Characteristics of Puumala and Dobrava infections in Croatia.

In this study, two different hantaviruses, Puumala virus (PUUV) and Dobrava virus (DOBV), were demonstrated for the first time to coexist and cause hemorrhagic fever with renal syndrome (HFRS) in Croatia. Phylogenetic analysis showed some differences among the nucleotide sequences of PUUV originating from Dinara mountain, which was more closely related to Austrian PUUV than other Croatian PUUV from Mala Kapela mountain. More consistency was found among the Croatian DOBV. HFRS was verified in 85 of 201 suspected cases recorded in 1995 during the largest HFRS outbreak in Croatia. Most of these cases were soldiers. With the exception of the coastal region and islands, all of Croatia was found to be an area endemic for HFRS. A statistically significantly higher proportion of DOBV-infected patients had acute renal failure, visual disturbance, severe thrombocytopenia, and elevated levels of nonsegmented leukocytes, creatine, and total bilirubin. The prevalence of gastrointestinal and electrocardiography disorders also was greater in DOBV-infected patients. Interestingly, significantly more PUUV-infected patients had elevated systolic blood pressure on admission to the hospital. Further prospective studies are necessary to shed more light on differences in HFRS severity associated with PUU and DOB viruses.

Role of peripheral blood mononuclear cell (PBMC) phenotype changes in the pathogenesis of haemorrhagic fever with renal syndrome (HFRS).

Hantaviruses cause an important human illness, HFRS. Blood samples from 22 HFRS-positive, six seronegative patients and 15 healthy controls were examined in 1995, during the largest HFRS epidemic in Croatia. Results of double- and triple-colour immunofluorescence analysis showed an increased percentage of cytotoxic T cells (CD3+CD8+) in seropositive patients compared with seronegatives and healthy controls. The majority of seropositive HFRS patients expressed activation and memory antigens on T and B lymphocytes. The percentage of CD23+ and CD21+ B lymphocytes was lower in seropositive patients. HFRS patients had elevated levels of sCD23 and five had elevated total IgE. The increased expression of both early and late T cell activation antigens, e.g. CD25, CD71 and HLA-DR, memory cells and sCD23 positively correlated with biochemical parameters (AST, ALT, urea, alpha2-globulin) during the acute phase of HFRS. The phenotypic changes observed, especially early and late T cell activation markers, as well as memory cells, could be useful parameters in the evaluation of HFRS course, and prognostic factors of HFRS severity. Additional attention should be paid to liver involvement in the pathogenesis of HFRS.

Nosocomial infections in critically ill infectious disease patients: results of a 7-year focal surveillance.

An incidence study on nosocomial infections in critically ill infectious disease patients was carried out in the intensive care unit (ICU) of a university hospital for infectious diseases over a 7-year period (1 January 1990 to 31 December 1996). A total of 660 patients who stayed in the ICU for over 48 h were prospectively observed. The patients were divided into two groups: one with central nervous system infections (442 patients) and the other with other severe infections (218 patients). The risk of nosocomial sepsis and pneumonia was significantly higher in patients suffering from severe central nervous system infections. The incidence of sepsis was 24.2% vs 11.4% (relative risk 1.95; 95% confidence interval 1.32-2.89); the incidence of pneumonia was 30.5% vs 14.7% (relative risk 2.09; 95% confidence interval 1.47-2.96). The incidence of urinary tract infection was 14.3% vs 13.3% (relative risk 1.07; 95% confidence interval 0.71-1.61). Density rates of nosocomial septic episodes were 21.1 +/- 37.1 vs 11.7 +/- 32.4 episodes/100 central venous-line days (P < 0.006). Nosocomial pneumonia occurred only in mechanically ventilated patients (36.9 +/- 61.2 vs 28.5 +/- 65.8 episodes per 1000 ventilatory days, P = 0.012). Nosocomial urinary tract infection occurred only in patients with urinary catheters (11.6 +/- 60.7 episodes/1000 urinary catheter days vs 18.7 +/- 90.1, P = 0.886). Multivariate regression analysis identified age, diagnosis of CNS infection, duration of urinary tract catheterization, the use of central venous lines and mechanical ventilation as independent risk factors of nosocomial sepsis. Duration of mechanical ventilation, use of steroids and diagnosis of CNS infection were independent risk factors of nosocomial pneumonia. A subanalysis identified tetanus patients to be at particular risk of nosocomial infections.

Antibiotic resistance among gram-negative nosocomial pathogens in the intensive care unit: results of 6-year body-site monitoring.

Results of 6-year body-site monitoring in an intensive care unit (ICU) are presented and antimicrobial resistance of gram-negative isolates analyzed. The study included 622 patients. Six hundred thirty-five bacterial isolates-causes of nosocomial sepsis, pneumonia, and urinary tract infections (UTIs)-were tested during the study. Gram-negative bacteria were the predominant isolates, causing 65% of cases of sepsis, 78.7% of pneumonias, and 70.2% of UTIs. Gram-negative isolates (454) were highly resistant to antimicrobials commonly used in the ICU, with the exception of imipenem. Resistance was 1.1% among pathogens responsible for UTIs, 6.7% among those causing sepsis, and 13.6% among those responsible for pneumonia. Klebsiella pneumoniae associated with pneumonia and sepsis was significantly less resistant to ciprofloxacin than were isolates from urine (22.8% and 13.9%, respectively, vs 44.4%). Pseudomonas aeruginosa strains responsible for pneumonia were less resistant to ceftazidime than were isolates causing sepsis and UTI (35.7% vs 51.3% and 51.5%, respectively). Acinetobacter calcoaceticus strains associated with UTI were significantly more resistant to netilmicin than were strains responsible for sepsis and pneumonia (83.3% vs 40.3% and 42.6%, respectively). The study confirmed that in addition to focused microbiologic surveillance, multiple-body-site monitoring can provide unique information about the sensitivity of the pathogens involved. The results suggest that antimicrobial resistance among nosocomial pathogens depends on the site of infection or the type of microbiologic specimen.

[An epidemic of hemorrhagic fever with renal syndrome in Croatia in 1995]. / Epidemija hemoragijske vrucice s bubreznim sindromom u Hrvatskoj 1995. godine.

In the spring of 1995, the largest outbreak of hemorrhagic fever with renal syndrome (HFRS) so far was recorded in Croatia. There were 125 patients reported to the National Croatian Institute of Public Health, Department of Epidemiology. The disease occurred simultaneously in several localities, some of them close to the previously known natural foci (Mala Kapela, western Slavonia); the focus on Dinara was newly discovered. War circumstances in Croatia were closely related to this outbreak. There were 50 patients hospitalized in the University Hospital of Infectious Diseases in Zagreb; 5 of them were civilians from Zagreb area and 45 soldiers (Mala Kapela 33, Dinara 7, western Slavonia 5). In all patients the disease was serologically proven (in 6 by indirect immunofluorescence method and in 44 by ELISA-test). Both previously known types of viruses--Hantaan and Puumala were diagnosed in each locality. In general, the illness was more severe in patients with Hantaan virus infection. Two patients died, the illness was severe in 25, moderately severe in 11 and mild in 12 patients. For the first time inflammatory lung changes were recorded in 13 out of 37 (35.1%) patients who were examined by X-ray in the early stage of the disease.

Pneumococcal meningitis in the elderly.

The authors reviewed 70 cases of Streptococcus pneumoniae meningitis occurring over a 5-years period (1985-1989). Clinical features, outcome and laboratory findings in elderly patients (> 60 years of age, 21 patients) were compared with those in younger patients (< 59 years of age, 49 patients). Mortality rate was 57% in elderly group vs. 20% in younger. Admission to the hospital was delayed in the elderly. Only 67.6% of them were admitted on the first two days of the illness vs. 81.6% of younger patients. Nearly 62% of them were deeply soporous or comatose on admission (Mathew-Lawson grade 3 and 4), while in the control group only 31% of patients had such severely altered mental status. Although glucose cerebrospinal fluid (CSF)/blood ratio tended to be lower in the elderly (0.09 vs 0.17) the difference did not reach statistical significance. Thrombocytes in the peripheral blood were lower in the elderly (113 x 10(9)/L vs. 148 x 10(9)/L, p < 0.05). When we compared laboratory findings in survivors and nonsurvivors from both groups, nonsurvivors had significantly lower glucose CSF/blood ratio (0.054 vs. 0.174, p = 0.008), and higher bilirubin levels in serum (27.9 vs 14.7, p = 0.003), but differences were more obvious in younger group of patients. Our results suggest that there is increased risk of death among elderly patients. It can be at least partially attributed to their later admittance to the hospital and because of that delayed start of the appropriate therapy and more severe conscious disturbances. All these factors contribute to the greater case-fatality ratio observed in elderly patients with pneumococcal meningitis.

[Hospital infections and resistance to new antibiotics in intensive care units: relation to diagnostic and therapeutic procedures]. / Bolnicke infekcije i rezistencija na neke novije antibiotike u jedinici intenzivne skrbi: ovisnost o dijagnosticko-terapijskim zahvatima.

The results of hospital infection surveillance over an eight-month period in the Intensive Care Unit (ICU) of the University Hospital of Infectious Diseases "Dr Fran Mihaljevic", Zagreb, are presented together with the results of the antibiotic resistance of isolated gram-negative bacteria in relation to the clinical material taken for culture. Of 110 strains of gram-negative bacteria isolated, 103 (93.6%) were resistant to ampicillin, 80 (72%) to gentamicin, 74 (67%) to cefotaxime, 50 (45.5%) to pefloxacin. Imipenem, ciprofloxacin, ceftazidime and amikacin were the most active representatives of their respective groups with 5, 25, 49 and 50% of resistant strains. Strains isolated in urinary tract infections were significantly less resistant to amikacin and ceftazidime (p < 0.05) than strains isolated from other sources. Our findings stress the need for close surveillance of antibiotic resistance in these selected groups of patients, and are particularly relevant for planning empirical anmtibiotic therapy of hospital infection in the ICU.

The clinical picture of rabies in a child.

An eight-year-old boy developed rabies 31 days after having been scratched by a dog and died 9 day later. Intensive supportive medical treatment was complicated by apnea, cardiac arrest, hypotension, increased secretion of antidiuretic hormone and severe hypoproteinemia. The treatment with intramuscular human antirabies immunoglobulin (HRIG) 2400 I.U. and intrathecal 1200 I.U. in combination with intramuscular interferon alpha 4 million I.U. was given every second day. The diagnosis of rabies was confirmed before death, on the third day of the disease, by direct fluorescent antibody staining of the saliva and cerebrospinal fluid for viral antigen. At the autopsy, the brain tissue specimens were tested for the presence of the virus by inoculation into the suckling mice brain and for the viral antigen by direct fluorescent antibody method. The brain tissue specimens collected at autopsy were also tested for virus by direct fluorescent antibody method.

Entry of ciprofloxacin into cerebrospinal fluid during bacterial, viral and tuberculous meningitis.

We studied the entry of ciprofloxacin into the cerebrospinal fluid (CSF) in 37 patients with various types of meningitis (bacterial meningitis 10 patients, viral 12 patients, tuberculous 7 patients). Eight patients were in the control group with normal CSF finding. Mean ciprofloxacin concentrations in the CSF 50-60 minutes after 200 mg of ciprofloxacin was given in infusion were 0.20 +/- 0.12 mg/L in patients with bacterial meningitis, which was significantly higher than in other tested groups (p = 0.0325). Ciprofloxacin achieved concentrations in the CSF 6.5-39% of serum (mean value 15% +/- 9%) in the bacterial meningitis group, while in the groups with viral and tuberculous meningitis the levels were significantly lower (approximately 9% of serum) but still higher than in the control group (approximately 5% of serum). Our data suggest that ciprofloxacin should be very cautiously used in selected patients with bacterial meningitis caused by multiple resistant strains of gram negative bacteria.

Ciprofloxacin in the treatment of gram-negative bacillary meningitis.

Gram-negative bacillary meningitis (typically caused by E. coli, K. pneumoniae, P. aeruginosa, A. calcoaceticus, and others) has been associated with head trauma, neurosurgical operations, pathologic anastomosis with nasal cavity, and CSF rhinorrhea, as well as with impaired host defenses. Intravenous ciprofloxacin was given to 20 patients with gram-negative bacillary meningitis. The dose of ciprofloxacin was 200 mg by intravenous infusion, over 30 minutes, every 12 hours for 10 days. Two patients also received intravenous cefotaxime and penicillin G. All patients were monitored daily. Of 20 patients, 18 had cure and therapy failed in two. Because relatively low concentrations of ciprofloxacin are achieved in the CSF, the drug should be used in the treatment of gram-negative bacillary meningitis only if the MICs of the causative pathogen and the ciprofloxacin concentration in CSF can be followed. A randomized, controlled study is needed to compare the efficacy of intravenous ciprofloxacin with standard antibiotic therapy in the treatment of this disease.

Plasma cholinesterase activity in patients during therapy with dexamethasone or prednisone.

We have studied the effects of i.v. dexamethasone and oral prednisone on plasma cholinesterase (ChE) activity in 13 male and 10 female patients during long-term treatment with dexamethasone or prednisone. A decrease in ChE activity--probably due to inhibition of ChE synthesis in the liver--was seen in all the patients. In individual patients there was a drop in enzyme activity of 14-57% (dexamethasone) and 23-69% (prednisone) respectively, compared with individual control values. After withdrawal of dexamethasone, ChE activity in most cases increased to above control values and the period necessary for complete restoration of ChE activity was variable (between 25-70 days). Our results suggest that the decrease in ChE activity in patients treated with dexamethasone or prednisone depends on the initial dose of the drug as well as on the duration of treatment.

[Subacute encephalitis caused by herpes simplex virus]. / Subakutni tok encefalitisa uzrokovanog virusom herpes simpleks.

The authors present a case of herpes-simplex encephalitis in a 58-year-old woman. The disease had a biphasic course and lasted 87 days. The clinical picture, laboratory data and the pathologic-anatomical changes of the disease are discussed. The authors also emphasize the importance of the encephalitic process in the brain stem, which can make the clinical picture even more complicated because of the appearance of respiratory disturbances.

Mononucleosis-like syndrome associated with a multisystem Coxsackie virus type B3 infection in adolescence.

We describe a severe multisystem Coxsackie virus type B3 infection in a previously healthy 14-year-old girl who presented with a mononucleosis-like syndrome (MS). Initial observations included a prominent cervical lymphadenopathy, exudative pharyngitis and leucocytosis with atypical lymphocytosis. At the end of the 2nd week of illness the patient developed meningoencephalomyelitis and haemolytic anaemia. Subclinical myocarditis was also recorded. Prolonged hepatitis recrudescing at the time of recovery coincided with serological evidence of a reactivated Epstein-Barr virus infection. The diagnosis was based on a significant rise in serum antibody titres against Coxsackie virus type B3, using the neutralization test. Intrathecal synthesis of antibodies to Coxsackie virus type B3 was also demonstrated. Generalized Coxsackie virus infections in adolescence are rare and an MS has not, to our knowledge, been associated with Coxsackie virus type B3 infection.

Bacampicillin, amoxycillin and talampicillin concentrations in bronchial secretions.

There are references in the literature describing the influence of bronchial inflammation on the antibiotic concentration in bronchial secretions, including netilmicin concentrations in the bronchial secretion of patients undergoing tracheotomy. Three semi-synthetic penicillins are compared--bacampicillin, amoxicillin and talampicillin--administered frequently in the treatment of various respiratory infections. The three antibiotics were administered successively for two days each, in the same patient, irrespective of other drugs. At the same time the cytologic evaluation of the degree of bronchial inflammation was done. The antibiotic concentrations in bronchial secretions and in sera were measured at the same time. The results showed that the concentration of antibiotics in bronchial secretions of patients undergoing tracheotomy was proportional to the degree of bronchial inflammation. Among the semi-synthetic penicillins investigated the highest degree of concentration in the bronchial secretion was obtained after the bacampicillin.

Characteristics of cerebrospinal fluid in tuberculous meningitis.

A retrospective study of 84 cases of tuberculous meningitis from a ten-year period is presented. Lumbar punctures had been performed, and the dynamics of cytologic changes in the cerebrospinal fluid (CSF) had been followed weekly during the course of the disease. The typical clinical picture, the course of the disease and cytologic characteristics of the CSF are noted. Of particular interest were some cases presenting atypical cytologic, as well as clinical, pictures of tuberculous meningitis. These patients had pleocytosis lasting as long as two years. In the first ten days, neutrophils predominated (60% to 80%); then mononuclear cells, such as lymphocytes, lymphoid cells, monocytoid cells and macrophages, became predominant. From the third week of the disease, plasmocytes (20%) were found in 30% of these cases. The presence of reticulomonocytes and reticulohistiocytic cells that could hardly be classified was also noted. By detailed analysis of the cytologic changes in the CSF, the suggestion of a diagnosis of tuberculous meningitis can be made before Koch's bacilli are found, even when the clinical picture and course of the disease are atypical.