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[Occupational ophthalmology and ergoophthalmology: a developing field].

In 1979 it was decided to activate, within the Institute of Occupational Health of the Milan "Università degli Studi", a new Unit of Ergophthalmology. This decision was taken owing to the progressive diffusion of "optical instruments", particularly computer-based equipment, in the world of work and to the relevance that this topic assumed among Italian occupational physicians. Since its beginning, one of the main characteristics of the Ergophthalmology Unit was an interdisciplinary approach, where occupational physicians, ophthalmologists, occupational hygienists and lighting engineers were collaborating on a daily basis. Research activities, which developed over many years and in several phases, were concerned with four main topics: 1. analysis and quantification of "near work load"; initially the investigations were mainly aimed at the evaluation of the observation distance in different tasks, followed by the development of a method which, by means of specifically designed electronic equipment, allows quantification of the accommodation and convergence required by the task; 2. development of a new method aimed at evaluating, by a photometric procedure, the luminance ratios in the "occupational visual field"; this research was carried out, both in the laboratory and during on-site investigations, in collaboration with the Dept. of Electrotechnics of Milan Polytechnic; 3. studies on the relationships between indoor microbial pollution and Computer Assisted Design work, considering that ocular conjunctiva and cornea, due to their external position, can be easily inoculated by micro-organisms present on periocular tissue and hands; this research showed that bacteria and fungi pathogenic for the eye (Staphylococcus aureus, Candida sp., Aspergillus sp.) are present on desk, keyboard and mouse, as well as in the conjunctival sac of the exposed operators; 4. studies on "blue light" and its effects on the Pigmented Retinal Epithelium (PRE) in workers exposed to halide lamps, like electricians, installers, maintenance staff, polymerization operators, etc.; the laboratory and on-site investigation that was carried out in cooperation with the Health Physics Dept. of the Milan ICP Hospital, showed that long-term exposure to low levels of irradiation could constitute an eye risk for these working populations.

Computer Terminals↗

Entomopathogenic nematodes in the European biocontrol market.

In Europe total revenues in the biocontrol market have reached approximately 200 million Euros. The sector with the highest turn-over is the market for beneficial invertebrates with a 55% share, followed by microbial agents with approximately 25%. Annual growth rates of up to 20% have been estimated. Besides microbial plant protection products that are currently in the process of re-registration, several microbial products have been registered or are in the process of registration, following the EU directive 91/414. Entomopathogenic nematodes (EPN) are exceptionally safe biocontrol agents. Until today, they are exempted from registration in most European countries, the reason why SMEs were able to offer economically reasonable nematode-based products. The development of technology for mass production in liquid media significantly reduced the product costs and accelerated the introduction of nematode products in tree nurseries, ornamentals, strawberries, mushrooms, citrus and turf. Progress in storage and formulation technology has resulted in high quality products which are more resistant to environmental extremes occurring during transportation to the user. The cooperation between science, industry and extension within the EU COST Action 819 has supported the development of quality control methods. Today four companies produce EPN in liquid culture, offering 8 different nematode species. Problems with soil insects are increasing. Grubs, like Melolontha melolontha and other scarabaeidae cause damage in orchards and turf. Since the introduction of the Western Corn Rootworm Diabrotica virgifera into Serbia in 1992, this pests as spread all over the Balkan Region and has reached Italy, France and Austria. These soil insect pests are potential targets for EPN. The development of insecticide resistance has opened another sector for EPN. Novel adjuvants used to improve formulation of EPN have enabled the foliar application against Western Flower Thrips and Plutella xylostella. To reach these markets, the product costs for EPN will have to further decrease in the future. One possibility to reduce application costs related with the use of EPN is the inoculative application to cause long term effects on pest populations.

Animals↗

Update on infective endocarditis.

With infective endocarditis afflicting 15,000 patients each year and with a mortality rate that still hovers at almost 40%, the disease remains a very serious health problem. Surprisingly, the incidence has not declined over the last 30 years, and now with more health care interventions, such as pacer/defibrillators, and an increasingly elderly population with degenerative valvular heart disease, the number susceptible to endocarditis is actually increasing. Given the weak evidence for endocarditis prophylaxis, there remains a large population at risk. Much has been learned recently about the pathogenesis of endocarditis, including the role of endothelial damage, platelet adhesion, and microbial adherence to the vegetation or intact valvular tissue. Three-fourths of patients have preexisting structural heart disease. Once infection is manifest, major cardiac complications include congestive heart failure, embolization, mycotic aneurysms, renal dysfunction, and abscess formation. The diagnosis of endocarditis has been enhanced recently by modifications in the Duke criteria to include the use of transesophageal echocardiography and microbial antibody titers. Surgery continues to play an important role, with criteria for emergency, urgent, and early surgery now defined. The major organisms involved in infective endocarditis include streptococci and staphylococcus (representing 75% or so of all cases). Enterococcal infections account for many of the remaining cases, although small series and case reports suggest almost all organisms that infect humans can be implicated at times. A sizeable number of "culture-negative" cases still occur despite all the improvements in diagnostic methodology. Recent guidelines for the diagnosis, treatment, and management of infective endocarditis from the American Heart Association are reviewed and the issues surrounding prophylaxis are summarized. International cooperative databases are now being developed that hold promise for a continual reexamination of the epidemiology of this highly aggressive disease and may help provide sorely needed prospective trial data that will enhance our understanding and treatment.

Anti-Infective Agents↗

Testing the efficacy of a molecular surveillance network: methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) genotypes in six hospitals in the metropolitan New York City area. The BARG Initiative Pilot Study Group. Bacterial Antibiotic Resistance Group.

Molecular fingerprinting techniques are rapidly becoming indispensable tools for hospital epidemiology. On the other hand, the relative complexity and unfamiliarity of these techniques to most hospital diagnostic laboratories limit their usefulness. In an attempt to provide a solution for this dilemma, we tested the feasibility and efficacy of a cooperative venture in which molecular typing of isolates recovered from patients in six hospitals was performed at two microbiology research laboratories with expertise in these techniques. In a small preliminary study, 30 methicillin-resistant Staphylococcus aureus (MRSA) and 30 vancomycin-resistant Enterococcus faecium (VREF) isolates were collected over a 3-week period from six hospitals in the metropolitan New York area and transported to the Laboratory of Microbiology at The Rockefeller University during the summer months of 1994. Nineteen of the 27 confirmed MRSA isolates were closely related strains carrying the same mecA and the same Tn554 polymorphs in a pulsed-field gel electrophoresis (PFGE) background represented by closely related subtypes of a single pattern, indicating the wide distribution of this MRSA clone among the participating hospitals. Typing of the same 27 MRSA isolates was also performed at the Tuberculosis Center of the Public Health Research Institute and identical results were obtained. The 29 confirmed VREF isolates were highly heterogeneous and belonged to as many as 23 distinct clonal types as defined by PFGE patterns and probing with vanA. Characterization of the 60 isolates by these methods was completed in one month of full-time effort by a single experienced laboratory assistant guided by a doctoral-level expert in molecular fingerprinting techniques. The collection of samples for both MRSA and VREF was not intended to address epidemiological questions but to determine the feasibility of a multicenter study. On the basis of our preliminary findings we are encouraged that a larger cooperative effort is possible and with the correct sampling method we believe that epidemiological and surveillance studies could be accomplished that would provide a tracking system to assist hospitals, clinics, and chronic care facilities in controlling the spread of multidrug-resistant pathogens.

Anti-Bacterial Agents↗

GENETIC RECOMBINATION BETWEEN THE RESISTANCE TRANSFER FACTOR AND THE CHROMOSOME OF ESCHIERICHIA COLI.

Ginoza, Herbert S. (National Aeronautics and Space Administration, Moffett Field, Calif.), and Robert B. Painter. Genetic recombination between the resistance transfer factor and the chromosome of Escherichia coli. J. Bacteriol. 87:1339-1345. 1964.-Genetic instability for high-level streptomycin and chloramphenicol resistance was observed in several strains of Escherichia coli infected with the resistance transfer factor (RTF) episome. The altered site was always found on the chromosome, and the resistance characteristics were similar to, if not identical with, the corresponding determinant found on the episome. The high-level drug resistance phenotype was ascribed to two separate loci acting cooperatively within the host. The instability phenomenon had been attributed to a genetic exchange mechanism in which the chromosome copies the drug-resistance information from the episome, thus giving rise to a diploid homogenote for this segment. In a reciprocal exchange system, the tetracycline-resistance marker on the chromosome was shown to recombine with the RTF episome lacking this information.

Chloramphenicol↗

Interferon-mediated development of influenza virus resistance in hybrids between Mx gene-bearing and control mouse embryo fibroblasts.

The presence of the gene Mx results in a greater interferon (IFN)-mediated antiviral resistance in cells challenged by orthomyxovirus. In the absence of IFN no difference in influenza virus yield was detected in Mx-bearing (Mx/Mx) or non-bearing (+/+) mouse embryo fibroblasts. Although the putative product of the gene Mx has been suggested to act in concert with IFN it is not clear whether Mx was itself induced by IFN. Binucleate heterokaryons were formed by the fusion of an Mx/Mx cell and an IFN-treated +/+ cell. Results show that no constitutive activity was present in the Mx cell that was not IFN-treated, which was capable of enhancing the marginal anti-influenza virus resistance characteristic of the IFN-treated +/+ cell. Heterokaryons between +/+ cells and IFN-treated Mx/Mx cells, however, showed resistance characteristic of the Mx-containing cell. Hybrids of fusions between IFN-pretreated +/+ cells and Mx/Mx cells that had been IFN-treated for 1 to 2 h revealed a graded response to influenza virus growth inhibition. Resistance in such hybrids increased commensurate with the development of the anti-influenza virus state in the Mx/Mx donor. No synergistic enhancement of influenza virus growth inhibition was observed. These data suggest that the product of the gene Mx is induced by IFN. Cybrids, constructed between nucleated +/+ or Mx/Mx cells and enucleated Mx/Mx cytoplasts, when subsequently treated with IFN and challenged with influenza virus, showed resistance characteristic only of the nucleated cell donor. Thus, no cytoplasmic component present in Mx-bearing cytoplasts is able to cooperate with the nuclear elements of a +/+ cell to induce a state of high influenza virus resistance. The simplest interpretation of these data is that specific resistance is not the result of modifications of virus growth or IFN activities but probably occurs by the IFN-mediated induction of the gene Mx, the product of which directly, or indirectly, interferes with orthomyxovirus replication.

Animals↗

Therapeutic and epidemiologic recommendations to reduce the spread of type-I beta-lactamase resistance.

The objectives of this United States Consensus Panel meeting were to evaluate the effectiveness of current surveillance systems for the detection of bacterial resistance as well as to formulate recommendations that can assist hospitals in determining actions that should be taken when a resistance problem is detected. These recommendations may be particularly helpful in controlling the emergence and spread of type-I beta-lactamase resistance. Numerous case reports of antimicrobial resistance among Enterobacter species, Pseudomonas aeruginosa, and other Gram-negative nosocomial pathogens known to produce type-I beta-lactamases have appeared in the literature since the introduction of the newer "third-generation" cephalosporins. The widespread use of these newer antimicrobial agents, often selected as standard therapy for serious hospital-acquired infections, has been associated with a corresponding increase in resistance to them. The failure of hospitalwide surveillance methods to describe the scope of this problem, especially among the most critically ill patients, may have resulted in a false sense of security among some infectious disease specialists and clinicians prescribing these antimicrobials as empiric therapy. High-level resistance in individual hospital units may be masked in hospitalwide antibiograms. A variety of conclusions and recommendations were formulated based on the collective experiences of the Consensus Panel members. Microbiology laboratories must make it a high priority to identify markers that will assist in rapidly identifying resistant organisms. Cooperative efforts are needed among users of commercial and automated microbiology test instruments to standardize results and to improve quality control, thereby making the data more directly comparable between laboratories.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

Sequential degradation of interstitial collagen by metalloproteinases extracted from tumors of murine ascites hepatomas.

Gelatinolytic and collagenolytic proteinases were separately isolated by different extraction methods from the mouse ascites hepatoma MH134, and from rat ascites hepatoma AH109A. The activities of two proteinases in each extract showed no significant differences, but after trypsin activation the activities of proteinases from the highly metastatic MH134 were significantly increased compared to the enzyme activities in AH109A, which has low metastatic potential. The total activities of collagenase and gelatinase were increased 7.2- and 5.1-fold; their specific activities were increased 5.2- and 4.8-fold, respectively. Gelatinase and collagenase from MH134 were characterized on gelatin zymography. The gelatinase had a molecular weight of 99 and activation by 4-aminophenylmercuric acetate (APMA) or trypsin resulted in its conversion to 79 or 79-95 kD, respectively. The collagenase revealed a major gelatinolytic band at 89 kD, which was converted to 85 and 70 kD by APMA-activation, and a minor gelatinolytic band at 60 kD. These proteinases could degrade native type I collagen to small fragments in a cooperative manner. Trypsin inhibitor, which affects the trypsin activation of latent gelatinase, was extracted together with gelatinase. The inhibitory activity of the enzyme from AH109A showed a 4.1-fold higher specific activity and 3.7-fold greater total activity than that from MH134. The proteinase(s) capable of activating the gelatinase was also extracted from MH134.

Animals↗

Correlation of thermodynamic and genetic properties in the Tn10 encoded TET gene control region.

The thermal stability of the Tn10 encoded tetracycline resistance (TET) gene control region is investigated by melting studies using purified DNA restriction fragments containing various amounts of flanking sequences. In order to study the thermodynamic properties of this control region under conditions, where enough flanking DNA is present to mimic the situation in the chromosome, the five step melting process of a 1450-bp DNA fragment is analyzed. Because most of the sequence of this DNA is not known, the assignment of the melting transitions to segments of the DNA is done by an experimental method. This employs the preparation of subfragments from the 1450-bp DNA and comparison of their denaturation profiles with the one of the intact sequence. This approach results in the complete assignment of the five denaturation steps. Rather than from the ends, the unwinding starts from the TET gene control region in the middle of the 1450-bp sequence. A clear correlation between the thermodynamic and genetic properties of this DNA is observed. The regulatory sequence forms a small cooperative unit with the lowest stability in the entire fragment. The thermal denaturation of the TET repressor. TET operator complex reveals, that the TET repressor specifically recognizes the double stranded TET operator DNA and stabilizes this structure by 2.4 degrees C. This results is also discussed as an example of the possible action of denaturing or stabilizing proteins on this genetic control region.

DNA Restriction Enzymes↗

Gliding motility mutants of Myxococcus xanthus.

Two gliding motility mutants of Myxococcus xanthus are described. The semimotile mutant (SM) originated by high-frequency segregation from the motile FB(t) strain. Segregation was enhanced by acridine dye treatment. SM cells glide only when apposed to other cells in a swarm. The nonmotile strain (NM) originated by mutation from SM. NM cells neither glide individually nor cooperatively. FB(t), SM, and NM are indistinguishable with respect to fine structure, vegetative growth rate, glycerol-induced microcyst formation, spheroplasting, bacteriophage sensitivity, and responses to light. The motility mutants are more resistant to penicillin and more sensitive to actinomycin D than is the gliding wild type. The NM mutant is also a morphogenetic mutant; it is unable to form fruiting bodies.

Acridines↗

Identification and characterization of a novel Ets-2-related nuclear complex implicated in the activation of the human interleukin-12 p40 gene promoter.

Interleukin-12 (IL-12) is a proinflammatory cytokine produced by antigen-presenting cells in response to many microbial infections. IL-12 plays an important role in the generation of T helper type-1 cells, which favor cell-mediated immune response. IL-12 is composed of two different subunits, p40 and p35, whose expression can be regulated concomitantly or differentially. Monocytic cells, the major producers of IL-12, can be primed by interferon-gamma (IFN-gamma) to produce optimal amounts of IL-12 in response to LPS stimulation as a consequence of bacterial infection. The priming effect is exerted primarily at the transcriptional level on the p40 promoter in conjunction with the effects of LPS, possibly by inducing specific transcription factors, which individually have no direct effect but which cooperatively can activate the promoter. We examined in detail one of these DNA-protein interactions observed around an Ets-2 element situated at -211/-207 of the p40 promoter, which is known to be a functionally critical site. This region interacts with a nuclear complex termed F1 that appears to be highly inducible by either IFN-gamma treatment for 16 h or lipopolysaccharide stimulation for 8 h. F1 binding to the Ets-2 site requires a considerable amount of spacing around the Ets-2 site, as revealed by gel mobility shift and in vitro methylation assays. Supershift experiments and DNA affinity purification indicated that both Ets-2 and a novel, antigenically related protein with an approximate molecular mass of 109 kDa are part of the F1 complex, together with additional components including IRF-1 and c-Rel. This novel protein is designated GLp109 for its inducibility by IFN-gamma or lipopolysaccharide. Its possible role in the activation of the IL-12 p40 promoter is discussed.

Animals↗

Mechanism of action of gentamicin components. Characteristics of their binding to Escherichia coli ribosomes.

The binding of gentamicin (Gm) to Escherichia coli ribosomes and ribosomal subunits has been studied. By means of equilibrium dialysis and of statistical interpretation of the data it was found that [3H]gentamicin C2 and 6'-N-[3H]methylgentamicin C1a interact with three classes of sites on tight-coupled 70-S species: a first class concerning the tight and non-cooperative interaction with one drug molecule (Kd = 0.6 microM), a second class in which about five Gm molecules bind cooperatively (mean Kd = 10 microM), and a third class of very high capacity in which up to 70 drug molecules may interact. The extreme cooperativity of the third class of sites induces such an increase in the affinity for Gm that it may allow the shift of molecules already bound from high-affinity sites towards lower-affinity sites. The alteration of a ribosomal protein, L6, in a gentamicin-resistant mutant of E. coli abolished the multiclass and the cooperative aspects of ribosomes--gentamicin interaction. The large ribosomal subunits from E. coli MRE 600 strain interact cooperatively with Gm, whereas 50-S particles from the resistant mutant bind the drug in a diffuse way with high capacity and low affinity. The small subunits from both strains behave identically towards Gm. A good correlation is observed in comparing the gentamicin concentrations capable of saturating the different ribosomal classes of sites with concentrations inducing its multiphasic effects on protein synthesis.

Drug Resistance, Microbial↗

Direct and indirect pathogenicity of beta-lactamase-producing bacteria in respiratory tract infection in children. Role of cephalosporins resistant to enzymatic hydrolysis.

A recent increase in the incidence of beta-lactamase-producing aerobic and anaerobic bacteria in upper respiratory tract infection has been associated with an increase in the failure rate of penicillin treatment of these infections. Experimental evidence for this correlation has been reported by many investigators, who have described the sheltering of susceptible pathogens by beta-lactamase-producing organisms as 'indirect pathogenicity'. The organisms implicated in mixed infections that cooperate are Staphylococcus aureus, Haemophilus influenzae, Branhamella (Moraxella) catarrhalis and Bacteroides spp., which are pathogenic and also normal oropharyngeal inhabitants. Since these bacteria exhibit both direct and indirect pathogenicity, effective treatment requires administration of antimicrobial therapy active against all microorganisms present in mixed infection. Oral third generation cephalosporins, which are resistant to enzymatic hydrolysis, seem to be suitable initial therapy.

Bacteria↗

Prevalence of fluoroquinolone resistance in Europe. Study Group 'Bacterial Resistance' of the Paul-Ehrlich-Society for Chemotherapy e. V.

Since 1984, when the first fluoroquinolone, norfloxacin, was marketed in Europe, there has been a marked increase in the usage of this class of drugs. In order to evaluate the influence of this drug usage on the prevalence of resistance to fluoroquinolones in clinical isolates of the family Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus, coagulase-negative staphylococci and Enterococcus faecalis we reviewed the susceptibility data from four collaborative surveys conducted between 1983 and 1990 by the Study Group 'Bacterial Resistance' of the Paul-Ehrlich-Society for Chemotherapy. All participating laboratories used the same standardized methods. Minimal inhibitory concentrations were determined by the broth microdilution method. More than 20,000 bacterial strains were tested. The results are presented for ciprofloxacin, which is regarded as the representative of the fluoroquinolones. Using > or = 4 mg/l as a breakpoint for resistance to ciprofloxacin, the prevalence of resistant strains of the family Enterobacteriaceae in Central Europe between 1983 and 1990 remained below 1%. In contrast, the resistance rates in P. aeruginosa were 0.7%, 1.0%, 3.8% and 7.0%, in S. aureus 0%, 0.5%, 6.6% and 6.8%, and in E. faecalis 2.2%, 0.7%, 4.9% and 7.7% in 1983, 1986, 1989 and 1990, respectively. The latest study carried out in cooperation with 78 laboratories from 12 European countries revealed great differences in the prevalence of resistance to fluoroquinolones from one species to another ranging from 0% with Proteus vulgaris and Salmonella spp. to 26.7% with Providencia stuartii.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Infective Agents↗

Dinuclear copper(II) complex as nitric oxide scavenger in a stimulated murine macrophage model.

Nitric oxide is a gaseous, short-living free radical which behaves as an important signaling molecule with pleiotropic capacities including vasodilatation, neurotransmission, and microbial and tumor cell killing, as well as in tissue damage and organ-specific autoimmune disorders. Here, a synthesized, dinuclear copper complex system in vitro obtained by the simple aza-phenolic ligand 2,6-bis[[bis-(2-aminoethyl)amino]methyl]phenol (L) and Cu(II) ion has been used. The stability constants of ligand L with Cu(II) ion were determined through potentiometric measurements in aqueous solution (37.1 +/- 0.1 degrees C, I = 0.15 M of NaCl) to mimic the biological medium. The measurements demonstrated that [Cu(2)H(-1)L(OH)](2+) (DCu) is the predominant species present in solution at pH 7.4. The molecular structure of the ligand in this species permits the cooperation of the two copper ions in assembling the substrate, thus the complex can be used as a receptor for small molecules such as NO. As a biological model, we chose the production of NO catalyzed by inducible nitric oxide synthase obtained from RAW 264.7 murine macrophage cell line stimulated with LPS, which enabled us to prove that NO is coordinated by the DCu complex, modifying its EPR spectra. The coordination of NO with DCu reduces the level of nitrite in the culture medium of stimulated RAW 264.7 macrophages without any inhibition in the expression of iNOS.

Animals↗

Microbiological diffusion assay II: design and applications.

Application of new equipment and new techniques was made to antibiotic diffusion assays. Accumulation of data and computation of potencies were made by an on-line computer. The system was tested by assaying cephalexin with the aid of Bacillus subtilis in an FDA single-dose design modified by reducing the number of standards to two. The influence of the thickness of the base layer and the form of the dose-response line were tested. Zone diameter was measured with a resolution of 0.01 mm. The potency of samples was measured with an error usually less than 3%. An error of 0.1 mm in measuring zone size would cause an error of 3% of potency. The usual calibration line was inadequate for extrapolation beyond a twofold range. A dose-response line derived from the Cooper equation was better for standard curves spanning more than a twofold range of concentrations. Precision was better on the plates with the 20-ml base layer. The two-dose method of assaying gave larger errors than the single-dose method. Large variances in measuring zone diameters are a reason for the low precision of diffusion assays and set an inherent limit on precision.

Analysis of Variance↗

The clinical impact of automated susceptibility reporting using a computer interface.

The rapid automated reporting capability of the Vitek-Sunquest interface was shown to have a direct clinical and monetary impact on patient management. The audit performed on autofiled positive culture results at Cooper Hospital/University Medical Center demonstrated an average savings of $243 per day in antimicrobial utilization. A further enhancement in the computer software for the Vitek and Sunquest systems was the development of the Bidirectional Computer Interface (BCI). The BCI upgrade allows the Microbiology laboratory to utilize both the Sunquest and Vitek IMS programs to generate a wide variety of epidemiology reports with a minimum of keyboard entry time.

Automation↗

Molecular epidemiology of extended-spectrum beta-lactamase-producing, fluoroquinolone-resistant isolates of Klebsiella pneumoniae in Taiwan.

Strains of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) have emerged worldwide. Concomitant ciprofloxacin resistance with ESBL production in K. pneumoniae isolates would severely restrict treatment options. Among 39 (18.5%) of 211 ESBL-KP isolates resistant to ciprofloxacin (MIC, >/=4 micro g/ml), 37 (95%) were high level resistant (MIC, >/=16 micro g/ml). These isolates were also cross resistant to the newer fluoroquinolones, including levofloxacin, gatifloxacin, gemifloxacin, and garenoxacin (BMS 284756). Sitafloxacin was most active against these ciprofloxacin-resistant ESBL-KP isolates with MICs for 67% of the isolates being </=2 micro g/ml. The molecular epidemiology of these multiresistant isolates was investigated by automated ribotyping and pulsed-field gel electrophoresis (PFGE). Ribotyping identified 18 different strains among the 39 ciprofloxacin-resistant ESBL-KP isolates. The majority (67%) of these isolates were contained in six ribogroups which were further confirmed by PFGE. The distribution of the six major strains of ciprofloxacin-resistant ESBL-KP within Taiwan included one (ribogroup 255.3-PFGE type E) with a nationwide distribution and several institution-specific strains. Interhospital cooperation appears necessary, with strict infection control practices coupled with restriction of fluoroquinolone and extended-spectrum beta-lactam use to control both the major epidemic strain and the more diverse strains observed within individual institutions.

Anti-Infective Agents↗