[Emergence of new pneumonia: besides severe acute respiratory syndrome]. / Le polmoniti emergenti: oltre la sindrome respiratoria acuta severa.

Important epidemiological modifications have been registered in respiratory infections, both in immunocompetent and immunocompromised hosts. Pathogens with modified antibiotic susceptibility patterns have emerged, which display an increased antibiotic resistance, such as S. pneumoniae, S. aureus, H. influenzae. This trait has a strong impact on the therapeutic choices, particularly when an empiric antibiotic treatment is selected. The prevalence of bacterial species showing non-susceptibility to the most common prescribed antibiotics (betalactams, macrolides etc.) follows a different geographic distribution. Some pathogens have acquired a new epidemiological role in patients affected with immune deficiencies: among them P. carinii and other bacterial, fungal and viral pathogens. The emergence of new, previously unknown, species, has been registered, both bacteria (C. pneumoniae) and viruses (Metapneumovirus, Hantavirus etc.). Such aspects must be considered in the diagnosis of respiratory infections, which should include diagnostic tests for the identification of such pathogens. Among the new respiratory infections severe acute respiratory syndrome (SARS) has quickly become a health care emergency, so that efforts have been made to identify the aetiological agent as well as the main epidemiological and clinical characteristics of the disease. Avian influenza has raised great interest immediately after the first cases of human infection caused by the avian virus, especially after the outbreaks in Asian countries and in the Netherlands. A crucial step in containing infection is the prevention of the disease; efforts are directed toward this endpoint.

Acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections in community-acquired pneumonia and exacerbations of COPD or asthma: therapeutic considerations.

Rates of acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections were determined in 115 adults hospitalized for community-acquired pneumonia (CAP), purulent exacerbations of COPD and acute exacerbations of bronchial asthma, by means of serology and molecular methods. Results were compared with those obtained in a matched control group. Common respiratory pathogens were isolated by cultures in 22.5% and 22.2% of CAP and exacerbated COPD patients, respectively. Cultures from exacerbated asthma patients were always negative. Serological and molecular evidence of current C. pneumoniae infection was obtained in 10.0%, 8.9% and 3.3% of CAP, COPD and asthma cases. The corresponding rates of acute M. pneumoniae infection were 17.5%, 6.7% and 3.3%, respectively. Finally, no difference was found between typical and atypical pathogen rates. These findings highlight the importance of taking into account C. pneumoniae and M. pneumoniae infections in guiding the choice of empirical antibacterial treatment for CAP and purulent exacerbations of COPD.

Cutaneous vasculitis and reactive arthritis following respiratory infection due to Chlamydia pneumoniae: report of a case.

Unlike Chlamydia trachomatis and C. psittaci, the association of C. pneumoniae infection with immunological complications, such as reactive arthritis (ReA) or erythema nodosum (EN) has been rarely reported. Here we present the case history of a patient with C. pneumoniae community acquired pneumonia (CAP) who subsequently developed a ReA and a cutaneous vasculitis. A 45-year-old HLA B27 negative male developed an asymmetric and additive arthritis and a cutaneous leukocytoclastic vasculitis with IgM and complement papillary deposition along hypodermic vessel walls about three weeks after the onset of respiratory symptoms. The diagnosis of chronic Chlamydia pneumoniae infection was based on serology and PCR. Cultural and serological investigations for other infectious agents commonly involved in ReA were negative. This is the first report on the occurrence of two immune-based complications, associated to Chlamydia pneumoniae infection. Therefore, since this infection is very common in our population, although often asymptomatic, should be systematically considered as a common causative agent of ReA and of vasculitis.

Urinary PGE(2) concentrations measured by a new EIA method in infants with urinary tract infections or renal malformations.

In this work PGE(2)concentrations were measured by a new EIA method in the urine of infants (mean age: 9.35+/-4.24 months) with recurrent urinary tract infections or renal malformations. Compared to healthy subjects, PGE(2)excretion rates resulted significantly higher in both pathological groups, in particular in subjects with obstructive uropathies (29.55+/-8.12 vs 18.37+/-4.64 pg/ml). We did not find any age- or pH-dependent difference in urinary excretion of PGE(2); none of the examined indices of renal function showed any significant relationship to PGE(2). These results suggest that this parameter, measured non-invasively in the urine, could help in the differential diagnosis between obstructive vs non-obstructive dilatation and in monitoring renal function in presence of recurrent UTI episodes.

Antibiotic prophylaxis in children with relapsing urinary tract infections: review.

Recurrent urinary tract infections (UTIs) are observed in 30-50% of children after the first UTI. Of these, approximately 90% occur within 3 months of the initial episode. The basic aim of antibiotic prophylaxis in children with malformative uropathy and/or recurrent UTIs, is to reduce the frequency of UTIs. The bacteria most frequently responsible for UTI are gram-negative organisms, with Escherichia coli accounting for 80% of urinary tract pathogens. In children with recurrent UTIs and in those treated with antibiotic prophylaxis there is a greater incidence of UTI due to Proteus spp., Klebsiella spp. and Enterobacter spp., whereas Pseudomonas spp., Serratia spp. and Candida spp. are more frequent in children with urogenital abnormalities and/or undergoing invasive instrumental investigations. Several factors are involved in the pathogenesis of UTI, the main ones being circumcision, periurethral flora, micturition disorders, bowel disorders, local factors and hygienic measures. Several factors facilitate UTI relapse: malformative uropathies, particularly of the obstructive type; vesico-ureteric reflux (VUR); previous repeated episodes of cystitis and/or pyelonephritis (3 or more episodes a year), even in the absence of urinary tract abnormalities; a frequently catheterized neurogenic bladder; kidney transplant. The precise mechanism of action of low-dose antibiotics is not yet fully known. The characteristics of the ideal prophylactic agent are presented in this review, as well as indications, dosages, side effects, clinical data of all molecules. While inappropriate use of antibiotic prophylaxis encourages the emergence of microbial resistance, its proper use may be of great value in clinical practice, by reducing the frequency and clinical expression of UTIs and, in some cases such as VUR, significantly helping to resolve the underlying pathology.

Interferon-alpha in viral and bacterial gastroenteritis: a comparison with C-reactive protein and interleukin-6.

The aim of the study was to identify serum markers able to differentiate bacterial and viral origin in acute diarrhoea. Interferon-alpha (INF-alpha), C-reactive protein (CRP) and interleukin-6 were determined on admission in the sera of 119 children aged between 1 mo and 14 y who were hospitalized for rotavirus (n = 60) or bacterial diarrhoea (Salmonella spp. 39 cases, Shigella spp. 15 cases, Campylobacter jejuni 5 cases). CRP concentration was >10 mg/l in 48.3% of children with viral gastroenteritis and 86.4% of children with bacterial gastroenteritis. IL6 concentration was >100 pg/ml in 11.7% and 26.3% of cases, respectively. INF-alpha was detected in 79.1% of children with rotavirus (sens 79%) and in 3.5% (spec 93%) with bacterial gastroenteritis. However the INF-alpha assay takes 48 h and pathogens are often identified from stools before interferon results are available. We found that serum markers are not discriminating enough to differentiate between viral and bacterial gastroenteritis in emergency cases.

Bombesin enhances monocyte and macrophage activities: possible role in the modulation of local pulmonary defenses in chronic bronchitis.

Increased lung levels of bombesin-related peptides (BRPs) have been described in smokers and in patients with chronic obstructive pulmonary diseases (COPDs). Moreover, previous studies have shown that BRPs are endowed with immunoregulatory activities. The aim of the present study was to assess the in vitro influence of synthetic bombesin on the activity of mononuclear phagocytes obtained from healthy donors and from COPD patients. Bombesin significantly enhanced in vitro phagocytosis of monocytes and alveolar macrophages in both groups of subjects, restoring deficient phagocytosis in a group of COPD patients. Moreover, bombesin stimulated superoxide anion production and interleukin-8 release by peripheral monocytes.

Flurithromycin ethylsuccinate in the treatment of lower respiratory tract bacterial infections.

Efficacy and tolerability of flurithromycin ethylsuccinate were evaluated in lower respiratory tract infections. One hundred and ten patients (38 women, 72 men; age range 18-87 years) were treated with on 375 mg tablet 12-hourly for a mean duration of 8.7 days. One hundred and five patients were evaluable for efficacy. Overall clinical cure rate was 62.9%; improvement was recorded in 19% of patients for a total satisfactory clinical response rate of 81.9%. Sputum production decreased in most patients, being absent after treatment in 47% (only one patient was negative at baseline); sputum was purulent or mucopurulent in 80% of subjects before and in 20% after treatment. Bacteriological evaluation was possible in 72 patients: pathogen eradication was achieved in 80.2% of cases. Eight patients out of 110 reported adverse reactions, mainly gastrointestinal; in one case treatment had to be discontinued. These results demonstrate that flurithromycin ethylsuccinate is safe and effective in the treatment of lower respiratory tract infections.

Proaggregating and procoagulant activities of human mesothelioma tumor cells at different stages of "in vitro" culture.

BACKGROUND: The mechanisms of the interactions between tumor cells and the hemostatic system are not completely understood; the purpose of this study was to elucidate whether tumor cells grown "in vitro" express the same proaggregating and procoagulant activities as cells isolated from tumor tissues, and whether the activities of such cultures are constant and consistent over time. METHODS: Tumor cells were collected and cultured from the pleural fluid of a 71-year-old patient with a sarcomatous malignant mesothelioma. Platelet aggregating activity was studied by adding tumor cells to platelet rich plasma or to washed, aequorin-loaded platelets. The procoagulant activity of the tumor cells was measured by the one-stage recalcification time of different humans plasma substrates. RESULTS: Cells harvested after 4 culture passages possessed low, ADP-dependent platelet aggregating activity, while those studied after 16 or 40 passages activated platelets through the production of thrombin. In the washed platelet system and in the presence of trace amounts of platelet poor plasma, the difference in the aggregating activity of various tumor cell populations was more evident. Normal mesothelial cells did not induce platelet aggregation. Procoagulant activity (tissue factor-like) was low in normal mesothelial cells and in tumor cells after 4 passages, and it was about 10 times higher in tumor cells after 16 or 40 passages. CONCLUSIONS: Results obtained with tumor cells cultured "in vitro" should be considered with caution because their effects are different from those of freshly isolated cells and may not be constant in the different culture passages.

Pefloxacin in lower respiratory tract infections.

To determine the efficacy and safety of pefloxacin in the treatment of lower respiratory tract infections, a multicentre trial involving four departments of respiratory diseases was performed. One hundred and eight patients were admitted to the study: most of them were affected with exacerbations of chronic bronchitis or with pneumonia complicating lung cancer. Isolation and identification of responsible microorganisms from bronchial secretions was possible in 78 patients. Seven patients were withdrawn, one for worsening of the underlying disease and six for early side-effects. Thus, of 108 patients recruited, 101 completed the course of therapy (pefloxacin 400 mg bd for 5-14 days) and could be submitted to final evaluation. Of these 43 (42.6%) were cured and 48 (47.5%) showed improvement. Eradication of responsible microorganisms was achieved in 70 (90.9%) of 77 patients microbiologically evaluated. Side-effects of moderate severity were observed in 12 patients (gastrointestinal disturbances in 11 and dyspnoea in one); these did not necessitate discontinuation of therapy.

[Activity of an ampicillin/sulbactam combination in respiratory infections]. / Attività dell'associazione ampicillina/sulbactam nelle infezioni respiratorie.

The combination of sulbactam (S) plus ampicillin (A) extends the activity of ampicillin (Amp) against beta-lactamase producing strains. This combination is therefore useful in many clinical situations including LRTI. A clinical trial was carried out to evaluate the clinical and bacteriological efficacy of S-Amp in LRTI in comparison with Amp alone. Concerning clinical outcome the results were satisfactory in 83.3% of cases for S-Amp group and 82.3% of cases for Amp group. Pathogen eradication was achieved in 87.5% and 70.5% of cases respectively for the S-Amp and Amp group.

[Ciprofloxacin by the intravenous route in the treatment of respiratory infections]. / La ciprofloxacina per via endovenosa nel trattamento delle infezioni respiratorie.

A clinical trial was performed to evaluate the efficacy of ciprofloxacin by iv administration in the treatment of respiratory infections. Twenty-two in-patients affected with acute lower respiratory tract infections, mainly infectious exacerbations of chronic obstructive lung disease (COLD), were treated with ciprofloxacin at the daily dosage of 400 mg iv, in two administrations. Overall clinical results were satisfactory (15 patients cured, 7 patients improved). Concerning bacteriological results, pathogen eradication was achieved in 83.3% of cases. Tolerability was good: no adverse events were observed.

Evaluation of systemic host defense mechanisms in chronic bronchitis.

Seventy-six chronic bronchitis patients were studied in order to determine the possible presence of disorders in their systemic defense mechanisms. No significant difference in lymphocyte subsets, in serum immunoglobulin and complement component (C3 and C4) levels was found in chronic bronchitis patients compared to normal adult controls. Skin tests for delayed hypersensitivity revealed a high frequency (39%) of hypoergic patients (with 1-2 positive reactions) in comparison to normal subjects. Altered values of many functional properties of both neutrophils and monocytes were demonstrated. The percentage of patients with intermediate (between 1 and 2 SD below the mean of controls) and defective (lower than 1.96 SD) values of chemotaxis, phagocytosis index and Candida killing was about 50%. Phagocytosis frequency and nitroblue tetrazolium reduction frequency were less frequently impaired.

Double-blind trial RU 41740 vs. placebo: immunological and clinical effects in a group of patients with chronic bronchitis.

A double-blind trail was performed to investigate the effects of RU 41740, a glycoprotein extract from Klebsiella pneumoniae, on host defenses and its efficacy in reducing the number of exacerbation in 29 evaluable patients with chronic bronchitis, out of 36 patients who entered the study. The drug enhanced the phagocytosis indexes of both polymorphonuclear and mononuclear phagocytes. Increased candidacidal activity of monocytes was also observed. These effects, already detectable after one course of therapy and during the entire period of treatment, were no longer detectable when tested 6 months after the end of treatment. A significantly (p less than 0.05) larger number of patients in the treated group than in the placebo group had no exacerbations during drug administration (0-3 months). Moreover, patients treated with RU 41740 had significantly fewer and shorter episodes of acute exacerbation. The positive decreases in these two parameters persisted throughout the follow-up.

Penetration of roxithromycin in bronchial secretions.

Roxithromycin sputum and serum concentrations after administration of therapeutic doses (150 mg in a single dose) were evaluated in six patients. Blood samples and pooled sputum samples were collected at corresponding time intervals up to 24 h after drug administration. Roxithromycin sputum levels were found to be almost always above serum concentrations, the highest sputum levels being 5.85 +/- 2.5 micrograms/ml in the interval ranging from 2 to 4 h after drug administration. Due to its antibacterial spectrum and favourable pharmacokinetic properties, roxithromycin, like other macrolide antibiotics, seems to be particularly indicated in the treatment of respiratory tract infections.

International experiences with ceftriaxone in the treatment of lower respiratory tract infections.

The clinical efficacy and tolerability of ceftriaxone in the treatment of pneumonia and other lower respiratory tract infections were evaluated in 827 patients (515 pneumonia, 312 other lower respiratory tract infections) reported in the international literature (daily dose: 1 of 2 g.i.v. or i.m. in most patients). Therapeutic success was achieved in 738 patients (89.2%). Microbiological results were evaluated in 295 patients. Eradication of the most common respiratory pathogens was achieved in 100% of cases and of Enterobacteriaceae in 85.7%-100%. Adverse effects occurred in 4.9% of patients. A large multicenter trial was carried out in Italy using a single daily dose of 1-2 g by i.v. or i.m. Six hundred ninety-six patients were admitted to the study (370 pneumonia, and 326 other lower respiratory tract infections). Therapeutic success was achieved in 668 cases (96%). Pathogens were eradicated in 88% of cases (184 pts evaluated). Side effects were observed in 4.6% of cases.