Telithromycin – a new ketolide antibiotic

Ketolidi su nova vrsta makrolidnih antibiotika, a strukturom su posebno prilagođeni za liječenje infekcija gornjeg i donjeg dijela dišnog sustava, uključujući i one uzrokovane rezistentnim uzročnicima. Ketolidi imaju sličan mehanizam djelovanja kao eritromicin i drugi makrolidi. Telitromicin je prvi ketolidni antibiotik koji je ušao u kliničku primjenu. Ovaj pregledni rad opisuje najnovija saznanja o telitromicinu, analizira njegovu in vitro i in vivo aktivnost, farmakodinamske i farmakokinetske značajke, te klinička istraživanja i primjenu lijeka. Telitromicin ima dobru aktivnost protiv gram-pozitivnih, gram-negativnih i atipičnih uzročnika respiratornih infekcija. Također pokazuje vrlo dobru učinkovitost i protiv Streptococcus pneumoniae rezistentnog na penicilin i makrolide. Farmakokinetske osobine i dobro prodiranje u tkiva omogućuju peroralnu primjenu telitromicina u jednoj dnevnoj dozi od 800 mg. Telitromicin se metabolizira u jetri, a izlučuje se putem žuči i bubrega. Kontrolirana klinička istraživanja bila su ograničena samo na respiratorne infekcije, uključujući pneumonije iz opće populacije, akutne egzarcebacije kronične opstruktivne plućne bolesti, sinusitis i streptokoknu anginu. Kliničko izlječenje i bakteriološka eradikacija bili su slični u usporedbi s kompariranim antibioticima. Brojna klinička istraživanja nedvojbeno su dokazala kliničku učinkovitost telitromicina u liječenju infekcija gornjeg i donjeg dijela dišnog sustava koje su uzrokovane tipičnim i atipičnim bakterijama, uključujući sojeve koji su rezistentni na beta-laktamske antibiotike i makrolide.Ketolides are a new class of macrolides designed to offer activity for the treatment of upper and lower respiratory tract infections, including those caused by resistant strains. Ketolides have a mechanism of action very similar to erythromycin and other macrolides. Telithromycin is the first member of this new class to be approved for clinical use. This review discusses recent developments of telithromycin with analysis of in vitro and in vivo activities, pharmacokinetics, pharmacodinamics, as well as clinical trials and clinical use. Telithromycin exhibits good activity against gram-positive, gram-negative and atypical respiratory tract pathogens. It has excellent activityagainst penicillin-resistant and macrolide-resistant Streptococcus pneumoniae. The pharmacokinetics and tissue penetration of telithromycin permit once daily oral administration of an 800 mg dose. It is primarily metabolised in the liver and that elimination is by a combination of biliary and urinary excretion. Clinical trial data have focused on respiratory infections including community-acquired pneumonia, acute exacerbations of chronic obstructive pulmonary disease, sinusitis and streptococcal pharyngitis. Clinical cure rates and bacteriological eradication have been similar to comparators. Telithromycin has similar safety profile to the newer macrolides. Numerous clinical trials support the clinical efficacy of the telithromycin in upper and lower respiratory tract infections caused by tipical and atypical pathogens including strains resistant to beta-lactams and macrolides

Editorial

Ptičja gripa i pandemija influence: očekivana realnostBird Flu and Influenza Pandemic: The Expected Realit

Editorial

Ptičja gripa i pandemija influence: očekivana realnostBird Flu and Influenza Pandemic: The Expected Realit

Recikliranje krhotina legura aluminija AlMgSi1 pomoću hladnog sabijanja

Current work elaborates possibilities for direct conversion of AlMgSi1 aluminium chips into solid billets by solid state recycling. Milling chips from an aluminium alloy were cold compressed in a closed cylindrical die by means of a 2,5 MN hydraulic press. Due to low initial relative density of the chips, several pre-compressions were needed. In order to establish the infl uence of chip geometry on the final density of billets different types of chips were cut by using various milling regimes. The infl uence of a compression regime due to various chip types were followed by load–stroke diagrams. Up to 97 % of density measured at extruded aluminium was attained for one type of chips. Results show that the shapes of the chips and their size (especially thickness) have a considerable infl uence on the final integrity of billets.Ovaj rad istražuje mogućnosti za izravnu konverziju krhotina aluminijske legure AlMgSi1 u čvrst pripremak. Aluminijiske krhotine su hladno sabijani u zatvorenoj matrici pomoću 2,5 MN hidrauličke preše. Zbog male početne gustoće krhotina bilo je potrebno izvršiti nekoliko pre-sabijanja u zavisnosti od tipa krhotina. Da bi se istražio utjecaj geometrije krhotine na krajnju gustoću uzoraka, rezanje krhotina je izvedeno različitim režimima. U radu je prikazan utjecaj tipa krhotine na krajnju gustoću uzoraka, kao i dijagram sila – put procesa sabijanja. Relativne gustoće pojedinih uzoraka prilikom sabijanja dostigle su i 97 % od gustoće ekstrudiranog aluminija. Rezultati istraživanja pokazuju da oblik i veličina (a naročito debljina) krhotine ima značajan utjecaj na krajnju gustoću uzoraka

Oseltamivir: pharmacokinetics, clinical efficacy and importance in influenza pandemic

Inhibitor neuraminidaze oseltamivir, za peroralnu primjenu, registriran je za liječenje i sprječavanje influence A i B u odraslih i u djece starije od jedne godine. Liječenje i profilaksa moraju se započeti unutar 48 sati od pojave prvih simptoma, odnosno od kontakta s bolesnikom. Oseltamivir (2 × 75 mg, 5 dana) je siguran i učinkovit lijek u liječenju i sprječavanju svih poznatih tipova virusa influence. Ublažuje težinu i skraćuje trajanje simptoma te smanjuje učestalost karakterističnih komplikacija (bronhitis, otitis, pneumonija). Liječenje oseltamivirom također znatno smanjuje uporabu antibiotika, hospitalizaciju bolesnika i stopu smrtnosti. Postekspozicijska profilaktička primjena oseltamivira (1 × 75 mg, 7 dana) imala je 89 %-tnu učinkovitost. Također i sezonska profilaksa u starijih ljudi pruža 92 %-tnu zaštitu. Nalazi brojnih kliničkih istraživanja u cijelom svijetu pokazuju da je oseltamivir vrlo siguran lijek s dobrom podnošljivošću, a samo u vrlo malog broja bolesnika registriraju se blage prolazne probavne smetnje (mučnina, povraćnje). Budući je oseltamivir učinkovit protiv svih virusa influence, Svjetska zdravstvena organizacija je preporučila nabavu i čuvanje oseltamivira za pandemijsku pojavu gripe.Oseltamivir, an orally-administered neuraminidase inhibitor, is licensed for the treatment and prophylaxis of influenza A and B in adults and children aged 1 year or older. Therapy and prophylaxis should begin within 48 hours of exposure. Oseltamivir (75 mg twice daily for 5 days) is safe and effective for the treatment and prevention of all known influenza subtypes, reducing the severity and duration of symptoms, as well as complications arising from influenza infection (bronchitis, otitis media, pneumonia). Treatment with oseltamivir also reduces the frequency of antibiotic use, hospital admission and mortality rate. Postexposure prophylaxis with oseltamivir, 75 mg once daily for 7 days, gave 89 % protection. Similarly, seasonal prophylaxis in elderly people provided 92 % protection. Results of numerous clinical studies around the world indicated that oseltamivir is a very well tolerated drug, with few patients reporting transient, and mostly mild gastrointestinal disturbances (nausea or vomiting). Since oseltamivir has been shown to be effective against pandemic strains of influenza, the World Health Organization has recommended the stockpiling of oseltamivir in the event of an influenza pandemic

Characteristics of clinical presentation of avian influenza in humans

Virusi influence A sa svojih 16 hemaglutinina (HA) i 9 neuraminidaza (NA) široko su rasprostranjeni među pticama selicama i močvaricama. Većina ptičjih sojeva ima malu patogenost, ali je nekoliko sojeva izrazito virulentno, poglavito tip H5N1. Do 1997. godine nije bilo podataka da H5N1 virus može inficirati i uzrokovati bolest u ljudi. U Hong Kongu se te godine pojavila epidemija uzrokovana virusom H5N1 u kojoj je oboljelo 18, a umrlo šest ljudi. U većine oboljelih registrirani su teži respiratorni simptomi s rendgenski utvrđenom pneumonijom. Akutni respiratorni distres sindrom i sindrom oštećenja više organa razvili su se u bolesnika sa smrtnim ishodom. Nakon 1997. godine virus je kontinuirano evoluirao, što je dovelo do promjena u antigenosti i pojačanoj virulenciji. Filogenetska analiza ukazuje da je genotip Z postao dominantan, te se počeo širiti na nepredviđen način u jugoistočnoj Aziji. Do sada je bolest zabilježena u više od 160 ljudi u jugoistočnoj Aziji, ali i u Turskoj i Iraku s 50 % mortalitetom. Većina bolesnika u početku bolesti ima vrućicu i simptome slične gripi. Gotovo svi bolesnici razvijaju i pneumoniju. Pored respiratornih simptoma, velik postotak bolesnika ima i gastrointestinalne tegobe, kao što su proljev, povraćanje i bolove u trbuhu. U težim slučajevima tijek bolesti je karakteriziran brzim razvojem difuznih plućnih infiltrata i znakovima akutnog respiratornog distres sindroma, te višestrukog zatajivanja organa. Osim toga, postoje izvještaji i o atipičnim prezentacijama i blažim oblicima bolesti. Najvažniji laboratorijski nalazi su leukopenija, poglavito limfopenija, trombocitopenija i blago povišenje vrijednosti aminotransferaza. Mehanička ventilacija i mjere intezivnog liječenja primjenjuju se u većine bolesnika, a liječenje antivirusnim lijekovima u pravilu je započinjalo sa zakašnjenjem.Influenza A viruses with their 16 hemagglutinins (HA) and 9 neuraminidases (NA) are widespread in migratory birds and water fowl. Most avian strains are of low pathogenicity, while few strains are highly pathogenic, especially subtype H5N1. Before 1997, there was no evidence indicating that H5N1 influenza virus could infect and cause disease in humans. The same year an outbreak caused by H5N1 occurred in Hong Kong resulting in six deaths among 18 people. Severe respiratory symptoms with radiological evidence of pneumonia were recorded in the majority of cases. Patients with lethal outcome developed acute respiratory distress syndrome and multiple organ dysfunction syndrome. Since 1997, H5N1 virus continued to evolve, with changes in antigenicity and enhanced pathogenicity. Phylogenetic analyses indicate that the Z genotype has become dominant, and has spread in an unprecedented fashion across Southeast Asia. So far, the desease was registered in 160 people, however in Turkey and Iraq with mortality rate of 50 %. Most patients have initial fever and an influenza- like symptoms. Amost all patients develop pneumonia. Besides respiratory symptoms, a large proportion of patients also complained of gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain. The course of the illness in severe cases was characterized by rapid development of diffuse infiltrates and manifestations of the acute respiratory distress syndrome, and multiorgan failure. Furthermore, atypical presentations, and milder cases have also been reported. Common laboratory findings have been leukopenia, particularly support as well as intensive care, while treatment with antiviral agents usually started with delay

Characteristics of clinical presentation of avian influenza in humans

Virusi influence A sa svojih 16 hemaglutinina (HA) i 9 neuraminidaza (NA) široko su rasprostranjeni među pticama selicama i močvaricama. Većina ptičjih sojeva ima malu patogenost, ali je nekoliko sojeva izrazito virulentno, poglavito tip H5N1. Do 1997. godine nije bilo podataka da H5N1 virus može inficirati i uzrokovati bolest u ljudi. U Hong Kongu se te godine pojavila epidemija uzrokovana virusom H5N1 u kojoj je oboljelo 18, a umrlo šest ljudi. U većine oboljelih registrirani su teži respiratorni simptomi s rendgenski utvrđenom pneumonijom. Akutni respiratorni distres sindrom i sindrom oštećenja više organa razvili su se u bolesnika sa smrtnim ishodom. Nakon 1997. godine virus je kontinuirano evoluirao, što je dovelo do promjena u antigenosti i pojačanoj virulenciji. Filogenetska analiza ukazuje da je genotip Z postao dominantan, te se počeo širiti na nepredviđen način u jugoistočnoj Aziji. Do sada je bolest zabilježena u više od 160 ljudi u jugoistočnoj Aziji, ali i u Turskoj i Iraku s 50 % mortalitetom. Većina bolesnika u početku bolesti ima vrućicu i simptome slične gripi. Gotovo svi bolesnici razvijaju i pneumoniju. Pored respiratornih simptoma, velik postotak bolesnika ima i gastrointestinalne tegobe, kao što su proljev, povraćanje i bolove u trbuhu. U težim slučajevima tijek bolesti je karakteriziran brzim razvojem difuznih plućnih infiltrata i znakovima akutnog respiratornog distres sindroma, te višestrukog zatajivanja organa. Osim toga, postoje izvještaji i o atipičnim prezentacijama i blažim oblicima bolesti. Najvažniji laboratorijski nalazi su leukopenija, poglavito limfopenija, trombocitopenija i blago povišenje vrijednosti aminotransferaza. Mehanička ventilacija i mjere intezivnog liječenja primjenjuju se u većine bolesnika, a liječenje antivirusnim lijekovima u pravilu je započinjalo sa zakašnjenjem.Influenza A viruses with their 16 hemagglutinins (HA) and 9 neuraminidases (NA) are widespread in migratory birds and water fowl. Most avian strains are of low pathogenicity, while few strains are highly pathogenic, especially subtype H5N1. Before 1997, there was no evidence indicating that H5N1 influenza virus could infect and cause disease in humans. The same year an outbreak caused by H5N1 occurred in Hong Kong resulting in six deaths among 18 people. Severe respiratory symptoms with radiological evidence of pneumonia were recorded in the majority of cases. Patients with lethal outcome developed acute respiratory distress syndrome and multiple organ dysfunction syndrome. Since 1997, H5N1 virus continued to evolve, with changes in antigenicity and enhanced pathogenicity. Phylogenetic analyses indicate that the Z genotype has become dominant, and has spread in an unprecedented fashion across Southeast Asia. So far, the desease was registered in 160 people, however in Turkey and Iraq with mortality rate of 50 %. Most patients have initial fever and an influenza- like symptoms. Amost all patients develop pneumonia. Besides respiratory symptoms, a large proportion of patients also complained of gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain. The course of the illness in severe cases was characterized by rapid development of diffuse infiltrates and manifestations of the acute respiratory distress syndrome, and multiorgan failure. Furthermore, atypical presentations, and milder cases have also been reported. Common laboratory findings have been leukopenia, particularly support as well as intensive care, while treatment with antiviral agents usually started with delay

Clinical and epidemiological characteristics of Q fever in hospitalized patients

Retrospektivno su analizirane kliničke i epidemiološke značajke Q-groznice u 25 bolesnika koji su hospitalizirani u Klinici za infektivne bolesti u Zagrebu od 1. siječnja do 31. prosinca 2004. godine. Dijagnoza Q-groznice postavljena je u svih bolesnika serološki, imunoenzimskim testom (ELISA). Bolest se pojavljivala od ožujka do srpnja. Svi bolesnici su se razboljeli sporadično, a stanovnici su grada Zagreba i njegove okolice. Trinaest (52, 0%) bolesnika s Q-groznicom inficirano je u mjestu stanovanja, 10 (40, 0%) u drugim dijelovima Hrvatske, dok su dva (8, 0%) bolesnika u inkubacijskom razdoblju boravila u Bosni i Hercegovini. Bilo je znatno više muškaraca, nego žena (22:3). Većina bolesnika (68, 0%) je bila u dobi od 21-40 godina. Vodeći simptomi bolesti bili su vrućica, glavobolja i kašalj, a najvažniji patološki laboratorijski nalazi ubrzana sedimentacija eritrocita i povišena vrijednost C-reaktivnog proteina. Rendgenskim slikanjem pluća u većine bolesnika otkriven je intersticijski infiltrat, smješten u jednom plućnom režnju (23 ili 92, 0%). Pleuralni izljev je registriran u dva (8, 0%) bolesnika. Bolesnici su liječeni azitromicinom, fluorokinolonima i doksiciklinom. Doksiciklin je pokazao najbolji klinički učinak. Svi bolesnici su izliječeni.We retrospectively analysed clinical and epidemiological characteristics of Q fever in 25 patients hospitalized at the University Hospital for Infectious Diseases in Zagreb from January 1 to December 31, 2004. The diagnosis of Q fever was confirmed by serology in all patients, by an enzyme-linked immunosorbent assay (ELISA). The disease occurred from March to July. All patients were sporadic cases, and they were inhabitants of Zagreb and its surrounding areas. Thirteen (52.0 %) patients with Q fever were infected in their place of living, 10 (40.0 %) in other parts of Croatia, while 2 (8.0 %) patients were in Bosnia and Hercegovina during the incubation period. There were significantly more males than females (22:3). Most of the patients (68.0 %) were aged 21–40 years. Main symptoms of disease were fever, headache, and cough, and most significant pathological laboratory findings were accelerated erythrocyte sedimentation rate and increased value of C- reactive protein. Chest X-ray revealed interstitial pulmonary infiltrates in the majority of patients, localized in a single pulmonary lobe (23 or 92.0 %). Pleural effusion was recorded in 2 (8.0 %) patients. The patients were treated with azithromycin, fluoroquinolone, and doxycycline. Doxycycline showed the best clinical efficacy. All patients were cured

Treatment of Diabetic Ketoacidosis Associated With Antipsychotic Medication Literature Review

This work was funded by the Croatian Science Foundation grant No UIP- 2014-09-1245 Biomarkers in schizophrenia - integration of complementary methods in longitudinal follow up of first episode psychosis patients. The authors received no other funding for this work

Clinical and epidemiological characteristics of Q fever in hospitalized patients

Retrospektivno su analizirane kliničke i epidemiološke značajke Q-groznice u 25 bolesnika koji su hospitalizirani u Klinici za infektivne bolesti u Zagrebu od 1. siječnja do 31. prosinca 2004. godine. Dijagnoza Q-groznice postavljena je u svih bolesnika serološki, imunoenzimskim testom (ELISA). Bolest se pojavljivala od ožujka do srpnja. Svi bolesnici su se razboljeli sporadično, a stanovnici su grada Zagreba i njegove okolice. Trinaest (52, 0%) bolesnika s Q-groznicom inficirano je u mjestu stanovanja, 10 (40, 0%) u drugim dijelovima Hrvatske, dok su dva (8, 0%) bolesnika u inkubacijskom razdoblju boravila u Bosni i Hercegovini. Bilo je znatno više muškaraca, nego žena (22:3). Većina bolesnika (68, 0%) je bila u dobi od 21-40 godina. Vodeći simptomi bolesti bili su vrućica, glavobolja i kašalj, a najvažniji patološki laboratorijski nalazi ubrzana sedimentacija eritrocita i povišena vrijednost C-reaktivnog proteina. Rendgenskim slikanjem pluća u većine bolesnika otkriven je intersticijski infiltrat, smješten u jednom plućnom režnju (23 ili 92, 0%). Pleuralni izljev je registriran u dva (8, 0%) bolesnika. Bolesnici su liječeni azitromicinom, fluorokinolonima i doksiciklinom. Doksiciklin je pokazao najbolji klinički učinak. Svi bolesnici su izliječeni.We retrospectively analysed clinical and epidemiological characteristics of Q fever in 25 patients hospitalized at the University Hospital for Infectious Diseases in Zagreb from January 1 to December 31, 2004. The diagnosis of Q fever was confirmed by serology in all patients, by an enzyme-linked immunosorbent assay (ELISA). The disease occurred from March to July. All patients were sporadic cases, and they were inhabitants of Zagreb and its surrounding areas. Thirteen (52.0 %) patients with Q fever were infected in their place of living, 10 (40.0 %) in other parts of Croatia, while 2 (8.0 %) patients were in Bosnia and Hercegovina during the incubation period. There were significantly more males than females (22:3). Most of the patients (68.0 %) were aged 21–40 years. Main symptoms of disease were fever, headache, and cough, and most significant pathological laboratory findings were accelerated erythrocyte sedimentation rate and increased value of C- reactive protein. Chest X-ray revealed interstitial pulmonary infiltrates in the majority of patients, localized in a single pulmonary lobe (23 or 92.0 %). Pleural effusion was recorded in 2 (8.0 %) patients. The patients were treated with azithromycin, fluoroquinolone, and doxycycline. Doxycycline showed the best clinical efficacy. All patients were cured