Empirical antimicrobial therapy of community-acquired urinary tract infections – the use of mathematical modelling in selecting a rational therapy

Izbor inicijalne empirijske antimikrobne terapije u liječenju infekcija mokraćnog sustava (IMS) značajni je faktor koji utječe na ishod liječenja. Inicijalna empirijska terapija treba imati vjerojatnost u više od 90 % da će antimikrobni spektar primijenjenog lijeka obuhvatiti mogućeg uzročnika(e) infekcije. Svrha rada je prikazati značaj matematičkog modela - formule u odabiru najpotentnijeg širokospektralnog antibiotika u inicijalnoj empirijskoj terapiji na temelju lokalnih mikrobioloških podataka o incidenciji uzročnika i njihovoj osjetljivosti. U dva vremenska perioda 2003. i 2009. god. obrađeno je 145 i 167 hospitaliziranih bolesnika liječenih zbog infekcija mokraćnog sustava. Na temelju lokalnih mikrobioloških podataka o incidenciji uzročnika i njihovoj osjetljivosti, korištenjem matematičkog modela-formule, dobili smo uvid u potentnost najčešće propisivanih antibiotika u inicijalnoj empirijskoj terapiji. Najveći udio izoliranih uropatogena iz urina odnosio se na E. coli i K. pneumoniae zajedno, 70% / 2003.god., 72 %/2009.g. Matematičkom analizom izoliranih uropatogena i njihove osjetljivosti na najčešće propisivane antibiotike u 2003. i 2009.god. dobili smo uvid u njihovu učinkovitost na većinu izoliranih uzročnika: 03/09.g amoksicilin/klavulonska kiselina (AMC): 80% / 77%, cefuroksim (CXM): 79% / 69%, gentamicin (GM): 82% / 75%, ciprofloksacin (CIP): 81% / 66%. Statistički značajna razlika (p<0,05) u smanjenoj potentnosti u empirijskoj primjeni u 2003. prema 2009.god. dokazana je za ciprofloksacin. Primjena matematičkog modela – formule pomaže u odluci odabira inicijalne empirijske antimikrobne terapije u liječenju infekcija mokraćnog sustava kao i u definiranju lokalnih antimikrobnih smjernica prema lokalnim podacima.The selection of initial empiric antibiotic therapy in the treatment of urinary tract infections (UTI) significantly affects the outcome of UTI. An initial, empirical therapy should have a probability of more than 90% that the spectrum of administered antimicrobial drug will cover possible cause(s) of infection. The aim of this study is to show the importance of using a mathematical model-formula to help in the selection of the most potent, broad-spectrum antimicrobial agent in initial empirical antibiotic therapy based on local microbiological data, the incidence of pathogens and their sensitivity. In the two time periods, in 2003 and 2009 we analyzed medical records of 145, that is, 167 hospitalized patients treated for urinary tract infections. Based on local microbiological data on the incidence of pathogens and their sensitivity, using a mathematical model formula we acquired an insight into the potency of the most commonly used antibiotics in the initial empirical therapy. The highest proportion of strains isolated from urine was related to Escherichia coli and Klebsiella pneumoniae 70%/2003, 72%/2009, respectively. A mathematical model – formula has showed the capacity of antimicrobial agent as having the highest overall level of activity against main isolates from urine: amoxicillin/clavulanic acid (AMC) in the years 2003/2009: 80% / 77%, cefuroxime (CXM) 79%/69%, gentamicin (GM) 82% / 75%, ciprofloxacin (CIP) 81%/ 66%. Statistically significant difference (p < 0.05) in reduced potency of empirical therapy was observed for ciprofloxacin in 2003 compared to 2009. Mathematical model-formula is a helping tool in choosing the initial empirical antimicrobial therapy in the treatment of urinary tract infections as well as in defining local antimicrobial guidelines for UTI

Multiple recurrent liver abscesses in an immunodeficient patient

Multipli recidivirajući jetreni apscesi su rijedak klinički entitet koji može predstavljati veliki dijagnostički i terapijski problem. Prikazali smo bolesnika koji je zbog septičnog stanja i recidivirajućih multiplih jetrenih apscesa u periodu od 1999. – 2007.god. višekratno liječen u više općih i kliničkih bolnica u Hrvatskoj. Učinjenom dodatnom imunološkom obradom dokazana je u prvom redu smanjena mikrobicidna aktivnost granulocitnih i monocitnih fagocita. U našem radu pokazali smo da se kod recidivirajućih multiplih apscesa jetre mora misliti na poremećaje u procesu fagocitoze, te je u takvih bolesnika u prvom redu potrebno uraditi funkcionalne testove fagocitoze, ali i T- i B-limfocita i NK-stanica. Primjena intravenskog imunoglobulina, koji ima ulogu u stimulaciji respiratornog praska i posljedično mikrobicidne aktivnosti, može smanjiti broj recidiva i povoljno utjecati na tijek bolesti.Multiple recurrent liver abscesses are uncommon clinical entity that can represent a significant diagnostic and therapeutic problem. We describe a patient who was, due to septic conditions and recurrent multiple hepatic abscesses, repeatedly treated in a number of general and clinical hospitals in Croatia in the period from 1999 to 2007. Additional immunological tests demonstrated a reduced microbicidal activities of granulocytes and monocytic phagocytes. Our paper shows that in patients with multiple recurrent liver abscesses, possible deficiencies in the process of phagocytosis have to be considered, and functional tests of phagocytes, T- and B-lymphocytes as well as NK-cells need to be performed. The administration of intravenous immunoglobulin, which has a role in stimulating the respiratory burst activity and, consequently, microbicidal phagocytic activity, can reduce the number of relapses, and favorably affect the course of disease

Prevalence and molecular epidemiology of West Nile and Usutu virus infections in Croatia in the ‘One health’ context, 2018

In 2018, Croatia reported the largest outbreak of West Nile virus (WNV) infections as well as the re-occurrence of human Usutu virus (USUV) infections. For the first time, fatal WNV and USUV infections were detected in wild birds. We analysed epidemiological characteristics and molecular epidemiology of WNV and USUV infections detected during 2018 transmission season. From April to November, 178 patients with neuroinvasive disease and 68 patients with febrile disease were tested for WNV and USUV. Viral RNA was detected in cerebrospinal fluid (CSF) and urine samples using a real-time RT-PCR. Positive samples were tested by nested RT-PCR and nucleotide sequencing. IgM/IgG antibodies were detected in serum/CSF samples using ELISA with confirmation of cross-reactive samples by virus neutralization test (VNT). WNV neuroinvasive disease was confirmed in 54 and WNV fever in seven patients from 10 continental Croatian counties. Areas affected in 2018 were those in which cases occurred in previous seasons, while in three areas human cases were reported for the first time. Phylogenetic analysis of six strains from patients residing in different geographic areas showed circulation of WNV lineage 2. In three patients, neuroinvasive USUV infection was confirmed by RT-PCR or VNT. Sequence analysis of one detected strain revealed USUV Europe 2 lineage. During the same period, a total of 2,574 horse and 1,069 poultry serum samples were tested for WNV antibodies using ELISA. Acute asymptomatic WNV infection (IgM antibodies) was documented in 20/0.7% horses. WNV IgG antibodies were found in 307/11.9% horses and in 125/12.7% poultry. WNV RNA was detected in two goshawks and USUV RNA was detected in one blackbird from north-western Croatia. In the Zagreb area, 3,670 female mosquitoes were collected. One Culex pipiens pool collected in July tested positive for USUV RNA. Our results highlight the importance of continuous multidisciplinary 'One health' surveillance of these emerging arboviruses

Severe West Nile Virus Neuroinvasive Disease: Clinical Characteristics, Short- and Long-Term Outcomes

West Nile Virus Neuroinvasive Disease (WNV NID) requires prolonged intensive care treatment, resulting in high mortality and early disability. Long-term results are lacking. We have conducted an observational retrospective study with a prospective follow-up of WNV NID patients treated at the Intensive Care Unit (ICU), University Hospital for Infectious Diseases, Zagreb, Croatia, 2013–2018. Short-term outcomes were vital status, length of stay (LOS), modified Rankin Scale (mRS), and disposition at discharge. Long-term outcomes were vital status and mRS at follow-up. Twenty-three patients were identified, 78.3% males, median age 72 (range 33–84) years. Two patients (8.7%) died in the ICU, with no lethal outcomes after ICU discharge. The median ICU LOS was 19 days (range 5–73), and the median hospital LOS was 34 days (range 7–97). At discharge, 15 (65.2%) patients had moderate to severe/mRS 3–5, 6 (26.0%) had slight disability/mRS 2–1, no patients were symptom-free/mRS 0. Ten (47.6%) survivors were discharged to rehabilitation facilities. The median time to follow-up was nine months (range 6–69). At follow-up, seven patients died (30.5%), five (21.7%) had moderate to severe/mRS 3–5, one (4.3%) had slight disability/mRS 2–1, six (26.1%) had no symptoms/mRS 0, and four (17.4%) were lost to follow-up. Briefly, ten (43.5%) survivors improved their functional status, one (4.3%) was unaltered, and one (4.3%) aggravated. In patients with severe WNV NID, intensive treatment in the acute phase followed by inpatient rehabilitation resulted in significant recovery of functional status after several months