Sub-picosecond exchange-relaxation in the compensated ferrimagnet Mn2Ru x Ga.

We study the demagnetization dynamics of the fully compensated half-metallic ferrimagnet Mn2Ru x Ga. While the two antiferromagnetically coupled sublattices are both composed of manganese, they exhibit different temperature dependencies due to their differing local environments. The sublattice magnetization dynamics triggered by femtosecond laser pulses are studied to reveal the roles played by the spin and intersublattice exchange. We find a two-step demagnetization process, similar to the well-established case of Gd(FeCo)3, where on a 5 ps timescale the two Mn-sublattices seem to have different demagnetization rates. The behaviour is analysed using a four-temperature model, assigning different temperatures to the two manganese spin baths. Even in this strongly exchange-coupled system, the two spin reservoirs have considerably different behaviour. The half-metallic nature and strong exchange coupling of Mn2Ru x Ga lead to spin angular momentum conservation at much shorter time scales than found for Gd(FeCo)3 which suggests that low-power, sub-picosecond switching of the net moment of Mn2Ru x Ga is possible.

Topical kanamycin: an effective therapeutic option in aerobic vaginitis.

Eighty-one patients with clinical diagnosis of aerobic vaginitis (AV) were included in the study. The patients were randomized for treatment, 45 with kanamycin (100 mg vaginal ovules for 6 days, consecutively) and 36 with meclocycline (35 mg vaginal ovules for 6 days, consecutively). The patients were examined before starting the study, 1-2 days after treatment and 30 days after the end of the study. At the first follow-up the patients showed different levels of symptom reduction. Reduction in the presence of leukocytes, vaginal mucosa burning and itching were statistically significant in the group treated with kanamycin with respect to the group treated with meclocycline. Moreover, there was also reduced isolation of Enterobacteriaeae (97%) in the group treated with kanamycin versus those treated with meclocycline (76%). At the second follow-up, vaginal homeostasis (normalization of pH and presence of lactobacilli) was more evident in the kanamycin-treated group. In conclusion, our data suggest that the topical use of kanamycin could be considered a specific antibiotic for the therapy of this new pathology.

Microbiological/clinical characteristics and validation of topical therapy with kanamycin in aerobic vaginitis: a pilot study.

The term 'aerobic vaginitis' defines a 'new' vaginal pathology that is neither classifiable as specific vaginitis nor as bacterial vaginosis. We studied a sample of 30 women with a clinical and microbiological diagnosis of aerobic vaginitis and compared the efficacy and tolerability of kanamycin and meclocycline, two products commercially available in Italy in the form of vaginal pessaries. In chronological order of enrollment, the patients were alternately treated with kanamycin or meclocycline; the dose of administration in both groups was of one pessary per day for 6 days. The evaluation of the therapeutic efficacy was carried out both at the first check-up (7th-8th day) and at a second check-up (13th-16th day). At the first follow-up carried out immediately at the end of therapy, the percentage of normalisation of clinical signs and symptoms was increased independently of the type of treatment in the case of moderate grade aerobic vaginitis, while kanamycin was produced a better effect in the group with severe aerobic vaginitis. Furthermore, at the second follow-up, a direct correlation with recovery of vaginal homeostasis was demonstrated by the normalisation of the vaginal pH and by the presence of lactobacilli, only in kanamycin treated group. In conclusion, our results showed the validity of the treatment with kanamycin intravaginally in this recently recognised disease.

Antibiotic resistance in Burkina Faso.

Burkina Faso is one of the Subsaharan African nations. No national services for monitoring of antibiotic resistance are available, so the number of reports of resistance patterns among hospital pathogens are inconsistent. In order to evaluate antibiotic resistance, a total of 1998 valuable microrganisms were analysed during 2000 at the Medical Centre St. Camille of Ouagadougou, Burkina Faso's capital. They were isolated as follows: 1012 from urine-culture, 503 from tonsil swabs, 398 from pus, 53 from sputum and 32 from blood-cultures. Escherichia coli was the most isolated microrganism from urine (44%); Enterococcus faecalis from tonsil swabs (96.4%), Staphylococcus aureus from pus (17%) and K. pneumoniae (70%) from sputum. In general, resistance to the old antibiotics, such as aminopenicillins and cotrimoxazole was shown. The most active antibiotic was norfloxacin, a rarely used antibiotic in this country. In conclusion, our study shows that it is necessary to create antibiotic-resistance surveillance centers in the developing countries to adopt an accurate therapy to avoid exporting of antibiotic resistance to the developed countries linked to increased emigration.

In vitro activity of levofloxacin against coagulase-positive and -negative staphylococci.

The in vitro activity of levofloxacin compared with that of ciprofloxacin, ofloxacin and norfloxacin were examined by conventional in vitro tests against 150 clinical isolates of staphylococci, subdivided according to species and susceptibility to methicillin. Although the minimum inhibitory concentrations (MICs) of all quinolones were highest in methicillin-resistant Staphylococcus aureus strains, the activity of levofloxacin was almost complete in methicillin-resistant S. epidermidis and methicillin-resistant S. haemolyticus when compared with ciprofloxacin and ofloxacin, which showed more than 30% resistance. Methicillin-susceptible S. aureus and S. epidermidis strains were susceptible to all quinolones with few differences between the antibiotics tested. The minimal bactericidal activity of levofloxacin was within the double dilution range of MIC values for all strains tested, demonstrating its potent role against staphylococci. In time-kill studies, levofloxacin exerted bactericidal activity within 3 h against all staphylococci. These in vitro results suggest that levofloxacin is a potent fluoroquinolone against coagulase-negative staphylococci and that it is both methicillin-susceptible and resistant. Further studies are necessary to determine the role of this drug in the treatment of infections sustained by these microorganisms.

Is levofloxacin as active as ciprofloxacin against Pseudomonas aeruginosa?

The in vitro activity of levofloxacin against 300 Pseudomonas aeruginosa isolated from hospitalized patients, with the exception of those recovered in intensive care or hematology units, was compared to ofloxacin, ciprofloxacin, piperacillin, amikacin, ceftazidime and imipenem. Imipenem showed the best activity (81.6%), followed by piperacillin (80.7%). The activity of levofloxacin was equal to that of ciprofloxacin (75.3%) but was more active than ofloxacin (58.1%). Moreover, the MIC values of levofloxacin did not show any statistical difference using two different inocula. Levofloxacin shows an excellent bactericidal activity being generally within one doubling dilution of the MIC. These results were also confirmed by the time-killing studies. In conclusion, according to the in vitro activity, levofloxacin could be considered a good option for the treatment of infections sustained by Pseudomonas aeruginosa, and clinical experiments are required to corroborate our in vitro data.

Novel streptogramin antibiotics.

Streptogramins represent a unique class of antibiotics remarkable for their antibacterial activity and their unique mechanism of action. These antibiotics are produced naturally as secondary metabolites by a number of Streptomyces species and have been classified into two main groups. They consist of at least two structurally unrelated compounds, group A or M (macrolactones) and group B or S (cyclic hexadepsipeptides). Both groups bind bacterial ribosomes and inhibit protein synthesis at the elongation step and they act synergistically in vitro against many microorganisms. Streptogramins A and B act synergistically in vivo; the mixture of the two compounds is more powerful than the individual components and their combined action is irreversible. The pharmacokinetic parameters of group A and B streptogramins in blood are similar. The major gap, limiting the therapeutic use of the natural compounds, was represented by the lack dissolution in water. The synthesis of water-soluble derivatives of pristinamycin I(A) and II(B) has allowed the development of injectable, first represented by quinupristin/dalfopristin (Synercid) and oral formulations, represented by RPR-106972, streptogramins with fixed compositions. Streptogramins have demonstrated activity against Gram-positive microorganisms in vitro and in vivo, including those with multi-drug resistance. Moreover, the absence of cross-resistance to macrolides in many of these microorganisms and the rarity of cross-resistance between the two groups of antibiotics associated with the rapid bacterial killing are the principal features of the streptogramins, offering the possibility for treating the rising number of infections that are caused by multi-resistant Gram-positive bacteria.

Netilmicin: in vitro activity, time-kill evaluation and postantibiotic effect on microorganisms isolated from ocular infections.

The in vitro activity of netilmicin and other antibiotics against ocular gram-positive and gram-negative microorganisms was evaluated. Netilmicin showed excellent activity against all the tested microorganisms, with more than 90% susceptibility. Many gentamicin- and tobramycin-resistant strains were still susceptible to netilmicin, although the minimum inhibitory concentration values of netilmicin were higher than those for the fully susceptible strains. In time-kill studies, netilmicin showed bactericidal activity within 1 h against Pseudomonas aeruginosa and Staphylococcus aureus. Moreover, netilmicin showed a postantibiotic effect of 2.4 h against P. aeruginosa and 1.5 h against S. aureus. These values were longer than those showed by ofloxacin, i.e. 2.1 and 1.4 h, respectively.

Distribution and antibiotic resistance of isolates from lower respiratory tract and blood cultures from patients in three Italian intensive care units: a 2-year comparison.

The distribution and antibiotic resistance of major pathogens isolated from patients in ICUs were studied by three Italian microbiological laboratories. Consecutive aerobic strains were collected over two different time periods from protected brushing bronchoscopy, broncho-alveolar lavage and blood cultures. A total of 420 strains were isolated during the first period (47.3% gram-negative and 52.7% gram-positive) and 412 over the second period (50.5% gram-negative and 49.5% gram-positive). Pseudomonas aeruginosa was the most frequently isolated organism from the respiratory tract followed by Staphylococcus aureus. Methicillin resistance was 47.9 and 44.5% in S. aureus and 63.0 and 65.1% in coagulase-negative staphylococci over the two periods. No glycopeptide-resistance was found in gram-positive organisms. Ceftazidime-resistance in Klebsiella pneumoniae was very high.

In vitro activity of ceftazidime, cefepime and imipenem on 1,005 Pseudomonas aeruginosa clinical isolates either susceptible or resistant to beta-lactams.

BACKGROUND: Recently, new 'fourth-generation' cephalosporins, such as cefepime and cefpirome, were introduced into antibacterial chemotherapy. METHODS: In order to explore whether these new cephalosporins offer real advantages against Pseudomonas aeruginosa, we matched the in vitro activity of cefepime with that of ceftazidime and imipenem as reference compounds. RESULTS: Among the 1,005 clinical isolates tested, 86.6% were susceptible to ceftazidime, whereas 80.7 and 76.9% were susceptible to imipenem and cefepime, respectively. Furthermore, the activity of the three compounds against a significant number of clinical isolates of P. aeruginosa expressing different resistance mechanisms to beta-lactam antibiotics was investigated. Among these isolates, 62.5% were still susceptible to ceftazidime, and 52.1 and 38.7% were inhibited by imipenem and cefepime, respectively. CONCLUSION: Ceftazidime and imipenem retained their activity against the majority of clinical P. aeruginosa isolates collected in Italy. Cefepime did not offer competitive advantages in terms of in vitro activity.

A kinetic study on the interaction between tazobactam (a penicillanic acid sulphone derivative) and active-site serine beta-lactamases.

The interaction between tazobactam and several chromosome- and plasmid-encoded (TEM, SHV, PSE types) class A and C beta-lactamases was studied by spectrophotometry. Tazobactam behaved as a competitive inhibitor or inactivator able to restore in several cases the efficiency of piperacillin as a partner beta-lactam. A detailed kinetic analysis permitted measurement of the acylation efficiency for some cephalosporinases and broad-spectrum beta-lactamases; the presence of a turn-over of acyl-enzyme complex was also evaluated.

Interaction of cefotetan and the metallo-beta-lactamases produced in Aeromonas spp. and in vitro activity.

Aeromonas spp. are increasingly being recognized as human pathogens. The presence of metallo-beta-lactamases in these organisms represents a potential problem in antimicrobial therapy. Mechanism-based inactivators of beta-lactamases are used to overcome the resistance of clinical pathogens to beta-lactam antibiotics, but no clinical useful inhibitors of the metallo-beta-lactamases are presently known. Studying the interaction between cefotetan and Aeromonas spp. producing metallo-beta-lactamase activity, we observed that cefotetan behaved as a transient inactivator for both the crude extracts of Aeromonas strains and the purified enzymes from Aeromonas hydrophila AE036 and Aeromonas schubertii MNSA20. The direct hydrolysis of cefotetan showed that it was a poor substrate for both purified enzymes. In view of the minimum inhibitory concentrations, cefotetan shows to be a useful antimicrobial agent against Aeromonas spp.

First identification of an SHV-12 extended-spectrum beta-lactamase in Klebsiella pneumoniae isolated in Italy.

A clinical isolate of Klebsiella pneumoniae highly resistant to third- and fourth-generation cephalosporins, cephamycins and aminoglycosides, was isolated in 1991 from urine. Analysis of a crude extract showed the presence of three beta-lactamases with isoelectric points of 6.6, 7.5 and 8.2. The enzyme with pI 8.2 was transferred by conjugation into Escherichia coli K-12 J53 and was responsible for the resistance to third-generation cephalosporins and monobactams, but not to other antibiotics. Kinetic studies of partially purified beta-lactamase from the transconjugant strain confirmed that the enzyme was able to hydrolyse ceftazidime, cefotaxime and aztreonam but not cephamycins. Analysis of the transconjugant showed the presence of two small non-conjugative plasmids of 14 and 6 kb. A polymerase chain reaction was performed using primers specific for the bla(SHV) gene and a fragment of the expected size (about 961 bp) was obtained with both the K. pneumoniae clinical isolate and the transconjugant. Nucleotide sequence analysis of the fragment showed that it encoded the enzyme SHV-12, derived from SHV-5 (with Gln-35 to Leu). This is the first report of an SHV-12-like enzyme isolated in Italy.

Levofloxacin in vitro activity and time-kill evaluation of Stenotrophomonas maltophilia clinical isolates.

The in vitro activity of levofloxacin and eight other antimicrobial agents against 60 clinical isolates of Stenotrophomonas maltophilia was determined by an agar dilution method using 10(4) and 10(6) cfu/spot inocula. At the lower inoculum, 85.0% of the isolates were susceptible to levofloxacin but only 58.3% were susceptible to ofloxacin; at the higher inoculum, 78.3% were susceptible to levofloxacin and 36.7% to ofloxacin. In time-kill studies, levofloxacin exerted bactericidal activity within 4 h. With ofloxacin and ciprofloxacin bacterial regrowth was observed after 8 h. Levofloxacin may represent an alternative drug in the treatment of infections caused by S. maltophilia.

In vitro selection of glycopeptide-resistant variants of Enterococci.

In order to study the possible phenotypic and genotypic changes related to glycopeptide pressure on enterococci, a study was undertaken using stepwise in vitro exposure to achieve the following objectives: (i) to evaluate the development of resistance and cross-resistance between vancomycin and teicoplanin; (ii) to determine the stability of the acquired level of resistance; (iii) to determine the phenotypic and genotypic changes related to glycopeptide pressure; and (iv) to assess the spectrum of antibiotic-susceptibility of all strains. Our results showed that no variants resistant to glycopeptides could be selected after in vitro glycopeptide exposure experiments. However some strains showed increased MIC values: 8 mg/l to vancomycin in eight strains selected by vancomycin itself, while teicoplanin produced intermediate values to vancomycin in only three strains. The phenotypes were stable in vitro after numerous passages in antibiotic-free medium and three out of nine strains with a changed MIC level, showed 40, 42 and 43 kDa proteins in cell membrane preparations. The profile of antibiotic resistance was comparable in all isogenic strains tested with the exception of three selected strains that became susceptible to penicillin G. The pressure produced by glycopeptides, particularly vancomycin has contributed to an increased level of MIC that can influence the acquisition and/or full expression of this resistance.

A Kinetic Study on the Interaction between Tazobactam (A Penicillanic Acid Sulphone Derivative) and Active-Site Serine beta-Lactamases.

The interaction between tazobactam and several chromosome- and plasmid-encoded (TEM, SHV, PSE types) class A and C beta-lactamases was studied by spectrophotometry. Tazobactam behaved as a competitive inhibitor or inactivator able to restore in several cases the efficiency of piperacillin as a partner beta-lactam. A detailed kinetic analysis permitted measurement of the acylation efficiency for some cephalosporinases and broad-spectrum beta-lactamases; the presence of a turn-over of acyl-enzyme complex was also evaluated.

In vitro activity of piperacillin/tazobactam against 615 Pseudomonas aeruginosa strains isolated in intensive care units.

From May 1996 to September 1997, 615 Pseudomonas aeruginosa strains isolated from patients in intensive care units collected from different Italian laboratories were studied. The susceptibility of piperacillin/tazobactam, in comparison with other antipseudomonal antibiotics, to their NCCLS breakpoints was evaluated: amikacin 79. 6%, carbenicillin 67.0%, ceftazidime 73.4%, ciprofloxacin 55.8%, imipenem 64.1%, piperacillin 88.1%, piperacillin/tazobactam 92.4% and ticarcillin/clavulanic acid 69.0%. Seventy-three strains were selected because of their resistance to piperacillin and the mechanisms underlying such a resistance were investigated. Isoelectric focusing and hydrolysis assays revealed the presence of 15 plasmid-mediated beta-lactamases. Chromosomal beta-lactamase derepression was demonstrated in 34 isolates. The remaining 24 piperacillin-resistant strains did not produce beta-lactamases and an 'intrinsic mechanism' of resistance was inferred. The piperacillin/tazobactam combination restored resistance in 25 piperacillin strains. Nine of these were derepressed for chromosomal beta-lactamase, 8 showed impermeability and 8 showed plasmid enzymes.