Activity of fosfomycin against nosocomial multiresistant bacterial pathogens from Croatia: a multicentric study.

AIM: To determine in vitro susceptibility of multiresistant bacterial isolates to fosfomycin. METHODS: In this prospective in vitro study (local non-random sample, level of evidence 3), 288 consecutively collected multiresistant bacterial isolates from seven medical centers in Croatia were tested from February 2014 until October 2016 for susceptibility to fosfomycin and other antibiotics according to Clinical and Laboratory Standards Institute methodology. Susceptibility to fosfomycin was determined by agar dilution method, while disc diffusion was performed for in vitro testing of other antibiotics. Polymerase chain reaction and sequencing were performed for the majority of extended spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) and carbapenem-resistant isolates. RESULTS: The majority of 288 multiresistant bacterial isolates (82.6%) were susceptible to fosfomycin. The 236 multiresistant Gram-negative isolates showed excellent susceptibility to fosfomycin. Susceptibility rates were as follows: Escherichia coli ESBL 97%, K. pneumoniae ESBL 80%, Enterobacter species 85.7%, Citrobacter freundii 100%, Proteus mirabilis 93%, and Pseudomonas aeruginosa 60%. Of the 52 multiresistant Gram-positive isolates, methicillin-resistant Staphylococcus aureus showed excellent susceptibility to fosfomycin (94.4%) and vancomycin-resistant enterococcus showed low susceptibility to fosfomycin (31%). Polymerase chain reaction analysis of 36/50 ESBL-producing K. pneumoniae isolates showed that majority of isolates had CTX-M-15 beta lactamase (27/36) preceded by ISEcp insertion sequence. All carbapenem-resistant Enterobacter and Citrobacter isolates had blaVIM-1 metallo-beta-lactamase gene. CONCLUSION: With the best in vitro activity among the tested antibiotics, fosfomycin could be an effective treatment option for infections caused by multiresistant Gram-negative and Gram-positive bacterial strains in the hospital setting.

Signal hyperintensities on brain magnetic resonance imaging in patients with primary Sjögren syndrome and frequent episodic tension-type headache: relation to platelet serotonin level and disease activity.

OBJECTIVE: To examine differences in number and size of signal hyperintensities (SH) on magnetic resonance imaging (MRI) between patients with primary Sjögren syndrome (pSS) and controls who all had frequent episodic tension-type headache (FETH), and to investigate their relation to platelet serotonin level (PSL), patient age, disease duration, and activity. METHODS: SH in 22 pSS patients with FETH were compared to 20 aged-matched controls with FETH, using the modified semiquantitative rating scale. Spectrofluorimetry was used for determination of PSL, and the European League Against Rheumatism SS Disease Activity Index (ESSDAI) for disease activity assessment. RESULTS: Statistically significant differences in the total number of SH were noted infratentorially (p = 0.025) and in the basal ganglia for lesions of diameter > 5 mm (p = 0.048). Significant correlations were found between disease duration and number of overall lesions > 5 mm (p = 0.04) and subcortical lesions of diameter 2-5 mm (p = 0.035). Number of periventricular SH inversely correlated to PSL (p = 0.019) and to patient age (p = 0.004), without association with markers of immunoinflammation and ESSDAI. CONCLUSION: Our study showed that SH on brain MRI are more common in specific regions of the brain in pSS patients with FETH than in controls with FETH, signifying a more widespread cerebral vasculopathy in SS patients with FETH. Periventricular SH seem to be associated to increased platelet serotonin release in pSS patients with FETH and correlated with disease duration, without correlation to the actual ESSDAI and markers of immunoinflammation, and might be linked with chronic immunoinflammation of low-grade intensity and vasculitis in pSS.

Actual drug-drug interactions in elderly patients discharged from internal medicine clinic: a prospective observational study.

PURPOSE: The aim of the study was to evaluate the incidence and type of actual drug-drug interactions (DDIs) that result in adverse drug reactions (ADRs) or diminished therapeutic effect in elderly patients within 30 days of discharge from an internal medicine clinic. METHODS: A prospective observational study was conducted at the Internal Medicine Clinic of University Hospital Dubrava, Zagreb, Croatia, between October and December 2011. Patients aged ≥ 65 years discharged from the Internal Medicine Clinic during the study period with a prescription for two or more medications were eligible for inclusion in the study. A total of 222 patients were ultimately enrolled in the study. For each patient, potential DDIs were identified using Lexi-Interact software. The follow-up visit was scheduled approximately 30 days after discharge. Causality between DDIs and ADRs or diminished therapeutic effect of drugs was assessed by two independent clinicians. RESULTS: Potential DDIs were identified in 190 (85.6 %) patients. Actual DDIs were detected in 21 (9.5 %) patients. In 19 patients, DDIs resulted in an ADR. Diminished therapeutic effect resulting from DDIs was detected in two patients. Angiotensin-converting enzyme inhibitors were the drug class most frequently associated with DDI-related ADRs. CONCLUSIONS: A significant incidence of actual DDIs suggests that DDIs play an important role in patient safety. Drug therapy should be initiated if absolutely necessary, and the number of drugs used to treat elderly patients should be minimized to reduce the incidence of DDI-related adverse patient outcomes.

The effect of pharmacotherapeutic counseling on readmissions and emergency department visits.

OBJECTIVE: To evaluate the impact of pharmacotherapeutic counseling on the rates and causes of 30-day post-discharge hospital readmissions and emergency department visits. SETTING: The study was conducted at the Medical Clinic of University Hospital Dubrava, Zagreb, Croatia. METHODS: The study included elderly patients prescribed with two or more medications for the treatment of chronic diseases. The patients randomized into the intervention group received pre-discharge counseling by the clinical pharmacologist about each prescribed medication. The control group received no counseling. MAIN OUTCOME MEASURES: The rates and causes of 30-day postdischarge hospital readmissions and emergency department visits. Medication compliance was also evaluated, using the pill count method. RESULTS: A total of 160 patients were randomly selected for the study. No significant difference was found in the readmission and emergency department visit rates between the intervention and control groups (p = 0.224). There were 34.9 % more compliant patients in the intervention group. Significantly more non-compliant patients in the control group were readmitted or visited emergency department because of the disease progression (p = 0.031). In the intervention group, significantly more patients were readmitted or visited emergency department because of an adverse drug reaction (p = 0.022). CONCLUSION: Pharmacotherapeutic counseling can reduce readmission and emergency department visit rates for disease progression. Improved patient knowledge about adverse drug reactions could be the reason for increased rates of readmissions and emergency department visits due to adverse drug reactions in the intervention group.

Platelet serotonin in primary Sjögren's syndrome: level and relation with disease activity.

Primary Sjögren's syndrome (pSS) is chronic autoimmune disorder of unknown ethiopathogenesis. In line with the concept of neuroimmunohormonal dysregulation in inflammatory rheumatic diseases, the aim of this study was to investigate platelet serotonin level (PSL) in patients with pSS and its relation with the activity and duration of the disease. Significantly lower PSL in pSS patients (N=61) was shown as compared to healthy controls (N=103). No correlation was found between PSL and the actual disease activity assessed by the recently developed EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Results suggest involvement of the serotonin system in the pathogenesis of pSS.

Pain relief in medical patients: does clinical judgment and prescribing knowledge suffice?

The aim of this study was to evaluate the quality of pain management in hospitalised patients. A cross-sectional study design that included all medical patients experiencing pain was used. Out of 167 patients hospitalized at the Department of Medicine at the University Hospital Zagreb, 41 patients were experiencing pain and 40 out of them received analgesics. Twenty-two out of 38 patients were treated for malignant pain, 16 for non-malignant pain, and 2 patients could not be classified. Adequate pain relief was reported in less than 25% of patients in both groups. Our study revealed under-prescribing of combination therapy, low utilization rates of strong opioids and prevailing "as needed" prescribing practice. In conclusion, unsatisfactory pain management in medical patients is often present if left solely to the clinical judgement and knowledge of the prescribing physician. Regular pain assessment, evidence-based guidelines, education and regular audits of implementation of these measures are a prerequisite for effective pain treatment, and should all be employed in patients experiencing pain.

Could a neurological disease be a part of Mozart's pathography?

As expected, since we recently celebrated the 250th anniversary of birth of Wolfgang Amadeus Mozart, there has been again a renewal of interest in his short but intensive life, as well as in the true reason of his untimely dead. Mozart lived and died in time when the medical knowledge was based mostly on subjective observations, without the established basics of standardized medical terminology and methodology. This leaves a great space for hypothesizing about his health problems, as well as about the cause of his death. The medical academic community attributed to Mozart approximately 150 different medical diagnoses. There is much speculation on the possible causes of Mozart's death: uremia, infection, rheumatic fever, trichinellosis, etc. Recently some authors have raised the question about a possible concomitant neurological disease. According to available records, Mozart has shown some elements of cyclotimic disorder, epilepsy and Gilles de la Tourette syndrome. Furthermore, the finding of a temporal fracture on (allegedly) Mozart's skull, gives a way to speculations about the possibility of a chronic subdural hematoma and its compressive effect on the temporal lobe. Despite numerous theories on Mozart's pathography that also include a concomitant neurological disorder, the medical and history records about Mozart's health status indicate that he probably had suffered from an infective illness, followed most likely by the reactivation of rheumatic fever, which was followed by strong immunologic reaction in the last days of his life. Taking all the above into consideration, it is reasonably to conclude that Mozart's neurological disturbances were caused by the intensity of the infective disease, and not primarily by a neurological disease.

Distributed lags time series analysis versus linear correlation analysis (Pearson's r) in identifying the relationship between antipseudomonal antibiotic consumption and the susceptibility of Pseudomonas aeruginosa isolates in a single Intensive Care Unit of a tertiary hospital.

The relationship between antibiotic consumption and selection of resistant strains has been studied mainly by employing conventional statistical methods. A time delay in effect must be anticipated and this has rarely been taken into account in previous studies. Therefore, distributed lags time series analysis and simple linear correlation were compared in their ability to evaluate this relationship. Data on monthly antibiotic consumption for ciprofloxacin, piperacillin/tazobactam, carbapenems and cefepime as well as Pseudomonas aeruginosa susceptibility were retrospectively collected for the period April 2006 to July 2007. Using distributed lags analysis, a significant temporal relationship was identified between ciprofloxacin, meropenem and cefepime consumption and the resistance rates of P. aeruginosa isolates to these antibiotics. This effect was lagged for ciprofloxacin and cefepime [1 month (R=0.827, P=0.039) and 2 months (R=0.962, P=0.001), respectively] and was simultaneous for meropenem (lag 0, R=0.876, P=0.002). Furthermore, a significant concomitant effect of meropenem consumption on the appearance of multidrug-resistant P. aeruginosa strains (resistant to three or more representatives of classes of antibiotics) was identified (lag 0, R=0.992, P<0.001). This effect was not delayed and it was therefore identified both by distributed lags analysis and the Pearson's correlation coefficient. Correlation coefficient analysis was not able to identify relationships between antibiotic consumption and bacterial resistance when the effect was delayed. These results indicate that the use of diverse statistical methods can yield significantly different results, thus leading to the introduction of possibly inappropriate infection control measures.

The incidence of potential drug-drug interactions in elderly patients with arterial hypertension.

OBJECTIVE: To assess the incidence and type of potential, clinically significant drug-drug interactions in elderly outpatients with arterial hypertension. SETTING: Three community pharmacies in Croatia. METHOD: Eligible patients were aged 65 or older, treated for arterial hypertension and received 2 or more drugs. Potential interactions were identified by Lexi-Interact software. The software categorized each potential interaction according to clinical significance in five groups: (A) No known interaction; (B) Specified agents may interact, but there is little to no evidence of clinical concern; (C) Specified agents may interact in a clinically significant manner. Monitoring therapy is suggested; (D) The two medications may interact in a clinically significant manner. Modification of therapy is suggested; (X) Contraindicated combination. Interactions of level C, D and X were considered clinically significant. MAIN OUTCOME MEASURE: The incidence and type of potential drug-drug interactions. RESULTS: There were 265 patients included in the study. Potential, clinically significant drug interactions were identified in 240 (90.6%) patients, out of which 97.9% had interactions with clinical significance C, 20.4% D, and 0.8% X. The median number of drug interactions per patient was 4. We identified 215 drug combinations with the potential to cause clinically significant interaction, out of which 83.3% had clinical significance C, 16.3% clinical significance D, and 0.4% clinical significance X. CONCLUSION: Drug-drug interactions are common in elderly hypertensive patients. Computer-based screening could help pharmacists and physicians to recognize potential, clinically significant interactions.

Clinical pharmacology consultation: a better answer to safety issues of drug therapy during pregnancy?

PURPOSE: drug safety classifications give a very basic estimation of risk and should only be used as general guideline when assessing risk of pregnancy-related drug exposure or planning treatment. We conducted a study to assess the strength of association between both the clinical pharmacologists' risk assessment and the FDA risk categorization, and adverse pregnancy outcomes. METHODS: we retrospectively reviewed records of 1,076 patients consecutively referred to the clinical pharmacology outpatient clinic for pregnancy-related drug exposure (2000-2008). Clinical pharmacologists' risk assessments were reviewed in relation to FDA drug categorization and available pregnancy outcomes. RESULTS: overall, clinical pharmacologists' risk estimation was in agreement with the FDA risk categorization system in only 28% of consulted women, and in only 9% of women with high-risk exposure (FDA DX). Clinical pharmacologists' risk assessment confirming high-risk drug exposure had a better positive predictive value for adverse pregnancy outcomes than the FDA DX categorization (25% vs 14% respectively), while the negative predictive values were similar (92% vs 94% respectively). Clinical pharmacologists' risk assessment was a better predictor of adverse pregnancy outcomes compared with FDA risk categorization (OR 2.11 [95%CI 1.5-3.1; p < 0.001] vs OR 1.52 [95%CI 1.1-2.1; p = 0.014] respectively). CONCLUSIONS: additional evaluation beyond the FDA drug classification is essential for safer and more rational drug use in pregnancy. Clinical pharmacologists who have undergone rigorous medical training are ideally placed to consult on administration of medicines in pregnant women, thus making the prescribing of treatments in that patient category substantially safer and more rational.

Is referring patients with a positive history of allergic drug reactions or atopy for allergy testing to local anesthetics justified?

Although no more than 1% of adverse reactions to local anesthetics (LA) are thought to be immunologically mediated, many patients continue to be referred to allergy clinics for allergy workup. We evaluated the impact of a history of drug hypersensitivity or atopy on results of allergy testing to LA, with the aim of determining the appropriateness of allergy testing to LA in such patients. We retrospectively analyzed medical records of 112 consecutive patients referred for allergy testing to LA in a 9-year period (1996-2005). Intradermal tests with diluted (1:10) LA were performed to identify patients at risk for immunoglobulin E (IgE)-mediated hypersensitivity reaction. The odds for being testpositive were calculated with regard to the defined risk factors (atopy, history of adverse reactions to LA or other drugs, underlying autoimmune disease). Eleven of 112 patients (9.8%) tested positive for allergy to LA. Atopy, history of adverse reactions to LA or other drugs and underlying autoimmune disease did not increase the odds for being test-positive. The prevalence of multiple drug hypersensitivity, IgE values and eosinophil count were not significantly higher among the patients who tested positive as compared to the patients who tested negative. According to our data, allergy testing to LA is not justified in patients with atopy or histories of adverse drug reactions other than to LA. Further studies using validated methods of allergy testing to LA coupled with analysis of defined risk factors are needed to definitively establish the indications for referral of patients for allergy testing to LA.

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

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

Two-year rehospitalization rates of patients with newly diagnosed or chronic schizophrenia on atypical or typical antipsychotic drugs: retrospective cohort study.

AIM: To determine if atypical antipsychotic agents reduce the rehospitalization rates of patients with newly diagnosed or chronic schizophrenia in comparison with typical antipsychotic drugs. METHODS: From January 1, 2003, to December 31, 2004, we retrospectively compared two-year rehospitalization rates of 135 patients with newly diagnosed schizophrenia and 398 patients with chronic schizophrenia (62% and 65% men, respectively), who were initially discharged from Vrapce Psychiatric Hospital, Zagreb, with the prescription of atypical (olanzapine, risperidone or clozapine) or typical (haloperidol or fluphenazine) antipsychotic treatment between January 1, 2002 and December 31, 2002. Time-to-readmission was determined with Kaplan-Meier formula for survival analysis. RESULTS: In the two-year follow-up, 52 (39%) newly diagnosed patients and 197 (47%) patients with chronic schizophrenia were rehospitalized. No significant differences in time-to-rehospitalization were observed with respect to the type of medications in patients with newly diagnosed schizophrenia (P=0.378) or patients with chronic schizophrenia (P=0.531). CONCLUSIONS: Rehospitalization rates of patients who were prescribed atypical antipsychotic drugs were similar to those of patients who were prescribed typical antipsychotic drugs for both the group with the first psychotic episode and group with chronic schizophrenia.

Application of a novel bone osteotomy plate leads to reduction in heat-induced bone tissue necrosis in sheep.

Previous studies have shown substantial effect thermal damage can have on new bone formation following osteotomy. In this study we evaluated the extent of thermal damage which occurs in four different methods of osteotomy and the effects it can have on bone healing. We further wanted to test whether a special osteotomy plate we constructed can lead to diminished heat generation during osteotomy and enhanced bone healing. The four methods evaluated included osteotomy performed by chisel, a newly constructed osteotomy plate, Gigly and oscillating saw. Twelve adult sheep underwent osteotomy performed on both tibiae. Bone fragments were stabilized using a fixation plate. Callus size was assessed using standard radiographs. Densitometry and histological evaluation were performed at 8 weeks following osteotomy. Temperature measurements were performed both in vivo during the operation, and ex vivo on explanted tibiae. The defects healed without complications and showed typical course of secondary fracture healing with callus ingrowth into the osteotomy gap. Radiographic examination of bone healing showed a tendency towards more callus formation in bones osteotomized using Gigly and oscillating saw, but this difference lacked significance. Use of Gigly and oscillating saw elicited much higher temperatures at the bone cortex surface, which subsequently lead to slightly impaired bone healing according to histological analysis. BMD was equal among all bones. In conclusion, the time required for complete healing of the defect differed depended greatly on the instruments used. The newly constructed osteotomy plate showed best results based on histological findings of capillary and osteoblast density.

Antibiotic use optimization program in the largest Croatian university hospital--benefits of restrictions on unlimited antibiotic use.

The aim of this study was to obtain the relevant information on antibiotic use in a 750-bed Croatian university hospital. The study has been designed as a 2-point prevalence interventional analysis. For each patient on antibiotic therapy, diagnosis, indication for treatment, antibiotic therapy, dosage and route of administration together with the results of microbiological studies (if available) were obtained. After the first prevalence analysis in 2001, a restriction on unlimited antibiotic use was introduced. The second analysis, performed in 2002, after restrictions on antibiotic use, revealed reductions in the rates of restricted release antibiotics and overall antibiotic use with decreases from 38.6% to 36.9% and 23.4% to 23.2% respectively (p = 0.87). The first survey showed that the 5 most often prescribed antibiotics in the therapy of bacterial infections were: gentamicin, other aminoglycosides, carbapenems, amoxycillin +clavulanate and vancomycin with proportions of 14.8%, 10.3%, 8.2%, 7% and 7% respectively. In the year 2002, the most prescribed antimicrobial drugs in the therapy of bacterial infections were: gentamicin, quinolones, vancomycin, carbapenems and cefuroxime with proportions of 18.6%, 11.4%, 9.7%, 9.3% and 8% respectively. A reduction in the proportions of doubtful antibiotic therapy, from 24.6% before the intervention, to 24.2% after the restrictions, accompanied by a 0.4% rise in the rates of indicated antibiotic therapy was also observed (p = 0.93). Our study shows that restrictions on formerly unlimited use of antimicrobials, even when leading to an improvement in their prescribing, do not necessarily cause rapid and significant reduction in the overall use of antibiotics or explicit positive financial effects.

Use of gastroprotective agents in recommended doses in hospitalized patients receiving NSAIDs: a drug utilization study.

OBJECTIVE: In recent years, studies investigated to what extend recommendations for co-prescribing gastroprotective agents in prevention of NSAID-induced gastrointestinal complications are followed in clinical practice. However, only a few studies have also taken into consideration the recommended dose of gastroprotectives prescribed in NSAID-induced ulcer prophylaxis. The aim of our study was to evaluate the prevalence of concomitant use of gastroprotectives with NSAIDs in hospitalized patients, with emphasis on the recommended dose of gastroprotectives for ulcer prophylaxis. METHOD: This observational, cross-sectional, drug utilization study included all adult patients receiving NSAIDs hospitalized in the Clinical Hospital Center Zagreb on the day of the study. Data on age, sex, comorbidities, indications for NSAID use, type/dose of NSAIDs and gastroprotectives, history of gastrointestinal events, active gastrointestinal symptoms and risk factors were evaluated. MAIN OUTCOME MEASURE: Study outcomes were: (1) prevalence of prescription of gastroprotectives among NSAID-users at risk; (2) prevalence of prescription of gastroprotective in recommended dose; (3) association between risk factors and prescription of GPAs. RESULTS: The rates of gastroprotectives prescription were significantly higher in NSAID-users with concomitant risk factors as compared to patients without risk factors [47/70 (67.1%) and 8/22 (36.4%), respectively; p=0.01072]. However, gastroprotection in recommended ulcer-preventive dose was low in both groups [8/70 (11.4%) and 9/92 (9.8%), respectively]. The number of concomitant risk factors did not increase the odds of receiving anti-ulcer therapy (odds ratio 0.7279). Thirty-three percent of patients with concomitant risk factors were not prescribed gastroprotectives. Ibuprofen, NSAID with the lowest risk of inducing gastrointestinal complications, was prescribed in only two patients. CONCLUSION: The results indicate high awareness among hospital physicians about possible NSAID-induced gastrointestinal complications, but insufficient knowledge about risk factors related to NSAID-induced gastrointestinal toxicity, recommended dose of gastroprotectives in NSAID-induced ulcer prophylaxis and gastrointestinal toxicity of different types of NSAIDs.

[Evaluation of justification for antibiotic use at the Internal Medicine Clinic of the Clinical Hospital in Zagreb]. / Procjena opravdanosti potrosnje antibiotika u Klinici za unutrasnje bolesti Klinickog bolnickog centra Zagreb.

OBJECTIVE: Resistance to antimicrobials as the result of unnecessary and inadequate use of antibiotics has become a global health problem. It is estimated that up to 50% of antimicrobials are used unnecessarily, and that they are the cause of approximately 25% of adverse drug reactions. Efforts are made to ensure a controlled use of antibiotics, which is the key strategy against development of resistance to antimicrobials. Since antimicrobial drugs are among the most commonly prescribed drugs in hospitals, a rational use of antibiotics would also help reduce health care costs. There are limited data on the use of antibiotics in Croatian hospitals. METHODS: This observational study was conducted at the University Department of Medicine, Zagreb University Hospital Center, with the aim to investigate the prevalence of antimicrobial use, indications for antibiotic use, and the necessity and adequacy of antibiotic therapy. The investigated parameters were: prescribed antibiotic (dose, route of administration, duration of therapy), indication for use of antibiotics (prophylaxis, treatment), diagnosis, presence of positive culture, indication documented in medical records, evaluation of antibiotic therapy by a specialist, and risk factors. The most important parameter in the evaluation of the necessity of antimicrobial use was the presence of culture days of treatment, and indication for treatment documented in medical records and evaluated by a specialist. The data were collected over 1 day using a standardized questionnaire. RESULTS: Fifty of 138 (37%) hospitalized patients were receiving 1 or more antibiotics, most of them (80%) for the treatment of infection. The most frequent diagnoses were sepsis (64%), urinary tract infection (25%), abdominal infection (21%), and pulmonary infection (7%). The median therapy duration was 4 days (minimum 1 day, maximum 121 days). The most frequently prescribed antibiotics were fluoroquinolones (23%), penicillins (23%), aminoglycosides (18%) and cephalosporins (11%). Thirty-nine patients received one or more reserve antibiotics. The median number of received antibiotics was 2 (minimum 1, maximum 5 antibiotics). Risk factors were present in 76% of patients. Fifty-nine percent patients were receiving antibiotics on the basis of culture; in most of them therapy was evaluated by a specialist (98%) and the indication was documented in medical records. Reserve antibiotics were prescribed in 34 patients, in 77% of them on the basis of positive culture. CONCLUSION: The high prescription rate of antibiotics (fluoroquinolones), concomitant use of antibiotics of a similar spectrum of activity and lack of sequential therapy emerged to be the parameters needing further evaluation. Other investigated parameters (number of antibiotics, duration of therapy, necessity of antibiotic therapy) were in accordance with similar studies conducted in hospitals. Further investigation with emphasis on local problems and prescription habits with the aim to optimize the use of antibiotics is needed.

[Privatization of the Croatian health care system: effect on indicators of health care accessibility in general medicine]. / Privatizacija u hrvatskom zdravstvenom sustavu: ucinak na neke pokazatelje dostupnosti usluge u ordinacijama opce medicine.

The aim of the privatization of the primary health care is to reduce cost and improve the quality of service by introducing the market-based system. In the Republic of Croatia, the privatization of the primary health care started in 1995. It was based on renting the existing facilities at a moderate price to the practitioner. After that, the practitioner registers the private practice and signs a contract with the obligatory health insurance institution. The aim of this article is to present a part of the project of long-term research of privatization related to the health care accessibility in general practices. The research sample consisted of three groups: privatized general practices, to-be-privatized general practices and non-privatized general practices during 1997 and 1999. Privatized general practices have exhibited a significant improvement in the number of registered patients, the scheduling of first visit appointments during working hours, the possibilities of scheduling follow-up visit appointments during working hours, scheduling visits by telephone, obtaining telephone advice after working hours and visiting the practitioner after working hours. This kind of research is vital in order to bring about the necessary changes in the existing system by scientifically approved methods.