone and complexed with copper(II) ions in both neutral and oxidative environment revealed that the enhancement of bactericidal action by Cu(II) was not statistically significant . Eur J Med Chem, 2003 Mar, 38(3), 313 - 8 Synthesis of some new 2,4-disubstituted thiazoles as possible antibacterial and anti-inflammatory agents; Holla BS et al.; A series of arylthioureas (1), aromatic aldehyde thiosemicarbazones (2) and 5-aryl-2-furfuraldehyde thiosemicarbazones (3) were condensed with 2,4-dichloro-5-fluorophenacyl bromide to yield respective arylaminothiazoles, arylidene/5-aryl-2-furfurylidene hydrazinothiazoles (4) . The newly synthesized compounds were characterized by IR, 1H-NMR and mass spectral studies . These compounds were also screened for their antibacterial and anti-inflammatory activities . Two of the newly synthesized compounds showed anti-inflammatory activity comparable with that of Ibuprofen. Arch Pharm (Weinheim), 2003 Mar, 336(1), 18 - 30 Synthesis, structure, and antibacterial activity of 4-imino-1, 4-dihydrocinnoline-3-carboxylic acid and 4-oxo-1, 4-dihydrocinnoline-3-carboxylic acid derivatives as isosteric analogues of quinolones; Stanczak A et al.; Chemical modification of cinnoxacin was studied with the aim of improving its antibacterial activity and spectrum . A series of 4-imino-1, 4-dihydrocinnoline-3-carboxylic acid derivatives was synthesized and their in vitro antibacterial activity was evaluated . These derivatives were designed as isosteric analogues of fluoroquinolones and are characterized by the presence of an imine group instead of an oxo group at the 4-position and a nitrogen atom in position 2 . The crystal structure of one analogue determined by X-ray diffraction shows the dipolar form of the compound in the solid state . The in vitro antibacterial activity of the synthesized compounds against Gram-positive and Gram-negative bacteria was examined . The MIC of the most active compounds lies in the range of the first generation of quinolones such as nalidixic acid . The compounds with dichlorobenzyl substituent show enhanced activity against Gram-positive bacteria. Am J Hematol, 2003 Apr, 72(4), 248 - 54 Neutropenia and agranulocytosis in England and Wales: incidence and risk factors; van Staa TP et al.; The objectives of this study were to estimate the incidence of idiosyncratic neutropenia and agranulocytosis in England and Wales and to evaluate their risk factors and outcomes . The study was conducted using data from the General Practice Research Database . All cases of idiosyncratic neutropenia or agranulocytosis were identified and the incidence was estimated . This was followed by a nested case-control study, estimating odds ratios with drug exposure from conditional logistic regression . From 1987 to 1999, 3,224 patients with idiosyncratic neutropenia (50 with agranulocytosis) were identified . The incidences of neutropenia and agranulocytosis were estimated to be 120 and 7 cases per million people per year, respectively . The adjusted odds ratios for neutropenia were 34.7 (95% confidence interval 12.0-99.7) for current users of thyroid inhibitors, 9.5 (4.4-20.8) for users of disease-modifying antirheumatic drugs, and 7.6 (4.9-11.9) for users of aminosalicylates . Other drugs with statistically significantly increased risks of neutropenia included antibacterial drugs, non-opioid analgesics, NSAIDs, antidepressants, ulcer-healing drugs, and anti-epileptics . The increase in risk of neutropenia predominantly occurred during the first months of treatment . For most drugs investigated in this study, there was no relationship to daily dose . The excess 1-year mortality was low among neutropenia and agranulocytosis cases and mostly explained by the underlying disease state . In conclusion, the highest risks of neutropenia were generally found in patients starting treatment . The excess 1-year mortality was low among neutropenia and agranulocytosis cases and can be mostly explained by the underlying disease state . Int J Pediatr Otorhinolaryngol, 2003 Apr, 67(4), 313 - 6 Emergence of ciprofloxacin-resistant pseudomonas in pediatric otitis media; Jang CH et al.; OBJECTIVE: The widespread use of fluoroquinolone otic drops has resulted in the emergence and subsequent increase of fluoroquinolone resistance, at rates greater than anticipated . To evaluate the patients with recurrent otorrhea that were unresponsive to topical ciprofloxacin . METHODS: Seventeen pediatric patients who were treated with refractory otorrhea between 2000 and 2001 were reviewed retrospectively . RESULTS: All patients had ciprofloxacin-resistant pseudomonas on culture and sensitivity test . Ciprofloxacin-resistant pseudomonas from these patients were multidrug resistant . Imipenem was the most sensitive antibiotic agent, followed by amikacin . Most patients were treated with intramuscular amikacin and two patients were treated with intravenous imipenem . CONCLUSION: In our series, resistance to cirpfloxacin in patients with otitis media is increasing recently . Culture and antibiotic sensitivity test may help guide management . Continuous surveillance is necessary to monitor antibiotic resistance and to guide antibacterial therapy. Paediatr Drugs, 2003, 5(4), 223 - 8 Ribosomal immunotherapy for recurrent respiratory tract infections in children; Bene MC et al.; Recurrent respiratory tract infections are common in children . They reflect the immaturity of the immune system in its encounter with environmental antigens . Little or no specific protective immune response has yet been established . These infections represent an important public health problem in terms of both treatment (anti-inflammatory or antibacterial drugs for children) and economy . Immunotherapy has been proposed as a means of preventing these recurrent infections by providing children with small doses of inactive bacterial antigens liable to trigger specific and protective immune responses . Among such drugs, ribosomal preparations (to which this review is limited) appear to be not only well tolerated, but also ideally targeted to induce mucosal responses . One preparation of ribosomal mucosal vaccine is commercially available in several countries . Numerous clinical trials in the world have confirmed the positive role of this mucosal ribosomal bacterial vaccine in significantly reducing the number of infections, courses of antibacterials, and absenteeism . In vitro and ex vivo investigations have confirmed that such vaccines indeed trigger protective specific immune responses. Bioorg Med Chem, 2003 Apr 17, 11(8), 1859 - 63 Effect of aryl ring fluorination on the antibacterial properties of C4 aryl-substituted N-methylthio beta-lactams; Long TE et al.; 4-Aryl-substituted N-thiolated beta-lactams are a new family of antibacterial agents possessing unique structure-activity profiles and a mode of action . Unlike traditional beta-lactam antibiotics, which require highly polar enzyme-binding groups, these lactams bear hydrophobic groups on their side chains . In this study, we examine the effect that increasing hydrophobicity, through fluorine substitution in the C(4) aryl ring, has on the antibacterial properties. Food Chem Toxicol, 2003 May, 41(5), 637 - 45 26-Week repeated oral dose toxicity study of the new quinolone antibacterial DW-116 in Sprague-Dawley rats; Kim JC et al.; The purpose of this study is to investigate the potential subchronic toxicity of DW-116 by a 26-week repeated oral dose in Sprague-Dawley rats . The test article, DW-116, was administered daily by gavage to male and female rats at dose levels of 0, 5, 25 and 125 mg/kg/day . At the end of the treatment period, 12 rats/sex/group were sacrificed, while six extra rats/sex in the vehicle control and highest dose groups were sacrificed after a 4-week recovery . During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights and histopathology were examined . There was no treatment-related mortality . An increase in the incidence of post-dosing salivation was observed in both sexes of the highest dose group . At the scheduled autopsy, an increase in the liver weight was observed in males of the highest dose group in a dose-dependent manner . Hematological investigations revealed a dose-dependent increase in the total white blood cell (WBC) and lymphocyte counts in males treated with the 125 mg/kg dose . Total bilirubin and alanine aminotransferase (ALT) values were also increased in males at the same dose . These effects were completely reversible during the recovery period . There were no adverse effects on body weight, food and water consumption, ophthalmoscopy, urinalysis, necropsy findings and histopathology in any treatment group . Based on these results, it was concluded that the 26-week repeated oral dose of DW-116 caused increases in the liver weight, WBC counts, total bilirubin and ALT values in males at a dose level of 125 mg/kg/day . The target organ was determined to be the liver and WBC in males, but not in females . The no-observed-adverse-effect level (NOAEL) was considered to be 25 mg/kg/day for males and 125 mg/kg/day for females. Chin J Traumatol, 2003 Apr, 6(2), 86 - 90 Anti-infective reconstituted bone xenograft used for primary bone grafting to repair contaminated defect in the radius in dogs; Yuan Z et al.; OBJECTIVE: To investigate the effect of anti-infective reconstituted bone xenograft as a primary graft to repair a segmental with severe contamination . METHODS: A canine model of contaminated defect of 1.5 cm in size in the radius was used, in which anti-infective reconstituted bone xenograft or reconstituted bone xenograft was implanted as a primary graft followed by internal fixation . The effectiveness of the two grafting materials in repairing a contaminated segmental defect was compared . RESULTS: The animals which had received implant of anti-infective reconstituted bone xenograft should largely healed defects 6 months after operation while the defects implanted with reconstituted bone xenograft remained unrepaired with bone infection . CONCLUSIONS: Besides its strong osteoinductive and osteoconductive activity, anti-infective reconstituted bone xenograft is highly antibacterial and can be used as a primary graft to repair the severely contaminated segmental defect. J Cardiovasc Pharmacol, 2003 Apr, 41(4), 506 - 17 Comparative effects of clarithromycin on action potential and ionic currents from rabbit isolated atrial and ventricular myocytes; Gluais P et al.; Prolongation of QT interval by several antibacterial drugs is an unwanted side effect that may be associated with development of ventricular arrhythmias . The macrolide antibacterial agent clarithromycin has been shown to cause QT prolongation . To determine the electrophysiologic basis for this arrhythmogenic potential, we investigated clarithromycin effects on (i) . action potentials recorded from rabbit Purkinje fibers and atrial and ventricular myocardium using conventional microelectrodes and (ii) . potassium and calcium currents recorded from rabbit atrial and ventricular isolated myocytes using whole-cell patch clamp recordings . We found that (i) . clarithromycin (3-100 microM) exerted concentration-dependent lengthening effects on action potential duration in all tissues, with higher efficacy and reverse frequency-dependence in Purkinje fibers . However, clarithromycin did not cause development of early afterdepolarizations, and the parameters other than action potential duration were almost unaffected; (ii) . clarithromycin (10-100 microM) reduced the delayed rectifier current . Significant blockade (approximately 30%) was found at the concentration of 30 microM . At 100 microM, it decreased significantly the maximum peak of the calcium current amplitude but failed to alter the transient outward and inwardly rectifier currents . It was concluded that these effects might be an explanation for the QT prolongation observed in some patients treated with clarithromycin. Phytochemistry, 2003 May, 63(1), 37 - 40 The lachrymatory principle of Petiveria alliacea; Kubec R et al.; The lachrymatory principle of Petiveria alliacea has been isolated from a fresh homogenate of the root . Its structure and geometric configuration have been determined as (Z)-thiobenzaldehyde S-oxide by means of NMR, IR, MALDI-MS and by comparison with an authentic compound obtained by synthesis . This unique compound represents only the third naturally occurring sulfine (thiocarbonyl S-oxide) to be reported . Its formation and possible subsequent rearrangements are discussed . Its antibacterial and antifungal activities are also reported. Dent Traumatol, 2003 Apr, 19(2), 90 - 5 Effect of minocycline on healing of replanted dog teeth after extended dry times; Bryson EC et al.; Minocycline is available as a locally administered tetracycline derivative antibiotic (Arestin, OraPharma, Inc., Warminster, PA, USA) which demonstrated antibacterial activity and anti-inflammatory action that may slow down resorptive processes after severe traumatic injuries to the dentition . A total of 48 premolar roots of six mongrel dogs were instrumented in an aseptic fashion with rotary nickel-titanium files and obturated with vertically condensed warm gutta percha . All accesses were sealed with glass ionomer, the roots extracted and then allowed to bench dry for 60 min . Group 1 consisted of 15 roots that were coated with minocycline and replanted and nine roots that were replanted without minocycline . Group 2 consisted of 24 roots, all of which were prepared with a uniform cemental defect down to sound dentin along the lateral aspect of the root, with a high-speed bur following the 60-min dry time . Half of the roots (12) were then coated with minocycline and replanted, and the other 12 roots were replanted without minocycline . After 4 months, the dogs were killed and the roots prepared for histological evaluation . About 5- microm thick cross-sections of the root and surrounding tissue taken every 90 microm were evaluated for healing . In addition, residual root mass was also measured in the roots of group 1 to determine the extent of root structure loss for each treatment method . The roots with and without minocycline treatment showed no significant differences between the remaining root mass or the percentage of favorably healed root surfaces . The use of minocycline is not currently recommended for prevention or attenuation of external root resorption following avulsion in a dog trauma model. Chemosphere, 2003 Jan, 50(3), 437 - 43 Effects of the antibacterial agents tiamulin, olanquindox and metronidazole and the anthelmintic ivermectin on the soil invertebrate species Folsomia fimetaria (Collembola) and Enchytraeus crypticus (Enchytraeidae); Jensen J et al.; Veterinary pharmaceutical products such as antibacterial agents and antiparasitics are widely used to control diseases and promote production in the agricultural sector . Exposure of non-target organisms are a likely result of using manure from treated live stocks or from dung dropped on the field by grazing animals . The aim of this study was to determine the toxic threshold levels of three antibacterial agents (tiamulin, olanquindox and metronidazole) and one anthelmintic (ivermectin) to two species of soil dwelling organisms (springtails and enchytraeids), that are often found in bio-solids such as manure or dung . The antibacterial agents were not toxic to adults and effects on reproduction occurred generally above concentrations normally found in soil or dung . The threshold values for toxicity (10% reduced reproduction or EC10 values) were in the range of 61-111 mg kg(-1) dry soil for springtails and 83-722 mg kg(-1) dry soil for enchytraeids . Ivermectin was significantly more toxic with EC10 values of 0.26 mg kg(-1) dry soil for the springtails and 14 mg kg(-1) dry soil for the enchytraeids . A comparison of these results with rough estimates of likely and worse case environmental concentrations indicates a potential risk of ivermectin to non-target species such as springtails and enchytraeids, whereas direct toxic effect of antibacterial agents is very unlikely to occur at environmental realistic concentrations . However, indirect effects of antibacterial agents driven through changes in the food web cannot be abolished at this stage. Int J Syst Evol Microbiol, 2003 Jan, 53(Pt 1), 15 - 20 Bosea eneae sp . nov., Bosea massiliensis sp . nov . and Bosea vestrisii sp . nov., isolated from hospital water supplies, and emendation of the genus Bosea (Das et al . 1996); La Scola B et al.; On the basis of phenotypic and DNA relatedness data, three novel species of the genus Bosea are proposed, Bosea massiliensis (63287T =CIP 106336T =CCUG 43117T), Bosea vestrisii (34635T =CIP 106340T =CCUG 43114T) and Bosea eneae (34614T =CIP 106338T =CCUG 43111T) . The original description of the genus Bosea included thiosulphate oxidation as a phenotypic feature, when the sole and type species of the genus, Bosea thiooxidans, was proposed . The three novel species described herein were not able to oxidize thiosulphate; thus, it is proposed that this characteristic be removed from the description of the genus and considered as specific for B . thiooxidans . The novel species of the genus Bosea proposed here form a well-separated cluster in the Bradyrhizobium group of the alpha-2 subclass of the Proteobacteria, on the basis of 16S rDNA gene sequence analysis . However, 16S rDNA gene sequence analysis was not sufficient to delineate the species; hence, DNA-DNA relatedness and phenotypic data were also required . All of the novel species described in this study are fastidious bacteria isolated from a hospital water supply, using co-cultivation with amoebae . This group of bacteria are hypothesized to be a potential cause of nosocomial infections . For treatment of infections caused by these novel bacteria, doxycycline appears to be the sole antibacterial compound with a consistently low MIC value. Proc Natl Acad Sci U S A, 2003 Apr 1, 100(7), 3584 - 8 Epub 2003 Mar 24. Enterobactin: an archetype for microbial iron transport; Raymond KN et al.; Bacteria have aggressive acquisition processes for iron, an essential nutrient . Siderophores are small iron chelators that facilitate cellular iron transport . The siderophore enterobactin is a triscatechol derivative of a cyclic triserine lactone . Studies of the chemistry, regulation, synthesis, recognition, and transport of enterobactin make it perhaps the best understood of the siderophore-mediated iron uptake systems, displaying a lot of function packed into this small molecule . However, recent surprises include the isolation of corynebactin, a closely related trithreonine triscatechol derivative lactone first found in Gram-positive bacteria, and the crystal structure of a ferric enterobactin complex of a protein identified as an antibacterial component of the human innate immune system. Infect Immun, 2003 Apr, 71(4), 2276 - 9 Interleukin-10 negatively regulates local cytokine and chemokine production but does not influence antibacterial host defense during murine pneumococcal meningitis; Zwijnenburg PJ et al.; To determine the role of endogenous interleukin-10 (IL-10) in local host defense during pneumococcal meningitis, the inflammatory responses of IL-10-gene-deficient and wild-type mice after the induction of meningitis were compared . The absence of IL-10 was associated with higher cytokine and chemokine concentrations and a more pronounced infiltrate, but antibacterial defense or survival was not influenced. Probl Tuberk, 2003, (1), 45 - 52 {Effects of immunomodulator leukinferon on the course of experimental tuberculosis}; Gedymin LE et al.; An experiment was conducted on 60 CBA mice intravenously inoculated with cultured Mycobacteria tuberculosis (MBT), Erdmann strain, in a dose of 0.025 mg . The specific features of tissue, cellular, and biochemical reactions were studied in the lung, liver, and spleen when leukinferon (LF) was included into tuberculosis treatment regimen . LF was shown to have a positive impact on the development of reparative reactions during tuberculous inflammation by reducing the time of abacillation and recovering the structure of diseased organs . By month 3 of follow-up, MBT were not detected in mice receiving antibacterial agents (ABA) and LF, while typical and changed forms of LF were identified in the cytoplasm of alveolar macrophages in mice treated with ABA alone . A specific feature of an inflammatory reaction as a significant proliferation of lymphocytes and macrophages with their ample infiltration of target organs was noted in animals receiving LF . This was followed by the activated production of alpha- and gamma-interferons and by the mobilization of an enzymatic link of anti-oxidant defense under chronic oxidative stress, which led to a reduction of resolution of inflammatory areas and to an increase in survival of animals which had not been given ABA, but treated with LF alone. Probl Tuberk, 2003, (1), 25 - 8 {Drug resistant tuberculosis in children and adolescents}; Aksenova VA et al.; The paper presents the results of a follow-up of children and adolescents who isolate drug-resistant Mycobacterium tuberculosis (MBT) strains of those with manifestations of tuberculosis and preserved sensitivity to antibacterial agents . Bacterial isolation in children and adolescents is scanty and multiple . There is a high rate of resistance to isoniazid, streptomycin, and rifampicin . The vast majority of children and adolescents who isolate drug-resistant MBT strains have been found to contact a patient who also isolate drug-resistant MBT . The drug sensitivity of MBT in patients is identical to that of sources of their contamination . Most patients with drug-resistant tuberculosis have been ascertained as having been registered in dispensaries and treated with drugs, which suggests that the use of chemotherapy in prophylactic doses, particularly in patients contacting a bacterial isolator, does not prevent local tuberculosis. Klin Med (Mosk), 2003, 81(1), 40 - 4 {The state of immune system and effects of current therapy and immunomodulators}; Tsimmerman IaS et al.; To test the conception about a pathogenetic role of correlation between gastric comtamination with Helicobacter pylori (Hp) and immune system disorders in duodenal ulcer (DU), immune status and its response to current pharmacotherapy were studied in 84 patients in an acute recurrence phase . The patients were divided into 4 representative groups to receive monotherapy with omeprasol (group 1), combination denol + amoxicillin + tinidasol (group 2), quadrotherapy with drugs of group 1 and 2 (group 3), the above quadrotherapy plus immunomodulating drugs (imunofan + tactivin + oligovit) (group 4) . In recurrent DU all the components of the immune system are affected especially cellular immunity . The response to the treatment was highest in group 1 and 4 (90% healing for 3 weeks), the worst in group 2 (68%) . The complex of antibacterial drugs produces a moderate immunosuppressive action . The addition of immunomodulating drugs to the quadrotherapy promotes correction of secondary immunodeficiency and secondary Hp resistance to antibacterial drugs . This leads to a rise in eradication effect from 33-55 to 84% and a decrease in the number of early recurrences (during the first 6-12 months) from 42.1-33.6 to 12.5%. Phytochemistry, 2003 Apr, 62(8), 1221 - 4 Antibacterial bromophenols from the marine red alga Rhodomela confervoides; Xu N et al.; Two bromophenols, together with three known compounds, were isolated from the methanolic extract of the marine alga, Rhodomela confervoides . By means of MS and NMR spectroscopic analyses, they were identified as 3-bromo-4-{2,3-dibromo-4,5-dihydroxyphenyl} methyl-5-(hydroxymethyl) 1,2-benzenediol (1) and 3-bromo-4-{2,3-dibromo-4,5-dihydroxyphenyl} methyl-5- (ethoxymethyl) 1,2-benzenediol (2) . Three known compounds were also isolated, namely 3-bromo-4-{2,3-dibromo-4,5-dihydroxyphenyl} methyl-5-(methoxymethyl) 1,2-benzenediol (3), 4,4'- methylenebis {5,6-dibromo-1,2-benzenediol} (4) and bis (2,3-dibromo-4,5-dihydroxybenzyl) ether (5) . Compound 5 was the most active against five strains of bacteria with the MIC less than 70 microg/ml, while compounds 2, 3 and 4 exhibited moderate activity. J Chromatogr A, 2003 Feb 21, 988(1), 135 - 43 Quantitation of the enantiomers of ofloxacin by capillary electrophoresis in the parts per billion concentration range for in vitro drug absorption studies; Awadallah B et al.; Ofloxacin, a chiral fluoroquinolone, possesses two optical isomers . The antibacterial activity of S-(-)-ofloxacin is reported to be 8-128 times higher than that of R-(+)-ofloxacin . A capillary zone electrophoresis method has been developed to quantify the enantiomers of ofloxacin in high diluted samples (20-700 ng/ml for each enantiomer) . After fluid-fluid extraction of ofloxacin from physiological solution electrokinetic injection was employed to improve the sensitivity . The method was optimised using a central composite design . Four experimental factors were investigated: the background electrolyte concentration, the methyl-beta-cyclodextrin concentration, the buffer pH and the temperature . The amount migrated into the capillary, determined by the peak area, the resolution between the ofloxacin enantiomers, the migration time and the generated current were evaluated as responses . The quantification limit is 11.4 ng/ml for S-ofloxacin and 10.8 ng/ml for R-ofloxacin . The method has shown good validation data in terms of precision and recovery rate. Pediatr Res, 2003 Jul, 54(1), 1 - 7 Epub 2003 Mar 19. Bacterial genomes and infectious diseases; Chan VL; The genome sequencing approach has proved to be highly effective and invaluable for gaining an insight on structure of bacteria genomes and the biology and evolution of bacteria . The diversity of bacteria genomes is beyond expectation . Gaining a full understanding of the biology and pathogenic mechanisms of these pathogens will be a major task because on an average only approximately 69% of the encoded proteins in each genome have known functions . Genome sequence analyses have identified novel putative virulence genes, vaccine candidates, targets for antibacterial drugs, and specific diagnostic probes . Microarray technology that makes use of the genomic sequences of human and bacterial pathogens will be a major tool for gaining full understanding of the complexity of host-pathogen interactions and mechanisms of pathogenesis. Bioorg Med Chem Lett, 2003 Mar 24, 13(6), 1151 - 5 Novel ether derivatives of mannopeptimycin glycopeptide antibiotic; Sum PE et al.; Novel ether derivatives of mannopeptimycin glycopeptide were synthesized to probe their SAR . Many of these derivatives exhibited potent antibacterial activity against methicillin resistant and vancomycin resistant strains . These ether derivatives were prepared via reductive ring cleavage of acetals to give a mixture of 6-O, 4-O, 3-O, and 2-O-ether isomers . Both 6-O-ether and 4-O-ether showed significantly enhanced antibacterial activity over the parent and the isovalerate esters. Bioorg Med Chem Lett, 2003 Mar 24, 13(6), 1097 - 100 Synthesis and antibacterial study of 10, 15, 20-triphenyl-5-(4-hydroxy-3-(trimethylammonium)methyl)phenylporphyrin as models for combination of porphyrin and alkylating agent; Zhang J et al.; 10, 15, 20-Triphenyl-5-(4-hydroxy-3-(trimethylammonium)methyl)phenylporphyrin 4 and its zinc complex 5 have been synthesized and antibacterial activities have been studied for 4 and its derivative . Compound 4 showed stronger inhibition than that of 10, 15, 20-triphenyl-5-(4-hydroxy-3-(dimethylamine)methyl)phenylporphyrin (2) and 10, 15, 20-triphenyl-5-(4-methoxy-3-(trimethylammonium)methyl)phenylporphyrin (6) . It is possible that antibacterial activity of compound 4 involved in photoinducing both o-quinone methide intermediate and singlet oxygen formation. Scand J Immunol, 2003 Mar, 57(3), 221 - 8 The formyl peptide N-formyl-methionyl-leucyl-phenylalanine downregulates the expression of FcgammaRs in interferon-gamma-activated monocytes/macrophages in vitro and in vivo; Beigier-Bompadre M et al.; N-Formyl peptides are cleavage products of bacterial and mitochondrial proteins that have pro-inflammatory activities and play an important role in antibacterial host defence . FcgammaRI is a receptor for the Fc portion of immunoglobulin G expressed in monocytes that mediates cytotoxicity and is upregulated by interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) . In this report, we demonstrate that N-formyl-methionyl-leucyl-phenylalanine (FMLP) downregulates the expression of FcgammaRI in IFN-gamma-treated monocytes, but not in IL-10-treated monocytes . We determine that supernatants obtained from monocytes treated with IFN-gamma and then exposed to FMLP induce the downregulation of FcgammaRI in naive monocytes . This effect is abrogated by the protease inhibitors phenylmethylsulphonyl fluoride and phosphoramidon, which inhibit serine and metalloproteases, respectively . Supernatants from FMLP-treated neutrophils also induce the downregulation of FcgammaRI, when added to naive monocytes . Similar observations were obtained in vivo in a mouse model of chronic inflammation . In vivo, FMLP also downregulates the expression of FcgammaRs in IFN-gamma-activated macrophages . Our results support the existence of a new mechanism through which FMLP could modulate the activity of monocytes/macrophages during bacterial infections. Drugs Aging, 2003, 20(4), 289 - 302 Fluoroquinolones in the elderly: safety considerations; Stahlmann R et al.; Fluoroquinolones such as ciprofloxacin, levofloxacin, moxifloxacin and gatifloxacin are widely used for the treatment of bacterial infections . Fluoroquinolone-induced adverse effects have not been reported to occur with increased frequency in the elderly, but large trials comparing the tolerability in aged and young individuals are not available . Renal function declines consistently with age and recommendations for dosage changes of renally eliminated fluoroquinolones (ofloxacin, levofloxacin, gatifloxacin) are related to changes in kidney function rather than to age per se . However, during routine clinical work, creatinine clearance data are usually not available; thus it seems more practical to recommend dosage adjustment for elderly individuals