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The in-vitro activity and tentative breakpoint of gemifloxacin, a new fluoroquinolone.

The in-vitro activity of gemifloxacin, a new fluoroquinolone, against a wide range (c. 700) of recent clinical isolates, was compared with that of three other fluoroquinolones and other relevant agents. Gemifloxacin inhibited 90% of the Enterobacteriaceae strains at 0.5 mg/L or less, exceptions being Serratia spp. (MIC(90) 1 mg/L) and strains possessing a putative mechanism of resistance to fluoroquinolones. Ninety per cent of Pseudomonas aeruginosa were inhibited by 4 mg/L. Gemifloxacin had good activity against respiratory pathogens, with 90% of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis being inhibited by 0.06 mg/L or less. Staphylococcus aureus (MSSA) were highly susceptible (MIC(90) 0.06 mg/L) but MRSA less susceptible (MIC(90) 8 mg/L) to gemifloxacin. Enterococcus spp. were markedly more susceptible to the study agent than to ciprofloxacin. Gemifloxacin showed good activity against Bacteroides fragilis (MIC(90) 0.5 mg/L) and anaerobic cocci. A tentative in-vitro breakpoint of 0.5 mg/L was studied using a 1 microg disc content for all genera except Pseudomonas where a 5 microg disc content was employed. The false sensitivity reporting rate was 0.5% and false resistance rate was 6.0%, which was considered acceptable. In conclusion, gemifloxacin is a highly active fluoroquinolone that should prove clinically useful in the treatment of a wide range of infections. Susceptibility testing criteria have been developed that should prove robust in a clinical laboratory.

Anti-Bacterial Agents↗

[In vitro activity of trovafloxacin, of other fluoroquinolones and of related antimicrobials against clinical isolates. Grupo colaborativo WHONET-Argentina].

The in vitro activity of trovafloxacin (TRV) has been evaluated in comparison with that of other antimicrobial agents against 5671 clinical isolates recovered by representative institutions of different provinces in our country. The resistance percentage to gentamicin and third generation cephalosporins among enterobacteriaceae was high: 17% and 16% respectively, with a considerable variation according to the analyzed species. The resistance to ciprofloxacin (CIP) and TRV affected approximately 9% of the isolates, without significant differences between both drugs. Fluoroquinolones (FQ) presented excellent activity on 166 isolates of Salmonella spp., 208 of Shigella flexneri and 76 of Shigella sonnei, where only one S.sonnei isolate was resistant to CIP, but susceptible to TRV. About half the isolates of Salmonella spp. and S.sonnei and almost all S.flexneri isolates were resistant to ampicillin, and more than 60% of Shigella spp. isolates were resistant to trimethoprim-sulfamethoxazole. A 41% of Staphylococcus aureus and 55% of coagulase-negative staphylococci isolates were resistant to oxacillin, presenting a highly associated multi-resistance. The resistance to FQ was also strongly related to oxacillin resistance, but the resistance to TRV was significantly lower than the CIP resistance: 9% vs 57% for S.aureus and 4% vs 41% for coagulase-negative staphylococci. A similar behavior was observed with Enterococcus spp., where 54% of the isolates were resistant to norfloxacin and only 13% were resistant to TRV. Neither Streptococcus pneumoniae (n = 193) nor Haemophilus influenzae (n = 139) isolates presented resistant to TRV.

Anti-Bacterial Agents↗

Antibacterial activity of lactic acid bacteria isolated from vacuum-packaged meats.

Lactic acid bacteria isolated from vacuum-packaged fresh meat stored at 4 degrees C were shown to produce antagonistic substances active against closely related bacteria. Growth medium, pH and growth temperature all affected the production of the inhibitory substances. Ten strains including aciduric Lactobacillus-type organisms, Carnobacterium spp. and Leuconostoc spp. were selected that produced protein-aceous substances that caused inhibition of indicator strains. These were considered to be bacteriocins or bacteriocin-like compounds based on their inactivation with protease, generally narrow spectra of antibacterial activity and bactericidal or bacteriostatic modes of action. Activity was not lost from supernatant fluids as a result of heat treatment at 62 degrees C for 30 min, except for the Leuconostoc strains. Inhibitory spectra of some strains included Enterococcus spp. and Listeria monocytogenes. Some strains were of interest because their inhibitory substances were detected in the supernatant fluid early in the growth cycle. The inhibitory substances differed in characteristics between strains and there is evidence that more than one bacteriocin-like substance may be produced by some strains.

Animals↗

Gastrointestinal tract colonization with vancomycin-resistant Enterococcus faecium in an animal model.

Vancomycin-resistant enterococci have become important nosocomial pathogens in many institutions. The gastrointestinal tract of susceptible hosts serves as the likely reservoir from which the organism is disseminated. To study factors promoting colonization and the efficacy of decontamination therapy with antimicrobial agents, a model of gastrointestinal colonization with vancomycin-resistant Enterococcus faecium was developed in CF1 mice. At baseline, all animals were colonized with non-vancomycin-resistant enterococci (5.0 log10 CFU/g), but vancomycin-resistant organisms were not detectable. Following gastric inoculation with 5 x 10(8) CFU of a clinical isolate of vancomycin-resistant E. faecium, the strain transiently colonized the gastrointestinal tract of 100% of mice but was undetectable by Day 14 (< or = 2.7 log10 mean CFU/g). In animals who received 5 mg of streptomycin per ml or 250 micrograms of vancomycin per ml in drinking water, colonization with the organism occurred at significantly higher bacterial counts than in controls at 7 days following inoculation (9.4 for vancomycin, 9.2 for streptomycin, and 5.1 log10 mean CFU/g for controls; P < 0.05). Fecal concentrations of vancomycin-resistant E. faecium persisted at high counts through Day 22 in mice receiving these antibiotics, but low counts were also still detected in 3 of 10 control animals. In mice with previously established vancomycin-resistant E. faecium colonization, oral administration of ramoplanin, a lipoglycodepsipeptide to which the strain was susceptible, suppressed growth of all enterococci in feces, including the vancomycin-resistant strain after 7 days of therapy (< or = 3.1 and < or = 3.3 log10 mean CFU/g for vancomycin and streptomycin groups, respectively). All mice had a recurrence of colonization with vancomycin-resistant E. faecium after the ramoplanin was discontinued. In summary, this animal model demonstrates the importance of antibiotics in predisposing to gastrointestinal colonization with vancomycin-resistant Enterococcus spp. Although treatment with ramoplanin temporarily suppressed the organism, recurrence of colonization due to relapse or reinfection occurred.

Administration, Oral↗

[Characteristics of Enterococcus strains isolated from neutropenic patients at the National Bone-Marrow Transplantation Center of Tunis].

The frequency of digestive colonization of neutropenic patients by Enterococci during the phase of pre-transplant and post-transplant of bone marrow is important indeed as 441 Enterococcus spp strains have been isolated from stool-cultures and other specimens whithin a period of 35 months in 80 patients. A quantitative stool culture was done on appropriate media. Simple bile-esculine agar (BE) and bile esculine-agar additionned with 6 mg/l of vancomycine (BEV) were used for detecting Enterococci. These organisms were taken into account, when then numeration was > 10(3) UFC/g of fecal sample on BE and in all cases on BEV. Species isolated were essentially Enterococcus faecalis (39.4%), Enterococcus faecium (34.4%) and Enterococcus casseliflavus (17%). These strains were characterized by a high frequency of high-level resistance to gentamicin (40.8%). Resistance to amoxicillin concerns 40% of E. faecium strains. Seventeen multiresistant strains of E. faecium isolated from 7 patients (colonized during a long period and receiving a gut decontamination treatment) were the subject of a phenotypic analysis (biotyping, antibiotyping and determination of MICs to beta-lactam, aminoglycosides and glycopeptides). This analysis showed that these strains are distinguishable, endogenic and specific for each patient, the common multiresistance trait resulted from the selective pressure of decontamination treatment used for our patient.

Adolescent↗

Prevalence of high level aminoglycoside and vancomycin resistance among enterococci in Turkey.

Enterococcus spp. have become the third most common cause of nosocomial infections. High-level aminoglycoside resistance (HLAR), an important clinical concern, has been associated with some species of enterococci. The synergistic effect obtained by the combination of aminoglycosides with penicillin or vancomycin disappears in strains that show high-level resistance (HLR) to the aminoglycosides. We evaluated the agar dilution and high content disk diffusion tests for the detection of HLAR for 60 isolated enterococci. In our study 4 strains of Enterococcus faecalis (6.6%) and 8 strains of Enterococcus faecium (13.3%), totally 20% were found to be highly resistant to gentamicin; 2 strains of E. faecalis (13.3%), 8 strains of E. faecium (3.3%), totally 16.6% showed HLR to streptomycin by agar dilution method and the same rates were found by high-content disk diffusion method. 2 strains of E. faecalis (3.3%), 4 strains of E. faecium (6.6%), totally 10% showed vancomycin resistance by agar dilution method. The ratio for beta lactamase activity was found to be 26.6% for E. faecalis and 3.3% for E. faecium. Our results demonstrate that high-content disk diffusion test should be performed by using both gentamicin and streptomycin in routine screening of HLAR among enterococci and the determination of beta lactamase activity at the same time is also useful for detecting resistance to a beta lactam agent.

Anti-Bacterial Agents↗

Comparative in vitro activity of ABT-773, a novel antibacterial ketolide.

The in vitro activities of ABT-773, erythromycin, clarithromycin, and azithromycin were compared. ABT-773 was the most active compound against macrolide-susceptible Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Staphylococcus epidermidis, Listeria monocytogenes, and Enterococcus spp. and multidrug-resistant Streptococcus pneumoniae. It also had good activity against gram-negative and atypical respiratory tract pathogens and Helicobacter pylori.

Anti-Bacterial Agents↗

Development of resistant bacteria isolated from dogs with otitis externa or urinary tract infections after exposure to enrofloxacin in vitro.

Minimum inhibitory concentrations for enrofloxacin were determined for 63 bacterial isolates from dogs with otitis externa or urinary tract infections. Development of resistant mutants was determined after exposing the isolates to enrofloxacin in vitro for up to five serial passages. Results indicated that Pseudomonas aeruginosa and Enterococcus spp isolates exposed to enrofloxacin developed resistance rapidly, whereas Klebsiella, Proteus, and Streptococcus spp were less likely to develop resistance. Despite the presence of enrofloxacin pressure, no resistant bacteria developed in the Escherichia coli and staphylococcal isolates. In many isolates, susceptibility patterns changed from susceptible to intermediate.

Animals↗

Are there patients with peritonitis who require empiric therapy for enterococcus?

Enterococci are an increasingly important cause of nosocomial infections. While the clinical impact of enterococci in cases of bacteremia and super-infections in selected patient populations has been well-established, their role as primary pathogens in polymicrobial intra-abdominal infections remains controversial. While it has been suggested that the presence of enterococci increases the rate of infectious post-operative complication, it has also been demonstrated that polymicrobial intra-abdominal infections involving enterococci can be treated successfully with appropriate surgical drainage and antibiotics, such as cephalosporins, that are not active against enterococci. Therefore, the question arises of whether or not antibiotic coverage against enterococci should be included in the empirical treatment of peritonitis in certain high-risk patient populations. An extensive literature review revealed some evidence arguing in favour of using empirical therapy with enterococcal coverage for intra-abdominal infections in the following cases: (i) immunocompromised patients with nosocomial, post-operative peritonitis; (ii) patients with severe sepsis of abdominal origin who have previously received cephalosporins and other broad-spectrum antibiotics selecting for Enterococcus spp.; (iii) patients with peritonitis and valvular heart disease or prosthetic intravascular material, which place them at high risk of endocarditis. The ideal therapeutic regimen for these high-risk patients remains to be determined, but empirical therapy directed against enterococci should be considered.

Anti-Bacterial Agents↗

In vitro and in vivo efficacy of vancomycin against Elizabethkingia species and the impact of increased vancomycin MICs.

UNLABELLED: This study aimed to evaluate the concordance of vancomycin susceptibility testing methods, its in vivo and in vitro efficacy, and the mechanisms underlying elevated MICs in Elizabethkingia spp. Vancomycin susceptibilities of 18 E. anophelis isolates were determined using multiple assays. The efficacy of vancomycin against five clinical isolates and one laboratory-induced mutant with an elevated vancomycin MIC was evaluated using time-kill assays and Galleria mellonella and murine models. Vancomycin MICs (16-32 mg/L) determined by broth microdilution were consistent with agar dilution, Etest, and MBC assay results. All isolates had zone diameters < 17 mm and were, thus, categorized as non-susceptible according to the CLSI criteria for Enterococcus spp. Time-kill assays of five clinical isolates demonstrated that vancomycin at a clinically relevant concentration (4 mg/L) exhibited poor bactericidal activity similar to that of teicoplanin. Vancomycin improved Galleria mellonella survival in a dose-dependent manner, whereas teicoplanin, dalbavancin, oritavancin, and daptomycin were ineffective. Murine models revealed that vancomycin at a human-equivalent dose (25 mg/kg twice daily) prolonged survival in most infections and modestly reduced bacterial load, while teicoplanin remained ineffective. Vancomycin efficacy was significantly reduced in G. mellonella and mice infected with a mutant strain exhibiting an elevated MIC (128 mg/L), which was attributable to spontaneous mutations in pbp4. In conclusion, E. anophelis were consistently non-susceptible to vancomycin as determined by multiple in vitro assays. However, vancomycin demonstrated unique in vivo activity among glycopeptides although this effect was abrogated by spontaneous mutations leading to elevated MICs. IMPORTANCE: Elizabethkingia anophelis is a multidrug-resistant pathogen associated with limited treatment options and high mortality. Most commonly considered agents, including fluoroquinolones, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole, are increasingly compromised by resistance, toxicity, or inconsistent efficacy. Although vancomycin is not routinely used for Gram-negative infections due to limited outer membrane permeability, case reports have suggested potential benefit in Elizabethkingia infections under critical conditions. In this study, we show that E. anophelis isolates are uniformly non-susceptible to vancomycin in vitro and exhibit minimal bactericidal activity. However, vancomycin conferred a modest but statistically significant survival benefit in two independent animal models. Importantly, this effect was lost in strains with vancomycin-induced MIC elevation, and genome analysis identified pbp4 mutations as a potential underlying mechanism. These findings suggest vancomycin may offer therapeutic benefit when no preferred options are available. They support cautious use in selected cases and highlight the need for continued monitoring of susceptibility and resistance development.

Vancomycin↗

Interlaboratory proficiency testing as a tool for improving performance in laboratories diagnosing bovine mastitis.

The National Veterinary and Food Research Institute (Finland) and the Veterinary Laboratories Agency of the Quality Assurance Unit, Department for Environment, Food and Rural Affairs, United Kingdom (previously the Ministry of Agriculture, Fisheries and Food) organized a proficiency testing program for laboratories analyzing veterinary mastitis samples. Three test samples with lyophilized strains of common aerobic bacteria were sent to the participating laboratories 7 times between 2000 and 2003. The participants returned 98% of the requested data. The overall performance of the laboratories varied from 63 to 93% in different testing rounds. All laboratories diagnosed Staphylococcus aureus and Escherichia coli correctly at every round. Improvement in diagnosing individual bacteria was observed for Staphylococcus epidermidis, Streptococcus dysgalactiae, Enterococcus spp. and Klebsiella spp. The overall performance of the laboratories improved with increased participation. The educational role of the program was important. Laboratories working in the veterinary field should implement a documented quality system covering all functions of the laboratory, as well as a planned quality assurance system.

Animals↗

A UK multicentre study of the antimicrobial susceptibility of bacterial pathogens causing urinary tract infection.

OBJECTIVES: To determine the prevalence of resistance amongst urinary tract pathogens against antimicrobials used to treat urinary tract infections (UTIs) in the UK to provide data to help direct empirical therapy. METHOD: During 1999-2000, a total of 1291 bacterial isolates causing UTI were collected from 8 centres in the UK. Isolates were cultured from patients with (1). community-acquired UTI in those less than 65 years old (397), (2). hospital-acquired UTI other than those admitted with pyelonephritis (394), (3). pyelonephritis (108) and (4). community-acquired UTI in those greater than 65 years old (392). After re-identification, MICs for a range of antimicrobials were determined and interpreted using NCCLS procedures and interpretive guidelines. RESULTS: Escherichia coli was the predominant pathogen in all categories but the total percentage for each category varied (56.3-77.3%). The next three pathogens of importance were Enterococcus faecalis, Klebsiella pneumoniae and Proteus mirabilis which varied in prevalence slightly from category to category. The activity of amoxycillin against E. coli (51.3% susceptible) was greatly reduced as a result of beta-lactamase production and only partially restored by the addition of clavulanic acid (78.8% susceptible). Cefuroxime was very active against E. coli using parenteral form breakpoints (97.1% susceptible) but less so using oral form breakpoints (68.6% susceptible). Cefuroxime was inactive against Enterococcus spp. and Pseudomonas spp. Nitrofurantoin was very active against isolates of E. coli (96.3% susceptible) and E. faecalis but not against K. pneumoniae, P. mirabilis or Pseudomonas aeruginosa. Overall susceptibility to trimethoprim ranged from 58.1% to 84.5% for the most prevalent pathogens. Ciprofloxacin was highly active against the UTI pathogens examined in this study with susceptibilities of between 88.6% and 97.7% for the most prevalent pathogens (E. coli, n=864, 97.7% susceptible) and was the only oral agent tested with activity against Pseudomonas spp. CONCLUSION: These data provide much needed information on the prevalence of antimicrobial resistance amongst pathogens currently causing UTI in the UK.

Adolescent↗

Comparison of activities of broad-spectrum beta-lactam compounds against 1,128 gram-positive cocci recently isolated in cancer treatment centers.

We report the in vitro activities of broad-spectrum beta-lactam antimicrobials tested against 1,128 gram-positive pathogens recently isolated from cancer patients. Cefepime and imipenem were more active than ceftazidime and ceftriaxone against these organisms. Only vancomycin demonstrated reliable activity against oxacillin-resistant staphylococci, Enterococcus spp., and Corynebacterium spp. The spectrum of gram-positive organisms against which cefepime and imipenem have activity provides an advantage over ceftazidime as empiric therapy for cancer patients, potentially reducing the need for the empiric addition of glycopeptides.

Anti-Bacterial Agents↗

Ampicillin-resistant Enterococcus raffinosus in an acute-care hospital: case-control study and antimicrobial susceptibilities.

A prospective study identified 9 (32%) of 28 ampicillin-resistant (MIC greater than or equal to 16 micrograms/ml) enterococcus isolates as Enterococcus raffinosus. A case-control study found no significant differences with respect to underlying diseases, catheterization, or surgery between patients with ampicillin-resistant E. raffinosus and those with ampicillin-susceptible Enterococcus spp. Prior treatment with antibiotics and prolonged hospitalization were more frequent among patients with ampicillin-resistant E. raffinosus. Patients with the same strain (determined by plasmid analysis) were frequently hospitalized concurrently.

Aged↗

In vitro activity of three carbapenem antibiotics. Comparative studies with biapenem (L-627), imipenem, and meropenem against aerobic pathogens isolated worldwide.

The in vitro activity of biapenem (formerly L-627 or LJC10, 627), a new carbapenem, was compared with that of imipenem and meropenem against > 6000 clinically significant pathogens isolated in six countries worldwide. Biapenem was active against members of the family Enterobacteriaceae with a 90% minimum inhibitory concentration (MIC90) ranging from < or = 0.06 to 2 micrograms/ml. Only Serratia spp. and Providencia spp. were less susceptible (MIC90, 8 micrograms/ml). Pseudomonas aeruginosa and Xanthomonas maltophilia displayed an MIC90 of > or = 8 micrograms/ml biapenem/ml whereas Acinetobacter spp. were susceptible at < or = 1 micrograms/ml. Oxacillin-resistant staphylococci were resistant to biapenem at > 8 micrograms/ml whereas oxacillin-sensitive staphylococci were susceptible at < or = 1 micrograms/ml. Biapenem, imipenem, and meropenem displayed poor activity against Ent. faecium (MIC90, > or = 8 micrograms/ml), and only imipenem displayed slightly better activity against Ent. faecalis (MIC90, 4 micrograms/ml). The rank order of activity against groups of isolates was Enterobacteriaceae (meropenem > biapenem > or = imipenem), Ps. aeruginosa (biapenem = meropenem = imipenem), oxacillin-sensitive staphylococci (imipenem > or = biapenem = meropenem), oxacillin-resistant staphylococci (biapenem = meropenem = imipenem), and Enterococcus spp. (biapenem = meropenem = imipenem). These in vitro suggest that further developmental work on biapenem is warranted.

Enterobacteriaceae↗

Polymicrobial keratitis secondary to Burkholderia ambifaria, enterococcus, and staphylococcus aureus in a patient with herpetic stromal keratitis.

PURPOSE: To report polymicrobial keratitis in a patient with herpetic stromal keratitis. The initial infecting organism, Burkholderia ambifaria, has not previously been reported to cause microbial keratitis. METHODS: Clinical evaluation and corneal culture were performed. RESULTS: A 59-year-old-man undergoing topical corticosteroid therapy for herpes simplex stromal keratitis developed corneal infection with B. ambifaria. The organism was reisolated 12 days after initiation of hourly therapy with topical levofloxacin 0.5%. At reculture Staphylococcus aureus and Enterococcus spp. were also isolated. The addition of topical amikacin and vancomycin led to resolution of the microbial keratitis. CONCLUSIONS: Burkholderia ambifaria infected a compromised cornea, exhibited an unusual sensitivity profile, and remained viable after 12 days of therapy with an antibiotic to which it was sensitive by in vitro tests.

Amikacin↗

The in-vitro activity of Bay y 3118, a new chlorofluoroquinolone.

The in-vitro activity of Bay y 3118, a new quinolone antimicrobial was compared with that of ciprofloxacin, sparfloxacin and three beta-lactams against 620 clinical isolates. Bay y 3118 was the most active quinolone against the majority of Enterobacteriaceae and Staphylococcus spp. The MIC90 for the members of the Enterobacteriaceae were < or = 0.12 mg/L except for Serratia spp. (1 mg/L) and in general Bay y 3118 was two-fold more active than ciprofloxacin or sparfloxacin. Strains of Pseudomonas aeruginosa were more susceptible to ciprofloxacin (MIC90 0.25 mg/L) than to Bay y 3118 (MIC90 0.5 mg/L) or sparfloxacin (MIC90 1.0 mg/L). Staphylococcus aureus was more susceptible to Bay y 3118 (MIC90 0.03 mg/L) and sparfloxacin (MIC90 0.06 mg/L) than to ciprofloxacin (MIC90 1 mg/L) and similar differences were noted for Staphylococcus saprophyticus and Staphylococcus epidermidis. Streptococcus pneumoniae was susceptible to Bay y 3118 (MIC90 0.03 mg/L) as were other streptococci. Enterococcus spp. was four-fold more susceptible to Bay y 3118 and sparfloxacin than to ciprofloxacin. All strains of Haemophilus influenzae and Moraxella spp. were inhibited by Bay y 3118 < or = 0.015 mg/L. Anaerobes were more susceptible to Bay y 3118 than to other quinolones; the MIC90 of Bay y 3118 for Bacteroides fragilis being 0.06 mg/L. Little effect was seen by increasing the inoculum from 10(4) cfu to 10(6). Bay y 3118 inhibited Chlamydia sp. at concentrations < or = 0.015 mg/L.

Anti-Bacterial Agents↗

Microbiological quality of reconstituted enteral formulations used in hospitals.

Contamination of enteral feeds may occur during preparation, storage, decanting, and administration to patients. The aim of this study was to investigate the microbiological quality of reconstituted enteral feeds, residual feeds from feed delivery systems, and the water used to reconstitute powdered feeds in hospital. Hazard Analysis Critical Control Points (HACCP) system was implemented to control microbiological contamination of the enteral feeding formulations. Before the implementation of the HACCP system microbiological analyses of feeds showed the presence of indicator organisms such as coliforms and Enterococcus spp. and unacceptably high levels of mesophilic aerobic microorganisms (>10(4) cfu/mL). After the implementation of the HACCP, the microbial quality of the feeds improved significantly, with counts of <10(1) cfu/mL. Blenders used in reconstituting feeds were found to be the main source of bacterial contamination.

Bacillus cereus↗