Antimicrobial activity of prulifloxacin in comparison with other fluoroquinolones against community-acquired urinary and respiratory pathogens isolated in Greece.

Prulifloxacin, the prodrug of ulifloxacin, is a broad-spectrum fluoroquinolone rather recently introduced in certain European countries. We compared the antimicrobial potency of ulifloxacin with that of other fluoroquinolones against common urinary and respiratory bacterial pathogens. The microbial isolates were prospectively collected between January 2007 and May 2008 from patients with community-acquired infections in Greece. Minimum inhibitory concentrations (MICs) were determined for ciprofloxacin, levofloxacin, moxifloxacin (for respiratory isolates only), and ulifloxacin using the E-test method. The binary logarithms of the MICs [log2(MICs)] were compared by using the Wilcoxon signed-ranks test. A total of 409 isolates were studied. Ulifloxacin had the lowest geometric mean MIC for the 161 Escherichia coli, 59 Proteus mirabilis, and 22 Staphylococcus saprophyticus urinary isolates, the second lowest geometric mean MIC for the 38 Streptococcus pyogenes respiratory isolates (after moxifloxacin), and the third lowest geometric mean MIC for the 114 Haemophilus influenzae and the 15 Moraxella catarrhalis respiratory isolates (after ciprofloxacin and moxifloxacin). Compared with levofloxacin, ulifloxacin had lower log2(MICs) against E. coli (p < 0.001), P. mirabilis (p < 0.001), S. saprophyticus (p < 0.001), and S. pyogenes (p < 0.001). Compared with ciprofloxacin, ulifloxacin had lower log2(MICs) against P. mirabilis (p < 0.001), S. saprophyticus (p = 0.008), and S. pyogenes (p < 0.001), but higher log2(MICs) against H. influenzae (p < 0.001) and M. catarrhalis (p = 0.001). In comparison with other clinically relevant fluoroquinolones, ulifloxacin had the most potent antimicrobial activity against the community-acquired urinary isolates studied and very good activity against the respiratory isolates.

DNA bacterial load in children with bacteremic pneumococcal community-acquired pneumonia.

This study was conducted to evaluate the association between pneumococcal DNA load and parapneumonic pleural effusion (PPE) in children with community-acquired pneumonia. Bacterial load was quantified and related to the presence of PPE with or without empyema in 72 otherwise healthy children aged ≤5 years who were hospitalised because of radiographically confirmed CAP and showed a real-time polymerase chain reaction that was positive for Streptococcus pneumoniae. The proportion of children with a high bacterial load (i.e. ≥265 DNA copies/mL) was larger among the subjects with PPE than those without it. Multivariate analysis showed that a high bacterial load was significantly associated with PPE (OR 8.65; 95% CI 1.10-67.8 vs a bacterial load of <125 copies/mL). Children with infection due to pneumococcal serotype 19A were at highest risk of developing PPE (OR 7.44; 95% CI 1.10-50.4 vs all other typeable serotypes). The patients with CAP due to pneumococcal serotypes that are not included in the 13-valent conjugate vaccine (PCV13) were more frequently affected by PPE than those with infections associated with serotypes included in the vaccine, except for serotype 19A. Bacterial loads of ≥265 DNA copies/mL are significantly associated with PPE, and serotype 19A is significantly associated with a high bacterial load and the development of PPE. The mean bacterial load of the patients with empyema was higher than that of patients with simple PPE. Although further studies are required, it seems that serotypes not included in PCV13 can play a major role in causing a higher bacterial load and PPE.

Activity of daptomycin on biofilms produced on a plastic support by Staphylococcus spp.

The aim of this study was to assess whether the novel lipopeptide daptomycin might be capable of disrupting or inhibiting the synthesis of biofilms produced by staphylococci. Fourteen recently isolated slime-producing methicillin-susceptible (MET-S) and methicillin-resistant (MET-R) strains (three MET-S Staphylococcus aureus, three MET-R S. aureus, three MET-S Staphylococcus epidermidis, three MET-R S. epidermidis and two vancomycin-intermediate S. aureus (VISA)) were tested. Slime formation on polystyrene plates was quantified spectrophotometrically. Daptomycin (2-64 mg/L) inhibited slime synthesis by > or =80% in MET-S strains, by 60-80% in MET-R S. aureus and by 70-95% in MET-R S. epidermidis. At 64 mg/L, biofilm synthesis decreased by 80% in the VISA isolates. Daptomycin also disrupted pre-formed biofilm: >50% breakdown of initial biofilm (5h) was observed in all strains. Disruption of mature biofilms (48 h), in terms of percentage, was more variable depending on the strain, ranging from ca. 20% in a MET-R S. epidermidis strain to almost 70% in two MET-S strains (one S. aureus and one S. epidermidis). Daptomycin at concentrations achievable during therapy promoted a statistically significant inhibition of slime synthesis (preventing biofilm building) and induced slime disruption (disaggregating its structure) both in initial and mature biofilms on a plastic support in all staphylococcal strains studied.

Activity of moxifloxacin on biofilms produced in vitro by bacterial pathogens involved in acute exacerbations of chronic bronchitis.

The aim of this study was to assess whether moxifloxacin is able to inhibit the synthesis of and to disrupt biofilms produced in vitro by bacterial pathogens involved in acute bacterial exacerbations of chronic bronchitis. Three strains each of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Staphylococcus aureus and Escherichia coli recently isolated from clinical respiratory specimens and capable of slime production were used. Biofilm formation on polystyrene plates was quantified spectrophotometrically by established methodologies. Moxifloxacin (0.5 mg/L) inhibited slime synthesis by >70% in S. aureus, H. influenzae and S. pneumoniae, 45-70% in E. coli and 35-70% in M. catarrhalis. Disruption of pre-formed structures was also promoted by moxifloxacin both for initial (5h) and mature (48 h) biofilms. Drug concentrations reached during therapy (0.5-4 mg/L) resulted in a breakdown of initial biofilm of 60-80% in H. influenzae and S. pneumoniae, 48-86% in S. aureus, 37-69% in M. catarrhalis and 51-71% in E. coli. Mature biofilms were less susceptible to degradation. Moxifloxacin at concentrations that can be achieved in the bronchial mucosa during therapy therefore promotes a significant inhibition of biofilm synthesis and induces slime disruption, a feature that may be instrumental in reducing the exacerbations so frequently observed in this condition.

In vitro activity of prulifloxacin against Escherichia coli isolated from urinary tract infections and the biological cost of prulifloxacin resistance.

Minimum inhibitory concentrations (MICs) and mutant prevention concentrations (MPCs) of prulifloxacin against 30 strains of Escherichia coli isolated from urinary tract infections as well as the 'biological cost' related to acquisition of resistance to the same drug in 10 uropathogenic E. coli were assessed. In terms of MIC(90), prulifloxacin was more potent than ciprofloxacin and levofloxacin. Prulifloxacin produced lower or equal MPC values than the other two fluoroquinolones (93.3% and 73.3% compared with levofloxacin and ciprofloxacin, respectively). Compared with susceptible strains, prulifloxacin-resistant mutants showed a reduced rate of growth (ranging from 20.0% to 98.0% in different culture media and incubation conditions) and a decreased fitness index (ranging from 0.959 to 0.999). They were also impaired in their ability to adhere to uroepithelial cells and urinary catheters (11.7-66.4% and 16.3-78.3% reduction, respectively) and showed a lower surface hydrophobicity (51.2-76.0%). They were more susceptible to ultraviolet irradiation (30.6-93.8% excess mortality), showed increased resistance to colicins and diminished transfer of plasmids (<1-8.5x10(-8) vs. 3.3x10(-7)-2.4x10(-4)). Synthesis of haemolysin and type I fimbriae and production of flagella were also adversely affected. This study demonstrates a strict relationship between acquisition of prulifloxacin resistance and loss of important virulence traits. In this transition, E. coli pays a severe biological cost that entails a general reduction of fitness, thus compromising competition with susceptible wild-type strains in the absence of the drug.

A therapeutic approach in the treatment of infections of the upper airways: thiamphenicol glycinate acetylcysteinate in sequential treatment (systemic-inhalatory route).

Eight hundred and seventeen patients with upper respiratory tract infections were treated with thiamphenicol glycinate acetylcisteinate (TGA) or other standard antibiotics for 6-10 days in a randomised trial. In 419 out of 817 patients, the symptomatology was severe and they were treated with TGA in sequential therapy (TGA 500 mg- as thiamphenicol- b.i.d. intramuscularly on the first day and TGA 500 mg b.i.d by aerosol during the following days) (n=151), or with antibiotics of comparison (n=268) given intramuscularly. In this group the disappearance of the symptomatology with TGA ranged from 90 percent of the patients with otitis media to 94 percent in pharyngotonsillitis and rhinosinusitis; in this latter group TGA was significantly better than cefazolin. In 398 patients with mild symptomatology TGA (250 mg as thiamphenicol- b.i.d.) was given by aerosol (n=149) and the antibiotics of comparison by oral route (n=249). In TGA patients, the disappearance of symptoms was achieved in 87 percent of those with rhinosinusitis, in 88 percent of those with pharyngotonsillitis and in 91 percent of those with otitis media. S. pyogenes, S. pneumoniae and H. influenzae were the most frequently isolated pathogens, and none of the isolated bacteria proved to be resistant to TGA. Microbiological eradication was obtained in TGA groups in a percentage of patients ranging from 90.2 to 96.0 percent in those with severe forms, and from 86.2 to 91.6 percent in those with a mild clinical picture. Investigators rated the TGA efficacy as excellent in 96-100 percent of the patients with severe forms and in 85.5-100 percent of the patients with mild forms, whereas in the group of patients with rhinosinusitis the comparison of TGA versus other treatment was significantly in favour of TGA. The Investigator rating of treatment tolerability significantly favoured TGA in sequential treatments in comparison to the other antibiotics. No patient dropped out from the trial because of adverse events.

Ideal microbiological and pharmacological characteristics of a quality antimicrobial agent: comparing original and generic molecules.

This article critically evaluates the main in vitro and in vivo studies published which compare generic with the original molecules, both those administered orally and parenterally. The authors indicate that caution should be used in assuming bioequivalence of the generic drug with its clinical efficacy in clinical practice. In fact, mild differences in the content of the active ingredient, less relevant in healthy volunteers, may have an impact in the actual population, which is heterogeneous for age, sex, weight, concomitant risk factors and severity of the underlying disease, as in critically ill patients, with consequences for the patient and ecosystem. Nowadays the requirements for authorization to commercialize a generic antimicrobial agent are focused on demonstration of bioequivalence to the original molecule, with a range variability of +/-20%. However this kind of trial is not sufficient to predict the actual profile in clinical practice, particularly in critically ill patients. Thus while generics can represent an opportunity for physicians, patients and healthcare systems the regulatory procedures do not seem exhaustive, and it is probably necessary to define an ad hoc technical standard of quality before their commercialization and to perform adequate clinical trials regarding efficacy and safety of the "equivalent molecule", especially for drugs used in critically ill patients.

The importance of the development of antibiotic resistance in Staphylococcus aureus.

Hospital- and community-acquired Staphylococcus aureus infections pose a substantial burden in terms of morbidity, mortality and health care costs. The introduction of new antibiotics to counter this pathogen has frequently been closely followed by the emergence of resistant strains. Most significantly, S. aureus isolates resistant to beta-lactams have become common, and many of these are also resistant to beta-lactamase-resistant penicillins. The rapid spread of methicillin-resistant S. aureus (MRSA) clones across the world often results in hospital outbreaks, but implementation of appropriate control measures usually reduces prevalence to sporadic levels. However, the recent emergence of MRSA infections in the community, affecting patients with no established risk factors for MRSA acquisition, is likely to impact significantly on future strategies for control of nosocomial MRSA. In contrast to other antibiotic classes, S. aureus resistance to glycopeptides did not emerge until nearly 40 years after their clinical introduction, and as a result this drug class has remained the mainstay of treatment for MRSA infections. However, a number of vancomycin-intermediate S. aureus isolates have emerged worldwide and four fully resistant S. aureus isolates have been reported in the USA. This raises the concern that the current first-line treatment for MRSA infection may become ineffective in an increasing proportion of cases in the near future. New classes of antibiotic are urgently needed to treat infections with this growing population of multidrug-resistant S. aureus, and the recently introduced oxazolidinone linezolid and the cyclic lipopeptide daptomycin are welcome additions to the ever-narrowing range of therapies effective against this pathogen.

Efficacy of N-acetyl-cysteine in combination with thiamphenicol in sequential (intramuscular/aerosol) therapy of upper respiratory tract infections even when sustained by bacterial biofilms.

A total of 102 patients with recurrent upper respiratory tract infections underwent microbiological exploration with appropriate sampling and direct biopsies of the infected sites. Therapy was then started and on day 1 each patient received two intramuscular injections of thiamphenicol glycinate acetylcysteinate (TGA). From day 2 to 10 sequential therapy with the same drug was continued employing TGA administered by aerosol. All putative etiologic agents recovered were susceptible to thiamphenicol and only 24 demonstrated the ability to produce in vitro biofilms. The organisms comprised 10 Staphylococcus aureus, 6 Streptococcus pyogenes, 4 Streptococcus pneumoniae and 3 Haemophilus influenzae. Of the 24 subjects in whom biofilms were demonstrated to be present in vivo by Scanning Electron Microscopy, clinical and bacteriological cure was obtained in 21 cases (87.5%) following sequential therapy with TGA. Failures were considered to be persistent signs and symptoms at day 15 after initiation of treatment and lack of eradication of 3 S. aureus strains, despite their in vitro susceptibility to thiamphenicol. Very few adverse events attributable to TGA were reported in this cohort of patients. In no case was discontinuation of treatment deemed necessary by the attending physician.

Susceptibility of Streptococcus pneumoniae to penicillin, azithromycin and telithromycin (PROTEKT 1999-2003).

Isolates of Streptococcus pneumoniae collected over the first 4 years of the PROTEKT study were tested for susceptibility to penicillin, azithromycin and telithromycin. A total of 20,750 isolates were collected from 39 countries. Penicillin non-susceptibility rates were stable over the study period; overall, 21.8% of isolates were resistant. Azithromycin resistance increased from 31.0% in Year 1 to 36.3% in Year 4. Resistance rates for penicillin and azithromycin varied between countries and were highest in France, Spain, South Africa, USA and the Far East. Multidrug resistance in S. pneumoniae did not change significantly over the 4 years, with an overall rate of 38.6%. Telithromycin retained good activity against S. pneumoniae (0.1% of isolates resistant), including multidrug-resistant isolates.

The Sentinel Project: an update on the prevalence of antimicrobial resistance in community-acquired respiratory Streptococcus pneumoniae and Haemophilus spp. in Italy.

A total of 460 Streptococcus pneumoniae and Haemophilus spp. collected from respiratory infections during 2000 was tested for their susceptibility to 15 selected antibiotics. Overall, penicillin resistance among pneumococci was 10.5%, while lack of susceptibility to macrolides, co-trimoxazole, tetracycline and chloramphenicol reached 35.2%, 26.2%, 22.6% and 6.0%, respectively. Amoxicillin/clavulanic acid and levofloxacin were the most potent compounds (100% and 99.9% susceptible strains, respectively). Among isolates of Haemophilus influenzae and Haemophilus parainfluenzae, beta-lactamase production (12.5% and 10%, respectively), and co-trimoxazole (19.9% and 40.0%) and clarithromycin (11.2% and 40.0%) resistance were the prevalent threats. This study confirms the trend observed in Italy since 1992: macrolide resistance among respiratory microorganisms is increasing, while several drugs including amoxicillin/clavulanic acid, third generation injectable cephalosporins and fluoroquinolones remain active on the great majority of these pathogens.

Antibiotic susceptibility and serotype distribution in Streptococcus pneumoniae circulating in Italy: results of the SEMPRE surveillance study (2000-2002).

During 2000-2002, 20 clinical microbiology centres collected 1623 Streptococcus pneumoniae isolates. Susceptibility to penicillin, amoxicillin, amoxicillin/clavulanic acid, cefaclor, cefuroxime, cefotaxime, clarithromycin, ciprofloxacin, levofloxacin, rifampicin and teicoplanin was determined locally by the Etest and/or by the microdilution method by three co-ordinating centres. Total resistance to penicillin increased from 15.2% to 16.1% and macrolide resistance increased from 37.9% to 43.7%. Overall, the most effective drugs (>99% susceptible strains) were amoxicillin, amoxicillin/clavulanic acid, levofloxacin and rifampicin. The most frequent serotypes were: 23F (15.8%), 3 (10.8%) 14 (9.1%), 19F (9.1%), 6B (7.2%), 19A (6.9%) and 6A (4.8%). In conclusion, penicillin and macrolide resistance is increasing in Italy, whilst fluoroquinolone currently remains active. The most common serotypes circulating are included in the heptavalent conjugate vaccine, with the exception of type 3.

Predicting the clinical efficacy of generic formulations of ceftriaxone.

Time above MIC (T>MIC) is regarded as the best pharmacokinetic/pharmacodynamic (PK/PD) parameter for predicting the clinical efficacy of cephalosporins. The concentration of non-protein-bound proprietary ceftriaxone (Rocephin, Roche) in body fluids exceeds this PK/PD criterion for the treatment of Streptococcus pneumoniae respiratory infections. However, the pharmaceutical quality of several generic products may be inferior to Rocephin. We have calculated the variations in fluid concentrations of 34 generic formulations of ceftriaxone and, by mathematical modelling, the implications for attainment of recommended PK/PD criteria, specifically: Treatment of S. pneumoniae infections based on the time that non-protein-bound ceftriaxone concentration in pleural fluid exceeds the CLSI (NCCLS) breakpoint of 4 mg/L for identification of resistant isolates. Impact upon Monte Carlo simulations in plasma for the treatment of S. pneumoniae infections based on T>MIC for 50% dosing interval. Rocephin exceeded the required PK/PD parameters at the mean and two standard deviation levels in both investigations. In contrast, most generic products failed to achieve required PK/PD levels in both investigations. As a consequence, some generic formulations of ceftriaxone may increase risks of clinical failure and/or emergence of resistant isolates.

Antimicrobial susceptibility patterns of contemporary pathogens from uncomplicated urinary tract infections isolated in a multicenter Italian survey: possible impact on guidelines.

During 2004 four Italian Laboratories assessed the prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in female out-patients. A total of 600 urine samples from individuals aged 18-65 were studied. The overall prevalence of Escherichia coli was 85.3%. Klebsiella pneumoniae, Staphylococcus saprophyticus, Proteus mirabilis, Enterococcus faecalis and other rarer species were far less represented. Determination of the antibiotic susceptibility pattern of the entire collection of E. coli (512 organisms) revealed that among the drugs analyzed ampicillin was the least active molecule with only 62.5% of the strains being inhibited. Amoxicillin-clavulanate and cefuroxime displayed a higher potency (87.7% and 89.2% respectively). Cotrimoxazole inhibited only 70.1% of the uropathogens. The three fluoquinolones tested had comparable activity ranging from 83.0% for ciprofloxacin, to 83.6% for levofloxacin and 84.9% for prulifloxacin, indicating an identical spectrum of cross resistance. Nitrofurantoin (96.7%) and fosfomycin (98.6%) were the most potent drugs. Against the whole collection of uropathogens, only cefuroxime, nitrofurantoin and fosfomycin overcame the threshold of 90% activity, with the fluoroquinolones and amoxicillin-clavulanate suffering from about 15% resistance. The results of this survey strongly support the conclusions of recent Italian guidelines concerning the best empiric treatment of UTI in this country today.

Parallel Western blot analysis for HIV-1 and HIV-2 antibodies: absence of HIV-2 infection in Italian subjects at risk for AIDS.

Since HIV-2 infection has been identified in some European countries, we investigated whether HIV-2 infection is present in groups of Italian subjects at risk for AIDS. Our results clearly indicate that the parallel Western blot assay for HIV-1 and HIV-2 antibodies can detect HIV-2 infection, which is presently not epidemic in Italy. Careful examination of the serological data is mandatory before announcing the detection of HIV-2-infected patients.

In vitro assessment of the postantibiotic effect of lomefloxacin against gram-positive and gram-negative pathogens.

We evaluated the postantibiotic effect (PAE) of lomefloxacin, a new difluorinated quinolone, on multiply drug-resistant gram-positive and gram-negative clinical pathogens. Lomefloxacin induced a PAE of about 2 hours in gram-negative and gram-positive bacteria exposed for 1 hour to concentrations corresponding to four times their minimum inhibitory concentrations (MIC). PAE values (hours) ranged from 1.8 with Serratia marcescens to 2.5 with Staphylococcus aureus. No significant differences in PAE values were found for ciprofloxacin or ofloxacin against the same pathogens. The PAE was increased when the time of drug exposure was increased to 2 hours. These results indicate that lomefloxacin has a PAE equivalent to that of other fluoroquinolones.

Role of global surveillance in combating bacterial resistance.

In recent years, one of the more alarming aspects of clinical microbiology has been the dramatic increase in the incidence of antibacterial resistance among pathogens causing nosocomial as well as community-acquired infections. Numerous antibacterial agents have lost their in vitro activity as a result of selective pressure exerted by antibacterial usage. There is a general consensus on the fact that emergence and spread of resistance may be delayed by improving hygiene measures, reducing inappropriate use of antibacterials, and adopting successful empirical therapy based on sound epidemiological data. As a consequence, worldwide international studies of antibacterial resistance surveillance have been established. Surveys such as the Alexander Project and the SENTRY Programme supply high quality data to participating countries, stimulate collaboration and provide the educational information required for clinical decision-making that may result in improved cure rates.

Stability in the presence of widespread beta-lactamases. A prerequisite for the antibacterial activity of beta-lactam drugs.

Bacterial resistance to the beta-lactam drugs is extremely widespread, as a result of extensive drug use. Loss of susceptibility is primarily attributable to hydrolysis by inactivating enzymes, namely the beta-lactamases. While the number of characterised beta-lactamases may exceed 100, only a few are a problem in the treatment of community-acquired infections (TEM-1, TEM-2, SHV-1, BRO-1). Chromosomally mediated and extended-spectrum beta-lactamases are usually dominant in nosocomial pathogens where oral antibiotic therapy is seldom used. Therefore, the threat posed by beta-lactamases must be considered in general practice. Several effective strategies have been implemented in order to overcome beta-lactamase-mediated resistance, e.g. use of non-beta-lactam drugs or beta-lactamase inhibitors. Another option has been the development of new beta-lactam compounds that possess a high intrinsic stability against the hydrolytic action of common beta-lactamases. Among these compounds, the oral third generation cephalosporins represent an important breakthrough. Cefetamet pivoxil, a new oral third generation cephalosporin, is characterised by excellent antimicrobial potency against Enterobacteriaceae, and Moraxella (Branhamella) catarrhalis and Haemophilus influenzae, irrespective of their ability to produce beta-lactamases. The Gram-positive respiratory pathogens, Streptococcus pyogenes and penicillin-susceptible S. pneumoniae, are also satisfactorily covered. The activity of cefetamet has recently been corroborated in a survey conducted in Italy involving 4191 isolates. However, cefetamet shows no activity against enterococci, staphylococci, Listeria, alpha-streptococci, Pseudomonas, Acinetobacter and anaerobes. Given this antibacterial profile, cefetamet pivoxil may provide a useful alternative to other oral antibacterial agents in the empirical therapy of acute community-acquired respiratory and urinary tract infections. From the results of the Italian survey, cefetamet emerged as the only agent among those considered (which included cefuroxime, cefaclor, cefalexin, cefadroxil, ampicillin, amoxicillin/clavulanic acid, ampicillin/sulbactam, doxycycline, erythromycin and clindamycin) that might be selected as the drug of choice in the empirical therapy of outpatient infections.

Multidrug-resistant gram-positive pathogens. An update on current microbiological patterns.

Although resistance has developed among Gram-positive pathogens to penicillins, cephalosporins, aminoglycosides, quinolones and macrolides, the glycopeptides seem to remain largely unaffected. However, the recent emergence and range of glycopeptide resistance in enterococci, well documented in the USA but not in the rest of the world, have prompted this European surveillance study. The European Glycopeptide Resistance Survey was undertaken in 1995 in 9 countries and involved 70 microbiological centres. The primary aims of the survey were as follows: (i) to perform a microbiological quality assurance assessment to evaluate the ability of participating laboratories to correctly identify the strains and assess their glycopeptide susceptibility; and (ii) to accurately determine the level of glycopeptide resistance among staphylococci, streptococci and enterococci in European hospitals. The in vitro activity of several other antibiotics was assessed on strains isolated from the Italian centres. In total, 7078 Gram-positive isolates were collected in Europe, and national coordinators used the National Committee for Clinical Laboratory Standards (NCCLS) agar dilution reference method to successfully retest 96% of these. According to mode minimum inhibitory concentrations (MICs), teicoplanin activity was similar to that of vancomycin against Staphylococcus aureus. In general, the range of MICs for teicoplanin was wider than that for vancomycin against coagulase-negative staphylococci. Against Enterococcus spp. and Streptococcus spp., teicoplanin was 4 times more active than vancomycin. The greatest number of glycopeptide refractory organisms was evident among enterococci; resistance was observed to be approximately 10 times more frequent in Enterococcus faecium than in E. faecalis. The results from the Italian isolates were similar to those from the overall study. In particular, teicoplanin was 2- to 8-fold more active than vancomycin against the majority of the enterococci. The incidence of enterococcal resistance was lower in Italy (0.6% for teicoplanin and 0.9% for vancomycin) than in Europe (1.7% for teicoplanin and 2.3% for vancomycin). This extensive survey confirms that teicoplanin is more active than vancomycin against enterococci and streptococci, and that both display similar potency against staphylococci.

Risk factors for carriage of respiratory pathogens in the nasopharynx of healthy children. Ascanius Project Collaborative Group.

OBJECTIVES: To assess risk factors for nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in a large sample of healthy children. METHODS: In this point prevalence survey nasopharyngeal specimens were obtained from 1723 healthy children, ages 1 to 7 years, attending day-care centers or schools in 18 Italian cities. Written questionnaires for obtaining information about the demographics and medical history of the children were completed by the parents in the presence of a pediatrician. RESULTS: The overall carrier rate of respiratory pathogens was 17.9% (S. pneumoniae, 3.5%; H. influenzae, 11.9%; M. catarrhalis, 4.1%). Only 5% of S. pneumoniae strains were penicillin-resistant whereas approximately 40% were erythromycin-resistant. Beta-lactamase production was found in 5.8% of H. influenzae and 88.7% of M. catarrhalis isolates. By multivariate analysis age (< or = 3 years), having older siblings, a history of prolonged full-time day-care attendance and living in a rural area significantly influenced the odds of carrying nasopharyngeal respiratory pathogens, particularly in children ages 1 to 5 years. Sex, breastfeeding, passive smoking and recent upper respiratory tract infections were not significant variables. Antibiotic treatment in the previous 3 months did not affect nasopharyngeal carriage, whereas repeated treatments with a macrolide were associated with carriage of S. pneumoniae. CONCLUSIONS: Our results suggest that there is a strong and long term relationship between exposure to large numbers of children in the first years of life and nasopharyngeal carriage of all respiratory pathogens. In addition antimicrobial restrictive guidelines should be tailored to local microbiologic sceneries.