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Thomas R Fritsche

Publications and source records attributed to Thomas R Fritsche.

At least 37 records · Page 2Linked to original sources
PubMed2006

Occurrence and characterization of carbapenemase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program (2000-2004).

Emergence and dissemination of Enterobacteriaceae isolates harboring carbapenemases in various geographic regions represents a significant threat to the management of nosocomial infections. Enterobacteriaceae isolates from the SENTRY Antimicrobial Surveillance Program (2000-2004) demonstrating decreased susceptibility to imipenem and meropenem (minimum inhibitory concentration [MIC], > or =2 mg/L) were evaluated for the production of metallo-beta-lactamases and serine carbapenemases using disk approximation and polymerase chain reaction (PCR) tests. Carbapenemase-producing strains were epidemiologically typed by automated riboprinting and pulsed-field gel electrophoresis (PFGE) to establish clonality. Among 37,557 Enterobacteriaceae (5 genus groups) evaluated, 119 (0.32%) had increased carbapenem MIC values, and a carbapenemase was identified in 51 (42.9%) of these strains. KPC-2 and KPC-3 were the most frequently occurring carbapenemases (24 isolates, 20.2%) in the United States and were detected in Klebsiella spp, Citrobacter spp., Enterobacter spp., and Serratia marcescens strains isolated in New York, Arkansas, and Virginia. SME-2-producing S. marcescens were isolated in the New York City area, Texas, and Ohio, while NMC-A was found in one E. cloacae strain from New York. In contrast, metallo-beta-lactamases were prevalent in Europe. IMP-1-producing E. cloacae (11 isolates) were detected in Turkey, while VIM-1-producing strains were found in Italy (Enterobacter spp.) and Greece (Klebsiella pneumoniae). Clonal dissemination of carbapenemase-producing strains was observed in several medical centers on both continents. The occurrence of carbapenemases in various Enterobacteriaceae remains rare but appears to be spreading geographically (not in Latin America), mainly with metallo-beta-lactamases being found in Mediterranean Europe and KPC enzymes in the New York City area.

Anti-Bacterial Agents↗
PubMed2006

Activity of retapamulin (SB-275833), a novel pleuromutilin, against selected resistant gram-positive cocci.

Retapamulin (SB-275833), the first pleuromutilin to be developed for human topical use, was tested against a selected population of staphylococci and beta-hemolytic streptococci. The MIC90 results for retapamulin were 0.12 microg/ml for Staphylococcus aureus and < or = 0.03 microg/ml for Streptococcus pyogenes; no cross-resistance was observed for organism subsets resistant to oxacillin, erythromycin, or mupirocin.

Anti-Bacterial Agents↗
PubMed2006

Daptomycin bactericidal activity and correlation between disk and broth microdilution method results in testing of Staphylococcus aureus strains with decreased susceptibility to vancomycin.

A total of 207 Staphylococcus aureus strains, including 105 well-characterized strains with decreased susceptibility to vancomycin (17 vancomycin-intermediate S. aureus [VISA] and 88 heteroresistant VISA [hVISA] strains) and 102 wild-type methicillin-resistant S. aureus (MRSA-WT) strains were tested by reference/standardized broth microdilution and disk diffusion methods, as well as by Etest (AB BIODISK, Solna, Sweden), against daptomycin and vancomycin. The lowest concentration of antimicrobial agent that killed > or = 99.9% of the initial inoculum was defined as the minimum bactericidal concentration (MBC) endpoint, and time-kill curves were performed in selected strains to further evaluate bactericidal activity. All MRSA-WT and hVISA strains were inhibited by < or = 1 microg/ml of daptomycin, while the VISA strains showed slightly higher daptomycin MICs (range, 0.5 to 4 microg/ml). All daptomycin MBC results were at the MIC or twofold higher. In contrast, 14.7% of MRSA-WT, 69.3% of hVISA, and all VISA strains showed a vancomycin MBC/MIC ratio of > or = 32 or an MBC of > or = 16 microg/ml (tolerant). The correlation coefficients between broth microdilution and disk diffusion method results were low for daptomycin (0.07) and vancomycin (0.11). Eight (3.8%) strains (all hVISA or VISA) were "nonsusceptible" to daptomycin by broth microdilution methods but susceptible by the disk diffusion method. For vancomycin, 35 (16.9%) strains were nonsusceptible by broth microdilution methods but susceptible by disk diffusion methods. In conclusion, daptomycin was highly bactericidal against S. aureus strains, and its bactericidal activity was not affected by decreased susceptibility to vancomycin. In contrast, many (one in seven) contemporary MRSA-WT, the majority of hVISA, and all VISA strains showed vancomycin MBC/MIC ratios consistent with tolerance, a predictor of poor clinical response. Disk diffusion tests generally failed to detect strains categorized as nonsusceptible to daptomycin or vancomycin by the reference broth microdilution method or Etest, and reassessment of breakpoints should be immediately attempted for MIC methods suggested as the test of choice.

Anti-Bacterial Agents↗
PubMed2006

Contemporary prevalence of BRO beta-lactamases in Moraxella catarrhalis: report from the SENTRY antimicrobial surveillance program (North America, 1997 to 2004).

A total of 7,860 community-acquired Moraxella catarrhalis isolates (SENTRY Antimicrobial Surveillance Program, 1997 to 2004) were tested by broth microdilution methods, and 399 randomly selected strains from North American sites were tested for BRO-1 and BRO-2 by PCR methods. Several antimicrobials remained very active, including amoxicillin-clavulanate (MIC90s, < or =0.25 microg/ml), azithromycin (MIC90s, < or =0.12 microg/ml), ceftriaxone (MIC90s, 0.5 microg/ml), and levofloxacin (MIC90s, < or =0.03 to 0.06 microg/ml). The BRO-2 incidence rates by year were 3 to 4% overall (96 to 97% for BRO-1) and were the highest in Canada (7.9%), with the incidence in the United States being only 2.0%.

Anti-Bacterial Agents↗
PubMed2006

Selection of a surrogate agent (vancomycin or teicoplanin) for initial susceptibility testing of dalbavancin: results from an international antimicrobial surveillance program.

The immediate lack of market-dominating commercial products (Vitek or MicroScan) for susceptibility testing of the new glycolipopeptide, dalbavancin, requires a surrogate marker agent to assist microbiologists in the correct categorization of potentially indicated species (staphylococci and streptococci). Error-rate analyses for 16,749 isolates using vancomycin or teicoplanin results to categorize dalbavancin susceptibilities demonstrated that both glycopeptide agents were highly predictive of dalbavancin-susceptible results (nearly 100%) with only a rare minor error. Vancomycin test results most reliably predict dalbavancin susceptibility until validated commercial reagents become available for direct testing in clinical practice.

Anti-Bacterial Agents↗
PubMed2006

Comparison of dalbavancin MIC values determined by Etest (AB BIODISK) and reference dilution methods using gram-positive organisms.

While standardized microdilution testing methodologies and quality control ranges exist for the novel glycolipopeptide dalbavancin, no testing methods have been described that are immediately available for routine use in clinical laboratories. In this study, we found that the dalbavancin Etest (AB BIODISK, Solna, Sweden) procedure demonstrated a high degree of agreement (100% within +/-2 log(2) dilution steps) with the standardized broth microdilution method, validating the use of the Etest as an alternative test for investigational or clinical purposes following regulatory approval.

Anti-Bacterial Agents↗
PubMed2006

Accuracy of three automated systems (MicroScan WalkAway, VITEK, and VITEK 2) for susceptibility testing of Pseudomonas aeruginosa against five broad-spectrum beta-lactam agents.

One hundred recent clinical Pseudomonas aeruginosa isolates were used to assess the quantitative (MIC) and qualitative (susceptibility category) accuracies of the MicroScan WalkAway, VITEK, and VITEK 2 automated susceptibility test systems when five-broad spectrum beta-lactams, aztreonam, cefepime, ceftazidime, imipenem, and piperacillin-tazobactam, were tested. Isolates were selected so that the MICs for the isolates overrepresented the MICs near the breakpoints to assess precisely the agreement between the results obtained with the automated systems and the results obtained by the reference tests. The categorical and MIC results from the automated systems were compared to the consensus result of three reference methods: broth microdilution, agar dilution, and disk diffusion. The consensus categorical testing (susceptibility and resistance) rates were 47 and 27%, respectively, for aztreonam; 59 and 14%, respectively, for cefepime; 44 and 43%, respectively, for ceftazidime; 71 and 19%, respectively, for imipenem; and 50 and 50%, respectively, for piperacillin-tazobactam. All systems tested exhibited a high, unacceptable level of very major (false-susceptible) errors for piperacillin-tazobactam (19 to 27%). Major (false-resistant) error rates were generally acceptable (0 to 3%), but minor error rates were elevated (8 to 32%) for cefepime (VITEK 2 and VITEK) and for aztreonam (all three systems), leading to consistent trends toward false resistance. Manufacturer reevaluation of these automated systems for the testing of selected beta-lactams with current clinical isolates of P. aeruginosa that exhibit contemporary resistance mechanisms would be prudent to minimize the potential for serious reporting errors.

Bacteriological Techniques↗
PubMed2006

International surveillance of Candida spp. and Aspergillus spp.: report from the SENTRY Antimicrobial Surveillance Program (2003).

During 2003, a total of 1,397 Candida isolates, 73 Aspergillus isolates, 53 Cryptococcus neoformans isolates, and 25 other fungal isolates from infected, normally sterile, body sites in patients hospitalized in North America, Europe, and Latin America were studied as a component of the longitudinal SENTRY Antimicrobial Surveillance Program. The MICs for seven antifungal agents were determined in a central laboratory (JMI Laboratories, North Liberty, IA) using testing methods promulgated by the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards). The rank order of Candida spp. occurrence was as follows: C. albicans (48.7%), C. parapsilosis (17.3%), C. glabrata (17.2%), C. tropicalis (10.9%), C. krusei (1.9%), and other Candida spp. (4.0%). C. albicans accounted for 51.5, 47.8, and 36.5% of candidal infections in North America, Europe, and Latin America, respectively. Ravuconazole, voriconazole, and fluconazole were highly active against C. albicans, C. parapsilosis, and C. tropicalis, with both former agents being more potent (MIC at which 90% of the isolates tested are inhibited [MIC90] of < or =0.008 to 0.12 microg/ml) than fluconazole (MIC90 of 0.5 to 2 microg/ml). C. glabrata isolates were less susceptible to these agents, with MIC90s of 1, 1, and 64 microg/ml, respectively. Ravuconazole and voriconazole were the most active agents tested against C. krusei (MIC90 of 0.5 microg/ml). Among Aspergillus spp., A. fumigatus was the most commonly (71.2% of isolates) recovered species; 96.2, 96.2, 84.6, and 11.5% of strains were inhibited by < or =1 microg/ml of ravuconazole, voriconazole, itraconazole, and amphotericin B, respectively. Of the antifungal agents tested, ravuconazole and voriconazole displayed the greatest spectrum of activity against pathogenic Candida and Aspergillus spp., regardless of geographic origin. These results extend upon previous findings from SENTRY Program reports (1997 to 2000), further characterizing species composition as seen in local clinical practice and demonstrating the potent activity of selected, newer triazole antifungal agents.

Antifungal Agents↗
PubMed2005

Oxazolidinone susceptibility patterns in 2004: report from the Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) Program assessing isolates from 16 nations.

OBJECTIVES: To investigate the activity of linezolid (an oxazolidinone), a potent choice for community- and hospital-acquired infections, via a worldwide surveillance network called the Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) Program. METHODS: A total of 4098 Gram-positive strains were collected from 42 laboratories located in North America (five sites in Canada), South America (10 sites), Europe (16 sites) and the Far East (11 sites). Each country or site submitted 200 isolates (Canada submitted 200 isolates for each of five sites; total 1000) for confirmation of organism identification and reference MIC processing. Nearly 25 comparator agents were tested along with quality control strains, and interpretative criteria from the CLSI, formerly the NCCLS, M100-S15 were applied. No linezolid resistance was detected in strains from 16 monitored countries in 2004. RESULTS: Linezolid remained highly active against Streptococcus pneumoniae, viridans group and beta-haemolytic streptococci (MIC90, 1 mg/L). Against Staphylococcus aureus, linezolid showed 99.5% of results at 0.5-2 mg/L with only one isolate at 4 mg/L. Oxacillin-resistant S. aureus rates varied between nations and ranged from 1.4% in Sweden to 29.5% in the UK to 65.2% in Mexico. Linezolid MIC values were generally one log2 dilution step lower for coagulase-negative staphylococci (CoNS) when compared with S. aureus. No CoNS strains produced a linezolid result at 4 mg/L. Compared with ZAAPS 2002 and 2003 results for enterococci where seven resistant strains were identified, the 2004 data revealed no resistance and 98.1% of linezolid MIC results were at 1 or 2 mg/L. Vancomycin-resistant enterococci (5.3% overall) varied markedly by country including a high of 47.2% in Korea. CONCLUSIONS: Linezolid continues to be effective in vitro against Gram-positive pathogens from five continents and no oxazolidinone-resistant strains were identified among the 4098 systemically collected strains (2004) or among 20 158 non-United States isolates for the entire ZAAPS Program (2002-04).

Acetamides↗
PubMed2005

Antimicrobial activity of daptomycin tested against clinical strains of indicated species isolated in North American medical centers (2003).

Daptomycin is a cyclic lipopeptide approved for use by the US Food and Drug Administration (FDA) for the treatment of complicated skin and skin structure infections caused by Staphylococcus aureus, groups A and B beta-hemolytic streptococci, and vancomycin-susceptible Enterococcus faecalis. We evaluated the daptomycin spectrum against these pathogens by testing 2759 clinical strains consecutively collected in more than 30 hospitals located across the United States and Canada. The isolates were susceptibility tested against daptomycin and many comparators by the reference broth microdilution method. Daptomycin was very active against indicated species with the highest MIC results being 1, 2, and 0.5 microg/mL for S. aureus, E. faecalis, and beta-hemolytic streptococci, respectively. All isolates tested were considered susceptible to daptomycin, according to Clinical and Laboratory Standards Institute and FDA breakpoints, and daptomycin was the most potent (lowest MIC90) among selected antimicrobials commonly used to treat Gram-positive infections. Resistance to oxacillin or vancomycin did not influence daptomycin activity against S. aureus or E. faecalis.

Academic Medical Centers↗
PubMed2005

Susceptibility patterns for amoxicillin/clavulanate tests mimicking the licensed formulations and pharmacokinetic relationships: do the MIC obtained with 2:1 ratio testing accurately reflect activity against beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis?

Amoxicillin/clavulanate has recently undergone formulation changes (XR and ES-600) that represent 14:1 and 16:1 ratios of amoxicillin/clavulanate. These ratios greatly differ from the 2:1 ratio used in initial formulations and in vitro susceptibility testing. The objective of this study was to determine if the reference method using a 2:1 ratio accurately reflects the susceptibility to the various clinically used amoxicillin/clavulanate formulations and their respective serum concentration ratios. A collection of 330 Haemophilus influenzae strains (300 beta-lactamase-positive and 30 beta-lactamase-negative) and 40 Moraxella catarrhalis strains (30 beta-lactamase-positive and 10 beta-lactamase-negative) were tested by the broth microdilution method against eight amoxicillin/clavulanate combinations (4:1, 5:1, 7:1, 9:1, 14:1, and 16:1 ratios; 0.5 and 2 microg/mL fixed clavulanate concentrations) and the minimum inhibitory concentration (MIC) results were compared with those obtained with the reference 2:1 ratio testing. For the beta-lactamase-negative strains of both genera, there was no demonstrable change in the MIC values obtained for all ratios analyzed (2:1 to 16:1). For the beta-lactamase-positive strains of H. influenzae and M. catarrhalis, at ratios >or=4:1 there was a shift in the central tendency of the MIC scatterplot compared with the results of testing 2:1 ratio. As a result, there was a 2-fold dilution increase in the MIC(50) and MIC(90) values, most evident for H. influenzae and BRO-1-producing M. catarrhalis strains. For beta-lactamase-positive strains of H. influenzae, the shift resulted in a change in the interpretive result for 3 isolates (1.0%) from susceptible using the reference method (2:1 ratio) to resistant (8/4 microg/mL; very major error) at the 16:1 ratio. In addition, the number of isolates with MIC values at or 1 dilution lower than the breakpoint (4/2 microg/mL) increased from 5% at 2:1 ratio to 32-33% for ratios 14:1 and 16:1. Our results indicate that, for the beta-lactamase-positive strains of H. influenzae and M. catarrhalis, the results of the amoxicillin/clavulanate reference 2:1 ratio testing do not accurately represent all the currently licensed formulations. Pharmacokinetic/pharmacodynamic (PK/PD) target attainment might be compromised when higher amoxicillin/clavulanate ratios are used clinically. With a better understanding of PK/PD parameters, reevaluation of the amoxicillin/clavulanate in vitro susceptibility testing should be considered by the standardizing authorities to reflect the licensed formulations and accurately predict clinical outcomes.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2005

Evaluation of PPI-0903M (T91825), a novel cephalosporin: bactericidal activity, effects of modifying in vitro testing parameters and optimization of disc diffusion tests.

OBJECTIVES: To evaluate bactericidal activity of PPI-0903M and in vitro testing parameters for this compound. METHODS: A total of 110 strains were tested to determine MIC and MBC values of PPI-0903M. MIC values were determined by reference broth microdilution whereas MBC was assessed by plating the broth from the MIC well and from those wells above the MIC for each organism onto appropriate drug-free growth media. Seventeen strains were tested by the kill-curve methodology to again evaluate the bactericidal activity of PPI-0903M. Broth microdilution results for 15 strains (in triplicate) were compared with the standard, reference method after modifying several testing parameters. Optimal disc content was assessed by testing seven reference strains with five PPI-0903M disc concentrations (5, 10, 30, 50 and 100 microg). RESULTS: PPI-0903MMBC/MIC ratios were < or = 4 in 90% of strains tested. Kill-curve studies showed >99.9% killing at concentrations < or = 4x MIC within 8 to 24 h against staphylococci and Enterobacteriaceae tested. PPI-0903M MIC results were rarely influenced by the test or medium changes evaluated [high inoculum, low calcium or reduced pH (5.0)]. Human serum had no effect on in vitro antimicrobial activity of PPI-0903M. The 10 microg disc content would be recommended for optimal correlation of MIC breakpoints of < or = 1-4 mg/L. CONCLUSIONS: PPI-0903M was generally bactericidal against tested species, and the MIC results were stable across numerous susceptibility test condition changes.

Anti-Bacterial Agents↗
PubMed2005

Emerging metallo-beta-lactamase-mediated resistances: a summary report from the worldwide SENTRY antimicrobial surveillance program.

The rates of occurrence of metallo-beta-lactamase-mediated resistances in Pseudomonas aeruginosa, Acinetobacter species, and Serratia marcescens, among other gram-negative bacilli, have escalated since 2000, severely limiting treatment options in Asia, Europe, and Latin America to non-beta-lactam antimicrobial classes. Clinical isolates harboring metallo-beta-lactamases have also recently been reported in western Canada and in Texas, signaling the need for development of accurate diagnostic tests by clinical laboratories to detect their presence and for new, and more potent, antimicrobial agents.

Acinetobacter↗
PubMed2005

Evaluation of alternative disk diffusion methods for detecting mecA-mediated oxacillin resistance in an international collection of staphylococci: validation report from the SENTRY Antimicrobial Surveillance Program.

To validate the current National Committee for Clinical Laboratory Standards recommendations of the cefoxitin disk as a preferred surrogate marker to detect oxacillin resistance in staphylococcal isolates, 304 staphylococcal isolates originating from 49 sites in 16 countries in the SENTRY Antimicrobial Surveillance Program (2003) were tested. Two hundred three Staphylococcus aureus and 101 coagulase-negative staphylococci (CoNS), of which >95% were bloodstream isolates, were evaluated by comparing the results of the National Committee for Clinical Laboratory Standards broth microdilution method for oxacillin with those of the disk diffusion test using oxacillin, cefoxitin and ceftizoxime disks. Discrepancies were resolved using the PBP2a latex agglutination test. For S. aureus, the cefoxitin disk performed without interpretive error followed by the ceftizoxime disk (1% major and 0.5% minor errors; > or =20 mm = susceptible); use of the oxacillin disk test had the highest error rates with 4.4% major and 1.5% minor errors, whereas the oxacillin minimal inhibitory concentration (MIC) test was 99.0% accurate. For CoNS, the oxacillin disk test had the highest error rate with 4.0% major errors, followed by the cefoxitin (3.0% major error rate) and the ceftizoxime (1% very major and 1% minor error: > or =20 mm = susceptible) disk tests. The oxacillin MIC test was also 99.0% accurate for CoNS testing. Modification of the ceftizoxime disk diffusion breakpoints for CoNS resulted in complete intermethod categorical agreement. The overall accuracy of the four tests was as follows: modified ceftizoxime disk (99.3%) > oxacillin MIC = cefoxitin disk (99.0%) > current ceftizoxime disk (98.4%) > oxacillin disk (94.7%). In conclusion, these results confirm the superior performance characteristics of cefoxitin and ceftizoxime disk tests as surrogate markers to detect oxacillin resistance; by using an international collection of clinically significant staphylococcal isolates, we also demonstrate its wide global application.

Bacterial Proteins↗
PubMed2005

Antimicrobial activity of LBM415 (NVP PDF-713) tested against pathogenic Neisseria spp. (Neisseria gonorrhoeae and Neisseria meningitidis).

LBM415 (NVP PDF-713), a novel peptide deformylase inhibitor, was tested by reference methods against 2 collections of pathogenic Neisseria, N. gonorrhoeae (157 strains) and N. meningitidis (100 strains). The collection included strains resistant to penicillin, tetracycline, and fluoroquinolones and were also tested against ceftriaxone, ciprofloxacin, penicillin, and tetracycline. The 50% and 90% minimum inhibitory concentration values for LBM415 were 1 and 2 microg/mL, and 4 and 8 microg/mL for N. meningitidis and N. gonorrhoeae, respectively. All comparison agents were more active than this peptide deformylase inhibitor against this genus.

Anti-Bacterial Agents↗
PubMed2005

Comparative activity of oral and parenteral cephalosporins tested against multidrug-resistant Streptococcus pneumoniae: report from the SENTRY Antimicrobial Surveillance Program (1997-2003).

A large international collection of Streptococcus pneumoniae (21605 strains) was analyzed to determine the comparative activity of selected oral (cefuroxime and cefpodoxime) and parenteral (ceftriaxone and cefepime) cephalosporins when tested against different antimicrobial resistance phenotypes including penicillin-resistant strains and strains displaying additional resistances to other agents (erythromycin, clindamycin, tetracycline, and trimethoprim/sulfamethoxazole). The multidrug-resistant (MDR) rate ranged from 17.6% (penicillin- and erythromycin-resistant only) to 5.7% (resistance to all 5 drugs). The parenteral cephalosporins retained wider activity for all MDR phenotypes studied with the resistance rates (minimum inhibitory concentration > or = 4 mug/mL) being lower for cefepime (1.3-1.9%) when compared with ceftriaxone (3.0-4.4%) or the orally administered cephalosporins, cefpodoxime (64.4-74.1%), and cefuroxime (69.3-79.1%). Our findings confirm that the parenteral cephalosporins, cefepime, and ceftriaxone possess significant activity against those MDR pneumococci responsible for an increasing number of serious respiratory tract infections.

Administration, Oral↗
PubMed2005

Reproducibility of gemifloxacin and comparison fluoroquinolone MIC results using Sensititre commercial dry-form panels.

This study examined the ability of commercial dry-form broth microdilution panels (Sensititre, TREK Diagnostics, Cleveland, OH) to produce accurate minimum inhibitory concentration (MIC) results for gemifloxacin, a new fluoroquinolone. Reproducibility for gemifloxacin was 100.0% for on-scale values within +/-1 log2 dilution for same- and between-day comparisons. Newer comparator fluoroquinolones (sparfloxacin, sitafloxacin, and moxifloxacin) also showed excellent reproducibility (100.0%) for on-scale results analyzed at +/-1 log2 dilution for same- and between-day comparisons. Newer and investigational fluoroquinolone agents, including gemifloxacin, can be tested with confidence using these dry-form MIC panels.

Anti-Bacterial Agents↗