Antibiotic susceptibility profiles of uncommon bacterial species causing severe infections in Italy.

This study presents the results of the italian "Severe infections project" involving bacteria that can be considered rare causes of disease. we isolated 30 uncommon human pathogens from a total of 60 strains (1.2% of all the isolates). The most frequent sources of uncommon human pathogens were primary bloodstream infections (48.3%) and pneumonia (20%). Species such as Comamonas testosteroni, Enterococcus hirae, Kluyvera ascorbata, Kluyvera cryocrescens, Leclercia adecarboxylata and Ochrobactrum anthropi were recovered from bacteremia patients. Clinically useful antimicrobial agents were tested against each isolate. Resistance to 4 or more antibiotics tested was found in Achromobacter xylosoxidans, O. anthropi, Pseudomonas stutzeri, Citrobacter braakii, Enterobacter sakazakii, K. ascorbata, Proteus penneri and Serratia plymuthica. About 16% of the Gram-negative species were resistant to third-generation cephalosporins and 28.6% of the staphylococci were oxacillin-resistant. the results from this study offer indications for empirical therapy for severe infections from uncommon human pathogens.

Comparative activity of cefodizime and ceftriaxone against respiratory pathogens in an in vitro pharmacodynamic model simulating concentration-time curves.

The duration of time that serum levels are above the minimum inhibitory concentration (MIC; T >MIC) seems to be an important pharmacodynamic parameter for beta-lactams. The aim of this study was to evaluate the bactericidal activity of cefodizime and ceftriaxone in a pharmacokinetic model mimicking the concentrations in bronchial mucus and in serum (total and free) obtained at 2, 4, 8, 12 and 24 h, after 1 g i.m. administration once daily. The species investigated were respiratory pathogens (1 strain of Staphylococcus aureus, 2 strains of Streptococcus pneumoniae, 1 strain b-lactamase negative and 1 strain beta-lactamase positive of Haemophilus influenzae, 1 strain of Escherichia coli and 1 strain of Klebsiella pneumoniae); MIC50s of the chosen strains were reported. In this in vitro model the concentrations (serum and bronchial mucus) for both antibiotics are generally at or above the MIC values of the tested strains until 24 hours. The killing curve showed rapid killing for both antibiotics: 99.9% killing (a 3-log reduction in growth) within 6 to 8 h, depending upon the microorganism tested. There was no significant difference in the log kill between cefodizime and ceftriaxone. These data confirm that T >MIC for beta-lactams is the pharmacodynamic parameter which best correlates with bactericidal efficacy. On the basis of the killing curve determined for cefodizime versus ceftriaxone at concentrations that these antibiotics can reach during therapy with 1 g i.m. once daily we expect reasonable clinical efficacy with monoadministration of cefodizime as well as for ceftriaxone in respiratory tract infections.

Correlation of trimethoprim and brodimoprim physicochemical and lipid membrane interaction properties with their accumulation in human neutrophils.

Dipalmitoylphosphatidylcholine vesicles were used as a biological membrane model to investigate the interaction and the permeation properties of trimethoprim and brodimoprim as a function of drug protonation. The drug-membrane interaction was studied by differential scanning calorimetry. Both drugs interacted with the hydrophilic phospholipid head groups when in a protonated form. An experiment on the permeation of the two drugs through dipalmitoylphosphatidylcholine biomembranes showed higher diffusion rate constants when the two drugs were in the uncharged form; lowering of the pH (formation of protonated species) caused a reduction of permeation. Drug uptake by human neutrophil cells was also investigated. Both drugs may accumulate within neutrophils; however, brodimoprim does so to a greater extent. This accumulation is probably due to a pH gradient driving force, which allows the two drugs to move easily from the extracellular medium (pH approximately 7.3) into the internal cell compartments (acid pH). Once protonated, both drugs are less able to permeate and can be trapped by the neutrophils. This investigation showed the importance of the physicochemical properties of brodimoprim and trimethoprim in determining drug accumulation and membrane permeation pathways.

Synergistic effect of deoxyspergualin (DSP) and cyclosporin A (CsA) in the prevention of spontaneous autoimmune diabetes in BB rats.

Dose-dependent side effects are frequently observed with immunosuppressive drugs of potential relevance for the immunotherapy of insulin-dependent diabetes mellitus (IDDM), such as CsA and DSP. If CsA and DSP acted synergistically in vivo, their combined use would allow using each compound at lower doses than those required when each drug is given in monotherapy. Consequently, dose-dependent side effects could be reduced and the therapeutic activity maintained or even enforced. Toward this end we studied the effects of combined treatment with CsA and DSP on the course of IDDM in the diabetes-prone (DP)-BB rat. The results show that two 'low' doses of CsA (2 mg/kg) and DSP (1 mg/kg) that are clinically ineffective in suppressing IDDM development in BB rats when administered alone under a prolonged prophylactic regimen (30-105 days old), may successfully prevent, but not cure, the disease when given contemporaneously under the same experimental conditions. The combined treatment was well tolerated, and no side effects were noticed. These data suggest that the combined use of CsA and DSP may deserve consideration for its possible application in the prevention/treatment of human IDDM and other autoimmune diseases.

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.

In vitro antimicrobial activity of Pistacia lentiscus L. extracts: preliminary report.

The in vitro antimicrobial activity of Pistacia lentiscus L. extracts was determined. Pistacia lentiscus L. extracts were tested on bacteria (Sarcina lutea, Staphylococcus aureus and Escherichia coli) and fungi (Candida albicans, Candida parapsilosis, Torulopsis glabrata and Cryptococcus neoformans). Of the different plant extractions, decoctions showed the best antibacterial activity, but the activity against fungal cells appears to be much more interesting.

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.

[Etiology and rational therapy of acute otitis media in adults]. / Eziologia e razionale terapeutico dell'otite media acuta nell'adulto.

Acute otitis media (AOM) is an infection frequently found in children, but tends to be less frequent with age and its frequency in adults is only about 1%. The etiology of AOM in children is prevalently bacterial; numerous studies have shown the most common etiological agents. But the etiology in adults has not been well studied. The authors examined 40 cases of AOM in adults, the pathologic material was obtained by needle aspiration; in 32 samples there was bacterial growth. In the majority of the cases (94%) the bacteria isolated were the same as those found in children: S. pneumoniae, H. influenzae and B. catarrhalis; much rarer were S. pyogenes and S. aureus. On the potential beta-lactamase producing strains, this activity was measured. From our findings we believe that there is the necessity to have a rational antibiotic therapy (due to the difficulty in obtaining pathologic material) with active drugs for the probable etiological agents of AOM.

Action of clindamycin-phosphate in foreign body infections due to Staphylococcus epidermidis in mice.

The virulence of Staphylococcus epidermidis strain slime producer was examined in an experimental model of foreign body infection in mice. In the course of this experimental infection the mice were injected with two antibiotics (clindamycin and cefazolin) active in vitro toward the Staphylococcus strain used. The results obtained after a week of antibiotic therapy show that clindamycin alone has a therapeutic action against the infection caused by S. epidermidis. Cefazolin showed a very poor therapeutic effect. The results are discussed on the basis of inflammatory reaction elicited from the foreign body and the characteristics of clindamycin in connection with the host's defense mechanisms.

In vitro study of dactimicin (ST 900) against methicillin-susceptible and -resistant staphylococci.

The current knowledge on the antimicrobial activity of dactimicin is poor and limited to the study of its activity against gram-negative bacilli. The new acquisition about the use of aminoglycoside antibiotics in infections due to Staphylococci, induced us to evaluate the behavior of this drug against methicillin-susceptible and -resistant Staphylococci, in comparison with fortimicin A and amikacin. Dactimicin (ST 900) shows good antibacterial activity and a strong bactericidal effect at MIC concentrations in all strains tested.

Enterococci and aminoglycosides: evaluation of susceptibility and synergism of their combination with piperacillin.

Some clinical isolates of enterococci were tested for susceptibility to gentamicin, tobramycin, amikacin and netilmicin. Five percent of Streptococcus faecalis tested demonstrated high level resistance (minimum inhibitory concentration (MIC) greater than 2024 micrograms/ml) to gentamicin, tobramycin and netilmicin, while amikacin had MICs greater than 128 micrograms/ml for all strains tested. Since a combination of a beta-lactam and streptomycin does not produce synergism against all strains of enterococci for an increase in the number of highly resistant strains, the effect of piperacillin plus gentamicin, tobramycin, and netilmicin was examined. The combination piperacillin + netilmicin seemed to be very effective against all enterococci tested.

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 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 micrograms/ml. It also had good antimicrobial activity against non-fermentative gram-negative strains: in fact it inhibited 90% of Acinetobacter and 80% of Pseudomonas aeruginosa tested at 3.12 micrograms/ml. Ofloxacin had good antimicrobial activity against Staphylococcus and Enterococcus tested.

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.

[ABAC, a closed system: problems and solutions, currency and perspectives]. / L'ABAC, un sistema chiuso: problemi e soluzioni, attualità e prospettive.

The ABAC System, as it is currently configured, uses pre-determined panels of antibiotics. This form of presentation is a limit for the use of the large number of new molecules, mainly active on Gram-negative bacteria. Therefore, the introduction of a new disposable, called "Gram-negative bacteria--new molecules" is suggested. Such a device will contain those additional and more widely tested antibiotics. According to recent studies concerning the pathology of Gram-positive organisms and the chemotherapeutic treatment for such pathology, changes in the disposable formulations for staphylococci and streptococci are proposed.

Incidence and antibiotic susceptibility of Haemophilus influenzae in clinical specimens.

Recent data report increasing Haemophilus influenzae ampicillin- and chloramphenicol-resistant strains. Authors report the results of one year investigation in Sicily. In 281 clinical specimens tested, Haemophilus influenzae has been isolated in 60 cases. From antibiotic susceptibility tests it can be observed that 58 strains show ampicillin-resistance.

[Evaluation of a new system for the simultaneous identification and antibiotic sensitivity testing of gram-negative bacilli by automation]. / Valutazione di un nuovo sistema per la identificazione e l'antibiogramma contemporanei di bacilli gram-negativi in automazione.

ABAC- IDENTIBIOGRAMMA II is a new system allowing the carry out of antimicrobial susceptibility testing on various bacterial groups and also the fully automatic simultaneous susceptibility testing and identification of Gram-negative bacilli (urinary and not). Particularly most species of Enterobacteriaceae and Aeromonas hydrophila, Acinetobacter sp., Pseudomonas sp. can be identified. This system has two important characteristics, due to a computerized program: that is the possibility of using sensitivity data as complement of the biochemical assays to obtain identification and the directions for use transmitted through the display. The validity of system and the reliability of its results have been verified.

[Choice of criteria in the revision of the ABAC system for the determination of sensitivity to antibiotics]. / Criteri di scelta nell'aggiornamento del sistema ABAC per la determinazione della sensibilità agli antibiotici.

The limitation of the ABAC system for the automated antibiotic sensitivity test is the fixed number of antibiotics to be assayed. This limit is partially overcome by the up-dating of ABAC disposables necessary both for bacterial infectious pathology (considerably various and dinamic) and bacterial resistance to antibiotics. Accordingly, research is constantly producing new antibiotics particularly in the beta-lactamine and aminoglycoside fields. In these groups new antibiotics must be found to substitute the old ones in the ABAC disposables, in particular in relation to Gram-negative bacteria (urinary or not). The preparation of a rotor for experimental use containing new antibiotics not present on the market is proposed to evaluate their validity through a rapid and standardized method.