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Biomedical subjects

G V Doern

Publications and source records attributed to G V Doern.

At least 91 records · Page 5Linked to original sources

In vitro activity of BAY 12-8039, a novel 8-methoxyquinolone, compared to activities of six fluoroquinolones against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

The in vitro activity of a novel 8-methoxyquinolone, BAY 12-8039, against recent clinical isolates of Streptococcus pneumoniae (n = 404), Haemophilus influenzae (n = 330), and Moraxella catarrhalis (n = 250) was evaluated. Activity was compared to those of six other fluoroquinolones: ciprofloxacin, clinafloxacin, levofloxacin, ofloxacin, sparfloxacin and trovafloxacin. BAY 12-8039 and clinafloxacin had the highest levels of activity against S. pneumoniae, both with a MIC at which 90% of the isolates were inhibited (MIC90) of 0.06 microg/ml. Trovafloxacin and sparfloxacin were the next most active agents versus S. pneumoniae (MIC90s = 0.12 microg/ml). No differences in activity against penicillin-susceptible, -intermediate, or -resistant strains of S. pneumoniae were noted for any of the fluoroquinolones tested. MIC90s for the seven fluoroquinolones ranged from 0.008 to 0.06 microg/ml versus H. influenzae and from 0.008 to 0.12 microg/ml for M. catarrhalis. The MICs for two strains of S. pneumoniae and one strain of H. influenzae were noted to be higher than those for the general population of organisms for all of the fluoroquinolones tested. Finally, the activity of BAY 12-8039 versus S. pneumoniae was found to be diminished when MIC determinations were performed with incubation of agar dilution plates or broth microdilution trays in 5 to 7% CO2 versus ambient air.

Anti-Infective Agents↗

Four-day incubation period for blood culture bottles processed with the Difco ESP blood culture system.

Blood culture records from 1994 to 1995 from five U.S. medical centers all using the Difco ESP continuous monitoring blood culture system were reviewed retrospectively. Among a total of 7,362 isolates of bacteria and yeasts, only 0.1% of possibly significant isolates would have been missed had blood cultures been routinely incubated for 4 days instead of the 5 days recommended by the manufacturer. Conversely, numerous contaminants, detected only on day 5, would have been eliminated by a 4-day incubation period.

Bacterial Typing Techniques↗

Multicenter laboratory evaluation of the bioMérieux Vitek antimicrobial susceptibility testing system with 11 antimicrobial agents versus members of the family Enterobacteriaceae and Pseudomonas aeruginosa.

A four-center study in which a total of 1,082 recent clinical isolates of members of the family Enterobacteriaceae and Pseudomonas aeruginosa were examined versus 11 antimicrobial agents with the bioMérieux Vitek susceptibility test system (Hazelwood, Mo.) and the GNS-F6 card was conducted. In addition, a challenge set consisting of the same 200 organisms was examined in each of the four participating laboratories. Results obtained with the Vitek system were compared to MICs determined by a standardized broth microdilution method. For purposes of comparison, susceptibility categories (susceptible, intermediate, or resistant) were assigned on the basis of the results of both methods. The result of the broth microdilution test was considered definitive. The total category error rate with the Vitek system and the recent clinical isolates (11,902 organism-antimicrobial comparisons) was 4.5%, i.e., 1.7% very major errors, 0.9% major errors, and 1.9% minor errors. The total category error rate calculated from tests performed with the challenge set (i.e., 8,800 organism-antimicrobial comparisons) was 5.9%, i.e., 2.2% very major errors, 1.1% major errors, and 2.6% minor errors. Very major error rates higher than the totals were noted with Enterobacter cloacae versus ampicillin-sulbactam, aztreonam, ticarcillin, and ticarcillin-clavulanate and with P. aeruginosa versus mezlocillin, ticarcillin, and ticarcillin-clavulanate. Major error rates higher than the averages were observed with Proteus mirabilis versus imipenem and with Klebsiella pneumoniae versus ofloxacin. Excellent overall interlaboratory reproducibility was observed with the Vitek system. The importance of inoculum size as a primary determinant in the accuracy of susceptibility test results with the Vitek system was clearly demonstrated in this study. Specifically, when an inoculum density fourfold higher than that recommended by the manufacturer was used, high rates of false resistance results were obtained with cell wall-active antimicrobial agents versus both the Enterobacteriaceae and P. aeruginosa.

Anti-Bacterial Agents↗

Lack of requirement for prolonged incubation of Septi-Chek blood culture bottles in patients with bacteremia due to fastidious bacteria.

A questionnaire survey for which there were 538 respondents from American clinical microbiology laboratories was used to assess the need for prolonged incubation of Septi-Chek blood culture bottles for the recovery of HACEK bacilli, Brucella species, Francisella tularensis, and nutritionally deficient streptococci from blood. Among a total of 219 reported isolates of these bacteria, in only 6 cases (2.7%) was incubation longer than 7 days required. Only 2 of 136 patients (1.5%) were noted to be bacteremic exclusively following incubation of Septi-Chek blood culture bottles for periods of greater than 7 days. It appeared from the results of this study, that incubation of Septi-Chek blood culture bottles for 7 days is usually sufficient in patients suspected of having bacteremia due to fastidious bacteria.

Bacteremia↗

Comparative activity of twelve beta-lactam drugs tested against penicillin-resistant Streptococcus pneumoniae from five medical centers: effects of serum protein and capsular material on potency and spectrum as measured by reference tests.

A total of 152 strains of Streptococcus pneumoniae from diverse geographic areas in the United States and with different levels of penicillin resistance were tested against five broad-spectrum cephalosporins, ampicillin, piperacillin, ticarcillin, and three beta-lactamase inhibitor combinations. Also, the effect of human serum proteins on the activity of selected "third-generation" cephalosporins was examined. The overall rank order of activity among the cephalosporins against penicillin-susceptible strains was: ceftriaxone (MIC90, 0.03 microgram/mL) > cefotaxime > ceftizoxime = cefuroxime > ceftazidime (MIC90, 0.5 microgram/mL). Only cefotaxime and ceftriaxone exhibited significant activity against penicillin-intermediate or -resistant isolates. Ampicillin, piperacillin, and penicillin were generally eight- to 16-fold more potent than ticarcillin and no increase in the effectiveness of these agents was observed with the addition of the beta-lactamase inhibitors (clavulanate, sulbactam, tazobactam). Ceftriaxone potency was significantly decreased (> or = four-fold) by the modest addition of 25% pooled human serum proteins and this change modified the rank order of potency against nonpenicillin-susceptible pneumococci to favor cefotaxime (41% resistant versus 71% for ceftriaxone; MICs at > or = 2 micrograms/mL). Induced high-level capsular production had no measurable effect on the MIC results of tested agents. These results confirm the continued activity advantages of cefotaxime and ceftriaxone against various populations of pneumococci compared to other alternative beta-lactams. The predictive value, however, of the utilized breakpoint concentrations of the cephalosporins, remains in question for pneumococcal infections other than those in the central nervous system and at unaltered, "usual" dosing.

Anti-Bacterial Agents↗

Accurate characterization of ofloxacin susceptibility with Enterobacteriaceae using a modified GNS F6 card and the bioMerieux Vitek System.

Routine antimicrobial susceptibility testing of Enterobacteriaceae using the Vitek System (bioMerieux Vitek, Hazelwood, MO) and the GNS-F6 card revealed discrepancies between the activity of ofloxacin and ciprofloxacin, primarily with isolates of Klebsiella pneumoniae. Specifically, during a one-year period, 12% of 618 ciprofloxacin-susceptible isolates were determined to be ofloxacin resistant with the GNS-F6 card. A similar problem, but one of lower magnitude, was observed with Serratia marsescens. That these represented false ofloxacin resistance results was confirmed by comparison of broth microdilution determinations of ofloxacin MICs with F6 results on a collection of 203 fresh clinical isolates of K. pneumoniae and 39 isolates of S. marsescens. The GNS-F6 card was then modified by the manufacturer to include a new formulation of ofloxacin and assessed using a collection of 224 recent clinical isolates of Enterobacteriaceae and Pseudomonas aeruginosa, and 78 stock cultures of enteric Gram-negative bacilli selected specifically because of disproportionately high rates of fluoroquinolone resistance. No ofloxacin false resistant results were observed with this collection when the modified GNS-F6 card was evaluated in comparison to a standardized broth microdilution MIC test. The current clinical version of the Vitek System appears to accurately assess ofloxacin susceptibility.

Anti-Infective Agents↗

In vitro activity of sanfetrinem (GV104326), a new trinem antimicrobial agent, versus Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

Sanfetrinem, formerly GV104326, is a new trinem antimicrobial agent with extensive in vitro activity for a variety of different bacteria. The activity of sanfetrinem was determined using a broth microdilution MIC method versus a large number of clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis obtained in a recent 30-center United States surveillance study. The sanfetrinem MIC50 and MIC90 values for these three organism groups were 0.015 and 0.5 microgram/ml, 0.25, and 0.5 microgram/ml, and 0.015 and 0.03, respectively.

Anti-Bacterial Agents↗

Antimicrobial resistance among lower respiratory tract isolates of Haemophilus influenzae: results of a 1992-93 western Europe and USA collaborative surveillance study. The Alexander Project Collaborative Group.

During 1992 and 1993, 2718 respiratory tract isolates of Haemophilus influenzae were obtained from two study centres in each of five West European countries and five study centres in the USA. beta-Lactamase production was assessed and MICs of 14 antimicrobial agents determined in a single co-ordinating laboratory using a broth microdilution method in Mueller-Hinton-lysed horse blood medium. The prevalence of strains producing beta-lactamase varied between 0 and 37.9%. In general, the highest prevalence was in study centres from Spain and the USA with slightly lower rates observed in France and the UK. Only a single confirmed beta-lactamase-negative, ampicillin resistant strain was recovered during the entire study. Erythromycin resistance, defined as an MIC of > or = 4.0 mg/L, was noted in 57.5% of isolates. Among the other antimicrobials tested, resistance rates > or = 1.0% were observed only with cefaclor (3.7%), chloramphenicol (1.4%) and co-trimoxazole (2.5%). In no case, was the prevalence of resistance or beta-lactamase production significantly greater in 1993 than in 1992.

Amoxicillin↗

Prevalence of antimicrobial resistance among 723 outpatient clinical isolates of Moraxella catarrhalis in the United States in 1994 and 1995: results of a 30-center national surveillance study.

Seven hundred twenty-three isolates of Moraxella catarrhalis obtained from outpatients with a variety of infections in 30 medical centers in the United States between 1 November 1994 and 30 April 1995 were characterized in a central laboratory. The overall rate of beta-lactamase production was 95.3%. When the National Committee for Clinical Laboratory Standards MIC interpretive breakpoints for Haemophilus influenzae were applied, percentages of strains found to be susceptible to selected oral antimicrobial agents were as follows: azithromycin, clarithromycin, and erythromycin, 100%; tetracycline and chloramphenicol, 100%; amoxicillin-clavulanate, 100%; cefixime, 99.3%; cefpodoxime, 99.0%; cefaclor, 99.4%; loracarbef, 99.0%; cefuroxime, 98.5%; cefprozil, 94.3%; and trimethoprim-sulfamethoxazole, 93.5%.

Anti-Bacterial Agents↗

Emergence of high rates of antimicrobial resistance among viridans group streptococci in the United States.

Three hundred fifty-two blood culture isolates of viridans group streptococci obtained from 43 U.S. medical centers during 1993 and 1994 were characterized. Included were 48 isolates of "Streptococcus milleri," 219 S. mitis isolates, 29 S. salivarius isolates, and 56 S. sanguis isolates. High-level penicillin resistance (MIC, > or = 4.0 micrograms/ml) was noted among 13.4% of the strains; for 42.9% of the strains, penicillin MICs were 0.25 to 2.0 micrograms/ml (i.e., intermediate resistance). In general, amoxicillin was slightly more active than penicillin. The rank order of activity for five cephalosporins versus viridans group streptococci was cefpodoxime = ceftriaxone > cefprozil = cefuroxime >> cephalexin. The percentages of isolates resistant (MIC, > or = 2 micrograms/ml) to these agents were 15, 17, 18, 20, and 96, respectively. The rates of resistance to erythromycin, tetracycline, and trimethoprim-sulfamethoxazole were 12 to 38%. Resistance to either chloramphenicol or ofloxacin was uncommon (i.e., < 1%). In general, among the four species, S. mitis was the most resistant and "S. milleri" was the most susceptible.

Anti-Bacterial Agents↗

Antimicrobial resistance of Streptococcus pneumoniae recovered from outpatients in the United States during the winter months of 1994 to 1995: results of a 30-center national surveillance study.

A total of 1,527 clinically significant outpatient isolates of Streptococcus pneumoniae were prospectively collected in 30 different U.S. medical centers between November 1994 and April 1995. Overall, 23.6% of strains were not susceptible to penicillin, with 14.1% intermediate and 9.5% high-level resistant. The frequencies of recovery of intermediate and high-level resistant strains varied considerably between different medical centers and in different geographic areas. In general, intermediate and high-level penicillin resistance was most common with isolates of S. pneumoniae recovered from pediatric patients. The in vitro activities of 22 other antimicrobial agents were assessed against this collection of isolates. Ampicillin was consistently 1 twofold dilution less active than penicillin. Amoxicillin and amoxicillin-clavulanate were essentially equivalent to penicillin in activity. The rank order of activity for cephalosporins was cefotaxime = ceftriaxone > or = cefpodoxime > or = cefuroxime > cefprozil > or = cefixime > cefaclor = loracarbef > cefadroxil = cephalexin. The National Committee for Clinical Laboratory Standards [Performance Standards for Antimicrobial Susceptibility Testing, Sixth Information Supplement (M100-S6), 1995] has established MIC breakpoints for resistance (i.e., > or = 2 micrograms/ml) with three cephalosporins versus S. pneumoniae, namely, cefotaxime, ceftriaxone, and cefuroxime. The overall percentages of strains resistant to these three antimicrobial agents were 3, 5, and 12, respectively. The overall frequency of resistance was 10% with all three macrolides examined in this study, clarithromycin, erythromycin, and azithromycin. The overall percentages of chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole resistance were 4.3, 7.5, and 18, respectively. The resistance percentages among the cephalosporins, macrolides, chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole were consistently higher among penicillin-intermediate strains than among susceptible isolates and even higher still among organisms expressing high-level penicillin resistance. Multiply resistant strains represented 9.1% of the organisms examined in this study. Finally, rifampin resistance was uncommon (i.e., 0.5%), and vancomycin resistance was not detected. The quinopristin-dalfopristin combination was consistently active at concentrations of 0.25 to 4 micrograms/ml, but rates of resistance could not be determined in the absence of established interpretive criteria for MIC results.

Adolescent↗

Proposed MIC quality control guidelines for National Committee for Clinical Laboratory Standards susceptibility tests using seven veterinary antimicrobial agents: ceftiofur, enrofloxacin, florfenicol, penicillin G-novobiocin, pirlimycin, premafloxacin, and spectinomycin.

The present multicenter study proposes broth microdilution quality control (QC) ranges for the antimicrobial agents ceftiofur, enrofloxacin, florfenicol, penicillin G-novobiocin, pirlimycin, premafloxacin, and spectinomycin, which are used in veterinary practice. Six separate laboratories tested replicates of National Committee for Clinical Laboratory Standards (NCCLS)-recommended QC organisms (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213, and Enterococcus faecalis ATCC 29212) on medium lots both common and unique to all laboratories. The proposed ranges were within 3 or 4 log2 dilution steps of the modal MICs for all organism-antimicrobial agent pairs, depending on their MIC distributions. With > or = 94.7% of all MIC results being within the proposed QC ranges, all combinations tested comply with NCCLS guidelines and all have been accepted by the NCCLS subcommittee developing susceptibility testing procedures for veterinary laboratories.

Anti-Bacterial Agents↗

Trends in antimicrobial susceptibility of bacterial pathogens of the respiratory tract.

Rates of antimicrobial resistance have been increasing in bacteria responsible for community-acquired lower respiratory tract infections in the United States. Nearly 100% of clinical isolates of Moraxella catarrhalis now produce beta-lactamase, an enzyme that renders this pathogen resistant to such agents as penicillin, ampicillin, and amoxicillin. However, this organism remains nearly uniformly susceptible to alternative oral antimicrobials, such as cephalosporins, macrolides, tetracyclines, beta-lactamase inhibitor combinations, and the combination of trimethoprim/sulfamethoxazole. The susceptibility of M. catarrhalis to these agents is not expected to change markedly in the next few years. A linear increase in the prevalence of beta-lactamase-mediated ampicillin resistance has been evident among isolates of nontypeable Haemophilus influenzae during the past decade in the United States. By the year 2000, 45-50% of isolates are likely to produce beta-lactamase. Although the susceptibility of this organism to alternative oral antimicrobials varies, rates of resistance to cefuroxime axetil, cefpodoxime, cefixime, azithromycin, and perhaps clarithromycin remain < 1%. The rate of penicillin resistance among isolates of Streptococcus pneumoniae, which has increased steadily in recent years, currently stands at approximately 25% in the United States and will likely reach 40-50% during the next 5-10 years. Because of cross-resistance, in general all beta-lactam antimicrobials have reduced activity against penicillin-resistant strains of S. pneumoniae. A 1994-1995 survey found that 3.4% of S. pneumoniae isolates were highly resistant to cefotaxime, and 4-8% were resistant to chloramphenicol, tetracycline, and the macrolides. Resistance to these antimicrobials has usually followed the emergence of penicillin resistance in other countries. Therefore, S. pneumoniae resistance to these drugs is expected to increase markedly during the next few years in the United States.

Bacteria↗

Selective media for detecting gastrointestinal carriage of vancomycin-resistant enterococci.

Nosocomial infection with vancomycin-resistant enterococci (VRE) has become a significant problem. Effective institution of infection control measures depends on rapid identification of carriage of the organism, especially in asymptomatic individuals. We compared two selective media for use in screening for the presence of VRE and found that an agar medium containing bile esculin azide supplemented with 8 mu g/ml of vancomycin was a useful and cost-effective means for primary screening for asymptomatic gastrointestinal carriage of VRE.

Anti-Bacterial Agents↗

Resistance among problem respiratory pathogens in pediatrics.

During the past two decades, the prevalence of beta-lactamase production with nontypable strains of Haemophilus influenzae has increased to about 35%. Fortunately, rates of resistance to other oral antimicrobials have not developed at a comparable pace. Amoxicillin/clavulanate, cefuroxime and cefpodoxime remain nearly uniformly active whereas rates of resistance to tetracycline, trimethoprim/sulfamethoxazole, chloramphenicol, cefaclor, loracarbef, cefprozil, azithromycin and clarithromycin remain low (1 to 5%). Virtually all clinical isolates of Moraxella catarrhalis produce beta-lactamase and are probably resistant to ampicillin and amoxicillin. However, alternative oral antimicrobials are almost always active. A compelling problem facing pediatricians today is the emergence of penicillin resistance with clinical isolates of Streptococcus pneumoniae. Currently, 15 to 25% of pneumococcal isolates in the United States have either intermediate (10 to 20%) or complete (3 to 5%) penicillin resistance caused by alterations in penicillin-binding proteins. Loss of activity of other beta-lactams is observed with penicillin-resistant S. pneumoniae. Third generation cephalosporins retain sufficient activity to warrant use in selected pneumococcal infections, even those caused by completely penicillin-resistant strains. Unfortunately, strains of S. pneumoniae with further alterations in penicillin-binding proteins have emerged such that even extended spectrum third generation cephalosporins lack activity. Rates of resistance to non-beta-lactam agents are also changing. The consequence of these changing patterns of resistance is that therapeutic options for pneumococcal infections in some patients are becoming increasingly limited.

Anti-Bacterial Agents↗

Multicenter clinical laboratory evaluation of a beta-lactamase disk assay employing a novel chromogenic cephalosporin, S1.

S1, a new chromogenic cephalosporin (International BioClinical, Inc., Portland, Oreg.), was used to detect beta-lactamase production among a variety of commonly encountered bacteria in a four-center collaborative study. Results of an S1 disk assay were compared with those obtained by a nitrocefin-based disk procedure (Cefinase; Becton-Dickinson Microbiology Systems, Cockeysville, Md.), with repetitive testing of five quality control organisms and with individual tests of recent clinical isolates of Neisseria gonorrhoeae (162 strains), Haemophilus influenzae (162 strains), Moraxella catarrhalis (155 strains), Staphylococcus aureus (161 strains), and Bacteroides fragilis (164 strains). The performances of the two beta-lactamase disk assays were comparable for the first three species cited above. However, the S1 assay appeared to be a more sensitive procedure than the Cefinase assay when applied to S. aureus and B. fragilis, with respect to both total numbers of positive results and length of time to a definitive positive endpoint.

Bacteria↗