[Russian results of the international epidemiological study of clinical aspects and resistance to antimicrobial medicines of cystitis uropathogens in females (ARESC): significance of empiric therapy].

A total of 656 female patients from Russia aged between 18 to 65 years with uncomplicated cystitis entered the international ARESC trial, of them 647 were eligible for final analysis. Positive cultural urine tests ( > 10(4) CFU/ml) were in 419 (64.7%) patients, 393 (93.8%) patients had monoinfection. The central laboratory of Genoa (to which the isolated samples were sent) has tested 416 uropathogens from 399 patients. The following pathogens were isolated: E. coli (72.6%), enterococcus (7.0%), Klebsiella pneumoniae (4.6%), Staphylococcus saprophyticus (3.6%), Proteus mirabilis (2.4%) and Staphylococcus aureus (1.7%). E. coli was most sensitive to phosphomycin (99.3%), mecillinam (97.3%), nitrofurantoin (94.7%), ciprofloxacin (87.4%). The lowest sensitivity was to ampicillin (42.1%) and cotrimoxasol (69.4%). As to the whole bacterial spectrum, the highest sensitivity was found to phosphomycin (96.5%), nitrofurantoin (85.6%) and citrofloxacin (82.8%), the less sensitivity--to ampicyllin (44.3%) and co-trimoxasol (70.1%). Phosphomycin, mecillinam (not registered in Russia) and nitrofurantoin showed activity in vitro and can be considered as drugs of choice for empiric therapy of cystitis. Because of high resistance of pathogens, co-trimoxasol (trimetoprim) and fluoroquinalones are not recommended as first-line treatment for uncomplicated cystitis in females.

Do different susceptibility breakpoints affect the selection of antimicrobials for treatment of uncomplicated cystitis?

Because of increasing antibiotic resistance in Escherichia coli, the main uropathogen of uncomplicated urinary tract infections (UTIs), updated susceptibility data are vital in guiding the selection of first-line treatment agents. interpretation of these data depends on the breakpoints adopted, that may vary among different guidelines.In this study we report the minimum inhibitory concentrations (MICs) of eight antibiotics and compare antimicrobial susceptibility results obtained in 2315 E. coli strains recently collected during the ARESC survey using EUCAST and CLSI breakpoints. We have also evaluated the clinical impact of breakpoint discrepancies on the overall susceptibility patterns.Fosfomycin, nitrofurantoin and mecillinam showed the highest susceptibility rates in all countries (>92%) according to both CLSI and EUCAST criteria. Minor category shifts were observed for ciprofloxacin, amoxicillin-clavulanic acid, ampicillin and trimethoprim/sulfamethoxazole. A large number of strains classified as intermediate resistant to cefuroxime according to CLSI are included by the EUCAST in the susceptible category.In conclusion, fosfomycin, mecillinam, and nitrofurantoin have preserved their in vitro activity in all countries investigated, regardless of the criteria adopted. They continue to represent effective options for the empiric therapy of female patients with uncomplicated cystitis. The use of different interpretative criteria for E. coli responsible for UTIs therefore has no influence on the decision to be taken by the physicians managing the patients.

[Clinical aspects and epidemiology of uncomplicated cystitis in women. German results of the ARESC Study]. / Klinik und Epidemiologie der unkomplizierten Zystitis bei Frauen. Deutsche Ergebnisse der ARESC-Studie.

OBJECTIVE: Uncomplicated cystitis in women is among the most frequent infections in the community setting. The German results of the international ARESC Study are reported concerning clinical aspects, epidemiology, and antimicrobial susceptibility of uropathogens. PATIENTS AND METHODS: Patients between 18 and 65 years of age with symptoms of uncomplicated cystitis were consecutively enrolled and investigated clinically including urinalysis and urine culture. Uropathogens were identified and their susceptibility was tested for nine antimicrobials RESULTS: In Germany a total of 442 patients were enrolled and 412 were eligible. A positive urine culture (cfu>/=10(4)/ml) was found in 335 (81.3%); 325 (97.1%) of them had a monoinfection. A total of 317 uropathogens were further analyzed in a central laboratory (Genua). Escherichia coli was the most frequent (76.7%), followed by Proteus mirabilis (4.7%), Staphylococcus saprophyticus (2.8%), Klebsiella pneumoniae (2.5%), enterococci (2.5%), and Staphylococcus aureus (2.2%). E. coli showed the highest rate of susceptibility to fosfomycin (97.9%) followed by mecillinam (97.5%), nitrofurantoin (95.4%), and ciprofloxacin (95.4%). The lowest rate was found for ampicillin (59.2%) followed by cotrimoxazole (74.0%). For the total spectrum the order was fosfomycin (96.1%), mecillinam (97.5%), ciprofloxacin (92.3%), and nitrofurantoin (86.3%). The lowest rates were found again for ampicillin (56.6%) and cotrimoxazole (73.9%). CONCLUSIONS: Fosfomycin, mecillinam (not available in Germany), and nitrofurantoin have preserved their in vitro activity and are suitable for empiric therapy. Because of increasing resistance rates cotrimoxazole (trimethoprim) and fluoroquinolones are generally not recommended as first-choice drugs for empiric therapy of female patients with uncomplicated cystitis.

In vitro activity of ceftibuten at sub-inhibitory concentrations in comparison with other antibiotics against respiratory and urinary tract pathogens.

Some new features of the in vitro activity of ceftibuten, an oral third generation cephalosporin, have been studied in reference to respiratory and urinary tract pathogens included in its antibacterial spectrum. At 0.25XMIC (minimum inhibitory concentration) and 0.5XMIC levels, ceftibuten was able to affect the biofilm production in 2/3 of both Escherichia coli and Proteus mirabilis strains, and reduced the number of strains capable of adhering to epithelial cells by about 35% in comparison to the control. Surface hydrophobicity was also influenced by ceftibuten and the other drugs at 0.25-0.5XMIC. In general, no marked variation in the virulence traits of the pathogens studied were found by exposing bacteria to sub-MICs of ceftibuten. Plasmid loss (from 1.8 to 37.2%), and Flac transfer inhibition (about 30-50% reduction in the number of recombinants) were detected under the experimental conditions used. This study confirms the excellent antibacterial properties of ceftibuten by adding new information about the effects of this antibiotic against pathogens often involved in respiratory and urinary tract infections that may be treated with this compound, supporting the appropriate use of this cephalosporin.

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.

Antifungal resistance in Candida spp. isolated in Italy between 2002 and 2005 from children and adults.

The activity of amphotericin B, fluconazole, flucytosine, itraconazole and voriconazole was tested in vitro against 618 clinical Candida spp. isolates, using the broth microdilution or the disk diffusion method (voriconazole). Amphotericin B and voriconazole were the most potent antifungal agents assayed (100% of susceptible strains). Resistance to fluconazole and itraconazole was detected in three (0.7%) and 11 (2.7%) isolates of Candida albicans and in four (3.7%) isolates of Candida glabrata. Flucytosine intermediate, resistant strains, or both, were observed in C. albicans (0.3% and 0.7%), C. glabrata (2.8% intermediate) and C. tropicalis (15.2% and 15.2%). C. krusei was the least susceptible species to azoles. No statistically significant differences in the rates of resistant isolates depending on site of infection and age of the patient were observed, with the exception of C. albicans and itraconazole (higher percentage of resistance in children). At present, acquired antifungal resistance represents an uncommon finding in most Candida spp. circulating in Northern Italy.

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.

In vitro activity of ertapenem against selected respiratory pathogens.

OBJECTIVES: The in vitro activity of ertapenem was evaluated in comparison to 21 selected agents against a large collection of recently isolated respiratory tract pathogens including: 180 Streptococcus pneumoniae, 100 Streptococcus pyogenes, 70 Haemophilus influenzae, 70 Moraxella catarrhalis, 100 methicillin-susceptible Staphylococcus aureus and 30 Klebsiella pneumoniae. Additional in vitro tests (time-kill curves with ertapenem alone and in combination with four other agents) for S. pneumoniae were carried out. METHODS: MIC determinations and time-kill curves were carried out following the procedures suggested by the NCCLS. RESULTS: According to NCCLS susceptibility breakpoints, ertapenem was comparable to the most potent compounds tested for all pathogens studied. Ertapenem was 100% active against penicillin-susceptible and -intermediate S. pneumoniae and against 60% of penicillin-resistant strains. Time-kill tests at 4x MIC confirmed a pronounced bactericidal potency of ertapenem against these organisms. Interactions of ertapenem with several other agents against pneumococci resulted in clear synergic interactions (98.4%). Indifference was extremely rare and antagonism was not observed. All S. pyogenes strains tested were inhibited by ertapenem, irrespective of their macrolide resistance phenotypes. Ertapenem was also fully active against H. influenzae (100% susceptible) and M. catarrhalis (MIC90 0.015-0.03 mg/L) even when capable of synthesizing beta-lactamases. Methicillin-susceptible S. aureus and K. pneumoniae, including extended-spectrum beta-lactamase-producing strains, were 100% susceptible to ertapenem. CONCLUSIONS: Our results indicate that ertapenem has a suitable spectrum of activity against organisms encountered in community-acquired bacterial respiratory tract infections.

In vitro activity of thiamphenicol against multiresistant Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus in Italy.

Thiamphenicol is a derivative of chloramphenicol characterized by a spectrum comparable to that of the parent compound against multiresistant pathogens but showing satisfactory tolerability. The in vitro activity of thiamphenicol and of 11 comparative drugs against 397 recently isolated antibiotic-resistant and/or invasive pneumococci and 52 multiply-resistant MRSA including 2 VISA strains was determined. Bactericidal activity against Haemophilus influenzae and the post-antibiotic effect on Streptococcus pneumoniae, H. influenzae, Staphylococcus aureus and Escherichia coli were also assessed. Against invasive pneumococci, thiamphenicol and chloramphenicol were the most potent non-beta-lactam molecules together with vancomycin and rifampin. Against high-level penicillin-resistant strains phenicol activities were superior to those of cefotaxime, ceftriaxone and imipenem. Against MRSA thiamphenicol and chloramphenicol were second only to the glycopetides and also inhibited the VISA strains. Thiamphenicol showed a significant PAE (0.33 to 2.9h) on all pathogens studied and a powerful bactericidal effect against beta-lactamase-positive and -negative H. influenzae. These results indicate a good in vitro activity of thiamphenicol against difficult-to-treat multiply resistant pathogens.

Evaluation of spontaneous contamination of ocular medications.

BACKGROUND: In order to evaluate whether single-dose ophthalmic preparations in 0.5-ml containers can safely be used within 24 h after the first opening, eigth different sterile ocular medications containing timolol, jaluronic acid, diclofenac, ketotifen, pilocarpine, formocortal, formocortal-gentamycin, and tetryzoline-feniramine (Farmigea, Italy) were opened and tested for spontaneous bacterial contamination after exposure to air. METHODS: Samples (10 microl) were collected from exposed ophthalmic preparations after 0, 2, 4, 8 and 24 h. RESULTS: No viable microorganisms were detected during and at the end of the evaluation period. In order to assess whether the resident or pathogenic ocular bacterial population due to repeated handling might contaminate the medications, about 10(5) cells of different species (Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pneumoniae, Streptococcus spp., Corynebacterium spp., Pseudomonas aeruginosa, Neisseria spp., Acinetobacter spp., Haemophilus influenzae, Escherichia coli and Candida albicans) were added to the containers and incubated at 37 degrees C or at room temperature. Samples were collected and the number of viable bacteria was estimated. The antibacterial effect of the ophthalmic compounds varied depending on the species considered. Tetryzoline-feniramine, pilocarpine, ketotifen and formocortal-gentamycin exhibited a frank bactericidal activity (<100 survivors after 18-24 h of exposure) against the great majority of the species tested. CONCLUSION: These results indicate that the risk of spontaneous contamination of ophthalmic preparations after their first opening is low, and that all preparations tested exhibit an aspecific antibacterial activity. As a consequence, the safe usage of these ocular medications could be extended from the recommended 3 h to at least 24 h after the first usage.

Antibiotic persistence: the role of spontaneous DNA repair response.

Persisters are a small proportion of a bacterial population that exists in a physiological state permitting survival despite the lethal activity of antibiotics. To explain this phenomenon, it has been suggested that persisters are bacteria repairing spontaneous errors of DNA synthesis. To verify this assumption, Escherichia coli AB1157 and its lexA3 derivative were exposed to a dose 6x MIC of various antibiotics representative of different molecular mechanisms of action (ampicillin, ceftriaxone, meropenem, amikacin, ciprofloxacin). Bacterial cell counts, after 24 hr of exposure to the antimicrobials, revealed a reduction of about 90% of viable organisms in the lexA3 strains in comparison to the lexA+. In several cases, the number of colony-forming units decreased below the limit of assay. This behavior was noted with all antibiotics used, alone or in combination (amikacin plus ceftriaxone and amikacin plus ciprofloxacin). The same experiments were repeated using E. coli AB1157 cultured in the presence of mitomycin C (0.25x MIC), and the number of survivors exceeded by about 90% the values found in the nonexposed control. In contrast, in the sulA background, mitomycin C reacted synergically with all the antibiotics tested causing a strong reduction of the survivors in comparison with the control. The addition of chloramphenicol (0.125x MIC), on the contrary, caused a reduction of the number of survivors of about 90%. These findings indicate that, when DNA repair is active (a mechanism known to block cell division), the number of survivors is greater than that observed with lexA3. Thus, in addition to other possible explanations, persisters might be a fraction of bacteria that during antibiotic treatment are not growing because they are repairing spontaneous errors of DNA synthesis.

Epidemiology of major respiratory pathogens.

A vast literature attests to the fact that Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis represent the prevailing bacterial pathogens of community-acquired lower respiratory tract infections. Their specific incidence as causative agents of the more common syndromes is known to vary even profoundly, depending on geographic area, and the same holds true for their rates of resistance to antimicrobial drugs. Europe does not escape the threat posed by the present pandemic spread of penicillin resistance in S. pneumoniae although, as expected, some countries like Spain and France are highly affected and others including Germany, Italy, The Netherlands and the Scandinavian region, are relatively spared. In several sites multiple resistance has been described in S. pneumoniae with the most affected drugs being penicillin, the macrolides, co-trimoxazole and tetracycline. In H. influenzae synthesis of beta-lactamases is the main resistance trait expressed. Lack of susceptibility to beta-lactams dictated by a different mechanism remains extremely rare. Large variations in the incidence of this character are apparent when considering European countries. France and Spain are again widely affected while Germany, The Netherlands and Italy display rates of beta-lactamase-positive H. influenzae of about 16%. M. catarrhalis must be considered generally resistant to non-protected aminopenicillins since over 90% of these organisms produce beta-lactamases.

Microbial epidemiology patterns of surgical infection pathogens.

Resistance, as assessed in vitro, has a number of serious consequences in clinical situations. Treatment failures are common when an inappropriate drug has been prescribed and this, in turn, may lead to hospitalization of patients who normally would have been treated on an outpatient basis, as well as to longer hospital stay for inpatients and to the use of alternative drugs, which may be more expensive and more toxic. These factors all contribute to increased health care costs, morbidity and mortality. Microbiological procedures may identify the causative pathogen and provide the appropriate susceptibility pattern to the physician, thus reducing the chances of therapeutic failures. However, for a number of reasons including cost--even in hospitals--not to mention general practice, infections are seldom diagnosed on an etiological basis. From what has been stated, the knowledge of bacterial epidemiology and resistance represents basic support for correct therapeutic decision-making.