Reactive Oxygen Species (ROS)-Mediated Antibacterial Oxidative Therapies: Available Methods to Generate ROS and a Novel Option Proposal.

The increasing emergence of multidrug-resistant (MDR) pathogens causes difficult-to-treat infections with long-term hospitalizations and a high incidence of death, thus representing a global public health problem. To manage MDR bacteria bugs, new antimicrobial strategies are necessary, and their introduction in practice is a daily challenge for scientists in the field. An extensively studied approach to treating MDR infections consists of inducing high levels of reactive oxygen species (ROS) by several methods. Although further clinical investigations are mandatory on the possible toxic effects of ROS on mammalian cells, clinical evaluations are extremely promising, and their topical use to treat infected wounds and ulcers, also in presence of biofilm, is already clinically approved. Biochar (BC) is a carbonaceous material obtained by pyrolysis of different vegetable and animal biomass feedstocks at 200-1000 °C in the limited presence of O2. Recently, it has been demonstrated that BC's capability of removing organic and inorganic xenobiotics is mainly due to the presence of persistent free radicals (PFRs), which can activate oxygen, H2O2, or persulfate in the presence or absence of transition metals by electron transfer, thus generating ROS, which in turn degrade pollutants by advanced oxidation processes (AOPs). In this context, the antibacterial effects of BC-containing PFRs have been demonstrated by some authors against Escherichia coli and Staphylococcus aureus, thus giving birth to our idea of the possible use of BC-derived PFRs as a novel method capable of inducing ROS generation for antimicrobial oxidative therapy. Here, the general aspects concerning ROS physiological and pathological production and regulation and the mechanism by which they could exert antimicrobial effects have been reviewed. The methods currently adopted to induce ROS production for antimicrobial oxidative therapy have been discussed. Finally, for the first time, BC-related PFRs have been proposed as a new source of ROS for antimicrobial therapy via AOPs.

Antibacterial and ATP Synthesis Modulating Compounds from Salvia tingitana.

A surface extract of the aerial parts of Salvia tingitana afforded a nor-sesterterpenoid (1) and eight new sesterterpenoids (2-̵9), along with five known sesterterpenoids, five labdane and one abietane diterpenoid, one sesquiterpenoid, and four flavonoids. The structures of the new compounds were established by 1D and 2D NMR spectroscopy, HRESIMS, and VCD data and Mosher's esters analysis. The antimicrobial activity of compounds was evaluated against 30 human pathogens including 27 clinical strains and three isolates of marine origin for their possible implications on human health. The methyl ester of salvileucolide (10), salvileucolide-6,23-lactone (11), sclareol (15), and manool (17) were the most active against Gram-positive bacteria. The compounds were also tested for the inhibition of ATP production in purified mammalian rod outer segments. Terpenoids 10, 11, 15, and 17 inhibited ATP production, while only 17 inhibited also ATP hydrolysis. Molecular modeling studies confirmed the capacity of 17 to interact with mammalian ATP synthase. A significant reduction of ATP production in the presence of 17 was observed in Enterococcus faecalis and E. faecium isolates.

Synthetic Pathways to Non-Psychotropic Phytocannabinoids as Promising Molecules to Develop Novel Antibiotics: A Review.

Due to the rapid emergence of multi drug resistant (MDR) pathogens against which current antibiotics are no longer functioning, severe infections are becoming practically untreatable. Consequently, the discovery of new classes of effective antimicrobial agents with novel mechanism of action is becoming increasingly urgent. The bioactivity of Cannabis sativa, an herbaceous plant used for millennia for medicinal and recreational purposes, is mainly due to its content in phytocannabinoids (PCs). Among the 180 PCs detected, cannabidiol (CBD), Δ8 and Δ9-tetrahydrocannabinols (Δ8-THC and Δ9-THC), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN) and some of their acidic precursors have demonstrated from moderate to potent antibacterial effects against Gram-positive bacteria (MICs 0.5-8 µg/mL), including methicillin-resistant Staphylococcus aureus (MRSA), epidemic MRSA (EMRSA), as well as fluoroquinolone and tetracycline-resistant strains. Particularly, the non-psychotropic CBG was also capable to inhibit MRSA biofilm formation, to eradicate even mature biofilms, and to rapidly eliminate MRSA persiter cells. In this scenario, CBG, as well as other minor non-psychotropic PCs, such as CBD, and CBC could represent promising compounds for developing novel antibiotics with high therapeutic potential. Anyway, further studies are necessary, needing abundant quantities of such PCs, scarcely provided naturally by Cannabis plants. Here, after an extensive overture on cannabinoids including their reported antimicrobial effects, aiming at easing the synthetic production of the necessary amounts of CBG, CBC and CBD for further studies, we have, for the first time, systematically reviewed the synthetic pathways utilized for their synthesis, reporting both reaction schemes and experimental details.

Synthesis and Antibacterial Activity of Cationic Amino Acid-Conjugated Dendrimers Loaded with a Mixture of Two Triterpenoid Acids.

To counteract the growing bacterial resistance, we previously reported the remarkable antimicrobial activity of amino acid-conjugated cationic dendrimers (CDs) against several Gram-negative species, establishing that the cationic lysine was essential for their potency. In this paper, CDs conjugated with lysine and arginine and encapsulating ursolic and oleanolic acids (UOACDs) were assumed to be excellent candidates for developing new antibacterial agents, possibly active against Gram-positive species. Indeed, both the guanidine group of arginine and the two triterpenoid acids are items known for directing antibacterial effects, particularly against Gram-positive bacteria. The cationic dendrimers were obtained by peripheral conjugation with the selected amino acids and by entrapping a physical mixture of the commercial triterpenoid acids. The cationic compounds were characterized and successfully tested against 15 Gram-positive isolates. Interesting minimum inhibitory concentration (MIC) values were obtained for all the dendrimer-drug agents, establishing that the antibacterial activity observed for the UOACDs strongly depended on the density and on the type of the cationic groups of the cationic amino acid-conjugated dendrimers and not on the presence and the release of UOA. Particularly, lysine was critical for potency, while arginine was critical for redirecting activity against Gram-positive species. Especially, a high cationic character, associated with a balanced content of lysine/arginine, produced a remarkable antimicrobial effect (MIC = 0.5-8.7 µM).

Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci.

Ursolic acid (UA), a pentacyclic triterpenoid acid found in many medicinal plants and aromas, is known for its antibacterial effects against multi-drug-resistant (MDR) Gram-positive bacteria, which seriously threaten human health. Unfortunately, UA water-insolubility, low bioavailability, and systemic toxicity limit the possibilities of its application in vivo. Consequently, the beneficial activities of UA observed in vitro lose their potential clinical relevance unless water-soluble, not cytotoxic UA formulations are developed. With a nano-technologic approach, we have recently prepared water-soluble UA-loaded dendrimer nanoparticles (UA-G4K NPs) non-cytotoxic on HeLa cells, with promising physicochemical properties for their clinical applications. In this work, with the aim of developing a new antibacterial agent based on UA, UA-G4K has been tested on different strains of the Enterococcus genus, including marine isolates, toward which UA-G4K has shown minimum inhibitory concentrations (MICs) very low (0.5-4.3 µM), regardless of their resistance to antibiotics. Time-kill experiments, in addition to confirming the previously reported bactericidal activity of UA against E. faecium, also established it for UA-G4K. Furthermore, cytotoxicity experiments on human keratinocytes revealed that nanomanipulation of UA significantly reduced the cytotoxicity of UA, providing UA-G4K NPs with very high LD50 (96.4 µM) and selectivity indices, which were in the range 22.4-192.8, depending on the enterococcal strain tested. Due to its physicochemical and biological properties, UA-G4K could be seriously evaluated as a novel oral-administrable therapeutic option for tackling difficult-to-treat enterococcal infections.

European emergence of ciprofloxacin-resistant Escherichia coli clonal groups O25:H4-ST 131 and O15:K52:H1 causing community-acquired uncomplicated cystitis.

A total of 148 E. coli strains displaying reduced susceptibility to ciprofloxacin (MIC > or = 2 microg/ml) and causing uncomplicated urinary tract infections in eight European countries during 2003 to 2006 were studied. Their phylogenetic groups, biochemical profiles, and antibiotic susceptibilities were determined. Determination of the O:H serotype, pulsed-field gel electrophoresis (PFGE), randomly amplified polymorphic DNA (RAPD) PCR, and multilocus sequence typing provided additional discrimination. The majority (82.4%) of the microorganisms (122/148) carried resistance to two or more additional drugs, with the pattern ciprofloxacin-trimethoprim-sufamethoxazole-tetracycline-ampicillin being the most represented (73 strains out of 148; 49.3%). Extended-spectrum beta-lactamase production was detected in 12/148 strains (8.1%), with CTX-M-15 being the most-common enzyme. Six strains out of the whole collection studied (4.0%) contained a qnrB-like gene. Overall, 55 different PFGE or RAPD PCR profiles could be distinguished, indicating a substantial heterogeneity. However, about one-third (51/148) of the strains belonged to two clonal groups: O15:K52:H1 (phylogenetic group B2, lactose-nonfermenting variant, ciprofloxacin MIC of 16 microg/ml) and O25:H4 sequence type 131 (ST-131) (phylogenetic group D, ciprofloxacin MIC of > or = 32 microg/ml). With the exception of Poland, strains of these two groups were isolated in samples from all participating countries but more frequently in samples from Spain and Italy. In some representative strains of the two main clonal groups, alterations in GyrA and ParC were the basic mechanism of fluoroquinolone resistance. In some members of the O25:H4 ST-131 group, displaying a ciprofloxacin MIC of > 32 microg/ml, additional OmpF loss or pump efflux overexpression was found. In the Mediterranean area, strains belonging to these two clonal groups played a major role in determining the high rate of fluoroquinolone-resistant E. coli strains observed in the community.

Recent findings from multinational resistance surveys: are we 'PROTEKTed' from resistance?

Continual monitoring of antimicrobial resistance rates is essential. Several large surveillance programmes have been established, including the international, longitudinal, multi-centre study PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin). Initiated in 1999, PROTEKT monitors the antibacterial susceptibility of common respiratory tract pathogens. This article reviews the findings from PROTEKT to date and anticipates future trends in antimicrobial resistance. Data from PROTEKT indicate that resistance patterns for Streptococcus pneumoniae and Haemophilus influenzae are changing, with an increasing prevalence of multi-drug resistant genotypes. Resistance to the ketolide telithromycin is very rare, with rates of S. pneumoniae susceptibility remaining >99%. The in vitro activity of telithromycin remains at a high level irrespective of pathogen genotype or phenotype.

Microbiological rationale for the utilisation of prulifloxacin, a new fluoroquinolone, in the eradication of serious infections caused by Pseudomonas aeruginosa.

Minimal inhibitory concentrations (MICs) of prulifloxacin were evaluated in comparison with ciprofloxacin, levofloxacin and moxifloxacin against a large collection (N = 300) of Pseudomonas aeruginosa strains characterised according to the CLSI/NCCLS microdilution method. Additional in vitro tests (time-kill curves and mutant prevention concentration (MPC) determinations) were carried out. Assuming a susceptibility breakpoint for prulifloxacin identical to that of ciprofloxacin, the new fluoroquinolone emerged as the most potent antibiotic (72% of susceptible strains versus 65%, 61% and 23% for ciprofloxacin, levofloxacin and moxifloxacin, respectively). Time-kill tests at 4x MIC confirmed the pronounced bactericidal potency of the drug against P. aeruginosa. Amongst the members of the fluoroquinolone class assessed, prulifloxacin produced the lowest MPC values (< or = 4 mg/L). Our in vitro results indicate that prulifloxacin represents the most powerful antipseudomonal drug available today.

In vitro fluconazole susceptibility of 1565 clinical isolates of Candida species evaluated by the disk diffusion method performed using NCCLS M44-A guidelines.

We determined the in vitro activity of fluconazole against 1565 clinical Candida spp. isolates collected from different specimens of non-AIDS outpatients and inpatients in 3 different regions of Italy. Susceptibility testing was performed by agar disk diffusion using the NCCLS document M44-A guidelines. Candida albicans was the most frequently isolated yeast (68%) followed by C. glabrata (15%), C. tropicalis (5%), C. parapsilosis (5%), and C. krusei (5%). Other yeasts represented 4% of all isolates. Of the 1565 isolates tested, 1449 (92.6%) were susceptible (S) to fluconazole, 43 (2.7%) were susceptible dose-dependent (S-DD) and 73 (4.7%) were resistant (R). Almost all (98.2%) of the C. albicans isolates were classified as S or S-DD. Despite its widespread use, fluconazole displayed good activity against the isolates we tested, and the disk diffusion method was confirmed as a reliable approach to the evaluation of in vitro susceptibility of yeasts to this antimycotic agent.

Seasonal variations in nasopharyngeal carriage of respiratory pathogens in healthy Italian children attending day-care centres or schools.

The aim of this study was to investigate seasonal variations in the prevalence of the nasopharyngeal carriage of respiratory pathogens and identify factors affecting colonisation patterns in healthy children. The nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis during two seasons (autumn and spring) was evaluated in 1580 healthy children aged 1-7 years by means of a cohort study conducted in day-care centres and schools in eight Italian cities. A questionnaire was used to obtain the epidemiological data. In all, 309 children (19.5%) carried one or more respiratory pathogens in the autumn, and 375 children (23.7%) in the spring. This variation was due to H. influenzae alone or in combination (autumn: S. pneumoniae 60, 3.8%; H. influenzae 206, 13.0%, M. catarrhalis 71, 4.5%; spring: S. pneumoniae 75, 4.7%; H. influenzae 288, 18.2%, M. catarrhalis 82, 5.2%). Colonisation with two or more pathogens increased from 9.1% in the spring to 17.3% in the autumn. Seasonal variations occur in the prevalence of the nasopharyngeal carriage of respiratory pathogens in healthy children attending day-care centres or schools in Italy. However, although statistically significant, the difference was slight and had limited clinical relevance. Therefore, seasonal influence on the nasopharyngeal carriage of respiratory pathogens in healthy children was negligible.

In vitro activity of fosfomycin against gram-negative urinary pathogens and the biological cost of fosfomycin resistance.

The aim of this study was to reassess the activity of fosfomycin against recently isolated uropathogens circulating in Italy and to evaluate the effect of fosfomycin resistance on the expression of several virulence traits using the rare mutant strains. In vitro activity of fosfomycin was evaluated using 441 Gram-negative organisms isolated from patients with uncomplicated urinary tract infections (UTIs). Fosfomycin was the most active antibiotic against Escherichia coli (99% susceptibility). The activity against Proteus mirabilis was more potent than that of co-trimoxazole and nitrofurantoin (87.5, 67 and 0% susceptibility, respectively). The other microorganisms, accounting for about 7% of all pathogens tested, showed variable susceptibilities to fosfomycin. Compared with susceptible strains, fosfomycin-resistant mutants showed a reduced rate of growth and were impaired in their ability to adhere to uroepithelial cells and to urinary catheters. They were also more resistant to UV irradiation and to phage T7 and showed diminished rates of colicin synthesis and transfer of plasmids.

Effect of fosfomycin alone and in combination with N-acetylcysteine on E. coli biofilms.

Four slime-producing uropathogenic Escherichia coli strains were used to investigate the activity of fosfomycin and N-acetylcysteine (NAC) against biofilms developed on 96-well polystyrene tissue culture plates. Biofilms aged, respectively, 5 (initial) and 48 h (mature) and two fosfomycin concentrations (128 and 2000 mg/l) were used. The effect of various levels (0.007-8 mg/ml) of NAC alone and in combination with fosfomycin on the formation or disruption of biofilms was assessed. Following exposure to the drugs, the percentage of residual slime relative to the control, ranged from 62.5-100 to 26.2-64.1% in the presence of 0.007 and 8 mg/ml of NAC. After treatment of pre-formed biofilms with NAC at the highest concentrations used, the remaining exopolysaccharide matrix was reduced to 25-68% of the amount found with the untreated control. Exposure to fosfomycin at 2000 mg/l reduced biofilms 40-57 and 41-49% for the initial and mature forms, respectively. Fosfomycin was more active at 2000 mg/l combined with NAC 2 mg/ml. Under these conditions initial and mature biofilms were reduced 66-80 and 60-73%, respectively. NAC, when used in combination, enhanced fosfomycin bactericidal activity producing a 99-99.9% reduction in viable cells. Fosfomycin and NAC at concentrations achievable in urine displayed a synergistic effect promoting both the formation of biofilms and reduction of sessile cell viability.

Bacteremic pneumococcal community-acquired pneumonia in children less than 5 years of age in Italy.

BACKGROUND: This study was designed to determine the proportion of bacteremic pneumococcal cases in a group of pediatric subjects with community-acquired pneumonia (CAP), the importance of the different serotypes and the impact of the currently available pneumococcal conjugate vaccines (PCVs). METHODS: The study involved children who were ≤5 years with radiographically confirmed CAP admitted to hospital in Italy between September 2008 and March 2011. A diagnosis of laboratory-confirmed bacteremic pneumococcal CAP was made in the presence of a culture and/or real-time polymerase chain reaction (PCR) positive for Streptococcus pneumoniae. RESULTS: A total of 510 children were included in the study. Pneumococcal CAP was diagnosed in 73 cases (14.3%): S. pneumoniae was identified by means of positive real-time PCR in 67 cases (91.8%), a positive blood culture in 1 (1.4%) and both in 5 (6.8%). Complicated pneumonia was observed significantly more often in the pneumococcal-positive cases (P=0.02) and empyema was the main complication (P=0.007). Serotype 19A was most frequently encountered (17 cases; 25.8%), followed by serotypes 14 (10 cases, 15.1%), 4 (5 cases, 7.6%) and 3 (4 cases, 6.1%). The theoretical coverage offered by the available PCVs was calculated to be 31% for PCV7, 37% for PCV10 and 71% for PCV13. CONCLUSIONS: In Italy, bacteremic pneumococcal CAP accounts for a significant number of CAP cases in children who were ≤5 years, with serotypes 19A and 14 being the most frequent. This suggests that PCV13 is the best means of preventing pneumococcal CAP.

Detection of Streptococcus pneumoniae and identification of pneumococcal serotypes by real-time polymerase chain reaction using blood samples from Italian children ≤ 5 years of age with community-acquired pneumonia.

Streptococcus pneumoniae is a leading cause of severe life-threatening infections. Laboratory identification and serotyping of this pathogens is desirable to monitor vaccine impact and coverage; however, especially in pediatric patients, the yield of traditional microbiological diagnostic procedures can be very low. The aim of this study was to develop real-time polymerase chain reaction (PCR)-based assays to be performed directly on blood samples to identify the most common capsular serotypes causing pneumonia in Italian children (≤ 5 years of ages) after the introduction of the 7-valent conjugate vaccine. Our real-time PCR-based assays showed high sensitivity (at least 35 fg of pneumococcal DNA), and they were validated with 49 well-characterized pneumococcal isolates, 8 nonpneumococcal isolates, 13 simulated blood clinical samples loaded with S. pneumoniae of known serotypes, and 46 blood clinical samples. All the strains tested and the simulated blood clinical samples were correctly typed by the technique. Real-time PCR allowed serotyping in 37/46 children ≤ 5 years of age (80.4%) in whom pneumonia was diagnosed in four Italian hospitals. Non-PCV7 serotypes accounted for at least 47.8% (22/46) of cases, serotype 19A being the most common (34.7%, 16/46). Although, it is not known at present whether the incidence of 19A serotype is attributable to the use of PCV7 only, expanding pneumococcal serotype coverage has clearly the potential to prevent a larger number of pneumonias in Italian children less than ≤ 5 years of age. Molecular methods are of increasing importance in the diagnosis of pneumococcal pneumonia and in monitoring serotype distribution and replacement.

The ARESC study: an international survey on the antimicrobial resistance of pathogens involved in uncomplicated urinary tract infections.

The ARESC (Antimicrobial Resistance Epidemiological Survey on Cystitis) study is an international survey to investigate the prevalence and susceptibility of pathogens causing cystitis. Female patients (n=4264) aged 18-65 years with symptoms of uncomplicated cystitis were consecutively enrolled in nine European countries as well as Brazil during 2003-2006. Pathogens were identified and their susceptibility to nine antimicrobials was determined. Escherichia coli accounted for 76.7% of isolates. Among E. coli, 10.3% of the isolates were resistant to at last three different classes of antimicrobial agents. Resistance was most common to ampicillin (48.3%), trimethoprim/sulfamethoxazole (29.4%) and nalidixic acid (18.6%). Fosfomycin, mecillinam and nitrofurantoin were the most active drugs (98.1%, 95.8% and 95.2% susceptible strains, respectively) followed by ciprofloxacin, amoxicillin/clavulanic acid and cefuroxime (91.7%, 82.5% and 82.4%, respectively). Resistance to ciprofloxacin was >10% in Brazil, Spain, Italy and Russia. Overall, Proteus mirabilis were more susceptible to beta-lactams and less susceptible to non-beta-lactams than E. coli, whereas Klebsiella pneumoniae strains, which are intrinsically resistant to ampicillin, were less susceptible to mecillinam (88.8%), fosfomycin (87.9%), cefuroxime (78.6%) and nitrofurantoin (17.7%). Resistance was rare in Staphylococcus saprophyticus, with the exception of ampicillin (36.4%) and trimethoprim/sulfamethoxazole (10.2%). In Italy, Spain, Brazil and Russia, the countries most affected by antimicrobial resistance, extended-spectrum beta-lactamase (ESBL) enzymes (mainly CTX-M type) were detected in 48 strains (39 E. coli, 6 K. pneumoniae and 3 P. mirabilis). Despite wide intercountry variability in bacterial susceptibility rates to the other antimicrobials tested, fosfomycin and mecillinam have preserved their in vitro activity in all countries investigated against the most common uropathogens.

Co-prescriptions with itraconazole and fluconazole as a signal for possible risk of drug-drug interactions: a four-year analysis from Italian general practice.

PURPOSE: To determine the prevalence of concomitant use of drugs potentially responsible for interactions among itraconazole and fluconazole users in general practice. METHODS: During the years 1999-2002, we obtained information from the 'Health Search Database', (HSD) an Italian general practice research database. Among a total sample of 457 672 eligible patients, we included those aged >16 years, and whose diagnoses could be classified as mycosis. Itraconazole and fluconazole users were then selected. A potentially drug-drug interaction (DDI) occurred when the use of concomitant drugs were recorded within +/-30 days from the date of the first azoles prescription. Interacting drugs were classified according to the summary of product characteristics (SPC) as provided by the Italian Pharmaceutical Repertory (REFI). RESULTS: From 18 323 cases of mycosis, we selected 4843 itraconazole and 1446 fluconazole users. Potentially interacting drugs were prescribed in 8.7% of itraconazole and 6.1% of fluconazole users. For itraconazole, calcium channel blockers were the most common interacting drugs (3.3%), followed by statins (1.7%) and clarithromycin (1.3%), whereas gestoden + ethynylestradiol (2.5%) and benzodiazepines (1.8%) resulted as the most common interacting drugs among fluconazole users. CONCLUSION: Data indicate a relevant prevalence of concomitant use of medications potentially leading to drug interactions among azoles users. Because of the wide use of these medications in general practice, they should be used with clinical monitoring in view of their known side effects as well as their potential risk for drug interaction.

Antibiotic prescribing for acute and recurrent cystitis in primary care: a 4 year descriptive study.

OBJECTIVES: To explore the antibiotic prescribing pattern for cystitis and the patient-related variables associated with prescription during a 4 year period among Italian general practitioners (GPs). METHODS: We obtained information from the 'Health Search Database' (HSD), an Italian general practice research database. From a total sample of 457 672 eligible patients aged >16 years registered up to December 2002, we included those whose diagnoses could be classified as acute (uncomplicated and complicated) and recurrent cystitis. Patients' features and prevalence of antibiotic users were assessed. RESULTS: Of 35 129 cases diagnosed during the period 1999-2002, 96.0% of them were acute cystitis (39.2% recorded as uncomplicated). The prevalence of cases with acute complicated and uncomplicated cystitis slightly increased during the 4 year period, whereas it remained stable for recurrent cystitis. Most of the cystitis cases reported no diagnostic tests. More than 70% of patients were prescribed with at least one antibiotic, with a 4-fold increased risk of antibiotic use for acute cystitis throughout the study period. The prevalence of antibiotic users reached 86.2% for both acute uncomplicated and complicated cystitis in 2002, and 81.5% for recurrent cystitis. Fluoroquinolones represented the most common antibiotics being prescribed although they markedly decreased during these years. Fosfomycin trometamol use increased dramatically, becoming the first choice for any type of cystitis. CONCLUSIONS: Data indicate an evident rise in antibiotic use mostly related to fosfomycin trometamol. They also indicate that such a prescriptive trend finds confirmation from the available evidence for acute uncomplicated cystitis, although the management of recurrent cystitis could be further improved.

European survey of glycopeptide susceptibility in Staphylococcus spp.

OBJECTIVE: To reassess the relative potencies of teicoplanin and vancomycin following several years of clinical usage. METHODS: The glycopeptide susceptibilities of clinical isolates of staphylococci collected from 70 hospitals in 1995 were determined using NCCLS (National Committee for Clinical Laboratory Standards) methods. RESULTS: In total, 2885 isolates of Staphylococcus aureus and 1480 isolates of coagulase-negative staphylococci were collected. S. aureus was significantly less susceptible to vancomycin (MIC50 1 mg/L) than teicoplanin (MIC50 0.5 mg/L), but the reverse was the case for S. haemolyticus and S. epidermidis. No S. aureus isolate was resistant (>/=32 mg/L) to either glycopeptide, but nine isolates of coagulase-negative staphylococci had an MIC of teicoplanin of 32 mg/L. Respiratory isolates of S. aureus were less susceptible to glycopeptides than those from other sites. Staphylococci from Belgium and Italy were less susceptible to teicoplanin than isolates from other countries. CONCLUSIONS: This European survey shows that in 10 years of clinical use there have been no major changes in the susceptibility of staphylococci to the glycopeptides.

In vitro activity of quinupristin/dalfopristin against selected bacterial pathogens isolated in Italy.

OBJECTIVE: To evaluate the activity of quinupristin/dalfopristin, a new injectable streptogramin, against 732 clinical strains recently isolated in Italy. METHODS: Susceptibility tests were performed according to NCCLS-guided MIC methodology. Pathogens included in the evaluation included 108 Staphylococcus aureus isolates, 124 coagulase-negative staphylococcal isolates, 158 Streptococcus pyogenes isolates, 30 Streptococcus agalactiae isolates, 30 b-hemolytic streptococcal isolates, 18 Streptococcus sanguis isolates, 80 Streptococcus pneumoniae isolates, 69 Enterococcal isolates, 40 Haemophilus influenzae isolates, 30 Moraxella catarrhalis isolates and, finally, 30 Gram-positive and 25 Gram-negative anaerobes. RESULTS: Quinupristin/dalfopristin inhibited Staphylococcus aureus and other Staphylococcus spp., irrespective of their oxacillin or erythromycin resistance phenotypes. Similarly, streptococci were fully inhibited by quinupristin/dalfopristin. Enterococcus faecalis was not included in the spectrum of this streptogramin, while isolates of Enterococcus faecium were inhibited by the new compound. Respiratory pathogens such as H. influenzae and M. catarrhalis were inhibited by quinupristin/dalfopristin as well as all Gram-negative anaerobes tested. CONCLUSIONS: These findings suggest a putative role for quinupristin/dalfopristin in the empirical treatment of severe nosocomial and community-acquired infections caused by pathogens often displaying resistance to multiple antibiotics. This drug may provide an alternative to glycopeptide compounds.

Antibacterial activity of oral antibiotics against community-acquired respiratory pathogens from three European countries.

Antimicrobial resistance is universally recognized as a major problem. A European resistance survey was established to monitor the activity of widely used oral antibiotics against common respiratory tract pathogens. Studies were conducted in Italy, Spain and Austria to monitor resistance patterns among respiratory Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus aureus and Klebsiella pneumoniae to amoxicillin, co-amoxiclav, penicillin, cefaclor, cefadroxil, cefalexin, cefprozil, cefuroxime, cefixime, ceftibuten, cefpodoxime, clarithromycin and azithromycin (the antibiotics tested varying slightly from country to country). Minimum inhibitory concentrations were determined using the NCCLS-recommended broth microdilution method. Among the antibiotics tested, cefpodoxime, an oral cephalosporin, was remarkably active against the major respiratory pathogens in all three countries. Cefpodoxime was more potent than cefaclor, cefixime and ceftibuten against pneumococci, especially against strains with decreased sensitivity to penicillin, and more active than cefaclor and cefuroxime against Gram-negative respiratory pathogens. Pneumococci and staphylococci displayed a very high level of in vitro macrolide resistance. These data indicate that cefpodoxime represents an appropriate choice in the treatment of community-acquired respiratory tract infection in the three countries surveyed.