Healthcare-Associated Bloodstream Infections Due to Multidrug-Resistant Acinetobacter baumannii in COVID-19 Intensive Care Unit: A Single-Center Retrospective Study.

Healthcare-associated infections are an emerging cause of morbidity and mortality in COVID-19 intensive care units (ICUs) worldwide, especially those caused by multidrug-resistant (MDR) pathogens. The objectives of this study were to assess the incidence of bloodstream infections (BSIs) among critically ill COVID-19 patients and to analyze the characteristics of healthcare-associated BSIs due to MDR Acinetobacter baumannii in an COVID-19 ICU. A single-center retrospective study was conducted at a tertiary hospital during a 5-month period. The detection of carbapenemase genes was performed by PCR and genetic relatedness by pulsed-field gel electrophoresis (PFGE) and multilocus-sequence typing. A total of 193 episodes were registered in 176 COVID-19 ICU patients, with an incidence of 25/1000 patient-days at risk. A. baumannii was the most common etiological agent (40.3%), with a resistance to carbapenems of 100%. The blaOXA-23 gene was detected in ST2 isolates while the blaOXA-24 was ST636-specific. PFGE revealed a homogeneous genetic background of the isolates. The clonal spread of OXA-23-positive A. baumannii is responsible for the high prevalence of MDR A. baumannii BSIs in our COVID-19 ICU. Further surveillance of resistance trends and mechanisms is needed along with changes in behavior to improve the implementation of infection control and the rational use of antibiotics.

MRSA surveillance programmes worldwide: moving towards a harmonised international approach.

Multinational surveillance programmes for methicillin-resistant Staphylococcus aureus (MRSA) are dependent on national structures for data collection. This study aimed to capture the diversity of national MRSA surveillance programmes and to propose a framework for harmonisation of MRSA surveillance. The International Society of Antimicrobial Chemotherapy (ISAC) MRSA Working Group conducted a structured survey on MRSA surveillance programmes and organised a webinar to discuss the programmes' strengths and challenges as well as guidelines for harmonisation. Completed surveys represented 24 MRSA surveillance programmes in 16 countries. Several countries reported separate epidemiological and microbiological surveillance. Informing clinicians and national policy-makers were the most common purposes of surveillance. Surveillance of bloodstream infections (BSIs) was present in all programmes. Other invasive infections were often included. Three countries reported active surveillance of MRSA carriage. Methodology and reporting of antimicrobial susceptibility, virulence factors, molecular genotyping and epidemiological metadata varied greatly. Current MRSA surveillance programmes rely upon heterogeneous data collection systems, which hampers international epidemiological monitoring and research. To harmonise MRSA surveillance, we suggest improving the integration of microbiological and epidemiological data, implementation of central biobanks for MRSA isolate collection, and inclusion of a representative sample of skin and soft-tissue infection cases in addition to all BSI cases.

Staphylococcus aureus bloodstream infections: diverging trends of meticillin-resistant and meticillin-susceptible isolates, EU/EEA, 2005 to 2018.

BackgroundInvasive infections caused by Staphylococcus aureus have high clinical and epidemiological relevance. It is therefore important to monitor the S. aureus trends using suitable methods.AimThe study aimed to describe the trends of bloodstream infections (BSI) caused by meticillin-resistant S. aureus (MRSA) and meticillin-susceptible S. aureus (MSSA) in the European Union (EU) and the European Economic Area (EEA).MethodsAnnual data on S. aureus BSI from 2005 to 2018 were obtained from the European Antimicrobial Resistance Surveillance Network (EARS-Net). Trends of BSI were assessed at the EU/EEA level by adjusting for blood culture set rate (number of blood culture sets per 1,000 days of hospitalisation) and stratification by patient characteristics.ResultsConsidering a fixed cohort of laboratories consistently reporting data over the entire study period, MRSA percentages among S. aureus BSI decreased from 30.2% in 2005 to 16.3% in 2018. Concurrently, the total number of BSI caused by S. aureus increased by 57%, MSSA BSI increased by 84% and MRSA BSI decreased by 31%. All these trends were statistically significant (p < 0.001).ConclusionsThe results indicate an increasing health burden of MSSA BSI in the EU/EEA despite a significant decrease in the MRSA percentage. These findings highlight the importance of monitoring antimicrobial resistance trends by assessing not only resistance percentages but also the incidence of infections. Further research is needed on the factors associated with the observed trends and on their attributable risk.

Characterization of macrolide resistance in bacteria isolated from macrolide-polluted and unpolluted river sediments and clinical sources in Croatia.

Environments polluted with excessively high levels of antibiotics released from manufacturing sites can act as a source of transferable antibiotic resistance (AR) genes to human commensal and pathogenic bacteria. The aim of this study was to evaluate AR of bacteria isolated from the Sava river sediments (Croatia) at the discharge site of effluents from azithromycin production compared to those from the upstream site and isolates collected in Croatian hospitals. A total of 228 environmental strains of azithromycin-resistant bacteria were isolated and identified, with 124 from the discharge site and 104 from the upstream site. In addition, a total of 90 clinical, azithromycin-resistant streptococcal and staphylococcal isolates obtained from the Croatian Reference Center for Antibiotic Resistance Surveillance were analyzed. PCR screening of isolates on 11 relevant macrolide-resistance genes (MRGs) showed that discharge isolates had greater detection frequencies for 4 gene targets (ermB, msrE, mphE and ermF) compared to upstream isolates. Among clinical isolates, the most frequently detected gene was ermB, followed by msrD, mefE and mefC. The discharge site demonstrated a greater abundance of isolates with co-occurrence of two different MRGs (predominantly msrE-mphE) than the upstream site, but a lower abundance than the clinical sources (most commonly msrD-mefE). The simultaneous presence of three or even four MRGs was specific for the discharge and clinical isolates, but not for the upstream isolates. When MRG results were sorted by gene mechanism, the ribosomal methylation (erm) and protection genes (msr) were the most frequently detected among both the discharge and the clinical isolates. Following sequencing, high nucleotide sequence similarity was observed between ermB in the discharge isolates and the clinical streptococcal isolates, suggesting a possible transfer of the ermB gene between bacteria of clinical and environmental origin. Our study highlights the importance of environmental bacterial populations as reservoirs for clinically relevant macrolide-resistance genes.

Successful containment of the first KPC-producing Klebsiella pneumoniae outbreak in Croatia.

AIM: We report the first outbreak caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae sequence type 258 (ST 258) clone that occurred in Croatia from May to December 2012. MATERIALS & METHODS: 23 carbapenem-resistant K. pneumoniae isolates were recovered from clinical and screening specimens of 12 patients hospitalized in a regional hospital. The first isolates from the 12 patients were typed using pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS: PCR detection showed that all isolates harbored the bla KPC-2 gene, together with bla TEM-116 and bla SHV-11. CONCLUSION: The rapid detection of KPC-producing K. pneumoniae and vigorous implementation of infection control measures were necessary to successfully control the outbreak.

Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study.

BACKGROUND: Gaps in the diagnostic capacity and heterogeneity of national surveillance and reporting standards in Europe make it difficult to contain carbapenemase-producing Enterobacteriaceae. We report the development of a consistent sampling framework and the results of the first structured survey on the occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in European hospitals. METHODS: National expert laboratories recruited hospitals with diagnostic capacities, who collected the first ten carbapenem non-susceptible clinical isolates of K pneumoniae or E coli and ten susceptible same-species comparator isolates and pertinent patient and hospital information. Isolates and data were relayed back to national expert laboratories, which made laboratory-substantiated information available for central analysis. FINDINGS: Between Nov 1, 2013, and April 30, 2014, 455 sentinel hospitals in 36 countries submitted 2703 clinical isolates (2301 [85%] K pneumoniae and 402 (15%) E coli). 850 (37%) of 2301 K pneumoniae samples and 77 (19%) of 402 E coli samples were carbapenemase (KPC, NDM, OXA-48-like, or VIM) producers. The ratio of K pneumoniae to E coli was 11:1. 1·3 patients per 10 000 hospital admissions had positive clinical specimens. Prevalence differed greatly, with the highest rates in Mediterranean and Balkan countries. Carbapenemase-producing K pneumoniae isolates showed high resistance to last-line antibiotics. INTERPRETATION: This initiative shows an encouraging commitment by all participants, and suggests that challenges in the establishment of a continent-wide enhanced sentinel surveillance for carbapenemase-producing Enterobacteriaeceae can be overcome. Strengthening infection control efforts in hospitals is crucial for controlling spread through local and national health care networks. FUNDING: European Centre for Disease Prevention and Control.

KPC-Producing Klebsiella pneumoniae Isolates in Croatia: A Nationwide Survey.

BACKGROUND: In the last few years, Klebsiella pneumoniae strains producing K. pneumoniae carbapenemase (KPC) enzymes have emerged as important multidrug-resistant pathogens in hospitalized patients. This report describes KPC-producing isolates collected through the Croatian antimicrobial resistance surveillance program in the early stage of their dissemination in Croatia. MATERIALS AND METHODS: Forty-eight KPC-producing K. pneumoniae isolates, collected during a period from February 2011 to August 2013, were analyzed in this study. Antimicrobial susceptibility profiles were determined using disk diffusion and E-test. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used for epidemiological analysis. Identification of ß-lactamase genes and associated antibiotic resistance mechanisms was performed by polymerase chain reaction and positive products were sequenced. Localization of blaKPC was investigated by S1 PFGE and Southern hybridization. RESULTS: Of 40 participating centers in Croatia, KPC isolates were recorded in 9 of them. They all had multidrug-resistant phenotype, but showed varying levels of resistance to carbapenems. All isolates displayed ST258, and PFGE showed that all but one were closely related. All isolates harbored blaKPC-2. Isolate with a unique PFGE pattern produced TEM-1, while others produced TEM-116. All isolates harbored blaSHV-11, but were negative for blaCTX-M and blaAmpC genes. All isolates contain one KPC-harboring plasmid, ranging in size from ∼60 to ∼210 kb, characterized as FIIs and IncR. CONCLUSION: This report describes that the early stage of KPC-producing K. pneumoniae dissemination in Croatia is associated with a prolific PFGE type belonging to ST258. So far, the spread of an outbreak strain is limited to the northwest region of the country.

Managing skin and soft-tissue infection and nosocomial pneumonia caused by MRSA: a 2014 follow-up survey.

As a follow-up to our 2009 survey, in order to explore opinion and practice on the epidemiology and management of meticillin-resistant Staphylococcus aureus (MRSA) in Europe, we conducted a second survey to elicit current opinions on this topic, particularly around antibiotic choice, dose, duration and route of administration. We also aimed to further understand how the management of MRSA has evolved in Europe during the past 5 years. Members of an expert panel of infectious diseases specialists convened in London (UK) in January 2014 to identify and discuss key issues in the management of MRSA. Following this meeting, a survey was developed comprising 36 questions covering a wide range of topics on MRSA complicated skin and soft-tissue infection and nosocomial pneumonia management. The survey instrument, a web-based questionnaire, was sent to the International Society of Chemotherapy for distribution to registered European infection societies and their members. This article reports the survey results from the European respondents. At the time of the original survey, the epidemiology of MRSA varied significantly across Europe and there were differing views on best practice. The current findings suggest that the epidemiology of healthcare-associated MRSA in Europe is, if anything, even more polarised, whilst community-acquired MRSA has become much more common. However, there now appears to be a much greater knowledge of current treatment/management options, and antimicrobial stewardship has moved forward considerably in the 5 years since the last survey.

Monoclonal outbreak of VIM-1-carbapenemase-producing Enterobacter cloacae in intensive care unit, University Hospital Centre Split, Croatia.

Emergence of carbapenem-resistant Enterobacteriaceae has become a substantial global health problem. The aim of this study was to analyze carbapenem-resistant isolates of Enterobacter cloacae that have emerged for the first time in the intensive care unit (ICU) at the University Hospital Centre Split, Croatia. The strains were selected in the period between June and August 2012, according to their susceptibility patterns to carbapenems. Resistant isolates were screened for metallo-ß-lactamase (MBL) production with the use of the imipenem-EDTA disk synergy test, and positive findings were confirmed by PCR. The type of VIM ß-lactamase gene was determined by sequencing of PCR products. The genetic relatedness was evaluated using pulsed-field gel electrophoresis analysis. The demographic and clinical data were retrospectively analyzed from medical records. Five patients were infected and one patient was colonized with a single clone of multidrug-resistant VIM-1-producing E. cloacae susceptible only to colistin. Three cases of lower respiratory tract infections, one case of bacteremia, and one case of intra-abdominal infection were identified. All cases were hospital-acquired after prolonged stay in ICU. All patients had serious underlying diseases and received a broad-spectrum antibiotic. Four patients died and two had unimprovable medical condition at the time of discharge from the hospital. MBL-producing E. cloacae can cause fatal infection in severely ill patients. Monoclonal outbreak highlights the need for continuous surveillance and good infection control practices to prevent further spread since the antibiotic therapy options for infections caused by such strains are strongly limited.

The significance of Chlamydia trachomatis in prostatitis syndrome.

Research and publication expenses were supported in part by the Croatian Science Foundation and PLIVA Croatia Ltd. (project no. 04/30 'Research on the aetiology, epidemiology, diagnostics, and treatment of patients with prostatitis syndrome').

Point prevalence survey on antibiotic use in a Croatian Infectious Disease Hospital.

Antibiotic use is the driving force for increasing antibiotic resistance. A large proportion of antibiotics in hospitals are used inadequately. The objective of this study was to evaluate antibiotic use at the Hospital for Infectious Diseases through point-prevalence surveys conducted in 2006, 2008, and 2009. Point prevalence surveys were part of the European Surveillance on Antimicrobial Consumption (ESAC) Hospital Care Subproject and patients' data were collected following ESAC protocol. Additionally, the adequacy of antimicrobial therapy and administration of the first line antibiotic according to the local guidelines were assessed by an infectious disease doctor and a clinical microbiologist. In the study period among the 599 patients admitted to hospital, 352 (58·8%) received antibiotics. Out of 448 antimicrobial treatments, 313 (69·9%) were administered parenterally and 135 (30·1%) orally. Altogether in years 2006, 2008, and 2009 the most commonly prescribed antibiotics were ceftriaxone (19·9%), co-amoxiclav (15·4%), ciprofloxacin (12·3%), narrow spectrum penicillins (6·5%), and penicillinase resistant penicillins (5·6%). Most (82·6%) of the treated infections were community acquired infections. The predominating diagnoses were urinary tract infections and infections with no primary site defined, followed by skin, soft tissue and bone and joint infections. The overall adequacy of antimicrobial therapy was 82% and the first line antibiotic according to the local guidelines was administered with high frequency for central nervous system and cardiovascular infections (100%), and low for ear, nose, and throat infections, urinary tract infections, lower respiratory tract and bone and joint infections (23·0%, 51·6%, 52·5%, 65·0%, respectively) which indicates a significant overuse of antibiotics for diagnoses listed. The results of an individual point prevalence survey provided reliable and representative data for the hospital. Point-prevalence surveys proved to be a valuable method for detecting targets for antibiotic prescribing improvement and they clearly showed that our local hospital guidelines offered too many choices of antibiotic treatment for each clinical indication and needed revision.

Antibiotic prescription rate for upper respiratory tract infections and risks for unnecessary prescription in Croatia.

Overprescribing of antibiotics in primary care has been recognized as public health problem. We investigated visits prescription rate of antibiotics to patients with upper respiratory tract infections (URTI) and unnecessary prescription for tonsillopharyngitis, in Croatia. In prospective observational study in November 2007. 25 GPs in Croatia recorded all patients' visits with URTI episode according ICPC-2. Clinical status of patients with tonsillopharyngitis were categorized according to Centor Criteria. 689 visits were analysed, 82% of visits were initial. Antibiotics were prescribed in 44.7% visits with URTI. There were no significant differences in antibiotic prescription rates regarding non-clinical factors. Antibiotics were prescribed to patients with tonsillopharyngitis in 62.2% visits. Unnecessary antibiotics were prescribed (Centor 1,2) in 49.6% visits with tonsillopharyngitis. Logistic regression analysis showed significant differences in unnecessary antibiotic prescription rates only with respect to the workday--Wednesday, CI (1.117-2.671), p = 0.0139. Leading antibiotic was amoxicillin + clavulonic acid, second was amoxicillin, the third were macrolides, the fourth was narrow spectrum penicillin and fifth were cephalosporins. This study shows over prescription for URTI. Unnecessary prescription for tonsillopharyngitis depend on non clinical factor--day of the week. This should be further explored and help to improved prescribe antibiotics.

The efficacy of gaseous ozone on some cariogenic bacteria.

The aim of this study is to analyze ozone impact on some cariogenic bacteria in ex vivo and in vitro conditions. The in vitro part of study inoculated dentine with strains of Streptococcus mutans ATCC 33402 and Lactobacillus paracasei ATCC 11974 bacteria. Samples of dentine before and after 40s ozone treatment were collected and anaerobically incubated. Samples of cariogenic dentine (N = 24) were collected from permanent molars within the ex vivo segment of the study, prior and after 40s ozone treatment and a number of colonies were counted after incubation. For the in vitro part of study, results have shown a statistically significant average value of reduction of Streptococcus mutans ATCC 33402 and Lactobacillus paracasei ATCC 11974 prior and after ozone treatment (p < 0.001). The ex vivo segment of the study has also demonstrated a statistically significant difference in the number of bacteria prior and after ozone implementation (p < 0.001). Gaseous ozone demonstrated a strong antimicrobial effect on cariogenic bacteria in both in vitro and ex vivo conditions and it can be used as an adjuvant in caries therapy.

[A report of rarely observed resistance pattern to carbapenems in a clinical isolate of Enterobacter cloacae]. / Prikaz rijetko videnog oblika otpornosti na karbapeneme u vrste Enterobacter cloacae.

The paper reports on the emergence of strain in which Enterobacter cloacae has demonstrated an unusual form of resistance to carbapenems mediated by enzyme IMI-1, class A beta-lactamase. The strain was isolated from a wound swab in the patient who had a surgical wound infection previously treated with meropenem. Limited choice of antibiotics that can treat infections caused by these pathogens indicates the necessity of accurate identification of multiple resistant gram-negative microorganisms and mechanisms of their resistance. Recognition of multiresistant gram-negative microorganisms emphasizes the importance of continuous microbiological monitoring of patients, especially in intensive care units. In the investigated institution there was no secondary spread of this strain. Identifying new mechanisms of resistance will be helpful to clinicians in selection of targeted therapy, while important for efficient prevention of spreading infections caused by multiple resistant microorganisms.

In vitro activity of tigecycline and comparators against Gram-negative pathogens isolated from blood in Europe (2004-2009).

Here we report on the antimicrobial resistance amongst Gram-negative isolates (excluding Acinetobacter spp.) collected from blood culture sources at European study sites as part of the global Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) from the study start in 2004 until August 2009. All isolates were collected and tested for minimum inhibitory concentrations using Clinical and Laboratory Standards Institute methodology. Over the collection period, extended-spectrum ß-lactamase (ESBL) production was recorded in 21.1% of Klebsiella pneumoniae, 2.6% of Klebsiella oxytoca and 11.3% of Escherichia coli, primarily in Croatia, Greece, Hungary, Italy, Poland, Romania and the Slovak Republic. ESBL rates stabilised amongst K. pneumoniae over 2006-2009, but doubled amongst E. coli in 2008-2009. The patterns of antimicrobial resistance changed accordingly for both organisms. Generally, Greece had the highest antimicrobial resistance for K. pneumoniae, Italy for E. coli, Serratia marcescens and Enterobacter spp., and Croatia for Pseudomonas aeruginosa. High resistance rates amongst K. pneumoniae were also seen in Croatia and Italy. Imipenem resistance amongst K. pneumoniae was reported exclusively in Greece (13.8%); amongst other Enterobacteriaceae, imipenem resistance was absent or low. Similarly, meropenem resistance was low amongst the Enterobacteriaceae except K. pneumoniae from Greece (42.6%). Across Europe, the most active antimicrobial agents against the Enterobacteriaceae were tigecycline, amikacin and the carbapenems, each with <10% resistance each year. Against the other antimicrobials, significant increases in non-susceptibility were reported for K. pneumoniae and E. coli, both important causative pathogens of bacteraemia.

Global distribution and epidemiologic associations of Escherichia coli clonal group A, 1998-2007.

Escherichia coli clonal group A (CGA) was first reported in 2001 as an emerging multidrug-resistant extraintestinal pathogen. Because CGA has considerable implications for public health, we examined the trends of its global distribution, clinical associations, and temporal prevalence for the years 1998-2007. We characterized 2,210 E. coli extraintestinal clinical isolates from 32 centers on 6 continents by CGA status for comparison with trimethoprim/sulfamethoxazole (TMP/SMZ) phenotype, specimen type, inpatient/outpatient source, and adult/child host; we adjusted for clustering by center. CGA prevalence varied greatly by center and continent, was strongly associated with TMP/SMZ resistance but not with other epidemiologic variables, and exhibited no temporal prevalence trend. Our findings indicate that CGA is a prominent, primarily TMP/SMZ-resistant extraintestinal pathogen concentrated within the Western world, with considerable pathogenic versatility. The stable prevalence of CGA over time suggests full emergence by the late 1990s, followed by variable endemicity worldwide as an antimicrobial drug-resistant public health threat.

[ISKRA guidelines on sore throat: diagnostic and therapeutic approach--Croatian national guidelines]. / Smjernice iskra za grlobolju: dijagnosticki i terapijski pristup--Hrvatske nacionalne smjernice.

Sore throat is most commonly caused by viruses, but when caused by bacteria, the most important is group A streptococcus (GAS). The aim of these guidelines is to determine optimal treatment for streptococcal sore throat and reasonable indications for tonsillectomy, as well as recommend how to differentiate streptococcal infection for which antibiotics are justified, from numerous other sore throats where antibiotics wont have a significant effect on disease course, but might contribute to bacterial resistance to antibiotics. The development of the guidelines was initiated by the Interdisciplinary Section for Antibiotic Resistance Control (ISKRA) of the Croatian Ministry of Health and Social Welfare in accordance with the principles of AGREE (Appraisal of Guidelines for Research and Evaluation) methodology which means that the guidelines are the result of consensus between all interested professional societies and institutions. For streptococcal sore throat diagnostics, the Working Group recommends evaluation of clinical presentation according to Centor criteria and for patients with Centor score 0-1, antibiotic therapy is not recommended nor bacteriological testing, while for patients with Centor score 2-4 bacteriological testing is recommended (rapid test or culture) as well as antibiotic therapy in case of positive result. The drug of choice for the treatment of streptococcal tonsillopharyngitis is oral penicillin taken for ten days (penicillin V) or in case of poor patient compliance benzathine penicillin G can be administered parenterally in a single dose. Other antibiotics (macrolides, clindamycin, cephalosporins, co-amoxiclav) are administered only in case of hypersensitivity to penicillin or in recurrent infections. Tonsillectomy is a widely accepted surgical procedure that decreases the number of sore throats in children and should be performed only if indications for this procedure are established. Absolute indications include five or more streptococcal infections per year, tonsillitis complications, permanent respiratory tract obstruction, obstructive sleep apnea syndrome and suspected tonsillar malignancy. Relative indications include chronic tonsillitis and occlusion disturbances.

[ISKRA guidelines on antimicrobial treatment and prophylaxis of urinary tract infections--Croatian national guidelines]. / ISKRA smjernice antimikrobnog lijecenja i profilakse infekcija mokracnog sustava--hrvatske nacionalne smjernice.

These guidelines refer to diagnosis, antimicrobial treatment and prophylaxis of urinary tract infections in adults and children older than 12 years of age and cover lower urinary tract in females, uncomplicated pyelonephritis, complicated UTI with or without pyelonephritis, asymptomatic bacteriuria and recurrent UTI. These guidelines do not cover sexually transmitted diseases. The guidelines are primarily intended for use by general practitioners and specialists working in primary health care and hospitals. The members of the Working Group for the development of guidelines on antimicrobial treatment and prophylaxis of urinary tract infections were appointed by the Croatian Ministry of Health and Social Welfare. The project was financially supported by the Dutch government and professional assistance was provided by international consultants. The evidence for this guidelines is based on a systematic review of the literature, local antibiotic resistance data, the existing clinical protocols on the treatment and prophylaxis of UTIs, as well as suggestions and comments made by colleagues physicians during more than 50 continuous medical education courses held in the last three years on antimicrobial treatment and prophylaxis of UTIs. Draft version of the guidelines was available for comments on the web site http://iskra.bfm.hr and during the two-month piloting period the guidelines were widely presented to general practitioners, specialists working in primary care and hospitals--urologists, gynecologists, infectious disease specialists, nephrologists. The final version of the guidelines was approved by the Intersectoral Coordination Mechanism for the Control of Antimicrobial Resistance (ISKRA) Board.

Research of urinary tract infections in family medicine physicians' offices--empiric antimicrobial therapy of urinary tract infections--Croatian experience.

In the period between October 1st and November 30th, 2006, we investigated a total of 3188 episodes of UTI (802 among males; 2386 among females) recorded in 108 family medicine offices in 20 cities in Croatia. The most common UTIs in women were acute uncomplicated cystitis (62%), complicated UTIs - cystitis and pyelonephritis (14%), urethritis (9%), acute uncomplicated pyelonephritis (6%), recurrent cystitis (5%), asymptomatic bacteriuria (3%) and recurrent pyelonephritis. The most common UTIs in men were complicated UTIs - cystitis and pyelonephritis (48%), urethritis (25%), prostatitis (24%) and asymptomatic bacteriuria (3%). Etiological diagnosis was made in 999 (31%) UTI episodes before antimicrobial therapy was given. The most frequently isolated causative pathogens were Escherichia coli (77%), Enterococcus faecalis (9%), Proteus mirabilis (5%), Klebsiella spp (3%), Streptococcus agalactiae (3%) and Enterobacter (1%). Antimicrobial drug was administered in 2939 (92.19%) UTI episodes, in 1940 (66.01%) as empirical therapy, and in 999 (34%) as targeted antimicrobial therapy. The most commonly administered drug in empirical therapy for acute uncomplicated cystitis, recurrent cystitis and urethritis in women was cephalexin, for acute uncomplicated pyelonephritis and complicated UTIs in women co-amoxiclav, and for UTIs in males ciprofloxacin. The results of this research of 3188 UTI episodes in family medicine physicians' offices provide a confirmatory answer to question whether empirical antimicrobial therapy of UTI prescribed by Croatian family practitioners is in accordance with the national guidelines.