[Efficacy of Lactobacillus Rhamnosus GR-1 and of Lactobacillus Reuteri RC-14 in the treatment and prevention of vaginoses and bacterial vaginitis relapses]. / Efficacia del Lactobacillus Rhamnosus GR-1 e del Lactobacillus Reuteri RC-14 nel trattamento e nella prevenzione delle recidive nelle vaginosi e nelle vaginiti batteriche.

AIM: The aim of this study was to investigate the efficacy of the use of Lactobacillus rhamnosus GR-1 and of Lactobacillus reuteri RC-14 administrated orally in the treatment and prevention of vaginoses and bacterial vaginitis relapses. METHODS: The study enrolled 50 women in good health, aged between 18 and 48 years, with assessed diagnosis of bacterial vaginosis and vaginitis. The women were randomized in two groups: group A comprised 25 patients with bacterial vaginitis and group B comprised 25 patients with vaginosis. Each patient was administered an antibiotic therapy and subsequently a therapy with Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 (Dicoflor Elle, Dicofarm, Roma, Italy) with two tablets daily for 15 days. After one week from the end of the therapy all patients have been controlled by vaginal swab and microscopic analysis of vaginal secretion. RESULTS: At the end of the study 46 patients had a complete Lactobacilli recolonization, two patients had no colonization and two dropped out. The results showed that 92% of the enrolled patients benefited from the treatment. CONCLUSION: The results of the present study shows that Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, taken orally, were helpful in vaginosis and bacterial vaginitis treatment and in relapse prevention, as they can re-establish the vaginal ecosystem remarkably.

Activity of Berberis aetnensis root extracts on Candida strains.

The antifungal activity of methanolic extract and alkaloidal fraction of Berberis aetnensis against Candida species was investigated. The crude extract was active against Candida species, this activity being higher than that of the alkaloidal fraction and berberine.

Antibacterial activity of propolis and its active principles alone and in combination with macrolides, beta-lactams and fluoroquinolones against microorganisms responsible for respiratory infections.

Propolis is produced by bees and is reported to have several pharmaceutical properties. Its antibacterial activity against strains causing upper respiratory tract infections is particularly important: propolis might be used as a therapeutic agent to prevent the bacterial infections that sometimes overlap viral infections. In this study the in vitro activity of both an alcoholic solution and a hydroglyceric extract of propolis, as well as its active principles, was tested against bacteria responsible for respiratory infections (Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis and Streptococcus pyogenes). We also evaluated the in vitro activity of a combination of propolis and its active principles and some beta-lactams, macrolides and fluoroquinolones. Our results, though not demonstrating a clearly synergistic activity between antibiotics and propolis and its constituents, show the possibility of using natural preparations, due to their antimicrobial and anti-inflammatory properties, to enhance antibacterial therapy.

Deoxyspergualin neither counteracts lipopolysaccharide (LPS) or Staphylococcus aureus enterotoxin-B (SEB) induced lethality in mice nor does it modulate the release of tumor necrosis factor-alpha.

To gain further insights into the immunopharmacological mode of action of the immunosuppressant antibiotic deoxyspergualin (DSP), its effects were evaluated in murine lethal endo- and exotoxemia. These are two cytokine-mediated macrophage and T cell dependent immunoinflammatory conditions that can be induced in D-Galactosamine (D-Gal) presensitized mice by the injections with either LPS or SEB, respectively. The results show that prophylactic treatment with DSP (2.5 or 5 mg/kg bd.wt. 48, 24 and 2 h prior to challenge) neither improved the rate of survival, nor influenced the massive increase in the blood levels of tumor necrosis factor-alpha which followed the challenge with LPS or SEB. In sharp contrast, these clinical and seroimmunological events were both markedly counteracted by prophylactic treatment with sodium fusidate, another immunosuppressive agent used as control.

Association study of a promoter polymorphism of UFD1L gene with schizophrenia.

Schizophrenia or schizoaffective disorders are often found in patients affected by DiGeorge/velo-cardio-facial syndrome (DGS/VCFS) as a result of hemizygosity of chromosome 22q11.2. We evaluated the UFD1L gene, mapping within the DGS/VCFS region, as a potential candidate for schizophrenia susceptibility. UFD1L encodes for the ubiquitin fusion degradation 1 protein, which is expressed in the medial telencephalon during mouse development. Using case control, simplex families (trios), and functional studies, we provided evidence for association between schizophrenia and a single nucleotide functional polymorphism, -277A/G, located within the noncoding region upstream the first exon of the UFD1L gene. The results are supportive of UFD1L involvement in the neurodevelopmental origin of schizophrenia and contribute in delineating etiological and pathogenetic mechanism of the schizophrenia subtype related to 22q11.2 deletion syndrome.

Bronchial reactivity to methacholine in HIV-infected individuals without AIDS.

To evaluate bronchial reactivity to methacholine in human immunodeficiency virus (HIV) infection, we submitted 25 HIV-seropositive subjects without full-blown AIDS and 25 HIV-seronegative subjects, all inmates in a drug rehabilitation center for previous intravenous drug abuse, to interview and to bronchial challenge with methacholine. Four (16 percent) HIV-seropositve and three (12 percent) HIV-seronegative subjects noted bronchospastic symptoms. Baseline FEV1 and MEF50 percent were within the normal range in every patient. Bronchial hyperreactivity to methacholine (PD20FEV1 < 1,400 micrograms) was found in two (8 percent) HIV-seropositive and in four (16 percent) HIV-seronegative subjects, with no significant difference in the frequency between the two groups. We conclude that HIV infection without AIDS in intravenous drug users does not appear to be associated with an increased frequency of bronchospastic disorders and to bronchial hyperreactivity to methacholine.

Antimicrobial activity of quinupristin/dalfopristin, a new injectable streptogramin with a wide Gram-positive spectrum.

Quinupristin/dalfopristin (Synercid) is a new injectable streptogramin antibiotic proposed for the treatment of severe antimicrobial infections, that has been shown to be active against Gram-positive, multi-resistant cocci. We compared the in vitro activity of quinupristin/dalfopristin with that of amoxycillin, ampicillin, penicillin, cefixime, ceftriaxone, clindamycin, erythromycin, imipenem, meropenem, oxacillin, piperacillin/tazobactam, teicoplanin and vancomycin. The susceptibility of 37 Staphylococcus aureus (14 MS, 23 MR), 26 Staphylococcus epidermidis (16 MS, 10 MR), 20 Streptococcus pneumoniae, 33 Group A Streptococcus pyogenes, 15 Streptococcus agalactiae, 10 Enterococcus faecalis (1 vancomycin-resistant), 15 Enterococcus faecium (9 van A) was evaluated. Quinupristin/dalfopristin was active against all Gram-positive species tested, including met-R S. aureus (MIC < or = 2 mg/l), met-R S. epidermidis (MIC < or = 2 mg/l), S. pneumoniae (MIC < or = 1 mg/l), ery-R and ery-S streptococci (MIC < or = 1 mg/l). The strains of E. faecalis were generally less susceptible. Time-kill studies confirmed that quinupristin/dalfopristin at 4 x MIC concentration showed a complete bactericidal effect (3 log reduction) in about 4 6 h against all strains tested. A post-antibiotic effect (PAE) of 3.9-5.2 h was observed at 4 x MIC concentration of quinupristin/dalfopristin against staphylococci. A prolonged PAE was obtained for S. pneumoniae (8 h), S. pyogenes (9 h) and S. agalactiae (7 h), while the shortest PAE was seen for E. faecalis and E. faecium (about 4 h).

Molecular mechanisms of resistance in Pseudomonas aeruginosa to fluoroquinolones.

Pseudomonas aeruginosa is important in the field of infectious disease especially with respect to its role in nosocomial infections. Infections with P. aeruginosa may be a problem as the organism has intrinsic resistance to several antibiotics and a capability in acquiring resistance during antibiotic therapy. Fluoroquinolones are sometimes used during antibiotic therapy of P. aeruginosa infections even though resistance to fluoroquinolones may develop. Six strains of P. aeruginosa were studied in an attempt to elucidate the mechanisms of resistance to fluoroquinolones. These included the electrophoresis patterns of the outer membrane proteins (OMPs), random amplified polymorphic DNA (RAPD) and polymerase chain reaction (PCR) analyses. A method is described that improved the clarity of the OMP gels. Resistance in these P. aeruginosa strains could depend not only on DNA-gyrase modifications but also on membranes alterations and on the presence (qualitative and quantitative) of the efflux pump formed by three subunits.

Minimal inhibitory concentrations and time-kill determination of moxifloxacin against aerobic and anaerobic isolates.

Moxifloxacin is a new oral 8-methoxy-quinolone with a wide spectrum of activity against Gram-negative and anaerobic bacteria, atypical micro-organisms and multi-resistant Gram-positive bacteria. This study was designed to assess the in vitro activity of moxifloxacin against Gram-positive bacteria with different resistance patterns, anaerobes and atypical micro-organisms such as Chlamydia and Mycoplasma. Moxifloxacin had good activity against Streptococcus pneumoniae with all strains inhibited by < or =0.12 mg/l. The minimal inhibitory concentrations (MICs) of moxifloxacin for Streptococcus pyogenes and Streptococcus agalactiae ranged from 0.03 to 0.5 mg/l while those of ciprofloxacin were about two- to four-fold higher (MICs=0.12-1 mg/l). Moxifloxacin was poorly active against enterococci but its activity against Clostridium and Bacteroides spp. was in the same range as that of metronidazole and superior to that of clindamycin. Moxifloxacin was substantially more active than both ciprofloxacin and sparfloxacin against Chlamydia.

The Italian Epidemiological Survey 1997-1999. Antimicrobial susceptibility data of Haemophilus influenzae, Haemophilus parainfluenzae and Moraxella catarrhalis in Italy.

The Italian Epidemiological Survey began a surveillance study with the aim of monitoring the antimicrobial resistance of respiratory pathogens. From 1997 to 1999, 2028 strains of Haemophilus influenzae and 523 strains of Haemophilus parainfluenzae were collected from 59 Clinical Microbiology Laboratories distributed throughout Italy. In 1998, the study was extended to include Moraxella catarrhalis and a total of 360 isolates were collected. There was a significant increase in the beta-lactamase production both for H. influenzae (from 5% in 1997 to 16% in 1999) and for H. parainfluenzae (from 5% in 1997 to 22% in 1999). Beta-lactamase production in M. catarrhalis was 84% in 1998 and 87% in 1999. Beta-lactamase production affected the susceptibility to unprotected penicillins (87% in H. influenzae, 85% in H. parainfluenzae and 34% in M. catarrhalis), and in part the susceptibility to cefaclor (about 98%). Amoxycillin/clavulanate, cefixime, ceftriaxone and ciprofloxacin were active against all strains of H. influenzae, H. parainfluenzae and M. catarrhalis.

Bactericidal kinetics and postantibiotic effect of sparfloxacin against selected species of respiratory pathogens.

We determined the bactericidal kinetics and postantibiotic effect (PAE) of sparfloxacin against Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, Klebsiella pneumonia, Streptococcus pneumoniae, and Staphylococcus aureus. Time-kill studies were performed by using 1 x and 4 x the minimum inhibitory concentrations (MICs) of sparfloxacin, ciprofloxacin, co-trimoxazole, amoxicillin/clavulanic acid and erythromycin (inoculum 10(5) and 10(7) CFU/ml). The PAE was induced by exposing the strains to 1xMIC and 4xMIC of sparfloxacin and ciprofloxacin for 1 h. Sparfloxacin was the most bactericidal of all the antibiotics tested, being active against Gram-positive and Gram-negative isolates with a 99.9% reduction within 3 to 6 h of exposure, depending upon strain, inoculum and concentration. The PAE of sparfloxacin against all species tested ranged from 1.1 to 2.6 hours; the most notable PAE occurring with M. catarrhalis.

Epidemiology of antibiotic resistance in human isolates of Enterobacteriaceae in Sicily.

The authors have studied the antimicrobial susceptibility of 1073 clinical isolates of various genera of Enterobacteriaceae (collected during the period July-December 1988) to ampicillin, piperacillin, cefotaxime, ceftazidime, ceftriaxone, aztreonam, imipenem, gentamicin, amikacin, netilmicin, norfloxacin, and ciprofloxacin. Antimicrobial susceptibility was determined by Bauer-Kirby disk diffusion method. Of 1073 tested bacteria, 704 (65.6%) produced beta-lactamase detectable by nitrocefin test. The highest percentage of resistant strains occurred with ampicillin (70%) followed by piperacillin (24%) and cefotaxime (19%). Lower percentages of resistant strains were found for gentamicin (10%), aztreonam (8%), netilmicin (7%), norfloxacin (5%) and amikacin (4%). Two percent of the strains were resistant to ciprofloxacin and 0.5% to imipenem. The incidence of resistance in Klebsiella sp., Enterobacter sp., E. coli and Proteus sp. was compared to that found among 872 strains isolated during July-Dec. 1984. In all the Enterobacteriaceae, mainly Enterobacter sp., the increase in the resistance was high for ampicillin, piperacillin and cefotaxime and lower for gentamicin.

In vitro activity of cefdinir against respiratory pathogens isolated in Sicily with reference to beta-lactamase production.

The in vitro activity of cefdinir (CI-983, FK-482), an orally absorbed aminothiazolyl cephalosporin, was evaluated against all 287 strains of Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Streptococcus pneumoniae and Streptococcus pyogenes in comparison with cefaclor, cefuroxime, amoxicillin, amoxicillin-clavulanic acid, erythromycin and cotrimoxazole. The bactericidal activity of cefdinir, cotrimoxazole, amoxicillin-clavulanic acid and erythromycin was determined against H. influenzae, M. catarrhalis and S. pneumoniae. With the exception of one beta-lactamase negative ampicillin-resistant strain of H. influenzae (resistant to all antibiotics tested), no resistance to cefdinir was observed (MIC < or = 1 mg/l). Cefdinir was active against H. influenzae, H. parainfluenzae and M. catarrhalis regardless of whether or not they produced beta-lactamase. In general, the inhibitory concentrations of cefdinir against H. influenzae, H. parainfluenzae and M. catarrhalis were similar to those of amoxicillin/clavulanic acid, one or two dilutions lower than those of cefuroxime and four dilutions lower than those of cefaclor and cotrimoxazole. Against S. pneumoniae and S. pyogenes cefdinir had the same activity as cefuroxime and amoxicillin but was more effective than the other antibiotics tested. Kinetic studies showed that cefdinir was rapidly bactericidal at concentrations 2 and 4 times the minimum inhibitory concentration (MIC): a reduction of 99.9% in CFU values was generally observed after 6-8 h.

Effect of a broad-spectrum cephalosporin on the oral and intestinal microflora in patients undergoing colorectal surgery.

The influence of ceftriaxone on oral and intestinal flora was investigated in 10 patients undergoing colorectal surgery. Ceftriaxone was given intravenously in one 2g dose before anesthesia. Saliva and feces samples were collected and analyzed on day 0, 3, 5, 14 and 28 after drug administration. All specimens were cultured quantitatively for aerobic and anaerobic microorganisms; representative colonies of each morphologic type of organism cultured were identified. The oral aerobic flora was somewhat affected by the administration of ceftriaxone. In all patients the number of Streptococci, Staphylococci and Neisseria decreased during the 5 days after ceftriaxone administration. No significant changes in the number of anaerobic commensal occurred. The oral microflora of all patients after 14 days had returned to normal. The aerobic fecal flora was considerably affected: in all patients enterobacteria were eliminated or strongly suppressed. Only minor changes in the number of aerobic gram-positive bacteria were observed, and the anaerobic intestinal flora showed only minor alterations. On day 28 the intestinal flora were normalized in all respects. No new colonizing microorganisms were isolated during the investigation period and no colonization with ceftriaxone-resistant bacteria was observed. No postoperative infection occurred and no adverse effects were registered.

The sensitivity of gram-negative and gram-positive bacteria to ofloxacin.

The in vitro antimicrobial activity of ofloxacin, a new fluorinated quinolone, was evaluated against 165 Gram-negative rods, both fermentative and non-fermentative, and against 57 Gram-positive strains (coagulase-positive and -negative staphylococci both methicillin-resistant and -susceptible, and Streptococcus faecalis). Minimal inhibitory concentrations were determined by using the macrodilution test and the activity was compared with nalidixic acid, norfloxacin, ampicillin, piperacillin, ceftazidime and gentamicin for Gram-negative rods; norfloxacin and gentamicin for Staphylococcus strains; and norfloxacin, ampicillin, piperacillin and gentamicin for enterococci. Ofloxacin inhibited all fermentative Gram-negative bacteria tested, in a range of 0.05-3.12 mcg/ml, and had good antimicrobial activity against non-fermentative Gram-negative strains: it inhibited 90% of Acinetobacter and 80% of P. aeruginosa tested, at 3.12 mcg/ml. Ofloxacin had a high antimicrobial activity against Staphylococcus and Enterococcus strains tested.

Bactericidal activity and postantibiotic effect of cefdinir (Cl 983, FK 482) against selected pathogens.

The bactericidal activity and the postantibiotic effect (PAE) of cefdinir (Cl 983, FK 482) (CDR), were determined against Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis and Escherichia coli (5 strains each) in comparison to erythromycin (E), cotrimoxazole (SXT) and amoxicillin-clavulanic acid (AMC). Kinetic studies of kill showed that CDR was rapidly bactericidal at concentrations 2 and 4 times the minimum inhibitory concentration (MIC): a reduction of 99.9% in CFU values was observed after 6-8 h for many of the isolates tested. As expected, a PAE was observed when S. aureus was treated with CDR at MIC (range of individual values for 5 strains 0.8-1.5 h) and 4 x MIC (range 1.1-1.4 h). Moreover, CDR showed a significant PAE at both its MIC and 4 x MIC against S. pneumoniae (range 0.5-1.0 h and 0.9-1.1 h), H. influenzae (range 0.4-0.7 h and 0.4-0.8 h), B. catarrhalis (range 0.5-0.7 h and 0.65-0.95 h) and E. coli (range 0.5-0.6 h and 0.5-0.7 h). The good bactericidal activity and the significant PAE of CDR against Gram-positive and Gram-negative bacteria (including respiratory pathogens) are a promising indication for the clinical efficacy of this cephalosporin in several bacterial infections.

Sulbactam/ampicillin in the treatment of otitis and sinusitis.

The importance of beta-lactamase-producing strains in acute otitis media and acute/chronic sinusitis, and the effectiveness of sulbactam/ampicillin were ascertained in vitro and in vivo. Of the strains isolated from 19 patients with otitis media, 40% are beta-lactamase producers whereas 44% of strains isolated from 22 patients with sinusitis produced beta-lactamase. When the most commonly isolated strains were treated with a range of antibiotics in vitro, they all showed 100% sensitivity to sulbactam/ampicillin. The clinical results for otitis media showed 63% recovery and 26% improvement, with only one (5%) failure (one patient did not complete treatment). For sinusitis the results were 55% recovery and 45% improvement, and no failures. For sinusitis, the end-of-treatment microbiological results showed complete eradication of the pathogens responsible for infection. The results indicate that sulbactam/ampicillin is an effective treatment for infections of the ear, nose and throat.

Synthesis and pharmacological evaluation of thieno[2,3-d]pyrimidin-2,4-dione and 5H-pyrimido [5,4-b]indol-2,4-dione derivatives.

Two series of novel derivatives based on the thienopyrimidine and pyrimidoindole ring systems, both N-substituted in position 3, have been synthesized. The compounds were obtained by reaction of N-amino groups of 5,6-dimethyl-thieno[2,3-d]pyrimidin-2,4-dione and of 5H-pyrimido[5,4-b]indol-2,4-dione with aromatic aldehydes. Some of these substances showed an appreciable analgesic activity, a good antiinflammatory activity, a low acute toxicity with an optimal gastric tolerance.

[A case of total spinal block during epidural anaesthesia]. / Un caso di blocco spinale totale durante anestesia peridurale lombare.

Most cases of total spinal block have been reported in the literature. The displacement of the catheter and the consequent dural perforation are the causes in large percentage of the patients (75%). The Authors describe this case for the importance of the causes and outcome of the patient. A 48 years old woman presented for hysterectomy for uterine fibromas. After having individualized the L3-L4 interspace, a test dose of 3 ml carbocaine 2% was injected. After that, the spinal block was obtained using ropivacaine 0.75% (total dose = 10 ml) injecting slowly, in following times, 5+5 ml of anaesthetic solution. The patient, perfectly conscious at first, presented a gradual increase of the difficulty in talking and breathing. Subsequently she showed a complete paralysis with loss of the consciousness, respiratory arrest, bilateral and symmetrical midriasis, as well as total areflexia. Endotracheal tube was placed. After eighty minutes from the end of the administration of the local anesthetic, spontaneous thoracic excursions appeared, even though of moderate ampleness, midriasis reduced. The patient recovered consciousness and sufficiently ventilated; therefore the endotracheal tube was removed.