Giuliana Gialdroni Grassi

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.

A multicenter study on clinical efficacy of ofloxacin in respiratory and urinary tract infections

SummaryA multicenter trial on the efficacy and tolerability of ofloxacin in upper and lower respiratory tract infections and urinary tract infections was carried out on 1,436 patients (926 males and 510 females; mean age 55.9 ± 18.4 years). Three dosage regimens were randomly applied: 200 mg, 300 mg and 400 mg ofloxacin b.i.d. by the oral route. The overall clinical outcome expressed as the ratio of the number of patients cured and improved to the number of patients treated was 279/324 (86%) in upper respiratory tract infections; 612/667 (91.8%) in lower respiratory tract infections and 418/445 (93.9%) in urinary tract infections. Out of 872 bacterial strains isolated in 802 patients, 742 (85.1%) were eradicated. Side effects not requiring interruption of therapy were observed in 65 patients (4.5%), while interruption was necessary in 23 patients (1.6%). The most frequent side effects were gastrointestinal disturbances. In conclusion ofloxacin showed a good clinical efficacy and tolerability in the treatment of respiratory and urinary tract infections.ZusammenfassungBei insgesamt 1436 Patienten (926 Männer und 510 Frauen) mit einem mittleren Alter von 55,9 ± 18,4 Jahren wurde Ofloxacin zur Behandlung von Infektionen der oberen oder tiefen Atemwege oder von Harnwegsinfektionen eingesetzt und seine Wirksamkeit und Verträglichkeit geprüft. Zufallsgemäß wurden drei Dosierungen verabreicht: 200 mg, 300 mg oder 400 mg Ofloxacin zweimal täglich per os. Das klinische Gesamtergebnis, ausgedrückt durch den Quotienten aus der Anzahl geheilter und gebesserter Patienten zur Anzahl behandelter Patienten war bei Infektionen der oberen Atemwege 279/324 (86%), bei tiefen Atemwegsinfektionen 612/667 (91,8%) und bei Harnwegsinfektionen 418/445 (93,9%). Bei 802 Patienten wurden 872 Bakterienstämme isoliert, davon wurden 742 (85,1%) eliminiert. Bei 65 Patienten (4,5%) wurden Nebenwirkungen beobachtet, die einen Therapieabbruch nicht erforderlich machten. Bei 23 Patienten (1,6%) mußte die Therapie wegen Nebenwirkungen beendet werden. Als häufigste Nebenwirkungen traten gastrointestinale Beschwerden auf. Insgesamt war bei der Behandlung von Atemwegsinfektionen und Harnwegsinfektionen mit Ofloxacin eine gute klinische Wirksamkeit und Verträglichkeit festzustellen.

Fosfomycin trometamol: Historical background and clinical development

SummaryA brief historical review of the clinical development of fosfomycin is given. Fosfomycin has attracted great interest because of its broad spectrum of activity and excellent tolerability. However, some problems have arsen because of the rapid emergence of resistant strains, and the poor bioavailability by oral route. Fosfomycin trometamol (a salt of fosfomycin with tromethamine) overcomes this difficulty: in fact when given by oral route it reaches very high and persistent urinary concentrations (up to 48 h). This behaviour allows a long-lasting bactericidal activity in urine to be obtained and the emergence of resistant variants to be prevented. These characteristics allowed proposing the drug for the “single dose therapy” of lower uncomplicated urinary tract infections. The clinical trials confirmed that this assumption was correct, demonstrating the excellent therapeutic activity of the drug in this indication.ZusammenfassungIn einem kurzen historischen Überblick wird die klinische Entwicklung des Fosfomycin dargestellt. Fosfomycin erweckte wegen seines breiten Wirkungsspektrums und seiner ausgezeichneten Verträglichkeit großes Interesse. Problematisch erschien jedoch die Beobachtung einer raschen Selektion resistenter Stämme und die geringe Bioverfügbarkeit der Substanz bei oraler Applikation. Diese Schwierigkeiten werden durch Fosfomycin Trometamol überwunden (ein Thromethamin-Salz des Fosfomycin). Auch bei oraler Gabe werden sehr hohe und anhaltende Urinkonzentrationen erreicht (bis zu 48 Stunden). Dadurch kommt es im Urin zur langdauernden bakteriziden Aktivität, womit die Gefahr einer Selektion resistenter Varianten vermieden wird. Wegen dieser Eigenschaften konnte Fosfomycin Trometamol als Medikament zur „Einzeldosistherapie“ der unkomplizierten Infektionen der unteren Harnwege vorgeschlagen werden. Die klinischen Studien zeigten, daß diese Überlegung richtig war, denn sie bestätigten, daß Fosfomycin Trometamol bei dieser Indikation eine ausgezeichnete therapeutische Wirkung hat.

In vitro Activity of Teichomycin against Isolates of Gram-Positive Bacteria

The in vitro activity of teichomycin has been evaluated against 189 clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis and group D streptococci. Teichomycin was as active as vancomycin, a chemically related antibiotic, on staphylococci and inhibited the in vitro growth of methicillin-resistant strains at the same concentration necessary to inhibit the sensitive ones. Against group D streptococci teichomycin was about three times more active than vancomycin (MIC50 = 0.125 mg/l, MIC90 = 0.4 mg/l). MBC:MIC ratios of both drugs against staphylococci were comparable, but teichomycin had higher bactericidal activity against group D streptococci, as shown also by killing curves. The activity of teichomycin was not significantly affected by variation of pH, even if the maximum activity was achieved at neutral pH, or by different methods of MIC evaluation. The antibiotic seemed more active when tested with a low inoculum (10(3)-10(5)/ml): a two- to threefold increase in MIC was observed at an inoculum of 10(7)/ml. A reduction of the in vitro activity could be shown when Penassay broth was used as culture medium.

Comparative Clinical Efficacy of Cefetamet Pivoxil in Lower Respiratory Tract Infection

SummaryCefetamet pivoxil, because of its activity against respiratory pathogens and its pharmacokinetic behaviour, is expected to have clinical efficacy in the treatment of lower respiratory tract infection (LRTI). This paper presents an overview of clinical trials conducted worldwide to investigate the efficacy and tolerability of cefetamet pivoxil in the treatment of adults and children with LRTI.A total of 626 adult patients, the majority of whom presented with exacerbations of chronic bronchitis (n = 500), received oral cefetamet pivoxil 500 or 1000mg twice daily for 5 to 10 days (n = 351) or a standard comparator agent (n = 275). The comparator agents were amoxicillin (750mg 3 or 4 times daily, or 1000mg twice daily), amoxicillin/clavulanic acid (625mg 3 times daily), or cefaclor (250 or 500mg 3 times daily) administered for 5 to 12 days. A satisfactory clinical outcome (cure + improvement) was achieved in 79 to 94% of evaluable patients.In 336 children, 240 received cefetamet pivoxil at 2 dosage levels (10 or 20 mg/kg twice daily) for 7 to 12 days and 96 received the standard comparator, cefaclor (10 mg/kg 3 times daily). Cefetamet pivoxil was clinically effective at both dosages, and did not differ significantly compared with cefaclor (clinical cure rates of 97 to 99% with cefetamet pivoxil and 96% with cefaclor). A separate analysis of 305 patients with community-acquired pneumonia showed clinical successes in 80 to 100% of adults, 75 to 78% of elderly patients, and 98% of children treated with cefetamet pivoxil.The overall incidence of adverse events determined in 4867 patients was about 10% in adults and 14% in children. Gastrointestinal disturbances were the most commonly reported adverse events.

Effects of Antimicrobial Agents on Some Phases of Neutrophil Chemotaxis

A variety of interactions exists between human phagocytes and antimicrobial agents. On one hand phagocytes may provide a protected environment for microorganisms by either inactivating or preventing entrance of I antibiotics (8). On the other hand, chemotherapeutic agents may modify bacterial surface structures or metabolism thus affecting pathogen-phagocyte interaction. They may also act directly on phagocytes by enhancing or suppressing their metabolism and/or functions such as adherence, locomotion, phagocytosis and microbicidal activities.

Evaluation of the Host Defense System in Asthmatic Patients

The efficiency of some components of the host defense system has been evaluated in 32 atopic patients with rhinitis, asthma or asthma and rhinitis. No alterations in components of complement (C3 and C4), serum immunoglobulins (IgG, IgA, and IgM) and neutrophil functional parameters were found. As expected, serum IgE values were higher than in controls. A decreased percentage of total circulating T lymphocytes, an increased percentage of Ia1-positive cells, but normal values of OKT4- and OKT8-positive T lymphocytes were demonstrated. However, a greater heterogeneity in the distribution of the suppressor-cytotoxic subset was shown in atopic patients.