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Biomedical subjects

M A Pfaller

Publications and source records attributed to M A Pfaller.

At least 127 records · Page 7Linked to original sources
PubMed2000

In vitro efficacy of six cephalosporins tested against Enterobacteriaceae isolated at 38 North American medical centres participating in the SENTRY Antimicrobial Surveillance Program, 1997-1998.

The SENTRY Antimicrobial Surveillance Program is an ongoing international collaboration that monitors the predominant bacterial and fungal pathogens and antimicrobial susceptibility patterns associated with community-acquired and nosocomial infections. SENTRY data on the current cephalosporin susceptibility patterns (1997-98) of North American isolates of clinically important Enterobacteriaceae were analyzed. Susceptibility to a selection of cephalosporins was assessed at a central laboratory using reference broth microdilution methods and interpretive criteria specified by the National Committee for Clinical Laboratory Standards. The third- and fourth-generation cephalosporins tested demonstrated excellent activity against Escherichia coli and Klebsiella pneumoniae, whereas some of the older agents maintained good efficacy. Extended spectrum beta-lactamases were detected in all regions of the United States and Canada (1.8-10.7%). Cefepime was the most active agent tested against pathogens with the potential for enzyme-mediated resistance due to Amp C. The third-generation agents maintained acceptable efficacy against Serratia marcescens, but were less effective against Citrobacter and Enterobacter species. The older cephalosporins were generally inadequate against these pathogens, in contrast to cefepime, which was the widest spectrum cephalosporin overall. Some significant regional variations in spectrum were detected.

Cefepime↗
PubMed2000

Evaluation of gemifloxacin (SB-265805, LB20304a): in vitro activity against over 6000 gram-positive pathogens from diverse geographic areas.

Gemifloxacin (GEMI), formerly SB-265805 and LB20304, is a newer fluoroquinolone with broad-spectrum activity against a wide variety of bacterial pathogens. The present investigation extended earlier observations by sampling an additional 6790 gram-positive organisms from more than 50 medical centres on three continents. The reference broth microdilution method with recommended medium supplements was used throughout. Selected results (number strains tested; MIC90 for GEMI/trovafloxacin in mg/l; % < or = 1 mg/l for GEMI/trovafloxacin) were: Staphylococcus aureus (3672; 2/2; 86/85), S. epidermidis (404; 1/>4; 92/71), Enterococcus faecalis (630; 4/>4; 76/66), E. faecium (216; > 4/>4; 15/11), Streptococcus pneumoniae (300; 0.06/0.25; 100/97), beta-haemolytic streptococci (150; 0.06/0.25; 100/100) and viridans group streptococci (150; 0.12/0.25; 99/97). Gemifloxacin appeared equal or superior to trovafloxacin in its overall gram-positive spectrum of activity pending a choice of the susceptible breakpoint concentration. Continued in vitro, pharmacodynamic and clinical investigations of gemifloxacin appear warranted.

Anti-Infective Agents↗
PubMed2000

In vitro activity of ceftiofur tested against clinical isolates of Escherichia coli and Klebsiella pneumoniae including extended spectrum beta-lactamase producing strains.

In vitro activity of ceftiofur, a cephalosporin used in veterinary practice was compared using ceftriaxone-resistant (producing extended spectrum beta-lactamase (ESBL)) and -susceptible clinical isolates of Esherichia coli and Klebsiella pneumoniae. The ceftriaxone-susceptible isolates exhibited a lower range of ceftiofur MICs (MIC50, 0.5 mg/l, MIC90 1.0 mg/l). Those isolates known to produce an ESBL were also resistant to ceftiofur (MIC50, > or = 32 mg/l). The latter isolates were also less susceptible to other comparator drugs (cefquinome, gentamicin and trimethoprim/sulphamethoxazole) in contrast to the ceftriaxone-susceptible strains. The clinical isolates showed high correlation between ceftriaxone and ceftiofur MICs (y = 2.6 + 0.89x, r = 0.95). Using the current ceftiofur susceptible breakpoint (< or = 2 mg/l) used for veterinary practice (respiratory tract pathogens), the ESBL-producing strains of E. coli and K. pneumoniae could be accurately separated from susceptible strains. This ceftiofur breakpoint MIC corresponds to the National Committee for Clinical Laboratory Standards ESBL screening concentration for ceftriaxone set at < or = 1 mg/l = negative for ESBL production. Ceftiofur was also observed to be very active in vitro against ampicillin-resistant, non-ESBL producing enteric isolates. This new cephem appears to be very potent against the tested Enterobacteriaceae and of potential wide clinical veterinary utility.

Animals↗
PubMed2000

Trends in antimicrobial susceptibility of bacterial pathogens isolated from patients with bloodstream infections in the USA, Canada and Latin America. SENTRY Participants Group.

From January through June of 1998, 4579 bloodstream infections (BSI) due to bacterial pathogens were reported from SENTRY hospitals in Canada, the USA and Latin America. Staphylococcus aureus, Escherichia coli, and coagulase-negative staphylococcus (CoNS) were the most common pathogens, together accounting for 55.2% of all BSI during this time period. Compared with the 5794 BSI reported from SENTRY from January through June of 1997, no major change was seen in the frequencies of occurrence of the most common bacterial causes of BSI. Between 1997 and 1998, the major change in antimicrobial resistance was an increase in oxacillin-resistance in both S. aureus and CoNS in all regions. These data demonstrate widespread antimicrobial resistance in Canada, Latin America and the USA, with a notable increase in oxacillin-resistance among staphylococci. Ongoing surveillance remains essential, and will enhance efforts to limit the scope of this worldwide problem.

Bacteremia↗
PubMed2000

Two-year assessment of the pathogen frequency and antimicrobial resistance patterns among organisms isolated from skin and soft tissue infections in Latin American hospitals: results from the SENTRY antimicrobial surveillance program, 1997-98. SENTRY Study Group.

OBJECTIVES: This study was conducted to evaluate the frequency of occurrence and antimicrobial susceptibility of bacterial isolates collected from patients with skin and soft tissue infections (SSTI) in Latin American hospitals, as part of the SENTRY Antimicrobial Surveillance Program. The dissemination of multidrug-resistant methicillin-resistant Staphylococcus aureus (MDR-MRSA) among the Latin American countries also was studied. MATERIAL AND METHODS: A total of 885 bacterial isolates were analyzed. At the monitoring laboratory, antimicrobial susceptibility testing utilizing the reference broth microdilution method and confirmation of species identification were performed. Enterobacteriaceae possibly producing extended-spectrum beta-lactamases (ESBL) and MDR-MRSA isolates were genotyped by ribotyping using the RiboPrinter and by pulsed-field gel electrophoresis. RESULTS: Staphylococcus aureus (31%) was the most common etiologic agent causing SSTI, followed by Escherichia coli (13.4%) and Pseudomonas aeruginosa (11%). Thirty-one percent of S. aureus isolates were resistant to oxacillin (methicillin). The presence of ESBL phenotypes was markedly higher among the Klebsiella pneumoniae (35.5%) than E. coli isolates (10. 2%). Meropenem was the compound with the highest susceptibility rate among the Enterobacteriaceae (100%) and P. aeruginosa (95%) isolates. A great genetic similarity was observed among the MDR-MRSA in Latin America. CONCLUSION: High resistance rates to antimicrobial drugs among the most frequent bacterial pathogens were observed in 10 medical centers in Latin America. This study also demonstrated a clonal dissemination of a MDR-MRSA strain in several nations.

Anti-Bacterial Agents↗
PubMed2000

Group B streptococci causing neonatal bloodstream infection: antimicrobial susceptibility and serotyping results from SENTRY centers in the Western Hemisphere.

OBJECTIVE: Group B streptococcal infection is a common cause of neonatal sepsis. Surveillance of antimicrobial susceptibility and serotype frequencies of invasive group B streptococci is important to ensure the effectiveness of therapeutic regimens and to guide vaccine development. STUDY DESIGN: Prospective surveillance of neonatal bloodstream infection was performed at all Western Hemisphere sites participating in the SENTRY Program. From January 1997 through December 1999, a total of 122 isolates of bloodstream infections with group B streptococci were collected and sent to the University of Iowa for antimicrobial susceptibility testing and serotyping. RESULTS: No isolates were resistant to penicillin. More than 25% of isolates from US hospitals and 14% of isolates from Canadian hospitals were erythromycin resistant. Seven percent of isolates from the United States and Canada were resistant to clindamycin. No clindamycin or erythromycin resistance was found among isolates from Latin America. Clindamycin and erythromycin resistance was most frequent among serotype V strains. CONCLUSIONS: No emerging resistance to penicillin was noted among bloodstream infection isolates of group B streptococci from a broad geographic area; erythromycin and clindamycin resistance was found in the United States and Canada and appeared most frequently among serotype V strains.

Anti-Bacterial Agents↗
PubMed2000

In vitro activity of newer fluoroquinolones for respiratory tract infections and emerging patterns of antimicrobial resistance: data from the SENTRY antimicrobial surveillance program.

In 1997, an international surveillance program, SENTRY Antimicrobial Surveillance Program, was initiated with the aim of tracking the emergence of antimicrobial resistance worldwide. Results from reference antimicrobial susceptibility testing of bacterial pathogens (from bloodstream, inpatient and outpatient lower respiratory tract, urinary tract, and skin and soft-tissue infections) were included in an extensive database used to define antimicrobial resistance patterns throughout the world. On the basis of 1997-1999 test results from the Americas, fluoroquinolones continue to demonstrate potent in vitro activity against Enterobacteriaceae and important pathogens (Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and atypicals) that cause community-acquired respiratory tract infections. At published breakpoint concentrations, gatifloxacin, levofloxacin, sparfloxacin, grepafloxacin, trovafloxacin, and ciprofloxacin inhibited approximately 100% of H. influenzae isolates, including those that demonstrated resistance to beta-lactams and macrolides. Fluoroquinolones were also active against numerous other gram-negative bacilli and demonstrated high activity against S. pneumoniae and beta-hemolytic or viridans group streptococci. New fluoroquinolones maintain activity against penicillin-resistant strains of S. pneumoniae, with a low overall resistance in this species, even among the most recent (1999) clinical isolates. The SENTRY Antimicrobial Surveillance Program will continue to monitor the antibacterial activity of these newer agents throughout the world, to identify emerging resistant strains and to facilitate possible intervention strategies as these newer compounds are used in the clinic setting.

Anti-Infective Agents↗
PubMed2000

Genetic relatedness of multidrug-resistant, methicillin (oxacillin)-resistant Staphylococcus aureus bloodstream isolates from SENTRY Antimicrobial Resistance Surveillance Centers worldwide, 1998.

We reviewed Staphylococcus aureus bloodstream infection isolates from SENTRY centers worldwide during 1998 to evaluate the molecular epidemiology of multiply drug-resistant methicillin (oxacillin)-resistant S. aureus (MDR-MRSA). MDR-MRSA was defined as a S. aureus isolate with a MIC for oxacillin at >2 microg/ml and with four or more additional resistances. A total of 325 unique patient isolates of MDR-MRSA from five continents were analyzed using ribotyping and pulsed-field gel electrophoresis (PFGE). The frequency of MDR-MRSA among all S. aureus BSI isolates ranged from only 2.2% in Canada to 35.6% in the Asia-Pacific region. Forty-eight ribotypes (RT) were distinguished, but over 80% of the isolates were contained within the 10 most prevalent RTs. The most common RT, RT 184.5, which included 30% of all MDR-MRSA, was found on four of five continents. PFGE provided superior discrimination and identified numerous clusters of possible clonal dissemination of MDR-MRSA within individual medical centers and between institutions that are in geographic proximity. In four instances, strains with indistinguishable PFGE patterns were found on more than one continent. The predominant PFGE subtype in South America (RT 893.5/Ia) was isolated from patients at centers in Brazil, Argentina, and Portugal, and closely related subtypes were isolated in Chile and Italy. There is great geographic variation in rates of methicillin- and multidrug-resistance among S. aureus bloodstream isolates worldwide. Although many MDR-MRSA strains group geographically, a few closely related epidemic strains have wide regional and even global range.

Anti-Bacterial Agents↗
PubMed2000

Activity and spectrum of 22 antimicrobial agents tested against urinary tract infection pathogens in hospitalized patients in Latin America: report from the second year of the SENTRY antimicrobial surveillance program (1998).

The potency and spectrum of various antimicrobial agents tested against 434 bacterial isolates causing urinary tract infection (UTI) in hospitalized patients in Latin America were evaluated. The genotypes of the extended-spectrum beta-lactamase-producing and selected multi-resistant isolates were also evaluated by molecular typing techniques. Escherichia coli (60.4%) was the most common aetiological agent causing UTI, followed by Klebsiella spp. (11.2%) and Pseudomonas aeruginosa (8.3%). In contrast, Enterococcus spp. isolates caused only 2.3% of UTIs. Fewer than 50% of E. coli isolates were susceptible to broad-spectrum penicillins. The resistance rates to ciprofloxacin and the new quinolones were also high among these isolates. The molecular characterization of ciprofloxacin-resistant E. coli showed that most of them have a double mutation in the gyrA gene associated with a single mutation in the parC gene. The Klebsiella pneumoniae isolates studied demonstrated high resistance rates to beta-lactam drugs, including broad-spectrum cephalosporins. The carbapenems were the compounds with the highest susceptibility rate among these isolates (100.0% susceptible) followed by cefepime (91.7% susceptible). Meropenem, imipenem and cefepime were also the most active drugs against Enterobacter spp. Among P. aeruginosa isolates, meropenem (MIC(50), 2 mg/L) was the most active compound, followed by imipenem (MIC(50), 4 mg/L), cefepime (MIC(50), 8 mg/L) and ceftazidime (MIC(50), 16 mg/L). The results presented in this report confirm that bacterial resistance continues to be a great problem in Latin American medical institutions.

Anti-Bacterial Agents↗
PubMed2000

Animal and human multidrug-resistant, cephalosporin-resistant salmonella isolates expressing a plasmid-mediated CMY-2 AmpC beta-lactamase.

Salmonella spp. are important food-borne pathogens that are demonstrating increasing antimicrobial resistance rates in isolates obtained from food animals and humans. In this study, 10 multidrug-resistant, cephalosporin-resistant Salmonella isolates from bovine, porcine, and human sources from a single geographic region were identified. All isolates demonstrated resistance to cephamycins and extended-spectrum cephalosporins as well as tetracycline, chloramphenicol, streptomycin, and sulfisoxazole. Molecular epidemiological analyses revealed eight distinct chromosomal DNA patterns, suggesting that clonal spread could not entirely explain the distribution of this antimicrobial resistance phenotype. However, all isolates encoded an AmpC-like beta-lactamase, CMY-2. Eight isolates contained a large nonconjugative plasmid that could transform Escherichia coli. Transformants coexpressed cephalosporin, tetracycline, chloramphenicol, streptomycin, and sulfisoxazole resistances. Plasmid DNA revealed highly related restriction fragments though plasmids appeared to have undergone some evolution over time. Multidrug-resistant, cephalosporin-resistant Salmonella spp. present significant therapeutic problems in animal and human health care and raise further questions about the association between antimicrobial resistance, antibiotic use in animals, and transfer of multidrug-resistant Salmonella spp. between animals and man.

Animals↗
PubMed2000

In vitro activities of ravuconazole (BMS-207147) against 541 clinical isolates of Cryptococcus neoformans.

The in vitro activities of the new triazole, ravuconazole (BMS-207147), were compared to those of fluconazole and itraconazole against 541 clinical isolates of Cryptococcus neoformans. Isolates were obtained from cerebrospinal fluid (396), blood (116), and miscellaneous clinical specimens (29). Overall, ravuconazole (MIC at which 90% of the isolates are inhibited [MIC(90)], 0.25 microg/ml) was more active than either itraconazole (MIC(90), 0.5 microg/ml) or fluconazole (MIC(90), 8 microg/ml). Among the isolates inhibited by > or =16 microg of fluconazole/ml, 90.2% were inhibited by < or =1 microg of ravuconazole/ml. On the basis of our findings and the favorable pharmacokinetic properties of ravuconazole, we suggest that ravuconazole may be useful for the treatment of infectious diseases due to C. neoformans and that further clinical studies to confirm these promising in vitro results are warranted.

Antifungal Agents↗
PubMed2000

Bloodstream infections due to Candida species: SENTRY antimicrobial surveillance program in North America and Latin America, 1997-1998.

An international program of surveillance of bloodstream infections (BSI) in the United States, Canada, and Latin America detected 306 episodes of candidemia in 34 medical centers (22 in the United States, 6 in Canada, and 6 in Latin America) in 1997 and 328 episodes in 34 medical centers (22 in the United States, 5 in Canada, and 7 in Latin America) in 1998. Of the 634 BSI, 54.3% were due to Candida albicans, 16.4% were due to C. glabrata, 14.9% were due to C. parapsilosis, 8.2% were due to C. tropicalis, 1.6% were due to C. krusei, and 4.6% were due to other Candida spp. The percentage of BSI due to C. albicans decreased very slightly in the United States between 1997 and 1998 (56.2 to 54.4%; P = 0.68) and increased in both Canada (52.6 to 70.1%; P = 0.05) and Latin America (40.5 to 44. 6%; P = 0.67). C. glabrata was the second most common species observed overall, and the percentage of BSI due to C. glabrata increased in all three geographic areas between 1997 and 1998. C. parapsilosis was the third most prevalent BSI isolate in both Canada and Latin America, accounting for 7.0 and 18.5% of BSI, respectively. Resistance to fluconazole (MIC, >/=64 microgram/ml) and itraconazole (MIC, >/=1.0 microgram/ml) was observed infrequently in both 1997 (2.3 and 8.5%, respectively) and 1998 (1.5 and 7.6%, respectively). Among the different species of Candida, resistance to fluconazole and itraconazole was observed in C. glabrata and C. krusei, whereas isolates of C. albicans, C. parapsilosis, and C. tropicalis were all highly susceptible to both fluconazole (98.9 to 100% susceptible) and itraconazole (96.4 to 100% susceptible). Isolates from Canada and Latin America were generally more susceptible to both triazoles than U.S. isolates were. Continued surveillance appears necessary to detect these important changes.

Antifungal Agents↗
PubMed2000

Postantifungal effects of echinocandin, azole, and polyene antifungal agents against Candida albicans and Cryptococcus neoformans.

The postantifungal effect (PAFE) of fluconazole, MK-0991, LY303366, and amphotericin B was determined against isolates of Candida albicans and Cryptococcus neoformans. Concentrations ranging from 0. 125 to 4 times the MIC were tested following exposure to the antifungal for 0.25 to 1 h. Combinations of azole and echinocandin antifungals (MK-0991 and LY303366) were tested against C. neoformans. Fluconazole displayed no measurable PAFE against Candida albicans or Cryptococcus neoformans, either alone or in combination with either echinocandin antifungal. MK-0991, LY303366, and amphotericin B displayed a prolonged PAFE of greater than 12 h against Candida spp. when tested at concentrations above the MIC for the organism and 0 to 2 h when tested at concentrations below the MIC for the organism.

Amphotericin B↗
PubMed2000

Evaluation of voriconazole pharmacodynamics using time-kill methodology.

Voriconazole is an investigational azole antifungal agent with activity against a variety of fungal species, including fluconazole-susceptible and -resistant Candida species and Cryptococcus neoformans. In this study, we employed in vitro time-kill methods to characterize the relationship between concentrations of voriconazole and its fungistatic activity against Candida albicans, Candida glabrata, Candida tropicalis, and C. neoformans. Isolates were exposed to voriconazole concentrations ranging from 0.0625 to 16 times the MIC, and the viable colony counts were determined over time. The 50 and 90% effective concentrations (EC(50) and EC(90), respectively) were determined at 8, 12, and 24 h following the addition of voriconazole. At each time point, near-maximal fungistatic activity, as indicated by the EC(90), was noted at a drug concentration of approximately three times the MIC. Additionally, EC(50) and EC(90) did not change over time, thus suggesting that the rate of activity was not improved by increasing concentrations. Voriconazole exhibits non-concentration-dependent pharmacodynamic characteristics in vitro.

Antifungal Agents↗
PubMed2000

Evaluation of the Etest method for determining voriconazole susceptibilities of 312 clinical isolates of Candida species by using three different agar media.

Performance of the Etest for voriconazole susceptibility testing of 312 isolates of Candida spp. was assessed against that of the National Committee for Clinical Laboratory Standards (NCCLS) microdilution broth method. The NCCLS method employed RPMI 1640 broth medium, and MICs were read after incubation for 48 h at 35 degrees C. Etest MICs were determined with RPMI agar containing 2% glucose (RPG), Casitone agar (CAS), and antibiotic medium 3 (AM3) agar and were read after incubation for 48 h at 35 degrees C. The Candida spp. isolates included C. albicans (n = 174), C. glabrata (n = 55), C. tropicalis (n = 31), C. parapsilosis (n = 39), C. krusei (n = 5), C. lusitaniae (n = 2), and C. guilliermondii (n = 6). The Etest results obtained using RPG correlated well with the reference MICs. Overall agreement ranged from 91% for C. glabrata to 100% for C. tropicalis, C. parapsilosis, C. guilliermondii, C. krusei, and C. lusitaniae. When CAS was used, agreement ranged from 80% for C. krusei to 100% for C. parapsilosis, C. guilliermondii, and C. lusitaniae. With AM3, agreement ranged from 58% for C. glabrata to 100% for C. lusitaniae and C. guilliermondii. The Etest method using RPG appears to be a useful method for determining voriconazole susceptibilities of Candida species.

Agar↗